Search

Background The indications for septoplasty are practice-based, rather than evidence-based. In addition, internationally accepted guidelines for the management of nasal obstruction associated with nasal septal deviation are lacking. Objective The objective was to determine the clinical effectiveness and cost-effectiveness of septoplasty, with or without turbinate reduction, compared with medical management, in the management of nasal obstruction associated with a deviated nasal septum. Design This was a multicentre randomised controlled trial comparing septoplasty, with or without turbinate reduction, with defined medical management; it incorporated a mixed-methods process evaluation and an economic evaluation. Setting The trial was set in 17 NHS secondary care hospitals in the UK. Participants A total of 378 eligible participants aged > 18 years were recruited. Interventions Participants were randomised on a 1: 1 basis and stratified by baseline severity and gender to either (1) septoplasty, with or without turbinate surgery (n = 188) or (2) medical management with intranasal steroid spray and saline spray (n = 190). Main outcome measures The primary outcome was the Sino-nasal Outcome Test-22 items score at 6 months (patient-reported outcome). The secondary outcomes were as follows: patient-reported outcomes – Nasal Obstruction Symptom Evaluation score at 6 and 12 months, Sino-nasal Outcome Test-22 items subscales at 12 months, Double Ordinal Airway Subjective Scale at 6 and 12 months, the Short Form questionnaire-36 items and costs; objective measurements – peak nasal inspiratory flow and rhinospirometry. The number of adverse events experienced was also recorded. A within-trial economic evaluation from an NHS and Personal Social Services perspective estimated the incremental cost per (1) improvement (of ≥ 9 points) in Sino-nasal Outcome Test-22 items score, (2) adverse event avoided and (3) quality-adjusted life-year gained at 12 months. An economic model estimated the incremental cost per quality-adjusted life-year gained at 24 and 36 months. A mixed-methods process evaluation was undertaken to understand/address recruitment issues and examine the acceptability of trial processes and treatment arms. Results At the 6-month time point, 307 participants provided primary outcome data (septoplasty, n = 152; medical management, n = 155). An intention-to-treat analysis revealed a greater and more sustained improvement in the primary outcome measure in the surgical arm. The 6-month mean Sino-nasal Outcome Test-22 items scores were −20.0 points lower (better) for participants randomised to septoplasty than for those randomised to medical management [the score for the septoplasty arm was 19.9 and the score for the medical management arm was 39.5 (95% confidence interval −23.6 to −16.4; p < 0.0001)]. This was confirmed by sensitivity analyses and through the analysis of secondary outcomes. Outcomes were statistically significantly related to baseline severity, but not to gender or turbinate reduction. In the surgical and medical management arms, 132 and 95 adverse events occurred, respectively; 14 serious adverse events occurred in the surgical arm and nine in the medical management arm. On average, septoplasty was more costly and more effective in improving Sino-nasal Outcome Test-22 items scores and quality-adjusted life-years than medical management, but incurred a larger number of adverse events. Septoplasty had a 15% probability of being considered cost-effective at 12 months at a £20,000 willingness-to-pay threshold for an additional quality-adjusted life-year. This probability increased to 99% and 100% at 24 and 36 months, respectively. Limitations COVID-19 had an impact on participant-facing data collection from March 2020. Conclusions Septoplasty, with or without turbinate reduction, is more effective than medical management with a nasal steroid and saline spray. Baseline severity predicts the degree of improvement in symptoms. Septoplasty has a low probability of cost-effectiveness at 12 months, but may be considered cost-effective at 24 months. Future work should focus on developing a septoplasty patient decision aid. Trial registration This trial is registered as ISRCTN16168569 and EudraCT 2017-000893-12. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/226/07) and is published in full in Health Technology Assessment; Vol. 28, No. 10. See the NIHR Funding and Awards website for further award information. Plain language summary Septoplasty is an operation to straighten the septum, which is the partition wall between the nostrils inside the nose. Septoplasty can be used as a treatment for people who have a bent septum and symptoms of a blocked nose, such as difficulty sleeping and exercising. Medical management (a saltwater spray to clear the nose followed by a nose steroid spray) is an alternative treatment to septoplasty. The Nasal AIRway Obstruction Study (NAIROS) aimed to find out whether septoplasty or medical management is a better treatment for people with a bent septum and symptoms of a blocked nose. We recruited 378 patients with at least moderately severe nose symptoms from 17 hospitals in England, Scotland and Wales to take part in the NAIROS. Participants were randomly put into one of two groups: septoplasty or medical management. Participants’ nose symptoms were measured both when they joined the study and after 6 months, using a questionnaire called the Sino-nasal Outcome Test-22 items. This questionnaire was chosen because patients reported that it included symptoms that were important to them. Other studies have shown that a 9-point change in the Sino-nasal Outcome Test-22 items score is significant. After 6 months, on average, people in the septoplasty group improved by 25 points, whereas people in the medical management group improved by 5 points. We saw improvement after septoplasty among patients with moderate symptoms, and among those with severe symptoms. Most patients who we spoke to after a septoplasty were happy with their treatment, but some would have liked more information about what to expect after their nose surgery. In the short term, septoplasty is more costly than medical management. However, over the longer term, taking into account all the costs and benefits of treatment, suggests that septoplasty would be considered good value for money for the NHS. Scientific summary Background The indications for septoplasty are practice-based, rather than evidence-based. In addition, internationally accepted guidelines for the management of nasal obstruction associated with nasal septal deviation are lacking. Objectives The study objectives are split into three different aspects: clinical effectiveness, economic evaluation and mixed-methods process evaluation. Objective 1 was to measure clinical effectiveness according to: subjective self-reported rating of nasal airway obstruction heterogeneity of estimated treatment effect, specifically according to severity of obstruction and gender objective measures of nasal patency number of adverse events (AEs) and additional interventions required technical failure in the surgical arm how well those agreeing to enter the trial reflect those screened for eligibility. Objective 2 was to conduct an economic evaluation from the perspective of the NHS and Personal Social Services. This entailed the following processes: conducting a cost-effectiveness analysis, with outcomes reported as incremental cost per ≥ 9-point improvement in the Sino-nasal Outcome Test-22 items (SNOT-22) scores and number of AEs conducting a cost–utility analysis, with outcomes reported as incremental cost per quality-adjusted life-year (QALY) gained designing a longer-term economic model to assess costs and health consequences beyond the 12-month follow-up period. Objective 3 was to conduct a mixed-methods process evaluation of the trial and interventions, to understand: barriers to optimal recruitment, and potential solutions to address these, through integration of the Qualitative research integrated within Trials (QuinteT) Recruitment Intervention (QRI) participants’ and healthcare professionals’ experiences of trial participation and the interventions, and perceived factors likely to influence wider implementation of trial findings. Methods The Nasal AIRway Obstruction Study (NAIROS) was a multicentre, non-blinded randomised controlled trial comparing the effectiveness of septoplasty, with or without turbinate surgery, with a standardised medical management package of 6 months of intranasal steroid spray and saline spray. Participants were randomised on a 1 : 1 basis between the septoplasty (within 8 weeks) and medical management arms. The trial included an integrated health economic evaluation and a mixed-methods process evaluation incorporating a QRI. The target sample size of 378 participants allowed for 20% dropout to deliver 90% power for detecting a minimal clinically important difference of 9 points in SNOT-22 scores. This assumed a two-sided type error rate of 5% and a standard deviation of 24 points in SNOT-22 scores at 6 months. Interventions The two interventions being compared were as follows. Septoplasty, with or without inferior turbinate reduction in the contralateral nostril, performed at the discretion of the investigating clinician, preferably performed within 8 weeks of randomisation or, if not, by 12 weeks. Medical management with 6 months of mometasone furoate 50 μg per dose nasal steroid spray, suspension (Nasonex®; Merck Sharp & Dohme Limited, Hoddesdon, UK), and isotonic nasal saline spray. Participants had the option of deferred surgery after 6 or 12 months post randomisation. Setting and participants We recruited 378 patients to the main trial from 17 NHS hospitals in Great Britain. Eligible patients were identified from general ear, nose and throat referrals. Of those recruited, 188 were randomised to septoplasty and 190 were randomised to medical management. Inclusion criteria Adults aged ≥ 18 years. Baseline Nasal Obstruction Symptom Evaluation (NOSE) scale score of ≥ 30. Septal deflection visible via nasoendoscopy. Capacity to provide informed consent/complete trial questionnaires. Exclusion criteria Prior septal surgery. Systemic inflammatory disease/use of oral steroid treatment in the previous 2 weeks. Granulomatosis with polyangiitis. Nasoendoscopic evidence of unrelated associated pathology. Intranasal recreational drug use in the previous 6 months. Breastfeeding, pregnancy or intended pregnancy for duration of involvement in the trial. Bleeding diathesis. Therapeutic anticoagulation. Contraindication to general anaesthesia. Immunocompromised. External bony deformity. Measurement of clinical outcomes Primary outcome The primary outcome was patient-reported assessment of nasal and general symptoms, using the SNOT-22 questionnaire, at 6 months (−2 weeks/+4 weeks). The SNOT-22 was also assessed at baseline and 12 months (± 2 weeks). Secondary outcomes Objective measures: peak nasal inspiratory flow and rhinospirometry (maximal inhalation volume and tidal breathing) at baseline and at 6 and 12 months. Patient-reported outcomes: SNOT-22 subscales at 12 months, NOSE score and Double Ordinal Airway Subjective Scale at baseline and at 6 and 12 months. Safety measures: number and characteristics of any AEs, surgical complications and reinterventions within 12 months. Quality of life, measured using the Short Form questionnaire-36 items (SF-36) at baseline and at 6 and 12 months. Healthcare utilisation questionnaire at baseline and at 6 and 12 months. Time and travel questionnaire at 12 months. Measurement of health economic outcomes To compare costs incurred by the NHS and Personal Social Services (PSS) with those incurred by participants in the management of a deviated septum. To compare QALYs, based on responses to the SF-36 administered at baseline and at 6 and 12 months, converted to Short Form questionnaire-6 Dimensions (SF-6D) utility scores, derived using the area under the curve method. To compare the cost-effectiveness of septoplasty with that of medical management at 12 months, measured in terms of the incremental: cost per improvement (of ≥ 9 points) in SNOT-22 scores cost per AE avoided cost per QALY gained. To compare the cost-effectiveness of septoplasty with that of medical management at 24 and 36 months in terms of the incremental cost per QALY gained (costs and QALYs were extrapolated using an economic model). Mixed-methods process evaluation outcomes The objectives for the mixed-methods process evaluation were addressed through observations of training and NAIROS meetings, interviews with health professionals and participants, audio-recording of recruitment discussions and review of screening logs. The QRI initiated with a ‘pre-recruitment’ phase to raise awareness about common recruitment issues/solutions learnt from previous trials. Phase 1 of the QRI investigated sources of recruitment difficulty that were specific to the NAIROS, informing ‘actions’ to optimise recruitment as the trial was under way (phase 2). Statistical analysis The primary statistical analysis was carried out on an intention-to-treat (ITT) basis, retaining patients in their randomised treatment groups. Multivariable linear regression models were used to compare the 6-month SNOT-22 scores between the treatment groups, adjusting any treatment effect by baseline SNOT-22 score and stratification factors at randomisation [(1) gender and (2) severity at baseline (according to three NOSE categories reported in the literature: 30–50, moderate; 55–75, severe; and 80–100, extreme)]. Sensitivity analyses, including a per-treatment and a per-protocol analysis, were also undertaken. Secondary outcomes were analysed in a way that was similar to the primary outcome analysis. Economic analysis The cost-effectiveness of septoplasty, compared with medical management, was evaluated by estimating the total costs incurred by the NHS and PSS to manage a deviated septum and averaging these costs across participants in each study arm. Both within-trial and model-based analyses were undertaken. The within-trial analysis estimated costs and effects over 12 months. Three different measures of effects were used: improvement (of ≥ 9 points) in SNOT-22 scores, number of AEs and QALYs. QALYs were derived from responses to the SF-36, which we converted into SF-6D scores (utilities) using a standardised algorithm and the area under the curve approach. An economic model was designed to extrapolate costs and benefits beyond the 12-month study follow-up period. Mixed-methods process evaluation analysis QuinteT Recruitment Intervention: thematic and content analyses were undertaken of interviews and audio-recorded consultations, and descriptive analyses of screening log data were undertaken. Qualitative process evaluation: a thematic analysis was undertaken using a coding framework, informed by normalisation process theory. Results Primary outcomes The ITT analysis found that, at 6 months, participants randomised to the septoplasty arm (n = 152) had SNOT-22 scores that were, on average, 20.0 points lower (i.e. better) than those of participants randomised to medical management (n = 155) [95% confidence interval (CI) −23.6 to −16.4 points; p < 0.0001]. This strong signal was confirmed by both sensitivity analyses and analysis of secondary outcomes. The mean SNOT-22 scores at 6 months were 19.9 points for the septoplasty arm and 39.5 points for the medical management arm. At 12 months, the adjusted mean difference for SNOT-22 scores between the two arms had reduced to −10.1 points (95% CI −14.5 to −5.6 points; p < 0.0001). This diminished effect at 12 months was predominantly due to SNOT-22 scores tending to reduce over time among those randomised to medical management. Overall, the improvement in SNOT-22 score in the surgical arm was both notably faster and greater, and was sustained over the trial period. Increased baseline severity of nasal obstruction was associated with greater improvements in the primary outcome. Gender had no impact on outcome improvement. Approximately 45 out of 190 (24%) participants discontinued allocated medical management treatment and had non-trial surgery, and 22 out of 188 (12%) of those randomised to septoplasty did not receive the surgical intervention. The per-protocol (treatment effect −19.7, 95% CI −23.4 to −16.0) and per-treatment analyses (treatment effect −19.3, 95% CI −23.3 to −15.3) confirmed a statistically significant greater improvement in the surgical arm. Secondary outcomes All secondary outcome measures, both patient-reported and objective measures, showed a greater improvement in the surgical arm. Turbinate reduction did not appear to add additional benefit in comparison with septoplasty alone. At 6 months, 80% of patients reported improvement in nasal breathing (74% at 12 months). Six out of 166 patients undergoing septoplasty were recommended to consider revision septoplasty. Adverse events Overall, there were 227 AEs: 132 in the surgical arm and 95 in the medical management arm. Fourteen serious adverse events occurred in the surgical arm and nine in the medical arm. At 6 months, 7 out of 174 (4%) participants experienced hospital re-admission with nasal bleeding, none of whom required operative reintervention. Twenty out of 172 (12%) participants reported infection requiring antibiotic treatment, 19 out of 171 (11%) participants reported decreased sense of smell, 18 out of 171 (11%) participants reported numbness of the upper teeth and 17 out of 171 (10%) participants reported change in appearance of the nose. Six nasal septal perforations (3%) and seven intranasal adhesions (4%) were noted at 6 and 12 months’ follow-up. Economic evaluation On average, septoplasty was more costly and more effective in terms of improvements in SNOT-22 score and QALYs than medical management. The incremental cost per improvement (of ≥ 9 points) in SNOT-22 score was £4855. The incremental cost per QALY gained was £27,114 and septoplasty had a 15% probability of being considered cost-effective at a £20,000 willingness-to-pay threshold for an additional QALY. This probability increased to 68% at a £30,000 threshold. Septoplasty was dominated by medical management when AEs were the outcome of interest, as it was more costly and associated with a greater number of AEs. The economic model estimated the incremental cost per QALY gained at 24 months (£13,221) and 36 months (£7368). Septoplasty had a 99% (at 24 months) and a 100% (at 36 months) probability of being considered cost-effective, compared with medical management, at a £20,000 threshold for an additional QALY. Mixed-methods process evaluation QuinteT Recruitment Intervention findings Data sources included 19 interviews with recruiters, 108 audio-recorded discussions and regular scrutiny of screening logs. Despite recruiters’ commitment to the NAIROS, there were challenges operationalising recruitment processes into routine clinical care, which restricted identification of potentially eligible patients. Analysis of recorded consultations revealed evidence of recruiters operationalising the pre-recruitment training, but also illuminated unanticipated challenges around explaining the trial arms, which undermined equipoise. Tailored actions were implemented in phase 2 to address these issues, through feedback/training for individuals/groups, ‘recruitment workshops’ with sites, and written guidance and webinars for professionals who interacted with patients throughout the clinical pathway. The recruitment target was reached successfully without a funding extension and without the need to open additional sites. Qualitative process evaluation Nine surgeons and five research nurses working on the NAIROS trial were interviewed and 39 interviews were conducted with 31 participants. Prior to the NAIROS, decisions regarding the appropriateness of surgery for individual patients were made on the basis of a complex and largely subjective combination of symptoms, history and patient anatomy. Surgeons indicated that they would welcome clearer criteria to guide decision-making. However, although some surgeons embraced a role for standardised outcome measures such as the NOSE and the SNOT-22 in decision-making, others were more reluctant; this could be a barrier to the implementation of trial findings. Although trial findings show that, as a group, participants in the surgical arm experienced more improvement than those in the medical management arm, the qualitative study demonstrated that individual experiences were varied. Although some patients in the medical management arm achieved little or no benefit from treatment, others did report positive effects, with a possible mechanism of action being a reduction in turbinate size. Patients undergoing medical management might benefit from individual advice regarding application of the sprays, taking into account distorted anatomy, to maximise effectiveness and reduce side effects. Although most participants were able to incorporate spray use into their daily routines, long-term spray use was perceived by some to be burdensome. Despite the large number of participants who perceived septoplasty to be effective in reducing their symptoms, there were still some participants who felt that they received little to no benefit from the operation. Participants reported being underprepared for the immediate post-surgery period. Limitations COVID-19 had a major impact on the study, resulting in the cessation of clinical measurements and objective outcomes from March 2020. From that time, all patient-reported outcomes were collected by post or online, or transcribed over the telephone. The ITT analysis is likely to offer an overestimate of the true impact of medical management in improving outcomes as 22% of participants in that arm received septoplasty before the 12-month outcome point. Conclusions Septoplasty, with or without turbinate reduction, is a clinically effective intervention. Participants with a deviated nasal septum with a moderate, severe or extreme baseline severity of nasal obstruction symptoms had an improvement in patient-reported outcomes at 6 and 12 months. This improvement surpassed that of standardised medical management. The results suggest that surgery has a low probability of being cost-effective at 12 months but may be considered cost-effective at 24 months. Impact on health services The NAIROS clearly demonstrates that adults presenting with nasal obstruction associated with a deviated nasal septum, in the absence of clinical evidence of a coexistent nasal/sinus disease and with a baseline NOSE score of > 30, can reliably be offered surgery in the knowledge that improvements in patient-reported outcomes are superior to improvements when treated with a nasal steroid/saline spray combination. Recommendations for research The most important research priority to emerge from the NAIROS is the need to develop a patient decision aid to explore management of a deviated nasal septum. The place of medical treatment in the management of nasal obstruction associated with a deviated nasal septum needs to be explored further. A prospective randomised trial would be required to examine the place of turbinate reduction surgery in nasal obstruction. Study registration This trial is registered as ISRCTN16168569 and EudraCT 2017-000893-12. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/226/07) and is published in full in Health Technology Assessment; Vol. 28, No. 10. See the NIHR Funding and Awards website for further award information.

Background The place of tonsillectomy in the management of sore throat in adults remains uncertain. Objectives To establish the clinical effectiveness and cost-effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults, and to evaluate the impact of alternative sore throat patient pathways. Design This was a multicentre, randomised controlled trial comparing tonsillectomy with conservative management. The trial included a qualitative process evaluation and an economic evaluation. Setting The study took place at 27 NHS secondary care hospitals in Great Britain. Participants A total of 453 eligible participants with recurrent sore throats were recruited to the main trial. Interventions Patients were randomised on a 1 : 1 basis between tonsil dissection and conservative management (i.e. deferred surgery) using a variable block-stratified design, stratified by (1) centre and (2) severity. Main outcome measures The primary outcome measure was the total number of sore throat days over 24 months following randomisation. The secondary outcome measures were the number of sore throat episodes and five characteristics from Sore Throat Alert Return, describing severity of the sore throat, use of medications, time away from usual activities and the Short Form questionnaire-12 items. Additional secondary outcomes were the Tonsil Outcome Inventory-14 total and subscales and Short Form questionnaire-12 items 6 monthly. Evaluation of the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes against baseline severity, as assessed by Tonsil Outcome Inventory-14 score at recruitment. The incremental cost per sore throat day avoided, the incremental cost per quality-adjusted life-year gained based on responses to the Short Form questionnaire-12 items and the incremental net benefit based on costs and responses to a contingent valuation exercise. A qualitative process evaluation examined acceptability of trial processes and ramdomised arms. Results There was a median of 27 (interquartile range 12–52) sore throats over the 24-month follow-up. A smaller number of sore throats was reported in the tonsillectomy arm [median 23 (interquartile range 11–46)] than in the conservative management arm [median 30 (interquartile range 14–65)]. On an intention-to-treat basis, there were fewer sore throats in the tonsillectomy arm (incident rate ratio 0.53, 95% confidence interval 0.43 to 0.65). Sensitivity analyses confirmed this, as did the secondary outcomes. There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). There were 47 re-admissions following tonsillectomy (20.3%), 35 relating to haemorrhage. On average, tonsillectomy was more costly and more effective in terms of both sore throat days avoided and quality-adjusted life-years gained. Tonsillectomy had a 100% probability of being considered cost-effective if the threshold for an additional quality-adjusted life year was £20,000. Tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Trial processes were deemed to be acceptable. Patients who received surgery were unanimous in reporting to be happy to have received it. Limitations The decliners who provided data tended to have higher Tonsillectomy Outcome Inventory-14 scores than those willing to be randomised implying that patients with a higher burden of tonsillitis symptoms may have declined entry into the trial. Conclusions The tonsillectomy arm had fewer sore throat days over 24 months than the conservative management arm, and had a high probability of being considered cost-effective over the ranges considered. Further work should focus on when tonsillectomy should be offered. National Trial of Tonsillectomy IN Adults has assessed the effectiveness of tonsillectomy when offered for the current UK threshold of disease burden. Further research is required to define the minimum disease burden at which tonsillectomy becomes clinically effective and cost-effective. Trial registration This trial is registered as ISRCTN55284102. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information. Plain language summary Tonsillectomy is an operation to take out the pair of tonsil glands at the back of the throat. It is an option for adults who suffer from repeated, severe sore throats. Adults who have a tonsillectomy say that they get fewer sore throats afterwards, but it is not clear whether or not they would have got better over time without the operation. There is pressure on doctors to limit the number of tonsillectomies carried out. At the same time, emergency hospital admissions for adults with severe throat infections have been increasing. NAtional Trial of Tonsillectomy IN Adults aimed to find out whether tonsillectomy is an effective and worthwhile treatment for repeated severe sore throats or whether patients would be better off treated without an operation. A total of 453 patients from 27 hospitals in Great Britain took part in the study. Patients were assigned at random to receive either tonsillectomy or conservative management (treatment as needed from their general practitioner). We measured how many sore throats patients had in the next 2 years by sending them text messages every week. We asked about the impact of their sore throats on their quality of life and time off work, and looked at the costs of treatment. We also interviewed 47 patients, general practitioners and hospital staff about their experiences of tonsillectomy and NAtional Trial of Tonsillectomy IN Adults. The typical patient in the tonsillectomy arm had 23 days of sore throat compared with 30 days of sore throat in the conservative management arm. Tonsillectomy resulted in higher quality of life. We looked to see whether or not it was only those with the most severe sore throats who benefited from tonsillectomy, but we found that patients with more or less severe sore throats at the start all did better with tonsillectomy. Patients who had a tonsillectomy were happy to have undertaken this. Our findings suggest a clear benefit of tonsillectomy using modest additional NHS resources for adults with repeated severe sore throats. Scientific summary Background Sore throats cost the NHS over £120M per annum, including ≈ £60M for general practitioner (GP) consultations and medical therapy. The place of tonsillectomy in the management of sore throat remains uncertain. Objectives Clinical To establish the clinical effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults. To report the number of adverse events (AEs), visits to the GP/walk-in clinic/accident and emergency, prescriptions issued and additional interventions required to manage sore throats and related events through weekly Sore Throat Alert Return (STAR) response data and primary care patient records. To adjust the estimate of effectiveness in the light of other baseline covariates, including severity of tonsillitis. To evaluate the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes. To assess to what extent trial participants were representative of the total population of sore throat patients referred to ear, nose and throat (ENT) clinics. To inform future research. Qualitative process evaluation To examine the acceptability of the trial, treatments and unforeseen consequences from the perspective of participants and stakeholders, including ENT staff and GPs. Economic evaluation To compare costs incurred by the NHS, Personal and Social Services (PSS) and participants to manage recurrent sore throats in adults. To compare quality-adjusted life-years (QALYs) using the area-under-the-curve method based on Short Form questionnaire-6 Dimension (SF-6D) scores derived from longitudinal Short Form questionnaire-12 items (SF-12) responses throughout the study and during self-reported sore throat episodes. To compare the cost-effectiveness measured in terms of the incremental: cost per sore throat day avoided cost per QALY gained net benefit – estimated based on self-reported number of sore throat days and responses to a contingent valuation questionnaire administered at baseline asking participants’ willingness to pay (WTP) to avoid a sore throat day. Methods Design A multicentre, randomised controlled trial comparing the effectiveness of tonsillectomy for recurrent sore throat with that of non-surgical conservative management in a 1 : 1 ratio over a 24-month period. Surgeons, participants and site staff could not be blinded to the allocated procedure. The main trial began following the completion of a feasibility study and included a qualitative process evaluation, as well as an economic evaluation. The design, conduct and reporting of the trial were informed by patients. Crossover of participants between arms was permitted. Interventions Tonsil dissection: dissection of the palatine tonsils preferably within 6 weeks, and no more than 8 weeks, following randomisation (dissection method at the discretion of the participating centres). Conservative (non-surgical) management (i.e. deferred surgery): participants entering the conservative management arm were asked to defer surgery for up to 24 months on the understanding that they would be reviewed at 12 months. Setting and participants A total of 453 patients were recruited to the main trial from 27 NHS secondary care hospitals in Great Britain. Eligible patients were identified via general ENT referrals and established sore throat-specific referral pathways, some of which were run by ENT nurse practitioners. Inclusion criteria Aged ≥16 years. Recurrent sore throats that fulfil current Scottish Intercollegiate Guidelines Network (SIGN) guidance for elective tonsillectomy. Exclusion criteria Previous tonsillectomy. Listed directly (i.e. added to waiting list without prior elective ENT outpatient appointment) during emergency admission (e.g. owing to peritonsillar abscess/quinsy). Primary sleep breathing disorder. Suspected malignancy. Tonsilloliths (as primary referral). Pregnant or breastfeeding. Bleeding diathesis (including haemophilia, sickle cell disease and platelet dysfunction). Therapeutic anticoagulation. Inability to complete self-reported questionnaires and sore throat returns. Main outcome measures Primary outcome The primary outcome measure was the total number of sore throat days over the 24 months following randomisation. The number of sore throat days was collected by a database that was designed for use in the trial (the STAR database). This database allowed participants to respond weekly to alerts by providing the number of sore throats that they had experienced in the previous 7 days (between 0 and 7 sore throat days). From the beginning of the trial, participants were able to choose their preferred method for receiving these alerts: e-mail, text message or interactive voice response (IVR) via telephone. Secondary outcomes A participant who had suffered from a sore throat in the past week (i.e. sore throat days >0) was asked to provide information on the severity of the sore throat(s) and additional data for health economics and other secondary outcomes in a STAR questionnaire. Quality-of-life data, reported as the SF-12 physical component score (PCS) and mental component score (MCS) and additional symptoms of tonsillitis, were collected every 6 months. The impact of alternative NHS sore throat pathways was measured by observation and statistical modelling of outcomes. The extent to which trial participants represented the total population of sore throat patients referred to ENT clinics was assessed through analysis of site screening logs. Adverse events Information regarding the AEs related to the trial intervention was collected during telephone calls at 1 and 2 weeks post tonsillectomy; all tonsillectomy arm serious adverse events (SAEs) were recorded throughout the duration of the trial for all participants. Economic evaluation The cost-effectiveness of tonsillectomy compared with conservative management was evaluated by estimating the total costs incurred by the NHS and PSS, and averaging these costs across participants in each trial arm. Three different analyses were undertaken: (1) a cost-effectiveness analysis (CEA), (2) a cost–utility analysis (CUA) and (3) a cost–benefit analysis (CBA). All three analyses measured costs using the same methodology but differed in their measure of effectiveness. An incremental cost-effectiveness ratio was estimated for the CEA and the CUA by dividing the difference in average total costs by the difference in average total effects. The CEA estimated the incremental cost per sore throat day avoided. The number of sore throat days was derived from the primary outcome data. The CUA estimated the incremental cost per QALY gained. QALYs were derived using the SF-6D algorithm, which estimates utility values based on responses to the SF-12, which was administered at baseline and 6, 12, 18 and 24 months post randomisation and at the time of a sore throat episode. The CBA estimated the incremental net benefit, comparing costs and benefits in monetary terms. Participants’ WTP values, estimated from the contingent valuation study, were multiplied by participants’ self-reported number of sore throat days to estimate the reduction in patient benefits in monetary terms; from this costs were subtracted to give the net benefit. Qualitative process evaluation Qualitative and cognitive interviews were carried out by researchers from Newcastle University for the feasibility study, pilot and main trial. Interviews were held with adult patients with acute tonsillitis who had been referred to ENT outpatient clinics for recurrent sore throats, ENT staff who were working at a National Trial of Tonsillectomy IN Adults (NATTINA) trial site and GPs. These interviews addressed the acceptability of the trial/treatments, unforeseen consequences from the perspective of participants and how patient experience may shape future research. Statistical analysis The primary statistical analysis was carried out on an intention-to-treat (ITT) basis, retaining patients in their randomised arms and including protocol violator and ineligible patients. Patients randomised to conservative management were asked to commit to ‘deferred surgery’. We anticipated that a number of patients would take the opportunity to switch to surgery. We also undertook sensitivity analyses, including a per-treatment (as treated) and a per-protocol analysis. The cumulative total number of sore throat days reported on a patient level was provided separately for each randomised arm. Negative binomial regression was used to compare these, adjusting for stratification variables (baseline severity as a fixed effect and site as a random effect). The summary comparative statistic reported is the incident rate ratio (IRR). The analysis took account of incomplete weekly returns by use of an exposure variable included in the model. The analysis of secondary outcomes followed a broadly similar strategy to the primary outcome. Analyses were adjusted for baseline severity and site, and repeated measures were analysed using random-effects models with appropriate error structure. Results Primary outcome The participants in this trial reported a median of 27 [interquartile range (IQR) 12–52] sore throats over the full 24 months of follow-up. Fewer sore throats were reported in the tonsillectomy arm (median 23, IQR 11–46) than in the conservative management arm (median 30, IQR 14–65). When the primary outcome (total sore throats) was compared between the two randomised arms on an ITT basis, a reduction in sore throats was seen in the tonsillectomy arm. The tonsillectomy arm had 0.53 [IRR, 95% confidence interval (CI) 0.43 to 0.65] times the total sore throat days over the 24-month period than those in the conservative management arm. Sensitivity analyses on the ITT population confirmed this result. The analysis of the per-protocol population of 224 participants had, on average, a greater reduction in the number of sore throats, with patients in the tonsillectomy arm having 0.42 (IRR 95% CI 0.31 to 0.55) times the total score throats compared with the conservative management arm. Around 25% of participants did not receive the treatment that they were randomised to, which meant that some opted not to receive a tonsillectomy and some opted to cross to tonsillectomy. There is evidence to suggest that those with larger numbers of sore throats following randomisation were more likely to either opt for or remain in the tonsillectomy arm. Conversely, those with slightly smaller numbers of sore throats following randomisation were more likely to remain in conservative management or opt out of the tonsillectomy arm. Despite these crossovers, the ITT, per-protocol and per-treated analyses all confirmed that there was a significant reduction in total sore throats for those randomised to tonsillectomy. Secondary outcome measures The benefits of tonsillectomy were also seen in the secondary outcome measures. Tonsillectomy Outcome Inventory-14 (TOI-14) scores improved in both arms, but show a greater improvement in the tonsillectomy arm than the conservative management arm, where at 12 months the difference between the mean scores was –13.17 units (95% CI –17.41 to –8.92 units), indicating a reduction in symptoms. The SF-12 MCS and SF-12 PCS also show significant and beneficial differences in favour of the tonsillectomy arm over time [SF-12 MCS scores 3.71 units higher (95% CI 2.10 to 5.47) and SF-12 PCS 2.77 units higher (95% CI 0.30 to 5.23) in the tonsillectomy arm than the conservative management arm]. Adverse events There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). Of these episodes, 35 were reported as SAEs: 8 as mild events, 22 as moderate events and 5 as severe events. No deaths were reported. Seventeen episodes were recorded as AEs, for which patients did not attend hospital. All episodes of bleeding were managed conservatively with no returns to theatre. Economic evaluation On average, tonsillectomy was more costly and more effective than conservative management. In the CEA, the incremental cost to avoid a sore throat episode was £24 per sore throat day. From the contingent valuation, the mean WTP to avoid a sore throat day was £43 (95% CI £2 to £100). In the CUA, tonsillectomy had an 87% probability of being considered cost-effective at a £5000 threshold for an additional QALY; this increased to 100% as the threshold values for an additional QALY increased. In the CBA, tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Qualitative study Trial processes were deemed as acceptable, with only a few sites experiencing barriers to treatment. The use of technology to collect data was particularly well received. However, there were some challenges with recruitment, particularly for staff who lacked equipoise. ENT staff alluded to having to negotiate surgery dates with patients, which, at times, meant that they had to deviate from trial protocols. Some patients did not fully understand the process of randomisation. Patients who had received surgery were unanimous in reporting to be happy to have undertaken this, despite the challenging recovery period. Limitations There was some evidence that those with the most severe extent of disease were reluctant to enter the study (around 5 points higher scores overall on the TOI-14). Some symptoms may not be a result of tonsillitis. Not all patients were offered, or chose, to watch the trial recruitment video. The ITT analysis is likely to offer a conservative underestimate of the true impact of tonsillectomy in reducing sore throat days, as a result of patients crossing over to receive tonsillectomy. A challenge of the economic evaluation was the progressive loss of data over the 24-month follow-up. Conclusions Tonsillectomy in adults is a clinically effective intervention. It was more costly but had a high probability of being considered cost-effective over the range of analyses conducted. Participants with recurrent tonsillitis, who met current UK NHS guidelines to undergo tonsillectomy, suffered significantly fewer sore throat days over 24 months than similar participants treated conservatively. How should health services react? Pre-NATTINA, UK guidelines were a translation of level 1 evidence in children, applied to adults. Access to tonsillectomy in the UK was governed by application of national guidance, which is predicated on a qualifying number of episodes of tonsillitis. NATTINA participants in the tonsillectomy arm reported, on average, fewer healthcare contacts, fewer sore throat days and higher QALYs than those in the conservative management arm. Within the UK, tonsillectomy is listed as a ‘procedure of limited clinical value’ (The Royal College of Surgeons of England. Procedures of Limited Clinical Value: Royal College of Surgeons Briefing. London: The Royal College of Surgeons of England; 2011). To the best of our knowledge, NATTINA is the first definitive trial to demonstrate that tonsillectomy performed according to the current UK national guidelines is effective for patients, and the probability of it being considered cost-effective is high. Guideline reassessment, in particular how guidelines translate into healthcare commissioning, is called for. How should practitioners and patients respond to these findings? We have identified communication issues at the primary–secondary care interface in our qualitative work. There is, therefore, a need to convert the findings of NATTINA into a practical decision support tool for patients and surgeons. Implications for research (in priority order) The top research priority to emerge from NATTINA is to determine the optimum timing of tonsillectomy in adults with recurrent acute tonsillitis. Work is required also to optimise metrics for disease burden severity, and to exploit the novel real-time data collection methods elaborated in NATTINA. There is also a need to better understand optimum treatment strategies, including oral steroids, for tonsillitis in primary care. Trial registration This trial is registered as ISRCTN55284102. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information.

Abstract Background Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson’s Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. Methods The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology – Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. Trial registration ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.

Abstract Background Septoplasty (surgery to straighten a deviation in the nasal septum) is a frequently performed operation worldwide, with approximately 250,000 performed annually in the US and 22,000 in the UK. Most septoplasties aim to improve diurnal and nocturnal nasal obstruction. The evidence base for septoplasty clinical effectiveness is hitherto very limited. Aims To establish, and inform guidance for, the best management strategy for individuals with nasal obstruction associated with a deviated septum. Methods/design A multicentre, mixed-methods, open label, randomised controlled trial of septoplasty versus medical management for adults with a deviated septum and a reduced nasal airway. Eligible patients will have septal deflection visible at nasendoscopy and a nasal symptom score ≥ 30 on the NOSE questionnaire. Surgical treatment comprises septoplasty with or without reduction of the inferior nasal turbinate on the anatomically wider side of the nose. Medical management comprises a nasal saline spray followed by a fluorinated steroid spray daily for six months. The recruitment target is 378 patients, recruited from up to 17 sites across Scotland, England and Wales. Randomisation will be on a 1:1 basis, stratified by gender and severity (NOSE score). Participants will be followed up for 12 months post randomisation. The primary outcome measure is the total SNOT-22 score at 6 months. Clinical and economic outcomes will be modelled against baseline severity (NOSE scale) to inform clinical decision-making. The study includes a recruitment enhancement process, and an economic evaluation. Discussion The NAIROS trial will evaluate the clinical effectiveness and cost-effectiveness of septoplasty versus medical management for adults with a deviated septum and symptoms of nasal blockage. Identifying those individuals most likely to benefit from surgery should enable more efficient and effective clinical decision-making, and avoid unnecessary operations where there is low likelihood of patient benefit. Trial registration EudraCT: 2017–000893-12, ISRCTN: 16168569. Registered on 24 March 2017.

Abstract Background Visually impaired older people (VIOP) have a higher risk of falling than their sighted peers, and are likely to avoid physical activity. The aim was to adapt the existing Falls Management Exercise (FaME) programme for VIOP, delivered in the community, and to investigate the feasibility of conducting a definitive randomised controlled trial (RCT) of this adapted intervention. Methods Two-centre randomised mixed methods pilot trial and economic evaluation of the adapted group-based FaME programme for VIOP versus usual care. A one hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle and Glasgow), delivered by third sector (voluntary and community) organisations. Participants were advised to exercise at home for an additional two hours over the week. Those randomised to the usual activities group received no intervention. Outcome measures were completed at baseline, 12 and 24 weeks. The potential primary outcome was the Short Form Falls Efficacy Scale – International (SFES-I). Participants’ adherence was assessed by reviewing attendance records and self-reported compliance to the home exercises. Adherence with the course content (fidelity) by instructors was assessed by a researcher. Adverse events were collected in a weekly phone call. Results Eighteen participants, drawn from community-living VIOP were screened; 68 met the inclusion criteria; 64 participants were randomised with 33 allocated to the intervention and 31 to the usual activities arm. 94% of participants provided data at the 12 week visit and 92% at 24 weeks. Adherence was high. The intervention was found to be safe with 76% attending nine or more classes. Median time for home exercise was 50 min per week. There was little or no evidence that fear of falling, balance and falls risk, physical activity, emotional, attitudinal or quality of life outcomes differed between trial arms at follow-up. Conclusions The intervention, FaME, was implemented successfully for VIOP and all progression criteria for a main trial were met. The lack of difference between groups on fear of falling was unsurprising given it was a pilot study but there may have been other contributory factors including suboptimal exercise dose and apparent low risk of falls in participants. These issues need addressing for a future trial. Trial registration Current Controlled Trials ISRCTN ID: 16949845 Registered: 21 May 2015.

Background: Persistent throat symptoms are commonly attributed to ‘laryngopharyngeal reflux’. Despite a limited evidence base, these symptoms are increasingly being treated in primary care with proton pump inhibitors. Objective: To assess the value of proton pump inhibitor therapy in patients with persistent throat symptoms. Design: This was a double-blind, placebo-controlled, randomised Phase III trial. Setting: This was a multicentre UK trial in eight UK ear, nose and throat departments. Participants: A total of 346 participants aged ≥ 18 years with persistent throat symptoms and a Reflux Symptom Index score of ≥ 10, exclusive of the dyspepsia item, were recruited. Intervention: Random allocation (1 : 1 ratio) to either 30 mg of lansoprazole twice daily or matched placebo for 16 weeks. Main outcome measure: Symptomatic response (i.e. total Reflux Symptom Index score after 16 weeks of therapy). Results: A total of 1427 patients were screened and 346 were randomised. The mean age was 52 years (standard deviation 13.7 years, range 20–84 years); 150 (43%) participants were male and 196 (57%) were female; 184 (53%) participants had a mild Reflux Symptom Index minus the heartburn/dyspepsia item and 162 (47%) had a severe Reflux Symptom Index minus the heartburn/dyspepsia item. A total of 172 patients were randomised to lansoprazole and 174 were randomised to placebo. Main outcomes: A total of 267 participants completed the primary end-point visit (lansoprazole, n = 127; placebo, n = 140), of whom 220 did so between 14 and 20 weeks post randomisation (‘compliant’ group); 102 received lansoprazole and 118 received placebo. The mean Reflux Symptom Index scores at baseline were similar [lansoprazole 22.0 (standard deviation 8.0), placebo 21.7 (standard deviation 7.1), overall 21.9 (standard deviation 7.5)]. The mean Reflux Symptom Index scores at 16 weeks reduced from baseline in both groups [overall 17.4 (standard deviation 9.9), lansoprazole 17.4 (standard deviation 9.9), placebo 15.6 (standard deviation 9.8)]. Lansoprazole participants had estimated Reflux Symptom Index scores at 16 weeks that were 1.9 points higher (worse) than those of placebo participants (95% confidence interval –0.3 to 4.2; padj = 0.096), adjusted for site and baseline severity. Secondary outcomes: Ninety-five (43%) participants achieved a Reflux Symptom Index score in the normal range (

Background: Looked-after children and care leavers (henceforth children in care) are young people placed under the care of local authorities, often because of a history of family abuse and/or neglect. These young people have significantly increased risk of substance use and mental health problems compared with peers. Aim: The Supporting Looked After Children and Care Leavers In Decreasing Drugs, and alcohol (SOLID) trial aimed to investigate the feasibility of a definitive randomised controlled trial comparing two behaviour change interventions to reduce risky substance use (illicit drugs and alcohol) in and improve the mental health of children in care aged 12–20 years. Methods: The study consisted of two phases: (1) a formative phase that adapted the motivational enhancement therapy and social behaviour and network therapy interventions for use with children in care and (2) a three-arm pilot randomised controlled trial (comparing motivational enhancement therapy, social behaviour and network therapy and usual care), and a linked process and economic (return on investment) evaluation. Trial feasibility was compared with prespecified STOP/GO criteria. Setting: Six local authority areas in the north-east of England. Participants: Children in care (aged 12–20 years) who screened positive for drug and/or alcohol use within the last 12 months were eligible for the trial. The formative and process evaluations included children in care, carers, social workers, and drug and alcohol workers. Outcome measures: The primary outcomes were recruitment and retention rates at 12 months’ follow-up. Baseline and 12-month follow-up questionnaires measured self-reported drug and alcohol use, mental health and health-related quality of life. The process evaluation considered acceptability and engagement with the interventions and trial procedures. Results: Formative findings (n = 65) highlighted the need for interventions to increase the emphasis on therapeutic relationships, use creative methods of engagement and support the identification of treatment goals wider than substance misuse. Within the randomised controlled trial, of 860 participants screened, 211 (24.5%) met the inclusion criteria. One hundred and twelve (53%) of the 211 eligible children were recruited and randomised. Just 15 of the 76 (20%) participants allocated to intervention attended any of the motivational enhancement therapy of social behaviour and network therapy sessions, and 60 (54%) participants completed the 12-month follow-up. The screening and recruitment of children in care required significantly more time and resource investment by researchers and children’s services than planned. The process evaluation (n = 116) demonstrated that, despite participants engaging in risky substance use, they did not often acknowledge this nor felt that they needed help. Children in care had complex, chaotic lives and children’s services departments were less research mature and extremely stretched; this, coupled with the multiple steps in the intervention pathway and study protocol, resulted in low adherence to the intervention and the trial. Conclusions: The SOLID trial demonstrated successful engagement with children in care to adapt the motivational enhancement therapy and social behaviour and network therapy interventions. However, the pilot randomised controlled trial found that a definitive trial is not feasible. The current screen, refer and treat pathway for children in care did not work. There is an urgent need to radically rethink how we deliver therapeutic services for children in care. A pragmatic evaluation design, coupled with additional research resource for children’s services, is needed to evaluate these novel models of care at scale. Trial registration: This study is registered as PROSPERO CRD42018098974 and Current Controlled Trials ISRCTN80786829. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 8, No. 13. See the NIHR Journals Library website for further project information.

BackgroundYoung people in state care, often due to abuse or neglect, have a four-fold increased risk of drug and alcohol use compared to their peers.AimThe SOLID study aimed to investigate the feasibility of a definitive randomised controlled trial, comparing two behaviour change interventions to reduce risky substance use (illicit drugs and alcohol), and improve mental health, in young people in care.MethodsWe recruited young people in care aged 12-20 years, self-reporting substance use within the previous 12 months and residing in 1 of 6 participating local authority sites in the North East of England. Participants were randomised to either i. Motivational Enhancement Therapy (MET), ii. Social Behaviour and Network Therapy (SBNT) or iii. Control (usual care). All interventions were delivered by trained drug and alcohol workers. Follow-up data were collected 12 months post recruitment. Feasibility for trial progression was compared to pre-specified stop: go criteria (recruitment of 60% of eligible participants, 80% of participants attending 60% of offered sessions and retention of 70% of participants at 12 month follow up).ResultsOf 1450 eligible participants, 860 (59%) were screened for drug and alcohol use by social workers, 211 (24.5%) met inclusion criteria for the trial and 112 young people (7.7%) consented and were randomised. Sixty of these 112 participants (54%) completed 12-month follow-up questionnaires. Only 15 out of the 76 (20%) participants allocated to an intervention arm attended any of the offered MET or SBNT sessions.ConclusionBy reference to pre-specified stop: go criteria it is not feasible to conduct a definitive trial for SOLID in its current format. Despite co-designing procedures with staff and young people in care, the screening, referral and treatment pathway did not work here. Future work may require dedicated clinically embedded research resource to evaluate effectiveness of new interventions in services.

Abstract Background Looked after children (LAC) and care leavers are young people who have been placed under the legal care of local authorities, in many instances due to a history of abuse and/or neglect. These young people have a significantly increased risk of substance use and mental disorder compared to their peers. The aim of the SOLID study is to assess the feasibility and acceptability of a definitive three-arm multi-centre randomised controlled trial (RCT) that compares the effectiveness of two interventions that aim to reduce risky drug and alcohol use and improve mental health among LAC aged 12 to 20 years with usual care. Methods All LAC aged 12 to 20 years residing in four local authorities in North East England will be screened by their social worker for risky drug and alcohol use using the CRAFFT (Car, Relax, Alone, Forget, Friends and Trouble) screening tool. Those who score ≥2 will be invited to take part in the trial after further eligibility checks. Informed consent will be taken and baseline data collected. Participants will then be randomised into either (i) Motivational Enhancement Therapy, (ii) Social Behaviour and Network Therapy, or (iii) control–usual care. Follow-up data will be collected 12 months post-baseline. The baseline and follow-up questionnaires will measure self-reported drug and alcohol use, mental health and well-being and health-related quality of life. The follow-up will also collect data on placement stability and self-reported sexual, antisocial and criminal behaviour. Participants will also be asked about the use of health and social services. A detailed process evaluation, using both qualitative and quantitative methods, will be conducted and involve LAC, their carers, social workers and drug and alcohol practitioners. Discussion Despite having an increased likelihood of risky substance misuse, there is a lack of evidence outlining specific interventions to decrease drug and alcohol use targeting LAC. This feasibility study will provide the information needed to develop a definitive trial. LAC will benefit from the results of this study and the further development of the interventions. Trial registration ISRCTN80786829

Background: The visually impaired have a higher risk of falling and are likely to avoid activity. Objectives: To adapt the existing Falls Management Exercise (FaME) programme, which is delivered in the community, for visually impaired older people (VIOP) and to investigate the feasibility of conducting a definitive randomised controlled trial of this adapted intervention. Design: Phase I – consultation with stakeholders to adapt the existing programme. Two focus groups were conducted, each with 10 VIOP across the study sites. Phase II – two-centre randomised pilot trial and economic evaluation of the adapted programme for VIOP versus usual care. Phases III and IV – qualitative interviews with VIOP and Postural Stability Instructors regarding their views and experiences of the research process, undertaking the intervention and its acceptability. Intervention: This was adapted from the group-based FaME programme. A 1-hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle upon Tyne and Glasgow) and was delivered by third-sector organisations. Participants were advised to also exercise at home for 2 hours per week. Those randomised to the usual activities group received no intervention. Outcome measures: These were completed at baseline, week 12 and week 24. The primary potential outcome measure used was the Short Form Falls Efficacy Scale – International. Secondary outcome assessment measures were activity avoidance, current activity, balance/falls risk, physical activity, loneliness, anxiety and depression, work and social adjustment, quality of life and economic costs. Participants’ compliance was assessed by reviewing attendance records and self-reported compliance with the home exercises. Instructors’ compliance with the course content (fidelity) was assessed by a researcher attending a sample of exercise sessions. Adverse events were collected in a weekly telephone call for all participants in both the intervention and control arm. Findings: An adapted exercise programme was devised with stakeholders. In the pilot trial, 82 participants drawn from community-living VIOP were screened, 68 met the inclusion criteria and 64 were randomised, with 33 allocated to the intervention and 31 to the usual activities arm. A total of 94% of participants provided data at week 12 and 92% at week 24. Adherence to the study was high. The intervention was found to be both safe and acceptable to participants, with 76% attending nine or more classes. Median time for home exercise was 50 minutes per week. There was little or no evidence that fear of falling, exercise, attitudinal or quality-of-life outcomes differed between trial arms at follow-up. Thematic analysis of the interviews with VIOP participants identified facilitators of and barriers to exercise, including perceived relevance to health, well-being and lifestyle, social interaction, self-perception and practical assistance. Instructors identified issues regarding level of challenge and assistance from a second person. Limitations: The small sample size and low falls risk of the study sample are study limitations. Conclusion: Although adaptation, recruitment and delivery were successful, the findings (particularly from qualitative research with instructors and participants) indicated that VIOP with low to moderate falls risk could be integrated into mainstream programmes with some adaptations. A future definitive trial should consider graduated exercises appropriate to ability and falls risk within mainstream provision. Other outcome measures may additionally be considered. Trial registration: Current Controlled Trials ISRCTN16949845. Funding: This project was funded by the NIHR Public Health Research programme and will be published in full in Public Health Research; Vol. 7, No. 4. See the NIHR Journals Library website for further project information.

The rising prevalence of cognitive impairment is an increasing challenge with the ageing of our populations but little is known about the burden in low- and middle- income Latin American and Caribbean countries (LAC) that are aging more rapidly than their developed counterparts. We examined life expectancies with cognitive impairment (CILE) and free of cognitive impairment (CIFLE) in seven developing LAC countries.Data from The Survey on Health, Well-being and Ageing in LAC (N = 10,597) was utilised and cognitive status was assessed by the Mini-Mental State Examination (MMSE). The Sullivan Method was applied to estimate CILE and CIFLE. Logistic regression was used to determine the effect of age, gender and education on cognitive outcome. Meta-regression models were fitted for all 7 countries together to investigate the relationship between CIFLE and education in men and women at age 60.The prevalence of CI increased with age in all countries except Uruguay and with a significant gender effect observed only in Mexico where men had lower odds of CI compared to women [OR = 0.464 95% CInt (0.268 - 0.806)]. Low education was associated with increased prevalence of CI in Brazil [OR = 4.848 (1.173-20.044)], Chile [OR = 3.107 (1.098-8.793), Cuba [OR = 2.295 (1.247-4.225)] and Mexico [OR = 3.838 (1.368-10.765). For males, total life expectancy (TLE) at age 60 was highest in Cuba (19.7 years) and lowest in Brazil and Uruguay (17.6 years). TLE for females at age 60 was highest for Chileans (22.8 years) and lowest for Brazilians (20.2 years). CIFLE for men was greatest in Cuba (19.0 years) and least in Brazil (16.7 years). These differences did not appear to be explained by educational level (Men: p = 0.408, women: p = 0.695).Increasing age, female sex and low education were associated with higher CI in LAC reflecting patterns found in other countries.