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Background Back pain frequently affects older people. Knowledge about back pain in older people and evidence to inform clinical care was lacking, particularly for older people with neurogenic claudication due to spinal stenosis, which is a debilitating condition. Objectives To understand and reduce the burden of back pain on older people by increasing knowledge about back pain in older people and developing evidence-based treatment strategies. Design We completed six work packages. These were not undertaken chronologically as there was overlap between work packages. Work package 1: Refine a physiotherapy intervention for neurogenic claudication. Work package 2: Feasibility of the Oxford Pain Activity and Lifestyle cohort study and Better Outcomes for Older people with Spinal Trouble randomised controlled trial. Work package 3: Development of a prognostic tool to identify when older people are at risk of mobility decline using data from the Oxford Pain Activity and Lifestyle cohort study. Work package 4: A randomised controlled trial of physiotherapy for neurogenic claudication and nested longitudinal qualitative study (Better Outcomes for Older people with Spinal Trouble randomised controlled trial). Work package 5: Predictors of participants’ response to treatment – prespecified subgroup analyses. Work package 6: Implementation planning. Setting Primary care and National Health Service Community and Secondary Care Trusts. Participants Community-dwelling adults over the age of 65 years and registered with primary care practices. Better Outcomes for Older people with Spinal Trouble trial participants reported back and/or leg pain consistent with neurogenic claudication. Interventions The Better Outcomes for Older people with Spinal Trouble programme was a physiotherapy-delivered combined physical and psychological group intervention for older people with neurogenic claudication. The comparator was a physiotherapy assessment and tailored advice (best practice advice). Main outcome measures The primary outcome for the Oxford Pain Activity and Lifestyle prognostic tool was mobility decline based on the EQ-5D-5L Mobility Question. The primary outcome for the Better Outcomes for Older people with Spinal Trouble trial was the Oswestry Disability Index at 12 months. Other outcomes included the Oswestry Disability Index walking item, 6-minute walk test and falls. The economic analyses used the EuroQol EQ-5D-5L to measure quality of life. Results Among Oxford Pain Activity and Lifestyle participants, 34% (1786/5304) reported back pain. A further 19.5% (1035/5304) reported back pain and associated leg pain, with 11.2% (n = 594/5304) reporting symptoms consistent with neurogenic claudication. Participants with back pain had worse quality of life compared to those without back pain and reported more adverse health states such as falls, frailty, low walking confidence and mobility decline. Those with neurogenic claudication were worst affected. At 2 years’ follow-up, among those reporting back pain at baseline, only 23% (489/2100) no longer reported symptoms. Recovery was lowest among participants reporting neurogenic claudication at baseline, with 90% still reporting symptoms. At 2 years’ follow-up, 18.6% of Oxford Pain Activity and Lifestyle participants reported mobility decline. Back pain with/without leg pain was not an independent predictor of mobility decline, but lower limb pain and the report of severe pain were independent predictors. Other predictors included slow walking pace, balance difficulties, low walking confidence, walking ability worse than last year, self-reported general health and comorbidity. In the Better Outcomes for Older people with Spinal Trouble trial, there was no significant difference in Oswestry Disability Index scores between treatment groups at 12 months (adjusted mean difference −1.4, 95% confidence interval −4.03 to 1.17), but at 6 months, scores favoured the Better Outcomes for Older people with Spinal Trouble programme (adjusted mean difference −3.7, 95% confidence interval −6.27 to −1.06). The Better Outcomes for Older people with Spinal Trouble programme resulted in greater improvements in the 6-minute walk test (mean difference 21.7 m, 95% confidence interval 5.96 to 37.38 m) and walking item (mean difference −0.2, 95% confidence interval −0.45 to −0.01) and reduced falls risk (odds ratio 0.6, 95% confidence interval 0.40 to 0.98) compared to best practice advice at 12 months. The probability that the Better Outcomes for Older people with Spinal Trouble programme is cost-effective ranged between 67% and 83% (National Health Service and Personal Social Services perspective) and between 79% and 89% (societal perspective) across cost-effectiveness thresholds between £15,000 and £30,000 per quality-adjusted life-year. From the embedded qualitative study, the Better Outcomes for Older people with Spinal Trouble programme was acceptable to participants, and enjoyable. Limitations Many of the data collected were self-reported and thus may be subject to recall bias or may have resulted in misclassification of participants. Conclusions Back pain is a substantial problem for older people, with the majority reporting persistent symptoms. We have developed an effective intervention to improve mobility and reduce falls in older people with neurogenic claudication; however, more effective interventions are needed for back pain generally. We have identified a set of self-reported questions that predict mobility decline in older people, so clinicians and their patients and families know when intervention is needed. Future work Develop and evaluate treatments for older people with back pain. Optimisation of the Better Outcomes for Older people with Spinal Trouble programme to better target pain-related disability. External validation of the Oxford Pain Activity and Lifestyle prognostic tool. Study registration This trial is registered as BOOST trial ISRCTN12698674. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: PTC-RP-PG-0213-20002) and is published in full in Programme Grants for Applied Research; Vol. 11, No. 9. See the NIHR Funding and Awards website for further award information. Plain language summary Back pain is a common problem for older people. This research aimed to increase our understanding of back pain in older people and to develop treatments to reduce the burden caused by back pain. The research was arranged in six work packages, and we completed three linked studies. Study 1: We enrolled 5409 older people in a cohort study. Participants answered questions about back pain, their health, mobility, falls and quality of life on enrolment and at 1 and 2 years’ follow-up. Back pain was reported by half of the participants, and 20% also reported leg pain. Back pain with/without leg pain is associated with reduced quality of life but also with being frail, falling and having walking problems. After 2 years, 77% of participants still reported being troubled by this pain. We developed a tool to identify when older people were at risk of reduced walking ability and to understand whether back pain was important here. Back and leg pain were not specifically linked to reduced walking, but severe pain was, suggesting that regardless of the type of pain, it needs to be treated. This tool could be used by clinicians and patients to know when they are at risk of reduced walking ability and to seek treatment. Study 2: We developed a group physiotherapy programme (the Better Outcomes for Older people with Spinal Trouble programme) for older people with a back-related condition called neurogenic claudication which results in pain spreading from the back into the legs and difficulties standing and walking. We tested the programme in a randomised controlled trial. The Better Outcomes for Older people with Spinal Trouble programme resulted in long-term improvements in walking, reduced falls, and short-term improvements in pain and disability. It is likely to be good value for the National Health Service. Study 3: We interviewed participants taking part in the Better Outcomes for Older people with Spinal Trouble trial to understand their experiences of the trial and whether the treatments helped. The Better Outcomes for Older people with Spinal Trouble programme was acceptable to participants, and they found it enjoyable. We are working with patient representatives and clinicians to make the Better Outcomes for Older people with Spinal Trouble programme available in routine care. Scientific summary Background Back pain (BP) is a common problem for older people but despite this, many older people either do not consult or general practitioners do not prioritise BP treatment for them due to the perception that nothing can be done. Many clinical trials exclude older people, and little attention has been paid to understanding the presentation of BP in older people and developing effective treatments. Older adults also experience leg pain referred from the lumbar spine. A common clinical presentation of spinal-related leg pain in older adults is neurogenic claudication (NC). It presents as symptoms radiating from the spine into the buttocks and legs which are provoked by walking or standing and relieved by sitting or lumbar flexion, often accompanied by BP. NC is particularly problematic for older people as it can cause severe pain and discomfort and substantially affect an individual’s confidence and ability to walk. Symptoms are thought to arise from pressure on nerves and blood vessels caused by degenerative changes narrowing the volume of the lumbar spinal canal. Narrowing may or may not be evident on imaging but when present, the condition is termed lumbar spinal stenosis. Physiotherapy is recommended prior to surgical intervention, but high-quality evidence to guide conservative care, including primary care management or physiotherapy, was lacking. Thus, we focused on NC to develop and test a physiotherapy intervention. We aimed to conduct a series of linked studies to increase knowledge and understanding about BP in older people and reduce the burden on older people by developing evidence-based treatment strategies. Objectives To describe the presentation and impact of BP in community-dwelling older adults. To refine a physiotherapy intervention for older people with NC and to evaluate the clinical and cost-effectiveness of this intervention in a randomised controlled trial (RCT). To understand the trial participants’ experiences, including acceptability and impact of the interventions. To understand the role of low BP in mobility decline through the development of a prognostic tool to predict when older people are at risk of mobility decline. To integrate findings into an implementation package. Methods We undertook three studies. A large population-based cohort study of community-dwelling older people recruited from primary care practices [the Oxford Pain Activity and Lifestyle (OPAL) cohort study]. We recruited older adults from primary care practices who were identified through electronic record searches and randomly selected eligible participants from two stratified age bands (65–74 and ≥ 75 years). In total, 5409 individuals (42.1% of eligible participants) from 35 general practices agreed to participate and followed up for 2 years by postal questionnaire. Participants provided data including demographics, socioeconomic factors, comorbidities, pain including low BP and its impact, other pain problems, physical activity, mobility, falls, frailty and quality of life. At baseline, we investigated the prevalence of BP and related leg pain within the cohort and estimated the association between different back and leg pain presentations and age-related adverse health states, including falls, frailty and mobility decline, using regression analyses. At 2 years, we estimated recovery rates. We investigated the role of back and leg pain in mobility decline by developing a prediction model for mobility decline at 2 years’ follow-up. Thirty-one candidate self-reported baseline predictors were prespecified. Missing data were imputed. Least Absolute Shrinkage and Selection Operator regression was used to select potential predictors. Model performance was assessed by calculating c-statistic, Brier score and decision-curve analysis. Models were internally validated using bootstrapping. The Better Outcomes for Older people with Spinal Trouble (BOOST) RCT of physiotherapy interventions for NC. We evaluated the clinical and cost-effectiveness of a physical and psychological group intervention (BOOST programme) compared to physiotherapy assessment and tailored advice [best practice advice (BPA)] for older people with NC. Participants were identified from spinal clinics (community and secondary care) and general practice records, and were randomised 2:1 to the BOOST programme or BPA. The primary outcome was the Oswestry Disability Index (ODI) at 12 months. Data were also collected at 6 months. Other outcomes included ODI walking item, 6-minute walk test (6MWT) and falls. The primary analysis was intention-to-treat. Prespecified subgroup analyses were also undertaken based on magnetic resonance imaging (MRI) parameters and other baseline factors including age, sex, frailty and physical capacity. The base-case economic evaluation was an intention-to-treat analysis conducted from a UK NHS and personal social services (PSS) perspective and separately from a societal perspective. Costs (2018–19 prices) were collected prospectively over 12 months. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained and the incremental net monetary benefit (INMB) of the BOOST programme in comparison to BPA. A longitudinal qualitative study embedded within the BOOST RCT. Embedded within the BOOST RCT was a longitudinal qualitative study. Semistructured interviews with participants were undertaken at baseline, 1 month after receiving their intervention and at 12 months. We analysed 30 sets of three interviews. We undertook an inductive thematic analysis and comparatively analysed data from the three time points to explore patients’ experiences with the trial interventions, including the impact on symptoms and their experiences of long-term exercise adherence. Results Oxford Pain Activity and Lifestyle cohort study Among OPAL participants, 34% (1786/5304) reported BP. A further 19.5% (1035/5304) reported BP and associated leg pain, with 11.2% (n = 594/5304) reporting symptoms consistent with NC. Participants with BP had worse quality of life compared to those without BP. All BP presentations were significantly associated with adverse health states. Those with NC were most affected. In particular, there was greater relative risk (RR) of low walking confidence [RR 3.11, 95% confidence interval (CI) 2.56 to 3.78], frailty (RR 1.88, 95% CI 1.67 to 2.11) and mobility decline (RR 1.74, 95% CI 1.54 to 1.97) compared to no BP. Of the participants reporting BP at baseline, 2139/2859 (74.8%) returned the 2-year follow-up questionnaire, and 23% of respondents no longer reported back or leg symptoms (489/2100). Recovery was highest among those reporting only BP at baseline (27.4%) and lowest among those reporting NC at baseline (10.9%). Participants reporting NC at baseline were most affected by symptoms at follow-up, reporting BP more frequently, with the highest proportion reporting very or extremely troublesome BP. They reported the highest pain interference ratings at follow-up, with the greatest proportion reporting severe interference with activity (26%). At baseline, the majority of OPAL participants reported no mobility problems (60.7%; 3146/5184) and 5.4% (280/5184) reported severe mobility problems. Two-year follow-up data were provided by 4115/5184 (79.4%) participants, with 18.6% (n = 765/4115) reporting mobility decline. We examined the univariable relationship between the baseline variables and the 2-year outcome. Nearly all the selected baseline factors had a univariate relationship with the outcome. Among those with mobility decline at 2 years, there were more reports of back and leg pain and greater numbers reporting multisite pain and widespread pain at baseline. The biggest difference in pain presentation was lower limb pain at baseline, which was reported by 68% of participants with mobility decline at follow-up, compared to 56% without. Baseline pain severity was also associated with mobility decline at follow-up. The multivariable analyses found that in addition to mobility status (no problems or mild problems) at baseline, 13 variables were identified as predictors of mobility decline at 2 years in ≥ 80% of the multiple imputed data sets. BP with/without leg pain was not an independent predictor of mobility decline, but lower limb pain and the report of severe pain were independent predictors. Demographic and socioeconomic factors (older age and those who perceived their income as inadequate) were also identified. There were multiple factors related to mobility, including participants who reported a slow usual walking pace, had difficulty maintaining their balance, had low confidence to walk long distances, rated their walking as worse compared to last year and reported sometimes using a walking aid outside, which were associated with a decline in mobility after 2 years. General health-related factors associated with decline in mobility at 2 years were having a higher body mass index, greater number of health conditions, problems in daily life due to physical tiredness, and poor self-reported general health. The multivariable model revealed a median c-statistic of 0.740 (range 0.737–0.743), indicating moderately good discrimination. The median Brier score was 0.136 (range 0.135–0.137). We developed a point scoring system to facilitate use in clinical practice. Better Outcomes for Older people with Spinal Trouble randomised controlled trial We analysed data from 435 trial participants with an average age of 74.9 years [standard deviation (SD) 6.0 years], and 57% (246/435) were female. At baseline, participants reported moderate disability levels [mean ODI 33 (SD 13.9)]. Their walking was markedly reduced [mean 6MWT 255 m (SD 99.1 m)] compared to healthy older adults. The primary outcome was obtained for 88.0% (383/435) and 87.4% (380/435) of participants at 6 months and 12 months, respectively, with 93.0% (403/435) contributing data to the primary analysis. There was no significant difference in ODI scores between treatment groups at 12 months [adjusted mean difference (MD) −1.4, 95% CI −4.03 to 1.17)], but at 6 months, ODI scores favoured the BOOST programme (adjusted MD –3.7, 95% CI –6.27 to –1.06). At 12 months, the BOOST programme resulted in greater improvements in walking capacity (6MWT MD 21.7 m, 95% CI 5.96 to 37.38 m) and ODI walking item (MD –0.2, 95% CI –0.45 to –0.01) and reduced falls risk (odds ratio 0.6, 95% CI 0.40 to 0.98) compared to BPA. No serious adverse events were related to either treatment. The economic analyses showed that the mean NHS and PSS costs over 12 months were £19,752 [standard error (SE) £118] in the BOOST arm versus £1827 (SE £169) in the BPA arm (p = 0.474). Mean (SE) QALY estimates were 0.620 (0.009) versus 0.599 (0.006), respectively (p = 0.093). The probability that the BOOST programme is cost-effective ranged between 67% and 83% (NHS and PSS perspective) and between 79% and 89% (societal perspective) across cost-effectiveness thresholds. INMBs ranged between £145 and £464 at cost-effectiveness thresholds between £15,000 and £30,000 per QALY. The Better Outcomes for Older people with Spinal Trouble qualitative study Interviews from 16 men and 14 women were included in this analysis. Fourteen participants were allocated to BPA and 16 were allocated to the BOOST programme. The symptoms of NC manifested both physically and psychologically, limiting participants’ ability to perform everyday activities as well their wider participation in social, leisure and recreational activities. Participants adopted coping strategies to minimise the impact of NC. Participants in the BOOST programme appeared more satisfied with their treatment compared to those allocated to BPA. Dissatisfaction among BPA participants seemed to arise from lack of feedback and follow-up. BOOST participants benefited from peer support and discussions. Most participants felt the exercises were appropriate and helpful, although this did not necessarily translate to improvements in pain. Dissatisfaction with the BOOST programme was mostly related to lack of pain relief. Pain remained a substantial problem for some participants. BOOST programme participants also talked about other improvements from the exercises, including improved posture, strength and confidence, highlighting the broader benefits of the BOOST programme. These types of changes were less evident in the narratives of BPA participants. BOOST participants reported benefit from the cognitive–behavioural component, including helping them to find their own solutions, manage flare-ups and understand the importance of long-term exercise. Reasons for stopping the home exercises were similar between treatment arms. These included competing priorities, lack of motivation and aggravation of pain. Adaptations allowed some BOOST participants to continue at least some of the exercises even when they were difficult. Participant narratives provided insight into ways to optimise the BOOST programme to improve long-term exercise adherence, including additional support to provide motivation for ongoing exercises (by the physiotherapist or by linking to exercise opportunities in the community), provide greater guidance on how to adapt exercises if they are painful, and to help plan integration into everyday life or transition to activities they enjoy. We have developed a package of implementation for the BOOST programme. Feedback from interview participants, patient and public involvement representatives and clinicians who delivered the BOOST programme and ongoing analyses of BOOST data will inform further refinement of the programme to better target pain-related disability. Conclusions Back pain is a substantial and persistent problem for older people, associated with reduced quality of life and age-related adverse health states. The impact is greatest on those with NC, but other presentations should not be ignored due to the high proportion of participants who reported ongoing symptoms. We developed a programme that successfully improved mobility and reduced falls among older people with NC, and future iterations of the programme will aim to reduce long-term pain-related disability. As it stands, the BOOST programme has a high probability of being cost-effective. There is a need to develop other interventions for the large number of older adults affected by BP, especially for those with more severe symptoms. Back and leg pain were not independent predictors of mobility decline, but severe pain was a predictor. This highlights a broader need to manage pain better in older people regardless of the type or presentation of pain. The developed prognostic tool has the potential to help clinicians, older people and their families to identify when an older person is at risk of declining mobility and to take preventative actions. We developed a scoring system so that it could be easily implemented in clinical practice, and future research will focus on external validation of this tool. Study registration This trial is registered as BOOST trial ISRCTN12698674. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: PTC-RP-PG-0213-20002) and is published in full in Programme Grants for Applied Research; Vol. 11, No. 9. See the NIHR Funding and Awards website for further award information.

Objectives To estimate the economic costs, health-related quality-of-life outcomes and cost-effectiveness of subthreshold micropulse laser (SML) versus standard laser (SL) for the treatment of diabetic macular oedema (DMO) with central retinal thickness (CRT) of

Abstract Background Emerging evidence suggests that structured and progressive exercise underpinned by a cognitive behavioural approach can improve functional outcomes in patients with neurogenic claudication (NC). However, evidence surrounding its economic benefits is lacking. Objectives To estimate the economic costs, health-related quality of life outcomes and cost-effectiveness of a physical and psychological group intervention (BOOST programme) versus best practice advice (BPA) in older adults with NC. Methods An economic evaluation was conducted based on data from a pragmatic, multicentre, superiority, randomised controlled trial. The base-case economic evaluation took the form of an intention-to-treat analysis conducted from a UK National Health Service (NHS) and personal social services (PSS) perspective and separately from a societal perspective. Costs (£ 2018–2019 prices) were collected prospectively over a 12 month follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained and the incremental net monetary benefit (INMB) of the BOOST programme in comparison to BPA. Sensitivity and pre-specified subgroup analyses explored uncertainty and heterogeneity in cost-effectiveness estimates. Results Participants (N = 435) were randomised to the BOOST programme (n = 292) or BPA (n = 143). Mean (standard error [SE]) NHS and PSS costs over 12 months were £1,974 (£118) in the BOOST arm versus £1,827 (£169) in the BPA arm (p = 0.474). Mean (SE) QALY estimates were 0.620 (0.009) versus 0.599 (0.006), respectively (p = 0.093). The probability that the BOOST programme is cost-effective ranged between 67 and 83% (NHS and PSS perspective) and 79–89% (societal perspective) at cost-effectiveness thresholds between £15,000 and £30,000 per QALY gained. INMBs ranged between £145 and £464 at similar cost-effectiveness thresholds. The cost-effectiveness results remained robust to sensitivity analyses. Conclusions The BOOST programme resulted in modest QALY gains over the 12 month follow-up period. Future studies with longer intervention and follow-up periods are needed to address uncertainty around the health-related quality of life impacts and cost-effectiveness of such programmes. Trial registration This study has been registered in the International Standard Randomised Controlled Trial Number registry, reference number ISRCTN12698674. Registered on 10 November 2015.

Background: The National Institute for Health and Care Excellence recommends macular laser to treat diabetic macular oedema with a central retinal subfield thickness of 24 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent > 20/320) in one/both eyes. Interventions: Participants were randomised 1 : 1 to receive 577 nm subthreshold micropulse laser or standard threshold macular laser (e.g. argon laser, frequency-doubled neodymium-doped yttrium aluminium garnet 532 nm laser); laser treatments could be repeated as needed. Rescue therapy with intravitreal anti-vascular endothelial growth factor therapies or steroids was allowed if a loss of ≥ 10 Early Treatment Diabetic Retinopathy Study letters between visits occurred and/or central retinal subfield thickness increased to > 400 µm. Main outcome measures: The primary outcome was the mean change in best-corrected visual acuity in the study eye at 24 months (non-inferiority margin 5 Early Treatment Diabetic Retinopathy Study letters). Secondary outcomes included the mean change from baseline to 24 months in the following: binocular best-corrected visual acuity; central retinal subfield thickness; the mean deviation of the Humphrey 10–2 visual field in the study eye; the percentage of people meeting driving standards; and the EuroQol-5 Dimensions, five-level version, National Eye Institute Visual Function Questionnaire – 25 and Vision and Quality of Life Index scores. Other secondary outcomes were the cost per quality-adjusted life-years gained, adverse effects, number of laser treatments and additional rescue treatments. Results: The DIAMONDS trial recruited fully (n = 266); 87% of participants in the subthreshold micropulse laser group and 86% of participants in the standard threshold macular laser group had primary outcome data. Groups were balanced regarding baseline characteristics. Mean best-corrected visual acuity change in the study eye from baseline to month 24 was –2.43 letters (standard deviation 8.20 letters) in the subthreshold micropulse laser group and –0.45 letters (standard deviation 6.72 letters) in the standard threshold macular laser group. Subthreshold micropulse laser was deemed to be not only non-inferior but also equivalent to standard threshold macular laser as the 95% confidence interval (–3.9 to –0.04 letters) lay wholly within both the upper and lower margins of the permitted maximum difference (5 Early Treatment Diabetic Retinopathy Study letters). There was no statistically significant difference between groups in any of the secondary outcomes investigated with the exception of the number of laser treatments performed, which was slightly higher in the subthreshold micropulse laser group (mean difference 0.48, 95% confidence interval 0.18 to 0.79; p = 0.002). Base-case analysis indicated no significant difference in the cost per quality-adjusted life-years between groups. Future work: A trial in people with ≥ 400 µm diabetic macular oedema comparing anti-vascular endothelial growth factor therapy alone with anti-vascular endothelial growth factor therapy and macular laser applied at the time when central retinal subfield thickness has decreased to

Background: Owing to the increasing prevalence of diabetes, the workload related to diabetic macular oedema and proliferative diabetic retinopathy is rising, making it difficult for hospital eye services to meet demands. Objective: The objective was to evaluate the diagnostic performance, cost-effectiveness and acceptability of a new pathway using multimodal imaging interpreted by ophthalmic graders to detect reactivation of diabetic macular oedema/proliferative diabetic retinopathy in previously treated patients. Design: This was a prospective, case-referent, cross-sectional diagnostic study. Setting: The setting was ophthalmic clinics in 13 NHS hospitals. Participants: Adults with type 1 or type 2 diabetes with previously successfully treated diabetic macular oedema/proliferative diabetic retinopathy in one/both eyes in whom, at the time of enrolment, diabetic macular oedema/proliferative diabetic retinopathy could be active or inactive. Methods: For the ophthalmic grader pathway, review of the spectral domain optical coherence tomography scans to detect diabetic macular oedema, and seven-field Early Treatment Diabetic Retinopathy Study/ultra-wide field fundus images to detect proliferative diabetic retinopathy, by trained ophthalmic graders. For the current standard care pathway (reference standard), ophthalmologists examined patients face to face by slit-lamp biomicroscopy for proliferative diabetic retinopathy and, in addition, spectral domain optical coherence tomography imaging for diabetic macular oedema. Outcome measures: The primary outcome measure was sensitivity of the ophthalmic grader pathway to detect active diabetic macular oedema/proliferative diabetic retinopathy. The secondary outcomes were specificity, agreement between pathways, cost–consequences, acceptability and the proportion of patients requiring subsequent ophthalmologist assessment, unable to undergo imaging and with inadequate quality images/indeterminate findings. It was assumed for the main analysis that all patients in whom graders diagnosed active disease or were ‘unsure’ or images were ‘ungradable’ required examination by an ophthalmologist. Results: Eligible participants with active and inactive diabetic macular oedema (152 and 120 participants, respectively) and active and inactive proliferative diabetic retinopathy (111 and 170 participants, respectively) were recruited. Under the main analysis, graders had a sensitivity of 97% (142/147) (95% confidence interval 92% to 99%) and specificity of 31% (35/113) (95% confidence interval 23% to 40%) to detect diabetic macular oedema. For proliferative diabetic retinopathy, graders had a similar sensitivity and specificity using seven-field Early Treatment Diabetic Retinopathy Study [sensitivity 85% (87/102), 95% confidence interval 77% to 91%; specificity 48% (77/160), 95% confidence interval 41% to 56%] or ultra-wide field imaging [sensitivity 83% (87/105), 95% confidence interval 75% to 89%; specificity 54% (86/160), 95% confidence interval 46% to 61%]. Participants attending focus groups expressed preference for face-to-face evaluations by ophthalmologists. In the ophthalmologists’ absence, patients voiced the need for immediate feedback following grader’s assessments, maintaining periodic evaluations by ophthalmologists. Graders and ophthalmologists were supportive of the new pathway. When compared with the reference standard (current standard pathway), the new grader pathway could save £1390 per 100 patients in the review of people with diabetic macular oedema and, depending on the imaging modality used, between £461 and £1189 per 100 patients in the review of people with proliferative diabetic retinopathy. Conclusions: For people with diabetic macular oedema, the ophthalmic grader pathway appears safe and cost saving. The sensitivity of the new pathway to detect active proliferative diabetic retinopathy was lower, but may still be considered acceptable for patients with proliferative diabetic retinopathy previously treated with laser. Suggestions from focus group discussions should be taken into consideration if the new pathway is introduced to ensure its acceptability to users. Limitations: Lack of fundus fluorescein angiography to confirm diagnosis of active proliferative diabetic retinopathy. Future work: Could refinement of the new pathway increase its sensitivity to detect proliferative diabetic retinopathy? Could artificial intelligence be used for automated reading of images in this previously treated population? Trial registration: Current Controlled Trials ISRCTN10856638 and ClinicalTrials.gov NCT03490318. 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. 25, No. 32. See the NIHR Journals Library website for further project information.

Background: Achilles tendon rupture affects > 11,000 people each year in the UK, leading to prolonged periods away from work, sports and social activities. Traditionally, the ruptured tendon is held still in a plaster cast for ≥ 8 weeks. Functional bracing is an alternative treatment that allows patients to mobilise earlier, but there is little evidence about how bracing affects patients’ recovery. Objectives: To measure the Achilles Tendon Rupture Score, quality of life, complications and resource use of patients receiving non-operative treatment for an Achilles tendon rupture treated with plaster cast compared with those treated with functional bracing. Design: This was a multicentre, randomised, pragmatic, two-group superiority trial. Setting: The setting was 39 NHS hospitals. Participants: A total of 540 adult patients treated non-operatively for Achilles tendon rupture were randomised from July 2016 to May 2018. Exclusion criteria included presenting after 14 days, having had previous rupture and being unable to complete questionnaires. Interventions: A total of 266 participants had a plaster cast applied, with their toes initially pointing to the floor. The cast was changed over 8 weeks to bring the foot into a walking position. A total of 274 patients had a functional brace that facilitated immediate weight-bearing. The foot position was adjusted within the brace over the same 8-week period. Main outcome measures: Achilles Tendon Rupture Score is patient reported and assesses symptoms and physical activity related to the Achilles tendon (score 0–100, with 100 being the best possible outcome). The secondary outcomes were quality of life, complications and resource use at 8 weeks and at 3, 6 and 9 months. Results: Participants had a mean age of 48.7 years, were predominantly male (79%) and had ruptured their tendon during sports (70%). Over 93% of participants completed follow-up. There was no statistically significant difference in Achilles Tendon Rupture Score at 9 months post injury (–1.38, 95% confidence interval –4.9 to 2.1). There was a statistically significant difference in Achilles Tendon Rupture Score at 8 weeks post injury in favour of the functional brace group (5.53, 95% confidence interval 2.0 to 9.1), but not at 3 or 6 months post injury. Quality of life showed the same pattern, with a statistically significant difference at 8 weeks post injury but not at later time points. Complication profiles were similar in both groups. Re-rupture of the tendon occurred 17 times in the plaster cast group and 13 times in the functional brace group. There was no difference in resource use. Conclusions: This trial provides strong evidence that early weight-bearing in a functional brace provides similar outcomes to traditional plaster casting and is safe for patients receiving non-operative treatment of Achilles tendon rupture. The probability that functional bracing is cost-effective exceeds 95% for the base-case imputed analysis, assuming a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. On average, functional brace is associated with lower costs (–£103, 95% confidence interval –£290 to £84) and more quality-adjusted life-years (0.015, 95% confidence interval –0.0013 to 0.030) than plaster cast. Limitations: Some patients declined to participate in the trial, but only a small proportion of these declined because they had a preference for one treatment or another. Overall, 58% of eligible patients agreed to participate, so the participants are broadly representative of the population under investigation. Future work: Although the UK Study of Tendo Achilles Rehabilitation provides guidance with regard to early management, rehabilitation following Achilles tendon rupture is prolonged and further research is required to define the optimal mode of rehabilitation after the initial cast/brace has been removed. Trial registration: Current Controlled Trials ISRCTN62639639. 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. 8. See the NIHR Journals Library website for further project information.

Background: Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy. Objective: To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV. Design: Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis. Setting: A total of 51 critical care units across the UK. Participants: Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT. Interventions: Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient’s condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient’s condition. Main outcome measures: The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life. Results: A total of 364 patients (invasive weaning, n = 182; non-invasive weaning, n = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57–351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5–297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; p = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2–11 days) vs. non-invasive weaning 1 day (IQR 0–7 days); adjusted mean difference –3.1 days, 95% CI –5.75 to –0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; p = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. Conclusions: A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections. Future work: In patients who fail a SBT, which factors predict an adverse outcome (reintubation, tracheostomy, death) if extubated and weaned using NIV? Trial registration: Current Controlled Trials ISRCTN15635197. 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. 23, No. 48. See the NIHR Journals Library website for further project information.

Background: Stroke is the second leading cause of mortality and leading cause of disability in South Africa yet published data on the economic costs of stroke is lacking particularly in rural settings. Methods: We estimate the total direct costs of stroke in 2012 from a health system perspective using a prevalence-based, bottom-up costing approach. Direct costs include diagnosis, inpatient and outpatient care. Analysis is based on the Agincourt health and socio-demographic surveillance system, which covers approximately 90,000 people. Published data from the SASPI study, Tintswalo Hospital Stroke register, and national cost databases were used. Sensitivity analysis was carried out to account for the variability in the data used. Results: The total direct costs of stroke were estimated to be R2.5–R4.2 million (US$283,500–US$485,000) in 2012 or 1.6–3% of the sub-district health expenditure. Of this, 80% was attributed to inpatient costs. Total costs were most sensitive to the underlying incidence rates and to assumptions regarding service utilisation. Conclusions: Our study provides a snapshot of costs incurred on stroke in rural South Africa. We show that stroke is a disease with high economic costs. Further studies that assess the lifetime costs of stroke are needed to better understand savings accrued from intervening at different stages of the disease.

Abstract Background Rural South Africa (SA) is undergoing a rapid health transition characterized by increases in non-communicable diseases; stroke in particular. Knowledge of the relative contribution of modifiable risk factors on disease occurrence is needed for public health prevention efforts and community-oriented health promotion. Our aim was to estimate the burden of stroke in rural SA that is attributable to high blood pressure, excess weight and high blood glucose using World Health Organization’s comparative risk assessment (CRA) framework. Methods We estimated current exposure distributions of the risk factors in rural SA using 2010 data from the Agincourt health and demographic surveillance system (HDSS). Relative risks of stroke per unit of exposure were obtained from the Global Burden of Disease Study 2010. We used data from the Agincourt HDSS to estimate age-, sex-, and stroke specific deaths and disability adjusted life years (DALYs). We estimated the proportion of the years of life lost (YLL) and DALY loss attributable to the risk factors and incorporate uncertainty intervals into these estimates. Results Overall, 38 % of the documented stroke burden was due to high blood pressure (12 % males; 26 % females). This translated to 520 YLL per year (95 % CI: 325-678) and 540 DALYs (CI: 343-717). Excess Body Mass Index (BMI) was calculated as responsible for 20 % of the stroke burden (3.5 % males; 16 % females). This translated to 260 YLLs (CI: 199-330) and 277 DALYs (CI: 211-350). Burden was disproportionately higher in young females when BMI was assessed. Conclusions High blood pressure and excess weight, which both have effective interventions, are responsible for a significant proportion of the stroke burden in rural SA; the burden varies across age and sex sub-groups. The most effective way forward to reduce the stroke burden requires both population wide policies that have an impact across the age spectra and targeted (health promotion/disease prevention) interventions on women and young people.

Background: The best treatment for fractures of the distal tibia remains controversial. Most of these fractures require surgical fixation, but the outcomes are unpredictable and complications are common. Objectives: To assess disability, quality of life, complications and resource use in patients treated with intramedullary (IM) nail fixation versus locking plate fixation in the 12 months following a fracture of the distal tibia. Design: This was a multicentre randomised trial. Setting: The trial was conducted in 28 UK acute trauma centres from April 2013 to final follow-up in February 2017. Participants: In total, 321 adult patients were recruited. Participants were excluded if they had open fractures, fractures involving the ankle joint, contraindication to nailing or inability to complete questionnaires. Interventions: IM nail fixation (n = 161), in which a metal rod is inserted into the hollow centre of the tibia, versus locking plate fixation (n = 160), in which a plate is attached to the surface of the tibia with fixed-angle screws. Main outcome measures: The primary outcome measure was the Disability Rating Index (DRI) score, which ranges from 0 points (no disability) to 100 points (complete disability), at 6 months with a minimum clinically important difference of 8 points. The DRI score was also collected at 3 and 12 months. The secondary outcomes were the Olerud–Molander Ankle Score (OMAS), quality of life as measured using EuroQol-5 Dimensions (EQ-5D), complications such as infection, and further surgery. Resource use was collected to inform the health economic evaluation. Results: Participants had a mean age of 45 years (standard deviation 16.2 years), were predominantly male (61%, 197/321) and had experienced traumatic injury after a fall (69%, 223/321). There was no statistically significant difference in DRI score at 6 months [IM nail fixation group, mean 29.8 points, 95% confidence interval (CI) 26.1 to 33.7 points; locking plate group, mean 33.8 points, 95% CI 29.7 to 37.9 points; adjusted difference, 4.0 points, 95% CI –1.0 to 9.0 points; p = 0.11]. There was a statistically significant difference in DRI score at 3 months in favour of IM nail fixation (IM nail fixation group, mean 44.2 points, 95% CI 40.8 to 47.6 points; locking plate group, mean 52.6 points, 95% CI 49.3 to 55.9 points; adjusted difference 8.8 points, 95% CI 4.3 to 13.2 points; p

The cardiovascular disease (CVD) burden in South Africa (SA) is increasing amongst all age groups and is predicted to become the prime contributor to overall morbidity and mortality in the over 50-year age group. Several factors contribute to this – an epidemiological transition, which has seen a rise in chronic non-communicable disease, and a demographic transition with much reduced fertility and a growing proportion of the population above 60 years. In parallel with unfolding urbanisation, the population burden of vascular risk factors namely hypertension, hypercholesterolemia, diabetes and obesity has increased. The scale of CVD burden poses a threat to the health system and calls for timely intervention. This paper discusses the burden of CVD in SA and current initiatives to address it. Evidence is presented from studies that focus on prevention including salt reduction and trans-fatty acids legislation. The economic and clinical impact of an inadequate private and public sector response is summarised. The paper documents lessons from other countries and proposes health systems strengthening measures that could improve care of patients with CVD.

Background: The importance of tackling economic, social and health-related inequities is increasingly accepted as a core concern for the post-Millennium Development Goal framework. However, there is a global dearth of high-quality, policy-relevant and actionable data on inequities within populations, which means that development solutions seldom focus on the people who need them most. INTREC (INDEPTH Training and Research Centres of Excellence) was established with this concern in mind. It aims to provide training for researchers from the INDEPTH network on associations between health inequities, the social determinants of health (SDH), and health outcomes, and on presenting their findings in a usable form to policy makers. Objective: As part of a baseline situation analysis for INTREC, this paper assesses the current status of SDH training in three of the African INTREC countries – Ghana, Tanzania, and South Africa – as well as the gaps, barriers, and opportunities for training. Methods: SDH-related courses from the three countries were identified through personal knowledge of the researchers, supplemented by snowballing and online searches. Interviews were also conducted with, among others, academics engaged in SDH and public health training in order to provide context and complementary material. Information regarding access to the Internet, as a possible INTREC teaching medium, was gathered in each country through online searches. Results: SDH-relevant training is available, but 1) the number of places available for students is limited; 2) the training tends to be public-health-oriented rather than inclusive of the broader, multi-sectoral issues associated with SDH; and 3) insufficient funding places limitations on both students and on the training institutions themselves, thereby affecting participation and quality. We also identified rapidly expanding Internet connectivity in all three countries, which opens up opportunities for e-learning on SDH, though the current quality of the Internet services remains mixed. Conclusions: SDH training is currently in short supply, and there is a clear role for INTREC to contribute to the training of a critical mass of African researchers on the topic. This work will be accomplished most effectively by building on pre-existing networks, institutions, and methods.

The establishment and strengthening of poisons centres was identified as a regional priority at the first African regional meeting on the Strategic Approach to International Chemicals Management (SAICM) in June 2006. At this meeting, the possibility of a subregional poisons centre, that is, a centre in one country serving multiple countries, was suggested. The WHO Headquarters following consultation with counterparts at the WHO Regional Office for Africa (AFRO) and the SAICM Africa Regional Focal Point successfully submitted a proposal to the SAICM Quick Start Programme (QSP) Trust Fund Committee for a feasibility study into a subregional poisons centre in the Eastern Africa subregion. However, before such a study could be conducted it was deemed necessary to carry out a literature review on the patterns and epidemiology of poisoning in this region so as to inform the feasibility study. The current paper presents the results of this literature review. The literature search was done in the months of June and July 2012 by two independent reviewers with no language or publication date restrictions using defined search terms on PUBMED. After screening, the eventual selection of articles for review and inclusion in this study was done by a third reviewer.