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Purpose The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. Design Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. Participants Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. Methods A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). Main Outcome Measures Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. Results The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%–99%) and specificity of 31% (95% CI, 23%–40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%–91%] and 48% [95% CI, 41%–56%], respectively) or UWF images (83% [95% CI, 75%–89%] and 54% [95% CI, 46%–61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%–93%] and 49% [95% CI, 42%–56%], respectively, for UWF versus 80% [95% CI, 69–88%] and 40% [95% CI, 34%–47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists’ assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. Conclusions The new pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementation.

Background/aimsSurveillance of people with previously successfully treated diabetic macular oedema (DMO) and proliferative diabetic retinopathy (PDR) adds pressure on ophthalmology services. This study evaluated a new surveillance pathway entailing multimodal imaging reviewed by trained ophthalmic graders and compared it with the current standard care (face-to-face evaluation by an ophthalmologist).MethodsCost analysis of the new ophthalmic grader pathway, compared with the standard of care, from the perspective of the UK National Health Service, based on evidence from the Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy study. Resource use data were prospectively obtained including times to undertake each procedure. Effectiveness was assessed in terms of sensitivity and specificity of referral decisions in the grader pathway. Costs (SDs) were analysed per 100 patients separately for DMO and PDR at 2018/2019 costs.ResultsFor DMO, where sensitivity was very high (97%), the cost difference (savings) for the grader’s pathway would be £1390 per 100 patients. For PDR, the cost would be reduced by £461 for seven-field Early Treatment for Diabetic Retinopathy Study (ETDRS) images and by £1889 for ultrawide field images, per 100 patients. Ultrawide images required less time to be obtained and read than seven-field ETDRS. The real savings would be in ophthalmologist time, which could be then redirected to the evaluation of people at high risk of visual loss.ConclusionsSurveillance of people with previously successfully treated DMO and PDR by trained ophthalmic graders can achieve satisfactory results and release ophthalmologist time.Trial registration numbersNCT03490318,ISRCTN10856638.

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.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.This was a prospective, case-referent, cross-sectional diagnostic study.The setting was ophthalmic clinics in 13 NHS hospitals.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.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.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.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.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.Lack of fundus fluorescein angiography to confirm diagnosis of active proliferative diabetic retinopathy.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?Current Controlled Trials ISRCTN10856638 and ClinicalTrials.gov NCT03490318.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inMore and more people are developing diabetes. Diabetic macular oedema and proliferative diabetic retinopathy are complications of diabetes, which could cause blindness. Thus, people with diabetic macular oedema and proliferative diabetic retinopathy need to be treated in a timely manner and reviewed in clinic for life. The population in the world is ageing. As a result, there are more people with eye diseases. There are also more treatments now for people with eye diseases. The workload in hospitals is increasing, making it difficult for the NHS to cope with the demand. There are not enough ophthalmologists (eye doctors) to look after patients. Delayed appointments and treatment mean that patients may lose sight. The goal of EMERALD (Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy) was to see if patients with treated and stable diabetic macular oedema or proliferative diabetic retinopathy could be followed by ‘ophthalmic graders’, who are not doctors but are trained to diagnose diabetic macular oedema and proliferative diabetic retinopathy. In EMERALD, trained ophthalmic graders examined photographs of the back of the eye of people with diabetic macular oedema and proliferative diabetic retinopathy. They checked if diabetic macular oedema and proliferative diabetic retinopathy remain inactive. If so, patients could continue follow-up with the ophthalmic graders. If diabetic macular oedema or proliferative diabetic retinopathy were active, graders would immediately refer patients to ophthalmologists. EMERALD found that graders were excellent at detecting diabetic macular oedema, and this could give ophthalmologists time to see other patients. Graders were not quite as good at detecting active proliferative diabetic retinopathy. However, considering that patients had already had treatment, this may still be safe. Patients participating in focus group discussions mentioned that they would prefer to see ophthalmologists, so they could ask questions about their eye condition. If this was not possible, they would like to have immediate results from graders and still see the ophthalmologist from time to time.

Background Optimising techniques to wean patients from invasive mechanical ventilation (IMV) remains a key goal of intensive care practice. The use of non-invasive ventilation (NIV) as a weaning strategy (transitioning patients who are difficult to wean to early NIV) may reduce mortality, ventilator-associated pneumonia and intensive care unit (ICU) length of stay. Objectives Our objectives were to determine the cost effectiveness of protocolised weaning, including early extubation onto NIV, compared with weaning without NIV in a UK National Health Service setting. Methods We conducted an economic evaluation alongside a multicentre randomised controlled trial. Patients were randomised to either protocol-directed weaning from mechanical ventilation or ongoing IMV with daily spontaneous breathing trials. The primary efficacy outcome was time to liberation from ventilation. Bivariate regression of costs and quality-adjusted life-years (QALYs) provided estimates of the incremental cost per QALY and incremental net monetary benefit (INMB) overall and for subgroups [presence/absence of chronic obstructive pulmonary disease (COPD) and operative status]. Long-term cost effectiveness was determined through extrapolation of survival curves using flexible parametric modelling. Results NIV was associated with a mean INMB of £620 ($US885) (cost-effectiveness threshold of £20,000 per QALY) with a corresponding probability of 58% that NIV is cost effective. The probability that NIV is cost effective was higher for those with COPD (84%). NIV was cost effective over 5 years, with an estimated incremental cost-effectiveness ratio of £4618 ($US6594 per QALY gained). Conclusions The probability of NIV being cost effective relative to weaning without NIV ranged between 57 and 59% overall and between 82 and 87% for the COPD subgroup. Electronic supplementary material The online version of this article (10.1007/s41669-020-00210-1) contains supplementary material, which is available to authorized users.

Background The Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT‐D) trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared with dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation. Objectives To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months. Patients/Methods In SELECT‐D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomization to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomization closed prematurely because of low recruitment when 92 of the planned 300 patients were recruited. Results Ninety‐two of 136 eligible patients were randomized to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomization was 14% with placebo and 4% with rivaroxaban (hazard ratio, 0.32; 95% confidence interval [CI], 0.06‐1.58). The major and clinically relevant non‐major bleeding rates were 0% and 0% with placebo; and 5% (95% CI, 1‐18) and 4% (95% CI, 1‐17) with rivaroxaban. In an exploratory analysis, 7 (15%) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT‐negative cohort (P = .03). Conclusion The SELECT‐D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence.

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.

Summary Background Patients with Achilles tendon rupture who have non-operative treatment have traditionally been treated with immobilisation of the tendon in plaster casts for several weeks. Functional bracing is an alternative non-operative treatment that allows earlier mobilisation, but evidence on its effectiveness and safety is scarce. The aim of the UKSTAR trial was to compare functional and quality-of-life outcomes and resource use in patients treated non-operatively with plaster cast versus functional brace. Methods UKSTAR was a pragmatic, superiority, multicentre, randomised controlled trial done at 39 hospitals in the UK. Patients (aged ≥16 years) who were being treated non-operatively for a primary Achilles tendon rupture at the participating centres were potentially eligible. The exclusion criteria were presenting more than 14 days after injury, previous rupture of the same Achilles tendon, or being unable to complete the questionnaires. Eligible participants were randomly assigned (1:1) to receive a plaster cast or functional brace using a centralised web-based system. Because the interventions were clearly visible, neither patients nor clinicians could be masked. Participants wore the intervention for 8 weeks. The primary outcome was patient-reported Achilles tendon rupture score (ATRS) at 9 months, analysed in the modified intention-to-treat population (all patients in the groups to which they were allocated, excluding participants who withdrew or died before providing any outcome data). The main safety outcome was the incidence of tendon re-rupture. Resource use was recorded from a health and personal social care perspective. The trial is registered with ISRCTN, ISRCTN62639639. Findings Between Aug 15, 2016, and May 31, 2018, 1451 patients were screened, of whom 540 participants (mean age 48·7 years, 79% male) were randomly allocated to receive plaster cast (n=266) or functional brace (n=274). 527 (98%) of 540 were included in the modified intention-to-treat population, and 13 (2%) were excluded because they withdrew or died before providing any outcome data. There was no difference in ATRS at 9 months post injury (cast group n=244, mean ATRS 74∙4 [SD 19∙8]; functional brace group n=259, ATRS 72∙8 [20∙4]; adjusted mean difference –1∙38 [95% CI –4∙9 to 2∙1], p=0·44). There was no difference in the rate of re-rupture of the tendon (17 [6%] of 266 in the plaster cast group vs 13 [5%] of 274 in the functional brace group, p=0·40). The mean total health and personal social care cost was £1181 for the plaster cast group and £1078 for the functional bract group (mean between-group difference –£103 [95% CI –289 to 84]). Interpretation Traditional plaster casting was not found to be superior to early weight-bearing in a functional brace, as measured by ATRS, in the management of patients treated non-surgically for Achilles tendon rupture. Clinicians may consider the use of early weight-bearing in a functional brace as a safe and cost-effective alternative to plaster casting. Funding UK National Institute for Health Research Health Technology Assessment Programme.

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., Highlights • We present the first estimates of costs of treating stroke in rural South Africa. • Stroke imposes a high economic burden in this setting. • Total direct costs of US$283,500 –US$485,000 represent 1.6-3% of the sub-district health expenditure. • Cost-of-illness studies for stroke can be conducted using available information sources.

BackgroundThe 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.ObjectivesTo 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.DesignThis was a multicentre randomised trial.SettingThe trial was conducted in 28 UK acute trauma centres from April 2013 to final follow-up in February 2017.ParticipantsIn 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.InterventionsIM 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 measuresThe 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.ResultsParticipants 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 p = 0.47). Secondary outcomes showed the same pattern, including a statistically significant difference in mean OMAS and EQ-5D scores at 3 and 6 months in favour of IM nail fixation. There were no statistically significant differences in complications, including the number of postoperative infections (13% in the locking plate group and 9% in the IM nail fixation group). Further surgery was more common in the locking plate group (12% in locking plate group and 8% in IM nail fixation group at 12 months). The economic evaluation showed that IM nail fixation provided a slightly higher quality of life in the 12 months after injury and at lower cost and, therefore, it was cost-effective compared with locking plate fixation. The probability of cost-effectiveness for IM nail fixation exceeded 90%, regardless of the value of the cost-effectiveness threshold.LimitationsAs wound dressings after surgery are clearly visible, it was not possible to blind the patients to their treatment allocation. This evidence does not apply to intra-articular (pilon) fractures of the distal tibia.ConclusionsAmong adults with an acute fracture of the distal tibia who were randomised to IM nail fixation or locking plate fixation, there were similar disability ratings at 6 months. However, recovery across all outcomes was faster in the IM nail fixation group and costs were lower.Future workThe potential benefit of IM nail fixation in several other fractures requires investigation. Research is also required into the role of adjuvant treatment and different rehabilitation strategies to accelerate recovery following a fracture of the tibia and other long-bone fractures in the lower limb. The patients in this trial will remain in longer-term follow-up.Trial registrationCurrent Controlled Trials ISRCTN99771224 and UKCRN 13761.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 25. See the NIHR Journals Library website for further project information.

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.

Despite increasing availability of perinatal interventions to prevent mother-to-child transmission (MTCT) of HIV in South Africa, MTCT remains high due to breastfeeding. To inform policy decisions in the country, cost-effectiveness of alternative infant-feeding interventions was conducted. Mathematical modelling was used to simulate post-natal transmission and mortality due to infant feeding in a hypothetical cohort of 1 000 HIV-exposed infants. Lifetime costs to the health system were calculated for each strategy. Interventions compared with current practice were: increasing coverage of extended nevirapine prophylaxis (ENP) to infants from 30% (base case) to 60% without changing current feeding practices; actively supporting breastfeeding with ENP to infants for 12 months; and actively supporting exclusive formula (replacement) feeding for 6 months. HIV-free survival at 24 months and disability-adjusted life years (DALYs) averted were estimated for typical rural and certain urban settings. Base-case analysis revealed that expanding coverage of nevirapine prophylaxis with breastfeeding is cost-saving and improves HIV-free survival. Changing feeding practices is beneficial, depending on context. Breastfeeding is dominant (less costly, more effective) in rural settings, whilst formula feeding is a dominant strategy in urban settings. Cost-effectiveness was most sensitive to proportion of women on lifelong antiretroviral therapy (ART) and infant mortality rate (IMR). When55% of women are on ART, breastfeeding dominates in the urban settings modelled, whilst formula feeding is cost-effective in rural settings when IMR ≤ 45/1000. The study concludes that strategies to support breastfeeding are essential. Strengthening health systems is critical to ensure optimal nevirapine delivery during breastfeeding. A case can be made for formula feeding or breastfeeding in HIV-infected women in specific contexts.

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 formto 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. Keywords: social determinants of health; health inequities; research; training; capacity building; e-learning; sub-Saharan Africa; Tanzania; South Africa; Ghana (Published: 3 April 2013) This paper is part of the thematic cluster Global Health Beyond 2015 . More papers from this cluster can be found at http://www.globalhealthaction.net Citation: Glob Health Action 2013, 6 : 19668 - http://dx.doi.org/10.3402/gha.v6i0.19668

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. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-2805-7) contains supplementary material, which is available to authorized users.

Background Newborn mortality, comprising a third of all under-5 deaths, has hardly changed in low and middle income countries (LMICs) including South Africa over the past decade. To attain the MDG 4 target, greater emphasis must be placed on wide-scale implementation of proven, cost-effective interventions. This paper reviews economic evidence on effective neonatal health interventions in LMICs from 2000–2013; documents lessons for South African policy on neonatal health; and identifies gaps and areas for future research. Methods A narrative review was performed in leading public health databases for full economic evaluations conducted between 2000 and 2013. Data extraction from the articles included in the review was guided by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist, and the quality of the included economic evaluations was assessed using the Quality of Health Economics Studies Instrument (QHES). Results Twenty-seven economic evaluations were identified, from South East Asia and sub-Saharan Africa, with those from sub-Saharan Africa primarily focused on HIV/AIDS. Packages of care to prevent neonatal mortality were more cost-effective than vertical interventions. A wide variability in methodological approaches challenges the comparability of study results between countries. In South Africa, there is limited cost-effectiveness evidence for the interventions proposed by the National Perinatal Morbidity and Mortality Committee. Conclusions Neonatal strategies have a strong health system focus but this review suggests that strengthening community care could be an additional component for averting neonatal deaths. While some evidence exists, having a more complete understanding of how to most effectively deploy scarce resources for neonatal health in South Africa in the post-2015 era is essential. Electronic supplementary material The online version of this article (doi:10.1186/s12962-015-0049-5) contains supplementary material, which is available to authorized users.

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.

Background In the context of an epidemiologic transition in South Africa, in which cardiovascular disease is increasing, little is known about the stroke burden, particularly morbidity in rural populations. Risk factors for stroke are high, with hypertension prevalence of more than 50%. Accurate, up-to-date information on disease burden is essential in planning health services for stroke management. This study estimates the burden of stroke in rural South Africa using the epidemiological parameters of incidence, mortality and disability adjusted life year (DALY) metric, a time-based measure that incorporates both mortality and morbidity. Methods Data from the Agincourt health and socio-demographic surveillance system was utilised to calculate stroke mortality for the period 2007–2011. Dismod, an incidence-prevalence-mortality model, was used to estimate incidence and duration of disability in Agincourt sub-district and ‘mostly rural’ municipalities of South Africa. Using these values, burden of disease in years of life lost (YLL), years lived with disability (YLD) and DALYs was calculated for Agincourt sub-district. Results Over 5 years, there were an estimated 842 incident cases of stroke in Agincourt sub-district, a crude stroke incidence rate of 244 per 100,000 person years. We estimate that 1,070 DALYs are lost due to stroke yearly. Of this, YLDs contributed 8.7% (3.5 – 10.5%) in sensitivity analysis). Crude stroke mortality was 114 per 100,000 person-years in 2007–11 in Agincourt sub-district. Burden of stroke in entire rural South Africa, a population of some 13,000,000 people, was high, with an estimated 33, 500 strokes occurring in 2011. Conclusions This study provides the first estimates of stroke burden in terms of incidence, and disability in rural South Africa. High YLL and DALYs lost amongst the rural populations demand urgent measures for preventing and mitigating impacts of stroke. Longitudinal surveillance sites provide a platform through which a changing stroke burden can be monitored in rural South Africa. Electronic supplementary material The online version of this article (doi:10.1186/s12883-015-0311-7) contains supplementary material, which is available to authorized users.