A hidden menace: Cardiovascular disease in South Africa and the costs of an inadequate policy response

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

Subthreshold micropulse laser versus standard laser for the treatment of central-involving diabetic macular oedema with central retinal thickness of <400\ub5: a cost-effectiveness analysis from the DIAMONDS trial

\ua9 Author(s) (or their employer(s)) 2023. 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 <400\ub5. Design An economic evaluation was conducted within a pragmatic, multicentre, randomised clinical trial, DIAbetic Macular Oedema aNd Diode Subthreshold. Setting 18 UK Hospital Eye Services. Participants Adults with diabetes and centre involving DMO with CRT<400\ub5. Interventions Participants (n=266) were randomised 1:1 to receive SML or SL. Methods The base-case used an intention-to-treat approach conducted from a UK National Health Service (NHS) and personal social services (PSS) perspective. Costs (2019–2020 prices) were collected prospectively over the 2-year 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 of SML in comparison to SL. Sensitivity analyses explored uncertainty and heterogeneity in cost-effectiveness estimates. Results One participant in the SL arm withdrew consent for data to be used; data from the remaining 265 participants were included in analyses. Mean (SE) NHS and PSS costs over 24 months were \ua3735.09 (\ua3111.85) in the SML arm vs \ua31099.70 (\ua3195.40) in the SL arm (p=0.107). Mean (SE) QALY estimates were 1.493 (0.024) vs 1.485 (0.020), respectively (p=0.780), giving an insignificant difference of 0.008 QALYs. The probability SML is cost-effective at a threshold of \ua320 000 per QALY was 76%. Conclusions There were no statistically significant differences in EQ-5D-5L scores or costs between SML and SL. Given these findings and the fact that SML does not burn the retina, unlike SL and has equivalent efficacy to SL, it may be preferred for the treatment of people with DMO with CRT<400\ub5

Treatment of Cancer‐Associated Venous Thromboembolism: 12‐month outcomes of the placebo versus rivaroxaban randomisation of the SELECT‐D Trial. (SELECT‐D: 12m)

Background The SELECT‐D trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared to 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 randomisation 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 randomisation closed prematurely due to low recruitment when 92 of the planned 300 patients were recruited. Results 92 of 136 eligible patients were randomised to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomisation, was 14% with placebo and 4% with rivaroxaban (Hazard Ratio 0.32; 95% 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 (15.2 %) 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=0.03). 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

Standard threshold laser versus subthreshold micropulse laser for adults with diabetic macular oedema : the DIAMONDS non-inferiority RCT

Background: The National Institute for Health and Care Excellence recommends macular laser to treat diabetic macular oedema with a central retinal subfield thickness of < 400 µm on optical coherence tomography. The DIAMONDS (DIAbetic Macular Oedema aNd Diode Subthreshold micropulse laser) trial compared standard threshold macular laser with subthreshold micropulse laser to treat diabetic macular oedema suitable for macular laser. Objectives: Determining the clinical effectiveness, safety and cost-effectiveness of subthreshold micropulse laser compared with standard threshold macular laser to treat diabetic macular oedema with a central retinal subfield thickness of < 400 µm. Design: A pragmatic, multicentre, allocation-concealed, double-masked, randomised, non-inferiority, clinical trial. Setting: Hospital eye services in the UK. Participants: Adults with diabetes and centre-involving 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 < 400 µm following anti-vascular endothelial growth factor injections would be of value because it could reduce the number of injections and, subsequently, costs and risks and inconvenience to patients. Limitations: The majority of participants enrolled had poorly controlled diabetes. Conclusions: Subthreshold micropulse laser was equivalent to standard threshold macular laser but required a slightly higher number of laser treatments. Trial registration: This trial is registered as EudraCT 2015-001940-12, ISRCTN17742985 and NCT03690050. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 50. See the NIHR Journals Library website for further project information

Plaster cast versus functional brace for non-surgical treatment of Achilles tendon rupture (UKSTAR): a multicentre randomised controlled trial and economic evaluation

This is the final version. Available from Elsevier via the DOI in this record. 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.UK National Institute for Health Research Health Technology Assessment Programm

The relationship between objectively measured attributes of the built environment and selected cardiovascular risk factors in a South African urban setting

BACKGROUND: Evidence concerning the relationship between objectively-measured attributes of the built environment with cardio-metabolic risk in populations from lower- and middle-income countries is lacking. In this paper, we describe the association between the objectively-measured built environment with body mass index, blood pressure and physical activity in adult South Africans. METHODS: This cross-sectional study included 341 adults aged ≥35 years drawn from the Cape Town arm of the Prospective Urban Rural Epidemiology (PURE) cohort study. All Cape Town PURE participants were invited to take part in the study. Actigraph GT3X accelerometer and Geographic Information Systems were used to measure physical activity and built environment attributes (community center, shopping center and taxi rank). RESULTS: In age and sex adjusted models (reference 500 m), access to community centers (1000 m) was positively related to body mass index [beta 4.70 (95%CI: 2.06 to 7.34)] and diastolic blood pressure [4.97 (0.00 to 9.95)]. Distance from a community center (1600 m) was positively related to diastolic blood pressure [6.58 (1.57 to 11.58)] and inversely with moderate-to-vigorous physical activity [− 69.30 (− 134.92 to − 3.70)]. Distance to a shopping center (1600 m) was positively related to body mass index [4.78 (1.11 to 8.45)] and shopping center (1000 m) was positively related to systolic blood pressure respectively [76.99 (0.03 to 83.95)]. CONCLUSION: Distance to community and shopping centers were significantly associated with BMI, systolic, diastolic blood pressure and moderate-to-vigorous physical activity. Future research should include multiple aspects of built environment variables in order to provide for a broader understanding of their effect on cardiovascular risk profile of African populations

A comparison of the cost-effectiveness of intramedullary nail fixation and locking plate fixation in the treatment of adult patients with an extra-articular fracture of the distal tibia

Aim The aim of this study was to compare the cost-effectiveness of intramedullary nail fixation and ‘locking’ plate fixation in the treatment of extra-articular fractures of the distal tibia. Patients and Methods An economic evaluation was conducted from the perspective of the United Kingdom National Health Service (NHS) and personal social services (PSS), based on evidence from the Fixation of Distal Tibia Fractures (UK FixDT) multicentre parallel trial. Data from 321 patients were available for analysis. Costs were collected prospectively over the 12-month follow-up period using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality adjusted life year (QALY) gained, and net monetary benefit. Sensitivity analyses were conducted to test the robustness of cost-effectiveness estimates. Results Mean NHS and PSS costs were significantly lower for patients treated with an intramedullary nail than for those treated with a locking plate (-£970, 95% confidence interval (CI) -1685 to -256; p = 0.05). There was a small increase in QALYs gained in the nail fixation group (0.01, 95% CI -0.03 to 0.06; p = 0.52). The probability of cost-effectiveness for nail fixation exceeded 90% at cost-effectiveness thresholds as low as £15 000 per additional QALY. The cost-effectiveness results remained robust to several sensitivity analyses. Conclusion This trial-based economic evaluation suggests that nail fixation is a cost-effective alternative to locking plate fixation

Economic burden of stroke in a rural South African setting

Stroke is the second leading cause ofmortality and leading cause of disability in South Africa yet published data on the economic costs of stroke is lacking particularly in rural settings. 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. e 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. Our study provides a snapshot of costs incurred on stroke in rural South Africa.We showthat 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.