FRAX-based fracture probabilities in South Africa.

The hip fracture rates in South Africa were used to create ethnic-specific FRAX® models to facilitate fracture risk assessment. INTRODUCTION: The aim of this study was to develop FRAX models to compute the 10-year probability of hip fracture and major osteoporotic fracture and assess their potential clinical application. METHODS: Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for the White, Black African, Coloured and Indian population of South Africa. Age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women to determine fracture probabilities at a femoral neck T score of -2.5 SD, or those equivalent to a woman with a prior fragility fracture. Fracture probabilities were compared with those from selected countries. RESULTS: Probabilities were consistently higher in Indian than in Coloured men and women, in turn, higher than in Black South Africans. For White South Africans, probabilities were lower than in Indians at young ages up to the age of about 80 years. When a BMD T score of -2.5 SD was used as an intervention threshold, FRAX probabilities in women age 50 years were approximately 2-fold higher than in women of the same age but with an average BMD and no risk factors. The increment in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T score of -2.5 SD was no longer a risk factor. Probabilities equivalent to women with a previous fracture rose with age and identified women at increased risk at all ages. CONCLUSIONS: These FRAX models should enhance accuracy of determining fracture probability amongst the South African population and help guide decisions about treatment.

Health systems strengthening to arrest the global disability burden: empirical development of prioritised components for a global strategy for improving musculoskeletal health.

INTRODUCTION: Despite the profound burden of disease, a strategic global response to optimise musculoskeletal (MSK) health and guide national-level health systems strengthening priorities remains absent. Auspiced by the Global Alliance for Musculoskeletal Health (G-MUSC), we aimed to empirically derive requisite priorities and components of a strategic response to guide global and national-level action on MSK health. METHODS: Design: mixed-methods, three-phase design.Phase 1: qualitative study with international key informants (KIs), including patient representatives and people with lived experience. KIs characterised the contemporary landscape for MSK health and priorities for a global strategic response.Phase 2: scoping review of national health policies to identify contemporary MSK policy trends and foci.Phase 3: informed by phases 1-2, was a global eDelphi where multisectoral panellists rated and iterated a framework of priorities and detailed components/actions. RESULTS: Phase 1: 31 KIs representing 25 organisations were sampled from 20 countries (40% low and middle income (LMIC)). Inductively derived themes were used to construct a logic model to underpin latter phases, consisting of five guiding principles, eight strategic priority areas and seven accelerators for action.Phase 2: of the 165 documents identified, 41 (24.8%) from 22 countries (88% high-income countries) and 2 regions met the inclusion criteria. Eight overarching policy themes, supported by 47 subthemes, were derived, aligning closely with the logic model.Phase 3: 674 panellists from 72 countries (46% LMICs) participated in round 1 and 439 (65%) in round 2 of the eDelphi. Fifty-nine components were retained with 10 (17%) identified as essential for health systems. 97.6% and 94.8% agreed or strongly agreed the framework was valuable and credible, respectively, for health systems strengthening. CONCLUSION: An empirically derived framework, co-designed and strongly supported by multisectoral stakeholders, can now be used as a blueprint for global and country-level responses to improve MSK health and prioritise system strengthening initiatives.

The impact of COVID-19 on rheumatology practice across Africa.

OBJECTIVES: To identify the changes in rheumatology service delivery across the five regions of Africa from the impact of the COVID-19 pandemic. METHODS: The COVID-19 African Rheumatology Study Group created an online survey consisting of 40 questions relating to the current practices and experiences of rheumatologists across Africa. The CHERRIES checklist for reporting results of internet e-surveys was adhered to. RESULTS: A total of 554 completed responses were received from 20 countries, which include six in Northern Africa, six in West Africa, four in Southern Africa, three in East Africa and one in Central Africa. Consultant grade rheumatologists constituted 436 (78.7%) of respondents with a mean of 14.5 ± 10.3 years of experience. A total of 77 (13.9%) rheumatologists avoided starting a new biologic. Face-to-face clinics with the use of some personal protective equipment continued to be held in only 293 (52.9%) rheumatologists' practices. Teleconsultation modalities found usage as follows: telephone in 335 (60.5%), WhatsApp in 241 (43.5%), emails in 90 (16.3%) and video calls in 53 (9.6%). Physical examinations were mostly reduced in 295 (53.3%) or done with personal protective equipment in 128 (23.1%) practices. Only 316 (57.0%) reported that the national rheumatology society in their country had produced any recommendation around COVID-19 while only 73 (13.2%) confirmed the availability of a national rheumatology COVID-19 registry in their country. CONCLUSION: COVID-19 has shifted daily rheumatology practices across Africa to more virtual consultations and regional disparities are more apparent in the availability of local protocols and registries.

Sex-based differences in outcomes with bivalirudin or unfractionated heparin for transcatheter aortic valve replacement: Results from the BRAVO-3 randomized trial.

BACKGROUND: Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. RESULTS: The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. CONCLUSIONS: There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

[Mitral valve repair with the MitraClip following surgical mitral annuloplasty failure]. / Réparation mitrale à l'aide du MitraClip après échec précoce d'une réparation chirurgicale.

Mitral repair using the MitraClip device is on ongoing expansion and has been evaluated in different patterns of mitral regurgitation. Nevertheless, surgical approaches to mitral regurgitation remain the standard of care, at least in absence of contraindication. We report the first Canadian experience of mitral valve repair with the MitraClip following surgical mitral annuloplasty failure. Therapeutic considerations and potential challenges are discussed.

Prostate Cancer: Epigenetic Alterations, Risk Factors, and Therapy.

Prostate cancer (PCa) is the most prevalent urological cancer that affects aging men in South Africa, and mechanisms underlying prostate tumorigenesis remain elusive. Research advancements in the field of PCa and epigenetics have allowed for the identification of specific alterations that occur beyond genetics but are still critically important in the pathogenesis of tumorigenesis. Anomalous epigenetic changes associated with PCa include histone modifications, DNA methylation, and noncoding miRNA. These mechanisms regulate and silence hundreds of target genes including some which are key components of cellular signalling pathways that, when perturbed, promote tumorigenesis. Elucidation of mechanisms underlying epigenetic alterations and the manner in which these mechanisms interact in regulating gene transcription in PCa are an unmet necessity that may lead to novel chemotherapeutic approaches. This will, therefore, aid in developing combination therapies that will target multiple epigenetic pathways, which can be used in conjunction with the current conventional PCa treatment.

A Canadian cost-effectiveness analysis of transcatheter mitral valve repair with the MitraClip system in high surgical risk patients with significant mitral regurgitation.

OBJECTIVE: In patients with significant mitral regurgitation (MR) at high risk of mortality and morbidity from mitral valve surgery, transcatheter mitral valve repair with the MitraClip System is associated with a reduction in MR and improved quality-of-life and functional status compared with baseline. The objective was to evaluate the cost-effectiveness of MitraClip therapy compared with standard of care in patients with significant MR at high risk for mitral valve surgery from a Canadian payer perspective. METHODS: A decision analytic model was developed to estimate the lifetime costs, life years, quality-adjusted life years (QALYs), and incremental cost per life year and QALY gained for patients receiving MitraClip therapy compared with standard of care. Treatment-specific overall survival, risk of clinical events, quality-of-life, and resource utilization were obtained from the Endovascular Valve Edge-to-Edge REpair High Risk Study (EVEREST II HRS). Health utility and unit costs (CAD $2013) were taken from the published literature. Sensitivity analyses were conducted to explore the impact of alternative assumptions and parameter uncertainty on results. RESULTS: The base case incremental cost per QALY gained was $23,433. RESULTS were most sensitive to alternative assumptions regarding overall survival, time horizon, and risk of hospitalization for congestive heart failure (CHF). Probabilistic sensitivity analysis showed MitraClip therapy to have a 92% chance of being cost-effective compared with standard of care at a willingness-to-pay threshold of $50,000 per QALY gained. STUDY LIMITATIONS: Key limitations include the small number of patients included in the EVEREST II HRS which informed the analysis, the limited data available to inform clinical events and disease progression in the concurrent comparator group, and the lack of a comparator group from a randomized control trial. CONCLUSION: MitraClip therapy is likely a cost-effective option for the treatment of patients at high risk for mitral valve surgery with significant MR.

Consultation Outcomes for Musculoskeletal Conditions at two Community Health Centres in Cape Town

"Objectives: To compare the proportion of patients with documented diagnoses and management plans when they presented with musculoskeletal complaints at two community health centres (CHCs) using two models of care: one with a rheumatology outreach service and the other with none. Secondly; to describe the profile of patients with rheumatoid arthritis (RA) who attended the CHC with the outreach service. Design: Cross-sectional. Subjects: A group of 59 patients at each CHC were compared regarding engagement of their musculoskeletal complaints by doctors and clinical nurse practitioners (CNPs). Secondly; 24 RA patients who attended Heideveld CHC were profiled. Results: A comparison of the ""overall engagement"" between the two CHCs [risk difference (RD) -0.06; 95 confidence interval (CI): -0.17-0.05; odds ratio (OR) 0.79; 95 CI: 0.51-1.24; chi-square 0.82; p-value 0.36] was not significantly different. Comparison between doctors (RD -0.05; 95 CI: -0.05-0.08; OR 0.80; 95 CI: 0.46-1.40; chi-square 0.41; p-value 0.52) was also not significantly different. The comparison between the CNPs at the two CHCs was statistically significant (RD 0.30; 95 CI: 0.14-0.45; OR 8.37; 95 CI: 1.05-66.60; Fisher's exact test 0.01); but the CI around OR was large. Patients with RA had a mean age of 60 years; an average of two co-morbidities and an average of three annual clinic visits. Eighty-three per cent resided in the drainage area of the clinic. Conclusion: There was no significant difference in engagement between the CHCs. The potential that CNPs seemed to show of being positively influenced by the outreach service should be further researched. Patients with RA had comorbidities that required management at primary healthcare level."

Quantitative ultrasound in relation to risk factors for low bone mineral density in South African pre-menopausal women.

SUMMARY: The study describes the association between risk factors and quantitative ultrasound bone measures in black and mixed-race pre-menopausal South African women. Despite some differences between the two study groups, the findings generally lend support to the use of ultrasound for epidemiological studies of bone mass in resource-limited settings. INTRODUCTION: Quantitative ultrasound at the calcaneus is a convenient and inexpensive method of estimating bone strength well suited to community-based research in countries with limited resources. This study determines, in a large sample of pre-menopausal South African women, whether characteristics associated with quantitative ultrasound measures are similar to those shown to be associated with bone mineral density as measured by dual X-ray absorptiometry. METHODS: This cross-sectional study included 3,493 women (1,598 black and 1,895 mixed race), aged 18-44 living in Cape Town. Study nurses administered structured interviews on reproductive history, lifestyle factors, and measured height and weight. Calcaneus quantitative ultrasound measurements were obtained using the Sahara device. Adjusted means of ultrasound measures according to categories of risk factors were obtained using multivariable regression analysis. RESULTS: Associations between quantitative ultrasound measures and age, body mass index, age at menarche, parity, and primary school physical activity were similar to those known for bone mineral density as measured by dual X-ray absorptiometry. There were no clear associations between quantitative ultrasound measures and educational level, alcohol use, cigarette smoking, and current calcium intake. CONCLUSION: The data give qualified support to the use of quantitative ultrasound as an epidemiological tool in large studies of bone strength in pre-menopausal women.

Bone status after cessation of use of injectable progestin contraceptives.

BACKGROUND: Women using injectable progestin contraceptives (IPCs) have lower bone mineral density than nonusers. We assessed whether bone loss is completely reversible after cessation of IPC use, whether different IPCs have different effects and whether effects vary by age at first use. STUDY DESIGN: In a cross-sectional study in Cape Town, South Africa, 3487 premenopausal black and mixed race women aged 18-44 years were interviewed for information on contraceptive history and risk factors for decreased bone mineral density, and ultrasound measurements of the left calcaneus were taken. Adjusted means of the ultrasound measures for categories of IPC use were obtained using multivariable linear regression. RESULTS: Current users of IPCs had the lowest ultrasound measures, while the measures of women who had ceased IPC use at least 2-3 years previously were similar to or greater than those of never users of IPCs. The effects of depot medroxyprogesterone acetate and norethisterone enanthate were similar. The calcaneus measures were unrelated to age at which use began after control for confounding factors. CONCLUSION: The data suggest that bone loss during IPC use is reversible and that this loss of bone is completely recovered several years after cessation of use.