Improving Experiences of the Menopause for Women in Zimbabwe and South Africa:Co-Producing an Information Resource

Women in sub-Saharan Africa report multiple impacts of menopause on daily life and have requested further information to support themselves. This study co-produced contextually relevant resources—booklets and poster—about menopause with women in Zimbabwe and South Africa. The study was conducted in four stages: interviews with women about the menopause; the development of prototype information resources; workshops with women to discuss country-specific resources; and the refinement of resources. During the interviews, women explained that they had not received or accessed much information about the menopause and thought the physical and psychological issues associated with the menopause had to be “endured”. Prototype information resources comprised booklets and a poster with contextually relevant images and information. Workshop participants suggested several changes, including the addition of more diverse images and further information about treatments. The resources were refined, translated into several African languages, and endorsed by the Ministry of Health in Zimbabwe and the South African Menopause Society in South Africa. Women will be able to access resources through healthcare clinics, community groups and churches. Working with women and other stakeholders enabled a development that was cognisant of experiences and needs. Work is now needed to improve access to treatments and support for menopause to reduce health inequities

Disparities in the Prevalence of Osteoporosis and Osteopenia in Men and Women Living in Sub-Saharan Africa, the UK, and the USA

PURPOSE: To review the rising prevalence of osteopenia and osteoporosis in sub-Saharan Africa and the challenges this poses to governments and healthcare services. Using existing studies, we compare the prevalence of osteopenia and osteoporosis in men and women from sub-Saharan Africa to US and UK cohorts. Context-specific disparities in healthcare are discussed particularly the challenges in diagnosis and treatment of osteoporosis. RECENT FINDINGS: There are few epidemiological data describing the burden of osteoporosis in sub-Saharan Africa. In the studies and cohorts presented here, osteoporosis prevalence varies by sex, country and area of residence, but is generally higher in African populations, than has previously been appreciated. Risk factors contributing to poorer bone health include HIV, malnutrition and "inflammaging." Reprioritization towards care of ageing populations is urgently required. Equitable access to implementable preventative strategies, diagnostic services, treatments and pathways of care for bone health (for example embedded within HIV services) need now to be recognized and addressed by policy makers

Cardiovascular Risk Factors Associated With Venous Thromboembolism

Importance It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective To estimate associations between major cardiovascular risk factors and VTE, i.e., deep-vein thrombosis (DVT) and pulmonary embolism (PE). Design Analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 731,728 participants; 75 cohorts; latest date of follow-up 2015), and UK Biobank (UKBB; 421,537 participants; latest date of follow-up 2016). Setting Approximately population-based prospective cohort studies. Participants Individuals without cardiovascular disease at baseline. Exposures A panel of several established cardiovascular risk factors. Main Outcomes and Measures Hazard ratios (HRs) per 1-SD higher risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (n=1041 VTE, n=25,131 CHD) and incident fatal/non-fatal outcomes in UKBB (n=2321 VTE, n=3385 CHD). HRs were adjusted for age, sex, smoking status, diabetes mellitus, and body-mass index. Results Adjusted HRs for VTE were: 2.67 (2.45-2.91) in ERFC and 1.81 (1.71-1.92) in UKBB per decade older age; 1.38 (1.20-1.58) in ERFC and 1.23 (1.08-1.40) in UKBB with smoking; 1.43 (1.35-1.50) in ERFC and 1.37 (1.32-1.41) in UKBB per 1-SD higher body-mass index; and 0.75 (0.61-0.93) in ERFC and 0.82 (0.71-0.94) in UKBB with current alcohol consumption. For the preceding factors, there were similar HRs for pulmonary embolism versus deep vein thrombosis in UKBB (except adiposity was more strongly associated with PE; P<0.01), and similar HRs for unprovoked versus provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than coronary heart disease. We noted inconsistent associations with diabetes and blood pressure for VTEs across ERFC and UKBB, and had limited ability to study lipid and inflammation markers. Conclusions and Relevance Older age, smoking, adiposity, and lower alcohol consumption were consistently associated with higher VTE risk.A study website (http://www.phpc.cam.ac.uk/ceu/erfc/list-of-studies/) includes a list that investigators have provided of funding agencies that have supported individual cohorts in the ERFC contributing to the present consortium. This research has been conducted using the UK Biobank resource (application 26865)

The Impact of Human Immunodeficiency Virus and Menopause on Bone Mineral Density: A Longitudinal Study of Urban-Dwelling South African Women

An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34/205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 [95% confidence interval -0.026, -0.001] g/cm2 , p = 0.040) and gained more weight 1.96 [0.32, 3.60] kg; p = 0.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (-0.092 [-0.042, -0.142] g/cm2 ; p = 0.001) than without HIV (-0.038 [-0.016, -0.060] g/cm2 , p = 0.001; interaction p = 0.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (-0.070 [-0.031, -0.108], p = 0.001) than women without HIV (-0.036 [-0.015, -0.057], p = 0.001, interaction p = 0.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Osteoporosis, Rather Than Sarcopenia, Is the Predominant Musculoskeletal Disease in a Rural South African Community Where Human Immunodeficiency Virus Prevalence Is High: A Cross-Sectional Study.

The rollout of antiretroviral therapy globally has increased life expectancy across Southern Africa, where 20.6 million people now live with human immunodeficiency virus (HIV). We aimed to determine the prevalence of age-related osteoporosis and sarcopenia, and investigate the association between HIV, bone mineral density (BMD), muscle strength and lean mass, and gait speed. A cross-sectional community-based study of individuals aged 20-80 years in rural South Africa collected demographic and clinical data, including HIV status, grip strength, gait speed, body composition, and BMD. Sarcopenia was defined by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) guidelines, and osteoporosis as BMD T-score ≤ -2.5 (if age ≥50 years). The mean ± standard deviation (SD) age of 805 black South African participants was 44.6 ± 14.8 years, 547 (68.2%) were female; 34 (13.2%) were men, and 129 (23.6%) women had HIV, with 88% overall taking anti-retroviral therapy. A femoral neck T-score ≤ -2.5, seen in four of 95 (4.2%) men and 39 of 201 (19.4%) women age ≥50 years, was more common in women with than without HIV (13/35 [37.1%] versus 26/166 [15.7%]; p = 0.003). Although no participant had confirmed sarcopenia, probable sarcopenia affected more men than women (30/258 [11.6%] versus 24/547 [4.4%]; p = .001]. Although appendicular lean mass (ALM)/height2 index was lower in both men and women with HIV, there were no differences in grip strength, gait speed, or probable sarcopenia by HIV status. Older age, female sex, lower ALM/height2 index, slower gait speed, and HIV infection were all independently associated with lower femoral neck BMD. In conclusion, osteoporosis rather than sarcopenia is the common musculoskeletal disease of aging in rural South Africa; older women with HIV may experience greater bone losses than women without HIV. Findings raise concerns over future fracture risk in Southern Africa, where HIV clinics should consider routine bone health assessment, particularly in aging women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy.

Globally, 1·7 million children are living with HIV, of which 90% are in sub-Saharan Africa. The remarkable scale-up of combination antiretroviral therapy has resulted in increasing numbers of children with HIV surviving to adolescence. Unfortunately, in sub-Saharan Africa, HIV diagnosis is often delayed with children starting antiretroviral therapy late in childhood. There have been increasing reports from low-income settings of children with HIV who have multisystem chronic comorbidities despite antiretroviral therapy. Many of these chronic conditions show clinical phenotypes distinct from those in adults with HIV, and result in disability and reduced quality of life. In this Review, we discuss the spectrum and pathogenesis of comorbidities in children with HIV in sub-Saharan Africa. Prompt diagnosis and treatment of perinatally acquired HIV infection is a priority. Additionally, there is a need for increased awareness of the burden of chronic comorbidities. Diagnostic and therapeutic strategies need to be collectively developed if children with HIV are to achieve their full potential

'How Poor are you?' - A comparison of four questionnaire delivery modes for assessing socio-economic position in rural Zimbabwe

Assessing socio-economic position can be difficult, particularly in developing countries. Collection of socio-economic data usually relies on interviewer-administered questionnaires, but there is little research exploring how questionnaire delivery mode (QDM) influences reporting of these indicators. This paper reports on results of a trial of four QDMs, and the effect of mode on poverty reporting

A rare mutation in SMAD9 associated with high bone mass identifies the SMAD-dependent BMP signalling pathway as a potential anabolic target for osteoporosis

Novel anabolic drug targets are needed to treat osteoporosis. Having established a large national cohort with unexplained high bone mass (HBM), we aimed to identify a novel monogenic cause of HBM and provide insight into a regulatory pathway potentially amenable to therapeutic intervention. We investigated a pedigree with unexplained HBM in whom previous sequencing had excluded known causes of monogenic HBM. Whole exome sequencing identified a rare (minor allele frequency 0.0023), highly evolutionarily conserved missense mutation in SMAD9 (c.65T>C, p.Leu22Pro) segregating with HBM in this autosomal dominant family. The same mutation was identified in another two unrelated individuals both with HBM. In silico protein modeling predicts the mutation severely disrupts the MH1 DNA-binding domain of SMAD9. Affected individuals have bone mineral density (BMD) Z-scores +3 to +5, mandible enlargement, a broad frame, torus palatinus/mandibularis, pes planus, increased shoe size, and a tendency to sink when swimming. Peripheral quantitative computed tomography (pQCT) measurement demonstrates increased trabecular volumetric BMD and increased cortical thickness conferring greater predicted bone strength; bone turnover markers are low/normal. Notably, fractures and nerve compression are not found. Both genome-wide and gene-based association testing involving estimated BMD measured at the heel in 362,924 white British subjects from the UK Biobank Study showed strong associations with SMAD9 (P-GWAS = 6 x 10(-16); P-GENE = 8 x 10(-17)). Furthermore, we found Smad9 to be highly expressed in both murine cortical bone-derived osteocytes and skeletal elements of zebrafish larvae. Our findings support SMAD9 as a novel HBM gene and a potential novel osteoanabolic target for osteoporosis therapeutics. SMAD9 is thought to inhibit bone morphogenetic protein (BMP)-dependent target gene transcription to reduce osteoblast activity. Thus, we hypothesize SMAD9 c.65T>C is a loss-of-function mutation reducing BMP inhibition. Lowering SMAD9 as a potential novel anabolic mechanism for osteoporosis therapeutics warrants further investigation. (c) 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

IMPORTANCE: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. EXPOSURES: A panel of several established cardiovascular risk factors. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE: Older age, smoking, and adiposity were consistently associated with higher VTE risk.This research has been conducted using the UK Biobank resource under Application Number 26865. This work was supported by underpinning grants from the UK Medical Research Council (grant G0800270), the British Heart Foundation (grant SP/09/002), the British Heart Foundation Cambridge Cardiovascular Centre of Excellence, UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (grant 268834), the European Commission Framework Programme 7 (grant HEALTH-F2-2012-279233), and Health Data Research UK. Dr Danesh holds a British Heart Foundation Personal Chair and a National Institute for Health Research Senior Investigator Award