Pregnancy Related Venous Thromboembolism-Associated with HIV Infection and Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection in pregnancy is associated with substantial morbidity and mortality. Improved access to effective antiretroviral therapy (ART) has shifted the spectrum of pregnancy-related complications among HIV-infected pregnant women. In addition to placental vascular complications and preterm delivery, increased rates of venous thromboembolism (VTE) have been described. HIV infection is characterized by immune activation, inflammation, and endothelial dysfunction, which contribute to the activation of coagulation and its prothrombotic consequences. Indeed, activated coagulation factors have been reported to be increased and natural anticoagulants reduced in HIV. Several mechanisms for this persistent prothrombotic balance on ART have been identified. These may include: co-infections, immune recovery, and loss of the gastrointestinal mucosal integrity with microbial translocation. In addition to the direct effects of HIV and ART, traditional venous and obstetric risk factors also contribute to the risk of VTE. A research priority has been to understand the mechanisms of VTE in HIV-infected pregnant women receiving suppressive ART and to translate this into HIV-specific thromboprophylaxis recommendations. Management requires a multidisciplinary approach and further studies are indicated to guide the prevention and management of pregnancy-associated VTE in this population. The current review describes the epidemiology, mechanisms, and management of VTE in HIV-infected women in pregnancy and the postpartum period.

Progress in transforming a health sciences postgraduate cohort in a south african research-intensive institution, 2008-2017.

BACKGROUND: Equity redress in the higher education and health sectors is a global discourse that seeks to address the inequalities caused by past discrimination practices. The apartheid regime in South Africa fragmented both the higher education and the health sectors, creating White and male dominated systems. Consequently, Black Africans and females were under-represented in these sectors. Furthermore, the provision of higher education including medical training was unequal between the different populations. As democracy was established in South Africa in 1994, it is necessary to assess whether transformation in population affinity and sex of postgraduate students in the higher education and health sector has occurred, as these individuals are crucial for providing the future academic workforce and also healthcare to the public. METHODS: The demographic profile of postgraduate students graduating in a health sciences facility in South Africa over the period 2008-2017 was retrospectively assessed. Survival analysis models were used to investigate the time taken to graduate. Log-rank tests were used to compare the completion rates. RESULTS: More females (53.3%) than males (41.9%) completed their postgraduate degree over the period 2008-2017 (p˂0.0001). In relation to population affinity, more White students (56.4%) than Black African students (40.8%) completed their degrees overall (p˂0.0001). CONCLUSION: While transformation occurred in the sex of graduating students over the ten year period, the same change has not occurred with regards to population affinity. The under-representation of Black African graduates is a major setback for efforts to diversify the South African higher education and health sectors. Transformation of the demographic profile of postgraduate students at South African institutions is vital for developing individuals who will contribute to equitable redress of academic staff in the higher education sector and also of the healthcare workforce. Diversified health personnel including highly skilled clinician scientists will aid in improving the provision of health care to communities particularly the underpriviledged rural areas, and also assist in training the next generation of healthcare staff. The challenges identified in this study may assist other countries where adequate transformation of the education and health sectors has not occurred.

Detecting subclinical anthracycline therapy-related cardiac dysfunction in patients attending Uganda Cancer Institute.

Aims: To investigate the incidence of anthracycline therapy-related cardiac dysfunction (ATRCD) and its predictors among Ugandan cancer patients. Patients & methods: The study recruited 207 cancer patients who were followed for 6 months after ending anthracycline therapy. Global longitudinal strain and troponin-I were the diagnostic tools. Results & conclusions: The cumulative incidences of subclinical and clinical ATRCD were 35.0 and 8.8% respectively. The predictors of clinical ATRCD were HIV infection (hazard ratio [HR]: 3.04; 95% CI: 1.26-7.32; p = 0.013), lower baseline global longitudinal strain (HR: 0.61; 95% CI: 0.53-0.71; p < 0.001) and development of subclinical ATRCD at the end of anthracycline therapy (HR: 6.61; 95% CI: 2.60-16.82; p < 0.001). Cardiac surveillance at baseline and at ending of anthracycline therapy is essential to identify high-risk patients.

Anthracyclines are drugs for treating many types of cancers. They may however be harmful to the heart. This anthracycline side effect will first cause subtle heart­cell injury that can be detected and treated if it is handled early. Therefore, this study aims to study patients in the Uganda Cancer Institute to find out how many patients can get and who are likely to get this side effect. We found that 35% of the patients had subtle heart­cell injury and 8.8% had a more severe form of heart­cell injury. The patients who lived with HIV, whose heart was weaker and who got subtle heart­cell injury immediately after treatment were more likely to get the severe form of the side effect. Patients who receive anthracycline therapy need to be monitored closely to prevent serious heart injury.

A biostatistical support system in health sciences: is this sustainable in a resource-restricted environment?

BACKGROUND: Training in biostatistics is important for strengthening capacity in health research. This is particularly true for Africa, where research output in the health sciences has been low. Training initiatives for the continent are therefore essential. The aim of the present study was to analyse the quality and financial sustainability of the expanded biostatistical support system at a South African health sciences institution between 2013 and 2017. METHODS: A cross-sectional investigation of the initiatives created between the years 2013 and 2017 in the University of the Witwatersrand, Faculty of Health Sciences Research Office was undertaken. An assessment of the one-on-one consultations carried out by postgraduate students and staff, financial costs of the support system and the number of postgraduate student graduations were analysed. RESULTS: The number of statistical consultations increased over the period examined. The consultations were highly recommended by the postgraduate students and staff (consulters). A clear rise in the number of Masters and PhD student graduates and an increase in research units were observed from 2013 to 2017, although these cannot be solely associated with the biostatistical support system. The finances for maintaining the support system are cost effective as the number of graduates increases. The total cost to the Research Office is US$ 225 per graduate per annum. CONCLUSIONS: The expansion of the biostatistical support system has indirectly contributed to an increased number of graduates and research publication units in the institution. While the current finances support the system, any increases in enrolments or growth in diversification of biostatistical requirements may place a strain on the financial sustainability. This service is of value to developed and developing countries.

Writing for publication: institutional support provides an enabling environment.

BACKGROUND: Due to the excessive service delivery loads in public hospitals supported by academic institutions in developing environments, researchers at these institutions have little time to develop scientific writing skills or to write up their research. It is imperative to expand the writing skills of researchers and train the next generation of health sciences academics in order to disseminate research findings. This study reports on the implementation of approaches for writing and publication and the extent of support to staff suffering from the overload of service delivery and of heavy teaching duties. METHODS: Workshops in scientific writing and writing retreats were initiated and were offered to all staff. RESULTS: Feedback from participants of the writing skills workshops indicated that the workshops provided an injection of confidence and proficiency. Protected writing time resulted in 132 papers submitted to journals and 95 in preparation from 230 participants of the writing retreats over a two year period. Staff commended the off-site, collegial environment, which also supported future collaboration with new-found colleagues. CONCLUSION: This enabling environment facilitates not only the development of writing skills per se, but also the dissemination of the generated scientific knowledge. In addition, the training in writing skills of this generation will be of value in the training of future cohorts in countries with similar health care deliverables.

Developing a biostatistical support system in a resource-restricted academic institution in Africa: making it happen.

BACKGROUND: In order to address and support biostatistics for health research, the Health Sciences Research Office of the University of the Witwatersrand sought to introduce training in biomedical statistics to sustain research and postgraduate education. The experiences encountered in setting up such statistical support in a limited resource, developing country are discussed here. METHODS: Two cross-sectional surveys (a) statistical needs assessment (2009) and (b) feedback (2010-11) on the statistical support through biostatistics courses and consultations were conducted. These surveys were supplemented with information such as graduations, research publication output and costs of setting up the support. RESULTS: Seventy-three percent of respondents favoured short courses with "hands-on" practice. Eighty-nine percent agreed that these courses should be run and coordinated by the Health Sciences Research Office instead of the departments. There was use of varied statistical packages requiring one package for standardised support. The numbers of postgraduate students attending short courses in statistics increased from 2010 to 2012 as did the numbers attending statistical consultations. Graduations and publication outputs increased over this period of time although this may not be directly linked solely to the biostatistical support system introduced. CONCLUSIONS: There is a distinct need for biostatistics training in developing countries and the process described in this study could be replicated in any health sciences institution, especially in a resource-restricted environment.

Clinical outcomes in patients with isolated left ventricular noncompaction and heart failure.

BACKGROUND: We prospectively evaluated long-term clinical outcomes of patients diagnosed with isolated left ventricular noncompaction (ILVNC) and heart failure from a sub-Saharan African population. METHODS AND RESULTS: Patients in this single-center study were followed at a tertiary care institution. Clinical follow-up was performed with the use of protocol-driven echocardiographic screening for ventricular thrombus every 4 months. Warfarin was maintained or initiated only if thrombus was detected with the use of echocardiography. Fifty-five patients were followed for 16.7 ± 5.9 (range 12-33) months. All individuals had left ventricular (LV) ejection fraction <50% (mean 29.6 ± 11.8%). Of the 55 patients, 7 (12.7%) died, and sudden cardiac death was the cause in 5 (71.4%). There were no differences in baseline clinical, echocardiographic, or electrocardiographic characteristics between survivors and nonsurvivors. Recurrent heart failure developed in 12 patients (21.8%); 1 patient developed a ventricular arrhythmia. No thromboembolic or major bleeding complications occurred in the 16 patients on warfarin; 1 episode of thromboembolism occurred in the 39 patients not on warfarin. Mean survival probability at 33 months was 0.64. CONCLUSIONS: Sudden cardiac death was the most common cause of death in patients with ILVNC and heart failure. Recurrent heart failure occurred in 21.8% of patients. Development of LV thrombus and cardioembolism is uncommon in this population.

Leading the transition to ethical human body sourcing in Africa: The South African experience.

BACKGROUND: The use of human bodies for anatomy education and research forms an integral part of the training of health professionals around the world. However, the ethical acquisition of human remains for this purpose has been a challenge in many countries, particularly for those on the African continent. South African institutions have however, been able to progressively transition to a more ethical approach to human body acquisition. The aim of the current study was to investigate the provenance of human bodies and the number used in South African health sciences institutions during the period 2017-2021. METHODS: an online self-administered anonymised questionnaire was circulated to all health sciences institutions in South Africa. Questions were focused on establishing the provenance and the associated number of bodies and body donor programmes. RESULTS: responses were received from thirteen of the fourteen South African institutions. All thirteen institutions use human bodies for teaching and research, with the majority of the institutions being reliant on bequests (77%) and family donations (62%), and less on unclaimed remains (46%). Most institutions have established body donor programmes. Four institutions were negatively affected by the effects of the pandemic. Memorial services, which continued during the pandemic, were conducted by eight of the thirteen institutions. CONCLUSION: South Africa is leading the transition to the ethical acquisition of human remains on the African continent. It is hoped that South African institutions will soon transform to the exclusive sourcing of bodies through willed donation and provide guidance and support for the other countries on the continent.

Population-based temporal trends and ethnic disparity in breast cancer mortality in South Africa (1999-2018): Joinpoint and age-period-cohort regression analyses.

Globally, breast cancer is the leading cause of cancer deaths, accounting for 15.5% of female cancer deaths in 2020. Breast cancer is also the leading cause of female cancers in South Africa. The rapid epidemiological transition in South Africa may have an impact on the trends in breast cancer mortality in the country. We therefore evaluated the trends in the breast cancer mortality in SA over 20 years (1999-2020). Methods: Joinpoint regression analyses of the trends in crude and age-standardized mortality rates (ASMR) of breast cancer among South African women were conducted from 1999 to 2018 using mortality data from Statistics South Africa. Age-period-cohort regression analysis was then conducted to evaluate the independent effect of age, period, and cohort on breast cancer mortality, and analysis was stratified by ethnicity. Results: The mortality rate of breast cancer (from 9.82 to 13.27 per 100,000 women) increased at around 1.4% per annum (Average Annual Percent Change (AAPC): 1.4%, 95% CI:0.8-2.0, P-value< 0.001). Young women aged 30-49 years (1.1%-1.8%, P-value< 0.001) had increased breast cancer mortality. The risk of breast cancer mortality increased among successive birth cohorts from 1924 to 1928 but decreased among recent cohorts born from 1989 to 1993. In 2018, the breast cancer mortality rate among Blacks (9.49/100,000 women) was around half of the rates among the non-Blacks. (Coloreds: 18.11 per 100,000 women; Whites: 17.77/100,000 women; Indian/Asian: 13.24 per 100,000 women). Conclusions: Contrary to the trends in high- and middle-income countries, breast cancer mortality increased in South Africa especially among young women. Breast cancer prevention programs should be intensified and should also target young women. The marked disparity in ethnic burden of breast cancer should be considered during planning and implementation of interventions.

Clinical and laboratory profile and outcomes of hospitalized COVID-19 patients with type 2 diabetes mellitus in Ghana - A single-center study.

BACKGROUND: In sub-Saharan Africa and particularly in Ghana, there is scarcity of published literature specifically on the impact of DM on outcomes in COVID-19 patients. Based on the difference in genetic makeup and demographic patterns in Africans compared to the Western world and with the rising burden of DM and other non-communicable diseases in Ghana there is a need to define the impact DM has on persons with COVID-19. This would ensure adequate risk stratification and surveillance for such patients as well as appropriate scale up of therapeutic management if needed. AIMS: This single-center study describes the clinical and laboratory profile and outcomes of COVID-19 in-patients with type 2 diabetes mellitus (DM) in Ghana. MATERIALS AND METHODS: Retrospective analysis was undertaken of the medical records of adults with COVID-19 hospitalized at a facility in Ghana from March to October 2020. Clinical, laboratory and radiological data and outcomes were analysed. Comparisons between COVID-19 patients with DM and non-diabetics were done with an independent t-test or a Mann-Whitney test when normality was not attained. Odds ratios (95% CI) were calculated using univariate logistic regression. RESULTS: Out of 175 COVID-19 patients, 64 (36.6%) had DM. Overall mean age was 55.9 ± 18.3 years; DM patients were older compared to non-diabetics (61.1 ± 12.8 vs. 53.0 ± 20.2 years, p = .049). Compared to non-diabetics, diabetics were more likely to have higher blood glucose at presentation, have hypertension, be on angiotensin 2 receptor blockers [OR, 95% CI 3.3 (1.6-6.7)] and angiotensin converting enzyme inhibitors [OR, 95% CI 3.1 (1.3-7.4)]; and be HIV negative (p < .05). Although the values were normal, diabetics had a higher platelet count but decreased lymphocytes, aspartate transaminase and alkaline phosphatase compared to non-diabetics (p < .05). There was no difference in clinical symptoms, severity or mortality between the two groups. DISCUSSION: The clinical profile of patients studied are similar to prior studies. However the outcome of this study showed that DM was not associated with worse clinical severity and in-hospital mortality. This could have been due to majority of DM patients in this study having relatively good blood glucose control on admission. Secondly, DM alone may not be a risk factor for mortality. Rather its concurrent existence with multiple co-morbidities (especially cardiovascular co-morbidities which may predispose to pro-inflammatory and pro-thrombotic states) may be driving the rise in severity and mortality risks reported in other studies. Furthermore, this study was conducted among an African population and Africa has been shown to be generally less severely hit by the COVID-19 pandemic compared to other regions outside the continent. This has been postulated to be due, among other factors, to inherent protective mechanisms in Africans due to early and repeated exposure to parasitic and other organisms resulting in a robust innate immunity. CONCLUSIONS: This study suggested that DM was not associated with more severe clinical symptoms or worse outcomes among hospitalized COVID-19 patients. Despite this, it is important that DM patients adhere to their therapy, observe the COVID-19 containment protocols and are prioritized in the administration of the COVID-19 vaccines. STUDY HIGHLIGHTS: In this retrospective, single-centre study on the clinical and laboratory profile and outcome of hospitalized DM patients with COVID-19, patients with DM did not have a more severe clinical profile or worse outcomes. They were, however, significantly older, more likely to have higher admission blood glucose, have hypertension, be on angiotensin 2 receptor blockers and angiotensin converting enzyme inhibitors; and be HIV negative compared to the cohort without DM. DM patients should be a priority group for the COVID-19 vaccines.

A comparative study of outcomes of burns across multiple levels of care.

BACKGROUND: Burn injuries are a significant contributor to the burden of diseases. The management of burns at specialised burn centres has been shown to improve survival. However, in low- and middle-income countries (LMICs) major burns are managed at non-specialised burn centres due to resource constraints. There is insufficient data on survival from treatment at non-specialised burn centres in LMICs. This study aimed to compare the outcomes of burns treatment between a specialised burn centre and five non-specialised centres. METHODS: A prospective cohort study was conducted on patients aged 18 years or above from January 1, 2021 to September 30, 2021. Participants were selected from the admission register at the emergency department. All burns irrespective of the mechanism of injury or %TBSA were included. Data were entered into REDCap. Statistical analysis of outcomes such as positive blood culture, length of hospital stay (LOHS) and 90-day mortality between specialised burn versus non-specialised centres was performed. Furthermore, an analysis of risk factors for mortality was performed and survival data computed. RESULTS: Of the 488 study participants, 36% were admitted to a specialised burn centre compared to 64% admitted to non-specialised centres. The demographic characteristics were similar between centres. Patients at the specialised burn centre compared to non-specialised centres had a significantly higher inhalation injury of 30.9% vs 7.7% (p < 0.001), > 10%TBSA at 83.4% vs 45.7% (p < 0.001), > 20%TBSA at 46.9% vs 16.6% (p < 0.001), and a median (IQR) ABSI score of 6 (5-7) vs 5 (4-6) (p < 0.0001). Furthermore, patients from specialised burn vs non-specialised centres had a longer median (IQR) time from injury to first burn excision at 7 (4-11) vs 5 (2-10) days, higher rate of burn sepsis 69% vs 35%, increased LOHS 17 (11-27) vs 12 (6-22) days, and 90-day mortality rates at 19.4% vs 6.4%. After adjusting for cofounding variables, survival data showed no difference between specialised burn and non-specialised centres (HR 1.8 95% CI 1.0-3.2, p = 0.05). CONCLUSION: Although it appears that the survival of burn patients managed at non-specialised centres in a middle-income country is comparable to those managed at specialised burn centres, there is uncounted bias in our survival data. Hence, a change in practice is not advocated. However, due to resource constraint specialised burn centres in addition to managing major burns should provide training and support to the non-specialised centres.

Population-Based Temporal Trends and Ethnic Disparity in Cervical Cancer Mortality in South Africa (1999-2018): A Join Point and Age-Period-Cohort Regression Analyses.

Cervical cancer is one of the leading causes of cancer deaths among women in low- and middle-income countries such as South Africa. The current impact of national cervical cancer control and sexual and reproductive health interventions in South Africa reduce its burden. The aim of this study was to assess the trends in cervical cancer mortality and its relation to breast and gynaecological cancers in South Africa from 1999 to 2018. We conducted joinpoint regression analyses of the trends in crude and age-standardised mortality rates (ASMR) for cervical cancer mortality in South Africa from 1999 to 2018. An age−period−cohort regression analysis was also conducted to determine the impact of age, period, and cohort on cervical cancer mortality trends. Analyses were stratified by ethnicity. Cervical cancer (n = 59,190, 43.92%, 95% CI: 43.65−44.18%) was responsible for about 43.9% of breast and gynecological cancer deaths. The mortality rate of cervical cancer (from 11.7 to 14.08 per 100,000) increased at about 0.9% per annum (Average Annual Percent Change (AAPC): 0.9% (AAPC: 0.9%, p-value < 0.001)), and young women aged 25 to 49 years (AAPC: 1.2−3.5%, p-value < 0.001) had increased rates. The risk of cervical cancer mortality increased among successive birth cohorts. In 2018, cervical cancer mortality rate among Blacks (16.74 per 100,000 women) was about twice the rates among Coloureds (8.53 deaths per 100,000 women) and approximately four-fold among Indians/Asians (4.16 deaths per 100,000 women), and Whites (3.06 deaths per 100,000 women). Cervical cancer control efforts should be enhanced in South Africa and targeted at ethnic difference, age, period, and cohort effects.

Child and adolescent food insecurity in South Africa: A household-level analysis of hunger.

Food insecurity impacts childhood nutritional status, physical and cognitive development, and increases lifetime risk for chronic disease. Previous South African studies have examined hunger at the sub-national level without a specific focus on children and adolescents. This study determines the national prevalence of childhood food insecurity, from birth to adolescence, and identifies factors associated with hunger within the household. Individual and household-level data were extracted from the South African National Health and Nutrition Examination Survey (SANHANES-1). Prevalence of food insecurity was assessed using the Community Childhood Hunger Identification Project (CCHIP) index. Multinomial logistic regression analyses were conducted on all households (with and without children) to determine the predictors of food insecurity, with additional analyses adjusting for child dependency and sociodemographic characteristics of household heads in households with children. Of 5 098 households surveyed, 68.6% had children and adolescents present (0-19 years). Of these households, 32.5% (95% Confidence Interval [CI]: 29.5-35.7) were experiencing hunger and 26.3% (95% CI: 23.9-28.8) were at risk of hunger. Among all the households, significant associations for experiencing hunger were the presence of children and adolescents: Adjusted Odds Ratio (AOR) = 1.68 (95% CI: 1.12-2.53); being female-headed: AOR = 1.53 (95% CI: 1.21-1.94) and informally-located; AOR = 1.6 (95% CI: 1.07-2.43). Of the racial groups, having a non-African household head, Coloured: AOR = 0.29 (95% CI: 0.19-0.44) and White/Indian/Asian: AOR = 0.12 (95% CI: 0.04-0.33) conferred lower odds of experiencing hunger; and, the household head having secondary/tertiary education conferred lower odds of experiencing hunger; AOR = 0.40 (95% CI: 0.28-0.56) as well as being at risk of hunger; AOR = 0.69 (95% CI: 0.52-0.92). Receiving social grants, pensions, or remittances more than doubled the odds of experiencing hunger; AOR = 2.15 (95% CI: 1.49-3.09). After adjusting for child dependency in households with children, having at least one older child (age 15-19 years old) did not change the odds of food insecurity. In summary, only 41% of South African households with children and adolescents were food secure. The associations between household head sociodemographics, household location and size on household food insecurity indicate a need for multi-sectoral interventions to bolster sustainable food systems for households with children and adolescents and to improve public protections for female-headed, African-headed and informally-located households dependent on social grants.

A Systematic Review of Acute Thoracic Aortic Dissections in Africa-The Need for a Registry.

In this systematic review, the available literature on the presentation and management of acute thoracic aortic dissections in Africa is examined. Though Africa has 17% of the world population, it accounts for approximately 1% of the available literature with much of our understanding coming from registries arising from the developed world, such as the International Registry of Acute Aortic Dissection. The literature from the African continent consists mainly of case reports, small case series, and few original studies. Case reports make an important contribution to our understanding of uncommon conditions but can skew our understanding of aortic dissections in this region by describing unusual presentations and management. In this review, we describe the available studies retrieved from large medical databases (Medline and Health Management Information Consortium) and motivate the need for national registries to provide a more accurate appreciation of the scope of the problem on this continent.

Is the Risk Really Shared? A Retrospective Analysis of Healthcare Costs of Patients With Type 2 Diabetes Mellitus on a Capitation Model.

OBJECTIVES: Private managed healthcare organizations in South Africa (SA) use a capitation model of care for patients within their healthcare delivery systems for the optimal management of type 2 diabetes mellitus (T2DM) to reduce healthcare costs. Few studies have categorized healthcare costs at a patient level to determine the actual healthcare costs incurred by private insurers for T2DM in SA. This study estimated the direct medical costs of patients with T2DM registered with a private health insurer over a 5-year period between 2 funding models: a capitated risk-sharing model (CM) versus a traditional fee-for-service (FFS) model. METHODS: This population-based cohort study used retrospective claims data of patients with T2DM from 2012 to 2016 of a private medical scheme in SA. Annual healthcare costs of T2DM were assessed. RESULTS: During the 5-year period, most of the identified patients with T2DM were enrolled in CM-534 (64%) of 828 in 2012, which rose to 789 (81%) of 971 in 2016. The median annual healthcare costs of the treatment and management of the patients with T2DM was significantly higher in CM ($2002 [interquartile range (IQR) 2106] in 2012 to $1095 [IQR 1042] in 2016) than FFS ($582 [IQR 772] to $296 [IQR 507]) (P<.0001). A total of 46 patients with T2DM incurred hospitalization costs of ≥$24 243 for a T2DM or other event; 33 were enrolled on CM. CONCLUSIONS: The patients with T2DM on CM accrue significantly higher annual healthcare costs than patients on FFS. The greatest portion of the overall T2DM healthcare costs was associated with high-cost hospitalization of T2DM complications.

The role of conventional echocardiographic parameters on detecting subclinical anthracycline therapy related cardiac dysfunction-The SATRACD study.

Background: Subclinical anthracycline therapy related cardiac dysfunction (ATRCD) can be detected with speckle tracking echocardiographic image (STE), which is not widely available in Uganda. We aimed to investigate the role of the two conventional echocardiographic parameters [mitral annular plane systolic excursion (MAPSE) and mitral annular peak systolic tissue Doppler velocity (S')] on diagnosing subclinical ATRCD. Method and results: 207 cancer patients who underwent anthracycline based chemotherapy were recruited at baseline and followed up until 6 months after ending anthracycline therapy. Comprehensive echocardiographic data were collected at each visit. Global longitudinal strain (GLS) by STE was used as the gold standard diagnostic test to define the case of subclinical ATRCD. Data of the 200 patients who had no evidence of clinical ATRCD were analyzed. One hundred and seventy-two (86.0%) were female, with a median age of 42 years and 47 (23.5%) patients were diagnosed with subclinical ATRCD at the end of anthracycline therapy by GLS criteria. The area under the curve (AUC), cutoff point, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of reduction of MAPSE (ΔMAPSE) were 0.6736 (95% CI: 0.5885, 0.7587), ≥ 2 mm, 74.5% (95% CI: 59.7%, 86.1%), 54.9% (95% CI: 46.7%, 63.0%), 33.7% (95% CI: 24.7%, 43.6%), and 87.5% (95% CI: 79.2%, 93.4%). The AUC, cutoff point, sensitivity, specificity, PPV, and NPV of reduction of S' (ΔS') were 0.6018 (95% CI: 0.5084, 0.6953), ≥ 0.5 cm/s, 61.7% (95% CI: 46.4%, 75.5%), 52.7% (95% CI: 44.4%, 60.9%), 29.0% (95% CI: 20.4%, 38.9%), and 76.1% (95% CI: 72.4%, 88.6%). When ΔMAPSE and ΔS' are used as parallel test, the net sensitivity and specificity is 89.4% and 28.8%, respectively, the net PPV and NPV is 27.8% and 90.0%, respectively. Conclusion: The ΔMAPSE and ΔS' showed fairly good accuracy, sensitivity and NPV to detect subclinical ATRCD in Ugandan cancer patients. These conventional echocardiographic parameters may serve as screening tools for detecting subclinical ATRCD in resource limited settings.

Evaluation of markers of fibrinolysis and coagulation in pregnant women with human immunodeficiency virus.

INTRODUCTION: Human immunodeficiency virus (HIV) in pregnant women is characterized by immune activation and inflammation despite suppressive antiretroviral therapy (ART). The extent to which ongoing inflammation contributes to activation of coagulation and fibrinolysis is unknown. MATERIALS AND METHODS: This cross-sectional study included pregnant women in the following three groups: HIV negative (n = 109), HIV infected virologically suppressed (n = 109) and HIV infected with HIV viral load (VL) of >50 copies/mL (n = 80). Fibrinolytic activity was evaluated by measuring d-dimer and plasminogen activator inhibitor-1 (PAI-1) as well as thrombin-antithrombin (TAT) complex concentrations, as an index of coagulation, in the first, second and third trimesters. RESULTS: In this population, with a mean age of 33 ± 6 years, pregnancy outcomes were recorded for 277 (93.0 %) participants with live births. HIV infected participants with virological suppression and VL of >50 copies/mL showed significantly increasing levels of d-dimer and PAI-1 in the first, second and third trimesters, as compared to HIV negative participants. No significant differences were observed between HIV infected participants with virological suppression and HIV infected participants with VL > 50 copies/mL for levels of first and third trimester d-dimer and PAI-1 in each trimester. In addition, TAT complex levels in the first trimester were significantly increased in HIV infected virologically suppressed participants as compared to HIV negative participants. CONCLUSION: HIV infected virologically suppressed pregnant women show evidence of persistently impaired markers of fibrinolysis. Future research should explore the risk of adverse pregnancy complications among HIV infected pregnant women in the modern era of ART.

Profile of antiphospholipid antibodies in HIV-infected and HIV-uninfected women with a history of thrombosis.

INTRODUCTION: Increased antiphospholipid antibodies (aPL) have been described in human immunodeficiency virus (HIV) infection. However, the association between aPL and the increased risk of thrombosis in HIV requires further clarification. METHODS: We reviewed the medical records of 215 consecutive women with a history of thrombosis and/or obstetric complications (158 HIV-uninfected and 57 HIV-infected) between July 2017 and March 2021. Participants (n = 215) without clinical criteria manifestations for antiphospholipid syndrome were included as matched controls. Testing for lupus anticoagulant (LAC), anticardiolipin (aCL) and anti-beta2-glycoprotein1 (aß2GP1) IgM and IgG was performed. RESULTS: Thirty-two (10.1%) HIV-uninfected and 15 (13.2%) HIV-infected participants were positive at baseline for one of the five criteria aPL, with no statistically significant difference. The profile of the HIV-infected participants with thrombosis (n = 11) included LAC in 15.8%, aCL IgG in 3.5% and aß2GP1 IgG in 1.8%. In contrast, the HIV-infected controls (n = 4), included aCL IgM in 1.8% and aß2GP1 IgM in 5.3%. Only LAC was significantly associated with thrombosis (p < 0.003). On repeat testing, in a HIV-infected sub-population, 2/7 with thrombosis were positive, while 3/3 controls tested negative. CONCLUSION: In contrast to earlier reports, the prevalence and expression of aPL in HIV-infected women with a history of thrombosis in the present study, in the era of antiretroviral therapy, were similar to HIV-uninfected women. Baseline LAC positivity was associated with a significantly increased risk for thrombosis in HIV. Future studies are recommended to explore additional coagulation abnormalities in HIV.

Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that occurs in previously healthy women. We identified prolactin, mainly its 16-kDa angiostatic and proapoptotic form, as a key factor in PPCM pathophysiology. Previous reports suggest that bromocriptine may have beneficial effects in women with acute onset of PPCM. METHODS AND RESULTS: A prospective, single-center, randomized, open-label, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard care (PPCM-Std; n=10) versus standard care plus bromocriptine for 8 weeks (PPCM-Br, n=10) was conducted. Because mothers receiving bromocriptine could not breast-feed, the 6-month outcome of their children (n=21) was studied as a secondary end point. Blinded clinical, hemodynamic, and echocardiographic assessments were performed at baseline and 6 months after diagnosis. Cardiac magnetic resonance imaging was performed 4 to 6 weeks after diagnosis in PPCM-Br patients. There were no significant differences in baseline characteristics, including serum 16-kDa prolactin levels and cathepsin D activity, between the 2 study groups. PPCM-Br patients displayed greater recovery of left ventricular ejection fraction (27% to 58%; P=0.012) compared with PPCM-Std patients (27% to 36%) at 6 months. One patient in the PPCM-Br group died compared with 4 patients in the PPCM-Std group. Significantly fewer PPCM-Br patients (n=1, 10%) experienced the composite end point of poor outcome defined as death, New York Heart Association functional class III/IV, or left ventricular ejection fraction <35% at 6 months compared with the PPCM-Std patients (n=8, 80%; P=0.006). Cardiac magnetic resonance imaging revealed no intracavitary thrombi. Infants of mothers in both groups showed normal growth and survival. CONCLUSIONS: In this trial, the addition of bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM, although the number of patients studied was small and the results cannot be considered definitive. Larger-scale multicenter and blinded studies are in progress to test this strategy more robustly.

Renogram image characteristics and the reproducibility of differential renal function measurement.

PURPOSE: Patient factors such as age and glomerular filtration rate (GFR), have been implicated as causes for poor reproducibility of differential renal function (DRF) estimates on 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renography. This study aims to investigate factors associated with the reproducibility of DRF measurements. METHODS: The association between age, GFR and imaged derived image characteristics and reproducibility of repeated DRF estimates calculated using the area under the curve method and the Rutland Patlak method was analysed for cohort 1 (n = 127). The association between these variables and reproducibility of DRF was tested with univariate linear regression. The univariate linear regression results were used to plan the multiple linear regression combinations.The associations between variables identified and reproducibility of DRF values were then tested in a second cohort (n = 227). RESULTS: The R2 values for goodness-to-fit for the multiple regression models ranged from 0.33 to 0.49 for cohort 1 and from 0.17 to 0.22 for cohort 2. Left kidney to background ratio (LKTBR) was significant in all the multiple linear regression combinations (P < 0.05). Right kidney to background ratio (RKTBR), right renal margins well defined, right renal margins poorly visualised, time visualisation right calyces and age were significant in most combinations. The reproducibility of DRF measurement was decreased when the kidney to background ratio (KTBR) was ≤2. CONCLUSION: Only LKTBR, RKTBR, right renal margins well defined, time visualisation right calyces and age predicted reproducibility for the measurement of DRF on 99mTc-MAG3 renograms. The KTBR should be incorporated into the renal processing software as a quality control step. The DRF values should be interpreted with caution if the KTBR is ≤2.0.