Strengthening HIV services for pregnant women: an opportunity to reduce maternal mortality rates in Southern Africa/sub-Saharan Africa

Reliable data from South Africa emanating from WHO recommendations for the Safe Motherhood programme underscores HIV/AIDS as the most common cause of maternal deaths. The strengthening of HIV services for pregnant women especially in countries with a high burden of HIV infection will reduce HIV-related and un-related maternal mortality rates. High-quality and complete data on maternal deaths is a critical foundation for reliably monitoring temporal trends in maternal deaths, and causes thereof, but needs substantial strengthening in many resource-constrained settings. HIV/AIDS is an increasing contributor to direct and indirect causes of maternal deaths in sub-Saharan Africa. A review of published data on maternal deaths and its association with HIV shows that reliable data come from the Confidential Enquiries into Maternal Deaths from South Africa, population-based surveys in sentinel populations, and facility-based data. Despite an increase in knowledge of the HIV status of pregnant women and the initiation of antiretroviral treatment, reversals in trends towards increased maternal deaths are not being observed. The strengthening of HIV services provides an opportunity to alter HIV epidemic trajectories and reduce maternal deaths.     

Defining male support during and after pregnancy from the perspective of HIV-positive and HIV-negative women in Durban, South Africa

Introduction: Greater male support during pregnancy and in the postpartum period may improve health outcomes for mothers and children. To develop effective strategies to engage men, we need to first understand the ways that men are currently engaged and the barriers to their greater involvement. Methods: We conducted in‐depth interviews in isiZulu with 30 HIV‐positive women and 16 HIV‐negative women who received prenatal care from a public clinic in Durban, South Africa. Interviews were audiotaped, transcribed, translated, and coded for analysis. Results: Although less than a quarter of women reported that their partners accompanied them to the clinic, they described receiving other material and psychosocial support from partners. More HIV‐positive women reported that their partners were not involved or not supportive, and in some cases direct threats and experiences with violence caused them to fear partner involvement. Discussion: We need to broaden the lens through which we consider male support during pregnancy and in the postpartum period and acknowledge that male involvement may not always be in the best interest of women. Engaging supportive partners outside of the clinic setting and incorporating other important social network members are important next steps in the effort to increase support for women.     

Quantifying the relationship of HIV infection with clinicopathological spectrum and outcome among patients with colorectal cancer in a South African population

IntroductionLiterature is limited on HIV and colorectal cancer (CRC) in sub-Saharan Africa despite it being the epicentre of the HIV epidemic,PurposeTo compare clinicopathological features and outcome of CRC in HIV-negative and HIV-positive patients.MethodsRetrospective analysis of a prospective CRC database. Demographic details, HIV status, anatomical site, disease stage, treatment and follow-up were documented.ResultsOf 715 patients with CRC, 145 and 570 tested positive and negative respectively for HIV. Median age was 45 (IQR 36–53 and 57 (IQR 45–66) years among HIV-positive and HIV-negative patients respectively (p<0.0001). Tumour differentiation differed between the two groups (p=0.003) but staging was not different (p=0.6). Surgical resection rate was 52% for HIV-positive patients versus 59% for HIV-negative patients (p=0.07). Median follow-up was 9 (IQR 2–20.5) months for HIV-positive patients and 12 (IQR 6–29) months for HIV-negative patients (p=0.154). Recurrence rate was 14.7% among HIV positive patients and 6.8% in HIV negative patients (p=0.089).ConclusionWhen compared with HIV-negative patients, HIV-positive patients with CRC presented at a younger age and tended to have lower surgical resection rates. There was no difference between the two groups with CRC in terms of anatomical sub-site distribution, disease staging and recurrence rates.     

The economic burden of idiopathic pulmonary fibrosis in Australia: a cost of illness study

Purpose

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease found mostly in elderly persons, characterized by a high symptom burden and frequent encounters with health services. This study aimed to quantify the economic burden of IPF in Australia with a focus on resource utilization and associated direct costs.

Methods

Participants were recruited from the Australian IPF Registry (AIPFR) between August 2018 and December 2019. Data on resource utilization and costs were collected via cost diaries and linked administrative data. Clinical data were collected from the AIPFR. A “bottom up” costing methodology was utilized, and the costing was performed from a partial societal perspective focusing primarily on direct medical and non-medical costs. Costs were standardized to 2021 Australian dollars ($).

Results

The average annual total direct costs per person with IPF was $31,655 (95% confidence interval (95% CI): $27,723–$35,757). Extrapolating costs based on prevalence estimates, the total annual costs in Australia are projected to be $299 million (95% CI: $262 million–$338 million). Costs were mainly driven by antifibrotic medication, hospital admissions and medications for comorbidities. Disease severity, comorbidities and antifibrotic medication all had varying impacts on resource utilization and costs.

Conclusion

This cost-of-illness study provides the first comprehensive assessment of IPF-related direct costs in Australia, identifies the key cost drivers and provides a framework for future health economic analyses. Additionally, it provided insight into the major cost drivers which include antifibrotic medication, hospital admissions and medications related to comorbidities. Our findings emphasize the importance of the appropriate management of comorbidities in the care of people with IPF as this was one of the main reasons for hospitalizations.

     

Long-term exposure to low concentrations of air pollution and decline in lung function in people with idiopathic pulmonary fibrosis: Evidence from Australia

Background and Objective

Little is known about the association between ambient air pollution and idiopathic pulmonary fibrosis (IPF) in areas with lower levels of exposure. We aimed to investigate the impact of air pollution on lung function and rapid progression of IPF in Australia.

Methods

Participants were recruited from the Australian IPF Registry (n = 570). The impact of air pollution on changes in lung function was assessed using linear mixed models and Cox regression was used to investigate the association with rapid progression.

Results

Median (25th–75th percentiles) annual fine particulate matter (<2.5 μm, PM_2.5) and nitrogen dioxide (NO₂) were 6.8 (5.7, 7.9) μg/m³ and 6.7 (4.9, 8.2) ppb, respectively. Compared to living more than 100 m from a major road, living within 100 m was associated with a 1.3% predicted/year (95% confidence interval [CI] −2.4 to −0.3) faster annual decline in diffusing capacity of the lungs for carbon monoxide (DLco). Each interquartile range (IQR) of 2.2 μg/m³ increase in PM_2.5 was associated with a 0.9% predicted/year (95% CI −1.6 to −0.3) faster annual decline in DLco, while there was no association observed with NO₂. There was also no association between air pollution and rapid progression of IPF.

Conclusion

Living near a major road and increased PM_2.5 were both associated with an increased rate of annual decline in DLco. This study adds to the evidence supporting the negative effects of air pollution on lung function decline in people with IPF living at low-level concentrations of exposure.     

Pulmonary oedema in the course of severe maternal outcome in South Africa: A cohort study combined with clinical audit

Objectives

To describe the incidence and outcomes of pulmonary oedema in women with severe maternal outcome during childbirth and identify possible modifiable factors through audit.

Methods

All women with severe maternal outcome (maternal deaths or near misses) who were referred to Tygerberg referral hospital from health facilities in Metro East district, South Africa, during 2014–2015 were included. Women with severe maternal outcome and pulmonary oedema during pregnancy or childbirth were evaluated using three types of critical incident audit: criterion-based case review by one consultant gynaecologist, monodisciplinary critical incident audit by a team of gynaecologists, multidisciplinary audit with expert review from anaesthesiologists and cardiologists.

Results

Of 32,161 pregnant women who gave birth in the study period, 399 (1.2%) women had severe maternal outcome and 72/399 (18.1%) had pulmonary oedema with a case fatality rate of 5.6% (4/72). Critical incident audit demonstrated that pre-eclampsia/HELLP-syndrome and chronic hypertension were the main conditions underlying pulmonary oedema (44/72, 61.1%). Administration of volumes of intravenous fluids in already sick women, undiagnosed underlying cardiac illness, administration of magnesium sulphate as part of pre-eclampsia management and oxytocin for augmentation of labour were identified as possible contributors to the pathophysiology of pulmonary oedema. Women-related factors (improved antenatal care attendance) and health care-related factors (earlier diagnosis and management) would potentially have improved maternal outcome.

Conclusions

Although pulmonary oedema in pregnancy is rare, among women with severe maternal outcome a considerable proportion had pulmonary oedema (18.1%). Audit identified options for prevention of pulmonary oedema and improved outcome. These included early detection and management of preeclampsia with close monitoring of fluid intake and cardiac evaluation in case of suspected pulmonary oedema. Therefore, a multidisciplinary clinical approach is recommended.     

Rheumatoid nodules: a narrative review of histopathological progression and diagnostic consideration

Clinical Rheumatology - Rheumatoid nodules (RNs) are the most common extra-articular manifestation of rheumatoid arthritis and are also seen in patients with other autoimmune and inflammatory...     

Diagnostic accuracy of a point-of-care urine tenofovir assay,and associations with HIV viraemia and drug resistance among people receiving dolutegravir and efavirenz-based antiretroviral therapy

Introduction

Novel point-of-care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout.

Methods

We conducted a cross-sectional evaluation among PLHIV receiving first-line ART containing tenofovir disoproxil fumarate at enrolment into a randomized trial in two South African public sector clinics. We calculated the diagnostic accuracy of the Abbott point-of-care immunoassay to detect urine TFV compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the association between point-of-care urine TFV results and self-reported adherence, viraemia ≥1000 copies/ml and HIV drug resistance, among people receiving either efavirenz or dolutegravir-based ART.

Results

Between August 2020 and March 2022, we enrolled 124 participants. The median age was 39 (IQR 34–45) years, 55% were women, 74 (59.7%) were receiving efavirenz and 50 (40.3%) dolutegravir. The sensitivity and specificity of the immunoassay to detect urine TFV ≥1500 ng/ml compared to LC-MS/MS were 96.1% (95% CI 90.0−98.8) and 95.2% (75.3−100.0), respectively. Urine TFV results were associated with short (p<0.001) and medium-term (p = 0.036) self-reported adherence. Overall, 44/124 (35.5%) had viraemia, which was associated with undetectable TFV in those receiving efavirenz (OR 6.01, 1.27−39.0, p = 0.014) and dolutegravir (OR 25.7, 4.20−294.8, p<0.001). However, in those with viraemia while receiving efavirenz, 8/27 (29.6%) had undetectable urine TFV, compared to 11/17 (64.7%) of those receiving dolutegravir. Drug resistance was detected in 23/27 (85.2%) of those receiving efavirenz and only 1/16 (6.3%) of those receiving dolutegravir. There was no association between urine TFV results and drug resistance.

Conclusions

Among PLHIV receiving ART, a rapid urine TFV immunoassay can be used to accurately monitor urine TFV levels compared to the gold standard of LC-MS/MS. Undetectable point-of-care urine TFV results were associated with viraemia, particularly among people receiving dolutegravir.

Trial registration

Pan-African Clinical Trials Registry: PACTR202001785886049.     

In vitro effects of 2-methyl-3-propylbutane-1,4-diol purified from Alstonia boonei on erythrocyte membrane stabilization and mitochondrial membrane permeabilization

A recent review on the ethnomedicinal, chemical, pharmacological, and toxicological properties of Alstonia boonei revealed the plant's potential in the treatment and management of a range of diseases. However, most of these pharmacological effects are only traceable to the crude form of the plant extract and not specific natural products. Phytochemical investigation of the methanol fraction of the methanol extract of the stem-bark of Alstonia boonei led to the isolation and identification of 2-methyl-3-propylbutane-1,4-diol. The structures were elucidated by the application of 1D-, and 2D-NMR spectroscopic analyses and by comparison with literature data. In this study, the membrane stabilizing activity, mitochondrial membrane permeability transition pore opening, cytochrome c release, mitochondrial ATPase activity, and prevention of mitochondrial lipid peroxidation activity of 2-methyl-3-propylbutane-1,4-diol (MPBD) isolated from A. boonei were determined. The results showed that MPBD significantly (p < .05) prevented peroxidation of mitochondrial membrane lipids and hemolysis using both the heat-induced and hypotonic solution-induced membrane stabilization assays. On the contrary, the compound caused large amplitude swelling of rat liver mitochondria in the absence of calcium, significant (p < .05) cytochrome c release and enhancement of mitochondrial ATPase activity in vitro. Our findings suggest that MPBD showed characteristic biological properties useful in modulating cell death.