School of Clinical Medicine (Journal Articles)

Permanent URI for this collectionhttps://hdl.handle.net/10539/37790

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The assessment and aetiology of drug-induced ischaemic priapism
(Springer Nature, 2024-12) Moodley, Divyen; Badenhorst, Anja; Choonara, Yahya; Adam, Ahmed
Ischaemic priapism is a urological emergency characterised by a prolonged, painful erection unrelated to sexual stimulation. While several aetiological factors contribute to this condition, the pharmacological causes have gained significant attention in recent years. This narrative review aims to comprehensively assess ischaemic priapism, specifically focusing on its pharmacological aetiology. We propose an approach and assessment strategy to the numerous factors associated with pharmacologically induced ischaemic priapism. By enhancing our understanding of the harmacological causes of this condition, healthcare professionals can improve patient management and reduce the long-term complications associated with ischaemic priapism.
Mobile Technology use in clinical research examining challenges and implivations for health promotion in South Africa: mixed methods study
(JMIR Publications, 2024) Norris, Shane A.; Mabetha, Khuthala; Soepnel, Larske M.; Mabena, Gugulethu; Motlhathedi, Molebogeng; Nyathi, Lukhanyo; Draper, Catherine E.
Background: The use of mobile technologies in fostering health promotion and healthy behaviors is becoming an increasingly common phenomenon in global health programs. Although mobile technologies have been effective in health promotion initiatives and follow-up research in higher-income countries and concerns have been raised within clinical practice and research in low- and middle-income settings, there is a lack of literature that has qualitatively explored the challenges that participants experience in terms of being contactable through mobile technologies. Objective: This study aims to explore the challenges that participants experience in terms of being contactable through mobile technologies in a trial conducted in Soweto, South Africa. Methods: A convergent parallel mixed methods research design was used. In the quantitative phase, 363 young women in the age cohorts 18 to 28 years were contacted telephonically between August 2019 and January 2022 to have a session delivered to them or to be booked for a session. Call attempts initiated by the study team were restricted to only 1 call attempt, and participants who were reached at the first call attempt were classified as contactable (189/363, 52.1%), whereas those whom the study team failed to contact were classified as hard to reach (174/363, 47.9%). Two outcomes of interest in the quantitative phase were "contactability of the participants" and "participants' mobile number changes," and these outcomes were analyzed at a univariate and bivariate level using descriptive statistics and a 2-way contingency table. In the qualitative phase, a subsample of young women (20 who were part of the trial for ≥12 months) participated in in-depth interviews and were recruited using a convenience sampling method. A reflexive thematic analysis approach was used to analyze the data using MAXQDA software (version 20; VERBI GmbH). Results: Of the 363 trial participants, 174 (47.9%) were hard to reach telephonically, whereas approximately 189 (52.1%) were easy to reach telephonically. Most participants (133/243, 54.7%) who were contactable did not change their mobile number. The highest percentage of mobile number changes was observed among participants who were hard to reach, with three-quarters of the participants (12/16, 75%) being reported to have changed their mobile number ≥2 times. Eight themes were generated following the analysis of the transcripts, which provided an in-depth account of the reasons why some participants were hard to reach. These included mobile technical issues, coverage issues, lack of ownership of personal cell phones, and unregistered number. Conclusions: Remote data collection remains an important tool in public health research. It could, thus, serve as a hugely beneficial mechanism in connecting with participants while actively leveraging the established relationships with participants or community-based organizations to deliver health promotion and practice.
Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
(Nature Research, 2023) Madhi, Shabir A.; Ahani, Bahar; Tuffy, Kevin M.; Aksyuk, Anastasia A.; Wilkins, Deidre; Abram, Michael E.; Dagan, Ron; Domachowske, Joseph B.; Guest, Johnathan D.; Ji, Hong; Kushnir, Anna; Leach, Amanda; Mankad, Vaishali S.; Simões, Eric A. F.; Sparklin, Benjamin; Speer, Scott D.; Stanley, Ann Marie; Tabor, David E.; Hamrén, Ulrika Wählby; Kelly, Elizabeth J.; Villafana, Tonya
Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.
Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa
(BMC, 2018) Evans, Denise; Hirasen, Kamban; Berhanu, Rebecca; Malete, Given; Ive, Prudence; Spencer, David; Badal‑Faesen, Sharlaa; Sanne, Ian M.; Fox, Matthew P.
Background: While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes. Methods: Retrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART. Results: Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03–6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47–7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively. Conclusions: Our results show that the need for third-line is low (5%), but that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second line and those who have been on PI-based regimen for extended periods.
Bone mineral density in midlife long-term users of hormonal contraception in South Africa: relationship with obesity and menopausal status
(BMC, 2018-04) Beksinska, Mags E.; Smit, Jenni A.; Kleinschmidt, Immo
Background: In South Africa, hormonal contraception is widely used in women over the age of 40 years. One of these methods and the most commonly used is depot-medroxyprogesterone acetate (DMPA) which has been found to have a negative effect on bone mass. Limited information is available on the effect of norethisterone enanthate (NET-EN) on bone mass, and combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass. The aim of this study was to investigate bone mineral density (BMD) in pre and perimenopausal women (40–49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study and review associations with body mass index (BMI) and menopausal status. Methods: One hundred and twenty seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Menopausal status was assessed, BMI and forearm BMD was measured at the distal radius using dual X-ray absorptiometry. Comparison analysis was conducted at baseline and 2.5 years. Results: There was no significant difference in BMD between the four contraceptive user groups (p = 0.26) with and without adjustment for age at baseline or at 2.5 years (p = 0.52). The BMD was found to be significantly associated with BMI (p = < 0.0001) with an increase of one unit of BMI translating to an increase of 0.0044 g/cm2 in radius BMD. Follicle stimulating hormone (FSH) level ≥ 25.8 mIU/mL was associated with a decrease of 0.017 g/cm2 in radius BMD relative to women with FSH < 25.8 mIU/mL. Significant interaction between FSH and BMI in their effect on BMD was observed (p = .006). Conclusion: This study found no evidence that long-term use of DMPA, NET-EN and COCs affects forearm BMD in this population at baseline or after 2.5 years of follow-up. This study also reports the complex relationship and significant interaction between FSH and BMI in their effect on BMD. BMD research in older women needs to ensure that women are assessed for menopausal status and BMI.
Life became harder with COVID19 exploring the experiences of the COVID19 pandemic among youth living in eThekwini district South Africa
(Biomed Central , 2024- 07) Closson, K.; Dong, E.; Zulu, Bongiwe; Dietrich, Janan; Zharima, Campion; Jesson, J.; Pakhomova, T.; Beksinska, Malgorzata; Kaida, A.
Background: In South Africa, pervasive age and gender inequities have been exacerbated by the COVID-19 pandemic and public health response. We aimed to explore experiences of the COVID-19 pandemic among youth in eThekwini district, South Africa. Methods: Between December 2021-May 2022 we explored experiences of the COVID-19 pandemic on youth aged 16–24 residing in eThekwini, South Africa. We collated responses to the open-ended question “Has the COVID-19 pandemic affected you in any other way you want to tell us about?” in an online survey focused on understanding the pandemic’s multi-levelled health and social effects. We used a thematic analysis to summarise the responses. Results: Of 2,068 respondents, 256 (12.4%, median age = 22, 60.9% women) completed the open-ended survey question (11% in isiZulu). Results were organized into three main themes encompassing (1) COVID-19-related loss, fear, grief, and exacerbated mental and physical health concerns; (2) COVID-19-related intensified hardships, which contributed to financial, employment, food, education, and relationship insecurities for individuals and households; and (3) positive effects of the pandemic response, including the benefits of government policies and silver linings to government restrictions. Conclusions: We found that South African youth experienced significant grief and multiple losses (e.g., death, income, job, and educational) during the COVID-19 pandemic. Trauma-aware interventions that provide economic and educational opportunities must be included in post-COVID recovery efforts.
Does engagement in HIV care affect screening diagnosis and control of noncommunicable diseases in sub-Saharan Africa: a systematic review and meta analysis
(Springer , 2024-02) Kileel, E.; Zheng, Amy; Bor, Jacob; Fox, Matthew; Crowther, Nigel; George, Jaya; Khoza, Siyabonga; Rosen, Sydney; Venter, Willem; Raal, Frederick; Hibberd, Patricia; Brennan, Alana
Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may provide opportunities to increase access to NCD services in under-resourced environments. We conducted a systematic review and meta-analysis to evaluate whether use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV in sub-Saharan Africa (SSA). A comprehensive search of electronic literature databases for studies published between 01 January 2011 and 31 December 2022 yielded 26 studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR 1.07; 95% CI 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR 2.10, 95% CI 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.
Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol
(BMC, 2018-04) Strehlau, Renate; van Aswegen, Tamryn; Potterton, Joanne
Objective: Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodeficiency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes. Methods: Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an age appropriate stimulation program, updated at 3 monthly intervals through the first year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV.
Development and feasibility of a wearable infant wrist band for the objective measurement of physical activity using accelerometery
(BMC, 2018) Prioreschi, Alessandra; Nappey, Thomas; Westgate, Kate; Olivier, Patrick; Brage, Soren; Micklesfield, Lisa Kim
Background: It is important to be able to reliably and feasibly measure infant and toddler physical activity in order to determine adherence to current physical activity guidelines and effects on early life development, growth and health. This study aimed to describe the development of an infant wearable wrist-worn band for the measurement of physical activity; to determine the feasibility of the device data for observational measurement of physical activity and to determine the caregiver reported acceptability of the infant wearable wrist band. Methods: After various iterations of prototypes and piloting thereof, a final wearable band was designed to fit an Axivity AX3 monitor. Mother and infant/toddler (aged 3–24 months) pairs (n = 152) were recruited, and mothers were asked for their child to wear the band with enclosed monitor at all times for 1 week (minimum 3 days). Feasibility was assessed by determining technical reliability of the data, as well as wear time and compliance according to requirements for observational measurement. Acceptability was assessed via questionnaire. Results: Technical reliability of the Axivity AX3 monitors in this age group was good. After excluding days that did not have at least 15 h of wear time, only 2% of participants had less than three valid days of data remaining, and 4% of participants had no data (due to device loss or data loss). Therefore, 94% of participants were compliant, having three or more days of wear with at least 15 h of wear per day, thus providing enough valid data for observational measurement. The majority (60%) of mothers reported being “very happy” with the safety of the device, while only 8% were “a little worried”. A large majority (86%) of mothers stated that the band attracted attention from others, although this was mostly attributed to curiosity about the function of the band. Most (80%) of participants rated the comfort of the band as “comfortable”, and 10% rated it as “very comfortable”. Conclusions: The infant wearable band proved to be feasible and acceptable according to the criteria tested, and compliance wearing the band was good. We have therefore provided a replicable, comfortable and acceptable pearable band for the measurement of infant and toddler physical activity.
The presence of occipital hair in the pilonidal sinus cavity—a triple approach to proof
(Springer, 2018-02) Doll, Dietrich; Bosche, F.; Hauser, A.; Moersdorf, P.; Sinicina, I.; Grunwald, J.; Reckel, F.; Luedi, M. M.
Purpose: Hair in the pilonidal sinus is not growing within the sinus cavity, as hair follicles are not present there. Not few pilonidal patients do not have intergluteal hair, which is said to be the causative agent of folliculitis and pilonidal genesis. So, what is the real source of the hair forming the typical pilonidal hair nest? Methods: A trifold approach was used: First, axial hair strength testing of pilonidal hair and body hair harvested from head, lower back (glabella sacralis), and cranial third of intergluteal fold. Hair strength match was compared clinically. Second, comparative morphological examination by expert forensic biologist of hair from sinus and dorsal body hair. Third, statistical Bayesian classification of every single sinus hair based on its strength was done to determine the most probable region of origin. Results: Using clinical hair strength comparison, in 13/20 patients, head hair is the stiffest hair, followed by intergluteal hair. Only in 6/20 patients, this is the case with hair from the glabella sacralis. According to comparative morphological comparison, a minimum of 5 of 13 hair nests with possible hair allocation examined contain hair from the occiput. In 5/18 nests, hair could not be determined to a specific location though. Statistical classification with correction for multiple testing shows that 2 nests have hair samples that are at least 100 times more probable to originate from head or lower back than from intergluteal fold. Conclusion: We saw our null hypothesis that hair in the sinus cavity is from the intergluteal region^ rejected by each of three different approaches. There is strong evidence that occipital hair is present regularly in pilonidal sinus nests. We should start thinking of occipital hair as an important hair source for the development of the pilonidal hair nest.

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