Steve Biko Academic Hospital

Introduction Bloodstream infections (BSIs) significantly contribute to the morbidity and mortality in paediatric burn patients from low- and middle-income countries; with common pathogens like Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa frequently being multidrug resistant (MDR). Due to the growing prevalence of MDR BSIs, antimicrobial stewardship needs to be improved with perhaps more targeted initial antimicrobial use. The study describes the aetiology, and timing of burn-associated BSIs and MDR infections in paediatric burn patients admitted to two paediatric surgery units in Tshwane District, South Africa. Methods This multi-centre retrospective review analysed paediatric burn patients (ages 0–12 years) admitted between January 2020 and December 2022 to two public hospitals in Tshwane District, South Africa. Collected data was from patient records and the National Health Laboratory System TrakCare database. BSIs were defined according to the CDC criteria. Results Of 245 burn patients admitted, 18.8% (n = 46) developed BSIs. From 63 positive blood cultures, the most common isolates were S. aureus (n = 19; 30%), Acinetobacter baumannii (n = 18; 29%), and P. aeruginosa (n = 10; 16%). Collectively, gram negative bacteria were responsible for most BSIs (n = 41; 65%). Candida spp accounted for 9% (n = 5). Thirty-five pathogens (56%) were MDR; this included methicillin-resistant S. aureus (MRSA) (n = 7; 11%), carbapenem-resistant A. baumannii (n = 16; 25%), and P. aeruginosa (n = 6; 10%). The median time to the first positive blood culture was 5 days (IQR: 3–12) (gram positive organisms: median: 5 days [IQR: 3–15}); gram negative organisms: median: 8 days [IQR: 4–20]; Fungal: median: 9 days [IQR: 8–27]; p-value 0.37). In the first week, S. aureus caused 32% of infections, including five MRSA cases. Gram negative bacteria dominated weeks two and three, with fungal and polymicrobial infections mainly in weeks two and four. Conclusion Our findings show that as gram positive and gram negative infections predominantly occurred early in the admission period, while polymicrobial infections are more frequently observed later. Consequently, initial targeted narrow-spectrum antimicrobial use is not possible. Instead, antimicrobial de-escalation should be prioritized once culture results are available. Efforts should shift from a focus on treating BSIs to preventing them through wound care and infection control measures. Broad-spectrum antibiotics should be used judiciously and quickly de-escalated to minimise antimicrobial resistance development.

Introduction Keloids have proved challenging to manage with various therapies providing variable success rates and recurrences. Alternative therapies or a multimodal approach is often necessary to ensure complete eradication and prevent recurrence. The use of radioactive creams or patches embedded with Holmium-166, Phosphorus-32 for superficial skin lesions has been documented to be safe and effective. The use of Rhenium-188 has proved effective in non-melanoma skin cancers. We report on the initial experience with Rhenium-188 SCT in the treatment of recurrent keloid lesions. Methods Patients with recurrent keloid lesions were recruited for therapy with Rhenium-188. These patients had failed most forms of therapy including surgery, intralesional steroids and radiation therapy. Treatment with ¹⁸⁸Re via a specialized unit (Rhenium SCT -Oncobeta) was applied onto the keloid lesion. A personalized treatment time was calculated for every patient. Topical ¹⁸⁸Rhenium delivered as a jelly like matrix containing an insoluble dirhenium-heptasulfide was applied to every target lesion in a single session. The goal is to deliver 30 Gy to the deepest part of the lesion per session (3 mm). Patients were followed up at 2 weeks, 1, 3, 6 and 12 months for side effects as well as clinical and cosmetic outcomes. Results A total of 58 lesions were treated. Majority of the lesions were in the head and neck region. The smallest area for treatment was 0.25cm² and the largest area treated was 46.25cm². With the exception of four patients (2 sessions to the same lesion), all the other patients received a single session of therapy. The mean activity administered was 256,7MBq (range: 35MBq– 663,50MBq). The treatment time averaged 350.89 min (range: 85–1304 min). There was complete response in 72% of the lesions. Hypopigmentation was the commonest expected long term side effect. After a median follow-up period of 37 months (range: 7–53), there was a 7% recurrence rate. Conclusion Treatment with ¹⁸⁸Re is a great alternative in patients with keloids that have had minimal success with other therapies. The use of the specialized applicator system provides great flexibility, reduced morbidity and great results that are comparable to other therapies. Clinical trial number Not applicable.

Breast cancer poses a significant global health challenge and includes various subtypes, such as endocrine-positive, HER2-positive, and triple-negative. Endocrine-positive breast cancer, characterized by estrogen and progesterone receptors, is commonly treated with aromatase inhibitors. However, resistance to these inhibitors can hinder patient outcomes due to genetic and epigenetic alterations, mutations in the estrogen receptor 1 gene, and changes in signaling pathways. Radiogenomics combines imaging techniques like MRI and CT scans with genomic profiling methods to identify radiographic biomarkers associated with resistance. This approach enhances our understanding of resistance mechanisms and metastasis patterns, linking them to specific genomic profiles and common metastasis sites like the bone and brain. By integrating radiogenomic data, personalized treatment strategies can be developed, improving predictive and prognostic capabilities. Advancements in imaging and genomic technologies offer promising avenues for enhancing radiogenomic research. A thorough understanding of resistance mechanisms is crucial for developing effective treatment strategies, making radiogenomics a valuable integrative approach in personalized medicine that aims to improve clinical outcomes for patients with metastatic endocrine-positive breast cancer.

Purpose This systematic review and meta-analysis evaluates xerostomia occurrence in prostate cancer (PC) patients undergoing [²²⁵Ac]Ac-prostate-specific membrane antigen ([²²⁵Ac]Ac-PSMA) therapy. Methods Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, comprehensive electronic searches were conducted across PubMed, Scopus, and Web of Science. The study included articles addressing xerostomia as a side effect of [²²⁵Ac]Ac-PSMA therapy in clinical settings, encompassing both tandem and monotherapy strategies. Methodological quality was assessed using the National Institutes of Health (NIH) Assessment Tool. Stata software was employed to perform pooled xerostomia rates, heterogeneity analysis, meta-regression, and publication bias analysis. Results Twenty studies met inclusion criteria, comprising 2949 [²²⁵Ac]Ac-PSMA cycles administered to 1207 PC patients. For [²²⁵Ac]Ac-PSMA monotherapy, the pooled rate of any-grade xerostomia was 84% (95%CI: 69–94%). Grade 1–2 xerostomia had a pooled rate 83% (95%CI: 71–93%), while therapy discontinuation due to xerostomia was 5% (95%CI: 0–13%). Grade 3 xerostomia was evident in 13% (95%CI: 7–20%). [²²⁵Ac]Ac/[¹⁷⁷Lu]Lu-PSMA tandem therapy resulted in lower pooled rate of 68% for grade 1–2 toxicity (95%CI: 17–100%). Indirect comparison revealed a two-fold decrease in xerostomia risk with tandem protocol compared to monotherapy. Significant heterogeneity was observed, primarily influenced by baseline median prostate-specific antigen values (p = 0.04). Publication bias was present in most xerostomia subgroups, with trim-and-fill analysis adjusting for effect size in specific categories. Conclusion Xerostomia is most pronounced in patients undergoing [²²⁵Ac]Ac-PSMA monotherapy. Tandem approach with [¹⁷⁷Lu]Lu-PSMA could reduce xerostomia rates and improve compliance. Further large-scale, prospective studies are necessary for generalization and result consolidation.

King-Denborough Syndrome (KDS) is a congenital myopathy (CM) characterised by myopathy, dysmorphic features and susceptibility to malignant hyperthermia. The objective of this study was to investigate the genotype-phenotype correlation in Black African patients presenting with CM, specifically those with KDS-like phenotypes, who remained undiagnosed for over 25 years. A cohort of 67 Black African patients with CM was studied, of whom 44 were clinically evaluated and diagnosed with KDS. Whole-exome sequencing (WES) was performed as part of an international genomics study (ICGNMD) to identify potential pathogenic mutations. Genomic assessments focused on identifying relevant genes, including RYR1 and STAC3 , and establishing genotype-phenotype correlations. The study identified RYR1 and STAC3 mutations as the predominant genetic causes of KDS in this cohort, with mutations in both genes exhibiting autosomal recessive inheritance. While RYR1 has previously been linked to autosomal dominant mutations, STAC3 , which was formerly associated exclusively with Native American Myopathy/Bailey-Bloch Myopathy, congenital hypotonia, and susceptibility to malignant hyperthermia, is now newly associated with CM-KDS in this study. This establishes the first genotype-phenotype correlation for 44 Black African individuals with KDS. This study marks a significant milestone in research on understudied African populations with CM, emphasising the lengthy diagnostic journey these patients endured. The findings highlight the pressing need for improved access to genomic medicine in underserved regions and underscore the importance of expanding research and diagnostic capabilities in Africa. This work contributes to the advancement of genetic medicine in underrepresented populations, facilitating better diagnostic and therapeutic outcomes.

Triple-negative breast cancer (TNBC) is difficult to treat and has a low five-year survival rate. In South Africa, a large percentage of the population still relies on traditional plant-based medicine. To establish the utility of both methanol and water-soluble extracts from the leaves of Tulbaghia violacea, cytotoxicity assays were carried out to establish the IC50 values against a TNBC cell line. Cell cycle and apoptosis assays were carried out using the extracts. To identify the molecular compounds, present in water-soluble leaf extracts, NMR spectroscopy was performed. Compounds of interest were then used in computational docking studies with the anti-apoptotic protein COX-2. The IC50 values for the water- and methanol-soluble extracts were determined to be 400 and 820 µg/mL, respectively. The water-soluble extract induced apoptosis in the TNBC cell line to a greater extent than in the normal cell line. RNAseq indicated that there was an increase in the transcription of pro-apoptotic genes in the TNBC cell line. The crude extract also caused these cells to stall in the S phase. Of the 61 compounds identified in this extract, five demonstrated a high binding affinity for COX-2. Based on these findings, the compounds within the extract show significant potential for further investigation as candidates for the development of cancer therapeutics, particularly for TNBC.

Atherosclerosis is a chronic progressive disease which is known to cause acute cardiovascular events as well as cerebrovascular events with high mortality. Unlike many other diseases, atherosclerosis is often diagnosed only after an acute or fatal event. At present, the clinical problems of atherosclerosis mainly involve the difficulty in confirming the plaques or identifying the stability of the plaques in the early phase. In recent years, the development of nanotechnology has come with various advantages including non-invasive imaging enhancement, which can be studied for the imaging of atherosclerosis. For targeted imaging and atherosclerosis treatment, nanoliposomes provide enhanced stability, drug administration, extended circulation, and less toxicity. This review discusses the current advances in the development of tailored liposomal nano-radiopharmaceutical-based techniques and their applications to atherosclerotic plaque diagnosis. This review further highlights liposomal nano-radiopharmaceutical localisation and biodistribution—key processes in the pathophysiology of atherosclerosis. Finally, this review discusses the direction and future of liposomal nano-radiopharmaceuticals as a potential clinical tool for the assessment and diagnosis of atherosclerotic plaque.

This study aimed to assess the organization, infrastructure, workforce, and adherence to protocols in neurocritical care across low- and middle-income countries (LMICs), with the goal of identifying key gaps and opportunities for improvement. We conducted a cross-sectional survey of 408 health care providers from 42 LMICs. The survey collected data on the presence of dedicated neurointensive care units, workforce composition, access to critical care technologies, and adherence to evidence-based protocols. Data were analyzed using descriptive statistics, and comparisons were made across different geographical regions (East Asia and the Pacific, Europe and Central Asia, Latin America and the Caribbean, the Middle East and North Africa, and South Asia and sub-Saharan Africa) and economic strata [low-income countries (LICs), lower middle-income countries (LoMICs), and upper middle-income countries (UMICs)]. Only 36.8% of respondents reported access to dedicated neurointensive care units: highest in the Middle East (100%), lowest in sub-Saharan Africa (11.5%), highest in LoMICs (42%), and lowest in LICs (13%). Access to critical care technologies, such as portable computed tomography scanners (9.3%; UMICs 11%, LICs 0%) and tele-intensive care unit services (14.9%; UMICs 19%, LICs 10%), was limited. Workforce shortages were evident, with many institutions relying on anesthesia residents for 24-h care. Adherence to protocols, including those for acute ischemic stroke (61.7%) and traumatic brain injury (55.6%), was highest in Latin America and the Caribbean (72% and 73%, respectively) and higher in UMICs (66% and 60%, respectively) but remained low in LICs (22% and 32%, respectively). The study highlights critical gaps in infrastructure, workforce, and technology across LMICs, yet it also underscores the potential for improvement. Strategic investments in neurointensive care unit capacity, workforce development, and affordable technologies are an unmet need in resource-limited settings. These findings offer a road map for policymakers and global health stakeholders to prioritize neurocritical care and reduce the disparities in patient outcomes globally.

Breast cancer is one of the leading causes of mortality among women, primarily due to its complex molecular landscape and heterogeneous nature. The tendency of breast cancer patients to develop metastases poses significant challenges in clinical management. Notably, mutations in the breast cancer gene 1 (BRCA1) significantly elevate breast cancer risk. The current research endeavors employ diverse molecular approaches, including RNA, DNA, and protein studies, to explore avenues for the early diagnosis and treatment of breast cancer. Recent attention has shifted towards long non-coding RNAs (lncRNAs) as promising diagnostic, prognostic, and therapeutic targets in the multifaceted progression of breast cancer. Among these, long intergenic non-coding RNAs (lincRNAs), a specific class of lncRNAs, play critical roles in regulating various aspects of tumorigenesis, including cell proliferation, apoptosis, epigenetic modulation, tumor invasion, and metastasis. Their distinctive expression patterns in cellular and tissue contexts underscore their importance in breast cancer development and progression. Harnessing lincRNAs' sensitivity and precision as diagnostic, therapeutic, and prognostic markers holds significant promise for the clinical management of breast cancer. However, the potential of lincRNAs remains relatively underexplored, particularly in the context of BRCA1-mutated breast cancer and other clinicopathological parameters such as receptor status and patient survival. Consequently , there is an urgent need for comprehensive investigations into novel diagnostic and prognostic breast cancer biomarkers. This review examines the roles of lincRNAs associated with BRCA1 in the landscape of breast cancer, highlighting the potential avenues for future research and clinical applications.

Objective To compare low‐cost “Suction Tube Uterine Tamponade” (STUT) treatment for refractory postpartum hemorrhage (PPH) with uterine balloon tamponade (UBT) using a randomized feasibility study. Methods After verbal assent, we allocated participants with refractory PPH by randomly ordered envelopes to STUT or routine UBT at 10 hospitals in South Africa and one tertiary referral center in Colombia between January 10, 2020, and May 3, 2024. In the STUT group, we inserted a 24 FG Levin stomach tube into the uterine cavity and applied suction. The control group received standard UBT, mainly the Elavi free‐flow balloon or the Bakri fixed volume balloon. There were fundamental differences between the South African and the Colombian sites, so the pre‐specified analysis combined data from the two countries by meta‐analysis. Results We enrolled 59 participants. The rate of the primary outcome (blood loss >1000 mL or laparotomy or death) was 8/27 (30%) in the STUT group versus 14/27 (52%) in the UBT group (risk ratio [RR] 0.56, 95% confidence interval [CI] 0.30–1.05, P = 0.07). Per protocol analysis was 7/26 (27%) versus 15/28 (54%) (RR 0.49, 95% CI 0.25–0.96, P = 0.04). Reporting severe pain during the procedures was less frequent in the STUT group (RR 0.46, 95% CI 0.25–0.86, P = 0.01). Most secondary outcomes favored the STUT group, with low certainty. Conclusions STUT was experienced as less painful than UBT. Results were consistent with reported observational findings and one other randomized trial evidence of greater effectiveness for suction than balloon tamponade.

Background Studies comparing oncological outcomes between robot‐assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) are often limited by bias because of their multi‐institutional and multiple surgeon design. Studies from a single institution and single surgeon are uncommon. Objective To compare oncological outcomes between RARP and ORP at a single institution by a single surgeon. Design, setting and participants A retrospective cohort study of 2376 men with localized prostate cancer who underwent either RARP or ORP, from 1995 to 2020 at single institution, by one surgeon was done. The first 100 cases were discounted in both cohorts to account for the learning curve. Measurements Positive surgical margin (PSM) and biochemical recurrence (BCR) rates were measured for each cohort. Results A total of 1566 men underwent ORP and 810 underwent RARP. BCR rates of 29.2% were found in the ORP group versus 19.5% in the RARP group ( p < 0.001). PSM rates of 15.4% were found in the ORP group versus 9.0% in the RARP group ( p < 0.001). A multivariate analysis of preoperative prostate specific antigen (PSA) and tumor stage (T) shows no statistically significant association with recurrence when controlled for surgical technique. Conclusions RARP produces better oncological outcomes when compared to ORP when performed by one experienced surgeon at a single institution. Patient summary In this large study of men with prostate cancer still localized to the prostate. We found that better cancer removal and chances of cancer recurrence are reduced by a robot‐assisted prostate removal technique, compared to the traditional open technique.

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. A gallium‐68 labelled kisspeptin‐10 (KP10), the minimal biologically active structure, has potential as a pan‐tumour radiopharmaceutical for the detection of cancers. Furthermore, a lutetium‐177 labelled KP10 could find therapeutic application in treating oncological diseases. DOTA (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid) was attached to the NH2‐terminus of KP10 as we posited from our previous publications that this modification would not impair biological activity. Here, we showed that the biological activity, as monitored by stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene, was indeed similar for KP10 and DOTA‐KP10. The optimisation of radiolabelling with gallium‐68 and lutetium‐177 is described. Stability in serum, plasma and whole blood was also investigated. Pharmacokinetics and biodistribution were established with micro‐PET/CT (positron emission tomography/computerised tomography) and ex vivo measurements. Dynamic studies with micro‐PET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half‐life of 18 ± 3 min. DOTA‐KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These results lay the foundation for the further development of DOTA‐KP10 analogues that have high binding affinity along with proteolytic resistance.

Background Optic nerve sheath diameter (ONSD) is a promising noninvasive parameter for intracranial pressure (ICP) assessment. However, in the setting of aneurysmal subarachnoid hemorrhage (aSAH), several previous studies have reported no association between ultrasonically measured ONSD and ICP. In this study, we evaluate ONSD in patients with aSAH using a novel method of automated real-time ultrasonographic measurements and explore whether factors such as having undergone surgery affects its association to ICP. Methods We prospectively included adult patients with aSAH undergoing invasive ICP monitoring. ONSD was obtained using a prototype ultrasound machine with software for real-time automated measurements at the bedside. Correlation between ONSD and ICP was explored, and the ability of ONSD to discriminate dichotomized ICP was evaluated. Abovementioned analyses were performed for the whole cohort and repeated for subgroups by whether the basal cisterns had been surgically entered before ultrasound examination. Results Twenty-six ultrasound examinations were performed in 20 patients. There was a positive correlation between ONSD and ICP ( R = 0.43; p = 0.03). In the subgroup where the basal cisterns had not been surgically entered before ultrasound examination, there was a stronger correlation ( R = 0.55; p = 0.01), whereas no correlation was seen in the subgroup where the basal cisterns had been surgically entered ( R = − 0.16; p = 0.70). ONSD displayed an ability to discriminate ICP dichotomized at ≥ 15 mm Hg (area under the curve [AUC] = 0.84, 95% confidence interval [CI] 0.65–0.96). Subgroup analysis revealed a perfect discriminatory ability (AUC = 1, 95% CI 0.81–1) where the basal cisterns had not been surgically entered and no discriminatory ability (AUC = 0.47, 95% CI 0.16–0.84) where the basal cisterns had been surgically entered before ultrasound examination. Conclusions Automatically measured ONSD correlated well with ICP and displayed a perfect discriminatory ability in patients with aSAH in whom the basal cisterns had not been entered surgically before ultrasound examination, and may be a clinically valuable noninvasive marker of ICP in these patients. Caution should be exercised in using ONSD in patients in whom the basal cisterns have been entered surgically before ONSD measurements, as no association was observed in this subgroup.

Raised intracranial pressure (ICP) occurs in about 15–20% of children with single-suture synostosis. Clinical and radiological manifestations remain blunt tools in the detection of raised ICP. This is due to the often subtle nature of the clinical presentation and poor sensitivity of the radiological features. Invasive monitoring of ICP in children has associated risks which limit its widespread use. Some of the relevant non-invasive techniques for assessing ICP and also perfusion have been reviewed and discussed in this chapter.

Purpose Contemporary antiretroviral (ARV) medications are used by millions of men for HIV treatment worldwide. Limited data exist on their direct effect on sperm motility. This pilot study hypothesizes that in vitro exposure to ARVs will reduce sperm kinematic and motility parameter values. Methods This laboratory-based experimental study analyzed sperm motility and kinematics after exposure to the ARVs Dolutegravir, Tenofovir, and Emtricitabine, individually and in combination. Each participant (n = 23) served as their experimental control. The Microptic SCA® Computer Assisted Sperm Analysis (CASA) system, Barcelona, Spain was used to generate quantitative data on sperm motility and the kinematics Straight-line velocity (VSL), Straightness index (STR), Linearity Index (LIN), Beat cross frequency (BCF), and the oscillation index (WOB). Results VSL, STR, LIN, and WOB of the non-progressive (grade c) spermatozoa were significantly decreased after ARV treatment. BCF of the medium velocity progressive sperm population (grade b) was significantly increased 90 min after exposure in the Tenofovir arm, and a significant decrease in the proportion of grade b spermatozoa was recorded at 90 min in all the antiretroviral arms when compared to the control arm. No impaired sperm motility was observed within the first 30 min of exposure. Conclusion Pharmacovigilance is a healthcare emergency as the fast-changing world of newer drugs leaves clinicians vulnerable. They must prescribe drugs whose long-term somatic and germline adverse effects are not fully understood. Guidelines and drugs are changing faster than we can monitor for side effects. Despite Dolutegravir being the only mainstream integrase inhibitor first-line ARV in South Africa for five years, its replacement, Cabotegravir, is already being launched. More research in this field is required, especially for commonly prescribed drugs. This preliminary pilot study concludes that the current first-line ARVs used by HIV patients and HIV-negative patients on pre-exposure prophylaxis (PrEP) can alter sperm motility and kinematics. Further research with a larger sample size is warranted to quantify its impact on human fertility, addressing the limitations of this study, before a comprehensive conclusion of the effects of ARVs on human male fertility can be drawn. Of particular importance would be to study the impact of ARVs on reactive oxygen species levels in semen and sperm DNA fragmentation.

Glioblastoma (GBM) is an aggressive brain tumor characterized by cellular and molecular diversity. This diversity presents significant challenges for treatment and leads to poor prognosis. Surgery remains the primary treatment of choice for GBMs, but it often results in tumor recurrence due to complex interactions between GBM cells and the peritumoral brain zone. Phytochemicals have shown promising anticancer activity in in-vitro studies and are being investigated as potential treatments for various cancers, including GBM. However, some phytochemicals have failed to translate their efficacy to pre-clinical studies due to limited penetration into the tumor microenvironment, leading to high toxicity. Thus, combining phytochemicals with nanotechnology has emerged as a promising alternative for treating GBM. This review explores the potential of utilizing specific nanoparticles to deliver known anticancer phytochemicals directly to tumor cells. This method has demonstrated potential in overcoming the challenges of the complex GBM microenvironment, including the tight blood–brain barrier while minimizing damage to healthy brain tissue. Therefore, employing this interdisciplinary approach holds significant promise for developing effective phyto-nanomedicines for GBM and improving patient outcomes.

Many maternal and neonatal deaths and stillbirths can be avoided if quality of care is improved. The South African National Department of Health implemented a multi-partner quality improvement (QI) programme between 2018 and 2022, in 21 facilities, with the aim to reduce maternal and perinatal mortality. We conducted a qualitative evaluation to explore QI team members’ perceptions of the factors shaping variation in team performance. The evaluation was conducted in 15 purposively selected facilities. We interviewed 47 team members from the 14 facilities consenting to participate in the evaluation, over three time points. We conducted 21 individual interviews and 18 group interviews. Data were thematically analysed using ATLAS.ti 8. Based on a preliminary assessment, six teams were rated as well-performing and eight, less well-performing. Patterns of divergence between well-performing and less well-performing teams were then examined through in-depth analysis of the full data set. Well-performing teams had a core team of members with a good understanding of the programme aims and QI methodology; a second in-charge member to ensure leader continuity; and leader stability throughout the implementation period. Well-performing teams were recruited from existing facility service teams who had a positive prevailing work culture. Team leaders’ enthusiasm for QI and their ability to mobilise member buy-in, and how well teams worked together, further affected teams’ performance. Existing facility contexts, how teams are set up, leadership—and member buy-in into the methodology, affect QI teams’ performance. Focusing on these as well as supporting leaders to foster a shared vision and culture of excellence; mitigating contextual and implementation barriers; and strengthening team members’ technical QI skills, has the potential to improve QI teams’ performance.

Multidrug-resistant tuberculosis (MDR-TB) patients are treated with a standardised, short World Health Organization (WHO) regimen which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to the development of QT prolongation in patients, inhibiting potassium (K+) uptake by targeting the voltage-gated (Kv)11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics to regulate other K+ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on sodium, potassium–adenosine triphosphatase (Na+,K+-ATPase) activity of CMs using rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25–5 mg/L). Thereafter, Na+,K+-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Furthermore, molecular docking of antibiotics with Na+,K+-ATPase was determined. Both antibiotics demonstrated dose–response inhibition of Na+,K+-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and, lastly, CFZ. Neither antibiotic, either individually or in combination, demonstrated cytotoxicity. Molecular docking revealed an interaction of both antibiotics with Na+,K+-ATPase, with BDQ showing higher protein-binding affinity than CFZ. The inhibitory effects of CFZ and BDQ, individually and in combination, on the activity of Na+,K+-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics.