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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 K + (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.

Background: Hypertension (HT) and obesity have both been on the rise in children. Each is associated with an increase in cardiovascular disease risk, and both track into adulthood., Objectives: This study aimed to identify the association of sodium intake (Na), potassium (K) intake, and sodium-to-potassium (Na/K) ratio with the development of HT and abdominal obesity amongst the Ellisras rural population over time., Methods: In this longitudinal study, data on dietary intake of Na and K were collected using a 24 h recall questionnaire from a total of 325 participants tracked from 1999 (5-12 years), 2001 (7-14 years), and 2015 (18-30 years). The averages of Na and K intake were analysed using local food tables and the South African Food Composition Database System (SAFOODS). In addition, blood pressure (BP) and anthropometric measurements (waist circumference (WC) and height) were also examined. Parametric (independent t -test) and Chi-square/Fishers exact tests were conducted to determine the difference between the years for numerical data and categorical variables. A generalised estimating equation (GEE) was used to assess the association of Na intake, K intake and their ratio on BP, WC, and waist-to-height ratio (WHtR)., Results: Our results indicate a significant positive association between K intake and WHtR, and even though the model was adjusted for age and sex, there was still an association with WHtR. The Na/K ratio was associated with both BP measurements and abdominal obesity, respectively. Furthermore, Na/K was shown to be associated with an increased risk of developing HT and abdominal obesity., Conclusions: In our study, we observed that an increase in the Na/K ratio is a predictor of HT and abdominal obesity over time compared to Na and K alone. However, more studies are required to further prove this.

An increase in childhood obesity has become a global concern since childhood obesity often leads to adulthood obesity. This study aimed to investigate whether there is seasonal variation in fat patterning, and whether fat patterning is associated with seasons among the Ellisras population aged 5-15 years. A total of 1986 children and adolescents (1034 boys and 952 girls) aged 5-15 enrolled in this cross-sectional study. Skinfold measurements were obtained using standard procedures. Obesity prevalence was determined using frequency analysis. The correlation between obesity and two seasons was tested using multinomial regression analysis. The results showed that girls aged 11-15 years had significantly ( p ≤ 0.03) larger median fat variables (triceps, biceps, and suprailiac) in spring compared to autumn. The prevalence of obesity ranged from 3-11% with boys being more obese (4-11%) than girls (3-7%) aged 5-15. Regression analysis showed a negative significant ( p ≤ 0.001) correlation between autumn and obesity by the subscapular/(subscapular+triceps) (SST) ratio, both unadjusted -2.991 (95%CI -3.233:-2.803) and adjusted -2.897 (95% CI -4.331:-1.629). The findings of the study showed that there was seasonal variation in fat patterning among boys and girls in the Ellisras population and that fat patterning is associated with seasons.

Background:  Basic palliative care teaching should be included in training curricula for health care providers (HCPs) at all levels of the health service to ensure that the goal set by the South African (SA) National Policy Framework and Strategy for Palliative Care, to have an adequate number of appropriately trained HCPs in South Africa, is achieved. Furthermore, palliative learning objectives for nurses and doctors should be standardised. Many SA medical schools have integrated elements of Palliative Medicine (PM) teaching into undergraduate medical training programmes for doctors; however, the degree of integration varies widely, and consensus and standardisation of the content, structure and delivery of such PM training programmes are not yet a reality., Aim:  This joint position paper aims to describe the current state of undergraduate medical PM teaching in South Africa and define the PM competencies required for an SA generalist doctor., Setting:  Palliative Medicine programme leads and teachers from eight medical schools in South Africa., Methods:  A survey exploring the structure, organisation and content of the respective medical undergraduate PM programmes was distributed to PM programme leads and teachers., Results:  Responses were received from seven medical schools. Through a process of iterative review, competencies were defined and further grouped according to suitability for the pre-clinical and clinical components of the curriculum., Conclusion:  Through mapping out these competencies in a spiralled medical curriculum, the authors hope to provide guidance to medical curriculum designers to effectively integrate PM teaching and learning into current curricula in line with the goals of the SA National Policy Framework and Strategy on Palliative Care (NPFSPC).

Background: Numerous studies have shown how diet, such as sodium (Na) and potassium (K) intake, is an important risk factor for non-communicable diseases (NCDs). This study aimed to assess the relationship between sodium intake, potassium intake; and sodium/potassium ratio with blood pressure (BP) and abdominal obesity amongst Ellisras rural children., Method: In this cross-sectional study, data on dietary intake of sodium and potassium were collected using a 24-h recall questionnaire from a total of 765 participants, aged 5-13 years. Blood pressure and anthropometric measurements were also collected. Generalised linear models and Pearson correlation were conducted to assess the association of sodium intake, potassium intake; and their ratio with BP, waist circumference (WC), and waist-to-height ratio (WHtR)., Results: In both age groups, less than 14.9% of males and 19.8% of females consumed above the recommended adequate intake (AI) of sodium. In addition, both age groups had more than 90% of males and females who consumed below the recommended AI of potassium. Moreover, the sodium/potassium ratio was above the WHO recommended level in more than 30% of males and females. The study found a significant, weak positive correlation of sodium intake with systolic BP (SBP), diastolic BP (DBP), and with WHtR. A significant, weak positive correlation was also found between sodium/potassium ratio and WHtR. In addition, a significant association was found between potassium intake and systolic BP., Conclusion: Although our study found a notable low average intake of sodium and potassium as compared to the recommended values. There was positive correlation found between sodium intake and BP. Furthermore, a positive correlation of sodium intake and sodium/potassium ratio with WHtR was also found.

Background: Lung cancer is the highest incident cancer globally and is associated with significant morbidity and mortality particularly if identified at a late stage. Poor patient outcomes in low- and middle-income countries (LMIC's) might reflect contextual patient and health system constraints at multiple levels, that act as barriers to prevention, disease recognition, diagnosis, and treatment. Lung cancer screening, even for high-risk patients, is not available in the public health sector in South Africa (SA), where the current HIV and tuberculosis (TB) epidemics often take precedence. Yet, there has been no formal assessment of the individual and health-system related barriers that may delay patients with lung cancer from seeking and accessing help within the public health care system and receiving the appropriate and effective diagnosis and treatment. This study aimed to derive consensus from health-system stakeholders in the urban Gauteng Province of SA on the most important challenges faced by the health services and patients in achieving optimum lung cancer management and to identify potential solutions., Methods: The study was undertaken among 27 participant stakeholders representing clinical managers, clinicians, opinion leaders from the public health sector and non-governmental organisation (NGO) representatives. The study compromised two components: consensus and engagement. For the consensus component, the Delphi Technique was employed with open-ended questions and item ranking from five rounds of consensus-seeking, to achieve collective agreement on the most important challenges faced by patients and the health services in achieving optimal lung cancer management. For the engagement component, the Nominal Group Technique was used to articulate ideas and reach an agreement on the group's recommendations for solution strategies and approaches., Results: Public health sector stakeholders suggested that a lack of knowledge and awareness of lung cancer, and the apparent stigma associated with the disease and its risk factors, as well as symptoms and signs, are critical to treatment delay. Furthermore, delays in up-referral of patients with suspected lung cancer from district health care level were attributed to inadequate knowledge arising from a lack of in-service training of nurses and doctors regarding oncologic symptoms, risk factors, need for further investigation, interpretation of x-rays and available treatments. At a tertiary level, participants suggested that insufficient availability of specialised diagnostic resources (imaging, cytological and pathological services including biomolecular assessment of lung cancer), theatres, cardiothoracic surgeons, and appropriate therapeutic modalities (chemotherapeutic agents and radiation oncology) are the main barriers to the provision of optimal care. It was suggested that a primary prevention programme initiated by the government that involves private-public partnerships may improve lung cancer management nationally., Conclusions: Considerable barriers to the early identification and treatment of lung cancer exist. Finding solutions to overcome both individual and health-system level obstacles to lung cancer screening and management are vital to facilitate early identification and treatment, and to improve survival. Furthermore, research on inexpensive biomarkers for asymptomatic disease detection, the introduction of diagnostic imaging tools that utilise artificial intelligence to compensate for inadequate human resources and improving clinical integration across all levels of the healthcare system are essential., Competing Interests: The authors have declared that no competing interests exist.

Metabolic syndrome (MetS) is a cluster of metabolic conditions that aggravate the likelihood of cardiovascular diseases and type 2 diabetes mellitus. This study was aimed to identify the best obesity index to determine MetS. This was a cross-sectional study and part of Ellisras Longitudinal Study where 593 (289 males and 304 females) adults aged 22-30 years took part. Confirmatory factor analysis was used to test the single-factor models of MetS defined by mid arterial pressure, fasting blood glucose, triglycerides and commonly selected obesity indices such as Neck circumference (NC), Body mass index (BMI), Waist circumference (WC) and Waist to height ratio (WHtR) as indicators of MetS. It was found that a single model fit built based on WC and WHtR suggested a better fit index than NC and BMI in males, whereas, a model built on NC obtained a better fit index for females than other factor models. In conclusion, the result of the present study suggests that in rural Ellisras adult's, WC and WHtR are the best obesity indices for determining MetS in males and NC in females than other indices. Hence, longitudinal studies are recommended to allow causality to be drawn between obesity indices and MetS.

Background: Evidence is lacking on the effects of binge alcohol consumption on metabolic syndrome in the rural South African population. The purpose of this study was to investigate the association between binge drinking and components of metabolic syndrome (MetS) amongst Ellisras rural young adults aged 21 to 31 years who are part of the Ellisras Longitudinal Study., Methods: Logistic regression analysis was applied to a total of 624 participants (306 males and 318 females) aged 21 to 31 years who took part in the Ellisras Longitudinal Study (ELS). The model was adjusted for covariates, including smoking, age, and gender. Binge alcohol consumption was assessed using a standardised questionnaire that was validated for the Ellisras rural community. A standardised method of determining the components MetS was used after fasting blood samples were collected from all the participants., Results: Binge drinking remained significantly associated with low levels of high-density lipoprotein cholesterol (HDL-C) (OR = 2.64, 95% CI = 1.23-5.65), after being adjusted for smoking, age, and gender. Other MetS components were not predicted. Instead, gender remained significantly associated with all MetS components, except triglycerides, at multivariate analysis. Age retained significance at multivariate analysis with waist girth (OR = 2.13, 95% CI = 1.37-3.34), triglycerides (OR = 2.30, 95% CI = 1.05-5.02), and the MetS composite (OR = 1.65, 95% CI = 1.12-2.41)., Conclusion: Binge drinking was significantly associated with lower levels of HDL-C. Future studies should investigate the relationship between alcohol abuse and the components of incident MetS in this population.

Context: When religious and spiritual (R/S) care needs of patients with advanced disease are met, their quality of life (QoL) improves. We studied the association between R/S support and QoL of patients with cancer at the end of life in Soweto, South Africa., Objectives: To identify R/S needs among patients with advanced cancer receiving palliative care services and to assess associations of receipt of R/S care with patient QoL and place of death., Methods: A prospective cohort study conducted from May 1, 2016 to April 30, 2018 at a tertiary hospital in Soweto, South Africa. Nurses enrolled patients with advanced cancer and referred them to the palliative care multidisciplinary team. Spiritual counselors assessed and provided spiritual care to patients. We compared sociodemographic, clinical, and R/S factors and QoL of R/S care recipients and others., Results: Of 233 deceased participants, 92 (39.5%) had received R/S care. Patients who received R/S care reported less pain (2.82 ± 1.23 vs. 1.93 ± 1.69), used less morphine, and were more likely to die at home than patients who did not (57.5% compared with 33.7%). On multivariate logistic regression analysis, adjusting for significant confounding influences and baseline African Palliative Care Association Palliative care Outcome Scale scores, receipt of spiritual care was associated with reduced pain and family worry (odds ratio 0.33; 95% CI 0.11-0.95 and odds ratio 3.43; 95% CI 1.10-10.70, respectively)., Conclusion: Patients with cancer have R/S needs. R/S care among our patients appeared to improve their end-of-life experience. More research is needed to determine the mechanisms by which R/S care may have improved the observed patient outcomes., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have declared that no competing interests exist.

The harm alcohol abuse does to physical and mental health is well established. The perception of cardiovascular disease risk factors and alcohol use requires attention. This study aims to investigate the association between alcohol usage and knowledge of cardiovascular diseases (CVDs) risk factors among Ellisras rural adolescents and young adults aged 14-22 years. In this cross-sectional study a total of 1409 subjects (736 boys and 673 girls), aged 14-22 years, from the Ellisras Longitudinal Study, South Africa completed a validated alcohol use and CVDs knowledge questionnaire. Logistic regression was used to estimate the association. The prevalence of alcohol intake increased with increasing age among girls (13.6% to 17.7%) and boys (10.3% to 16.9%) and reached a statistically significant difference ( p < 0.024) at an older age category (20-22 years). There was a significant ( p < 0.05) association between alcohol use and a positive response on the following knowledge statements: The fact that cardiovascular disease attacked all age groups and mostly elderly people (the odds ratio (OR) ranged between 0.5 95% confidence interval (CI) = 0.33-0.74 and OR = 2.86 95% CI = 1.27-6.42). Medical doctors can help to diagnose somebody with cardiovascular diseases (OR ranged between 2.25 95% CI = 1.49-3.39 and OR = 0.75 95% CI = 0.65-0.87). The condition for cardiovascular diseases developed over a long period (OR ranged between 1.75 95% CI = 1.16-2.64 and OR = 2.23 95% CI = 1.34-4.07). The prevalence of alcohol use in Ellisras rural adolescents and young adults begins between the ages of 14 and 16 years and increases with age. Binge drinking was more evident on Fridays and Saturdays among the Ellisras rural adolescents and young adults with girls showing a significantly higher prevalence of binge drinking compared to boys on a Friday.

Context: Identifying factors that affect terminally ill patients' preferences for and actual place of death may assist patients to die wherever they wish., Objective: The objective of this study was to investigate factors associated with preferred and actual place of death for cancer patients in Johannesburg, South Africa., Methods: In a prospective cohort study at a tertiary hospital in Johannesburg, South Africa, adult patients with advanced cancer and their caregivers were enrolled from 2016 to 2018. Study nurses interviewed the patients at enrollment and conducted postmortem interviews with the caregivers., Results: Of 324 patients enrolled, 191 died during follow-up. Preferred place of death was home for 127 (66.4%) and a facility for 64 (33.5%) patients; 91 (47.6%) patients died in their preferred setting, with a kappa value of congruence of 0.016 (95% CI = -0.107, 0.139). Factors associated with congruence were increasing age (odds ratio [OR]: 1.03, 95% CI: 1.00-1.05), use of morphine (OR: 1.87, 95% CI: 1.04-3.36), and wanting to die at home (OR: 0.44, 95% CI: 0.24-0.82). Dying at home was associated with increasing age (OR 1.03, 95% CI 1.00-1.05) and with the patient wishing to have family and/or friends present at death (OR 6.73, 95% CI 2.97-15.30)., Conclusion: Most patients preferred to die at home, but most died in hospital and fewer than half died in their preferred setting. Further research on modifiable factors, such as effective communication, access to palliative care and morphine, may ensure that more cancer patients in South Africa die wherever they wish., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The understanding of patients with cancer of their condition and their wishes regarding care as they approach end of life (EoL) have been studied more in high-income countries than in low- and middle-income countries (LMICs)., Patients and Methods: Data were analyzed from a cohort study (N = 221) of patients with advanced cancer who were recruited from a palliative care center in Soweto, South Africa (LMIC), between May 2016 and June 2017. Patients were asked about their understanding of their illness, estimated life expectancy, EoL care communication, and EoL care preferences., Results: Only 13 patients (5.9%) acknowledged that they were terminally ill; nine patients (4.1%) estimated accurately that they had months, not years, left to live. A total of 216 patients (97.7%) reported that they had not had an EoL care discussion with their physician, and 170 patients (76.9%) did not want to know their prognosis even if the doctor knew it. Most patients preferred comfort care (72.9%; n = 161) to life-extending care (14.0%; n = 31), and did not want to be kept alive using extreme measures (80.5%; n = 178) or have their doctors do everything possible to extend their lives (78.3%; n = 173). Finally, 127 patients (57.5%) preferred to die at home, and 51 (23.1%) preferred to die in the hospital. Most patients (81.0%; n = 179) had funeral plans., Conclusion: South African patients demonstrated less awareness of the fact that they were terminally ill, were less likely to have discussed their prognosis with their doctor, and more strongly preferred comfort care to life-extending EoL care than US and other LMIC patients in prior research. These differences highlight the need for culturally appropriate, patient-centered EoL care for South African patients with advanced cancer as well as to determine individual preferences and needs in all EoL settings.

Context: In sub-Saharan Africa, late diagnosis with cancer is common. Many dying patients rely on family members for care; little is known about the challenges African informal caregivers face., Objectives: To better understand the challenges of informal caregivers at the end of life in South Africa, both at home and in inpatient facilities., Methods: We included advanced cancer patients and caregivers from a public hospital in Johannesburg, South Africa. Study nurses interviewed patients and caregivers about their experiences. Using univariate and multivariate analyses, we determined the factors associated with greater caregiver difficulty, focusing on patients dying at home vs. in inpatient facilities., Results: Among 174 informal caregivers, 62 (36%) reported "a lot" of challenges. These caregivers struggled most with keeping the patient clean (16%) and with patient interactions (34%). Symptoms associated with greater difficulty included pain (odds ratio [OR] 2.4 [95% CI 1.2-4.7]), urinary incontinence (OR 2.3 [95% CI 1.1-4.9]), fecal incontinence (OR 2.4 [95% CI 1.0-5.7]), insomnia (OR 2.9 [95% CI 1.3-6.9]), fatigue (OR 6.3 [95% CI 1.8-21.6]), extremity weakness (OR 2.9 [95% CI 1.3-6.9]), shame (OR 4.2 [95% CI 1.5-12.0]), and sadness (OR 2.3 [95% CI 1.1-4.8]). Caregivers of patients dying at home reported the greatest difficulty with patients' physical symptoms; caregivers of those dying in facilities reported the greatest difficulty with emotional symptoms., Conclusion: Informal caregivers of patients dying at home reported challenges with practical functional care; this effect was reduced in the inpatient setting. Skills training for these caregivers could relieve some of this burden., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Unhealthy lifestyle characteristics such as low physical activity (PA) and high plasma glucose levels (PGLs) may lead to the development of type 2 diabetes mellitus in adulthood. The aim of this study was to investigate (i) the level of physical activity; (ii) the prevalence of pre-diabetes and (iii) the relationship between PA and plasma glucose level in a rural Ellisras adult population aged 18 to 28 years. A total of 713 young adults (349 males and 364 females) who took part in the Ellisras Longitudinal Study participated in the study. Fasting plasma glucose levels were analysed using Accutrend glucose meters. Physical activity data was collected using a validated questionnaire. Linear regression was used to assess the relationship between PA and pre-diabetes. The prevalence of pre-diabetes was between 45.7% and 50.2% and that of physical inactivity was 67.3% and 71.0% for males and females, respectively. There was no significant ( p > 0.05) relationship between PA and pre-diabetes (beta = 1.016; 95% Confidence Interval from 0.352 to 2.777). The health benefits of PA increased with the increasing frequency, duration and intensity of exercise. The prevalence of pre-diabetes was found to be very high in this population. Our results suggest that greater physical activity is associated with low plasma glucose levels.

Inhalable clofazimine-containing dry powder microparticles (CFM-DPI) and native clofazimine (CFM) were evaluated for activity against Mycobacterium tuberculosis in human monocyte-derived macrophage cultures and in mice infected with a low-dose aerosol. Both formulations resulted in 99% killing at 2.5 μg/ml in vitro. In mice, 480 μg and 720 μg CFM-DPI inhaled twice per week over 4 weeks reduced numbers of CFU in the lung by as much as log(10) 2.6; 500 μg oral CFM achieved a log(10) 0.7 reduction.