An investigation into symptoms of depression and anxiety and emotion regulation among older adolescents from low-income settings in South Africa.

INTRODUCTION: Mental health conditions (MHC) among adolescents in low- and middle-income countries, including South Africa, are estimated to be high. Adaptive emotion regulation (ER) skills can protect against MHC among adolescents. In South Africa, there is limited adolescent mental health prevalence data as well as little understanding of the associations between MHC and ER among adolescents. This study aimed to address these gaps by describing the psychosocial characteristics of older South African adolescents from low-income settings as well as investigating associations between depression and anxiety symptoms and ER. METHODS: We selected 12 schools in collaboration with two NGOs. Learners aged 15-18-years were recruited to complete a tablet-based survey. ER, depression, anxiety, and other psychosocial measures were included. Two multiple linear regression models were used to determine associations between depression symptoms, anxiety symptoms, other psychosocial factors, and ER. RESULTS: Of the 733 participants from 12 Western Cape schools, 417 (56.90%) screened at risk for clinically significant anxiety symptoms, 423 (57.70%) participants for depression symptoms, 229 (31.40%) participants for PTSD symptoms and 263 (35.90%) for risky alcohol use. Depression and anxiety scores were found to be significantly positively correlated with ER difficulties and adolescents struggled most with identifying and utilizing adaptive ER strategies. The adjusted linear regression model reported that female gender, clinically significant depressive, anxiety, post-traumatic stress symptoms and risky-alcohol use were all significantly associated with poorer ER scores, while self-esteem was significantly associated with better ER scores. CONCLUSION: These findings contribute to the South African adolescent mental health literature and to the research gap on the links between depression and anxiety and ER. Future research should consider further exploration of the relationships between psychosocial factors and ER to inform the urgent development and testing of appropriate adolescent interventions in this setting.

Project ASPIRE: A feasibility randomized controlled trial of a brief intervention for reducing risk of depression and alcohol-related harms among South African adolescents.

OBJECTIVE: Brief interventions could reduce adolescents' risk of depression and alcohol-related harms, but evidence of their feasibility and acceptability for low-and middle-income countries is lacking. To address this gap, we conducted a feasibility trial of the ASPIRE intervention, a four-session multi-component counselling intervention for South African adolescents. METHOD: We recruited 117 adolescents who met our inclusion criteria. Participants were randomly assigned to the ASPIRE intervention or a comparison condition. Outcomes were assessed at baseline, six-week, and three-month post-randomization time points. Primary outcomes were based on feasibility of study procedures and intervention delivery (assessed on seven predetermined progression criteria). Clinical outcomes (risk of depression and alcohol harms) were secondary. RESULTS: Despite modifications to all study procedures arising from Covid-19 restrictions, five of the seven key progression criteria were fully met, including: feasibility of data collection and outcome measures, counsellor competencies, randomization and blinding, adverse advents, and acceptability of the intervention. The progression criterion for recruitment and intervention retention were not fully met. CONCLUSION: Findings suggest that the ASPIRE intervention was generally feasible to deliver and acceptable to adolescents. However, modifications to the trial design and intervention delivery are needed to optimize the validity of a definitive randomized controlled trial of the ASPIRE intervention.

The in silico and in vitro analysis of donepezil derivatives for Anopheles acetylcholinesterase inhibition.

Current studies on Anopheles anticholinesterase insecticides are focusing on identifying agents with high selectivity towards Anopheles over mammalian targets. Acetylcholinesterase (AChE) from electric eel is often used as the bioequivalent enzyme to study ligands designed for activity and inhibition in human. In this study, previously identified derivatives of a potent AChE, donepezil, that have exhibited low activity on electric eel AChE were assessed for potential AChE-based larvicidal effects on four African malaria vectors; An. funestus, An. arabiensis, An. gambiae and An. coluzzii. This led to the identification of four larvicidal agents with a lead molecule, 1-benzyl-N-(thiazol-2-yl) piperidine-4-carboxamide 2 showing selectivity for An. arabiensis as a larvicidal AChE agent. Differential activities of this molecule on An. arabiensis and electric eel AChE targets were studied through molecular modelling. Homology modelling was used to generate a three-dimensional structure of the An. arabiensis AChE for this binding assay. The conformation of this molecule and corresponding interactions with the AChE catalytic site was markedly different between the two targets. Assessment of the differences between the AChE binding sites from electric eel, human and Anopheles revealed that the electric eel and human AChE proteins were very similar. In contrast, Anopheles AChE had a smaller cysteine residue in place of bulky phenylalanine group at the entrance to the catalytic site, and a smaller aspartic acid residue at the base of the active site gorge, in place of the bulky tyrosine residues. Results from this study suggest that this difference affects the ligand orientation and corresponding interactions at the catalytic site. The lead molecule 2 also formed more favourable interactions with An. arabiensis AChE model than other Anopheles AChE targets, possibly explaining the observed selectivity among other assessed Anopheles species. This study suggests that 1-benzyl-N-(thiazol-2-yl) piperidine-4-carboxamide 2 may be a lead compound for designing novel insecticides against Anopheles vectors with reduced toxic potential on humans.

Discovery of Novel Acetylcholinesterase Inhibitors by Virtual Screening, In Vitro Screening, and Molecular Dynamics Simulations.

Alzheimer's disease is the most common neurodegenerative disease and currently poses a significant socioeconomic problem. This study describes the uses of computer-aided drug discovery techniques to identify novel inhibitors of acetylcholinesterase, a target for Alzheimer's disease. High-throughput virtual screening was employed to predict potential inhibitors of acetylcholinesterase. Validation of enrichment was performed with the DUD-E data set, showing that an ensemble of binding pocket conformations is critical when a diverse set of ligands are being screened. A total of 720 compounds were submitted for in vitro screening, which led to 25 hits being identified with IC50 values of less than 50 µM. The majority of these hits belonged to two scaffolds: 1-ethyl-3-methoxy-3-methylpyrrolidine and 1H-pyrrolo[3,2-c]pyridin-6-amine both of which are noted to be promising compounds for further optimization. As various possible binding poses were suggested from molecular docking, molecular dynamics simulations were employed to validate the poses. In the case of the most active compounds identified, a critical, stable water bridge formed deep within the binding pocket was identified potentially explaining in part the lack of activity for subsets of compounds that are not able to form this water bridge.

Optimization of covalent docking for organophosphates interaction with Anopheles acetylcholinesterase.

Organophosphates (OPs) used as potent insecticides for malaria vector control, covalently phosphorylate the catalytic serine residue of Anopheles gambiae AChE (AgAChE) in a reaction that liberates their leaving groups. In the recent 10-year insecticide use assessment, OPs were the most frequently used World Health Organization prequalified insecticides. Molecular modelling programs are best suited to display molecular interactions between ligands and the target proteins. The docking modes that generate ligand poses closer to the binding site show high accuracy in predicting the ligand binding mode. The implicit solvation approach such as molecular mechanics-generalized born surface area (MM-GBSA) is a more reliable method to predict ligand onformations and binding affinities. Apart from covalent docking studies being scarce, current molecular docking programs do not adequately possess the covalent docking reaction algorithm to display the molecular mechanism of OPs at the AgAChE catalytic site. This results into OP docking studies commonly being conducted through noncovalent pannels. The aim of this study was to establish the optimim covalent docking system for OPs through manual customization of Schrödinger's Glide covalent docking reaction algorithm. To achieve this, a newly customized covalent reaction algorithm was assessed on a set of ligands covering aromatic, non-aromatic and hydrophobic OPs and compared to the noncovalent docking results in terms of reliability based on the reported X-ray diffraction molecular interactions and crystal poses. The study established that by virtue of omitting the well-known OP hydrolysis, noncovalent mode suggested molecular interactions that were further from the catalytic triad and could not otherwise occur when the molecule is hydrolyzed as in the customized covalent docking mode. Moreover, the MM-GBSA concurred with the optimized covalent docking in eliminating such inaccurate molecular interactions. Additionally, the covalent docking mode confined the interactions and ligand poses to the catalytic site indicating relatively high accuracy and reliability. This study reports the optimized covalent docking panel that effectively confirmed the molecular mechanisms of OPs, as well as indentifying the corresponding amino acid residues required to stabilize the aromatic, non-aromatic and hydrophobic OPs at the AgAChE catalytic site in line with the reported X-ray diffraction studies. As such, the proposed manual customization of the Schrödinger's Glide covalent docking platform can be used to reliably predict molecular interactions between OPs and AgAChE target.

Lobostemon trigonus (Thunb.) H. Buek, a medicinal plant from South Africa as a potential natural microbicide against HIV-1.

ETHNOPHARMACOLOGICAL RELEVANCE: There have been different methods proposed to prevent the sexual transmission of HIV-1 and many of them have centered on the use of anti-retrovirals as microbicides. Given that a large section of the African population still relies on herbal medicine, Lobostemon trigonus (L. trigonus), a traditionally used medicinal plant in South Africa to treat HIV-1 was further investigated for its potential as a natural microbicide to prevent the sexual transmission of HIV-1. METHODS: The aerial parts of L. trigonus were oven-dried at 80 °C, ground, extracted with boiling water for 30 min and then filtered. The aqueous extract produced was then bioassayed using different HIV-1 inhibition assays. The active components were purified and chemically profiled using ultra-performance liquid chromatography/quadrupole time-of flight mass spectrometry (UPLC-qTOF-MS). The mechanism of HIV-1 inhibition was determined by fusion arrest assay and time of addition assay. Molecular modelling and molecular dynamic simulations, using Schrödinger, were used to better understand the molecule's mechanism of entry inhibition by evaluating their docking affinity and stability against the gp120 of HIV-1. RESULTS: The aqueous extract of this plant had a broad spectrum of activity against different subtypes of the virus; neutralizing subtype A, B and C in the TZM-bl cells, with IC50 values ranging from 0.10 to 7.21 µg/mL. The extract was also inhibitory to the virus induced cytopathic effects in CEM-SS cells with an EC50 of 8.9 µg/mL. In addition, it inhibited infection in peripheral blood mononuclear cells (PBMC) and macrophages with IC50 values of 0.97 and 4.4 µg/mL, respectively. In the presence of vaginal and seminal simulants, and in human semen it retained its inhibitory activity albeit with a decrease in efficiency, by about 3-fold. Studies of the mode of action suggested that the extract blocked HIV-1 attachment to target cells. No toxicity was observed when the Lactobacilli strains, L. acidophilus, L. jensenii, and L. crispatus that populate the female genital tract were cultured in the presence of L. trigonus extract. UPLC-qTOF-MS analyses of the purified fraction of the extract, confirmed the presence of six compounds of which four were identified as rosmarinic acid, salvianolic acids B and C and lithospermic acid. The additional molecular dynamic simulations provided further insight into the entry inhibitory characteristics of salvianolic acid B against the HIV-1 gp120, with a stable pose being found within the CD4 binding site. CONCLUSION: The data suggests that the inhibitory effect of L. trigonus may be due to the presence of organic acids which are known to possess anti-HIV-1 properties. The molecules salvianolic acids B and C have been identified for the first time in L. trigonus species. Our study also showed that the L. trigonus extract blocked HIV-1 attachment to target cells, and that it has a broad spectrum of activity against different subtypes of the virus; thus, justifying further investigation as a HIV-1 microbicide.

A Cytotoxic Bis(1,2,3-triazol-5-ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation.

The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis(aryl) analogue afforded a bis(carbene) AuI -CNC pincer complex suitable for oxidation to the redox-stable [AuIII (CNC)Cl]+ cation. Although the ligand salt and the [AuIII (CNC)Cl]+ complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the AuIII complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [AuIII (CNC)Cl]+ complex behaves as a partial DNA intercalator. In silico screening indicated that the [AuIII (CNC)Cl]+ complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic π-type interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O⋅⋅⋅Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the AuIII ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro.

Addressing the mental health needs of adolescents in South African communities: a protocol for a feasibility randomized controlled trial.

BACKGROUND: Like many low- and middle-income countries, almost half of the proportion of the South African population is under the age of 25. Given the peak age of onset for most mental health problems is in adolescence, it is vital that adolescents have access to mental health counselling. There are several initiatives to increase access to mental health counselling in South Africa, primarily through the integration of counselling for common mental disorders (CMD) into primary health care services, but adolescents (15-18 years of age) generally do not utilize these services. To address this gap, we will undertake a study to explore the feasibility of conducting a trial of the effectiveness of a community-based mental health counselling intervention for adolescents at-risk for a CMD. METHODS: The study is a feasibility trial of the ASPIRE intervention, a four-session blended multi-component counselling intervention adapted for South African adolescents at risk for depression and alcohol use disorders. We will enrol 100 adolescents from community settings and randomly assign them to the ASPIRE intervention or a comparison condition. Feasibility measures, such as rates of recruitment, consent to participate in the trial and retention, will be calculated. Qualitative interviews with participants and counsellors will explore the acceptability of the intervention. The primary outcomes for a subsequent trial would be reductions in symptoms of depression and days of heavy drinking which will be measured at baseline, 6 weeks, and 3 months post-randomization. DISCUSSION: This feasibility trial using a mixed-methods design will allow us to determine whether we can move forward to a larger effectiveness trial of the ASPIRE intervention. TRIAL REGISTRATION: The trial is registered with the Pan African Clinical Trials Registry (PACTR20200352214510). Registered 28 February 2020-retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9795.

Task Sharing or Task Dumping: Counsellors Experiences of Delivering a Psychosocial Intervention for Mental Health Problems in South Africa.

Given task-sharing mental health counselling to non-specialist providers is a recognised strategy to increase service capacity, ensuring that their training, supervision, and support needs are met is necessary to facilitate the sustainable delivery of a high-quality service. Using in-depth interviews, we qualitatively explored the experiences of 18 facility-based counsellors (FBCs) tasked with delivering a counselling intervention within chronic disease services offered within primary care facilities participating in the project MIND cluster randomised controlled trial. Findings show that project MIND training with a strong emphasis on role playing and skills rehearsal improved FBCs' confidence and competence, complemented by highly structured supervision and debriefing provided by a registered counsellor, were key strategies for supporting the implementation of task-shared mental health counselling. FBCs perceived many benefits to providing mental health counselling in primary healthcare but systemic interventions are needed for sustained implementation.

The changing landscape of infective endocarditis in South Africa.

BACKGROUND: Little is known about the current clinical profile and outcomes of patients with infective endocarditis (IE) in South Africa (SA). OBJECTIVES: To provide a contemporary and descriptive overview of IE in a representative SA tertiary centre. METHODS: We conducted a retrospective review of the records of patients admitted to Groote Schuur Hospital, Cape Town, between 2009 and 2016 fulfilling universal criteria for definite or possible IE, in search of demographic, clinical, microbiological, echocardiographic, treatment and outcome information. RESULTS: A total of 105 patients fulfilled the modified Duke criteria for IE. The median age of the cohort was 39 years (interquartile range (IQR) 29 - 51), with a male preponderance (61.9%). The majority of the patients (72.4%) had left-sided native valve endocarditis, 14.3% had right-sided disease, and 13.3% had prosthetic valve endocarditis. A third of the cohort had rheumatic heart disease. Although 41.1% of patients with left-sided disease had negative blood cultures, the three most common organisms cultured in this subgroup were Staphylococcus aureus (18.9%), Streptococcus spp. (16.7%) and Enterococcus spp. (6.7%). Participants with right-sided endocarditis were younger (29 years, IQR 27 - 37) and were mainly intravenous drug users (73.3%), and the majority cultured positive for S. aureus (73.3%) with frequent septic pulmonary complications (40.0%). The overall in-hospital mortality was 16.2%, with no deaths in the group with right-sided endocarditis. Predictors of death in our patients were heart failure (odds ratio (OR) 8.16, 95% confidence interval (CI) 1.77 - 37.70; p=0.007) and age >45 years (OR 4.73, 95% CI 1.11 - 20.14; p=0.036). Valve surgery was associated with a reduction in mortality (OR 0.09, 95% CI 0.02 - 0.43; p=0.001). CONCLUSIONS: IE remains an important clinical problem in a typical teaching tertiary care centre in SA. In this setting, it continues to affect mainly young people with post-inflammatory valve disease and congenital heart disease. The in-hospital mortality associated with IE remains high. Intravenous drug-associated endocarditis caused by S. aureus is an important IE subset, comprising ~10% of all cases, which was not reported 15 years ago, and culture-negative endocarditis remains highly prevalent. Heart failure in IE carries a significant risk of death and needs a more intensive level of care in hospital. Finally, cardiac surgery was associated with reduced mortality, with the largest impact in patients with heart failure.

Novel N-benzylpiperidine carboxamide derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease.

A series of fifteen acetylcholinesterase inhibitors were designed and synthesised based upon the previously identified lead compound 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (5) which showed good inhibitory activity (IC50 0.03 ±â€¯0.07 µM) against acetylcholinesterase. A series of compounds were prepared wherein the ester linker in the original lead compound was exchanged for a more metabolically stable amide linker and the indanone moiety was exchanged for a range of aryl and aromatic heterocycles. The two most active analogues 1-benzyl-N-(5,6-dimethoxy-8H-indeno[1,2-d]thiazol-2-yl)piperidine-4-carboxamide (28) and 1-benzyl-N-(1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) piperidine-4-carboxamide (20) afforded in vitro IC50 values of 0.41 ±â€¯1.25 and 5.94 ±â€¯1.08 µM, respectively. In silico screening predicts that 20 will be a blood brain-barrier permeant, and molecular dynamic simulations are indicative of a close correlation between the binding of 20 and the Food and Drug Administration-approved cholinesterase inhibitor donepezil (1).

The changing landscape of infective endocarditis in South Africa

Background. Little is known about the current clinical profile and outcomes of patients with infective endocarditis (IE) in South Africa (SA). Objectives. To provide a contemporary and descriptive overview of IE in a representative SA tertiary centre. Methods. We conducted a retrospective review of the records of patients admitted to Groote Schuur Hospital, Cape Town, between 2009 and 2016 fulfilling universal criteria for definite or possible IE, in search of demographic, clinical, microbiological, echocardiographic, treatment and outcome information. Results. A total of 105 patients fulfilled the modified Duke criteria for IE. The median age of the cohort was 39 years (interquartile range (IQR) 29 - 51), with a male preponderance (61.9%). The majority of the patients (72.4%) had left-sided native valve endocarditis, 14.3% had right-sided disease, and 13.3% had prosthetic valve endocarditis. A third of the cohort had rheumatic heart disease. Although 41.1% of patients with left-sided disease had negative blood cultures, the three most common organisms cultured in this subgroup were Staphylococcus aureus (18.9%), Streptococcus spp. (16.7%) and Enterococcus spp. (6.7%). Participants with right-sided endocarditis were younger (29 years, IQR 27 - 37) and were mainly intravenous drug users (73.3%), and the majority cultured positive for S. aureus (73.3%) with frequent septic pulmonary complications (40.0%). The overall in-hospital mortality was 16.2%, with no deaths in the group with right-sided endocarditis. Predictors of death in our patients were heart failure (odds ratio (OR) 8.16, 95% confidence interval (CI) 1.77 - 37.70; p=0.007) and age >45 years (OR 4.73, 95% CI 1.11 - 20.14; p=0.036). Valve surgery was associated with a reduction in mortality (OR 0.09, 95% CI 0.02 - 0.43; p=0.001). Conclusions. IE remains an important clinical problem in a typical teaching tertiary care centre in SA. In this setting, it continues to affect mainly young people with post-inflammatory valve disease and congenital heart disease. The in-hospital mortality associated with IE remains high. Intravenous drug-associated endocarditis caused by S. aureus is an important IE subset, comprising ~10% of all cases, which was not reported 15 years ago, and culture-negative endocarditis remains highly prevalent. Heart failure in IE carries a significant risk of death and needs a more intensive level of care in hospital. Finally, cardiac surgery was associated with reduced mortality, with the largest impact in patients with heart failure

A multicentre, cross-sectional study investigating the prevalence of hypertensive disease in patients presenting for elective surgery in the Western Cape Province, South Africa.

BACKGROUND: Hypertension is common, affecting over one billion people worldwide. In sub-Saharan Africa, hypertensive disease not only affects the older population but is becoming increasingly prevalent in younger individuals. In South Africa (SA), >30% of the adult population has hypertension, making it the single most common cardiovascular risk factor and the predominant contributor to cardiovascular disease and mortality. Elevated blood pressure is the most common perioperative comorbidity encountered in non-cardiac surgical patients, with an overall prevalence of 20 - 25%, and it remains poorly controlled in low- and middle-income countries. Hypertension in the perioperative setting may adversely affect patient outcome. It therefore not only flags possible perioperative challenges to anaesthesiologists, but also identifies patients at risk of long-term morbidity and mortality. OBJECTIVES: To determine the prevalence and severity of hypertension in elective adult surgical patients in the Western Cape Province, SA. RESULTS: The study population included all elective surgical patients from seven hospitals in the Western Cape during a 1-week period. Hypertension, defined as having had a previous diagnosis of hypertension or meeting the blood pressure criteria of >140/90 mmHg, was identified in 51.8% of patients during preoperative assessment. Significantly, newly diagnosed hypertension was present in 9.9% of all patients presenting for elective surgery. Although 98.1% of the known hypertensive patients were on antihypertensive therapy, 36.9% were inadequately controlled. There are numerous reasons for this, but notably 32.1% of patients admitted to forgetting to take their medication, making patient factors the most common reason for treatment non-compliance. CONCLUSIONS: The perioperative period may be an important opportunity to identify undiagnosed hypertensive patients. The perioperative encounter may have a significant public health implication in facilitating appropriate referral and treatment of patients with hypertension to decrease long-term cardiovascular complications in SA.

Optimising perioperative care for hip and knee arthroplasty in South Africa: a Delphi consensus study.

BACKGROUND: A structured approach to perioperative patient management based on an enhanced recovery pathway protocol facilitates early recovery and reduces morbidity in high income countries. However, in low- and middle-income countries (LMICs), the feasibility of implementing enhanced recovery pathways and its influence on patient outcomes is scarcely investigated. To inform similar practice in LMICs for total hip and knee arthroplasty, it is necessary to identify potential factors for inclusion in such a programme, appropriate for LMICs. METHODS: Applying a Delphi method, 33 stakeholders (13 arthroplasty surgeons, 12 anaesthetists and 8 physiotherapists) from 10 state hospitals representing 4 South African provinces identified and prioritised i) risk factors associated with poor outcomes, ii) perioperative interventions to improve outcomes and iii) patient and clinical outcomes necessary to benchmark practice for patients scheduled for primary elective unilateral total hip and knee arthroplasty. RESULTS: Thirty of the thirty-three stakeholders completed the 3 months Delphi study. The first round yielded i) 36 suggestions to preoperative risk factors, ii) 14 (preoperative), 18 (intraoperative) and 23 (postoperative) suggestions to best practices for perioperative interventions to improve outcomes and iii) 25 suggestions to important postsurgical outcomes. These items were prioritised by the group in the consecutive rounds and consensus was reached for the top ten priorities for each category. CONCLUSION: The consensus derived risk factors, perioperative interventions and important outcomes will inform the development of a structured, perioperative multidisciplinary enhanced patient care protocol for total hip and knee arthroplasty. It is anticipated that this study will provide the construct necessary for developing pragmatic enhanced care pathways aimed at improving patient outcomes after arthroplasty in LMICs.

The relationship between pre-operative hypertension and intra-operative haemodynamic changes known to be associated with postoperative morbidity.

Hypertension is not consistently associated with postoperative cardiovascular morbidity and is therefore not considered a major peri-operative risk factor. However, hypertension may predispose to peri-operative haemodynamic changes known to be associated with peri-operative morbidity and mortality, such as intra-operative hypotension and tachycardia. The objective of this study was to determine whether pre-operative hypertension was independently associated with haemodynamic changes known to be associated with adverse peri-operative outcomes. We performed a five-day multicentre, prospective, observational cohort study which included all adult inpatients undergoing elective, non-cardiac, non-obstetric surgery. We recruited 343 patients of whom 164 (47.8%) were hypertensive. An intra-operative mean arterial pressure of < 55 mmHg occurred in 59 (18.2%) patients, of which 25 (42.4%) were hypertensive. Intra-operative tachycardia (heart rate> 100 beats.min-1 ) occurred in 126 (38.9%) patients, of whom 61 (48.4%) were hypertensive. Multivariable logistic regression did not show an independent association between the stage of hypertension and either clinically significant hypotension or tachycardia, when controlled for ASA physical status, functional status, major surgery, duration of surgery or blood transfusion. There was no association between pre-operative hypertension and peri-operative haemodynamic changes known to be associated with major morbidity and mortality. These data, therefore, support the recommendation of the Joint Guidelines of the Association of Anaesthetists of Great Britain and Ireland (AAGBI) and the British Hypertension Society to proceed with elective surgery if a patient's blood pressure is < 180/110 mmHg.

Lost to follow-up: Challenges to conducting orthopaedic research in South Africa.

Loss to follow-up poses a major problem for clinicians and researchers, and several factors that may increase its risk have been postulated. The objective of this study was to describe potential factors that contribute to loss to follow-up as seen in orthopaedic patients participating in a research study and attending the sole public orthopaedic service provider in the Northern Cape Province of South Africa (SA). All patients who underwent ankle fracture surgery at Kimberley Provincial Hospital between January 2012 and July 2013 were included, and the number of follow-up visits attended by each participant was recorded prospectively. Demographic information pertaining to travel distance, social circumstances and comorbid conditions was captured and reviewed. A total of 268 patients (male n=112, 41.8% and female n=156, 58.2%) were included. The mean (standard deviation (SD)) age was 42.3 (13.8) years (95% confidence interval (CI) 40.6 - 43.9, n=266) and the mean body mass index (BMI, kg/m2) was 28.0 (6.5) (95% CI 27.2 - 28.8, n=251), the BMI for females being 30.2 (6.1) (95% CI 29.3 - 31.2, n=152) compared with 24.6 (5.7) (95% CI 23.4 - 25.7, n=99) for males. After excluding local patients living within 5 km of the hospital (n=77), the mean travel distance was 460 km (range 10 - 910). There was a significant association between the number of follow-up visits attended and travel distance (incidence rate ratio (IRR) 0.999, 95% CI 0.999 - 1.000; p=0.030), BMI (IRR 0.980, 95% CI 0.966 - 0.994; p=0.004) and HIV status (IRR 0.841, 95% CI 0.725 - 0.975; p=0.022). The main factors identified in this study that influenced the number of follow-up visits attended were travel distance, BMI and HIV status. BMI was a unique finding in our study. It was identified to be a significant contributing factor to the loss to follow-up. BMI was not a contributing factor in other studies.

Investigating the psychosocial determinants of child health in Africa: The Drakenstein Child Health Study.

BACKGROUND: Early life psychobiological and psychosocial factors play a key role in influencing child health outcomes. Longitudinal studies may help elucidate the relevant risk and resilience profiles, and the underlying mechanisms that impact on child health, but there is a paucity of birth cohort data from low and middle-income countries (LMIC). We describe the rationale for and present baseline findings from the psychosocial component of the Drakenstein Child Health Study (DCHS). METHODS: We review the psychosocial measures used in the DCHS, a multidisciplinary birth cohort study in a peri-urban area in South Africa, and provide initial data on psychological distress, depression, substance use, and exposure to traumatic stressors and intimate partner violence (IPV). These and other measures will be assessed longitudinally in mothers in order to investigate associations with child neurodevelopmental and health outcomes. RESULTS: Baseline psychosocial data is presented for mothers (n=634) and fathers (n=75) who have completed antenatal assessments to date. The sample of pregnant mothers is characterized by multiple psychosocial risk factors, including a high prevalence of psychological distress and depression, high levels of substance use, and high exposure to traumatic stressors and IPV. DISCUSSION: These data are consistent with prior South African studies which have documented a high prevalence of a multitude of risk factors during pregnancy. Further longitudinal assessment of mothers and children may clarify the underlying psychobiological and psychosocial mechanisms which impact on child health, and so inform clinical and public health interventions appropriate to the South African and other LMIC contexts.

[Nursing knowledge and attitude of day care personnel towards health promotion of babies]. / Verpleegkundiges se persepsie van die kennis waaroor dagmoeders moet beskik om te voldoen aan die gesondheidsbevordering van babas.

Currently it is more acceptable that women work. Besides women who are obliged to work to contribute to the income of their families, a large number of women work due to a need for social stimulation. While their mothers are at work during the day, the babies are left in substitute care out of necessity. Health promotion of babies is necessary and is the duty of the substitute caregiver. These women, however, do not always have the knowledge of, or positive attitude towards, health promotion. The purpose of this study, was to determine the knowledge and skills that the day mother should have in order to promote the health of babies (age 0-12 month). The qualititative research approach was used, within which a descriptive study had been done. A comprehensive literature study had initially been done regarding the health promotion of babies in substitute care. A programme had been compiled regarding the knowledge and skills that a day mother must possess in order to promote the health of babies. This program was then submitted to a group of selected experts for evaluation according to the Delphi technique. According to the data, it is quite clear that the day mother should be knowledgeable and skilled in order to satisfy the baby's physiological, security and affiliation needs as well as the need for appreciation and self-actualization.