"It's important to take your medication everyday okay?" An evaluation of counselling by lay counsellors for ARV adherence support in the Western Cape, South Africa.

There is growing interest in standard care programmes for antiretroviral (ARV) adherence support. In South Africa, individual counselling following ARV initiation is a main strategy for supporting adherence in the public sector. Egan's client-centred "Skilled Helper" counselling model is the predominant model used in HIV counselling in this context. This study evaluated counselling delivered by lay ARV adherence counsellors in Cape Town in terms of adherence to Egan's model. Thirty-eight transcripts of counselling sessions with non-adherent patients were analysed based on the methods of content analysis. These sessions were conducted by 30 counsellors. Generally counsellors' practice adhered neither to Egan's model nor a client-centred approach. Inconsistent with evidence-based approaches to counselling for ARV adherence support, counsellors mainly used information-giving and advice as strategies for addressing clients' non-adherence. Recommendations for improving practice are made. The question as to how appropriate strategies from developed countries are for this setting is also raised.

Behaviour change counselling for ARV adherence support within primary health care facilities in the Western Cape, South Africa.

Health care systems have been described as ideal settings for behaviour change counselling interventions. There is little research evaluating the feasibility of implementing such interventions in routine practice in primary care facilities. We implemented an intervention called Options for Health within routine adherence counselling practice in 20 antiretroviral facilities in Cape Town, South Africa. Lay counsellors were trained to use Options to help clients to optimise ARV adherence and reduce sexual risk behaviour. Counsellors delivered the intervention to 9% of eligible patients over 12 months. Interviews with counsellors revealed barriers to implementation including a lack of counselling space, time pressure and patient resistance to counselling. Counsellors felt that Options was not appropriate for use with all patients and adherence problems, and used parts of the intervention as it suited their needs. Findings revealed weaknesses in the current adherence counselling system that have implications for the feasibility of behaviour change counselling within this context.

Diagnostic performance of dobutamine stress echocardiography: A South African experience.

BACKGROUND: Dobutamine stress echocardiography (DSE) is a well-established modality for the diagnosis of coronary artery disease, but there are no reported diagnostic data in southern Africa. Objectives. To compare the safety, sensitivity and specificity of a South African (SA) DSE programme with larger, international series. Methods. All patients undergoing DSE from 2019 to 2021 at a single SA centre were included. A new wall motion abnormality (≥2 segments) signified inducible ischaemia. Results. A total of 106 patients (mean (standard deviation) age 61 (11) years, 68% male) were analysed. Six patients (6%) experienced chest pain during DSE and 4 (4%) developed an atrial arrhythmia. The sensitivity and specificity for epicardial coronary stenosis were 77% and 74%, respectively, changing to 82% and 72% when excluding those who had previous coronary artery bypass surgery. Conclusion. The sensitivity, specificity and safety of an SA DSE programme were comparable to international series. A DSE programme is feasible in a resource-constrained environment.

Infective endocarditis in patients after percutaneous pulmonary valve implantation with the stent-mounted bovine jugular vein valve: Clinical experience and evaluation of the modified Duke criteria.

AIMS: Percutaneous pulmonary valve implantation (PPVI) has proven good hemodynamic results. As infective endocarditis (IE) remains a potential complication with limited available clinical data, we reviewed our patient records to improve future strategies of IE prevention, diagnosis and treatment. METHODS: Medical records of all patients diagnosed with Melody® valve IE according to the modified Duke criteria were retrospectively analyzed in three Belgian tertiary centers. RESULTS: 23 IE episodes in 22 out of 240 patients were identified (incidence 2.4% / patient year) with a clear male predominance (86%). Median age at IE was 17.9 years (range 8.2-45.9 years) and median time from PPVI to IE was 2.4 years (range 0.7-8 years). Streptococcal species caused 10 infections (43%), followed by Staphylococcus aureus (n = 5, 22%). In 13/23 IE episodes a possible entry-point was identified (57%). IE was classified as definite in 15 (65%) and as possible in 8 (35%) cases due to limitations of imaging. Echocardiography visualized vegetations in only 10 patients. PET-CT showed positive FDG signals in 5/7 patients (71%) and intracardiac echocardiography a vegetation in 1/1 patient (100%). Eleven cases (48%) had a hemodynamically relevant pulmonary stenosis at IE presentation. Nine early and 6 late percutaneous or surgical re-interventions were performed. No IE related deaths occurred. CONCLUSIONS: IE after Melody® valve PPVI is associated with a relevant need of re-interventions. Communication to patients and physicians about risk factors is essential in prevention. The modified Duke criteria underperformed in diagnosing definite IE, but inclusion of new imaging modalities might improve diagnostic performance.

Qualitative and quantitative detection of SARS-CoV-2 RNA in untreated wastewater in Western Cape Province, South Africa.

Recent studies have shown that the detection of SARS-CoV-2 genetic material in wastewater may provide the basis for a surveillance system to track the environmental dissemination of this virus in communities. An effective wastewater-based epidemiology (WBE) system may prove critical in South Africa (SA), where health systems infrastructure, testing capacity, personal protective equipment and human resource capacity are constrained. In this proof-of-concept study, we investigated the potential of SARS-CoV-2 RNA surveillance in untreated wastewater as the basis for a system to monitor COVID-19 prevalence in the population, an early warning system for increased transmission, and a monitoring system to assess the effectiveness of interventions. The laboratory confirmed the presence (qualitative analysis) and determined the RNA copy number of SARS-CoV-2 viral RNA by reverse transcription polymerase chain reaction (quantitative) analysis from 24-hour composite samples collected on 18 June 2020 from five wastewater treatment plants in Western Cape Province, SA. The study has shown that a WBE system for monitoring the status and trends of COVID-19 mass infection in SA is viable, and its development and implementation may facilitate the rapid identification of hotspots for evidence-informed interventions.

High fat programming induces glucose intolerance in weanling Wistar rats.

We sought to determine whether maintenance on a high fat diet during defined periods of gestation and lactation induced glucose intolerance in weanling Wistar rats or affected food intake, weight, and glucose concentrations in mothers. Experimental groups comprised mothers and their weanling offspring maintained on a high fat diet during gestation and lactation (HFGL), during gestation only (HFG), or during lactation only (HFL). Maternal food intake, body weight, and fasting blood glucose concentrations were determined during lactation. Glucose tolerance was measured in the three-week-old weanling offspring. After overnight fasting, oral glucose tolerance tests were performed in the weanlings. Glucose was collected at (0), 10, 15, 30 and 60 min. HFGL and HFL weanlings had greater glucose concentrations compared to control weanlings at 10, 15, 30 and 60 min. For HFG weanlings, greater glucose concentrations were only found at 30 min, which normalized at 60 min. In all of the experimental groups, the highest glucose concentrations were demonstrated at 30 min, whereas the peak was achieved at 15 min in the control weanlings. Overt glucose intolerance was induced in weanlings maintained on a high fat diet throughout both gestation and lactation or throughout lactation only. Further, weanlings maintained on a high fat diet solely throughout gestation displayed milder glucose intolerance. Developmental programming with a high fat diet during defined periods of gestation and lactation induces glucose intolerance in weanling rats.

Opportunity costs of gastrointestinal endoscopic training in Canada.

BACKGROUND: No data exist to define the opportunity costs related to instruction in endoscopic procedures in Royal College of Physicians and Surgeons of Canada-accredited teaching centres. Academic and institutional administrators expect staff to achieve acceptable performance standards. There is a need to measure some of the effects of training activity in the establishment of such standards. OBJECTIVE: To measure the effect of resident training in colonoscopy on real procedure times and, as a secondary goal, to estimate procedural losses related to the process of training. METHODS: Real procedure times for ambulatory colonoscopy in a single academic, hospital-based endoscopy unit were documented. Times for certified endoscopy instructors functioning solo were compared with times for procedures involving trainees at several levels of colonoscopic experience. Procedural reductions associated with resident training were estimated based on the parameters derived from the results. The analysis was executed retrospectively using prospectively collected data. RESULTS: Resident training prolonged procedure times for ambulatory colonoscopy by 50%. The trainee effect was consistent, although variable in degree, among a variety of endoscopy instructors. Such increased procedure times have the potential to reduce case throughput and endoscopist remuneration. CONCLUSIONS: Resident training in colonoscopy in a Canadian certified training program has significant negative effects on case throughput and endoscopist billings. These factors should be considered in any assessment of performance in similar training environments.

Prevalence of hypertension in adults with intellectual disability in the Netherlands.

BACKGROUND: Literature on the prevalence of hypertension in people with intellectual disability (ID) is mostly based on file studies or on measurements limited to the age group below 50 years. We measured and calculated the prevalence of hypertension in adults with ID and studied the distribution of hypertension in relation to age, gender, diagnosis of Down's syndrome and level of ID. METHODS: In an observational cross-sectional study, standardized blood pressure measurements were obtained from 258 randomly selected adult clients of three Dutch care providers for people with ID. Hypertension was defined as a mean systolic blood pressure above 140 mm Hg on repeated measurements. RESULTS: The overall prevalence rate of hypertension was 17.4% (95% CI 12.28-22.46). This was comparable to the prevalence in the general Dutch population. No accurate blood pressure measurement could be performed in 28.4% of people with severe and profound ID owing to repetitive physical activity or resistance. Hypertension was significantly related to older age and absence of Down's syndrome; no correlation with gender or level of ID could be shown. RECOMMENDATION: The risk factor hypertension should be detected and treated in the same manner as in the general population following national guidelines.

Emphysema in young adult survivors of moderate-to-severe bronchopulmonary dysplasia.

Improved survival following extreme preterm birth complicated by bronchopulmonary dysplasia (BPD) is resulting in an increasing number of affected infants surviving to adulthood. The aim of the present pilot study was to describe the functional and structural pulmonary sequelae of moderate and severe BPD in a population of adult survivors. All babies were cared for at one institution (King Edward Memorial Hospital, Subiaco, Australia). Subjects born between 1980 and 1987 with birthweight <1,500 g and requiring supplementary oxygen at 36 weeks post-menstrual age were identified from a complete neonatal database and recruited prospectively. Local physicians were concurrently asked to refer suitable patients. Demographics, respiratory symptoms and examination results, pulmonary function tests and computed tomography images were acquired. In total, 21 subjects were studied. Of these, 12 were female, the median (range) age was 19 (17-33) yrs and 15 (71%) had persistent respiratory symptoms. The median (range) forced expiratory volume in one second (FEV(1)) z-score was -0.77 (-8.20-1.37), the forced expiratory flow at 25-75% of forced vital capacity was -1.81 (-6.00-0.75) and the diffusing capacity of the lung for carbon monoxide was -5.04 (-13.17- -1.24). Computed tomography was carried out on 19 subjects and all had abnormal findings, with emphysema being the most common, present in 84% of subjects. The extent of radiological emphysema was inversely related to the FEV(1) z-score. Young adult survivors of moderate and severe bronchopulmonary dysplasia may be left with residual functional and characteristic structural pulmonary abnormalities, most notably emphysema.

Liquid-vapor equilibrium of the systems butylmethylimidazolium nitrate-CO2 and hydroxypropylmethylimidazolium nitrate-CO2 at high pressure: influence of water on the phase behavior.

Ionic liquids (IL) are receiving increasing attention due to their potential as "green" solvents, especially when used in combination with SC-CO2. In this work liquid-vapor equilibria of binary mixtures of CO2 with two imidazolium-based ionic liquids (IL) with a nitrate anion have been experimentally determined: butylmethylimidazolium nitrate (BMImNO3) and hydroxypropylmethylimidazolium nitrate (HOPMImNO3), using a Cailletet apparatus that operates according to the synthetic method. CO2 concentrations from 5 up to 30 mol % were investigated. It was found that CO2 is substantially less soluble in HOPMImNO3 than in BMImNO3. Since these ILs are very hygroscopic, water easily can be a major contaminant, causing changes in the phase behavior. In case these Ils are to be used in practical applications, for instance, together with CO2 as a medium in supercritical enzymatic reactions, it is very important to have quantitative information on how the water content will affect the phase behavior. This work presents the first systematic study on the influence of water on the solubility of carbon dioxide in hygroscopic ILs. It was observed that the presence of water reduces the absolute solubility of CO2. However, at fixed ratios of CO2/IL, the bubble point pressure remains almost unchanged with increasing water content. In order to explain the experimental results, the densities of aqueous mixtures of both ILs were determined experimentally and the excess molar volumes calculated.

A toxicological assessment of Athrixia phylicoides aqueous extract following sub-chronic ingestion in a rat model.

Athrixia phylicoides is an aromatic, indigenous shrub used to brew "bush tea." Surveys have shown that the consumption of bush tea is widespread and commercialization of the extract holds economic and developmental potential. Aqueous extracts of A. phylicoides are non-toxic to brine shrimp and renal cell lines; however, verification in a mammalian model is needed. In this study, daily ingestion of high doses of aqueous A. phylicoides extract by mature Wistar rats was tested for potential toxicity over a 3-month period. Three-month-old Wistar rats were randomized into a control group (receiving no extract) and three experimental groups receiving 30, 90, or 180 mg dried aqueous A. phylicoides extract/kg body mass/day. After 90 days of daily extract ingestion, blood and tissue were harvested. There was no morbidity or mortality during the study. Food and water intake, as well as body mass and stool production, were unaffected by the consumption of the extract. Urine production was increased in the 90 and 180 mg/kg groups suggesting that A. phylicoides is mildly diuretic. Serum alkaline phosphatase, creatinine, and urea levels were normal for all groups. Histopathology showed no signs of any extract induced toxicity in the liver, kidneys, gastrointestinal tract, and other tissues studied.

Aspalathin, a C-glucosyl dihydrochalcone from rooibos improves the hypoglycemic potential of metformin in type 2 diabetic (db/db) mice.

Metformin is the first line therapy of type 2 diabetics, but continued reduction of their life expectancy warrants further investigation into alternative treatment strategies. This study reports on the combinational use of metformin with aspalathin, a C-glucosyl dihydrochalcone with known glucose lowering and antioxidant properties, as an effective hypoglycemic therapy in a type 2 diabetic (db/db) mouse model. When tested as a monotherapy, a low dose of aspalathin (13 mg/kg) showed no effect, while a high dose (130 mg/kg) has already displayed a better potential than metformin in protecting against diabetes associated symptoms in db/db mice. Thus, it remains of interest to determine whether this dihydrochalcone can improve the efficacy of metformin. The results showed that this combination therapy was more effective than the use of metformin as a monotherapy in ameliorating diabetes associated symptoms, including abnormal raised fasting plasma glucose levels, impaired glucose tolerance, as well as excessively increased body weights and fat content. The treated mice also had reduced food and water consumption when compared to untreated controls, with a pronounced effect evident in the last week of treatment. Therefore, this study supports further investigations into the ameliorative effect of combination therapy of metformin and aspalathin against diabetes associated symptoms.

MicroRNA Expression Varies according to Glucose Tolerance, Measurement Platform, and Biological Source.

Dysregulated microRNA (miRNA) expression is observed during type 2 diabetes (T2D), although the consistency of miRNA expression across measurement platform and biological source is uncertain. Here we report miRNA profiling in the whole blood and serum of South African women with different levels of glucose tolerance, using next generation sequencing (NGS) and quantitative real time PCR (qRT-PCR). Whole blood-derived miRNAs from women with newly diagnosed T2D (n = 4), impaired glucose tolerance (IGT) (n = 4), and normal glucose tolerance (NGT) (n = 4) were subjected to NGS, whereafter transcript levels of selected miRNAs were quantified in the whole blood and serum of these women using qRT-PCR. Of the five significantly differentially expressed miRNAs identified by NGS, only the directional increase of miR-27b in women with IGT compared to NGT was confirmed in whole blood and serum, using qRT-PCR. Functional enrichment of miR-27b gene targets identified biological pathways associated with glucose transport and insulin regulation. In conclusion, this study showed poor correlation in miRNA expression profiled using NGS and qRT-PCR and in whole blood and serum. The consistent increased expression of miR-27b in women with IGT compared to NGT across measurement platform and biological source holds potential as a biomarker for risk stratification in our population.

Polyphenols, autophagy and doxorubicin-induced cardiotoxicity.

Doxorubicin is a highly effective, first line chemotherapeutic agent used in the management of hematological and solid tumors. The effective use of doxorubicin in cancer therapy has been severely limited owing to its well-documented cardiotoxic side effect. Oxidative stress, lipid peroxidation, apoptosis as well as dysregulation of autophagy, has been implicated as a major contributor associated with doxorubicin-induced cardiotoxicity. Increased oxidative stress and lipid peroxidation are known to enhance the production of reactive oxygen species, while autophagy has been reported to protect the cell from stress stimuli or, alternatively, contribute to cell death. Nonetheless, to date, no single chemical synthesized drug is available to prevent the harmful action of doxorubicin without reducing its anti-cancer efficacy. Therefore, the search for an effective and safe antagonist of doxorubicin-induced cardiotoxicity remains a challenge. In recent years, there has been much interest in the role plant-derived polyphenols play in the regulation of oxidative stress and autophagy. Therefore, the present review renders a concise overview of the mechanism associated with doxorubicin-induced cardiotoxicity as well as giving insight into the role plant-derived phytochemical play as a possible adjunctive therapy against the development of doxorubicin-induced cardiotoxicity.

Solubility of Carbon Dioxide in Secondary Butyl Alcohol at High Pressures: Experimental and Modeling with CPA.

Mixtures of carbon dioxide and secondary butyl alcohol at high pressures are interesting for a range of industrial applications. Therefore, it is important to have trustworthy experimental data on the high-pressure phase behavior of this mixture over a wide range of temperatures. In addition, an accurate thermodynamic model is necessary for the optimal design and operation of processes. In this study, bubble points of binary mixtures of CO2 + secondary butyl alcohol were measured using a synthetic method. Measurements covered a CO2 molar concentration range of (0.10-0.57) % and temperatures from (293 to 370) K, with pressures reaching up to 11 MPa. The experimental data were modelled by the cubic plus association (CPA) equation of state (EoS), as well as the more simple Soave-Redlich-Kwong (SRK) EoS. Predictive and correlative modes were considered for both models. In the predictive mode, the CPA performs better than the SRK because it also considers associations.

Risperidone-associated adverse drug reactions and CYP2D6 polymorphisms in a South African cohort.

BACKGROUND: Contradictory information exists regarding the influence of CYP2D6 polymorphisms on adverse drug reactions (ADRs) (extrapyramidal symptoms (EPS) and weight gain) related to risperidone treatment. This prompted us to evaluate the influence of CYP2D6 genetic variation in a cohort of South African patients who presented with marked movement disorders and/or weight gain while on risperidone treatment. METHODS: Patients who were experiencing marked risperidone ADRs were recruited from Weskoppies Public Psychiatric Hospital. As poor or intermediate metabolism was expected, comprehensive CYP2D6 sequence variations were evaluated using XL-PCR + Sequencing. RESULTS: No statistically significant association was found between CYP2D6 poor metabolism and risperidone ADRs. An inverse relationship between EPS and weight gain was however identified. A novel CYP2D6 allele was identified which is unlikely to affect metabolism based on in silico evaluation. CONCLUSION: CYP2D6 variation appeared not to be a good pharmacogenetic marker for predicting risperidone-related ADRs in this naturalistic South African cohort. Evaluation of a larger cohort would be needed to confirm these observations, including an examination of the role of potential intermediaries between the hypothesised genetic and clinical phenotypes.

A trial of lansoprazole in refractory gastric ulcer.

BACKGROUND: The proton-pump inhibitor, lansoprazole, a more potent gastric acid inhibitor with a longer action than H2-receptor antagonists, should heal refractory gastric ulcers more effectively. METHODS: Lansoprazole's efficacy in healing refractory gastric ulcer(s) (i.e. after 6 weeks of treatment with H2-receptor antagonists, antacids or sucralfate at recommended dosages, and/or a relapse within 1 year of documented gastric ulcer), was compared by a two-dose regimen in a four-centre, randomized, parallel group study. One hundred and eighteen patients (59 per group) with an endoscopically confirmed gastric ulcer > or = 3 mm, received lansoprazole 30 or 60 mg daily. We assessed efficacy endoscopically at 4 and 8 weeks, and again after documented healing during a maintenance phase of lansoprazole 30 mg/day at 2 and 4 months. RESULTS: Demographic and anthropometric data were comparable. Healing rates at 4 weeks were 63% (30 mg) vs. 66% (60 mg) (95% CI, -14 to 21%) and cumulatively at 8 weeks, 83% (30 mg) vs. 81% (60 mg) (95% CI, -12 to 16%). Two and 4 months after documented healing, 86% and 78% of intention-to-treat patients remained in remission. CONCLUSION: Lansoprazole 30 or 60 mg/day appear equally effective in healing refractory gastric ulcers, while maintenance therapy of 30 mg/day effectively prevented an ulcer relapse.

Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co-therapy with amoxycillin and clarithromycin.

BACKGROUND: Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication. AIM: To compare the eradication and duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based combination therapies. METHODS: Healthy adult patients with endoscopically confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study. All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry and 14-17 days later. Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site). RESULTS: Sixty-two patients were randomized to a treatment arm, of which 58 could be included in an intention-to-treat and key-point-available analysis. H. pylori eradication rates were identical, at 93% (95% CI: 73-98% (1 week), 78-99% (2 week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal. CONCLUSION: An eradication regimen, based on a 2-week course of single dose lansoprazole with 1 week of antibiotic co-therapy, is effective in eradicating H. pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing.

Helicobacter pylori lipopolysaccharide stimulates gastric mucosal pepsinogen secretion.

The effect of Helicobacter pylori lipopolysaccharide on guinea pig gastric mucosal pepsinogen secretion has been examined using an Ussing chamber technique. Luminal addition of H. pylori lipopolysaccharide resulted in a fifty-fold stimulation of pepsinogen secretion compared to a twelve-fold increase with E. coli lipopolysaccharide. Electron microscopy showed marked degranulation of zymogen granules but no evidence of chief cell disruption.