Challenges in recruiting children to a multidrug-resistant TB prevention trial.

BACKGROUND: Recruitment to randomised clinical trials can be challenging and slow recruitment has serious consequences. This study aimed to summarise and reflect on the challenges in enrolling young children to a multidrug-resistant TB (MDR-TB) prevention trial in South Africa.METHODS: Recruitment to the Tuberculosis Child Multidrug-resistant Preventive Therapy Trial (TB-CHAMP) was tracked using an electronic recruiting platform, which was used to generate a recruiting flow diagram. Structured personnel questionnaires, meeting minutes and workshop notes were thematically analysed to elucidate barriers and solutions.RESULT: Of 3,682 (85.3%) adult rifampicin (RIF) resistant index cases with pre-screening outcomes, 1597 (43.4%) reported having no children under 5 years in the household and 562 (15.3%) were RIF-monoresistant. More than nine index cases were pre-screened for each child enrolled. Numerous barriers to recruitment were identified. Thorough recruitment planning, customised tracking data systems, a dedicated recruiting team with strong leadership, adequate resources to recruit across large geographic areas, and excellent relationships with routine TB services emerged as key factors to ensure successful recruitment.CONCLUSION: Recruitment of children into MDR-TB prevention trials can be difficult. Several MDR-TB prevention trials are underway, and lessons learnt from TB-CHAMP will be relevant to these and other TB prevention studies.

Characteristics and drinking behaviour of patients on antiretroviral therapy who drink and attend HIV clinics in Tshwane, South Africa: Implications for intervention.

BACKGROUND: Patients on antiretroviral therapy (ART) who drink alcohol are at risk of poor medication adherence and negative health outcomes. OBJECTIVES: To explore the drinking behaviour of patients on ART and assess the associations between drinking, adherence to ART and viral load, and in particular factors associated with binge drinking (≥6 drinks per occasion) at least monthly. METHODS: We recruited 623 HIV patients from six hospitals in the Tshwane metropole who scored positive on the Alcohol Use Disorders Identification Test (AUDIT-C) but were 'non-dependent' drinkers into a randomised controlled trial. This article reports on baseline data. RESULTS: Of the patients, 51% reported drinking in the past week, 60% of men and 33% of women consumed ≥6 standard drinks on a typical drinking day, and 19% of men and 5% of women were identified as drinking at harmful levels. Over a quarter reported having a friend or relative, or a doctor or other healthcare worker, express concern about their drinking or suggest that they cut down. AUDIT total scores were significantly negatively correlated with self-reported adherence to ART and positively correlated with viral load. Number of years on ART was not significantly associated with binge drinking. Persons who were employed part time (odds ratio (OR) 1.474) or were self-employed (OR 2.135) were more likely to binge-drink than unemployed persons. Beer drinkers (OR 1.716) were more at risk for binge drinking than non-beer drinkers, and persons who drank monthly or less (OR 0.053) or 2 - 4 times a month (OR 0.168) were less at risk for bingeing than those who drank ≥4 times per week. CONCLUSIONS: The high volume of alcohol consumed per occasion by patients on ART, especially beer and spirits drinkers, is a concern. Interventions that address structural drivers of heavy drinking and target HIV patients at risk of heavy drinking are needed.

Screening and managing a low-risk pregnant population using continuous-wave Doppler ultrasound in a low-income population: A cohort analytical study.

BACKGROUND: In South Africa (SA), the largest category of perinatal deaths is unexplained stillbirths. Two-thirds of these occur in the antenatal period and most fetuses are macerated, but at antenatal clinics the mothers were generally regarded as healthy, with low-risk pregnancies. Innovative methods are urgently required to detect fetuses at risk of stillbirth and manage the mothers appropriately. OBJECTIVES: To determine the prevalence of raised resistance indices (RIs) of the umbilical artery in a low-risk, low-income population and ascertain whether use of this information can prevent perinatal deaths. METHODS: A descriptive study was performed in Mamelodi township, east of Pretoria, SA, on pregnant women attending antenatal clinics draining to two community health centres (CHCs). These women, classified as having low-risk pregnancies, were screened for placental insufficiency using a continuous-wave Doppler ultrasound apparatus (Umbiflow) between 28 and 32 weeks' gestation. When a raised RI was detected, the mother was referred to a high-risk clinic and managed according to a standard protocol. A cohort analytical study compared women who attended antenatal care at the same clinics as the Umbiflow group but did not have an Umbiflow test with those who had an Umbiflow test. The outcomes of all the deliveries in Mamelodi were recorded. The prevalences of abnormal RIs, absent end-diastolic flow (AEDF), stillbirths and neonatal deaths were the main outcome measures. RESULTS: An Umbiflow RI was performed in 2 868 women, and pregnancy outcome was available for 2 539 fetuses (88.5%); 297 fetuses (11.7%) were regarded as at high risk. AEDF was found in 1.5% of the population screened with an outcome. There were 29 perinatal deaths in the Umbiflow group (low risk n=18, high risk n=11). The perinatal mortality rate for 12 168 women attending the CHCs and the antenatal clinics draining to the CHCs who did not have an RI was 21.3/1 000 births, significantly higher than that in the Umbiflow group (11.4/1 000 births) (risk ratio 0.58, 95% confidence interval 0.42 - 0.81). CONCLUSIONS: The prevalence of AEDF in this low-risk population is ~10 times higher than that previously recorded. Use of the information prevented a number of perinatal deaths, most of which would have been macerated stillbirths. Screening a low-risk pregnant population using continuous-wave Doppler ultrasound may substantially reduce the prevalence of unexplained stillbirths in SA.

Acceptability of obtaining hair samples for assessing antiretroviral therapy (ART) exposure amongst alcohol drinking ART recipients in Tshwane, South Africa.

To achieve the maximal therapeutic benefits of antiretroviral therapy (ART), high adherence is required. In South Africa, ART recipients are usually counselled by their health care providers to stop drinking alcohol, as heavy alcohol use compromises ART adherence. Patients who continue drinking alcohol tend to hide their alcohol-related adherence challenges from their health care providers. Objective measures of ART adherence/exposure may help to better identify drinkers who could benefit from ART adherence enhancement interventions. To evaluate the acceptability of collecting hair samples to objectively assess ART exposure among alcohol drinkers, we conducted four mixed-gender focus group discussions (FGDs) with alcohol drinking ART recipients at two ART sites in Tshwane, South Africa. Data were analysed using content analysis. ART recipients found hair sample testing for ART exposure to be novel and therefore expected that some ART recipients would initially be hesitant to provide a sample. Participants thought that the acceptability of hair sample collection could be enhanced by providing a full explanation of how the hair sample would be obtained and what the testing would entail. Participants also viewed hair sample testing as a viable and desirable alternative to blood sample testing for ART exposure. Some worries about the possible use of hair samples for witchcraft and the symbolic nature of hair were brought up, but these were not seen as insurmountable concerns. In conclusion, hair sample testing is a potentially acceptable method of assessing ART exposure amongst ART recipients who drink alcohol.

Life cycle assessment of facile microwave-assisted zinc oxide (ZnO) nanostructures.

The life cycle assessment of several zinc oxide (ZnO) nanostructures, fabricated by a facile microwave technique, is presented. Key synthesis parameters such as annealing temperature, varied from 90°C to 220°C, and microwave power, varied from 110W to 710W, are assessed. The effect of these parameters on both the structural characteristics and the environmental sustainability of the nanostructures is examined. The nanostructures were characterized by means of X-ray diffraction (XRD), focused ion beam scanning electron microscopy (FIB-SEM), ultraviolet-visible spectroscopy (UV-Vis), Photoluminescence (PL) and Brunauer-Emmett-Teller (BET) analysis. Crystalline size was found to be 22.40nm at 110W microwave power, 24.83nm at 310W, and 24.01nm at 710W. Microwave power and synthesis temperature were both directly proportional to the surface area. At 110W the surface area was 10.44m2/g, at 310W 12.88m2/g, and at 710W 14.60m2/g; while it was found to be 11.64m2/g at 150°C and 18.09m2/g at 220°C. Based on these, a life cycle analysis (LCA) of the produced ZnO nanoparticles was carried out, using the ZnO surface area (1m2/g) as the functional unit. It was found that the main environmental weaknesses identified during the production process were; (a) the use of ethanol for purifying the produced nanomaterials and (b) the electricity consumption for the ZnO calcination, provided by South Africa's fossil-fuel dependent electricity source. When the effect of the key synthesis parameters on environmental sustainability was examined it was found that an increase of either microwave power (from 110 to 710W) or synthesis temperatures (from 90 to 220°C), results in higher sustainability, with the environmental footprint reduced by 27% and 41%, respectively. Through a sensitivity analysis, it was observed that an electricity mix based on renewable energy could improve the environmental sustainability of the nanoparticles by 25%.

Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of novel quinoline bearing dihydropyridines.

A new series of eight quinoline bearing dihydropyridine derivatives (A1-A8) were synthesized in high yield and in short reaction time by a four component reaction of 2-chloro-3-fomyl quinoline, malononitrile, arylamines and dimethyl acetylenedicarboxylate in the presence of a catalytic amount of triethylamine. The compounds were fully characterized by IR, NMR and GC-MS. These compounds were screened for potential biological activity in an A549 lung cancer cell line and were also evaluated for their antibacterial activities against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 whilst their molecular docking properties in an enzymatic system were also determined. Compounds A2, A3, A4 and A8 showed anti-proliferative activity; with A4 having the highest toxicity at 250µg/mL and A8 has high toxicity at 125, 250 and 500µg/mL, respectively. Antibacterial results indicated that A4 have significant activity against tested microorganisms at the minimum inhibitory concentration (MIC) values of 32µg/mL against Pseudomonas aeruginosa and Escherichia coli, and 16µg/mL against Staphylococcus aureus. Docking of A1 with human mdm2 indicated the lowest binding energy (-6.111Kcal/mol) thereby showing strong affinity of the ligand molecule with the receptor which has been stabilized by strong hydrogen bond interactions in the binding pocket. This confirms that A1 is a better inhibitor for E3 ubiquitin-protein ligase mdm2.

Shape-selective dependence of room temperature ferromagnetism induced by hierarchical ZnO nanostructures.

We report on the room temperature ferromagnetism of various highly crystalline zinc oxide (ZnO) nanostructures, such as hexagonally shaped nanorods, nanocups, nanosamoosas, nanoplatelets, and hierarchical nano "flower-like" structures. These materials were synthesized in a shape-selective manner using simple microwave assisted hydrothermal synthesis. Thermogravimetric analyses demonstrated the as-synthesized ZnO nanostructures to be stable and of high purity. Structural analyses showed that the ZnO nanostructures are polycrystalline and wurtzite in structure, without any secondary phases. Combination of electron paramagnetic resonance, photoluminescence, and X-ray photoelectron spectroscopy studies revealed that the zinc vacancies (VZn) and singly ionized oxygen vacancies (VO(+)) located mainly on the ZnO surface are the primary defects in ZnO structures. A direct link between ferromagnetism and the relative occupancy of the VZn and VO(+) was established, suggesting that both VZn and VO(+) on the ZnO surface plays a vital role in modulating ferromagnetic behavior. An intense structure- and shape-dependent ferromagnetic signal with an effective g-value of >2.0 and a sextet hyperfine structure was shown. Moreover, a novel low field microwave absorption signal was observed and found to increase with an increase in microwave power and temperature.