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.

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.

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.