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1.  Patient‐reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life 
Lane, Athene | Metcalfe, Chris | Young, Grace J. | Peters, Tim J. | Blazeby, Jane | Avery, Kerry N. L. | Dedman, Daniel | Down, Liz | Mason, Malcolm D. | Neal, David E. | Hamdy, Freddie C. | Donovan, Jenny L. | Bonnington, Sue | Bradshaw, Lynne | Cooper, Debbie | Elliott, Emma | Herbert, Pippa | Holding, Peter | Howson, Joanne | Jones, Mandy | Lennon, Teresa | Lyons, Norma | Moody, Hilary | Plumb, Claire | O'Sullivan, Tricia | Salter, Liz | Tidball, Sarah | Thompson, Pauline | Adam, Tonia | Askew, Sarah | Atkinson, Sharon | Baynes, Tim | Blaikie, Jan | Brain, Carole | Breen, Viv | Brunt, Sarah | Bryne, Sean | Bythem, Jo | Clarke, Jenny | Cloete, Jenny | Dark, Susan | Davis, Gill | De La Rue, Rachael | Denizot, Jane | Dewhurst, Elspeth | Dimes, Anna | Dixon, Nicola | Ebbs, Penny | Emmerson, Ingrid | Ferguson, Jill | Gadd, Ali | Geoghegan, Lisa | Grant, Alison | Grant, Collette | Gray, Catherine | Godfrey, Rosemary | Goodwin, Louise | Hall, Susie | Hart, Liz | Harvey, Andrew | Hoult, Chloe | Hawkins, Sarah | Holling, Sharon | Innes, Alastair | Kilner, Sue | Marshall, Fiona | Mellen, Louise | Moore, Andrea | Napier, Sally | Needham, Julie | Pearse, Kevin | Pisa, Anna | Rees, Mark | Richards, Elliw | Robson, Lindsay | Roxburgh, Janet | Samuel, Nikki | Sharkey, Irene | Slater, Michael | Smith, Donna | Taggart, Pippa | Taylor, Helen | Taylor, Vicky | Thomas, Ayesha | Tomkies, Briony | Trewick, Nicola | Ward, Claire | Walker, Christy | Williams, Ayesha | Woodhouse, Colin | Wyber, Elizabeth | Aning, Jonathan | Bollina, Prasad | Catto, Jim | Doble, Andrew | Doherty, Alan | Durkan, Garett | Gillatt, David | Hughes, Owen | Kocklebergh, Roger | Kouparis, Anthony | Kynaston, Howard | Leung, Hing | Mariappan, Param | McNeill, Alan | Paez, Edgar | Paul, Alan | Persad, Raj | Powell, Philip | Prescott, Stephen | Rosario, Derek | Rowe, Edward | Schwaibold, Hartwig | Tulloch, David | Wallace, Mike | Bahl, Amit | Benson, Richard | Beresford, Mark | Ferguson, Catherine | Graham, John | Herbert, Chris | Howard, Grahame | James, Nick | Law, Alastair | Loughrey, Carmel | McClaren, Duncan | Patterson, Helen | Pedley, Ian | Robinson, Angus | Russell, Simon | Staffurth, John | Symonds, Paul | Thanvi, Narottam | Vasanthan, Subramaniam | Wilson, Paula | Appleby, Helen | Ash, Dominic | Aston, Dean | Bolton, Steven | Chalmers, Graham | Conway, John | Early, Nick | Geater, Tony | Goddall, Lynda | Heymann, Claire | Hicks, Deborah | Jones, Liza | Lamb, Susan | Lambert, Geoff | Lawrence, Gill | Lewis, Geraint | Lilley, John | MacLeod, Aileen | Massey, Pauline | McQueen, Alison | Moore, Rollo | Penketh, Lynda | Potterton, Janet | Roberts, Neil | Showler, Helen | Slade, Stephen | Steele, Alasdair | Swinscoe, James | Tiffany, Marie | Townley, John | Treeby, Jo | Wilkinson, Joyce | Williams, Lorraine | Wills, Lucy | Woodley, Owain | Yarrow, Sue | Bhattarai, Selina | Deshmukh, Neeta | Dormer, John | Fernando, Malee | Goepel, John | Griffiths, David | Grigor, Ken | Mayer, Nick | Oxley, Jon | Robinson, Mary | Varma, Murali | Warren, Anne | Brindle, Lucy | Davis, Michael | Khazragui, Hanan | Noble, Sian | Taylor, Hilary | Tazewell, Marta | Turner, Emma | Wade, Julia | Walsh, Eleanor | Baker, Susan | Bellis‐Sheldon, Elizabeth | Bougard, Chantal | Bowtell, Joanne | Brewer, Catherine | Burton, Chris | Charlton, Jennie | Christoforou, Nicholas | Clark, Rebecca | Coull, Susan | Croker, Christine | Currer, Rosemary | Daisey, Claire | Delaney, Gill | Donohue, Rose | Drew, Jane | Farmer, Rebecca | Fry, Susan | Haddow, Jean | Hale, Alex | Halpin, Susan | Harris, Belle | Hattrick, Barbara | Holmes, Sharon | Hunt, Helen | Jackson, Vicky | Johnson, Donna | Le Butt, Mandy | Leworthy, Jo | Liddiatt, Tanya | Martin, Alex | Mauree, Jainee | Moore, Susan | Moulam, Gill | Mutch, Jackie | Nash, Alena | Parker, Kathleen | Pawsey, Christopher | Purdie, Michelle | Robson, Teresa | Smith, Lynne | Snoeck, Jo | Stenton, Carole | Steuart‐Feilding, Tom | Sully, Chris | Sutton, Caroline | Torrington, Carol | Wilkins, Zoe | Williams, Sharon | Wilson, Andrea | Grant, Adrian | Roberts, Ian | Ashby, Deborah | Cowan, Richard | Fayers, Peter | Mellon, Killian | N'Dow, James | O'Brien, Tim | Sokhal, Michael | Baum, Michael | Adolfson, Jan | Albertsen, Peter | Dearnaley, David | Schroeder, Fritz | Roberts, Tracy | Zietman, Anthony
Bju International  2016;118(6):869-879.
To present the baseline patient‐reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external‐beam conformal radiotherapy for localized prostate cancer and to compare results with other populations.
Materials and Methods
A total of 1643 randomized men, aged 50–69 years and diagnosed with clinically localized disease identified by prostate‐specific antigen (PSA) testing, in nine UK cities in the period 1999–2009 were included. Validated PROMs for disease‐specific (urinary, bowel and sexual function) and condition‐specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire‐Urinary Incontinence [ICIQ‐UI], 2001 onwards; the International Continence Society short‐form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12‐item short‐form health survey [SF‐12]; EuroQol quality‐of‐life survey, the EQ‐5D‐3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men's age at biopsy and PSA testing time points for selected measures.
A total of 1438 participants completed biopsy questionnaires (88%) and 77–88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65–70 years), whilst urinary bother and physical health were somewhat worse than in younger men (49–54 years, all P < 0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (P < 0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments.
The ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were similar to those observed in populations screened for prostate cancer and control subjects without cancer.
PMCID: PMC5113698  PMID: 27415448
prostate cancer; treatment; functional status; quality of life; protect trial; ISRCTN 20141297
2.  Record linkage to correct under‐ascertainment of cancers in HIV cohorts: The Sinikithemba HIV clinic linkage project 
International Journal of Cancer  2016;139(6):1209-1216.
The surveillance of HIV‐related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu‐Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage (PRL) methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non‐Hodgkin's lymphoma and non‐AIDS defining cancers (NADCs) before and after inclusion of linkage‐identified cancers with 95% confidence intervals (CIs). A total of 8,721 records of HIV‐positive patients were linked with 35,536 cancer records. Between 2004 and 2010, we identified 448 cancers, 82% (n = 367) were recorded in the cancer registry only, 10% (n = 43) in the HIV cohort only and 8% (n = 38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91–212) to 877 (95% CI 744–1,041) per 100,000 person‐years after inclusion of linkage‐identified cancers. Incidence rates were highest for KS (432, 95% CI 341–555), followed by cervix (259, 95% CI 179–390) and NADCs (294, 95% CI 223–395) per 100,000 person‐years. Ascertainment of cancer in HIV cohorts is incomplete, PRL is both feasible and essential for cancer ascertainment.
What's new?
The surveillance of HIV‐related cancers is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. While probabilistic record linkage has been widely used in Europe and America, it has not been fully exploited in resource‐limited settings. This study demonstrates the utility of record linkage in correcting under‐ascertainment of cancers in HIV cohorts and a high cancer incidence among HIV‐positive patients on antiretroviral therapy in South Africa. There is a need for a systematic approach to cancer surveillance in HIV‐positive people in the South African antiretroviral therapy era.
PMCID: PMC5084785  PMID: 27098265
record linkage; HIV; cancer; South Africa
3.  Molecular detection of Acanthamoeba spp., Naegleria fowleri and Vermamoeba (Hartmannella) vermiformis as vectors for Legionella spp. in untreated and solar pasteurized harvested rainwater 
Parasites & Vectors  2016;9:539.
Legionella spp. employ multiple strategies to adapt to stressful environments including the proliferation in protective biofilms and the ability to form associations with free-living amoeba (FLA). The aim of the current study was to identify Legionella spp., Acanthamoeba spp., Vermamoeba (Hartmannella) vermiformis and Naegleria fowleri that persist in a harvested rainwater and solar pasteurization treatment system.
Pasteurized (45 °C, 65 °C, 68 °C, 74 °C, 84 °C and 93 °C) and unpasteurized tank water samples were screened for Legionella spp. and the heterotrophic plate count was enumerated. Additionally, ethidium monoazide quantitative polymerase chain reaction (EMA-qPCR) was utilized for the quantification of viable Legionella spp., Acanthamoeba spp., V. vermiformis and N. fowleri in pasteurized (68 °C, 74 °C, 84 °C and 93 °C) and unpasteurized tank water samples, respectively.
Of the 82 Legionella spp. isolated from unpasteurized tank water samples, Legionella longbeachae (35 %) was the most frequently isolated, followed by Legionella norrlandica (27 %) and Legionella rowbothamii (4 %). Additionally, a positive correlation was recorded between the heterotrophic plate count vs. the number of Legionella spp. detected (ρ = 0.710, P = 0.048) and the heterotrophic plate count vs. the number of Legionella spp. isolated (ρ = 0.779, P = 0.0028) from the tank water samples collected. Solar pasteurization was effective in reducing the gene copies of viable V. vermiformis (3-log) and N. fowleri (5-log) to below the lower limit of detection at temperatures of 68–93 °C and 74–93 °C, respectively. Conversely, while the gene copies of viable Legionella and Acanthamoeba were significantly reduced by 2-logs (P = 0.0024) and 1-log (P = 0.0015) overall, respectively, both organisms were still detected after pasteurization at 93 °C.
Results from this study indicate that Acanthamoeba spp. primarily acts as the vector and aids in the survival of Legionella spp. in the solar pasteurized rainwater as both organisms were detected and were viable at high temperatures (68–93 °C).
PMCID: PMC5057267  PMID: 27724947
Rainwater harvesting; Solar pasteurization; Legionella; Acanthamoeba; Vermamoeba; Naegleria
4.  Draft Genome Sequence of Alternaria alternata Isolated from Onion Leaves in South Africa 
Genome Announcements  2016;4(5):e01022-16.
Alternaria alternata (Fr.) Keissler strain PPRI 21032 was isolated from onion leaves collected in Roodeplaat, Pretoria, South Africa. The whole genome of this strain was sequenced and produced a total of 33.12 Mb with a GC content of 50.9%. The whole genome comprises 11,701 predicted coding sequences.
PMCID: PMC5034144  PMID: 27660793
5.  Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs 
Scientific Reports  2016;6:27311.
To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1–2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways.
PMCID: PMC4893621  PMID: 27265371
6.  Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial 
Trials  2016;17:123.
A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The ‘Prostate Cancer: Evidence of Exercise and Nutrition Trial’ investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures.
The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation).
The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery.
Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.
PMCID: PMC4780152  PMID: 26948468
Cohort; Randomised control trial; Prostate cancer; Radical prostatectomy; Physical activity; Nutrition; Intervention
7.  Resistance related metabolic pathways for drug target identification in Mycobacterium tuberculosis 
BMC Bioinformatics  2016;17:75.
Increasing resistance to anti-tuberculosis drugs has driven the need for developing new drugs. Resources such as the tropical disease research (TDR) target database and AssessDrugTarget can help to prioritize putative drug targets. Hower, these resources do not necessarily map to metabolic pathways and the targets are not involved in dormancy. In this study, we specifically identify drug resistance pathways to allow known drug resistant mutations in one target to be offset by inhibiting another enzyme of the same metabolic pathway. One of the putative targets, Rv1712, was analysed by modelling its three dimensional structure and docking potential inhibitors.
We mapped 18 TB drug resistance gene products to 15 metabolic pathways critical for mycobacterial growth and latent TB by screening publicly available microarray data. Nine putative targets, Rv1712, Rv2984, Rv2194, Rv1311, Rv1305, Rv2195, Rv1622c, Rv1456c and Rv2421c, were found to be essential, to lack a close human homolog, and to share >67 % sequence identity and >87 % query coverage with mycobacterial orthologs. A structural model was generated for Rv1712, subjected to molecular dynamic simulation, and identified 10 compounds with affinities better than that for the ligand cytidine-5′-monophosphate (C5P). Each compound formed more interactions with the protein than C5P.
We focused on metabolic pathways associated with bacterial drug resistance and proteins unique to pathogenic bacteria to identify novel putative drug targets. The ten compounds identified in this study should be considered for experimental studies to validate their potential as inhibitors of Rv1712.
Electronic supplementary material
The online version of this article (doi:10.1186/s12859-016-0898-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4745158  PMID: 26856535
8.  Indicated Prevention of Fetal Alcohol Spectrum Disorders in South Africa: Effectiveness of Case Management 
In the Western Cape Province of South Africa (ZA) a subculture of binge drinking produces the highest global documented prevalence of fetal alcohol spectrum disorders (FASD). FASD prevention research activities in ZA use the Comprehensive Prevention approach from the United States Institute of Medicine. Case management (CM) was delivered as a method of indicated prevention to empower heavy drinking pregnant women to achieve cessation or a reduction in drinking. CM activities incorporated life management, Motivational Interviewing (MI) techniques and the Community Reinforcement Approach (CRA). Data were collected at baseline, 6, 12 and 18 months. Mean drinking decreases 6 months into CM; but overall alcohol consumption rose significantly over time to levels higher than baseline at 12 and 18 months. Alcohol consumption drops significantly from before pregnancy to the second and third trimesters. AUDIT scores indicate that problematic drinking decreases significantly even after the vulnerable fetus/baby was born. CM significantly increases client happiness, which correlates with reduced weekend drinking. CM was successful for women with high-risk drinking behaviour, and was effective in helping women stop drinking, or drink less, while pregnant, reducing the risk of FASD.
PMCID: PMC4730467  PMID: 26703708
alcohol exposure; case management; pregnancy; happiness; fetal alcohol spectrum disorders; South Africa; reduction in alcohol consumption
9.  HIV Risk Among Men Who Have Sex With Men, Women Who Have Sex With Women, Lesbian, Gay, Bisexual and Transgender Populations in South Africa: A Mini-Review 
The Open AIDS Journal  2016;10:49-64.
The HIV epidemic in South Africa is characterized mainly by heterosexual transmission. Recently, the importance of targeting key populations and marginalized groups, including men who have sex with men (MSM) and transgender people, has been added to the national agenda.
This mini-review explores the current state of empirical research on HIV risk and MSM, women who have sex with women (WSW), lesbian, gay, bisexual and transgender (LGBT) populations in South Africa in order to assess the current state of research and identify gaps in the literature.
Peer-reviewed empirical social and behavioral articles on HIV prevalence and risk focusing on MSM, WSW, and LGBT populations published since 2006 were included in this mini-review.
In total 35 articles were included: 30 on MSM, gay, and/or bisexual male-identified populations, three on WSW, lesbian, and/or bisexual female-identified populations, two on LGB youth, and none on transgender populations.
Despite South Africa being the country with the largest number of people living with HIV in the world, there is a limited amount of research in South Africa on HIV and non-normative gender identities and sexualities, especially WSW, lesbian, and/or bisexual female-identified populations, transgender populations, and LGB youth. Research with MSM, WSW, and LGBT populations should be prioritized in South Africa in order to appropriately inform HIV prevention strategies that meet the specific needs of these marginalized groups.
PMCID: PMC4893624  PMID: 27347271
Bisexuality; HIV; Homosexuality; Men who have sex with men; South Africa; Transgender persons; Women who have sex with women
10.  Fatal attraction: vegetation responses to nutrient inputs attract herbivores to infectious anthrax carcass sites 
Parasites can shape the foraging behaviour of their hosts through cues indicating risk of infection. When cues for risk co-occur with desired traits such as forage quality, individuals face a trade-off between nutrient acquisition and parasite exposure. We evaluated how this trade-off may influence disease transmission in a 3-year experimental study of anthrax in a guild of mammalian herbivores in Etosha National Park, Namibia. At plains zebra (Equus quagga) carcass sites we assessed (i) carcass nutrient effects on soils and grasses, (ii) concentrations of Bacillus anthracis (BA) on grasses and in soils, and (iii) herbivore grazing behaviour, compared with control sites, using motion-sensing camera traps. We found that carcass-mediated nutrient pulses improved soil and vegetation, and that BA is found on grasses up to 2 years after death. Host foraging responses to carcass sites shifted from avoidance to attraction, and ultimately to no preference, with the strength and duration of these behavioural responses varying among herbivore species. Our results demonstrate that animal carcasses alter the environment and attract grazing hosts to parasite aggregations. This attraction may enhance transmission rates, suggesting that hosts are limited in their ability to trade off nutrient intake with parasite avoidance when relying on indirect cues.
PMCID: PMC4213624  PMID: 25274365
anthrax; camera traps; disease transmission; foraging ecology; host–pathogen contact; parasite avoidance
11.  Diagnostic delays and clinical decision-making with centralized Xpert MTB/RIF testing in Durban, South Africa 
We conducted a retrospective study among HIV-infected adult (≥18 years) pulmonary tuberculosis (TB) suspects who underwent Xpert MTB/RIF (Xpert) testing at McCord Hospital and its adjoining HIV clinic in Durban, South Africa.
To determine if Xpert testing performed at a centralized laboratory accelerated time to TB diagnosis.
We obtained data on sputum smear microscopy (AFB), Xpert and the rationale for treatment initiation from medical records. The primary outcome was “total diagnostic time,” defined as time from sputum collection to clinicians’ receipt of results. A linear mixed-effects model compared the duration of steps in the diagnostic pathway across testing modalities.
Among 403 participants, the median “total diagnostic time” for AFB and Xpert was 3.3 and 6.4 days, respectively (P <0.001). When compared to AFB, the median delay for Xpert “laboratory processing” was 1.4 days (P<0.001) and “result transfer to clinic” was 1.7 days (P<0.001). Among 86 Xpert-positive participants who initiated treatment, 49 (57%) started treatment based on clinical suspicion or AFB-positive results, while only 32 (37%) started treatment based on Xpert-positive results.
In our setting, Xpert results took twice as long as AFB results to reach clinicians. Replacing AFB with centralized Xpert may delay TB diagnoses in some settings.
PMCID: PMC4197409  PMID: 25314255
Tuberculosis; HIV/AIDS; Xpert MTB/RIF assay; diagnostic testing; South Africa
12.  Point-of-Care Clinical Ultrasound for Medical Students 
Ultrasound International Open  2015;1(2):E58-E66.
Our institution has recently implemented a point-of-care (POC) ultrasound training program, consisting of an e-learning course and systematic practical hands-on training. The aim of this prospective study was to evaluate the learning outcome of this curriculum.
Materials and Methods:
16 medical students with no previous ultrasound experience comprised the study group. The program covered a combination of 4 well-described point-of-care (POC) ultrasound protocols (focus assessed transthoracic echocardiography, focused assessment with sonography in trauma, lung ultrasound, and dynamic needle tip positioning for ultrasound-guided vascular access) and it consisted of an e-learning course followed by 4 h of practical hands-on training. Practical skills and image quality were tested 3 times during the study: at baseline, after e-learning, and after hands-on training.
Practical skills improved for all 4 protocols; after e-learning as well as after hands-on training. The number of students who were able to perform at least one interpretable image of the heart increased from 7 at baseline to 12 after e-learning, p<0.01, and to all 16 students after hands-on-training, p<0.01. The number of students able to cannulate an artificial vessel increased from 3 to 8 after e-learning and to 15 after hands-on training.
Medical students with no previous ultrasound experience demonstrated a considerable improvement in practical skill after interactive e-learning and 4 h of hands-on training.
PMCID: PMC5023212  PMID: 27689155
abdomen; heart; vascular; ultrasound
13.  Understanding HIV-infected patients’ experiences with PEPFAR-associated transitions at a Centre of Excellence in KwaZulu Natal, South Africa: a qualitative study 
AIDS care  2015;27(10):1298-1303.
South Africa was the largest recipient of funding from the President’s Emergency Plan for AIDS Relief (PEPFAR) for antiretroviral therapy (ART) programs from 2004–2012. Funding decreases have led to transfers from hospital and non-governmental organization-based care to government-funded, community-based clinics. We conducted semi-structured interviews with 36 participants to assess patient experiences related to transfer of care from a PEPFAR-funded, hospital-based clinic in Durban to either primary care clinics or hospital based clinics. Participant narratives revealed the importance of connectedness between patients and the PEPFAR-funded clinic program staff, who were described as respectful and conscientious. Participants reported that transfer clinics were largely focused on dispensing medication and on throughput, rather than holistic care. Although participants appreciated the free treatment at transfer sites, they expressed frustration with long waiting times and low perceived quality of patient-provider communication, and felt that they were treated disrespectfully. These factors eroded confidence in the quality of the care. The transfer was described by participants as hurried with an apparent lack of preparation at transfer clinics for new patient influx. Formal (e.g., counseling) and informal (e.g., family) social supports, both within and beyond the PEPFAR-funded clinic, provided a buffer to challenges faced during and after the transition in care. These data support the importance of social support, adequate preparation for transfer, and improving the quality of care in receiving clinics, in order to optimize retention in care and long-term adherence to treatment.
PMCID: PMC4548805  PMID: 26300297
South Africa; HIV; ART; Decentralization; PEPFAR; Transitions in care
14.  Hopkinson bar techniques for the intermediate strain rate testing of bovine cortical bone 
Detailed knowledge of the dynamic viscoelastic properties of bone is required to understand the mechanisms of macroscopic bone fracture in humans, and other terrestrial mammals, during impact loading events (e.g. falls, vehicle accidents, etc.). While the dynamic response of bone has been studied for several decades, high-quality data remain limited, and it is only within the last decade that techniques for conducting dynamic compression tests on bone at near-constant strain rates have been developed. Furthermore, there appears to be a lack of published bone data in the intermediate strain rate (ISR) range (i.e. 1–100 s−1), which represents a regime in which many dynamic bone fractures occur. In this paper, preliminary results for the dynamic compression of bovine cortical bone in the ISR regime are presented. The results are obtained using two Hopkinson-bar-related techniques, namely the conventional split Hopkinson bar arrangement incorporating a novel cone-in-tube striker design, and the recently developed wedge bar apparatus. The experimental results show a rapid transition in the strain rate sensitive behaviour of bovine cortical bone in the ISR range. Finally, a new viscoelastic model is proposed that captures the observed transition behaviour.
PMCID: PMC3982653  PMID: 24711493
Hopkinson bar; wedge bar; intermediate strain rate; bovine cortical bone; constitutive model; viscoelasticity
15.  Usability and Feasibility of PIERS on the Move: An mHealth App for Pre-Eclampsia Triage 
JMIR mHealth and uHealth  2015;3(2):e37.
Pre-eclampsia is one of the leading causes of maternal death and morbidity in low-resource countries due to delays in case identification and a shortage of health workers trained to manage the disorder. Pre-eclampsia Integrated Estimate of RiSk (PIERS) on the Move (PotM) is a low cost, easy-to-use, mobile health (mHealth) platform that has been created to aid health workers in making decisions around the management of hypertensive pregnant women. PotM combines two previously successful innovations into a mHealth app: the miniPIERS risk assessment model and the Phone Oximeter.
The aim of this study was to assess the usability of PotM (with mid-level health workers) for iteratively refining the system.
Development of the PotM user interface involved usability testing with target end-users in South Africa. Users were asked to complete clinical scenario tasks, speaking aloud to give feedback on the interface and then complete a questionnaire. The tool was then evaluated in a pilot clinical evaluation in Tygerberg Hospital, Cape Town.
After ethical approval and informed consent, 37 nurses and midwives evaluated the tool. During Study 1, major issues in the functionality of the touch-screen keyboard and date scroll wheels were identified (total errors n=212); during Study 2 major improvements in navigation of the app were suggested (total errors n=144). Overall, users felt the app was usable using the Computer Systems Usability Questionnaire; median (range) values for Study 1 = 2 (1-6) and Study 2 = 1 (1-7). To demonstrate feasibility, PotM was used by one research nurse for the pilot clinical study. In total, more than 500 evaluations were performed on more than 200 patients. The median (interquartile range) time to complete an evaluation was 4 min 55 sec (3 min 25 sec to 6 min 56 sec).
By including target end-users in the design and evaluation of PotM, we have developed an app that can be easily integrated into health care settings in low- and middle-income countries. Usability problems were often related to mobile phone features (eg, scroll wheels, touch screen use). Larger scale evaluation of the clinical impact of this tool is underway.
PMCID: PMC4417132  PMID: 25887292
pulse oximetry; mHealth app; predictive model; usability analysis; design methodology
16.  ‘We keep her status to ourselves’: Experiences of stigma and discrimination among HIV-discordant couples in South Africa, Tanzania and Ukraine 
Sahara J  2015;12(1):10-17.
In HIV-discordant relationships, the HIV-negative partner also carries the burden of a stigmatised disease. For this reason, couples often hide their HIV-discordant status from family, friends and community members. This perpetuates the silence around HIV-discordant relationships and impacts on targeted HIV prevention, treatment and counselling efforts. This article reports on experiences of stigma and discrimination among HIV-discordant couples in South Africa, Tanzania and Ukraine. During 2008, HIV-discordant couples who had been in a relationship for at least one year were recruited purposively through health-care providers and civil society organisations in the three countries. Participants completed a brief self-administered questionnaire, while semi-structured interviews were conducted with each partner separately and with both partners together. Interviews were analysed using thematic content analysis. Fifty-one couples were recruited: 26 from South Africa, 10 from Tanzania, and 15 from Ukraine. Although most participants had disclosed their HIV status to someone other than their partner, few were living openly with HIV discordance. Experiences of stigma were common and included being subjected to gossip, rumours and name-calling, and HIV-negative partners being labelled as HIV-positive. Perpetrators of discrimination included family members and health workers. Stigma and discrimination present unique and complex challenges to couples in HIV sero-discordant relationships in these three diverse countries. Addressing stigmatisation of HIV-discordant couples requires a holistic human rights approach and specific programme efforts to address discrimination in the health system.
PMCID: PMC4396513  PMID: 25778765
HIV-discordance; stigma; discrimination; couples; South Africa; Tanzania; Ukraine; sérodiscordants pour le VIH; stigmatisation; discrimination; couples; Afrique du Sud; Tanzanie; Ukraine
17.  Community-based mental health support for orphans and vulnerable children in South Africa: A triangulation study 
Community-based care is receiving increasing global attention as a way to support children who are orphaned or vulnerable due to the HIV/AIDS pandemic. Using both qualitative and quantitative methodology, this study assesses community-based responses to the well-being of orphans and vulnerable children (OVC) and compares these responses with the actual mental health of OVC in order to evaluate the South African government's approach of funding community-based organisations (CBOs) that support and care for OVC. The study results show that the activities of CBOs mainly extend government services and address poverty. Although this should not be seen as insignificant, the paper argues that CBOs give very little attention to the mental health of OVC.
PMCID: PMC4007579  PMID: 24799952
18.  Details for Manuscript Number SSM-D-06-00290R2 “Internalized Stigma, Discrimination, and Depression among Men and Women Living with HIV/AIDS in Cape Town, South Africa” 
Social science & medicine (1982)  2007;64(9):1823-1831.
AIDS stigmas interfere with HIV prevention, diagnosis and treatment and can become internalized by people living with HIV/AIDS. However, the effects of internalized AIDS stigmas have not been investigated in Africa, home to two-thirds of the more than 40 million people living with AIDS in the world. The current study examined the prevalence of discrimination experiences and internalized stigmas among 420 HIV positive men and 643 HIV positive women recruited from AIDS services in Cape Town, South Africa. The anonymous surveys found that 40% of persons with HIV/AIDS had experienced discrimination resulting from having HIV infection and one in five had lost a place to stay or a job because of their HIV status. More than one in three participants indicated feeling dirty, ashamed, or guilty because of their HIV status. A hierarchical regression model that included demographic characteristics, health and treatment status, social support, substance use, and internalized stigma significantly predicted cognitive-affective depression. Internalized stigma accounted for 4.8% of the variance in cognitive-affective depression scores over and above the other variables. These results indicate an urgent need for social reform to reduce AIDS stigmas and the design of interventions to assist people living with HIV/AIDS to adjust and adapt to the social conditions of AIDS in South Africa.
PMCID: PMC4271649  PMID: 17337318
Internalized stigma; AIDS; coping; South Africa; Discrimination; Depression
19.  Australian graduating nurses’ knowledge, intentions and beliefs on infection prevention and control: a cross-sectional study 
BMC Nursing  2014;13:43.
In recent year, national bodies have been actively addressing the increasing concern on the spread of healthcare-associated infections (HAIs). The current study measures the knowledge, intentions and beliefs of third-year Australian nursing students on key infection prevention and control (IPC) concepts.
A cross-sectional study of final-year undergraduate nursing students from Schools of Nursing at six Australian universities was undertaken. Students were asked to participate in an anonymous survey. The survey explored knowledge of standard precautions and transmission based precautions. In addition intentions and beliefs towards IPC were explored.
349 students from six universities completed the study. 59.8% (95% CI 58.8–60.8%) of questions were answered correctly. Significantly more standard precaution questions were correctly answered than transmission-based precaution questions (p < 0.001). No association was found between self-reported compliance with IPC activities and gender or age. Certain infection control issues were correlated with the percentage of correctly answered transmission-based precaution questions. The participants were most likely to seek infection control information from an infection control professional.
Knowledge on transmission-based precautions was substandard. As transmission-based precautions are the foundation of IPC for serious organisms and infections, education institutions should reflect on the content and style of educational delivery on this topic.
Electronic supplementary material
The online version of this article (doi:10.1186/s12912-014-0043-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4266973  PMID: 25516721
Drug and alcohol dependence  2013;133(2):10.1016/j.drugalcdep.2013.07.013.
Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD).
Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes.
Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p<.001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p=.008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters.
There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy.
PMCID: PMC3829200  PMID: 23932841
alcohol use and abuse; women; prenatal alcohol use; fetal alcohol spectrum disorders; South Africa; dysmorphology; cognition
21.  Facial affect recognition and exit examination performance in medical students: a prospective exploratory study 
BMC Medical Education  2014;14:245.
Facial affect recognition (FAR) abilities underpin emotional intelligence (EI). The latter is suggested to predict academic success and to be important for clinician-patient interaction. It is therefore of interest to investigate the possible association between FAR and academic performance in undergraduate medical students.
We assessed the association between the ability to recognize emotions through facial expression and exit examination performance, a measure of clinical proficiency, in undergraduate medical students stratified by gender at a South African tertiary institution using a prospective descriptive design. Data on the perception of facial expressions and exit examination marks were obtained from 144 (61%) females and 93 (39%) males with a mean age of 24.1 ± 1.6 years. Facial affect recognition measures on the Hexagon and Animation tasks were individually correlated with academic performance indicators using Pearson correlation.
The perceptual discrimination of anger was associated with improved performance in anaesthetics (r = .24; p = .004) and urology (r = .24; p = .001), while the recognition of happiness was associated with decreased performance in obstetrics (r = −.21, p = .002). Gender was an effect modifier in the relationship between perceptual discrimination of anger and urology performance (p = .03), with a strong positive relationship for males, but a non-significant relationship for females.
There was no overall correlation between FAR and overall academic performance or with gender. However, subject (specialty) specific findings with recognition of specific emotions and with gender as effect modifier poses interesting questions about EI and FAR and prompts further research into FAR as a useful tool. Being an objective test and offering a more focused assessment makes FAR worthy of further application.
PMCID: PMC4261890  PMID: 25431251
Emotional intelligence; Facial affect recognition; Examination performance; Undergraduate medical students; Gender
22.  Housing conditions and mental health of orphans in South Africa 
Health & place  2013;24:10.1016/j.healthplace.2013.08.004.
Literature from the developed world suggests that poor housing conditions and housing environments contribute to poor mental health outcomes, although research results are mixed. This study investigates the relationship between housing conditions and the socio-emotional health of orphans and vulnerable children (OVC) in South Africa. The results of the study are mainly inconclusive, although it is suggested that methodological considerations play a vital role in explaining the mixed results. However, a positive relationship was found between living in informal settlements and better socio-emotional health of the OVC. We speculate that the historical context of informal settlement formation in South Africa helps to explain this unexpected result.
PMCID: PMC3834074  PMID: 24013088
housing conditions; orphans; mental health; informal settlements
23.  Distribution of Indigenous Bacterial Pathogens and Potential Pathogens Associated with Roof-Harvested Rainwater 
The harvesting of rainwater is gaining acceptance among many governmental authorities in countries such as Australia, Germany, and South Africa, among others. However, conflicting reports on the microbial quality of harvested rainwater have been published. To monitor the presence of potential pathogenic bacteria during high-rainfall periods, rainwater from 29 rainwater tanks was sampled on four occasions (during June and August 2012) in a sustainable housing project in Kleinmond, South Africa. This resulted in the collection of 116 harvested rainwater samples in total throughout the sampling period. The identities of the dominant, indigenous, presumptive pathogenic isolates obtained from the rainwater samples throughout the sampling period were confirmed through universal 16S rRNA PCR, and the results revealed that Pseudomonas (19% of samples) was the dominant genus isolated, followed by Aeromonas (16%), Klebsiella (11%), and Enterobacter (9%). PCR assays employing genus-specific primers also confirmed the presence of Aeromonas spp. (16%), Klebsiella spp. (47%), Legionella spp. (73%), Pseudomonas spp. (13%), Salmonella spp. (6%), Shigella spp. (27%), and Yersinia spp. (28%) in the harvested rainwater samples. In addition, on one sampling occasion, Giardia spp. were detected in 25% of the eight tank water samples analyzed. This study highlights the diverse array of pathogenic bacteria that persist in harvested rainwater during high-rainfall periods. The consumption of untreated harvested rainwater could thus pose a potential significant health threat to consumers, especially children and immunocompromised individuals, and it is recommended that harvested rainwater be treated for safe usage as an alternative water source.
PMCID: PMC3993141  PMID: 24487540
24.  The influence of secondary structure, selection and recombination on rubella virus nucleotide substitution rate estimates 
Virology Journal  2014;11:166.
Annually, rubella virus (RV) still causes severe congenital defects in around 100 000 children globally. An attempt to eradicate RV is currently underway and analytical tools to monitor the global decline of the last remaining RV lineages will be useful for assessing the effectiveness of this endeavour. RV evolves rapidly enough that much of this information might be inferable from RV genomic sequence data.
Using BEASTv1.8.0, we analysed publically available RV sequence data to estimate genome-wide and gene-specific nucleotide substitution rates to test whether current estimates of RV substitution rates are representative of the entire RV genome. We specifically accounted for possible confounders of nucleotide substitution rate estimates, such as temporally biased sampling, sporadic recombination, and natural selection favouring either increased or decreased genetic diversity (estimated by the PARRIS and FUBAR methods), at nucleotide sites within the genomic secondary structures (predicted by the NASP method).
We determine that RV nucleotide substitution rates range from 1.19 × 10-3 substitutions/site/year in the E1 region to 7.52 × 10-4 substitutions/site/year in the P150 region. We find that differences between substitution rate estimates in different RV genome regions are largely attributable to temporal sampling biases such that datasets containing higher proportions of recently sampled sequences, will tend to have inflated estimates of mean substitution rates. Although there exists little evidence of positive selection or natural genetic recombination in RV, we show that RV genomes possess pervasive biologically functional nucleic acid secondary structure and that purifying selection acting to maintain this structure contributes substantially to variations in estimated nucleotide substitution rates across RV genomes.
Both temporal sampling biases and purifying selection favouring the conservation of RV nucleic acid secondary structures have an appreciable impact on substitution rate estimates but do not preclude the use of RV sequence data to date ancestral sequences. The combination of uniformly high substitution rates across the RV genome and strong temporal structure within the available sequence data, suggests that such data should be suitable for tracking the demographic, epidemiological and movement dynamics of this virus during eradication attempts.
Electronic supplementary material
The online version of this article (doi:10.1186/1743-422X-11-166) contains supplementary material, which is available to authorized users.
PMCID: PMC4175276  PMID: 25224517
Rubella virus; Congenital rubella syndrome; Nucleotide substitution rates; Synonymous substitution rates; Recombination; Nucleic acid secondary structure; Bayesian phylogenetic analyses
25.  The Linkage Outcomes of a Large-scale, Rapid Transfer of HIV-infected Patients From Hospital-based to Community-based Clinics in South Africa 
Open Forum Infectious Diseases  2014;1(2):ofu058.
The rapid transfer of nearly 4000 HIV-infected patients from a hospital-based clinic to community-based clinics had an estimated success of 82%. Close collaboration between transferring and receiving clinics is necessary to ensure that the health gains from PEPFAR funding are maintained.
 President's Emergency Plan for AIDS Relief (PEPFAR) funding changes have resulted in human immunodeficiency virus (HIV) clinic closures. We evaluated linkage to care following a large-scale patient transfer from a PEPFAR-funded, hospital-based HIV clinic to government-funded, community-based clinics in Durban.
 All adults were transferred between March and June 2012. Subjects were surveyed 5–10 months post-transfer to assess self-reported linkage to the target clinic. We validated self-reports by auditing records at 8 clinics. Overall success of transfer was estimated using linkage to care data for both reached and unreached subjects, adjusted for validation results.
 Of the 3913 transferred patients, 756 (19%) were assigned to validation clinics; 659 (87%) of those patients were reached. Among those reached, 468 (71%) had a validated clinic record visit. Of the 46 who self-reported attending a different validation clinic than originally assigned, 39 (85%) had a validated visit. Of the 97 patients not reached, 59 (61%) had a validated visit at their assigned clinic. Based on the validation rates for reached and unreached patients, the estimated success of transfer for the cohort overall was 82%.
 Most patients reported successful transfer to a community-based clinic, though a quarter attended a different clinic than assigned. Validation of attendance highlights that nearly 20% of patients may not have linked to care and may have experienced a treatment interruption. Optimizing transfers of HIV care to community sites requires collaboration with receiving clinics to ensure successful linkage to care.
PMCID: PMC4281821  PMID: 25734128
PEPFAR; transfer of HIV care; South Africa; linkage to care; community-based clinics

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