Phase I of the DiaVACCS screening trial: Study design, methods, population demographics and baseline results.

BACKGROUND: Human papillomavirus (HPV)-based primary screening guidelines are based on screening test performance and prevalence data generated in high-resource areas with low HIV infection rates. There is an urgent need for local data on infection and disease prevalence, as well as screening test performance, among both HIV-positive and HIV-negative South African (SA) women, in order to inform updated screening guidelines. Objectives. This study describes the baseline characteristics of participants in the cross-sectional phase of the multicentric DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) screening trial. The objective was to determine the prevalence of positive screening and pre-invasive disease using different tests and strategies in the SA HIV-positive and HIV-negative population. METHODS: A total of 1  104 women aged 25 - 65 years and eligible for screening were included, 465 HIV positive and 639 HIV negative. Visual inspection and molecular and cytological screening tests were done on self-sampled and healthcare worker-collected specimens. All participants who screened positive and 49.1% of those who screened negative were invited for colposcopy and biopsy, and those qualifying for treatment were recalled for large loop excision of the transformation zone as part of the trial. The worst histology result for each participant was used, and for untested women, multiple imputation was used to estimate verification biasadjusted histology values. RESULTS: Visual inspection was positive in 50.4% of HIV-positive v. 20.9% of HIV-negative women, cytology (atypical squamous cells of undetermined significance) in 39.9% v. 17.0%, and high-risk HPV DNA in 41.2% v. 19.6%. Overall, high-grade squamous intraepithelial lesion-positive cytology peaked in the age group 30 - 39 years at 16.7%. After adjustment for verification bias, histological diagnosis of cervical intraepithelial neoplasia (CIN)2+ was suspected in 44.7% v. 23.5% and CIN3+ in 23.3% v. 10.2% of HIV-positive and negative women, respectively. Invasive cancer was diagnosed in 15 women (1.95% of histological studies performed), and verification bias adjustment suggested 20 cases (1.8% of the study population). CONCLUSION: The baseline findings from the DiaVACCS trial confirm a high prevalence of HPV-related cervical pathology in the SA HIV-negative screening population, showing a clear need to reach these women with a screening programme. Among HIV-positive women, prevalence values were almost doubled. The prevalence of existing invasive cervical cancer was 1 - 2% of all women. Further analysis of the performance of single and multiple screening tests between the two subgroups will contribute to the choice of the most effective strategies to identify women at risk of developing invasive cancer.

The ethical imperative to relieve suffering for people with tuberculosis by ensuring access to palliative care.

Patients diagnosed with tuberculosis (TB) continue to experience clinical uncertainty and high mortality and to bear a high burden of symptoms and other concerns. Additional concerns may be family support needs and stigma, particularly the latter, as TB and human immunodeficiency virus (HIV) coinfection are common. Human rights covenants, global health policy and the End TB Strategy all recommend palliative care as an essential component of care services. As established in the resolution adopted by the World Health Assembly (WHA) on "Strengthening of palliative care as a component of comprehensive care throughout the life course", there is a "need for palliative care across disease groups (non-communicable diseases, and infectious diseases, including HIV and multidrug-resistant tuberculosis), and across all age groups". We address the ethical imperative to respect the dignity and fundamental rights of people with TB by providing palliative care. We review the evidence for the need for person-centred palliative care and highlight novel models that utilise the skills and training functions of specialist palliative care to achieve better care. We outline simple recommendations for the delivery of specialist and generalist palliative care, offer suggestions on how to ensure optimal coverage by enabling access to appropriate good-quality palliative care at all points of the health system, including alongside treatment. Finally, we set out the current priorities for research and policy to ensure that quality care is delivered to all who need it irrespective of treatment outcome, to minimise distress and to optimise engagement in treatment and care.

Assessment and management of venous thrombo-embolism risk during pregnancy and the puerperium (SAVE): The South African cohort.

BACKGROUND: Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Pregnancy and the puerperium are hypercoagulable states and increase the risk of VTE. There is a paucity of South African (SA) data related to use of thromboprophylaxis during pregnancy and the puerperium. OBJECTIVES: To evaluate local practice of VTE risk stratification among SA pregnant women and senior doctors' attitudes to VTE prophylaxis. METHODS: This was a cross-sectional descriptive study of conveniently sampled sites in the private and public health sectors. Patients with confirmed pregnancy and an underlying medical condition were enrolled after giving informed consent. Assessments were made based on the participating doctors' questionnaires and case report forms. In essence, this was a local evaluation of a specific group of patients by a specific group of doctors. RESULTS: Two hundred and twenty patients were enrolled at six sites. In the participating doctors' opinion, 126/220 women assessed (57.2%) were at risk of VTE during pregnancy and the postpartum period (information was missing for 1 woman during the postpartum period). Of the women at risk of VTE, 23/126 (18.3%) were at high risk, 59/126 (46.8%) at moderate risk and 44/126 (34.9%) at low risk. Of the women identified as at risk of VTE, 104/127 (81.9%) received some form of VTE prophylaxis; 94/127 (74.0%) were at risk during pregnancy and 32/126 (25.4%) during the postpartum period. Of those who received pharmacological treatment, 15/15 received low-molecular-weight heparin during pregnancy and before delivery and 87/100 during the puerperium. Thirty-four patients received thromboprophylaxis for only 5 - 10 days after caesarean delivery, and 2 received mechanical thromboprophylaxis during pregnancy. CONCLUSIONS: Doctors participating in the study were generally aware of VTE risk during pregnancy and the puerperium. Pharmacological thromboprophylaxis was the most commonly used intervention to reduce VTE risk. Mechanical thromboprophylaxis was underutilised. Adherence to VTE guidelines, specifically in terms of duration of thromboprophylaxis and its utilisation during pregnancy, was suboptimal.

'I didn't know so many people cared about me': support for patients who interrupt drug-resistant TB treatment.

SETTING: Early interventions for patients who interrupt their treatment for drug-resistant tuberculosis (DR-TB) are rarely reported and assessed. A novel, patient-centred intervention for patients at risk of loss to follow-up (LTFU) from DR-TB treatment was implemented in Khayelitsha, South Africa, in September 2013. OBJECTIVE: To explore the experiences and perceptions of patients, key support persons, health care workers (HCWs) and programme managers of a patient-centred model. DESIGN: This was a qualitative study consisting of 18 in-depth interviews with patients, key support persons, HCWs, key informants and one focus group discussion with HCWs, between July and September 2017. Data were coded and thematically analysed. RESULTS: The model was well perceived and viewed positively by patients, care providers and programme managers. 'Normalisation' and tolerance of occasional treatment interruptions, tracing, tailored management plans and peer support were perceived to be beneficial for retaining patients in care. Although the model was resource-demanding, health workers were convinced that it 'needs to be sustained,' and proposed solutions for its standardisation. CONCLUSION: An intervention based on early tracing of patients who interrupt treatment, peer-delivered counselling and individualised management plans by a multidisciplinary team was considered a beneficial and acceptable model to support patients at risk of LTFU from DR-TB treatment.

A randomised trial comparing laparoscopy with laparotomy in the management of women with ruptured ectopic pregnancy.

BACKGROUND: Ruptured ectopic pregnancy (REP) is a common gynaecological emergency in resource-poor settings, where laparotomy is the standard treatment despite laparoscopic surgery being regarded as the optimal treatment. There is a lack of prospective randomised data comparing laparoscopic surgery with laparotomy in the surgical management of women with REP. OBJECTIVE: To compare operative laparoscopy with laparotomy in women with REP. METHODS: This was a randomised parallel study. One hundred and forty women with suspected REP were randomised to undergo operative laparoscopy or laparotomy. The outcome measures were operating time, hospital stay, pain scores and analgesic requirements, blood transfusion, time to return to work, and time to full recovery. RESULTS: Operating time was significantly longer in the laparoscopy group (67.3 v. 30.5 minutes, p<0.001). Duration of hospital stay, pain scores and need for analgesia were significantly less in the laparoscopy group. Women in this group returned to work 8 days earlier and their time to full recovery was significantly shorter compared with those in the laparotomy group. Significantly more women undergoing laparotomy required blood transfusion than women in the laparoscopy group. In the latter group, 14.5% of women required blood transfusion compared with 26.5% in the laparotomy group (p=0.01). CONCLUSION: Operative laparoscopy in women treated for REP is feasible in a resource-poor setting and is associated with significantly less morbidity and a quicker return to economic activity.

A randomised trial comparing laparoscopy with laparotomy in the management of women with ruptured ectopic pregnancy

Background. Ruptured ectopic pregnancy (REP) is a common gynaecological emergency in resource-poor settings, where laparotomy is the standard treatment despite laparoscopic surgery being regarded as the optimal treatment. There is a lack of prospective randomised data comparing laparoscopic surgery with laparotomy in the surgical management of women with REP.Objective. To compare operative laparoscopy with laparotomy in women with REP.Methods. This was a randomised parallel study. One hundred and forty women with suspected REP were randomised to undergo operative laparoscopy or laparotomy. The outcome measures were operating time, hospital stay, pain scores and analgesic requirements, blood transfusion, time to return to work, and time to full recovery.Results. Operating time was significantly longer in the laparoscopy group (67.3 v. 30.5 minutes, p<0.001). Duration of hospital stay, pain scores and need for analgesia were significantly less in the laparoscopy group. Women in this group returned to work 8 days earlier and their time to full recovery was significantly shorter compared with those in the laparotomy group. Significantly more women undergoing laparotomy required blood transfusion than women in the laparoscopy group. In the latter group, 14.5% of women required blood transfusion compared with 26.5% in the laparotomy group (p=0.01). Conclusion. Operative laparoscopy in women treated for REP is feasible in a resource-poor setting and is associated with significantly less morbidity and a quicker return to economic activity

Osteosarcoma patient outcomes at a South African tertiary hospital

Background. Osteosarcoma is the most common primary malignant bone tumour. There is a high incidence of late presentation in the developing world, posing additional challenges in the treatment of this aggressive disease. Objective. To evaluate clinical outcomes of patients with osteosarcoma at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), a tertiary hospital in South Africa, and compare these with similar studies in the developing world.Methods. This was a retrospective study of 61 patients treated at CMJAH between 2007 and 2011, with a minimum follow-up of 1.3 years (range 1.3 - 6.3).Results. An average of 4.5 months elapsed before patients were first seen at the CMJAH tumour unit. Fifty-eight patients (95.1%) initially sought conventional medical care. Three patients (4.9%) presented with pathological fractures. All the patients underwent biopsy, performed an average of 3 weeks after arrival at the tumour unit. In most cases the delay was due to limited access to magnetic resonance imaging. Most patients (n=41, 67.2%) were at Enneking stage 2B, 4 (6.6%) were at stage 2A and 16 (26.2%) were at stage 3. Of the patients, 13 (21.3%) underwent limb salvage procedures, 33 (54.1%) had amputations, 4 (6.6%) refused further treatment and 11 (18.0%) received palliative care only; 55 patients (90.2%) received chemotherapy. Two patients developed local recurrence, one of whom had an amputation and the other further wide excision. Two patients received palliative radiotherapy. Of the patients, 82.0% were HIV-negative, 4.9% HIV-positive and the rest of unknown status. At the time of the study, all but two patients, who came from other countries, were traceable or known to have died. Our overall 1-year and 5-year survival rates were 62.7% (95% confidence interval (CI) 49.1 - 73.9) and 38.1% (95% CI 24.6 - 51.4), respectively. Male patients and those with a higher Enneking stage had a poorer prognosis.Conclusion. Although most patients sought conventional medical care, unacceptable delays worsened survival. However, our survival rates are better than those in other developing countries. We advocate that professional, public and political awareness of osteosarcoma be improved as a matter of urgency, to facilitate rapid tertiary referral and expedite management

Patient support interventions to improve adherence to drug-resistant tuberculosis treatment: A counselling toolkit.

In response to the growing burden of drug-resistant tuberculosis (DR-TB) in South Africa (SA), Médecins Sans Frontières (MSF), with local government health departments, piloted a decentralised model of DR-TB care in Khayelitsha, Western Cape Province, in 2007. The model takes a patient-centred approach to DR-TB treatment that is integrated into existing TB and HIV primary care programmes. One essential component of the model is individual and family counselling to support adherence to and completion of treatment. The structured and standardised adherence support sessions have been compiled into a DR-TB counselling toolkit. This is a comprehensive guide that focuses on DR-TB treatment literacy, adherence strategies to encourage retention in care, and provision of support throughout the patient's long treatment journey. Along with other strategies to promote completion of treatment, implementation of a strong patient support component of DR-TB treatment is considered essential to reduce rates of loss from treatment among DR-TB patients. We describe our experience from the implementation of this counselling model in a high DR-TB burden setting in Khayelitsha, Cape Town, SA.

The Vaccine and Cervical Cancer Screen project 2 (VACCS 2): Linking cervical cancer screening to a two-dose HPV vaccination schedule in the South-West District of Tshwane, Gauteng, South Africa.

BACKGROUND: Cervical cancer is a preventable disease with a high prevalence in South Africa (SA), where screening is opportunistic. Primary prevention is now possible through HPV vaccination. In VACCS 1 the feasibility of linking cervical cancer with HPV vaccination was demonstrated. OBJECTIVES: To investigate the feasibility of linking HPV self-testing with a two-dose HPV vaccination schedule and to compare results with VACCS 1. METHODS: The project was conducted in five schools in the South-West District of Tshwane, Gauteng, SA. Leaflet information on cervical cancer and screening was provided, with requests for consent and assent for a two-dose HPV vaccination of schoolgirls. Female caregivers were invited to take part in HPV self-screening. RESULTS: Of 965 girls invited for vaccination, 519 (53.7%) had full consent and 518 (99.8%) received at least one vaccine dose. The invited uptake rate was 53.7% and 495 girls received both doses, giving a completion rate of 95.4% v. 82.6% in VACCS 1. Of 1 135 self-screen kits handed out, 560 (49.3%) were not returned. The mean age (standard deviation) of the 160 women who participated in self-screening was 38.7 (7.7) years. HPV testing was negative in 116 women (72.5%), 15 women (9.4%) tested positive for HPV 16 and/or 18, and 27 (16.9%) were positive for non-16/18 oncogenic HPV. CONCLUSION: Data from the VACCS projects suggest that school-based vaccine programmes can be successfully implemented. A two-dose schedule allowed for higher completion rates. Linking self-collected HPV screening to HPV vaccination is feasible, is a promising and viable screening strategy, and reached the appropriate age group for screening.

The vaccine and cervical cancer screen (VACCS) project: acceptance of human papillomavirus vaccination in a school-based programme in two provinces of South Africa.

BACKGROUND: The incidence of cervical cancer in South Africa (SA) remains high, and the current screening programme has had limited success. New approaches to prevention and screening tactics are needed. OBJECTIVES: To investigate acceptance of school-based human papillomavirus (HPV) vaccination, as well as the information provided, methods of obtaining consent and assent, and completion rates achieved. METHODS: Information on cervical cancer and HPV vaccination was provided to 19 primary schools in Western Cape and Gauteng provinces participating in the study. Girls with parental consent and child assent were vaccinated during school hours at their schools. RESULTS: A total of 3 465 girls were invited to receive HPV vaccine, of whom 2 046 provided written parental consent as well as child assent. At least one dose of vaccine was delivered to 2 030 girls (99.2% of the consented cohort), while a total of 1 782 girls received all three doses. Sufficient vaccination was achieved in 91.6% of the vaccinated cohort. Of all invited girls, 56.9% in Gauteng and 50.7% in the Western Cape were sufficiently vaccinated. CONCLUSION: This implementation project demonstrated that HPV vaccination is practical and safe in SA schools. Political and community acceptance was good, and positive attitudes towards vaccination were encountered. During the study, which mimicked a governmental vaccine roll-out programme, high completion rates were achieved in spite of several challenges encountered.

The adoption of social media and social media marketing by dentists in South Africa.

OBJECTIVES: The purpose of the study was to identify and understand social media usage behaviour of dentists in South Africa, in general and in particular as part of their marketing strategy and to consider the potential determinants associated with these behaviours. METHODS: Dentists who are members of the South African Dental Association were requested to anonymously complete an online questionnaire. Apart from demographic information, respondents were asked to report on their use of social media and their adoption of social media marketing. One-on-one interviews were also conducted with three dentists, to gain a deeper understanding of their adoption of this marketing option. RESULTS: South African dentists have started to embrace social media and 50.2% interact through these channels at least once a day. The most popular social media platforms are GooglePlus and Facebook. Respondents use social media mainly for personal purposes, including staying connected to family and friends.. Only 13.2% of those responding currently use social media as a marketing tool, but the majority (83.5%) predict that such usage will increase in future. CONCLUSION: Social media marketing is a growing trend and will become more significant in future. Although respondents used social media regularly for personal purposes, most are only now starting to use it as a marketing tool.

Variability of yellow tulp (Moraea pallida Bak.) toxicity.

Yellow tulp (Moraea pallida Bak.), collected predominantly during the flowering stage from a number of sites in South Africa, showed large variation in digoxin equivalent values, indicating variability in yellow tulp toxicity. Very low values were recorded for tulp collected from certain sites in the Northern Cape.

Evaluation of activated charcoal as treatment for Yellow tulp (Moraea pallida) poisoning in cattle.

The efficacy of activated charcoal as a treatment for cattle (n = 57) poisoned by Yellow tulp (Moraea pallida) was investigated. Treatment with activated charcoal resulted in full recovery, irrespective of the degree of posterior paresis, provided that this clinical sign did not develop within the first 12 hours after initial exposure to Yellow tulp-infested grazing. For instance, despite treatment, 1 of 7 cattle succumbed after manifesting mild posterior paresis 6 to 8 h after initial exposure and 3 of 3 treated cattle died after developing severe posterior paresis within 6 to 12 h.

Changes in sheep oesophageal diameter and function during Geigeria ornativa (vermeerbos) poisoning and subsequent recovery.

Changes in the oesophageal diameter and function together with changes in body weight, feed intake and the cardiac pulmonary flow index were investigated during experimentally induced poisoning with Geigeria ornativa and subsequent recovery. This was performed under varying conditions for individual sheep. Results showed an increase in the oesophageal diameter index (ODI) during vermeersiekte, accompanied with a decrease in oesophageal function (OF). Cessation of G. ornativa intake resulted in a considerable although incomplete recovery of the ODI. Recovery of the OF for the different sheep, however, varied between 0 and 100%. Detrimental changes in the oesophageal diameter and function were also measured in sheep receiving only subclinical doses of G. ornativa. Decreases in body weight and feed intake commenced 1 to 3 weeks before the onset of vermeersiekte, while indications of a decline in these 2 parameters were also noticed with ingestion of subclinical amounts of G. ornativa. An increase in the cardiac pulmonary flow index (CPFI) to a value indicating the onset of heart failure was found in 1 of the sheep showing clinical signs of vermeersiekte. The CPFI returned to normal after termination of G. ornativa intake.

Evaluation of a strict protocol approach in managing women with severe disease due to abortion.

AIM: To evaluate whether the introduction of a strict protocol approach based on the systemic evaluation of critically ill pregnant women with complications of abortion affected outcome. SETTING: Indigent South Africans managed in the regional and tertiary hospitals of the Pretoria Academic Complex. METHOD: Since 1997 a standard definition of severe acute maternal morbidity (SAMM) has been used in the Pretoria Academic Complex. All cases of SAMM and maternal deaths were entered on the Maternal Morbidity and Mortality Audit System programme. A comparison of outcome of severely ill women who had complications of abortion was made between 1997-1998 (original protocol) and 2002-2004 (strict protocol). OUTCOME MEASURES: The mortality index and prevalence of organ system failure or dysfunction. RESULTS: In 1997-1998 there were 43 women with SAMM who survived and a further 10 maternal deaths due to complications of abortion, compared with 107 women with SAMM and 7 maternal deaths during 2002-2004. The mortality index declined from 18.9% in 1997-1998 to 6.1% in 2002-2004 (p = 0.02, odds ratio 0.28, 95% confidence limits 0.10 - 0.79). Significantly more women had hypovolaemic shock in 2002-2004 compared with 1997-1998 (54.4% v. 35.8%, p = 0.04), but fewer women had immune system failure including septic shock (18.4% v. 47.2%, p = 0.0002) and metabolic dysfunction (0 v. 5.7%, p = 0.03) and there was a trend to less renal failure (10.5% v. 22.6%, p = 0.06) and cardiac failure (4.4% v. 13.2%, p = 0.08). CONCLUSION: The strict protocol approach based on systemic evaluation in managing critically ill pregnant women with complications of abortion, coupled with an intensive, regular feedback mechanism, has been associated with a reduction in the mortality index.

Impact of the Choice on Termination of Pregnancy Act on maternal morbidity and mortality in the west of Pretoria.

AIM: To evaluate the impact of the Choice on Termination of Pregnancy Act on maternal morbidity and mortality in the west of Pretoria. SETTING: Indigent South Africans managed in two public hospitals in the west of Pretoria. METHOD: Data were collected on all abortions (incomplete or induced) treated in the hospitals in the study area in 1997-1998 and 2003-2005. All cases of severe acute maternal morbidity and maternal deaths due to abortion were identified for these time periods. Data exclude referrals from outside the west of Pretoria. OUTCOME MEASURES: The case fatality rate (CFR), mortality index (MI) and maternal mortality ratio (MMR) due to abortions. RESULTS: In 1997-1998 there were 2 050 abortions, of which 80.2% were regarded as being incomplete, and in 2003-2005 there were 3 999 abortions, of which 42.8% were regarded as incomplete. Twenty-four women who were critically ill due to complications of abortion presented in 1997-1998 (a rate of 3.05/1 000 births), compared with 50 (2.76/1 000 births) in 2003-2005. There were 5 deaths in 1997-1998 (CFR of 2.4/1 000 abortions) compared with 1 death in 2003-2005 (CFR 0.25/1 000 abortions) (p = 0.01, relative risk (RR) 0.1, 95% confidence interval (CI) 0.01 - 0.89). The MI fell from 21.7% to 2.0% (p = 0.02, RR 0.1, 95% CI 0.01 - 0.89). The MMR was 63.6/100 000 births in 1997-1998 compared with 5.54/100 000 in 2003-2005 (p = 0.017, RR 0.09, 95% CI 0.01 - 0.74). CONCLUSION: The introduction of the Choice on Termination of Pregnancy Act has been associated with a massive reduction in women presenting with incomplete abortions. The prevalence of critically ill women due to complications of abortion has not changed, but the CFR, MI and MMR have declined significantly.

Urine cytology as a screening test for bladder infiltration in cervical cancer.

Ultrasound is currently used as a screening test for bladder infiltration in patients with advanced-stage cervical cancer at our institution. Cystoscopy is reserved for patients with abnormal bladder ultrasound findings. This study was undertaken to reevaluate this policy and to compare the results of different screening tests. The study was carried out in Pretoria academic complex. All newly diagnosed cervical carcinoma patients stage II and above were included in this study. The standard staging investigations were done on all patients. In addition, urine midstream and catheter specimens were sent for cytology. Cystoscopy and biopsy were performed on all patients. Two hundred twenty-eight patients were enrolled into this study. At cystoscopy, 47 patients had bladder mucosa suspicious of malignant infiltration, of which 17 had bladder mucosa infiltration diagnosed on histology. Urine catheter cytology has a sensitivity of 94% and specificity of 82% for bladder mucosa infiltration. The predictive value of a positive test is 31% and for a negative test is 99%. Catheter urine cytology is a very useful screening test for bladder infiltration in patients with cervical cancer. Cystoscopy should be reserved for patients with abnormal urine cytology in resource-poor settings with a large burden of disease.

A novel nonsense mutation in the EYA1 gene associated with branchio-oto-renal/branchiootic syndrome in an Afrikaner kindred.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by the associations of hearing loss, branchial arch defects and renal anomalies. Branchiootic (BO) syndrome is a related disorder that presents without the highly variable characteristic renal anomalies of BOR syndrome. Dominant mutations in the human homologue of the Drosophila eyes absent gene (EYA1) are frequently the cause of both BOR and BO syndromes. We report a South African family of Afrikaner descent with affected individuals presenting with pre-auricular abnormalities and either hearing loss or bilateral absence of the kidneys. Genetic analysis of the pedigree detected a novel EYA1 heterozygous nonsense mutation in affected family members but not in unaffected family members or a random DNA panel. Through mutational analysis, we conclude that this particular mutation is the cause of BOR/BO syndrome in this family as a result of a truncation of the EYA1 protein that ablates the critical EYA homologous region. To the best of our knowledge, this is the first case of BOR/BO syndrome reported in Africa or in those of the Afrikaner descent.