Renal disease in the elderly – a new entity?

Chronic renal disease (CRD) in adults is fairly common worldwide. CRD is often associated with cardiovascular mortality, which is increasing. In adults CRD is associated with systemic hypertension, diabetes mellitus and systemic lupus erythematosus (SLE) or glomerulonephritis (GN).http://www.cmej.org.zaam201

Anatomical pathology

No abstract available.http://www.cmej.org.za/index.php/cme

The histology of peau d’orange in breast cancer : what are the implications for surgery?

INTRODUCTION: Surgery is sometimes performed on patients with peau d'orange (dermal oedema) of the breast. This may be done to achieve local control of cancer after neo-adjuvant chemotherapy or in resectable locally advanced disease. Conventional practice is not to place excision lines through areas of peau d'orange for fear of recurrence in such an area. The question can be asked whether this wisdom is still valid in modern practice. No formal cohort studies documenting the histopathology of the skin in areas of peau d'orange have been published, and available descriptions are scanty. AIM: To describe the histopathological features of peau d'orange. METHOD: Consecutive patients undergoing mastectomy for cancer in whom peau d'orange was present were selected over a period of 2 years. Blocks of skin were excised from areas of peau d'orange and examined histologically. The presence, nature and location of malignant cells were recorded and correlated with lymph node pathology. Prior administration of neo-adjuvant chemotherapy was noted. RESULTS: Twenty-six mastectomy specimens were examined. Tumour islands in lymphatics were identified in 10 of the 26 specimens. These tumour groups were found in lymph vessels of both the superficial and deep dermal plexuses. In 1 specimen the presence of malignant cells was equivocal. Metastatic tumour was present in axillary lymph nodes in 19 of 22 specimens. Fourteen patients had been treated with neo-adjuvant chemotherapy, and 5 of their specimens exhibited the presence of tumour cell groups in lymphovascular channels. CONCLUSION: Tumour cells were present in the lymphatic vessels in areas of peau d'orange in 38% of the specimens studied. It would be expected that placing an excision line in such an area would result in an incomplete cancer operation in a high percentage of, but not all, cases.http://www.hmpg.co.za/journaldetail.php?journalno=

HPV L1 capsid protein detection in high-risk human papillomavirus-positive cervical smears

BACKGROUND: The L1 capsid protein is a viral nuclear protein that encapsidates the human papillomavirus (HPV) DNA to build new infectious particles. Previous studies in immune-competent patients have shown that detectable L1 protein in lowgrade squamous intraepithelial lesion (LSIL) smears is associated with remission in 60-75% of cases. Thus, the test can reduce interventions by approximately 75%. OBJECTIVE: This study was performed to evaluate the use of HPV L1 capsid protein detection on cytology samples in a population with relatively high human immunodeficiency virus (HIV) prevalence and with known high-risk HPV (hrHPV) DNA results. SETTING: Samples were obtained during a cervical cancer screening study at primary healthcare clinics in the Tshwane district, Gauteng. The HIV prevalence of the target group was estimated to be between 20% and 30%. METHOD: Conventional cervical cytology smears of 575 women were microscopically assessed and diagnosed. In addition, women were tested for the presence of HPV DNA on a cervical or vaginal sample. Immunocytochemical analysis was performed on morphologically abnormal smears and on a 52 control group smears reported to be negative for HPV DNA and morphological abnormalities. The detection of L1 capsid protein was carried out with the Cytoactiv® HPV L1 screening set, an antibody-based immunocytochemical stain. RESULTS: A cytological diagnosis of LSIL was made in 19 women (3.3%), high-grade squamous intraepithelial lesions (HSILs) in 42 (7.5%) and malignancy in 1 (0.2%). Of the LSIL cases, 10 of 19 (52.6%) stained positive for the presence of the L1 protein, while only one of 42 HSIL (2.4%) cases stained positive. Three hundred and four cases (52.9%) tested positive for hrHPV DNA, including women with LSIL, HSIL and malignancy. All of the control cases stained negative for the L1 capsid protein. CONCLUSION: hrHPV was not a useful triage test for women with abnormal cellular morphology in this population. Promising results were reported for Cytoactiv® immunostaining as a triage test for patients with LSIL, but it added no value to samples known to be HPV-negative or reported to be morphologically negative. The immunostaining of smears reported to be HSIL or worse were almost universally negative, supporting the diagnostic accuracy of cytology and the expectation of persistence or progression of these lesions.The Cancer Association of South Africahttp://www.sajgo.co.za/index.php/sajgoam201

Practice intentions of clinical associate students at the University of Pretoria, South Africa

INTRODUCTION : Like those in so many other countries, the South African health system faces a human resources crisis with rural areas most affected. The clinical associate program was initiated to develop a mid-level medical worker specifically for district health in underserved areas in South Africa. The University of Pretoria (UP) started its three-year Bachelor of Clinical Medical Practice (BCMP) degree program in 2009 using a practice-based authentic learning approach in 20 urban and rural district and secondary hospitals. With the first cohort at the brink of graduation, the objectives of this study were to determine the practice intentions, practice preferences and factors associated with the practice intentions of clinical associate students at the University of Pretoria. METHODS : This was a cross-sectional study of first-, second- and third-year clinical associate students studying at UP. The measurement tool was a self-administered electronic questionnaire. The majority of questions were closed-ended and these were of different types including multiple choice and Likert scale. The dependent variable of interest in the study was urban–rural practice intention. Bivariate and multivariate analysis was conducted using Stata v12. RESULTS : A total of 149 of the 216 registered BCMP students at UP participated in the study. Amongst the 146 participants that provided a response regarding their practice intentions directly after graduating, 87 (59.6%) intended to practise in a rural area. Intention to practise in a rural area was found to be significantly associated with self-description of having lived most of one’s life in a rural area (p=0.002). If given complete freedom of choice, 53.4% of participants indicated a preference to practise in a rural area and 46.6% had an urban preference. Only one participant intended to emigrate within 5 years of graduating. If the BCMP degree was internationally recognised, 25.0% of participants would prefer to practise abroad. At some point following completion of the BCMP degree, 93.9% of participants intended to undertake further studies, with medical degrees and postgraduate clinical associate qualifications being the most popular choices. CONCLUSIONS : As a substantial proportion of clinical associate students intend to practise in rural areas in South Africa, they could be a potential solution to the critical shortage of health professionals in rural settings in South Africa. Universities should continue their drive to recruit clinical associate students from rural areashttp://www.rrh.org.auhb201

Microscopic diversity in oral Kaposi sarcoma

Kaposi sarcoma is the most common HIV-associated neoplasm, frequently presenting and highlight the histomorphological spectrum of oral Kaposi sarcoma. One hundred and thirty-five cases diagnosed between 1990 and 2011 were retrieved from the archives of the Oral and Dental Hospital of the University of Pretoria, South Africa. Following histological review, each case was placed into one of seven categories based on the predominant pattern of growth. These histological divisions included lesions designated as solid, lymphangioma-like, telangiectatic, desmoplastic, lymphangiectatic, ecchymotic and anaplastic. The presence of co-existent pathology was identified in 25 cases, largely represented by superimposed candidiasis. Concomitant cytomegalovirus and non-necrotizing granulomatous inflammation were also observed. Whilst the prognostic significance of these variants is yet to be determined, the appreciation and recognition of such morphologic diversity remains essential in distinguishing these lesions from possible mimickers.National Research Foundation of South Africa.http://www.elsevier.com/wps/find/journaldescription.cws_home/623240/description#descriptionhb2013ay201

Molecular characterisation of gastrointestinal stromal tumours in a South African population

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Pathogenesis is linked to activating mutations identified in two proto-oncogenes, v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homologue KIT (KIT) and the platelet-derived growth factor α (PDGFRα). In addition, these mutations affect response to treatment with tyrosine kinase inhibitors. In the present study, we report on the molecular characterisation of GISTs in the South African population. Tumour DNA was extracted from 46 GIST samples, followed by cycle sequencing of KIT exons 11, 13 and 17 and PDGFRα exons 12, 14 and 18. Fragment length analysis was used to detect a 6-bp duplication in KIT exon 9. Wild-type duplications were analysed further by PCR and sequencing of additional KIT and PDGFRα exons was performed. Overall, 78.3% of the samples had a mutation in KIT or PDGFRα. Of these, mutations were detected in KIT exon 11 (88.9%), PDGFRα exon 18 (8.3%) and KIT exon 9 (2.8%). Mutations varied from simple substitutions and duplications to large deletions (some with nucleotide insertions) resulting in missense mutations. In addition, seven single nucleotide polymorphisms were detected in 17 patients, one of which appears novel. The incidence of mutations in KIT exon 11 and PDGFRα exon 18 is consistent with the literature, however, the low incidence of KIT exon 9 mutations detected was unexpected. In contrast to previous western and Asian studies, this mutation appears to be rare in the South African population. The present study contributes to the molecular understanding of GISTs in the South African population.http://www.spandidos-publications.com/ol/am201

Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men

BACKGROUND : Prostate cancer incidence and mortality rates are significantly increased in African–American men, but limited studies have been performed within Sub–Saharan African populations. As mitochondria control energy metabolism and apoptosis we speculate that somatic mutations within mitochondrial genomes are candidate drivers of aggressive prostate carcinogenesis. METHODS : We used matched blood and prostate tissue samples from 87 South African men (77 with African ancestry) to perform deep sequencing of complete mitochondrial genomes. Clinical presentation was biased toward aggressive disease (Gleason score >7, 64%), and compared with men without prostate cancer either with or without benign prostatic hyperplasia. RESULTS : We identified 144 somatic mtDNA single nucleotide variants (SNVs), of which 80 were observed in 39 men presenting with aggressive disease. Both the number and frequency of somatic mtDNA SNVs were associated with higher pathological stage. CONCLUSIONS : Besides doubling the total number of somatic PCa-associated mitochondrial genome mutations identified to date, we associate mutational load with aggressive prostate cancer status in men of African ancestry.NIH R21- CA170081, Australian Prostate Cancer Research Centre NSW, the J. Craig Venter Institute, the Garvan Institute, the Petre Foundation, Australia, the Cancer Association of South Africa (CANSA).http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0045hb201

Integrating oral PrEP delivery among African women in a large HIV endpoint-driven clinical trial

INTRODUCTION : Global guidelines emphasize the ethical obligation of investigators to help participants in HIV-endpoint trials reduce HIV risk by offering an optimal HIV prevention package. Oral pre-exposure prophylaxis (PrEP) has increasingly become part of state-of-the-art HIV prevention. Here we describe the process of integrating oral PrEP delivery into the HIV prevention package of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. METHODS : ECHO was an open-label randomized clinical trial that compared HIV incidence among women randomized to one of three effective contraceptives. In total, 7830 women aged 16 to 35 years from 12 sites in four African countries (Eswatini, Kenya, South Africa and Zambia) were enrolled and followed for 12 to 18 months, from 2015 to 2018. Part-way through the course of the trial, oral PrEP was provided to study participants either off-site via referral or on site via trained trial staff. PrEP uptake was compared between different contraceptive users using Chi-squared tests or t-tests. HIV seroincidence rates were compared between participants who never versus ever initiated PrEP using exact Poisson regression. RESULTS : PrEP access in ECHO began through public availability in Kenya in May 2017 and was available at all sites by June 2018. When PrEP became available, 3626 (46.3%) eligible women were still in follow-up in the study, and of these, 622 (17.2%) initiated PrEP. Women initiating PrEP were slightly older; more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p < 0.05). PrEP initiation did not differ across study randomized groups (p = 0.7). Two-thirds of PrEP users were continuing PrEP at study exit. CONCLUSIONS : There is a need for improved HIV prevention services in clinical trials with HIV endpoints, especially trials among African women. PrEP as a component of a comprehensive HIV prevention package provided to women in a large clinical trial is practical and feasible. Provision of PrEP within clinical trials with HIV outcomes should be standard of prevention.The ECHO Trial was funded by Bill & Melinda Gates Foundation, US Agency for International Development and the President’s Emergency Plan for AIDS Relief, Swedish International Development Cooperation Agency, South African Medical Research Council and UN Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development. IB received funding from the South African Medical Research Council under the SAMRC Clinician Researcher MD PhD Development Programme.https://onlinelibrary.wiley.com/journal/17582652am2020Family Medicin

Clinical outcomes of intrauterine device insertions by newly trained providers : the ECHO trial experience

ACKNOWLEDGEMENTS : We thank the women who participated in this study for their motivation and dedication and the communities that supported this work. We also want to thank Sister Modiege Didi Maria Mojapelo (Refilwe Bophelo Clinic/NGO, Lanseria, South Africa), who served as one of the ECHO clinical trainers and certified ECHO clinicians in nine South African sites. The ECHO Trial is dedicated to the memory of Ward Cates.OBJECTIVES : To assess the rates of failed insertion, expulsion, and perforation when intrauterine device (IUD) insertions were done by newly trained clinicians, and to examine factors that may affect these outcomes. STUDY DESIGN : We evaluated skill-based outcomes following IUD insertion at 12 African sites in a secondary analysis of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial. Before trial initiation, we provided competency-based IUD training to clinicians and offered ongoing clinical support. We used Cox proportional hazards regression to examine factors associated with expulsion. RESULTS : Among 2582 IUD acceptors who underwent first attempted IUD insertion, 141 experienced insertion failure (5.46%) and seven had uterine perforation (0.27%). Perforation was more common among breastfeeding women within three months postpartum (0.65%) compared with non-breastfeeding women (0.22%). We recorded 493 expulsions (15.5 per 100 person-years, 95% confidence interval [CI] 14.1─16.9): 383 partial and 110 complete. The risk of IUD expulsion was lower among women older than 24 years (aHR 0.63, 95% CI 0.50─0.78) and may be higher among nulliparous women. (aHR 1.65, 95% CI 0.97─2.82). Breastfeeding (aHR 0.94, 95% CI 0.72─1.22) had no significant effect on expulsion. IUD expulsion rate was highest during the first three months of the trial. CONCLUSIONS : IUD insertion failure and uterine perforation rates in our study were comparable to those reported in the literature. These results suggest that training, ongoing support, and opportunities to apply new skills were effective in ensuring good clinical outcomes for women receiving IUD insertion by newly trained providers. IMPLICATIONS : Data from this study support recommendations to program managers, policymakers, and clinicians that IUDs can be inserted safely in resource-constrained settings when providers receive appropriate training and support.The Bill & Melinda Gates Foundation, the American people through the United States Agency for International Development, the Swedish International Development Cooperation Agency, the South Africa Medical Research Council, and the United Nations Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development.https://www.sciencedirect.com/journal/contraception-xam2024Family MedicineMedical MicrobiologySDG-03:Good heatlh and well-bein