The caregiver's experience of childhood cancer treatment in South Africa.

Background: This study explored the treatment-related, financial and psychological experiences of caregivers during cancer treatment of their children in South Africa's (SA) public and private sectors. Methods: In this exploratory study, three focus groups were conducted with caregivers of children undergoing cancer treatment in SA's public healthcare sector. A fourth small focus group with two parents in the private sector was conducted online. A mixed-methods approach was employed using a combination of thematic analysis and grounded theory. Results: Of the 20 public sector caregivers, many expressed frustration at the number of visits to primary healthcare clinics before being referred. Caregivers had difficulties coping with and accepting the diagnosis, alongside managing continued care for the child and other children at home. Support received by family and community members was varied. Financial strain was an important concern. The two private sector parents indicated greater levels of support and no financial hardship, but expressed similar levels of emotional stress. Conclusion: These caregiver experiences indicate that improvements are urgently needed in the recognition of childhood cancer symptoms at primary healthcare level in SA. They also highlight a need for increased financial support from government through social grants, travel allowances and nutritional support.

Evaluation of alignment of the reimbursement medicines list for children in Albania with the WHO essential medicines list for children.

Background: The WHO Essential Medicine List for Children was released on the 30th anniversary of the general Essential Medicine List in 2007, to recognise special needs for medicines in children, and to promote the inclusion of paediatric medicines in national procurement programmes. This study aimed to investigate the alignment of the medicines included in the Albanian reimbursement medicines list of the Mandatory Healthcare Insurance Fund (AMHIF) and the Essential Medicine List for Children. Methods: A quantitative evaluation was performed to compare the paediatric medicines included in the 2022 list of the AMHIF and the 2021 WHO Essential Medicine List for Children. In addition, vaccines in the Albanian vaccination programmes for children were compared to the ones listed on the WHO Essential Medicine List for Children. Results: Both lists had a total of 284 active ingredients in common, whereas 14 of 24 vaccines were found to be in common in the Essential Medicine List for Children list and the Albanian vaccination programmes. Conclusions: This is the first study in Albania to investigate the alignment of the WHO EMLc and AMHIF list. In case of the same active ingredient there were many deviations in terms of dosage form, strength and indication.

Comparing in-person, blended and virtual training interventions; a real-world evaluation of HIV capacity building programs in 16 countries in sub-Saharan Africa.

We sought to evaluate the impact of transitioning a multi-country HIV training program from in-person to online by comparing digital training approaches implemented during the pandemic with in-person approaches employed before COVID-19. We evaluated mean changes in pre-and post-course knowledge scores and self-reported confidence scores for learners who participated in (1) in-person workshops (between October 2019 and March 2020), (2) entirely asynchronous, Virtual Workshops [VW] (between May 2021 and January 2022), and (3) a blended Online Course [OC] (between May 2021 and January 2022) across 16 SSA countries. Learning objectives and evaluation tools were the same for all three groups. Across 16 SSA countries, 3023 participants enrolled in the in-person course, 2193 learners participated in the virtual workshop, and 527 in the online course. The proportions of women who participated in the VW and OC were greater than the proportion who participated in the in-person course (60.1% and 63.6%, p<0.001). Nursing and midwives constituted the largest learner group overall (1145 [37.9%] vs. 949 [43.3%] vs. 107 [20.5%]). Across all domains of HIV knowledge and self-perceived confidence, there was a mean increase between pre- and post-course assessments, regardless of how training was delivered. The greatest percent increase in knowledge scores was among those participating in the in-person course compared to VW or OC formats (13.6% increase vs. 6.0% and 7.6%, p<0.001). Gains in self-reported confidence were greater among learners who participated in the in-person course compared to VW or OC formats, regardless of training level (p<0.001) or professional cadre (p<0.001). In this multi-country capacity HIV training program, in-person, online synchronous, and blended synchronous/asynchronous strategies were effective means of training learners from diverse clinical settings. Online learning approaches facilitated participation from more women and more diverse cadres. However, gains in knowledge and clinical confidence were greater among those participating in in-person learning programs.

SDG indicator 3.b.3 - an analysis of its robustness and challenges for measuring access to medicines for children.

BACKGROUND: Sustainable Development Goal (SDG) indicator 3.b.3 monitors progress in medicines' accessibility for adults and has significant limitations when applying to medicines for children. An adapted indicator methodology was developed to fill this gap, but no proof of its robustness exists. We provide this evidence through sensitivity analyses. METHODS: Data on availability and prices of child medicines from ten historical datasets were combined to create datasets for analysis: Dataset 1 (medicines selected at random) and Dataset 2 (preference given to available medicines, to better capture affordability of medicines). A base case scenario and univariate sensitivity analyses were performed to test critical components of the methodology, including the new variable of number of units needed for treatment (NUNT), disease burden (DB) weighting, and the National Poverty Line (NPL) limits. Additional analyses were run on a continuously smaller basket of medicines to explore the minimum number of medicines required. Mean facility scores for access were calculated and compared. RESULTS: The mean facility score for Dataset 1 and Dataset 2 within the base case scenario was 35.5% (range 8.0-58.8%) and 76.3% (range 57.2-90.6%). Different NUNT scenarios led to limited variations in mean facility scores of + 0.1% and -0.2%, or differences of + 4.4% and -2.1% at the more critical NPL of $5.50 (Dataset 1). For Dataset 2, variations to the NUNT generated differences of + 0.0% and -0.6%, at an NPL of $5.50 the differences were + 5.0 and -2.0%. Different approaches for weighting for DB induced considerable fluctuations of 9.0% and 11.2% respectively. Stable outcomes with less than 5% change in mean facility score were observed for a medicine basket down to 12 medicines. For smaller baskets, scores increased more rapidly with a widening range. CONCLUSION: This study has confirmed that the proposed adaptations to make SDG indicator 3.b.3 appropriate for children are robust, indicating that they could be an important addition to the official Global Indicator Framework. At least 12 child-appropriate medicines should be surveyed to obtain meaningful outcomes. General concerns that remain about the weighting of medicines for DB and the NPL should be considered at the 2025 planned review of this framework.

Evaluating the impact of single exit pricing (SEP) on medicine product withdrawal from the private healthcare market in South Africa.

BACKGROUND: The introduction of medicine pricing policies in South Africa (SA) in the form of single exit pricing (SEP) provided a mechanism to improve medicine price transparency and reduce the medicine price and inflation. However, regulation of medicine prices may have further unforeseen effects on the availability of medicine. This research presents the impact of SEP on discontinuation of medicine products on the private healthcare market in SA. OBJECTIVES: To evaluate the impact of SEP legislation on the availability of medicines in the SA private health sector in terms of withdrawal of medicines from the market. METHODS: A descriptive, quantitative analysis of all registered medicines on the SA market by stock-keeping units (SKUs) was done to establish medicine products that were withdrawn from the market by SKUs during a 14-year period (2001 - 2014). RESULTS: A total of 152 manufacturers discontinued 3 691 SKUs between 2001 and 2014. The mean number of discontinuations per generic manufacturer was 22.34 (standard deviation (SD) 58.11), while innovator manufacturers discontinued a mean of 27.61 (41.89). The largest number of SKUs were commercially withdrawn in 2002 (n=603), followed by discontinuations in 2003 (n=463) and 2004 (n=407). There was a negative correlation between number of discontinued SKUs per year and SEP increase (Pearson's correlation coefficient r ‒0.414; p=0.14). The results showed that SEP and a transparent pricing policy may have had an impact on SKU withdrawal from the market prior to SEP implementation. CONCLUSIONS: The result of reduced product availability on the market and its impact on the cost and quality of healthcare to the patient need to be regularly monitored and evaluated to ascertain if direct price regulations achieve the intended outcomes. Other intended or unintended effects on pharmaceutical market dynamics should also be evaluated.

Evaluating the impact of the single exit price policy on a basket of originator medicines in South Africa from 1999 to 2014 using a time series analysis.

BACKGROUND: Affordability and availability of quality medicines to all its citizens has been a key priority area for South Africa since democracy in 1994. In order to introduce transparency in the private market the government introduced the Single Exit Price (SEP) for medicines in 2004, for all prescription medicines, comprising of a fixed ex-factory price with a logistics fee component (and value added tax) for medicines sold to all purchasers other than the State. This is complemented with a provision for an annual regulated maximum percentage increase. The study evaluates the impact of the SEP on a basket of originator medicines, in terms of costs, immediate price reductions and projected price reductions. METHOD: This is an analytical, quantitative study. A basket of medicines was selected, based on the WHO/HAI list, and adapted to include registered medicines in South Africa. Prices of 50 originator medicines were assessed from 1999 to 2014 in terms of the single exit price and the changes in prices in accordance with legislation using a time series analysis methodology. RESULTS: Of the 50 originator medicines investigated 35 showed a statistically significant change in level. For the Global Core list, the percentage change ranged from 2.45-39.12% (mean = 19.87%, SD = 10.62%, IQR = 10.2%). The range for the Regional Core list was 1.77-42.17% (mean = 23.38%, SD = 12.43%, IQR = 15.65%). The Supplementary list was 11.68-55.86% (mean = 22.97%, SD = 16.26%, IQR = 17.34). This study indicates that the SEP regulation had an impact on medicine pricing in South Africa in both the short and long term. Most medicines investigated showed a smaller yearly increase in price compared to before regulations due to the controlled pricing environment introduced by Government. CONCLUSION: This study provides evidence of the impact of medicine pricing intervention from a middle-income country, and other developing countries looking at introducing medicine price controls can draw useful lessons.

Is there transparency in the pricing of medicines in the South African private sector?

Recent investigations by the Competition Commission of South Africa (SA) of suspected excessive pricing of cancer medicines in SA by three global pharmaceutical companies have once again drawn attention to increasing medicine pricing transparency and warrant further public debate.

Cerebral white matter lesions after pre-eclampsia.

BACKGROUND: Women who have had pre-eclampsia in their previous pregnancies demonstrate a greater prevalence of cerebral white matter lesions several years after the pregnancy than women who have been normotensive during their pregnancy. Both the pathophysiology and the timing of development of these lesions are uncertain. White matter lesions, in the general population, are associated with an increased risk of stroke, dementia and death. AIMS AND OBJECTIVES: The objective of the study was to determine the prevalence of cerebral white matter lesions amongst women with severe pre-eclampsia at delivery, 6months and 1year postpartum and to establish the possible pathophysiology and risks factors. METHODS: This was a longitudinal study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria South Africa. Ninety-four women with severe pre-eclampsia were identified and recruited during the delivery admission. Magnetic resonance imaging (MRI) of the brain was performed post - delivery and at 6months and 1year postpartum. RESULTS: Cerebral white matter lesions were demonstrated in 61.7% of women at delivery, 56.4% at 6months and 47.9% at 1year. Majority of the lesions were found in the frontal lobes of the brain. The presence of lesions at 1year post-delivery was associated with the number of drugs needed to control blood pressure during pregnancy (OR 5.1, 95% CI 2.3-11.3, p<0.001). The prevalence of WMLs at 1year was double in women with chronic hypertension at 1year compared to those women who were normotensive (65.1% vs 32.3%). CONCLUSION: Women who require 2 or more drugs to control blood pressure during pregnancy have an increased risk of developing cerebral white matter lesions after delivery.

The thoracic surface anatomy of adult black South Africans: A reappraisal from CT scans.

Surface landmarks or planes taught in anatomy curricula derive from standard anatomical textbooks. Although many surface landmarks are valid, clear age, sex, and population differences exist. We reappraise the thoracic surface anatomy of black South Africans. We analyzed 76 (female = 42; male = 34) thoracoabdominal CT-scans. Patients were placed in a supine position with arms abducted. We analyzed the surface anatomy of the sternal angle, tracheal, and pulmonary trunk bifurcation, azygos vein termination, central veins, heart apex, diaphragm, xiphisternal joint, and subcostal plane using standardized definitions. Surface anatomy landmarks were mostly within the normal variation limits described in previous studies. Variation was observed where the esophagus (T9) and inferior vena cava (IVC) (T8/T9/T10) passed through the diaphragm. The bifurcations of the trachea and pulmonary trunk were inferior to the sternal angle. The subcostal plane level was positioned at L1/L2. The origin of inferior mesenteric artery was mostly inferior to the subcostal plane. Sex differences were noted for the plane of the xiphisternal joint (P = 0.0082), with males (36%) intersecting at T10 and females (36%) intersecting at T9. We provide further evidence for population variations in surface anatomy. The clinical relevance of surface anatomical landmarks depends on descriptions of normal variation. Accurate descriptions of population, sex, age, and body type differences are essential. Clin. Anat. 29:1018-1024, 2016. © 2016 Wiley Periodicals, Inc.

Takayasu arteritis in pregnancy.

Takayasu arteritis is a chronic, granulomatous arteritis affecting large and medium-sized arteries. During pregnancy, maternal and foetal complications are largely as a consequence of maternal arterial hypertension. We present a case of a 35-year-old para one gravida two patient with Takayasu arteritis (group III disease) complicated by chronic hypertension and a severely dilated ascending aorta. Good blood pressure control during pregnancy is an important measure in reducing obstetric morbidity.

Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening.

The present study reports the identification of human sex hormone binding globulin (SHBG)-interacting proteins in the brain using a phage display-based screening technology. Phage display is a system in which a foreign protein is displayed on the surface of a bacteriophage as a fusion protein with one of the coat proteins of the bacteriophage. T7 phage clones expressing normal human brain proteins (human normal brain phage-display cDNA expression library) were screened using SHBG as bait. The bound phage clones were then identified by DNA sequencing and by BLAST search analysis. Of the twenty binding proteins analyzed, three were found to be membrane-associated proteins: synaptosomal associated protein 25 (SNAP25), Thy-1 cell surface antigen and zonadhesin. Further studies will determine if the interactions of SHBG with these proteins have any role in the internalization and cell signaling events or whether they contribute to steroid delivery to specific cells.

Internalization of sex hormone-binding globulin into neurons and brain cells in vitro and in vivo.

BACKGROUND: Sex hormone-binding globulin (SHBG) is a 94-kDa homodimer that binds steroids and is made in the hypothalamus. We have demonstrated that infusions of SHBG into the hypothalami of rats increase their female sexual receptivity except when SHBG is coupled to dihydrotestosterone (DHT) suggesting that SHBG has an active function in behavioral neuroendocrinology. METHODS: This study examines the possibility that SHBG is internalized by neuronal and/or non-neuronal brain cells as one possible mode of action using in vitro and in vivo techniques. RESULTS: First, analysis of the uptake of radiolabeled SHBG ((125)I-SHBG) found (125)I-SHBG uptake in HT22 hippocampal cells stably transfected with cDNA for ER beta (HT22-ER beta). The addition of DHT to (125)I-SHBG significantly inhibited (125)I-SHBG uptake in HT22-ER beta cells but not in HT22-ER alpha or HT22 wild-type cells. SHBG internalization was specific as it did not occur in either the human neuroblastoma cell line SK-N-SH or the glioma cell line C6. Second, SHBG was labeled with a fluor (Alexa-555), and infused into the lateral cerebroventricles of ovariectomized rats. Optimal SHBG uptake was seen 10 min after these infusions. SHBG uptake was seen in specific parts of the choroid plexus and periventricular cells as well as into cells in the paraventricular nucleus, the medial forebrain bundle, and the habenula. CONCLUSIONS: These studies suggest that SHBG is internalized by brain cells, which may be affected by the presence of ER beta. The gonadal steroids have numerous effects in brain and the discovery that the steroid-binding protein SHBG is taken up into neurons and brain cells may demand a change in thinking about how steroids are delivered to brain cells to affect neurophysiology.

Mycobacterium avium binds to mouse intestinal mucus aldolase.

SETTING: Mycobacterium avium complex (MAC) is known to colonize the gastrointestinal tract of human immunodeficiency virus (HIV) infected patients before causing bacteremia and disseminated disease. However, the mechanism involved in the gastrointestinal colonization is not known. OBJECTIVE: To identify putative intestinal mucus receptors which serve as anchor for MAC colonization. DESIGN: C57BL/6 mouse intestinal mucus was subjected to single and two-dimensional electrophoresis and blotted on nitrocellulose membranes. MAC specific mucus proteins were identified by probing the mucus western blots with biotinylated proteins derived from M.avium strain 101 (MAC101). RESULTS: Biotinylated MAC 101 proteins recognized a 39 kDa intestinal mucus glycoprotein. The protein displaying an isoelectric point (pI) of 9.0, was found to be periodate sensitive but resistant to sialidase, heparinase I and chondroitinase ABC. The internal amino acid sequence of the 39 kDa protein displayed homology with fructose-1-6-bisphosphate aldolase B (aldolase). The proclivity between MAC adhesins and aldolase was confirmed by probing rabbit muscle aldolase with MAC proteins. Furthermore, both 25 and 31 kDa MAC adhesins, superoxide dismutase and heparin binding protein, respectively, were found to bind to aldolase. CONCLUSIONS: MAC binds to intestinal mucus aldolase, conceivably facilitating intestinal colonization of the organism.

UDP-glucuronosyltransferase in the rat olfactory bulb: identification of the UGT1A6 isoform and age-related changes in 1-naphthol glucuronidation.

Xenobiotic glucuronidation represents a major metabolic protection of the brain against chemical aggressions at blood-brain interfaces. We previously observed that glucuronidation of 1-naphthol was very effective in olfactory bulb, which is a pathway for the entry of foreign molecules into the brain. In this work, we showed that 1-naphthol glucuronidation varied according to age. It was very high at birth, then decreased markedly in 3-month-old rats and increased again significantly during aging. By Western blot and reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated the presence in the olfactory bulb of the UDP-glucuronosyltransferase (UGT) 1A6 isoform, which catalyzes the glucuronidation of phenols, such as 1-naphthol. Quantitative RT-PCR indicated that the mRNA levels encoding UGT1A6 did not significantly change according to age, thus suggesting that other differently regulated UGT isoforms were present and would account for the variations of 1-naphthol glucuronidation observed.