Nelson Mandela Academic Hospital

BACKGROUND: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

BACKGROUND: A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS: In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS: In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS: The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).

BACKGROUND: There is limited information about the challenges of cancer management and attempts at improving outcomes in Africa. Even though South and North Africa are better resourceds to tackle the burden of breast cancer, similar poor prognostic factors are common to all countries. The five-year overall Survival rate for breast cancer patients does not exceed 60% for any low and middle-income country (LMIC) in Africa. In spite of the gains achieved over the past decade, certain characteristics remain the same such as limited availability of breast conservation therapies, inadequate access to drugs, few oncology specialists and adherence to harmful socio-cultural practices. This review on managing breast cancer in Africa is authored by African oncologists who practice or collaborate in Africa and with hands-on experience with the realities. METHODS: A search was performed via electronic databases from 1999 to 2016. (PubMed/Medline, African Journals Online) for all literature in English or translated into English, covering the terms "breast cancer in Africa and developing countries". One hundred ninety were deemed appropriate. RESULTS: Breast tumors are diagnosed at earlier ages and later stages than in highincome countries. There is a higher prevalence of triple-negative cancers. The limitations of poor nursing care and surgery, inadequate access to radiotherapy, poor availability of basic and modern systemic therapies translate into lower survival rate. Positive strides in breast cancer management in Africa include increased adaptation of treatment guidelines, improved pathology services including immuno-histochemistry, expansion and upgrading of radiotherapy equipment across the continent in addition to more research opportunities. CONCLUSION: This review is an update of the management of breast cancer in Africa, taking a look at the epidemiology, pathology, management resources, outcomes, research and limitations in Africa from the perspective of oncologists with local experience.

A total of 33 children were treated for acute traumatic dislocation of the elbow between 1994 and 2002; 30 dislocations were posterior and three anterior. Eight children had a pure dislocation and 25 had an associated fracture of the elbow. Two had compound injuries. Two children had injury to the ulnar nerve, one to the radial nerve and one to the median nerve together with injury to the brachial artery. Twenty required open reduction. Complications included pseudarthrosis of the medial epicondyle in one child and loss of flexion and rotation of between 10 degrees and 30 degrees in ten others. Meticulous clinical and radiological assessment is mandatory in children with dislocation of the elbow to exclude associated injuries. The results were excellent to good in 22 patients, fair in ten and poor in one.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are now major threats in areas of South Africa with a high prevalence of TB and human immunodeficiency virus (HIV) infection. The role of exogenous reinfection as a cause of MDR and XDR TB in these settings has not been determined. METHODS: We reviewed data from patients with culture-positive TB who later developed MDR or XDR TB in Tugela Ferry, KwaZulu-Natal, South Africa during 2005-2006. We performed spoligotyping on initial isolates (obtained at the time of treatment initiation) and follow-up isolates obtained from these patients. RESULTS: We identified 23 patients who developed MDR or XDR TB after being treated for less resistant TB between June 2005 and June 2006. Both initial and follow-up isolates were available for spoligotyping for 17 of these patients. In all cases, the follow-up isolates' spoligotypes differed from those of the initial isolate, indicating exogenous reinfection. Two genotypes (shared type [ST] 34 and ST 60, associated with MDR and XDR TB, respectively) were responsible for 85% of reinfections. All 17 patients had been hospitalized; all 15 whose HIV infection status was known were HIV-infected. CONCLUSIONS: Exogenous reinfection is an important mechanism for the development of MDR and XDR TB. In addition to strengthening TB treatment programs, effective infection control strategies are urgently needed to reduce the transmission of MDR and XDR TB.

BACKGROUND: The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.

BACKGROUND: During development, the placenta can be said to be the most important organ, however, the most poorly researched. There is currently a broader understanding of how specific insults during development affect the fetal brain, and also the importance of placental signaling in neurodevelopmental programming. Epigenetic responses to maternal and fetal signals are an obvious candidate for transforming early life inputs into long-term programmatic outcomes. As a mediator of maternal and environmental signals to the developing fetus, epigenetic processes within the placenta are particularly powerful such that alterations of placental gene expression, downstream function, and signalling during foetal development have the potential for dramatic changes in developmental programming. SUMMARY: In this article, we reviewed emerging evidence for a placental role in prenatal neurodevelopmental programming with a specific focus on nutrient and prenatal stress signals integration into chromatin changes; this new understanding, we hope will provide the means for lowering developmentally based disorder risk, and new therapeutic targets for treatment in adulthood. KEY MESSAGES: Based on this review, the placenta is a potent micro-environmental player in neurodevelopment as it orchestrates a series of complex maternal-foetal interactions. Maternal insults to this microenvironment will impair these processes and disrupt foetal brain development resulting in the prenatal programming of neurodevelopmental disorders. These findings should inspire advance animal model and human research drive to appraise gene-environment impacts during pregnancy that will target the developmental cause of adult-onset mental disorders.

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.

N-trimethyl chitosan chloride (TMC) is a polycation that enhances drug transport across epithelia by opening tight junctions. The degree of quaternization of TMC determines the number of positive charges available on the molecule for interactions with the negatively charged sites on the epithelial membrane and thereby influences its drug absorption-enhancing properties. The effects of six different TMC polymers (degree of quarternization between 12% and 59%) on the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers and on the transport of hydrophilic and macromolecular model compounds across Caco-2 cells were determined. All the TMC polymers were able to decrease the TEER markedly in a slightly acidic environment (pH 6.2). However, only TMC polymers with higher degrees of quaternization (> 22%) were able to reduce the TEER in a neutral environment (pH 7.4). The maximum reduction in TEER (47.34 +/- 6.0% at a concentration of 0.5% w/v and pH 7.4) was reached with TMC with a degree of quaternization of 48%, and this effect did not increase further with higher degrees of quaternization of TMC. In agreement with the TEER results, the transport of model compounds across Caco-2 cell monolayers increased with an increase in the degree of quaternization of TMC. However, the transport reached a maximum for TMC with a degree of quaternization of 48% (25.3% of the initial dose for [14C]mannitol and 15.2% of the initial dose for [14C]PEG 4000), and this effect did not increase further with higher degrees of quaternization of TMC. Therefore, the increase in the effects of TMC on intestinal epithelia did not directly correlate up to the maximum quaternization degree of this polymer, but reached an optimum value already at an intermediate degree of quaternization (ca. 48%).

Abstract Rationale Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to ∼6 months remains an aspirational goal for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Objectives To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB (i.e., without resistance to fluoroquinolones or aminoglycosides). Methods Participants were randomly assigned (1:1 ratio) to a ∼6-month all-oral regimen that included levofloxacin, bedaquiline, and linezolid, or the standard-of-care (SOC) ⩾9-month World Health Organization (WHO)-approved injectable-based regimen. The primary endpoint was a favorable WHO-defined treatment outcome (which mandates that prespecified drug substitution is counted as an unfavorable outcome) 24 months after treatment initiation. The trial was stopped prematurely when bedaquiline-based therapy became the standard of care in South Africa. Measurements and Main Results In total, 93 of 111 randomized participants (44 in the comparator arm and 49 in the interventional arm) were included in the modified intention-to-treat analysis; 51 (55%) were HIV coinfected (median CD4 count, 158 cells/ml). Participants in the intervention arm were 2.2 times more likely to experience a favorable 24-month outcome than participants in the SOC arm (51% [25 of 49] vs. 22.7% [10 of 44]; risk ratio, 2.2 [1.2–4.1]; P = 0.006). Toxicity-related drug substitution occurred more frequently in the SOC arm (65.9% [29 of 44] vs. 34.7% [17 of 49]; P = 0.001)], 82.8% (24 of 29) owing to kanamycin (mainly hearing loss; replaced by bedaquiline) in the SOC arm, and 64.7% (11 of 17) owing to linezolid (mainly anemia) in the interventional arm. Adverse event–related treatment discontinuation in the safety population was more common in the SOC arm (56.4% [31 of 55] vs. 32.1% [17 of 56]; P = 0.007). However, grade 3 adverse events were more common in the interventional arm (55.4% [31 of 56] vs. 32.7 [18 of 55]; P = 0.022). Culture conversion was significantly better in the intervention arm (hazard ratio, 2.6 [1.4–4.9]; P = 0.003) after censoring those with bedaquiline replacement in the SOC arm (and this pattern remained consistent after censoring for drug replacement in both arms; P = 0.01). Conclusions Compared with traditional injectable-containing regimens, an all-oral 6-month levofloxacin, bedaquiline, and linezolid–containing MDR/RR-TB regimen was associated with a significantly improved 24-month WHO-defined treatment outcome (predominantly owing to toxicity-related drug substitution). However, drug toxicity occurred frequently in both arms. These findings inform strategies to develop future regimens for MDR/RR-TB. Clinical trial registered with www.clinicaltrials.gov (NCT 02454205).

BACKGROUND: High efficacy and safety, coupled with in-office, short contact protocols have made photodynamic therapy (PDT) with aminolevulenic acid (ALA) for the treatment of actinic keratoses a mainstay option over the last decade. Clinical improvement in photoaged skin has also been reported to accompany PDT treatments. The study objective was to maximize epidermal penetration and subsequent activation of ALA for the treatment of photodamaged facial skin, utilizing a microneedle roller prior to incubation and combined irradiation with red light and broadband pulsed light in a single treatment. MATERIALS AND METHODS: A full-face treatment of 21 patients was performed with 630 nm light and broadband pulsed light after multiple passes with a microneedle roller and 1-hour ALA incubation. The primary endpoint was clinical improvement, scored during two separate live assessments by three physicians blinded to previous scores, using a 5-point standardized photoaging scale. The secondary endpoint was evaluation of patient satisfaction based on a quartile scale comparing baseline to 6-month post-treatment photography. RESULTS: Statistically significant improvement was seen in the global photoaging scores, as well as sub-components of the scale (fine lines, mottled pigmentation, sallowness, tactile roughness, and telangiectasias) at 3 months as compared with baseline live assessment, and at 6-month live assessment compared with the 3 months. In addition, 90% of patients judged clinical improvement to be greater than 50% at 6 months compared to baseline photography. CONCLUSION: Use of a microneedle roller to "pre-treat" prior to application of ALA appears to be well tolerated and allows for even absorption and perhaps deeper penetration of ALA following a defined incubation period. Use of red light and broadband pulsed light allowed for deeper activation of ALA, potentially accounting for marked clinical improvement in photoaging.

There were 507 deaths associated with hypertensive disorders of pregnancy (eclampsia, preeclampsia, and chronic hypertension) in South Africa over the triennium 1999-2001. Eclampsia was associated with 289 deaths, preeclampsia with 139, and the remaining 79 with chronic hypertension, hemolysis, elevated lever enzymes, and low platelet count (HELLP) syndrome, liver rupture and acute fatty liver. The major final cause of death was intracranial hemorrhage. Other causes included HELLP syndrome and liver rupture. Contributory causes include pulmonary edema, renal failure/impairment, and disseminated intravascular coagulation. Deaths from eclampsia occurred at all levels of health care, in particular, there was still a considerable number of deaths at level I hospitals. Most deaths from eclampsia occurred at low parity (parity 0 = 51%), while 13% of deaths in noneclamptics occurred in women of parity > or = 5. Similarly, most deaths from eclampsia occurred in women aged < or = 24 years, while most in the noneclamptic group were aged 25 years and greater. The most common avoidable factors were patent-oriented problems--women who either presented late for antenatal care or late to hospital when symptomatic. Administrative factors also played a major role, in that there was a delay in referral due to the unavailability of transport. The lack of protocols of management or failure to follow clinical protocols of care contributed towards avoidable medical factors. Most women presented as an emergency event and failure of resuscitation/achievement of hemodynamic stabilization constituted a significant avoidable factor. Clear protocols for management of hypertension in pregnancy at all levels of health care are required.

OBJECTIVE: The investigation sought to establish the awareness of breast and cervical cancers among women of African descent, in both rural and urban areas, especially considering the oppression and deprivation experienced by this group. DESIGN: Two groups of randomly selected women in a rural (n = 70) and urban (n = 70) area were interviewed using a structured questionnaire assessing their knowledge and attitudes regarding breast and cervical cancer and screening options. RESULTS: The age range of the sample was 21-59 years with a mean of 35.23 years. Almost one-fifth of the women had not heard of these cancers, and almost half were unaware of the breast self-examination technique. Over one-third did not know about tests for breast cancer and more than half were unaware of tests for cervical cancer. Generally lower awareness levels were found in older and rural women who were also significantly more inclined to consult traditional healers (than doctors) about lumps in their breast or abnormal cervical bleeding. CONCLUSION: The findings are of great concern and represent a significant challenge in post-apartheid South Africa. The need for vigorous health promotion programmes cannot be sufficiently emphasised, especially in view of the benefits of early detection and treatment. There also needs to be particular focus on rural women, considering the inadequate health care resources in their communities and the socio-economic hardships facing them. Women in these communities must be empowered with knowledge about their health and illness prevention options.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

The recruitment and training of clinical psychologists remain important challenges for South African psychology in the post-apartheid period. Specifically, the challenges are to address issues of equity and redress, develop relevant policy, curricula and practices, and to produce graduates who are able and willing to work in the context of diversity and disadvantage. In this article we selectively review the progress made in responding to these challenges. Our conclusion is one of concern, since clinical psychology's track record in terms of training leaves much to be desired. While there is a greater degree of engagement with issues of equity and access, training still remains racially skewed and redress is largely confined to simply providing institutional access. Furthermore, the ‘silences' and paucity of attempts at transforming recruitment and selection processes, policy, curricula and training practices are of even greater concern. We argue that while there are constraints to transforming training in terms of the tensions and contradictions between mainstream professional training requirements, social conditions and ‘relevant’ discourses and practices, a far more substantive engagement with, and commitment to the fundamental issues are required. This review concludes with the assertion that clinical psychology is rapidly running out of time to remedy its deficiencies and maintain its respectability as a helping profession for the entire nation. Some tentative suggestions are offered for the way forward.

The difficulty of diagnosing active tuberculosis (TB) and lack of rapid drug susceptibility testing (DST) at the point of care remain critical obstacles to TB control. This report describes a high-intensity mycobacterium-specific-fluorophage (φ(2)GFP10) that for the first time allows direct visualization of Mycobacterium tuberculosis in clinical sputum samples. Engineered features distinguishing φ(2)GFP10 from previous reporter phages include an improved vector backbone with increased cloning capacity and superior expression of fluorescent reporter genes through use of an efficient phage promoter. φ(2)GFP10 produces a 100-fold increase in fluorescence per cell compared to existing reporter phages. DST for isoniazid and oxofloxacin, carried out in cultured samples, was complete within 36 h. Use of φ(2)GFP10 detected M. tuberculosis in clinical sputum samples collected from TB patients. DST for rifampin and kanamycin from sputum samples yielded results after 12 h of incubation with φ(2)GFP10. Fluorophage φ(2)GFP10 has potential for clinical development as a rapid, sensitive, and inexpensive point-of-care diagnostic tool for M. tuberculosis infection and for rapid DST.

AIMS: This study examines clinical and pathologic features of primary cutaneous adenoid cystic carcinoma (ACC), with emphasis on biological behavior of these tumors. A total of 27 cases of primary cutaneous ACC with detailed follow-up information were evaluated. Clinically, these were solitary, slow-growing lesions, half of which were in the head and neck area. The median age was 62 years with a male predilection. Surgical excision was the treatment of choice. Histologically, the lesions were similar to those seen in the salivary glands. Tumors were classified as grade 1 (17), grade 2 (3), and grade 3 (7). The mitotic count was generally low (mean=1.9/mm), except in 2 high-grade tumors (>10 mitotic figures/mm). Sixteen cases showed perineural invasion. Immunohistochemically, cytokeratin positivity was noted in 13/13 cases, and CD117 was observed in 10/10 cases, with luminal/cytoplasmic staining for epithelial membrane antigen (14/16) and at least focal luminal expression for carcinoembryonic antigen (11/16), smooth muscle actin (10/13), and S100 staining (9/13). Eighteen cases had follow-up data (median 54 mo), 9 of which had local recurrences (50%). Three cases showed metastatic disease. No statistical difference was noted between tumor grade and local recurrence (P=0.77). Primary cutaneous ACC is a distinct entity with a more indolent behavior compared with its salivary counterpart. The cutaneous lesions tend to recur locally but have a low metastatic potential.

OBJECT: The presence of the apolipoprotein E-epsilon4 (APOE-epsilon4) allele is reported to be associated with poor outcome after traumatic brain injury (TBI). This study was performed to determine if the presence of the APOE-epsilon4 allele influenced outcome in a cohort of black patients with TBI who had homogeneous neuropathological findings. METHODS: Venous blood was collected at the time of admission to determine the APOE genotype in black Zulu-speaking patients who presented with traumatic cerebral contusions. The frequency of the APOE-epsilon4 allele's appearance was correlated with outcome at a minimum of 6 months of follow up. Univariate and multivariate analyses were performed to determine independent risk factors and to control for confounding factors. In 110 black Zulu-speaking patients with traumatic cerebral contusions, genotypes for APOE were analyzed. Eleven of 45 (24.4%) with the APOE-epsilon4 allele experienced a poor outcome, compared with 10 (15.4%) of 65 without this allele (p = 0.34). Both patients with homozygous APOE-epsilon4 alleles experienced a good outcome (Glasgow Outcome Score 5). Univariate and multivariate analysis revealed no significant relationship in patients with the APOE-epsilon4 allele with regard to age, admission Glasgow Comas Scale score, contusion volume, type of neurosurgical management, and outcome. The risk of a poor outcome was, however, greater in patients with the APOE-epsilon4 allele (relative risk 1.59; 95% confidence interval 0.74-3.42). CONCLUSIONS: The authors recorded no relationship between APOE-epsilon4 allele status and outcome after TBI in black patients. Given the high regional susceptibility to the APOE gene, further studies, possibly even community-based investigations and studies conducted in other geographic areas, are probably warranted.

Bousquet, F., A. Botta, L. Alinovi, O. Barreteau, D. Bossio, K. Brown, P. Caron, P. Cury, M. D'Errico, F. DeClerck, H. Dessard, E. Enfors Kautsky, C. Fabricius, C. Folke, L. Fortmann, B. Hubert, D. Magda, R. Mathevet, R. B. Norgaard, A. Quinlan, and C. Staver. 2016. Resilience and development: mobilizing for transformation. Ecology and Society 21(3):40. https://doi.org/10.5751/ES-08754-210340

Hemopure (hemoglobin glutamer-250 [bovine]; HBOC-201) is a hemoglobin (Hb)-based oxygen carrier registered with the Medicines Control Council of South Africa. It is indicated for the treatment of adult patients who are acutely anemic, for the purpose of maintaining tissue oxygen delivery thus eliminating, delaying, or reducing the need for allogeneic red blood cells (RBCs). Hemopure is a volume expander, and circulatory volume must be carefully monitored for signs of fluid overload. Hemopure is not as effective as RBCs for restoring Hb content and concentration, but in cases of severe anemia where allogeneic blood is not an option or is unavailable, it may offer an immediate alternative for improving oxygen transport. This document provides clinical recommendations on the safe and effective use of Hemopure based on the postmarketing experience in South Africa as well as a better understanding of Hemopure properties reflected in recent publications.