The gunshot-related injuries in trauma (GRIT) study: A profile of patients affected by gunshot-related orthopaedic injuries across South Africa.

BACKGROUND: South Africa (SA) has one of the highest gun-related mortality rates in the world - 20 people per day. The available data, however, do not reflect the substantial number of patients suffering non-lethal firearm injuries. Gunshot-related injury has been recognised as a highly costly healthcare problem by individual treating centres in SA and other countries; however, no 'national picture' has been examined in detail. OBJECTIVES: To explore the burden of gunshot-related orthopaedic injuries across SA. METHODS: A multicentre research network was established in SA, and 37 orthopaedic units across 9 provinces participated. A prospective, observational cohort study was performed during a 2-week period in 2019. Patients were screened, enrolled and reported by local orthopaedic teams. Patients were included if they had at least one acute gunshot-related orthopaedic fracture referred to the orthopaedic service. Patients were asked additional questions around baseline health-related quality-of-life (HRQOL) and personal circumstances. Follow-up was at 8 weeks after injury. RESULTS: Thirty-seven centres enrolled 135 patients over the 2-week study period. Western Cape Province had the highest number of reported cases (n=52; 39%), followed by Gauteng (n=35; 26%) and KwaZulu-Natal (n=29; 21%). The median age of patients was 30.5 years and the majority were male (89%). Forty-three percent of patients had been either shot or stabbed prior to this injury. Fifty-two percent of all patients required fracture fixation surgery and 11% required wound debridement without fracture fixation. HRQOL data were collected successfully at baseline, but follow-up data were available for <25% of cases. CONCLUSIONS: Gunshot-related orthopaedic injuries represent a significant burden of disease in the SA healthcare environment. This study highlights several areas for further research in the management of the injuries and associated outcomes.

Development and validation of the simultaneous determination of artemisone, clofazimine and decoquinate with HPLC.

The aim of this study was to develop and validate a novel HPLC method for the simultaneous analysis of artemisone, clofazimine and decoquinate. Detection was obtained at two wavelengths; 284 nm (clofazimine) and 210 nm (artemisone and decoquinate). Gradient elution was used with mobile phase A (A) consisting of 0.005 M sodium octanesulphonic-acid (pH 3.5) and mobile phase B (B) of HPLC grade acetonitrile. The flow rate was set to 1.0 ml/min with (A) at 35% and (B) at 65% for 2 min, followed by a gradient shift of 10/90% ((A)/(B)) over a duration of 4 min. After 10 min, the initial gradient conditions were readjusted to 35/65% ((A)/(B)). Distinctive peaks were identified for clofazimine, artemisone and decoquinate, respectively. The proposed HPLC assay method was validated and found to be reliable, reproducible and accurate for simultaneous analysis of the three compounds.

Concussion management application for amateur sports.

Concussion management has become one of the most popular topics in sports medicine. Significant resources are being invested in developing protocols for professional sport associations such as the NFL and FIFA. These protocols are often expensive and require substantial resources to implement. The problem, however, runs much deeper than just professional sports. Currently there exists little infrastructure to effectively manage concussion in amateur settings such as high school, club and university sport. A more holistic approach is required to ensure that the same standard of concussion management is being implemented across the board, regardless of the available medical and financial resources. An application was developed that will allow for easily accessible baseline testing and access to a player's concussion history from anywhere in the world. The application will be used to monitor players from the day they start playing sport until they potentially become professional sport players.

Association between breast milk fatty acids and HIV-1 transmission through breastfeeding.

A residual mother-to-child transmission of HIV through breastfeeding persists despite prophylaxis. We identified breast milk fatty acids (FA) associated with postnatal HIV transmission through breastfeeding in a case-control study. Cases (n=23) were HIV-infected women with an infant who acquired HIV after 6 weeks of age. Controls (n=23) were matched on infant׳s age at sample collection. Adjusting for maternal antenatal plasma CD4 T cell count, cis-vaccenic acid (18:1n-7) and eicosatrienoic acid (20:3n-3) were associated with HIV transmission in opposite dose-response manner: OR (tertile 3 versus tertile 1): 10.8 and 0.16, p for trend=0.02 and 0.03, respectively. These fatty acids correlated with HIV RNA load, T helper-1 related cytokines, IL15, IP10, and ß2 microglobulin, positively for cis-vaccenic acid, negatively for eicosatrienoic acid. These results suggested a change in FA synthesis by mammary gland cells leading to increased cis-vaccenic acid in milk of mothers who transmitted HIV to their infant during breastfeeding.

A phase 2, randomized, double-blind, multicenter trial to evaluate the safety and efficacy of three dosing regimens of isavuconazole compared with fluconazole in patients with uncomplicated esophageal candidiasis.

Esophageal candidiasis is a frequent cause of morbidity in immunocompromised patients. Isavuconazole is a novel, broad-spectrum antifungal developed for the treatment of opportunistic fungal infections. This phase 2 trial compared the efficacy and safety of three oral dosing regimens of isavuconazole with an oral fluconazole regimen in the primary treatment of uncomplicated esophageal candidiasis. The isavuconazole regimens were as follows: 200 mg on day 1 and then 50 mg once daily (arm A), 400 mg on day 1 and then 400 mg once-weekly (arm B), and 400 mg on day 1 and then 100 mg once daily (arm C). Patients in arm D received fluconazole at 200 mg on day 1 and then 100 mg once daily. The minimum treatment duration was 14 days. The primary endpoint was the rate of endoscopically confirmed clinical response at end of therapy. Safety and tolerability were also assessed. Efficacy was evaluated in 153 of 160 enrolled patients. Overall, 146 (95.4%) achieved endoscopically confirmed clinical success. Each of the isavuconazole regimens was shown to be not inferior to fluconazole, i.e., arm A versus D, -0.5% (95% confidence interval [CI] -10.0 to 9.4), arm B versus D, 3.5% (95% CI, -5.6 to 12.7), and arm C versus D, -0.2% (95% CI, -9.8 to 9.4). The frequency of adverse events was similar in arm A (n = 22; 55%), arm B (n = 18; 45%), and arm D (n = 22; 58%), but higher in arm C (n = 29; 71%). In summary, efficacy and safety of once-daily and once-weekly isavuconazole were comparable with once-daily fluconazole in the primary treatment of uncomplicated esophageal candidiasis.

Novel non-invasive protein and peptide drug delivery approaches.

Protein and peptide based therapeutics are typically administered by injection due to their poor uptake when administered via enteral routes of drug administration. Unfortunately, chronic administration of these drugs through multiple injections presents certain patient related problems and it is difficult to mimic the normal physiological release patterns via this mode of drug administration. A need therefore exists to non-invasively deliver these drugs by means of alternative ways such as via the oral, pulmonary, nasal, transdermal and buccal administration routes. Although some attempts of needle free peptide and protein drug delivery have progressed to the clinical stage, relatively limited success has been achieved in terms of commercially available products. Despite the low frequency of clinical breakthroughs with noninvasive protein drug delivery this far, it remains an active research area with renewed interest not only due to its improved therapeutic potential, but also due to the attractive commercial outcomes it offers. It is the aim of this review article to reflect on the main strategies investigated to overcome the barriers against effective systemic protein drug delivery in different routes of drug administration. Approaches based on chemical modifications and pharmaceutical technologies are discussed with reference to examples of drugs and devices that have shown potential, while attempts that have failed are also briefly outlined.

Use of dried blood spots for the determination of genetic variation of interleukin-10, killer immunoglobulin-like receptor and HLA class I genes.

Optimal methods for using dried blood spots (DBSs) for population genetics-based studies have not been well established. Using DBS stored for 8 years from 21 pregnant South African women, we evaluated three methods of gDNA extraction with and without whole-genome amplification (WGA) to characterize immune-related genes: interleukin-10 (IL-10), killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I. We found that the QIAamp DNA mini kit yielded the highest gDNA quality (P< 0.05; Wilcoxon signed rank test) with sufficient yield for subsequent analyses. In contrast, we found that WGA was not reliable for sequence-specific primer polymerase chain reaction (SSP-PCR) analysis of KIR2DL1, KIR2DS1, KIR2DL5 and KIR2DL3 or high-resolution HLA genotyping using a sequence-based approach. We speculate that unequal template amplification by WGA underrepresents gene repertoires determined by sequence-based approaches.

Di-µ-hydroxido-bis-[tris-(4,4,4-trifluoro-1-phenyl-acetyl-acetonato-κO,O')hafnium(IV)] dimethyl-formamide disolvate.

The binuclear molecule of the title compound, [Hf(2)(C(10)H(6)F(3)O(2))(6)(OH)(2)]·2C(3)H(7)NO, lies across an inversion centre and contains a Hf(IV) atom which is eight-coordinated and surrounded by three chelating ß-diketonato tris-(4,4,4-trifluoro-1-phenyl-acetyl-acetonate (tfba(-)) ligands and two bridging OH(-) groups in a distorted square-anti-prismatic geometry. The Hf-O bond lengths vary from 2.073 (2) to 2.244 (2) Šand the O-Hf-O bite angles vary from 73.49 (9) to 75.60 (9)°. Weak O-H⋯O hydrogen-bonding inter-actions are observed between the bridging hy-droxy groups and the dimethylformamide solvent mol-ecules. The unit cell contains solvent-accessible voids of 131 Å(3), but the residual electron density in the difference Fourier map suggests no solvent mol-ecule occupies this void.

Tetra-kis(5,7-dimethyl-quinolin-8-olato-κN,O)hafnium(IV) dimethyl-formamide disolvate.

In the title compound, [Hf(C(11)H(10)NO)(4)]·2C(3)H(7)NO, the Hf(IV) atom is coordinated by four N,O-donating bidentate 5,7-dimethyl-8-quinolino-late (Ox(-)) ligands arranged to give a distorted square-anti-prismatic coordination polyhedron. The average Hf-O and Hf-N distances are 2.098 and 2.298 Å, respectively, and the average O-Hf-N bite angle is 70.2°. The crystal packing is controlled by π-π inter-actions between Ox(-) ligands of neighbouring mol-ecules, giving rise to a three-dimensional supra-molecular grid network. The inter-planar distances vary from 3.441 (1) to 3.509 (1) Å, while the centroid-centroid distances vary from 3.688 (2) to 3.759 (12) Å. A non-classical C-H⋯O hydrogen bond is observed between the complex and one of the solvate mol-ecules.

Tetra-kis(1,3-diphenyl-propane-1,3-dionato)hafnium(IV).

In the title compound, [Hf(C(15)H(11)O(2))(4)], the Hf(IV) atom is coordinated by four 1,3-diphenyl-propane-1,3-dionato ligands with an average Hf-O distance of 2.17 (3) Šand O-Hf-O bite angles varying from 74.5 (1) to 75.02 (9)°. The coordination polyhedron shows a slightly distorted Archimedean square-anti-prismatic geometry. The crystal packing is stabilized by weak C-H⋯O inter-actions.

Di-µ-hydroxido-bis[tris(1,1,1,5,5,5-hexa-fluoro-acetyl-acetonato-κO,O')hafnium(IV)] acetone solvate.

The binuclear title compound, [Hf(2)(C(5)HF(6)O(2))(6)(OH)(2)]·C(3)H(6)O, contains an Hf(IV) atom which is eight coordinated and surrounded by three chelating ß-diketonato 1,1,1,5,5,5-hexa-fluoro-acetyl-acetonate (hfaa) ligands and two bridging OH groups situated on a twofold rotation axis. The HfO(8) coordination polyhedron shows a slightly distorted Archimedean square anti-prismatic coordination with average Hf-O, C-O, C-C(Me) distances of 2.19 (2), 1.26 (2) and 1.49 (2) Å, respectively, and an O-Hf-O bite angle of 75.3 (5)°. Weak O-H⋯O hydrogen bonding inter-actions are observed between one of the bridging hydr-oxy groups and the disordered solvent mol-ecule.

Tetra-kis(quinolin-8-olato-κN,O)hafnium(IV) toluene disolvate.

In the title compound, [Hf(C(9)H(6)NO)(4)]·2C(7)H(8), the hafnium metal centre is coordinated by four N,O-donating bidentate quinolin-8-olate ligands arranged to give a square-anti-prismatic coordination polyhedron with a slightly distorted dodeca-hedral geometry. The average Hf-O and Hf-N distances are 2.096 (3) and 2.398 (3) Å, respectively, and the average O-Hf-N bite angle is 70.99 (11)°. The crystal packing is controlled by π-π inter-actions between quinoline ligands of neighbouring mol-ecules and hydrogen-bonding inter-actions. The inter-planar distances vary between 3.138 (1) and 3.208 (2) Å, while the centroid-centroid distances range from 3.576 (1) to 4.074 (1) Å.

Tetra-kis(1,1,1-trifluoro-acetyl-acetonato-κO,O')hafnium(IV) toluene disolvate.

In the title compound, [Hf(C(5)H(4)F(3)O(2))(4)]·2C(7)H(8), the Hf(IV) atom, lying on a twofold rotation axis, is coordinated by eight O atoms from four 1,1,1-trifluoro-acetyl-acetonate ligands with an average Hf-O distance of 2.173 (1) Šand O-Hf-O bite angles of 75.69 (5) and 75.54 (5)°. The coordination polyhedron shows a slightly distorted Archimedean square antiprismatic geometry. The asymmetric unit contains a toluene solvent mol-ecule. The crystal structure involves C-H⋯.F hydrogen bonds.

Smoking in pregnancy -- what does my patient know ?

A recent study by the Medical Research Council (MRC) Perinatal Mortality Research Unit at Tygerberg Hospital found that 39% of pregnant women smoked cigarettes.1 Smoking in pregnancy is clearly recognised in the literature as an important, dose-related, preventable risk factor for poor perinatal outcome.2 Aprevious MRC finding that 47% of South African coloured women smoke during pregnancy3 stands in sharp contrast to the prevalence in developed countries, for example 15.8% in the USA.4 In a developing country, where poverty in itself increases perinatal mortality and morbidity, this increase in cigarette smoking may have further negative effects on perinatal outcome, despite efforts to optimize antenatal care. It is, therefore, of concern that despite current knowledge of the harmful effects of smoking in pregnancy, such a large percentage of pregnant women at Tygerberg Hospital are smokers. We wondered to what extent pregnant patients at Tygerberg Hospital are aware of the harmful effects of cigarette smoking during pregnancy and after childbirth.

A randomized, double blind, comparative trial of micafungin (FK463) vs. fluconazole for the treatment of oesophageal candidiasis.

AIM: To determine efficacy and safety of intravenous micafungin vs. intravenous fluconazole in the treatment of oesophageal candidiasis. METHODS: A total of 523 patients > or =16 years with documented oesophageal candidiasis were randomized (1:1) in this controlled, non-inferiority study to receive either micafungin (150 mg/day) or fluconazole (200 mg/day). Response was evaluated clinically and endoscopically. Post-treatment assessments were performed at 2 and 4 weeks after discontinuation of therapy. RESULTS: Median duration of therapy was 14 days. For the primary end-point of endoscopic cure, treatment difference was -0.3% (micafungin 87.7%, fluconazole 88.0%). Documented persistent invasive disease at the end of therapy was reported in 2.7% and 3.9% of patients, respectively. Both 84.8% of micafungin and 88.7% of fluconazole patients remained recurrence free at 4-weeks post-treatment. The overall therapeutic response rate was 87.3% for micafungin and 87.2% for fluconazole. The incidence of drug-related adverse events was 27.7% for micafungin and 21.3% for fluconazole. Six (2.3%) micafungin- and two (0.8%) fluconazole-treated patients discontinued therapy; rash was the most common event leading to discontinuation. CONCLUSION: Intravenous micafungin (150 mg daily) is well tolerated and as efficacious as intravenous fluconazole (200 mg daily) in the primary treatment of oesophageal candidiasis, achieving high rates of clinical and endoscopic cure.

The acceptability of male circumcision as an HIV intervention among a rural Zulu population, Kwazulu-Natal, South Africa.

Epidemiological and biological studies provide compelling evidence for the protective effect of male circumcision against the acquisition of HIV. Three randomized controlled trials are currently underway to assess the impact of male circumcision as an HIV intervention in traditionally non-circumcising areas with high levels of heterosexually-transmitted infection. This study explores the acceptability of male circumcision among the rural Zulu around Hlabisa and Mtubatuba, KwaZulu-Natal, South Africa. A cross-sectional convenience sample of 100 men and 44 women was surveyed, and two male focus groups held, to ascertain circumcision preferences within the population. Four in-depth interviews with service providers assessed the feasibility of promoting male circumcision. Fifty-one per cent of uncircumcised men and 68% of women favoured male circumcision of themselves or their partners; while 50% of men and 73% of women would circumcise their sons. For men, the main predictors of circumcision preference pertained to beliefs surrounding sexual pain and pleasure; for women, knowledge about the relationship between male circumcision status and STI acquisition was the key indicator for circumcision preference. Among both sexes the main barrier to circumcision was fear of pain and death. The greatest logistical barrier was that circumcision can presently only be carried out by trained hospital doctors.

Assessing fitness to stand trial: the utility of the Fitness Interview Test (revised edition).

OBJECTIVE: In Canada most evaluations of fitness to stand trial are conducted on an inpatient basis. This costs time and money, and deprives those defendants remanded for evaluation of liberty. This research assessed the predictive efficiency of the Fitness Interview Test, revised edition (FIT) as a screening instrument for fitness to stand trial. METHOD: We compared decisions about fitness to stand trial, based on the FIT, with the results of institution-based evaluations for 2 samples of men remanded for inpatient fitness assessments. RESULTS: The FIT demonstrates excellent utility as a screening instrument. The FIT shows good sensitivity and negative predictive power, which suggests that it can reliably screen those individuals who are clearly fit to stand trial, before they are remanded to an inpatient facility for a fitness assessment. CONCLUSION: We discuss the implications for evaluating fitness to stand trial, particularly in terms of the need for community-based alternatives to traditional forensic assessments.