Burden, risk factors, neurosurgical evacuation outcomes, and predictors of mortality among traumatic brain injury patients with expansive intracranial hematomas in Uganda: a mixed methods study design.

BACKGROUND: Expansive intracranial hematomas (EIH) following traumatic brain injury (TBI) continue to be a public health problem in Uganda. Data is limited regarding the neurosurgical outcomes of TBI patients. This study investigated the neurosurgical outcomes and associated risk factors of EIH among TBI patients at Mulago National Referral Hospital (MNRH). METHODS: A total of 324 subjects were enrolled using a prospective cohort study. Socio-demographic, risk factors and complications were collected using a study questionnaire. Study participants were followed up for 180 days. Univariate, multivariable, Cox regression analyses, Kaplan Meir survival curves, and log rank tests were sequentially conducted. P-values of < 0.05 at 95% Confidence interval (CI) were considered to be statistically significant. RESULTS: Of the 324 patients with intracranial hematomas, 80.6% were male. The mean age of the study participants was 37.5 ± 17.4 years. Prevalence of EIH was 59.3% (0.59 (95% CI: 0.54 to 0.65)). Participants who were aged 39 years and above; PR = 1.54 (95% CI: 1.20 to 1.97; P = 0.001), and those who smoke PR = 1.21 (95% CI: 1.00 to 1.47; P = 0.048), and presence of swirl sign PR = 2.26 (95% CI: 1.29 to 3.95; P = 0.004) were found to be at higher risk for EIH. Kaplan Meier survival curve indicated that mortality at the 16-month follow-up was 53.4% (95% CI: 28.1 to 85.0). Multivariate Cox regression indicated that the predictors of mortality were old age, MAP above 95 mmHg, low GCS, complications such as infection, spasticity, wound dehiscence, CSF leaks, having GOS < 3, QoLIBRI < 50, SDH, contusion, and EIH. CONCLUSION: EIH is common in Uganda following RTA with an occurrence of 59.3% and a 16-month higher mortality rate. An increased age above 39 years, smoking, having severe systemic disease, and the presence of swirl sign are independent risk factors. Old age, MAP above 95 mmHg, low GCS, complications such as infection, spasticity, wound dehiscence, CSF leaks, having a GOS < 3, QoLIBRI < 50, ASDH, and contusion are predictors of mortality. These findings imply that all patients with intracranial hematomas (IH) need to be monitored closely and a repeat CT scan to be done within a specific period following their initial CT scan. We recommend the development of a protocol for specific surgical and medical interventions that can be implemented for patients at moderate and severe risk for EIH.

Design and Solidification of Fast-Releasing Clofazimine Nanoparticles for Treatment of Cryptosporidiosis.

Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and Drug Administration (FDA) with a good safety record, was recently identified as a lead hit for cryptosporidiosis through a high-throughput phenotypic screen. Cryptosporidiosis requires fast-acting treatment as it leads to severe symptoms which, if untreated, result in morbidity for infants and small children. Consequently, a fast-releasing oral formulation of clofazimine in a water-dispersible form for pediatric administration is highly desirable. In this work, clofazimine nanoparticles were prepared with three surface stabilizers, hypromellose acetate succinate (HPMCAS), lecithin, and zein, using the flash nanoprecipitation (FNP) process. Drug encapsulation efficiencies of over 92% were achieved. Lyophilization and spray-drying were applied and optimized to produce redispersible nanoparticle powders. The release kinetics of these clofazimine nanoparticle powders in biorelevant media were measured and compared with those of crystalline clofazimine and the currently marketed formulation Lamprene. Remarkably improved dissolution rates and clofazimine supersaturation levels up to 90 times equilibrium solubility were observed with all clofazimine nanoparticles tested. Differential scanning calorimetry indicated a reduction of crystallinity of clofazimine in nanoparticles. These results strongly suggest that the new clofazimine nanoparticles prepared with affordable materials in this low-cost nanoparticle formulation process can be used as viable cryptosporidiosis therapeutics.