Association of the Verbal Component of the GCS With Mortality in Patients With Encephalopathy Who Are Not Undergoing Mechanical Ventilation.

BACKGROUND AND OBJECTIVES: The utility of the Glasgow Coma Scale (GCS) in intubated patients is limited due to reliance on language function evaluation. The Full Outline of Unresponsiveness (FOUR) Score was designed to circumvent this shortcoming, instead adding evaluations of brainstem reflexes (FOUR B) and specific respiratory patterns (FOUR R). We aimed to determine whether the verbal component of the GCS (GCS V) among nonintubated patients with encephalopathy significantly contributes to mortality prediction and to assess GCS vs FOUR Score performance. METHODS: All prospectively consented patients ≥18 years of age admitted to the Internal Medicine service at Zambia's University Teaching Hospital from October 3, 2017, to May 21, 2018, with a GCS score ≤10 have undergone simultaneous GCS and FOUR Score assessments. The patients were not eligible for mechanical ventilatory support per local standards. Patients' demographics and clinical characteristics were presented as either percentage frequencies or numerical summaries of spread. The predictive power of the GCS without the Verbal component vs total GCS vs FOUR Score on mortality was estimated with the area under the receiver operating characteristic curve (AU ROC). RESULTS: Two hundred thirty-five patients (50% women, mean age 47.5 years) were enrolled. All patients were Black. Presumed etiology was CNS infection (64, 27%), stroke (63, 27%), systemic infection (39, 16.6%), and metabolic encephalopathy (3, 14.5%); 14.9% had unknown etiology. In-hospital mortality was 83%. AU ROC for GCS Eye + Motor score (0.662) vs total GCS score (0.641) vs total FOUR Score (0.657) did not differ. Odds ratio mortality for GCS score >6 vs ≤6 was 0.32 (95% confidence interval [CI] 0.14-0.72, p = 0.01); for FOUR Score >10 vs ≤10, it was 0.41 (95% CI 0.19-0.86, p = 0.02). DISCUSSION: Absence of a verbal component of GCS had no significant impact on the performance of the total GCS, and either GCS or FOUR Score is an acceptable scoring tool for mortality prediction in the resource-limited setting. These findings need further validation in the countries with readily available mechanical ventilatory support. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the verbal component of the GCS does not significantly contribute to a total GCS score in mortality prediction among patients with encephalopathy who are not intubated.

LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis.

We conducted a prospective cohort study to determine the prevalence of leukotriene A4 hydrolase (LTA4H) polymorphisms in Zambian adults with tuberculous meningitis (TBM) and its association with mortality. We completed genotype testing on 101 definite cases of TBM and 119 consecutive non-TBM controls. The distribution of genotypes among TBM patients was as follows: C/C (0.83), C/T (0.14), T/T (0.03). There was no significant difference in genotype distribution between TBM and non-TBM patients. We found no relationship between LTA4H polymorphism and survival. Prospective studies are needed to determine the benefit of adjuvant steroids in TBM based upon population LTA4H genotype. ANN NEUROL 2021;90:994-998.

Estimating the period prevalence of non-convulsive status epilepticus among comatose adults at the University Teaching Hospital in Lusaka, Zambia.

OBJECTIVE: In Western settings, non-convulsive status epilepticus (NCSE) and non-convulsive seizures (NCSz) are associated with high mortality. In comatose patients, interictal epileptiform discharges (IEDs) identified on routine electroencephalogram (EEG) are predictive of NCSE/NCS. Little is known regarding the prevalence, causes, or outcomes of NCSE/NCSz in sub-Saharan Africa (SSA). We sought to investigate the prevalence of IEDs and NCSE/NCSz at a single teaching institution in SSA. METHODS: From October 3, 2017, to May 21, 2018, adult inpatients on the internal medicine service at Zambia's University Teaching Hospital (UTH) with a Glasgow Coma Score (GCS) of ≤10 were identified, excluding patients with mechanical ventilation or open head wounds. Signed consent by a proxy was required for enrollment and 30-minute EEG. Chart abstractions provided coma duration, presence/absence of clinical seizures during/prior to admission, history of epilepsy, and presumed coma etiology. A structured neurological examination was completed. Patients were followed to discharge or death. Risk factors for IEDs were evaluated. RESULTS: Of 392 eligible patients, 250 had EEGs. EEGs were not completed on eligible patients due to death (74), improved GCS (37), transfer within UTH (25), or lack of proxy (6). NCSE occurred in 22 of 250 (8.8%), NCSz in 3 of 250 (1.2%), and IEDs in 46 of 250 (18.4%) patients. Of the 250, 197 (78.8%) died. No specific risk factors for IEDs were identified. SIGNIFICANCE: If the association between IEDs and NCSE among monitored populations in developed settings holds true for SSA, a projected 17%-21% of comatose African adults have NCSE. No clinical characteristics identified those at risk.

Prospective Cohort Study on Performance of Cerebrospinal Fluid (CSF) Xpert MTB/RIF, CSF Lipoarabinomannan (LAM) Lateral Flow Assay (LFA), and Urine LAM LFA for Diagnosis of Tuberculous Meningitis in Zambia.

Tuberculous meningitis (TBM) is a devastating infection of the central nervous system lacking an adequate point-of-care diagnostic test. We conducted a prospective cohort study of 550 Zambian adults with suspected TBM to determine the diagnostic accuracy of cerebrospinal fluid (CSF) Xpert MTB/RIF, CSF lipoarabinomannan (LAM), urine LAM, CSF total protein, and CSF glucose compared with the gold standard of CSF culture. We categorized patients with a positive CSF tuberculosis (TB) culture as definite TBM. We also assessed inpatient and 1-year mortality on definite TBM patients when CSF Xpert MTB/RIF results were available in real time to treating physicians relative to a historical comparison cohort in whom Xpert results were not available in real time. Of the 550 patients, 474 (86.2%) were HIV-infected and 105/550 (19.1%) had definite TBM based on a positive CSF culture. The sensitivity/specificity of the diagnostic tests were CSF Xpert MTB/RIF, 52.9%/94.2%; CSF LAM, 21.9%/94.2%; urine LAM, 24.1%/76.1%; and CSF glucose <40 mg/dl, and total protein, >100 mg/dl, 66.3%/90%. A model including CSF Xpert MTB/RIF, CSF LAM, CSF glucose, and CSF total protein demonstrated an area under the receiver operating curve of 0.90. The inpatient and 1-year mortality for definite TBM was 43% and 57%, respectively. There was low sensitivity for the diagnosis of TBM across all diagnostics tests. CSF Xpert MTB/RIF and CSF LAM are highly specific for the diagnosis of TBM. Despite the use of Xpert MTB/RIF for diagnostic purpose in real time, TBM was still associated with a high mortality in Zambian patients.

Evaluation of dysprosia aerogels as drug delivery systems: a comparative study with random and ordered mesoporous silicas.

Biocompatible dysprosia aerogels were synthesized from DyCl3·6H2O and were reinforced mechanically with a conformal nano-thin-polyurea coating applied over their skeletal framework. The random mesoporous space of dysprosia aerogels was filled up to about 30% v/v with paracetamol, indomethacin, or insulin, and the drug release rate was monitored spectrophotometrically in phosphate buffer (pH = 7.4) or 0.1 M aqueous HCl. The drug uptake and release study was conducted comparatively with polyurea-crosslinked random silica aerogels, as well as with as-prepared (native) and polyurea-crosslinked mesoporous silica perforated with ordered 7 nm tubes in hexagonal packing. Drug uptake from random nanostructures (silica or dysprosia) was higher (30-35% w/w) and the release rate was slower (typically >20 h) relative to ordered silica (19-21% w/w, <1.5 h, respectively). Drug release data from dysprosia aerogels were fitted with a flux equation consisting of three additive terms that correspond to drug stored successively in three hierarchical pore sites on the skeletal framework. The high drug uptake and slow release from dysprosia aerogels, in combination with their low toxicity, strong paramagnetism, and the possibility for neutron activation render those materials attractive multifunctional vehicles for site-specific drug delivery.