Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis

BACKGROUND Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients. METHODS We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization. RESULTS A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08). CONCLUSIONS Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.)

A Retrospective Analysis of the Haemodynamic and Metabolic Effects of Fluid Resuscitation in Vietnamese Adults with Severe Falciparum Malaria

BACKGROUND: Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults. METHODS: Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation. RESULTS: 43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m(2) (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: -0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (r(s) = 0.7, p<0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO(2)/FiO(2) ratio). There was no correlation between the oxygen delivery (DO(2)) and base deficit at the 63 time-points where they were assessed simultaneously (r(s) = -0.09, p = 0.46). CONCLUSIONS: In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Application of Taguchi Method to Investigation of Optimal Abrasive Jet Polishing Parameters

The surface finish of N-BK7 optical glass is improved by abrasive jet polishing (AJP) process. Taguchi's method is employed to investigate optimal AJP parameters. The important parameters that influence the N-BK7 surface finish are determined by Analysis of variance (ANOVA). The optimal parameters are found based on Taguchi's experimental results and signal noise ratio (S/N). These optimal parameters are: polishing time of 45 min, pump pressure of 5 kgf/cm2, standoff distance of 12 mm, abrasive grain type of Al2O3, abrasive grain concentration of 20 %, and impact angle of 40°. The surface finish (Ra) of the N-BK7 is improved significantly from 0.350 µm to 0.018 µm

Microencapsulation of flaxseed oil using polyphenol-adducted flaxseed protein isolate-flaxseed gum complex coacervates

This study aimed to evaluate the applicability of polyphenol-adducted flaxseed protein isolate (FPI)-flaxseed gum (FG) complex coacervates to encapsulate flaxseed oil (FO). FPI was covalently adducted with flaxseed polyphenol (FPP) or hydroxytyrosol (HT). β-sheet was major secondary structure of FPI and its covalent conjugation with polyphenols further increased the β-sheet content. The extent of increase of this ordered structure was found to depend on the type of aducted polyphenol. Subsequently, complex coacervation between polyphenol adducted FPI and FG was studied in terms of optimum complex coacervation pH and protein-to-gum ratio. Compared to FPI and FPI-polyphenol adducts, FPI/FG, (FPI-FPP)/FG and (FPI-HT)/FG complex coacervates had significantly higher random coil and significantly lower β-sheet contents suggesting that these complex coacervates had less ordered structure. Finally, the spray-dried microcapsule powders of FO were produced using FPI/FG, (FPI-FPP)/FG and (FPI-HT)/FG as shell materials. Physicochemical properties of these microcapsules, including surface oil, microencapsulation efficiency and stability against oxidation, were determined. The optimum pH for complex coacervation between FPI/FG, (FPI-FPP)/FG and (FPI-HT)/FG was very close (4.6 ± 0.1) and the optimum protein-to-gum ratio of 6.0 was also identical. All these microcapsules had irregular shape with wrinkled surface morphology. The microcapsules produced using (FPI-HT)/FG complex coacervates had lowest surface oil (1%, w/w) and highest microencapsulation efficiency (95.4%). The microcapsules encapsulated using (FPI-FPP)/FG complex coacervates had the highest stability against oxidation as measured by peroxide value and p-anisidine value. Overall the complex coacervates produced using polyphenol adducted FPI and FG were found to be better than FPI/FG complex coacervates as encapsulating shell materials for oxygen-sensitive oil