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.
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.
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).
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.).
Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain ...infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3 and 4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. 41 participants were randomised to placebo, 39 to aspirin 81 mg/day, and 40 to aspirin 1000 mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120 (76.7%) and baseline brain imaging revealed ≥1 infarct in 40/114 (35.1%) participants. The primary safety outcome occurred in 5/36 (13.9%) given placebo, and in 8/35 (22.9%) and 8/40 (20.0%) given 81 mg and 1000 mg aspirin, respectively (p=0.59). The primary efficacy outcome occurred in 11/38 (28.9%) given placebo, 8/36 (22.2%) given aspirin 81 mg, and 6/38 (15.8%) given 1000 mg aspirin (p=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (P
= 0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32 (34.4%) events in placebo vs. 4/27 (14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000 mg; p=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A
and upregulation of pro-resolving CSF protectins. The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial.
Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with ...amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.
We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks.
A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval CI, 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (-0.42 log10 colony-forming units CFU per milliliter per day vs. -0.31 and -0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy.
Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.).
Background: The COVID-19 pandemic has been disseminating fear in the community, which has affected people’s quality of life, especially those with health problems. Health literacy (HL), eHealth ...literacy (eHEAL), and digital healthy diet literacy (DDL) may have potential impacts on containing the pandemic and its consequences. This study aimed to examine the association between the fear of COVID-19 scale (FCoV-19S) and the health-related quality of life (HRQoL), and to examine the effect modification by HL, eHEAL, and DDL on this association. Methods: A cross-sectional study was conducted in 11 hospitals across Vietnam from 7 April to 31 May 2020. Data were collected on 4348 outpatients, including demographic characteristics, HL, eHEAL, DDL, FCoV-19S, and HRQoL. Multiple linear regression and interaction models were used to explore associations. Results: Patients with higher FCoV-19S scores had lower HRQoL scores (unstandardized coefficient, B = −0.78, p < 0.001). HL (B = 0.20, p < 0.001), eHEAL (B = 0.24, p < 0.001), and DDL (B = 0.20, p < 0.001) were positively associated with higher HRQoL scores. The negative impact of FCoV-19S on HRQoL was significantly attenuated by higher eHEAL score groups (from one standard deviation (SD) below the mean, B = −0.93, p < 0.001; to the mean, B = −0.85, p < 0.001; and one SD above the mean, B = −0.77, p < 0.001); and by higher DDL score groups (from one SD below the mean, B = −0.92, p < 0.001; to the mean, B = −0.82, p < 0.001; and one SD above the mean, B = −0.72, p < 0.001). Conclusions: eHealth literacy and digital healthy diet literacy could help to protect patients’ health-related quality of life from the negative impact of the fear of COVID-19 during the pandemic.
Background. Tuberculous meningitis (TBM) is the most devastating form of tuberculosis, yet very little is known about the pathophysiology. We hypothesized that the genotype of leukotriene A₄ ...hydrolase (encode by LTA4H), which determines inflammatory eicosanoid expression, influences intracerebral inflammation, and predicts survival from TBM. Methods. We characterized the pretreatment clinical and intracerebral inflammatory phenotype and 9-month survival of 764 adults with TBM. All were genotyped for single-nucleotide polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal fluid (CSF) leukocyte and cytokine concentrations. Results. LTA4H genotype predicted survival of human immunodeficiency virus (HIV)=uninfected patients, with TT-genotype patients significantly more likely to survive TBM than CC-genotype patients, according to Cox regression analysis (univariate P = .040 and multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF proinflammatory cytokine concentrations, with intermediate and lower concentrations in those with CT and CC genotypes. Increased CSF cytokine concentrations correlated with more-severe disease, but patients with low CSF leukocytes and cytokine concentrations were more likely to die from TBM, HIV infection independently predicted death due to TBM (hazard ratio, 3.94; 95% confidence interval, 2.79-5.56) and was associated with globally increased CSF cytokine concentrations, independent of LTA4H genotype. Conclusions. LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from TBM. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals.
Abstract Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. ...However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children’s Hospital from January 2022 to June 2023. The median age was 85 (range: 2–188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2–7) days. We observed independent factors related to PICU admission, including CRP $$\ge $$ ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39–4.56, p = 0.002), albumin $$\le $$ ≤ 30 (g/L) (OR 3.18, 95% CI 1.63–6.02, p = 0.001), absolute lymphocyte count $$\le $$ ≤ 2 (× 10 9 /L) (OR 2.18, 95% CI 1.29–3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38–4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28–4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte $$\le $$ ≤ 2 (× 10 9 /L) (OR 2.48, 95% CI 1.10–5.61, p = 0.029), albumin $$\le $$ ≤ 30 (g/L) (OR 2.53, 95% CI 1.22–5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12–4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.
Abstract
This work emphasizes the effect of the physical activation using CO
2
and steam agents on the physicochemical properties of activated carbon produced from
Dicranopteris linearis
(
D. ...linearis
), a fern species widely distributed across tropic and subtropic ecoregions. The
D. linearis
-derived chars produced under pyrolysis at 400 °C for 1 h were activated in various CO
2
-steam proportions. As revealed by the IR and Raman spectra, the structure of the activated chars was heavily dependent on the relative proportion of CO
2
and steam. The total specific surface area (SSA) of the activated chars proportionally increased with the increase in steam proportion and was comparable to the values of commercial activated char products. Specifically, the activation under CO
2
−
and steam-saturated conditions has correspondingly resulted in SSA increasing from 89 to 653 m
2
g
−1
and from 89 to 1015 m
2
g
−1
. Steam also enhanced the development of mesoporous structures of the
D. linearis
-derived char products, thereby extending their potential applications, particularly for industries that require high rigidity in the product such as pharmaceutical and cosmetic sectors.
This study deals with the preparation and characterization of platinum/reduced graphene oxide (Pt/rGO) as an efficient cathode for dye-sensitized solar cells. Herein, the Pt/rGO material was ...synthesized by co-precipitation from hexachloroplatinic acid (H
2
PtCl
6
) and graphene oxide (GO) precursors. The fabrication of cathodes from Pt/rGO composite paste was carried out using screen-printing paste. The electrochemical behaviors of as-prepared cathodes were analyzed by cyclic voltammetry; the performance of fabricated DSSCs was measured by current density–voltage (J-V) curves and electrochemical impedance spectroscopy. The structural characteristics of the Pt/rGO binary composites were confirmed by Fourier-transform infrared spectroscopy, Raman spectroscopy, x-ray diffraction (XRD), and transmission electron microscopy. Empirical data showed that choosing ascorbic acid as a reducing agent at a ratio of 5:1 between ascorbic acid weight and precursor mixture weight, as well as a GO weight percentage of 20% fabricated DSSCs successfully with a conversion efficiency of 6.25%, which was approximately 90% compared to that of pure commercial Pt material. Characterization results indicated that the Pt nanoparticles were homogeneously distributed on the rGO sheets with an average diameter of less than 25 nm. The Pt/rGO hybrid composite is highly expected to replace Pt in the fabrication of cathodes in DSSCs for low-cost DSSC production in the promising future.
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This work specifically emphasizes the effect of the silica phase contained in the fern Dicranopteris linearis (D. linearis), a common shrub occurring widely throughout tropical and ...subtropical regions, on biochar surface properties. Slow pyrolysis was performed in the temperature range from 400 to 900 °C under various ambient reaction conditions, i.e., non-biochar-oriented conditions (open pyrolysis) and biochar-oriented conditions (closed and N2-supported pyrolysis). The resulting changes in micromorphology and different surface properties, specific surface area and surface charge, were elucidated. Open pyrolysis resulted in excessive decomposition of biomass and condensation of silica, while the closed and N2-supported pyrolysis methods showed notable enhancement of biochar yield. The presence of silica as an inter-embedded part of the fern D. linearis and the derived biochars likely supported a carbon-silica structural model in which these two components might be integrated or decomposed during pyrolysis. In general, joint processing of organic carbon and silica greatly altered the surface properties. At lower temperatures and during N2-supported pyrolysis, condensation of organic compounds limited the development of high surface charge densities. At higher temperatures and during open pyrolysis, intensification of the silica phase was accompanied with an increasing number of charged surface sites, thereby increasing the surface charge density. Based on the porous structure, large surface area (up to 701 m2 g−1) and high surface charge density (up to 0.5 μmol(−) m−2), D. linearis-derived biochars can be highlighted as potential agro-environmental materials.
...the notebook is made available, along with its data (Rule 8), in a manner encouraging public exploration and contribution (Rules 9–10). https://doi.org/10.1371/journal.pcbi.1007007.g001 Rule 1: ...Document the process, not just the results Computational notebooks’ interactivity makes it quick and easy to try out and compare different approaches or parameters—so quick and easy that we often fail to document those interactive investigations at the time we perform them. ...the advice long provided regarding paper lab scientific notebooks becomes even more critical: make sure to document all your explorations, even (or perhaps especially) those that led to dead ends. Version control systems compare differences in these JSON files, not differences in the user-friendly notebook graphical user interface (GUI). Because of this, reported differences between versions of a given notebook are usually difficult for users to find and understand because they are expressed as changes in the abstruse JSON metadata for the notebook. Perform preparatory steps, like data cleaning, directly in the notebook and avoid manual interventions. Because notebooks’ interactivity make them vulnerable to accidental overwriting or deletion of critical steps by the user, if your analysis runs quickly, make a habit of regularly restarting your kernel and rerunning all cells to make sure you did not accidentally delete a step while cleaning your notebook (and if you did, retrieve the code for it from version control).
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