Tuberculous meningitis remains highly lethal. In this trial, an intensified regimen of levofloxacin and higher-dose rifampin added to standard therapy was compared with standard antituberculosis ...therapy alone. The intensified regimen did not result in a higher survival rate.
Early treatment with antituberculosis chemotherapy and adjunctive treatment with glucocorticoids reduce the rate of death and disability from tuberculous meningitis, but the disease still kills or disables almost half the patients with the condition.
1
,
2
The current guidelines recommend treatment with four antituberculosis drugs for at least the first 2 months of therapy, followed by treatment with two drugs (rifampin and isoniazid) for an additional 7 to 10 months.
3
,
4
However, these recommendations are based on data from pulmonary tuberculosis and do not take into account the differential ability of antituberculosis drugs to penetrate the brain.
Rifampin is considered to . . .
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.
Sporadic emergence of the highly pathogenic avian influenza (HPAI) H5N1 virus infection in humans is a serious concern because of the potential for a pandemic. Conventional or quantitative RT-PCR is ...the standard laboratory test to detect viral influenza infections. However, this technology requires well-equipped laboratories and highly trained personnel. A rapid, sensitive, and specific alternative screening method is needed.
By a luminescence-linked enzyme immunoassay, we have developed a H5N1 HPAI virus detection kit using anti-H5 hemagglutinin monoclonal antibodies in combination with the detection of a universal NP antigen of the type A influenza virus. The process takes 15 minutes by use of the fully automated luminescence analyzer, POCube.
We tested this H5/A kit using 19 clinical specimens from 13 patients stored in Vietnam who were infected with clade 1.1 or clade 2.3.4 H5N1 HPAI virus. Approximately 80% of clinical specimens were H5-positive using the POCube system, whereas only 10% of the H5-positive samples were detected as influenza A-positive by an immunochromatography-based rapid diagnostic kit.
This novel H5/A kit using POCube is served as a rapid and sensitive screening test for H5N1 HPAI virus infection in humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)—associated tuberculous meningitis is unknown. Methods. We conducted a randomized, ...double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, perprotocol, and prespecified subgroup analyses. Results. A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio HR, 1.12; 95% confidence interval CI,.81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI,.87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions. Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis.
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.
Objectives:
We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), ...health-related behaviors (HB), and preventive behaviors (PB).
Methods:
A cross-sectional study was conducted on 8,291 outpatients aged 18–85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety.
Results:
People with UHC had higher odds of depression (OR = 2.11;
p
< 0.001) and anxiety (OR = 2.86;
p
< 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (
p
< 0.001); and were significantly lower for those had UHC and interacted with “unchanged/more” physical activity (
p
< 0.001), or “unchanged/more” drinking (
p
< 0.001 for only anxiety), or “unchanged/healthier” eating (
p
< 0.001), and high PB score (
p
< 0.001), as compared to those without UHC and without S-COVID-19-S, “never/stopped/less” physical activity, drinking, “less healthy” eating, and low PB score, respectively.
Conclusion:
S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors.
Even with antituberculosis therapy, tuberculous meningitis causes death or severe disability in more than half of affected adults. In this double-blind, placebo-controlled trial, conducted in ...Vietnam, dexamethasone treatment was associated with a reduced risk of death as compared with placebo (31.8 percent vs. 41.3 percent).
Dexamethasone treatment was associated with a reduced risk of death but the proportion of survivors with severe disability is not reduced.
Tuberculous meningitis is the severest form of infection with
Mycobacterium tuberculosis,
causing death or severe neurologic deficits in more than half of those affected in spite of antituberculosis chemotherapy.
1
,
2
Attenuation of the inflammatory response in bacterial and mycobacterial meningitis may improve outcome by reducing the likelihood or severity of neurologic complications. Early studies suggested that corticosteroids reduced cerebrospinal fluid inflammation and time to recovery in patients with tuberculous meningitis, but the studies were too small to confirm any effect on survival.
3
–
7
Concern remained that corticosteroids might reduce the case fatality rate but increase the number of disabled patients. . . .
This study theoretically reports the comprehensive kinetic mechanism of the aniline + OH reaction in the range of 200–2000 K and 0.76–7600 Torr. The temperature- and pressure-dependent behaviors, ...including time-resolved species profiles and rate coefficients, were studied within the stochastic RRKM-based master equation framework with the reaction energy profile, together with molecular properties of the species involved, characterized at the M06-2X/aug-cc-pVTZ level. Hindered internal rotation and Eckart tunneling treatments were included. The H-abstraction from the −NH2 moiety (to form C6H5NH (P1)) is found to prevail over the OH-addition on the C atom at the ortho site of aniline (to form 6-hydroxy-1-methylcyclohexa-2,4-dien-1-yl (I2)) with the atmospheric rate expressions (in cm3/molecule/s) as k abstraction(P1) = 3.41 × 101 × T –4.56 × exp (−255.2 K/T) for 200–2000 K and k addition(I2) = 3.68 × 109 × T –7.39 × exp (−1163.9 K/T) for 200–800 K. The U-shaped temperature-dependent characteristics and weakly positive pressure dependence at low temperatures (e.g., T ≤ 800 K and P = 760 Torr) of k total(T) are also observed. The disagreement in k total(T) between the previous calculations and experimental studies is also resolved, and atmospheric aniline is found to be primarily removed by OH radicals (τOH ∼ 1.1 h) in the daytime. Also, via TD-DFT simulations, it is recommended to include P1 and I2 in any atmospheric photolysis-related model.
Summary
What is known and objective
Despite the numerous studies investigating drug‐induced Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the understanding and quantitative data in ...developing countries remain limited. The study aimed to describe and quantify the drug‐related risk of SJS/TEN in a resource‐limited context using the Vietnamese spontaneous reporting database (VSRD) of adverse drug reactions.
Methods
Spontaneous reports relating to medium‐ and late‐onset severe cutaneous adverse reactions (MLOSCAR) and SJS/TEN recorded in the VSRD from 2010 to 2015 were retrospectively analysed. The demographic characteristics and drug information were described and compared between SJS/TEN and other MLOSCAR reports. The drug‐induced SJS/TEN signals were estimated using subgrouped disproportionality analysis with calculation of the reporting odds ratio (ROR) and the respective 95% confidence interval (CI).
Results
The VSRD received 2,849 MLOSCAR reports, 136 of which focus on SJS/TEN over a 6‐year period. About 60% of SJS/TEN patients were male, and the majority of them were adults (mean age 42.5 ± 22.9). Up to 91.8% of drugs induced SJS/TEN within 1‐28 days, and 45% SJS/TEN cases were evaluated as life‐threatening. Positive signals were generated with carbamazepine (n = 25, ROR 95% CI = 11.99 7.07‐19.92), allopurinol (n = 15, ROR 95% CI = 4.2 2.20‐7.59), traditional/herbal medicines (n = 7, ROR 95% CI = 2.76 1.12‐5.86), colchicine (n = 4, ROR 95% CI = 6.22 1.69‐18.72), valproic acid (n = 3, ROR 95% CI = 8.71 1.89‐30.19) and meloxicam (n = 3, ROR 95% CI = 7.09 1.55‐24.29), which are well known for SJS/TEN. Cefixime (n = 5, ROR 95% CI = 3.34 1.13‐8.00) and paracetamol (n = 22, ROR 95% CI = 5.23 3.10‐8.49) also generated positive signals despite their popularity in Vietnam.
What is new and conclusion
This first Vietnamese population‐based study has highlighted original characteristics and signals of drug‐induced SJS/TEN, which are relatively consistent with other worldwide data and typical for a developing country.
Selection flow chart for SJS/TEN and MLOSCAR reports in the Vietnamese Spontaneous Reporting Database
Determining the best therapy for HIV-associated cryptococcal meningitis in resource-poor settings is controversial. In this trial in Vietnam, initial therapy with amphotericin B with flucytosine had ...better outcomes than amphotericin B alone or with fluconazole.
There are approximately 1 million cases of cryptococcal meningitis annually and 625,000 deaths.
1
Treatment guidelines recommend induction therapy with amphotericin B deoxycholate (0.7 to 1 mg per kilogram of body weight per day) and flucytosine (100 mg per kilogram per day).
2
However, this treatment has not been shown to reduce mortality, as compared with amphotericin B monotherapy.
2
,
3
Flucytosine is frequently unavailable where the disease burden is greatest, and concerns about cost and side effects have limited its use in resource-poor settings.
4
Fluconazole is readily available, is associated with low rates of adverse events, and has good penetration into cerebrospinal . . .
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