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.)

Strategic Agility Orientation? The Impact of CEO Duality on Corporate Entrepreneurship in Privatized Vietnamese Firms

This study examines the impact of CEO duality (a chief executive operating chair of board and leader of a firm) of newly privatized Vietnamese firms on the level of corporate entrepreneurship; this understanding is used to throw light on the extent to which a position of strategic agility is achieved. Specifically, does CEO duality enable firms to keep consistent with their vision, while remaining flexible in their business model? Data from a survey of 114 CEOs of board and top management team members in privatized firms in Vietnam were collected and examined through a combination of agency theory and stewardship theory. The research finds that CEO duality does not necessarily lead to a higher degree of entrepreneurial activity in privatized Vietnamese firms. The results have policy implications for shaping corporate governance, and management implications for firms striving to be competitive, in ways that advance corporate entrepreneurship in economies such as Vietnam that are both emerging and pursuing privatization

Combination Antifungal Therapy for Cryptococcal Meningitis

Background 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. Methods 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. Results 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. Conclusions 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

The antimicrobial resistance patterns and associated determinants in Streptococcus suis isolated from humans in southern Vietnam, 1997-2008

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus suis </it>is an emerging zoonotic pathogen and is the leading cause of bacterial meningitis in adults in Vietnam. Systematic data on the antimicrobial susceptibility profiles of <it>S. suis </it>strains isolated from human cases are lacking. We studied antimicrobial resistance and associated resistance determinants in <it>S. suis </it>isolated from patients with meningitis in southern Vietnam.</p> <p>Methods</p> <p><it>S. suis </it>strains isolated between 1997 and 2008 were investigated for their susceptibility to six antimicrobial agents. Strains were screened for the presence and expression of tetracycline and erythromycin resistance determinants and the association of <it>tet</it>(M) genes with <it>Tn</it>916- like transposons. The localization of tetracycline resistance gene <it>tet</it>(L) was determined by pulse field gel electrophoresis and Southern blotting.</p> <p>Results</p> <p>We observed a significant increase in resistance to tetracycline and chloramphenicol, which was concurrent with an increase in multi-drug resistance. In tetracycline resistance strains, we identified <it>tet</it>(M), <it>tet</it>(O), <it>tet</it>(W) and <it>tet</it>(L) and confirmed their expression. All <it>tet</it>(M) genes were associated with a <it>Tn</it>916-like transposon. The co-expression of <it>tet</it>(L) and other tetracycline resistance gene(s) encoding for ribosomal protection protein(s) was only detected in strains with a minimum inhibitory concentration (MIC) of tetracycline of ≥ 64 mg/L</p> <p>Conclusions</p> <p>We demonstrated that multi-drug resistance in <it>S. suis </it>causing disease in humans in southern Vietnam has increased over the 11-year period studied. We report the presence and expression of <it>tet</it>(L) in <it>S. suis </it>strains and our data suggest that co-expression of multiple genes encoding distinct mechanism is required for an MIC ≥ 64 mg/L to tetracycline.</p

Randomized controlled trial of artesunate or artemether in Vietnamese adults with severe falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Both artemether and artesunate have been shown to be superior to quinine for the treatment of severe falciparum malaria in Southeast Asian adults, although the magnitude of the superiority has been greater for artesunate than artemether. These two artemisinin derivatives had not been compared in a randomized trial.</p> <p>Methods</p> <p>A randomized double blind trial in 370 adults with severe falciparum malaria; 186 received intramuscular artesunate (2.4 mg/kg immediately followed by 1.2 mg/kg at 12 hours then 24 hours then daily) and 184 received intramuscular artemether (3.6 mg per kilogram immediately followed by 1.8 mg per kilogram daily) was conducted in Viet Nam. Both drugs were given for a minimum of 72 hours.</p> <p>Results</p> <p>There were 13 deaths in the artesunate group (7 percent) and 24 in the artemether group (13 percent); P = 0.052; relative risk of death in the patients given artesunate, 0.54; (95 percent confidence interval 0.28-1.02). Parasitaemia declined more rapidly in the artesunate group. Both drugs were very well tolerated.</p> <p>Conclusions</p> <p>Intramuscular artesunate may be superior to intramuscular artemether for the treatment of severe malaria in adults.</p

Seasonal Changes in Sleep Duration in African American and African College Students Living In Washington, D.C.

Duration of nocturnal melatonin secretion, a marker of “biological night” that relates to sleep duration, is longer in winter than in summer in patients with seasonal affective disorder (SAD), but not in healthy controls. In this study of African and African American college students, we hypothesized that students who met criteria for winter SAD or subsyndromal SAD (S-SAD) would report sleeping longer in winter than in summer. In addition, based on our previous observation that Africans report more “problems” with change in seasons than African Americans, we expected that the seasonal changes in sleep duration would be greater in African students than in African American students. Based on Seasonal Pattern Assessment Questionnaire (SPAQ) responses, African American and African college students in Washington, D.C. (N = 575) were grouped into a winter SAD/S-SAD group or a no winter diagnosis group, and winter and summer sleep length were determined. We conducted a 2 (season) × 2 (sex) × 2 (ethnicity) × 2 (winter diagnosis group) ANCOVA on reported sleep duration, controlling for age. Contrary to our hypothesis, we found that African and African American students with winter SAD/S-SAD report sleeping longer in the summer than in the winter. No differences in seasonality of sleep were found between African and African American students. Students with winter SAD or S-SAD may need to sacrifice sleep duration in the winter, when their academic functioning/efficiency may be impaired by syndromal or subsyndromal depression, in order to meet seasonally increased academic demands

Features of trastuzumab-related cardiac dysfunction: deformation analysis outside left ventricular global longitudinal strain

BackgroundCancer therapy-related cardiac dysfunction due to trastuzumab has been well-known for many years, and echocardiographic surveillance is recommended every 3 months in patients undergoing trastuzumab treatment, irrespective of the baseline cardiotoxicity risk. However, the potential harm and cost of overscreening in low- and moderate-risk patients have become great concerns.ObjectivesThis study aimed to identify the incidence of early cancer therapy-related cardiac dysfunction (CTRCD) and the behaviours of left and right heart deformations during trastuzumab chemotherapy in low- and moderate-risk patients.MethodsWe prospectively enrolled 110 anthracycline-naïve women with breast cancer and cardiovascular risk factors who were scheduled to receive trastuzumab. The left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS), and right ventricular and left atrial longitudinal strains were evaluated using echocardiography at baseline, before every subsequent cycle and 3 weeks after the final dose of trastuzumab. The baseline risk of CTRCD was graded according to the risk score proposed by the Heart Failure Association (HFA) Cardio-Oncology Working Group and the International Cardio-Oncology Society (ICOS). CTRCD and its severity were defined according to the current European Society of Cardiology (ESC) guidelines.ResultsTwelve (10.9%) patients had asymptomatic CTRCD. All CTRCD occurred sporadically during the first 9 months of the active trastuzumab regimen in both low- and moderate-risk patients. While CTRCD was graded as moderate severity in 41.7% of patients and heart failure therapy was initiated promptly, no irreversible cardiotoxicity or trastuzumab interruption was recorded at the end of follow-up. Among the left and right heart deformation indices, only LV-GLS decreased significantly in the CTRCD group during the trastuzumab regimen.ConclusionsCTRCD is prevalent in patients with non-high-risk breast cancer undergoing trastuzumab chemotherapy. Low- and moderate-risk patients show distinct responses to trastuzumab. The LV-GLS is the only deformation index sensitive to early trastuzumab-related cardiac dysfunction