Epidemiology, Modern Diagnostics, and the Management of Mucorales Infections.

Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with current antifungal therapies. Current diagnostic methods have inadequate sensitivity and specificity and may have issues with accessibility or turnaround time. Patients with diabetes mellitus and immune compromise are predisposed to infection with these environmental fungi, but COVID-19 has established itself as a new risk factor. Mucorales also cause healthcare-associated outbreaks, and clusters associated with natural disasters have also been identified. Robust epidemiological surveillance into burden of disease, at-risk populations, and emerging pathogens is required. Emerging serological and molecular techniques may offer a faster route to diagnosis, while newly developed antifungal agents show promise in preliminary studies. Equitable access to these emerging diagnostic techniques and antifungal therapies will be key in identifying and treating mucormycosis, as delayed initiation of therapy is associated with higher mortality.

Harnessing new mHealth technologies to Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART trial): a protocol for a randomised controlled trial.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem globally. Long, complex treatment regimens coupled with frequent adverse events have resulted in poor treatment adherence and patient outcomes. Smartphone-based mobile health (mHealth) technologies offer national TB programmes an appealing platform to improve patient care and management; however, clinical trial evidence to support their use is lacking. This trial will test the hypothesis that an mHealth intervention can improve treatment success among patients with MDR-TB and is cost-effective compared with standard practice. METHODS AND ANALYSIS: A community-based, open-label, parallel-group randomised controlled trial will be conducted among patients treated for MDR-TB in seven provinces of Vietnam. Patients commencing therapy for microbiologically confirmed rifampicin-resistant or multidrug-resistant tuberculosis within the past 30 days will be recruited to the study. Participants will be individually randomised to an intervention arm, comprising use of an mHealth application for treatment support, or a 'standard care' arm. In both arms, patients will be managed by the national TB programme according to current national treatment guidelines. The primary outcome measure of effectiveness will be the proportion of patients with treatment success (defined as treatment completion and/or bacteriological cure) after 24 months. A marginal Poisson regression model estimated via a generalised estimating equation will be used to test the effect of the intervention on treatment success. A prospective microcosting of the intervention and within-trial cost-effectiveness analysis will also be undertaken from a societal perspective. Cost-effectiveness will be presented as an incremental cost per patient successfully treated and an incremental cost per quality-adjusted life-year gained. ETHICS: Ethical approval for the study was granted by The University of Sydney Human Research Ethics Committee (2019/676). DISSEMINATION: Study findings will be disseminated to participants and published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: ACTRN12620000681954.

Burden of injuries in Vietnam: emerging trends from a decade of economic achievement.

BACKGROUND: Vietnam has been one of the fastest-growing world economies in the past decade. The burden of injuries can be affected by economic growth given the increased exposure to causes of injury as well as decreased morbidity and mortality of those that experience injury. It is of interest to evaluate the trends in injury burden that occurred alongside Vietnam's economic growth in the past decade. METHODS: Results from Global Burden of Disease 2017 were obtained and reviewed. Estimates of incidence, cause-specific mortality, years lived with disability, years of life lost, disability-adjusted life years were analysed and reported for 30 causes of injury in Vietnam from 2007 to 2017. RESULTS: Between 2007 and 2017, the age-standardised incidence rate of all injuries increased by 14.6% (11.5%-18.2%), while the age-standardised mortality rate decreased by 11.6% (3.0%-20.2%). Interpersonal violence experienced the largest increase in age-standardised incidence (28.3% (17.6%-40.1%)), while exposure to forces of nature had the largest decrease in age-standardised mortality (47.1% (37.9%-54.6%)). The five leading causes of injury in both 2007 and 2017 were road injuries, falls, exposure to mechanical forces, interpersonal violence and other unintentional injuries, all of which increased in incidence from 2007 to 2017. Injury burden varied markedly by age and sex. CONCLUSIONS: The rapid expansions of economic growth in Vietnam as well as improvements in the Sociodemographic Index have occurred alongside dynamic patterns in injury burden. These results should be used to develop and implement prevention and treatment programme.

Population Pharmacokinetic Model and Meta-analysis of Outcomes of Amphotericin B Deoxycholate Use in Adults with Cryptococcal Meningitis.

There is a limited understanding of the population pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAmB) for cryptococcal meningitis. A PK study was conducted in n = 42 patients receiving DAmB (1 mg/kg of body weight every 24 h [q24h]). A 2-compartment PK model was developed. Patient weight influenced clearance and volume in the final structural model. Monte Carlo simulations estimated drug exposure associated with various DAmB dosages. A search was conducted for trials reporting outcomes of treatment of cryptococcal meningitis patients with DAmB monotherapy, and a meta-analysis was performed. The PK parameter means (standard deviations) were as follows: clearance, 0.03 (0.01) × weight + 0.67 (0.01) liters/h; volume, 0.82 (0.80) × weight + 1.76 (1.29) liters; first-order rate constant from central compartment to peripheral compartment, 5.36 (6.67) h-1; first-order rate constant from peripheral compartment to central compartment, 9.92 (12.27) h-1 The meta-analysis suggested that the DAmB dosage explained most of the heterogeneity in cerebrospinal fluid (CSF) sterility outcomes but not in mortality outcomes. Simulations of values corresponding to the area under concentration-time curve from h 144 to h 168 (AUC144-168) resulted in median (interquartile range) values of 5.83 mg · h/liter (4.66 to 8.55), 10.16 mg · h/liter (8.07 to 14.55), and 14.51 mg · h/liter (11.48 to 20.42) with dosages of 0.4, 0.7, and 1.0 mg/kg q24h, respectively. DAmB PK is described adequately by a linear model that incorporates weight with clearance and volume. Interpatient PK variability is modest and unlikely to be responsible for variability in clinical outcomes. There is discordance between the impact that drug exposure has on CSF sterility and its impact on mortality outcomes, which may be due to cerebral pathology not reflected in CSF fungal burden, in addition to clinical variables.