High dose fluconazole in salvage therapy for HIV-uninfected cryptococcal meningitis.

BACKGROUND: The 2010 Infectious Diseases Society of America (IDSA) guidelines for management of cryptococcal diseases recommend high dose fluconazole (≥ 800 mg/day), either alone or with other antifungal drugs, as alternative anticryptococcal choices. But evidence for its use in the treatment of HIV-uninfected cryptococcal meningitis (CM) remains sparse. METHODS: A retrospective analysis of HIV-uninfected CM patients who received fluconazole 800 mg/day for salvage therapy from January 2011 to December 2016 at Huashan Hospital, Shanghai, China was performed. Efficacy and safety were assessed, and mortality and prognostic factors evaluated. RESULTS: A total of 44 patients were studied including 19 refractory to amphotericin B induction therapy, 8 refractory to fluconazole consolidation therapy (400 mg/d), and 17 intolerant of antifungal drugs. For salvage, 11 patients received triple therapy of high dose fluconazole, amphotericin B and flucytosine, 20 received dual therapy of high dose fluconazole and flucytosine, 13 received monotherapy of high dose fluconazole. Median duration of high dose fluconazole in salvage regimens was 136.5 days (range, 1-667 days). Clinical response rates were 72.1% (31/43) and 83.7% (36/43) when assessed at 2 weeks and the end of salvage therapy, respectively. Adverse events possibly related to high dose fluconazole occurred in 54.5% (24/44) of the patients, and all were mild or moderate. From the initiation of salvage therapy, 1-year all-cause mortality was 13.6% (6 of 44 patients) among the study population with no significant difference in refractory or intolerant patients. CONCLUSIONS: Adherence to guideline recommendations of high dose fluconazole, alone or in combination with other antifungals, was safe and often effective for salvage therapy of HIV-uninfected CM patients

Fostering coastal resilience to climate change vulnerability in Bangladesh, Brazil, Cameroon and Uruguay: a cross-country comparison

© 2017, Springer Science+Business Media B.V. This paper describes a comparative study of four different cases on vulnerability, hazards and adaptive capacity to climate threats in coastal areas and communities in four developing countries: Bangladesh, Brazil, Cameroon and Uruguay. Coastal areas are vulnerable to sea-level rise (SLR), storm surges and flooding due to their (i) exposure, (ii) concentration of settlements, many of which occupied by less advantaged groups and (iii) the concentration of assets and services seen in these areas. The objective of the paper is twofold: (i) to evaluate current evidence of coastal vulnerability and adaptive capacity and (ii) to compare adaptation strategies being implemented in a sample of developing countries, focusing on successful ones. The followed approach for the case evaluation is based on (i) documenting observed threats and damages, (ii) using indicators of physical and socioeconomic vulnerability and adaptive capacity status and (iii) selecting examples of successful responses. Major conclusions based on cross-case comparison are (a) the studied countries show different vulnerability, adaptive capacity and implementation of responses, (b) innovative community-based (CBA) and ecosystem-based adaptation (EbA) and (c) early warning systems are key approaches and tools to foster climate resilience. A recommendation to foster the resilience of coastal communities and services is that efforts in innovative adaptation strategies to sea-level rise should be intensified and integrated with climate risk management within the national adaption plans (NAPAs) in order to reduce the impacts of hazards