Geographic expansion of artemisinin resistance.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the global standard of care for uncomplicated falciparum malaria. First reports of ACT resistance came from western Cambodia and the Thailand-Cambodia border in 2002-2004. The subsequent emergence and expansion of Plasmodium falciparum strains resistant to the artemisinin component and ACT are now threatening the efficacy of falciparum malaria treatment. METHODS: We performed a literature review on the history and the current degree of geographic expansion of artemisinin and ACT resistance. Resistance against artemisinins is defined as >5% of patients carrying PfKelch13 (K13) mutations, all of whom have been found to have persistent parasitaemia by microscopy on Day 3 after treatment. RESULTS: Several studies including the multi-centre Tracking Resistance to Artemisinin Collaboration study investigated artemisinin resistance in Southeast Asia and beyond and demonstrated increasing prevalence of P. falciparum infections with slow parasite clearance rates in the Greater Mekong Subregion (GMS). K13 mutations were strongly associated with delayed P. falciparum parasite clearance, and the prevalence of the mutation PfKelch13 C580Y is increasing in the GMS. Resistance to ACT regimens is now well established in western Cambodia and in eastern Thailand, southern Laos and southern Vietnam. Moreover, the prevalence of slow P. falciparum parasite clearance has continuously increased over the past 10-15 years at the Thailand-Myanmar border, in nearly all regions of Myanmar, and at the Myanmar-China border. CONCLUSION: Multidrug resistant malaria is a rapidly increasing problem, but fortunately still limited to Southeast Asia, in particular to the GMS. In the long-term it may threaten global progress in malaria control but is not yet of concern with regards to malaria prophylaxis, as ACTs are not used for prevention in travellers, current ACT regimens are still effective in most malaria endemic areas outside the GMS and the preferred travellers' prophylaxis atovaquone-proguanil and doxycycline remain protective. However, artemsinin resistance in the GMS is of real concern to travellers as it will affect the choice of malaria treatment including standby-emergence treatment.

Neurologic Functional Outcomes of Decompressive Hemicraniectomy Versus Conventional Treatment for Malignant Middle Cerebral Artery Infarction: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aims of this study were to evaluate decompressive hemicraniectomy (DHC) versus conventional treatment (CT) for patients with malignant middle cerebral artery (MCA) infarction and to investigate the impact of age and surgical timing on neurologic function and mortality. METHODS: We searched English and Chinese databases for randomized controlled trials or observational studies published before August 2016. Outcomes included good functional outcome (GFO), mortality, and National Institutes of Health Stroke Scale and Barthel index scores. RESULTS: This meta-analysis included 25 studies (1727 patients). There were statistically significant differences between DHC and CT groups in terms of GFO (P < 0.0001), mortality (P < 0.00001), and National Institutes of Health Stroke Scale and Barthel index scores (P < 0.0001) at different follow-up points. Significant differences were observed between the groups in survival with moderately severe disability (P < 0.00001); no differences were observed in survival with severe disability. In the subgroup analysis, in the DHC group, GFO was less in patients >60 years old (9.65%) versus ≤60 years old (38.94%); more patients >60 years old had moderately severe or severe disability (55.27%) compared with patients ≤60 years old (44.21%). CONCLUSIONS: DHC could significantly improve GFO and reduces mortality of patients of all ages with malignant MCA infarction compared with CT, without increasing the number of patients surviving with severe disability. However, patients in the DHC group more frequently had moderately severe disability. Patients >60 years old with malignant MCA infarction had a higher risk of surviving with moderately severe or severe disability and less GFO.