Bmc Med
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Plasmodium falciparum infections with slow parasite clearance following artemisinin-based therapies are widespread in the Greater Mekong Subregion. A molecular marker of the slow clearance phenotype has been identified: single genetic changes within the propeller region of the Kelch13 protein (pfk13; Pf3D7_1343700). Global searches have identified almost 200 different non-synonymous mutant pfk13 genotypes. Most mutations occur at low prevalence and have uncertain functional significance. To characterize the impact of different pfk13 mutations on parasite clearance, we conducted an individual patient data meta-analysis of the associations between parasite clearance half-life (PC1/2) and pfk13 genotype based on a large set of individual patient records from Asia and Africa. ⋯ Pooled analysis associated 20 pfk13 propeller region mutant alleles with the slow clearance phenotype, including 15 mutations not confirmed previously.
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Naltrexone is an opioid antagonist used in many different conditions, both licensed and unlicensed. It is used at widely varying doses from 3 to 250 mg. The aim of this review was to extensively evaluate the safety of oral naltrexone by examining the risk of serious adverse events and adverse events in randomised controlled trials of naltrexone compared to placebo. ⋯ Naltrexone does not appear to increase the risk of serious adverse events over placebo. These findings confirm the safety of oral naltrexone when used in licensed indications and encourage investments to undertake efficacy studies in unlicensed indications.
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Recently, studies have examined the underlying patient and practice factors for missed appointments, but less is known about the impact on patient health. People with one or more long-term conditions who fail to attend appointments may be at risk of premature death. This is the first study to examine the effect of missed primary healthcare appointments on all-cause mortality in those with long-term mental and physical health conditions. ⋯ Missed appointments represent a significant risk marker for all-cause mortality, particularly in patients with mental health conditions. For these patients, existing primary healthcare appointment systems are ineffective. Future interventions should be developed with a particular focus on increasing attendance by these patients.
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Knowledge of HIV-1 molecular transmission clusters (MTCs) is important, especially in large-scale datasets, for designing prevention programmes and public health intervention strategies. We used a large-scale HIV-1 sequence dataset from nine European HIV cohorts and one Canadian, to identify MTCs and investigate factors associated with the probability of belonging to MTCs. ⋯ A high proportion (>40%) of individuals belonged to MTCs. Notably, the HIV epidemic dispersal appears to be driven by subtype B viruses spread within MSM networks. Expansion of regional epidemics seems mainly associated with recent MTCs, rather than the growth of older, established ones. This information is important for designing prevention and public health intervention strategies.
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The original article [1] contained an error in the presentation of Figure 1; this error has now been rectified and Figure 1 is now presented correctly.