Oskar Bordeaux
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Schizophr Res
No full textThere is still no consensus regarding the indications of long-acting injectable antipsychotics (LAIs) in early psychosis (EP). This umbrella review synthesizes findings from systematic reviews and meta-analyses on the risk-benefit balance of LAIs in EP. Eligible systematic reviews and meta-analyses on LAIs in EP were identified by a MEDLINE search from inception until June 2024. Data were synthesized narratively. Seven systematic reviews and four meta-analyses published from 2007 to 2024 were identified. They included 220 to 14,313 participants recruited in 58 primary unique randomized controlled trials or observational studies. All LAIs were considered in most reviews. Inclusion criteria and diagnoses differed widely across the selected reviews. The reviews and meta-analyses consistently showed a positive impact of LAIs on symptomatic outcome in people with EP, although there was no consensus on whether LAIs outperformed oral anti-psychotics (OAPs). Most reported a greater reduction of treatment discontinuation due to inefficacy or nonadherence with LAIs vs. OAPs, although meta-analyses found no difference between LAIs vs. OAPs regarding all-cause discontinuation. Findings regarding relapse prevention were inconclusive. Similar rates of metabolic adverse drug reaction and potentially lower rates of extrapyramidal symptoms were observed with LAIs vs. OAPs. LAIs should be considered according to users' preferences and could be particularly useful for people with a poor medication adherence risk profile. Further high-quality observational studies in real-life prescribing conditions are needed to support robust recommendations for clinical practice regarding indications of LAIs in EP
High-throughput Plant Metabolomics and Predictive Modelling
No full textThis chapter explores advances and methodologies in high-throughput metabolic phenotyping through metabolomics and predictive modeling to enhance the understanding of plant metabolism. Key techniques, data analysis tools, and applications in plant science research are discussed. The potential of predictive modeling to identify new metabolic pathways and markers associated with plant performance and improve crop traits is highlighted. Future directions and challenges in the field are also examined
Droit de la peine. Peine complémentaire - La mesure de remise en état n'est pas une peine (Cass. crim., 18 mars 2025, n° 24-84.120, B : JurisData n° 2025-002866)
No full textLancet Glob Health
Full text linkBACKGROUND: In response to increasing resistance to non-nucleoside reverse transcriptase inhibitors, millions of people living with HIV have switched to dolutegravir-based antiretroviral therapy, so understanding the possible emergence of dolutegravir resistance is essential. We aimed to predict how dolutegravir resistance in South Africa will change over time. METHODS: For this modelling study, we used the Modelling Antiretroviral Drug Resistance in South Africa (MARISA) model, a deterministic compartmental model calibrated to reproduce the HIV-1 epidemic in South Africa from 2005 to 2035 using data from the International Epidemiology Databases to Evaluate AIDS collaboration and the literature. Key parameters for modelling dolutegravir-resistance evolution were acquisition rates of dolutegravir-resistance mutations, reversion rates of dolutegravir-resistance mutations, the effect of resistance to nucleoside reverse transcriptase inhibitors on dolutegravir-resistance acquisition, the effect of dolutegravir resistance on dolutegravir-treatment efficacy, the probability of transmitting dolutegravir drug-resistance mutations compared with the probability of transmitting wild-type HIV, and the proportion of people with virologic failure on dolutegravir-based antiretroviral therapy with detectable drug levels. Model outcomes were estimated transmitted dolutegravir resistance and estimated acquired dolutegravir resistance. FINDINGS: We estimated a substantial increase in the number of individuals on dolutegravir-based antiretroviral therapy after its introduction in 2020, increasing from 0 to approximately 7 million people (7·08-7·15) living with HIV on dolutegravir in 2035. We estimated the proportion of people living with HIV with viral suppression (ie, viral load <1000 copies per mL) on dolutegravir-based antiretroviral therapy to be 93% (uncertainty range 92·2-94·3) in 2035. We estimated that acquired dolutegravir resistance in people living with HIV on failing dolutegravir-based antiretroviral therapy would increase rapidly, from 18·5% (uncertainty range 12·5-25·4) in 2023 to 41·7% (29·0-54·0) in 2035. For transmitted dolutegravir resistance, we estimated an increase from 0·1% (0·0-0·2) in 2023 to 5·0% (1·9-11·9) in 2035. We estimated that resistance-mitigation strategies involving rapid switching to protease-inhibitor-based antiretroviral therapy could effectively reduce the increase in acquired dolutegravir resistance and slow the increase in transmitted dolutegravir resistance. INTERPRETATION: Although dolutegravir-based antiretroviral therapy maintains high virological suppression, acquired and transmitted dolutegravir resistance are likely to increase. This increase will likely be greater in settings where HIV RNA monitoring, genotypic-resistance testing, and options to switch antiretroviral therapy regimens are scarce. FUNDING: US National Institutes of Health National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation, and University of Zurich Research Priority Program Evolution in Action
