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Background/Purpose: Caffeine is the most commonly used psychostimulant worldwide. Although its large intake is suspected toworsen psychotic symptoms because of increasing dopamine neurotransmission, schizophrenic patients are heavier caffeine consumers than the general population. This study aims to assess the impact of a caffeine restriction policy in a psychiatric hospital on patient psychopathology, hospitalization characteristics, and psychotropic prescribing patterns. Methods: It is a retrospective cross-sectional study based on electronic health records of a psychiatric hospital in the French-speaking area of Belgium. Two different periodswere compared, the first (n = 142), in 2017,when caffeinewas available in the institution and the second (n = 119), between November 2018 andNovember 2019 after the restriction of access to caffeinewas implemented. Adult inpatients with schizophrenia or schizoaffective disorder admitted for an acute hospitalization were included. Antipsychotic exposure, benzodiazepine daily dose, Global Assessment of Functioning scores, length of hospital stay, and some other factors were tested for their potential association with the decaffeinated period. Results: After adjusting for potential confounders, reduced caffeine availability inside the hospital was significantly associated with higher Global Assessment of Functioning scores at discharge (adjusted odds ratio [aOR] = 2.86, 95% confidence interval [CI] = 1.77–4.62) and shorter hospital stays (aOR = 0.68, 95% CI = 0.47–0.99) but was not associated with change in antipsychotic exposure at discharge (aOR= 1.04,95%CI = 0.64–1.7) or benzodiazepine daily dose (aOR = 0.89, 95% CI = 0.61–1.29). Conclusions: Limiting access to caffeine in psychiatric hospitals is a simple and inexpensive intervention that

Aim: To explore the evolution of antipsychotic polypharmacy (APP) and other psychotropic prescribing patterns during psychiatric hospitalisations, to detect characteristics associated with APP on admission and at discharge, and to examine clozapine prescribing patterns. Methods: Data on adult inpatients diagnosed with schizophrenia spectrum disorders were collected retrospectively from 6 Belgian hospitals. Results: Of the 516 patients included, APP prescribing increased significantly from 47.9% on hospital admission to 59.1% at discharge. On admission and at discharge, APP was associated with prior clozapine use (ORadmission=2.53, CI=1.1-5.84, ORdischarge=11.01, CI=4.45-27.28), treatment with a first-generation antipsychotic (ORadmission=26.79, CI=13.08-54.86, ORdischarge=25.2, CI=12.2-52.04), increased antipsychotic exposure (ORadmission=8.93, CI=5.13-15.56, ORdischarge=19.89, CI=10-39.54), and a greater number of hypno-sedatives (ORadmission=1.88, CI=1.23-2.88, ORdischarge=4.18, CI=2.53-6.91), and negatively associated with involuntary admission (ORadmission=0.31, CI=0.14-0.7, ORdischarge=0.3, CI=0.13-0.68). When using an alternative definition of monotherapy (i.e., including patients with an add-on low-dose antipsychotic for sleep disorders), alcohol use disorder (ORadmission=0.26, CI=0.13-0.54) and higher age (ORdischarge=0.53, CI=0.29-0.95) were negatively associated with APP, and living in a residential facility (ORdischarge=2.39, CI=1.21-4.71) and a higher daily dosage of benzodiazepines during the stay (ORdischarge=1.32, CI=1.03-1.69) increased the odds of being discharged on APP. Although 28.1% of patients were eligible for clozapine treatment, only 9.3% were being treated with clozapine on admission, and 11% at discharge. Seven of the ten patients with a new clozapine prescription were directly being prescribed a combination of antipsychotics, without a prior trial of clozapine monotherapy. Conclusion: Suboptimal prescriptions of antipsychotics in patients

More than two years on, the COVID-19 pandemic continues to wreak havoc around the world and has battle-tested the pandemic-situation responses of all major global governments. Two key areas of investigation that are still unclear are: the molecular mechanisms that lead to heterogenic patient outcomes, and the causes of Post COVID condition (AKA Long-COVID). In this paper, we introduce the HYGIEIA project, designed to respond to the enormous challenges of the COVID-19 pandemic through a multi-omic approach supported by network medicine. It is hoped that in addition to investigating COVID-19, the logistics deployed within this project will be applicable to other infectious agents, pandemic-type situations, and also other complex, non-infectious diseases. Here, we first look at previous research into COVID-19 in the context of the proteome, metabolome, transcriptome, microbiome, host genome, and viral genome. We then discuss a proposed methodology for a large-scale multi-omic longitudinal study to investigate the aforementioned biological strata through high-throughput sequencing (HTS) and mass-spectrometry (MS) technologies. Lastly, we discuss how a network medicine approach can be used to analyze the data and make meaningful discoveries, with the final aim being the translation of these discoveries into the clinics to improve patient care. View Full-Text

Background: Although Atorvastatin (ATV), is generally well tolerated, patients can experience muscle complaints. The occurrence of this discomfort is difficult to predict owing to high inter-individual variability. Muscle side effects are thought to be linked to intramuscular accumulation of ATV. The present study aimed at investigating the relative implication of influx and efflux transporters expressed in the muscle tissue (OATP2B1 and MRP1) in promoting or limiting the access of the drug into the cells. In addition, the impact of common single nucleotide polymorphisms (SNPs) in SLCO2B1 coding for OATP2B1 (rs12422149; c.935G>A) and ABCC1 coding for MRP1 (rs45511401; c.2012G>T) towards ATV transport was evaluated. Methods: HEK293 cells were stably transfected with plasmids containing full-length cDNA coding for the wild-type or the variant SLCO2B1 and/or ABCC1 to generate single and double stable transfectant HEK293 recombinant models overexpressing variant or wild-type OATP2B1 (influx) and/or MRP1 (efflux) proteins. Variant plasmids were generated using site directed mutagenesis. Expression analyses were performed through fluorescent microscopy and flow cytometry to validate the recombinant models. Accumulation and efflux experiments were carried out at different concentrations. ATV was quantified by LC-MS/MS and kinetic parameters were then compared between single and double HEK-transfectant expressing the wild-type and variant proteins. Results: Our results confirm the involvement of OATP2B1 and MRP1 in ATV cellular transport as we showed that intracellular accumulation of ATV was boosted by OATP2B1 overexpression whereas ATV accumulation was decreased by MRP1 overexpression. In double-transfectants, it was observed that the increased ATV intracellular accumulation driven by OATP2B1 influx was partially counteracted by MRP1 efflux. Finally, the c.935G>A SNP in SLCO2B1 was associated with decreased ATV OATP2B1-mediated influx whereas the c.2012G>T SNP in ABCC1 ap

Background : Antipsychotic polypharmacy (APP) is common worldwide in schizophrenia, while switch to antipsychotic monotherapy reduces adverse effects. Canada has been the leader in deprescribing policies in the last decades. Aims : To detect factors, including countries, associated with successful antipsychotic deprescribing after a psychiatric hospitalisation. Methods : Retrospective data were collected in a tertiary care hospital in Montreal (QC, Canada) and compared to data collected in 6 Belgian hospitals, in 2020-2021. Adult inpatients with a diagnosis of schizophrenia or schizoaffective disorder and discharged from a psychiatric unit after an acute hospitalisation were included. Results : At discharge, the daily number of antipsychotics had decreased in 22.2% of the 63 Canadian and 9.9% of the 516 Belgian patients, and increased in 17.5% of the Canadian and 24.3% of the Belgian patients. Living in a residential facility (OR=2.51, 95% CI 1.05-4.39), ≥2 previous antipsychotic trials (OR=15.38, 95% CI 3.62-65.36), having an antipsychotic side effect (OR=1.86, 95% CI 1.01-3.44), being in a general hospital (OR=2.28, 95% CI 1.09-4.75) and in Canada (OR=4.13, 95% CI 1.48-11.5) increased the odds of successful antipsychotic deprescribing at hospital discharge. Patients with a LAI (OR=0.51, 95% CI 0.26-0.98), prior clozapine use (OR=0.36, 95% CI 0.13-0.95), a greater antipsychotic exposure (OR=0.35, 95% CI 0.2-0.61) and a higher number of hypno-sedatives (OR=0.65, 95% CI 0.43-0.98) were less likely to have a deprescription. Conclusion : Antipsychotic deprescribing is feasible and already performed in identifiable patients, settings or situations. Patients hospitalised in Canada are more likely to have a deprescription than in Belgium.

Introduction: A high prevalence of antipsychotic polypharmacy (APP) and low utilisation of clozapine is considered as inappropriate prescribing that can lead to suboptimal treatment, increased risk of poor response or adverse effects. Objectives: To explore the evolution of prevalence of APP and associated factors as well as clozapine prescribing patterns between hospital admission and discharge. Methods: We collected retrospective data on adult inpatients diagnosed with schizophrenia spectrum disorders in 2020-2021 in 6 Belgian hospitals. Results: Of the 516 patients analysed, APP prescribing significantly increased from 47.9% on hospital admission to 59.1% at discharge. Both on admission and at discharge, APP was associated with treatment with a first-generation antipsychotic, not being treated with an antidepressant nor a mood stabilizer, high antipsychotic dosage, increased number of psychoactive cotreatments and total medicines. A lower number of comorbidities (OR=0.68, CI=0.50- 0.91), no treatment with benzodiazepines (OR=0.02, CI=0.01- 0.09) nor with trazodone or sedative antihistamines (OR=0.06, CI=0.01-0.03) and two or more previous antipsychotic trials (OR= 4.91, CI=1.30-18.57) was associated with APP on admission only. APP at discharge was more frequent in patients with antipsychotic adverse effects (OR=2.57, CI=1.10-6.00), prior clozapine use (OR =16.30, CI=3.27-81.22) and not involuntary admitted (OR=0.26 CI=0.08-0.88). Contrary to admission, treatment with benzodiazepines was associated with APP at discharge (OR=10.9, CI= 3.38-5.38). Only 9.3% of admitted patients were treated with clozapine. Although 28.1% were eligible, clozapine was introduced to 10 patients leading to 11% being discharged on it. Conclusions: Inappropriate prescribing of antipsychotics to schizophrenia patients persist after psychiatric hospitalisations and are associated with identifiable characteristics.

Sickle cell disease is the most common genetic disease affecting more than five million people worldwide. For its treatment, compounds such as senicapoc and voxelotor have recently proven their efficacy in clinical studies with sickle cell patients. However, their low aqueous solubility and sensitivity to metabolism make them poorly bioavailable by the oral route. This project aims to develop self-emulsifying systems to increase the aqueous solubility and oral bioavailability of senicapoc and voxelotor. Self-emulsifying systems loaded with senicapoc and voxelotor were developed and optimized. These formulations increased both the aqueous solubility and cellular transport of senicapoc and voxelotor through enterocyte monolayers (Caco-2). The lipid formulation loaded with voxelotor significantly increased its oral bioavailability compared to a suspension., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2021