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The Journal of Emergency Medicine May 2024
Topics: Humans; Venlafaxine Hydrochloride; Electrocardiography; Epilepsy; Long QT Syndrome; Antidepressive Agents, Second-Generation; Male; Female; Seizures; Adult
PubMed: 38763732
DOI: 10.1016/j.jemermed.2023.11.027 -
Journal of Environmental Management Jun 2024Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO-based ICPB system has been widely...
Efficient degradation of venlafaxine using intimately coupled high-active crystal facets exposed TiO and biodegradation system: Kinetic studies, biofilm stress behavior and transformation mechanism.
Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO-based ICPB system has been widely studied. There are many ways to improve the degradation efficiency of the ICPB process, but no crystal facet engineering method has been reported yet. In this work, a new ICPB system coated with NaF-TiO exposing high energy facets was designed to degrade biorecalcitrant psychotropic drug - venlafaxine (VNF). Initially, the TiO crystal surface was modified with NaF, resulting in the formation of NaF-TiO with a 14.4% increase in the exposure ratio of (001). The contribution rate of ·OH was increased by 9.5%, and the contribution rate of h was increased by 33.2%. Next, NaF-TiO was loaded onto the surface of the sponge carrier, and then the ICPB system was constructed after about 15 days of biofilm formation. After the ICPB system was acclimated with VNF, the removal rate of COD decreased significantly (the lowest was 62.7%), but that of ammonia nitrogen remained at 50.5 ± 6.0% and the extracellular polymeric substance (EPS) secretion increased by 84.1 mg/g VSS. According to the high throughput results, at the phylum level, Proteobacteria and Chloroflexi together maintain the nitrogen removal capability and structural stability of the ICPB system. The relative abundance of Bacteroidota was significantly increased by 14.2%, suggesting that there may be some correlation between Bacteroidota and certain metabolites of the anti-depressant active ingredients. At the genus level, the Thauera (3.1%∼11.5%) is the major bacterial group that secretes EPS, protecting biofilm against external influences. Most of the changes in microorganisms are consistent with the decontamination properties and macroscopic appearance of EPS in the ICPB system. Finally, the degradation efficiency of ICPB system for VNF was investigated (92.7 ± 3.8%) and it was mostly through hydroxylation and demethylation pathways, with more small molecular products detected, providing the basis for biological assimilation of VNF. Collectively, the NaF-TiO based ICPB system would be lucrative for the future degradation of venlafaxine.
Topics: Venlafaxine Hydrochloride; Biofilms; Titanium; Biodegradation, Environmental; Kinetics; Water Pollutants, Chemical; Wastewater; Catalysis
PubMed: 38759549
DOI: 10.1016/j.jenvman.2024.121159 -
European Journal of Nutrition May 2024Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation...
PURPOSE
Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels.
METHODS
A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression.
RESULTS
Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ = 96.36, p = 0.000). The n-3 index (χ = 10.59, p = 0.001), EPA (χ = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ = 10.71, p = 0.001) were increased, while C22:4n6 (χ = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05).
CONCLUSION
These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.
PubMed: 38758363
DOI: 10.1007/s00394-024-03421-y -
International Journal of Clinical... May 2024Venlafaxine is frequently prescribed for patients with depression. To control the concentration of venlafaxine within the therapeutic window for the best treatment...
BACKGROUND
Venlafaxine is frequently prescribed for patients with depression. To control the concentration of venlafaxine within the therapeutic window for the best treatment effect, a model to predict venlafaxine concentration is necessary.
AIM
Our objective was to develop a prediction model for venlafaxine concentration using real-world evidence based on machine learning and deep learning techniques.
METHOD
Patients who underwent venlafaxine treatment between November 2019 and August 2022 were included in the study. Important variables affecting venlafaxine concentration were identified using a combination of univariate analysis, sequential forward selection, and machine learning techniques. Predictive performance of nine machine learning and deep learning algorithms were assessed, and the one with the optimal performance was selected for modeling. The final model was interpreted using SHapley Additive exPlanations.
RESULTS
A total of 330 eligible patients were included. Five influential variables that affect venlafaxine concentration were venlafaxine daily dose, sex, age, hyperlipidemia, and adenosine deaminase. The venlafaxine concentration prediction model was developed using the eXtreme Gradient Boosting algorithm (R = 0.65, mean absolute error = 77.92, root mean square error = 93.58). In the testing cohort, the accuracy of the predicted concentration within ± 30% of the actual concentration was 73.49%. In the subgroup analysis, the prediction accuracy was 69.39% within the recommended therapeutic range of venlafaxine concentration within ± 30% of the actual value.
CONCLUSION
The XGBoost model for predicting blood concentration of venlafaxine using real-world evidence was developed, guiding the adjustment of regimen in clinical practice.
PubMed: 38753076
DOI: 10.1007/s11096-024-01724-y -
International Journal of Clinical... May 2024Venlafaxine dose regimens vary considerably between individuals, requiring personalized dosing.
BACKGROUND
Venlafaxine dose regimens vary considerably between individuals, requiring personalized dosing.
AIM
This study aimed to identify dose-related influencing factors of venlafaxine through real-world data analysis and to construct a personalized dose model using advanced artificial intelligence techniques.
METHOD
We conducted a retrospective study on patients with depression treated with venlafaxine. Significant variables were selected through a univariate analysis. Subsequently, the predictive performance of seven models (XGBoost, LightGBM, CatBoost, GBDT, ANN, TabNet, and DT) was compared. The algorithm that demonstrated optimal performance was chosen to establish the dose prediction model. Model validation used confusion matrices and ROC analysis. Additionally, a dose subgroup analysis was conducted.
RESULTS
A total of 298 patients were included. TabNet was selected to establish the venlafaxine dose prediction model, which exhibited the highest performance with an accuracy of 0.80. The analysis identified seven crucial variables correlated with venlafaxine daily dose, including blood venlafaxine concentration, total protein, lymphocytes, age, globulin, cholinesterase, and blood platelet count. The area under the curve (AUC) for predicting venlafaxine doses of 75 mg, 150 mg, and 225 mg were 0.90, 0.85, and 0.90, respectively.
CONCLUSION
We successfully developed a TabNet model to predict venlafaxine doses using real-world data. This model demonstrated substantial predictive accuracy, offering a personalized dosing regimen for venlafaxine. These findings provide valuable guidance for the clinical use of the drug.
PubMed: 38733475
DOI: 10.1007/s11096-024-01729-7 -
World Psychiatry : Official Journal of... Jun 2024Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative...
Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.
Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.
PubMed: 38727044
DOI: 10.1002/wps.21205 -
Die Anaesthesiologie Jun 2024
Topics: Humans; Venlafaxine Hydrochloride; Heart Arrest; Extracorporeal Membrane Oxygenation; Male; Female; Adult
PubMed: 38717642
DOI: 10.1007/s00101-024-01412-6 -
MedRxiv : the Preprint Server For... Apr 2024Currently, placebo-controlled clinical trials report mean change and effect sizes, which masks information about heterogeneity of treatment effects (HTE). Here, we...
Currently, placebo-controlled clinical trials report mean change and effect sizes, which masks information about heterogeneity of treatment effects (HTE). Here, we present a method to estimate HTE and evaluate the null hypothesis (H) that a drug has equal benefit for all participants (HTE=0). We developed measure termed 'estimated heterogeneity of treatment effect' or which estimates variability in drug response by comparing distributions between study arms. This approach was tested across numerous large placebo-controlled clinical trials. In contrast with variance-based methods which have not identified heterogeneity in psychiatric trials, reproducible instances of treatment heterogeneity were found. For example, heterogeneous response was found in a trial of venlafaxine for depression (p=0.034), and two trials of dasotraline for binge eating disorder (Phase 2, p=0.002; Phase 3, 4mg p=0.011; Phase 3, 6mg p=0.003). Significant response heterogeneity was detected in other datasets as well, often despite no difference in variance between placebo and drug arms. The implications of eHTE as a clinical trial outcomes independent from central tendency of the group is considered and the important of the eHTE method and results for drug developers, providers, and patients is discussed.
PubMed: 38712180
DOI: 10.1101/2024.04.23.24306211 -
Cureus Apr 2024Narcolepsy Type 1 is a sleep disorder, with cataplexy as its cardinal feature, characterized by sudden decrease or loss of muscle tone triggered by strong emotions....
Narcolepsy Type 1 is a sleep disorder, with cataplexy as its cardinal feature, characterized by sudden decrease or loss of muscle tone triggered by strong emotions. Cataplexy can be misdiagnosed as epileptic seizures given its clinical similarity to atonic seizures. The low prevalence of the disease added another layer of complexity in providing timely and accurate diagnosis. We report a case of a young man with recurrent episodes of falling and an inability to respond, initially misinterpreted as epileptic seizures due to findings in routine electroencephalography (EEG). Anti-seizure medications were ineffective, and subsequent ambulatory EEG revealed no epileptic activity during events. A detailed history uncovered symptoms of cataplexy and daytime sleepiness, leading to the correct diagnosis of narcolepsy type I confirmed by polysomnogram (PSG) and mean sleep latency test (MSLT). Discontinuation of anti-seizure medications and treatment with venlafaxine successfully resolved cataplexy. The case highlights the importance of a thorough clinical history in distinguishing cataplexy from seizures, as well as the caution against relying solely on EEG findings for epilepsy diagnosis. Ambulatory EEG can help exclude epileptic events, and PSG with MSLT are necessary to confirm narcolepsy type I.
PubMed: 38707044
DOI: 10.7759/cureus.57540 -
Chemosphere Jun 2024Elevated usage of pharmaceutical products leads to the accumulation of emerging contaminants in sewage. In the current work, Ganoderma lucidum (GL) was used to remove...
Elevated usage of pharmaceutical products leads to the accumulation of emerging contaminants in sewage. In the current work, Ganoderma lucidum (GL) was used to remove pharmaceutical compounds (PCs), proposed as a tertiary method in sewage treatment plants (STPs). The PCs consisted of a group of painkillers (ketoprofen, diclofenac, and dexamethasone), psychiatrists (carbamazepine, venlafaxine, and citalopram), beta-blockers (atenolol, metoprolol, and propranolol), and anti-hypertensives (losartan and valsartan). The performance of 800 mL of synthetic water, effluent STP, and hospital wastewater (HWW) was evaluated. Parameters, including treatment time, inoculum volume, and mechanical agitation speed, have been tested. The toxicity of the GL after treatment is being studied based on exposure levels to zebrafish embryos (ZFET) and the morphology of the GL has been observed via Field Emission Scanning Electron Microscopy (FESEM). The findings conclude that GL can reduce PCs from <10% to >90%. Diclofenac and valsartan are the highest (>90%) in the synthetic model, while citalopram and propranolol (>80%) are in the real wastewater. GL effectively removed pollutants in 48 h, 1% of the inoculum volume, and 50 rpm. The ZFET showed GL is non-toxic (LC is 209.95 mg/mL). In the morphology observation, pellets GL do not show major differences after treatment, showing potential to be used for a longer treatment time and to be re-useable in the system. GL offers advantages to removing PCs in water due to their non-specific extracellular enzymes that allow for the biodegradation of PCs and indicates a good potential in real-world applications as a favourable alternative treatment.
Topics: Wastewater; Water Pollutants, Chemical; Animals; Zebrafish; Reishi; Waste Disposal, Fluid; Pharmaceutical Preparations; Malaysia; Sewage; Biodegradation, Environmental; Diclofenac
PubMed: 38697564
DOI: 10.1016/j.chemosphere.2024.142209