Environmentally Relevant Levels of Antiepileptic Carbamazepine Altered Intestinal Microbial Composition and Metabolites in Amphibian Larvae.

There is growing concern about the potential ecological risks posed by pharmaceutical residues in the aquatic environment. However, our understanding of the toxic effects of antiepileptic pharmaceuticals, such as carbamazepine (CBZ), on aquatic animal larvae is still limited. In this study, the tadpoles of the black-spotted pond frog (Pelophylax nigromaculatus) were exposed to environmentally relevant concentrations of CBZ (0.3 and 3.0 µg/L) for 30 days, and their growth, intestinal microbial composition, and metabolites were investigated to assess the potential toxic effects of CBZ in non-targeted aquatic organisms. Some tadpoles died during exposure, but there was no significant among-group difference in the survival and growth rates. CBZ exposure significantly altered the composition of tadpole intestinal microbiota. Relative abundances of some bacterial genera (e.g., Blautia, Prevotella, Bacillus, Microbacterium, etc.) decreased, while others (e.g., Paucibacter, etc.) increased in CBZ-exposed tadpoles. Interestingly, CBZ-induced alterations in some bacteria might not necessarily lead to adverse outcomes for animals. Meanwhile, small molecular intestinal metabolites related to energy metabolism, and antioxidant and anti-inflammatory activities were also altered after exposure. Taken together, environmentally relevant levels of CBZ might alter the metabolic and immune performances of amphibian larvae by modifying the abundance of some specific bacteria and the level of metabolites in their intestines, thereby potentially causing a long-term effect on their fitness.

Development of a novel LED-IoT photoreactor for enhanced removal of carbamazepine waste driven by solar energy.

This study introduces an innovative LED-IoT photoreactor, representing a significant advancement in response to the demand for sustainable water purification. The integration of LED-IoT installations addresses the challenge of intermittent sunlight availability, employing LEDs with a spectrum mimicking natural sunlight. Passive Infra-Red (PIR) sensors and Internet of things (IoT) technology ensure consistent radiation intensity, with the LED deactivating in ample sunlight and activating in its absence. Utilizing a visible light-absorbing photocatalyst developed through sol-gel synthesis and mild-temperature calcination, this research demonstrates a remarkable carbamazepine removal efficiency exceeding 95% under LED-IoT system illumination, compared to less than 90% efficiency with sunlight alone, within a 6-h exposure period. Moreover, the designed photocatalytic system achieves over 60% mineralization of carbamazepine after 12 h. Notably, the photocatalyst demonstrated excellent stability with no performance loss during five further cycles. Furthermore, integration with renewable energy sources facilitated continuous operation beyond daylight hours, enhancing the system's applicability in real-world water treatment scenarios. A notable application of the LED-IoT system at an operating sewage treatment plant showed nearly 80% efficiency in carbamazepine removal from sewage in the secondary settling tank after 6 h of irradiation, coupled with nearly 40% mineralization efficiency. Additionally, physicochemical analyses such as XPS and STA-FTIR confirm that the carbamazepine photooxidation process does not affect the surface of the photocatalyst, showing no adsorption for degradation products.

Enhanced Selective Degradation of Pharmaceutical and Personal Care Products by ß-Cyclodextrin-Decorated ZIF-67 Nanocomposites in Reclaimed Water.

A peroxymonosulfate oxidation system was developed via modification of ß-cyclodextrin (ß-CD) on the surface of Fe2+-doped ZIF-67 (CD/Fe@ZIF-67) as an activator. The 99.7% carbamazepine, 91.3% bisphenol A (BPA), and 95.4% diclofenac (DCF) degradation efficiency were achieved within 10 min, 60, and 1 min, respectively. The hydrophobicity of these three pollutants is positively correlated with their adsorption kinetic constants by CD/Fe@ZIF-67 due to the introduction of ß-CD. Scavenger experiments and electron spin resonance spectra confirmed that carbamazepine was preferentially oxidized by SO4•- [λ(SO4•-)(70.5%) > λ(•OH)(28.2%) > λ(O2•-)(1.3%)], where SO4•- and O2•- played dominant roles in the degradation of BPA [λ(SO4•-)(71.7%) > λ(O2•-)(22.8%) > λ(•OH)(5.5%)], and O2•- was responsible for DCF removal [λ(O2•-) = 93.2%]. Additionally, the particulate catalyst was immobilized in the shell side of a ceramic membrane in a membrane reactor for catalyst recovery. This reactor achieved nearly 100% removal efficiency under optimal conditions: 0.036 wt % catalyst loading, 0.5 mM peroxymonosulfate concentration, 1 L inflow, 10 mg/L initial carbamazepine concentration, and 0.012 L/min hydraulic retention time. In summary, this study elucidates the active role of ß-CD in a polymetallic/peroxymonosulfate system and provides valuable insights into the development of effective oxidation methods for pharmaceutical and personal care products in wastewater.

Chronic Treatment with Oxcarbazepine Attenuates Its Anticonvulsant Effect in the Maximal Electroshock Model in Mice.

The objective of this study was to assess the impact of acute and chronic treatment with oxcarbazepine on its anticonvulsant activity, neurological adverse effects, and protective index in mice. Oxcarbazepine was administered in four protocols: once or twice daily for one week (7 × 1 or 7 × 2) and once or twice daily for two weeks (14 × 1 or 14 × 2). A single dose of the drug was employed as a control. The anticonvulsant effect was evaluated in the maximal electroshock test in mice. Motor and long-term memory impairment were assessed using the chimney test and the passive avoidance task, respectively. The concentrations of oxcarbazepine in the brain and plasma were determined via high-performance liquid chromatography. Two weeks of oxcarbazepine treatment resulted in a significant reduction in the anticonvulsant (in the 14 × 1; 14 × 2 protocols) and neurotoxic (in the 14 × 2 schedule) effects of this drug. In contrast, the protective index for oxcarbazepine in the 14 × 2 protocol was found to be lower than that calculated for the control. No significant deficits in memory or motor coordination were observed following repeated administration of oxcarbazepine. The plasma and brain concentrations of this anticonvulsant were found to be significantly higher in the one-week protocols. Chronic treatment with oxcarbazepine may result in the development of tolerance to its anticonvulsant and neurotoxic effects, which appears to be dependent on pharmacodynamic mechanisms.

Degradation of organic pollutants by the Cl-/PMS process.

The viewpoints on whether high concentrations of chloride ion (Cl-) promote or inhibit the oxidation activity of activated persulfates are still inconclusive. Furthermore, the degradation of organic pollutants by the persulfates in the presence of high Cl- concentrations without any activation medium has not yet been studied. In this work, the efficiency and mechanism of degradation of organic pollutants such as carbamazepine (CBZ), sulfadiazine (SDZ), and phenol (PN) by Cl--activated PMS (denoted as Cl-/PMS) were investigated. Results showed that Cl- could effectively activate PMS for the complete removal of CBZ, SDZ, and PN with reaction kinetic constants of 0.4516 min-1, 0.01753 min-1, and 0.06805 min-1, respectively. Parameters such as PMS dose, Cl- concentration, solution pH, and initial concentrations of organic pollutants that affect the degradation efficiencies of the Cl-/PMS process were optimized. Unlike conventional activated persulfates, it was confirmed that the free chlorine was the main active species in the Cl-/PMS process. Finally, the degradation by-products of CBZ and SDZ as well as their toxicity were detected, and a possible degradation pathway for CBZ and SDZ was proposed. Though higher toxic chlorinated by-products were generated, the Cl-/PMS process was still an efficient oxidation method for the removal of organic pollutants in aqueous solutions which contain high concentrations of Cl-.

Safety and efficacy of carbamazepine in the treatment of trigeminal neuralgia: A metanalysis in biomedicine.

Trigeminal neuralgia is a debilitating condition characterized by severe facial pain. Carbamazepine has been widely used as a first-line treatment option for trigeminal neuralgia, but there is a need to evaluate its safety and efficacy based on existing evidence. This meta-analysis aims to systematically assess the available literature and provide a comprehensive evaluation of the safety and efficacy of carbamazepine in the treatment of trigeminal neuralgia. A thorough search of electronic databases yielded a total of 15 relevant studies that met the inclusion criteria. The pooled analysis of these studies revealed that carbamazepine demonstrated significant efficacy in reducing pain intensity and frequency in patients with trigeminal neuralgia. Moreover, the drug was generally well-tolerated, with the most common adverse events being mild and transient. Subgroup analyses based on different dosages and treatment durations further supported the overall findings. However, caution should be exercised in patients with certain comorbidities or specific populations, as some rare but severe adverse events were reported. In conclusion, this meta-analysis provides strong evidence supporting the safety and efficacy of carbamazepine as a valuable therapeutic option for the management of trigeminal neuralgia. These results can guide clinicians in making informed decisions regarding the use of carbamazepine and contribute to optimizing treatment strategies for patients with trigeminal neuralgia. Further research is warranted to explore long-term safety and efficacy outcomes, as well as to compare carbamazepine with alternative treatment modalities.

Kloos Syndrome (Paralysis of Time). A Psychopathological Rare Case.

A case of Kloos syndrome is presented, a rare psychopathological manifestation in psychiatry characterized by the experience of "time paralysis" related to an epileptic focus in the left temporoparietal areas. This syndrome was identified through a detailed psychopathological analysis and detected by an electroencephalographic record. The patient's symptoms disappeared after receiving antiepileptic treatment with Carbamazepine. In this case report we highlight the detailed phenomenological and clinical analysis, as well as the importance of carrying out complementary tests when we are faced with unusual or sudden-onset symptoms without any trigger, as took place in the case exposed.

Molecular identification of HLA-B75 serotype markers by qPCR: A more inclusive pharmacogenetic approach before carbamazepine prescription.

Genetic screening for HLA-B*15:02 before prescribing carbamazepine is standard practice to prevent severe cutaneous adverse reactions in Asian populations. These reactions are associated not only with this allele but also with closely related HLA-B75 serotype markers-HLA-B*15:11 and HLA-B*15:21-which are prevalent in several Asian countries. However, a reliable method for identifying HLA-B75 serotype markers is still not available. We developed an in-house quantitative PCR (qPCR) for HLA-B75 screening and validated it using 303 anonymized DNA samples. Due to inadequate quality control, the qPCR results for 11 samples were excluded. We analyzed the sensitivity and specificity of the test using 93 HLA-typed samples. The concordance between the qPCR method and an established screening method was assessed using 199 HLA-screened samples tested for HLA-B*15:02 at Songklanagarind Hospital, Songkhla, Thailand. All discordant results were confirmed by Sanger sequencing. The qPCR method demonstrated a sensitivity of 100% (95% confidence interval = 83.16%-100.00%) and a specificity of 100% (95% confidence interval = 95.07%-100.00%). Concordance analysis revealed a 96.5% agreement between methods (192/199; 44 positive and 148 negative results). All discordant results were due to HLA-B75 markers not being HLA-B*15:02 (two samples with HLA-B*15:11 and five samples with HLA-B*15:21). In conclusion, this qPCR method could be useful for identifying HLA-B75 carriers at risk of carbamazepine-induced reactions in Asian populations where carriers of HLA-B*15:02, HLA-B*15:11, or HLA-B*15:21 are common.

Novel sunlight-induced monochloramine activation system for efficient microcontaminant abatement.

As an eco-friendly and sustainable energy, solar energy has great application potential in water treatment. Herein, simulated sunlight was for the first time utilized to activate monochloramine for the degradation of environmental organic microcontaminants. Various microcontaminants could be efficiently degraded in the simulated sunlight/monochloramine system. The average innate quantum yield of monochloramine over the wavelength range of simulated sunlight was determined to be 0.068 mol/Einstein. With the determined quantum yield, a kinetic model was established. Based on the good agreement between the simulated and measured photolysis and radical contributions to the degradation of ibuprofen and carbamazepine, the major mechanism of monochloramine activation by simulated sunlight was proposed. Chlorine radical (Cl∙) and hydroxyl radical (HO∙) were major radicals responsible for microcontaminant degradation in the system. Moreover, the model facilitated a deep investigation into the effects of different reaction conditions (pH, monochloramine concentration, and water matrix components) on the degradation of ibuprofen and carbamazepine, as well as the roles of the involved radicals. The differences between simulated and measured degradation data of each microcontaminant under all conditions were less than 10 %, indicating the strong reliability of the model. The model could also make good prediction for microcontaminant degradation in the natural sunlight/monochloramine system. Furthermore, the formation of disinfection byproducts (DBPs) was evaluated at different oxidation time in simulated sunlight/monochloramine with and without post-chloramination treatment. In real waters, organic components showed more pronounced suppression on microcontaminant degradation efficiency than inorganic ions. This study provided a systematic investigation into the novel sunlight-induced monochloramine activation system for efficient microcontaminant degradation, and demonstrated the potential of the system in practical applications.

The Role of EEG microstates in predicting oxcarbazepine treatment outcomes in patients with newly-diagnosed focal epilepsy.

PURPOSE: Microstates represent the global and topographical distribution of electrical brain activity from scalp-recorded EEG. This study aims to explore EEG microstates of patients with focal epilepsy prior to medication, and employ extracted microstate metrics for predicting treatment outcomes with Oxcarbazepine monotherapy. METHODS: This study involved 25 newly-diagnosed focal epilepsy patients (13 females), aged 12 to 68, with various etiologies. Patients were categorized into Non-Seizure-Free (NSF) and Seizure-Free (SF) groups according to their first follow-up outcomes. From pre-medication EEGs, four representative microstates were identified by using clustering. The temporal parameters and transition probabilities of microstates were extracted and analyzed to discern group differences. With generating sample method, Support Vector Machine (SVM), Logistic Regression (LR), and Naïve Bayes (NB) classifiers were employed for predicting treatment outcomes. RESULTS: In the NSF group, Microstate 1 (MS1) exhibited a significantly higher duration (mean±std. = 0.092±0.008 vs. 0.085±0.008, p = 0.047), occurrence (mean±std. = 2.587±0.334 vs. 2.260±0.278, p = 0.014), and coverage (mean±std. = 0.240±0.046 vs. 0.194±0.040, p = 0.014) compared to the SF group. Additionally, the transition probabilities from Microstate 2 (MS2) and Microstate 3 (MS3) to MS1 were increased. In MS2, the NSF group displayed a stronger correlation (mean±std. = 0.618±0.025 vs. 0.571±0.034, p < 0.001) and a higher global explained variance (mean±std. = 0.083±0.035 vs. 0.055±0.023, p = 0.027) than the SF group. Conversely, Microstate 4 (MS4) in the SF group demonstrated significantly greater coverage (mean±std. = 0.388±0.074 vs. 0.334±0.052, p = 0.046) and more frequent transitions from MS2 to MS4, indicating a distinct pattern. Temporal parameters contribute major predictive role in predicting treatment outcomes of Oxcarbazepine, with area under curves (AUCs) of 0.95, 0.70, and 0.86, achieved by LR, NB and SVM, respectively. CONCLUSION: This study underscores the potential of EEG microstates as predictive biomarkers for Oxcarbazepine treatment responses in newly-diagnosed focal epilepsy patients.

Correlation of drug dose estimated from national prescription registers with mean blood level of antiseizure medication in pregnancy.

PURPOSE: The purpose was to examine the correlation of antiseizure medication drug dose estimated from prescription fill records from prescription registers with blood levels during pregnancy. METHODS: We conducted a Nation-wide study of mothers who gave birth in Denmark between 1 January 2014 and 31 December 2018 using data from Danish Prescription and Laboratory Registers. We identified mothers with blood level measurements of antiseizure medication. The main exposure was estimated antiseizure medication dosage estimated from pregnancy-filled prescriptions in the Danish Prescription Register. The main outcome was the correlation of estimated dose with mean blood level of antiseizure medication in pregnancy. For privacy reasons, the number of blood level measurement and prescription fills were rounded to nearest 10, but proportions reported as exact values. RESULTS: Among 298 560 pregnancies, we identified pregnancies with recorded prescription fill from the prescription register for valproate (N = 90), lamotrigine (N = 1360), levetiracetam (N = 340), topiramate (N = 100), and carbamazepine (N = 60). In these pregnancies, blood level measurements were available in 50 (53%) pregnancies for valproate, 850 (62%) pregnancies for lamotrigine, 320 (93%) pregnancies for levetiracetam, 50 (68%) pregnancies for carbamazepine, and 40 (35%) pregnancies for topiramate. Pearsons's correlation coefficients for the correlation of estimated antiseizure medication dose with mean blood levels were 0.67 (p < 0.0001) for valproate, 0.63 (p < 0.0001) for lamotrigine, 0.63 (p < 0.0001) for levetiracetam, 0.76 (<0.0001) for carbamazepine and 0.89 (<0.0001) for topiramate. CONCLUSIONS: Dose of antiseizure medication estimated from prescription fills was a good proxy for blood levels and thus for biological exposure in pregnancy, suggesting that administrative prescription fill records may be a valuable resource for estimating exposure to antiseizure medication in pregnancy.

Trigeminal neuralgia.

Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors. The pathophysiology of TN is multifactorial and involves genetic predisposition, anatomical changes, and neurophysiological factors, leading to hyperexcitable neuronal states, central sensitization and widespread neural plasticity changes. Neurovascular compression of the trigeminal root, which undergoes major morphological changes, and focal demyelination of primary trigeminal afferents are key aetiological factors in TN. Structural and functional brain imaging studies in patients with TN demonstrated abnormalities in brain regions responsible for pain modulation and emotional processing of pain. Treatment of TN involves a multifaceted approach that considers patient-specific factors, including the type of TN, with initial pharmacotherapy followed by surgical options if necessary. First-line pharmacological treatments include carbamazepine and oxcarbazepine. Surgical interventions, including microvascular decompression and percutaneous neuroablative procedures, can be considered at an early stage if pharmacotherapy is not sufficient for pain control or has intolerable adverse effects or contraindications.

Reactive layered hydroxide membrane for advanced water treatment: Micropollutant degradation and antifouling potential.

The effective removal of micropollutants by water treatment technologies remains a significant challenge. Herein, we develop a CoFe layered double hydroxide (CoFeLDH) catalytic membrane for peroxymonosulfate (PMS) activation to achieve efficient micropollutant removal with improved mass transfer rate and reaction kinetics. This study found that the CoFeLDH membrane/PMS system achieved an impressive above 98% degradation of the probe chemical ranitidine at 0.1 mM of PMS including five more micropollutants (Sulfamethoxazole, Ciprofloxacin, Carbamazepine, Acetaminophen and Bisphenol A) at satisfactory level (above 80%). Moreover, significant improvements in water flux and antifouling properties were observed, marking the membrane as a specific advancement in the removal of membrane fouling in water purification technology. The membrane demonstrated consistent degradation efficiency for several micropollutants and across a range of pH (4-9) as well as different anionic environments, thereby showing it suitability for scale-up application. The key role of reactive species such as SO4•-, and O2• - radicals in the degradation process was elucidated. This is followed by the confirmation of the occurrence of redox cycling between Co and Fe, and the presence of CoOH+ that promotes PMS activation. Over the ten cycles, the membrane could be operated with a flux recovery of up to 99.8% and maintained efficient performance over 24 h continuous operation. Finally, the efficiency in degrading micropollutants, coupled with reduced metal leaching, makes the CoFeLDH membrane as a promising technology for application in water treatment.

Bio-electrochemical degradation of carbamazepine (CBZ): A comprehensive study on effectiveness, degradation pathway, and toxicological assessment.

Recent attention on the detrimental effects of pharmaceutically active compounds (PhACs) in natural water has spurred researchers to develop advanced wastewater treatment methods. Carbamazepine (CBZ), a widely recognized anticonvulsant, has often been a primary focus in numerous studies due to its prevalence and resistance to breaking down. This study aims to explore the effectiveness of a bio-electrochemical system in breaking down CBZ in polluted water and to assess the potential harmful effects of the treated wastewater. The results revealed bio-electro degradation process demonstrated a collaborative effect, achieving the highest CBZ degradation compared to electrodegradation and biodegradation techniques. Notably, a maximum CBZ degradation efficiency of 92.01% was attained using the bio-electrochemical system under specific conditions: Initial CBZ concentration of 60 mg/L, pH level at 7, 0.5% (v/v) inoculum dose, and an applied potential of 10 mV. The degradation pathway established by identifying intermediate products via High-Performance Liquid Chromatography-Mass Spectrometry, revealed the complete breakdown of CBZ without any toxic intermediates or end products. This finding was further validated through in vitro and in vivo toxicity assays, confirming the absence of harmful remnants after the degradation process.

Effects of Polymers on Cocrystal Growth in a Drug-Drug Coamorphous System: Relations between Glass-to-Crystal Growth and Surface-Enhanced Crystal Growth.

Coamorphous and cocrystal drug delivery systems provide attractive crystal engineering strategies for improving the solubilities, dissolution rates, and oral bioavailabilities of poorly water-soluble drugs. Polymeric additives have often been used to inhibit the unwanted crystallization of amorphous drugs. However, the transformation of a coamorphous phase to a cocrystal phase in the presence of polymers has not been fully elucidated. Herein, we investigated the effects of low concentrations of the polymeric excipients poly(ethylene oxide) (PEO) and poly(vinylpyrrolidone) (PVP) on the growth of carbamazepine-celecoxib (CBZ-CEL) cocrystals from the corresponding coamorphous phase. PEO accelerated the growth rate of the cocrystals by increasing the molecular mobility of the coamorphous system, while PVP had the opposite effect. The coamorphous CBZ-CEL system exhibited two anomalously fast crystal growth modes: glass-to-crystal (GC) growth in the bulk and accelerated crystal growth at the free surface. These two fast growth modes both disappeared after doping with PEO (1-3% w/w) but were retained in the presence of PVP, indicating a potential correlation between the two fast crystal growth modes. We propose that the different effects of PEO and PVP on the crystal growth modes arose from weaker effects of the polymers on cocrystallization at the surface than in the bulk. This work provides a deep understanding of the mechanisms by which polymers influence the cocrystallization kinetics of a multicomponent amorphous phase and highlights the importance of polymer selection in stabilizing coamorphous systems or preparing cocrystals via solid-based methods.

Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy.

Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia. Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy. Design, Setting, and Participants: A model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023. Intervention: No HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers. Main Outcomes and Measures: Life-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios. Results: HLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, -A$83 to A$374; US$76; 95% CI, -US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, -0.0247 to -0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations. Conclusions and Relevance: The results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference-A Case Study.

BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

Protecting against micropollutants in water storage tanks using in-situ TiO2 coated quartz optical fibers.

Photocatalyst-coated optical fibers (P-OFs) using UV-A LEDs offer a highly promising solution for the degradation of micropollutants within municipal, reuse, industrial or home distribution systems, by integrating P-OFs into water storage tanks. P-OFs have photocatalysts attached to bundles of optical fibers, enabling their direct deployment within tanks. This eliminates the necessity for photocatalyst slurries, which would require additional membrane or separation systems. However, a current limitation of P-OFs is light management, specifically light oversaturation of the coated photocatalysts and short light transmission distances along fibers. This study overcomes this limitation and reveals strategies to improve the light dissipation uniformity along P-OFs, and demonstrates the performance of P-OFs on degrading a model micropollutant, carbamazepine (CBZ). Key tunable variables of fibers and light emission conditions, including photocatalyst coating patchiness (p), minimum light incident angles (θm), radiant flux launched to fibers (Φi), and fiber diameters (D), were modeled to establish their relationships with the light dissipation uniformity in TiO2-coated quartz optical fibers (TiO2-QOFs). We then validated modeling insights by conducting experiments to examine how these variables influence the generation of evanescent waves which are localized energy on fiber surfaces, leading to either photocatalyst activation or the recapture of unused light back into fibers. We observed substantial enhancements in evanescent waves generation by decreasing p and increasing θm, resulting in uniform light dissipation which reduces light oversaturation and improves light transmission distances. Moreover, these optimizations led to a remarkable three-fold improvement in CBZ degradation rates and a 65% reduction in energy consumption. Such improvement substantially reduces the capital and operational cost and enhances practicality of energy-efficient photocatalysis without additional chemical oxidants for micropollutant degradation in water storage tanks.

Porous-carbon/manganese composite catalyst transformed from waste biomass as peroxymonosulfate activator for carbamazepine degradation.

Activation of peroxymonosulfate (PMS) with solid catalysts for organic pharmaceutical degradation still faces challenge due to the demand of inexpensive catalysts. In this study, manganese-oxidizing microalgae (MOM) and its associated biogenic manganese oxides (BMO) were employed to prepare biomass-transformed porous-carbon/manganese (B-PC/Mn) catalyst through high-temperature calcination (850 °C). Remarkably, 100 % of carbamazepine (CBZ) was degraded within 30 min in the B-PC/Mn/PMS system. The degradation kinetic constant was 0.1718 min-1, which was 44.0 times higher than that of the biomass-transformed porous carbon mixed with MnOx activated PMS system. 1O2 was generated in the B-PC/Mn/PMS system, which is responsible for CBZ degradation. The MOM-BMO-associated structure greatly increased the specific surface areas and the contents of the C = O and pyrrolic-N groups, which facilitated PMS activation. The structure also induced the generation of Mn5C2, which exhibited a strong adsorption towards PMS. This study provides a novel strategy for preparing catalysts by using waste biomass.

Biological degradation of organic micropollutants in GAC filters-temporal development and spatial variations.

The capacity for organic micropollutant removal in granular activated carbon (GAC) filters for wastewater treatment changes over time. These changes are in general attributed to changes in adsorption, but may in some cases also be affected by biological degradation. Knowledge on the degradation of organic micropollutants, however, is scarce. In this work, the degradation of micropollutants in several full-scale GAC and sand filters was investigated through incubation experiments over a period of three years, using 14C-labeled organic micropollutants with different susceptibilities to biological degradation (ibuprofen, diclofenac, and carbamazepine), with parallel 16S rRNA gene sequencing. The results showed that the degradation of diclofenac and ibuprofen in GAC filters increased with increasing numbers of bed volumes when free oxygen was available in the filter, while variations over filter depth were limited. Despite relatively large differences in bacterial composition between filters, a degradation of diclofenac was consistently observed for the GAC filters that had been operated with high influent oxygen concentration (DO >8 mg/L). The results of this comprehensive experimental work provide an increased understanding of the interactions between microbial composition, filter material, and oxygen availability in the biological degradation of organic micropollutants in GAC filters.