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Impact of EfOM in the elimination of PPCPs by UV/chlorine: Radical chemistry and toxicity bioassays.Water Research Oct 2021The UV/chlorine process as a potential tertiary municipal wastewater treatment alternative for removing refractory PPCPs has been widely investigated. However, the role...
The UV/chlorine process as a potential tertiary municipal wastewater treatment alternative for removing refractory PPCPs has been widely investigated. However, the role of effluent organic matter (EfOM) on the radical chemistry and toxicity alteration is unclear. The elimination of two model PPCPs, primidone (PRM) and caffeine (CAF), by the co-exposure of UV and free chlorine was investigated to elucidate the impact of EfOM. Experimental results indicated that both OH and reactive chlorine species (RCS) were importantly involved in the decay of PRM at acidic condition, while ClO played dominant role at alkaline pH. The decay of CAF was dominated by ClO under all conditions. Chlorine dose, initial contaminant concentration, solution pH, and water matrix affect the process efficiency at varying degree resulting from their specific effect on the radical speciation in the system. Presence of EfOM isolate remarkably inhibited the decay of PRM and CAF by preferentially scavenging RCS and particularly ClO. Good correlations (linear for PRM and exponential for CAF) between UV absorbance at 254 nm and the observed pseudo first-order rate constants (k') for all EfOM solutions were obtained, demonstrating the importance of aromatic moieties in inhibiting the degradation of targeted contaminants by UV/chlorine process. Degradation of PRM/CAF in reconstituted effluent spiked with the major effluent constituents (i.e., EfOM isolates, Cl, HCO, and NO) was comparable to the results obtained with the real WWTP effluent and fit well to the correlation between k' and UV absorbance at 254 nm, suggesting that EfOM isolates can be used to determine the efficiency of UV/chlorine process in real effluent. EfOM serves as the main precursor of adsorbable organic chlorine in the UV/chlorine treatment. Bioassays indicated that chlorine-containing compounds could induce oxidative stress, mitochondrial dysfunction, and increase the cell DNA damage. Among evaluated treatment conditions, the nature of EfOM, hydrophobic versus transphilic fraction, is likely the predominant factor affecting the cytotoxicity. Meanwhile the UV/chlorine treatment can significantly reduce the cytotoxicity of EfOM isolates. However, adding high level of selected contaminants (e.g., PRM and CAF) can inhibit this phenomenon due to the competition with reactive radicals.
Topics: Biological Assay; Caffeine; Chlorine; DNA Damage; Oxidative Stress
PubMed: 34543976
DOI: 10.1016/j.watres.2021.117634 -
International Journal of Molecular... Sep 2021Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019).... (Review)
Review
Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.
Topics: Anticonvulsants; COVID-19; Cannabidiol; Carbamazepine; Clobazam; Drug Interactions; Epilepsy; Humans; Nutrients; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34502487
DOI: 10.3390/ijms22179582 -
Journal of Neurosurgery Mar 2022Deep brain stimulation (DBS) is traditionally performed on an awake patient with intraoperative recordings and test stimulation. DBS performed under general anesthesia...
OBJECTIVE
Deep brain stimulation (DBS) is traditionally performed on an awake patient with intraoperative recordings and test stimulation. DBS performed under general anesthesia with intraoperative MRI (iMRI) has demonstrated high target accuracy, reduced operative time, direct confirmation of target placement, and the ability to place electrodes without cessation of medications. The authors describe their initial experience with using iMRI to perform asleep DBS and discuss the procedural and radiological outcomes of this procedure.
METHODS
All DBS electrodes were implanted under general anesthesia by a single surgeon by using a neuronavigation system with 3-T iMRI guidance. Clinical outcomes, operative duration, complications, and accuracy were retrospectively analyzed.
RESULTS
In total, 103 patients treated from 2015 to 2019 were included, and all but 1 patient underwent bilateral implantation. Indications included Parkinson's disease (PD) (65% of patients), essential tremor (ET) (29%), dystonia (5%), and refractory epilepsy (1%). Targets included the globus pallidus pars internus (12.62% of patients), subthalamic nucleus (56.31%), ventral intermedius nucleus of the thalamus (30%), and anterior nucleus of the thalamus (1%). Technically accurate lead placement (radial error ≤ 1 mm) was obtained for 98% of leads, with a mean (95% CI) radial error of 0.50 (0.46-0.54) mm; all leads were placed with a single pass. Predicted radial error was an excellent predictor of real radial error, underestimating real error by only a mean (95% CI) of 0.16 (0.12-0.20) mm. Accuracy remained high irrespective of surgeon experience, but procedure time decreased significantly with increasing institutional and surgeon experience (p = 0.007), with a mean procedure duration of 3.65 hours. Complications included 1 case of intracranial hemorrhage (asymptomatic) and 1 case of venous infarction (symptomatic), and 2 patients had infection at the internal pulse generator site. The mean ± SD voltage was 2.92 ± 0.83 V bilaterally at 1-year follow-up. Analysis of long-term clinical efficacy demonstrated consistent postoperative improvement in clinical symptoms, as well as decreased drug doses across all indications and follow-up time points, including mean decrease in levodopa-equivalent daily dose by 53.57% (p < 0.0001) in PD patients and mean decrease in primidone dose by 61.33% (p < 0.032) in ET patients at 1-year follow-up.
CONCLUSIONS
A total of 205 leads were placed in 103 patients by a single surgeon under iMRI guidance with few operative complications. Operative time trended downward with increasing institutional experience, and technical accuracy of radiographic lead placement was consistently high. Asleep DBS implantation with iMRI appears to be a safe and effective alternative to standard awake procedures.
Topics: Deep Brain Stimulation; Electrodes, Implanted; Essential Tremor; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Parkinson Disease; Retrospective Studies; Subthalamic Nucleus; Treatment Outcome
PubMed: 34359029
DOI: 10.3171/2020.12.JNS202572 -
Chemosphere Dec 2021Endorheic lakes (or terminal lakes, TLs) have no natural outlet other than evaporation and slow infiltration. Some TLs receive reclaimed wastewater which contains poorly...
Endorheic lakes (or terminal lakes, TLs) have no natural outlet other than evaporation and slow infiltration. Some TLs receive reclaimed wastewater which contains poorly removed trace organic contaminants (TrOCs). To determine if TLs accumulate TrOCs we conducted a preliminary assessment of the occurrence of ten TrOCs in three TLs receiving reclaimed wastewater and one TL which does not directly receive reclaimed wastewater. Five of ten TrOCs (carbamazepine, DEET, fluoxetine, primidone, and trimethoprim) were present in all four TLs' surface waters (~0.3-1109 ng/L), six (caffeine, carbamazepine, DEET, diphenhydramine, primidone, and trimethoprim) were present in sediment samples (0.1-77 ng/gDW) and in soil samples (0.1-137 ng/gDW). Concentrations of caffeine, carbamazepine, diphenhydramine, fluoxetine and meprobamate were significantly higher in TLs receiving wastewater from a secondary treatment plant compared to those TLs which received tertiary treated wastewater. Carbamazepine, fluoxetine, sulfamethoxazole, and trimethoprim were present at concentrations greater than is typical of other U.S. freshwater lakes, but other TrOC concentrations were present at lower concentrations than in other freshwater lakes. We conclude that some TrOCs may accumulate in TLs, but to a lesser extent than would be expected based on the accumulation of dissolved constituents alone, which indicates that there are other unidentified processes in TLs that contribute to TrOC losses. Other TLs across the globe may have similar levels of TrOCs due to anthropogenic influence and treated wastewater inputs.
Topics: Carbamazepine; Lakes; Sulfamethoxazole; Wastewater; Water Pollutants, Chemical
PubMed: 34242983
DOI: 10.1016/j.chemosphere.2021.131408 -
Analytical Methods : Advancing Methods... Jul 2021Pharmaceuticals and personal care products (PPCPs) can enter agricultural fields through wastewater irrigation, biosolid amendments, or urine fertilization. Numerous...
Pharmaceuticals and personal care products (PPCPs) can enter agricultural fields through wastewater irrigation, biosolid amendments, or urine fertilization. Numerous studies have assessed the risk of PPCP contamination, however there are no standardized methodologies for sample treatment, making the interpretation of results challenging. Various time periods between sampling and analysis have been reported (shipping, storage, etc.), but literature is lacking in the evaluation of PPCP degradation amidst this process. This study assessed the stability of 20 pharmaceuticals (200 μg L) in soil and crops stored at -40 °C for 7, 30, and 310 days. After 310 days, caffeine, meprobamate, trimethoprim, primidone, carbamazepine, anhydro-erythromycin and dilantin were found to be stable (≥75% recovery) in all matrices. On the other hand, acetaminophen, amitriptyline, bupropion, lamotrigine, sulfamethoxazole, naproxen, ibuprofen, and paroxetine were unstable after 30 days in at least one of the matrices investigated. Due to variations in analyte stability, fortification with isotopically-labelled surrogates at the point of sample collection was evaluated in comparison to fortification after shipment and storage, immediately prior to extraction. Chromatographic peak areas of stable analytes were found to be reproducible (±15%) in field-fortified samples, indicating that no additional error occurred during sample handling under field conditions despite having a less controlled environment. Unstable analytes revealed notable differences in peak areas between fortification times, suggesting that fortification immediately after sample collection is crucial to account for analyte losses during shipping and storage, resulting in accurate quantification of PPCPs.
Topics: Cosmetics; Pharmaceutical Preparations; Soil; Soil Pollutants; Wastewater
PubMed: 34142694
DOI: 10.1039/d1ay00623a -
JAMA Neurology Aug 2021Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease.
IMPORTANCE
Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease.
OBJECTIVE
To quantify and model the putative hazard of cardiovascular disease secondary to eiASM use.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study covered January 1990 to March 2019 (median [IQR] follow-up, 9 [4-15], years). The study linked primary care and hospital electronic health records at National Health Service hospitals in England. People aged 18 years or older diagnosed as having epilepsy after January 1, 1990, were included. All eligible patients were included with a waiver of consent. No patients were approached who withdrew consent. Analysis began January 2021 and ended August 2021.
EXPOSURES
Receipt of 4 consecutive eiASMs (carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, or topiramate) following an adult-onset (age ≥18 years) epilepsy diagnosis or repeated exposure in a weighted cumulative exposure model.
MAIN OUTCOMES AND MEASURES
Three cohorts were isolated, 1 of which comprised all adults meeting a case definition for epilepsy diagnosed after 1990, 1 comprised incident cases diagnosed after 1998 (hospital linkage date), and 1 was limited to adults diagnosed with epilepsy at 65 years or older. Outcome was incident cardiovascular disease (ischemic heart disease or ischemic or hemorrhagic stroke). Hazard of incident cardiovascular disease was evaluated using adjusted propensity-matched survival analyses and weighted cumulative exposure models.
RESULTS
Of 10 916 166 adults, 50 888 (0.6%) were identified as having period-prevalent cases (median [IQR] age, 32 [19-50] years; 16 584 [53%] female), of whom 31 479 (62%) were diagnosed on or after 1990 and were free of cardiovascular disease at baseline. In a propensity-matched Cox proportional hazards model adjusted for age, sex, baseline socioeconomic status, and cardiovascular risk factors, the hazard ratio for incident cardiovascular disease was 1.21 (95% CI, 1.06-1.39) for those receiving eiASMs. The absolute difference in cumulative hazard diverges by more than 1% and greater after 10 years. For those with persistent exposure beyond 4 prescriptions, the median hazard ratio increased from amedian (IQR) of 1.54 (1.28-1.79) when taking a relative defined daily dose of an eiASM of 1 to 2.38 (1.52-3.56) with a relative defined daily dose of 2 throughout a maximum of 25 years’ follow-up compared with those not receiving an eiASM. The hazard was elevated but attenuated when restricting analyses to incident cases or those diagnosed when older than 65 years.
CONCLUSIONS AND RELEVANCE
The hazard of incident cardiovascular disease is higher in those receiving eiASMs. The association is dose dependent and the absolute difference in hazard seems to reach clinical significance by approximately 10 years from first exposure.
Topics: American Medical Association; Periodicals as Topic; United States
PubMed: 34081094
DOI: 10.1001/jamaneurol.2021.2135 -
Epileptic Disorders : International... Jun 2021To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of...
OBJECTIVE
To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of antiseizure medications in patients with epilepsy according to skin rash history.
METHODS
We analysed patients with a history of skin rash presenting for up to 12 weeks after initiating antiseizure medication. The history of skin rash was verified by medical charts, interviews, and identification of skin lesions by patients based on illustrative images. The minimum follow-up period was eight months. The control group comprised epilepsy patients with regular antiseizure medication use for at least 12 weeks without skin rash. We included 109 cases and 99 controls.
RESULTS
The median (interquartile range) period from the index rash was six years (2-11). Carbamazepine was the trigger medication in 48% of cases and induced skin rashes in all patients with cross-sensitivity and carbamazepine exposure. Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reactions with eosinophilia and systemic symptoms affected 36% of cases. Carbamazepine- or oxcarbazepine-induced maculopapular exanthema occurred earlier (median: one week) than that induced by other antiseizure medications (median: three weeks) (p=0.006). Cross-sensitivity was more common in patients with at least one episode of Stevens-Johnson syndrome (29%) and Stevens-Johnson/toxic epidermal necrolysis overlap (50%) than in patients with maculopapular exanthema (8%) (p=0.01). Although most cases were mild, the pattern of antiseizure medication use differed from that of controls, with a lower proportion of antiseizure medication typically associated with severe cutaneous adverse reactions (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and lamotrigine) (p<0.001). Most cases exposed to high-risk medication, however, did not develop cross-sensitivity.
SIGNIFICANCE
Cutaneous adverse reaction history may influence antiseizure medication use. Cross-sensitivity is more common in severe cases and most patients are affected by mild, self-limited skin rashes. Further research should consider the relevance of mild skin rashes in lifelong epilepsy treatment.
Topics: Anticonvulsants; Carbamazepine; Epilepsy; Exanthema; Humans; Oxcarbazepine; Stevens-Johnson Syndrome
PubMed: 34080983
DOI: 10.1684/epd.2021.1288 -
Clinical Epidemiology 2021To determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs).
OBJECTIVE
To determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs).
METHODS
In the Medication use and AD (MEDALZ) cohort of 70,719 Finnish community dwellers with clinically verified incident AD diagnosis in 2005-2011, we identified all incident users of AEDs using national Prescription register. AEDs were classified as older (valproate, carbamazepine, clonazepam, phenytoin, levetiracetam, primidone) or newer (pregabalin, gabapentin, oxcarbazepine, lamotrigine, topiramate). We matched each user to 2 non-users. Incident hip fractures until 2015 were identified from the Care register for health care. We calculated inverse probability of treatment weighted hazard ratios (HR), with 95% confidence intervals, using Cox regression.
RESULTS
Altogether 5522 incident users were identified and matched to 11,044 non-users (in both groups, women: 65%; median age: 81 years). Altogether 53.3% of users initiated with newer AEDs (pregabalin 79.8%, gabapentin 10.2%) while 46.7% initiated with older AEDs (valproate 67.6%, carbamazepine 13.0%). Age- and sex-adjusted IR of hip fracture per 100 person-years was 1.8 (95% CI 1.6-1.9) in non-users and 2.0 (95% CI 1.8-2.2) in users. Increased risk of hip fracture was observed in users (HR 1.17, 95% CI 1.05-1.30) compared with non-users. The risk was higher for short duration of use (<14 weeks, HR 3.64, 95% CI 2.90-4.58) than for medium duration (14 to <64 weeks, HR 1.74, 95% CI 1.48-2.05) or ≥64 weeks' use (HR 1.23, 95% CI 1.08-1.40), compared to non-users with same follow-up time. Older AEDs had HR of 1.46 (1.03-2.08) compared with newer AEDs.
CONCLUSION
Our results imply that AED use is associated with an increased risk of hip fracture in people with AD. These findings prompt careful consideration before prescribing AEDs to persons with AD. Persons with AD treated with antiepileptics should be carefully monitored due to their increased risk of falling and fractures.
PubMed: 33911901
DOI: 10.2147/CLEP.S278306 -
Osteoporosis International : a Journal... Oct 2021People with epilepsy who take certain medications are at risk for developing osteoporosis and fractures of the vertebrae that commonly go undiagnosed. By using...
UNLABELLED
People with epilepsy who take certain medications are at risk for developing osteoporosis and fractures of the vertebrae that commonly go undiagnosed. By using technology available in a bone density scan, we observed at least one fracture in many subjects with bone density in the normal and osteopenic range.
PURPOSE/INTRODUCTION
Chronic use of antiepileptic drugs (AEDs), both enzyme-inducing (phenytoin, phenobarbital, carbamazepine, and primidone) and non-enzyme-inducing (i.e., valproate), is recognized as a cause of secondary osteoporosis. Vertebral compression fractures (VF) are the most common type of osteoporotic fractures and may confer an increased risk of future hip, wrist, and vertebral fractures. Vertebral compression fractures in the general population are frequently asymptomatic, and under-diagnosed. The purpose of this study is to describe the prevalence of VF in a cohort of male veterans with epilepsy on chronic AEDs.
METHODS
The cohort for this study consisted of 146 male veterans who carried a diagnosis of epilepsy and were chronic users of AEDs known to cause osteoporosis (phenobarbital, phenytoin, carbamazepine, primidone, and valproate). Chronic AED use was defined as receiving an AED for at least 2 years. Subjects were previously seen in the osteoporosis clinic and had been evaluated by a dual-energy X-Ray absormetry (DXA) instrument including morphometric studies following a standard vertebral fracture assessment (VFA) protocol during the same DXA imaging acquisition session.
RESULTS
The mean age was 63 years. Low bone mineral density defined as osteoporosis or osteopenia was observed in 29% and 43% respectively. We observed at least one VF in 41 % of the subjects who had normal BMD, 54% in the osteopenic range, and 75% in the osteoporotic range.
CONCLUSIONS
By performing a VFA in addition to standard bone densitometric studies, we disclosed a large prevalence of compression fractures in individuals with epilepsy chronically treated with AEDs who had BMDs in the normal and osteopenic ranges. The addition of VFA or other imaging methods to evaluate VF should be included in the evaluation of bone health in individuals with epilepsy receiving AEDs since it may modify treatment recommendations to prevent future osteoporotic fractures.
Topics: Absorptiometry, Photon; Bone Density; Fractures, Compression; Humans; Male; Middle Aged; Osteoporotic Fractures; Pharmaceutical Preparations; Prevalence; Seizures; Spinal Fractures
PubMed: 33822290
DOI: 10.1007/s00198-021-05926-2 -
Environmental Science and Pollution... Aug 2021From 2001 to 2014, 13 surveys were conducted in the Baltic Sea, to determine its pollution of 50 micropollutants. The investigations focused mostly on the German western...
From 2001 to 2014, 13 surveys were conducted in the Baltic Sea, to determine its pollution of 50 micropollutants. The investigations focused mostly on the German western Baltic Sea; in 2008, one survey covered the entire Baltic Sea. Various groups of herbicides (such as triazines, phenoxyacetic acid, phenylurea), perfluoroalkyl substances, pharmaceuticals, and industrial products were analyzed during these surveys. The highest concentrations (median 1 to 4 ng/L) were observed for atrazine, simazine, chloridazone, 2,4-dichlorophenoxyacetic acid, benzotriazole, primidone, and carbamazepine. Most micropollutants exhibited a relatively homogenous spatial distribution, though some herbicides show elevated concentrations in certain regions (e.g., Odra estuary), indicating a riverine input. The data set was analyzed, both for seasonal influences and long-time trends. Some herbicides exhibited higher concentrations during summertime. Both upward- and downward-directed time trends could be identified for some herbicides and perfluorinated compounds. For most of the detected compounds, a low-risk quotient was calculated. Only the occurrence of carbendazim could potentially pose a higher risk to the Baltic Sea.
Topics: Baltic States; Environmental Monitoring; Estuaries; Risk Assessment; Seasons; Water Pollutants, Chemical
PubMed: 33755886
DOI: 10.1007/s11356-021-13254-5