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Addiction (Abingdon, England) Oct 2022There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.
METHODS
Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs).
RESULTS
Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision.
CONCLUSIONS
Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.
Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Carbamazepine; Diazepam; Female; Humans; Male; Network Meta-Analysis; Seizures; Substance Withdrawal Syndrome
PubMed: 35194860
DOI: 10.1111/add.15853 -
Journal of Hazardous Materials May 2022Concerns about environmental contamination by organic micropollutants (OMPs) are increasing, due to their potential bioaccumulative and toxic properties. This study...
Concerns about environmental contamination by organic micropollutants (OMPs) are increasing, due to their potential bioaccumulative and toxic properties. This study evaluated the risk posed by OMPs to aquatic ecosystems in Swedish freshwaters. The assessment was based on measured environmental concentrations (MEC) of OMPs in surface waters upstream and downstream of Swedish wastewater treatment plants (WWTPs). A novel optimised risk quotient (RQ) was used to identify potential high-risk substances in the aquatic environment. A secondary objective was to assess the impact of WWTP effluent on aquatic ecosystems using a novel impact factor (I) based on the risk quotient (RQ). Among the 126 substances investigated, four compounds (metformin, N,N-dimethyltetradecylamine, oxazepam, and venlafaxine) were identified as likely to pose a risk to aquatic ecosystems in Swedish surface waters (RQ>1), and five compounds (clindamycin, gemfibrozil, sertraline, o-desmethylvenlafaxine, and diclofenac) were identified as posing a moderate risk to aquatic ecosystems ( 0.1
Topics: Ecosystem; Environmental Monitoring; Fresh Water; Sweden; Wastewater; Water Pollutants, Chemical
PubMed: 35121296
DOI: 10.1016/j.jhazmat.2022.128302 -
Drugs in R&D Mar 2022Urine is conventionally used as a specimen to document diazepam-related crimes; however, few reports have described the pharmacokinetics of diazepam and its metabolites...
BACKGROUND
Urine is conventionally used as a specimen to document diazepam-related crimes; however, few reports have described the pharmacokinetics of diazepam and its metabolites in urine.
OBJECTIVE
This study aimed to investigate the pharmacokinetics of diazepam and its metabolites, including glucuronide compounds, in the urine of Chinese participants.
METHODS
A total of 28 volunteers were recruited and each participant ingested 5 mg of diazepam orally. Ten milliliters of urine were collected from each participant at post-consumption timepoints of prior (zero), 1, 2, 4, 8, 12, and 24 h and 2, 3, 6, 12, and 15 days. All samples were extracted by solid-phase extraction and analyzed using high-performance liquid chromatography-tandem mass spectrometry. Diazepam and its main metabolites, except for temazepam, were detected in the urine of volunteers. Pharmacokinetic parameters were analyzed using the pharmacokinetic software DAS according to the non-compartment model.
RESULTS
Urinary diazepam peaked at 2.38 ng/mL (C) and 1.93 h (T). The urinary metabolite nordiazepam peaked at 1.17 ng/mL and 100.21 h; temazepam glucuronide (TG) peaked at 145.61 ng/mL and 41.14 h; and oxazepam glucuronide (OG) peaked at 101.57 ng/mL and 165.86 h. The elimination half-life (t) and clearance (CLz/F) for diazepam were 119.58 h and 65.77 L/h, respectively. The t of the metabolites nordiazepam, TG, and OG was 310.58 h, 200.17 h, and 536.44 h, respectively. Finally, this study found that both diazepam and its main metabolites in urine were detectable for at least 15 days, although there were individual differences.
CONCLUSION
The results regarding diazepam pharmacokinetics in urine would be of great help in forensic science and drug screening.
Topics: China; Chromatography, High Pressure Liquid; Diazepam; Humans; Nordazepam; Solid Phase Extraction
PubMed: 35099786
DOI: 10.1007/s40268-021-00375-y -
European Review For Medical and... Jan 2022Drug-facilitated sexual assault (DFSA) is an act of sexual violence towards a victim who is incapacitated due to the voluntary or involuntary consumption of intoxicating... (Review)
Review
OBJECTIVE
Drug-facilitated sexual assault (DFSA) is an act of sexual violence towards a victim who is incapacitated due to the voluntary or involuntary consumption of intoxicating substances. Sexual assaults are generally considered underreported and the toxicological analysis of DFSA cases is particularly challenging when there is a time delay from assault to medical examination. The aim of this review was to investigate typical toxicological findings in global DFSA cases and describe a typical DFSA case.
MATERIALS AND METHODS
A database search was conducted in PubMed using relevant search terms in order to identify studies reporting toxicological results in DFSA cases.
RESULTS
In total, 22 studies were included, covering toxicological findings in DFSA cases in North America, Europe, Asia, South Africa and Australasia from 1996 to 2018. Biological matrices used for analysis included blood, urine and hair. Toxicological findings were comparable among countries, with ethanol, cocaine, cannabis, benzodiazepines, amphetamines and analgesics being among the most frequently detected substances. Ethanol was frequently detected in combination with one or more drugs. A variety of benzodiazepines were observed, with the most common being diazepam, clonazepam, alprazolam, and oxazepam. The majority of cases involved women (87%-100%).
CONCLUSIONS
The findings suggest that a diverse range of substances are associated with DFSA and that victims are rendered vulnerable through recreational substance consumption at social events. As such, typical DFSA cases appear to be opportunistic in nature and primarily involves women in their mid-twenties and an acquaintance as the perpetrator.
Topics: Benzodiazepines; Crime Victims; Female; Forensic Toxicology; Humans; Sex Offenses; Substance Abuse Detection
PubMed: 35048994
DOI: 10.26355/eurrev_202201_27767 -
Molecules (Basel, Switzerland) Dec 2021In 2017, the Swedish Environmental Protection Agency published a report on advanced wastewater treatment for the removal of pharmaceutical residues and stated that...
Total Release of 21 Indicator Pharmaceuticals Listed by the Swedish Medical Products Agency from Wastewater Treatment Plants to Surface Water Bodies in the 1.3 Million Populated County Skåne (Scania), Sweden.
In 2017, the Swedish Environmental Protection Agency published a report on advanced wastewater treatment for the removal of pharmaceutical residues and stated that advanced treatment should be implemented where it will make the largest difference from an environmental perspective. However, the report also concluded that this need cannot be specified with existing data, but consideration must be made of local conditions. Two considerations are (1) the discharged amount of pharmaceutical into receiving water bodies and (2) the turnover of water in the recipient, where the highest risks are related to recipients with a low water turnover and low dilution. The current project comprised eight different WWTPs distributed throughout the entire County Skåne (Scania) in Sweden, with a population of ca. 1,300,000 persons. In total, 21 of 22 pharmaceuticals were analyzed according to the list proposed by the Swedish Medical Products Agency 2015. The results show that large amounts of pharmaceuticals are released from the WWTPs yearly to Scanian recipients. The total discharge of pharmaceuticals from the eight treatment plants adds up to 71 kg of these 21 substances alone, mainly comprising metoprolol, which is a drug that lowers blood pressure, and the analgesic drug diclofenac. Additionally, carbamazepine, losartan, naproxen and oxazepam were present in significant concentrations. These represented three illnesses that are very common: high blood pressure, inflammation/pain and depression/anxiety. The concentrations were generally in line with previous national Swedish screenings. It was estimated that, when one million cubic meters (1,000,000 m) of wastewater is discharged, almost 4 kg of the 21 pharmaceuticals is released. The total volume wastewater release by the >90 WWTPs in Scania was estimated to 152,887,000 m, which corresponded to 590 kg/year. The investigated 21 drugs cover only a small part of many hundred pharmaceuticals that are in use in Sweden. Thus, most likely, one or several tons of pharmaceuticals leak out to the Scanian recipients annually. The analysis of river samples shows that the dilution of wastewater is a key parameter in reducing concentrations. However, some locations have remarkably high concentrations, which occur when the volume wastewater is large in relation to the flow in the river. These kinds of regional results are of importance when selecting where advanced treatment should be prioritized in a first instance, as requested by the Swedish EPA.
Topics: Environmental Monitoring; Geography; Humans; Pharmaceutical Preparations; Research; Rivers; Sweden; Wastewater; Water Pollutants, Chemical; Water Purification
PubMed: 35011310
DOI: 10.3390/molecules27010077 -
International Journal of Environmental... 2022'Voodoo' is a new substance of abuse that recently spread among youth in Egypt. It has numerous potentially dangerous effects on humans. However, to date the composition...
BACKGROUND
'Voodoo' is a new substance of abuse that recently spread among youth in Egypt. It has numerous potentially dangerous effects on humans. However, to date the composition of the main constituents of this compound is unknown.
PURPOSE
We sought to identify the active components of this unknown substance"voodoo".
METHODS
Three samples were collected and analysed by high-performance liquid chromatography with photodiode array detector (HPLC-PAD), gas chromatography/mass spectrometry (GC/MS), and ultra-performance liquid chromatography/mass spectrometry (UPLC-MS/MS) using targeted multiple reaction monitoring (MRM).
RESULTS
HPLC-PAD analysis showed that samples 1 and 2 had some common major peaks, the same retention time, and similar spectra, whereas sample 3 showed different peaks. GC/MS analysis revealed the presence of various putatively identified bioactive compounds, including quinazolines, morphinan alkaloid, cannabinoids, penitrem A, and the well-known synthetic cannabinoid FUB-AMB (methyl(2S)-2-{[1-[(4-fluorophenyl)methyl]indazole-3-carbonyl]amino}-3 methylbutanoate). UPLC-MS/MS analysis revealed the presence of common compounds such as tetrahydrocannabinol (THC), amphetamine, 3,4-methylenedioxyamphetamine, tramadol, and oxazepam.
CONCLUSION
We concluded that Voodoo is a mixture of substances of abuse at varying concentrations.
PubMed: 35002018
DOI: 10.1080/03067319.2020.1715384 -
Frontiers in Microbiology 2021The demand for energy and chemicals is constantly growing, leading to an increase of the amounts of contaminants discharged to the environment. Among these,...
The demand for energy and chemicals is constantly growing, leading to an increase of the amounts of contaminants discharged to the environment. Among these, pharmaceutical molecules are frequently found in treated wastewater that is discharged into superficial waters. Indeed, wastewater treatment plants (WWTPs) are designed to remove organic pollution from urban effluents but are not specific, especially toward contaminants of emerging concern (CECs), which finally reach the natural environment. In this context, it is important to study the fate of micropollutants, especially in a soil aquifer treatment (SAT) context for water from WWTPs, and for the most persistent molecules such as benzodiazepines. In the present study, soils sampled in a reed bed frequently flooded by water from a WWTP were spiked with diazepam and oxazepam in microcosms, and their concentrations were monitored for 97 days. It appeared that the two molecules were completely degraded after 15 days of incubation. Samples were collected during the experiment in order to follow the dynamics of the microbial communities, based on 16S rRNA gene sequencing for Archaea and Bacteria, and ITS2 gene for Fungi. The evolution of diversity and of specific operating taxonomic units (OTUs) highlighted an impact of the addition of benzodiazepines, a rapid resilience of the fungal community and an evolution of the bacterial community. It appeared that OTUs from the genus were more abundant at the beginning of the biodegradation process, for diazepam and oxazepam conditions. Additionally, Tax4Fun tool was applied to 16S rRNA gene sequencing data to infer on the evolution of specific metabolic functions during biodegradation. It finally appeared that the microbial community in soils frequently exposed to water from WWTP, potentially containing CECs such as diazepam and oxazepam, may be adapted to the degradation of persistent contaminants.
PubMed: 34912306
DOI: 10.3389/fmicb.2021.742000 -
Case Reports in Psychiatry 2021Benzodiazepine (BZD) misuse is a worldwide problem that healthcare professionals encounter in daily practice. High-dose BZD withdrawal is usually a long process that may...
Benzodiazepine (BZD) misuse is a worldwide problem that healthcare professionals encounter in daily practice. High-dose BZD withdrawal is usually a long process that may require referral to an inpatient rehabilitation unit. Relapses after withdrawal are common. BZD withdrawal can cause complications including seizures, suicidal behavior, anxiety, and depression. Guidelines describe tapering protocols for modest doses; however, protocols for exceptionally high-dose BZD withdrawal are not well described. Herein, we describe a BZD tapering protocol for a patient with daily use of high-dose (1800 mg) oxazepam (OXP). The BZD tapering was administered in an inpatient psychiatric hospital, and the outcome was evaluated monthly after discharge for three months. This report describes a unique case of high-dose OXP withdrawal and also outlines an optional protocol to apply when clinicians encounter these unusual cases.
PubMed: 34777889
DOI: 10.1155/2021/2140723 -
Molecules (Basel, Switzerland) Oct 2021Partially and exhaustively methylated β-cyclodextrins [(2-methyl)-β-CD (MCD), heptakis-(2,6-di--methyl)-β-CD (DIMEB), and heptakis-(2,3,6-tri--methyl)-β-CD (TRIMEB)]...
Partially and exhaustively methylated β-cyclodextrins [(2-methyl)-β-CD (MCD), heptakis-(2,6-di--methyl)-β-CD (DIMEB), and heptakis-(2,3,6-tri--methyl)-β-CD (TRIMEB)] have been compared in the hydrolysis and enantiodiscrimination of benzodiazepine derivative ()- or ()-oxazepam hemisuccinate (OXEMIS), using nuclear magnetic resonance (NMR) spectroscopy as an investigation tool. After 6 h, MCD induced an 11% hydrolysis of OXEMIS, remarkably lower in comparison with underivatized β-CD (48%), whereas no hydrolysis was detected in the presence of DIMEB or TRIMEB after 24 h. DIMEB showed greater ability to differentiate OXEMIS enantiomers in comparison to TRIMEB, by contrast MCD did not produce any splitting of racemic OXEMIS resonances. Both enantiomers of OXEMIS underwent deep inclusion of their phenyl pendant into cyclodextrins cavities from their wider rims, but tighter complexes were formed by DIMEB with respect to TRIMEB.
Topics: Hydrolysis; Magnetic Resonance Spectroscopy; Methylation; Models, Molecular; Molecular Structure; Oxazepam; beta-Cyclodextrins
PubMed: 34770758
DOI: 10.3390/molecules26216347 -
The Science of the Total Environment Feb 2022Over a period of 12 months, the fate of three hormones, 12 antibiotics and 30 pharmaceutically active substances (PhACs) was investigated during open-air storage...
Over a period of 12 months, the fate of three hormones, 12 antibiotics and 30 pharmaceutically active substances (PhACs) was investigated during open-air storage without and with composting of anaerobically digested and dewatered sewage sludge. The effect of oxidation conditions during storage on degradation of hormones and PhACs in the sludge biomass was also examined. Under summer and winter conditions in Uppsala County, Sweden, two field-scale sludge windrows were constructed: open-air storage of sewage sludge windrow without composting (NO-COM)) and open-air storage windrow with composting (COM). NO-COM achieved effective removal of ∑Hormones (85%) and ∑Antibiotics (95%), but lower removal of ∑PhACs (34%), during the study year. The top layers of the sludge pile had significantly lower concentrations of ∑PhACs (3100-5100 ng/g ash) than deeper layers (8000-11,000 ng/g ash). After one year of composting, the degradation in the COM windrow resulted in concentrations of ∑Hormones (
oxazepam (0.0805 day). In conclusion, composting of sludge was effective in degrading the target hormones, antibiotics, and PhACs. Topics: Composting; Pharmaceutical Preparations; Sewage; Soil; Sweden
PubMed: 34740644
DOI: 10.1016/j.scitotenv.2021.151271