Association Between Opioid and Benzodiazepine Use and All-Cause Mortality in Individuals with Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study.

Background: Opioids and benzodiazepines are frequently prescribed for managing pain and anxiety in chronic obstructive pulmonary disease (COPD) patients. This study aimed to determine whether opioid use, with or without benzodiazepine use, is associated with increased all-cause mortality in COPD patients. Methods: This prospective cohort study included adults aged ≥20 years with COPD from the US National Health and Nutrition Examination Survey 2007-2012. The primary outcome was all-cause mortality, which were obtained through linkage to registries. Weighted Cox proportional hazards regression models were used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Additionally, subgroup and sensitivity analyses were used to evaluate the robustness of our findings. Results: This study enrolled 811 participants, representing 10.84 million COPD individuals in the United States (mean [standard error] age, 58.7 [0.6] years). During a median follow-up of 9.6 years, mortality rates were 57.8 per 1000 person-years in patients using only opioids, 41.3 per 1000 person-years in patients using only benzodiazepines, 45.7 per 1000 person-years in patients using both opioids and benzodiazepines, and 27.0 per 1000 person-years in patients using neither. In the fully adjusted model, COPD patients prescribed both opioids and benzodiazepines (HR: 1.76; 95% CI: 1.11-2.78) and those prescribed opioids only (HR: 1.68; 95% CI: 1.13-2.49) had significantly higher all-cause mortality compared to non-users. After adjusting for propensity scores, the mortality risk for opioid-only users slightly increased (HR: 1.87; 95% CI: 1.25-2.81). Further, subgroup analysis revealed an elevated mortality risk in patients over 60 years receiving coprescriptions or opioids only, but not in younger participants. In contrast, benzodiazepine-only users aged 60 or younger showed increased mortality risk. Conclusion: Opioid use, with or without benzodiazepine use, was associated with higher mortality in COPD patients over 60, while benzodiazepine-only use was associated with higher mortality aged 60 or younger.

Comparison of Remimazolam and Propofol in Recovery of Elderly Outpatients Undergoing Gastrointestinal Endoscopy: A Randomized, Non-Inferiority Trial.

Purpose: We designed this trial to compare the recovery time of remimazolam and propofol in elderly patients undergoing painless gastrointestinal endoscopy. Patients and Methods: In this randomized, non-Inferiority trial, 360 patients aged 65 years or older, scheduled for elective outpatient gastrointestinal endoscopy, were randomly assigned to the remimazolam combined with fentanyl (RF) group or the propofol combined with fentanyl (PF) group. The primary outcome was the post-anesthesia care unit (PACU) stay time, defined as the time from the end of the examination to scoring 9 points using the Modified Post-Anesthetic Discharge Scoring System (MPADSS) criteria. Secondary outcomes included sedation-related adverse events, recall, injection pain, as well as postoperative Quality of Recovery-15 (QoR-15) scores and Pittsburgh Sleep Quality Index (PSQI) scores at 1 day, 1 week, and 1 month postoperatively. Results: A total of 351 patients completed the study, with 174 receiving remimazolam and 177 receiving propofol. The PACU stay time in RF group was non-inferior to that in PF group [14 (11, 18) vs 13 (10, 17), mean difference 1 (95% confidence interval 0, 2), P=0.084 for noninferiority]. However, remimazolam was associated with lower rate of hypoxemia [4.7% (8/180) vs 12.4% (22/180), P=0.011], reduced use of vasoactive drugs [1 (0, 1) vs 1 (1, 2), P<0.001], less injection pain [2 (1.2%) vs 35 (21.3%), P<0.001], and lower recall [20 (11.8%) vs 36 (20.3%), P=0.034]. There were no differences in the QoR-15 scores and PSQI scores at postoperative 1 day, 1 week, and 1 month between groups. Conclusion: This non-inferiority study revealed that in elderly outpatients undergoing gastrointestinal endoscopy, remimazolam achieved recovery times comparable to propofol, with fewer associated complications.

When Should Pharmacological Interventions for Insomnia Be Recommended?

This commentary on a case describes how social determinants of health also contribute to insomnia and then suggests how to balance risks and benefits of different strategies for managing chronic insomnia. Behaviorally induced insufficient sleep syndrome can exacerbate morning side effects of prescription sleep aids, and there are potentially serious long-term risks (eg, dementia, falls, death) associated with chronic benzodiazepine use. Before trying sleeping pills, chronic insomnia should be treated with cognitive behavioral therapy.

Long Term Users of Benzodiazepine Attending the Department of Medicine in a Tertiary Care Hospital.

Although comprehensive epidemiological data related to long term use and abuse of benzodiazepine (BZD) in our country is scarce, undocumented clinical observation suggests that the prevalence is quite high and constitutes a significant public health problem. This cross-sectional study was carried out in the Department of Medicine, Shaheed Ziaur Rahman Medical College hospital, Bogra, from 1st October 2015 to 31st March 2016. The objectives of the study were to evaluate the indication, dosage, duration and untoward effects of use of benzodiazepine for one month or longer among the patients attending the inpatient and outpatient departments of medicine. A total of 100 cases of long term benzodiazepine users aged between 18 to 72 years with mean age of 44.0±15.02 years were taken for the study. Male to female ratio of the cases was 1.08:1.00, 97.0% were Muslims, 96.0% were married; 77.0% were rural dwellers. Fifty four (54.0%) cases were from middle class society and 39.0% were housewives by occupation. The benzodiazepine dosage ranged from <5mg to 10mg equivalent to diazepam, with mean dose of 7.5±1.71 and the duration ranged from 1-60 months. Benzodiazepine tolerance was found in 21.0% and dependence in 18.0%. The common reason for taking was benzodiazepine for long duration was the different anxiety disorders in 63.0% followed sleep disturbance in 33.0%. Common cause of long term continuation reported by the respondents was rapid relief of symptoms (51.0%) and lack of awareness (21.0%). In 56.0% cases, the drugs were prescribed by providers other than registered physicians. Only 23.0% of patients were counseled beforehand regarding the probable hazards of long term use of the drugs and the counseling were provided only by registered physicians. In conclusion, it can be said that, large scale epidemiologic studies are warranted to evaluate the weight of burden of benzodiazepines abuse in our community and the needs for changes in clinical approach.

Comparing subjective quality of recovery between remimazolam- and propofol-based total intravenous anesthesia for surgical procedures: a meta-analysis.

BACKGROUND: Remimazolam is a novel ultra-short-acting benzodiazepine that has been recently introduced as an alternative to propofol for general anesthesia. While both agents have been compared in terms of safety and efficacy, their relative effects on postoperative quality of recovery (QoR) remain unclear. Therefore, this meta-analysis aimed to compare the effects of remimazolam and propofol on subjective QoR in surgical patients who underwent general anesthesia. METHODS: Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to May 28, 2024 to identify randomized controlled trials comparing remimazolam and propofol in terms of postoperative QoR. The Cochrane risk-of-bias tool (RoB 2) was used to assess study quality. QoR score on postoperative day (POD) 1 (primary outcome), QoR scores on PODs 2-3, QoR dimensions, time to loss of consciousness, other recovery characteristics, and rescue analgesia requirement were evaluated using random-effects meta-analyses. RESULTS: This meta-analysis included 13 studies published between 2022 and 2024 involving 1,418 patients. QoR was evaluated using either the QoR-15 (10 studies) or QoR-40 (3 studies) questionnaire. The pooled results indicated no significant difference in the QoR scores on POD 1 (standardized mean difference: 0.02, 95% confidence interval [CI]: - 0.20, 0.23, P = 0.88, I2 = 73%) and PODs 2-3 between remimazolam and propofol. Furthermore, no significant differences were observed in QoR dimensions, length of postanesthesia care unit (PACU) stay, and time to extubation as well as in the risks of agitation and postoperative nausea and vomiting. Patients administered remimazolam exhibited slower anesthetic induction (mean difference (MD): 32.27 s) but faster recovery of consciousness (MD: - 1.60 min) than those administered propofol. Moreover, remimazolam was associated with a lower risk of rescue analgesia requirement in the PACU (risk ratio: 0.62, 95% CI: 0.43, 0.89, P = 0.009, I2 = 0%) but not in the ward. CONCLUSION: Remimazolam is a potential alternative to propofol for general anesthesia as it offers similar QoR to the latter and has advantages in terms of consciousness recovery and immediate postoperative analgesia requirement.

Consumption patterns and factors associated with inappropriate prescribing of benzodiazepines in Primary Health Care settings.

BACKGROUND: Benzodiazepines are frequently prescribed to treat anxiety and insomnia, but long-term use has been associated with the development of dependence, tolerance, and cognitive decline, especially among older adults. This study aimed to investigate the pattern of consumption and factors associated with inappropriate prescribing of benzodiazepines in primary health care. METHODS: This is a cross-sectional analytical study, using dispensing records of diazepam, clonazepam, and nitrazepam from public pharmacies in a Brazilian municipality between 2018 and 2022. Metrics for benzodiazepine consumption were DDD (Defined Daily Dose) and DDD/1000PD (per 1000 population per day). Long-term/prolonged benzodiazepine use was defined as consuming at least 90 DDD and at least 2 dispensations per year. To ascertain associations between long-term use and predictor variables, a multivariate logistic regression model was utilized. FINDINGS: A total of 40402 participants were included, with an average age of 55 years (SD = 0.30), 38.5% were older aged. Diazepam and nitrazepam exceeded the daily dose recommended. There was a reduction in diazepam consumption during the study period, as calculated by DDD/1.000PD, while the consumption of other benzodiazepines remained stable. However, a significant increase in diazepam consumption is noted when considering the last decade. Prolonged use was observed in 29.1% of participants, with a significant prevalence among the older people (34.8% of them were long-term users) and advancing age was identified as a risk factor for long-term use. Higher PDDs were also associated with long-term use and aging. Participants who used different benzodiazepines during the period had a higher risk of prolonged use. CONCLUSIONS: These results provide insights into the prevalence of problematic utilization of benzodiazepines in primary health care. Authorities and health care providers must take steps to encourage gradual cessation of prolonged benzodiazepine prescriptions and the embrace of suitable strategies for addressing anxiety and insomnia within primary health care settings.

[An analysis of 4695 acute poisoning cases in Tianjin-Heibei from 2020-2022].

Objective: To study and analyze the epidemiological regularity of acute poisoning in Tianjin-Hebei region from 2020 to 2022, and to provide reference for the treatment and prevention of related patients. Methods: In December 2023, the analysis results and clinical data of 4695 patients with drug poisoning from January 2020 to December 2022 in multiple centers of Tianjin-Hebei region were collected as research objects. Gender, age, type of drug poisoning, season and poisoning route of the research objects were analyzed, and statistical analysis was conducted as well. Results: The sex ratio of men and women was 1∶1.16 (2173/2522). The poisoning of antidepressants and benzodiazepines were the most common drug poisonings, accounting for 1550 and 1274 cases respectively (33%, 27.1%). Paraquat poisoning has decreased year by year, while the poisonings of herbicides with low toxicity such as diquat, glyphosate and cremart have increased. The number of cases reached a peak during May to August which was the poisoning season, while was relatively fewer during October to December. Conclusion: Effective intervention measures should be taken according to the age of high incidence of poisoning, different seasons and populations. Essential drug poisoning prevention measures should be established and improved. The systems of sedative drug management and use should be established, and pesticide management and storage need to be strengthened.

Spherical cellulose/chitosan aerogel-supported MOF-199 for the magnetic solid-phase extraction of benzodiazepines from urine.

Metal-organic frameworks (MOFs) are promising materials for sample pretreatment. The performance improvement of powdered MOFs is hindered by their aggregation and difficult recovery. To overcome these issues, a biodegradable lightweight spherical aerogel was used as a support for the in situ growth of copper-based MOFs (MOF-199). Furthermore, Fe3O4 nanoparticles were incorporated into the aerogel to achieve magnetic properties. Thus, hybrid aerogel spheres containing MOF-199 supported on magnetic oxidized cellulose nanofiber/carboxymethyl chitosan (MOF-199@mag-CNF/CMC) were fabricated. The effects of Fe3O4 loading amount and organic-ligand concentration on the properties (spherical geometry and mechanical strength) of the hybrid aerogel spheres were studied. Their potential application in the extraction of benzodiazepines (BZPs) from urine samples prior to liquid chromatography-mass spectrometry was evaluated. The highly dispersed MOF-199 crystals on the spherical aerogel effectively overcame the inherent structural shrinkage of the bare aerogel spheres; thus, the MOF-199@mag-CNF/CMC aerogel spheres were robust and could withstand repeated use for at least eight consecutive extraction cycles. Further, MOF-199@mag-CNF/CMC exhibited improved BZP extraction efficiency, which was 2.5-11.6 times higher than that of bare Cu2+@mag-CNF/CMC aerogel spheres, primarily due to additional π-π interaction and H-bonding as well as improved specific surface area. Parameters influencing the extraction and desorption processes were also comprehensively investigated. Under optimal conditions, this method provided a wide linear range of 0.1-10 µg/L (R2 > 0.995) and good precision (2.8-6.7% for intra-day; 1.9-7.8 % for inter-day). The limits of detection and quantification ranged from 0.02 to 0.11 µg/L and from 0.06 to 0.33 µg/L, respectively. The recoveries for the urine samples spiked with three concentrations of BZPs ranged from 73.9 % to 114.1 %. The proposed method is simple, sensitive and eco-friendly and can be used for the determination of BZPs from urine for clinical and forensic examinations.

Association of reductions in rescue medication requirements with vagus nerve stimulation: Results of long-term community collected data from a seizure diary app.

OBJECTIVE: To assess the impact of vagus nerve stimulation (VNS) on quality of life contributors such as rescue medications. METHODS: Using the seizure diary application SeizureTracker™ database, we examined trends in rescue administration frequency before and after the first recorded VNS magnet swipe in patients with drug-resistant epilepsy who had 1) At least one VNS magnet swipe recorded in the diary, and 2) Recorded usage of a benzodiazepine rescue medication (RM) within 90 days prior to the first swipe. A paired Wilcoxon rank-sum test was used to assess changes in RM usage frequency between 30-, 60-, 90-, 180- and 360-day intervals beginning 30 days after first magnet swipe. Longitudinal changes in RM usage frequency were assessed with a generalized estimating equation model. RESULTS: We analyzed data of 95 patients who met the inclusion criteria. Median baseline seizure frequency was 8.3 seizures per month, with median baseline rescue medication usage frequency of 2.1 administrations per month (SD 3.3). Significant reductions in rescue medication usage were observed in the 91 to 180 day interval after first VNS magnet swipe, and at 181 to 360 days and at 361 to 720 days, with the magnitude of reduction increasing over time. Decreases in rescue medication usage were sustained when controlling for patients who did not record rescue medication use after the first VNS magnet swipe (N=91). Significant predictors of reductions in rescue medication included baseline frequency of rescue medication usage and time after first VNS magnet swipe. SIGNIFICANCE: This retrospective analysis suggests that usage of rescue medications is reduced following the start of VNS treatment in patients with epilepsy, and that the magnitude of reduction may progressively increase over time.

The Pharmaceutical Future of Remimazolam as Compared to Propofol and Midazolam: A Literature Review.

INTRODUCTION: Remimazolam is an ultra-short-acting benzodiazepine with a predictable and quick recovery that was FDA approved in 2020. As a relatively new medication, it is not as mainstream as other sedatives such as propofol or midazolam. This research aims to highlight the differences, benefits, and drawbacks of remimazolam in comparison to other short-term sedatives in order to bring greater awareness, and to consolidate the current knowledge of the effects of remimazolam. METHODS: The PubMed database was used to search for current relevant research to review. The search terms used were: "remimazolam", "midazolam", "propofol", and procedural sedation. The search also used qualifiers using only publications in English and published within the last five years. This query yielded 26 articles which were reviewed for content and relevance. RESULTS: Sixteen of the reviewed studies resulted in common themes suggesting remimazolam to be an effective alternative for procedural sedation with fewer adverse effects. Primarily, remimazolam is observed to have decreased procedural hypotension, bradycardia, and injection site pain. With no studies demonstrating an increased frequency of bradycardia, remimazolam is theorized to be superior to propofol in respect to sedation-associated bradycardia. One specific study notes a 14% decrease in frequency of bradycardia compared to propofol. Further benefits of remimazolam over propofol include the availability of an effective and reliable antidote, flumazenil. CONCLUSION: In being that remimazolam has primarily been used and studied in short-term sedation, we can only confidently conclude remimazolam's safety in these settings. There is little research being done in the way of ICU sedation or general anesthesia, but with the relatively similar, or decreased rates of adverse events with remimazolam, we suspect an increase in clinical research of remimazolam in these settings. With continued robust research, remimazolam could become more widely accepted as a safe alternative to current sedatives.

Cannabis Laws and Utilization of Medications for the Treatment of Mental Health Disorders.

Importance: Mental health disorders are prevalent yet undertreated health conditions in the US. Given perceptions about the potential effect of cannabis on individuals with mental health disorders, there is a need to understand the association of cannabis laws with psychotropic use. Objective: To investigate the association of medical and recreational cannabis laws and dispensary openings with the dispensing of psychotropic medications used to treat mental health disorders in the US. Design, Setting, and Participants: This cross-sectional study of 10 013 948 commercially insured patients used a synthetic control method to examine the association of cannabis policies with prescribing. Data on all patients dispensed prescriptions for each of the 5 classes of psychotropic medications from January 1, 2007, to December 31, 2020, were extracted from Optum's deidentified Clinformatics Data Mart Database. Statistical analysis was performed from September 2022 to November 2023. Exposures: The 4 exposure variables measured were whether medical or recreational cannabis laws were in effect and whether medical or recreational cannabis dispensaries were open in each state and calendar quarter. Main Outcome and Measures: One measure of the extensive margins of dispensing and 2 measures of the intensive margins of dispensing were constructed for 5 medication classes (benzodiazepines, antidepressants, antipsychotics, barbiturates, and sleep medications). Results: The primary sample (the benzodiazepine sample) included 3 848 721 patients (mean [SD] age, 46.1 [11.4] years; 65.4% women; 53.7% aged 35-54 years). Medical cannabis laws were associated with a 12.4% reduction in the benzodiazepine fill rate (average treatment effect on the treated [ATT], -27.4; 95% CI, -14.7 to 12.0; P = .001), recreational cannabis laws were associated with a 15.2% reduction in the fill rate (ATT, -32.5; 95% CI, -24.4 to 20.1; P = .02), and medical cannabis laws were associated with a 1.3% reduction in the mean number of benzodiazepine fills per patient (ATT, -0.02; 95% CI, -0.02 to 0.02; P = .04). Medical dispensaries were associated with a 3.9% reduction in mean days' supply per benzodiazepine fill (ATT, -1.7; 95% CI, -0.8 to 0.6; P = .001), while recreational dispensaries were associated with a 6.2% reduction (ATT, -2.4; 95% CI, -1.0 to 0.9; P < .001). Medical cannabis laws were associated with a 3.8% increase in antidepressant fills (ATT, 27.2; 95% CI, -33.5 to 26.9; P = .048), and medical dispensaries were associated with an 8.8% increase (ATT, 50.7; 95% CI, -32.3 to 28.4; P = .004). The mean number of antipsychotic medication fills per patient increased by 2.5% (ATT, 0.06; 95% CI, -0.04 to 0.05; P = .02) after medical cannabis laws and by 2.5% (ATT, 0.06; 95% CI, -0.04 to 0.04; P = .02) after medical dispensary openings. Findings for the other drug classes showed substantial heterogeneity by state and direction of association. Conclusions and Relevance: This cross-sectional study of commercially insured patients suggests that there may have been meaningful heterogeneous associations between cannabis policy and state and between cannabis policy and drug class (eg, decreases in dispensing of benzodiazepines but increases in dispensing of antidepressants and antipsychotics). This finding suggests additional clinical research is needed to understand the association between cannabis use and mental health. The results have implications for patient substance use and mental health-related outcomes.

Unraveling the Role of Bromodomain and Extra-Terminal Proteins in Human Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is the most common type of uterine sarcoma, associated with poor prognosis, high rates of recurrence, and metastasis. Currently, the molecular mechanism of the origin and development of uLMS is limited. Bromodomain and extra-terminal (BET) proteins are involved in both physiological and pathological events. However, the role of BET proteins in the pathogenesis of uLMS is unknown. Here, we show for the first time that BET protein family members, BRD2, BRD3, and BRD4, are aberrantly overexpressed in uLMS tissues compared to the myometrium, with a significant change by histochemical scoring assessment. Furthermore, inhibiting BET proteins with their small, potent inhibitors (JQ1 and I-BET 762) significantly inhibited the uLMS proliferation dose-dependently via cell cycle arrest. Notably, RNA-sequencing analysis revealed that the inhibition of BET proteins with JQ1 and I-BET 762 altered several critical pathways, including the hedgehog pathway, EMT, and transcription factor-driven pathways in uLMS. In addition, the targeted inhibition of BET proteins altered several other epigenetic regulators, including DNA methylases, histone modification, and m6A regulators. The connections between BET proteins and crucial biological pathways provide a fundamental structure to better understand uterine diseases, particularly uLMS pathogenesis. Accordingly, targeting the vulnerable epigenome may provide an additional regulatory mechanism for uterine cancer treatment.

Comparative Study of the Anxiolytic Activity of Songorine in Elevated Plus Maze Test and by Recording Ultrasonic Vocalizations.

It was found that the diterpene alkaloid songorine administered per os to mice at a dose of 25 µg/kg provides a pronounced anxiolytic effect during elevated plus maze testing comparable to the effect of the benzodiazepine anxiolytic phenazepam. Recording of ultrasonic vocalizations of animals revealed an increase in the number of short high-frequency (50 kHz) signals under the action of songorine and the reference drug, which confirms their anti-anxiety properties.

Case-control analysis of hip fractures with concurrent benzodiazepine and opioid use and surgery class at a single teaching institution.

In this study, we analyze the relationship between polypharmacy and surgical treatment in a population at a single teaching institution. The design of the study is a case-control analysis of hip fractures. The setting is at a single teaching institution located in Galveston, Texas, USA. Over a 5-year period, we conducted a retrospective review of patients within our medical record who underwent surgery for a hip fracture, identified by current procedural terminology codes 27235 and 27236. Our primary variable was a prescription of opioids, benzodiazepines, or both 30 days preoperatively and surgery performed. The main outcome measures were prescription of controlled medications and surgical class. We used descriptive analysis to summarize each variable as mean or frequency for continuous and categorical variables and subsequently assessed the association between demographic variables and drug prescription and surgical class. Of the 378 patients who met our inclusion criteria, 68.0% were females and 32.0% were males. The average age was 77.8 years. Most patients had a displaced hip fracture (61%). Most patients underwent a hip hemiarthroplasty (233, 61.6%) versus either a closed reduction with percutaneous pinning (125, 33.1%) or hip open reduction internal fixation (20, 5.3%). There was no significant difference between polypharmacy and hip fracture surgery; however, reported alcohol use was significant in both groups. In our patient population, opioid and/or benzodiazepine prescriptions were not significantly linked to hip fracture surgery, but documented alcohol use was found to be significant in both groups. We noted a higher prevalence of opioid and benzodiazepine prescriptions than was previously reported. As patients age, we should be cautious about the effects of polypharmacy and alcohol use and their impacts on the elderly.

Comparison of Remimazolam and Dexmedetomidine for Sedation in Awake Endotracheal Intubation in Scoliosis Surgery: A Retrospective Analysis.

BACKGROUND Awake endotracheal intubation (AEI) involves the placement of an endotracheal tube in patients who can maintain spontaneous respirations. This retrospective study aimed to compare sedation with remimazolam during AEI with that of dexmedetomidine in patients who underwent scoliosis correction surgery. MATERIAL AND METHODS This is a retrospective study based on data from 98 patients who had AEI procedures between January and December 2023. The remimazolam group included 55 patients, and the dexmedetomidine group included 43 patients. Remimazolam 0.05 mg/kg was injected 1 min before intubation, while dexmedetomidine 1 ug/kg was pumped 10 min before intubation. Evaluations of AEI, hemodynamics, and respiratory adverse events were then compared between the 2 groups. RESULTS There was no significant difference in demographic data between the groups. After administrating sedation, dexmedetomidine led to a larger reduction of mean arterial pressure (MAP) and heart rate (HR) than did remimazolam (11.30±1.86 vs 8.33±2.28 mmHg, P<0.001; 12.28±2.50 vs 2.85±1.82 beats/min, P<0.001). When conducting intubation, the increase of MAP in the remimazolam group was lower than that in the dexmedetomidine group (7.40±2.81 vs 9.26±5.08 mmHg, P=0.024), while the difference in HR change was not significant (7.53±5.41 vs 8.37±5.31 beats/min, P=0.441). When combined with local anesthesia, the success rate of AEI, time of AEI procedure, attempt times, increase of MAP during intubation, depth of sedation, and respiratory adverse events were comparable between the groups (P>0.05). CONCLUSIONS With local anesthesia, remimazolam and dexmedetomidine sedation can facilitate AEI for patients with scoliosis. However, remimazolam is associated with more stable hemodynamics.

Molecular Aspects of the Interactions between Selected Benzodiazepines and Common Adulterants/Diluents: Forensic Application of Theoretical Chemistry Methods.

Benzodiazepines are frequently encountered in crime scenes, often mixed with adulterants and diluents, complicating their analysis. This study investigates the interactions between two benzodiazepines, lorazepam (LOR) and alprazolam (ALP), with common adulterants/diluents (paracetamol, caffeine, glucose, and lactose) using infrared (IR) spectroscopy and quantum chemical methods. The crystallographic structures of LOR and ALP were optimized using several functionals (B3LYP, B3LYP-D3BJ, B3PW91, CAM-B3LYP, M05-2X, and M06-2X) combined with the 6-311++G(d,p) basis set. M05-2X was the most accurate when comparing experimental and theoretical bond lengths and angles. Vibrational and 13C NMR spectra were calculated to validate the functional's applicability. The differences between LOR's experimental and theoretical IR spectra were attributed to intramolecular interactions between LOR monomers, examined through density functional theory (DFT) optimization and quantum theory of atoms in molecules (QTAIM) analysis. Molecular dynamics simulations modeled benzodiazepine-adulterant/diluent systems, predicting the most stable structures, which were further analyzed using QTAIM. The strongest interactions and their effects on IR spectra were identified. Comparisons between experimental and theoretical spectra confirmed spectral changes due to interactions. This study demonstrates the potential of quantum chemical methods in analyzing complex mixtures, elucidating spectral changes, and assessing the structural stability of benzodiazepines in forensic samples.