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Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

OBJECTIVES: Long-term benzodiazepine use is common despite known risks. In the original Eliminating Medications Through Patient Ownership of End Results (EMPOWER) Study set in Canada, patient education led to increased rates of benzodiazepine cessation. We aimed to determine the effectiveness of implementing an adapted EMPOWER quality improvement (QI) initiative in a US-based healthcare system. DESIGN: We used a pre-post design with a non-randomised control group. SETTING: A network of primary care clinics. PARTICIPANTS: Patients with ≥60 days supply of benzodiazepines in 6 months and ≥1 risk factor (≥65 years of age, a concurrent high-risk medication prescribed or a diazepam equivalent daily dose ≥10) were eligible. INTERVENTION: In March 2022, we engaged 22 primary care physicians (PCPs), and 308 of their patients were mailed an educational brochure, physician letter and flyer detailing benzodiazepine risks; the control group included 4 PCPs and 291 of their patients. PRIMARY AND SECONDARY MEASURES: The primary measure was benzodiazepine cessation by 9 months. We used logistic regression and a generalised estimating equations approach to control for clustering by PCP, adjusting for demographics, frailty, number of risk factors, and diagnoses of arthritis, depression, diabetes, falls, and pain. RESULTS: Patients in the intervention and control groups were comparable across most covariates; however, a greater proportion of intervention patients had pain-related diagnoses and depression. By 9 months, 26% of intervention patients (81 of 308) had discontinued benzodiazepines, compared with 17% (49 of 291) of control patients. Intervention patients had 1.73 greater odds of benzodiazepine discontinuation compared with controls (95% CI: 1.09, 2.75, p=0.02). The unadjusted number needed to treat was 10.5 (95% CI: 6.30, 34.92) and the absolute risk reduction was 0.095 (95% CI: 0.03 to 0.16). CONCLUSIONS: Results from this non-randomised QI initiative indicate that patient education programmes using the EMPOWER brochures have the potential to promote cessation of benzodiazepines in primary care.

Status epilepticus (SE) is a life-threatening development of self-sustaining seizures that becomes resistant to benzodiazepines when treatment is delayed. Benzodiazepine pharmacoresistance is thought in part to result from internalization of synaptic GABAA receptors, which are the main target of the drug. The naturally occurring neurosteroid allopregnanolone is a therapy of interest against SE for its ability to modulate all isoforms of GABAA receptors. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been partially effective in combination with benzodiazepines in mitigating SE-associated neurotoxicity. In this study, allopregnanolone as an adjunct to midazolam or midazolam-ketamine combination therapy was evaluated for efficacy against cholinergic-induced SE. Adult male rats implanted with electroencephalographic (EEG) telemetry devices were exposed to the organophosphorus chemical (OP) soman (GD) and treated with an admix of atropine sulfate and HI-6 at 1 minute after exposure followed by midazolam, midazolam-allopregnanolone, or midazolam-ketamine-allopregnanolone 40 minutes after seizure onset. Neurodegeneration, neuronal loss, and neuroinflammation were assessed 2 weeks after GD exposure. Seizure activity, EEG power integral, and epileptogenesis were also compared among groups. Overall, midazolam-ketamine-allopregnanolone combination therapy was effective in reducing cholinergic-induced toxic signs and neuropathology, particularly in the thalamus and hippocampus. Higher dosage of allopregnanolone administered in combination with midazolam and ketamine was also effective in reducing EEG power integral and epileptogenesis. The current study reports that there is a promising potential of neurosteroids in combination with benzodiazepine and ketamine treatments in a GD model of SE. SIGNIFICANCE STATEMENT: Allopregnanolone, a naturally occurring neurosteroid, reduced pathologies associated with soman (GD) exposure such as epileptogenesis, neurodegeneration, and neuroinflammation, and suppressed GD-induced toxic signs when used as an adjunct to midazolam and ketamine in a delayed treatment model of soman-induced status epilepticus (SE) in rats. However, protection was incomplete, suggesting that further studies are needed to identify optimal combinations of antiseizure medications and routes of administration for maximal efficacy against cholinergic-induced SE.

The objective of this review was to evaluate the efficacy and safety of propofol in the treatment of critically ill patients diagnosed with alcohol withdrawal syndrome (AWS). A review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) criteria, and Embase, MEDLINE (PubMed), Cochrane CENTRAL, and Web of Science were queried for results through June 2024. Studies providing efficacy or safety data associated with propofol with a reported diagnosis of AWS in critically ill patients were included. Studies evaluating pediatric patients, those without quantitative and qualitative outcome data, and those not readily translatable to English were excluded. Five retrospective cohort analyses of 218 patients were included in this systematic review. Patients were found to have both significant and non‐significant increases in time to resolution of AWS symptoms when treated with propofol versus the AWS standard of care. Adjunct treatment with propofol was generally associated with reductions in total benzodiazepine use and increases in both ICU length of stay and duration of mechanical ventilation. The results of this systematic review provide the evidence necessary to support the use of propofol as an efficacious and safe medication in the management of severe and refractory AWS. Further investigation is required to determine optimal dosing strategies and durations of therapy. The results of this systematic review demonstrate the clinical utility of propofol as part of the management strategy for severe and refractory AWS. [ABSTRACT FROM AUTHOR]

Rationale: Benzodiazepines (BZDs) construct a large group of psychoactive drugs acting as depressants of the central nervous system (CNS) and used in medicine as sedatives and anxiolytic and antiepileptic agents. The illicit use of these materials is a worldwide problem, and for many years, part of the benzodiazepines have been abused as rape drugs. For example, flunitrazepam (Rohypnol) is most commonly linked by media reports to drug‐facilitated sexual assaults, more commonly referred to as "date rape." Furthermore, there are growing concerns for other misuses of these drugs. Over the last few years, there was an increase in the number, type, and availability of new psychoactive substances (NPS) belonging to the benzodiazepine group, challenging standard forensic labs to fully identify the chemical structure of new, unknown benzodiazepines. Methods: This work demonstrates a new application of the automated tool for the detection and identification of benzodiazepine analogues using high‐resolution‐accurate‐mass LC‐MS analysis, followed by "Compound Discoverer" (CD) software data processing, to automatically detect various benzodiazepine analogues by picking peaks and compare them to in silico calculated modifications made on a predefined basic backbone. Subsequently, a complete structural elucidation for the proposed molecular formula is obtained by MS/MS data analysis of the suspected component. Results: This method was found to be useful for the automated detection and putative identification of a series of nine "unknown" benzodiazepine analogues, at concentrations in the low ng/mL range. Conclusions: We hereby present a general demonstration of this powerful tool for the forensic community in the detection and identification of hazardous unknown compounds. [ABSTRACT FROM AUTHOR]

In recent years Scotland has been experiencing a disproportionally high number of drug related deaths compared to other European countries, causing significant individual, societal and economic burden. A possible cause of this is the increase in average number of substances involved in Scottish drug related deaths, as well as the changing pattern of substances involved. Opioids, cocaine, and alcohol have been consistently involved in the culture of drug use in Scotland, however recently National Records Scotland have identified that designer benzodiazepines such as etizolam, and prescription drugs such as gabapentinoids are increasingly being detected in Scottish toxicology reports. A systematic literature review following PRISMA guidelines was conducted through searching PubMed and Google Scholar to identify peer-reviewed articles published in English between 2013 and 2023 that investigated Scottish population data on gabapentinoids and etizolam to establish their contribution to the rise in Scottish drug related deaths. 18 studies were included in the review. A high use prevalence of etizolam and gabapentinoids in Scotland has been identified, with both substance-related deaths showing recent increase, marked since 2015. This pattern is replicated in the Scottish prison system. There has also been a significant increase of gabapentinoids prescriptions in Scotland. Polydrug use was identified as the most common determinant of both etizolam and gabapentinoids related adverse effects and fatality in Scotland, especially concurrent opioid use. The results indicate the literature on individual characteristics of Scottish at-risk users of gabapentinoids and etizolam is limited, however the data shows both substances are being used by older cohort, with adverse effects seen more in older women. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of intranasal (IN) and intramuscular (IM) administrations of azaperone (3 mg kg-1), midazolam (0. 3 mg kg-1), and ketamine (7 mg kg-1) combination (AMK) in pigs. Study design: Randomized clinical trial. Animals: sixteen adult male pigs, immunocastrated, of mixed lineage. Methods: In phase I, these animals were randomly assigned to intranasal (GIN, n = 8) and intramuscular (GIM, n = 8) groups for arterial blood sample collection at 10, 20, 30, 45, 60, and 90 min after AMK administrations for gas and electrolyte analysis. In phase II, performed 1 week after phase I, the 16 pigs were allocated to both groups (GIM, n = 16/GIN, n = 16) and submitted to the same chemical restraint (CR) protocol, with a 96-h interval between administrations. Behavioral parameters (degree of CR, muscle relaxation, loss of postural reflex, and sound stimulus response) and vital parameters (pulse rate, respiratory rate, oxygen saturation, and rectal temperature) were evaluated after recumbency (Trec) and at 5, 15, 30, 45, 60, and 90 min after administrations. In addition, the latency period and duration of CR were determined. Results: Latency to recumbency and duration of CR in GIN were shorter. CR scores did not vary between groups. Muscle relaxation was more intense in GIN at Trec. An initial tachycardia was observed, followed by a reduction in heart rate from T5 to T90 in both treatments (p < 0.05). The respiratory rate was higher at T45, T60, and T90 in GIN compared to baseline. Rectal temperature reduced in GIM from T45 onwards. PaCOt2 elevated at T90 in the GIM (p < 0.05) and there was an incidence of mild hypoxemia in 47% of the animals in the GIM. Conclusions and clinical relevance: IN administration was as effective as IM administration in promoting safe chemical restraint, with minimal changes in homeostasis, with a shorter duration and latency period. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines are frequently prescribed drugs; however, their prolonged use can lead to tolerance, dependence, and other adverse effects. Despite these risks, long-term use remains common, presenting a public health concern. This study aims to explore the beliefs and opinions held by the public regarding benzodiazepines, as understanding these perspectives may provide insights into their usage patterns. Methods: We collected public tweets published in English between January 1, 2019, and October 31, 2020, that mentioned benzodiazepines. The content of each tweet and the characteristics of the users were analyzed using a mixed-method approach, including manual analysis and semi-supervised machine learning. Results: Over half of the Twitter users highlighted the efficacy of benzodiazepines, with minimal discussion of their side effects. The most active participants in these conversations were patients and their families, with health professionals and institutions being notably absent. Additionally, the drugs most frequently mentioned corresponded with those most commonly prescribed by healthcare professionals. Conclusions: Social media platforms offer valuable insights into users' experiences and opinions regarding medications. Notably, the sentiment towards benzodiazepines is predominantly positive, with users viewing them as effective while rarely mentioning side effects. This analysis underscores the need to educate physicians, patients, and their families about the potential risks associated with benzodiazepine use and to promote clinical guidelines that support the proper management of these medications. Clinical trial number: Not applicable. Significant outcomes: • Most Twitter users consider benzodiazepines effective, with only 5% mentioning side effects. • A significant percentage of users reported combining benzodiazepines with other psychopharmacological drugs, or even with alcohol and other addictive substances. • Our results indicate an alarming minimization of the risks associated with benzodiazepine use. [ABSTRACT FROM AUTHOR]

Background: A combination of remimazolam and propofol could produce more stable sedation. A good medication regimen should consider not only efficacy but also safety, especially hypotension. The aim of the current study was to compare the incidence and amount of hypotension by propofol versus remimazolam-propofol combinations in day-surgery hysteroscopy. Methods: Patients were randomly assigned to receive either propofol (Group P, n = 125) or remimazolam-propofol combinations (Group RP, n = 125) at a 1:1 ratio. Intravenous injection of sufentanil 0.1ug/kg were administered before sedative medication. In group P, a bolus of 2.5 mg/kg propofol was administered. In group RP, intravenous anesthesia was commenced with 0.125 mg/kg remimazolam and 1 mg/kg propofol. After loss of consciousness, propofol was maintained at 6 mg/kg/h. The primary outcomes were the incidence and amount of hypotension during surgery. Hypotension was defined as a MAP less than 65mmHg for at least 1 min. The amount of hypotension was assessed by time-weighted average intraoperative MAP under a threshold of 65 mmHg. The secondary outcomes were various anesthesia related parameters and some adverse events. Results: In group P, 25 patients (20.0%) experienced hypotension during hysteroscopy compared with 9 patients (7.2%) in group RP, for a difference of 12.8% (RR 2.778, 95%CI [1.352–5.709]). The combination of remimazolam and propofol resulted in significantly lower TWA (Time Weighted Average) threshold 0.14 (0.10–0.56) mmHg in group RP compared to 0.31 (0.15–0.67) mmHg in group P. The total dose of propofol was nearly double in group P compared to group RP. A significantly higher frequency of injection pain and low oxygen saturation was observed in the group P than that of the group RP. Hiccup was observed only in group RP. The incidences of body movement, bradycardia and vomiting were no significant difference between groups. Conclusion: The incidence and amount of hypotension by remimazolam-propofol combinations was significantly less than that by propofol sedation in day-surgery hysteroscopy. The optimization of medication regimen would attenuate the harm of hypotension and contribute to patients' rapid recovery in day surgery. Trial registration : Chinese Clinical Trial Registry, ChiCTR2400079888 (date: 15/01/2024), [ABSTRACT FROM AUTHOR]

Context: Pain and symptom management at the end of life (EoL) can pose unique challenges, particularly when symptoms are refractory to conventional methods. Dexmedetomidine, originally approved for sedation in ventilated patients, has been demonstrated to be beneficial in pain management and palliative care settings by functioning as an alpha-2 agonist. Methods: A retrospective review of inpatient palliative care unit (IPU) records from January 2020 to December 2023 was conducted. Twenty-five adult patients receiving continuous dexmedetomidine for refractory pain at the EoL were identified. These patients were further evaluated for concurrent opioid, benzodiazepine, and chlorpromazine usage. Results: Patients experienced predominantly cancer-related pain, and had a median infusion duration of 5 days. Dexmedetomidine's initial dosing differed between the intensive care unit (ICU) and IPU settings. There was a trend toward a decreased opioid requirement 24 hours after initiation. Patients transferred from the ICU showed a progressive increase in opioid use. Conclusion: This study contributes to understanding dexmedetomidine's role in managing refractory symptoms at the EoL in the palliative care setting. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines and z-drugs increase the fall risk in older adults. There is a lack of real-world data examining the association between falls and deprescribing medications. Objective: In a retrospective cohort study of older adults with chronic benzodiazepine or z-drug use receiving care at an academic health system from January 2017 to December 2020, we explored the association between medication discontinuation and falls. Methods: Chronic use was defined as ≥ 3 medication dispensings and cumulative days' supply ≥ 45 days within 100 days in 2018. Discontinuation was defined as a dispensing gap of ≥ 180 days within 1 year of chronic use eligibility, with a secondary definition requiring a gap of ≥ 90 days. Non-discontinuers (n = 524) were matched 4:1 to discontinuers (n = 131) if they had a fill in the same month as the matched discontinuation index date. The association between discontinuation and a fall during 2.25-year follow-up was assessed using Cox proportional hazards models. The analysis was repeated using a gap of ≥ 90 days (n = 279 discontinuers; 1116 matched non-discontinuers). Results: The cumulative incidence of falls-related acute visits was 6.9% for discontinuers and 9.7% for non-discontinuers [adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.31–1.31]. Using the 90-day-gap definition, the cumulative incidence was 9.3% for discontinuers and 8.5% for non-discontinuers (HR 1.12, 95% CI 0.70–1.77). Conclusion: Benzodiazepine/z-drug discontinuation was not associated with reduced risk of falls. However, the relationship between discontinuation and falls varies depending on the definitions used. It is essential to examine different discontinuation definitions in larger studies while considering other relevant clinical outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines reduce postoperative nausea and vomiting (PONV); however, conflicting results have been reported regarding the use of remimazolam, a novel benzodiazepine. Objective: This meta-analysis examines whether remimazolam reduces PONV incidence compared with propofol or volatile agents used in general anesthesia. Material and methods: Electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, were searched on 31 July 2023. The primary outcome was the incidence of PONV. Secondary outcomes included PONV severity, rescue antiemetic use, amounts of remifentanil used, and participant satisfaction scores. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. The risk of bias (RoB) was assessed using the Cochrane RoB2 tool. Results: A total of 1514 adult patients from 11 randomized controlled trials were included. The incidences of PONV in the remimazolam and control groups were 16.1% and 16.5%, respectively. Remimazolam did not increase the incidence of PONV (OR 0.62; 95% CI, 0.37–1.04; p = 0.0676; I2 = 48%). Subgroup analysis showed a significant reduction in PONV with remimazolam vs. volatile agents (OR 0.25; 95% CI, 0.13–0.47; P = 0.0000; I2 = 0%) but not vs. propofol (OR 1.04; 95% CI, 0.70–1.56; p = 0.8332; I2 = 0%). More remifentanil was used in the remimazolam group vs. the volatile group, with no significant difference between remimazolam and propofol groups. Participant satisfaction scores were higher with remimazolam. Conclusion: Remimazolam did not increase PONV risk compared to propofol and reduced PONV incidence compared to volatile agents, with higher participant satisfaction. To validate the present findings, further well-planned large clinical trials are required. [ABSTRACT FROM AUTHOR]

Background: Minimalist transcatheter aortic valve replacement (TAVR) under monitored anesthesia care (MAC) emphasizes early recovery. Remimazolam is a novel benzodiazepine with a short recovery time. This study hypothesized that remimazolam is non-inferior to dexmedetomidine in terms of recovery after TAVR. Methods: In this retrospective observational study, remimazolam was compared to dexmedetomidine in patients who underwent TAVR under MAC at a tertiary academic hospital between July 2020 and July 2022. The primary outcome was timely recovery after TAVR, defined as discharge from the intensive care unit within the first day following the procedure. Propensity score matching was used to compare timely recovery between remimazolam and dexmedetomidine, applying a non-inferiority margin of -10%. Results: The study included 464 patients, of whom 218 received remimazolam and 246 received dexmedetomidine. After propensity score matching, 164 patients in each group were included in the analysis. Regarding timely recovery after TAVR, remimazolam was non-inferior to dexmedetomidine (152 of 164 [92.7%] in the remimazolam group versus 153 of 164 [93.3%] in the dexmedetomidine group, risk difference [95% CI]: -0.6% [-6.7%, 5.5%]). The use of remimazolam was associated with fewer postoperative vasopressors/ inotropes (21 of 164 [12.8%] vs. 39 of 164 [23.8%]) and temporary pacemakers (TPMs) (76 of 164 [46.3%] vs. 108 of 164 [65.9%]) compared to dexmedetomidine. Conclusions: In patients undergoing TAVR under MAC, remimazolam was non-inferior to dexmedetomidine in terms of timely recovery. Remimazolam may be associated with better postoperative recovery profiles, including a lesser need for vasopressors/inotropes and TPMs. [ABSTRACT FROM AUTHOR]

Aims: Alzheimer's disease and related diseases (ADRD) is a progressive and inexorable disease. In France, acetylcholinesterase inhibitors and memantine were reimbursed for subjects with ADRD, until 2 modifications of their reimbursement rate (2012, 2018). We aimed to study the consequences of these measures on ADRD subjects' healthcare use. Methods: We analysed data from the FRA‐DEM cohort, including subjects with presumed incident ADRD identified since 2011 in the French health insurance system. We studied the healthcare use of subjects identified with incident ADRD in 2011, 2013, 2015, 2017 and 2019, notably the annual number of defined daily doses of various psychotropic groups. We performed 2 multivariate multinomial logistic regressions with the subcohort year as the dependent variable. Results: In total, 165 120 subjects were included. A progressive decrease in exposure to antidementia drugs was observed between 2011 and 2019. Consultations with private neurologists or psychiatrists, and exposure to risperidone, antidepressants and benzodiazepines increased in the 2019 subcohort, following the 2018 reimbursement withdrawal. Meanwhile, the use of nursing/allied healthcare and emergency care increased over the subcohort years, whereas we observed a decrease in general practitioner consultations. Conclusion: These results suggest increases in private neurologist or psychiatrist consultations and exposure to recommended drugs after the reimbursement withdrawal, contrary to the fears expressed. However, antidementia drug exposure decreased long before the reimbursement modifications, probably due to the growing evidence of the modest effect of these drugs, and exposure to benzodiazepines increased after the reimbursement withdrawal. [ABSTRACT FROM AUTHOR]

Appropriate status epilepticus (SE) management is key to minimize admission to the pediatric intensive care unit (PICU). We retrospectively describe 115 children admitted to the PICU of the tertiary-care referral hospital of Padova for seizures, SE, and SE-related complications (59% from second-level hospitals, 41% from the referral hospital) and compare SE management among hospitals. Compared with the referral center, in second-level hospitals, anesthetics were more often administered as first/second drug (P <.001), and intubation was more frequent (P <.001). Intubation was significantly associated with SE onset at home (P =.045) and benzodiazepine-associated respiratory depression (P =.044). There was no association between intubation and SE duration, etiology, PICU length of stay, and morbidity at discharge. In conclusion, adherence to treatment protocols on SE management after the first-line drug differs between referral center and second-level hospitals. Lack of association with SE characteristics and patient's outcome suggests PICU admission could be due to inappropriate invasive management. [ABSTRACT FROM AUTHOR]

This document is a compilation of summaries of four different articles from various medical journals. The first article discusses the use of a two-bag N-acetylcysteine (NAC) system for acetaminophen poisoning, comparing its effectiveness and safety to the FDA-approved three-bag system. The second article examines the use of physostigmine in the treatment of anticholinergic toxicity, finding that patients treated with physostigmine alone were less likely to be intubated. The third article explores the use of dexmedetomidine in non-intubated patients, concluding that it is a safe and useful adjunct in the care of agitated toxicological patients. The fourth article compares the acute effects of mescaline, lysergic acid diethylamide (LSD), and psilocybin in a randomized, double-blind, placebo-controlled study, finding that the subjective experiences were similar at the studied doses. These articles provide valuable insights for toxicologists and poison centers in the treatment of various toxicological conditions. [Extracted from the article]

Background: Inhaled corticosteroids (ICS) are effective in managing asthma and chronic obstructive pulmonary disease (COPD) but increase the risk of pneumonia. Benzodiazepines (BZD), commonly prescribed for comorbid psychiatric disorders in asthma or COPD patients, are also associated with pneumonia. This study investigates the risk of pneumonia associated with the concomitant use of ICS and BZD. Methods: Data from the FDA Adverse Event Reporting System from Q4 2013 to Q3 2023 were extracted. Reports involving asthma or COPD patients were included. Disproportionality analysis and logistic regression analysis were performed to assess the risk of pneumonia associated with the combined use of ICS and BZD. Additive and multiplicative models were used to further confirm the results. Additionally, subgroup analyses were conducted based on gender, age, and disease type. Results: A total of 238,411 reports were included. The combined use of ICS and BZD was associated with a higher reporting of pneumonia (ROR: 2.41, 95% CI 2.25–2.58). Using additive and multiplicative methods, the results remained significant. The strongest risk signals were observed in specific drug combinations, such as mometasone with clonazepam, budesonide with temazepam, and mometasone with zopiclone. Subgroup analyses showed higher pneumonia risks in females, patients over 60 years old, and those with asthma. Conclusion: Our findings identified a significantly elevated pneumonia risk with the combined use of ICS and BZD. These results highlighted the necessity for cautious co-prescription of ICS and BZD and suggested the need for more comprehensive clinical studies to assess this interaction. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol is the most common substance use disorder in the United States. Despite this prevalence, there remains significant heterogeneity in medical management of alcohol withdrawal syndrome (AWS). While the 2020 American Society of Addition Medicine continues to recommend the use of benzodiazepines as first-line therapy for AWS, there is increasing use of phenobarbital in patients at high risk of severe AWS. Despite phenobarbital's favorable pharmacologic profile, historically, clinical utilization on general medicine services has been low and often restricted. In this project, we have examined practice patterns and associated clinical outcomes in adult patients experiencing AWS on the general medicine service pre and post implementation of a phenobarbital-based protocol for the treatment of severe AWS at our institution. Methods: This quality improvement study evaluated changes in management of AWS on general medicine units associated with implementation of a phenobarbital-based protocol and order set in the electronic medical record (EMR). Our primary outcome measures were receipt of a phenobarbital loading dose, concomitant benzodiazepine administration, and total benzodiazepine dose. Safety outcomes were also explored to assess clinical impacts of this protocol implementation. The project was determined "not research" by our Institutional Review Board. Results: Phenobarbital-protocol implementation was associated with increased frequency of receiving a phenobarbital loading dose (49.5% vs 9.4%; P <.001), decreased use of concomitant benzodiazepine/phenobarbital (4.3% vs 28.9%; P <.001), and decreased total benzodiazepine dose (7.8 vs 15.5 mg; P <.001). Regarding safety, there was no significant pre/post difference in the rate of ICU transfer, but among those transferred there was a trend toward decreased mechanical ventilation rate (100% vs 28.6%; P =.051), and a significantly reduced ICU length of stay (median 11 vs 3 days; P =.04). There were no pre/post differences in seizures, delirium or use of adjunct medications. Conclusions: This quality improvement study demonstrates a marked change in provider prescribing practices for treating AWS after implementation of an institutional phenobarbital-based protocol. We observed no difference in overall clinical outcomes after protocol implementation, although a larger follow-up study is needed to confirm this and to further explore the shorter ICU length of stay for patients with AWS postimplementation. [ABSTRACT FROM AUTHOR]

Insomnia disorder is a global public health issue, commonly treated with hypnotics. However, long-term use of benzodiazepine derivatives (BZDs), especially polypharmacy with this kind of drug, carries risks for dependence and abuse. This study using large-scale medical insurance records investigated the causes of polypharmacy through the treatment of insomnia disorder. A cross-sectional study analyzed anonymized medical record data from July 2014 to March 2018 provided by a nationwide Japanese health insurance association covering 405,952 individuals. Outpatients prescribed at least one sleep medication were included. Demographic data, pharmacological classification of the drugs, and comorbidities were assessed using hierarchical logistic regression analysis to explore their associations with polypharmacy. Of the 33,212 outpatients who were prescribed sleep medications, 32.5 % were prescribed multiple types. After adjusting for demographics and type of sleep medications as covariates, hypnotic polypharmacy was significantly associated with younger age, the presence of certain kinds of comorbidities, and using BZD anxiolytics before bedtime with the highest adjusted odds ratios (8.01–9.39) when referenced with BZD hypnotics. On the other hand, usage of orexin receptor antagonists, melatonin receptor agonists, and Z-drugs indicated lower odds ratios (0.74–0.87). Hypnotic polypharmacy is relatively common in the Japanese general population. With the introduction of non-pharmacological therapy in mind, assessing patients' comorbidities and avoiding the use of benzodiazepines, especially BZD anxiolytics, before bedtime would be recommended to prevent polypharmacy. • Among hypnotic users, 32.5 % received hypnotic polypharmacy. • Younger age and presence of certain comorbidities increased the odds of polypharmacy. • Using benzodiazepines was significantly associated with hypnotic polypharmacy. • Using benzodiazepine anxiolytics before bedtime showed the highest polypharmacy odds. • Orexin antagonists and melatonin agonists showed lower odds for polypharmacy. [ABSTRACT FROM AUTHOR]

Objectives. To examine trends in overdose deaths by intent and drug category to better understand the recent decrease in overdose suicides amid the overdose epidemic. Methods. We examined trends in rates of overdose deaths by intent (unintentional, suicide, or undetermined) across 9 drug categories from 1999 to 2022 using US National Vital Statistics System mortality data. Results. Unintentional overdoses involving synthetic opioids, polydrug toxicity involving synthetic opioids, psychostimulants, and cocaine increased exponentially with annual percentage changes ranging from 15.0% to 104.9% during 2010 to 2022. The death rates also increased for suicides involving these drugs, especially for psychostimulants (annual percentage change = 12.9% for 2010–2022; P <.001). However, these drugs accounted for relatively small percentages of overdose suicides. The leading drug categories among suicides were antidepressants, prescription opioids, and benzodiazepines, though these deaths have decreased or leveled off in recent years. Conclusions. Different drugs commonly involved in suicides and unintentional overdoses may contribute to their divergent trends. Public Health Implications. Amid the overdose epidemic, safe storage of medications remains a crucial strategy to prevent overdose suicides. The large increases in suicides involving psychostimulants warrant monitoring. (Am J Public Health. 2024;114(10):1081–1085. https://doi.org/10.2105/AJPH.2024.307745) [ABSTRACT FROM AUTHOR]

As the rate of total shoulder arthroplasty (TSA) and preoperative benzodiazepine use rise, there is an increased need to understand the impact of preoperative benzodiazepine use on postoperative opioid consumption following TSA, especially amid the current opioid epidemic. The relationship between preoperative benzodiazepine use and chronic opioid use postoperatively has been well described following other orthopedic procedures; however, the impact on patients undergoing TSA remains unclear. This study aims to identify the impact of preoperative benzodiazepine use on opioid use following TSA. A retrospective chart review of 4488 patients undergoing primary TSA (Current Procedural Terminology code 23472) at a single institution from 2014 to 2022 was performed. Patient demographics, surgical variables, comorbidities, Distressed Communities Index (DCI), and clinical outcomes, including readmission and revision, were collected. The Charlson Comorbidity Index (CCI) was used to assess preoperative health status. Opioid use in morphine milligram equivalents (MMEs) and benzodiazepine use were also recorded using the Prescription Drug Monitoring Program Database. Opioid use was collected at 30-, 60-, and 90-day intervals both before and after each patient's date of surgery. Statistical analysis included stepwise logistic regression to identify variables independently affecting benzodiazepine use pre- and postoperatively. Overall, 16% of patients used benzodiazepines within 90 days before their date of surgery. Of those patients, 46.4% were also using preoperative opioids, compared with just 30.0% of patients who were benzodiazepine-naïve (P <.001). Preoperative benzodiazepine use was also associated with increased pre- and postoperative total opioid use in MMEs and the number of opioid prescriptions across all time points when compared to benzodiazepine-naïve patients (P <.001). Furthermore, 37.4% of preoperative benzodiazepine users went on to prolonged opioid use (filled prescriptions >30 days after surgery) compared to 19.0% of those who were benzodiazepine-naïve (P <.001). This study demonstrates a significant association between preoperative benzodiazepine use and increased and prolonged opioid use following TSA. Further exploration of risk factors contributing to preoperative benzodiazepine use may help to reduce overall opioid use in patients undergoing TSA. [ABSTRACT FROM AUTHOR]

Background Overuse of medical care is a pervasive problem. Studies using hypothetical scenarios suggest that physicians' risk literacy influences medical decisions; real-world correlations, however, are lacking. We sought to determine the association between physicians' risk literacy and their real-world prescriptions of potentially hazardous drugs, accounting for conflicts of interest and perceptions of benefit--harm ratios in low-value prescribing scenarios. Setting and sample Cross-sectional study--conducted online between June and October 2023 via field panels of Sermo (Hamburg, Germany)--with a convenience sample of 304 English general practitioners (GPs). Methods GPs' survey responses on their treatment-related risk literacy, conflicts of interest and perceptions of the benefit--harm ratio in low-value prescribing scenarios were matched to their UK National Health Service records of prescribing volumes for antibiotics, opioids, gabapentin and benzodiazepines and analysed for differences. Results 204 GPs (67.1%) worked in practices with ≥6 practising GPs and 226 (76.0%) reported 10--39 years of experience. Compared with GPs demonstrating low risk literacy, GPs with high literacy prescribed fewer opioids (mean (M): 60.60 vs 43.88 prescribed volumes/1000 patients/6 months, p=0.016), less gabapentin (M: 23.84 vs 18.34 prescribed volumes/1000 patients/6 months, p=0.023), and fewer benzodiazepines (M: 17.23 vs 13.58 prescribed volumes/1000 patients/6 months, p=0.037), but comparable volumes of antibiotics (M: 48.84 vs 40.61 prescribed volumes/1000 patients/6 months, p=0.076). High-risk literacy was associated with lower conflicts of interest (θ = 0.12, p=0.031) and higher perception of harms outweighing benefits in low-value prescribing scenarios (p=0.007). Conflicts of interest and benefit--harm perceptions were not independently associated with prescribing behaviour (all ps >0.05). Conclusions and relevance The observed association between GPs with higher risk literacy and the prescription of fewer hazardous drugs suggests the importance of risk literacy in enhancing patient safety and quality of care. [ABSTRACT FROM AUTHOR]

Objective: Using benzodiazepines and certain antidepressants is associated with an increased risk of motor vehicle crashes due to impaired driving skills. Hence, several countries prohibit people who use these drugs from driving. Traffic regulations for driving under the influence of these drugs are, however, largely based on single-dose studies with healthy participants. The effects of drugs on chronic users may be different because of potential development of tolerance or by adapting behavior. In this study, we test the effects of anti-depressants, hypnotics, or anxiolytics use on driving performance in patients who use these drugs for different durations and compare the effects to healthy controls' performance. Methods: Sixty-six healthy controls and 82 medication users were recruited to perform four drives in a driving simulator. Patients were divided into groups that used anti-depressants, hypnotics, or anxiolytics, for shorter or longer than 3 years (i.e. LT3− or LT3+, respectively). The minimum term of use was 6 months. Driving behavior was measured in terms of longitudinal and lateral control (speed variability and Standard Deviation of Lateral Position: SDLP), brake reaction time, and time headway. Impaired driving performance was defined as performing similar to driving with a Blood Alcohol Concentration of 0.5‰ or higher, determined by means of non-inferiority analyses. Results: Reaction time analyses revealed inconclusive findings in all groups. No significant performance differences between matched healthy controls, LT3− (n = 2), and LT3+ (n = 8) anxiolytics users were found. LT3+ antidepressants users (n = 12) did not perform inferior to their matched controls in terms of SDLP. LT3− hypnotics users (n = 6) showed more speed variability than their matched healthy controls, while this effect was not found for the LT3+ group (n = 14): the latter did not perform inferior to the healthy controls. Regarding Time Headway, no conclusions about the LT3− hypnotics group could be drawn, while the LT3+ group did not perform inferior compared to the control group. Conclusions: The small number of anxiolytics users prohibits drawing conclusions about clinical relevance. Although many outcomes were inconclusive, there is evidence that some elements of complex driving performance may not be impaired (anymore) after using antidepressants or hypnotics longer than 3 years. [ABSTRACT FROM AUTHOR]

Background: Although changes to prescribing guidelines appear to have resulted in fewer prescriptions from doctors, no recent study has looked at changes to where prescription drugs of misuse are obtained and how they have differed by gender and race among adolescents and young adults. Objectives: This study examines trends in the source of prescription drug misuse between 2015 and 2019 for adolescents and young adults and observes how they have differed between demographic groups in this population. Methods: Data were from the 2015 – 2019 National Survey on Drug Use and Health. Trend analysis was performed using logistic regression models with year as a predictor of prescription drug source, with separate models created for individual demographic groups. Results: Findings indicate that the likelihood of having received a prescription benzodiazepine or stimulant from friends or family for free has decreased for many groups, while the likelihood of having purchased benzodiazepines or stimulants from a drug dealer or stranger has increased. Changes observed for prescription opioids include increased likelihood of receiving from a doctor for 12–17-year-olds and increased likelihood of stealing from friends/family for many groups. Conclusion: Possible explanations for these changes and implications for practice and policy are discussed. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate substance use and its association with eating attitudes and behaviors among male Palestinian refugees. Methods: In a cross-sectional study, male Palestinian refugees(N = 566) were recruited to fill out self-administrated questionnaire on eating attitudes and behaviors (EAT-26) and to give urine samples to test current illicit drug use. Results: The response rate was 47.7%. Substance use was highly prevalent among participants (28.9%). The percentage of participants with eating disorders (ED) among substance users was as follows: Any illicit drug (30.8%), benzodiazepine (32.6%), methamphetamines(40.7%), amphetamine (39.3%), tetrahydrocannabinol (25.8%), barbiturates (20%),and alcohol (12.50%). Obese participants were at higher risk of having ED(OR = 2.344, p <.05) than underweight participants. Binge eaters were more likely to be tetrahydrocannabinol users (OR = 2.745, p <.05). Increased riskof self-induced vomiting behavior was associated with binge behavior (OR = 5.97, p <.05, laxative use (OR = 26.38, p <.01), barbiturates use (OR = 59.36, p <.05), waterpipe smoking (OR = 8.62, p <.05), vape smoking (OR = 10.37, p <.05), and inversely associated with age (OR = 0.832, p <.001). Conclusion: Findings from this study demonstrated a substantially increased frequency of substance use among Palestinian refugees with ED and unhealthy weight control behaviors. This study highlighted new challenge for the health system to deal with new emerging health conditions among male refugees. [ABSTRACT FROM AUTHOR]

Objective: The study's objectives were (i) demonstrating the trends of sociodemographic, substance use, and clinical characteristics of pregnant women admitted to substance use treatment facilities from 2011 to 2018 and (ii) mining their patterns of association of polysubstance use. Methods: We used the Treatment Episode Data Set – Admissions (TEDS-A) of pregnant women between 2011 and 2018. The Cochran–Armitage test was employed to test the trend, and Market Basket Analysis (MBA) was used for mining association rules to identify polysubstance use patterns. Results: Over the years, some cohorts consistently showed majority admissions. Among these, age (30–39 years), education (12 or more years), injection as a route, and medication-assisted opioid therapy showed a significantly increasing trend. Admissions increased significantly with heroin (66%) and methamphetamine (46%) and decreased between 23% and 43% with alcohol, marijuana/hashish, cocaine/crack, other opiates/synthetics, and benzodiazepines. Basket analysis revealed some patterns of polysubstance co-occurrence consistent over the years. For instance, the co-occurrences of {alcohol, marijuana/hashish} or {methamphetamine, marijuana/hashish} were the most common. Conclusions: The findings on trends and long-run polysubstance use patterns may help to find pregnant women's most vulnerable cohorts for effective interventions to minimize the health risk for them and their fetuses. [ABSTRACT FROM AUTHOR]

AbstractIntroductionAimMethodsResultsDiscussion and implicationsConclusionsThe prevalence of sleep disorders and use of sleep medication, particularly melatonin, are rising among adolescents and young adults (13–24 years). In Denmark, melatonin is approved for use in children with autism and ADHD up to 18 years of age, with other prescriptions being off-label in these age groups. The perspectives of medical practitioners on prescribing sleep medications to this age group remain largely unexplored.This study aims to investigate the considerations of general practitioners (GPs) and child and adolescent psychiatrists (psychiatrists) when prescribing and deprescribing sleep medications for 13–24-year-olds.We conducted qualitative semi-structured interviews with 10 GPs and six psychiatrists. Data were analyzed using an inductive approach.Psychiatrists typically prescribed melatonin with the expectation that deprescription would occur in general practice. Despite the universal goal of deprescription, it was hindered by various challenges. GPs identified patient motivation and a clear focus on deprescription as facilitative factors and expressed a need for enhanced emphasis on these aspects in general practice.The findings align with existing prescription trends and literature on factors that promote and inhibit deprescription. The study underscores the complexities of deprescribing sleep medications for adolescents and young adults, suggesting the need for expanded guidelines and enhanced continuing education for GPs.The research highlights significant discrepancies among medical practitioners regarding the deprescription process of sleep medications for young individuals, complicated by multiple factors. This underscores the need for better guidelines and further studies. [ABSTRACT FROM AUTHOR]

AbstractSynthesis and illicit use of designer benzodiazepines are growing concerns, with these new psychoactive substances (NPS) posing serious health consequences and new hurdles for toxicologists. Consumption marker identification and characterization is paramount in confirming their use. The benzodiazepine core structure is a fusion of benzene and a seven-membered heterocycle with two nitrogen atoms forming the diazepine ring. Minor variations on the core structure produce different classes of benzodiazepines with marked differences in physiological effects. The present review provides a comprehensive designer benzodiazepines metabolism overview and suggests suitable human consumption biomarkers for toxicology casework. A systematic literature search of PubMed®, ScopusTM, Web of ScienceTM, and Cochrane databases was conducted independently by two coauthors adhering to PRISMA guidelines. Data from 30 in vitro and in vivo models of designer benzodiazepines metabolism from January 2007 to February 2023 were included. 1,4-benzodiazepines (n = 10), 2,3-benzodiazepines (n = 1), triazolo-benzodiazepines (n = 9), and thieno-triazolo-benzodiazepines (n = 3) study design, sample pretreatment, analytical techniques, and major metabolites detected in various matrices are addressed. Metabolites following hydroxylation and phase II glucuronide conjugation were the most prevalent analytes. N-Glucuronidation of parent azole-fused benzodiazepines, and nitro-reduced and N-acetylated metabolites of nitro-containing designer benzodiazepines were also common. From these data, we propose a generic metabolic pathway for designer benzodiazepines. The sporadic illicit market presents challenges in toxicological casework and necessitates comprehensive biomarker investigations, especially in cases with legal implications. There are few metabolism data for many designer benzodiazepines, emphasizing the need for research focusing on closing these gaps. [ABSTRACT FROM AUTHOR]

Abstract\nKEY POINTSObjective Is the involvement of the regular general practitioner (GP) in the decision to initiate opioid treatment for chronic non-cancer pain (CNCP) associated with two main risk factors for serious adverse events: increased opioid dose and the concomitant use of prescribed benzodiazepines or benzodiazepine-related medications? Design and setting An anonymous web-based survey was conducted in the county of Rogaland, Norway, during the spring of 2021. Subjects GPs who self-reported applying at least once for reimbursement of opioids prescribed to treat CNCP. They were asked to answer the survey based on the last patient for whom they recalled submitting a reimbursement application. Main outcome measures 1) Total opioid dose in daily oral morphine equivalents (OMEQ). 2) Concurrent use of benzodiazepines and/or benzodiazepine-related drugs. Results The daily opioid dose was lower when the surveyed GPs initiated the opioid treatment (36 OMEQ, n = 25), than when others had initiated the treatment (108 OMEQ, n = 31, p = 0.001). For concurrent use of benzodiazepine or benzodiazepine-related drugs, no significant difference was found (33%, n = 9 with GP involvement vs. 47%, n = 16, p = 0.279 with no GP involvement). Conclusions GP involvement in the initiation of opioid medication for CNCP was associated with a lower opioid dose being prescribed. Implications GP involvement in the initiation of opioid prescriptions may facilitate safer prescribing.Opioid treatment against chronic non-cancer pain (CNCP) can be reimbursed in Norway. High opioid doses and the concomitant use of other medications with addictive properties, particularly benzodiazepines, increase the risk of serious adverse events. When the general practitioner (GP) in the survey had initiated the opioid treatment, this was associated with a lower opioid dose, but not with less concomitant use of benzodiazepines. [ABSTRACT FROM AUTHOR]

Background: There is a growing concern that opioids and benzodiazepines can depress the respiratory drive and could contribute to worsening respiratory failure and higher exacerbation frequency in COPD. However, the relationship between the exacerbation rate and medication taken is poorly understood in patients with chronic respiratory failure due to COPD. Methods: As part of a service evaluation project, we analysed 339 patients with COPD who were established on long-term non-invasive ventilation (LT-NIV) at our tertiary centre. We investigated the relationship between benzodiazepine and opioid prescription and clinical outcomes as well as their impact on the exacerbation rate and overall survival following setup. Results: Before LT-NIV setup, 40 patients took benzodiazepines and 99 patients took opioids. Neither benzodiazepine nor opioid use was associated with changes in daytime blood gases, overnight hypoxia or annual exacerbations before NIV setup, but patients taking opioids were more breathless as assessed by modified Medical Research Council scores (3.91 ± 0.38 vs. 3.65 ± 0.73, p < 0.01). Long-term NIV significantly reduced the number of yearly exacerbations (from 3.0/2.0–5.0/ to 2.8/0.71–4.57/, p < 0.01) in the whole cohort, but the effect was limited in those who took benzodiazepines (from 3.0/2.0–7.0/ to 3.5/1.2–5.5/) or opioids (3.0/2.0–6.0/ to 3.0/0.8–5.5/). Benzodiazepine use was associated with reduced exacerbation-free survival and overall survival (both p < 0.05). However, after adjustment with relevant covariates, the relationship with exacerbation-free survival became insignificant (p = 0.12). Opioids were not associated with adverse outcomes. Conclusions: Benzodiazepines and opiates are commonly taken in this cohort. Whilst they do not seem to contribute to impaired gas exchange pre-setup, they, especially benzodiazepines, may limit the benefits of LT-NIV. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Non-restorative sleep (NRS) affects not only individuals' health, but also company productivity, highlighting the importance of measures in the workplace to improve sleep. This study aimed to examine the clustering of the presence of restorative sleep (RS) and lifestyle habits in a Japanese working population and to explore the characteristics of these clusters. The subjects were 58,150 Japanese working men aged 40−59 years who underwent health check-ups across the country from April 2015 to March 2016. Data for the presence of RS, the frequency and amount of drinking, smoking/exercise habits, and body mass index obtained from health check-ups were clustered with latent class analysis. In addition, the characteristics of each cluster were examined from the perspectives of lifestyle-related disease-associated blood test results obtained from health check-ups and the status of medical treatment at medical institutions as determined from medical claims data. Consequently, RS and lifestyle habits were found to form five clusters. The "NRS, no exercise, drinkers" cluster showed the highest probability of not achieving RS. An "Obese, occasional binge drinkers" cluster with a higher percentage of patients with sleep-apnea syndrome and a "Nondrinkers" cluster with proportions of those taking sleeping pills/anxiolytics and antidepressants/antipsychotics were observed. Furthermore, the "Daily smokers and drinkers" and "RS and drinkers" clusters showed a relatively high probability of achieving RS. These findings suggest that some individuals may not be aware of the sleep disorders caused by their drinking and smoking habits. Measures to improve sleep must be tailored to the characteristics of each cluster. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusions\nKEY POINTSBipolar disorders (BD) are characterized by highly recurrent nature, necessitating adequate maintenance treatment for long-term disorder control. This study aimed to investigate real-world prescribing patterns among outpatients with BD, focusing on the utilisation of antidepressants (AD) and benzodiazepines (BDZ).We analysed prescription patterns of the five main groups of psychotropic medications (antipsychotics, mood stabilizers, AD, BDZ, and anticholinergic medications) and their relationships with basic socio-demographic and clinical data in a sample of 107 clinically stable BD outpatients (75.7% female, age 44.8 ± 11.7).Maintenance therapy predominantly involved polypharmacy (92.5%), with mood stabilizers (87.9%) and antipsychotics (80.4%, predominantly second-generation) being the most commonly prescribed. Our findings highlight a high percentage of patients prescribed AD (50.5%) and BDZ (54.2%). BDZ patients, compared to the non-BDZ group in maintenance treatment, were significantly older with longer psychiatric history and a decreased likelihood of comorbid personality disorder diagnoses.This study offers insights into prescribing practices within a university psychiatric clinic in the Western Balkans. The prevalent use of polypharmacy in real-world clinical settings, along with high percentage of patients prescribed AD and BDZ, suggests a gap between guideline recommendations and clinical practice, indicating a lack of consensus or standardized approaches in clinical practice.Study uncovers prescribing practices in a Western Balkans university psychiatric clinic, revealing high polypharmacy prevalence (92.5%) among clinically stable bipolar disorder (BD) outpatients.Most BD outpatients received mood stabilizers, particularly lamotrigine, and second-generation antipsychotics, notably olanzapine, with a minority on monotherapy.Antidepressant and benzodiazepine usage was notably high despite guidelines favouring monotherapy, reflecting challenges in managing residual morbidity.AD usage in BD type I is discouraged due to risks, while their use in BD type II is considered in certain scenarios, emphasising tailored treatment.High mean daily BDZ dose (approximately 3.5mg lorazepam equivalents) in non-acute outpatient BD maintenance therapy raises concerns about potential long-term implications for patient health and underscores the need for vigilant monitoring of prescribing practices.Study uncovers prescribing practices in a Western Balkans university psychiatric clinic, revealing high polypharmacy prevalence (92.5%) among clinically stable bipolar disorder (BD) outpatients.Most BD outpatients received mood stabilizers, particularly lamotrigine, and second-generation antipsychotics, notably olanzapine, with a minority on monotherapy.Antidepressant and benzodiazepine usage was notably high despite guidelines favouring monotherapy, reflecting challenges in managing residual morbidity.AD usage in BD type I is discouraged due to risks, while their use in BD type II is considered in certain scenarios, emphasising tailored treatment.High mean daily BDZ dose (approximately 3.5mg lorazepam equivalents) in non-acute outpatient BD maintenance therapy raises concerns about potential long-term implications for patient health and underscores the need for vigilant monitoring of prescribing practices. [ABSTRACT FROM AUTHOR]

Introduction Military Service Members, Veterans, and other patient populations who experience traumatic brain injury (TBI) may have increased risk of early neurodegenerative diseases relative to those without TBI history. Some evidence suggests that exposure to psychotropic medications may play a role in this association. The Long-term Impact of Military-relevant Brain Injury Consortium—Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) prospective longitudinal study provides an ideal setting to examine the effects of psychotropic medication exposure on long-term neurological health of those with and without mild TBI history. In this study, we sought to develop and pilot test a self-report electronic survey instrument to measure participants' psychotropic medication histories for use across LIMBIC-CENC study sites. Materials and Methods We developed a new survey instrument measuring psychotropic medication history and fielded it among Service Members and Veterans enrolled in a single site of the LIMBIC-CENC study to evaluate response rates and patterns, and to compare survey responses to prescription data extracted from participants' Veterans Affair (VA) records. Descriptive statistics estimated survey respondents' lifetime psychotropic medication exposures by their TBI history and other demographic and clinical characteristics of interest. We also compared survey responses to participants' VA outpatient prescription records to estimate sensitivity and negative predictive values (NPVs) for participants' self-reported medication exposures relative to this single prescription data source. Results Among 310 Veterans enrolled at the study site, 249 completed the survey (response rate = 80%), of whom 248 also had VA health records and were included in the analysis. Most (69%) had a history of mild TBI. Over three-fourths of survey respondents (78%) reported ever having used prescription opioids, 26% reported benzodiazepines, 50% reported muscle relaxants, 42% reported antidepressants, 13% reported non-benzodiazepine sedative-hypnotics, 15% reported stimulants, 7% reported mood stabilizers, and 6% reported antipsychotics. Veterans with, versus without, a history of mild TBI were more likely to self-report psychotropic medication history as well as have confirmed receipt of VA prescriptions for each medication class. Using VA records as a criterion standard, the sensitivity of the survey for detecting VA prescriptions ranged from 19% to 84%, while the NPVs ranged from 64% to 97%. Sensitivity and NPVs were similar for participants with, versus without, mild TBI history. Conclusions Service Members and Veterans may receive psychotropic medications from multiple sources over their lifetimes. Valid methods to examine and quantify these exposures among those with a history of TBI are important, particularly as we evaluate causes of neurodegenerative disorders in this population over time. The measurement of Veterans' lifetime psychotropic medication exposures using a self-report survey, in combination with health care records, holds promise as a valid approach, but further testing and refinement are needed. [ABSTRACT FROM AUTHOR]

The use of alprazolam in pregnancy can adversely affect maternal and neonatal health. This study examined neonatal outcomes following exposure to alprazolam in pregnancy. Women prescribed alprazolam during pregnancy (n = 48) between 2014 and 2018 were identified from routinely-collected state administrative prescribing records and perinatal data. Two comparison groups of women; 1) prescribed alprazolam outside of pregnancy (n = 96) and 2) women never prescribed alprazolam (n = 96) were also identified. The health of women and their children was examined using administrative hospital, mortality and perinatal data and compared to the comparison groups using generalized linear models. Prenatal alprazolam exposure was not associated with a reduction in average birth weight or gestational age. However, neonates prenatally exposed to alprazolam were more likely be classified as having low birth weight for gestational age compared with alprazolam comparison group (OR: 4.46, 95% CI: 1.54–12.95) and the non-alprazolam comparison group (OR: 3.27, 95% CI: 1.22–8.79). There were no cases of perinatal mortality or floppy baby syndrome in alprazolam-exposed neonates. While the use of alprazolam during pregnancy was not associated with an increased risk of severe adverse neonatal outcomes (e.g. perinatal mortality), it was associated with neonates being born with a low birth weight for gestational age. [ABSTRACT FROM AUTHOR]

Background: Despite widespread consensus on the need to reduce benzodiazepine (BZD) use in older adults, prescription rates in the U.S. have paradoxically increased over the past few decades. Objective: We examined (1) the characteristics of the BZD adverse reaction cases in patients aged 50 and older that were admitted to a healthcare facility (HCF) and experienced major effects/death, and (2) the associations between the concomitant use of opioids and/or antidepressants and HCF admission and major effects/death among BZD cases. Methods: We used the 2015–2022 National Poison Data System (NPDS), which contained data from 55 America's Poison Centers. We fitted two multivariable logistic regression models to examine the associations between the co-use of opioids and/or antidepressants and HCF admission and major effects/death. Results: Of the BZD cases that were examined (N = 1979), 14.9% or 295 cases were admitted to healthcare facilities, and 8.5% of those who were followed up (77 out of 893 cases) experienced major effects or death. The number of co-used substances, co-use of opioids and antidepressants, atypical antipsychotics, anticonvulsants, muscle relaxants, and Gabapentin were associated with greater odds of healthcare admission. Co-use of opioids and healthcare admission were associated with greater odds of major effects/death. Conclusions: Adverse reactions and healthcare admissions are likely to be prevented when healthcare providers limit and carefully monitor BZD prescribing, especially for those who are on other medications, including prescription opioids and antidepressants. [ABSTRACT FROM AUTHOR]

Background: Heautoscopic hallucinations are rare visual experiences consisting of the perception of the image of one's own body or face within space. Method: The point of view can be internal, like in front of a mirror, or external. Results: Heautoscopic phenomena are classified among the disorders of somatoagnosia, or disorders related to the alteration of the body schema. It is not clear which sensory system is primarily involved in the generation of this alteration. Discussion: This case report discusses a 21-year-old male student with first episode psychosis who presented heautoscopic hallucinations. His neurological and medical examinations were unremarkable. By explaining the theoretical background on the heterogeneity of autoscopic phenomena in psychiatric and neurological disease, our clinical observation contributes for the first time to enrich the literature on autoscopic hallucinations in patients with non-affective psychosis. [ABSTRACT FROM AUTHOR]

Herein we report the crystal structures of two benzodiazepines obtained by reacting N,N′‐(4,5‐diamino‐1,2‐phenylene)bis(4‐methylbenzenesulfonamide) (1) or 4,5‐(4‐methylbenzenesulfonamido)benzene‐1,2‐diaminium dichloride (1·2HCl) with acetone, giving 2,2,4‐trimethyl‐8,9‐bis(4‐methylbenzenesulfonamido)‐2,3‐dihydro‐5H‐1,5‐benzodiazepine, C26H30N4O4S2 (2), and 2,2,4‐trimethyl‐8,9‐bis(4‐methylbenzenesulfonamido)‐2,3‐dihydro‐5H‐1,5‐benzodiazepin‐1‐ium chloride 0.3‐hydrate, C26H31N4O4S2+·Cl−·0.3H2O (3). Compounds 2 and 3 were first obtained in attempts to recrystallize 1 and 1·2HCl using acetone as solvent. This solvent reacted with the vicinal diamines present in the molecular structures, forming a 5H‐1,5‐benzodiazepine ring. In the crystal structure of 2, the seven‐membered ring of benzodiazepine adopts a boat‐like conformation, while upon protonation, observed in the crystal structure of 3, it adopts an envelope‐like conformation. In both crystalline compounds, the tosylamide N atoms are not in resonance with the arene ring, mainly due to hydrogen bonds and steric hindrance caused by the large vicinal groups in the aromatic ring. At a supramolecular level, the crystal structure is maintained by a combination of hydrogen bonds and hydrophobic interactions. In 2, amine‐to‐tosyl N—H...O and amide‐to‐imine N—H...N hydrogen bonds can be observed. In contrast, in 3, the chloride counter‐ion and water molecule result in most of the hydrogen bonds being of the amide‐to‐chloride and ammonium‐to‐chloride N—H...Cl types, while the amine interacts with the tosyl group, as seen in 2. In conclusion, we report the synthesis of 1, 1·2HCl and 2, as well as their chemical characterization. For 2, two synthetic methods are described, i.e. solvent‐mediated crystallization and synthesis via a more efficient and cleaner route as a polycrystalline material. Salt 3 was only obtained as presented, with only a few crystals being formed. [ABSTRACT FROM AUTHOR]

Remazolam is a new ultra-short-acting benzodiazepine that produces sedation by acting on γ-aminobutyric acid type A (GABAA) receptors. Remazolam has characteristics of rapid onset of action, short half-life, high clearance, and no accumulation in the body. It also has a low incidence of injection pain and mild effects on hepatic and renal function, respiration, and haemodynamics. Additionally, it can be rapidly reversed by flumazenil. The clinical research progress on remazolam in the areas of procedural sedation, induction, and maintenance of general anesthesia were reviewed to provide references for its clinical application. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study, we compared neonatal and maternal outcomes after exposure of different psychopharmacological classes of drugs. Both psychiatric diseases and pharmacological treatment of these are associated with lower birth weights, lower APGAR scores, and NICU admission. Therefore, we tried to rule out the role of psychotropics as if no differences were found between pharmacological classes, the lower birthweights might not be attributable to these. We divided our groups in exposed to atypical antipsychotic drugs, Selective Serotonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCA), benzodiazepines, and different combinations of psychotropic drugs. The last group included SSRIs combined with benzodiazepines, methylphenidate, lithium, and classic antipsychotic drugs. We used univariate regression analysis to see which factors from our rich dataset including pharmacological class, are associated with birth weight, APGAR scores, gestational age, and NICU admission. The significant associations from univariate analyses were further analyzed using ancova analysis or logistic regression where applicable. We found no clinically relevant differences in neonatal and maternal outcomes between the different exposed pharmacological classes. However, our dataset may have been too small to draw firm conclusions. [ABSTRACT FROM AUTHOR]

Several medications are associated with delirium; however, studies with adequate statistical power are limited, and it is difficult to determine the effects of the various concomitant medications used in clinical practice. Therefore, in this study, we aimed to comprehensively evaluate the safety signals of delirium-associated drugs using a spontaneous adverse event reporting system. The JAPIC AERS (Food and Drug Administration Adverse Event Reporting System pre-processed by the Japan Pharmaceutical Information Center) was used for the analysis in this pharmacovigilance study. The reporting odds ratio (ROR) for delirium was adjusted for using multivariate logistic regression analysis with sex, age, indication, and melatonin receptor agonist use, and 22 drug categories were targeted as covariates. After excluding patients with missing information, 7,527,568 patients were included in the study. Delirium signals were detected even after adjusting for covariates in 17 drug categories, including benzodiazepines (adjusted ROR, 1.76; 95% confidence interval [CI], 1.64–1.89), opioids (adjusted ROR, 4.42; 95% CI, 4.21–4.64), and tricyclic antidepressants (adjusted ROR, 2.44; 95% CI, 2.20–2.71). These findings suggest that many drug classes, such as benzodiazepines, are independent risk factors for delirium and strengthen the evidence of an association between delirium and medications. [ABSTRACT FROM AUTHOR]

Background: Medication utilization has been increasing in the U.S. year‐over‐year for several decades. As older adults take more medications, there is a higher risk of them being exposed to drug–drug or drug‐disease interactions. The American Geriatrics Society in 2019 updated their Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults. The objective of this study was to assess the prevalence of utilization of medications included in the 2019 Beers Criteria. Methods: An analysis was conducted using the Medicare Part D Provider Utilization and Payment Data Public Use File for calendar‐year 2020. Medications identified in the 2019 Beers Criteria were applied to the analysis. Two categories of medications were assessed: (1) "Avoid" and (2) "Use With Caution." Results: In 2020, 56 million prescriptions were dispensed to Medicare patients 65 years and older that are recommended to be avoided without exception (4.7% of all prescriptions) totaling $957 million in medication costs. The most utilized medication classes in this category were benzodiazepines (25,949,994 prescriptions), "Z‐drugs" (6,204,909 prescriptions), long‐acting sulfonylureas (5,306,577 prescriptions), 1st‐generation antihistamines (5,049,289 prescriptions), and tricyclic antidepressants (4,190,062 prescriptions). Additionally, 135 million prescriptions were dispensed to Medicare beneficiaries 65 years and older for medications which the Beers Criteria states to use caution (11.3% of all prescriptions) exceeding $2.85 billion in medication costs. The most utilized medications for this category were diuretics (74,599,126 prescriptions), selective serotonin reuptake inhibitors (30,033,121 prescriptions), serotonin and norepinephrine reuptake inhibitors (11,858,968 prescriptions), tramadol (11,450,878 prescriptions), and mirtazapine (5,737,304 prescriptions). Conclusion: Even with the existence of the AGS Beers Criteria for PIM Use in Older Adults and its continued updated versions, 16% of medications dispensed to Medicare Part D were potentially inappropriate. Future studies are needed to assess if this has led to worsened outcomes among older adults who utilized these PIM. [ABSTRACT FROM AUTHOR]

In recent years the still relatively new short-acting benzodiazepine remimazolam has been approved and clinically implemented in several countries and regions. Remimazolam is also now approved in the EU and the market launch in Germany is expected in the not too distant future. This is therefore a good point in time to summarize the current evidence for various areas of application, including general anesthesia, sedation and intensive care medicine as well as different dosing schemes. [ABSTRACT FROM AUTHOR]

Introduction There is a longstanding debate about whether health care is more efficiently provided by the public or private sector. The debate is particularly relevant to the Military Health System (MHS), which delivers care through a combination of publicly funded federal facilities and privately contracted providers. This study compares outcomes, treatments, and costs for MHS patients obtaining care for low back pain (LBP) from public versus private providers. Materials and Methods A retrospective cohort study was completed using TRICARE Prime claims data from April 2015 to December 2018. The cohort was identified using International Classification of Diseases Ninth Revision and Tenth Revision diagnostic codes and then followed for 12 months after the index diagnosis to assess treatments, outcomes, and costs. Claims were classified as originating from either public or private providers. The primary outcome measure was resolution of LBP, defined as an absence of LBP diagnoses during the 6-to-12-month window following the index event. Instrumental variable models were used to assess the impact of care setting (i.e. private versus public), conditioning on the covariates. A regional measure of the fraction of private care was used as an instrument. Results Resolution of LBP was achieved for 79.7% of 144,866 patients in the cohort. No significant association was found between resolution of LBP and fraction of privately provided care. Higher fraction of private care was associated with a greater likelihood of opioid treatments (odds ratio, 1.22; 95% CI, 1.02-1.46) and a lower likelihood of benzodiazepine (odds ratio, 0.56; 95% CI, 0.45-0.70) and physical therapy (odds ratio 0.55; 95% CI, 0.42-0.74) treatments; manual therapy was not significantly associated with the fraction of private care. There was a significant negative association between the fraction of private care and cost (coefficient −0.27; 95% CI, −0.44, −0.10). Conclusion This study found that privately provided care was associated with significantly higher opioid prescribing, less use of benzodiazepines and physical therapy, and lower costs. No systematic differences in outcomes (as measured by resolved cases) were identified. The findings suggest that publicly funded health care within the MHS context can attain quality comparable to privately provided care, although differences in treatment choices and costs point to possibilities for improved care within both systems. [ABSTRACT FROM AUTHOR]

Introduction Clinical practice guidelines (CPGs) and clinical recommendations (CRs) are developed to aide and guide providers in treating a variety of conditions, including traumatic brain injury (TBI). There is little knowledge on the impact that CPGs and CRs have on provider practice. One TBI recommendation that was able to be tracked in medical record codes was the use of benzodiazepines (BZD). Because of potential for misuse, diversion, addiction, cognitive impairment, and brain healing interference, the DoD and Department of Veterans Affairs (VA) jointly discourage prescribing BZD after TBI. As part of an effort to look at translation of CPG guidance into clinical practice, our objective was to examine the issuance of BZD prescriptions, including dose, type, and prescribing provider, prescribing setting, and primary diagnosis at issuance among U.S. service members with mild Traumatic Brian Injury (mTBI). Materials and Methods Using DoD data sourced from the Comprehensive Ambulatory/Professional Encounter Record (CAPER) databases of the Military Health System (MHS) Medical Data Repository (MDR), we identified all U.S. service members with a first lifetime diagnosis of mTBI from October 1, 2015 to September 30, 2016. Data on prescriptions issued to this group during a period of active treatment for a mTBI were obtained from the Pharmacy Detail Transaction Service (PDTS) databases of the MDR and identified BZD prescriptions based on the American Hospital Formulary Service (AHFS) therapeutic classification system. We validated coding assumptions through structured review of the clinical record contained within the Armed Forces Health Longitudinal Technology Application (AHLTA) of 30 randomly selected cohort members. Results Among U.S. service members, 4.5% filled a BZD prescription while under active medical treatment for a recent mTBI. These service members were more likely female and older when compared to their counterparts not prescribed BZD. Among service members under active treatment for mTBI during the study period, 52.6% (n  = 7,935) filled a prescription; of these, 8.5% (n  = 676) filled a BZD prescription. Of U.S. service members filing a BZD prescription while undergoing active treatment for an mTBI, 64.6% (n  = 437) filled prescriptions for BZD and antidepressants, 54.9% (n  = 371) filled prescriptions for both BZD and NSAIDS, and 42.2% (n  = 285) concurrently filled prescriptions for BZD and opioids. Conclusions This effort to examine the translation of CPG recommendations into practice through evaluation of medical record data indicates that providers are prescribing BZD to patients under active treatment for an acute mTBI. The mTBI CPG recommends that the BZD class of medications be avoided in patients healing from brain injury. However, the team recognizes there are confounding factors that may impact the medications that are prescribed for patients with mTBI. Additional work to understand how CPGs and CRs are received and utilized by providers may elucidate opportunities to close the gap between clinical practice guidance and clinical practice. [ABSTRACT FROM AUTHOR]

Article #1 discusses a clinical trial that examined the effects of delaying intubation in comatose patients with acute poisoning. The study found that delaying intubation was safe and resulted in lower rates of ICU admission and complications. However, the lack of deaths suggests that more research is needed, particularly involving confirmed overdoses. Article #2 explores lead exposure in veterinary workers who handle lead shielding during radiography. The study found that the use of lead shielding is associated with lead exposure, but wearing disposable gloves can significantly reduce this exposure. However, the study had limitations, such as potential bias from the questionnaire and the lack of evaluation of hand washing. Article #3 focuses on the use of angiotensin II (AT2) for treating refractory shock. While AT2 has shown improvement in blood pressures, its impact on mortality is still unclear. The study aims to determine if adding AT2 improves 30-day mortality in patients with severe, refractory shock. However, the study is retrospective and underpowered, so further research is needed to establish its effectiveness. The study found that there was no significant difference in mortality between the AT2 group and the control group, and baseline characteristics differed between the two groups. Overall, the study concluded that AT2 was not associated with improved mortality or organ dysfunction in patients with severe shock. [Extracted from the article]

[Display omitted] • Investigates the impact of clonazepam on Megaselia scalaris larval development for PMI estimation. • Utilizes the S9 fraction to assess the effect on larval growth of Phase I and II metabolites. • Megaselia scalaris larvae exposed to clonazepam show accelerated development. • Findings suggest potential accuracy implications for PMI estimation in forensic cases. Fly colonization patterns and development are crucial in estimating the post-mortem interval (PMI) of decomposing corpses. Understanding the potential effects of xenobiotics on species development in cadaveric entomofauna is essential for accurate PMI estimation, given their presence in decomposing bodies. Benzodiazepines, commonly prescribed for their anxiolytic, hypnotic, and muscle relaxant effects, are of forensic interest due to their potential for abuse, dependence, intoxication, and overdose-related deaths. This study aimed to explore the effect of clonazepam and its metabolites on Megaselia scalaris , a species commonly used to estimate PMI, the alteration of which could impact the accuracy of said estimation. The S9 biotransformation fraction, an in vitro model consisting of an array of metabolic enzymes, was used to generate phase I and II metabolites for evaluating their effect on M. scalaris development, representing an innovative approach to this type of study. Megaselia scalaris larvae were reared in synthetic growth media under controlled conditions. The study compared different groups: control, clonazepam, and clonazepam with S9 fraction. Larvae were measured daily to determine growth rate, and clonazepam concentrations were analyzed using HPLC-DAD. Results showed that larvae grown in media containing clonazepam or clonazepam with S9 fraction developed faster than control larvae, reaching their pupal stage earlier. Growth rates were also altered in treated groups. In conclusion, the presence of clonazepam and its metabolites accelerated the life cycle of M. scalaris , potentially impacting the accuracy of PMI estimation. These findings underscore the importance of considering xenobiotics in forensic entomological studies for precise post-mortem interval determination. [ABSTRACT FROM AUTHOR]

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Objectives: Among residents who had a residential medication management review (RMMR), there is a lack of studies assessing exposure to polypharmacy and potentially inappropriate medications (PIMs) in people with dementia. This study compared the exposure to polypharmacy and PIMs in residents with dementia and without dementia receiving RMMR. Methods: A retrospective analysis was performed using data of 16,261 residents living in 343 Australian residential aged care facilities who had an RMMR in 2019. Medication use was assessed as polypharmacy (defined as ≥9 medications) and use of ≥1 PIMs using the 2019 updated Beers criteria. Dementia diagnosis was determined with ICD‐10 coding from medical records. Descriptive analyses reported resident demographics and patterns of medication use. Pearson's χ2 tests and logistic regression analysis were conducted to compare medication exposure between residents with and without dementia. Results: Among 16,261 residents, 6781 (42%) had dementia. Residents with dementia were significantly more likely to be exposed to polypharmacy and PIMs, compared to those without dementia (74% vs. 70% and 83% vs. 73%, p <.001 respectively). Residents with dementia had 1.31 times the odds of exposure to polypharmacy (adjusted OR: 1.31, 95% CI: 1.22–1.41, p <.001) and 1.88 times the odds of being prescribed ≥1 PIMs than people without dementia (adjusted OR: 1.88, 95% CI: 1.73–2.04, p <.001). Conclusions: In a study of residents receiving RMMR, polypharmacy and PIMs were highly common, and those with dementia were more likely to be exposed to inappropriate polypharmacy. There is a need for targeted deprescribing strategies to immediately address inappropriate prescribing in residents, particularly those living with dementia. [ABSTRACT FROM AUTHOR]