Search

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.

Background: Remimazolam tosilate represents the novel ultrashort-acting benzodiazepine drug. This work focused on exploring whether remimazolam tosilate was effective and safe in anesthesia for short otolaryngology surgery in adults, and optimize its medication regimen, thus providing a theoretical basis for its widespread clinical application. Methods: The present unicentric, double-blind, randomized controlled study enrolled altogether 85 otolaryngology surgery patients aged 18–60 years, and they were divided as remimazolam (RM, 42 cases) or midazolam (MD, 43 cases) group. Efficacy outcomes included successful sedation time, sedation effect (Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score), bispectral index values (BIS), and postoperative recovery. The safety outcomes were patient vital signs at each time point (before induction (T0), 2 min and 5 min after trial drug treatment (T1 and T2 separately), during successful intubation (T3), at the end of surgery (T4), during extubation (T5), and at the time of exiting the room (T6)), any adverse reactions (AEs) during perioperative period, and patient satisfaction with anesthesia experience. Results: Demographics were not significantly different in both groups (P > 0.05). RM group had significantly decreased successful sedation time relative to MD group (P < 0.05), while increased successful sedation rate (100%) relative to MD group (90.70%, P = 0.116). RM group showed decreased MOAA/S score and BIS value compared with MD group at T1 and T2 (P < 0.05). The spontaneous respiration recovery time and extubation time were not significantly different in both groups (P > 0.05), but RM group exhibited decreased discharge time compared with MD group (P < 0.05). Compared with MD group, the RM group had lower blood pressure (BP) at T3 (P < 0.05); whereas higher heart rate (HR) and respiration rate (RR) at T1 and T2 (P < 0.05). Difference in AEs was not of statistical significance. Finally, RM group exhibited the increased satisfaction of anesthesia experience compared with MD group (P < 0.05). Conclusion: Remimazolam tosilate is effective on anesthesia for short otolaryngology surgery. Remimazolam shows the rapid onset, stable circulation, fast postoperative recovery, no increase in perioperative AEs, and high satisfaction with anesthesia experience compared with midazolam. Trial Registration: https://www.chictr.org.cn/ (ChiCTR2200067123) on 27/12/2022. This study was consistent with CONSORT guidelines. [ABSTRACT FROM AUTHOR]

Background: Medication for mental health problems represents a significant proportion of overall medication use and the prescription of psychotropic medicine has increased in many western countries over the last decades. Childhood violence (CV) is strongly associated with mental health problems, which in turn may increase the likelihood of being prescribed psychotropic medication. However, the association between CV and prescription of benzodiazepines (BDZ) and antidepressants is rarely described, and no such study has been performed among the Indigenous Sami people. Methods: Data from the SAMINOR 2 Questionnaire Survey (2012) was linked to the Norwegian Prescription Database. Information on filled prescriptions for BDZ and antidepressants in 2004–2019 was collected for 11,296 persons (55.8% women, 22.6% Sami). Gender-stratified chi-square tests and two-sample t-tests were used to test for differences between groups. Logistic regression was applied to investigate the association between CV and filled prescriptions for BDZ and antidepressants. Results: During the 16-year study period, 16.7% of all women filled at least one prescription for BDZ. The figures were significantly lower among Sami women (14.1%) compared to non-Sami women (17.4%) (p =.003). Among all women, 23.6% filled at least one prescription for antidepressants, with no difference between ethnic groups. Filled prescriptions among men were 10.0% and 14.2%, respectively, with no difference between ethnic groups. During each year, and in total, a significantly higher proportion of women exposed to CV received at least one prescription for BDZ and antidepressants, respectively, compared to women not exposed to CV, with no differences between ethnic groups. Among men, the pattern was similar. Conclusion: A lower proportion of Sami women filled prescriptions for BDZ than non-Sami women. Those who reported exposure to CV filled prescriptions for BDZ and antidepressants more often than those who did not report CV. There were no overall differences between Sami and non-Sami; the dispensing rates of antidepressants and BDZ were similar for Sami and non-Sami, and the effects of CV on the dispensing of antidepressants and BDZ were also similar. This study highlights the importance of preventing CV, and of identifying a history of CV when treating adults with mental health problems. [ABSTRACT FROM AUTHOR]

Delirium after solid organ transplantation is an important factor affecting the prognosis of organ transplant recipients, but it lacks sufficient clinical attention at present. The pathophysiological mechanisms are not yet clear, which are closely related to the type of transplant organ, recipient's age, blood glucose variability, high-dose glucocorticoid therapy, and other factors. It is crucial to identify and early intervene the risk factors for delirium after solid organ transplantation for improving patients' prognosis. This article reviewed the literature on delirium after solid organ transplantation in recent years at home and abroad, clarified the definition, classification, clinical manifestations, and diagnostic criteria of postoperative delirium, summarized the risk factors for delirium after solid organ transplantation, highlighted the characteristics of transplant recipients that are different from other patients, and summarized their prognosis and prevention and treatment methods. The aim is to enhance clinical attention to delirium after solid organ transplantation and improve the prognosis of recipients. [ABSTRACT FROM AUTHOR]

Introduction: Racial and ethnic disparities in potentially inappropriate medication (PIM) use among older adults with dementia are unclear. Methods: Data were drawn from the baseline visits of participants who were ≥60 years old and diagnosed with dementia in the National Alzheimer's Coordinating Center Uniform Data Set (NACCUDS) recruited from National Institute on Aging (NIA)‐funded Alzheimer's Disease Research Centers (ADCs) throughout the United States. PIM utilization was evaluated using the 2019 American Geriatrics Society Beers Criteria for PIM Use in Older Adults. We estimated the association between race and ethnicity and the following outcomes and estimation models: (1) any PIM use, any PIM in each drug class, and any PIM best avoided in dementia patients using logistic regression models, (2) total number of medications, total number of PIMs, and anticholinergic burden scale (ACBS) using Poisson or negative binomial regression models, and (3) proportion of total medications that were PIMs using generalized linear models (GLM). Results: Compared to White participants, Black, Hispanic, and Asian participants reported taking fewer total medications (incidence rate ratio [IRR] ± standard error[SE] = 0.903 ± 0.017, 0.875 ± 0.021, and 0.912 ± 0.041, respectively, all p < 0.01). Asian participants were less likely to be exposed to any PIM (odds ratio [OR] ± SE = 0.619 ± 0.118, p < 0.05). Compared to White participants, Black participants were less likely to be exposed to benzodiazepine (OR ± SE = 0.609 ± 0.094, p < 0.01) and antidepressant (OR ± SE = 0.416 ± 0.103, p < 0.001) PIMs, but greater antipsychotic (OR ± SE = 1.496 ± 0.204, p < 0.01), cardiovascular (OR ± SE = 2.193 ± 0.255, p < 0.001), and skeletal muscle relaxant (OR ± SE = 2.977 ± 0.860, p < 0.001) PIMs. Hispanic participants were exposed to greater skeletal muscle relaxant PIMs and had lower anticholinergic burden. Asian participants were exposed to fewer benzodiazepine PIMs. Discussion: Significant racial and ethnic disparities in exposure to PIMs and PIMs by medication category in dementia research participants who have access to dementia experts found in the study suggest that disparities may be wider in the larger community. [ABSTRACT FROM AUTHOR]

Data are accumulating on the hydrolytic activity of serum albumin towards esters and organophosphates. Previously, with the help of the technology of proton nuclear magnetic resonance (1H NMR) spectroscopy, we observed the yield of acetate in the solution of bovine serum albumin and p-nitrophenyl acetate (NPA). Thus, we showed that albumin possesses true esterase activity towards NPA. Then, using the methods of molecular docking and molecular dynamics, we established site Sudlow I as the catalytic center of true esterase activity of albumin. In the present work, to expand our understanding of the molecular mechanisms of albumin pseudoesterase and true esterase activity, we investigated—in experiments in vitro and in silico—the interaction of anticoagulant warfarin (WRF, specific ligand of site Sudlow I) and benzodiazepine diazepam (DIA, specific ligand of site Sudlow II) with albumins of different species, and determined how the binding of WRF and DIA affects the hydrolysis of NPA by albumin. It was found that the characteristics of the binding modes of WRF in site Sudlow I and DIA in site Sudlow II of human (HSA), bovine (BSA), and rat (RSA) albumins have species differences, which are more pronounced for site Sudlow I compared to site Sudlow II, and less pronounced between HSA and RSA compared to BSA. WRF competitively inhibits true esterase activity of site Sudlow I towards NPA and does not affect the functioning of site Sudlow II. Diazepam can slow down true esterase activity of site Sudlow I in noncompetitive manner. It was concluded that site Sudlow I is more receptive to allosteric modulation compared to site Sudlow II. [ABSTRACT FROM AUTHOR]

Catatonia is a neuropsychiatric syndrome that is an increasingly recognized cause of acute behavioural changes in children and adolescents with neurodevelopmental disorders (NDD). Literature suggests that catatonia can present differently in this population and can be missed due to diagnostic overshadowing. Catatonia is a treatable condition, and management strategies in children with NDD include benzodiazepines and electroconvulsive therapy (ECT). Untreated, it can cause significant morbidity including severe medical complications, and therefore timely recognition and management of catatonia in children and adolescents with NDD is essential. In this case series, we present three cases of children ages 7, 14, and 10, with diagnoses of autism spectrum disorder, Down syndrome, and Prader-Willi syndrome, respectively. All were admitted to a pediatric inpatient unit for acute behavioural regression. Each had symptoms consistent with catatonia, resulting in trials of benzodiazepine therapy with inadequate response, and were then treated with bilateral ECT. In all cases, marked improvement was noted after ECT, with no apparent adverse effects. The cases are used to highlight the nuances of diagnosis and management of catatonia in children and adolescents with NDD. This includes insights on how presentations of catatonia may differ in this population, challenges with the use of available diagnostic tools, and how these patients may respond differently to recommended treatments such as benzodiazepines. The case series aims to increase clinicians' awareness of pediatric catatonia when children and adolescents with NDD present with acute behavioural changes, and to encourage consideration of the full spectrum of treatments, including bilateral ECT. [ABSTRACT FROM AUTHOR]

This article reports the findings of an online survey designed to collect information about substance use (licit, illicit, or pharmaceutical) and mental health (depression or anxiety) among social workers. Among the 489 participants, Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) screenings indicated symptoms of depression and anxiety at a higher prevalence than those of the general Canadian population. There were relatively few correlations between mental health scores and substance use. PHQ-9 total score significantly predicted past-year antidepressant use and past-year sleeping medication use. GAD-7 total score significantly predicted past-year benzodiazepine use and past-year melatonin use. Effects of substances (e.g. cannabis, alcohol, benzodiazepines, cocaine, ecstasy) were predominantly beneficial or nonproblematic (e.g. enjoyment/pleasure; socializing enhanced; concentration/focus improved). Subjective experiences of social workers should be sought to understand potential relationships between mental health scores and enhancement effects of substance use. Substances are being used, at least in part, for their performance-enhancing effects to meet the expectations of day-to-day life. Interventions can shift toward root causes, with institutions held more accountable for supporting social workers and promoting "workplace care." [ABSTRACT FROM AUTHOR]

Background: Delirium, which is prevalent in critical care settings, remains underexplored in acute coronary syndrome (ACS) patients in the cardiac intensive care unit (CICU). Aim: To investigate the prevalence and clinical significance of delirium in patients with ACS admitted to the CICU. Study Design: A prospective study (n = 106, mean age 74.2 ± 5.7 years) assessed delirium using the confusion assessment method‐intensive care unit (CAM‐ICU) tool in 21.7% of ACS patients during their CICU stay. Baseline characteristics, geriatric conditions and clinical procedures were compared between delirious and nondelirious patients. The outcomes included in‐hospital mortality, 30‐day and 6‐month mortality, acute adverse events and length of CICU stay and hospital stay (LOS). Results: Delirious patients who were older and had a higher incidence of coronary artery disease underwent more complex procedures (e.g., pacemaker placement). Multivariate analysis identified central venous catheter insertion, urinary catheterization and benzodiazepine use as independent predictors of delirium. Delirium was correlated with prolonged LOS (p <.001) and increased in‐hospital, 30‐day and 6‐month mortality (p <.001). Conclusions: Delirium in ACS patients in the CICU extends hospitalization and increases in‐hospital, 30‐day and 6‐month mortality. Early recognition and targeted interventions are crucial for mitigating adverse outcomes in this high‐risk population. Relevance to Clinical Practice: This study highlights the critical impact of delirium on outcomes in hospitalized patients with ACS in the CICU. Delirium, often overlooked in ACS management, significantly extends hospitalization and increases mortality rates. Nurses and physicians must be vigilant in identifying delirium early, particularly in older ACS patients or those with comorbidities. Recognizing independent predictors such as catheterization and benzodiazepine use allows for targeted interventions to reduce delirium incidence. Integrating routine delirium assessments and preventive strategies into ACS management protocols can improve outcomes, optimize resource utilization and enhance overall patient care in the CICU setting. [ABSTRACT FROM AUTHOR]

Background: The misuse of psychotropic medication has increased during the past decade, especially among adolescents. The aim of our study was to describe the prevalence and patterns of the nonmedical use of benzodiazepines (BDZ) and Z‐hypnotics among school‐aged adolescents through the lens of sex. In addition, we sought to analyze the temporal evolution of the nonmedical use of these drugs during the period 2016–2021. Methods: The temporal evolution of the nonmedical use of these drugs was analyzed based on survey data collected in 2016, 2018 and 2021, which includes the first years of the COVID‐19 pandemic. To assess the possible effect of the COVID‐19 pandemic, the year at survey was conducted was introduced as a categorical variable. We used data from the Spanish State Survey on Drug Use in Secondary Education, which covers drug use among students aged 14–18 years. Using multivariate logistic regression models, we estimated the independent effect of different variables (sociodemographic data, use of other psychoactive substances, risk perception and availability) on the nonmedical use of BDZ and Z‐hypnotics. Results: In total, survey data from 95,700 adolescents were included in our analysis. The nonmedical use of BDZ and Z‐hypnotics increased among adolescents during the study period. The adjusted odds ratio (AOR) from 2016 to 2018 was 1.11 (95% CI 0.94–1.31) and from 2018 to 2021 the AOR was 1.26 (95% CI 1.08–1.46), using 2016 and 2018, respectively, as reference years. The nonmedical use of BDZ and Z‐hypnotics was more likely in adolescent girls than boys (AOR = 2.11). The nonmedical use of prescription opioids (AOR = 3.44), novel psychoactive substances and other illicit psychoactive drugs (AOR = 4.10) were risk factors for the nonmedical use of BDZ and Z‐hypnotics in both sexes. Use of cannabis (AOR = 1.38) was a predictor of nonmedical use in female adolescents only. Conclusions: This study shows that the trend of the nonmedical use of BDZ and Z‐hypnotics among school‐aged adolescents in Spain increased between 2016 and 2021. Among adolescents aged 14 to 18, the probability of nonmedical use of these psychoactive substances was twice as high for female adolescents as for male adolescents. [ABSTRACT FROM AUTHOR]

Given the high rates of physical trauma and pain among service members, opioid-prescribing practices and use patterns have significant implications for the well-being of service members and can affect military medicine and personnel readiness. This study measured the association between prescribed opioid and benzodiazepine medications and subsequently reported injuries (accidental, alcohol and drug related, self-inflicted, and violence related) among active duty military members. Participants were service members who entered the military between January 1, 2005, and June 30, 2010. In a nested case–control design, we compared individuals with injuries to individuals without injuries with respect to their opioid and benzodiazepine prescriptions in the 30 days before the injury of an index case. We used a multiintercept, logistic regression model to compare coefficient estimates by injury type. Overall, approximately 17% of individuals with an injury and 4% of individuals without an injury had a recorded opioid prescription. Individuals with an injury of any type had greater odds of prior exposure to opioid prescriptions than controls. Although a dose–response effect was observed for all injury types, it reached a plateau sooner for natural or environmental accidents and selfinflicted injuries relative to alcohol-related and drug-related injuries, violence-related injuries, vehicle accidents, accidental falls, and other accidents. Benzodiazepine prescriptions were found in 3.5% of individuals with an injury and 0.5% of individuals without an injury. The association between benzodiazepine prescriptions and injuries was strongest for natural and environmental accidents. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy (AC) for colorectal cancer (CRC) has led to substantial improvement in survival. Several clinical trials advocate the initiation of AC within 6-8 weeks of surgical resection based on evidence of improved survival with early initiation of AC. We aim to evaluate factors that predict initiation and completion of AC, subsequently improving survival. Methods: We identified 451 patients who underwent resection for CRC between 2014 and 2022. One hundred ten patients had stage II/III colorectal cancer who underwent resection followed by AC. Multivariable logistic regression analysis was performed to identify factors significantly predicting delay in AC >8 weeks. Secondary outcomes included chemotherapy completion rate, recurrence-free survival, and overall survival. Results: The final analysis included 110 patients. The median time to initiation of adjuvant chemotherapy (TIAC) was 6.9 weeks (IQR: 5.8-9.5). In total, 36.4% of patients had a delay >8 weeks to initiation of AC, and only 40% completed treatment. The surgical approach (open vs laparoscopic vs robotic) had no effect on the TIAC. On multivariable logistic regression analysis, preoperative albumin ≥3.5 (OR = .31; 95% CI: .12-.80) was an independent predictor of timely initiation of AC. Completion of AC was associated with a higher overall survival. Discussion: Preoperative nutritional status predicted delay in initiation of AC. Patients with a delay in AC beyond eight weeks had a lower rate of AC completions and worse survival. It is imperative to optimize this aspect of treatment as it correlates with survival. [ABSTRACT FROM AUTHOR]

A population‐based cohort study has found that concomitant use of antidepressants and benzodiazepines in the first trimester of pregnancy did not substantially increase risk overall for congenital malformations. Digestive system malformations were the only defects for which a significant risk remained in adjusted analyses. Study results were published online July 2, 2024, in Lancet Psychiatry. [ABSTRACT FROM AUTHOR]

Deaths due to unintentional opioid overdose among youth living in the United States have risen at an extraordinary rate over the past 4 years.1 After remaining stable over the preceding decade, the rate of drug overdose deaths increased more than 2.3-fold from 2019 to 2021 to a record high of 5.49 deaths per 100,000 youth.1 This rise in fatal overdoses is largely due to increased prevalence of illicitly manufactured fentanyl in the drug supply. In 2021, fentanyl was identified in 77.1% of overdose deaths among US adolescents, a 23.5-fold increase from 2010, compared to 13.3% for benzodiazepines, 5.8% for prescription opioids, and 2.3% for heroin.1 Compared to other phases of the opioid crisis, fentanyl-related overdoses are characterized by extraordinarily broad geographic and sociodemographic reach. [ABSTRACT FROM AUTHOR]

Alcohol use disorder is associated with a variety of complications, including alcohol withdrawal syndrome (AWS), which may occur in those who decrease or stop alcohol consumption suddenly. AWS is associated with a range of signs and symptoms, which are most commonly treated with GABAergic medications. Is phenobarbital an effective treatment for AWS? Studies retrieved included two prospective, randomized, double-blind studies and three systematic reviews. These studies provided estimates of the effectiveness and safety of phenobarbital for treatment of AWS. Based on the available literature, phenobarbital is reasonable to consider for treatment of AWS. Clinicians must consider the individual patient, clinical situation, and comorbidities when selecting a medication for treatment of AWS. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed benzodiazepine use, rapid inpatient tapers are typically the only option to treat benzodiazepine withdrawal. Substance use disorder bridge clinics can provide the high-touch care needed to manage outpatient benzodiazepine tapers in patients at high risk due to other substance use disorders. Objective: Describe the implementation and short-term outcomes of an outpatient benzodiazepine taper protocol to treat benzodiazepine withdrawal in a substance use disorder bridge clinic. Methods: The clinical team developed a 4- to 6-week intensive outpatient taper protocol using diazepam. Patients with benzodiazepine use disorder were eligible if they had benzodiazepine withdrawal, lacked a prescriber, wanted to stop benzodiazepines completely, and agreed to daily visits. For patients who initiated a taper between April 2021 and December 2022, we evaluated the proportion of patients who completed a taper (i.e., tapered to a last prescribed dose of diazepam 10 mg/d or less); likelihood of remaining on the taper over time; and seizure, overdose, or death documented at the study institution during or within 1 month of taper completion or discontinuation. Other sec- ondary outcomes included HIV testing and prevention, hepatitis C testing, and referrals to recovery coaching or psychiatry. Results: Fifty-four patients initiated a total of 60 benzodiazepine tapers. The population was mostly male (61%) and non-Hispanic White (85%). Nearly all patients had opioid use disorder (96%), and most (80%) were taking methadone or buprenorphine for opioid use disorder before starting the taper. Patients reported using multiple substances in addition to benzodiazepines, most commonly fentanyl (75%), followed by cocaine (41%) andmethamphetamine (21%). Fourteen patients (23%) completed a taper with a median duration of 34 days (IQR 27.8--43.5). Most tapers were stopped when the patient was lost to follow-up (57%), or the team recommended inpatient care (18%). Two patients had a seizure, and 4 had a presumed opioid-involved overdose during or within 1 month after the last taper visit, all individuals who did not complete a taper. No deaths occurred during or within 1 month of taper completion or discontinuation. Challenges included frequent loss to follow-up in the setting of other unstable substance use. Patients received other high-priority care during the taper including HIV testing (32%), PrEP initiation (6.7%), hepatitis C testing (30%), and referrals to recovery coaches (18%) and psychiatry (6.7%). Conclusions:Managing benzodiazepine withdrawal with a 4- to 6-week intensive outpatient taper in patients with benzodiazepine and opioid use disorders is challenging. More work is needed to refine patient selection, balance safety risks with feasibility, and study long-term, patient-centered outcomes. [ABSTRACT FROM AUTHOR]

Aim: Benzodiazepine prescription is a growing phenomenon among the elderly population. However, information related to the frequency of these drugs among the elderly population attending in emergency departments (ED) and its impact over prognosis is scarce. The aim of this study is to assess the prevalence of benzodiazepine prescription and to analyze its association with short‐term prognosis in elderly patients attended in ED. Methods: A retrospective analysis of the EDEN (Emergency Department Elderly in Need) cohort was conducted. This registry included all elderly patients attending in 52 Spanish EDs for any condition, between April 1st and 7th in 2019. Socio‐demographic data, comorbidities, and medication were recorded by consulting the patient's electronic health records. The assessed outcomes consisted on new ED visit, hospitalization, and mortality at 30 days after the first ED visit, associated with the use of benzodiazepines at baseline in comparison with no prescription of benzodiazepines. Crude and adjusted logistic regression analyses including patient's comorbidities were performed. Two sensitivity analyses were performed considering concomitant prescription of other central nervous system depressants as well as direct discharge from the ED. Results: 25 557 patients were evaluated (mean age 78 [IQR: 71–84]). 7865 (30.8%) patients were taken benzodiazepines at admission. After adjustment for comorbidities and other central nervous system drugs, benzodiazepine prescription was associated with ED revisit [OR: 1.10 (95%CI: 1.03–1.18)]. Similar results were found in the sensitivity analysis, eliminating patients with central nervous depressors [OR: 1.11 (1.03–1.25)] and patients discharged to home [OR: 1.13 (1.04–1.23)]. No association was found between the use of these drugs and new hospitalizations [OR: 0.90 (0.77–1.05)] or mortality 30 days after discharge [OR: 1.01 (0.88–1.18)]. The results held for all three outcomes in the sensitivity analyses. Conclusion: The use of benzodiazepines is a frequent phenomenon among the elderly population attended in the ED, being associated with an increased risk of new visits to the emergency room, but not with an increased risk of 30‐day hospitalization or mortality. [ABSTRACT FROM AUTHOR]

Background: Incident benzodiazepine prescriptions in primary care for anxiety decreased between 2003 and 2018. However, from 2008, incident prescribing of benzodiazepines for anxiety increased among those aged 18–34 years. There are increasing concerns around prescribing of benzodiazepines. Further, although guidelines state benzodiazepines should only be prescribed short term, in 2017, 44% of incident prescriptions were prescribed for longer than the recommended duration of 2–4 weeks. Aim: To understand when and why GPs prescribe benzodiazepines for anxiety in young adults. Design and setting: A qualitative study was undertaken using in-depth interviews with 17 GPs from 10 general practices in South West England. Method: Interviews were conducted by telephone or videocall. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and data analysed using reflexive thematic analysis. Results: GPs described caution in prescribing benzodiazepines for anxiety in young adults, but thought they had an important role in acute situations. GPs described caution in prescribing duration, but some thought longer-term prescriptions could be appropriate. In light of these views, some GPs questioned whether primary care needs to revisit how clinicians are using benzodiazepines. GPs perceived that some young adults requested benzodiazepines and suggested this might be because they wanted quick symptom relief. GPs noted that refusing to prescribe felt uncomfortable and that the number of young adults presenting to general practice, already dependent on benzodiazepines, had increased. Conclusion: Patient-driven factors for prescribing benzodiazepines suggest there are current unmet treatment needs among young adults with anxiety. Given increases in prescribing in this age group, it may be timely to revisit the role of benzodiazepines in the management of people with anxiety in primary care. [ABSTRACT FROM AUTHOR]

Background: Chronic treatment-resistant depression (TRD) poses a major challenge for clinicians. Ketamine has shown a rapid but short-lived antidepressant effect in several studies involving TRD patients with different demographic and clinical profiles. Our study aimed to assess the antidepressant effect of serial infusion sessions of ketamine in patients with chronic TRD and evaluate the severity of symptoms after relapse and the general psychiatric health of the responding patients. Methods: In this single arm open-label study, six infusions of ketamine at 0.5 mg/kg were administered to chronic TRD patients for approximately two weeks. Response and remission rates, side effects, adverse events and after-relapse symptoms were evaluated, and patients were followed for three months. Results: 23 patients underwent at least one infusion session, and 18 patients completed the six sessions. Twelve (66.67%) patients responded to the treatment at some point, and 11 (61.11%) patients maintained response after the end of the treatment protocol. One infusion was not sufficient to achieve a response (P > 0.9999, z = 1.81), and more than half of the responders met the response criteria after the third infusion. Only one patient (5.56%) achieved remission at the end of the infusion phase. All but one ketamine responders relapsed within one month after the end of the treatment. There was no statistical difference between baseline and after-relapse MADRS scores (P = 0.7886, 95% CI=-5.512-4.312, R2 = 0,008411). However, a high incidence of serious adverse events related to suicidality was evident; one of the non-responding patients attempted suicide and several attempts to sedate this patient with benzodiazepines failed. Two responding patients ended up with a suicidal attempt or severe suicidal thoughts. Conclusions: Introducing rapid-acting antidepressant to manage TRD patients in clinical practice demands further investigation, and the benefit-to-harm ratio should be assessed in the light of the increased risk of suicidality. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to observe whether there is a difference in the anesthetic effect of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery, so as to provide reference for clinical application. Methods: Fifty patients, aged 18–65 years, ASA I-II, scheduled for hysteroscopy under total intravenous anesthesia were selected. The patients were randomly divided into two groups (n = 25): remimazolam tosilate group (group T) and remimazolam besylate group (group R). The main observation index was the induction dose of remimazolam; secondary observation indicators were sleep time, anesthesia maintenance time, recovery time, induction maintenance dose of alfentanil, maintenance dose of remimazolam, and incidence of adverse events during anesthesia (hypertension, hypotension, bradycardia, tachycardia). Results: There was no significant difference in anesthesia induction dose, recovery time, sleep time, anesthesia maintenance time, and incidence of adverse events during anesthesia (body movement, cough, hypertension, hypotension, bradycardia, tachycardia) between the two groups (P > 0.05). Conclusion: There was no significant difference in the anesthetic effect of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery. Clinical trial Registration: Chinese Clinical Trial Registry, ChiCTR2400081688. [ABSTRACT FROM AUTHOR]

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]

Background: Status epilepticus (SE) is defined as 5 min or more of seizure activity or two recurrent seizures without a return to baseline. Healthcare providers encounter a challenge when a patient with SE is pregnant. SE is not only detrimental to the mother but can also put the baby at risk of severe harm. SE must be treated rapidly and therefore healthcare providers have very little time to thoroughly review the risk and benefits of available antiseizure medication in this population. Aim: To evaluate the current available evidence related to the management of SE in pregnancy. Design: A literature search of PubMed, CINAHL, ProQuest Nursing & Allied Health Source, and Web of Science databases was conducted (2012–2022) using the following search terms: 'pregnancy', 'pregnant women' OR 'gestation' AND 'status epilepticus', 'generalized status epilepticus', 'generalized convulsive status epilepticus', 'non convulsive status epilepticus' OR 'non‐convulsive status epilepticus'. Full‐text randomised controlled trials, clinical trials, observational studies, and case reports published in English were included. Data were extracted and the quality of the studies was evaluated using the Mixed Methods Appraisal Tool. Results: The literature described 29 pregnancies and 30 total foetuses. Intravenous benzodiazepine use for emergent control was reported in 45% of patients. Phenytoin and levetiracetam were primarily utilised for urgent control, with a variety of agents used for refractory SE. Ninety‐seven percent of maternal outcomes were reported as positive. The most common outcome was the birth of a healthy term infant. There were seven cases of pregnancy loss. Conclusion: Publications pertaining to the treatment of SE in pregnancy are limited to case reports and small observational studies. Use of a benzodiazepine followed by levetiracetam or phenytoin is appropriate, whereas valproic acid should be utilised only when necessary due to the risk of major congenital malformation. [ABSTRACT FROM AUTHOR]

Background: Remimazolam, an ultra-short-acting anesthetic with flumazenil as a reversal agent, typically facilitates patient awakening postoperatively. However, our case reveals an unusual occurrence: despite flumazenil initially restoring consciousness, re-sedation due to remimazolam ensued six hours later. Case: A 65-year-old woman underwent total intravenous general anesthesia with remimazolam and remifentanil during the 140-min surgery. Despite an initially smooth recovery, she progressively became drowsy upon transfer to the general ward, eventually reaching a stuporous state. Multiple interventions, including opioid reversal (intravenous patient-controlled analgesia discontinuation, and naloxone administration) were attempted. Neurological consultation revealed no issues; however, immediate improvement after flumazenil administration suggested remimazolam’s involvement. The patient was discharged without complications. Conclusions: This case challenges our understanding of remimazolam’s dynamics, emphasizing the necessity for vigilant post-anesthesia monitoring, even in seemingly low-risk cases. It advocates for standardized response protocols to promptly manage unforeseen events and ensure patient safety. [ABSTRACT FROM AUTHOR]

For the past 60 years, benzodiazepines such as chlordiazepoxide, diazepam, and alprazolam have been used as pharmaceutical medications for the treatment of myriad conditions including anxiety, seizures, and insomnia. In more recent years, novel benzodiazepine derivatives have emerged as illicit substances in powders and counterfeit tablets on the illicit drug market. In 2016, bromazolam, a brominated derivative of alprazolam, emerged on the illicit drug market in Europe, but the substance was not reported in the USA until 2019–2020. In this study, we report the emergence and subsequent prevalence of bromazolam in postmortem blood in the state of Indiana during 2023. Analysis was completed by a solvent protein precipitation extraction with acetonitrile and detection by liquid chromatography with quadrupole time of flight mass spectrometry. During 2023, bromazolam was detected in 94 cases across 25 counties in Indiana. It was never the sole substance detected and was commonly detected alongside fentanyl (83 cases), norfentanyl (77 cases), 4-anilino- N -phenethylpiperidine (76 cases), acetylfentanyl (49 cases), methamphetamine (32 cases), naloxone (25 cases), 11-nor-9-carboxy-tetrahydrocannabinol (24 cases), and benzoylecgonine (20 cases). After official query with the Indiana Department of Health, it was found that bromazolam was specifically included in the cause of death certification in 31 fatalities (32.9%). Due to the scarcity of information regarding this novel benzodiazepine derivative in postmortem toxicology and its involvement in fatalities, it is important that forensic toxicology laboratories consider adding bromazolam to their comprehensive scope of analysis. [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]

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: The number of methamphetamine-related deaths has been increasing in recent decades. However, current data primarily rely on a few large-scale national surveys, highlighting the need for diverse data sources. Post-mortem studies offer advantages that compensate for the limitations of cohort studies. In this study, we aimed to (1) examine mortality rates and years of potential life lost, (2) compare proportionate mortality with previous cohort studies, and (3) quantitatively investigate causes of death as potential risk factors associated with each manner of death. Methods: We analyzed 740 cases from 2013 to 2019 in Taiwan. Results: The mean age of cases was 38.4 years, with a notable loss of 30 or more years of potential life, and 79.6% were male. The crude mortality rate was 0.45 per 100,000 person-years. The proportionate mortality indicated that autopsy dataset, compared to cohort studies, provided more accurate estimations for accidental deaths, equivalent suicides, underestimated natural deaths, and overestimated homicides. Accidental deaths were evident in 67% of cases with 80% attributed to drug intoxication. Multiple substances were detected in 61% of cases, with psychiatric medications detected in 43% of cases. Higher methamphetamine concentrations and a greater proportion of multiple substances and benzodiazepines were detected in suicidal deaths. Among accidental deaths, traffic accidents (7.9%) were the second most common cause, particularly motorcycle riders. Conclusion: Using autopsy dataset as a secondary source, we identified that over half of the cases involved drug intoxicationrelated accidental deaths. The significant proportion of cases involving multiple substances, psychiatric medications, and drugimpaired driving raises concerns. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and mental health issues. It affects approximately 1.78% of the general population; an estimated 4:1 ratio between women and men is observed. It significantly impacts quality of life and carries both clinical and social stigma. This study aims to evaluate the relationship between drug use and mental health in female patients with fibromyalgia. Methods: This study is prospective, observational, and cross-sectional. A questionnaire was administered to 544 subjects, achieving a representative sample size from a population of 800,000 subjects by using an algorithm for proportion estimation with a known sampling frame. The selection was non-random, making the sampling non-probabilistic. Logistic regression models were applied to assess the effect of drug use on perception of mental health; presence of symptoms such as comprehension and memory problems, insomnia, depression, and anxiety; and severity of cognitive symptoms and non-restorative sleep. To quantify the impact, odds ratios and confidence intervals have been observed. Results: The findings indicate the non-recommended use of medications and reveal the ineffectiveness and adverse effects of drug interactions on mental health. The use of benzodiazepines and sedative-hypnotics is significantly associated with a negative perception of mental health. Benzodiazepines do not improve symptoms or significantly reduce their severity. SSRI antidepressants do not enhance mental health perception; however, when used exclusively, they are effective in reducing the severity, but not the prevalence, of cognitive symptoms. Conclusions: The results highlight the complexity of pharmacological management in FM and raise concerns about the inappropriate use of ineffective or counterproductive drug interactions affecting patients' mental health. They underscore the need for multidisciplinary and personalized strategies that include close and careful monitoring, as well as the simultaneous use of non-pharmacological treatments that have demonstrated evidence in improving quality of life without negatively affecting mental health, such as patient education, psychological therapy, physiotherapy, and mindfulness. [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]