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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]

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]

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]

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]

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]

Natural products derived from various sources, including plants, have garnered significant interest as alternative therapeutic options. Among these, Tualang honey, extracted from the nectar of Tualang trees (Koompassia excelsa (Becc.) Taub.), has a long history of traditional use due to its therapeutic properties. This review aims to examine the pharmacological activities of Tualang honey, encompassing both in vitro and in vivo studies. A systematic search was conducted in multiple databases, including PubMed, Springer, Scopus, Wiley, and Science Direct, up until December 2022 to identify relevant studies on the pharmacological activities of Tualang honey. Two independent reviewers were involved in article selection, followed by data extraction and assessment of methodological quality using Syrcle's risk of bias tool. 123 articles were included, collectively describing the pharmacological activities of Tualang honey, including antimicrobial, anticancer, anti-inflammatory, antioxidant, antinociceptive, neuroprotective effects, and others. Tualang honey has significant promise as an alternative treatment option for treating a wide range of pathological diseases due to its wide range of pharmacological properties. Tualang honey's diverse array of pharmacological actions indicates its potential for multiple medicinal uses. [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]

Assess the changes in post‐traumatic stress disorder (PTSD), burnout, anxiety, depression, jobstrain, and isostrain levels over time among healthcare workers in emergency departments (EDs) after successive outbreaks of COVID‐19. A prospective, multicenter study was conducted in 3 EDs and an emergency medical service. Healthcare workers who participated in our previous study were invited to participate in a follow‐up 16 and 18 months and completed the questionnaires to assess symptoms of PTSD, burnout, anxiety, depression, jobstrain, and isostrain. Among the 485 healthcare workers asked to participate, 211 (43.5%) completed the survey at inclusion (122 were followed up at 3 months) and 59 participate to the follow‐up study. At 16 months, 10.9% of healthcare workers had symptoms of PTSD and 17.4% at 18 months. At inclusion, 33.5% and 11.7% of healthcare workers had symptoms of anxiety and depression, respectively. A decrease in anxiety between inclusion and 16 months (p = 0.02) and an increase between 16 and 18 months (p = 0.009) was observed. At inclusion, 40.8% of all healthcare workers had symptoms of burnout. There was an increase in symptoms of burnout between inclusion and 18 months (p = 0.006). At inclusion, 43.2% and 29.5% of healthcare workers were exposed to jobstrain and isostrain, respectively. Jobstrain were higher among paramedics and administrative staff compared to physicians (p = 0.001 and p = 0.026, respectively). Successive outbreaks of COVID‐19 led to long‐term mental health consequences among ED healthcare workers that differed according to occupation. This must be taken into account to rethink the management of teams. [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]

Objective: The objective of this study was to determine the proportion of Australians dispensed psychotropic medications between 2013 and 2022 according to their age. Methods: Services Australia provided a de-identified 10% random Pharmaceutical Benefits Scheme sample that allowed us to determine, for each year, the proportion of Australians dispensed at least one script for antipsychotics, antidepressants, anxiolytics, or hypnotics. The classification of medications followed Anatomical Therapeutic Chemical coding. Participants were stratified into 10-year age groups from 0–9 to ⩾90 years, and sex was coded as male/female. We retrieved population numbers from the Australian Bureau of Statistics. Results: The number of records per year ranged from 1,540,520 to 1,746,402, and 54.10% were for females. A greater proportion of older adults, particularly those aged ⩾70 years, were dispensed antipsychotics, antidepressants, anxiolytics and hypnotics than any other age group. The proportion of people who dispensed antipsychotics, anxiolytics and hypnotics declined between 2013 and 2022 but increased for antidepressants, most markedly for adolescents and young adults. Females were more frequently dispensed antidepressants, anxiolytics and hypnotics than males, but males were more frequently dispensed antipsychotics than females, albeit not in later life. Conclusion: Older age groups and females are the most frequent recipients of psychotropic medications dispensed in Australia. [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]

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]

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]

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]

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]

Introduction Sleep-related disorders are associated with pain, fatigue, and deficits in cognitive performance, which may interfere with successful rehabilitation. The study objectives were to (1) quantify outpatient prescriptions for insomnia medications during the first year following combat-related amputations, (2) examine longitudinal changes in prescriptions for insomnia medications, and (3) analyze patient characteristics associated with prescriptions for insomnia medications. Material and Methods This was a retrospective study of DoD casualty records from the Expeditionary Medical Encounter Dataset and prescriptions for outpatient medications from the Pharmacy Data Transaction Service. Patients were a total of 1,651 U.S. service members who sustained major limb amputations in Operations Iraqi and Enduring Freedom from 2001 through 2017 and had outpatient prescriptions for any medication during the first year postinjury. Prescriptions for medications recommended for insomnia were low-dose antidepressants, anxiolytic sedatives, benzodiazepines, melatonin receptor agonist, and low-dose quetiapine. These prescription medications were analyzed by medication type, postinjury time, and patient characteristics during the first year postinjury. Results During the first year postinjury, 78% of patients (1,291 of 1,651) had outpatient prescriptions for insomnia medications, primarily anxiolytic sedative drugs (e.g. zolpidem), averaging a total of 86 prescription days (median = 66). The prevalence of these prescriptions declined substantially during the first year, from 57% of patients during the first quarter to 28% during the fourth quarter postinjury. In univariate analyses, multiple patient characteristics, including high Injury Severity Score, continued opioid and non-opioid analgesic prescriptions, and diagnoses of chronic pain, mood disorder, and posttraumatic stress disorder, were significantly associated with higher prevalence and duration of outpatient prescriptions for insomnia medications. Conclusions The present results indicate a high prevalence of outpatient prescriptions for insomnia medications following combat-related amputations, a prevalence that is substantially higher than previously reported among active duty personnel. These findings can inform DVA/DoD guidelines for amputation care and insomnia among military subpopulations. The results highlight the need for more research on the treatment of insomnia during early postinjury rehabilitation among patients who sustained serious combat injuries. [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]

The fruit of Morinda citrifolia, also known as the noni tree, has been extensively used in Polynesian culture as an alternative medicine to various diseases. Recent studies have pointed out its anxiolytic activity in vitro and in mouse models. Despite the effectiveness of developed anxiolytic drugs in the market, the potential side effects of these medications have led people to resort to traditional medicine such as M. citrifolia. However, evidence regarding its anti-anxiety characteristics is still lacking to this day. Hence, this preliminary study implemented combined network pharmacology and molecular docking to validate its anti-anxiety claims. This study highlighted the bioactive compounds of the M. citrifolia fruit part to have excellent absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, particularly their outstanding oral bioavailability and blood–brain barrier penetration, both of which are essential considerations to ensure the effectiveness of anxiolytic drugs to arrive at the site of action. Moreover, noni fruit metabolites target genes involved in glutamatergic synapse pathways, which have been significantly associated with anxiety. Through molecular docking, selected compounds exhibited a strong binding affinity towards GRIA2 and PRKCA, both of which have connections with glutamatergic pathways. With all things considered, the results established that the noni fruit potentially contains therapeutic agents that elicit anti-anxiety potential. Through this, the promotion of a more sustainable, accessible, and affordable treatment of anxiety could be developed. [ABSTRACT FROM AUTHOR]

Background People living in care homes often have problems with pain, anxiety and depression. Whether being on analgesia, anxiolytics or antidepressants has any bearing on pain severity and quality of life (QoL) in this population, requires further investigation. Objectives (i) to examine the relationship between pain, anxiety and depression and medication use in care home residents and (ii) to compare those on medications to treat pain, anxiety and depression, and those who were not, and associations with pain severity and overall QoL. Methods This was a secondary analysis of a randomised controlled trial testing a falls prevention intervention in care homes. We recorded pain, anxiety and depression, QoL measurements and prescribed medication use. Results In 1589 participants, the mean age was 84.7 years (±9.3 SD), 32.2% were male and 67.3% had a diagnosis of dementia. 54.3% and 53.2% of participants had some level of pain and anxiety or depression respectively, regardless of prescribed medication use. There was a direct association between pain severity and being on any analgesia, opioid analgesia, and antidepressants, but no associations between pain severity and use of paracetamol and anxiolytics. QoL was best for residents with no pain and not on any analgesia, anxiolytics or antidepressants and worst for those with moderate-extreme pain and taking at least two of these classes of medications. Conclusion Many care home residents live with pain, anxiety and depression. Addressing residents' pain may also increase their quality of life, but using medication alone to reach this goal may be inadequate. [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]

Purpose: Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels. Methods: A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression. Results: Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ2 = 96.36, p = 0.000). The n-3 index (χ2 = 10.59, p = 0.001), EPA (χ2 = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ2 = 10.71, p = 0.001) were increased, while C22:4n6 (χ2 = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05). Conclusion: These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms. [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]

Why you should read this article: • To enhance your awareness of the categories, risks and effects of various new psychoactive substances • To recognise the challenges involved in identifying new psychoactive substances • To consider psychosocial and pharmacological interventions that you could use with people who misuse new psychoactive substances. The use of new psychoactive substances is a growing concern across healthcare services in the UK. To date, more than 1,000 types of new psychoactive substances have been identified and they have a wide range of effects, potency and mechanisms of action, which can result in overdose and death. This article reviews the challenges experienced by nurses including in identifying new psychoactive substances, their associated risks and various psychosocial and pharmacological interventions. Currently, evidence surrounding the appropriate nursing interventions required for the misuse of new psychoactive substances is limited. Further research and training opportunities are required for nurses to manage service users who present having taken new psychoactive substances, particularly in hospital, substance misuse and mental health settings. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the effects of policy interventions on psychotropics polypharmacy among Japanese older adults. The study determined the proportion of patients prescribed with psychotropics, antidepressants, antipsychotics, hypnotics and anxiolytics. Study limitations include the use of the DeSC Healthcare Inc. database, estimated number of patients who switched medications, and impact of the coronavirus pandemic.

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]

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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]

Background: Anxiety transcends a natural emotion, evolving into a pathological condition with the potential to trigger cascading cardiovascular and psychiatric disorders. Although conventional allopathic medicine offers treatment options, concerns regarding their side effects and long-term efficacy remain prevalent. Medicinal plants contain natural compounds that may be promising sources of therapeutic drugs. Aims and Objectives: This study aims to compare the anxiolytic potential of ethanolic and aqueous extracts of Ocimum sanctum (OS). The growing appeal of plant-based therapies for anxiety stems from perceived advantages in safety and tolerability compared to synthetic drugs. Materials and Methods: The anxiolytic activity of aqueous and ethanolic extract of OS is evaluated with an elevated plus maze test. A total of 36 Wistar albino rats (150-200 g) were used and randomly divided into six groups of six animals each. The effects of the test drug at different doses, 100 and 200 mg/kg, were compared with the standard anxiolytic drug diazepam at 2 mg/kg body weight and the control group using distilled water at 0.5 mL/kg body weight. Results: The behavioral changes suggested reduced anxiety and openarm exploration in plus-maze indicates reduced anxiety in animals treated with OS extracts. The changes are significantly (P < 0.001) comparable with the standard drug diazepam. Conclusion: The ethanolic extracts of OS are more significant than aqueous extracts for evaluating anti-anxiety activity in a dose-dependent manner. In addition, ethanolic extracts are more likely to contain a wider range of bioactive compounds, which are thought to be responsible for the anti-anxiety effects of OS. [ABSTRACT FROM AUTHOR]

Ongoing global research actions seek to comprehensively understand the adverse impact of stress and anxiety on the physical and mental health of both human beings and animals. Niaprazine (NIA) is a chemical compound that belongs to the class of piperazine derivatives. This compound has recently gained renewed attention due to its potential therapeutic properties for treating certain conditions such as anxiety. Despite its potential benefits, the behavioral effects of NIA have not been thoroughly investigated. This study aimed to examine NIA's potential as an anti-anxiety and anti-stress agent. After administering either vehicle or NIA in their drinking water to mice for 14 days, we conducted behavioral analyses using the Marble Burying Test and the Elevated Plus Maze test. NIA-treated mice spend more time in the open arms and bury fewer marbles. Moreover, a stability study confirmed the linear relationship between NIA concentration and its response across concentrations encompassing the NIA mother solution and the NIA solutions administered to mice. Also, a preliminary synaptic toxicity analysis showed no direct damage to cortical nerve endings. Here, we show that NIA can modulate anxiety-related behaviors without significantly impacting exploratory activity or adverse effects. Our work describes new findings that contribute to the research on safer and more tolerable anxiety management options. [ABSTRACT FROM AUTHOR]

Background: Fatal drug overdoses have involved both xylazine and fentanyl. Xylazine is a non-opioid substance used in veterinary medicine. This study aimed to model changes in fatal xylazine-involved drug overdose deaths from 2019 to 2023 in Connecticut using overdose death data from the Office of the Chief Medical Examiner. Methods: Xylazine-involved drug overdose fatality rates were calculated by number of deaths per year per 100,000 population from 2019 to 2023. We used joinpoint regression modeling to evaluate quarterly overdose rates across age, number of drugs, and drug types with a significance level of p < 0.05. Results: From 2019 to 2023, there were 1116 xylazine-involved fatal overdoses with a cumulative rate of 31.3 deaths per 100,000. Xylazine-involved overdose death rates were significantly higher in Hispanic populations compared to both non-Hispanic White and Black populations (p < 0.05). The joinpoint analyses showed that xylazine-fentanyl mortality rates significantly increased by 0.18 per 100,000 per quarter from 2019 to 2022. Xylazine-fentanyl overdoses involving at least 4 or 5 substances significantly increased. Windham, Hartford, New London, and New Haven counties had the highest xylazine-involved death rates. Conclusion: Xylazine-fentanyl deaths increased from 2019 to 2023, and often involved multiple substances (e.g., cocaine, ethanol, benzodiazepines, and oxycodone). Results show Hispanic populations, those aged 35–49, and 50+ experienced high rates of xylazine-fentanyl overdose deaths. Vulnerable populations in Connecticut for special consideration for future intervention and local resource allocation are recommended. [ABSTRACT FROM AUTHOR]

Serotonin syndrome is a potentially life-threatening condition caused by a toxic excess of serotonin leading to overstimulation of the nervous system. Because it is a diagnosis of exclusion, it can be underrecognized, making the true incidence unknown. The classic triad of serotonin syndrome includes neuromuscular excitation, autonomic instability and altered mental status. If left unrecognized and untreated, patients are at a high risk of mortality. The most common class of medication that carries an increased risk of serotonin syndrome, when used in combination, is selective serotonin reuptake inhibitors (SSRIs); however, medications that increase serotonin production, increase serotonin release, inhibit serotonin metabolism and stimulate serotonin receptors can increase the possibility of serotonin syndrome. We report a case that details the presentation and treatment of a 25-year-old man who developed serotonin syndrome in the setting of rapid titration of risperidone, trazodone, and sertraline. The patient presented to the ED with acute agitation, diaphoresis, and altered mental status. He also had lower extremity myoclonus and was tremulous with an oral temperature of 100°F (37.8°C) and heart rate of 103 beats per minute. Serotonin syndrome was confirmed and the patient was treated successfully with benzodiazepines before being discharged from the hospital after 4 days. [ABSTRACT FROM AUTHOR]

Remimazolam is a new reversible γ-aminobutyric acid type A agonist benzodiazepine that displays a fast onset of action, short recovery time with a safe cardiopulmonary profile and favorable pharmacokinetics in comparison with other intravenous sedatives. [ABSTRACT FROM AUTHOR]

Background: Women with gynecologic disorders requiring a hysterectomy often have co-existing psychiatric diagnoses. A change in the dispensing pattern of antidepressant (AD) and antianxiety (AA) medications around the time of hysterectomy may be due to improvement in gynecologic symptoms, such as pelvic pain and abnormal bleeding, or the emotional impact of the hysterectomy. Unfortunately, these dispensing patterns before and after hysterectomy are currently undescribed. Objectives: To model the dispensing patterns of AD and AA medications over time among women with psychiatric disorders before and after benign hysterectomy for endometriosis and uterine fibroids; and to characterize clusters of patients with various dispensing behaviors based on these patterns. Design: Retrospective cohort study. Methods: This is a study of women who underwent a benign hysterectomy using data from the Merative MarkertScan® Research Databases (Ann Arbor, MI, USA). Inclusion criteria were reproductive-aged women (18–50 years), diagnosis of at least one mood or anxiety disorder, and at least one dispensing of AD or AA medications. We measured monthly adherence and persistence of AD/AA medication use over 12 months after hysterectomy. Group-based-trajectory modeling (GBTM) was used to identify trajectory groups of monthly AD/AA medication dispensing over the study period. Multinomial logistic regression was used to identify factors independently associated with individual dispensing trajectory patterns. Results: For a total of 11,607 patients, 6 dispensing trajectory groups were identified during the study period: continuously high (27.0%), continuously moderate (21.9%), continuously low (17.9%), low-to-high (10.0%), moderate-to-low (9.8%), and low-to-moderate (13.4%). Compared with the continuously high group, younger age, no history of a mood disorder, and uterine fibroids were clinical predictors of low dispensing. The discontinuation rate at 3 months after hysterectomy was higher at 88.6% in the continuously low group and at 66.5% in the continuously low-to-moderate group. Conclusions: This study demonstrates that GBTM identified six distinct trajectories of AD/AA medication dispensing in the perioperative period. Trajectory models could be used to identify specific dispensing patterns for targeting interventions. Plain language summary: Dispensing patterns of antidepressant and antianxiety medications for psychiatric disorders after benign hysterectomy in reproductive-aged women: Results from the group-based trajectory modeling Women with gynecologic disorders often have coexisting psychiatric diagnoses. A change in the dispensing pattern of antidepressant and antianxiety medications may be due to improvement in gynecologic symptoms or the emotional impact of the hysterectomy. However, static measures, such as the proportion of days covered or medication possession ratio, may not adequately predict meaningful dispensing patterns. Using the group-based trajectory modeling, 6 distinct patterns of medication dispensing over the perioperative periods of women with benign hysterectomy are identified and therefore used to assess how certain clinical characteristics influence these dispensing patterns. This study concludes that trajectory modeling may be a more appropriate approach to investigating dispensing patterns among women with preexisting psychiatric conditions. [ABSTRACT FROM AUTHOR]

Purpose. This systematic review aims to consolidate key findings regarding the efficacy of pain relief medications administered prior to pan‐retinal photocoagulation (PRP) for diabetic retinopathy (DR). Methods. A comprehensive search of major databases from 1993 to 2023 was conducted. Clinical trials comparing pain relief drugs before PRP in patients diagnosed with DR requiring PRP treatment were eligible for inclusion. The assessment of pain scores involved the use of various scales, such as the visual analog scale (VAS), numerical rating scale (NRS), verbal rating scale (VRS), and other ordinal pain scales. In addition, laser parameters were taken into consideration during the analysis. Results. Twenty‐two clinical trials from initial 150 studies were included in the review. Nine studies evaluated the pain relief effects of nonsteroidal anti‐inflammatories NSAIDs (selective NSAID and nonselective NSAID), two studies compared the effects of opioids (conventional opioids and atypical opioids), and eleven studies investigated the effects of benzodiazepines, lidocaine, and other sedatives. Conclusion. This review synthesizes findings from multiple studies reporting pain as an adverse outcome of PRP in patients with advanced DR. Based on the evidence from reviewed clinical trials, the administration of lidocaine 2% via transconjunctival, retrobulbar, or peribulbar block along with specific NSAIDs, such as topical ketorolac administrated 24 hours before treatment or oral diclofenac potassium (50 mg) prior to PRP, demonstrated beneficial effects among patients with DR. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences. Methods: Using a modified Dixon's up-and-down allocation approach, we sequentially enrolled male and female patients aged 19–60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer's Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved. Results: We included 22 male and 22 female patients. Based on Dixon's up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18–0.20) mg/kg in the male group and 0.29 (0.29–0.30) mg/kg in the female group. Conclusions: There was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients. Trial registration: This study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022). [ABSTRACT FROM AUTHOR]

Background: People who use illicit drugs cumulate medical and psychosocial vulnerabilities, justifying a rounded health approach. Both caregivers and patients can form barriers to accessing care, leading to inadequate care. This study aimed to identify the needs and expectations of such patients in general practice. Methods: Qualitative research was conducted using semi-structured interviews with 23 people with illicit substance use disorder in Brussels in 2020. Multicentric recruitment was conducted to obtain a heterogeneous mix of sociodemographic profiles and care trajectories. Thematic analysis was performed using RQDA package software. Results: Participants highlighted several vulnerabilities. These include the presence of significant self-stigmatization and guilt, sometimes to the extent of self-dehumanization, even after years of care, and overdoses masking suicide attempts and early memory disorders. Multiple substance use, smoking in almost all participants, and misuse of benzodiazepines were also noted. The majority of participants expressed the need for an open-minded, non-stigmatizing and empathic GP with a holistic approach that could guide them throughout their life course. The competencies of the GPs in the field of addiction seemed secondary to the participants. Knowledge and good collaboration with the mental health network were assets. Conclusion: Participants expressed the need for GPs with good interpersonal skills, including a non-stigmatizing attitude. The care coordinator role of the GP was highlighted as a key element, as it was a holistic approach focusing on global health (including the social determinants of health) and not only on substance use disorders. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusions\nKey PointsTo evaluate the effectiveness and safety of long-term use of silexan in patients with a wide range of anxiety disorders.A retrospective chart review was conducted on 50 patients diagnosed with various anxiety disorders who were prescribed silexan. The primary outcomes measured included the resolution of anxiety symptoms, changes in Generalized Anxiety Disorder-7 (GAD-7) scores, and Clinical Global Impressions-Improvement (CGI-I) scores. The duration of silexan use and any reported adverse events were also recorded.Silexan effectively resolved anxiety symptoms in 35 patients, with 24 out of 25 patients who received silexan for more than 12 weeks showing significant improvement. Median GAD-7 and CGI-I scores decreased significantly (p<0.001). By the end of the follow-up period, 46% of patients had minimal anxiety and 24% had mild anxiety. No adverse events were reported during the study period.Long-term use of silexan is feasible, safe, and effective in managing a wide range of anxiety disorders in real-world clinical settings.While silexan has shown promising results in the treatment of anxiety disorders in various clinical trials, there is a significant gap in our understanding of its effects in long-term use.The present study supports the long-term use of silexan as a safe and effective alternative or adjunct to conventional anxiolytics.Using silexan as an alternative or adjunct to traditional anxiolytics may provide additional treatment options, potentially reducing the burden of these prevalent and disabling conditions.Silexan may be an appropriate choice for patients seeking natural or complementary treatments for anxiety.While silexan has shown promising results in the treatment of anxiety disorders in various clinical trials, there is a significant gap in our understanding of its effects in long-term use.The present study supports the long-term use of silexan as a safe and effective alternative or adjunct to conventional anxiolytics.Using silexan as an alternative or adjunct to traditional anxiolytics may provide additional treatment options, potentially reducing the burden of these prevalent and disabling conditions.Silexan may be an appropriate choice for patients seeking natural or complementary treatments for anxiety. [ABSTRACT FROM AUTHOR]

A 57-year-old man developed worsening early morning headaches, muscle cramps and falls over 12 months. He had widespread fasciculation and was diagnosed with motor neurone disease, and treated with nocturnal hypoventilation. Based on this diagnosis, he made significant personal and financial decisions including retiring and selling his house. He subsequently developed a lump in his right breast and was found to have gynaecomastia. This triggered genetic testing for Kennedy's disease leading to the correct diagnosis. This case highlights an unusual presentation of a rare disease leading to misdiagnosis and major repercussions for the patient. Recent genetic analysis from the 100 000 genome project suggests Kennedy's disease may be four times more prevalent in the population than previously thought, highlighting the need to consider genetic testing, especially if there is a suggestion of multisystem disease. [ABSTRACT FROM AUTHOR]

Background and aim: Bromazolam, a novel designer benzodiazepine (NBD), exhibits potent sedative, hypnotic and anxiolytic effects, raising concerns regarding its potential for misuse and fatal outcomes, particularly when combined with opioids such as fentanyl. Despite limited documented fatalities globally, its use poses a significant threat, exacerbated by under‐reporting and a lack of routine testing. This study analysed NBD‐related deaths in a major US city over a 4‐year period. Methods: Analysis of accidental overdose deaths involving NBDs in San Francisco, CA, USA from 2020 to 2023, was performed utilizing medico‐legal death investigations including comprehensive forensic toxicology, pathology and demographic information. San Francisco conducts thorough investigations into all non‐natural and sudden unexpected deaths, including routine alcohol and drug testing of decedents under its jurisdiction, including etizolam, flualprazolam, flubromazolam and bromazolam analysis. Results: There was a sudden surge in bromazolam‐related deaths, with 44 fatalities documented in 2023, contrasting with relatively fewer deaths related to other NBDs. Bromazolam fatalities frequently involved co‐ingestion with opioids, primarily fentanyl, and stimulants such as methamphetamine and cocaine. Demographic characteristics indicated a predominance of males, with a significant proportion lacking fixed addresses. Blood concentrations of bromazolam increased during the study period, suggesting heightened availability and/or purity in the community. Conclusion: There was a surge in bromazolam‐related deaths during 2023 in San Francisco, CA, USA, contrasting with relatively stable numbers of deaths associated with other NBDs over the preceding years. The findings underscore the urgency for enhanced death investigation, testing and reporting to facilitate targeted harm reduction strategies for individuals at risk of bromazolam‐related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Objective The study aims to describe our experience with the implementation of phenobarbital as a primary sedation strategy during neonatal extracorporeal membrane oxygenation (ECMO). Study Design Retrospective chart review in a level IV neonatal intensive care unit between 2011 and 2021 comparing neonatal ECMO patients before and after the implementation of a sedation-analgesia (SA) protocol using scheduled phenobarbital as the primary sedative. Groups were compared for neonatal and ECMO characteristics, cumulative SA doses, and in-hospital outcomes. Comparison between groups was performed using Mann–Whitney test on continuous variables and chi-square on nominal variables. Results Forty-two patients were included, 23 preprotocol and 19 postprotocol. Birth, pre-ECMO, and ECMO clinical characteristics were similar between groups except for a lower birth weight in the postprotocol group (p = 0.024). After standardization of phenobarbital SA protocol, there was a statistically significant reduction in median total morphine dose (31.38–17.65 mg/kg, p = 0.006) and median total midazolam dose (36.21–6.36 mg/kg, p < 0.001). There was also a reduction in median total days on morphine by 7.5 days (p = 0.026) and midazolam by 6.6 days (p = 0.003). There were no differences in ECMO duration or in-hospital outcomes between groups. Conclusion In this cohort, short-term use of phenobarbital as primary sedation strategy during neonatal ECMO was associated with reduced opioid and midazolam burden. Such reduction, however, did not affect in-hospital outcomes. Key Points Prolonged sedation on ECMO puts infants at risk for iatrogenic withdrawal. Phenobarbital is a feasible sedation strategy for ECMO. Phenobarbital sedation strategy may mitigate risk by decreasing opioid and midazolam burden. [ABSTRACT FROM AUTHOR]

Background: Anxiety is one of the common mental disorders. Non-fatal health loss is one of the consequences of anxiety disorders. Oxidative stress may also play a role in anxiety disorders. As an antioxidant, Vitamin C can create stable ascorbate free radicals and lower reactive oxygen species. In addition, Vitamin C can prevent damage caused by free radicals. Oxidative stress can also lead to depression, schizophrenia, and bipolar disorder. Aim and Objectives: The aim and objectives of the study are to compare the antianxiety effects of Vitamin C, buspirone, and diazepam in albino rats using elevated plus maze and hole board apparatus. Materials and Methods: 36 albino rats of either sex were divided into 6 groups of 6 rats each and drugs were administered orally. Group 1 received distilled water 10 ml/kg, Group 2 received Vitamin C 200 mg/kg, Group 3 received buspirone 10 mg/kg, Group 4 received diazepam 1 mg/kg, Group 5 received buspirone 10 mg/kg + Vitamin C 200 mg/kg, and Group 6 received diazepam 1 mg/kg + Vitamin C 200 mg/kg. Antianxiety effects of these drugs were tested after 14 days of drug administration using hole board apparatus and elevated plus maze. The methods used for statistical analysis were mean, standard deviation, confidence interval, median, interquartile range (IQR), frequency and percentage, ANOVA, Kruskal-Wallis test, and Fisher's exact test. Results: On average time spent in open arms by Group 5 was 98.00 sec (IQR: 19.75-138.00) which was higher than other groups, but it was not statistically significant (P = 0.845). The time spent in closed arms in seconds by Group 4 was 245 ± 28.863, which was higher than other groups, but it was not statistically significant (P = 0. 805). On average head dip by Group 5 was 9.83 ± 4.708, which was higher than other groups, but it was not statistically significant (P = 0.141). Conclusion: Group 5 rats that received buspirone and Vitamin C, followed by Group 6 rats that received diazepam and Vitamin C had spent more time and had more entries into the open arms. Furthermore, Groups 5 and 6 animals had a greater number of head dips in the hole board apparatus compared to the behavior of all animals in other groups. Buspirone and diazepam are known anxiolytics. When these drugs were given in combination with Vitamin C, the antianxiety behaviors in rats were more compared to the drugs given alone in the present study but it was not statistically significant. [ABSTRACT FROM AUTHOR]

Medicines acting on the central nervous system can be inappropriately used. The aim of this study was to clarify the key concepts on misuse of prescription medicines, mapping the existing body of evidence on this topic in the European Union and identifying the main medicines misused, risk factors, and morbidity/mortality consequences of this behavior. Three databases – PubMed, Scopus, and Web of Science – were searched. Retrieved articles were added to other studies previously identified from additional sources (e.g., PubMed alerts). Following the PRISMA-ScR flow diagram, the final list was screened for article selection. A total of 1,637 abstracts were reviewed, resulting in the inclusion of 136 articles. Most studies reported misuse of prescription opioids (66%), benzodiazepines/z-drugs, gabapentinoids, and antidepressants. Risk factors included history of substance use/addiction, mental health or alcohol disorders, female sex, older age, low income/deprivation, and psychoactive substance concomitant use. The main consequences addressed were adverse drug reactions, poisonings, emergency visits, and deaths. The medicines with highest potential misuse were opioids, benzodiazepines/z-drugs, and gabapentinoids. The considerable variety of data among EU countries suggests the need to invest in systematic centralized research to identify and understand prescription drug misuse at country-level across the EU. [ABSTRACT FROM AUTHOR]