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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]

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]

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: 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]

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]

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]

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]

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]

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]

Background: The main sedative which is propofol in painless gastroenteroscopy, has a high risk of reducing blood pressure and respiratory depression. Remimazolam (a short-acting benzodiazepine) is expected to be widely used in painless gastroenteroscopy due to its rapid onset, rapid metabolism and light respiratory and circulation inhibition. Methods: A randomized, single-blind, parallel, controlled study, 123 outpatients who were undergoing painless colonoscopy and ramdomly divided into group A, B and C, in Hangzhou First People's Hospital, July-December 2021. All patients were intravenously injected with 5 µg sufentanil for analgesic preconditioning. The group A was induced by 0.2 mg/kg remimazolam besylate. The group B was induced by 0.25 mg/kg remimazolam besylate. And the group C was inducted by 2.0 mg /kg propofol. If the patients had limb movement or MOAA/S score > 3 and so on, remimazolam besylate was added at 2.5 mg/ time in group A and B, and propofol emulsion injection was added at 0.5 mg/kg/ time in group C. During the operation, according to the actual situation, remimazolam was per added 2.5 mg in the experimental group, and propofol was 0.5 mg/kg in the control group. Heart rate (HR), non-invasive blood pressure (BP), respiratory rate (RR), pulse oxygen saturation (SpO2), and improved vigilance/sedation score (MOAA/S) of patients was recorded from entering endoscopy room to get out of the anesthesia recovery room, also including perioperative adverse events, other medications or treatments, the time of patients waking up and leaving the hospital. Results: The successful rate of induction in three groups was 100%. There was no significant difference in the sedation completion rate among the three groups (Group A:90.2%, Group B: 92.7%, Group C: 92.7%, P = 1.000). The rate of adverse events after administration: group A(27.0%) and B(36.8%) both lower than group C(71.0%),P < 0.001;There was no significant difference between group A and group B, P > 0.744;The average time from the last drug administration to meet the discharge criteria of the subjects in three groups was as follows: The average time of group A(16.2 min) and Group B(16.5 min) both shorter than group C(19.6 min), P = 0.001; There was no significant difference between group A and group B, P = 0.742. Conclusions: This study revealed that remimazolam is a safe and effective medication for colonoscopy sedation, the security of remimazolam is better than propofol, and the sedative effect with the initial dose of 0.25 mg/kg of remimazolam is optimal. Trial registration: China Clinical Trial Center with registration number: 2100052615,02/11/2021. [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion (I/R) injury is a major factor in liver damage following hepatic resection and liver transplantation, with anesthetics demonstrating the ability to shield organs from this type of injury. Methods: Hypoxia-reoxygenation (H/R) was used to create in vitro I/R hepatocyte cell injury models. The CCK-8 assay, flow cytometer, LDH assay, and ELSIA were utilized to assess hepatocyte injury. The in vivo I/R injury rat model was then built. HE and TUNEL staining were used to assess liver tissue damage. Western-blot was applied to assess the activation of the MAPK/ERK pathway. Results: Remimazolam (RMZL) remarkably improved cell viability and decreased apoptosis in H/R-induced hepatocyte injury. RMZL reduced the release of H/R-induced inflammatory mediators (TNF-α and IL-6) as well as LDH levels. We also discovered that RMZL inhibited p38 and ERK1/2 phosphorylation in vivo and in vitro. The stimulation of MAPK/ERK, on the other hand, abolished RMZL's anti-inflammation effects in H/R-induced hepatocyte injury. Furthermore, RMZL reduced liver tissue injury in I/R rats. Conclusion: RMZL prevented hepatic I/R damage by inhibiting MAPK/ERK signaling. [ABSTRACT FROM AUTHOR]

This research work aimed to identify the main components that are responsible for the sedative properties of hop cones and allocate their targets. This investigation was performed through molecular docking, molecular dynamic simulations, root mean square fluctuation (RMSF) analysis, and DFT calculation techniques. The tested compounds from Humulus lupulus were compared to diazepam and paroxetine. Molecular docking showed that two-thirds of the compounds had a good affinity to gamma-aminobutyric acid (GABA), outperforming diazepam, while only three surpassed paroxetine on the SERT. Compounds 3,5-dihydroxy-4,6,6-tris(3-methylbut-2-en-1-yl)-2-(3-methylbuta noyl)cyclohexa-2,4-dien-1-one (5) and (S,E)-8-(3,7-dimethylocta-2,6-dien-1-yl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one (15) showed stable binding and favorable energy parameters, indicating their potential for targeting GABA receptors and the SERT. This study provides a basis for future clinical research on these promising compounds. [ABSTRACT FROM AUTHOR]

Objective: The study aims to identify the drugs associated with drug withdrawal syndrome in the Food and Drug Administration Adverse Event Reporting System (FAERS) and estimate their risks of causing withdrawal syndrome. Methods: All the data were collected from FAERS from the first quarter of 2004 to the third quarter of 2023. Disproportionality analyses of odds ratio (ROR) and proportional reported ratio were conducted to identify potential adverse effects signal of drug withdrawal syndrome. Results: A total of 94,370 reports related to withdrawal syndrome from the data. The top 50 drugs with most frequency reported were analyzed, and 29 exhibited a positive signal based on the number of reports. The top three categories of drugs with positive signals included opioids, antidepressant drugs and antianxiety drugs. Other classifications included opioid antagonist, muscle relaxant, antiepileptic drugs, analgesics, hypnotic sedative drugs and antipsychotic drugs. Conclusion: Our analysis of FAERS data yielded a comprehensive list of drugs associated with withdrawal syndrome. This information is vital for healthcare professionals, including doctors and pharmacists, as it aids in better recognition and management of withdrawal symptoms in patients undergoing treatment with these medications. [ABSTRACT FROM AUTHOR]

Objectives: Individuals who die by suicide often consult their general practitioners (GPs) in their final weeks of life. The aim of this study was to gain a deeper knowledge of the clinical characteristics and GP assessments and treatments among individuals who consulted their GPs during the month preceding suicide. Further, we compared these features in those with and without contact with psychiatric services (PC and NPC, respectively) during the two years that preceded the suicide. Design: A nationwide retrospective explorative study investigating medical records. Setting: Primary care in Sweden. Participants: Individuals who died by suicide in Sweden in 2015 with a GP visit within 30 days of death. Results: The study cohort corresponds to one fifth (n = 238) of all suicides that occurred in Sweden in 2015 (n = 1179), representing all those with available primary care records showing contact with a GP during the final 30 days of life (NPC: n = 125; PC: n = 113). The mean age was 58 years ± 19. Patients in the NPC group were older (NPC: 63 years ± 19 vs. PC: 53 years ± 18, p < 0.0001) and presented psychiatric symptoms less often (NPC: 50% vs. PC: 67%, p < 0.006). Somatic symptoms were as common as psychiatric symptoms for the whole sample, being present in more than half of individuals. Suicide risk was noted in only 6% of all individuals. Referral to psychiatric services occurred in 14%, less commonly for the NPC group (NPC: 6% vs. PC: 22%, p < 0.001). Cardiovascular or respiratory symptoms were noted in 19%, more often in the NPC group (NPC: 30% vs. PC: 6%, p < 0.001), as were diagnoses involving the circulatory system (all 10%, NPC:14% vs. PC: 5%, p < 0.020). Conclusion: A high level of somatic symptoms was observed in primary care patients both with and without psychiatric contact, and this might have influenced GPs' management decisions. Psychiatric symptoms were noted in two thirds of those with psychiatric contact but only half of those without. While GPs noted psychiatric symptoms in over half of all individuals included in the study, they seldom noted suicide risk. These findings highlight the need for increased attention to psychiatric symptoms and suicide risk assessment, particularly among middle-aged and older individuals presenting with somatic symptoms. Strengths and limitations of this study: The National Cause of Death Register has excellent coverage of suicide deaths and access to medical records was very good. The medical record review provided detailed information regarding primary care utilization before death by suicide. Because of the lack of statistical power, due to the limited number of persons with GP contact during the last month of life, we chose not to correct for multiple comparisons. Our study approach did not capture the reasons behind GPs' documentation of elevated suicide risk. No systematic inter-rater reliability (IRR) testing was made, however, reviewers received training and continuous support from the research group. [ABSTRACT FROM AUTHOR]

Real-world evidence on the association between natural medicinal products and the recurrence of sleep disorders is currently limited, particularly when compared to the evidence reported for prescription hypnotics. In a retrospective cohort analysis, we investigated patients with sleep disorders prescribed either the natural medicinal product Neurexan (Nx4), benzodiazepines, or nonbenzodiazepines (Z-drugs) using the IQVIA Disease Analyzer database, which encompasses electronic medical records nationwide in Germany. A 1:1 matching procedure based on age, sex, prevalent depression, anxiety or adjustment disorder, and the number of medical consultations in the past 12 months resulted in four cohorts: patients prescribed Nx4 were matched with those prescribed Z-drugs (two cohorts with 8594 matched patients each), and another cohort of patients prescribed Nx4 were matched with those prescribed benzodiazepines (7779 matched pairs). Results from multivariable-adjusted Cox regression models demonstrated that Nx4 was associated with a significantly lower risk of recurrent sleep disorder diagnosis within 30–365 days after prescription compared to both Z-drugs (HR = 0.65, 95%CI = 0.60–0.70, p < 0.001) and benzodiazepines (HR = 0.85, 95%CI = 0.79–0.93, p < 0.001). Additionally, Nx4 was associated with a lower prevalence of depression compared to Z-drugs (HR = 0.90, 95%CI = 0.83–0.98, p = 0.020) and benzodiazepines (HR = 0.89, 95%CI = 0.82–0.97, p = 0.009). These findings suggest an association between Nx4 and improved sleep and mental health outcomes. However, due to inherent limitations in the study design, the causality of this relationship cannot be stated. [ABSTRACT FROM AUTHOR]

Background: Remimazolam is a relatively new benzodiazepine with growing use in procedural sedation and general anaesthesia. Initiated by case reports, the physical incompatibility of remimazolam with ringer's acetated and ringer's lactated solution has been reported. More recently, remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam, have been investigated and suggested safe for coadministration with remimazolam. Apart from case reports, incompatibility for other frequently used drugs remains unknown. Methods: Sixty-five drugs and intravenous fluids were tested for possible precipitation with remimazolam in a simulated y-site administration. Equal volumes of the test drug were injected into the remimazolam solution, examined and photo documented at 1, 15, 30 and 60 min after mixture. Examination was taken by two independent investigators. pH was measured before, and 60 min after mixing the drugs. Results: Seventeen (26.15%) drugs or fluids showed precipitation, 47 (72.31%) did not show any sign of interaction. Propofol could not be assessed, because of the turbidity of the substance itself. Precipitation occurred immediately and remained stable in all timestamps. The incompatible drug-remimazolam-mixtures had a median pH of 7.15 (6.67, 8.01), the non-precipitating mixtures a median pH of 4.75 (3.8, 5.6). The pH-values of both groups were significantly different (Mann-Whitney-U-test; p <.00001). There is an increasing risk for precipitation with more basic baseline pH-levels of the tested drug. No interaction was seen in baseline pH below 5. Conclusions: Remimazolam (Byfavo®) is incompatible with ampicillin/ sulbactam, calcium gluconate, clindamycin, dexamethasone, dimenhydrinate, an 148mval/l electrolyte - glucose 1% solution (E148G1®), furosemide, a 4% gelatine volume expander (gelafundin®), heparin sodium, insulin, meropenem, sodium bicarbonate 8.4%, prednisolone, the crystalloid infusions jonosteril® and sterofundin®, thiopental and tranexamic acid. The results strongly affirm remimazolam's safety requirements: A separate line for remimazolam and an approved compatible baseline infusion is mandatory and an alternative way to administer bolus medication is required. [ABSTRACT FROM AUTHOR]

Background: Remimazolam tosilate (RT) is a new, ultrashort-acting benzodiazepine. Here, we investigated the efficacy and safety of RT for general anesthesia in patients undergoing Laparoscopic Cholecystectomy (LC). Methods: In this study, 122 patients undergoing laparoscopic cholecystectomy were randomly allocated to receive either remimazolam tosilate (Group RT) or propofol group (Group P). RT was administered as a slow bolus of 0.3 mg kg− 1 for induction, followed by 1.0–2.0 mg kg− 1 h− 1 for maintenance of general anesthesia. Propofol was started at 2 mg kg− 1 and followed by 4–10 mg kg− 1 h− 1 until the end of surgery. The primary outcome was the time to bispectral index (BIS) ≤ 60. The secondary outcome included the time to loss of consciousness (LoC), and the time to extubation. Adverse events were also assessed. Results: A total of 112 patients were recruited for study participation. Among them, the time to BIS ≤ 60 in Group RT was longer than that in Group P (Group RT: 89.3 ± 10.7 s; Group P: 85.9 ± 9.7 s, P > 0.05). While the time to LoC comparing remimazolam and propofol showed no statistical significance (Group RT: 74.4 ± 10.3 s; Group P: 74.7 ± 9.3 s, P > 0.05). The time to extubation in Group RT was significantly longer than that in Group P (Group RT: 16.0 ± 2.6 min; Group P: 8.8 ± 4.3 min, P < 0.001). Remimazolam tosilate had more stable hemodynamics and a lower incidence of hypotension during general anesthesia. Conclusions: Remimazolam tosilate can be safely and effectively used for general anesthesia in patients undergoing Laparoscopic Cholecystectomy. It maintains stable hemodynamics during induction and maintenance of general anesthesia compared with propofol. Further studies are needed to validate the findings. Trial registration: Chictr.org.cn ChiCTR2300071256 (date of registration: 09/05/2023). [ABSTRACT FROM AUTHOR]

Background: The management of preoperative anxiety in pediatric patients, as well as its implications, has remained challenging for anesthesiologists. In this study, we compared the safety and efficacy of intranasal dexmedetomidine, midazolam, and ketamine as surgical premedication in children. Methods: This double-blinded randomized clinical trial was conducted at two tertiary hospitals in January 2014, on 90 children aged between 2-7 years old. The participants' American Society of Anesthesiologists (ASA) physical status was I or II, and they were scheduled for elective unilateral inguinal herniorrhaphy. Using the block randomization method, the patients were randomly assigned to three groups, each receiving intranasal dexmedetomidine (2 µg/Kg), midazolam (0.2 mg/Kg), and ketamine (8 mg/Kg) 60 min before induction of anesthesia. Anxiety and sedation state were evaluated before drug administration, and then every 10 min for the next 50 min. Parental separation anxiety, mask acceptance, postoperative agitation, pain, nausea, and vomiting were also recorded and compared between these groups. All the statistical analyses were performed using SPSS software (version 21.0). P<0.05 was considered statistically significant. Results: Ketamine indicated the strongest sedative effect 10, 20, and 30 min after administration of premedication (P<0.001, P=0.03, P=0.01, respectively). However, dexmedetomidine was more effective than other drugs after 40 and 50 min (P<0.001). Other variables indicated no statistically significant difference. Conclusion: In case of emergencies, intranasal ketamine, with the shortest time of action, could be administered. Intranasal dexmedetomidine, which was revealed to be the most potent drug in this study, could be administrated 40-50 min before elective pediatric surgeries. Trial registration number: IRCT2013081614372N1. [ABSTRACT FROM AUTHOR]

Introduction: Elderly with cancer often have multimorbidity, which determines a higher risk of polypharmacy. This is related to negative clinical results such as adverse drug reaction and emergence service visits. Furthermore, polypharmacy increases the risk of using potentially inappropriate medications. Objective: To evaluate the use of potentially inappropriate medication in elderly with multiple myeloma and associated factors. Methods: The study was conducted with older adults with multiple myeloma treated at outpatient oncology and hematology services in a southeastern Brazilian capital. Potentially inappropriate medications were classified using the American Geriatric Society/Beers 2019 Criteria. Variables were described using frequency and proportions, performing multiple logistic regression to identify factors associated with the use of potentially inappropriate medications. Results: One hundred fifty-three older adults with multiple myeloma were included, with a median age of 70.9 years. The median number of medications was 8, and 63% of patients used polypharmacy. More than half (54%) of the patients used potentially inappropriate medications, and proton pump inhibitors (46%) and benzodiazepines (8%) were the most employed therapeutic classes. Older adults who used potentially inappropriate medications differed from those who did not use them in the following characteristics: income up to three minimum wages, higher schooling level, private service, multimorbidity, hypertension, cardiovascular disease, chronic kidney disease, depression, adverse event, and polypharmacy. Higher schooling levels and polypharmacy were independently associated with the use of potentially inappropriate medications in the multivariate analysis. Conclusion: Potentially inappropriate medication use was high in patients with multiple myeloma studied. The use of polypharmacy and higher schooling levels were independently and positively associated with the use of potentially inappropriate medications. [ABSTRACT FROM AUTHOR]

Purpose: Despite the evidence of higher effectiveness of psychological interventions for insomnia compared to pharmacological ones, drug prescriptions for insomnia remain frequent. This study has assessed patterns of prescriptions of BZDs for insomnia before and after the delivery of a training in psychological interventions to professionals working in the services of a Department of Mental Health in northern Italy. Methods: The intervention consisted in two training sessions about psychological interventions for insomnia delivered to professionals of the participating services. The prevalence of users with a prescription of BZDs for insomnia in an index period after the delivery of the training was compared to the prevalence in an index period before the training. Results: Among 727 people assessed for BZDs prescription at pre-intervention, 306 (42.1%, 95% CI 0.39–0.46) had a prescription, and 344 (49.2%, 95% CI 0.45–0.53) had a prescription among 699 people assessed at post-intervention, corresponding to a significant odds ratio of 1.33 to be prescribed with BZDs in the second index period compared to the first one. Psychological interventions were offered to a small group of patients. Conclusion: Prescribing attitudes of BZDs for insomnia were not modified after the training and delivery of a psychological intervention in a mental healthcare outpatient setting. Prescribing habits should be addressed more directly in training, and professionals should be more aware of risks of BZDs assumption. The failure in changing drug prescriptions in this study should prompt more real-world studies of the application of evidence-based strategies, particularly in outpatient mental health settings. [ABSTRACT FROM AUTHOR]

Background: Medication use around widowhood has been poorly described for most medication classes. Medication use patterns can reflect health consequences of spousal loss, as previously shown for psychotropic drugs. Methods: We used data from nationwide health registers (2008–2020) to describe the patterns of use of dispensed medications in all widowed Swedes aged ≥65 years followed between 2 years before and 2 years after spousal death. All prescription drugs used by at least 5% of the cohort were considered according to their therapeutic subgroups (Anatomical Therapeutic Chemical [ATC] classification system 2nd level). We used group‐based trajectory models to cluster widowed individuals into up to 4 distinct longitudinal patterns of monthly medication use. We ranked the therapeutic subgroups with similar patterns according to their plausibility to reflect potential health effects of spousal loss, compared to those of psycholeptics (mainly anxiolytics, hypnotics) and psychoanaleptics (mainly antidepressants) as the references. Results: From 212,111 widowed adults included (68% female and 70% aged ≥75 years), we observed a significant increasing trend in medication use, especially after spousal death, for 21 out of the 39 different therapeutic subgroups that were used by at least 5% (most represented pharmacological groups: cardiovascular system, nervous system, and alimentary tract and metabolism). This increasing trend often concerned only a small proportion of individuals, with varying magnitude and speed of change in medication use across therapeutic subgroups. The patterns of use of antiepileptics, laxatives, skin emollients/protectives, analgesics, and drugs for anemia, constipation, or peptic ulcers, were the closest to those of references, displaying the largest changes in use, and were therefore ranked as the most likely to reflect health effects of spousal loss. Conclusion: Our results confirmed the increase in psychotropic medications' use in widowed older adults and identified several potential physical health effects of spousal loss that warrant further research. [ABSTRACT FROM AUTHOR]

Procedural sedation and analgesia is an essential activity in the emergency department for managing pain and anxiety during a variety of medical procedures. Various pharmacotherapy options, including opioid analgesics, antiemetics, anticholinergics, sedatives, and ketamine have been utilized, all with their unique efficacy and safety profiles. This review highlights the challenges associated with using certain agents and discusses emerging trends such as the use of newer synthetic opioids and the expanding use of dexmedetomidine. Overall, the selection of the optimal agents for procedural sedation and analgesia should be guided based on the unique characteristics of each agent tailored to the needs of the specific procedure, along with consideration for individual patient characteristics. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify factors associated with long-term opioid use and to assess the association between long-term use and death. Retrospective cohort study combining several population-wide databases and covering a population of five million inhabitants, including all adults who were initiated on opioid treatment from 2014 to 2018 for non-cancer pain. We used logistic regression models to identify factors associated with chronic opioid use and carried out survival analyses using multivariable Cox regression modelling for all-cause mortality during follow-up using inverse probability of treatment weighting (IPTW) and propensity scores based on the probability of using opioids chronically. Among 760,006 patients, 82,423 (10.85%) used opioids for 90 days or more after initiation. Initial therapy characteristics associated with higher risk for long-term use were initiating with long- and short-acting opioids (when compared to tramadol, odds ratio [OR]: 2.63, 95% confidence interval [CI]: 2.57, 2.69 and OR: 1.60, 95%CI: 1.46, 1.76, respectively), using higher daily doses (when compared to 50 morphine milligramme equivalent [MME] or less, prescribing 50 to 89 daily MME, OR: 1.76, 95%CI: 1.65, 1.87; 90 to 119 daily MME, OR: 2.44, 95%CI: 1.99, 3.01; and more than 120 daily MME, OR: 1.77, 95%CI: 1.64, 1.91), and overlapping with gabapentinoids (OR: 2.26, 95%CI: 2.20, 2.32), benzodiazepines (OR: 1.32, 95%CI: 1.30, 1.35), and antipsychotics (OR: 1.21, 95%CI: 1.16, 1.26). After IPTW, chronic opioid use was associated with higher risk of all-cause mortality when compared to short-term use (Hazard Ratio (HR): 1.37, 95%CI: 1.32, 1.42). Sensitivity analyses provided similar results. These findings may help healthcare managers to identify and address patients at higher risk of long-term use and riskier prescription patterns. [ABSTRACT FROM AUTHOR]

Background: Treatment of anorexia nervosa (AN) sometimes requires hospitalisation, which is often lengthy, with little ability to predict individual trajectory. Depicting specific profiles of treatment response and their clinical predictors could be beneficial to tailor inpatient management. The aim of this research was to identify clusters of weight recovery during inpatient treatment, and their clinical predictors. Methods: A sample of 181 inpatients who completed a treatment programme for AN was included in a retrospective study. A latent class mixed model approach was used to identify distinct weight‐gain trajectories. Clinical variables were introduced in a multinomial logistic regression model as predictors of the different classes. Results: A four‐class quadratic model was retained, able to correctly classify 63.7% of the cohort. It encompassed a late‐rising, flattening, moderate trajectory of body mass index (BMI) increase (class 1), a late‐rising, steady, high trajectory (class 2), an early‐rising, flattening, high trajectory (class 3) and an early‐rising, steady, high trajectory (class 4). Significant predictors of belonging to a class were baseline BMI (all classes), illness duration (class 2), and benzodiazepine prescription (class 3). Conclusion: Predicting different kinetics of weight recovery based on routinely collected clinical indicators could improve clinician awareness and patient engagement by enabling shared expectations of treatment response. Highlights: Treatment of anorexia nervosa lacks tailored strategies to optimise individual patients' management.Latent class mixed model approach is a promising strategy to analyse treatment response as a dynamic entity.Baseline body mass index, duration of illness and benzodiazepine prescription are significant indicators of distinct weight recovery profiles. [ABSTRACT FROM AUTHOR]

The current study examined the relationship between PTSD and nonmedical use of benzodiazepines (BZDs) based on level of John Henry Active Coping (JHAC) among African American incarcerated men. Data were derived from the Helping Incarcerated Men (HIM) Study (n = 208). Nonmedical use of BZDs was measured for the 30 days before incarceration. Current PTSD diagnosis and JHAC were determined using DSM-5 criteria and the JHAC Scale. Adjusted logistic regression analyses showed PTSD diagnosis was significantly associated with nonmedical BZD use (p =.011), but that JHAC did not significantly mitigate this relationship. African American incarcerated men may experience an unmet need with regards to mental health treatment. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) with progressive myoclonic epilepsy (PME) affects the nervous system. Symptoms appear in early childhood and include muscle weakness, difficulty walking, seizures, and cognitive decline. Despite introducing various therapies to restore acid ceramidase function or reduce ceramide accumulation and gene therapy to correct genetic mutations, there are still unknown underlying molecular mechanisms related to this disorder. This article reports a novel variant c.118G>C in the ASAH1 gene. The patient presented with clinical manifestations such as progressive muscle weakness and myoclonic convulsions. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epileptic discharge. A significant temporal interval was observed between the initial diagnosis of SMA and the subsequent manifestation of myoclonic seizures. The proband was genetically assessed through whole exome sequencing (WES) followed by variant confirmation and bioinformatics analysis. According to this article's findings and previous research, further diagnostic testing and management are needed to determine the severity and progression of the patient's condition. [ABSTRACT FROM AUTHOR]

Alcohol and drug use (ADU) poses a significant barrier to optimal HIV treatment outcomes for adolescents and youths living with HIV (AYLHIV). We aimed to investigate the prevalence and correlates of ADU among ALHIV in Ugandan fishing communities, areas characterized by high HIV and poverty rates. AYLHIV aged 18–24, who knew they were HIV-positive, were selected from six HIV clinics. Substance use was determined through self-report in the last 12 months and urine tests for illicit substances. Utilizing a socioecological framework, the study structured variables into a hierarchical logistic regression analysis to understand the multi-layered factors influencing ADU. Self-reported past 12 months substance use was 42%, and 18.5% of participants had a positive urine test for one or more substances, with alcohol, benzodiazepines, and marijuana being the most commonly used. With the addition of individual-level socio-demographics, indicators of mental health functioning, interpersonal relationships, and community factors, the logistic regression analysis revealed greater exposure to adverse childhood experiences increased the odds of substance use (Odds Ratio [OR] = 1.24; 95% Confidence Interval [CI]: 1.03–1.55). Additionally, exposure to alcohol advertisements at community events significantly raised the odds of substance use (OR = 3.55; 95% CI: 1.43–8.83). The results underscore the high prevalence among AYLHIV and emphasize the need for comprehensive interventions targeting individual (e.g., life skills education and mental health supports), interpersonal (e.g., peer support and family-based interventions), community (e.g., community engagement programs, restricted alcohol advertisements and illicit drug access), and policies (e.g., integrated care models and a national drug use strategy), to address ADU. [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]

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: The practice of palliative sedation continues to raise ethical questions among people, which in turn leads to its varied acceptance and practice across regions. As part of the Palliative Sedation European Union (EU) project, the aim of the present study was to determine the perceptions of palliative care experts regarding the practice of palliative sedation in eight European countries (The Netherlands, Belgium, Germany, UK, Italy, Spain, Hungary, and Romania). Methods: A specifically designed survey, including questions on the most frequently used medications for palliative sedation, their availability per countries and settings, and the barriers and facilitators to the appropriate practice of palliative sedation was sent to expert clinicians involved and knowledgeable in palliative care in the indicated countries. A purposive sampling strategy was used to select at least 18 participating clinicians per consortium country. Descriptive statistical analysis was conducted on the survey data. Results: Of the 208 expert clinicians invited to participate, 124 participants completed the survey. Midazolam was perceived to be the most frequently used benzodiazepine in all eight countries. 86% and 89% of expert clinicians in Germany and Italy, respectively, perceived midazolam was used "almost always", while in Hungary and Romania only about 50% or less of the respondents perceived this. Levomepromazine was the neuroleptic most frequently perceived to be used for palliative sedation in the Netherlands, Spain, Germany, and the United Kingdom. Between 38- 86% of all eight countries´ expert clinicians believed that opioid medications were "almost always" used during palliative sedation. The perceived use of IV hydration and artificial nutrition "almost always" was generally low, while the country where both IV hydration and artificial nutrition were considered to be "very often" given by a third of the expert clinicians, was in Hungary, with 36% and 27%, respectively. Conclusions: Our study provides insight about the differences in the perceived practice of medication during palliative sedation between eight European countries. In countries where palliative care services have been established longer perceptions regarding medication use during palliative sedation were more in line with the recommended European guidelines than in Central and Eastern European countries like Romania and Hungary. [ABSTRACT FROM AUTHOR]

Background: It is unclear how primary care physicians manage insomnia after the introduction of novel hypnotics such as orexin receptor antagonists and melatonin receptor agonists. This Web-based questionnaire survey aimed to examine treatment strategies for insomnia in Japanese primary care practice. Methods: One-hundred-and-seventeen primary care physicians were surveyed on the familiarity of each management option for insomnia on a binary response scale (0 = "unfamiliar"; 1 = "familiar") and how they managed insomnia using a nine-point Likert scale (1 = "I never prescribe/perform it"; 9 = "I often prescribe/perform it"). Physicians who were unfamiliar with a management option were deemed to have never prescribed or performed it. Results: Regarding medication, most physicians were familiar with novel hypnotics. Suvorexant was the most used hypnotic, followed by lemborexant and ramelteon. These novel hypnotics averaged 4.8–5.4 points and 4.0–4.7 points for sleep onset and sleep maintenance insomnia, respectively. By contrast, most benzodiazepines were seldom used below two points. Regarding psychotherapy, only approximately 40% of the physicians were familiar with cognitive behavioral therapy for insomnia (CBT-I) and they rarely implemented it, at an average of 1.5–1.6 points. More physicians were familiar with single-component psychotherapies (i.e., relaxation, sleep restriction therapy, and stimulus control) compared to CBT-I, and 48–74% of them implemented it slightly more often, with scores ranging from 2.6 to 3.4 points. Conclusion: This study suggests that Japanese primary care physicians seldom use CBT-I to treat insomnia. In addition, they use novel sleep medications more frequently than benzodiazepines in terms of pharmacotherapy. The use and availability of CBT-I in Japanese primary care might be facilitated by: educating primary care physicians, implementing brief or digital CBT-I, and/or developing collaborations between primary care physicians and CBT-I specialists. [ABSTRACT FROM AUTHOR]

Background: Data on overuse of diagnostic and therapeutic resources underline their contribution to the decline in healthcare quality. The application of "Do Not Do" recommendations, in interaction with gender biases in primary care, remains to be fully understood. Therefore, this study aims to identify which low-value practices (LVPs) causing adverse events are susceptible to be applied in primary care setting with different frequency between men and women. Methods: A consensus study was conducted between November 1, 2021, and July 4, 2022, in the primary care setting of the Valencian Community, Spain. Thirty-three of the 61 (54.1%) health professionals from clinical and research settings invited, completed the questionnaire. Participants were recruited by snowball sampling through two scientific societies, meeting specific inclusion criteria: over 10 years of professional experience and a minimum of 7 years focused on health studies from a gender perspective. An initial round using a questionnaire comprising 40 LVPs to assess consensus on their frequency in primary care, potential to cause serious adverse events, and different frequency between men and women possibly due to gender bias. A second round-questionnaire was administered to confirm the final selection of LVPs. Results: This study identified nineteen LVPs potentially linked to serious adverse events with varying frequencies between men and women in primary care. Among the most gender-biased and harmful LVPs were the use of benzodiazepines for insomnia, delirium, and agitation in the elderly, and the use of hypnotics without a previous etiological diagnosis. Conclusions: Identifying specific practices with potential gender biases, mainly in mental health for the elderly, contributes to healthcare promotion and bridges the gap in gender inequalities. Trial registration: NCT05233852, registered on 10 February 2022. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol. Methods: This was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient's immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient's liver function and adverse events. Results: Data from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3+, CD4+, CD8+, and NK cells and the CD4+/CD8+ ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased(P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug(P > 0.05). Conclusion: The effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety. Trial registration: The trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022). [ABSTRACT FROM AUTHOR]

Background: Remimazolam is a recently developed, ultrashort-acting benzodiazepine that is used as a general anesthetic. Some cases of remimazolam anaphylaxis have been reported, but its characteristics are not fully understood. We present an interesting case report and review of the literature to better understand remimazolam anaphylaxis. Case presentation: A 75-year-old man scheduled for robot-assisted gastrectomy was administered remimazolam for the induction of general anesthesia. After intubation, low end-expiratory CO2, high airway pressure and concurrent circulatory collapse were observed. Bronchoscopy revealed marked tracheal and bronchial edema, which we diagnosed as anaphylaxis. The patient suffered cardiac arrest after bronchoscopy but recovered immediately with intravenous adrenaline administration and chest compressions. We performed skin prick tests for the drugs used during induction except for remimazolam, considering the high risk of systemic adverse reactions to remimazolam. We diagnosed remimazolam anaphylaxis because the skin prick test results for the other drugs used during anesthesia were negative, and these drugs could have been used without allergic reactions during the subsequent surgery. Furthermore, this patient had experienced severe anaphylactic-like reactions when he underwent cardiac surgery a year earlier, in which midazolam had been used, but it was not thought to be the allergen at that time. Based on these findings, cross-reactivity to remimazolam and midazolam was suspected. However, the patient had previously received another benzodiazepine, brotizolam, to which he was not allergic, suggesting that cross-reactivity of remimazolam may vary among benzodiazepines. In this article, we reviewed the 11 cases of remimazolam anaphylaxis that have been described in the literature. Conclusions: Remimazolam is an ultrashort-acting sedative; however, it can cause life-threatening anaphylaxis. In addition, its cross-reactivity with other benzodiazepines is not fully understood. To increase the safety of this drug, further research and more experience in its use are needed. [ABSTRACT FROM AUTHOR]

Background: Delirium is a common neuropsychiatric syndrome without an FDA-approved treatment. Commonly used modalities show little improvement in outcomes; therefore, prevention efforts are imperative. Abnormalities in the sleep/wake cycle have been linked to delirium, and melatonin has been proposed to replace the hypothesized low levels of endogenous melatonin and restore sleep/wake cycle synchronization. Objectives: The primary objective of this study was to evaluate the association between melatonin, benzodiazepines (BZDs) or zolpidem (ZLP), and the use of as-needed antipsychotics and BZDs for delirium in noncritically ill adult patients. Methods: This was a multicenter retrospective cohort study of noncritically ill adult patients admitted to two separate health systems from August 2012 to December 2018 receiving either melatonin or nonmelatonin medications (ZLP or BZDs) for sleep. The coprimary endpoint was the proportion of patients receiving a pro re nata (PRN) antipsychotic or BZD 5 days from the patient's first dose of melatonin, BZD, or ZLP. Secondary outcomes included evaluation of the coprimary outcome in patients 65 years of age or older, total number of PRN antipsychotic and BZD doses, and length of stay. Results: Two hundred and twenty-five patients were included in the final analysis. Administration of BZD or ZLP was associated with a higher risk of subsequent BZD administration as compared with melatonin (OR 2.78, 95% CI 1.2–1.87) and ZLP (OR 2.78, 95% CI 1.25–6.17). BZD or ZLP had no impact on PRN antipsychotic use compared with melatonin (OR 1.09, 95% CI 0.51–2.35) and ZLP (OR 1.16, 95% CI 0.56–2.4). Conclusion: Melatonin use was found to be associated with a significant decrease in PRN BZD use in noncritically ill patients hospitalized on general floors; however, there was no observed association with overall PRN antipsychotic use. These results suggest that using melatonin may help decrease utilization of medications commonly used to manage delirium. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol and substance use are increasing in older adults, many of whom have depression, and treatment in this context may be more hazardous. We assessed alcohol and other substance use patterns in older adults with treatment‐resistant depression (TRD). We examined patient characteristics associated with higher alcohol consumption and examined the moderating effect of alcohol on the association between clinical variables and falls during antidepressant treatment. Methods: This secondary and exploratory analysis used baseline clinical data and data on falls during treatment from a large randomized antidepressant trial in older adults with TRD (the OPTIMUM trial). Multivariable ordinal logistic regression was used to identify variables associated with higher alcohol use. An interaction model was used to evaluate the moderating effect of alcohol on falls during treatment. Results: Of 687 participants, 51% acknowledged using alcohol: 10% were hazardous drinkers (AUDIT‐10 score ≥5) and 41% were low‐risk drinkers (score 1–4). Benzodiazepine use was seen in 24% of all participants and in 21% of drinkers. Use of other substances (mostly cannabis) was associated with alcohol consumption: it was seen in 5%, 9%, and 15% of abstainers, low‐risk drinkers, and hazardous drinkers, respectively. Unexpectedly, use of other substances predicted increased risk of falls during antidepressant treatment only in abstainers. Conclusions: One‐half of older adults with TRD in this study acknowledged using alcohol. Use of alcohol concurrent with benzodiazepine and other substances was common. Risks—such as falls—of using alcohol and other substances during antidepressant treatment needs further study. Key points: Approximately half of older adults with treatment‐resistant depression acknowledged drinking alcoholAmong drinkers, 24% were also using benzodiazepine and 10% were using other substances like cannabisUse of other substances (mostly cannabis) was associated with alcohol consumption [ABSTRACT FROM AUTHOR]

β‐Phenyl‐γ‐aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. The use of phenibut is legal in the USA and it is widely available online without a prescription. Increased public awareness of phenibut has led to a growing number of reports of acute intoxication and withdrawal. In this review, we describe the pharmacology of phenibut, the presentation and management of acute intoxication, and regulatory issues, placing particular emphasis on the treatment of acute withdrawal, for which there are no comparative studies. Among 29 cases of phenibut withdrawal, patients were successfully treated with baclofen, benzodiazepines, and phenobarbital, as individual agents or in various combinations. Ancillary medications included antipsychotics, dexmedetomidine, gabapentin, and pregabalin. After stabilization, a number of patients did well on baclofen tapers, whereas others were weaned off benzodiazepines or phenobarbital. Phenobarbital may be preferred over baclofen, or used as an added agent, in patients at risk for seizures. As long as phenibut remains legal, cases of phenibut intoxication and withdrawal are likely to increase. As urine or plasma drug screening for phenibut is not widely available, it is vital that clinicians obtain a detailed medication history in patients presenting to the emergency department with nonspecific symptoms that may represent phenibut intoxication or withdrawal. Further, clinicians may wish to consult an addiction specialist or toxicologist in these situations. [ABSTRACT FROM AUTHOR]

Background: Holocaust survivors (HS) experience higher rates of physiological and psychological morbidities, increasing their vulnerability to perioperative complications. Limited information exists regarding their perioperative neurocognitive disorders. This study aimed to assess the rates of preoperative cognitive impairment, postoperative delirium, and other complications among HS aged 75+ undergoing elective surgery. Methods: This is a single‐center retrospective cohort study that analyzed prospectively collected data. All surgical patients born before 1945 who underwent elective noncardiac surgery at a tertiary hospital in Israel during 2020–2021 were included. The HS group was identified through the hospital's information system. Preoperative cognitive impairment was assessed using the Mini‐Cog test. Postoperative delirium was defined as a combined outcome, which included a positive 4A's‐Test (4AT) result during the postanesthesia care unit stay up to the second postoperative day, a positive 3‐Minute Diagnostic Confusion Assessment Method (3D‐CAM) test administered by the geriatric team, and identification through the medical records using the Chart‐based Delirium Identification Instrument (CHART‐DEL). We used multivariable regression to assess the risk factors for postoperative delirium. Results: Out of 1332 eligible patients, 422 (32%) were HS, while the others served as controls. Both groups had a similar rate of preoperative cognitive impairment (24%, p = 0.89) and postoperative delirium (16%, p = 0.95). HS exhibited a higher risk of the composite adverse events (24% vs. 20%, p = 0.05, aOR [95% CI] 1.3 [1.0–1.7]), driven mainly by falls during hospitalization (4% vs. 2%, p = 0.03, aOR 2.1 [1.1–4.1]). HS patients were more likely to be childless (33% vs. 11%, p = 0.001) and had higher rates of chronic antidepressant and benzodiazepine use. Conclusions: HS achieving longevity do not face increased risks of preoperative cognitive impairment and postoperative delirium. However, special care is still warranted due to their elevated rate of other complications during hospitalization. [ABSTRACT FROM AUTHOR]

Tetanus is a life-threatening, vaccine-preventable disease caused by an endotoxin produced by Clostridium tetani. We report a case of severe tetanus in an adult male with a history of intravenous drug use. The patient presented with a 1-day history of inability to open his jaw and a right lower extremity necrotic wound. Initial management consisted of tetanus toxoid, human tetanus immunoglobulin, antimicrobials and intermittent lorazepam. Due to progressive symptoms, wound debridement and placement of an advanced airway in the operating room ensued. Episodes of tetany were associated with fever, autonomic instability, acute desaturations and preemptive ventilator triggering despite maximum doses of continuous propofol and midazolam. Neuromuscular blockade with cisatracurium was added, resulting in control of tetany. Despite initial control, NMB could not be weaned due to recurrent spasms. Intravenous dantrolene was therefore sought as an alternative antispasmodic. Following an initial load, patient was successfully liberated from cisatracurium. Dantrolene was therefore converted to enteral to facilitate gradual down-titration of intravenous sedatives with subsequent conversion to oral benzodiazepines. After a prolonged hospital course, the patient was able to be discharged home. Dantrolene was thus effectively utilized as an adjunctive antispasmodic agent to facilitate liberation from cisatracurium and continuous sedation. [ABSTRACT FROM AUTHOR]

Objectives: Anxiety is a global problem that is readily treatable with psychosocial interventions, though many individuals do not benefit following participation in extant treatment protocols. Accordingly, clarification of process‐related variables that may be leveraged to enhance outcomes appears warranted. Emotion regulation (ER) is a robust correlate of anxiety symptoms and is often targeted in behavioural treatments applied to anxiety‐related problems. Yet, some evidence suggests ER difficulties may be a proxy variable for emotional avoidance (EA). Clarifying the relative influence of ER and EA on anxiety symptom severity may improve specificity in targeting behavioural processes within psychosocial treatments designed to alleviate anxiety‐related suffering. Accordingly, we examined relations of ER and EA to anxiety symptom severity after accounting for anxiety sensitivity and anxiolytic medication use in a community‐based treatment‐seeking sample. Design: A four‐step hierarchical linear regression analysis of cross‐sectional data provided by a community‐based treatment‐seeking sample. Methods: Totally, 120 participants (Mage = 39.18; Female = 58.3%) completed a questionnaire packet upon intake to an anxiety disorders clinic. Results: EA and ER were strongly correlated, and each accounted for significant variance over and above model covariates. EA was a dominant risk factor for anxiety symptom severity, as ER was not a significant predictor (p =.073) following the inclusion of EA in the model (p =.006). Conclusions: EA appears to be a dominant risk factor, and ER a proxy risk factor, for anxiety symptom severity. EA may be an avenue for greater treatment specificity for those with anxiety symptoms. [ABSTRACT FROM AUTHOR]

Simple Summary: In the last days and weeks of life, many patients with cancer develop delirium with fluctuating confusion, altered levels of consciousness, hallucinations, restlessness, and, sometimes, agitation, which fluctuate over time. This condition can be very distressing for the patient and their family. In this article, the authors reviewed different treatments for delirium in patients receiving palliative care. Previous studies have shown that certain medications, such as neuroleptics and benzodiazepines, may be helpful in controlling the terminal agitation associated with end-of-life delirium. However, further research is needed to confirm these findings and find new treatment options to address this challenging issue. End-of-life delirium affects a vast majority of patients before death. It is highly distressing and often associated with restlessness or agitation. Unlike delirium in other settings, it is considered irreversible, and non-pharmacologic measures may be less feasible. The objective of this review is to provide an in-depth discussion of the clinical trials on delirium in the palliative care setting, with a particular focus on studies investigating pharmacologic interventions for end-of-life delirium. To date, only six randomized trials have examined pharmacologic options in palliative care populations, and only two have focused on end-of-life delirium. These studies suggest that neuroleptics and benzodiazepines may be beneficial for the control of the terminal restlessness or agitation associated with end-of-life delirium. However, existing studies have significant methodologic limitations. Further studies are needed to confirm these findings and examine novel therapeutic options to manage this distressing syndrome. [ABSTRACT FROM AUTHOR]