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Sepsis is one of the leading causes of death in critical patients worldwide and its occurrence is related to the excessive activation of macrophages. Chloride loss worsens the prognosis of patients with sepsis but the underlying mechanism is currently unclear. In this study, we founded that macrophages deficient in intracellular Cl - secrete more inflammatory cytokines such as IL-1β, IL-6 and TNF-α compared with control group. The intracellular chloride level decreased in WNK1 deficiency or activity inhibited macrophages with more severe inflammatory response after LPS treatment. Remimazolam, as classic GABAa receptor agonist, alleviates excessive inflammation cascade by promoting macrophage chloride influx during sepsis progression. Collectively, this study proves that macrophage WNK1 acts as a negative regulator of inflammatory response by sensing chloride to maintain intracellular chloride balance during sepsis coupled with hypochloremia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bone cancer pain (BCP) is a complex clinical challenge, with current treatments often falling short of providing adequate relief. Remimazolam, a benzodiazepine receptor agonist recognized for its anxiolytic effects, has emerged as a potential agent in managing BCP. This study explores the analgesic properties of remimazolam and its interaction with the translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, in spinal astrocytes. In the context of BCP, previous research has indicated that TSPO expression in spinal astrocytes may serve a protective regulatory function in neuropathic pain models. Building on this, the BCP mice received various doses of remimazolam on the 15th day post-inoculation, and pain behavior was assessed over time. The results showed that BCP induced an upregulation of TSPO and astrocyte activation in the spinal dorsal horn, alongside increased extracellular signal-regulated kinase (ERK) signaling and inflammatory cytokine expression. Remimazolam administration resulted in a dose-dependent reduction of pain behaviors, which corresponded with a decrease in both ERK pathway activation and inflammatory factor expression. This suggests that remimazolam's analgesic effects are mediated through its action as a TSPO agonist, leading to the attenuation of neuroinflammation and pain signaling pathways. Importantly, the analgesic effects of remimazolam were reversed by the TSPO antagonist PK11195, underscoring the pivotal role of TSPO in the drug's mechanism of action. This reversal also reinstated the heightened levels of ERK activity and inflammatory mediators, further confirming the involvement of TSPO in the modulation of these pain-related processes. These findings open new avenues for the therapeutic management of bone cancer pain, positioning remimazolam as a promising candidate for further investigation and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Insomnia is a common sleep disorder, associated with multiple health concerns. Current medications for insomnia are associated with higher safety risks if clinical practice guidelines or monograph recommendations are not followed. This study aims to understand real-world prescribing practices among patients with insomnia in Canada, including medication utilization, potentially inappropriate medication use, cost incurred, and lines of treatment., Methods: This retrospective observational study utilized longitudinal drug claims data from 2018 to 2020 from the Canadian IQVIA National Private Drug Plan and Ontario Drug Benefit databases. Patients with any claims for medications approved for insomnia in Canada were identified. Four types of inappropriate medication usage were defined: (1) elevated daily dose; (2) extended duration of use for benzodiazepines (BZD) and/or Z-drugs; (3) combination use; and (4) opioid overlap with BZD and/or Z-drugs., Results: In 2019, 597,222 patients with insomnia were identified; 64% were female, with an average age of 55 years. Inappropriate medication use was noted in 52.5% of adult patients (aged 18-65 years) and 69.5% of senior patients (aged >65 years). Extended duration was the most common inappropriate medication usage category. The annual cost of medications for insomnia was $54.8 million, and $30.3 million (55.2%) met inappropriate medication use criteria., Conclusion: High prevalence of inappropriate medications usage in insomnia raises serious safety concerns for patients suffering from insomnia, particularly seniors, while also placing a substantial burden on the Canadian public and private health systems. This highlights an unmet need for better education regarding current guidelines and more effective and safer treatment options., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Background: Benzodiazepines are frequently prescribed to treat anxiety and insomnia, but long-term use has been associated with the development of dependence, tolerance, and cognitive decline, especially among older adults. This study aimed to investigate the pattern of consumption and factors associated with inappropriate prescribing of benzodiazepines in primary health care., Methods: This is a cross-sectional analytical study, using dispensing records of diazepam, clonazepam, and nitrazepam from public pharmacies in a Brazilian municipality between 2018 and 2022. Metrics for benzodiazepine consumption were DDD (Defined Daily Dose) and DDD/1000PD (per 1000 population per day). Long-term/prolonged benzodiazepine use was defined as consuming at least 90 DDD and at least 2 dispensations per year. To ascertain associations between long-term use and predictor variables, a multivariate logistic regression model was utilized., Findings: A total of 40402 participants were included, with an average age of 55 years (SD = 0.30), 38.5% were older aged. Diazepam and nitrazepam exceeded the daily dose recommended. There was a reduction in diazepam consumption during the study period, as calculated by DDD/1.000PD, while the consumption of other benzodiazepines remained stable. However, a significant increase in diazepam consumption is noted when considering the last decade. Prolonged use was observed in 29.1% of participants, with a significant prevalence among the older people (34.8% of them were long-term users) and advancing age was identified as a risk factor for long-term use. Higher PDDs were also associated with long-term use and aging. Participants who used different benzodiazepines during the period had a higher risk of prolonged use., Conclusions: These results provide insights into the prevalence of problematic utilization of benzodiazepines in primary health care. Authorities and health care providers must take steps to encourage gradual cessation of prolonged benzodiazepine prescriptions and the embrace of suitable strategies for addressing anxiety and insomnia within primary health care settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Barboza Zanetti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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

Aims: The South Korean government implemented the narcotics information management system (NIMS) on 18 May 2018 to manage benzodiazepine receptor agonists (BzRAs) and narcotics effectively and establish a reporting mechanism for these drugs. This study assessed the effects of NIMS on inappropriate use of BzRAs., Methods: Using national patient sample data from 2016 to 2020, we analysed adult outpatients who were prescribed oral BzRAs. We conducted a time series and segmented regression analysis using selected indicators to analyse the monthly variations related to the inappropriate use of these medications., Results: The study revealed no significant changes in the indicators of inappropriate BzRA use following the NIMS implementation. Contrary to expectations, there was a significant increase in the proportion of patients exceeding defined daily dose (DDD) and in those receiving concurrent prescriptions of multiple BzRAs, following the implementation of NIMS. The immediate impact of the COVID-19 pandemic was an increase in DDD exceedance; however, overall, this did not significantly affect BzRA use., Conclusions: The introduction of NIMS did not significantly enhance the management of BzRA misuse. Additional measures, including continuous monitoring, system improvements and comprehensive education for prescribers and patients, are recommended to ensure the appropriate use of psychotropic medications., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Alcohol Withdrawal Syndrome (AWS) is a potentially life-threatening complication of alcohol use disorder (AUD) that can be challenging to recognize in hospitalized patients. Our institution implemented universal AUD screening for all patients admitted to a non-critical care venue using the Prediction of Alcohol Withdrawal Severity Scale (PAWSS). At risk patients were then further assessed, utilizing the Glasgow Modified Alcohol Withdrawal Scale (GMAWS), and medicated according to a predetermined protocol. This study sought to determine whether this protocol decreased hospital length of stay, lowered the total benzodiazepine dose administered, and decreased adverse events attributable to AWS., Methods: This retrospective cohort study was conducted over a 6-year period from 2014 to 2020. The study included patients with an ICD-10 code diagnosis of AWS and subsequently divided them into two groups: pre- and post-protocol introduction. Outcome measures were compared pre- versus post-protocol introduction., Results: There were 181 patient encounters pre- and 265 patient encounters post-protocol. There was no statistically significant difference in median length of stay between the two groups (2.956 days pre and 3.250 days post-protocol, p = 0.058). Post-protocol, there was a statistically significant reduction in median total benzodiazepine dose (13.5 mg and 9 mg lorazepam equivalents pre- and post-protocol, p < 0.001) and in occurrence of delirium tremens (7.7 % pre and 2.3 % post-protocol, p = 0.006)., Conclusion: Protocol implementation did not reduce length of stay in patients with AUD but was associated with a significant reduction in total benzodiazepine dose and, when adjusted, a non-statistically significant decrease in progression to delirium tremens in hospitalized patients, after applying Bonferroni adjustment., Competing Interests: Declaration of competing interest None of the authors have a financial conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

While vulvar lichen sclerosus (VLS) causes intense pruritus, associated risks of mood disorders and prescription patterns and impact of concurrent sexual dysfunction are unknown. We queried TriNetX Diamond Network between 2009 and 2022, conducting three comparisons after propensity-score matching for demographics and relevant comorbidities: (1) women with lichen sclerosus (LS) sparing the vulva vs. women with VLS; (2) VLS patients who received treatment within 6 months of diagnosis vs. patients who did not and (3) VLS patients with vs. without sexual dysfunction. Outcomes included new depressive episodes, anxiety disorder, major depressive disorder (MDD), and prescriptions of antidepressants or benzodiazepines. After matching, VLS was associated with increased depressive episode [risk ratio (RR) 1.39], anxiety disorder (RR 1.93), and MDD (RR 2.00) diagnoses compared to LS sparing the vulva. Next, VLS treatment was associated with decreased risk of depressive episode (RR 0.60) and anxiety disorder (RR 0.72). Finally, concurrent sexual dysfunction was associated with increased benzodiazepine (RR 3.50), vaginal estrogen (RR 6.20), antipruritic agents (RR 3.90), and topical anti-inflammatory (RR 2.61) prescriptions. In conclusion, vulvar involvement is associated with increased risk of antidepressant and benzodiazepine prescriptions, and diagnosis of depressive episode, anxiety disorder, or MDD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Schizophrenia is a serious mental disorder, and monitoring remission is a widely used measure of effectiveness of the treatment provided. It is very important to identify possible factors correlating with remission. In our substudy of BeSt InTro, a randomized controlled trial of three antipsychotic drugs, 126 patients with ICD-10 diagnoses F20-29 (F23 excluded) were randomized to one of the second-generation antipsychotic drugs amisulpride, aripiprazole or olanzapine. Remission rate was calculated at seven assessment points, with and without using the time criterion of six months included in the consensus remission criteria. Because of drop-out (n = 77), we had data for 49 patients at one-year follow-up. These data were used to calculate the one-year remission rate to 55 % (27/49), without taking into consideration the 6-month time criterion. When we applied the consensus remission criteria with the 6-month time criterion included, the one-year remission rate was calculated for 59 patients: 29 % (17/59). Antipsychotic drug naivety and low negative symptom load at baseline correlated highly with belonging to the remission group. Use of amisulpride was more probable to lead to remission than that of aripiprazole, but it was not more probable than the use of olanzapine (in per-protocol analyses). Negative symptoms showed the largest resistance to treatment. The lack of remission for the majority of the participants in this closely monitored antipsychotic drug trial is alarming and could act as a reminder that novel treatment principles are needed, especially targeted towards the negative symptoms in schizophrenia., Competing Interests: Declaration of competing interest The authors have declared that there are no conflicts of interest in relation to this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Preventing emergence delirium is a clinical goal for pediatric anesthesia, yet there is no consensus on its prevention. This study investigated the hypothesis that a continuous infusion or a single bolus of remimazolam can reduce the incidence of emergence delirium in children., Methods: A total of 120 children aged 1 to 6 yr were randomly and equally allocated into three groups: group RC, which received a continuous infusion of remimazolam at 1 mg · kg-1 · h-1; group RB, which received a single bolus of remimazolam at 0.2 mg · kg-1 at the beginning of wound closure; and group C, which received a continuous infusion of saline at 1 ml · kg-1 · h-1 and a single bolus of saline at 0.2 ml · kg-1 at the beginning of sutures. The primary outcome was the incidence of emergence delirium assessed by the Pediatric Anesthesia Emergence Delirium scale. Secondary outcomes included the number of rescue propofol administrations in the postanesthesia care unit, recovery time, and adverse events., Results: Emergence delirium was observed in 14 of 40 (35%) patients in group C, 2 of 40 (5%) patients in group RC (vs. group C, P = 0.001; risk ratio, 95% CI: 0.14, 0.04 to 0.59), and 3 of 39 (7.7%) patients in group RB (vs. group C, P = 0.003; risk ratio, 95% CI: 0.22, 0.07 to 0.71). Ten of 40 patients in group C, 2 of 40 patients in group RC (vs. group C, P = 0.012; risk ratio, 95% CI: 0.20, 0.05 to 0.86), and 2 of 39 patients in group RB (vs. group C, P = 0.014; risk ratio, 95% CI: 0.21, 0.05 to 0.88) needed rescue propofol. No differences in the recovery time and adverse effects were detected., Conclusions: Both continuous infusion and single bolus administration of remimazolam can effectively reduce the occurrence of emergence delirium in children., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

Background: Phenobarbital may offer advantages over benzodiazepines for severe alcohol withdrawal syndrome (SAWS), but its impact on clinical outcomes has not been fully elucidated., Objective: The purpose of this study was to determine the clinical impact of phenobarbital versus benzodiazepines for SAWS., Methods: This retrospective cohort study compared phenobarbital to benzodiazepines for the management of SAWS for patients admitted to progressive or intensive care units (ICUs) between July 2018 and July 2022. Patients included had a history of delirium tremens (DT) or seizures, Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar) >15, or Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score ≥4. The primary outcome was hospital length of stay (LOS). Secondary outcomes included progressive or ICU LOS, incidence of adjunctive pharmacotherapy, and incidence/duration of mechanical ventilation., Results: The final analysis included 126 phenobarbital and 98 benzodiazepine encounters. Patients treated with phenobarbital had shorter median hospital LOS versus those treated with benzodiazepines (2.8 vs 4.7 days; P < 0.0001); a finding corroborated by multivariable analysis. The phenobarbital group also had shorter median progressive/ICU LOS (0.7 vs 1.3 days; P < 0.0001), and lower incidence of dexmedetomidine ( P < 0.0001) and antipsychotic initiation ( P < 0.0001). Fewer patients in the phenobarbital group compared to the benzodiazepine group received new mechanical ventilation ( P = 0.045), but median duration was similar (1.2 vs 1.6 days; P = 1.00)., Conclusion and Relevance: Scheduled phenobarbital was associated with decreased hospital LOS compared to benzodiazepines for SAWS. This was the first study to compare outcomes of fixed-dose, nonoverlapping phenobarbital to benzodiazepines in patients with clearly defined SAWS and details a readily implementable protocol., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Clinical practice guidelines (CPGs) and clinical recommendations (CRs) are developed to aide and guide providers in treating a variety of conditions, including traumatic brain injury (TBI). There is little knowledge on the impact that CPGs and CRs have on provider practice. One TBI recommendation that was able to be tracked in medical record codes was the use of benzodiazepines (BZD). Because of potential for misuse, diversion, addiction, cognitive impairment, and brain healing interference, the DoD and Department of Veterans Affairs (VA) jointly discourage prescribing BZD after TBI. As part of an effort to look at translation of CPG guidance into clinical practice, our objective was to examine the issuance of BZD prescriptions, including dose, type, and prescribing provider, prescribing setting, and primary diagnosis at issuance among U.S. service members with mild Traumatic Brian Injury (mTBI)., Materials and Methods: Using DoD data sourced from the Comprehensive Ambulatory/Professional Encounter Record (CAPER) databases of the Military Health System (MHS) Medical Data Repository (MDR), we identified all U.S. service members with a first lifetime diagnosis of mTBI from October 1, 2015 to September 30, 2016. Data on prescriptions issued to this group during a period of active treatment for a mTBI were obtained from the Pharmacy Detail Transaction Service (PDTS) databases of the MDR and identified BZD prescriptions based on the American Hospital Formulary Service (AHFS) therapeutic classification system. We validated coding assumptions through structured review of the clinical record contained within the Armed Forces Health Longitudinal Technology Application (AHLTA) of 30 randomly selected cohort members., Results: Among U.S. service members, 4.5% filled a BZD prescription while under active medical treatment for a recent mTBI. These service members were more likely female and older when compared to their counterparts not prescribed BZD. Among service members under active treatment for mTBI during the study period, 52.6% (n = 7,935) filled a prescription; of these, 8.5% (n = 676) filled a BZD prescription. Of U.S. service members filing a BZD prescription while undergoing active treatment for an mTBI, 64.6% (n = 437) filled prescriptions for BZD and antidepressants, 54.9% (n = 371) filled prescriptions for both BZD and NSAIDS, and 42.2% (n = 285) concurrently filled prescriptions for BZD and opioids., Conclusions: This effort to examine the translation of CPG recommendations into practice through evaluation of medical record data indicates that providers are prescribing BZD to patients under active treatment for an acute mTBI. The mTBI CPG recommends that the BZD class of medications be avoided in patients healing from brain injury. However, the team recognizes there are confounding factors that may impact the medications that are prescribed for patients with mTBI. Additional work to understand how CPGs and CRs are received and utilized by providers may elucidate opportunities to close the gap between clinical practice guidance and clinical practice., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: This study aimed to investigate the effects of combining remimazolam with estazolam on hemodynamics and pain levels after laparoscopic gastrointestinal surgery., Methods: A total of 184 patients who underwent laparoscopic gastrointestinal surgery were enrolled in this double-blind randomized controlled trial. The patients were divided into four groups: Study Group 1(Remimazolam), Study Group 2(Estazolam), Study Group 3(Remimazolam + Estazolam), and Control Group. Anesthesia induction included intravenous injection of remimazolam and estazolam in the study groups, while the control group received normal saline. Hemodynamic parameters, stress responses, anxiety levels, and pain intensity were assessed at various time points., Results: The results showed that the combination of remimazolam and estazolam significantly improved hemodynamic parameters compared to the control group. Study Group 3 exhibited the lowest anxiety levels and stress responses among all groups. Furthermore, Study Group 3 had the lowest pain intensity scores at different postoperative time points., Conclusion: The combination of remimazolam and estazolam effectively stabilized hemodynamics, reduced anxiety levels, and alleviated pain intensity after laparoscopic gastrointestinal surgery. These findings suggest that this combination therapy has the potential to improve surgical outcomes and patient comfort., (© 2024. The Author(s).)

Drugs have actions that may be classified as therapeutic effects and side effects; side effects are actions that do not contribute to therapeutic benefit. Some side effects are neutral; others, experienced as undesirable or unpleasant, are recorded as adverse effects. Some drug actions are therapeutic for some disorders and adverse for others; or therapeutic during acute illness and adverse during maintenance treatment. As an example, anticholinergic action may be adverse when a tricyclic antidepressant is used to treat depression but therapeutic when the drug is used to treat irritable bowel syndrome with diarrhea. In clinical practice, side or adverse effects of a drug may be leveraged to manage troublesome symptoms. As an example, the sedative effect of a low dose of trazodone may be useful for some patients with insomnia. With this background, studies have examined whether the increase in appetite and weight associated with olanzapine and mirtazapine may be effective against anorexia and cachexia associated with cancer and cancer chemotherapy. The subject is important because cachexia may be present in 30%-50% of patients with cancer (with higher prevalence in patients with more advanced cancer) and because the presence of cachexia is associated with a higher risk of disease progression and mortality. Many randomized controlled trials (RCTs) have examined pharmacologic interventions such as progestins, corticosteroids, anamorelin, and medical cannabis for cancer related cachexia; most results have been disappointing. A recent RCT found that olanzapine (2.5 mg/d for 12 weeks) improved appetite, weight, other nutritional parameters, and quality of life in patients with locally advanced or metastatic cancer treated with chemotherapy. Another RCT, however, found that mirtazapine (30 mg/d for 8 weeks) brought no nutritional or anthropometric gain in patients with cancer and anorexia. It is concluded that olanzapine but not mirtazapine merits further investigation in patients with cancer who have anorexia and cachexia., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Objective: Guidelines recommend deprescribing benzodiazepine receptor agonists (BZRA) in older adults, yet implementation in clinical practice remains limited. Adapting effective, evidence-based interventions to a new context is a resource-saving strategy. In Canada, the D-PRESCRIBE intervention comprised a patient educational brochure and a pharmaceutical opinion inviting physicians to revise BZRA prescribing and consider safer alternatives. Due to its effectiveness on BZRA deprescribing among Canadian older adults, we aimed to adapt the D-PRESCRIBE intervention to the Belgian community setting., Design: Recommendations from the ADAPT guidance, that provides a systematic approach for adapting interventions to new contexts, were followed. We conducted a mixed-methods study that comprised (1) group discussions and cognitive interviews to assess the acceptability and need for adaptation of the intervention's components and (2) a survey on the adapted pharmaceutical opinion. A research committee involving stakeholders' representatives decided on the adaptations, respecting the core functions of both tools. Changes in intervention components were reported following the Model for Adaptation Design and Impact framework., Setting: Belgian French-speaking community setting., Participants: Six older adults (≥65 years), six general practitioners (GPs) and seven pharmacists participated in the group discussions or interviews. 46 GPs and 91 pharmacists responded to the survey., Results: Participants welcomed the brochure positively. Still, some changes in the vocabulary, wording, photos and icons were made for several purposes including making the patient feel concerned about the brochure and softening the use of fear. The pharmaceutical opinion aroused mixed perceptions. Its name, layout and content were adapted to enhance its acceptability and fit with our healthcare system, practices and national guidelines. The survey highlighted several enablers and barriers to its use from the perspectives of GP and pharmacist., Conclusions: The Canadian D-PRESCRIBE intervention was adapted to the Belgian setting following a thorough and transparent process. Its feasibility will be tested in a future pilot study (NCT:05929417)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In France, general practitioners (GPs) prescribe benzodiazepines and Z-drugs (BZD/ZDs) widely, and especially to older adults. Several characteristics of patients and/or GPs linked to BZD/ZD overprescription have been described in the general population but not among older patients in primary care., Objectives: To estimate the proportion of GP consultations by patients aged 65 and over that resulted in a BZD/ZD prescription, and determine whether any GP-related factors predicted BZD/ZD overprescription in this setting., Methods: We analyzed sociodemographic and practice-related GP characteristics, and aggregated data on consultations recorded prospectively by 117 GPs in a database between 2000 and 2010. Next, we used logistic regression models to look for factors potentially associated with BZD/ZD overprescription (defined as an above-median prescription rate)., Results: The GPs' mean age at inclusion was 47.4 (7.1), and 87.9% were male. During the study period, the median (95% confidence interval) proportion of consultations with patients aged 65 and over resulting in a BZD/ZD prescription was 21.8% (18.1-26.1) (range per GP: 5-34.1%). In a multivariable analysis, a greater number of chronic disease (OR [95% CI] = 2.10 [1.22-3.64]), a greater number of drugs prescribed per consultation (5.29 [2.72-10.28]), and shorter study participation were independently associated with BZD/ZD overprescription., Conclusions: BZD/ZD overprescription was associated with a greater chronic disease burden and the number of drugs prescribed per consultation but not with any sociodemographic or practice-related GP characteristics. Targeted actions are needed to help GPs limit their prescription of BZD/ZDs to older patients with multiple comorbidities and polypharmacy., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT 3 ) RA, and dexamethasone for preventing chemotherapy-induced nausea and vomiting in patients receiving carboplatin-containing chemotherapy., Patients and Methods: Chemotherapy-naïve patients scheduled to receive carboplatin (AUC ≥5) were randomly assigned to receive either olanzapine 5 mg once daily (olanzapine group) or placebo (placebo group) in combination with aprepitant, a 5-HT 3 RA, and dexamethasone. The primary end point was the complete response (CR; no vomiting and no rescue therapy) rate in the overall phase (0-120 hours). Secondary end points included the proportion of patients free of nausea and safety., Results: In total, 355 patients (78.6% male, median age 72 years, 100% thoracic cancer), including 175 and 180 patients in the olanzapine and placebo groups, respectively, were evaluated. The overall CR rate was 86.9% in the olanzapine group versus 80.6% in the placebo group. The intergroup difference in the overall CR rate was 6.3% (95% CI, -1.3 to 13.9). The proportions of patients free of chemotherapy-induced nausea in the overall (88.6% in the olanzapine group v 75.0% in the placebo group) and delayed (89.7% v 75.6%, respectively) phases were significantly higher in the olanzapine group than in the placebo group (both P < .001). Somnolence was observed in 43 (24.6%) and 41 (22.9%) patients in the olanzapine and placebo groups, respectively, and no events were grade ≥3 in severity., Conclusion: The addition of olanzapine was not associated with a significant increase in the overall CR rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.

Background: Down syndrome (DS), or Trisomy 21, is defined by the existence of an additional chromosome 21. Various physiological considerations in DS patients might lead to challenges in adequate pain management and sedation after surgery. The aim of this systematic review and meta-analysis is to evaluate the variations of the requirement needed for pain management and sedation in patients with DS who have undergone surgery compared to patients without DS., Methods: A systematic review and meta-analysis of studies were conducted, focusing on critically ill patients with DS who were admitted to Intensive care units (ICUs) post-surgery and received opioids and/or benzodiazepines. Searches were conducted in four databases from their inception to November 18, 2023 (Pubmed, Scopus, Cochrane Library, and Web of Science). The primary outcome measured was the dosage of Oral Morphine Equivalent (OME) administered in the days following surgery. Fixed-effect models were used, an approach advisable when only a limited number of studies are available., Results: Out of the 992 studies initially screened, the systematic review included ten studies, encompassing 730 patients, while the meta-analysis consisted of seven studies, encompassing 533 patients. Of the seven studies included in the analysis, 298 patients were identified to have DS, and 235 patients served as controls. Patients with DS showed a slight increase in OME needs on the first day, but this increase was not statistically significant (mean difference [MD] = 0.09; 95% Confidence Interval [CI]: [-0.02, 0.20]; P = 0.11). There was also no significant difference in the requirement for Midazolam on the first day among DS patients (MD = 0.01; CI [-0.16, 0.19]; P = 0.88). In addition, the duration of mechanical ventilation was not statistically significant in patients with DS compared with the control group (MD = -1.46 hours; 95% CI [-9.74, 6.82]; P = 0.73)., Conclusion: Patients with Down syndrome did not require more sedation or analgesia in the first three days after surgery than patients without Down syndrome. Additionally, the two groups showed no significant difference in the duration of mechanical ventilation., (© 2024. The Author(s).)

Remimazolam is a novel ultra-short-acting benzodiazepine with a unique pharmacokinetic profile that makes it an attractive option for use in general anesthesia. This review paper provides an in-depth analysis of remimazolam's applications in the field of general anesthesia, focusing on its pharmacological properties, clinical efficacy, safety profile, and potential advantages compared to other anesthetic agents. Remimazolam acts on GABAa receptors, offering rapid onset and recovery times due to its unique metabolic pathway involving tissue esterases. Clinical trials have demonstrated its efficacy in procedural sedation and general anesthesia, showing a favorable safety profile with minimal cardiovascular and respiratory depression. Compared to traditional anesthetics such as propofol, remimazolam presents distinct advantages, including predictable pharmacokinetics, reduced risk of prolonged sedation, and a reliable safety margin. These attributes position remimazolam as a promising agent in various clinical settings. The purpose of this review is to synthesize current evidence on remimazolam and discuss its potential to improve clinical outcomes in anesthesia practice., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhang et al.)

Background: Remimazolam is manifested by rapid action, hemodynamic stability, and fast recovery. Our study aimed to investigate whether the quality of recovery (QoR) after remimazolam anesthesia in patients undergoing transurethral resection of bladder tumor, which is predominantly performed in the elderly population, is not inferior to that after conventional anesthesia using sevoflurane., Methods: Thirty-four patients were randomly allocated into either of group S (n = 17, receiving sevoflurane anesthesia), or group R (n = 17, receiving remimazolam anesthesia). The QoR was assessed by Korean version of QoR-15 questionnaire, on the day before and after the surgery. Scores acquired for each individual item, QoR-15 scores categorized into 5 dimensions (physical comfort, physical independence, psychological support, emotional state, and pain), and overall global score were subjected to comparative analysis. The primary outcome was postoperative global QoR-15, and a noninferiority delta value of 8.0 was employed., Results: The postoperative global QoR-15 in the group S was 141 (134-146), and in the groups R was 133 (128-142) (P = .152). The mean difference of global QoR-15 (group S-group R) was 1.471 (95% confidence interval of -10.204 to 13.146), and the lower 95% confidence interval margin was lower than the noninferiority margin of -8.0. When comparing the QoR-15 sorted by 5 dimensions, pain scored higher in the group S (20 [18-20]) compared to the group R (15 [15-20], P = .032)., Conclusion: The postoperative QoR following transurethral resection of bladder tumor was found to be lower in patients anesthetized with remimazolam in comparison to those anesthetized with sevoflurane., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Treatment guidelines for the management of pediatric status epilepticus (PSE) are often institution-specific. We aim to characterize deviation from our hospital-based PSE treatment guidelines, the total dosage of benzodiazepines administered, and the need for intubation. The study population included all patients with an ICD -10 code for PSE who required admission to the Pediatric Intensive Care Unit (PICU) from April 2019 to April 2022. There were 66 PICU admissions. All patients with concern for PSE and altered mental status are admitted to the PICU. The cohort was divided between those treated according to the PSE protocol (benzodiazepine dose (0.05 mg/kg- 0.2 mg/kg) versus those who had low dose (≤0.05 mg/kg) and high-dose benzodiazepine (> 0.2 mg/kg) totals. The dosage was calculated as the total dose of benzodiazepines received pre-hospital and in the ED before intubation or transport. Forty-one (62 %) of patients received high-dose benzodiazepines (median 0.34 mg/kg [IQR 0.29-0.56], 19 (29 %) received recommended-dose benzodiazepines (median 0.13 mg/kg [IQR 0.09,0.15] and 6 (9 %) received low-dose (median 0.05 mg/kg [IQR 0.03,0.05]. The high-dose group was 15.9 (95 % CI = 3.7, 99.9) times more likely to be intubated controlling for the location of care (tertiary versus community hospital), and the age of the patient. The recommended-dose and low-dose groups required intubation with much less frequency., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Low back pain is a common reason for presentation to the Emergency Department (ED). However, there are limited large-scale, recent data on the epidemiology, disposition, and medication administration for this condition. The objective of this was to assess the incidence, admission rates, medication administrations, and discharge prescriptions among ED visits for low back pain in the United States., Methods: This was a cross-sectional study of ED presentations for low back pain from 1/1/2016 to 12/31/2023 using the Epic Cosmos database. All ED visits for adults with low back pain identified by ICD-10 codes were included. Outcomes included admission rates, distribution of opioid, benzodiazepine, (non-benzodiazepine) muscle relaxant, acetaminophen, NSAID, and corticosteroid medications administered in the ED, and distribution of opioid, benzodiazepine, muscle relaxant, and corticosteroid medications given upon discharge. Subgroup analyses were performed by specific medication., Results: Of 207,154,419 ED encounters, 12,241,240 (5.9%) were due to back pain with 1,957,299 of these (16.0%) admitted. The admission rate increased over time from 12.8% to 17.1%. The most common medication given in the ED was opioids (40.7%), followed by acetaminophen (37.8%), NSAIDs (22.6%), muscle relaxants (18.4%) benzodiazepines (12.8%), and corticosteroids (5.5%). The most common medications prescribed upon discharge were muscle relaxants (32.1%), followed by opioids (23.2%), corticosteroids (12.2%), and benzodiazepines (3.0%)., Conclusion: Low back pain represents a common reason for presentation to the ED, and admissions have been increasing over time. Opioids remain the most common ED medication, whereas muscle relaxants have arisen as the most common discharge prescription. These findings can help inform health policy decisions, resource allocation, and evidence-based interventions for medication administration., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: INTRODUCTION: Nurses have a central role in educating patients and families about treatment options and how to integrate them into action plans for neurologic conditions. In recent years, a growing number of intranasal formulations have become available as rescue therapy for neurologic conditions or symptoms including migraine, opioid overdose, and seizures. Rescue therapies do not replace maintenance medications or emergency care but are designed to enable rapid treatment of urgent or disabling conditions in community settings. Yet, discussion of rescue therapies for neurologic conditions remains limited in nursing literature. CONTENT: Intranasal formulations are specifically formulated for delivery and absorption in the nose and have several characteristics that are well suited as rescue therapies for neurologic conditions. Intranasal formulations include triptans for migraine, naloxone and nalmefene for opioid overdose, and benzodiazepines for seizure clusters in patients with epilepsy. Therapeutic attributes discussed here include ease of use in community settings by nonmedical professionals, relatively rapid onset of action, and favorable safety profile and patient experience. This information is critical for nurses to make informed decisions about rescue therapy options, incorporate these into plans of care, and educate patients, care partners, and other healthcare providers. CONCLUSION: Rescue therapies are increasingly important in the care of people with neurologic conditions. Various formulations are available and continue to evolve, offering easy and quick ways for nurses, patients, and nonmedical care partners to administer critical rescue medications. For nurses overseeing medication management, the attributes of intranasal rescue therapies should be considered in the context of providing patients with the right care at the right time., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone., Method: A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment., Results: BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ2 = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05)., Conclusions: Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced.

Background: Remimazolam, a novel benzodiazepine, shows promise as an alternative to traditional sedatives and hypnotic agents in procedural sedation and general anaesthesia. While preliminary research indicates potential advantages over conventional agents, such as faster onset, predictable duration, and improved safety profile, the extent and quality of existing evidence remain unclear. This scoping review aims to investigate the current clinical role of remimazolam and provide a broad and comprehensive overview., Methods: The proposed review will adhere to the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews. A comprehensive search will be conducted across major peer-reviewed databases and grey literature will be sought. All studies involving individuals undergoing procedural sedation or general anaesthesia with remimazolam will be eligible. Data extraction will encompass trial and participant characteristics, intervention details, reported outcomes, comparative efficacy versus midazolam and propofol, patient and operator experience and economic costs., Results: We will provide a descriptive summary supplemented by statistics, figures and tables where applicable., Conclusion: The outlined scoping review aims to assess the clinical use of remimazolam in procedural sedation and as the hypnotic component of general anaesthesia. The review will map the current body of evidence of remimazolam and identify knowledge gaps, contributing to understanding its clinical implications and guiding future research efforts in procedural sedation and general anaesthesia., (© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: General practitioners (GPs) make numerous care decisions throughout their workdays. Extended periods of decision making can result in decision fatigue, a gradual shift toward decisions that are less cognitively effortful. This study examines whether observed patterns in GPs' prescribing decisions are consistent with the decision fatigue phenomenon. We hypothesized that the likelihood of prescribing frequently overprescribed medications (antibiotics, benzodiazepines, opioids; less effortful to prescribe) will increase and the likelihood of prescribing frequently underprescribed medications (statins, osteoporosis medications; more effortful to prescribe) will decrease over the workday., Methods: This study used nationally representative primary care data on GP-patient encounters from the Bettering the Evaluation and Care of Health program from Australia. The association between prescribing decisions and order of patient encounters over a GP's workday was assessed with generalized linear mixed models accounting for clustering and adjusting for patient, provider, and encounter characteristics., Results: Among 262,456 encounters recorded by 2,909 GPs, the odds of prescribing antibiotics significantly increased by 8.7% with 15 additional patient encounters (odds ratio [OR] = 1.087; confidence interval [CI] = 1.059-1.116). The odds of prescribing decreased significantly with 15 additional patient encounters by 6.3% for benzodiazepines (OR = 0.937; CI = 0.893-0.983), 21.9% for statins (OR = 0.791; CI = 0.753-0.831), and 25.0% for osteoporosis medications (OR = 0.750; CI = 0.690-0.814). No significant effects were observed for opioids. All findings were replicated in confirmatory analyses except the effect of benzodiazepines., Conclusions: GPs were increasingly likely to prescribe antibiotics and were less likely to prescribe statins and osteoporosis medications as the workday wore on, which was consistent with decision fatigue. There was no convincing evidence of decision fatigue effects in the prescribing of opioids or benzodiazepines. These findings establish decision fatigue as a promising target for optimizing prescribing behavior., Highlights: We found that as general practitioners progress through their workday, they become more likely to prescribe antibiotics that are reportedly overprescribed and less likely to prescribe statins and osteoporosis medications that are reportedly underprescribed.This change in decision making over time is consistent with the decision fatigue phenomenon. Decision fatigue occurs when we make many decisions without taking a rest break. As we make those decisions, we become gradually more likely to make decisions that are less difficult.The findings of this study show that decision fatigue is a possible target for improving guideline-compliant prescribing of pharmacologic medications., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided by a Small Research Grant from the Royal Society of Edinburgh (grant ID: 2156). The funding agreement ensured that authors’ independence in designing the study, interpreting the data, writing, and publishing the report. The BEACH project itself was funded through arm’s length research agreements with the following organizations: Abbott Australasia; AbbVie; AstraZeneca (Australia); Australian Government Department of Health; Australian Government Department of Veterans’ Affairs; Aventis Pharma; Bayer Australia; bioCSL (Australia); GlaxoSmithKline Australia; Janssen-Cilag; Merck, Sharp and Dohme (Australia); National Prescribing Service; Novartis Pharmaceuticals Australia; Pfizer Australia; Roche Product; Sanofi-Aventis Australia; Wyeth Australia.

Objectives: This study aims to compare the sedative effects of remimazolam and midazolam during impacted tooth extraction to provide a comfortable sedation treatment for patients with dental anxiety., Methods: A prospective randomized controlled trial was conducted, in which 60 patients undergoing intravenous sedation for mandibular impacted third molar extraction were evenly divided into either the remimazolam or midazolam group. Prior to receiving a nerve blocker, the patients were sedated with remimazolam or midazolam. Various parameters were recorded and analyzed, including onset time, awakening time, recovery time, modified dental anxiety scale (MDAS) scores before and after surgery, patient-doctor satisfaction levels, postoperative side effects within 24 hours, heart rate (HR), and mean arterial pressure (MAP) at different time points., Results: Compared with the midazolam group, patients in the remimazolam group demonstrated significantly shorter onset, awakening, and recovery times as well as lower postoperative MDAS scores and higher levels of patient-doctor satisfaction. Fewer postoperative side effects were reported in the remimazolam group, although the differences were not statistically significant., Conclusions: The use of remimazolam demonstrates faster onset and recovery, superior efficacy in reducing dental anxiety, and enhanced satisfaction among patients and doctors, thereby presenting distinct advantages for sedation treatment for patients with dental anxiety.

Objective: To compare the effects of general anesthesia between remimazolam and propofol in pediatric patients undergoing binocular strabismus day surgery. Methods: Prospectively, 60 pediatric patients, American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ, scheduled to undergo binocular strabismus daytime surgery in Beijing Tongren Hospital under general anesthesia with laryngeal mask airway from December 2021 to May 2022 were selected. They were randomly divided into Remimazolam group and Propofol group with 30 cases in each group, according to the ratio of 1∶1 by SPSS program. Patients in Remimazolam group were induced by remimazolam, remifentanil and micuronium chloride, and maintained by remimazolam and remifentanil. Patients in Propofol group were induced by propofol, remifentanil and micuronium chloride, and maintained by propofol and remifentanil. Patients in Remimazolam group were given 0.1 mg of flumazenil for antagonism 3 minutes after operation, while children in Propofol group waited for natural awakening. The primary outcome was the time from drug withdrawal to laryngeal mask removal after operation. The secondary outcomes included the time for consciousness loss during induction, intraoperative hemodynamic data [mean arterial pressure (MAP) and heart rate], the success rate of sedation, the awareness rate during operation, and the incidence of adverse events after admission to postanesthesia care unit(PACU). Results: The Remimazolam group included 12 males and 18 females, aged (5.0±1.4) years. There were 14 males and 16 females in the Propofol group, aged (5.3±1.3) years. The time from drug withdrawal to laryngeal mask removal in Remimazolam group was (6.5±1.2) min, which was shorter than that in Propofol group of (10.7±1.9) min ( P <0.001). The time for consciousness loss during induction was (38.1±4.8) s in Remimazolam group, which was longer than that in Propofol group of (31.6±4.9) s ( P <0.001). The variability of MAP and heart rate of patients during operation in Remimazolam group was lower than that in Propofol group (all P <0.05). There was no significant difference in sedation success rate, intraoperative awareness and adverse reactions in PACU between the two groups (all P >0.05). Conclusion: In pediatric patients with binocular strabismus during daytime surgery, general anesthesia with remimazolam can shorten the time from drug withdrawal to laryngeal mask removal after operation without increasing the incidence of postoperative adverse reactions and can provide more stable hemodynamics.

Catatonia is a neuropsychiatric disorder characterized by motor, affective and cognitive-behavioural signs, which lasts from hours to days. Intensive research over the past two decades has led to catatonia being recognized as an independent diagnosis in the International Classification of Diseases, 11th Revision (ICD-11) since 2022. Catatonia is found in 5-18% of inpatients on psychiatric units and 3.3% of inpatients on medical units. However, in an unknown number of patients, catatonia remains unrecognized and these patients are at risk of life-threatening complications. Hence, recognizing the symptoms of catatonia early is crucial to initiate appropriate treatment to achieve a favourable outcome. Benzodiazepines such as lorazepam and diazepam, electroconvulsive therapy, and N-methyl-D-aspartate antagonists such as amantadine and memantine, are the cornerstones of catatonia therapy. In addition, dopamine-modulating second-generation antipsychotics (for example, clozapine and aripiprazole) are effective in some patient populations. Early and appropriate treatment combined with new screening assessments has the potential to reduce the high morbidity and mortality associated with catatonia in psychiatric and non-psychiatric settings., (© 2024. Springer Nature Limited.)

Objectives: Exposure to critical illness and intensive care may lead to long-term psychologic and physical impairments. To what extent ICU survivors become prolonged users of benzodiazepines after exposure to critical care is not fully explored. This study aimed to describe the extent of onset of prolonged high-potency benzodiazepine use among ICU survivors not using these drugs before admission, identify factors associated with this use, and analyze whether such usage is associated with increased mortality., Design: Retrospective cohort study., Setting: Sweden, including all registered ICU admissions between 2010 and 2017., Patients: ICU patients surviving for at least 3 months, not using high-potency benzodiazepine before admission, were eligible for inclusion., Interventions: Admission to intensive care., Measurements and Main Results: A total of 237,904 patients were screened and 137,647 were included. Of these 5338 (3.9%) became prolonged users of high-potency benzodiazepines after ICU discharge. A peak in high-potency benzodiazepine prescriptions was observed during the first 3 months, followed by sustained usage throughout the follow-up period of 18 months. Prolonged usage was associated with older age, female sex, and a history of both somatic and psychiatric comorbidities, including substance abuse. Additionally, a longer ICU stay, a high estimated mortality rate, and prior consumption of low-potency benzodiazepines were associated with prolonged use. The risk of death between 6 and 18 months post-ICU admission was significantly higher among high-potency benzodiazepine users, with an adjusted hazard ratio of 1.8 (95% CI, 1.7-2.0; p < 0.001). No differences were noted in causes of death between users and nonusers., Conclusions: Despite the lack of evidence supporting long-term treatment, prolonged usage of high-potency benzodiazepines 18 months following ICU care was notable and associated with an increased risk of death. Considering the substantial number of ICU admissions, prevention of benzodiazepine misuse may improve long-term outcomes following critical care., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: Olanzapine and risperidone have emerged as the most widely used drugs as short-term prescription in the treatment of behavioral disturbances in dementia. The present systematic review and meta-analysis was hence performed to investigate the effectiveness and safety profile of olanzapine and risperidone in the treatment of behavioral and psychological symptoms of dementia (BPSD), aiming to provide updated suggestion for clinical physicians and caregivers., Design: Prospective controlled clinical studies were included, of which available data was extracted. Outcomes of BEHAVE-AD scores with the variation of grades, specific behaviors variables, as well as safety signals were pooled for the analysis by odds rates and weighted mean differences, respectively., Data Sources: Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang., Eligibility Criteria: Prospective, controlled clinical studies, conducted to compare the effectiveness and safety profile of olanzapine and risperidone in the treatment of BPSD., Data Extraction and Synthesis: Interested data including baseline characteristics and necessary outcomes from the included studies were extracted independently by 2 investigators. BEHAVE-AD scale was adopted to assess the efficacy in the present study. All behaviors were evaluated at the time of the initiation of the treatment, as well as the completion of drugs courses. Adverse events were assessed with the criteria of Treatment Emergent Symptom Scale, or Coding Symbols for a Thesaurus of Adverse Reaction Terms dictionary. Weighted mean difference was used for the pooled analysis., Results: A total of 2427 participants were included in the present meta-analysis. Comparative OR on response rate, and remarkable response rate between olanzapine and risperidone was 0.65 (95% CI: 0.51-0.84; P = .0008), and 0.62 (95% CI: 0.50-0.78; P < .0001), respectively. There were statistical differences observed by olanzapine on the improvement of variables including delusions (WMD, -1.83, 95% CI, -3.20, -0.47), and nighttime behavior disturbances (WMD, -1.99, 95% CI, -3.60, -0.38) when compared to risperidone., Conclusion: Our results suggested that olanzapine might be statistically superior to risperidone on the reduction of BPSD of Alzheimer's disease, especially in the relief of delusions and nighttime behavior disturbances. In addition, olanzapine was shown statistically lower risks of agitation, sleep disturbance, and extrapyramidal signs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Few studies describe contemporary alcohol withdrawal management in hospitalized settings or review current practices considering the guidelines by the American Society of Addiction Medicine (ASAM)., Methods: We conducted a retrospective cohort study of patients hospitalized with alcohol withdrawal on medical or surgical wards in 19 Veteran Health Administration (VHA) hospitals between October 1, 2018, and September 30, 2019. Demographic and comorbidity data were obtained from the Veteran Health Administration Corporate Data Warehouse. Inpatient management and hospital outcomes were obtained by chart review. Factors associated with treatment duration and complicated withdrawal were examined., Results: Of the 594 patients included in this study, 51% were managed with symptom-triggered therapy alone, 26% with fixed dose plus symptom-triggered therapy, 10% with front loading regimens plus symptom-triggered therapy, and 3% with fixed dose alone. The most common medication given was lorazepam (87%) followed by chlordiazepoxide (33%), diazepam (14%), and phenobarbital (6%). Symptom-triggered therapy alone (relative risk [RR], 0.68; 95% confidence interval [CI], 0.57-0.80) and front loading with symptom-triggered therapy (RR, 0.75; 95% CI, 0.62-0.92) were associated with reduced treatment duration. Lorazepam (RR, 1.20; 95% CI, 1.02-1.41) and phenobarbital (RR, 1.28; 95% CI, 1.06-1.54) were associated with increased treatment duration. Lorazepam (adjusted odds ratio, 4.30; 95% CI, 1.05-17.63) and phenobarbital (adjusted odds ratio, 6.51; 95% CI, 2.08-20.40) were also associated with complicated withdrawal., Conclusions: Overall, our results support guidelines by the ASAM to manage patients with long-acting benzodiazepines using symptom-triggered therapy. Health care systems that are using shorter acting benzodiazepines and fixed-dose regimens should consider updating alcohol withdrawal management pathways to follow ASAM recommendations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Remimazolam, an ultra-short-acting benzodiazepine recognized and approved as an anesthetic and sedative in multiple countries, offers a distinctive pharmacokinetic profile, boasting advantages such as rapid onset, short action duration, and rapid recovery. These attributes may contribute to enhanced hemodynamic stability and a diminished risk of respiratory depression compared to other sedatives., Evidence Acquisition: We conducted the first comprehensive systematically structured narrative review to evaluate the role and potential application of remimazolam in cardiac surgery. Twenty-one studies published from 2021 to 2023 delved into remimazolam's application in open cardiac surgery, cardiac catheterization or electrophysiology laboratories, and high-risk cardiovascular patients undergoing non-cardiac surgery., Evidence Synthesis: Overall, remimazolam usage was apparently linked to potentially superior hemodynamic stability compared to other hypnotic drugs. However, findings regarding the reduction in postoperative delirium incidence with remimazolam and the doses of remimazolam for anesthesia induction and maintenance were inconsistent across the studies., Conclusions: Though remimazolam has demonstrated potential safety, efficacy, and ease-of-use for both anesthesia induction and maintenance in cardiac surgery patients and high-risk cardiovascular patients undergoing non-cardiac surgery, further research is imperative to delve into specific patient subgroups (e.g., the elderly or emergent procedures) so as to ascertain optimal dose ranges to suit diverse clinical scenarios.

Objectives: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death., Design: A retrospective multicenter cohort study., Setting: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States., Patients: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF., Interventions: None., Measurements and Main Results: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40)., Conclusions: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice., Competing Interests: This article was supported by an Institutional National Research Service Award (T32) funded by the National Institute of Health, National Heart, Lung, and Blood Institute (T32 HL007085). Dr. Ho disclosed government work. Dr. Sottile’s institution received funding from the National Heart, Lung, and Blood Institute; he received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Benzodiazepine (BZD) dependence poses a significant challenge in mental health, prompting the exploration of treatments like repetitive transcranial magnetic stimulation (rTMS). This research aims to assess the impact of rTMS on alleviating symptoms of BZD dependence. A randomized control trial was employed to study 40 BZD-dependent inpatients. Their symptoms were quantified using the Hamilton Anxiety Rating Scale (HAMA), Montgomery-Åsberg Depression Rating Scale (MADRS) and Pittsburgh Sleep Quality Index (PSQI). Participants were divided into a conventional treatment group (daily diazepam with gradual tapering) with supportive psychotherapy and another group receiving the same treatment supplemented with rTMS (five weekly sessions for 2 weeks). Significant improvements were observed in both groups over baseline in MADRS, HAMA and PSQI scores at the 2nd, 4th, 8th and 12th week assessments (p < 0.05). The group receiving rTMS in addition to conventional treatment exhibited superior improvements in all measures at the 8th and 12th weeks. The addition of rTMS to conventional treatment methods for BZD dependence significantly betters the recovery in terms of depression, anxiety and sleep quality, highlighting the role of rTMS as an effective adjunct therapy., (© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background and Objectives: Patient monitoring systems provide critical information but often produce loud, frequent alarms that worsen patient agitation and stress. This may increase the use of physical and chemical restraints with implications for patient morbidity and autonomy. This study analyzes how augmenting alarm thresholds affects the proportion of alarm-free time and the frequency of medications administered to treat acute agitation., Methods: Our emergency department's patient monitoring system was modified on June 28, 2022 to increase the tachycardia alarm threshold from 130 to 150 and to remove alarm sounds for several arrhythmias, including bigeminy and premature ventricular beats. A pre-post study was performed lasting 55 days before and 55 days after this intervention. The primary outcome was change in number of daily patient alarms. The secondary outcomes were alarm-free time per day and median number of antipsychotic and benzodiazepine medications administered per day. The safety outcome was the median number of patients transferred daily to the resuscitation area. We used quantile regression to compare outcomes between the pre- and post-intervention period and linear regression to correlate alarm-free time with the number of sedating medications administered., Results: Between the pre- and post-intervention period, the median number of alarms per day decreased from 1332 to 845 (-37%). This was primarily driven by reduced low-priority arrhythmia alarms from 262 to 21 (-92%), while the median daily census was unchanged (33 vs 32). Median hours per day free from alarms increased from 1.0 to 2.4 (difference 1.4, 95% CI 0.8-2.1). The median number of sedating medications administered per day decreased from 14 to 10 (difference - 4, 95% CI -1 to -7) while the number of escalations in level of care to our resuscitation care area did not change significantly. Multivariable linear regression showed a 60-min increase of alarm-free time per day was associated with 0.8 (95% CI 0.1-1.4) fewer administrations of sedating medication while an additional patient on the behavioral health census was associated with 0.5 (95% CI 0.0-1.1) more administrations of sedating medication., Conclusion: A reasonable change in alarm parameter settings may increase the time patients and healthcare workers spend in the emergency department without alarm noise, which in this study was associated with fewer doses of sedating medications administered., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Benzodiazepines and antidepressants are effective agents for the treatment of generalized anxiety disorder (GAD), with the HAM-A frequently used as a primary outcome measure. The GAD literature is inconsistent regarding which medications are more effective for somatic versus psychic symptoms of GAD, and treatment guidelines do not advocate for prescribing based on subtype. This meta-analysis aimed to determine whether benzodiazepines and antidepressants have a differential impact on the somatic versus psychic subscales of the HAM-A in GAD., Methods: An electronic search was undertaken for randomized controlled trials of either benzodiazepines or antidepressants for GAD that reported treatment response using the HAM-A subscales. Data were extracted by independent reviewers. A random effects assessment of weighted mean difference with 95% confidence intervals and subgroup difference was applied. All analysis was done on SPSS 26. An assessment of bias, and of quality of evidence was performed., Results: 24 randomized controlled trials met the inclusion criteria: 18 antidepressant trials, 5 benzodiazepine trials and 1 of both. 14 studies were assessed as having between some and high risk of bias, while 10 were assessed as having low risk of bias. Benzodiazepines (WMD of 1.81 [CI 1.03, 2.58]) were significantly more effective than antidepressants (WMD of 0.83 [CI 0.64, 1.02]) for reducing somatic symptoms of GAD (Chi 2  = 5.81, p = 0.02), and were also more effective (WMD of 2.46 [CI 1.83, 3.09]) in reducing psychic symptoms than antidepressants (WMD of 1.83 [CI 1.55, 2.10]), although this comparison did not reach statistical significance (Chi 2  = 3.31, p = 0.07)., Conclusion: The finding that benzodiazepines were significantly more effective than antidepressants for somatic symptoms needs to be weighed up against potential benefits of antidepressants over benzodiazepines. It may be useful for future treatment guidelines for GAD to explicitly consider symptom subtype., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Benzodiazepines are commonly misused medications frequently implicated in overdose deaths. Data show that benzodiazepine prescribing is associated with increased misuse. We sought to determine national trends in benzodiazepine prescribing from the emergency department (ED)., Methods: This is a retrospective review of the National Hospital Ambulatory Medical Care Survey from 2012 to 2019. Our primary outcome was to evaluate trends in ED visits where a benzodiazepine was prescribed at discharge. Secondarily, we identified commonly prescribed benzodiazepines and assessed trends over time. We examined demographic data and used descriptive statistics and Spearman rho or Pearson correlation coefficient as applicable., Results: Between 2012 and 2019, there were 13,848,578 visits where benzodiazepines were prescribed at ED discharge. In 2012 and 2019, there were 1,407,478 visits (1.1% of all ED visits) and 1,361,372 visits (0.9%), respectively, where benzodiazepines were prescribed (mean [SD], 1,731,072 [287,623] [1.26%]), with no trend ( P = 0.31). Common benzodiazepines prescribed were diazepam (5,980,279 visits, 43.2% of all prescriptions), alprazolam (3,306,549, 23.9%), and clonazepam (2,105,963, 15.2%), with no changes over time. Fifteen percent of prescriptions were for patients 65 years or older., Conclusion: Despite reports of increased misuse, there was no change in ED discharge benzodiazepine prescribing. Concerningly, alprazolam, a benzodiazepine with high misuse potential, was frequently prescribed despite limited ED indications, and there was a large percentage of visits where benzodiazepines were prescribed to older adults despite warnings for adverse effects in this population. Future studies should assess rational prescribing and the role of targeted interventions to curb inappropriate use., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Introduction: Prescribing of ethanol may be an alternative to benzodiazepines for managing alcohol withdrawal syndrome. We present our experience of oral ethanol prescribing within an acute United Kingdom National Health Service setting., Methods: A retrospective review of patients presenting with alcohol withdrawal who were managed with oral ethanol or benzodiazepines was performed from data collected across two acute care settings. Ethanol prescribing inclusion: high risk of delirium tremens, or a history of harmful alcohol consumption (typically ≥30 units/day; in which 1 unit = 8 grams of alcohol; one standard United States drink = 14 grams of alcohol) or known to have a history of severe alcohol withdrawal, alcohol-related seizures or delirium tremens. Inverse propensity score weighting was used to partially account for variance between the two patient populations., Results: Fifty (82 per cent male; average age 50.9 years) and 93 (84 per cent male; average age 46.5 years) patients in receipt of benzodiazepines or ethanol, respectively, were included. The likelihood of hospital admission was significantly reduced when individuals were managed with ethanol (odds ratio 0.206 (95 per cent confidence interval; 0.066-0.641), Wald chi-square P  = 0.006). In those not admitted, the treatment type had no significant impact on length of stay or the number of occasions a pharmacological agent was required. In those admitted, treatment had no significant effect on length of stay., Discussion: We offer preliminary evidence to support a role of oral ethanol in the management of patients with alcohol withdrawal. We have implemented a robust and translatable guideline. Despite limitations in the data set the impact of ethanol in reducing the likelihood of admission remained significant., Conclusions: In individuals at significant risk of severe alcohol withdrawal, prescribing ethanol as part of a comprehensive care plan, may reduce unplanned admissions. The preliminary findings presented here warrant further assessment through prospective studies.

Introduction: Previous research has raised concerns about high prevalence of drug-related problems, polypharmacy and inappropriate benzodiazepine prescribing in nursing homes (NHs) and confirmed lack of studies from Central and South-Eastern Europe. The aim of our study was to determine the prevalence and characteristics of polypharmacy, hyperpolypharmacy and inappropriate benzodiazepine prescribing in NH residents in Croatia., Methods: Data from 226 older NH residents from five Croatian NHs were collected using the InterRAI Long-Term Care Facilities assessment form. The prevalence and determinants of polypharmacy/hyperpolypharmacy and patterns of inappropriate benzodiazepine prescribing were documented., Results: The prevalence of polypharmacy (49.6%) and hyperpolypharmacy (25.7%) among NH residents was high. In our study, 72.1% of NH residents were prescribed at least one psychotropic agent, 36.7% used 2-3 psychotropics and 6.6% used 4+ psychotropics. Among benzodiazepine users (55.8%), 28% of residents were prescribed benzodiazepines in higher than recommended geriatric doses, 75% used them for the long term and 48% were prescribed concomitant interacting medications. The odds of being prescribed polypharmacy/hyperpolypharmacy were significantly higher for older patients with polymorbidity (6+ disorders, proportional odds ratio (POR) = 19.8), type II diabetes (POR = 5.2), ischemic heart disease (POR = 4.6), higher frailty (Clinical Frailty Scale (CFS ≥5); POR = 4.3) and gastrointestinal problems (POR = 4.8)., Conclusions: Our research underscores the persistent challenge of inappropriate medication use and drug-related harms among older NH residents, despite existing evidence and professional campaigns. Effective regulatory and policy interventions, including the implementation of geriatrician and clinical pharmacy services, are essential to address this critical issue and ensure optimal medication management for vulnerable NH populations.

Background: Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population., Methods: A total of 2742 patients with MDD (males/females = 816/1926, aged 14-60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use., Results: The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001)., Limitations: The cross-sectional design of this study precludes establishing causal relationships., Conclusion: Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts with any financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the impact of vagus nerve stimulation (VNS) on quality of life contributors such as rescue medications., Methods: Using the seizure diary application SeizureTracker™ database, we examined trends in rescue administration frequency before and after the first recorded VNS magnet swipe in patients with drug-resistant epilepsy who had 1) At least one VNS magnet swipe recorded in the diary, and 2) Recorded usage of a benzodiazepine rescue medication (RM) within 90 days prior to the first swipe. A paired Wilcoxon rank-sum test was used to assess changes in RM usage frequency between 30-, 60-, 90-, 180- and 360-day intervals beginning 30 days after first magnet swipe. Longitudinal changes in RM usage frequency were assessed with a generalized estimating equation model., Results: We analyzed data of 95 patients who met the inclusion criteria. Median baseline seizure frequency was 8.3 seizures per month, with median baseline rescue medication usage frequency of 2.1 administrations per month (SD 3.3). Significant reductions in rescue medication usage were observed in the 91 to 180 day interval after first VNS magnet swipe, and at 181 to 360 days and at 361 to 720 days, with the magnitude of reduction increasing over time. Decreases in rescue medication usage were sustained when controlling for patients who did not record rescue medication use after the first VNS magnet swipe (N=91). Significant predictors of reductions in rescue medication included baseline frequency of rescue medication usage and time after first VNS magnet swipe., Significance: This retrospective analysis suggests that usage of rescue medications is reduced following the start of VNS treatment in patients with epilepsy, and that the magnitude of reduction may progressively increase over time., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [SW, CRM & PM reported personal fees (speakers bureau) from LivaNova outside the submitted work. R.M. is the cofounder/owner of Seizure Tracker, LLC, which has received funding from Courtagen, Engage Therapeutics, Greenwich Biosciences, Neurelis, UCB, Xenon Pharmaceuticals, and grants from TuberousSclerosis Alliance. SC is the co-founder/owner of EpilepsyAI, LLC, which has received funding from Neurelis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential Competing Interest.]., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Insomnia disorder is a global public health issue, commonly treated with hypnotics. However, long-term use of benzodiazepine derivatives (BZDs), especially polypharmacy with this kind of drug, carries risks for dependence and abuse. This study using large-scale medical insurance records investigated the causes of polypharmacy through the treatment of insomnia disorder., Methods: A cross-sectional study analyzed anonymized medical record data from July 2014 to March 2018 provided by a nationwide Japanese health insurance association covering 405,952 individuals. Outpatients prescribed at least one sleep medication were included. Demographic data, pharmacological classification of the drugs, and comorbidities were assessed using hierarchical logistic regression analysis to explore their associations with polypharmacy., Results: Of the 33,212 outpatients who were prescribed sleep medications, 32.5 % were prescribed multiple types. After adjusting for demographics and type of sleep medications as covariates, hypnotic polypharmacy was significantly associated with younger age, the presence of certain kinds of comorbidities, and using BZD anxiolytics before bedtime with the highest adjusted odds ratios (8.01-9.39) when referenced with BZD hypnotics. On the other hand, usage of orexin receptor antagonists, melatonin receptor agonists, and Z-drugs indicated lower odds ratios (0.74-0.87)., Conclusions: Hypnotic polypharmacy is relatively common in the Japanese general population. With the introduction of non-pharmacological therapy in mind, assessing patients' comorbidities and avoiding the use of benzodiazepines, especially BZD anxiolytics, before bedtime would be recommended to prevent polypharmacy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this study. Akiyoshi Shimura received lecture fees from Sumitomo Pharma, Nobel Pharma, and Eisai outside of the submitted work and is a board member of Children and Future Co., Ltd. Yoshikazu Takaesu received lecture fees from Takeda Pharmaceutical, Sumitomo Pharma, Otsuka Pharmaceutical, Meiji Seika Pharma, Kyowa Pharmaceutical, Eisai, MSD, Yoshitomi, and research funding from Otsuka Pharmaceutical, Meiji Seika Pharma, MSD, and Eisai. Yuichi Inoue received lecture fees from Eisai, Otsuka Pharmaceutical, Takeda Pharmaceutical, Astellas Pharma, and MSD outside the submitted work and grants from Philips Japan, Koike Medical, and Teijin Pharma outside the submitted work. The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Long-term opioid prescription to manage chronic non-cancer pain (CNCP) is rapidly rising, despite the lacking evidence supporting their safety and efficacy. Co-prescribing opioids with other dependence-forming medications (DFMs) causes fatal side effects. Clinicians are advised to avoid combinations of DFMs and, where suitable, deprescribe to improve patient safety., Aim: To review the number of patients registered to the Grange Medical Centre (Nuneaton, Warwickshire) who are co-prescribed an opioid and either benzodiazepine/gabapentinoid for CNCP and to reduce usage of these DFMs., Method: The 'Model for Improvement' is used as a QIP framework. A database search was conducted on 5 October 2023 to identify the cohort of interest. The introduced changes included devising a resource pack outlining the up-to-date non-pharmacological pain management, support channels, and a medication review invitation sent to the identified patients. A pain management template has also been developed to be used by GPs and clinical pharmacists to support the medication review. Guided by the Plan-Do-Study-Act cycle, data will be re-measured to detect incremental changes in practice., Results: In total, 123 patients were receiving co-prescriptions of opioids along with either benzodiazepine/gabapentinoid for CNCP out of the enlisted 12 360 patients. The majority were in the 70-79 years age range. It was also noted that around 66% of patients were females. The QIP's first cycle is currently being implemented., Conclusion: This QIP addresses a pressing need to reduce the usage of DFMs. The interim results will guide the change model in the Grange Medical Centre GP surgery and inform scoping of relevant clinical questions to improve patient safety., (© British Journal of General Practice 2024.)