Effects of vatinoxan in rats sedated with a combination of medetomidine, midazolam and fentanyl.

BACKGROUND: Alpha2-adrenoceptor agonists (α2-agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α2-agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α2-adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α2-agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl. RESULTS: Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1-41.6), range (median) versus 0.9 (0-8.0) mL /kg/min] were significantly higher without vatinoxan. CONCLUSIONS: Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl.

Identification of post-mortem product of zolpidem degradation by hemoglobin via the Fenton reaction.

Zolpidem, N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide, is a hypnotic agent widely used in clinical practice but is detected in many clinical cases of fatal intoxication and suicide. In forensic toxicology, the precise determination of zolpidem concentration in blood is a must to provide concrete evidence of death by zolpidem poisoning. However, the concentrations of zolpidem in blood at autopsy often differ from those at the estimated time of death. In the present study, we found that zolpidem was degraded by hemoglobin (Hb) via the Fenton reaction at various temperatures. The mechanism underlying zolpidem degradation involved the oxidation of its linker moiety. The MS and MS/MS spectra obtained by liquid chromatography quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap-MS) showed the formation of 2-hydroxy-N,N-dimethyl-2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)acetamide (2-OH ZOL) in Hb/H2O2 solution incubated with zolpidem and in the blood of several individuals who died from ingestion of zolpidem. These results suggest that 2-OH ZOL is the post-mortem product of zolpidem degradation by Hb via the Fenton reaction.

Direct injection ultra-performance liquid chromatography-tandem mass spectrometry for the high-throughput determination of etomidate and etomidate acid in wastewater.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography-tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements.

ED50 of ciprofol combined with sufentanil for fiberoptic bronchoscopy of different patient populations with pulmonary tuberculosis.

BACKGROUND: Ciprofol is a promising sedative. This study aims to explore the median effective dose (ED50) of ciprofol in inhibiting responses to fiberoptic bronchoscopy in patients with pulmonary tuberculosis (PTB) of different genders and ages when combined with 0.15 µg/kg sufentanil, and to evaluate its efficacy and safety, providing a reference for the rational use of ciprofol in clinical practice. METHODS: PTB patients who underwent bronchoscopy examination and treatment at The Third People's Hospital of Changzhou between May 2023 and June 2023 were selected and divided into four groups using a stratified random method. All patients received intravenous injection of 0.15 µg/kg sufentanil followed by injection of the test dose of ciprofol according to Dixon's up-and-down method. The initial dose of ciprofol in all four groups was 0.4 mg/kg, with an adjacent ratio of 1:1.1. The next patient received a 10% increase in the dose of ciprofol if the previous patient in the same group experienced positive reactions such as choking cough, frowning, and body movements during the endoscopy. Otherwise, it was judged as a negative reaction, and the next patient received a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study of the group was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points in all groups. The Probit regression analysis method was used to calculate the ED50 of ciprofol in the four groups and compare between the groups. RESULTS: The ED50 of ciprofol combined with 0.15 µg/kg sufentanil for bronchoscopy in the four groups were 0.465 mg/kg, 0.433 mg/kg, 0.420 mg/kg and 0.396 mg/kg, respectively. CONCLUSION: The ED50 of ciprofol used for fiberoptic bronchoscopy varied among PTB patients of different genders and ages. TRIAL REGISTRATION: The Chinese Clinical Trial Registry, ChiCTR2300071508, Registered on 17 May 2023.

Evaluation of a noncontrolled, pre-euthanasia, intramuscular sedation drug protocol including alfaxalone 4%, medetomidine, and acepromazine for injured or ill raccoons.

Background: As a major animal control service provider in the city of Guelph and Wellington County in Ontario, the Guelph Humane Society transports and presents injured or ill raccoons requiring humane euthanasia to the Ontario Veterinary College Health Sciences Centre (OVC-HSC). Issues around handling, transportation, and delays before euthanasia have recently raised some concerns for welfare and the need for means of improving this process. Objective: Investigation of a noncontrolled sedation and analgesia protocol for injured or ill raccoons intended to improve animal welfare by allowing humane handling, transport, and euthanasia following administration by an animal protection officer (APO). Animals and procedure: Twenty-seven injured or ill raccoons requiring transport and euthanasia, as determined by the Guelph Humane Society APOs, were included in the study. Each raccoon was administered acepromazine (0.05 mg/kg), alfaxalone (4 mg/kg), and medetomidine (0.15 mg/kg), intramuscularly, before being transported to the OVC-HSC for humane euthanasia. Results: The combination of acepromazine, alfaxalone, and medetomidine was suitable for administration by APOs and provided the desired sedation depth to allow transport and humane euthanasia. Transit time was the only predictor of sedation depth upon arrival at the OVC-HSC. Two raccoons showed mild physical response to intracardiac injection for euthanasia. Numerical cutoff points of an in-hospital visual analog score of sedation of ≥ 70/100 and duration of sedation of < 62 min showed zero probability of response to euthanasia. Conclusion and clinical relevance: Administration of acepromazine, alfaxalone, and medetomidine at the stated doses provided acceptable sedation and analgesia to improve animal welfare during transport and eventual euthanasia of raccoons.

Évaluation d'un protocole médicamenteux sans groupe témoin de sédation intramusculaire, pré-euthanasie, comprenant de l'alfaxalone 4 %, de la médétomidine et de l'acépromazine pour les ratons laveurs blessés ou malades. Contexte: En tant que fournisseur majeur de services de contrôle des animaux dans la ville de Guelph et dans le comté de Wellington en Ontario, la Guelph Humane Society transporte et présente les ratons laveurs blessés ou malades nécessitant une euthanasie sans cruauté au Ontario Veterinary College Health Sciences Centre (OVC-HSC). Les problèmes liés à la manutention, au transport et aux délais avant l'euthanasie ont récemment soulevé des inquiétudes quant au bien-être et à la nécessité de trouver des moyens d'améliorer ce processus. Objectif: Enquête sur un protocole de sédation et d'analgésie sans groupe témoin pour les ratons laveurs blessés ou malades destiné à améliorer le bien-être des animaux en permettant une manipulation, un transport et une euthanasie sans cruauté après administration par un agent de protection des animaux (APO). Animaux et procédure: Vingt-sept ratons laveurs blessés ou malades nécessitant un transport et une euthanasie, tel que déterminé par les APO de la Guelph Humane Society, ont été inclus dans l'étude. Chaque raton laveur a reçu de l'acépromazine (0,05 mg/kg), de l'alfaxalone (4 mg/kg) et de la médétomidine (0,15 mg/kg), par voie intramusculaire, avant d'être transporté à l'OVC-HSC pour une euthanasie sans cruauté. Résultats: La combinaison d'acépromazine, d'alfaxalone et de médétomidine convenait à l'administration par un APO et fournissait la profondeur de sédation souhaitée pour permettre le transport et l'euthanasie sans cruauté. Le temps de transit était le seul prédicteur de la profondeur de la sédation à l'arrivée à l'OVC-HSC. Deux ratons laveurs ont montré une légère réponse physique à une injection intracardiaque pour l'euthanasie. Les seuils numériques d'un score analogique visuel de sédation à l'hôpital ≥ 70/100 et d'une durée de sédation < 62 min ont montré une probabilité nulle de réponse à l'euthanasie. Conclusion et pertinence clinique: L'administration d'acépromazine, d'alfaxalone et de médétomidine aux doses indiquées a fourni une sédation et une analgésie acceptables pour améliorer le bien-être des animaux pendant le transport et l'euthanasie éventuelle des ratons laveurs.(Traduit par Dr Serge Messier).

Global trend of nondrug and nonsedativehypnotic treatment forinsomnia: a bibliometric study.

OBJECTIVE: To present a bibliometric analysis of global scientific publications on the nondrug and nonsedative hypnotic treatment of insomnia with regard to influential institutions, publications, countries, research hotspots, trends, and frontiers. METHODS: A literature review was conducted by searching the Web of Science Core Collection (WoSCC) and China National Knowledge Infrastructure (CNKI) databases to identify all publications related to the nondrug and nonsedative hypnotic treatment of insomnia from 2000 to 2021. Eligible publications were reviewed, including annual publication increments, citation analyses, international collaborations, and keyword analyses. The data were analysed using CiteSpace (vers5.8.R3, 6.1.R2 and 6.1.6, College of Computing and Informatics, Philadelphia, PA, USA) and virtualized by knowledge maps. RESULTS：In total, 9832 publications were included in this analysis. The results from the WoSCC showed that the United States of America (Count = 2268, 40.33%), Stanford University (Count = 141, 2.51%), and the United States Department of Health and Human Services were the leading country, institute, and funding agency regarding the number of publications, respectively. 'Cognitive-behavioural therapy" was the most popular research topic generated from the cocited reference. The most frequently co-occurring keywords were insomnia, cognitive behavioural therapy, disorder, depression, quality of life, Meta-analysis, older adult, sleep, prevalence and efficacy, while keywords including clinical practice guideline, guideline, and Tai Chi remained popular after 2021. Circadian rhythm was the strongest research frontier for 2000-2021. In China, Chengdu University of Traditional Chinese Medicine (Count = 69, 4.79%) was the most productive institute in this field. The most frequently co-occurring keywords from Chinese literature were sleep disorder, sleep quality, acupuncture and moxibustion, Parkinson's disease, transcranial magnetic stimulation, health education, music therapy, chronic insomnia, quality of life, and nonmotor symptoms. Traditional Chinese medicine was the strongest research frontier for 2019-2021. CONCLUSION: This bibliometric study provides an exhaustive mapping encompassing pertinent institute, publications, influential articles, researchers and topics of the global trend of nondrug and nonsedative hypnotic treatment for insomnia. The results show that the research trend has shifted from primary studies on the efficacy and safety of nondrug and nonsedative hypnotic treatment for insomnia to comorbidity studies. Clinical practice guidelines will potentially become the research frontier for this field post-2021. The findings are important for researchers, clinicians, journal editors, and policy-makers working in the field of nondrug and nonsedative hypnotic treatment for insomnia to understand the strengths and potentials in the current studies and guide future clinical practice, research, and science policy.

The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP.

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

Comparison of Remimazolam Tosilate and Propofol Sedation on the Early Postoperative Quality of Recovery in Patients Undergoing Day Surgery: A Prospective Randomized Controlled Trial.

Purpose: Remimazolam tosilate is a novel ultrafast-acting benzodiazepine that has a rapid emergence even after continuous infusion when using flumazenil. So far, relatively few articles are still focusing on the quality of recovery after general anesthesia with remimazolam, especially in day surgery. This study aimed to compare the early postoperative quality of recovery of remimazolam tosilate with flumazenil and propofol in patients undergoing day surgery. Patients and Methods: 137 patients scheduled for day surgery were randomly divided into the remimazolam tosilate or propofol group. The primary endpoint was the incidence of overall recovery assessed with the early postoperative quality of recovery scale (PostopQRS) on postoperative day 1 (POD 1). The Richmond Agitation-Sedation Scale (RASS) scores in the post-anesthesia care unit (PACU), extubation time, postoperative recovery profiles, and perioperative data were documented. Any adverse events were recorded. Results: The incidence of overall recovery on POD1 was 47.7% in the remimazolam tosilate group and 65.1% in the propofol group (odds ratio, 0.52; 95% confidence interval (CI) 0.26 to 1.06; P = 0.072). In general, the overall recovery of the PostopQRS increased over time, and its interaction between time and group was significant (P = 0.003). Among the five dimensions of PostopQRS, there exist statistical differences between groups including emotional state and cognitive recovery. Upon arrival at the PACU, the remimazolam group was more sedated and took longer to recover to a RASS score similar to propofol. The frequency of application of vasoactive drugs during anesthesia was similar in both groups (P = 0.119). Despite rapid emergence with remimazolam after flumazenil reversal, re-sedation (10.8%) or somnolence (60%) in the PACU was observed, and the length of PACU stay in patients treated with remimazolam tosilate was longer than that of the propofol (35 min vs 30 min, P<0.001). Conclusion: General anesthesia with remimazolam tosilate in conjunction with flumazenil reversal permits rapid recovery of consciousness in day surgery, but there was a notable occurrence of re-sedation or somnolence observed in PACU.

Association between regulator inspection and ratings on primary care prescribing: an observational study in England 2014 to 2019.

BACKGROUND: Healthcare regulators in many countries undertake inspections of healthcare providers and publish inspection outcomes with the intention of improving quality of care. Comprehensive inspections of general practices in England by the Care Quality Commission began for the first time in 2014. It is assumed that inspection and rating will raise standards and improve care, but the presence and extent of any improvements is unknown. We aim to determine if practice inspection ratings are associated with past performance on prescribing indicators and if prescribing behaviour changes following inspection. METHODS: Longitudinal study using a dataset of 6771 general practices in England. Practice inspection date and score was linked with monthly practice-level data on prescribing indicators relating to antibiotics, hypnotics and non-steroidal anti-inflammatory drugs. The sample covers practices receiving their first inspection between September 2014 and December 2018. Regression analysis and the differential timing of inspections is used to identify the impact on prescribing. RESULTS: Better-rated practices had better prescribing in the period before inspections began. In the six months following inspections, no overall change in prescribing was observed. However, the differences between the best and worse rated practices were reduced but not fully. The same is also true when taking a longer-term view. There is little evidence that practices responded in anticipation of inspection or reacted differently once the ratings were made public. CONCLUSION: While some of the observed historic variation in prescribing behaviour has been lessened by the process of inspection and ratings, we find this change is small and appears to come from both improvements among lower-rated practices and deteriorations among higher-rated practices. While inspection and rating no doubt had other impacts, these prescribing indicators were largely unchanged.

Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation.

BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

Insomnia.

Sleep significantly impacts health. Insomnia, characterized by difficulty with sleep onset, maintenance, and subsequent daytime symptoms, is increasingly prevalent and increases the risk of other medical comorbidities. The pathophysiology involves hyperarousal during non-REM sleep and altered sleep homeostasis. The 3P model explains the development and persistence of insomnia. Assessment is primarily clinical and based on appropriate history while distinguishing from other sleep disorders. "Somnomics" suggests a personalized approach to management. Cognitive behavioral therapy for insomnia is the first-line treatment in addition to other nonpharmacological strategies. Medications are a secondary option with weak supporting evidence.

Barriers, facilitators and needs to deprescribe benzodiazepines and other sedatives in older adults: a mixed methods study of primary care provider perspectives.

BACKGROUND: Benzodiazepines and other sedative hypnotic drugs (BSHs) are frequently prescribed for sleep problems, but cause substantial adverse effects, particularly in older adults. Improving knowledge on barriers, facilitators and needs of primary care providers (PCPs) to BSH deprescribing could help reduce BSH use and thus negative effects. METHODS: We conducted a mixed methods study (February-May 2023) including a survey, semi-structured interviews and focus groups with PCPs in Switzerland. We assessed barriers, facilitators and needs of PCPs to BSH deprescribing. Quantitative data were analyzed descriptively, qualitative data deductively and inductively using the Theoretical Domain Framework (TDF). Quantitative and qualitative data were integrated using meta-interferences. RESULTS: The survey was completed by 126 PCPs (53% female) and 16 PCPs participated to a focus group or individual interview. The main barriers to BSH deprescribing included patient and PCP lack of knowledge on BSH effects and side effects, lack of PCP education on treatment of sleep problems and BSH deprescribing, patient lack of motivation, PCP lack of time, limited access to cognitive behavioral therapy for insomnia and absence of public dialogue on BSHs. Facilitators included informing on side effects to motivate patients to discontinue BSHs and start of deprescribing during a hospitalization. Main PCP needs were practical recommendations for pharmacological and non-pharmacological treatment of sleep problems and deprescribing schemes. Patient brochures were wished by 69% of PCPs. PCPs suggested the brochures to contain explanations about risks and benefits of BSHs, sleep hygiene and sleep physiology, alternative treatments, discontinuation process and tapering schemes. CONCLUSION: The barriers and facilitators as well as PCP needs and opinions on patient material we identified can be used to develop PCP training and material on BSH deprescribing, which could help reduce the inappropriate use of BSHs for sleep problems.

Combination administration of alprazolam and N-Ethylmaleimide synergistically enhances sleep behaviors in mice with no potential CNS side effects.

Background: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported. Objective: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp). Methods: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping. Results: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring. Conclusions: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.

Management of physical and psychological trauma resulting from motor vehicle crashes in Australian general practice: a mixed-methods approach.

BACKGROUND: In Australia, motor vehicle crashes (MVC)-related health data are available from insurance claims and hospitals but not from primary care settings. This study aimed to identify the frequency of MVC-related consultations in Australian general practices, explore the pharmacological management of health conditions related to those crashes, and investigate general practitioners' (GPs) perceived barriers and enablers in managing these patients. METHODS: Mixed-methods study. The quantitative component explored annual MVC-related consultation rates over seven years, the frequency of chronic pain, depression, anxiety or sleep issues after MVC, and management with opioids, antidepressants, anxiolytics or sedatives in a sample of 1,438,864 patients aged 16 + years attending 402 Australian general practices (MedicineInsight). Subsequently, we used content analysis of 81 GPs' qualitative responses to an online survey that included some of our quantitative findings to explore their experiences and attitudes to managing patients after MVC. RESULTS: MVC-related consultation rates remained stable between 2012 and 2018 at around 9.0 per 10,000 consultations. In 2017/2018 compared to their peers, those experiencing a MVC had a higher frequency of chronic pain (48% vs. 26%), depression/anxiety (20% vs. 13%) and sleep issues (7% vs. 4%). In general, medications were prescribed more after MVC. Opioid prescribing was much higher among patients after MVC than their peers, whether they consulted for chronic pain (23.8% 95%CI 21.6;26.0 vs. 15.2%, 95%CI 14.5;15.8 in 2017/2018, respectively) or not (15.8%, 95%CI 13.9;17.6 vs. 6.7%, 95% CI 6.4;7.0 in 2017/2018). Qualitative analyses identified a lack of guidelines, local referral pathways and decision frameworks as critical barriers for GPs to manage patients after MVC. GPs also expressed interest in having better access to management tools for specific MVC-related consequences (e.g., whiplash/seatbelt injuries, acute/chronic pain management, mental health issues). CONCLUSION: Chronic pain, mental health issues and the prescription of opioids were more frequent among patients experiencing MVC. This reinforces the relevance of appropriate management to limit the physical and psychological impact of MVC. GPs identified a lack of available resources (e.g. education, checklists and management support tools) for managing MVC-related consequences, and the need for local referral pathways and specific guidelines to escalate treatments.

Reducing the risks when using benzodiazepines to treat insomnia: A public health approach.

Benzodiazepines are widely used but can cause considerable harm, including sedation, addiction, falls, fractures, and cognitive impairment, especially with long-term use and in elderly patients. The authors propose a public health approach to reduce the potential for harm when using benzodiazepines to treat insomnia. Primary prevention involves judicious patient selection and patient education. Secondary prevention requires keeping the duration of use as short as possible according to guidelines. Tertiary prevention, for patients who have been taking a benzodiazepine for a long time, uses shared decision-making to introduce a gradual and carefully monitored taper.

Procedural sedation by advanced practice providers in the emergency medical service in the Netherlands: a retrospective study.

BACKGROUND: Procedural sedation and analgesia (PSA) is a technique of administering sedatives to induce a state that allows the patient to tolerate painful procedures while maintaining cardiorespiratory function, a condition that is frequently desired prehospital. Non-physician prehospital clinicians often have a limited scope of practice when it comes to providing analgesia and sedation; sometimes resulting in a crew request for back-up from physician-staffed prehospital services.". This is also the case if sedation is desirable. Advanced practice providers (APPs), who are legally authorized and trained to carry out this procedure, may be a solution when the physician-staffed service is not available or will not be available in time. METHODS: The aim of this study is to gain insight in the circumstances in which an APP, working at the Dutch ambulance service "RAV Brabant MWN" from January 2019 to December 2022, uses propofol for PSA or to provide sedation. With this a retrospective observational document study we describe the characteristics of patients and ambulance runs and evaluates the interventions in terms of safety. RESULTS: During the study period, the APPs administered propofol 157 times for 135 PSA and in 22 cases for providing sedation. The most common indication was musculoskeletal trauma such as fracture care or the reduction of joint dislocation. In 91% of the situations where propofol was used, the predetermined goal e.g. alignment of fractured extremity, repositioning of luxated joint or providing sedation the goal was achieved. There were 12 cases in which one or more adverse events were documented and all were successfully resolved by the APP. There were no cases of laryngospam, airway obstruction, nor anaphylaxis. None of the adverse events led to unexpected hospitalization or death. CONCLUSION: During the study period, the APPs performed 135 PSAs and provided 22 sedations. The success rate of predetermined goals was higher than that stated in the literature. Although there were a number of side effects, their incidences were lower than those reported in the literature, and these were resolved by the APP during the episode of care. Applying a PSA by an APP at the EMS "RAV Brabant MWN" appears to be safe with a high success rate.

Tranquilisers and sedatives misuse and associated factors among adolescents in Estonia: findings from cross-sectional ESPAD surveys, 2003-2019.

OBJECTIVES: This study aimed to (1) to describe trends of tranquilliser and sedative (TS) misuse in Estonia during 2003-2019 and (2) to analyse the associations between TS misuse and explanatory factors (perceived access to TS, medical use of TS, family-related, friends-related, school-related factors, risk behaviour and leisure time physical activity). DESIGN: A cross-sectional study. SETTING: Data were collected from the European School Survey Project on Alcohol and Other Drugs (ESPAD) from 2003 to 2019 in Estonia. PARTICIPANTS: Estonian schoolchildren aged 15-16 years old (n=11 328), 48.6% were boys. OUTCOME MEASURES: Prevalence, crude and adjusted ORs with 95% CIs for TS misuse. RESULTS: The prevalence of lifetime TS misuse significantly increased from 2003 (5.0% of boys and 12.6% of girls) to 2019 (11.3% and 17.5%, respectively) (p<0.001). Among boys, TS misuse increased significantly among those reporting medical use of TS from 21.1% to 41.4% in 2003-2019 (p=0.006). Medical use of TS multiplied the odds of misuse by 6.89 (95% CI 5.15 to 9.24) for boys and by 4.53 (95% CI 3.58 to 5.73) for girls. Perceived easy access to TS increased the odds of misuse by 6.57 (95% CI 4.13 to 10.46) times for boys and by 4.66 (95% CI 3.25 to 6.70) times for girls. Having many friends who misuse TS increased the odds of misuse by 3.27 (95% CI 2.16 to 4.95) times for boys and by 5.07 (95% CI 3.79 to 6.77) times for girls. Furthermore, higher odds of TS misuse were observed among adolescents who smoked cigarettes and engaged in less sports. CONCLUSIONS: TS misuse prevalence among Estonian adolescents increased significantly from 2003 to 2019. Misuse was strongly associated with medical use, perceived easy access and friends' TS misuse. These findings emphasise the need for targeted prevention strategies, including improving prescription practices, limiting TS access and promoting healthy behaviours and positive peer relationships among adolescents.

Effects of propofol, ketamine-propofol mixture in pediatric dental patients undergoing intravenous sedation: a clinical study.

This study aimed to evaluate the clinical effects, complications (peri- and postoperative), depth of sedation, recovery times, and changes in anxiety levels in paediatric dental patients receiving intravenous sedation with propofol and ketamine-propofol mixtures. This prospective clinical study included 69 healthy children (ASA 1) aged 3-7 years. The patients were assigned randomly to propofol group (n = 23), which received propofol; 1:3 ketofol group (n = 23), which received 1:3 ketofol; or 1:4 ketofol group (n = 23), which received 1:4 ketofol. The bispectral index (BIS) and Ramsay Sedation Scale (RSS) score were recorded at intervals of 5 min to measure the depth of sedation, and vital signs were evaluated. Peri- and postoperative complications and recovery times were recorded. Anxiety levels were also evaluated using the Facial Image Scale (FIS) and changes in saliva cortisol levels (SCLs) before and after the intravenous sedation procedure. The Kruskal‒Wallis test and Wilcoxon signed-rank test were used to determine pre- and posttreatment parameters. Dunn's test for post hoc analysis was used to determine the differences among groups. Children's pre- and posttreatment anxiety levels did not differ significantly according to FIS scores, and increases in SCLs were detected in 1:3 ketofol and 1:4 ketofol groups after dental treatment was completed. Compared with those in the other groups, the BIS values of the patients in 1:4 ketofol indicated a slightly lower depth of sedation. The recovery time of the patients in 1:3 ketofol was longer than that of patients in propofol and 1:4 ketofol. The incidence of postoperative complications (agitation, hypersalivation, nausea/vomiting, and diplopia) did not differ among the groups. Ketamine-propofol combinations provided effective sedation similar to that of propofol infusion without any serious complications during dental treatment performed under intravenous sedation. The ketofol infusion increased the anxiety level of paediatric dental patients to a greater extent than the propofol infusion.

Characterising incident opioid use among incident users of prescription sedative hypnotics: A national cohort study.

OBJECTIVE: To evaluate co-prescribing of sedatives hypnotics and opioids. DESIGN: Retrospective study evaluating the association of patient characteristics and comorbidities with coprescribing. SETTING AND PARTICIPANTS: Using the national Merative MarketScan Database between 2005 and 2018, we identified patients who received an incident sedative prescription with or without subsequent, incident opioid prescriptions within a year of the sedative prescription in the USA. OUTCOME MEASURES: Coprescription of sedative-hypnotics and opioids. RESULTS: A total of 2 632 622 patients (mean (SD) age, 43.2 (12.34) years; 1 297 356 (62.5%) female) received incident prescriptions for sedatives over the course of the study period. The largest proportion of sedative prescribing included benzodiazepines (71.1%); however, z-drugs (19.9%) and barbiturates (9%) were also common. About 557 845 (21.2%) patients with incident sedatives also received incident opioid prescriptions. About 59.2% of these coprescribed patients received opioids coprescription on the same day. Multivariate logistic regression findings showed that individuals with a comorbidity index score of 1, 2 or ≥3 (aOR 1.19 (95% CI 1.17 to 1.21), 1.17 (95% C 1.14 to 1.19) and 1.25 (95% C 1.2 to 1.31)) and substance use disorder (1.21 (95% C 1.19 to 1.23)) were more likely to be coprescribed opioids and sedatives. The likelihood of receiving both opioid and sedative prescriptions was lower for female patients (aOR 0.93; 95% CI 0.92 to 0.94), and those receiving a barbiturate (aOR 0.3; 95% CI 0.29 to 0.31) or z-drugs (aOR 0.67; 95% CI 0.66 to 0.68) prescriptions at the index date. CONCLUSIONS: Coprescription of sedatives with opioids was associated with the presence of comorbidities and substance use disorder, gender and types of sedatives prescribed at the index date. Additionally, more than half of the coprescribing occurred on the same day which warrants further evaluation of current prescribing and dispensing best practice guidelines.

Comparison of the recovery time of remimazolam besylate and propofol for gastrointestinal endoscopy sedation in elderly patients.

Background: Recovery time is a crucial factor in ensuring the safety and effectiveness of both patients and endoscopy centers. Propofol is often preferred due to its fast onset and minimal side effects. Remimazolam is a new intravenous sedative agent, characterized by its rapid onset of action, quick recovery and organ-independent metabolism. Importantly, its effect can be specifically antagonized by flumazenil. The primary goal of this study is to compare the recovery time of remimazolam besylate and propofol anesthesia during endoscopic procedures in elderly patients. Methods: 60 patients aged 65-95 years who underwent gastrointestinal endoscopy were randomly and equally assigned to two groups: the remimazolam group (Group R) and the propofol group (Group P). The primary measure was the recovery time, defined as the time from discontinuing remimazolam or propofol until reaching an Observer's Assessment of Alertness and Sedation scale (OAA/S) score of 5 (responds readily to name spoken in normal tone). The time required to achieve an OAA/S score of 3 (responds after name spoken loudly or repeatedly along with glazed marked ptosis) was also recorded and compared. Results: The recovery time for Group R (2.6 ± 1.6 min) was significantly shorter than that for Group P (10.8 ± 3.0 min), with a 95% confidence interval (CI): 6.949-9.431 min, p <0.001. Similarly, the time to attain an OAA/S score of 3 was significantly less in Group R (1.6 ± 0.9 min) compared to Group P (9.6 ± 2.6 min), with a 95% CI: 6.930-8.957 min, p <0.001. Conclusion: Our study demonstrated that remimazolam anesthesia combined with flumazenil antagonism causes a shorter recovery time for elderly patients undergoing gastrointestinal endoscopy compared to propofol. Remimazolam followed by flumazenil antagonism provides a promising alternative to propofol for geriatric patients, particularly during gastrointestinal endoscopy.