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Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

OBJECTIVES: Long-term benzodiazepine use is common despite known risks. In the original Eliminating Medications Through Patient Ownership of End Results (EMPOWER) Study set in Canada, patient education led to increased rates of benzodiazepine cessation. We aimed to determine the effectiveness of implementing an adapted EMPOWER quality improvement (QI) initiative in a US-based healthcare system. DESIGN: We used a pre-post design with a non-randomised control group. SETTING: A network of primary care clinics. PARTICIPANTS: Patients with ≥60 days supply of benzodiazepines in 6 months and ≥1 risk factor (≥65 years of age, a concurrent high-risk medication prescribed or a diazepam equivalent daily dose ≥10) were eligible. INTERVENTION: In March 2022, we engaged 22 primary care physicians (PCPs), and 308 of their patients were mailed an educational brochure, physician letter and flyer detailing benzodiazepine risks; the control group included 4 PCPs and 291 of their patients. PRIMARY AND SECONDARY MEASURES: The primary measure was benzodiazepine cessation by 9 months. We used logistic regression and a generalised estimating equations approach to control for clustering by PCP, adjusting for demographics, frailty, number of risk factors, and diagnoses of arthritis, depression, diabetes, falls, and pain. RESULTS: Patients in the intervention and control groups were comparable across most covariates; however, a greater proportion of intervention patients had pain-related diagnoses and depression. By 9 months, 26% of intervention patients (81 of 308) had discontinued benzodiazepines, compared with 17% (49 of 291) of control patients. Intervention patients had 1.73 greater odds of benzodiazepine discontinuation compared with controls (95% CI: 1.09, 2.75, p=0.02). The unadjusted number needed to treat was 10.5 (95% CI: 6.30, 34.92) and the absolute risk reduction was 0.095 (95% CI: 0.03 to 0.16). CONCLUSIONS: Results from this non-randomised QI initiative indicate that patient education programmes using the EMPOWER brochures have the potential to promote cessation of benzodiazepines in primary care.

Status epilepticus (SE) is a life-threatening development of self-sustaining seizures that becomes resistant to benzodiazepines when treatment is delayed. Benzodiazepine pharmacoresistance is thought in part to result from internalization of synaptic GABAA receptors, which are the main target of the drug. The naturally occurring neurosteroid allopregnanolone is a therapy of interest against SE for its ability to modulate all isoforms of GABAA receptors. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been partially effective in combination with benzodiazepines in mitigating SE-associated neurotoxicity. In this study, allopregnanolone as an adjunct to midazolam or midazolam-ketamine combination therapy was evaluated for efficacy against cholinergic-induced SE. Adult male rats implanted with electroencephalographic (EEG) telemetry devices were exposed to the organophosphorus chemical (OP) soman (GD) and treated with an admix of atropine sulfate and HI-6 at 1 minute after exposure followed by midazolam, midazolam-allopregnanolone, or midazolam-ketamine-allopregnanolone 40 minutes after seizure onset. Neurodegeneration, neuronal loss, and neuroinflammation were assessed 2 weeks after GD exposure. Seizure activity, EEG power integral, and epileptogenesis were also compared among groups. Overall, midazolam-ketamine-allopregnanolone combination therapy was effective in reducing cholinergic-induced toxic signs and neuropathology, particularly in the thalamus and hippocampus. Higher dosage of allopregnanolone administered in combination with midazolam and ketamine was also effective in reducing EEG power integral and epileptogenesis. The current study reports that there is a promising potential of neurosteroids in combination with benzodiazepine and ketamine treatments in a GD model of SE. SIGNIFICANCE STATEMENT: Allopregnanolone, a naturally occurring neurosteroid, reduced pathologies associated with soman (GD) exposure such as epileptogenesis, neurodegeneration, and neuroinflammation, and suppressed GD-induced toxic signs when used as an adjunct to midazolam and ketamine in a delayed treatment model of soman-induced status epilepticus (SE) in rats. However, protection was incomplete, suggesting that further studies are needed to identify optimal combinations of antiseizure medications and routes of administration for maximal efficacy against cholinergic-induced SE.

AbstractObjectiveMethodsResultsConclusions\nKEY POINTSBipolar disorders (BD) are characterized by highly recurrent nature, necessitating adequate maintenance treatment for long-term disorder control. This study aimed to investigate real-world prescribing patterns among outpatients with BD, focusing on the utilisation of antidepressants (AD) and benzodiazepines (BDZ).We analysed prescription patterns of the five main groups of psychotropic medications (antipsychotics, mood stabilizers, AD, BDZ, and anticholinergic medications) and their relationships with basic socio-demographic and clinical data in a sample of 107 clinically stable BD outpatients (75.7% female, age 44.8 ± 11.7).Maintenance therapy predominantly involved polypharmacy (92.5%), with mood stabilizers (87.9%) and antipsychotics (80.4%, predominantly second-generation) being the most commonly prescribed. Our findings highlight a high percentage of patients prescribed AD (50.5%) and BDZ (54.2%). BDZ patients, compared to the non-BDZ group in maintenance treatment, were significantly older with longer psychiatric history and a decreased likelihood of comorbid personality disorder diagnoses.This study offers insights into prescribing practices within a university psychiatric clinic in the Western Balkans. The prevalent use of polypharmacy in real-world clinical settings, along with high percentage of patients prescribed AD and BDZ, suggests a gap between guideline recommendations and clinical practice, indicating a lack of consensus or standardized approaches in clinical practice.Study uncovers prescribing practices in a Western Balkans university psychiatric clinic, revealing high polypharmacy prevalence (92.5%) among clinically stable bipolar disorder (BD) outpatients.Most BD outpatients received mood stabilizers, particularly lamotrigine, and second-generation antipsychotics, notably olanzapine, with a minority on monotherapy.Antidepressant and benzodiazepine usage was notably high despite guidelines favouring monotherapy, reflecting challenges in managing residual morbidity.AD usage in BD type I is discouraged due to risks, while their use in BD type II is considered in certain scenarios, emphasising tailored treatment.High mean daily BDZ dose (approximately 3.5mg lorazepam equivalents) in non-acute outpatient BD maintenance therapy raises concerns about potential long-term implications for patient health and underscores the need for vigilant monitoring of prescribing practices.Study uncovers prescribing practices in a Western Balkans university psychiatric clinic, revealing high polypharmacy prevalence (92.5%) among clinically stable bipolar disorder (BD) outpatients.Most BD outpatients received mood stabilizers, particularly lamotrigine, and second-generation antipsychotics, notably olanzapine, with a minority on monotherapy.Antidepressant and benzodiazepine usage was notably high despite guidelines favouring monotherapy, reflecting challenges in managing residual morbidity.AD usage in BD type I is discouraged due to risks, while their use in BD type II is considered in certain scenarios, emphasising tailored treatment.High mean daily BDZ dose (approximately 3.5mg lorazepam equivalents) in non-acute outpatient BD maintenance therapy raises concerns about potential long-term implications for patient health and underscores the need for vigilant monitoring of prescribing practices. [ABSTRACT FROM AUTHOR]

Introduction Military Service Members, Veterans, and other patient populations who experience traumatic brain injury (TBI) may have increased risk of early neurodegenerative diseases relative to those without TBI history. Some evidence suggests that exposure to psychotropic medications may play a role in this association. The Long-term Impact of Military-relevant Brain Injury Consortium—Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) prospective longitudinal study provides an ideal setting to examine the effects of psychotropic medication exposure on long-term neurological health of those with and without mild TBI history. In this study, we sought to develop and pilot test a self-report electronic survey instrument to measure participants' psychotropic medication histories for use across LIMBIC-CENC study sites. Materials and Methods We developed a new survey instrument measuring psychotropic medication history and fielded it among Service Members and Veterans enrolled in a single site of the LIMBIC-CENC study to evaluate response rates and patterns, and to compare survey responses to prescription data extracted from participants' Veterans Affair (VA) records. Descriptive statistics estimated survey respondents' lifetime psychotropic medication exposures by their TBI history and other demographic and clinical characteristics of interest. We also compared survey responses to participants' VA outpatient prescription records to estimate sensitivity and negative predictive values (NPVs) for participants' self-reported medication exposures relative to this single prescription data source. Results Among 310 Veterans enrolled at the study site, 249 completed the survey (response rate = 80%), of whom 248 also had VA health records and were included in the analysis. Most (69%) had a history of mild TBI. Over three-fourths of survey respondents (78%) reported ever having used prescription opioids, 26% reported benzodiazepines, 50% reported muscle relaxants, 42% reported antidepressants, 13% reported non-benzodiazepine sedative-hypnotics, 15% reported stimulants, 7% reported mood stabilizers, and 6% reported antipsychotics. Veterans with, versus without, a history of mild TBI were more likely to self-report psychotropic medication history as well as have confirmed receipt of VA prescriptions for each medication class. Using VA records as a criterion standard, the sensitivity of the survey for detecting VA prescriptions ranged from 19% to 84%, while the NPVs ranged from 64% to 97%. Sensitivity and NPVs were similar for participants with, versus without, mild TBI history. Conclusions Service Members and Veterans may receive psychotropic medications from multiple sources over their lifetimes. Valid methods to examine and quantify these exposures among those with a history of TBI are important, particularly as we evaluate causes of neurodegenerative disorders in this population over time. The measurement of Veterans' lifetime psychotropic medication exposures using a self-report survey, in combination with health care records, holds promise as a valid approach, but further testing and refinement are needed. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study, we compared neonatal and maternal outcomes after exposure of different psychopharmacological classes of drugs. Both psychiatric diseases and pharmacological treatment of these are associated with lower birth weights, lower APGAR scores, and NICU admission. Therefore, we tried to rule out the role of psychotropics as if no differences were found between pharmacological classes, the lower birthweights might not be attributable to these. We divided our groups in exposed to atypical antipsychotic drugs, Selective Serotonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCA), benzodiazepines, and different combinations of psychotropic drugs. The last group included SSRIs combined with benzodiazepines, methylphenidate, lithium, and classic antipsychotic drugs. We used univariate regression analysis to see which factors from our rich dataset including pharmacological class, are associated with birth weight, APGAR scores, gestational age, and NICU admission. The significant associations from univariate analyses were further analyzed using ancova analysis or logistic regression where applicable. We found no clinically relevant differences in neonatal and maternal outcomes between the different exposed pharmacological classes. However, our dataset may have been too small to draw firm conclusions. [ABSTRACT FROM AUTHOR]

Several medications are associated with delirium; however, studies with adequate statistical power are limited, and it is difficult to determine the effects of the various concomitant medications used in clinical practice. Therefore, in this study, we aimed to comprehensively evaluate the safety signals of delirium-associated drugs using a spontaneous adverse event reporting system. The JAPIC AERS (Food and Drug Administration Adverse Event Reporting System pre-processed by the Japan Pharmaceutical Information Center) was used for the analysis in this pharmacovigilance study. The reporting odds ratio (ROR) for delirium was adjusted for using multivariate logistic regression analysis with sex, age, indication, and melatonin receptor agonist use, and 22 drug categories were targeted as covariates. After excluding patients with missing information, 7,527,568 patients were included in the study. Delirium signals were detected even after adjusting for covariates in 17 drug categories, including benzodiazepines (adjusted ROR, 1.76; 95% confidence interval [CI], 1.64–1.89), opioids (adjusted ROR, 4.42; 95% CI, 4.21–4.64), and tricyclic antidepressants (adjusted ROR, 2.44; 95% CI, 2.20–2.71). These findings suggest that many drug classes, such as benzodiazepines, are independent risk factors for delirium and strengthen the evidence of an association between delirium and medications. [ABSTRACT FROM AUTHOR]

Background: Medication utilization has been increasing in the U.S. year‐over‐year for several decades. As older adults take more medications, there is a higher risk of them being exposed to drug–drug or drug‐disease interactions. The American Geriatrics Society in 2019 updated their Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults. The objective of this study was to assess the prevalence of utilization of medications included in the 2019 Beers Criteria. Methods: An analysis was conducted using the Medicare Part D Provider Utilization and Payment Data Public Use File for calendar‐year 2020. Medications identified in the 2019 Beers Criteria were applied to the analysis. Two categories of medications were assessed: (1) "Avoid" and (2) "Use With Caution." Results: In 2020, 56 million prescriptions were dispensed to Medicare patients 65 years and older that are recommended to be avoided without exception (4.7% of all prescriptions) totaling $957 million in medication costs. The most utilized medication classes in this category were benzodiazepines (25,949,994 prescriptions), "Z‐drugs" (6,204,909 prescriptions), long‐acting sulfonylureas (5,306,577 prescriptions), 1st‐generation antihistamines (5,049,289 prescriptions), and tricyclic antidepressants (4,190,062 prescriptions). Additionally, 135 million prescriptions were dispensed to Medicare beneficiaries 65 years and older for medications which the Beers Criteria states to use caution (11.3% of all prescriptions) exceeding $2.85 billion in medication costs. The most utilized medications for this category were diuretics (74,599,126 prescriptions), selective serotonin reuptake inhibitors (30,033,121 prescriptions), serotonin and norepinephrine reuptake inhibitors (11,858,968 prescriptions), tramadol (11,450,878 prescriptions), and mirtazapine (5,737,304 prescriptions). Conclusion: Even with the existence of the AGS Beers Criteria for PIM Use in Older Adults and its continued updated versions, 16% of medications dispensed to Medicare Part D were potentially inappropriate. Future studies are needed to assess if this has led to worsened outcomes among older adults who utilized these PIM. [ABSTRACT FROM AUTHOR]

In recent years the still relatively new short-acting benzodiazepine remimazolam has been approved and clinically implemented in several countries and regions. Remimazolam is also now approved in the EU and the market launch in Germany is expected in the not too distant future. This is therefore a good point in time to summarize the current evidence for various areas of application, including general anesthesia, sedation and intensive care medicine as well as different dosing schemes. [ABSTRACT FROM AUTHOR]

Introduction There is a longstanding debate about whether health care is more efficiently provided by the public or private sector. The debate is particularly relevant to the Military Health System (MHS), which delivers care through a combination of publicly funded federal facilities and privately contracted providers. This study compares outcomes, treatments, and costs for MHS patients obtaining care for low back pain (LBP) from public versus private providers. Materials and Methods A retrospective cohort study was completed using TRICARE Prime claims data from April 2015 to December 2018. The cohort was identified using International Classification of Diseases Ninth Revision and Tenth Revision diagnostic codes and then followed for 12 months after the index diagnosis to assess treatments, outcomes, and costs. Claims were classified as originating from either public or private providers. The primary outcome measure was resolution of LBP, defined as an absence of LBP diagnoses during the 6-to-12-month window following the index event. Instrumental variable models were used to assess the impact of care setting (i.e. private versus public), conditioning on the covariates. A regional measure of the fraction of private care was used as an instrument. Results Resolution of LBP was achieved for 79.7% of 144,866 patients in the cohort. No significant association was found between resolution of LBP and fraction of privately provided care. Higher fraction of private care was associated with a greater likelihood of opioid treatments (odds ratio, 1.22; 95% CI, 1.02-1.46) and a lower likelihood of benzodiazepine (odds ratio, 0.56; 95% CI, 0.45-0.70) and physical therapy (odds ratio 0.55; 95% CI, 0.42-0.74) treatments; manual therapy was not significantly associated with the fraction of private care. There was a significant negative association between the fraction of private care and cost (coefficient −0.27; 95% CI, −0.44, −0.10). Conclusion This study found that privately provided care was associated with significantly higher opioid prescribing, less use of benzodiazepines and physical therapy, and lower costs. No systematic differences in outcomes (as measured by resolved cases) were identified. The findings suggest that publicly funded health care within the MHS context can attain quality comparable to privately provided care, although differences in treatment choices and costs point to possibilities for improved care within both systems. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Article #1 discusses a clinical trial that examined the effects of delaying intubation in comatose patients with acute poisoning. The study found that delaying intubation was safe and resulted in lower rates of ICU admission and complications. However, the lack of deaths suggests that more research is needed, particularly involving confirmed overdoses. Article #2 explores lead exposure in veterinary workers who handle lead shielding during radiography. The study found that the use of lead shielding is associated with lead exposure, but wearing disposable gloves can significantly reduce this exposure. However, the study had limitations, such as potential bias from the questionnaire and the lack of evaluation of hand washing. Article #3 focuses on the use of angiotensin II (AT2) for treating refractory shock. While AT2 has shown improvement in blood pressures, its impact on mortality is still unclear. The study aims to determine if adding AT2 improves 30-day mortality in patients with severe, refractory shock. However, the study is retrospective and underpowered, so further research is needed to establish its effectiveness. The study found that there was no significant difference in mortality between the AT2 group and the control group, and baseline characteristics differed between the two groups. Overall, the study concluded that AT2 was not associated with improved mortality or organ dysfunction in patients with severe shock. [Extracted from the article]

Background: Gabapentinoids (GBP) and benzodiazepines (BZ) are commonly prescribed in older adults and their package inserts list edema and vertigo as adverse drug reactions. These adverse drug reactions may be treated with symptomatic drug therapies without discontinuing the culprit drugs or decreasing their dose, thereby initiating a prescribing cascade and often resulting in polypharmacy. Whether prescribing cascades occur in the treatment of edema and dizziness among Japanese patients treated with GBP and BZ has not been investigated, including treatment with mirogabalin, a class drug of GBP marketed in Japan. Objective: We aimed to investigate prescribing cascades with GBP-induced and BZ-induced edema and dizziness treated with loop diuretics (LD) and anti-vertigo drugs (AVD), respectively, among older adults. Methods: A prescription sequence symmetry analysis design was used to detect signals of prescribing cascades associated with edema and dizziness induced by GBP and BZ (exposure drugs). Loop diuretics and AVD were the outcome drugs used to identify prescribing cascades following the initiation of exposure drugs. The study population consisted of enrollees of a large-scale health claims database provided by DeSC Healthcare, Inc., between April 2014 and March 2021. Subjects eligible for a prescription sequence symmetry analysis were patients aged ≥ 65 years prescribed an outcome drug within 90 days before and after exposure drug initiation. A signal of a prescribing cascade was detected if secular trend-adjusted sequence ratios were statistically significant on comparison of the frequencies of outcome drug initiation before and after exposure drug initiation. Results: We identified 2671 patients with prescriptions of a GBP-LD combination, 4009 with a GBP-AVD combination, 8675 with a BZ-LD combination, and 9462 with a BZ-AVD combination. The adjusted sequence ratios for GBP-LD and BZ-LD cascades were significantly larger than one (adjusted sequence ratio [95% confidence interval], 1.69 [1.56–1.83]; 1.35 [1.29–1.41], respectively), indicating positive signals of prescribing cascades. No signal was detected for the GBP-AVD or BZ-AVD cascade (0.89 [0.83–0.94]; 0.90 [0.87–0.94], respectively). The adjusted sequence ratio for the mirogabalin cascade was higher than that for pregabalin (2.23 [1.84–2.71] vs 1.59 [1.46–1.73]). Conclusions: Our study provides good evidence that LD-prescribing cascades associated with edema would be a class effect of GBP and BZ. Edema emerging around 1 month after GBP initiation should be carefully differentiated from pathological edema, and undue LD prescription as a prescribing cascade should be avoided. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines are the preferred treatment for alcohol withdrawal. Phenobarbital is an alternative in the setting of prescriber expertise or benzodiazepine contraindication. Objective: To evaluate the efficacy and safety of a phenobarbital dosing strategy aimed at treating a spectrum of alcohol withdrawal symptoms across various patient populations. Methods: Retrospective review of patients admitted with concerns of alcohol withdrawal between May 2018 and November 2022. Patients were separated into a before-after cohort of lorazepam or phenobarbital. The primary outcome was hospital length of stay (LOS). Secondary outcomes were intensive care unit (ICU) LOS, escalation of respiratory support, increased level of care (LOC), and incidence of delirium tremens and/or seizures. Results: Two hundred and seventy-seven patients received lorazepam and 198 received phenobarbital. Hospital LOS was longer in the phenobarbital cohort compared with the lorazepam cohort (6.9 vs 9.3 days). There was no difference in ICU LOS. Level of care increases were fewer in the phenobarbital cohort (4 events vs 19 events). There were higher rates of non-invasive respiratory interventions in the lorazepam cohort and higher rates of mechanical ventilation in the phenobarbital cohort. Utilization of phenobarbital was attributed to a reduction in delirium tremens and seizures. Conclusion and Relevance: This study is novel because of the broad application of a phenobarbital order set across multiple levels of care and patient admission diagnoses. A risk targeted split load intravenous phenobarbital order set can safely be administered to patients with fewer escalations of care, seizures, delirium tremens, and respiratory care escalation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Background: Potentially inappropriate medications (PIMs) are prevalent in older adults with dementia and subsequent falls or fall-related injuries. The present study determined the risk of falls or fall-related injuries associated with PIM use in older adults with dementia. Methods: The National Health Insurance Service-Elderly Cohort Database 2.0 (NHIS-ECDB 2.0) was used for this self-controlled case series (SCCS) study. This study included 1430 participants who went through exposure and non-exposure periods of PIM application among patients with dementia and experienced outcome events of falls or fall-related injuries between January 2016 and December 2019. The incidence of falls or fall-related injuries during the exposure and post-exposure periods was compared with that during the non-exposure period. Beers Criteria were used to define PIMs in patients with dementia. Negative binomial regression was conducted. The incidence rate ratio (IRR) was used to determine the risk of falls or fall-related injuries. Results: During the exposure periods in which falls or fall-related injuries occurred, the mean number of PIMs among patients with dementia was 3.76 (SD = 2.99), and the most commonly used PIMs among patients with dementia were first-generation antihistamines (n = 283; 59.1%). Compared to the non-exposure period, the adjusted IRR during the exposure period was 1.57 (95% CI = 1.39–1.76). The risk of falls or fall-related injuries was increased when PIM use in patients with dementia was initiated (1–14 days: IRR = 2.76, 95% CI = 2.31–3.28; 15–28 days: IRR = 1.95, 95% CI = 1.48–2.56; ≥ 29 days: IRR = 1.17, 95% CI = 1.01–1.35). Especially, an increased risk of falls or fall-related injuries was associated with greater PIM use among patients with dementia. Conclusion: Among older adults with dementia, PIMs significantly increase the risk of falls and fall-related injuries. Therefore, strategies should be developed to manage PIM prescriptions in patients with dementia to prevent falls. [ABSTRACT FROM AUTHOR]

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

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

Background: When considering changing hypnotic pharmacotherapy, lemborexant has attracted attention as a candidate due to its effectiveness and safety profile. However, few studies have investigated switching patterns in clinical practice. Research design and methods: We conducted a retrospective cohort study using a nationwide claims database. Patients prescribed a single hypnotic who either subsequently switched to (switching cohort) or were additionally prescribed (add-on cohort) lemborexant between July 2020 and December 2021 were identified. Proportion of successful switching was defined as remaining on lemborexant alone or without any hypnotic at 6 months after lemborexant initiation. Results: The success proportion was 70.1% in the switching cohort (n = 4,861) and 38.6% in the add-on cohort (n = 9,423). In the add-on cohort, the success proportion was lower in patients with a hypnotic history of ≥180 days (31.4%) and in patients whose prescribed hypnotic was a benzodiazepine or non-benzodiazepine (31.5% and 37.6%, respectively). Conclusion: The proportion of successful switching was higher in patients who switched to lemborexant than in those who added lemborexant as a concomitant treatment. The lower success proportion in the add-on cohort might be related to clinically more severe insomnia, and/or a concomitant prescription of benzodiazepine or non-benzodiazepine, from which discontinuation may be challenging. [ABSTRACT FROM AUTHOR]

Summary The aim of this study is to describe the patterns of prescription of benzodiazepine‐receptor agonists in hospitalised patients in four psychogeriatric units in Switzerland. This is a retrospective cross‐sectional study that included patients aged 65 years or more hospitalised in one of the four psychogeriatric units of a university hospital in Switzerland during 2019. The presence, type and dose of benzodiazepine‐receptor agonists was assessed at admission and at discharge. Three‐hundred and eighty‐six patients (214 women, 78.2 ± 8.1 years) were included in the study; 33.4% of patients had at least one benzodiazepine‐receptor agonist at admission and 22.5% at discharge. The relative reduction of benzodiazepine‐receptor agonists prescription in standardised dose was 78%. Age was found to be a protective factor against benzodiazepine‐receptor agonists prescription at admission (adjusted odds ratio 0.94, confidence interval 0.91–0.98), and diagnosis of substance abuse was found to be a risk factor (adjusted odds ratio 4.43, confidence interval 1.42–17.02). Longer hospital stays (> 14 days) were associated with higher reduction of benzodiazepine‐receptor agonists. The prevalence of a prescription of benzodiazepine‐receptor agonists at admission was high, but during the psychogeriatric hospitalisation benzodiazepine‐receptor agonists prescription decreased both in absolute and relative terms. [ABSTRACT FROM AUTHOR]

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

Background: Postoperative nausea and vomiting (PONV) refers to nausea and vomiting that occurs within 24-h after surgery or in the post-anesthesia care unit (PACU). Previous studies have reported that the use of remimazolam, a newer benzodiazepine (BDZ) hypnotic, for anesthesia results in less PONV. In this study, we compared the rate of PONV between sevoflurane and remimazolam after general anesthesia. Methods: In this prospective randomized controlled trial, participants aged 20-80 years who underwent elective laparoscopic cholecystectomy or hemicolectomy were randomized to either the remimazolam or sevoflurane group. The primary outcome was PONV incidence for 24-h after surgery. Secondary outcomes comprised of PONV at 30-min post-surgery, postoperative additional antiemetic use, and Quality of Recovery-15 (QOR- 15) score at 24-h postoperatively. Results: Forty patients were enrolled in the study. The remimazolam group exhibited significantly lower rates of PONV for 24-h after surgery than did the sevoflurane group (remimazolam group vs. sevoflurane group; 5% vs. 45%, P = 0.003, respectively). The use of dexamethasone, a rescue antiemetic administered within 24 h of surgery, was substantially lower in the remimazolam group than in the sevoflurane group (0% in remimazolam vs. 30% in sevoflurane, P = 0.020). The QOR-15 score at 24-h after surgery showed no significant difference between the two groups. Conclusions: Compared to sevoflurane, opting for remimazolam as an intraoperative hypnotic may decrease the incidence of PONV and reduce antiemetic use for 24 h after laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Introduction: Benzodiazepine (BDZP) and/or z‐hypnotic dispensing during pregnancy has increased globally, as have rates of autism spectrum disorder (ASD) and attention‐deficit hyperactivity disorder (ADHD). This systematic review and meta‐analysis aimed to estimate the association between gestational exposure to BDZP and/or z‐hypnotics and diagnosis of ASD or ADHD in offspring. Methods: We searched MEDLINE, EMBASE, and SCOPUS from inception till December 2023 for relevant English‐language articles. Outcomes of interest were risk of ASD and ADHD, two independent primary outcomes, in children exposed anytime during pregnancy to BDZP and/or z‐hypnotics versus those unexposed. Secondary outcomes were trimester‐wise analyses. Using a random effects model, we pooled the overall and trimester‐wise hazard ratios (HRs), with 95% confidence intervals (CIs), separately for risk of ASD and ADHD. Results: We found six eligible retrospective cohort studies and no case–control studies. There was no increased risk of ASD associated with anytime gestational BDZP and/or z‐hypnotic exposure (primary outcome, HR, 1.10; 95% CI, 0.81–1.50; 4 studies; n = 3,783,417; 80,270 exposed, 3,703,147 unexposed) nor after first trimester exposure (HR, 1.15; 95% CI, 0.83–1.58; 3 studies; n = 1,539,335; 70,737 exposed, 1,468,598 unexposed) or later trimester exposures. A very small but significantly increased risk of ADHD was noted with anytime gestational exposure to these drugs (primary outcome, HR, 1.07; 95% CI, 1.03–1.12; 4 studies; n = 2,000,777; 78,912 exposed, 1,921,865 unexposed) and also with (only) second trimester exposure (HR, 1.07; 95% CI, 1.03–1.12; 3 studies; n = 1,539,281; 33,355 exposed, 1,505,926 unexposed). Findings were consistent in sensitivity analyses. Conclusion: Gestational exposure to benzodiazepines or z‐hypnotics was not associated with an increased risk of ASD and with only a marginally increased risk of ADHD in offspring. Given the likelihood of confounding by indication and by unmeasured variables in the original studies, our findings should reassure women who need these medications for severe anxiety or insomnia during pregnancy. [ABSTRACT FROM AUTHOR]

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

Background 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. [ABSTRACT FROM AUTHOR]

Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. In this regard, there is the potential for death. Additionally, the rise in fake Xanax tablets containing etizolam and other counterfeit medications has been exacerbated by the difference in regulations regarding these substances in different countries as well as the illegal drug trade. Healthcare providers may also play a role through the over- or underprescribing of certain medications. Thus, in order to combat the rise in counterfeit medications such as fake Xanax, international cooperation, regulation, and enforcement of laws pertaining to the manufacture, prescription, and distribution of these substances are needed. [ABSTRACT FROM AUTHOR]

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. 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. 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%). 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. [ABSTRACT FROM AUTHOR]

Background: This study examines the implementation and perceptions of a pharmacist consultant deprescribing program aimed at reducing the risk of falls in older adults using opioids and benzodiazepines. Methods: This qualitative study conducted interviews with healthcare providers. The interviews were conducted from August to December 2021 and analyzed using inductive coding techniques. Results: Five participants, predominantly female MDs or PA-Cs from rural clinics, were interviewed. The participants adopted a pharmacist-led deprescribing program due to their heightened awareness of the opioid crisis, dedication to patient safety, and a desire for opioid deprescribing education. Initially, concerns included patient resistance and provider-driven barriers. However, over time, patient attitudes shifted toward greater openness to the program. The providers emphasized several critical needs for the success of the program: guaranteed access to pharmacists, tailored patient education, resources specific to providers, and financial support, including telehealth options. These factors were deemed essential to overcoming initial barriers and ensuring effective implementation. Conclusion: Integrating pharmacists into primary care settings shows promise for deprescribing opioids and benzodiazepines in older adults. Future research should explore telehealth options for patient–pharmacist consultations and expand the application of these findings to other healthcare settings. The study highlights the importance of awareness, patient education, access to resources (pharmacists), and provider support in addressing deprescribing among older adults. [ABSTRACT FROM AUTHOR]

Background: Tolerance and dependence stand out as the most relevant risks observed during benzodiazepine (BZD) treatments. Objectives: To evaluate the degree of dependence of patients on BZD treatments using the Tyrer test; to define a profile of patients at risk of developing BZD dependence; and to discuss the role of the pharmaceutical care offered by the community pharmacy during dispensing. Methods: Prospective cross-sectional descriptive observational study (August 2020–February 2021) involving 127 patients using BZD. They voluntarily answered a questionnaire during the dispensing pharmaceutical care service. The study was evaluated and codified (code: DAA-CLO-2020-01) by the Spanish Agency for Drugs and Health Products (AEMPS), and statistical analysis was performed with SPSS 25.0. Results: 19.05% of patients using BZD were suspected of suffering from BZD tolerance, and 77.88% of all patients were identified as being at a high risk of BZD dependence. The Tyrer test for dependence indicated a mean score of 5.59 out of 13 points. An 18-fold increased risk of developing dependence was detected in the case of coexistence of high anxiety or depression. Conclusions: The community pharmacy, through protocolized care practices and supported by tools such as the Tyrer test, can play a decisive role in the detection, prevention, and resolution of the risks associated with BZD treatments. [ABSTRACT FROM AUTHOR]

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

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Background Methods Results Conclusions The pharmacodynamics of propofol in children have previously been described with the proprietary bispectral index (BIS) as an effect‐site marker, and it has been suggested that the rate of onset of propofol might be age dependent, that is, a shorter time to peak effect in younger children. However, these analyses were potentially confounded by co‐administered drugs, in particular opioids and benzodiazepines. Thus, the goal of this prospective study was to characterize the influence of age and weight on the onset of hypnotic effects from propofol, reflected by the time to peak of propofol effect‐site concentration in the absence of additional drugs.A total of 46 healthy children aged 2–12 years presenting for elective surgery were included in our observational cohort study. Solely propofol was administered via a target‐controlled infusion pump programmed with the Paedfusor pharmacokinetic model. The BIS and infusion pump data were recorded. The effect of an induction “bolus” was recorded having stopped the pump once a propofol plasma target concentration of 7 μg.mL−1 was achieved. A direct‐response and an indirect‐response model in the context of nonlinear mixed‐effects modeling was used to characterize and compare BIS data in children aged 2–6 years and older children aged 8–12 years.Time to peak of propofol effect‐site concentration had a difference (p‐value <.01) for age and weight, that is 84 [74, 96] (median [IQR] secs for children aged 2–6 years vs. 99 [91, 113] secs for children aged 8–12 years and 82 [71, 95] secs for weight 11–25 kg vs. 99 [91, 114] secs for weight 30–63 kg). The plasma effect‐site equilibration rate constant for propofol had a heterogeneous distribution with a median of 2.36 (IQR: 2.05–2.93; range: 0.83–7.31) per minute but showed a weight‐dependent effect in patients with weight below 45 kg.In children, the age and weight have an influence on time to peak effect of propofol. In the absence of opioids and benzodiazepines, time to peak effect was approximately 20% longer in children aged 8–12 years as compared to younger children. Such clinically relevant age and weight effects are an important consideration in the individualized titration of propofol dosing. [ABSTRACT FROM AUTHOR]

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

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

Background: Benzodiazepines and opioids are commonly administered to severely ill children in the pediatric intensive care unit (PICU) for analgesia and sedation. Long-term opioid medication often results in iatrogenic withdrawal syndrome (IWS) as well as tolerance when the dosage of benzodiazepines and opioids are gradually lowered or entirely stopped. Objectives: This review aimed to review and summarize existing knowledge and information on IWS in pediatrics. Conclusion: IWS in critically ill children is difficult to diagnose and manage. However, detecting and successfully managing IWS is critical to minimizing potentially negative effects during a patient's ICU stay and after discharge. Further research is required to ascertain the exact and reliable prevalence of IWS among pediatric patients, as well as the benefits and drawbacks of existing assessment tools and treatments. [ABSTRACT FROM AUTHOR]

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

An efficient in situ condensation of citronellal, the main constituent of Eucalyptus citriodora essential oil (51%), with different amine derivatives of 2,3-diaminomaleonitrile and 3-[(2-aminoaryl)amino]dimedone has led to novel chiral benzodiazepine structures. All reactions were precipitated in ethanol and pure products were obtained in good yields (58–75%) without any purification. The synthesized benezodiazepines were characterized by spectroscopic techniques, namely 1H-NMR, 13C-NMR, 2D NMR and FTIR. Differential Scanning Calorimetry (DSC) and HPLC were used to confirm the formation diastereomeric mixtures of benzodiazepine derivatives. [ABSTRACT FROM AUTHOR]

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

5N‐Benzoyl‐1,5‐benzodiazepin‐2‐ones with various substituents were synthesized and their atropisomeric properties were analyzed. For the rotational isomers (E/Z) based on the amide bond [N−C(=O)], the E‐isomers were preferentially formed regardless of the substituents. Atropisomers (aR/aS) due to the Ar−N(CO) (sp2‐sp2) axis were isolated using chiral HPLC, and the rotational barrier (ΔG≠) in thermal isomerization was measured. The rotation barrier about the Ar−N(CO) axis was affected by both the substituents at the C6‐position and the p‐substituents on the benzoyl group. The substituents at C6 (R1) caused both steric and electronic effects. On the other hand, the p‐substituents (R2) on the benzoyl group caused electronic effects: the electron‐donating group (EDG) lowered the ΔG≠ value, whereas the electron‐withdrawing group (EWG) raised it. The ΔG≠ values were linearly correlated with the magnitude of the electronic effect (Hammett σ constants) of functional groups (R2). The EDG causes an increase in the electron density on the carbonyl moiety in the amide, which may disturb the planarity of the amide bond, resulting in a decrease in the ΔG≠ value. [ABSTRACT FROM AUTHOR]

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

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

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

Purpose: The prevalence of benzodiazepines and related drugs (BZRDs) use during pregnancy increased sharply in recent years. Thus, there are concerns regarding the pregnancy outcomes following exposure to BZRDs. Methods: Two electronic databases were thoroughly searched to identify related clinical studies published from inception until June 2023. English-language cohort studies with high-quality comparing antenatal BZRDs exposure to an unexposed group on any delivery outcome were included. Results: Ten cohort studies that estimated adverse neonatal outcomes associated with exposure to BZRDs during pregnancy were included. Exposure to BZRDs during pregnancy was associated with an increased risk of congenital malformation [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05–1.13, p < 0.001], heart malformation (OR 1.13, 95% CI 1.04–1.22, p = 0.003), preterm birth (OR 1.45, 95% CI 1.23–1.7, p < 0.001), SGA (OR 1.18, 95% CI 1.08–1.29, P < 0.001), LBW (OR 1.42, 95% CI 1.25–1.6, p = 0.001) or low Apgar score (OR 1.42, 95% CI 1.08–1.87, p = 0.011),compared with no exposure. Further analyses limited to the first trimester exposure yielded consistent results. Conclusions: Exposure to BZRDs during pregnancy may be associated with several adverse neonatal outcomes. However, we could not rule out the potential indication confounding factor, further studies with high-quality that control for important confounders are still needed to verify our findings. [ABSTRACT FROM AUTHOR]

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

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

Ecstasy/Molly/MDMA is a widely used substance often taken in combination with other drugs in different contexts. The current study assessed ecstasy use patterns, concurrent substance use and the context of ecstasy use among an international sample of adults (N = 1,732). Participants were 87% white, 81% male, 42% college educated, 72% employed, with a mean age of 25.7 (SD = 8.3). Using the modified UNCOPE, risk for ecstasy use disorder was 22% overall, and significantly higher among younger individuals and those with greater frequency and quantity of use. Participants reporting risky ecstasy use endorsed significantly higher use of alcohol, nicotine/tobacco, cannabis, cocaine, amphetamine, benzodiazepines, and ketamine compared to those at lower risk. Great Britain (aOR = 1.86; 95% CI [1.24, 2.81]) and Nordic countries (aOR = 1.97; 95% CI [1.11, 3.47]) were approximately 2 times more likely to exhibit risk for ecstasy use disorder than the United States, Canada, Germany, and Australia/New Zealand. Taking ecstasy at home emerged as a common setting followed by electronic dance music events and music festivals. The UNCOPE may be a useful clinical tool for detecting problematic ecstasy use. Harm reduction interventions for ecstasy should target young people, substance co-administration, and context of use. [ABSTRACT FROM AUTHOR]

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

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

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