Anticholinergic and sedative medication use in older community-dwelling people: A national population study in the Netherlands.

PURPOSE: To identify the proportion of older adults with a high anticholinergic/sedative load and to identify patient subgroups based on type of central nervous system (CNS)-active medication used. METHODS: A cross-sectional study of a nationwide sample of patients with anticholinergic/sedative medications dispensed by 1779 community pharmacies in the Netherlands (90% of all community pharmacies) in November 2016 was conducted. Patients aged older than 65 years with a high anticholinergic/sedative load defined as having a drug burden index (DBI) greater than 1 were included. Proportion of patients with a high anticholinergic/sedative load was calculated by dividing the number of individuals in our study population by the 2.4 million older patients using medications dispensed from study pharmacies. Patient subgroups based on type of CNS-active medications used were identified with latent class analysis. RESULTS: Overall, 8.7% (209 472 individuals) of older adults using medications had a DBI greater than 1. Latent class analysis identified four patient subgroups (classes) based on the following types of CNS-active medications used: "combined psycholeptic/psychoanaleptic medication" (class 1, 57.9%), "analgesics" (class 2, 17.9%), "antiepileptic medication" (class 3, 17.8%), and "anti-Parkinson medication" (class 4, 6.3%). CONCLUSIONS: A large proportion of older adults in the Netherlands had a high anticholinergic/sedative load. Four distinct subgroups using specific CNS-active medication were identified. Interventions aiming at reducing the overall anticholinergic/sedative load should be tailored to these subgroups.

Unlawful dispensing practice of diazepam: a simulated client approach in community pharmacies in the north-west of Dar-es-Salaam region, Tanzania.

BACKGROUND: The use of psychotropic substances is controlled in most parts of the world due to their potential of abuse and addiction. Diazepam is one of the psychotropic substances which can be dispensed in community pharmacies in Tanzania. As per good dispensing practices and pharmacy laws, diazepam in the community pharmacies should strictly be stored in a controlled box and dispensed only by prescription. However, to our understanding little had been reported on availability and dispensing practices of diazepam in Tanzania. METHODS: A descriptive cross-sectional study which involved 178 randomly selected registered community pharmacies in Kinondoni district was conducted from January to March 2018. Simulated client approach was used to assess the availability and dispensers practice about dispensing of diazepam. Location of pharmacies was categorized as being at the centre or periphery of the Kinondoni district. Chi-squared test was used for the analysis of categorical data using SPSS version 23. The p-value of < 0.05 was considered significant. RESULT: The total of 178 community pharmacies were visited, the majority of the dispensers (89.1%) encountered were female. Most (69.1%) of the studied pharmacies were located at the centre of Kinondoni district. Diazepam was available in 91% of community pharmacies and 70% of dispensers issued diazepam without prescription. CONCLUSION: Diazepam was available in most of the community pharmacies in Kinondoni district, and the majority of the dispensers dispensed diazepam without prescription. This calls for the regulatory authorities to be more vigilant on the availability of diazepam and enhance the provision of ethical pharmacy practice in the community pharmacies.

Sleep- and Wake-Promoting Drugs: Where Are They Being Sourced, and What Is Their Impact?

Background: Recent decades have seen both an increased number of shift workers in order to deliver services 24/7, and increased potential for social interactions at all hours of the day. People have sought to engage in strategies, which either promote vigilance or facilitate sleep, with the use of sleep- and wake-promoting drugs representing one strategy. Methods: We investigated use of sleep- and wake-promoting drugs in participants (n = 377) who completed a survey investigating the type and source of sleep- and wake-promoting drugs, and their impact on sleep and performance outcomes. Results: The most commonly reported wake-promoting drugs were amphetamine and dextroamphetamin salts, modafinil, and illicit substances including methamphetamine and cocaine, while the most commonly reported sleep-promoting drugs were benzodiazepines and antihistamines. Use of a sleep-promoting drug in the past month was associated with higher odds of having poorer sleep quality (OR = 3.15) and moderate-high insomnia (OR = 3.30), while use of a wake-promoting drug was associated with poor sleep quality (OR = 3.76), or making a fatigue-related error (OR = 2.65). Conclusions: These findings represent novel data on the use and source of sleep- and wake-promoting- drugs, and suggest that despite their use, poor sleep and performance outcomes persist, likely representing individuals struggling to keep up with the 24/7 world.

Benzodiazepine and Z-drug prescribing in Ireland: analysis of national prescribing trends from 2005 to 2015.

AIMS: The aim of this study was to examine prescribing trends for benzodiazepines and Z-drugs to General Medical Services (GMS) patients in Ireland. METHODS: A repeated cross-sectional analysis of the national pharmacy claims database was conducted for GMS patients aged ≥16 years from 2005 to 2015. Prescribing rates per 1000 eligible GMS population were calculated with 95% confidence intervals (CIs). Negative binomial regression was used to determine longitudinal trends and compare prescribing rates across years, gender and age groups. Duration of supply and rates of concomitant benzodiazepine and Z-drug prescribing were determined. Age (16-44, 45-64, ≥65 years) and gender trends were investigated. RESULTS: Benzodiazepine prescribing rates decreased significantly from 225.92/1000 population (95% CI 224.94-226.89) in 2005 to 166.07/1000 population (95% CI 165.38-166.75) in 2015 (P < 0.0001). Z-drug prescribing rates increased significantly from 95.36/1000 population (95% CI 94.73-96.00) in 2005 to 109.11/1000 population (95% CI 108.56-109.67) in 2015 (P = 0.048). Approximately one-third of individuals dispensed either benzodiazepines or Z-drugs were receiving long-term prescriptions (>90 days). The proportion of those receiving >1 benzodiazepine and/or Z-drug concomitantly increased from 11.9% in 2005 to 15.3% in 2015. Benzodiazepine and Z-drug prescribing rates were highest for older women (≥65 years) throughout the study period. CONCLUSIONS: Benzodiazepine prescribing to the GMS population in Ireland decreased significantly from 2005 to 2015, and was coupled with significant increases in Z-drug prescribing. The study shows that benzodiazepine and Z-drug prescribing is common in this population, with high proportions of individuals receiving long-term prescriptions. Targeted interventions are needed to reduce potentially inappropriate long-term prescribing and use of these medications in Ireland.

Defining Over-Sedation: Literature Review and National Survey of Dental Hospitals Within the United Kingdom.

AIMS: To review the literature, to investigate whether there was aconsensus on what encompasses over-sedation, and to determine the guidance employed for the administration of flumazenil. METHODS: A literature search was performed following which a self-designed questionnaire was emailed to 14 sedation leads within UK Dental Hospitals. RESULTS: 10 documents in the literature review met the inclusion criteria. In their definitions of over-sedation, loss of consciousness and respiratory depression were the main terms used; but a variety of terms were also seen, indicating a lack of agreement. Fourteen dental institutes were contacted of which nine (64%) responded. Thirty-seven per cent of sedation leads who responded stated they were unaware of a definition for over-sedation. Seventy-seven percent stated that when flumazenil was used this was recorded in a drugs book, with a broad range of justifications given. CONCLUSION: This study shows that there is a lack of uniformity both from clinicians and the literature, in what encompasses over-sedation. This makes formulating an accepted definition of over-sedation difficult. In order to ensure accurate reporting, monitoring and auditing of such events, a clear definition for over-sedation is required and can be used to provide clarity when flumazenil is to be administered.

Rapid-sequence intubation: a review of the process and considerations when choosing medications.

OBJECTIVE: To summarize published data regarding the steps of rapid-sequence intubation (RSI); review premedications, induction agents, neuromuscular blockers (NMB), and studies supporting use or avoidance; and discuss the benefits and deficits of combinations of induction agents and NMBs used when drug shortages occur. DATA SOURCE: A search of Medline databases (1966-October 2013) was conducted. STUDY SELECTION AND DATA EXTRACTION: Databases were searched using the terms rapid-sequence intubation, fentanyl, midazolam, atropine, lidocaine, phenylephrine, ketamine, propofol, etomidate thiopental, succinylcholine, vecuronium, atracurium, and rocuronium. Citations from publications were reviewed for additional references. DATA SYNTHESIS: Data were reviewed to support the use or avoidance of premedications, induction agents, and paralytics and combinations to consider when drug shortages occur. CONCLUSIONS: RSI is used to secure a definitive airway in often uncooperative, nonfasted, unstable, and/or critically ill patients. Choosing the appropriate premedication, induction drug, and paralytic will maximize the success of tracheal intubation and minimize complications.

A content analysis of legal policy responses to xylazine in the illicit drug supply in the United States.

BACKGROUND: Xylazine is a veterinary sedative that is quickly spreading in the U.S. illicit drug supply and is increasingly associated with fatal overdoses and severe wounds. In response, xylazine has been deemed an emerging public health threat and several policy initiatives have been introduced to combat its spread and negative broad health impact. We aimed to synthesize trends in all-time U.S. policy responses to xylazine in the drug supply. METHODS: In April 2024, we systematically identified and categorized proposed and enacted policy initiatives that related to human xylazine consumption by searching LexisNexis and Thomas Reuters Westlaw legal databases. RESULTS: Of 58 unique policy initiatives, most were introduced in 2023 (n = 37/58, 64 %) and concentrated in Northeastern states. Penalties for xylazine possession, often tied to state drug scheduling changes, were the most common provision (n = 34/58; 59 %) and Schedule III was the most frequently proposed scheduling level (n = 17/30; 57 %). Other provisions included proposals to enhance: test strip access (n = 11/58; 19 %), public awareness and education (n = 3/58; 5 %), xylazine-specific research (n = 4/58; 7 %), and surveillance (n = 8/58; 14 %). CONCLUSION: U.S. state and federal policy responses to xylazine grew rapidly in 2023, were most concentrated in states affected most by xylazine, and scheduling was the most commonly proposed policy approach. Research measuring policy effects should be prioritized as policies are implemented.

Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: Triangulating from toxicology, drug-testing and law enforcement.

BACKGROUND AND AIMS: Xylazine is a non-opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. METHODS: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co-detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug-testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug-testing postal service with the date, location, purchase intent and co-detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. RESULTS: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug-testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. CONCLUSIONS: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies.

Recent increase in detection of alprazolam in Victorian heroin-related deaths.

OBJECTIVES: To examine the rate of detection of alprazolam among cases of heroin-related death (HRD) in Victoria, including the relationship between alprazolam supply and HRDs. DESIGN AND SETTING: Population-based study of community alprazolam supply in Victoria and HRDs reported to the Victorian coroner from January 1990 to December 2010. MAIN OUTCOME MEASURES: Number of prescriptions for alprazolam supplied; defined daily dose (DDD) per 1000 population per 04 of alprazolam; number of cases of HRD in which alprazolam was detected through postmortem toxicological testing. RESULTS: Alprazolam supply increased by 1426%, from 0.42 DDD/1000/04 in 1990, to 6.41 in 2010. For every 1 unit increase in DDD/1000/04, the proportion of cases of HRD in which alprazolam was detected increased at an incidence rate ratio of 2.4 (95% CI, 2.1-2.8; P < 0.001). Alprazolam was detected among increasing proportions of HRDs, from 5.3% in 2005 to a peak of 35.3% in 2009. CONCLUSION: The increase in detection of alprazolam among cases of HRD, particularly since 2005, and the disproportionate increase in prescribing of the high-dose 2 mg formulation compared with other formulations suggest a need to examine alprazolam prescribing and to identify inappropriate prescribing and the circumstances of diversion from licit to illicit use.

Impact of a national propofol shortage on duration of mechanical ventilation at an academic medical center.

OBJECTIVE: To measure the impact of a national propofol shortage on the duration of mechanical ventilation. DESIGN: Before-after study. SETTING: Three, noncardiac surgery, adult intensive care units at a 320-bed academic medical center. PATIENTS: Consecutive patients requiring mechanical ventilation ≥48 hrs, administered a continuously infused sedative ≥24 hrs, extubated, and successfully discharged from the intensive care unit were compared between before (December 1, 2008 to May 31, 2009) and after (December 1, 2009, to May 31, 2010) a propofol shortage. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sedation drug use and common factors affecting time on mechanical ventilation were collected and if found either to differ significantly (p ≤ .10) between the two groups or to have an unadjusted significant association (p ≤ .10) with time on mechanical ventilation were included in a multivariable model. The unadjusted analyses revealed that the median (interquartile range) duration of mechanical ventilation increased from 6.7 (9.8; n = 153) to 9.6 (9.5; n = 128) days (p = .02). Fewer after-group patients received ≥24 hrs of continuously infused propofol (94% vs. 15%, p < .0001); more received ≥24 hrs of continuously infused lorazepam (7% vs. 15%, p = .037) and midazolam (30% vs. 81%, p < .0001). Compared with the before group, the after group was younger, had a higher admission Acute Physiology and Chronic Health Evaluation II score, was more likely to be admitted by a surgical service, have acute alcohol withdrawal, and be managed with pressure-controlled ventilation as the primary mode of mechanical ventilation. Of these five factors, only the Acute Physiology and Chronic Health Evaluation II score, admission service, and use of a pressure-controlled ventilation affected duration of mechanical ventilation across both groups. Although a regression model revealed that Acute Physiology and Chronic Health Evaluation II score (p < .0001), admission by a medical service (p = .009), and use of pressure-controlled ventilation (p = .02) each affected duration of mechanical ventilation in both groups, inclusion in either the before- or after-propofol shortage groups (i.e., high vs. low use of propofol) did not affect duration of mechanical ventilation (p = .35). CONCLUSIONS: An 84% decrease in propofol use in the adult intensive care units at our academic institution as a result of a national shortage did not affect duration of mechanical ventilation.

Impact of addition of propofol to ED formulary.

STUDY OBJECTIVES: Access to propofol remains a challenge for many emergency physicians. This report examines changes in patient care after the introduction of propofol to an emergency department formulary. METHODS: The Procedural Sedation in the Community Emergency Department registry is a prospective multicentered database of community emergency physician-directed procedural sedation cases. Medication selection and patient outcome were compared at a single Procedural Sedation in the Community Emergency Department registry study site before and after credentialing of emergency physicians for the use of propofol. Analysis was done through analysis of variance and χ(2) test. RESULTS: Over a 36-month period, 573 patients were entered into the registry from the single study site, 255 before and 318 after propofol introduction. The percentage of propofol use increased from 26% of procedural sedation cases in the first 3 months of availability to 69% in the final 3 months analyzed. Before propofol use, 46% of cases were completed with a single agent compared with after propofol use, in which 66% were completed with a single agent (P < .001). Complications decreased from 9% of patients before propofol use to 3% of patients after propofol use (P < .05), whereas sedation failures decreased from 5.1% to 4.1% (P < .02). CONCLUSION: Granted access to propofol, emergency physicians will preferentially use this medication over prior procedural sedation agents with fewer procedural sedation complications and greater procedural success.

It Takes a Village : Contending With Drug Shortages During Disasters.

Critical drug shortages have been widely documented during the coronavirus disease 2019 (COVID-19) pandemic, particularly for IV sedatives used to facilitate mechanical ventilation. Surges in volume of patients requiring mechanical ventilation coupled with prolonged ventilator days and the high sedative dosing requirements observed quickly led to the depletion of "just-in-time" inventories typically maintained by institutions. This manuscript describes drug shortages in the context of global, manufacturing, regional and institutional perspectives in times of a worldwide crisis such as a pandemic. We describe etiologic factors that lead to drug shortages including issues related to supply (eg, manufacturing difficulties, supply chain breakdowns) and variables that influence demand (eg, volatile prescribing practices, anecdotal or low-level data, hoarding). In addition, we describe methods to mitigate drug shortages as well as conservation strategies for sedatives, analgesics and neuromuscular blockers that could readily be applied at the bedside. The COVID-19 pandemic has accentuated the need for a coordinated, multi-pronged approach to optimize medication availability as individual or unilateral efforts are unlikely to be successful.

Predictors of clinicians' underuse of daily sedation interruption and sedation scales.

PURPOSE: The purpose of the study is to identify predictors of underuse of sedation scales and daily sedation interruption (DSI). METHODS: We surveyed all physicians and seven nurses in every Belgian intensive care unit (ICU), addressing practices and perceptions on guideline recommendations. Underuse was defined for sedation scales as use less than 3× per day and for DSI as never using it. Classification trees and logistic regressions identified predictors of underuse. RESULTS: Underuse of sedation scales and DSI was found for 16.6% and 32.5% of clinicians, respectively. Strongest predictors of underuse of sedation scales were agreeing that using them daily takes much time and being a physician (rather than a nurse). Further predictors were confidence in their ability to measure sedation levels without using scales, for physicians, and nurse/ICU bed ratios less than 1.98, for nurses. The strongest predictor of underuse of DSI among physicians was the perception that DSI impairs patients' comfort. Among nurses, lack of familiarity with DSI, region, and agreeing DSI should only be performed upon medical orders best predicted underuse. CONCLUSIONS: Workload considerations hamper utilization of sedation scales. Poor familiarity, for nurses, and negative perception of impact on patients' comfort, for physicians, both reduce DSI utilization. Targeting these obstacles is essential while designing quality improvement strategies to minimize sedative use.

Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project.

A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project.