Real or fake? Sourcing and marketing of non-prescribed benzodiazepines amongst two samples of people who regularly use illicit drugs in Australia.

INTRODUCTION: There is concern around non-prescribed benzodiazepine use, particularly with increasing detections of counterfeit products containing high-risk novel compounds. The aims of this study were to investigate how and which non-prescribed benzodiazepines are being sourced; forms, appearance and packaging; and awareness of risks associated with non-prescribed benzodiazepines. METHODS: Data were collected from a sample of Australians who inject drugs or use ecstasy and/or other illicit stimulants on a monthly or more frequent basis, and who reported past 6-month use of non-prescribed benzodiazepines (n = 235 and n = 250, respectively). Data were collected on source, diversion from a known/trusted prescription, product name and aesthetic characteristics for the last non-prescribed benzodiazepine obtained. RESULTS: Amongst participants who injected drugs, 71% reported that their last non-prescribed benzodiazepines were diverted from a known/trusted prescription, compared to 59% of participants who used ecstasy/other stimulants. Sourcing via cryptomarkets was rare. Across both samples, the majority reported last obtaining substances sold/marketed as diazepam or alprazolam. Participants sourcing via non-diverted means were twice as likely to obtain alprazolam. Known sourcing of novel compounds was rare. Amongst participants who used ecstasy/other stimulants, 36% reported confidence in the content/dose of non-prescribed benzodiazepines even when the source is unknown. DISCUSSION AND CONCLUSIONS: Most participants obtained substances sold as classic/registered benzodiazepines, mostly via diverted prescriptions, with a substantial minority potentially unaware of counterfeits circulating. While diverted use undeniably presents risks, tightening of prescriptions in Australia could inadvertently lead to greater supply of novel benzodiazepines as seen internationally, reinforcing prioritisation of demand and harm reduction strategies.

Surgical Patient Compliance With Healthcare Facility-Provided In-home Opioid Disposal Products: A Systematic Review.

OBJECTIVE: The aim of this study was to review the literature regarding the use of an in-home opioid disposal product on unused opioids after surgery. BACKGROUND: The opioid epidemic in the United States is a major cause of concern for healthcare facilities. The misuse and diversion of retained opioids after a surgical procedure continues to contribute to this problem. METHODS: A comprehensive search of the Cumulative Index of Nursing and Allied Health Literature, OVID, and PubMed databases with keywords including opioid, analgesics, narcotics, medical waste disposal, medical disposal, refuse disposal, and opioid disposal resulted in 286 articles. Articles were screened based on strict inclusion and exclusion criteria. RESULTS: Eight studies determined that an in-home opioid disposal product provided by a healthcare facility produced rates of opioid disposal between 19% and 71%. CONCLUSIONS: The provision of an in-home opioid disposal product by a healthcare facility is likely to increase the disposal of unused opioid medications in the postoperative surgical patient population.

Drug Enforcement Agency 2014 Hydrocodone Rescheduling Rule and Opioid Dispensing after Surgery.

BACKGROUND: In 2014, the U.S. Drug Enforcement Agency reclassified hydrocodone from Schedule III to Schedule II of the Controlled Substances Act, resulting in new restrictions on refills. The authors hypothesized that hydrocodone rescheduling led to decreases in total opioid dispensing within 30 days of surgery and reduced new long-term opioid dispensing among surgical patients. METHODS: The authors studied privately insured, opioid-naïve adults undergoing 10 general or orthopedic surgeries between 2011 and 2015. The authors conducted a differences-in-differences analysis that compared overall opioid dispensing before versus after the rescheduling rule for patients treated by surgeons who frequently prescribed hydrocodone before rescheduling (i.e., patients who were functionally exposed to rescheduling's impact) while adjusting for secular trends via a comparison group of patients treated by surgeons who rarely prescribed hydrocodone (i.e., unexposed patients). The primary outcome was any filled opioid prescription between 90 and 180 days after surgery; secondary outcomes included the 30-day refill rate and the amount of opioids dispensed initially and at 30 days postoperatively. RESULTS: The sample included 65,136 patients. The percentage of patients filling a prescription beyond 90 days was similar after versus before rescheduling (absolute risk difference, -1.1%; 95% CI, -2.3% to 0.1%; P = 0.084). The authors estimated the rescheduling rule to be associated with a 45.4-mg oral morphine equivalent increase (difference-in-differences estimate; 95% CI, 34.2-56.7 mg; P < 0.001) in initial opioid dispensing, a 4.1% absolute decrease (95% CI, -5.5% to -2.7%; P < 0.001) in refills within 30 days, and a 37.7-mg oral morphine equivalent increase (95% CI, 20.6-54.8 mg; P = 0.008) in opioids dispensed within 30 days. CONCLUSIONS: Among patients treated by surgeons who frequently prescribed hydrocodone before the Drug Enforcement Agency 2014 hydrocodone rescheduling rule, rescheduling did not impact long-term opioid receipt, although it was associated with an increase in opioid dispensing within 30 days of surgery.

An Automated Software Application Reduces Controlled Substance Discrepancies in Perioperative Areas.

BACKGROUND: Perioperative controlled substance diversion and tracking have received increased regulatory focus throughout the United States. The authors' institution developed and implemented an automated web-based software application for perioperative controlled substance management. The authors hypothesized that implementation of such a system reduces errors as measured by missing controlled substance medications, missing controlled substance kits (a package of multiple controlled substance medications), and missing witness signatures during kit return. METHODS: From December 1, 2014 to March 31, 2017, the authors obtained missing controlled substance medication, controlled substance kit, and witness return signature data during the preimplementation, implementation, and study period of the controlled substance management application at a single university hospital. This before and after study was based on a QI project at the authors' institution. The authors included all cases requiring anesthesia services. The primary outcome of this study was the rate of missing controlled substance medications. Secondary outcomes included rates for kits not returned to pharmacy and missing kit return witness signatures. RESULTS: There were 54,302 cases during the preimplementation period, 57,670 cases during the implementation period, and 65,911 cases during the study period. The number of missing controlled substance medication (difference 0.7 per 1,000 cases; 95% CI, 0.38-1.02; P < 0.001) and kit return errors (difference 0.45 per 1,000 cases; 95% CI, 0.24-0.66, P < 0.001) declined after implementation of the application. There was no difference in the number of missing witness return signatures (difference 0.09 per 1,000 cases; 95% CI, -0.08 to 0.26, P = 0.350). A user survey with 206 of 485 (42%) response rate demonstrated that providers believed the new application managed controlled substances better than the previous system. CONCLUSIONS: A software application that tracks perioperative controlled substance kits with deep integration into the electronic health record and pharmacy systems is associated with a decrease in management errors.

Application of Prescription Drug Monitoring Program to detect underreported controlled substance use in patients evaluated for liver transplant.

Presurgical controlled substance use predicts postoperative complications, increased readmissions, and mortality. We aimed to examine if a Prescription Drug Monitoring Program (PDMP) would detect underreported controlled substance use in patients undergoing liver transplant evaluation. We performed a retrospective cohort study at a tertiary referral center of patients undergoing liver transplant evaluation in 2017. PDMP reviews were performed on all 360 patients and urine drug screen (UDS) results were reviewed when available to evaluate dispensed controlled substances. These results were compared to the patient's self-reported medication list at evaluation to identify any underreporting. The primary outcome was the number of self-reported controlled substance discrepancies on the medication list identified by PDMP and UDS at the time of evaluation. Among the 360 patients, 87 (24%) had a discrepancy where PDMP revealed a controlled substance prescription that the patient did not report on their medication list. Seventy-seven (67/87) of these discrepancies involved opiates. Of the 360 patients, 219 (61%) had a negative UDS, but 70 (32%) of these patients had at least one controlled substance listed on PDMP. PDMP is a promising screening tool when used in conjunction with the UDS for detecting underreported controlled substance use in liver transplant candidates.

Scheduling synthetic cathinone substances under the Controlled Substances Act.

BACKGROUND AND RATIONALE: Cathinones are amphetamine analogues that produce stimulant effects with rewarding properties. For many decades, synthetic cathinones have been used in the United States (USA) for abuse purposes, leading to concern about public safety by the federal government. Under the Controlled Substances Act (CSA), the federal government may place drugs with high abuse potential but no currently accepted medical use into Schedule I of the CSA. The process of scheduling an abusable drug involves both the Department of Health and Human Services (HHS), through the Food and Drug Administration (FDA) and the National Institute on Drug Abuse (NIDA), and the Department of Justice, through the Drug Enforcement Administration (DEA). RESULTS: This paper details how numerous synthetic cathinones were placed under CSA control between 1973 and 2018, with an emphasis on 10 cathinones that were placed into Schedule I in 2017 (butylone, naphyrone, pentylone, pentedrone, 3-fluoro-N-methylcathinone (FMC), 4-FMC, 4-methyl-N-ethylcathinone, 4-methyl-pyrrolidinopropiophenone, alpha-pyrrolidinobutiophenone, and α-pyrrolidinopentiophenone). A summary is provided of the scientific and medical analysis performed by HHS, in the form of an Eight-Factor Analysis (8FA), as prescribed by the CSA. This 8FA was then evaluated and signed by the Assistant Secretary for Health at HHS and transmitted to DEA, which permanently placed the 10 cathinones into Schedule I after public notices were published into the Federal Register. DISCUSSION AND CONCLUSIONS: Understanding the scientific data, analysis, and complex process utilized by the US federal government in the CSA scheduling of cathinones with abuse potential and no accepted medical use is important for transparency in governmental decision-making.

Evaluating short- and long-term impacts of a Medicaid "lock-in" program on opioid and benzodiazepine prescriptions dispensed to beneficiaries.

BACKGROUND: Insurance-based "lock-in" programs (LIPs) have become a popular strategy to address controlled substance (CS) (e.g., opioid) misuse. However, little is known about their impacts. We examined changes in CS dispensing to beneficiaries in the 12-month North Carolina Medicaid LIP. METHODS: We analyzed Medicaid claims linked to Prescription Drug Monitoring Program (PDMP) records for beneficiaries enrolled in the LIP between October 2010 and September 2012 (n=2702). Outcomes of interest were 1) number of dispensed CS prescriptions and 2) morphine milligram equivalents (MMEs) of dispensed opioids while a) locked-in and b) in the year following release. RESULTS: Compared to a period of stable CS dispensed prior to LIP enrollment, numbers of dispensed CS during lock-in and post-release were lower (count difference per person-month: -0.05 (95% CI: -0.11, 0.01); -0.23 (95% CI: -0.31, -0.15), respectively). However, beneficiaries' average daily MMEs of opioids were elevated during both lock-in and post-release (daily mean difference per person: 18.7 (95% CI: 13.9, 23.6); 11.1 (95% CI: 5.1, 17.1), respectively). Stratification by payer source revealed increases in using non-Medicaid (e.g., out-of-pocket) payment during lock-in that persisted following release. CONCLUSION: While the LIP reduced the number of CS dispensed, the program was also associated with increased acquisition of CS prescriptions using non-Medicaid payment. Moreover, beneficiaries acquired greater dosages of dispensed opioids from both Medicaid and non-Medicaid payment sources during lock-in and post-release. Refining LIPs to increase beneficiary access to substance use disorder screening and treatment services and provider use of PDMPs may address important unintended consequences.

Quality requirements for allergen extracts and allergoids for allergen immunotherapy

All allergen products for allergen immunotherapy currently marketed in the European Union are pharmaceutical preparations derived from allergen-containing source materials like pollens, mites and moulds. Especially this natural origin results in particular demands for the regulatory requirements governing allergen products. Furthermore, the development of regulatory requirements is complicated by the so far missing universal link between certain quality parameters, in particular biological potency, on the one hand and clinical efficacy on the other hand. As a consequence, each allergen product for specific immunotherapy has to be assessed individually for its quality, safety and efficacy. At the same time, biological potency of allergen products is most commonly determined using IgE inhibition assays based on human sera relative to product-specific in house references, ruling out full comparability of products from different manufacturers. This review article aims to summarize the current quality requirements for allergen products including the special requirements implemented for control of chemically modified allergen extracts (allergoids) (AU)

No disponible

Ensuring safe prescribing of controlled substances for pain following surgery by developing a transitional pain service.

Chronic postsurgical pain is a significant complication following major surgery, which impairs patient's quality of life. Opioid medications are the mainstay of most postoperative analgesic regimens. Growing evidence suggests inherent risks associated with opioids used for postoperative pain. Beyond common opioid-related side effects, increased mortality in the community and developing persistent opioid problems have been reported. There is a paucity of literature regarding the safe and effective management of postoperative pain as patients transition from the hospital to home/community. The introduction of a transitional pain service, whose aim is to optimize pain control, monitor and appropriately wean patients off opioid medications, prevent unnecessary readmissions post-discharge, and reduce disability associated with the development of chronic post surgical pain, will be of benefit to patients and the healthcare system.

The effects of North Carolina's prescription drug monitoring program on the prescribing behaviors of the state's providers.

State-level prescription drug monitoring programs (PDMPs) show promise as a key strategy to respond to the epidemic of the misuse and abuse of controlled substances (CS), particularly opioid analgesics, in the United States. Undocumented concerns have been expressed that these PDMPs may have a "chilling effect" on providers' willingness to prescribe these substances to their patients. Using data from North Carolina's PDMP for the 3-year period from 2009 through 2011, we examined whether rapid increases in (1) the number of providers who queried the system, and (2) the number of days on which they queried it, would be related to their prescribing practices in regards to CS. We hypothesized that neither marker of PDMP utilization would be associated with a decrease in either patients receiving CS prescriptions or CS prescriptions filled. We found no association between either of these variables and the number of patients who filled prescriptions for CS or the number of prescriptions for CS filled. However, we did find a slight positive relationship between the growth in the utilization of the PDMP and the number of prescriptions filled for opioid analgesics. Concerns that PDMPs may constrain prescribing behavior with regards to CS are not supported.