Economic Evaluation of Interventions to Address Opioid Misuse: A Systematic Review of Methods Used in Simulation Modeling Studies.

OBJECTIVES: Several evidence-based interventions exist for people who misuse opioids, but there is limited guidance on optimal intervention selection. Economic evaluations using simulation modeling can guide the allocation of resources and help tackle the opioid crisis. This study reviews methods employed by economic evaluations using computer simulations to investigate the health and economic effects of interventions meant to address opioid misuse. METHODS: We conducted a systematic mapping review of studies that used simulation modeling to support the economic evaluation of interventions targeting prevention, treatment, or management of opioid misuse or its direct consequences (ie, overdose). We searched 6 databases and extracted information on study population, interventions, costs, outcomes, and economic analysis and modeling approaches. RESULTS: Eighteen studies met the inclusion criteria. All of the studies considered only one segment of the continuum of care. Of the studies, 13 evaluated medications for opioid use disorder, and 5 evaluated naloxone distribution programs to reduce overdose deaths. Most studies estimated incremental cost per quality-adjusted life-years and used health system and/or societal perspectives. Models were decision trees (n = 4), Markov (n = 10) or semi-Markov models (n = 3), and microsimulations (n = 1). All of the studies assessed parameter uncertainty though deterministic and/or probabilistic sensitivity analysis, 4 conducted formal calibration, only 2 assessed structural uncertainty, and only 1 conducted expected value of information analyses. Only 10 studies conducted validation. CONCLUSIONS: Future economic evaluations should consider synergies between interventions and examine combinations of interventions to inform optimal policy response. They should also more consistently conduct model validation and assess the value of further research.

A comparison of trends in opioid dispensing patterns between Medicaid pharmacy claims and prescription drug monitoring program data.

PURPOSE: Public and private payers have implemented benefit limitations to reduce high-risk opioid prescriptions. The effect of these policies on the increase of out-pocket payment is unclear. To understand this gap, we compared the discrepancies in trends between opioid prescription fills vs claims among Medicaid beneficiaries. METHODS: Data from the Oregon Prescription Drug Monitoring Program (PDMP) and Oregon Medicaid administrative claims were used to identify Medicaid beneficiaries 18 years and older enrolled at least one full month from 2015 to 2017. Generalized linear models assessed the trends in the monthly rates of opioid PDMP prescription fills and pharmacy claims per 1000 eligible members. Rates by morphine equivalent dose (MED) tier (<50, 50-89, 90-120, >120 MED) and co-prescribed opioid and benzodiazepine were also assessed. RESULTS: During the study period, an average of 495 355 Medicaid members had 2 797 054 opioid PDMP fills and 2 472 155 opioid Medicaid pharmacy claims. Study participants had 15.4 (95% confidence interval [CI] 13.6 to 17.0; P < .001) more prescriptions per 1000 member per month in the PDMP data (114.1 [SD 7.4]) compared with the Medicaid claims data (98.7 [SD 7.9]). Similarly, there were 1.9 more co-occurring opioid/benzodiazepine prescriptions per 1000 members per month observed in the PDMP data than the Medicaid claims data (95% CI 1.7 to 2.1; P < .001). At each MED tier, the PDMP fills were consistently higher than the claims (P < .001). CONCLUSIONS: Higher rate of fills in the PDMP compared to pharmacy claims suggests that there may be an increasing trend of out-of-pocket payment among Medicaid beneficiaries.

Impact of Abuse Deterrent Formulations of Opioids in Patients With Chronic Pain in the United States: A Cost-Effectiveness Model.

OBJECTIVE: Opioid abuse is a significant public health problem in the United States. We evaluate the clinical effectiveness and economic impact of abuse-deterrent formulations (ADF) of opioids relative to non-ADF opioids in preventing abuse. METHODS: We developed a cost-effectiveness model simulating 2 cohorts of 100 000 noncancer, chronic-pain patients newly prescribed either ADF or non-ADF extended-release (ER) opioids and followed them over 5 years, tracking new events of opioid abuse and opioid-related overdose deaths in addition to tracking 5-year cumulative costs of therapeutic use and abuse of ADF and non-ADF opioids. Patients in each cohort entered the model for therapeutic opioid use from where they could continue in that pathway, discontinue opioid use, or abuse opioids or die of opioid overdose-related or unrelated causes. In addition, one-way sensitivity and scenario analysis were conducted. RESULTS: Over a 5-year time period, using ADF opioids prevented an additional 2300 new cases of opioid abuse at an additional cost of approximately $535 million to the healthcare sector. Threshold analyses showed that a 40% decrease in ADF opioid costs was required to attain cost neutrality between the 2 cohorts, whereas a 100% effectiveness in abuse reduction still did not result in cost neutrality. A 43% decrease in diversion with ADFs relative to non-ADFs was required to attain cost neutrality. Including a societal perspective produced results directionally similar to the base-case analysis findings. CONCLUSION: ADF opioids have the potential to prevent new cases of opioid abuse, but at substantially higher costs to the health system.

First Opioid Prescription and Subsequent High-Risk Opioid Use: a National Study of Privately Insured and Medicare Advantage Adults.

BACKGROUND: National guidelines make recommendations regarding the initial opioid prescriptions, but most of the supporting evidence is from the initial episode of care, not the first prescription. OBJECTIVE: To examine associations between features of the first opioid prescription and high-risk opioid use in the 18 months following the first prescription. DESIGN: Retrospective cohort study using data from a large commercial insurance claims database for 2011-2014 to identify individuals with no recent use of opioids and follow them for 18 months after the first opioid prescription. PARTICIPANTS: Privately insured patients aged 18-64 and Medicare Advantage patients aged 65 or older who filled a first opioid prescription between 07/01/2011 and 06/30/2013. MAIN OUTCOMES AND MEASURES: High-risk opioid use was measured by having (1) opioid prescriptions overlapping for 7 days or more, (2) opioid and benzodiazepine prescriptions overlapping for 7 days or more, (3) three or more prescribers of opioids, and (4) a daily dosage exceeding 120 morphine milligram equivalents, in each of the six quarters following the first prescription. KEY RESULTS: All three features of the first prescription were strongly associated with high-risk use. For example, among privately insured patients, receiving a long- (vs. short-) acting first opioid was associated with a 16.9-percentage-point increase (95% CI, 14.3-19.5), a daily MME of 50 or more (vs. less than 30) was associated with a 12.5-percentage-point increase (95% CI, 12.1-12.9), and a supply exceeding 7 days (vs. 3 or fewer days) was associated with a 4.8-percentage-point increase (95% CI, 4.5-5.2), in the probability of having a daily dosage of 120 MMEs or more in the long term, compared to a sample mean of 4.2%. Results for the Medicare Advantage patients were similar. CONCLUSIONS: Long-acting formulation, high daily dosage, and longer duration of the first opioid prescription were each associated with increased high-risk use of opioids in the long term.

The impact of cancer drug wastage on economic evaluations.

BACKGROUND: The objective of this study was to determine the impact of modeling cancer drug wastage in economic evaluations because wastage can result from single-dose vials on account of body surface area- or weight-based dosing. METHODS: Intravenous chemotherapy drugs were identified from the pan-Canadian Oncology Drug Review (pCODR) program as of January 2015. Economic evaluations performed by drug manufacturers and pCODR were reviewed. Cost-effectiveness analyses and budget impact analyses were conducted for no-wastage and maximum-wastage scenarios (ie, the entire unused portion of the vial was discarded at each infusion). Sensitivity analyses were performed for a range of body surface areas and weights. RESULTS: Twelve drugs used for 17 indications were analyzed. Wastage was reported (ie, assumptions were explicit) in 71% of the models and was incorporated into 53% by manufacturers; this resulted in a mean incremental cost-effectiveness ratio increase of 6.1% (range, 1.3%-14.6%). pCODR reported and incorporated wastage for 59% of the models, and this resulted in a mean incremental cost-effectiveness ratio increase of 15.0% (range, 2.6%-48.2%). In the maximum-wastage scenario, there was a mean increase in the incremental cost-effectiveness ratio of 24.0% (range, 0.0%-97.2%), a mean increase in the 3-year total incremental budget costs of 26.0% (range, 0.0%-83.1%), and an increase in the 3-year total incremental drug budget cost of approximately CaD $102 million nationally. Changing the mean body surface area or body weight caused 45% of the drugs to have a change in the vial size and/or quantity, and this resulted in increased drug costs. CONCLUSIONS: Cancer drug wastage can increase drug costs but is not uniformly modeled in economic evaluations. Cancer 2017;123:3583-90. © 2017 American Cancer Society.

Using prescription monitoring program data to characterize out-of-pocket payments for opioid prescriptions in a state Medicaid program.

BACKGROUND: Out-of-pocket payment for prescription opioids is believed to be an indicator of abuse or diversion, but few studies describe its epidemiology. Prescription drug monitoring programs (PDMPs) collect controlled substance prescription fill data regardless of payment source and thus can be used to study this phenomenon. OBJECTIVE: To estimate the frequency and characteristics of prescription fills for opioids that are likely paid out-of-pocket by individuals in the Oregon Medicaid program. RESEARCH DESIGN: Cross-sectional analysis using Oregon Medicaid administrative claims and PDMP data (2012 to 2013). SUBJECTS: Continuously enrolled nondually eligible Medicaid beneficiaries who could be linked to the PDMP with two opioid fills covered by Oregon Medicaid. MEASURES: Patient characteristics and fill characteristics for opioid fills that lacked a Medicaid pharmacy claim. Fill characteristics included opioid name, type, and association with indicators of high-risk opioid use. RESULTS: A total of 33 592 Medicaid beneficiaries filled a total of 555 103 opioid prescriptions. Of these opioid fills, 74 953 (13.5%) could not be matched to a Medicaid claim. Hydromorphone (30%), fentanyl (18%), and methadone (15%) were the most likely to lack a matching claim. The 3 largest predictors for missing claims were opioid fills that overlapped with other opioids (adjusted odds ratio [aOR] 1.37; 95% confidence interval [CI], 1.34-1.4), long-acting opioids (aOR 1.52; 95% CI, 1.47-1.57), and fills at multiple pharmacies (aOR 1.45; 95% CI, 1.39-1.52). CONCLUSIONS: Prescription opioid fills that were likely paid out-of-pocket were common and associated with several known indicators of high-risk opioid use.

The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013.

IMPORTANCE: It is important to understand the magnitude and distribution of the economic burden of prescription opioid overdose, abuse, and dependence to inform clinical practice, research, and other decision makers. Decision makers choosing approaches to address this epidemic need cost information to evaluate the cost effectiveness of their choices. OBJECTIVE: To estimate the economic burden of prescription opioid overdose, abuse, and dependence from a societal perspective. DESIGN, SETTING, AND PARTICIPANTS: Incidence of fatal prescription opioid overdose from the National Vital Statistics System, prevalence of abuse and dependence from the National Survey of Drug Use and Health. Fatal data are for the US population, nonfatal data are a nationally representative sample of the US civilian noninstitutionalized population ages 12 and older. Cost data are from various sources including health care claims data from the Truven Health MarketScan Research Databases, and cost of fatal cases from the WISQARS (Web-based Injury Statistics Query and Reporting System) cost module. Criminal justice costs were derived from the Justice Expenditure and Employment Extracts published by the Department of Justice. Estimates of lost productivity were based on a previously published study. EXPOSURE: Calendar year 2013. MAIN OUTCOMES AND MEASURES: Monetized burden of fatal overdose and abuse and dependence of prescription opioids. RESULTS: The total economic burden is estimated to be $78.5 billion. Over one third of this amount is due to increased health care and substance abuse treatment costs ($28.9 billion). Approximately one quarter of the cost is borne by the public sector in health care, substance abuse treatment, and criminal justice costs. CONCLUSIONS AND RELEVANCE: These estimates can assist decision makers in understanding the magnitude of adverse health outcomes associated with prescription opioid use such as overdose, abuse, and dependence.

The Impact of Misuse and Diversion of Opioid Substitution Treatment Medicines: Evidence Review and Expert Consensus.

BACKGROUND/AIMS: Opioid substitution treatment (OST) improves outcomes in opioid dependence. However, controlled drugs used in treatment may be misused or diverted, resulting in negative treatment outcomes. This review defines a framework to assess the impact of misuse and diversion. METHODS: A systematic review of published studies of misuse and diversion of OST medicines was completed; this evidence was paired with expert real-world experience to better understand the impact of misuse and diversion on the individual and on society. RESULTS: Direct impact to the individual includes failure to progress in recovery and negative effects on health (overdose, health risks associated with injecting behaviour). Diversion of OST has impacts on a community that is beyond the intended OST recipient. The direct impact includes risk to others (unsupervised use; unintended exposure of children to diverted medication) and drug-related criminal behavior. The indirect impact includes the economic costs of untreated opioid dependence, crime and loss of productivity. CONCLUSION: While treatment for opioid dependence is essential and must be supported, it is vital to reduce misuse and diversion while ensuring the best possible care. Understanding the impact of OST misuse and diversion is key to defining strategies to address these issues.

The Burden of Undiagnosed Opioid Abuse Among Commercially Insured Individuals.

OBJECTIVES: Estimate the prevalence and healthcare costs of undiagnosed opioid abuse among commercially insured individuals. STUDY DESIGN: Retrospective analysis of de-identified pharmacy and medical claims data and publicly-available survey data (no IRB approval required). METHODS: This study focused on commercially insured individuals. Rates of prescription pain-reliever abuse/dependence ("abuse") among individuals ages ≥12 were calculated using National Survey on Drug Use and Health (NSDUH) public-use data for 2006-2011 and assumed to capture both diagnosed and undiagnosed opioid abuse. Rates of undiagnosed opioid abuse were calculated as the difference between NSDUH rates and published rates of diagnosed opioid abuse. OptumHealth Reporting and Insights claims data were used to estimate the healthcare costs of undiagnosed abuse. Diagnosed abusers ages 12-64 were identified using ICD-9-CM diagnosis codes for opioid abuse/dependence. Pre-diagnosis costs were assumed to be a proxy for undiagnosed opioid abuse costs. The ratio of undiagnosed to diagnosed abuse costs was calculated as the ratio of annual per-patient healthcare costs between pre-diagnosis and post-diagnosis periods. RESULTS: While rates of diagnosed opioid abuse among commercially insured individuals increased from 0.07% in 2006 to 0.19% in 2011, rates of undiagnosed abuse decreased from 0.42% to 0.38% over the same time period. Annual per-patient healthcare costs of undiagnosed abusers were 69.2% of those of diagnosed abusers. CONCLUSIONS: Per-patient healthcare costs of undiagnosed abusers among the commercially insured are estimated to be lower than those of diagnosed abusers. However, the higher prevalence of undiagnosed opioid abuse implies that undiagnosed abuse represents a substantial burden to commercial payers.

Appropriateness of clopidogrel use according to current recommendations.

BACKGROUND: Clopidogrel is widely used in cardiovascular prevention. However, the prescription of clopidogrel in clinical practice does not match the recommendations concerning its indication and treatment duration. OBJECTIVE: To assess the appropriateness of clopidogrel prescription according to the accepted indications. METHODS: We undertook a retrospective observational analytical audit of the electronic clinical records in the region of Valencia, Spain (5 million inhabitants), selecting those patients on treatment with clopidogrel between 2007 and 2010. The primary outcome measure was the duration of the treatment. RESULTS: A total of 45721 patients started clopidogrel treatment during the study period. Treatment was for cardiologic disorders (CD) in 56.85% of the patients, neurologic disorders (ND) in 37.06% and peripheral arterial disease in 6.08%. Treatment duration was longer than that expected from clinical recommendations in 38.8% of the CD patients and 87.8% of the ND patients. The estimated avoidable cost ranged from 2 to 4.4 million Euros per year, according to whether a cheaper generic clopidogrel or a more expensive version was considered. CONCLUSIONS: Almost 40% of the cardiologic patients and 90% of the neurologic patients received excess treatment. Adjustment of treatment duration to international recommendations would result in savings of between 80.1 and 176.3 Euros per year and per patient treated.

Global trends in testosterone prescribing, 2000-2011: expanding the spectrum of prescription drug misuse.

OBJECTIVE: To provide the first multinational survey of temporal trends in testosterone prescribing, given that anecdotal evidence indicates that it is increasing in some countries, including Australia. DESIGN: Sales data for all testosterone products were obtained for 41 countries for each year from 2000 to 2011. For each testosterone product type (injectable, implantable, oral, transdermal), units sold were converted into defined monthly doses per year, reflecting total testosterone prescribing per product. MAIN OUTCOME MEASURES: National testosterone prescribing rate overall and per product type on a per capita basis. RESULTS: For every region and 37 of 41 countries, there was a major and progressive increase in defined monthly doses per year per capita over the 11 years surveyed. In most countries, the increases were steeper for the last half of the survey period. The proportion of testosterone prescribing represented by transdermal testosterone products, a surrogate measure of prescribing for older men, increased even more than did the total usage of testosterone products. CONCLUSIONS: In the absence of any new indications, off-label testosterone prescribing has increased in most countries in 2000-2011, especially over the last half of the period. The increased testosterone prescribing appears to be primarily for older men and driven by clinical guidelines that endorse testosterone prescribing for age-related functional androgen deficiency (andropause). By eliminating the fundamental distinction between pathological and functional androgen deficiency, these guidelines tacitly promote increased testosterone prescribing, bypassing the requirement for high-quality clinical evidence of safety and efficacy and creating dramatic increases in prescription of testosterone products.

Application of ATC/DDD methodology to evaluate of antibiotic use in a general hospital in Turkey.

BACKGROUND: The aim of this study is to evaluate in-house antibiotic use in a state hospital in Turkey with its cost, using the ATC/DDD index, which is an accepted standard method. METHODS: This study was performed as a point prevalence study in a state hospital with 372 beds. All in-house patients using antibiotics on July 19, 2011 were included in the study. Indications for antibiotic use and information about the patients were recorded on special forms. Antibiotic use and cost analysis were evaluated using the ATC/DDD index, which is also suggested by the WHO to be used in similar studies. FINDINGS: 147 patients out of 308 patients who were in-house were identified to use antibiotics with appropriate indications for prophylaxis or treatment in 61% of the patients. The rate of appropriate antibiotic use was identified to be in 78%, while this rate was 38.9% in surgical clinics. The daily cost of the antibiotics consumed on the date of the study was calculated as 4104.79 TL (=2476.80 USD). DISCUSSION: The rate of inappropriate use of antibiotics seems to be high in our hospital. This will result in both increased costs and also increased nosocomial infection rates with resistant species. Infectious disease specialists should take more active roles in the in-house antibiotic use, hospitals should prepare and implement their own principles of antibiotic use, and microbiology laboratories should be used more effectively. These measures would decrease the conspicuous shortcomings in the antibiotic use.

Urban scaling of opioid analgesic sales in the United States.

Opioid misuse is a public health crisis in the United States. The origin of this crisis is associated with a sharp increase in opioid analgesic prescribing. We used the urban scaling framework to analyze opioid prescribing patterns in US commuting zones (CZs), i.e., groups of counties based on commuting patterns. The urban scaling framework postulates that a set of scaling relations can be used to predict health outcomes and behaviors in cities. We used data from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System (ARCOS) to calculate counts of oxycodone/hydrocodone pills distributed to 607 CZs in the continental US from 2006 to 2014. We estimated the scaling coefficient of opioid pill counts by regressing log(pills) on log(population) using a piecewise linear spline with a single knot at 82,363. Our results show that CZs with populations below the knot scaled superlinearly (ß = 1.36), i.e., larger CZs had disproportionally larger pill counts compared to smaller CZs. On the other hand, CZs with populations above the knot scaled sublinearly (ß = 0.92), i.e., larger CZs had disproportionally smaller pill counts compared to smaller CZs. This dual scaling pattern was consistent across US census regions. For CZs with population below the knot, the superlinear scaling of pills is consistent with the explanation that an increased number of successful matches between prescribers and users will lead to higher prescribing rates. The non-linear scaling behavior observed could be the result of a combination of factors, including stronger health care systems and prescribing regulation in largely populated commuting zones, as well as high availability of other opioids such as heroin in these commuting zones. Future research should explore potential mechanisms for the non-linearity of prescription opioid pills.

Considering the child welfare system burden from opioid misuse: research priorities for estimating public costs.

The negative impact of opioids on those who misuse them has been widely documented. Despite significant spillover effects in the form of elevated rates of child maltreatment and child welfare system (CWS) involvement for children affected by parental opioid misuse, the public costs of opioid misuse to the CWS remain largely undocumented. This work seeks to understand the value and limitations of public data in estimating the costs of the opioid epidemic on the CWS. National data from federal sources are combined with best estimates of the association between opioid misuse and child services system utilization. The limitations of this work are explored, and future research priorities are outlined. Ultimately, this work illustrates the need to (1) improve data quality related to parental opioid misuse and CWS linkages; (2) better estimate the number of children and families coming into contact with the CWS as a result of parental opioid misuse; (3) improve predictions of CWS trajectories, including investigation, service provision, and foster care entry among this population; and (4) better estimate the CWS costs associated with patterns of system involvement resulting from parental opioid misuse. This information is crucial to ensuring the production of high-quality system involvement and cost projections related to the opioid crisis.

Characteristics of New Opioid Use Among Medicare Beneficiaries: Identifying High-Risk Patterns.

BACKGROUND: Opioid prescription patterns, including long-term use, multiple prescribers, and high opioid doses, increase the risk for adverse outcomes; however, previous research in older adult populations has primarily described opioid dose patterns using average daily dose measures or using very high thresholds (i.e., > 100 morphine milligram equivalents [MME] per day). OBJECTIVE: To describe prescription patterns by peak dose among older adults who have newly initiated opioid use in 2014 and describe long-term opioid use and the use of multiple pharmacies and prescribers among those with peak opioid doses over 50 and over 90 MME per day. METHODS: This was a retrospective cohort study of Medicare Part D prescription claims data (5% sample) for beneficiaries aged 65 years and older who were prescribed ≥ 1 opioid prescription in 2014 and did not have an opioid prescription in the preceding 180 days. Within a 1-year period of follow-up, we used prescription claims to characterize individuals' opioid exposure, measuring long-term opioid use (≥ 90 days of continuous opioid supply), unique opioid prescribers, and unique opioid-dispensing pharmacies. Peak MME was defined as the maximum daily MME received across all overlapping opioid prescriptions in the observation period. RESULTS: 144,127 beneficiaries without an opioid prescription in the previous 6 months filled ≥ 1 opioid prescription in 2014. During the 1-year follow-up period, 6.5% of beneficiaries transitioned to long-term opioid use; 39.5% received opioid prescriptions from > 1 prescriber; 18.1% filled opioid prescriptions from > 1 pharmacy; and 21.8% had a peak MME of 50-89. Among the 28.1% of beneficiaries exposed to a peak MME > 50, 8.6% developed long-term opioid use; 7.0% had 3 or more opioid dispensing pharmacies; and 28.0% had 3 or more opioid prescribers. Among the 6.2% of beneficiaries exposed to a peak MME ≥ 90, 18.5% developed long-term opioid use; 13.0% had 3 or more opioid dispensing pharmacies; and 39.6% had 3 or more opioid prescribers. CONCLUSIONS: High doses of opioids were prescribed for about one quarter (28%) of Medicare beneficiaries with new opioid use in 2014. Having multiple opioid prescribers or multiple opioid dispensing pharmacies was common, especially among those prescribed higher doses. These prescription patterns can be particularly helpful to identify older adults with increased opioid-related risk. DISCLOSURES: No funding supported this study. Raman reports research grants from GlaxoSmithKline not related to this study. Roberts was supported by a CTSA grant from NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research (#KL2TR000119). The other authors have no potential conflicts to report.

Nonmedical prescription psychiatric drug use and the darknet: A cryptomarket analysis.

BACKGROUND: Nonmedical prescription psychiatric drug use (NMPDU) is an increasing global health problem, with recent concern focusing on darknet cryptomarkets as sources of procurement. There is a shortage of evidence regarding comparative worldwide NMPDU trends, due in part to data collection difficulties. This problem is particularly marked for non-opioid drugs, particularly those psychiatric drugs which act on the central nervous system (CNS) and have high misuse potential and are associated with high levels of dependency and fatal overdose. This paper therefore has two goals: 1) to report on the kinds of psychiatric prescription drugs available on cryptomarkets, and 2) to use this data to uncover temporal and geographical trends in sales of these products, potentially informing policy regarding NMPDU more generally. METHOD: Digital trace data collected from 31 cryptomarkets in operation between September 2013 and July 2016 was analysed by country of origin descriptively and for trends in the sales for 7 psychiatric drug groupings, based on their main indication or intended use in psychiatric practice. RESULTS: Sedatives (such as diazepam and alprazolam) and CNS stimulants (mainly Adderall, modafinil and methylphenidate) had the greatest share of sales, but usage and trends varied by location. The UK has high and rising levels of sedative sales, whilst the USA has the greatest stimulant sales and increasing sedative rates. Sales of drugs used in the treatment of opioid dependency are also substantial in the USA. The picture is less clear in mainland Europe with high sales levels reported in unexpected Central and Northern European countries. There is evidence of a move towards the more potent sedative alprazolam - already implicated as a source of problematic NMPDU in the USA - in Australia and the UK. Sales of drugs such as antidepressants, antipsychotics, mood stabilisers and antidementia drugs - all drugs with limited abuse potential - were negligible, indicating minimal levels of online cryptomarket procurement for self-medicating mental health problems. CONCLUSION: Predominantly, psychiatric drugs with potent sedative, stimulant or euphoriant effects are sold on cryptomarkets and this varies by country. With some caveats regarding the limitations of cryptomarket digital trace data taken into account, the study of trends of these products sold online over time may offer a novel and increasingly important window onto wider drug purchasing habits.

Antimicrobial use-related problems and their costs in surgery ward of Jimma University Medical Center: Prospective observational study.

INTRODUCTION: Antibiotics are among the most commonly misused of all drugs, which results in antibiotic resistance and waste of resources and it has not been studied in Ethiopia. Therefore, this study was carried out to assess antibiotic use-related problems and their costs among patients hospitalized at the surgical ward of Jimma University Medical Center. METHODS: Hospital-based prospective observational study was used to assess the prevalence, cost, and determinants of antibiotic use-related problems; multiple stepwise backward logistic regression analysis was done for a P value of < 0.25 to look for predictors of antibiotic use-related problems. Written informed consent was obtained and confidentiality was secured. RESULTS: Among 300 participants, antibiotic use-related problems (ABURPs) were found in 69.3% of the study participants. The direct total cost attributed to these problems was approximated to a minimum of 2230.15 US$. Independent predictors for antibiotic use-related problems were: indication for antibiotic use like: use of antibiotic for prophylaxis; p < 0.0001, antibiotic use for both therapeutic & prophylaxis; p < 0.0001, CDC wound class I and II; p = 0.016 and; p = 0.002 respectively, overall poly-pharmacy and greater than 2 antibiotic exposure during hospital stay; p = 0.019and p = 0.006 respectively and hospital stay for ≥21 days; p = 0.007. CONCLUSION: The prevalence of antibiotic use-related problems was high and resulted in extra cost. Antibiotic use for prophylaxis, prophylaxis, and treatment, poly-pharmacy, greater than 2 antibiotic exposures during the hospital stay, CDC wound class I and II, and duration of hospital stay of ≥ 21 days was found to be independent predictors of antibiotic use-related problems.