Abuse-related Events Research Articles

The Financial Burden of Opioid-Related Abuse among Surgical and Non-Surgical Patients in Florida: A Longitudinal Study.

Florida is one of the eight states labeled as a high-burden opioid abuse state and is an epicenter for opioid use and misuse. The aim of our study was to measure multi-year total room charges and costs billed for opioid abuse-related events and to compare the costs of inpatient opioid abusers and non-opioid abusers for Florida hospitals from 2011 to 2017. We constructed a retrospective case-control longitudinal study design on inpatient administrative discharge data across 173 hospitals. Opioid abuse was defined using both ICD-9-CM and ICD-10-CM systems. We found a statistically significant association between opioid abuse diagnosis and total room charge. On average, opioid abuse status increased the room charges by 8.1%. We also noticed year-to-year variations in opioid abuse had a remarkable influence on hospital finances. We showed that since 2015, the differences significantly increased from 4–5% to 13–14% for both room charges and cost, which indicates the financial burden due to opioid abuse becoming more frequent. These findings are important to policymakers and hospital administrators because they provide crucial insight into Florida’s opioid crisis and its economic burden on hospitals.

Combining big data search analytics and the FDA Adverse Event Reporting System database to detect a potential safety signal of mirtazapine abuse.

This study sought to detect a potential safety signal of mirtazapine abuse by combining two different sources of surveillance, specifically Google Analytics (Google, Inc., Mountain View, CA, USA) and the FDA Adverse Event Reporting System database. Data from the first quarter of 2004 to the second quarter of 2017 were collected and analysed. The search interest over time, the frequencies of abuse-related terms in the search analytics domain, and the odds ratio of abuse events in FDA Adverse Event Reporting System were determined. Correlations between the two aforementioned domains using quarterly data from the timeline series were also assessed. Our results suggest a positive correlation between abuse-related searches in the Google domain and abuse-related events in FDA Adverse Event Reporting System database. These results indicate that these methods can be used in combination with each other as a pharmacovigilance supplementary tool to detect drug safety signals.

Children’s Coping Following Sexual Abuse: The Roles of Abuse Characteristics, Abuse Stress, and Maternal Support

Although the use of coping strategies is recognized as playing a vital role in predicting the development of trauma-related symptoms, little research has identified what factors may contribute to the utilization, and perceived efficacy of, coping strategies following childhood sexual abuse (CSA). Research has not determined whether aspects of the CSA (e.g., duration, severity) and CSA-related factors such as abuse stressors (e.g., coercion, threats), abuse-related events (e.g., familial disruptions, legal system involvement), and maternal emotional support and blame/doubt correspond with children’s coping use and perceived effectiveness. The current study investigated whether CSA characteristics, abuse stress, and maternal support were related to children’s utilization and perceived efficacy of active/social, internalized, angry, and avoidant coping strategies among 141 sexually abused children aged 7–12 (M= 9.72, SD= 1.50). Children used nearly 7 types of coping strategies (M= 6.71, SD = 1.63). Longer CSA duration was associated with utilization of internalized and avoidant coping, and maternal blame/doubt predicted the use of avoidant coping. Girls utilized angry coping more frequently than boys. CSA characteristics and abuse stress were largely unrelated to children’s perceived coping efficacy. Minority children reported higher levels of perceived efficacy of internalized strategies than white children. CSA duration may be important in understanding children’s utilization of internalized and avoidant coping strategies and maternal blame/doubt may be related to children’s use of avoidant coping. However, CSA characteristics and abuse stress may ultimately have little bearing on sexually abused children’s use and perceived efficacy of coping strategies.

Modeling the potential impact of abuse-deterrent opioids on medical resource utilization

Objectives: To extend a previously published manuscript on a model for estimating potential avoided medical events and cost savings in the US associated with the introduction of extended-release abuse-deterrent opioids and incorporate new methods of evaluating abuse deterrence using human abuse potential studies.Methods: A model was developed to estimate reductions in abuse-related events and annual savings in the US. Model inputs included: opioid abuse prevalence, abuse-deterrent opioid cost and effectiveness at deterring abuse, and opioid abuse-related events and costs. Direct (medical and drug) and indirect (work loss) cost savings (2017 US$) and abuse-related events were estimated assuming the replacement of the entire extended-release opioid market (brand and generic) by brand abuse-deterrent opioids.Results: Replacing the extended-release opioid market with abuse-deterrent opioids is estimated to lower annual abuse-related medical events by ∼13–31% (e.g. 78,000–186,000 emergency department visits) and lower annual medical costs by ∼$640 M–$1,538 M, depending on the abuse-deterrent technology (physical/chemical barrier or agonist/antagonist). Replacement of extended-release oxycodone with extended-release abuse-deterrent oxycodone is associated with the largest amount of cost savings and highest number of avoided medical events, followed by replacing extended-release morphine with an extended-release abuse-deterrent opioid. Replacement of transdermal fentanyl is associated with the smallest amount of cost savings and lowest number of avoided medical events.Conclusion: Agonist/antagonist abuse-deterrent opioid technology is associated with higher annual medical cost savings and more avoided events than physical/chemical barrier technology. Total net savings are dependent upon the abuse-deterrent opioid price relative to non-abuse-deterrent opioids.

Assessment of potentially abuse-related events in two phase 3 studies of NKTR-181, a novel opioid analgesic, using the MADDERS® system (Misuse, Abuse, and Diversion Drug Event Reporting System)

Objective: To prospectively evaluate the abuse potential of NKTR-181, a novel opioid analgesic, in two phase 3 clinical trials using a newly developed reporting system: the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS®).Methods: SUMMIT-07 was an enriched enrollment randomized withdrawal study that examined the safety and efficacy of NKTR-181 across 12 weeks in opioid-naïve subjects with chronic low back pain. SUMMIT-LTS was a 52 week open-label study in opioid-naïve and experienced subjects with chronic low back pain or noncancer pain rolled over from SUMMIT-07 or enrolled de novo. System evaluations were triggered by adverse events of interest and drug accountability discrepancies signaling potentially abuse-related events. Each event was assigned a primary classification and supplementary classification(s) by investigators and by a blinded, independent committee of substance abuse experts (adjudicators). At the final study visit, investigators administered a survey to subjects to identify overlooked events of interest.Results: Seventy-nine (6.6%) of 1189 subjects were associated with 86 events in SUMMIT-07 and 51 (8.0%) of 638 subjects were associated with 59 events in SUMMIT-LTS. Most events were attributed to “Withdrawal” and, primarily in SUMMIT-07, “Therapeutic Error” (unintentional overuse) or “Misuse” (intentional overuse for a therapeutic purpose) of study medication. Adjudicators identified five possible “Abuse” events (three NKTR-181, two placebo) in SUMMIT-07 and four possible “Abuse” events (all NKTR-181) in SUMMIT-LTS.Conclusions: The MADDERS® system discerns potentially abuse-related events and identified low rates of withdrawal and a low risk of abuse potential, diversion or addiction associated with NKTR-181 in phase 3 trials.

Comparison of Quetiapine Abuse and Misuse Reports to the FDA Adverse Event Reporting System With Other Second-Generation Antipsychotics.

Background:Second-generation antipsychotics (SGAs) are assumed to have little abuse potential. However, reports of quetiapine abuse have emerged as prescribing has increased in recent years. The US Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) provides postmarketing information regarding adverse drug events (ADEs). This is the first study to analyze quetiapine abuse-related ADEs reported to FAERS to determine whether a disproportionate rate of such events have been reported when compared with other commonly used SGAs.Methods:A cross-sectional analysis of FAERS data from January 1, 2015, to December 31, 2017, was performed. The total number of all-cause and abuse-related ADEs reported to FAERS regarding quetiapine, olanzapine, aripiprazole, and risperidone were identified, along with demographic and mortality data. The proportional reporting ratio (PRR) was calculated to assess disproportionate reporting of abuse-related adverse drug reactions between quetiapine and each of three alternative SGA medications.Results:Abuse-related ADEs represented 11% (3144/27 962) of total ADEs reported for quetiapine, 8% for olanzapine (1548/19 228), 5% (1380/29 699) for aripiprazole, and 3% (1168/45 518) for risperidone. The PRRs (95% confidence interval) for quetiapine versus olanzapine, aripiprazole, and risperidone were 1.40 (1.32-1.48), 2.42 (2.28-2.57), and 4.38 (4.10-4.68), respectively, indicating that abuse-related events were significantly more likely to be reported with quetiapine than each comparator drug. In addition, more deaths were reported among the abuse-related events regarding quetiapine (673) than olanzapine (200), aripiprazole (88), and risperidone (143).Conclusion:This study corroborates recent evidence indicating that quetiapine might possess a significantly higher abuse potential than other commonly used SGAs. Although prospective studies are needed to better understand the abuse potential of quetiapine, increased vigilance in monitoring for signs of substance abuse might be warranted when prescribing quetiapine.

Reports of gabapentin and pregabalin abuse, misuse, dependence, or overdose: An analysis of the Food And Drug Administration Adverse Events Reporting System (FAERS).

Reports of gabapentinoid (gabapentin and pregabalin) misuse have increased in recent years. Pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) provides a useful examination of adverse drug event (ADE) reporting for safety signal detection. This study was conducted to analyze epidemiological information on the nature and extent of gabapentin/pregabalin abuse utilizing the FAERS database. A query was designed utilizing SafeRx, an indexed, searchable database of FAERS data from October 2012-December 2016. All-cause and abuse-related (including abuse/misuse/dependence/overdose events) ADE reports for gabapentin and pregabalin were isolated, as well as limited demographic data. The proportional reporting ratio (PRR) was calculated to compare signal detection. A total of 10,038 all-cause ADEs were reported to FAERS for gabapentin, including 576 (5.7%) abuse-related events. For pregabalin, 571 all-cause ADEs were identified, including 58 (10.2%) related to abuse. Compared to all-cause ADEs, those involved in abuse-related events were younger and more likely to be male. The PRR of pregabalin versus gabapentin abuse-related events was 1.77. Though not traditionally thought of as drugs of abuse, over 600 cases of gabapentinoid abuse were reported in the time frame analyzed, prompting the need for further study and regulatory investigation.

Projecting the cost, utilization, and patient care impact of prescribing extended release non-abuse-deterrent opioids to chronic pain patients.

To estimate healthcare resource utilization, associated costs, and number needed to harm (NNH) from a physician's decision to prescribe extended-release (ER) non-abuse-deterrent opioids (non-ADO) as compared to ER ADOs in a chronic pain population. A 12-month probabilistic simulation model was developed to estimate the reduction of misuse and/or abuse from a physician's prescribing decisions for 10,000 patients. Model inputs included probabilities for opioid misuse and/or abuse-related events, opioid discontinuation, and switching from ADO to non-ADO. Estimated reductions in abuse associated with ADOs were obtained from positive subjective measures using human abuse liability studies. The model was run separately for commercial, Medicare, Medicaid, and Veterans Administration (VA) populations. The difference in healthcare resource utilization and associated costs (2015 USD) between the ADO and non-ADO simulations was calculated. NNH for non-ADO was also calculated. Misuse and/or abuse-related events for patients prescribed ER non-ADOs ranged from 223-1,410 and associated costs ranged from $20-$98 per patient for commercial and Medicare populations, respectively. Prescribing ER ADOs were associated with 87, 289, 264, and 417 fewer misuse and/or abuse-related events, saving $8, $35, $21, and $29 per patient in commercial, VA, Medicaid, and Medicare populations, respectively. NNH ranged from 185 in the commercial population to 40 in the Medicare population. Results were sensitive to decreases in the probability of misuse and/or abuse events but showed reductions. A physician's decision to prescribe ER ADOs could lead to large reductions in misuse and/or abuse-related events and associated costs across many patient populations.

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651).

Estimates of Charges Associated With Emergency Department and Hospital Inpatient Care for Opioid Abuse-Related Events

ABSTRACTThe economic burden of prescription opioid abuse is substantial; however, no study has estimated the monetary burden of hospital services (emergency department [ED] and inpatient) using a single, nationally representative database. We sought to estimate total and average (adjusted for demographic and clinical factors) charges billed for opioid abuse–related events, and magnitude of difference in charges between ED visits resulting in inpatient admission to the same hospital and treat-and-release ED visits in the United States. We used the 2006, 2007, and 2008 files of the Healthcare Cost and Utilization Project's Nationwide Emergency Departments Sample (HCUP-NEDS) to identify events and charges assigned opioid abuse, dependence, or poisoning ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) diagnosis codes (304.0X, 304.7X, 305.5X, 965.00, 965.02, 965.09). Using methods to account for the complex sampling design of the NEDS and a log-linked gamma regression model, we estimated national total and mean charges (in 2010 USD). Total charges were $9.8, $9.6, and $9.5 billion for 2006, 2007, and 2008, respectively. Medicaid-covered events had the highest total charges ($3 billion), followed by events covered by Medicare ($2 billion) for each year. The national estimate of adjusted, mean, per-event charges, was $18,891 (95% confidence interval [CI] = $18,167–$19,616). Compared with events covered by private insurance, mean charges for Medicare- and Medicaid-covered events were higher (t = 28.14, P < .001; t = 6.42, P < .001, respectively), whereas self-paid events had significantly lower charges (t = −11.14, P < .001). ED visits resulting in subsequent inpatient admission had approximately 6 times higher charges than treat-and-release visits. This study provides estimates of differences in hospital costs of opioid abuse by insurance status, resulting in a better understanding of the economic burden of opioid abuse on the health care system.

Two formats for eliciting retrospective reports of child sexual and physical abuse: effects on apparent prevalence and relationships to adjustment.

This study compared two common questionnaire formats for eliciting retrospective child abuse reports. Self-defined formats ask participants whether they were abused, using that term. Researcher-defined formats ask about particular abuse-related events, allowing researchers to specify criteria for identifying abuse histories. Adjustment was measured by self-report inventories of depressive and posttraumatic symptoms and global self-esteem. Participants were 542 college women and men. Significantly less abuse was reported on the self- versus researcher-defined formats. Self-defined abuse was more frequent if participants met criteria for researcher-defined sexual or dual abuse versus physical abuse and if they reported relatively frequent childhood physical violence, severe sexual acts, and marginally, sexual perpetrators who were incestuous. Relationships of adjustment with researcher-defined versus self-defined abuse were stronger, and relationships between adjustment and researcher-defined abuse were independent of self-defined abuse. Discussion addressed methods of eliciting retrospective abuse histories for research and for clinical purposes.

Regional Cerebral Blood Flow During Script-Driven Imagery in Childhood Sexual Abuse-Related PTSD: A PET Investigation

The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.

Stress, appraisal, and coping in child sexual abuse: a theoretical and empirical review.

A review of theories to predict the mental health effects of child sexual abuse suggests that existing models have not adequately defined stress and coping constructs and have not specified how those variables might interact with other environmental factors. This article outlines a transactional model that conceptualizes sexual abuse as a stressor consisting of a series of abuse events, abuse-related events, and disclosure-related events that each tend to increase risk for maladaptive outcomes. The model also proposes that cognitive appraisals and coping responses mediate the effects of these events, that developmental and environmental factors may moderate relationships between sexual abuse stressors and victim responses, and that victims' initial responses may effect subsequent levels of abuse-related stress. Empirical studies relevant to the major components of this model are reviewed, and the implications of these findings for future research are considered.