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Item Association between Prescribed Opioid Dose and Risk of Motor Vehicle Crashes(Wolters Kluwer, 2023) Quinn, Patrick D.; Chang, Zheng; Pujol, Toyya A.; Bair, Matthew J.; Gibbons, Robert D.; Kroenke, Kurt; D’Onofrio, Brian M.; Medicine, School of MedicineOpioid-involved motor vehicle traffic fatalities have increased over the past 2 decades. However, the extent to which prescribed opioids increase the risk of motor vehicle crashes remains uncertain. This study used real-world healthcare claims data to examine the association between prescription opioid dose and motor vehicle crash risk. Using nationwide US commercial insurance claims data for 2010 to 2018, we identified 772,404 adults who received incident, noncancer opioid therapy. We examined associations between daily prescription opioid dose, calculated in morphine milligram equivalents (MME) from filled prescription claims, and risk of motor vehicle crashes, assessed as diagnoses of motor vehicle injuries in claims for emergency visits, inpatient hospitalizations, and ambulance transportation. We estimated associations using a within-individual design, which ruled out all time-stable confounding. We complemented the design with time-varying statistical adjustment for other pharmacotherapies and a negative control pain pharmacotherapy analysis (with incident cyclic antidepressant prescriptions). During 2,150,009 person-years of follow-up, there were 12,123 motor vehicle crashes (5.64 crashes per 1000 person-years). In within-individual comparisons, crash risk was greater during opioid prescription periods involving doses ≤60 MME/day (odds ratio [OR], 3.86; 95% confidence interval [CI], 3.54, 4.21), >60 to 120 MME/day (OR, 5.46; 95% CI, 4.44, 6.73), and >120 MME/day (OR, 3.45; 95% CI, 2.31, 5.15) than during off-treatment periods. The negative control analysis supported the specificity of the results to opioids rather than to other processes associated with pharmacologic pain management. These findings suggest that the receipt of prescription opioids, even at doses ≤60 MME/day, is associated with an increased risk of motor vehicle crashes.Item Association of Mental Health Conditions and Treatments With Long-term Opioid Analgesic Receipt Among Adolescents(American Medical Association, 2018-05-01) Quinn, Patrick D.; Hur, Kwan; Chang, Zheng; Scott, Eric L.; Krebs, Erin E.; Bair, Matthew J.; Rickert, Martin E.; Gibbons, Robert D.; Kroenke, Kurt; D’Onofrio, Brian M.; Medicine, School of MedicineImportance: Adults with mental health conditions are more likely than those without to receive long-term opioid therapy. Less is known about opioid therapy among adolescents, especially those with mental health conditions. Objective: To examine associations between preexisting mental health conditions and treatments and initiation of any opioid and long-term opioid therapy among adolescents. Design, Setting, and Participants: A cohort of 1 224 520 incident opioid recipients without cancer diagnoses aged 14 to 18 years at first receipt was extracted from nationwide commercial health care claims data from January 1, 2003, to December 31, 2014. Analysis was conducted from August 19, 2016, to November 16, 2017. Associations between preexisting mental health conditions and treatments and any opioid receipt were examined by comparing recipients with nonrecipients matched on sex, calendar year and years of age of first enrollment, and months of enrollment (prior to the index month for recipients, ever for nonrecipients). Associations between preexisting mental health conditions and treatments and subsequent long-term opioid therapy were examined among recipients with at least 6 months' follow-up using Cox proportional hazards regressions adjusted for demographics. Exposures: Mental health condition diagnoses and treatments recorded in inpatient, outpatient, and filled-prescription claims prior to opioid receipt. Main Outcomes and Measures: Opioid receipt, defined as any opioid analgesic prescription claim, and long-term opioid therapy, defined as more than 90 days' supply within a 6-month window having no gaps in supply of more than 32 days. Results: Of the 1 224 520 new opioid recipients included, the median age at first receipt was 17 years (interquartile range, 16-18 years), and 51.1% were female. Median follow-up after first receipt was 625 days (interquartile range, 255-1268 days). Adolescents with anxiety, mood, neurodevelopmental, sleep, and nonopioid substance use disorders and most mental health treatments were significantly more likely to receive any opioid (odds ratios from 1.13 [95% CI, 1.10-1.16] for nonopioid substance use disorders to 1.69 [95% CI, 1.58-1.81] for nonbenzodiazepine hypnotics). Among the 1 000 453 opioid recipients (81.7%) who had at least 6 months' follow-up, the cumulative incidence of long-term opioid therapy was 3.0 (95% CI, 2.8-3.1) per 1000 recipients within 3 years after first opioid receipt. All preexisting mental health conditions and treatments were strongly associated with higher rates of long-term opioid therapy (adjusted hazard ratios from 1.73 [95% CI 1.54-1.95] for attention-deficit/hyperactivity disorder to 8.90 [95% CI, 5.85-13.54] for opioid use disorder). Conclusions and Relevance: Commercially insured adolescents with many types of preexisting mental health conditions and treatments were modestly more likely to receive any opioid and were substantially more likely to subsequently transition to long-term opioid therapy relative to those without, although overall rates of long-term opioid therapy were low.Item Associations of opioid prescription dose and discontinuation with risk of substance-related morbidity in long-term opioid therapy(Wolters Kluwer, 2022) Quinn, Patrick D.; Chang, Zheng; Bair, Matthew J.; Rickert, Martin E.; Gibbons, Robert D.; Kroenke, Kurt; D’Onofrio, Brian M.; Medicine, School of MedicineEfforts to reduce opioid-related harms have decreased opioid prescription but have provoked concerns about unintended consequences, particularly for long-term opioid therapy (LtOT) recipients. Research is needed to address the knowledge gap regarding how risk of substance-related morbidity changes across LtOT and its discontinuation. This study used nationwide commercial insurance claims data and a within-individual design to examine associations of LtOT dose and discontinuation with substance-related morbidity. We identified 194,839 adolescents and adults who initiated opioid prescription in 2010 to 2018 and subsequently received LtOT. The cohort was followed for a median of 965 days (interquartile range, 525-1550), of which a median of 176 days (119-332) were covered by opioid prescription. During follow-up, there were 17,582 acute substance-related morbidity events, defined as claims for emergency visits, inpatient hospitalizations, and ambulance transportation with substance use disorder or overdose diagnoses. Relative to initial treatment, risk was greater within individual during subsequent periods of >60 to 120 (adjusted odds ratio [OR], 1.29; 95% CI, 1.12 to 1.49) and >120 (OR, 1.48; 95% CI, 1.24-1.76) daily morphine milligram equivalents. Risk was also greater during days 1 to 30 after discontinuations than during initial treatment (OR, 1.19; 95% CI, 1.05-1.35). However, it was no greater than during the 30 days before discontinuations, indicating that the risk may not be wholly attributable to discontinuation itself. Results were supported by a negative control pharmacotherapy analysis and additional sensitivity analyses. They suggest that LtOT recipients may experience increased substance-related morbidity risk during treatment subsequent to initial opioid prescription, particularly in periods involving higher doses.Item Attention-deficit/hyperactivity disorder medication and seizures(American Academy of Neurology, 2018-03-27) Wiggs, Kelsey K.; Chang, Zheng; Quinn, Patrick D.; Hur, Kwan; Gibbons, Robert; Dunn, David; Brikell, Isabell; Larsson, Henrik; D'Onofrio, Brian M.; Psychiatry, School of MedicineOBJECTIVE: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures. METHODS: We followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication. RESULTS: Patients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24-2.42 males; OR = 2.31, 95% CI = 2.22-2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60-0.85) and without (OR = 0.71, 95% CI = 0.62-0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59-1.30) and without (OR = 1.01, 95% CI = 0.80-1.28) a seizure history. CONCLUSIONS: Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures.Item Evidence of familial confounding of the association between cannabis use and cerebellar-cortical functional connectivity using a twin study(Elsevier, 2022) Sepe-Forrest, Linnea; Kim, Dae-Jin; Quinn, Patrick D.; Bolbecker, Amanda R.; Wisner, Krista M.; Hetrick, William P.; O'Donnell, Brian F.; Psychiatry, School of MedicineCerebellar-cortical resting-state functional connectivity (rsFC) has been reported to be altered in cannabis users. However, this association may be due to genetic and environmental confounding rather than a causal relationship between cannabis use and changes in rsFC. In this co-twin control study, linear mixed models were used to assess relationships between the number of lifetime cannabis uses (NLCU) and age of cannabis onset (ACO) with cerebellar-cortical rsFC. The rsFC with seven functional networks was evaluated in 147 monozygotic and 82 dizygotic twin pairs. Importantly, the use of genetically informed models in this twin sample facilitated examining whether shared genetic or environmental effects underlie crude associations between cannabis measures and connectivity. Individual-level phenotypic analyses (i.e., accounting for twin-pair non-independence) showed that individuals in the full sample with earlier ACO and higher NLCU had lower cerebellar rsFC within the VA, DA, and FP networks. Yet, there were no significant differences in cerebellar-cortical rsFC between monozygotic twins who were discordant for cannabis measures. These findings suggest shared genetic or environmental confounds contribute to associations between cannabis use and altered cerebellar-cortical rsFC, rather than unique causal impacts of cannabis use on cerebellar-cortical rsFC.Item Incident and long-term opioid therapy among patients with psychiatric conditions and medications: a national study of commercial health care claims(Wolters Kluwer, 2017-01) Quinn, Patrick D.; Hur, Kwan; Chang, Zheng; Krebs, Erin E.; Bair, Matthew J.; Scott, Eric L.; Rickert, Martin E.; Gibbons, Robert D.; Kroenke, Kurt; D’Onofrio, Brian M.; Medicine, School of MedicineThere is growing evidence that opioid prescribing in the United States follows a pattern in which patients who are at the highest risk of adverse outcomes from opioids are more likely to receive long-term opioid therapy. These patients include, in particular, those with substance use disorders (SUDs) and other psychiatric conditions. This study examined health insurance claims among 10,311,961 patients who filled prescriptions for opioids. Specifically, we evaluated how opioid receipt differed among patients with and without a wide range of preexisting psychiatric and behavioral conditions (ie, opioid and nonopioid SUDs, suicide attempts or other self-injury, motor vehicle crashes, and depressive, anxiety, and sleep disorders) and psychoactive medications (ie, antidepressants, benzodiazepines, hypnotics, mood stabilizers, antipsychotics, and medications used for SUD, tobacco cessation, and attention-deficit/hyperactivity disorder). Relative to those without, patients with all assessed psychiatric conditions and medications had modestly greater odds of subsequently filling prescriptions for opioids and, in particular, substantially greater risk of long-term opioid receipt. Increases in risk for long-term opioid receipt in adjusted Cox regressions ranged from approximately 1.5-fold for prior attention-deficit/hyperactivity disorder medication prescriptions (hazard ratio [HR] = 1.53; 95% confidence interval [CI], 1.48-1.58) to approximately 3-fold for prior nonopioid SUD diagnoses (HR = 3.15; 95% CI, 3.06-3.24) and nearly 9-fold for prior opioid use disorder diagnoses (HR = 8.70; 95% CI, 8.20-9.24). In sum, we found evidence of greater opioid receipt among commercially insured patients with a breadth of psychiatric conditions. Future studies assessing behavioral outcomes associated with opioid prescribing should consider preexisting psychiatric conditions.Item Neuro-ophthalmologic and blood biomarker responses in ADHD following subconcussive head impacts: a case–control trial(Frontiers Media, 2023-11-22) Nowak, Madeleine K.; Kronenberger, William G.; Rettke, Devin; Ogbeide, Osamudiamen; Klemsz, Lillian M.; Quinn, Patrick D.; Mickleborough, Timothy D.; Newman, Sharlene D.; Kawata, Keisuke; Psychiatry, School of MedicineIntroduction: This clinical trial aimed to determine the influence of attention-deficit/hyperactivity disorder (ADHD) on neuro-ophthalmologic function and brain-derived blood biomarkers following acute subconcussive head impacts. Methods: The present trial consisted of age- and sex-matched samples with a ratio of 1:1 between two groups with a total sample size of 60 adults (age ± SD; 20.0 ± 1.8 years). Soccer players diagnosed with and medicated daily for ADHD were assigned into an ADHD group (n = 30). Soccer players without ADHD were assigned into a non-ADHD group (n = 30). Participants performed 10 soccer headers with a soccer ball projected at a velocity of 25mph. King-Devick test (KDT), near point of convergence (NPC), and serum levels of NF-L, tau, GFAP, and UCH-L1 were assessed at baseline (pre-heading) and at 2 h and 24 h post-heading. Results: There were no statistically significant group-by-time interactions in outcome measures. However, at baseline, the ADHD group exhibited lower neuro-ophthalmologic functions compared to the non-ADHD group (NPC: p = 0.019; KDT: p = 0.018), and persisted at 2 h-post (NPC: p = 0.007; KDT: p = 0.014) and 24 h-post heading (NPC: p = 0.001). NPC significantly worsened over time in both groups compared to baseline [ADHD: 2 h-post, 1.23 cm, 95%CI:(0.77, 1.69), p < 0.001; 24 h-post, 1.68 cm, 95%CI:(1.22, 2.13), p = 0.001; Non-ADHD: 2 h-post, 0.96 cm, 95%CI:(0.50, 1.42), p < 0.001; 24 h-post, 1.09 cm, 95%CI:(0.63, 1.55), p < 0.001]. Conversely, improvements in KDT time compared to baseline occurred at 2 h-post in the non-ADHD group [-1.32 s, 95%CI:(-2.55, -0.09), p = 0.04] and at 24 h-post in both groups [ADHD: -4.66 s, 95%CI:(-5.89, -3.43), p < 0.001; Non-ADHD: -3.46 s, 95%CI:(-4.69, -2.23), p < 0.001)]. There were no group-by-time interactions for GFAP as both groups exhibited increased levels at 2 h-post [ADHD: 7.75 pg./mL, 95%CI:(1.41, 14.10), p = 0.019; Non-ADHD: 7.91 pg./mL, 95%CI:(1.71, 14.14), p = 0.015)] that returned to baseline at 24 h-post. NF-L levels increased at 2 h-post heading in the ADHD group [0.45 pg./mL, 95%CI:(0.05, 0.86), p = 0.032], but no significant NF-L changes were observed in the non-ADHD group over time. Discussion: Ten soccer headers elevated GFAP levels and NPC impairment in both groups. However, persisting group difference in NPC, blunted KDT performance, and increased NF-L levels in the ADHD group suggest that ADHD may reduce neuro-ophthalmologic function and heighten axonal response to soccer headers.Item Patient race and opioid misuse history influence provider risk perceptions for future opioid-related problems(American Psychological Association, 2020-09) Hirsh, Adam T.; Anastas, Tracy M.; Miller, Megan M.; Quinn, Patrick D.; Kroenke, Kurt; Psychology, School of ScienceIn response to the dual public health crises of chronic pain and opioid use, providers have become more vigilant about assessing patients for risk of opioid-related problems. Little is known about how providers are making these risk assessments. Given previous studies indicating that Black patients are at increased risk for suboptimal pain care, which may be related to stereotypes about drug abuse, the current study examined how patient race and previous opioid misuse behaviors impact providers' risk assessments for future prescription opioid-related problems. Physician residents and fellows (N = 135) viewed videos and read vignettes about 8 virtual patients with chronic pain who varied by race (Black/White) and history of prescription opioid misuse (absent/present). Providers rated patients' risk for future prescription opioid-related adverse events, misuse/abuse, addiction, and diversion, and also completed measures of implicit racial attitudes and explicit beliefs about race differences in pain. Two significant interactions emerged indicating that Black patients were perceived to be at greater risk for future adverse events (when previous misuse was absent) and diversion (when previous misuse was present). Significant main effects indicated that Black patients and patients with previous misuse were perceived to be at greater risk for future misuse/abuse of prescription opioids, and that patients with previous misuse were perceived to be at greater risk of addiction. These findings suggest that racial minorities and patients with a history of prescription opioid misuse are particularly vulnerable to any unintended consequences of efforts to stem the dual public health crises of chronic pain and opioid use.Item Toward more rigorous and informative nutritional epidemiology: The rational space between dismissal and defense of the status quo(Taylor & Francis, 2023) Brown, Andrew W.; Aslibekyan, Stella; Bier, Dennis; da Silva, Rafael Ferreira; Hoover, Adam; Klurfeld, David M.; Loken, Eric; Mayo-Wilson, Evan; Menachemi, Nir; Pavela, Greg; Quinn, Patrick D.; Schoeller, Dale; Tekwe, Carmen; Valdez, Danny; Vorland, Colby J.; Whigham, Leah D.; Allison, David B.; Health Policy and Management, Richard M. Fairbanks School of Public HealthTo date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo will require ongoing, unflinching scrutiny of research questions, practices, and reporting-and a willingness to admit that "good enough" is no longer good enough. As such, a workshop entitled "Toward more rigorous and informative nutritional epidemiology: the rational space between dismissal and defense of the status quo" was held from July 15 to August 14, 2020. This virtual symposium focused on: (1) Stronger Designs, (2) Stronger Measurement, (3) Stronger Analyses, and (4) Stronger Execution and Reporting. Participants from several leading academic institutions explored existing, evolving, and new better practices, tools, and techniques to collaboratively advance specific recommendations for strengthening nutritional epidemiology.Item Treatment of Adolescent Substance Use Disorders and Co-Occurring Internalizing Disorders: A Critical Review and Proposed Model(Bentham Science Publishers, 2015) Hulvershorn, Leslie A.; Quinn, Patrick D.; Scott, Eric L.; Department of Psychiatry, IU School of MedicineBACKGROUND: The past several decades have seen dramatic growth in empirically supported treatments for adolescent substance use disorders (SUDs), yet even the most well-established approaches struggle to produce large or long-lasting improvements. These difficulties may stem, in part, from the high rates of comorbidity between SUDs and other psychiatric disorders. METHOD: We critically reviewed the treatment outcome literature for adolescents with co-occurring SUDs and internalizing disorders. RESULTS: Our review identified components of existing treatments that might be included in an integrated, evidence-based approach to the treatment of SUDs and internalizing disorders. An effective program may involve careful assessment, inclusion of parents or guardians, and tailoring of interventions via a modular strategy. CONCLUSIONS: The existing literature guides the development of a conceptual evidence-based, modular treatment model targeting adolescents with co-occurring internalizing and SUDs. With empirical study, such a model may better address treatment outcomes for both disorder types in adolescents.