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Kathryn Duensing,1 Robert Twillman,1– 3 Stephen Ziegler,4,5 M Soledad Cepeda,6 David Kern,6 Maribel Salas,7,8 Gregory Wedin9 1RKT Consulting, LLC, Lenexa, KS, USA; 2Behavioral Health Section, Saint Luke’s Health System, Kansas City, MO, USA; 3Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, Kansas City, KS, USA; 4Center for Effective Regulatory Policy and Safe Access, Denver, CO, USA; 5College of Professional Studies, Purdue University, Fort Wayne, IN, USA; 6Department of Epidemiology, Janssen Research & Development, Titusville, NJ, USA; 7Department of Epidemiology, Clinical Safety and Pharmacovigilance, Daiichi Sankyo, Basking Ridge, NJ, USA; 8University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 9Upsher-Smith Laboratories, LLC, Pharmacovigilance and Risk Management, Maple Grove, MN, USACorrespondence: Robert TwillmanSaint Luke’s Health System, Kansas City, MO, USATel +1 913-205-3746Email Bob.Twillman@gmail.comIntroduction: Opioid overdose deaths in the United States have climbed sharply over the past two decades. Simultaneously, increased awareness of inadequately treated chronic pain has resulted in increased opioid analgesic prescribing. The correlation between these two phenomena has led policymakers to posit that they are causally linked, and to implement policy changes supporting safe opioid prescribing.Purpose: To evaluate the impact of its Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) program, the US Food and Drug Administration (FDA) requested the opioid manufacturers responsible for implementing that program provide information regarding opioid policy changes from 2016 to 2018. FDA also requested a survey of state requirements for pain and opioid prescribing continuing education (CE), the number of prescribers affected by those requirements, the extent to which a REMS-compliant CE program would meet each state’s requirements, and the number of relevant CE programs available.Results: Results indicate that 527 federal and state opioid-related policies (statutes, rules/regulations, and guidelines) were approved during the 2016– 2018 study period. While the largest number of these policies focused on prescription drug monitoring programs, 170 specifically imposed limits on opioid prescribing and an additional 35 specifically referred to, or incorporated, the Centers for Disease Control and Prevention opioid prescribing guideline. We also found that 46 states and the District of Columbia mandated some amount of pain or opioid prescribing CE for prescribers renewing their licenses. These mandates potentially affected as many as 1.7 million prescribers. In 69% of cases, a REMS-compliant CE program would fully meet the state mandates for various types of prescribers.Conclusion: The severity and complexity of the problems of pain management and opioid overdose have led to large-scale intervention by policymakers. Assessing the impact of these changes is difficult, at best, but will be necessary if interventions are to be refined to increase their effectiveness.Keywords: opioids, FDA blueprint, prescribing, law, policy, CDC, REMS

Judith J Stephenson,1 M Soledad Cepeda,2 Jie Zhang,3,4 Jade Dinh,4 Kelsey Hall,4 Daina B Esposito,4– 6 David M Kern2 1Scientific Affairs, HealthCore, Inc, Wilmington, DE, USA; 2Epidemiology, Janssen Research and Development, Titusville, NJ, USA; 3Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA; 4Safety and Epidemiology, HealthCore, Inc., Wilmington, DE, USA; 5Ciconia, Inc, Westford, MA, USA; 6Epidemiology, Boston University, Boston, MA, USACorrespondence: Judith J StephensonHealthCore, Inc., 123 Justison Street, Suite 200, Wilmington, DE 19801, USATel +1 302-230-2142Email jstephenson@healthcore.comBackground/Rationale: Little is known about the reasons for visiting multiple doctors/pharmacies, known as doctor/pharmacy shopping, to obtain opioids.Objective: To investigate patients’ self-reported reasons for doctor/pharmacy shopping and assess whether doctor/pharmacy shopping behavior can be used as a surrogate measure of opioid abuse/misuse.Methods: We conducted a cross-sectional web-based survey among adult patients with ≥ 2 pharmacy claims for immediate-release or extended-release/long-acting opioids between 7/1/2015 and 12/31/2016, identified from a large United States (US) commercial claims database. Patients were classified into no, mild, moderate, or severe shopping categories based on their claims. Reasons for doctor/pharmacy shopping and opioid abuse/misuse were determined from patient responses to the Prescription Opioid Misuse and Abuse Questionnaire.Results: A random sample of 10,081 patients was invited to participate in the survey and 1085 (11%) completed surveys. The most frequently reported reasons for doctor/pharmacy shopping were convenience, availability, price, and multiple morbidities requiring pain management. Among patients in the no, minimal, moderate, and severe shopping categories, only 7.8%, 8.5%, 11.8% and 12.6% reported opioid abuse/misuse, respectively.Conclusion: In this commercially-insured population, patient-reported reasons for doctor/pharmacy shopping do not suggest opioid abuse/misuse. Less than 15% of patients with shopping behavior in the past 3 months reported any reasons attributable to opioid abuse/misuse, indicating that shopping behavior in this population may not be a good surrogate for abuse/misuse.Keywords: doctor/pharmacy shopping, prescription opioid, abuse and misuse &nbsp

The quantum Lefschetz formula explains how virtual fundamental classes (or structure sheaves) of moduli stacks of stable maps behave when passing from an ambient target scheme to the zero locus of a section. It is only valid under special assumptions (genus $0$, regularity of the section and convexity of the bundle). In this paper, we give a general statement at the geometric level removing these assumptions, using derived geometry. Through a study of the structure sheaves of derived zero loci we deduce a categorification of the formula in the $\infty$-categories of quasi-coherent sheaves. We also prove that Manolache's virtual pullbacks can be constructed as derived pullbacks, and use them to recover the classical Quantum Lefschetz formula when its hypotheses are satisfied., 24 pages; comments are very much welcome. V2: Major revision; corrected several mistakes and improved exposition

Additional file 1. APPENDIX Fig. 1. Study design illustration for drug eras, switching and combination therapy classification. A) Drug eras are illustrated assuming a 30-day supply for each medication fill and allowing for a 30-day gap between the end of supply and the next fill. The drug era ends if another fill is not received within this gap. (B) If drug eras of two classes overlap at least 30 days (Drug Class B and Drug Class C) then it is classified as combination therapy, otherwise it is a switch between two classes (Drug Class A to Drug Class B).