Most states now legally mandate providers to access the Prescription Drug Monitoring Program (PDMP) database before prescribing controlled substances like opioids. We exploit variation in the ...adoption of these “must access” mandates between 2010 and 2017 to evaluate their impact on prescribing behavior. We find that counties in “must access” PDMP states have 5.5 fewer retail opioid prescriptions per 100 persons compared to counties in “voluntary access” PDMP states. We find evidence of geographic spillovers in opioid prescribing behavior. Our results underscore the importance recognizing the potential for cross‐border shopping when designing interventions to combat opioid misuse.
Selective inhibition of protein tyrosine kinases is gaining importance as an effective therapeutic approach for the treatment of a wide range of human cancers. However, as extensively documented for ...the BCR-ABL oncogene in imatinib-treated leukaemia patients, clinical resistance caused by mutations in the targeted oncogene has been observed. Here, we look at how structural and mechanistic insights from imatinib-insensitive Bcr-Abl have been exploited to identify second-generation drugs that override acquired target resistance. These insights have created a rationale for the development of either multi-targeted protein kinase inhibitors or cocktails of selective antagonists as antitumour drugs that combine increased therapeutic potency with a reduced risk of the emergence of molecular resistance.
Acetaminophen has long been assumed to selectively alleviate physical pain, but recent research has started to reveal its broader psychological effects. Building on this work, we find suggestive ...evidence that acetaminophen affects the basic social process of trust across a national survey and five lab experiments. In a national community sample (MIDUS II), acetaminophen usage was negatively associated with neighborhood trust and feelings of social integration. In a series of lab experiments (N = 767), acetaminophen reduced the influence of self-generated expectations on investments in a trust game. When we manipulated trust game investor expectations, acetaminophen increased investments regardless of expectations. These results provide the first demonstration that an over-the-counter drug can impact trust-related behavior. Overall, the findings paint a complex picture of how situational factors may influence drug effects.
Current regulations require that when seeking approval for new drugs, pharmaceutical companies must demonstrate their short‐ but not long‐term safety and efficacy. Instead, post‐approval, clinicians ...report adverse reactions to regulators, who may issue additional safety warnings. We investigate the incentives this creates for pharmaceutical companies to seek approval for new drugs with unknown long‐term effects. We first construct models predicting that (1) long‐run effects can be reasonably approximated from observational follow‐up of short‐term randomized control trials, and (2) companies will trade‐off short‐term sales against possible later adverse demand effects. We then test whether regulator warnings over diabetic, analgesic, analeptic, or psychoanaleptic drugs sold in the US and UK hospital and retail sectors affect the sales of individual drugs or the share prices of companies that sell them. With some exceptions, we find that pharmaceutical companies generally face no adverse market reaction in sales or share price from newly issued warnings in these four drug categories.
Zusammenfassung
Ärzte, die Cannabisarzneimittel zulasten der gesetzlichen Krankenversicherung verschreiben, sind verpflichtet, an einer bis zum 31.03.2022 laufenden nichtinterventionellen ...Begleiterhebung zur Anwendung dieser Cannabisarzneimittel teilzunehmen. Im Rahmen der Erhebung werden anonymisierte Behandlungsdaten gesammelt und ausgewertet. Die Ergebnisse der Begleiterhebung sind unter anderem Grundlage für den Gemeinsamen Bundesausschuss (G-BA), um die zukünftige Übernahme der Behandlungskosten im Rahmen einer Therapie mit Cannabisarzneimitteln nach dem Sozialgesetzbuch (SGB) V zu regeln. Die Übermittlung der Daten zur Begleiterhebung erfolgt über ein Onlineportal, welches vom Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) betrieben wird. Die erste Datenerhebung erfolgt nach einer Therapiedauer von einem Jahr oder, wenn die Therapie mit dem gewählten Cannabisarzneimittel vor Ablauf eines Jahres beendet wird, direkt nach Beendigung der Therapie.
Zum Zeitpunkt der Zwischenauswertung am 01.02.2019 lagen 4153 vollständige Datensätze vor. Am häufigsten (69 %) werden „Schmerzen“ als primär therapierte Symptomatik genannt. Nach Häufigkeit folgen Spastik (11 %) sowie Anorexie/Wasting (8 %). Die beobachteten Nebenwirkungen entsprechen denen, die auch in den Fachinformationen der beiden Fertigarzneimittel Sativex® (GW Pharma Ltd, Salisbury, Wiltshire, UK) und Canemes® (AOP Orphan Pharmaceuticals AG, Wien, Österreich) aufgeführt sind. In der Mehrzahl der Fälle war die nicht ausreichende Wirkung Grund für einen Therapieabbruch. Die Hauptindikation „Schmerz“ entspricht der, die sich schon in den Jahren 2005 bis 2016 im Erlaubnisverfahren zum Erwerb von Cannabis zu medizinischen Zwecken abzeichnete. Weiterführende Auswertungen und Subgruppenanalysen werden erfolgen, wenn höhere Fallzahlen vorliegen.
Obesity is a complex disease that is regulated by both central and peripheral mechanisms. New medicines for the treatment and prevention of obesity will need to overcome the powerful compensatory ...responses of the overlapping, and often redundant, networks that have evolved to safeguard efficient energy use. Despite great progress in the identification of central signals that regulate satiety, and considerable investment in the development of appetite-controlling medications, success has been modest so far. Here we review the main enzymes that are involved in different stages of lipid metabolism -- from digestion and absorption through synthesis and storage to mobilization and oxidation -- which might be successfully targeted by new pharmacotherapies.
The combination of drugged and drunk driving is an important policy topic as some states and countries have liberalized prohibitions on substance use to varying degrees. In this study, we analyze the ...effect of legal access to alcohol on suspected drug impaired accidents. We find that accidents with suspected drug impairment significantly increase when a driver gains legal access to alcohol at age 21. Our findings suggest that even if alcohol and drug consumption are substitutes, as much of the literature suggests, potential interactive effects may offset the reduction in decreased alcohol consumption from drugs.
The rise in drug overdose deaths in the United States since the turn of the millennium has been extraordinary. A popular narrative paints a picture whereby opioid overdoses among white, male, ...less-educated, rural workers have been caused by reduced economic opportunities borne by such people. In this article, we causally test the validity of this theory by using Bartik-type variables to explore the relationship between local economic conditions and county opioid overdose death rates. We add to the literature by exploring how both employment and wage growth in different types of industries are related to opioid overdose deaths for the population as a whole, as well as for rural (vs. urban), male (vs. female) and white (vs. black) populations. We find mixed evidence. Our results confirm that wage and employment growth in industries more likely to employ low-skill workers are important protective factors for rural, white males. However, we also find evidence that economic improvements in low-skill industries are just as important in protecting blacks and women against opioid overdoses, and for workers in metro counties. We also find evidence that employment growth in high-paying industries has led to increases in opioid overdoes rates.
Highly active antiretroviral therapy (HAART) based on combinations of drugs that target key enzymes in the life-cycle of human immunodeficiency virus (HIV) has considerably reduced morbidity and ...mortality from HIV infection since its introduction in the mid-1990s. However, the growing problem of the emergence of HIV strains that are resistant not only to individual drugs, but to whole drug classes, means that agents with new mechanisms of action are needed. Here, we describe the discovery and development of enfuvirtide (Fuzeon), the first drug to inhibit the entry of HIV-1 into host cells.
Drug development is a risky business. Success or failure often depends on selecting one or two molecules for development from many choices offered by the engines of high-throughput discovery. A lead ...candidate needs to possess adequate bioactivity, appropriate physical-chemical properties to enable formulation development, the ability to cross crucial membranes, reasonable metabolic stability and appropriate safety and efficacy in humans. Predicting how a drug will behave in humans before clinical testing requires a battery of sophisticated in vitro tests that complement traditional in vivo animal safety assessments. This review discusses how to strategically identify which non-clinical studies should be performed to provide the required guidance and comfort to stakeholders involved in clinical drug testing.
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