Five-Year Sales for Newly Marketed Prescription Drugs With and Without Initial Orphan Drug Act Designation.

This study evaluates sales revenue earned in the first 5 years for newly marketed brand-name drugs with and without an initial orphan drug designation.

The Role of Real-World Evidence in FDA-Approved New Drug and Biologics License Applications.

The US Food and Drug Administration (FDA) is open to accepting real-world evidence (RWE) to support its assessment of medical products. However, RWE stakeholders lack a shared understanding of FDA's evidentiary expectations for the use of RWE in applications for new drugs and biologics. We conducted a systematic review of publicly available FDA approval documents from January 2019 to June 2021. We sought to quantify, by year, how many approvals incorporated RWE in any form, and the intended use of RWE in those applications. Among approvals with RWE intended to support safety and/or effectiveness, we classified whether and how those studies impacted FDA's benefit-risk considerations, whether those studies were incorporated into the product label, and the therapeutic area of the medical product. Finally, we qualified FDA's documented feedback where available. We found that 116 approvals incorporated RWE in any form, with the proportion of approvals incorporating RWE increasing each year. Of these approvals, 88 included an RWE study intended to provide evidence of safety or effectiveness. Among these 88 approvals, 65 of the studies influenced FDA's final decision and 38 were included in product labels. The 88 approvals spanned 18 therapeutic areas. FDA's feedback on RWE study quality included methodological issues, sample size concerns, omission of patient level data, and other limitations. Based on these findings, we would anticipate that future guidance on FDA's evidentiary expectations of RWE use will incorporate fit-for-purpose real-world data selection and careful attention to study design and analysis.

Clinical Approaches to Cannabis: A Narrative Review.

Cannabis use in the United States is growing at an unprecedented pace. Most states in the United States have legalized medical cannabis use, and many have legalized nonmedical cannabis use. In this setting, health care professionals will increasingly see more patients who have questions about cannabis use, its utility for medical conditions, and the risks of its use. This narrative review provides an overview of the background, pharmacology, therapeutic use, and potential complications of cannabis.

Compliance to Online Retail of Electronic Nicotine Delivery Systems (ENDS) in India before and after the 2018 Ban Order of the Government of India.

Since their launch globally in 2012, electronic nicotine delivery systems (ENDS) were positioned as a harm reduction strategy and cessation device but it is yet to be proven to have clinical safety or public health benefits. Instead, recent reports suggest that the tobacco industry targeted youth and sponsored research whose evidence was used to mislead policymaking. On August 28, 2018, Ministry of Health & Family Welfare's advisory banned the sale, purchase, and trade of ENDS. A survey was done in two waves. The first survey was done between August 10 and 25 2018 all websites which sold ENDS product were mapped and documented. The survey was repeated (November 30, 2018) were after the restriction to trade on ENDS was proposed by the Department of Customs. The two waves of survey found that no website, whether comprehensive e-commerce portals or dedicated ENDS marketing platforms fully complied with government orders. National and states government enforcement agencies are currently unaware of internet-based sale of ENDS. Although some states have given specific directions to stop the sale and delivery of ENDS within the state through e-commerce, there is limited monitoring and legal compliance by seller. Public health advocates need to stay vigilant and monitor the online sale and point of sale retail of ENDS to ensure strict compliance of national and state regulations.

County-Level Recreational Marijuana Policies and Local Policy Changes in Colorado and Washington State (2012-2019).

Policy Points In 2012, Colorado and Washington were the first states to legalize recreational marijuana through voter-initiated ballots. In these states, counties could restrict or ban local marijuana facilities through a variety of regulatory methods such as ordinances and zoning. County-level recreational marijuana policies in Washington and Colorado vary substantially, with 69.2% of Washington counties and 23.4% of Colorado counties allowing all types of recreational marijuana facilities as of April 1, 2019. After Colorado and Washington legalized recreational marijuana, many counties modified their marijuana policies over time, with shifts in county policy often preceded by advocacy and information-seeking activities. CONTEXT: In 2012, Colorado and Washington were the first states to legalize recreational marijuana. Both allowed local governments to further regulate the availability of marijuana facilities in their jurisdictions. As early adopters, these states are important quasi-natural experiments to examine local marijuana policy and policy change processes, including key stakeholders and arguments. METHODS: We conducted a policy scan of county-level recreational marijuana ordinances and regulations in Colorado and Washington. Data collected included policy documents from counties in both states and newspaper articles. We used a mixed-methods approach to describe the types of county-level recreational marijuana policies enacted by April 1, 2019; identify key policy stakeholders involved in local policy debates; and explore arguments used in support or opposition of county policies. We also selected four counties that represent three county policy environments (all marijuana facility types allowed, some marijuana facility types allowed, all marijuana facility types prohibited) and described the policy changes within these counties since recreational marijuana was legalized. FINDINGS: By April 1, 2019, Colorado counties were less likely than Washington counties to allow marijuana facilities-48.4% of Colorado counties prohibited recreational marijuana facilities in their jurisdiction compared to 23.1% of Washington counties. Since state legalization, several counties in both states have made substantial marijuana facility policy modifications, often preceded by information-seeking activities. Primary stakeholders involved in policy debates included elected officials, law enforcement, individual growers/farmers, marijuana business license applicants, parents, and residents. Proponents referenced local economic gain, reduced crime, and potential health benefits of marijuana as arguments in favor of permitting local facilities, whereas opponents pointed to economic loss, negative health and public health issues, public safety concerns, and existing federal law. Both sides referenced local public opinion data to support their position. CONCLUSIONS: By early 2019, a patchwork of local marijuana policies was in place in Colorado and Washington. We identify key areas of policy and public health research needed to inform future local marijuana policy decisions, including the impact of legalization on public health outcomes (particularly for youth) and public safety.

Cannabis legalisation: should doctors be concerned?

A referendum on the Cannabis Legalisation and Control Bill was held in New Zealand. The Bill was meant to oversee government control over the production, supply and use of cannabis and reduce cannabis-related harm. Public health control was proposed over cannabis market by imposing licenses and cultivation, the quality and strength of marketed cannabis, and sale restrictions. Under this Bill, cannabis was only meant to be available to adults aged over 20 years through licenced stores. The potency of cannabis was to be limited. Cannabis use and was going to be permitted in private homes and specifically licensed premises. The Electoral Commission announced on 6 November 2020 that 50.7% of voters opposed the Bill and 48.4% supported it. Despite the outcome of the referendum, legalisation of cannabis may remain a live issue for many people, and doctors need to have an informed view about the impact of legalisation on mental health conditions. Experience from other countries shows that access to and potency of cannabis increased with legalisation. Despite the intent to prevent harm, cannabis legislation has been associated with adverse effects on mental health, emergency hospital presentations and crime. Public health strategies, including educating public about harm associated with cannabis, surveillance of potency and labelling, increasing minimal age for legal recreational cannabis use and bolstering treatment capacity for problematic cannabis use, including those with psychiatric disorders, should be funded by revenue generated from cannabis legislation.

Compliance With Cannabis Act Regulations Regarding Online Promotion Among Canadian Commercial Cannabis-Licensed Firms.

Importance: As global jurisdictions shift toward cannabis legalization, 2 areas of public health importance relate to exposure to youth and to truthful promotion. Although Canada's Cannabis Act specifies many prohibitions related to cannabis promotion, no systematic monitoring or enforcement among licensed firms exists. Compliance with marketing regulations has effects beyond Canadian citizens because of the global outreach of websites and social media. Objectives: To evaluate compliance among licensed firms with the Cannabis Act and analyze trends among violations regarding promotional material. Design, Setting, and Participants: This cross-sectional study evaluated cannabis-licensed firms after cannabis legalization. Data were extracted from online public platforms, including company websites, Facebook, Instagram, and Twitter, from October 1, 2019, to March 31, 2020. Descriptive statistics, Poisson regression, and logistic regression were used to analyze the associations of covariates with promotion violations. Main Outcomes and Measures: The primary outcome was characterization of type and prevalence of promotion violations. Secondary outcomes were the role of various covariates (namely, licensed firm characteristics and online platforms) in the frequency and probability of violations. Hypotheses were formulated before data collection. Results: Among 261 licensed firms, 211 (80.8%) had an online platform, including 204 (96.7%) with websites, 128 (60.7%) with Facebook, 123 (58.3%) with Instagram, and 123 (58.3%) with Twitter. Of all licensed firms with an online platform, 182 (86.3%) had at least 1 violation. Compared with websites, the risk of violations was significantly higher on Facebook (rate ratio [RR], 1.24; 95% CI, 1.11-1.39) and Instagram (RR, 1.19; 95% CI, 1.05-1.34). The most common violations included lack of age restrictions, brand glamorization, and omission of risk information. With websites as the reference group, lack of age restrictions was approximately 15 times more likely to occur on Facebook (odds ratio [OR], 14.76; 95% CI, 8.06-27.05); the odds of an age restriction violation were also higher on Instagram (OR, 2.48; 95% CI, 1.43-4.32) and Twitter (OR, 4.03; 95% CI, 2.29-7.09). For unsubstantiated claims, the odds of violations were significantly decreased on Facebook (OR, 0.23; 95% CI, 0.11-0.48) and Instagram (OR, 0.28; 95% CI, 0.14-0.57). The odds of glamorization were associated with an increase on Instagram (OR, 2.90; 95% CI, 1.72-4.88). Conclusions and Relevance: In this cross-sectional study, widespread violations were observed in online Canadian cannabis promotion. To protect public health and safety amid legalization, decision-makers should make explicit federal regulation and enforcement regarding promotional activities of cannabis retailers. These results suggest that policy and enforcement of cannabis promotion in Canada would have an international impact, from ease of access to online media and downstream consequences of unregulated promotion.

Looking back from 2020, how cannabis use and related behaviours changed in Canada.

BACKGROUND: The Canadian government legalized non-medical cannabis use by adults in October 2018 to minimize associated harms and redirect profits from criminals. In October 2019, a wider array of products, including edibles, was legalized, with entry into the legal market beginning in December. DATA AND METHODS: Three quarters (the first quarters of 2018 and 2019 and the fourth quarter of 2020) of the National Cannabis Survey were used to examine changes in cannabis use (overall use and daily or almost daily (DAD) use), consumption methods, products and sources. RESULTS: Cannabis use in the past three months was higher in late 2020 (20.0%) than in 2019 (17.5%) and 2018 (14.0%), and this was particularly the case among: females (for whom rates rose to equal male rates for the first time), adults aged 25 and older, and some provinces. Similarly, DAD use, at 7.9% also increased. Higher percentages of Canadians reported getting at least some of their cannabis from legal sources or growing it, and fewer were relying on friends and family or illegal sources in 2020. DISCUSSION: This study spans three years-from before legalization to about two years after. It provides a more complete picture of the law's impact on cannabis use and related behaviours, given the more established legal cannabis industry better equipped to compete with the black market on price, convenience and selection. Findings demonstrate that change is continuing, and, as before, some cautions and assurances remain. The impact of the COVID-19 pandemic on cannabis use continues to be difficult to measure. Monitoring remains important, given the ever-changing provincial retail landscapes; the introduction of new products; and the pressure by the industry to remove or adjust potency limits, and allow widespread delivery, farm-gate sales and cannabis lounges.

Evaluation of State Cannabis Laws and Rates of Self-harm and Assault.

Importance: State cannabis laws are changing rapidly. Research is inconclusive about their association with rates of self-harm and assault. Existing studies have not considered variations in cannabis commercialization across states over time. Objective: To evaluate the association of state medical and recreational cannabis laws with self-harm and assault, overall and by age and sex, while considering varying degrees of commercialization. Design, Setting, and Participants: Using a cohort design with panel fixed-effects analysis, within-state changes in claims for self-harm and assault injuries before and after changes in cannabis laws were quantified in all 50 US states and the District of Columbia. Comprehensive claims data on commercial and Medicare Advantage health plan beneficiaries from January 1, 2003, to December 31, 2017, grouped by state and month, were evaluated. Data analysis was conducted from January 31, 2020, to January 21, 2021. Exposures: Categorical variable that indexed the degree of cannabis legalization in each state and month based on law type (medical or recreational) and operational status of dispensaries (commercialization). Main Outcomes and Measures: Claims for self-harm and assault injuries based on International Classification of Diseases codes. Results: The analysis included 75 395 344 beneficiaries (mean [SD] age, 47 [22] years; 50% female; and median follow-up, 17 months [interquartile range, 8-36 months]). During the study period, 29 states permitted use of medical cannabis and 11 permitted recreational cannabis. Point estimates for populationwide rates of self-harm and assault injuries were higher in states legalizing recreational cannabis compared with states with no cannabis laws, but these results were not statistically significant (adjusted rate ratio [aRR] assault, recreational dispensaries: 1.27; 95% CI, 0.79-2.03;self-harm, recreational dispensaries aRR: 1.15; 95% CI, 0.89-1.50). Results varied by age and sex with no associations found except for states with recreational policies and self-harm among males younger than 40 years (aRR <21 years, recreational without dispensaries: 1.70; 95% CI, 1.11-2.61; aRR aged 21-39 years, recreational dispensaries: 1.46; 95% CI, 1.01-2.12). Medical cannabis was generally not associated with self-harm or assault injuries populationwide or among age and sex subgroups. Conclusions and Relevance: Recreational cannabis legalization appears to be associated with relative increases in rates of claims for self-harm among male health plan beneficiaries younger than 40 years. There was no association between cannabis legalization and self-harm or assault, for any other age and sex group or for medical cannabis. States that legalize but still constrain commercialization may be better positioned to protect younger male populations from unintended harms.

Why are certain age bands used for children in paediatric studies of medicines?

Rational prescribing of medicines requires evidence from clinical trials on efficacy, safety and the dose to be prescribed, based on clinical trials. Regulatory authorities assess these data and information is included in the approved summary of product characteristics. Regulatory guidelines on clinical investigation of medicinal products in the paediatric population generally propose that studies are done in defined age groups but advise that any classification of the paediatric population into age categories is to some extent arbitrary or that the age groups are intended only as a guide. The pharmaceutical companies tend to plan their studies using age groups the regulatory guidelines suggest, to avoid problems when applying for marketing authorisation. These age bands end up in the paediatric label, and consequently into national paediatric formularies. The age bands of the most commonly used age-subsets: neonates, infant/toddlers, children and adolescents, are more historical than based on physiology or normal development of children. Particularly problematic are the age bands for neonates and adolescents. The age of 12 years separating children from adolescents, and the upper limit of the adolescents set by the definition of paediatric age in healthcare, which varies according to the region, are particularly questionable. Modern pharmacometric methods (modelling and simulation) are being increasingly used in paediatric drug development and may allow assessment of growth and/or development as continuous covariables. Maybe time has come to reconsider the rational of the currently used age bands.

Challenges in clinical trials for children and young people.

There is a well-known knowledge gap regarding the efficacy and safety of medicines in children of all ages and children are often treated with medicines off-label. Children are thus deprived of treatment based on the same quality of information that guides treatment in adults. The knowledge gap regarding efficacy and safety of medicines in children has been acknowledged by authorities and is reflected in legislation both in North America and in the European Union. Recent reports on the effects of legislation indicates that paediatric clinical trials remain a challenge.Paediatric clinical trials are needed in the entire developmental age spectrum and are especially needed in certain therapy areas. Paediatric clinical trials have special features compared with trials in adults, and these need to be taken into account. These special features include scientific issues related to small samples and heterogeneity, the consent/assent procedure, the need for age-appropriate study information, specific outcomes and safety issues related to development and maturation. Competence in paediatric clinical trials is required in both designing, planning, co-ordinating and organising paediatric clinical trials, as well as research infrastructure and networks to increase power and disseminate information and expert advice. Strengthening of paediatric clinical research is essential to facilitate generating the data that will let children enjoy new medical advances in a similar manner as adults.

Perceptions of Marijuana Use for Glaucoma from Patients, Cannabis Retailers, and Glaucoma Specialists.

PURPOSE: As marijuana's popularity continues to grow, patients with glaucoma will encounter conflicting opinions on marijuana's role in glaucoma therapy. This study seeks to define the differing perceptions among glaucoma specialists, medical marijuana dispensaries, and glaucoma patients in a state with legalized marijuana. DESIGN: Cross-sectional study. PARTICIPANTS: Medical marijuana dispensaries in Colorado, members of the American Glaucoma Society (AGS), and patients with glaucoma at the University of Colorado glaucoma clinic. METHODS: First, medical marijuana dispensary employees were surveyed using a mystery call approach and a brief phone script. Dispensary employees were questioned as to whether marijuana was recommended and whether marijuana was safe and effective. Second, a self-administered survey was distributed to AGS members to determine the history of recommending marijuana and influencing factors for or against this recommendation. Third, the self-administered glaucoma patient survey assessed demographics, history of glaucoma, knowledge and rate of marijuana use, and perceptions of marijuana use. All surveys were conducted from October 2018 to March 2019. MAIN OUTCOME MEASURES: The proportion of medical marijuana dispensaries and glaucoma specialists recommending marijuana for the treatment of glaucoma, and the proportion of patients with glaucoma using marijuana as a treatment for glaucoma. RESULTS: A total of 203 of the 300 medical marijuana dispensaries called were successfully contacted (68%). Of these, 103 respondents (51%) recommended marijuana products for the treatment of glaucoma. The remaining 100 (49%) deferred making a recommendation or were unsure. Of the 1308 AGS members, 290 (22%) responded to the survey. Twenty-two respondents (7.6%) reported that they had recommended marijuana for the treatment of glaucoma, with the majority of these (86.4%) having done so infrequently. Among the 231 respondents with glaucoma, most (58.9%) had heard about the possible use of marijuana for glaucoma, but only 2.6% had used marijuana as a treatment for glaucoma. CONCLUSIONS: Few glaucoma specialists have recommended marijuana as a treatment for glaucoma, and an even smaller percentage of patients report its use as a treatment for their glaucoma. In contrast, many marijuana dispensary employees endorse its use. As legal access and public acceptance of marijuana escalate, physicians should be aware of these perceptions when educating patients.

General characteristics, economic burden, causative drugs and medical errors associated with medical damage litigation involving severe cutaneous adverse drug reactions in China.

WHAT IS KNOWN AND OBJECTIVE: To investigate the general characteristics, economic burden, causative drugs and medical errors associated with litigation involving severe cutaneous adverse drug reactions (SCADRs) in China, with the aims of improving rational medication use and reducing the extent of damage from SCADRs. METHODS: This study analysed 150 lawsuit judgements involving SCADRs from 2005 to 2019, collected from China Judgments Online. RESULTS AND DISCUSSION: In total, 50% of lawsuits stemmed from SCADRs occurring in general hospitals. The average time elapsed from the date of occurrence of the SCADRs to the end of litigation procedures was 1055 days. Of the patients involved, 51% were female and more than two thirds (69%) were under 60 years old. The most common outcome of SCADRs was death (39%), followed by disabilities (30%). The average responsibility of the medical provider was 48 ± 29%. The average amount of compensation was $43 424. Of the cases studied, 51% of SCADRs were Stevens-Johnson syndrome or toxic epidermal necrolysis, which together accounted for 75% of cases with known clinical subtype. The overall average economic burden of SCADRs was $99 178, of which indirect costs made up the largest proportion (more than 60%). The most common causative drug groups were antimicrobial drugs (49%), Chinese patent medicine and Chinese herbal medicine (17%), and antipyretic analgesics (16%). Finally, 61% of medical errors were found to stem from violation of duty of care, 20% from violation of informed consent and 18% from violations related to the medical record writing and management system. WHAT IS NEW AND CONCLUSION: Severe cutaneous adverse drug reactions not only severely affect patient survival and quality of life, but also impose a heavy economic burden in terms of health care and societal costs. Medical providers should be better educated on strategies to reduce risk to patients and establish mechanisms of risk sharing and management.

Current cannabis-related situation in the Asia-Pacific region.

PURPOSE OF REVIEW: We present information on cannabis policy, demand, and supply in the Asia-Pacific region. METHOD: A systematic review of peer-reviewed articles using PubMed, MEDLINE, and reliable sources was conducted. We classified the policy implemented in each country into conducting research, legalization of medical and recreational use, decriminalization, cultivation, and others. RECENT FINDINGS: In Australia, New Zealand, and Thailand, medical use has been approved, whereas it is limited in South Korea and Singapore and illegal in other countries. Except Australia, none of the Asia-Pacific region countries allows recreational use. China and Japan are expected to approve medical use, whereas Australia and New Zealand work on decriminalization. Most cultivation is allowed and regulated for medical use. Cannabis seizures have changed in accordance with these policies. Although the national surveys of four countries, that is, Australia, New Zealand, Japan, and Thailand were conducted in different years, the use of cannabis among the general population has increased. SUMMARY: Any change in the legal status of cannabis must be undertaken with caution and fully evaluated at each stage to determine the extent to which these changes are leading to increased numbers of users, oversupply, and health risks including cannabis-related harm.

The association between legalization of cannabis use and traffic deaths in Uruguay.

BACKGROUND AND AIMS: While cannabis use has been found to impair motor vehicle driving, the association between cannabis legalization and motor vehicle fatalities is unclear. In Uruguay in December 2013, cannabis for recreational purposes was legalized. This study assessed the association between implementation of this law and changes in traffic fatality rates. DESIGN: Interrupted time-series analysis of traffic fatality rates of light motor vehicle drivers and motorcyclists in urban and rural settings. Changes are reported as step and trend effects against modeled trends in the absence of legalization. SETTING: Uruguay, Montevideo and four rural provinces (Colonia, Florida, Río Negro and San José) from 1 January 2012 to 31 December 2017. Cases and measurement Weekly traffic fatalities of light motor vehicle drivers and motorcyclists per type of vehicle. Data were gathered from the National Road Safety Agency of Uruguay and the Ministry of Transport and Public Works, respectively. RESULTS: Cannabis legalization was associated with a 52.4% immediate increase [95% confidence interval (CI) = 11.6, 93.3, P = 0.012] in the light motor vehicle driver's fatality rate. However, no significant change in the motorcyclists' fatality rate was observed. In Montevideo the legislation was associated with an absolute increase in its light motor vehicle driver's fatality rate by 0.06 (95% CI = 0.01, 0.11, P = 0.025), but no significant associations were observed in rural settings. CONCLUSIONS: In Uruguay, the 2013 legislation legalizing recreational cannabis consumption may have been associated with an increase in fatal motor vehicle crashes, particularly in light motor-vehicle drivers and urban settings.

Ability of Primary Care Health Databases to Assess Medicinal Products Discussed by the European Union Pharmacovigilance Risk Assessment Committee.

This study measured the exposure to different categories of medicinal products discussed by the European Union (EU) Pharmacovigilance Risk Assessment Committee from September to November 2018 in four electronic primary care health databases: IQVIA Medical Research Data-UK, IQVIA Medical Research Data-France, IQVIA Medical Research Data-Germany, and Clinical Practice Research Datalink Aurum, in the entire lifespan of each database until August 31, 2018. The assessment of 83 centrally authorized products and 45 nationally authorized products showed that coverage was better for products marketed for longer duration and worse for orphan drugs. The ability to detect associations against hypothetical comparators was better for more common events and for larger effect sizes. Coverage of advanced therapies was worse for those typically administered in a specialized rather than primary care setting. This study shows that to enable better informed regulatory decisions there is a need to access complementary data sources, particularly capturing secondary care prescribing.

Opioid-limiting legislation associated with decreased 30-day opioid utilization following anterior cervical decompression and fusion.

BACKGROUND CONTEXT: Since 2016, 35 of 50 US states have passed opioid-limiting laws. The impact on postoperative opioid prescribing and secondary outcomes following anterior cervical discectomy and fusion (ACDF) remains unknown. PURPOSE: To evaluate the effect of opioid-limiting regulations on postoperative opioid prescriptions, emergency department (ED) visits, unplanned readmissions, and reoperations following elective ACDF. STUDY DESIGN/SETTING: Retrospective review of prospectively-collected data. PATIENT SAMPLE: Two hundred and eleven patients (101 pre-law, 110 post-law) undergoing primary elective 1-3 level ACDF during specified pre-law (December 1st, 2015-June 30th, 2016) and post-law (June 1st, 2017-December 31st, 2017) study periods were evaluated. METHODS: Demographic, medical, surgical, clinical, and pharmacological data was collected from all patients. Total morphine milligram equivalents (MMEs) filled was compared at 30-day postoperative intervals, before and after stratification by preoperative opioid-tolerance. Thirty- and 90-day ED visit, readmission, and reoperation rates were calculated. Independent predictors of increased 30-day and chronic (>90 day) opioid utilization were evaluated. RESULTS: Demographic, medical, and surgical factors were similar pre-law versus post-law (all p>.05). Post-law, ACDF patients received fewer opioids in their first postoperative prescription (26.65 vs. 62.08 pills, p<.001; 202.23 vs. 549.18 MMEs, p<.001) and in their first 30 postoperative days (cumulative 30-day MMEs 444.14 vs. 877.87, p<.001). Furthermore, post-law reductions in cumulative 30-day MMEs were seen among both opioid-naïve (363.54 vs. 632.20 MMEs, p<.001) and opioid-tolerant (730.08 vs. 1,122.90 MMEs, p=.022) patient populations. Increased 30-day opioid utilization was associated with surgery in the pre-law period, preoperative opioid exposure, preoperative benzodiazepine exposure, and number of levels fused (all p<.05). Chronic (>90 day) opioid requirements were associated with preoperative opioid exposure (odds ratio 4.42, p<.001) but not with pre/post-law status (p>.05). Pre- and post-law patients were similar in terms of 30- or 90-day ED visits, unplanned readmissions, and reoperations (all p>.05). CONCLUSIONS: Implementation of mandatory opioid prescribing limits effectively decreased 30-day postoperative opioid utilization following ACDF without a rebound increase in prescription refills, ED visits, unplanned hospital readmissions, or reoperations for pain.

Marijuana use trends among college students in states with and without legalization of recreational use: initial and longer-term changes from 2008 to 2018.

BACKGROUND AND AIMS: Young adult college students in the United States are likely to be affected by marijuana liberalization trends. However, changes in students' marijuana use following recreational marijuana legalization (RML) have not been examined in more than one RML state at a time, or beyond 1-2 years post-legalization. DESIGN: Cross-sectional National College Health Assessment survey administered twice yearly from 2008 to 2018. SETTING: A total of 587 4-year colleges and universities in 48 US states. PARTICIPANTS: Undergraduates aged 18-26 years attending college in US states that did (n = 234 669 in seven states) or did not (n = 599 605 in 41 states) enact RML between 2008 and 2018. MEASUREMENTS: Self-reported marijuana use (past 30 days) and individual and contextual covariates, institution-provided institutional and community covariates and publicly available dates when states enacted RML. FINDINGS: Adjusting for covariates, state differences and state-specific linear time trends (accounting for pre-RML trends), prevalence of 30-day marijuana use increased more among students exposed to RML [odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.19-1.28, P < 0.001] than among non-RML state students throughout the same time-period; the results were similar for frequent use (≥ 20 days) (OR = 1.18, 95% CI = 1.10-1.27, P < 0.001). Interaction models supported stronger RML effects among students who were female, residing off-campus and aged 21 years and older; sexual orientation did not moderate RML effects. In the earliest states to enact RML (2012) there were increases in use prevalence in the second through the sixth year post-RML compared to pre-RML. In the second legalization group (2015) there were increases in the first and second year post-RML, and greater increases in the third year. In the later states (2016-17), increases were observed in both years after RML. CONCLUSIONS: In US states that enacted recreational marijuana legislation from 2012 to 2017 there was evidence for a general trend towards greater increases in marijuana use by college students and differential impact by gender, legal using age and campus residence.