Background

Tapentadol (TAP) and tramadol (TRA) provide pain relief through similar monoaminergic and opioid agonist properties.

Objective

To compare clinical effects and medical outcomes between TAP and TRA exposures reported to the National Poison Data System of the American Association of Poison Control Centers.

Methods

A retrospective cohort study was conducted analyzing national data for single medication TAP or TRA cases reported from June 2009 through December 2011. Case outcomes, dichotomized as severe versus mild; clinical effects; and use of naloxone were compared.

Results

There were 217 TAP and 8566 TRA cases. Significantly more severe outcomes were associated with TAP exposures for an all-age comparison (relative risk [RR] = 1.24; 95% CI = 1.04-1.48), and for the <6-year-old age group (RR = 5.76; 95% CI = 2.20-15.11). Patients with TAP exposures had significantly greater risk of respiratory depression (RR = 5.56; 95% CI = 3.50-8.81), coma (RR = 4.16; 95% CI = 2.33-7.42), drowsiness/lethargy (RR = 1.38; 95% CI = 1.15-1.66), slurred speech (RR = 3.51; 95% CI = 1.98-6.23), hallucination/delusion (RR = 7.25; 95% CI = 3.61-14.57), confusion (RR = 2.54; 95% CI = 1.56-4.13) and use of naloxone (RR = 3.80; 95% CI = 2.96-4.88). TRA exposures had significantly greater risk of seizures (RR = 7.94; 95% CI = 2.99-20.91) and vomiting (RR = 1.96; 95% CI = 1.07-3.60).

Conclusion

TAP was associated with significantly more toxic clinical effects and severe outcomes consistent with an opioid agonist. TRA was associated with significantly higher rates of seizures and vomiting.

Introduction

In response to the opioid epidemic, California state officials sought to fund a variety of projects aimed at reducing opioid-related deaths. We describe the California Poison Control System's (CPCS) successful effort in integrating itself into the state's public health response to the opioid epidemic and describe poison control center staff attitudes and perceptions regarding the role of poison control centers at treating opioid withdrawal and addiction.

Methods

The CPCS created a leadership team and a separate 24/7 hotline, called the CPCS-Bridge line, to field calls from frontline health care providers interested in initiating medications for opioid use disorder for their patients. The implementation process also included training of all CPCS staff. In addition, the leadership team conducted an anonymous survey study to analyze attitudes and perceptions of poison center staff on the role of the poison center in the management of opioid use disorder. Descriptive statistics were used to characterize the data.

Results

Calls to the new hotline increased over time, along with CPCS-initiated outreach and advertisement. A majority of questions received by the hotline were related to uncomplicated buprenorphine starts in special populations. A pre-training survey was completed by 27 (58%) of CPCS specialists, many of whom had no prior experience treating patients with opioid use disorder. Only one specialist (2%) did not believe that poison centers should play a role in opioid addiction.

Conclusions

The California Poison Control System successfully created a hotline to assist frontline health care providers in treating patients with opioid use disorder and highlight the critical role of poison centers in the public health domain. Increased federal funding to poison centers is likely to be mutually beneficial to all parties involved.

Objectives

The Internet may be the first source of information used by parents during a suspected poisoning of their children. Our primary aim was to assess the reliability of the Internet as a resource for information for parents to initially manage a suspected poisoning involving their child without outside consultation.

Methods

We distributed a self-administered survey to English-speaking parents to evaluate their Internet access behaviors so we could emulate their search strategies for a poisoning. A panel of clinical toxicologists performed an evaluation of Websites to determine the proportion that provided accurate and adequate information on common substances involved in poisonings.

Results

Of 21 parents surveyed, 15 (71%) used the Internet daily, with Google and Yahoo being the most commonly used search engines. Seven parents (39%) were somewhat to very likely to utilize the Internet during a poisoning scenario with prescription medications involving their child. Overall, only 27 (38%) of the Websites reviewed advised the user to call the poison center with the proper 800 telephone number, whereas no Website provided adequate information to manage the poisoning without outside consultation. Few Websites provided information on the toxic dose (13%), how to determine whether to manage the poisoning at home or in a hospital (22%), or first aid (28%).

Conclusions

The information provided on the Internet for substances involved in poisonings is variable and often incomplete. Reliance on the Internet for poisonings could create needless delays and inappropriate assessments and actions to manage a pediatric poisoning incident.

Introduction

Since 2012, eighteen states and the District of Columbia have legalized recreational cannabis. Past research suggests this policy change is associated with increased cannabis exposures however this has not yet been studied in California, despite its status as the world's largest legal cannabis market.

Methods

This observational, retrospective study analyzed trends in cannabis exposures reported to the California Poison Control System (CPCS) from 2010 to 2020. We assessed shifts in exposures before and after the legalization of recreational cannabis in November 2016, the establishment of recreational retail sales in January 2018, and the institution of a statewide shelter-in-place order due to the COVID-19 pandemic in March 2020 using interrupted time-series analysis and reviewed all records to identify specific products associated with exposures.

Results

Between 2010 and 2020 edible exposures increased from near zero to 79% of exposures in 2020. Cannabis exposures significantly increased following recreational legalization in 2016 (by an estimated 2.07 exposures per month [CI: 0.60, 3.55]; p < 0.01) and initiation of retail sales in 2018 (0.85 [CI: 0.12, 1.58]; p < 0.05). There was no significant change in cannabis exposures following the first shelter-in-place order of the COVID-19 pandemic (1.59 [CI: -1.61, 3.68]; p = 0.43). Cannabis exposures for those thirteen and under increased significantly both after recreational legalization (1.04 [CI: 0.38, 1.70]) and after the opening of the retail sales market (0.73 [CI: 0.34, 1.12]), but not following the shelter-in-place order (1.59 [CI: -1.61, 3.68]), nor was there a significant change for those older than thirteen.

Conclusions

Our findings suggest that cannabis legalization is linked to increased exposures, particularly for products such as gummies and candy edibles among children under the age of thirteen. Clinicians should be aware of these risks and communicate them to patients, and policymakers should consider stronger regulations on packaging to reduce these exposures.Key pointsQuestion: How have cannabis exposures changed following legalization of recreational use, the opening of the recreational retail sales market, and the institution of shelter-in-place orders during the COVID-19 pandemic?Findings: In this retrospective review of 10,757 cases reported to the California Poison Control System (CPCS) between 2010 and 2020, exposures increased significantly after the legalization of recreational cannabis use and the opening of the recreational retail sales market, particularly among children, who primarily consumed candies and gummies.Meaning: Stronger regulation of cannabis edibles that mimic other products is warranted to decrease exposures among children.

Background

Cannabis exposures reported to the California Poison Control System increased following the initiation of recreational cannabis sales on 1 January 2018 (i.e., "commercialization"). We evaluated whether local cannabis control policies adopted by 2021 were associated with shifts in harmful cannabis exposures.

Methods

Using cannabis control policies collected for all 539 California cities and counties in 2020-2021, we applied a differences-in-differences design with negative binomial regression to test the association of policies with harmful cannabis exposures reported to California Poison Control System (2011-2020), before and after commercialization. We considered three policy categories: bans on storefront recreational retail cannabis businesses, overall restrictiveness, and specific recommended provisions (restricting product types or potency, packaging and labeling restrictions, and server training requirements).

Results

Localities that ultimately banned storefront recreational retail cannabis businesses had fewer harmful cannabis exposures for children aged <13 years (rate ratio = 0.82; 95% confidence interval = 0.65, 1.02), but not for people aged >13 years (rate ratio = 0.97; 95% confidence interval = 0.85, 1.11). Of 167 localities ultimately permitting recreational cannabis sales, overall restrictiveness was not associated with harmful cannabis exposures among children aged <13 years, but for people aged >13 years, a 1-standard deviation increase in ultimate restrictiveness was associated with fewer harmful cannabis exposures (rate ratio = 0.93; 95% confidence interval = 0.86, 1.01). For recommended provisions, estimates were generally too imprecise to detect associations with harmful cannabis exposures.

Conclusion

Bans on storefront retail and other restrictive approaches to regulating recreational cannabis may be associated with fewer harmful cannabis exposures for some age groups following statewide commercialization.

Parthenolide, a natural product from the feverfew plant and member of the large family of sesquiterpene lactones, exerts multiple biological and therapeutic activities including anti-inflammatory and anti-cancer effects. Here, we further study the parthenolide mechanism of action using activity-based protein profiling-based chemoproteomic platforms to map additional covalent targets engaged by parthenolide in human breast cancer cells. We find that parthenolide, as well as other related exocyclic methylene lactone-containing sesquiterpenes, covalently modify cysteine 427 of focal adhesion kinase 1 (FAK1), leading to impairment of FAK1-dependent signaling pathways and breast cancer cell proliferation, survival, and motility. These studies reveal a functional target exploited by members of a large family of anti-cancer natural products.