PC-FACS

Abstract

PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PC-FACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at [email protected] PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PC-FACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at [email protected] Pavisian B, MacIntosh BJ, Szilagyi G, et al. Effects of cannabis on cognition in patients with MS: a psychometric and MRI study. Neurology 2014;82:1879-1887. Rahn EJ, Deng L, Thakur GA, et al. Prophylactic cannabinoid administration blocks the development of paclitaxel-induced neuropathic nociception during analgesic treatment and following cessation of drug delivery. Mol Pain 2014;10:27. Gates PJ, Albertella L, Copeland J. The effects of cannabinoid administration on sleep: a systematic review of human studies Sleep Med Rev 2014 March 7. [Epub ahead of print]. Lutge EE, Gray A, Siegfried N. The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS. Cochrane Database Syst Rev 2013;4:CD005175. Koppel BS, Brust JC, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82:1556-1563. Van den Elsen GAH, Ahmed AIA, Lammers M, et al. Efficacy and safety of medical cannabinoids in older subjects: a systematic review. Ageing Res Rev 2014;14:56-64. Bottorff JL, Bissell LJ, Balneaves LG, et al. Perceptions of cannabis as a stigmatized medicine: a qualitative descriptive study. Harm Reduct J 2013;10:2. Salomonsen-Sautel S, Min SJ, Sakai JT, Thurstone C, Hopfer C. Trends in fatal motor vehicle crashes before and after marijuana commercialization in Colorado. Drug Alcohol Depend 2014;140:137-144. Wang GS, Roosevelt G, Heard K. Pediatric marijuana exposures in a medical marijuana state. JAMA Pediatr 2013;167:630-633. Ache K, Harrold J, Harris P, Dougherty M, Casarett D. Are advance directives associated with better hospice care? J Am Geriat Soc 2014;62:1091-1096. Wolfe J, Orellana L, Cook EF, et al. Improving the care of children with advanced cancer by using an electronic patient-reported feedback intervention: results from the PediQUEST randomized controlled trial. J Clin Oncol 2014;32:1119-1126. Huffman JC, Mastromauro CA, Beach SR, et al. Collaborative care for depression and anxiety disorders in patients with recent cardiac events: the Management of Sadness and Anxiety in Cardiology (MOSAIC) randomized clinical trial. JAMA Intern Med 2014;174:927-935. Dev R, Hui D, Del Fabbro E, et al. Association between hypogonadism, symptom burden, and survival in male patients with advanced cancer. Cancer 2014;120:1586-1593. Sinha M, Jang YC, Oh J, et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science 2014;344:649-652. Xafis V, Wilkinson D, Gillam L, Sullivan J. Balancing obligations: should written information about life-sustaining treatment be neutral? J Med Ethics 2014 Apr 24. [Epub ahead of print]. Payot A, Gendron S, Lefebvre F, Doucet H. Deciding to resuscitate extremely premature babies: how do parents and neonatologists engage in the decision? Soc Sci Med 2007;64 When we began planning this issue on cannabinoids, we didn't know how timely it would be. Yet recent events remind us that medicine has a sociocultural context: the August 3rd New York Times featured a full-page advertisement congratulating New York State on passing the Compassionate Care Act and advocating for the use of marijuana varietals for multiple sclerosis (MS) and cancer symptoms. Cannabinoids may be helpful analgesics for neuropathic pain in HIV, diminish symptoms of MS, and help manage chemotherapy-associated nausea. However, there is no clinical evidence that cannabinoids (in whole leaf or any pharmaceutical formulation) are superior to available treatments. I've seen them work, whatever that means. However, cannabinoids are not risk-free,1 and although these risks may be less important to palliative care patients than to others, they are significant for a society contemplating widespread access. It's also possible that “Big Marijuana” would promote as recklessly in the 21st century as “Big Tobacco” did in the 20th.2 In the United States, we have two U.S. Food and Drug Administration–approved cannabinoid drugs—dronabinol and nabilone—and may soon have a third—nabiximols, which is already available in Canada and England. But the uncertain chemical composition of whole-leaf marijuana limits meaningful discussions. Perhaps greater use of pharmaceutical cannabinoids will allow us to figure out what we're talking about. Sincerely, Thomas B. Strouse, MD, Senior Section Editor, Psychosocial 1.Volkow ND, Baler RD, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med 2014;370:2219-2227.2.Richter KP, Levy S. Big marijuana—lessons from big tobacco. N Engl J Med 2014;371:399-401. In patients with multiple sclerosis (MS), cannabis exacerbates problems with working memory,1 information processing speed, and executive dysfunction.2 Are there neural correlates of these effects? This was a cross-sectional imaging study of cognition among MS patients who smoke cannabis. Eligible individuals had an MS diagnosis; regularly used cannabis (positive urine test for metabolites); and had no history of brain injury, illicit drug use (excluding cannabis), alcohol abuse, concurrent neurologic or psychiatric diseases, or steroid use within 3 months. Controls (nonusers) were group-matched on demographic and disease-related variables. Participants abstained from cannabis for 12 hours before testing. Imaging data collected were an fMRI performed during completion of a working memory test (N-Back), resting-state fMRI, and structural MRI (lesion and normal-appearing brain tissue volumes, diffusion tensor imaging). Neuro-psychological data collected were verbal memory (Selective Reminding Test Revised), visual memory (10/36 Spatial Recall Test), information processing speed (Paced Auditory Serial Addition Test [PASAT], Symbol Digit Modalities Test), and attention (Word List Generation). Participants (N = 39) were mean age 42 years and 31% female. No between-group differences in resting-state networks or structural MRI variables were found. Cannabis users had more diffuse cerebral activation across all N-Back trials. They made more errors on the 2-Back task (P = 0.006), displaying greater activation than controls in working memory regions (parietal [P = 0.007] and anterior cingulate [P =0.001]). The cannabis group performed worse on the 2-second PASAT (P < 0.02) and 10/36 test (P < 0.03). Global cognitive impairment did not correlate with frequency of cannabis use or urine concentration of cannabis metabolites (both r = 0.32; both P = 0.17). The key finding in this well-designed trial in patients with MS is that marijuana, used primarily for spasticity, exacerbated baseline difficulties with some elements of cognition. Verbal memory and attention were unimpaired, but increasing task complexity demonstrated deficits that correlated with marijuana use. As with all other agents, the use of cannabinoids for symptom management in hospice and palliative medicine patients should be based on patients' goals of care, the efficacy of the drug's use (not explored in this article), and potential side effects that may limit the ability to work or complete complex tasks as shown in this study. Marijuana, like most of our interventions, is not an entirely benign drug. Chronic marijuana use causes functional changes in the brains of patients with MS that correlate with impaired cognition, most noticeably as task complexity increases. Tommie W. Farrell, MD, Texas Tech University Health and Science Center School of Medicine, Lubbock, TX. Pavisian B, MacIntosh BJ, Szilagyi G, et al. Effects of cannabis on cognition in patients with MS: a psychometric and MRI study. Neurology 2014;82:1879-1887. 1.Ghaffar O, Feinstein A. Multiple sclerosis and cannabis: a cognitive and psychiatric study. Neurology 2008;71: 164-169.2.Honarmand K, Tierney MC, O'Connor P, Feinstein A. Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology 2011;76:1153-1160. Neuropathic pain is a dose-limiting chemotherapy side effect and a major factor in treatment discontinuation.1,2 Can prophylactic cannabinoids help prevent paclitaxel-induced nociception? This preclinical study built on prior findings that cannabinoid agonists suppress paclitaxel-induced neuropathic nociception in animal models through activation of both CB1 and CB2 cannabinoid receptor subtypes.3,4 The investigators administered to rats WIN55,212-2 (a CB1 and CB2 agonist) and AM1710 (a CB2-preferring agonist) before, during, and after paclitaxel treatment, continuously infusing these cannabinoids subcutaneously via osmotic mini-pumps. Development of mechanical and cold allodynia (common clinical manifestations of paclitaxel-induced neuropathy) was then evaluated. Pharmacological specificity was assessed using CB1 and CB2 antagonists. Impact on transcriptional regulation of mRNA markers of astrocytes (GPAF), microglia (CD11b), and cannabinoid receptors (CB1, CB2) was assessed in lumbar spinal cords of paclitaxel- and vehicle-treated rats. Both WIN55,212-2 and AM1710 blocked the development of paclitaxel-induced mechanical and cold allodynia; effects persisted for 2-3 weeks following drug cessation. WIN55,212-2 suppressed development of both mechanical and cold allodynia. CB1 activation dominated the suppression of mechanical hypersensitivity; blockade by either CB1 or CB2 antagonists did not significantly alter cold allodynia. AM1710 suppressed mechanical allodynia but only suppressed cold allodynia at the highest dose. CB2 mediated the anti-allodynic effects of AM1710; the duration of efficacy was longer than that induced by WIN55,212-2. mRNA expression of GFAP was marginally increased by paclitaxel treatment; expression of CD11b was unchanged. Both WIN55,212-2 and AM1710 increased CB1 and CB2 mRNA expression in lumbar spinal cords; AM630 (a CB2 antagonist) blocked this effect. This preclinical study using an animal model for paclitaxel-induced mechanical and cold allodynia showed cannabinoids prevent the development of neuropathy and continue to protect against neuropathy even after discontinued. The contribution of the CB1 and CB2 receptors to antinociception varied, with CB1 being more important in preventing mechanical allodynia, and the selective CB2 agonist produced a longer duration of benefit. Other than up-regulation of cannabinoid receptors, the mechanism of the antinociceptive action remains unclear because microglia or astrocyte mRNA expression was not significantly increased. Although prior preclinical studies3,4 have shown that CB1 and CB2 receptors mediate antinoceptive effects, a randomized, controlled trial showed no statistical difference between cannabinoids and placebo in treating patients with established chemotherapy-induced peripheral neuropathy.5 Cannabinoids prevent paclitaxel-induced peripheral neuropathic pain in an animal model but need to be evaluated in controlled human studies before their prophylactic use can be recommended. Egidio Del Fabbro, MD, Virginia Commonwealth University, Richmond, VA. Rahn EJ, Deng L, Thakur GA, et al. Prophylactic cannabinoid administration blocks the development of paclitaxel-induced neuropathic nociception during analgesic treatment and following cessation of drug delivery. Mol Pain 2014;10:27. 1.Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C. Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur J Cancer. 2008;44(11):1507-1515.2.Kannarkat G, Lasher EE, Schiff D: Neurologic complications of chemotherapy agents. Curr Opin Neurol 2007;20:719-725.3.Pascual D, Goicoechea C, Suardíaz M, Martín MI. A cannabinoid agonist, WIN55,212-2, reduces neuropathic nociception induced by paclitaxel in rats. Pain 2005;118:23-34.4.Rahn EJ, Zvonok AM, Thakur GA, et al. Selective activation of cannabinoid CB2 receptors suppresses neuropathic nociception induced by treatment with the chemotherapeutic agent paclitaxel in rats. J Pharmacol Exp Ther 2008;327: 584-591.5.Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage 2014;47:166-173. Use of cannabis for medical purposes remains contested. This literature review searched eight electronic databases for clinical studies that included cannabinoid administration and one or more quantitative measures of sleep. A custom-built assessment of article quality and risk of bias was applied. Thirty-nine articles met the inclusion criteria. Many studies were old; sample sizes were often small. Studies overwhelmingly contained a substantial risk of bias, often not controlling for other substance use, using measures without psychometric validation, and failing to blind participants. Conclusions cannot be drawn, but evidence suggests that cannabis use may cause a decrease in slow wave sleep time, and correspondingly more time spent in stage 2 sleep, but no consistent effect on total sleep time. There may be a small dose effect. Medicinal cannabis users with preexisting sleep-interrupting symptoms (e.g., pain) may benefit. This Cochrane review searched CENTRAL/CCTR; MEDLINE; Embase; and journals, reference lists, and conference proceedings for quasirandomized/randomized, controlled trials of cannabis, smoked or ingested, versus placebo or other treatment. Primary outcomes were mortality and morbidity (frequency, type, duration of episodes of infection; malignancies; AIDS incidence; hospital admissions; other illnesses). Secondary outcomes included weight, appetite, pain, mood, and quality of life. Eight articles (seven studies) were included. Studies had short durations (21-84 days). Insufficient information and bias risk prevent conclusions; evidence for substantial effects was slim. Data from one study (N = 139) could be analyzed. Participants who received dronabinol were more likely to gain 2 kg or more than participants receiving placebo (RR, 2.1; 95% CI, 0.7-6.1). Mean weight gain among dronabinol recipients was 0.1 kg, versus -0.4 kg (placebo). This systematic review searched MEDLINE, Embase, PsycINFO, Web of Science, and Scopus for studies evaluating cannabis for symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. Effectiveness varied with different formulations (oral cannabis extract, nabiximols, tetrahydrocannabinol). In patients with MS, some benefit was reported for spasticity, central pain/painful spasms, and urinary dysfunction. Little evidence of effectiveness was found for other neurologic conditions. Risk of serious adverse psychopathologic effects was nearly 1%. Most commercially available cannabinoids target CB1 receptors, except nabiximols, which also contain cannabidiol which targets nonclassic (CB1, CB2) receptors There is conflicting data concerning cannabinoids' effects on sleep architecture. Cannabidiol may actually be activating. The most consistent finding is subjective sleep improvement for those in pain. Cannabinoids increased weight (predominantly fat), reduced nausea and peripheral neuropathic pain (numbers needed to treat [NNT], 5), and minimally reduced protease inhibitor levels in HIV-infected individuals. Weight gain was only 0.1 kg on average, which may not be clinically relevant. HIV-infected individuals treated with cannabinoids experience more severe adverse events (8.3%) relative to placebo. For patients with MS, subjective but not objective spasticity is reduced, central pain improves (NNT, 5-8), and bladder spasms improve only with nabiximols, suggesting that cannabidiol is the important cannabinoid. Posture and balance worsen with cannabinoids. The data do not justify the widespread use of “medicinal cannabis” and self-prescribing. The development of cannabinoids selective for CB2 receptors, “orphan receptors,” and transient potential receptors will have a greater therapeutic index and safety margin and should be pursued in clinical trials. My fear is that widespread public use of “medicinal cannabis” will contaminate these trials. Commercially available cannabinoids improve sleep in individuals with pain and improve several other symptoms in patients with HIV and MS. Mellar P. Davis, MD, FCCP, FAAHPM, Taussig Cancer Institute, The Cleveland Clinic, Cleveland, OH. Gates PJ, Albertella L, Copeland J. The effects of cannabinoid administration on sleep: a systematic review of human studies Sleep Med Rev 2014 March 7. [Epub ahead of print]. Lutge EE, Gray A, Siegfried N. The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS. Cochrane Database Syst Rev 2013;4:CD005175. Koppel BS, Brust JC, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82:1556-1563. International Web-based surveys show a low percentage of older users of medical cannabis, but in the Netherlands, more than 33% of prescription users are older than 60 years.1,2 Is medical marijuana safe and effective for older people? This Dutch systematic review searched PubMed, Embase, CINAHL, and Cochrane Library databases for therapeutic studies of cannabis for older patients. Eligible studies were prospective, controlled, intervention trials that included exclusively older participants (age 65 years or older) or provided separate results for this subgroup and that studied and reported the efficacy, safety, or pharmacokinetics of medical cannabinoids. Quality assessment was conducted using a modified Effective Practice and Organization of Care form. A consensus-based risk of bias table was constructed. Five studies met the inclusion criteria (N = 267); all were randomized, controlled trials with crossover design. Interventions studied were oral tetrahydro-cannabinol (THC; three studies) and oral THC combined with cannabidiol (two studies). Meta-analysis was infeasible because of the great clinical and methodological diversity across studies; four of five studies showed a moderate to high risk of bias in several domains. Results were analyzed through qualitative, descriptive summarization. No evidence of efficacy was found to support the use of medical cannabis to improve dyskinesia, breathlessness, and chemotherapy-induced nausea and vomiting. Two studies showed THC to be beneficial in treating anorexia and behavioral symptoms in dementia; small sample sizes and low/moderate methodological quality prevented definitive conclusions. Despite the relatively low doses used, adverse events were more frequently reported with cannabinoids versus control; most adverse events concerned neuropsychiatric symptoms (e.g., drowsiness, tiredness, somnolence). American society is increasingly open to the potential therapeutic uses of marijuana and cannabinoid pharmaceuticals. Twenty-three states and the District of Columbia have legalized medical cannabis, and two have legalized recreational use (Colorado and Washington). Medical marijuana may provide symptom relief for some acute and chronic medical conditions, particularly in our aging population. In this review, adverse effects deterred treatment, with improvement seen only in anorexia and dementia. Palliative medicine providers, who often care for elderly patients with multiple comorbidities, may benefit from recognizing the potential palliative value of cannabinoids. Cannabis has shown potential benefit as an appetite stimulant, antiemetic, antispasmodic, and analgesic but has been inadequately studied in the elderly.3 Better studies are needed to evaluate the safety and efficacy of cannabinoids in the geriatric population. The potential value of medical cannabis in elderly patients will hopefully drive more research on its safety and effectiveness in this vulnerable population. David B. Brecher, MD, FAAFP, FAAHPM, Tacoma General Hospital, MultiCare Health System, Tacoma, WA. Van den Elsen GAH, Ahmed AIA, Lammers M, et al. Efficacy and safety of medical cannabinoids in older subjects: a systematic review. Ageing Res Rev 2014;14:56-64. 1.Hazekamp A, Heerdink ER. The prevalence and incidence of medicinal cannabis on prescription in the Netherlands. Eur J Clin Pharmacol 2013;69:1575-1580.2.Hazekamp A, Ware MA, Muller-Vahl KR. The medicinal use of cannabis and cannabinoids—an international cross-sectional survey on administration forms. J Psychoactive Drugs 2013;45:199-210.3.Ben Amar M. Cannabinoids in medicine: a review of their therapeutic potential. J Ethnopharmacol 2006;105: 1-25. Despite changes in public attitudes toward marijuana, users of cannabis for therapeutic purposes (CTP) continue to experience stigma and risk related to CTP use, particularly in interactions with authorities including employers, landlords, and law enforcement.1,2 How do users perceive and respond to the stigma associated with CTP? This Canadian, qualitative, descriptive study utilized qualitative methods, inductive analysis, and purposive sampling to develop an in-depth understanding of the experiences of CTP users. Participants were recruited through four community-based cannabis dispensaries in British Columbia and an online forum (2007-2008). Eligible individuals were age 19 years or older and reported using CTP in the last 30 days and for more than six consecutive months. Data were collected in semistructured, individual face-to-face or telephone interviews lasting 1-3 hours. Interview transcripts were analyzed using an inductive thematic approach. Participants (N = 23) were mean age 45 years (range, 25-66) and 57% female with an average annual income of $21,000. Participants described many experiences of stigma associated with their CTP use, arising in interactions with family, close friends, and others. Three dimensions of stigma were identified: others' negative views of cannabis as a recreational drug, others' assumption of or perspective on illegal activity surrounding cannabis use, and participants' vulnerabilities related to poverty and particular illnesses/disabilities. Most participant experiences touched on one or more dimensions. Participants described efforts to negotiate social censorship, disapproval, threats, and isolation. Principal coping strategies were keeping CTP use undercover, convincing others of CTP benefits, being responsible in their use of CTP, and actively defending their right to choose their medication. More than 80% of Americans favor legalizing medical cannabis, and 23 states and the District of Columbia have already done so.3 The number of patients using medical cannabis ranges from 1% of the population in Vermont to 21% in Colorado, with a national average of 7%.4 There is data supporting medical cannabis for HIV neuropathy and wasting, chemotherapy-related nausea, and multiple sclerosis-related spasticity,5 although many websites promote its use for diverse diseases ranging from Alzheimer's to arthritis.6 What this study showed is that even where medical cannabis is legal, patients feel stigmatized by health care professionals, workers, and family for using it. They react by becoming socially withdrawn, not telling others and limiting their interactions with health care providers. Even when medicines are legal, patients may feel stigmatized by their use and respond by withdrawing; therefore, asking about this issue is important. Robert M. Arnold, MD, FAAHPM, University of Pittsburgh Palliative and Supportive Institute, UPMC Health System, Pittsburgh, PA. Bottorff JL, Bissell LJ, Balneaves LG, et al. Perceptions of cannabis as a stigmatized medicine: a qualitative descriptive study. Harm Reduct J 2013;10:2. 1.Hathaway AD. Cannabis users' informal rules for managing stigma and risk. Deviant Behav 2004;25:559-577.2.Johnson BD, Ream GL, Dunlap E, Sifaneck SJ. Civic norms and etiquettes regarding marijuana use in public settings in New York City. Subst Use Misuse 2008;43:895-918.3.Wikipedia website. Medical cannabis in the United States. Wikipedia website. Available from http://en.wikipedia.org/wiki/Medical_cannabis_in_the_United_States. Accessed July 19, 2014.4.ProCon.org. How many people in the United States use medical marijuana? Available from http://medicalmarijuana.procon.org/view.answers.php?questionID=001199. Accessed July 19, 2014.5.Grant I, Hampton Atkinson J, Gouax B, Wilsey B. Medical marijuana: clearing away the smoke. Open Neurol J 2012;6: 18-25.6.ProCon.org. Disease/conditions. Available from http://medicalmarijuana.procon.org/view.subissues.php?issueID=000029. Accessed July 19, 2014. Medical marijuana became legal and commercially available in Colorado mid-2009. This retrospective data analysis utilized records from the Fatality Analysis Reporting System from 1994-2011. Analyses were completed for Colorado and all 34 states that did not have medical marijuana laws through 2011. Colorado's post-commercialization period for marijuana was defined as July 2009-2011. Temporal changes in proportions of drivers in a fatal motor vehicle crash (MVC) who were alcohol-impaired (≥ 0.08 g/dl) or marijuana-positive were examined. In Colorado, the trend in proportion of drivers in fatal MVCs who were marijuana-positive was negative before mid-2009 (t = -2.4; P = 0.02), and positive after mid-2009 (t = 4.8; P = 0.0001). This proportion was erratic over the precommercialization period, then climbed sharply from 5.9% in the first half of 2009 to 10% in late 2011. No significant changes were seen in states without legalized marijuana, or in proportions of drivers in fatal MVCs who were alcohol-impaired in Colorado or other states. This retrospective cohort study was conducted in a tertiary-care children's hospital emergency department (ED) in Colorado. Eligible individuals were age 12 years or younger and evaluated for toxic ingestion from 2005-2011. The proportion of marijuana ingestions before/after modification of relevant Colorado drug enforcement laws (before/after October 2009) was compared. Participants (N = 1378) were 790 before and 588 after; median age (IQR) 2.6 years (1.6-3.0) and 2.3 years (1.5-3.6), respectively; and 57% male. From 2005 to September 30, 2009, no patients age 12 years or younger presented at the ED with marijuana ingestion. From October 1, 2009, through 2011, 14 patients in this age bracket had confirmed marijuana ingestion (urine toxicology screen). The age of exposed patients ranged from 8 months to 12 years; 64% were male. Most had central nervous system effects (e.g., lethargy, somnolence); respiratory insufficiency was the most serious symptom. These two studies demonstrate that there are hidden costs to medical marijuana use. Although the overall car crash fatality did not increase in Colorado after 2009, marijuana's role in these deaths doubled after legalization. Tests are currently not quantitative and it is not known whether there is a safe threshold. In the pediatric intoxication study, important takeaways are that the “medications” were often in candy, baked goods, or soft drinks; that ingestions were not acknowledged, whether unobserved or socially embarrassing, leading to invasive and expensive work-ups; and that most of these “medications” belonged to grandparents, who are potentially hospice and palliative care patients. There is no child-proofing or warning required at present for medical marijuana. Patients and families should be made aware of impaired driving concerns and alerted to keep “medications” in any form, including food substances, out of the reach of children. Medical marijuana poses an increased risk of vehicular death and child injury. Marcia Levetown, MD, FAAHPM, HealthCare Communication Associates, Houston, TX. Salomonsen-Sautel S, Min SJ, Sakai JT, Thurstone C, Hopfer C. Trends in fatal motor vehicle crashes before and after marijuana commercialization in Colorado. Drug Alcohol Depend 2014;140:137-144. Wang GS, Roosevelt G, Heard K. Pediatric marijuana exposures in a medical marijuana state. JAMA Pediatr 2013;167:630-633. Growing evidence suggests that advance directives (ADs) are associated with less aggressive treatments and better patient outcomes in various health care settings.1-3 Do patients with versus without ADs at hospice enrollment have different patterns of care and outcomes? This retrospective cohort study used electronic health records from three hospices participating in the Coalition of Hospices Organized to Investigate Comparative Effectiveness (CHOICE) network. Eligible individuals were admitted to hospice between 2008 and 2012. Extracted data included documentation of AD at time of admission, demographic and clinical data, site of care, and Palliative Performance Status score. Propensity score was used to create a logistic regression model that accommodated nonrandom assignment between groups (AD, no AD). Outcomes of interest were timing of enrollment in hospice relative to death, rates of voluntary withdrawal from hospice, and site of death. Of the total participants (N = 49,370), participants with ADs (n = 35,968) were mean age 81 years (IQR, 75-90), 42% male, and 91% white; part