8/8/2018 This Talk…. Sources of Topics • ACP Journal Club Advances in Primary Care: • Residency Journal Clubs Recent Important Papers • Faculty Suggestion Douglas C. Bauer, MD Guiding Principles Departments of Medicine and • Practical, Applicable, Interesting Epidemiology & Biostatistics • Topics that are not being covered elsewhere…. No Disclosures Topics! Case - Which of the Following Statements About Cannabis is False? 1- Cannabis: its legal, are we ready? A- It can administered orally, topically, inhaled or made 2- Knee injections for OA: benefits and harms synthetically B- 29 states have laws legalizing some use of medical 3- COPD treatment escalation cannabis 4- Firearms and public health C- RCT’s show reduction of chronic pain and spasticity 5- Coffee and mortality D- State legalization of cannabis is associated with reduced opiate use in that state E- Fatal car crashes are not associated with cannabis use 1
8/8/2018 Cannabis Legal Landscape Case - Which of the Following Statements about Cannabis is False? • 29 states allow public medical cannabis programs A- It can administered orally, topically, inhaled or made – Legal in 14 states : Alaska, Colorado, Maine, Michigan, synthetically Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont, Washington, Hawaii, and California. B- 29 states have laws legalizing some use of medical – California: $3.7 billion sales in first year (heavily taxed) cannabis • 175-250 million adults worldwide used in 2012 C- RCT’s show reduction of chronic pain and spasticity – Estimated 3-5% of world population – 14.0% US adolescents used in the past 30 days in 2015 D- State legalization of cannabis is associated with • Federal laws reduced opiate use in that state – restrict study E- Fatal car crashes are not associated with cannabis use http://www.ncsl.org/research/health/state- medical-marijuana-laws.aspx Cannabis- Some Fun Facts Cannabinoids and CB1 Signal • Genus Cannabis-> tetrahydrocannabinol THC Endocannabanoids stimulates: CB1 CNS receptors modify cell • Spiritual use Assyrians 2500 BC response to neuro-transmitters CB2- effect inflammation, vascular • Smoking, vaporizing, eaten (tea, edibles), extracts cells – Effect onset minutes to hours Modify normal responses of cell • Euphoric and physical effects: THC/CBD react with same receptors • Highly biased advocates on both THC agonist, CBD antagonist- sides!! creates the imbalance of response https://www.youtube.com/watch?v=lkNIRZXraY4 https://en.wikipedia.org/wiki/Cannabis 2
8/8/2018 Meta-Analysis Cannabanoids Chronic Pain Reduction • 79 RCTs (only 4 with low risk of bias) 8 Trials • Benefits (heterogeneity diff preparations): >30% in pain – Chemo N/V response (28): 47 v 20% (OR= 3.82) Overall – Spasticity reduction (14): 0.76 scale (OR= 1.44) - OR 1.41 p=0.06 – HIV weight gain (4): less than megestrol (1) Neuropathic (6) – Sleep disorders (2-13): various indications- possible – Tourette Syndrome tic reduction (2): small benefit - OR 1.38 – Psychosis, anxiety, depression, glaucoma: insufficient Cancer (2) data to assess. - OR 1.41 Whiting, JAMA. 2015;313(24):2456-2473. Whiting, JAMA. 2015;313(24):2456-2473. Opiates and Cannabinoids Opioid Scripts and Cannabis • Opiate mortality 320% 2000-2015 • Baseline average opiate dose= 23.08/state • Implementation of MCL (any) • Can cannabis reduce opiate use? • 2.11 million reduction of daily doses per year • Active dispensaries (3.7 million) • Longitudinal Medicare D for opiates by state – Hydrocodone -2.3 mil (17%) – Predictor- medical – Morphine -0.361 mil (21%) cannabis law • Home cultivation (1.8 million) – Outcome- daily opioid – -1.3 mil hydrocodone (9%) doses – All statistically significant… – Bradford JAMA Intern Med. Published online April 2, 2018 3
8/8/2018 Cannabis and Memory Cannabis and Psych Disorders • Cognitive function • National Epidemiologic Survey on Alcohol and Related CARDIA cohort Conditions • 34,653 responders • 2852 (84.3%) past use, – Compare 2 waves 392 (11.6%) ongoing • 3 memory scales as • Subs Use OR 6.2 primary outcome • ETOH OR 2.7 • Verbal memory 0.13 units lower per 5 yr. use (p = .02) • Cannabis OR 9.5 • OR, for every 5 yr. of use • Any drug OR 2.6 1 of 2 participants will remember 1 word fewer • No association with from a list of 15 words Mood Disorders Auer et al. JAMA Intern Med. 2016 Blanco JAMA Psychiatry. 2016 Cannabis Recap Driving and Cannabis • Driving requires sensory, • Existing data behind motor, cognition societal opinion • April 20 th counterculture • Pain benefits/opiate “High Holiday” lowering • National Highway Traffic Safety Administration’s • Opportunities for synthetic • 25 years of data cannabinoids • Need for POC testing • RRI 1.12 (most in young) (breathalyzer) • Same excess mortality as Superbowl Sunday – Rapid decline in blood levels Staples JAMA Intern Med. 2018 4
8/8/2018 Case - COPD treatment Case - COPD treatment 56 year old woman with 25 pack years smoking 56 year old woman with 25 pack years smoking had PFTs due to persistent cough. Her FEV1 is had PFTs due to persistent cough. Her FEV1 is 80% predicted c/w (GOLD stage 1) COPD. In 80% predicted c/w (GOLD stage 1) COPD. In addition to smoking cessation you suggest which addition to smoking cessation you suggest which of the following to help slow deterioration of her of the following to help slow deterioration of her FEV1 over time. FEV1 over time. A- Starting a LABA A- Starting a LABA B- Starting a LAMA B- Starting a LAMA C- Starting a Steroid inhaler C- Starting a Steroid inhaler D- Short acting beta-agonist D- Short acting beta-agonist COPD- Is Common! Treat Gold 1-2 Disease? • Worldwide 12% prevalence • U.S. 14% age 40-70 • RCT 841 Chinese Patients- double blind • Stage 1-2, 80% of patients • Debate on how to Rx early stage disease 256 discontinued trial 383 Placebo 388 Tioptropium (LAMA) -Similar on baseline characteristics (80% smokers) - Same GOLD stage- all FEV1 >50% predicted https://samadimd.com Zhou et al. N Engl J Med. 2017 Sep 7;377(10):923-935 http://doi.org/10.15326/jcopdf.2.3.2014.0151 5
8/8/2018 Results Case – More COPD Tioptropium vs PBO Your next patient is a 66 year old ex-smoker • Average FEV1 diff whose FEV1 is 45% predicted. She is currently on =157ml p<0.001 albuterol monotherapy but has progressive cough and dyspnea. You suggest that she starts: • Range FVC diff =110-164 (NS) A- LAMA daily B- LABA, Glucocorticoid (inhaled)– dual therapy • COPD C- LABA, LAMA, Glucocorticoid- triple therapy exacerbations 29% D- Warn patient about short term increase CV risk vs 39% p=0.001 E- B and D NNT 10 per 2 yrs F- C and D COPD RCT Dual vs. Triple Therapy Case- More COBD • LAMA (umeclidinium)+LABA(vilanterol)+ Your next patient is a 66 year old ex-smoker GC (fluticasone) vs. LAMA+GC vs. whose FEV1 is 45% predicted. She is currently on LABA+LAMA albuterol monotherapy but has progressive cough • Outcome: 1 yr. Mod/Severe exacerbation and dyspnea. You suggest that she starts: • Lipson et al. N Engl J Med. 2018 Apr 18. A- LAMA daily Time to 1 st Flair B- LABA, Glucocorticoid (inhaled)– dual therapy HR= 0.85 C- LABA, LAMA, Glucocorticoid- triple therapy Rate D- Warn patient about short term increase CV risk 0.91 1.07 1.21 E- B and D RR 1 0.85 0.75 F- C and D 6
8/8/2018 New LAMA or LABA and CVD Case- Knee OA • Taiwan case-control study: longitudinal CVD Your next patient is a 55 year old female with risk with new LAMA or LABA use chronic R knee pain which limits her weekend hiking. Based upon her exam and xrays, she has knee OA. NSAID’s and Tylenol are unhelpful. What is the next step? A- Serial intra-articular knee injections B- Referral to structured exercise program C- Referral to yoga program D- Knee replacement consultation 1.5X increase in CV risk for 30 days of starting. Risk gone (or even reduced) with prevalent use Wang. JAMA Intern Med. 2018;178(2) Case- Knee OA Knee OA • Common complaint in Your next patient is a 55 year old female clinical practice with chronic R knee pain which limits her weekend hiking. Based upon her exam and • 9 million US adults, xrays, she has knee OA. NSAID’s and leading cause of Tylenol are unhelpful. What is the next disability step? • Inflammation-related A- Serial intra-articular knee injections damage B- Referral to structured exercise program • Benefits and harms of C- Referral to yoga program steroid injections D- Knee replacement consultation unclear 7
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