This Talk. Sources of Topics ACP Journal Club Advances in - - PowerPoint PPT Presentation

8/8/2018 1

Advances in Primary Care: Recent Important Papers

Douglas C. Bauer, MD Departments of Medicine and Epidemiology & Biostatistics No Disclosures

This Talk….

Sources of Topics

• ACP Journal Club
• Residency Journal Clubs
• Faculty Suggestion

Guiding Principles

• Practical, Applicable, Interesting
• Topics that are not being covered

elsewhere….

Topics!

1- Cannabis: its legal, are we ready? 2- Knee injections for OA: benefits and harms 3- COPD treatment escalation 4- Firearms and public health 5- Coffee and mortality Case - Which of the Following Statements About Cannabis is False?

A- It can administered orally, topically, inhaled or made synthetically B- 29 states have laws legalizing some use of medical cannabis C- RCT’s show reduction of chronic pain and spasticity D- State legalization of cannabis is associated with reduced opiate use in that state E- Fatal car crashes are not associated with cannabis use

8/8/2018 2 Case - Which of the Following Statements about Cannabis is False?

A- It can administered orally, topically, inhaled or made synthetically B- 29 states have laws legalizing some use of medical cannabis C- RCT’s show reduction of chronic pain and spasticity D- State legalization of cannabis is associated with reduced opiate use in that state E- Fatal car crashes are not associated with cannabis use

Cannabis Legal Landscape

• 29 states allow public medical cannabis programs

– Legal in 14 states: Alaska, Colorado, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont, Washington, Hawaii, and California. – California: $3.7 billion sales in first year (heavily taxed)

• 175-250 million adults worldwide used in 2012

– Estimated 3-5% of world population – 14.0% US adolescents used in the past 30 days in 2015

• Federal laws

– restrict study

http://www.ncsl.org/research/health/state- medical-marijuana-laws.aspx

Cannabis- Some Fun Facts

• Genus Cannabis-> tetrahydrocannabinol THC
• Spiritual use Assyrians 2500 BC
• Smoking, vaporizing, eaten (tea, edibles), extracts

– Effect onset minutes to hours

• Euphoric and physical effects:
• Highly biased advocates on both

sides!!

https://en.wikipedia.org/wiki/Cannabis

Cannabinoids and CB1 Signal

Endocannabanoids stimulates: CB1 CNS receptors modify cell response to neuro-transmitters CB2- effect inflammation, vascular cells Modify normal responses of cell THC/CBD react with same receptors THC agonist, CBD antagonist- creates the imbalance of response

https://www.youtube.com/watch?v=lkNIRZXraY4

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Meta-Analysis Cannabanoids

• 79 RCTs (only 4 with low risk of bias)
• Benefits (heterogeneity diff preparations):

– Chemo N/V response (28): 47 v 20% (OR= 3.82) – Spasticity reduction (14): 0.76 scale (OR= 1.44) – HIV weight gain (4): less than megestrol (1) – Sleep disorders (2-13): various indications- possible – Tourette Syndrome tic reduction (2): small benefit – Psychosis, anxiety, depression, glaucoma: insufficient data to assess.

Whiting, JAMA. 2015;313(24):2456-2473.

Chronic Pain Reduction

8 Trials >30% in pain Overall

• OR 1.41 p=0.06

Neuropathic (6)

• OR 1.38

Cancer (2)

• OR 1.41

Whiting, JAMA. 2015;313(24):2456-2473.

Opiates and Cannabinoids

• Opiate mortality 320% 2000-2015
• Can cannabis reduce opiate use?
• Longitudinal Medicare D for opiates by state

– Predictor- medical cannabis law – Outcome- daily opioid doses

Opioid Scripts and Cannabis

• Baseline average opiate dose= 23.08/state
• Implementation of MCL (any)
• 2.11 million reduction of daily doses per year
• Active dispensaries (3.7 million)

– Hydrocodone -2.3 mil (17%) – Morphine -0.361 mil (21%)

• Home cultivation (1.8 million)

– -1.3 mil hydrocodone (9%) – All statistically significant…

– Bradford JAMA Intern Med. Published online April 2, 2018

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Cannabis and Memory

• Cognitive function

CARDIA cohort

• 2852 (84.3%) past use,

392 (11.6%) ongoing

• 3 memory scales as

primary outcome

• Verbal memory 0.13 units

lower per 5 yr. use (p = .02)

• OR, for every 5 yr. of use

1 of 2 participants will remember 1 word fewer from a list of 15 words

Auer et al. JAMA Intern Med. 2016

Cannabis and Psych Disorders

• National Epidemiologic Survey on Alcohol and Related

Conditions

• 34,653 responders

– Compare 2 waves

• Subs Use OR 6.2
• ETOH OR 2.7
• Cannabis OR 9.5
• Any drug OR 2.6
• No association with

Mood Disorders

Blanco JAMA Psychiatry. 2016

Driving and Cannabis

• Driving requires sensory,

motor, cognition

• April 20th counterculture

“High Holiday”

• National Highway Traffic

Safety Administration’s

• 25 years of data
• RRI 1.12 (most in young)
• Same excess mortality as

Superbowl Sunday

Staples JAMA Intern Med. 2018

Cannabis Recap

• Existing data behind

societal opinion

• Pain benefits/opiate

lowering

• Opportunities for synthetic

cannabinoids

• Need for POC testing

(breathalyzer)

– Rapid decline in blood levels

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Case - COPD treatment

56 year old woman with 25 pack years smoking had PFTs due to persistent cough. Her FEV1 is 80% predicted c/w (GOLD stage 1) COPD. In addition to smoking cessation you suggest which

• f the following to help slow deterioration of her

FEV1 over time. A- Starting a LABA B- Starting a LAMA C- Starting a Steroid inhaler D- Short acting beta-agonist

Case - COPD treatment

56 year old woman with 25 pack years smoking had PFTs due to persistent cough. Her FEV1 is 80% predicted c/w (GOLD stage 1) COPD. In addition to smoking cessation you suggest which

• f the following to help slow deterioration of her

FEV1 over time. A- Starting a LABA B- Starting a LAMA C- Starting a Steroid inhaler D- Short acting beta-agonist

COPD- Is Common!

• Worldwide 12% prevalence
• U.S. 14% age 40-70
• Stage 1-2, 80% of patients
• Debate on how to Rx early stage disease

https://samadimd.com http://doi.org/10.15326/jcopdf.2.3.2014.0151

Treat Gold 1-2 Disease?

• RCT 841 Chinese Patients- double blind

383 Placebo 388 Tioptropium (LAMA)

• Similar on baseline characteristics (80% smokers)
• Same GOLD stage- all FEV1 >50% predicted

256 discontinued trial

Zhou et al. N Engl J Med. 2017 Sep 7;377(10):923-935

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Results

Tioptropium vs PBO

• Average FEV1 diff

=157ml p<0.001

• Range FVC diff

=110-164 (NS)

• COPD

exacerbations 29% vs 39% p=0.001 NNT 10 per 2 yrs

Case – More COPD

Your next patient is a 66 year old ex-smoker whose FEV1 is 45% predicted. She is currently on albuterol monotherapy but has progressive cough and dyspnea. You suggest that she starts: A- LAMA daily B- LABA, Glucocorticoid (inhaled)– dual therapy C- LABA, LAMA, Glucocorticoid- triple therapy D- Warn patient about short term increase CV risk E- B and D F- C and D

Case- More COBD

Your next patient is a 66 year old ex-smoker whose FEV1 is 45% predicted. She is currently on albuterol monotherapy but has progressive cough and dyspnea. You suggest that she starts: A- LAMA daily B- LABA, Glucocorticoid (inhaled)– dual therapy C- LABA, LAMA, Glucocorticoid- triple therapy D- Warn patient about short term increase CV risk E- B and D F- C and D

COPD RCT Dual vs. Triple Therapy

• LAMA (umeclidinium)+LABA(vilanterol)+

GC (fluticasone) vs. LAMA+GC vs. LABA+LAMA

• Outcome: 1 yr. Mod/Severe exacerbation
• Lipson et al. N Engl J Med. 2018 Apr 18.

Rate 0.91 1.07 1.21 RR 1 0.85 0.75

Time to 1st Flair HR= 0.85

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New LAMA or LABA and CVD

• Taiwan case-control study: longitudinal CVD

risk with new LAMA or LABA use

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

Your next patient is a 55 year old female with 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

Case- Knee OA

Your next patient is a 55 year old female with 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

Knee OA

• Common complaint in

clinical practice

• 9 million US adults,

leading cause of disability

• Inflammation-related

damage

• Benefits and harms of

steroid injections unclear

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A High Quality Trial of Knee Steroid Injections!

JAMA | Original Investigation

Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis A Randomized Clinical Trial

Timothy E. McAlindon, DM, MPH; Michael P. LaValley, PhD; William F. Harvey, MD; Lori Lyn Price, MAS; Jeffrey B. Driban, PhD; Ming Zhang, PhD; Robert J. Ward, MD

McAlindon et al, Jama May 16 2017

Study Design

• 2-year double blind RCT, 140 adults >45

– Symptomatic knee OA and synovitis

• Randomized to knee injections every 3 mo.

– 40 mg triamcinalone (1 ml) – Saline (1 ml)

• Outcomes:

– MR cartilage changes (0, 12, 24 mo.) – Pain on exam, WOMAC survey (every 3 mo.)

McAlinndon, Jama 2017

Serial MR Results

Outcome Triamcinalone (N=70) Saline (N=70) Cartilage Thickness (mm) Baseline 2 Year Change Baseline 2 Year Change Between Group Difference p-value Index Compart 2.43

• 0.21

2.34

• 0.10
• 0.11

(-0.16, -0.03)

• Both groups lost cartilage thickness
• Steroid group lost 0.11mm more…
• Clinical importance?

Pain and Function Results

• No difference in

pain score

• No difference in

self-reported function

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What Else Helps Knee OA?

X PLOS ONE April 2017

Trial of Yoga for OA

• RCT of Canadian women with knee OA

– Only 31 women, average age 68 – Three groups: yoga, traditional exercise, control group with meditation

• One hour supervised instruction 3 times a

week for 3 months

• Outcomes: Pain, mobility and strength

– Knee OA Score: Minimial Clinically Important Difference (MCID) = 8 unit change – Blinded assessment

Yoga and Traditional Exercise

p=0.003

Knee OA Summary

• Intra-articular knee corticosteroid

injections may hasten loss of cartilage

• No overall improvement in pain or function
• Likely significant placebo effect
• Individual patients may benefit. Whom?
• Exercise helps, yoga may be even

better…

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Firearms and Public Health

• Firearm death rates vary between

states, as do firearm laws

• 36,352 deaths (2015)

– 60.6% from suicide and 35.7% from homicide

• 7.9% more deaths in 2015 than in

2014

• U.S. death rate 11.3 per 100000

– range 3.1 in Mass. to 20.4 in Kentucky

Steinbrook JAMA Intern Med, 2018

Gun Laws and Firearm Deaths

• >3000 US

counties

• Compared

red to blue counties

• Red- least

restrictive gun laws

• Blue- most

restrictive

Kaufman JAMA Intern Med 2018

State Score 0-12 Based on 0-2 points Following categories: 1- dealer regs 2- background checks 3- license to buy 4- junk gun regs 5- reporting lost or stolen guns 6- multiple purchases Scores: 0- majority 10- California

Firearm Suicide

• Represents 2/3 of firearm related deaths

– Most lawfully purchased guns – Tightly associated with home state laws

Increase 35-43% Increase 22-35% No Increase

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Firearm Homicide

• Highest rates were for counties in states

with the weakest state laws

– Guns for crime more likely to cross states

Increase 33-38% Increase 15-22% NS No Increase

Firearm Conclusions

• 36,352 deaths from firearm injury in 2015
• A public health problem

– Smoking, traffic accidents, MD mistakes – Screen gun ownership with depression – Fund gun fatality research

• Because Congress has been unwilling or

unable to act, the need for effective state firearm laws and policies in the United States has never been greater as is funding for research on the topic

• Steinbrook JAMA Intern Med. 2018

Case- Coffee and Health?

Your brother drinks 5 cups of coffee a day and has done so for years without apparent ill effects. What advice to you give him? A- Reduce to 2 cups/d as more may increase risk of pancreatic cancer B- Reduce to 2 cups/d as more likely causes CVD C- Reduce to 4 cups/d as more likely increases mortality D- Carry on, moderate use may prolong life

Case- Coffee and Health?

Your brother drinks 5 cups of coffee a day and has done so for years without apparent ill effects. What advice to you give him? A- Reduce to 2 cups/d as more may increase risk of pancreatic cancer B- Reduce to 2 cups/d as more likely causes CVD C- Reduce to 4 cups/d as more likely increases mortality D- Carry on, moderate use may prolong life

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Coffee Please!

• Most common source
• f caffeine
• 2.25 billion cups/d
• Linked to lower

inflammation markers, insulin resistance

• Little data on cause-

specific mortality among coffee drinkers

• ORIGINAL RESEARCH

Annals Intern Med, August 15 2017

Study Design

• Population-based prospective cohort:

– 10 European countries, >500,000 adults

• Daily, weekly, monthly coffee consumption
• Registry based mortality assessment

– All-cause – Cause-specific: cancer, CVD, GI, respiratory, external causes and suicide

• Adjusted for potential confounders…

Coffee Consumption and All-Cause Mortality

*Upper quartile: >4 cups of coffee per day

• Highest mortality among non-users
• Dose-dependent reduction in both men and women (p-

trend highly significant)

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Coffee Consumption and Cause-Specific Mortality Coffee and Mortality: Summary

• Huge prospective cohort analysis confirms

that coffee associated with lower mortality

• Extends to both cancer and CVD
• Not RCT but consistency and dose-

response suggests causal relationship

• Weak signal for increased ovarian cancer

among highest quartile: caution advised

Final Take-Ways

• Counsel about safe cannabis use

– Driving is a big concern

• COPD- treatment escalation

– LAMA early, add on late

• Knee OA- avoid serial steroids injections
• Firearms- counsel to prevent suicide
• Coffee- likely reduces mortality so enjoy it!

Thank You for Listening!