Cannabis use and IBS.

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Higher Odds of Irritable Bowel Syndrome Among Hospitalized Patients using Cannabis: A Propensity-Matched Analysis.

Running Title: Cannabis use and IBS.

Adeyinka Charles Adejumo MD

^1,2

Tokunbo Opeyemi Ajayi MD

³

Oluwole Muyiwa Adegbala MD

⁴

, Terence N. Bukong, Ph.D.

^2,5,*

Author Affiliation(s)

1. Department of Medicine, North Shore Medical Center, Salem, Massachusetts, United States of America.

2. Department of Medicine, University of Massachusetts Medical School, Worcester Massachusetts, United States of America.

3. Johns Hopkins Medicine, Howard County General Hospital, Columbia, Maryland, United States of America.

4. Department of Medicine, Englewood Hospital and Medical Center, Englewood, New Jersey, United States of America

5. INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Québec, Canada.

*Corresponding Author:

Terence N. Bukong, Ph.D.

INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531 Boulevard des Prairies, Laval (Québec) H7V 1B7 Canada

E-mail: [email protected]

Phone: 450-687-5010 Ext. 4148

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Supplementary Information

Table S1: ICD-9-CM diagnosis codes.

Conditions ICD-9-CM Codes

Irritable Bowel Syndrome 564.1

Constipation 564.0x

Diarrhoea 564.5x, 787.91x

Abdominal Pain 789.0x

Cannabis Abuse 304.3, 304.3x, 305.2, 305.2x

Alcohol Abuse† 303.x, 305.x, V11.3, 291

Tobacco Abuse† 305.1, V15.82, 989.84

Amphetamine and Psychostimulant Abuse 305.7x, 304.4x

Hallucinogen Abuse 305.3x, 304.5x

Opiod Abuse 305.5x, 304.0x

Cocaine Abuse 305.6x, 304.2x

Sedative Abuse 305.4x, , 304.1x

Antidepressant Abuse 305.8x

Mixed Drug Abuse 305.9x, 304.6x, 304.7x, 304.8x, 304.9x

Drug Induced Mental Disorders 292.x

Regional Enteritis (Crohn's Disease) 555.x

Ulcerative Colitis 556.x

Vascular Insufficiency of Intestine/Ischemic Colitis 557.x Unspecified noninfectious gastroenteritis and colitis:

Radiation, Allergic, Eosinophilic, Toxic, Collagenous, Microscopic e.t.c

558.x

Gastrointestinal cancer 150.x-159.x, 197.8, 199.x, 234.9

Pseudomembranous Colitis 008.45

Iron Deficiency Anemia 280.x

Weight Loss 783.21

Rectal Bleeding 569.3

History of Mental Illness V11.x

Family History of IBS V18.59

Obese 278.0x, V85.3x, V85.4x

Hypertension 401.x

Acute Reaction to Stress 308.x

Mood Disorder 296.x

Depression 296.2x, 296.3x, 296.5x, 311.x

Mania 296.0x, 296.1x, 296.4x

Anxiety Disorders 300.x

History of Mental Illness V11.x

History of Psychological Stress V15.4x, V62.x

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†Past and current use

Table S2: Adjusted Odds Ratio for having a diagnosis of IBS with Cannabis use disorder and risk factors for IBS.

AOR 95% CI p-value

Cannabis Use Disorder 2.033 1.53-2.71

<0.000 1 Demographics

Female 2.922 2.58-3.30 <0.000

1 Age:

45-65-years vs. <45-years 0.928 0.82-1.06

<0.000 1

>-65-years vs. <45-years 0.495 0.42-0.59 Race

Blacks vs. White 0.747 0.64-0.87

<0.000 1

Hispanics vs. White 0.8 0.67-0.95

Others vs. White 0.496 0.38-0.64

Health insurance

Medicare vs. Private 1.043 0.91-1.20 0.0791

Medicaid vs. Private 0.871 0.76-1.00

Self-pay & others† vs. Private 1.077 0.91-1.28 Household income††

Lowest vs. Highest Quartile 0.791 0.68-0.92 0.0005 Second Quartile vs. Highest Quartile 1.004 0.88-1.15

Third Quartile vs. Highest Quartile 0.874 0.76-1.01 Hospital related factors

Hospital region

Midwest vs. Northeast 1.131 0.96-1.34 0.0222

South vs. Northeast 1.031 0.89-1.20

West vs. Northeast 0.864 0.72-1.04

Hospital financial control

Private, non-profit vs. Government 1.257 1.06-1.50 0.0047 Private, for-profit vs. Government 1.402 1.14-1.72

Hospital teaching type

Urban, non-teaching vs. Rural 1.442 1.19-1.75 0.0007 Urban, teaching vs. Rural 1.4 1.16-1.68

Comorbidities

Tobacco 1.162 1.05-1.29 0.0047

Alcohol abuse 0.339 0.24-0.47

<0.000 1 Family history of IBS

20.79 5

11.76- 36.77

<0.000 1

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Obese 0.796 0.70-0.90 0.0003

Hypertension 1.208 1.09-1.34 0.0002

Acute reaction to stress 2.333 0.97-5.62 0.0592

History of mental illness 0.467 0.08-2.72 0.4004

History of psychological stress 0.373 0.25-0.56

<0.000 1

Schizophrenia 0.432 0.26-0.72 0.0011

Depression 1.742 1.55-1.96

<0.000 1

Mood disorders 1.79 1.49-2.13

<0.000 1

Anxiety disorder 3.493 3.10-3.89 <0.000

1

†Others include un-insured, medically indigent (free), charity, workers compensation etc;

††Annual income stratified by residence zip-code, 1st quartile:$1-$39,999, 2nd quartile:$40,000-

$50,999, 3rd quartile:$51,000-$65,999, 4th quartile:$66,000+

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Table S3: Power calculation to estimate requires sample size for propensity scored matching

Fixed elements Value

Alpha 0.05

Response probability 0.091

Test predictor Cannabis use disorder

Test predictor's Odds Ratio 2

Power 0.9

Computed output Value

Actual power 0.9

Required total sample size 14256

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Table S4: Adjusted Odds Ratio of Propensity matched (1:10) case control analysis AO

R 95% CI p-value

Cannabis Use Disorder 1.69 1.19-

2.39

0.0033 Demographics

Female 0.8 0.42-

1.51

0.4848 Age:

45-65-years vs. <45-years

1.16 0.91- 1.47

<0.000 1

>-65-years vs. <45-years 0.79 0.52- 1.18

Race 0.4833

Blacks vs. White 0.99 0.77-

1.27

Hispanics vs. White 1.18 0.91-

1.52

Others vs. White 1.24 0.73-

2.10

Health insurance† 0.4530

Medicare vs. Private 1.09 0.91-

1.30

Medicaid vs. Private 1.04 0.86-

1.27 Self-pay & others vs. Private 0.88 0.70-

1.10

Household income†† 0.7085

Lowest vs. Highest Quartile 1.02 0.81- 1.28 Second Quartile vs. Highest Quartile 0.93 0.78-

1.10 Third Quartile vs. Highest Quartile 1.03 0.84-

1.25 Hospital related factors

Hospital region 0.8203

Midwest vs. Northeast 1.02 0.84-

1.24

South vs. Northeast 1.06 0.89-

1.26

West vs. Northeast 1.11 0.89-

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1.38

Hospital financial control 0.6033

Private, non-profit vs. Government 1.12 0.88- 1.44 Private, for-profit vs. Government 1.1 0.81-

1.49

Hospital teaching type 0.6036

Urban, non-teaching vs. Rural 0.89 0.65- 1.23

Urban, teaching vs. Rural 0.87 0.65-

1.17 Comorbidities

Tobacco 0.89 0.75-

1.05

0.1760

Alcohol abuse 1.38 0.67-

2.84

0.3766

Family history of IBS 0.45 0.04-

5.70

0.5395

Obese 0.96 0.80-

1.16

0.6851

Hypertension 0.89 0.75-

1.07

0.2047

Acute reaction to stress 0.47 0.10-

2.21 0.3371

History of mental illness 1.21 0.15-

10.17 0.8590 History of psychological stress 1.08 0.52-

2.22

0.8399

Schizophrenia

1.13 0.55- 2.33

0.7375

Depression

0.82 0.56- 1.19

0.2867

Mood Disorders

0.78 0.51- 1.20

0.2632

Anxiety disorder

0.61 0.28- 1.31

0.2051

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Table S5: Adjusted Odds Ratio for having a diagnosis of IBS with Cannabis use disorder and risk factors for IBS, using the 2012 HCUP NIS data.

AOR 95% CI p-value

Cannabis Use Disorder 2.40 2.10-2.75 <0.0001

Demographics

Female 2.63 2.50-2.78 <0.0001

Age: <0.0001

45-65-years vs. <45-years 0.79 0.75-0.84

>-65-years vs. <45-years 0.42 0.39-0.46

Race <0.0001

Blacks vs. White 0.79 0.74-0.84

Hispanics vs. White 0.69 0.64-0.75

Others vs. White 0.51 0.46-0.57

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Health insurance† <0.0001

Medicare vs. Private 1.18 1.11-1.26

Medicaid vs. Private 0.82 0.77-0.88

Self-pay & others vs. Private 1.32 1.23-1.41

Household income†† <0.0001

Lowest vs. Highest Quartile 0.78 0.73-0.83 Second Quartile vs. Highest Quartile 0.79 0.75-0.84 Third Quartile vs. Highest Quartile 0.83 0.79-0.88

Hospital related factors

Hospital region <0.0001

Midwest vs. Northeast 1.12 1.05-1.19

South vs. Northeast 1.05 0.99-1.11

West vs. Northeast 0.89 0.83-0.95

Private, non-profit vs. Government 1.15 1.07-1.23 Private, for-profit vs. Government 1.07 0.98-1.16

Hospital teaching type <0.0001

Urban, non-teaching vs. Rural 1.25 1.16-1.34 Urban, teaching vs. Rural 1.14 1.06-1.23

Comorbidities

Tobacco 1.24 1.18-1.30 <0.0001

Alcohol abuse 0.30 0.26-0.35 <0.0001

Family history of IBS

20.6

4 15.35-27.74 <0.0001

Obese 0.89 0.84-0.95 0.0002

Hypertension 1.00 0.95-1.05 0.9328

Acute reaction to stress 2.92 2.05-4.18 <0.0001

History of mental illness 0.05 0.00-0.79 0.0332

History of psychological stress 0.21 0.17-0.27 <0.0001

Schizophrenia 0.37 0.29-0.48 <0.0001

Depression 1.69 1.60-1.79 <0.0001

Mood disorder 1.88 1.61-2.2 <0.0001

Anxiety disorder 3.61 3.44-3.78 <0.0001

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Table S6: Adjusted Odds Ratio of Propensity matched (1:1) Case Control Analysis, NIS 2010-2014.

AOR 95% CI p-value

Cannabis Use Disorder 1.48 1.17 1.89 0.0012

Demographics

Female 1.12 0.84 1.49 0.4345

Age: 0.99 0.98 0.99 <0.0001

Race <0.0001

Blacks vs. White 1.29 1.05 1.57

Hispanics vs. White 1.70 1.35 2.15

Others vs. White 2.03 1.43 2.89

Health insurance† <0.0001

Medicare vs. Private 1.18 1.00 1.40

Medicaid vs. Private 1.43 1.19 1.73

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Self-pay & others vs. Private 0.85 0.70 1.03

Household income 0.0663

Lowest vs. Highest Quartile 0.85 0.71 1.02 Second Quartile vs. Highest

Quartile 0.97 0.81 1.17

Third Quartile vs. Highest Quartile

1.07 0.89 1.28 Hospital related factors

Hospital region 0.4441

Midwest vs. NorthEast 1.09 0.91 1.32

South vs. NorthEast 1.10 0.92 1.32

West vs. NorthEast 1.19 0.97 1.46

Private, non-profit vs.

Government

0.75 0.62 0.90 Private, for-profit vs. Government 0.95 0.78 1.17

Hospital teaching type 0.7223

Urban, non-teaching vs. Rural 0.92 0.74 1.14 Urban, teaching vs. Rural 0.92 0.75 1.13

Comorbidities

Tobacco 1.01 0.88 1.15 0.8808

Alcohol abuse 1.30 0.91 1.84 0.1513

Acute reaction to stress 1.28 0.71 2.32 0.4185

History of mental illness 1.23 0.59 2.57 0.5867

History of psychological stress 1.54 0.96 2.44 0.0708

Obesity 1.23 1.06 1.42 0.0078

Hypertension 1.02 0.89 1.16 0.8166

Depression 1.05 0.88 1.26 0.5720

Anxiety disorder 0.97 0.69 1.38 0.8756

Schizophrenia 1.40 0.92 2.12 0.1143

Mania 1.04 0.84 1.28 0.7345

Bipolar disorder 1.06 0.84 1.35 0.6136