1 Scholarly Report submitted in partial fulfillment of the MD Degree at Harvard Medical School Date: 1 February 2017 Student Name: Victor Babatunde, B.Sc. Scholarly Report Title: Does Illicit Drug Use Influence Inpatient Adverse Events, Death, Length of stay and Discharge after Orthopaedic Trauma? Mentor Name and Affiliations: David Ring, MD PhD, Orthopaedic Hand and Upper Extremity Service Clinic, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA. Collaborator, with Affiliations: Mariano E. Menendez, MD, Orthopaedic Hand and Upper Extremity Service Clinic, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA. 2 ABSTRACT TITLE: Does illicit drug use influence inpatient adverse events, death, length of stay and discharge after orthopaedic trauma? Victor D. Babatunde, Mariano E. Menendez, David Ring. Purpose: The prevalence of illicit drug use, such as opiates (including prescription opioids), cocaine, cannabis, in adults is increasing, but the risks of illicit drug use after orthopaedic trauma are not well studied. Our primary null hypothesis was that illicit drug use is not associated with inpatient adverse events after admission for musculoskeletal trauma. Secondary study questions addressed the association of illicit drug use with mortality, prolonged hospital stay, and nonroutine discharge. Methods: Using the Nationwide Inpatient Sample (NIS) database, we identified an estimated 7,118,720 orthopedic trauma inpatients from 2002-2011 and separated them into 2 groups: illicit drug users (1.5%) and non-illicit illicit drug users (98.5%). Multivariable regression modeling was used to determine the association between illicit drug use and the each of the outcome variables. Results: Illicit drug use was associated with higher odds of inpatient adverse events (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.6-1.7; P<0.001), lower likelihood of inpatient death (OR, 0.79; 95% CI, 0.72-0.88; P<0.001), prolonged hospital stay (OR, 1.4; 95% CI, 1.4-1.5; P<0.001) and higher odds of being discharged nonroutinely (OR, 1.3; 95% CI, 1.3-1.4; P<0.001). Conclusion: Our results indicate that illicit drug use was associated with increased likelihood of inpatient medical adverse events, prolonged hospital stay, and nonroutine discharge after orthopaedic trauma. Prompt recognition and proactive treatment measures for patients who have a history of illicit drug use may inform the management of orthopedic trauma inpatients. 3 TABLE OF CONTENTS Introduction …………………………………………………………………………………................................. 5 Student role…………………………………………………………………………………................................... 7 Methods …………………………………………………………………………………....................................... 8 Results ………………………………………………………………………………….......................................... 11 Discussion …………………………………………………………………………………................................... 12 Acknowledgements………………………………………………………………………….............................. 15 References ………………………………………………………………………………………………………………….. 16 Figures & Tables…………………………………………………………………………………………………………. 23 4 GLOSSARY OF ABBREVIATIONS ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification NIS Nationwide Inpatient Sample AHRQ Agency for Healthcare Research and Quality OR Odds Ratio CI Confidence Interval 5 INTRODUCTION Illicit drugs are substances such as opiates (including prescription opioids), cocaine, cannabis, amphetamine, sedatives, heroin, hallucinogens, inhalants, or prescription psychotherapeutics used non-medically.[1] The prevalence of illicit drug use, especially opioid abuse, has been steadily increasing since the 1990’s. [2],[3] A 2010 survey estimated that 22.6 million (8.9%) of Americans aged 12 years and older used illicit drugs.[1] Approximately 7.1 million (2.7%) Americans carry a diagnosis of drug abuse or dependence.[1] Studies have found that alcohol and substance use disorders are commonly under- diagnosed by healthcare professionals.[4–6] Several adverse health conditions are associated with illicit drugs including metabolic acidosis, hepatitis, stroke, myocardial infarct, cardiac arrhythmias, pulmonary edema, lung injury, placental abruption, psychosis, status asthmaticus, aspiration of foreign bodies, and nasal mucosa atrophy (including perforated nasal septum), many times creating a need for mechanical ventilation.[7–13] Some recommend that all critically ill patients be screened for the presence of these disorders. [10] Illicit drug users are more likely to sustain trauma.[14,15] Traumatic injury is the leading cause of death in the first four decades of life in the United States and more than 70 million people are injured annually.[16],[17] The cost of trauma exceeds $80 billion each year, which results in more disability and lost productivity than heart disease and cancer combined. [18,19] Furthermore, trauma patients often abuse more than one psychoactive compound.[20] It has been found that illicit drug use has been detected in more than 70% of trauma patients.[21,22] This is largely because chronic substance use lends itself to a lifestyle associated with trauma, as substance use often adversely affects victims’ sensorium, oculomotor skills, judgment, and reasoning.[22] Several studies have investigated the effects of illicit drug use among trauma patients.[3,9,11,12,14,23–26] A retrospective study of 4,932 consecutive trauma patients showed that methamphetamine users were more likely to receive mechanical ventilation, undergo an operation, leave against medical advice, die from their injuries, and incur a 6 higher cost of care.[24] Another study demonstrated epidemic increases in cocaine and opiate use among trauma patients, and a separate study found that trauma patients who tested positive for cocaine or marijuana use had longer in-hospital stays and increased ICU admissions.[3,26] In a prospective study examining orthopedic patients, 628 patients were screened for both alcohol and illicit drugs including cocaine, opiates and marijuana. Patients who tested positive for some of these illicit drugs were found to have more severe orthopedic trauma injuries and required longer hospitalizations.[14]Although illicit drug use has been associated with increased in-hospital adverse events, there is scant published evidence on the impact of illicit drug use, particularly in the orthopedic trauma patient population.[14,20,25] In this study, we aimed to assess the prevalence of illicit drug use in the orthopaedic trauma population, and to determine its influence on inpatient adverse events, in-hospital mortality, length of stay, and discharge disposition. Our primary null hypothesis was that illicit drug use is not associated with inpatient adverse events. Secondary study questions addressed the association of illicit drug use with mortality, prolonged hospital stay, and nonroutine discharge. 7 STUDENT ROLE In the project entitled “does illicit drug use influence inpatient adverse events, death, length of stay and discharge after orthopaedic trauma”, I developed the research question. After preliminary background research, it was clear that there was a paucity of data in the topic area. It also became apparent that the rising prevalence of illicit drug use was becoming a pressing issue for hospitals. All authors (Babatunde, V Menendez, ME and Ring, D) contributed towards refining the final research question and hypotheses. I and the other co-authors (Menendez, ME and Ring, D) decided to study the impact of illicit drug use on in-hospital outcomes of orthopedic trauma patients. The study design and methods was a collaborative effort among all authors. I collected and examined data from the nationwide inpatient sample database in order to answer our research question. I conducted statistical analysis on the acquired national dataset to answer our question. In the course of my research, I received statistical assistance from one of the co-authors- Menendez, ME. Over several months, I continued to refine and conduct more complex analysis. All authors contributed towards interpreting data. After executing the research, we had compelling results that we hoped to publish. I wrote the draft of the entire manuscript, including abstract, introduction, methods, results and discussions. The other co-authors reviewed my manuscript and provided suggestions and edits. All authors participated in the final version of the manuscript, and approved its submission. All authors agreed to submit our manuscript to the Journal of Surgical Orthopedic Advances. I completed all submission processes, including formatting manuscript to the journal’s requirements. The PI- most senior author- Ring, D, paid the journal submission fee. Our manuscript was accepted and published. I am the first author of this publication. 8 MATERIALS & METHODS This retrospective cohort study was conducted using discharge data from the Nationwide Inpatient Sample (NIS), queried from 2002-2011. The NIS is part of a family of databases and software tools developed for the Healthcare Cost and Utilization Project run by the Agency for Healthcare Research and Quality (AHRQ). The NIS is the largest publicly available all-payer inpatient hospital database in the United States. Each year, the NIS contains discharge data from about 1000 randomly selected hospitals in participating states across the country, to approximate a 20% stratified sample of hospitals. It contains data approximating 8 million inpatient records unweighted and around 40 million hospitalizations weighted.[27] The quality control and reliability of the NIS have been previously described.[28] The NIS contains valuable information about patient characteristics including age, sex, and race; provider factors such as hospital bed size, location, and teaching status; and in-hospital events such as length of stay, mortality, and discharge disposition. The NIS uses the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to identify medical diagnoses and procedures. Approval of our institutional review board was not required to carry out this study, because all data were adequately de-identified and publicly available. All patients with ICD-9-CM primary diagnosis codes for orthopedic trauma (codes 805-829) were identified and included. Fractures sustained were further divided into three groups: neck and trunk (805-809), upper extremity (810-819) and lower extremity (820-829) fractures. Patients below the age of 18, and those sustaining polytrauma were excluded from analysis. We identified patients with concomitant comorbidity of illicit drug use using the AHRQ comorbidity drug abuse measure supplied in the NIS database. This aggregate measure for illicit drug use includes the following ICD-9-CM codes: 292.0, 292.82-292.89, 292.9, 304.00-304.93, 305.20-305.93, 648.30-648.34. [29] In our analysis of orthopedic trauma patients, we examined the prevalence of illicit drug use, patient demographics, and hospital characteristics (Table 1). Explanatory variables consisted of age, sex, race/ethnicity (white, black, hispanic, other, and unknown), insurance status (private insurance, Medicare, Medicaid, no insurance, and 9 other), household income based on postal ZIP code analysis ($1-$38,999, $39,000-$47,999, $48,000-$62,999, and ≥$63,000), fracture site (neck & trunk, upper extremity, lower extremity), weekend or weekday admission, discharge disposition (routine, home health care, rehabilitation/skilled nursing facility, hospital transfer, against medical advice, and other), hospital location (urban and rural), hospital region (Northeast, Midwest, South, West), hospital teaching status (non teaching and teaching), and hospital bed size (small, medium, large). From 2002 to 2011, there was an estimated 7,118, 720 hospitalizations for orthopedic trauma. Our study sample was aged 69 20 years and predominantly comprised female patients (64%) and white patients (62%; Table 1). The response variables consisted of (1) inpatient adverse events, (2) in-hospital deaths, (3) prolonged hospital stay, and (4) nonroutine discharge. Adverse events studied include wound complications, pneumonia, peripheral thrombosis, urinary tract infections, acute myocardial infarction, acute renal failure, transfusion of blood products, acute posthemorrhagic anemia, pulmonary insufficiency, and induced mental disorder.[30] A prolonged stay was defined as an average length of stay greater than the 75th percentile.[31]. Discharge disposition status was dichotomized to routine (home) and nonroutine (short-term hospital, skilled nursing facility, intermediate care, another type of facility, home health care, against medical advice, and death). Based on the large weighted sample size, a normal distribution of the data was assumed and p value of < 0.001 was considered statistically significant in all analyses. In bivariate analyses, the Pearson chi-square test was used for analysis of categorical data, while the independent-samples T test was used for continuous data. To evaluate the independent effect of illicit drug use on inpatient outcomes (adverse events, death, prolonged stay, and nonroutine discharge) after orthopedic trauma, multivariable binary logistic regression analyses were performed. Each multivariate model was adjusted for patient- and provider-related characteristics, and results were reported as the odds ratio (OR) with respect to the 95% confidence interval (CI). The prevalence of illicit drug use diagnosed in the study population was 1.5%. There has been a steady increase over time in the prevalence of illicit drug use, from 1.1 % in 10 2002 to 1.9% in 2011(Figure 1). Patients who were illicit drug users were more likely to be male (66% vs. 35%) and younger (43 16 years vs. 69±20 years) and be of the black race (18% vs. 5.3 %) and the hispanic race (9.7% vs. 6.4%) (P<0.001). Compared to non-illicit drug users, users of illicit drug were more likely to have Medicaid (23% vs. 6.5%) and to be uninsured (23% vs. 5.6%) (P<0.001). Additionally, the most prevalent median household income of illicit drug users was lower than that of non-illicit drug users (($1- $38,999) vs. ($39,000-$47,999)(P<0.001) (Table 1). When compared to non-illicit drug users, patients who were illicit drug users had a higher prevalence of alcohol abuse (35% vs. 3.9%), obesity (4.3% vs. 4.1%) and psychoses (11% vs. 2.9%) (P<0.001) (Table 2). 11 RESULTS When compared with patients who did not use illicit drugs, illicit drug users were more likely to develop pulmonary insufficiency (1.2% vs. 0.80%) and induced mental disorders (9.5% vs. 2.5%) (P<0.001) (Table 3). In bivariate analysis, patients who used illicit drugs had fewer inpatient adverse events than those who did not use illicit drugs (26% vs. 34%) (P<0.001). However, after controlling for demographics (e.g. age, sex, race, etc.), comorbidity burden and provider-related factors, multivariable logistic regression modeling revealed that illicit drug use was an independent predictor of inpatient adverse events (OR, 1.6; 95% CI, 1.6-1.7; P<0.001) (Table 4). The in-hospital mortality rate was significantly lower in illicit drug users (0.40%) than non-illicit drug users (1.50%) (P<0.001) (Table 3). Even after isolating the independent effect of illicit drug use on in-hospital mortality rate with use of multivariable regression modeling, we found lower odds of in-hospital mortality in the illicit drug use population (OR, 0.79; 95% CI, 0.72-0.88; P<0.001) (Table 4). The hospital length of stay was significantly longer in patients who were illicit drug users (5.5±7.2 days) than in those who were not illicit drug users (4.9±4.8 days)(P<0.001). In adjusted analysis, illicit drug use was associated with increased odds for prolonged hospital stay (OR, 1.4; 95% CI, 1.4-1.5; P<0.001) (Table 4). Patients who were illicit drug users were more frequently discharged routinely (64%) when compared with patients who were not illicit drug users (34%). However, multivariable logistic regression modeling showed that illicit drug use was independently associated with increased odds of nonroutine discharge (OR, 1.3; 95% CI, 1.3-1.4; P<0.001) (Table 4). 12 DISCUSSION The prevalence of illicit drug use in adults is increasing, but the risk for these patients after orthopaedic trauma remains largely unexplored. Characterizing this population of orthopaedic trauma patients, and examining the outcomes of their hospital stay would offer a better understanding of the clinical impact of illicit drug use, and provide impetus for the implementation of better practices and management. In our study, illicit drug use was associated with increased likelihood of inpatient medical adverse events, prolonged hospital stay, and nonroutine discharge after orthopaedic trauma. There are several limitations to consider. First, the NIS data set is based on billing data from ICD-9-CM codes and may only identify a subset of illicit drug users. Second, the NIS database does not provide detail about mechanism of injury and fracture severity, so we could not adjust for trauma severity (e.g. Injury Severity Score or the Mortality Risk Score for Trauma).[32] Third, we were unable to determine if patients who were coded with the diagnosis of illicit drug use disorders had active disorders or were previously treated and no longer using. Finally, we can only comment on in-hospital events using this database. Chronic use of illicit drugs has been linked to pulmonary dysfunction.[33,34] This may explain why we observed higher complication rates of pulmonary insufficiency in the illicit drug use population. However, the exact mechanisms by which illicit drugs cause pulmonary adverse events are incompletely understood. They might result from both the direct toxic effects of the drugs on the respiratory mucosa as well as indirect damage from smoking and injection practices. [35,36] Previous research has also demonstrated that substance misuse is associated with psychiatric symptoms and comorbidities including anxiety, depression, psychosis, aggression, and impaired attention and judgement.[37–39] This is consistent with our findings, where we observed more induced mental disorders in the illicit drug-using cohort. These psychological disorders hamper social and occupational functioning. When psychiatric illnesses are identified, they should be treated in order to reduce harm and improve cognitive and behavioral functions.[37] 13 With regards to patient mortality, it is difficult to make a clear judgment about the effects of illicit drug use. Our results paradoxically and unexpectedly showed a lower mortality rate among the illicit drug-using population than those with no history of drug use. Although our analysis adjusted for age, comorbidities, and other demographic variables, there still may be additional unknown factors influencing mortality. Inpatients that are illicit drug users may, on average, be healthier than inpatient non-drug users in ways that age and comorbidities don’t entirely capture. Similar findings to our results were seen in a prospective study of spinal infections in which illicit drug users had a lower mortality rate after 1 year of treatment, compared to non-drug users.[40] Our results are also comparable to national studies which found that the use of tobacco, another psychoactive substance, did not lead to an increased risk of mortality after bariatric surgery, cranial surgery, cardiac surgery, lower extremity amputations. [41–46] However, other national studies demonstrated increased likelihood of mortality for tobacco users following major surgeries. [47–49] Future research in orthopaedic trauma should attempt to stratify illicit drug users in orthopedic trauma: current users, past users or never-users in order to better understand the effects of illicit drug use on mortality. Corroborating with the existing literature, we similarly found patients with the illicit drug use as a secondary diagnosis to trauma experienced longer inpatient days.[12,14,50,51] This may be sequela of the increased risk of pulmonary complications and other associated adverse events. Longer hospitalizations, combined with increased morbidity of these patients, suggest greater utilization of healthcare resources. Economic analyses on the cost of healthcare utilization for patients with substance abuse has supported the fact that illicit drug users tend to generate more health care costs. [52–54] Our findings also agree with prior research that found that patients who used illicit drugs were more likely to be discharged non-routinely.[24] We hypothesize that the increased nonroutine discharges suggest either transfer to detoxification and rehabilitation facilities, low rates of completed care, or a higher proportion of patients leaving the hospital against medical advice. [55,56] In a study of substance abuse patients, 14 nearly 20% of hospitalized patients with a primary or secondary substance abuse diagnosis left the hospital against medical advice.[50] Higher in-hospital complication rates, economic outlay, and unmet substance abuse treatment needs have not gone unnoticed. The American College of Surgeons has recommended that all trauma patients be offered alcohol use screening and brief intervention as part of routine trauma care.[57] Several hospitals have already begun hospital-wide illicit drug and alcohol screening for patients.[58] Effective screening and intervention for substance use disorders in health care settings constitutes a national priority.[59] The National Drug Control Strategy and the Patient Protection and Affordable Care Act of 2010 emphasize prevention, screening, early identification, and integration of interventions and treatments of individuals with substance use disorders into the healthcare system.[60,61] Prompt identification of trauma patients who have a history of illicit drug use may prove beneficial in improving inpatient outcomes for the trauma population. When treating intoxicated patients, for example, orthopaedic surgeons may consider delaying non-emergent procedures until the patient is no longer intoxicated to decrease morbidity rates.[14] Careful discharge planning must also be included in the management. Recognizing the signs, symptoms, and behaviors of intoxication and withdrawals from illicit drug use may speed up screening, and augment proactive measures for orthopedic trauma inpatients.[37] 15 ACKNOWLEDGEMENTS I would like to thank the staff, research fellows and coordinator at the Hand and Upper Extremity service, Massachusetts General Hospital, for their technical support. I would also thank the staff at Cannon Society, Harvard Medical School for their constant support and mentoring. 16 REFERENCES 1. Agency for Healthcare Research and Quality, Rockville M. HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). 2002- 2011. http://www.hcup- us.ahrq.gov/nisoverview.jsp. 2. 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Alcohol and drug dependence symptom items as brief screeners for substance use disorders: results from the Clinical Trials Network. J. Psychiatr. Res. 2012;46:360–9. 23 FIGURES & TABLES Figure 1. The prevalence of illicit drug use in patients after orthopaedic trauma significantly increased from 2002-2011 (P<0.001). 24 Table 1: Demographic Characteristics of study population (N=7,118,720) All Illicit Drug Use Parameter P value Patients No Yes Total 100% 98.5% 1.5% Sex Male 36% 35% 66% <0.001 Female 64% 65% 34% Age (mean ±SD) 69±20 69±20 43±16 <0.001 Race/Ethnicity White 62% 62% 50% Black 5.5% 5.3% 18% Hispanic 6.5% 6.4% 9.7% <0.001 Other 3.7% 3.7% 3.3% Unknown 23% 23% 19% Insurance Status Private Insurance 27% 27% 27% Medicare 54% 55% 15% Medicaid 6.8% 6.5% 23% <0.001 Uninsured 5.9% 5.6% 23% Other 6.3% 6.2% 12% Median Household Income $1-$38,999 24% 24% 38% $39,000-$47,999 26% 26% 26% <0.001 $48,000-$62,999 25% 25% 21% ≥$63,000 25% 25% 16% Hospital teaching Status Nonteaching 58% 58% 38% <0.001 Teaching 42% 42% 62% 25 Hospital Bed Size Small 12% 12% 8.0% Medium 25% 25% 24% <0.001 Large 63% 63% 68% Hospital Location Urban 85% 85% 92% <0.001 Rural 15% 15% 8% Hospital Region Northeast 19% 19% 19% Midwest 24% 24% 19% <0.001 South 38% 38% 39% West 19% 19% 23% Weekend Admission No 74% 74% 70% <0.001 Yes 26% 26% 30% Fracture Site Neck &Trunk 21% 21% 25% Upper Extremity 13% 13% 16% <0.001 Lower Extremity 66% 66% 58% Entire Length of Stay (mean±SD) (d) 4.9±4.8 4.9±4.8 5.5±7.2 <0.001 Discharge disposition Routine 34% 34% 64% Home health care 10% 10% 10% Rehabilitation or skilled nursing 52% 52% 21% facility <0.001 Hospital transfer 2.1% 2.1% 2.0% Against Medical Advice 0.30% 0.30% 2.3% Other 1.5% 1.5% 0.40% 26 Table 2 : Comorbidities in patients with and without illicit drug use (N=7,118,720) Illicit Drug All P Parameter Use Patients value No Yes AIDS 0.10% 0.10% 1.2% <0.001 Alcohol abuse 4.4% 3.9% 35% <0.001 Deficiency anemia 15.9% 16% 9.4% <0.001 Rheumatoid arthritis/collagen vascular 2.8% 2.8% 1.6% <0.001 diseases Chronic blood loss anemia 1.7% 1.0% 1.7% <0.001 Congestive heart failure 11% 11% 3.2% <0.001 Chronic pulmonary disease 17% 17% 17% 0.10 Coagulopathy 3.1% 3.1% 3.0% 0.020 Depression 9.9% 9.8% 12% <0.001 Diabetes (uncomplicated) 15% 15% 7.2% <0.001 Diabetes with chronic complications 2.8% 2.8% 1.9% <0.001 Hypertension 51% 51% 25% <0.001 Hypothyroidism 13% 13% 3.8% <0.001 Liver disease 1.2% 1.2% 5.9% <0.001 Lymphoma 0.50% 0.50% 0.20% <0.001 Fluid & electrolyte disorders 17% 17% 13% <0.001 Metastatic cancer 0.80% 0.80% 0.30% <0.001 Other neurological disorders 12% 12% 7.4% <0.001 Obesity 4.1% 4.1% 4.3% <0.001 Paralysis 2.2% 2.2% 1.8% <0.001 Peripheral vascular disorders 4.2% 4.2% 1.9% <0.001 Psychoses 3.1% 2.9% 11% <0.001 Pulmonary circulation disorders 1.8% 1.8% 0.80% <0.001 Renal failure 6.8% 6.9% 2.5% <0.001 27 Solid tumor without metastasis 1.8% 1.8% 0.50% <0.001 Peptic ulcer disease 0.10% 0.10% 0.10% <0.001 Valvular disease 6.1% 6.2% 1.7% <0.001 Weight loss 2.2% 2.2% 2.0% <0.001 28 Table 3 : Outcomes in patients with and without illicit drug use (N=7,118,720) Illicit Drug Parameter All Patients Use P value No Yes Adverse Events 34% 34% 26% <0.001 Wound Complications 1.0% 1.0% 1.0% 0.25 Pneumonia 3.0% 3.0% 2.4% <0.001 Pulmonary embolism 0.40% 0.40% 0.30% <0.001 Peripheral Thrombosis 0.80% 0.80% 0.80% 0.038 Urinary tract infection 11% 11.2% 5.1% <0.001 Acute myocardial infarction 1.1% 1.1% 0.30% <0.001 Acute renal failure 3.6% 3.6% 2.0% <0.001 Transfusion 16% 16% 8.6% <0.001 Acute posthemorrhagic anemia 11% 12% 6.2% <0.001 Fat embolism 0.10% 0.10% 0.10% 0.014 Pulmonary insufficiency 0.80% 0.80% 1.2% <0.001 Induced Mental disorders 2.6% 2.5% 9.5% <0.001 Prolonged length of stay 20% 20% 24% <0.001 Nonroutine discharge 66% 66% 36% <0.001 Mortality 1.5% 1.5% 0.40% <0.001 29 Table 4: Risk adjusted Multivariable analysis evaluating whether illicit drug use is associated with worse inpatient outcomes Unadjusted [OR Adjusted [OR Outcomes 95%(CI)] 95%(CI)] P value Adverse Events 0.67 (0.66-0.68) 1.6 (1.6-1.7) <0.001 Death 0.24(0.22-0.27) 0.79 (0.72-0.88) <0.001 Prolonged hospital stay 1.2(1.2-1.3) 1.4 (1.4-1.5) <0.001 Nonroutine discharge 0.29(0.28-0.29) 1.3 (1.3-1.4) <0.001 OR was adjusted for age, sex, comorbidities, insurance status, race, household income, fracture type, day of admission, hospital location, hospital region, hospital bedsize, and hospital teaching status.