Integrating Clinical Practice Guidelines for Smoking Cessation Into Mental Health Care for Veterans With Posttraumatic Stress Disorder

• Sponsor: US Department of Veterans Affairs (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00118534
• Collaborator: (none)
• Enrollment: 943
• Locations: 11
• Arms: 2
• Duration (Months): 59
• Patients Per Site: 85.7
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The primary study objective is to conduct a prospective, randomized controlled clinical trial that compares the effectiveness of two approaches for delivering smoking cessation treatment for veterans with posttraumatic stress disorder (PTSD). An approach where smoking cessation treatment is integrated into mental health care for PTSD and delivered by mental health providers (experimental condition) will be compared to specialized smoking cessation clinic referral (VA's usual standard of care).

Secondary study objectives are to (a) compare the cost outcomes and cost-effectiveness of IC versus USC, (b) identify treatment process variables that explain (mediate) observed differences in smoking abstinence rates for the two study conditions, and (c) determine whether cessation from smoking is associated with worsening of symptoms of PTSD and/or depression.

Condition or Disease	Intervention/Treatment	Phase
Mental Health; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Tobacco Use Disorder	Behavioral: Integrated Care for Smoking Cessation in PTSD patients; Behavioral: Standard of Care	N/A

Detailed Description

Intervention: The research will test the effectiveness of integrating evidence-based, efficacious treatments for tobacco use disorder into mental health care for patients with chronic PTSD. Two different methods for delivering smoking cessation treatment will be compared in a randomized, controlled clinical effectiveness trial conducted at four Department of Veterans Affairs (VA) medical centers. Smokers undergoing mental health care for PTSD who want to quit smoking will be randomly assigned to either (1) guideline-concordant smoking cessation treatment integrated within ongoing mental health care for PTSD, and delivered by mental health providers (Integrated Care (IC), experimental condition), or (2) specialized smoking cessation treatment, delivered separately from PTSD treatment by a smoking cessation clinic (Usual Standard of Care (USC), comparison condition).

Primary Hypothesis: IC will be more effective than USC on measures of smoking-related clinical outcomes.

Secondary Hypothesis: The following treatment process variables will predict smoking abstinence at 12-months post randomization: (a) number of smoking cessation treatment sessions received, (b) type and duration of protocol medications prescribed by providers (bupropion, transdermal nicotine patch, and nicotine gum), (c) degree of subjects' compliance with prescribed protocol medication, and (d) number of quit attempts marked by abstinence of 7 days or more.

Treatment process variables that predict smoking abstinence will be present to a significantly greater degree in IC than USC.

Primary Outcomes: The primary outcome measure will be the point-prevalence of smoking abstinence by self-report for the 7 days prior to assessments, obtained at months 3, 6, 9, and 12 following randomization to study conditions. Verification of smoking abstinence will be obtained by CO readings (abstinence < 10 ppm) obtained at each assessment interval. Salivary cotinine levels (abstinence < 20 ng/ml) will be measured to verify abstinence at months 9 and 12 only, as subjects may still be using nicotine replacement medicines at earlier assessment intervals, confounding cotinine assays.

Study Abstract: Individuals with posttraumatic stress disorder (PTSD) are far more likely to smoke than those without mental illness and they smoke more heavily. Tobacco use likely contributes to the heightened overall mortality and specific risks for smoking related diseases among veterans with PTSD and commonly co-occurring mental disorders.

Symptoms of PTSD and associated mental disorders are linked to the maintenance of tobacco dependence, premature dropout from smoking cessation treatment, and relapse to smoking following quit attempts. Many efficacious tobacco use treatments exist, but a number of barriers limit the effectiveness of current methods for delivering these treatments in VA health care settings, particularly for the mentally ill. Novel approaches to smoking cessation for individuals with PTSD are needed to circumvent these barriers by integrating evidence-based tobacco use treatment into ongoing mental health care. The research proposed here will test the effectiveness of integrating evidence-based treatment for nicotine dependence into mental health care for patients with chronic posttraumatic stress disorder (PTSD). Two different methods for delivering smoking cessation treatment will be compared in a prospective, randomized controlled clinical effectiveness trial conducted at four Department of Veterans Affairs (VA) medical centers. Smokers undergoing mental health care for PTSD (n=440) will be randomly assigned to either: (1) practice guideline-concordant smoking cessation treatment that is integrated within ongoing mental health care for PTSD and delivered by mental health providers (Integrated Care [IC]) or 2) smoking cessation treatment delivered separately from PTSD treatment by smoking cessation specialists (Usual Standard of Care [USC]). Specific aims of the proposed investigation are (1) to demonstrate that IC is more effective than USC in reducing smoking in psychiatric patients with PTSD and (2) to demonstrate that a number of treatment process variables, including the amount or dose of intervention and patient-specific factors, predict abstinence from tobacco use in smokers with PTSD. Intent-to-treat analyses and analyses for treatment completers will be conducted, using a Generalized Estimating Equations approach. If the study hypothesis is confirmed, system-wide implementation of the experimental intervention (IC) for veterans with PTSD would double the number of patients who stop smoking compared to the usual standard of care for tobacco use disorder. Study findings may have implications for integrating smoking cessation treatment into mental health care for patients with disorders other than PTSD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 943 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CSP #519 - Integrating Practice Guidelines for Smoking Cessation Into Mental Health Care for PTSD (SCP)
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Integration of smoking cessation therapy with PTSD therapy.	Behavioral: Integrated Care for Smoking Cessation in PTSD patients; Smoking cessation therapy is integrated with PTSD therapy.; Other Names: Integrated Care (IC)
Active Comparator: Arm 2 Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.	Behavioral: Standard of Care; Patients interested in quitting smoking are referred to a separate smoking cessation clinic, per standard of care.

Outcome Measures

Primary Outcome Measures

1. Bioverified 12-Month Prolonged Abstinence Between 6 and 18 Months Postrandomization [between 6 and 18 months]

   The primary outcome measure was 12-month bio-verified prolonged abstinence from tobacco between 6 and 18 months postrandomization. Prolonged abstinence excluded tobacco use before 6 months postrandomization. Prolonged abstinence defined non-abstinence as 1) smoking for 7 consecutive days or at least once a week for 2 consecutive weeks, or 2) using non-cigarette tobacco for 7 consecutive days or at least once a week for 2 consecutive weeks. Self-reported prolonged abstinence was verified by exhaled CO ≤ 8ppm and urine cotinine <100 ng/mL cotinine equivalents at the 9-18 month visits. If CO or cotinine was missing, a single measure was used for verification. If both CO and cotinine were missing at any visit between 9 and 15 months, patients reporting prolonged abstinence were considered abstinent if all other available bioverification data confirmed abstinence. Patients who lacked CO and cotinine readings at 18 months or failed to attend the 18 month visit were considered nonabstinent.

Secondary Outcome Measures

1. Self-reported 12-month Prolonged Abstinence Between 6 and 18 Months [between 6 and 18 months]

   A secondary outcome was self-reported 1-year prolonged abstinence between 6 and 18 months post-randomization. Prolonged abstinence excluded tobacco use prior to 6 months post-randomization to allow for initial treatment episode completion and recovery from early relapses. Prolonged abstinence defined non-abstinence as: 1) smoking for 7 consecutive days or at least once a week for 2 consecutive weeks, or 2) using non-cigarette tobacco for 7 consecutive days or at least once a week for 2 consecutive weeks.

2. Clinician Administered PTSD Scale (CAPS) [Baseline and 18 months]

   Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was CAPS at 18 months. The range is 0-136; five rationally derived severity score ranges for interpreting CAPS total score have been proposed and are as follows: 0-19 = asymptomatic/few symptoms, 20-39 = mild PTSD/subthreshold, 40-59 = moderate PTSD/threshold, 60-79 = severe PTSD symptomatology, and >80 = extreme PTSD symptomology. A rationally derived 15-point change in CAPS total severity score has been proposed as a marker of clinically significant change. The above severity ranges and 15-point marker are preliminary (Frank W. Weathers et. al., "Clinician-administered PTSD Scale: A Review of the First Ten Years of Research", Depression and Anxiety 13: 132-156 (2001)). The results are reported in mean change from baseline.

3. PTSD Checklist [Baseline and 3 months]

   Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 3 month assessment.

4. PTSD Checklist [Baseline and 6 months]

   Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 6 month assessment.

5. PTSD Checklist [Baseline and 9 months]

   Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 9 month assessment.

6. PTSD Checklist [Baseline and 12 months]

   Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 12 month assessment.

7. PTSD Checklist [Baseline and 15 months]

   Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 15 month assessment.

8. PTSD Checklist [Baseline and 18 months]

   Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 18 month assessment.

9. Patient Health Questionnaire-9 (PHQ-9) [Baseline and 3 months]

   The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 3 month assessment.

10. Patient Health Questionnaire-9 (PHQ-9) [Baseline and 6 months]

    The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 6 month assessment.

11. Patient Health Questionnaire-9 (PHQ-9) [Baseline and 9 months]

    The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 9 month assessment.

12. Patient Health Questionnaire-9 (PHQ-9) [Baseline and 12 months]

    The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 12 month assessment.

13. Patient Health Questionnaire (PHQ-9) [Baseline and 15 months]

    The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 15 month assessment.

14. Patient Health Questionnaire-9 (PHQ-9) [Baseline and 18 months]

    The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 18 month assessment.

15. 7-day Point Prevalence Abstinence - Self Reported [3 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

16. 7-day Point Prevalence Abstinence - Self Reported [6 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

17. 7-day Point Prevalence Abstinence - Self Reported [9 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

18. 7-day Point Prevalence Abstinence - Self Reported [12 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

19. 7-day Point Prevalence Abstinence - Self Reported [15 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

20. 7-day Point Prevalence Abstinence - Self Reported [18 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

21. 7-day Point Prevalence Abstinence - Bio-Verified [3 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

22. 7-day Point Prevalence Abstinence - Bio-Verified [6 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

23. 7-day Point Prevalence Abstinence - Bio-Verified [9 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

24. 7-day Point Prevalence Abstinence - Bio-Verified [12 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

25. 7-day Point Prevalence Abstinence - Bio-Verified [15 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

26. 7-day Point Prevalence Abstinence - Bio-Verified [18 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

27. 30-day Point Prevalence Abstinence - Self Reported [3 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

28. 30-day Point Prevalence Abstinence - Self Reported [6 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

29. 30-day Point Prevalence Abstinence - Self Reported [9 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

30. 30-day Point Prevalence Abstinence - Self Reported [12 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

31. 30-day Point Prevalence Abstinence - Self Reported [15 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

32. 30-day Point Prevalence Abstinence - Self Reported [18 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.

33. 30-day Point Prevalence Abstinence - Bio-Verified [3 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

34. 30-day Point Prevalence Abstinence - Bio-Verified [6 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

35. 30-day Point Prevalence Abstinence - Bio-Verified [9 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

36. 30-day Point Prevalence Abstinence - Bio-Verified [12 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

37. 30-day Point Prevalence Abstinence - Bio-Verified [15 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

38. 30-day Point Prevalence Abstinence - Bio-Verified [18 months]

    Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Receive a minimum of four mental health treatment sessions from the SOPP that span at least a 1-month interval

• SOPP treatment plan must indicate intent to deliver ongoing PTSD care for at least 1 year, including visits at least once per month

• Diagnosis of PTSD resulting from military trauma using DSM-IV criteria

• Current nicotine use, smoking greater at least 10 cigarettes per day for at least 16 of the past 30 days prior to randomization

• Demonstrated motivation to quit smoking

Exclusion Criteria:

• Use of smokeless tobacco or smoke pipes or cigars

• Any psychotic disorder that is not in remission

• Bipolar disorder that is not in remission

• Any substance dependence disorder that is not in remission (current substance abuse disorder and substance dependence disorder in remission for more than 1 month are not exclusions)

• Imminent risk for suicide or violence, as determined during routine assessment by SOPP clinical staff

• Severe psychiatric symptoms or psychosocial instability likely to prevent participation in the study protocol (i.e., attendance at scheduled sessions, ability to read study materials, and/or ability to comprehend interventions), as determined during routine assessment by SOPP clinical staff

• Gross impairment from organic mental disorder, as determined during routine assessment by SOPP clinical staff

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Medical Center, Tuscaloosa	Tuscaloosa	Alabama	United States	35404
2	VA San Diego Healthcare System, San Diego	San Diego	California	United States	92161
3	VA Medical Center, DC	Washington	District of Columbia	United States	20422
4	Southeast Veterans Healthcare System, New Orleans	New Orleans	Louisiana	United States	70112
5	VA Medical Center, Minneapolis	Minneapolis	Minnesota	United States	55417
6	VA Medical Center, Portland	Portland	Oregon	United States	97201
7	VA Medical Center, Philadelphia	Philadelphia	Pennsylvania	United States	19104
8	VA Medical Center, Providence	Providence	Rhode Island	United States	02908
9	Michael E. DeBakey VA Medical Center (152)	Houston	Texas	United States	77030
10	VA Medical Center, Hampton	Hampton	Virginia	United States	23667
11	VA Puget Sound Health Care System, Seattle	Seattle	Washington	United States	98108

Sponsors and Collaborators

• US Department of Veterans Affairs

Investigators

• Study Chair: Miles E McFall, PhD, VA Puget Sound Health Care System, Seattle

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Department of Veterans Affairs
• ClinicalTrials.gov Identifier: NCT00118534
• Other Study ID Numbers: 519
• First Posted: Jul 11, 2005
• Last Update Posted: May 5, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by US Department of Veterans Affairs: addictive disorders; clinical trial; cost effectiveness; mental health; military or environmental exposure; multi-site trial; nicotine; nicotine replacement; post traumatic stress; post traumatic stress disorder; psychiatric; psychological; PTSD; smoking cessation; smoking cessation medications; substance abuse
• Additional relevant MeSH terms: Disease; Substance-Related Disorders; Tobacco Use Disorder; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic

Study Results

Participant Flow

Recruitment Details	Recruitment occurred between November 2004 and December 2007, with follow-up continuing until July 2009.943 patients were recruited from outpatient PTSD clinics at 10 VA medical centers and followed up for a minimum of 18 months.
Pre-assignment Detail	Patients gave written informed consent before enrollment.

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Period Title: Overall Study
STARTED	472	471
COMPLETED	472	471
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Integrated Care	Standard of Care	Total
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.	Total of all reporting groups
Overall Participants	472	471	943
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54.4	54.7	54.56
Sex: Female, Male (Count of Participants)
Female	28 5.9%	32 6.8%	60 6.4%
Male	444 94.1%	439 93.2%	883 93.6%
Region of Enrollment (participants) [Number]
United States	472 100%	471 100%	943 100%

Outcome Measures

1. Primary Outcome

Title	Bioverified 12-Month Prolonged Abstinence Between 6 and 18 Months Postrandomization
Description	The primary outcome measure was 12-month bio-verified prolonged abstinence from tobacco between 6 and 18 months postrandomization. Prolonged abstinence excluded tobacco use before 6 months postrandomization. Prolonged abstinence defined non-abstinence as 1) smoking for 7 consecutive days or at least once a week for 2 consecutive weeks, or 2) using non-cigarette tobacco for 7 consecutive days or at least once a week for 2 consecutive weeks. Self-reported prolonged abstinence was verified by exhaled CO ≤ 8ppm and urine cotinine <100 ng/mL cotinine equivalents at the 9-18 month visits. If CO or cotinine was missing, a single measure was used for verification. If both CO and cotinine were missing at any visit between 9 and 15 months, patients reporting prolonged abstinence were considered abstinent if all other available bioverification data confirmed abstinence. Patients who lacked CO and cotinine readings at 18 months or failed to attend the 18 month visit were considered nonabstinent.
Time Frame	between 6 and 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number [participants]	42 8.9%	21 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Integrated Care, Standard of Care
	Comments	The target sample size (n=1400)was designed to have 90% power to detect the difference between 6% and 11% prolonged abstinence rates in SCC and IC, respectively, using a 2-sided .05 level Chi-square test. Final enrollment was 943. The recruitment period was not extended because the achieved sample size provided 78% power to detect the hypothesized prolonged abstinence rates, and the study continued to the end of planned follow-up.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.09
	Confidence Interval	(2-Sided) 95%; 1.22 to 3.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Self-reported 12-month Prolonged Abstinence Between 6 and 18 Months
Description	A secondary outcome was self-reported 1-year prolonged abstinence between 6 and 18 months post-randomization. Prolonged abstinence excluded tobacco use prior to 6 months post-randomization to allow for initial treatment episode completion and recovery from early relapses. Prolonged abstinence defined non-abstinence as: 1) smoking for 7 consecutive days or at least once a week for 2 consecutive weeks, or 2) using non-cigarette tobacco for 7 consecutive days or at least once a week for 2 consecutive weeks.
Time Frame	between 6 and 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number [participants]	73 15.5%	33 7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Integrated Care, Standard of Care
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.43
	Confidence Interval	(2-Sided) 95%; 1.58 to 3.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Clinician Administered PTSD Scale (CAPS)
Description	Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was CAPS at 18 months. The range is 0-136; five rationally derived severity score ranges for interpreting CAPS total score have been proposed and are as follows: 0-19 = asymptomatic/few symptoms, 20-39 = mild PTSD/subthreshold, 40-59 = moderate PTSD/threshold, 60-79 = severe PTSD symptomatology, and >80 = extreme PTSD symptomology. A rationally derived 15-point change in CAPS total severity score has been proposed as a marker of clinically significant change. The above severity ranges and 15-point marker are preliminary (Frank W. Weathers et. al., "Clinician-administered PTSD Scale: A Review of the First Ten Years of Research", Depression and Anxiety 13: 132-156 (2001)). The results are reported in mean change from baseline.
Time Frame	Baseline and 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [Units on a scale]	-7.2	-7.0

4. Secondary Outcome

Title	PTSD Checklist
Description	Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 3 month assessment.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	-2.0	-0.9

5. Secondary Outcome

Title	PTSD Checklist
Description	Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 6 month assessment.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	1.6	2.2

6. Secondary Outcome

Title	PTSD Checklist
Description	Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 9 month assessment.
Time Frame	Baseline and 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	-1.4	-0.9

7. Secondary Outcome

Title	PTSD Checklist
Description	Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 12 month assessment.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	-1.6	-1.4

8. Secondary Outcome

Title	PTSD Checklist
Description	Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 15 month assessment.
Time Frame	Baseline and 15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	-1.8	-0.9

9. Secondary Outcome

Title	PTSD Checklist
Description	Severity of PTSD was a predetermined secondary outcome. One of the measurements for this was PTSD Checklist (range, 17-85; scores of greater or equal to 50 indicate a PTSD diagnosis) at every assessment. The results are reported as the mean change from baseline for the 18 month assessment.
Time Frame	Baseline and 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	-3.2	-2.4

10. Secondary Outcome

Title	Patient Health Questionnaire-9 (PHQ-9)
Description	The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 3 month assessment.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of Smoking Cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	0.6	0.9

11. Secondary Outcome

Title	Patient Health Questionnaire-9 (PHQ-9)
Description	The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 6 month assessment.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	0.9	1.0

12. Secondary Outcome

Title	Patient Health Questionnaire-9 (PHQ-9)
Description	The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 9 month assessment.
Time Frame	Baseline and 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	1.1	1.3

13. Secondary Outcome

Title	Patient Health Questionnaire-9 (PHQ-9)
Description	The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 12 month assessment.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	1.6	1.2

14. Secondary Outcome

Title	Patient Health Questionnaire (PHQ-9)
Description	The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 15 month assessment.
Time Frame	Baseline and 15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	1.1	1.2

15. Secondary Outcome

Title	Patient Health Questionnaire-9 (PHQ-9)
Description	The Patient Health Questionnaire 9 (PHQ-9; range, 0-27; scores of 10-14, 15-19, and greater than or equal to 20 indicate mild, moderate, and severe depression,respectively) measured depression at every assessment. The results are reported as the mean change from baseline for the 18 month assessment.
Time Frame	Baseline and 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Mean (95% Confidence Interval) [units on a scale]	-0.2	-0.3

16. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	126 26.7%	65 13.8%

17. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	132 28%	63 13.4%

18. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	122 25.8%	60 12.7%

19. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (90% Confidence Interval) [participants]	117 24.8%	70 14.9%

20. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	119 25.2%	63 13.4%

21. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	111 23.5%	73 15.5%

22. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	67 14.2%	37 7.9%

23. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	78 16.5%	34 7.2%

24. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	70 14.8%	35 7.4%

25. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	66 14%	44 9.3%

26. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	67 14.2%	36 7.6%

27. Secondary Outcome

Title	7-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	86 18.2%	51 10.8%

28. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	126 26.7%	65 13.8%

29. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	132 28%	63 13.4%

30. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	122 25.8%	60 12.7%

31. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	117 24.8%	70 14.9%

32. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	119 25.2%	63 13.4%

33. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Self Reported
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	111 23.5%	73 15.5%

34. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	67 14.2%	37 7.9%

35. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	78 16.5%	34 7.2%

36. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	70 14.8%	35 7.4%

37. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	66 14%	44 9.3%

38. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	67 14.2%	36 7.6%

39. Secondary Outcome

Title	30-day Point Prevalence Abstinence - Bio-Verified
Description	Predetermined secondary smoking outcomes included 7- and 30-day point prevalence abstinence at each assessment, where abstinence was defined as no tobacco use in the prior 7 or 30 days, respectively. Self-reported point prevalence abstinence was determined for all patients, with patients not completing a visit presumed to be nonabstinent. Exhaled carbon monoxide (CO) was obtained at every in person assessment. Urine cotinine levels, using Accutest® NicAlert™ test strips, were ascertained at assessments when patients self-reported no use of tobacco or nicotine replacement therapy in the prior 7 days. Laboratory assays of urine cotinine were obtained when self-reported abstinence disagreed with NicAlert™ results. If bioverification data were missing or did not confirm abstinence, patients were considered nonabstinent at that visit.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Integrated Care	Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.	Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
Measure Participants	472	471
Number (95% Confidence Interval) [participants]	86 18.2%	51 10.8%

Adverse Events

Arm/Group Title	Integrated Care		Standard of Care
Arm/Group Description	Integration of smoking cessation therapy with PTSD therapy.		Per standard of care, patients are referred to a smoking cessation clinic for their smoking cessation therapy.
All Cause Mortality
	Integrated Care		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Integrated Care		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	218/472 (46.2%)		220/471 (46.7%)
Cardiac disorders
AV nodal reentrant tachycardia	0/472 (0%)	0	1/471 (0.2%)	1
Angina attack	0/472 (0%)	0	2/471 (0.4%)	2
Atrial fibrillation	1/472 (0.2%)	1	3/471 (0.6%)	3
Atrial fibrillation with rapid ventricular response	0/472 (0%)	0	1/471 (0.2%)	1
Atrial flutter	3/472 (0.6%)	4	1/471 (0.2%)	1
Bradycardia	0/472 (0%)	0	1/471 (0.2%)	1
Cardiac arrest	0/472 (0%)	0	1/471 (0.2%)	1
Chest pain - cardiac	1/472 (0.2%)	1	0/471 (0%)	0
Congestive cardiac failure aggravated	1/472 (0.2%)	2	1/471 (0.2%)	2
Congestive heart failure	4/472 (0.8%)	6	2/471 (0.4%)	2
Constrictive pericarditis	0/472 (0%)	0	1/471 (0.2%)	1
Coronary artery disease	4/472 (0.8%)	4	9/471 (1.9%)	11
Coronary artery occlusion	2/472 (0.4%)	2	0/471 (0%)	0
Coronary artery stenosis	1/472 (0.2%)	2	0/471 (0%)	0
Coronary occlusion	1/472 (0.2%)	2	0/471 (0%)	0
Heart attack	2/472 (0.4%)	2	2/471 (0.4%)	2
Myocardial infarction	8/472 (1.7%)	10	2/471 (0.4%)	2
Non STEMI	0/472 (0%)	0	1/471 (0.2%)	1
Non-Q wave MI	1/472 (0.2%)	1	0/471 (0%)	0
Non-ischemic cardiomyopathy	1/472 (0.2%)	1	0/471 (0%)	0
Paroxysmal atrial fibrillation	0/472 (0%)	0	1/471 (0.2%)	1
Paroxysmal supraventricular tachycardia	1/472 (0.2%)	1	0/471 (0%)	0
Right heart failure	0/472 (0%)	0	1/471 (0.2%)	1
Supraventricular tachycardia	0/472 (0%)	0	1/471 (0.2%)	1
Unstable angina	1/472 (0.2%)	1	1/471 (0.2%)	1
Ventricular fibrillation	1/472 (0.2%)	1	0/471 (0%)	0
Ventricular tachycardia	1/472 (0.2%)	1	0/471 (0%)	0
Congenital, familial and genetic disorders
Arteriovenous malformations	0/472 (0%)	0	1/471 (0.2%)	2
Maxillary hypoplasia	1/472 (0.2%)	1	0/471 (0%)	0
Phimosis	1/472 (0.2%)	1	0/471 (0%)	0
Eye disorders
Alternating exotropia	0/472 (0%)	0	1/471 (0.2%)	1
Amaurosis fugax	0/472 (0%)	0	1/471 (0.2%)	1
Cataract	1/472 (0.2%)	1	1/471 (0.2%)	1
Diplopia	0/472 (0%)	0	1/471 (0.2%)	1
Macular degeneration	0/472 (0%)	0	1/471 (0.2%)	2
Gastrointestinal disorders
Abdominal pain	2/472 (0.4%)	2	0/471 (0%)	0
Achalasia	1/472 (0.2%)	2	0/471 (0%)	0
Acute pancreatitis	0/472 (0%)	0	1/471 (0.2%)	2
Alcoholic pancreatitis	1/472 (0.2%)	1	0/471 (0%)	0
Bleeding duodenal ulcer	0/472 (0%)	0	1/471 (0.2%)	1
Bleeding gastric ulcer	0/472 (0%)	0	1/471 (0.2%)	1
Blood in stool	1/472 (0.2%)	1	0/471 (0%)	0
Bowel obstruction	0/472 (0%)	0	1/471 (0.2%)	1
Chronic pancreatitis	2/472 (0.4%)	2	0/471 (0%)	0
Constipation	2/472 (0.4%)	2	3/471 (0.6%)	3
Constipation chronic	0/472 (0%)	0	1/471 (0.2%)	1
Crohn's disease	1/472 (0.2%)	1	0/471 (0%)	0
GERD	1/472 (0.2%)	1	0/471 (0%)	0
GI bleed	0/472 (0%)	0	1/471 (0.2%)	1
GI tract bleed	0/472 (0%)	0	1/471 (0.2%)	1
Gastritis	2/472 (0.4%)	2	0/471 (0%)	0
Gastrointestinal bleed	0/472 (0%)	0	1/471 (0.2%)	1
Gastrointestinal motility disorder	0/472 (0%)	0	1/471 (0.2%)	1
Gastroparesis	0/472 (0%)	0	1/471 (0.2%)	1
Heartburn	1/472 (0.2%)	1	0/471 (0%)	0
Left lower quadrant pain	1/472 (0.2%)	1	0/471 (0%)	0
Nausea	2/472 (0.4%)	2	0/471 (0%)	0
Pancreatic mass	0/472 (0%)	0	1/471 (0.2%)	1
Pancreatitis	3/472 (0.6%)	3	0/471 (0%)	0
Perforated colon	0/472 (0%)	0	1/471 (0.2%)	1
Persistent vomiting	0/472 (0%)	0	1/471 (0.2%)	1
Rectal disorder	1/472 (0.2%)	1	0/471 (0%)	0
Right inguinal hernia	0/472 (0%)	0	1/471 (0.2%)	1
Small bowel obstruction	1/472 (0.2%)	1	0/471 (0%)	0
Upper abdominal pain	0/472 (0%)	0	1/471 (0.2%)	1
Uvulitis	0/472 (0%)	0	1/471 (0.2%)	1
Vomiting	0/472 (0%)	0	2/471 (0.4%)	3
Vomiting blood	0/472 (0%)	0	1/471 (0.2%)	1
Vomiting post chemotherapy	1/472 (0.2%)	1	0/471 (0%)	0
General disorders
Unevaluable event	8/472 (1.7%)	9	8/471 (1.7%)	10
Chest pain	6/472 (1.3%)	6	8/471 (1.7%)	9
Cyst	0/472 (0%)	0	1/471 (0.2%)	1
Death NOS	2/472 (0.4%)	2	2/471 (0.4%)	2
Died in sleep	1/472 (0.2%)	1	0/471 (0%)	0
Disease complication	1/472 (0.2%)	1	0/471 (0%)	0
Edema	1/472 (0.2%)	1	0/471 (0%)	0
Edema of lower extremities	0/472 (0%)	0	1/471 (0.2%)	1
Hernia	0/472 (0%)	0	2/471 (0.4%)	2
Non-cardiac chest pain	1/472 (0.2%)	1	1/471 (0.2%)	1
Opiate withdrawal symptoms	1/472 (0.2%)	1	0/471 (0%)	0
Ulcer	1/472 (0.2%)	1	0/471 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/472 (0.2%)	1	0/471 (0%)	0
Cholelithiasis	2/472 (0.4%)	2	0/471 (0%)	0
Gallbladder pain	1/472 (0.2%)	1	0/471 (0%)	0
Gallbladder stones	1/472 (0.2%)	1	0/471 (0%)	0
Hepatic lesion	1/472 (0.2%)	1	0/471 (0%)	0
Hepatitis acute	1/472 (0.2%)	1	0/471 (0%)	0
Obstructive jaundice	1/472 (0.2%)	1	0/471 (0%)	0
Infections and infestations
Abdominal abscess	1/472 (0.2%)	1	0/471 (0%)	0
Abscess intestinal	1/472 (0.2%)	1	0/471 (0%)	0
Abscess limb	0/472 (0%)	0	1/471 (0.2%)	1
Abscess on buttock	1/472 (0.2%)	1	0/471 (0%)	0
Acute appendicitis	0/472 (0%)	0	2/471 (0.4%)	2
Acute bronchitis	1/472 (0.2%)	1	0/471 (0%)	0
Appendicitis	1/472 (0.2%)	1	0/471 (0%)	0
Appendicitis perforated	1/472 (0.2%)	1	0/471 (0%)	0
Asymptomatic neurosyphilis	1/472 (0.2%)	1	0/471 (0%)	0
Bacterial meningitis	1/472 (0.2%)	1	0/471 (0%)	0
Breast abscess	1/472 (0.2%)	1	0/471 (0%)	0
Cellulitis	3/472 (0.6%)	3	3/471 (0.6%)	3
Cellulitis of arm	1/472 (0.2%)	1	1/471 (0.2%)	1
Cellulitis of leg	1/472 (0.2%)	1	2/471 (0.4%)	3
Clostridium difficile colitis	1/472 (0.2%)	1	0/471 (0%)	0
Community acquired pneumonia	0/472 (0%)	0	1/471 (0.2%)	1
Condyloma	1/472 (0.2%)	1	0/471 (0%)	0
Creutzfeldt-Jakob disease	1/472 (0.2%)	1	0/471 (0%)	0
Diabetic foot infection	1/472 (0.2%)	1	0/471 (0%)	0
Diverticulitis	4/472 (0.8%)	5	1/471 (0.2%)	1
Ear infection	0/472 (0%)	0	1/471 (0.2%)	1
Ear infection viral	0/472 (0%)	0	1/471 (0.2%)	1
Gastroenteritis	1/472 (0.2%)	1	1/471 (0.2%)	1
HIV infection	0/472 (0%)	0	1/471 (0.2%)	1
Hepatitis C	0/472 (0%)	0	2/471 (0.4%)	2
Hip osteomyelitis	1/472 (0.2%)	1	0/471 (0%)	0
Infection urinary tract	0/472 (0%)	0	1/471 (0.2%)	1
Legionnaire's disease	0/472 (0%)	0	1/471 (0.2%)	1
Lyme disease	0/472 (0%)	0	1/471 (0.2%)	1
MRSA wound infection	1/472 (0.2%)	1	0/471 (0%)	0
Methicillin-resistant staphylococcal aureus infection	0/472 (0%)	0	2/471 (0.4%)	3
Mouth abscess	1/472 (0.2%)	1	0/471 (0%)	0
Nasal abscess	0/472 (0%)	0	1/471 (0.2%)	1
Neurosyphilis	1/472 (0.2%)	1	0/471 (0%)	0
Osteomyelitis	1/472 (0.2%)	1	0/471 (0%)	0
Pharyngitis	1/472 (0.2%)	1	0/471 (0%)	0
Pneumonia	6/472 (1.3%)	6	9/471 (1.9%)	9
Pneumonia streptococcal	0/472 (0%)	0	1/471 (0.2%)	1
Postoperative wound infection	1/472 (0.2%)	1	1/471 (0.2%)	1
Respiratory infection	0/472 (0%)	0	1/471 (0.2%)	1
Sialadenitis	0/472 (0%)	0	1/471 (0.2%)	1
Sinusitis	0/472 (0%)	0	2/471 (0.4%)	2
Spinal osteomyelitis	0/472 (0%)	0	1/471 (0.2%)	1
Surgical wound infection	1/472 (0.2%)	1	1/471 (0.2%)	1
UTI	1/472 (0.2%)	1	1/471 (0.2%)	1
Upper respiratory infection	1/472 (0.2%)	1	1/471 (0.2%)	1
Urinary tract infection	2/472 (0.4%)	2	0/471 (0%)	0
Viral gastroenteritis	0/472 (0%)	0	2/471 (0.4%)	2
Viral hepatitis	0/472 (0%)	0	1/471 (0.2%)	1
Viral pneumonia	0/472 (0%)	0	1/471 (0.2%)	1
Viral upper respiratory tract infection	1/472 (0.2%)	1	0/471 (0%)	0
Injury, poisoning and procedural complications
Accident at home	0/472 (0%)	0	1/471 (0.2%)	1
Accidental overdose	0/472 (0%)	0	1/471 (0.2%)	1
Achilles tendon injury	1/472 (0.2%)	1	0/471 (0%)	0
Acute alcoholic intoxication	0/472 (0%)	0	1/471 (0.2%)	1
Alcohol intoxication	1/472 (0.2%)	1	0/471 (0%)	0
Animal bite	1/472 (0.2%)	1	0/471 (0%)	0
Automobile accident	1/472 (0.2%)	1	0/471 (0%)	0
Broken leg	1/472 (0.2%)	1	0/471 (0%)	0
Cardiac procedure complication	1/472 (0.2%)	1	0/471 (0%)	0
Cat bite	0/472 (0%)	0	1/471 (0.2%)	1
Cataract operation complication	1/472 (0.2%)	1	0/471 (0%)	0
Collapse of lung	1/472 (0.2%)	1	0/471 (0%)	0
Coronary stent occlusion	0/472 (0%)	0	1/471 (0.2%)	1
Crushing injury of trunk	0/472 (0%)	0	1/471 (0.2%)	1
Cycling accident	1/472 (0.2%)	1	1/471 (0.2%)	1
Delayed recovery from anesthetic	1/472 (0.2%)	1	0/471 (0%)	0
Drug toxicity	0/472 (0%)	0	1/471 (0.2%)	1
Dumping syndrome	0/472 (0%)	0	1/471 (0.2%)	1
Fall	3/472 (0.6%)	3	9/471 (1.9%)	10
Fibula fracture	1/472 (0.2%)	1	0/471 (0%)	0
Fractured ribs	1/472 (0.2%)	1	0/471 (0%)	0
Implant failure	2/472 (0.4%)	3	0/471 (0%)	0
Implantable defibrillator malfunction	1/472 (0.2%)	1	1/471 (0.2%)	1
Incision site complication	1/472 (0.2%)	1	0/471 (0%)	0
Incisional hernia	0/472 (0%)	0	2/471 (0.4%)	2
Laceration	1/472 (0.2%)	1	0/471 (0%)	0
Limb injury	0/472 (0%)	0	1/471 (0.2%)	1
Medication error	1/472 (0.2%)	1	0/471 (0%)	0
Motor vehicle accident	1/472 (0.2%)	1	4/471 (0.8%)	4
Nerve injury	1/472 (0.2%)	1	0/471 (0%)	0
Overdose	2/472 (0.4%)	2	3/471 (0.6%)	3
Overdose effect	1/472 (0.2%)	1	0/471 (0%)	0
Post biopsy bleeding	1/472 (0.2%)	1	0/471 (0%)	0
Post procedural bleeding	1/472 (0.2%)	1	1/471 (0.2%)	1
Postoperative complication	1/472 (0.2%)	6	0/471 (0%)	0
Postoperative hypotension	1/472 (0.2%)	1	0/471 (0%)	0
Procedural complication	1/472 (0.2%)	1	0/471 (0%)	0
Rupture tendon	0/472 (0%)	0	1/471 (0.2%)	1
Spider bite	1/472 (0.2%)	1	0/471 (0%)	0
Sports injury	0/472 (0%)	0	1/471 (0.2%)	1
Suture granuloma	1/472 (0.2%)	1	0/471 (0%)	0
Investigations
Biopsy larynx normal	1/472 (0.2%)	1	0/471 (0%)	0
Blood carbon monoxide increased	0/472 (0%)	0	1/471 (0.2%)	1
Blood sugar increased	1/472 (0.2%)	1	2/471 (0.4%)	2
Cardiac catheterization	1/472 (0.2%)	1	0/471 (0%)	0
Coronary angiogram	0/472 (0%)	0	1/471 (0.2%)	1
Elevated prostate specific antigen [PSA]	1/472 (0.2%)	1	0/471 (0%)	0
Weight gain	0/472 (0%)	0	1/471 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	1/472 (0.2%)	1	1/471 (0.2%)	1
Diabetes	1/472 (0.2%)	1	1/471 (0.2%)	1
Diabetes mellitus	4/472 (0.8%)	4	0/471 (0%)	0
Gout	0/472 (0%)	0	1/471 (0.2%)	1
Hyperglycemia	1/472 (0.2%)	2	1/471 (0.2%)	1
Hyperkalemia	1/472 (0.2%)	1	2/471 (0.4%)	3
Hypoglycemia	0/472 (0%)	0	1/471 (0.2%)	1
Ketoacidosis	0/472 (0%)	0	1/471 (0.2%)	1
Potassium deficiency	1/472 (0.2%)	1	0/471 (0%)	0
Type II diabetes mellitus	0/472 (0%)	0	1/471 (0.2%)	1
Unspecified nutritional deficiency	0/472 (0%)	0	1/471 (0.2%)	1
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis	0/472 (0%)	0	1/471 (0.2%)	1
Arthritis	1/472 (0.2%)	1	0/471 (0%)	0
Avascular necrosis	1/472 (0.2%)	1	0/471 (0%)	0
Back pain	0/472 (0%)	0	1/471 (0.2%)	1
Bunion	0/472 (0%)	0	1/471 (0.2%)	1
Bursitis	0/472 (0%)	0	1/471 (0.2%)	1
Cervical spinal stenosis	0/472 (0%)	0	2/471 (0.4%)	2
Complete rupture of rotator cuff	0/472 (0%)	0	1/471 (0.2%)	1
Costochondritis	1/472 (0.2%)	1	0/471 (0%)	0
"Degeneration of intervertebral disc, site unspecified"	1/472 (0.2%)	1	0/471 (0%)	0
Degenerative joint disease	2/472 (0.4%)	2	1/471 (0.2%)	1
Dupuytren's contracture	2/472 (0.4%)	2	0/471 (0%)	0
Herniated disc	1/472 (0.2%)	1	1/471 (0.2%)	1
Intervertebral disc disorder	1/472 (0.2%)	1	0/471 (0%)	0
Knee pain	1/472 (0.2%)	1	0/471 (0%)	0
Leg pain	2/472 (0.4%)	2	1/471 (0.2%)	1
Low back pain	1/472 (0.2%)	1	0/471 (0%)	0
Lumbar disc degeneration	0/472 (0%)	0	1/471 (0.2%)	1
Lumbar disc herniation	0/472 (0%)	0	1/471 (0.2%)	1
Lumbar spinal stenosis	2/472 (0.4%)	2	0/471 (0%)	0
Muscle spasms	0/472 (0%)	0	1/471 (0.2%)	1
Musculoskeletal chest pain	1/472 (0.2%)	1	2/471 (0.4%)	2
Myositis	0/472 (0%)	0	1/471 (0.2%)	1
Pain in arm	1/472 (0.2%)	1	0/471 (0%)	0
Rheumatoid arthritis	1/472 (0.2%)	1	0/471 (0%)	0
Rotator cuff injury	1/472 (0.2%)	1	0/471 (0%)	0
Rotator cuff tear	2/472 (0.4%)	2	0/471 (0%)	0
Shoulder bursitis	0/472 (0%)	0	1/471 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/472 (0.2%)	1	0/471 (0%)	0
Adenocarcinoma of kidney	0/472 (0%)	0	1/471 (0.2%)	1
Adenocarcinoma of prostate	0/472 (0%)	0	1/471 (0.2%)	1
Adenocarcinoma of the prostate recurrent	1/472 (0.2%)	1	0/471 (0%)	0
Basal cell carcinoma	0/472 (0%)	0	2/471 (0.4%)	2
Bladder cancer	2/472 (0.4%)	4	2/471 (0.4%)	2
Bladder cancer recurrent	0/472 (0%)	0	1/471 (0.2%)	1
Bladder carcinoma	0/472 (0%)	0	1/471 (0.2%)	2
Bladder neoplasm	1/472 (0.2%)	3	0/471 (0%)	0
Bladder transitional cell carcinoma	1/472 (0.2%)	1	0/471 (0%)	0
Breast cancer	1/472 (0.2%)	1	0/471 (0%)	0
Breast ductal carcinoma	0/472 (0%)	0	1/471 (0.2%)	1
Carcinoma hepatocellular	2/472 (0.4%)	2	1/471 (0.2%)	1
Colon cancer metastatic	1/472 (0.2%)	1	0/471 (0%)	0
Colon neoplasm	1/472 (0.2%)	1	0/471 (0%)	0
Esophageal adenocarcinoma lower third in situ	1/472 (0.2%)	1	0/471 (0%)	0
Esophageal cancer	0/472 (0%)	0	2/471 (0.4%)	3
Laryngeal squamous cell carcinoma	0/472 (0%)	0	1/471 (0.2%)	1
Lentigo maligna	0/472 (0%)	0	1/471 (0.2%)	1
Lung cancer	4/472 (0.8%)	5	4/471 (0.8%)	4
Lung cancer metastatic	1/472 (0.2%)	1	1/471 (0.2%)	1
Lung neoplasm	0/472 (0%)	0	1/471 (0.2%)	1
Malignant hepatic neoplasm	1/472 (0.2%)	1	0/471 (0%)	0
"Malignant neoplasm of colon, unspecified"	1/472 (0.2%)	1	0/471 (0%)	0
Melanocytic naevus	0/472 (0%)	0	1/471 (0.2%)	1
Melanoma	1/472 (0.2%)	1	0/471 (0%)	0
Metastatic disease	0/472 (0%)	0	1/471 (0.2%)	1
Non-small cell lung cancer	2/472 (0.4%)	3	1/471 (0.2%)	1
Oral carcinoma in situ	0/472 (0%)	0	1/471 (0.2%)	1
Pancreatic adenocarcinoma	0/472 (0%)	0	1/471 (0.2%)	1
Pancreatic cancer	0/472 (0%)	0	1/471 (0.2%)	1
Pituitary adenoma	0/472 (0%)	0	1/471 (0.2%)	1
Prostate adenoma	0/472 (0%)	0	1/471 (0.2%)	1
Prostate cancer	6/472 (1.3%)	7	5/471 (1.1%)	7
Renal cancer stage II	1/472 (0.2%)	1	0/471 (0%)	0
Renal cell carcinoma	2/472 (0.4%)	2	1/471 (0.2%)	1
Renal clear cell carcinoma	0/472 (0%)	0	1/471 (0.2%)	1
Skin cancer	0/472 (0%)	0	1/471 (0.2%)	1
Squamous cell carcinoma	2/472 (0.4%)	2	0/471 (0%)	0
Squamous cell carcinoma of lung	2/472 (0.4%)	4	1/471 (0.2%)	1
Squamous cell carcinoma of skin	1/472 (0.2%)	1	0/471 (0%)	0
Throat cancer	1/472 (0.2%)	1	0/471 (0%)	0
Transitional cell carcinoma of the bladder stage unspecified	1/472 (0.2%)	1	0/471 (0%)	0
Nervous system disorders
Benign essential tremor	1/472 (0.2%)	1	0/471 (0%)	0
Carotid artery stenosis	3/472 (0.6%)	4	0/471 (0%)	0
Cerebrovascular accident	1/472 (0.2%)	1	0/471 (0%)	0
Cervical myelopathy	1/472 (0.2%)	1	0/471 (0%)	0
Cervical radiculopathy	2/472 (0.4%)	2	0/471 (0%)	0
Demyelinating polyneuropathy	1/472 (0.2%)	1	0/471 (0%)	0
Diabetic coma	0/472 (0%)	0	1/471 (0.2%)	1
Drug-induced encephalopathy	1/472 (0.2%)	1	0/471 (0%)	0
Forehead headache	1/472 (0.2%)	1	0/471 (0%)	0
Headache	1/472 (0.2%)	1	1/471 (0.2%)	1
Hepatic encephalopathy	0/472 (0%)	0	1/471 (0.2%)	3
Lumbar radiculopathy	1/472 (0.2%)	1	2/471 (0.4%)	2
Migraine	1/472 (0.2%)	1	0/471 (0%)	0
Myelitis transverse	0/472 (0%)	0	1/471 (0.2%)	2
Neuropathy peripheral	0/472 (0%)	0	1/471 (0.2%)	1
Oversedation	1/472 (0.2%)	1	1/471 (0.2%)	1
Peroneal nerve palsy	0/472 (0%)	0	1/471 (0.2%)	1
Radiculopathy	1/472 (0.2%)	1	0/471 (0%)	0
Seizure	1/472 (0.2%)	1	1/471 (0.2%)	1
Seizures	0/472 (0%)	0	1/471 (0.2%)	1
Simple partial seizures	0/472 (0%)	0	1/471 (0.2%)	1
Stroke	2/472 (0.4%)	2	2/471 (0.4%)	3
Syncope	3/472 (0.6%)	3	2/471 (0.4%)	2
Transient ischaemic attack	2/472 (0.4%)	2	1/471 (0.2%)	1
Upper motor neurone lesion	1/472 (0.2%)	1	0/471 (0%)	0
Psychiatric disorders
Acute psychosis	0/472 (0%)	0	1/471 (0.2%)	1
Addiction relapse	1/472 (0.2%)	1	0/471 (0%)	0
Aggression	1/472 (0.2%)	1	1/471 (0.2%)	1
Alcohol abuse	0/472 (0%)	0	5/471 (1.1%)	5
Alcohol withdrawal syndrome	2/472 (0.4%)	2	0/471 (0%)	0
Altercation	1/472 (0.2%)	1	0/471 (0%)	0
Anger	1/472 (0.2%)	1	0/471 (0%)	0
Anxiety	1/472 (0.2%)	1	1/471 (0.2%)	1
Attempted suicide	1/472 (0.2%)	1	1/471 (0.2%)	1
Auditory and visual hallucinations	0/472 (0%)	0	1/471 (0.2%)	1
Auditory hallucinations	0/472 (0%)	0	2/471 (0.4%)	2
Confusion	1/472 (0.2%)	1	0/471 (0%)	0
Delirium	1/472 (0.2%)	1	0/471 (0%)	0
Depression	1/472 (0.2%)	1	7/471 (1.5%)	7
Depression worsened	0/472 (0%)	0	2/471 (0.4%)	2
Dissociation	0/472 (0%)	0	1/471 (0.2%)	1
Drug abuse	2/472 (0.4%)	3	1/471 (0.2%)	1
Drug-induced psychosis	1/472 (0.2%)	1	0/471 (0%)	0
Homicidal ideation	4/472 (0.8%)	6	6/471 (1.3%)	6
Hypomania	1/472 (0.2%)	1	0/471 (0%)	0
Major depression	0/472 (0%)	0	1/471 (0.2%)	1
Mental disorder	3/472 (0.6%)	3	8/471 (1.7%)	8
Mental status changes	0/472 (0%)	0	1/471 (0.2%)	2
Opioid abuse	1/472 (0.2%)	1	0/471 (0%)	0
Paranoia	0/472 (0%)	0	1/471 (0.2%)	2
Polysubstance dependence	0/472 (0%)	0	1/471 (0.2%)	1
Psychiatric disorder NOS	2/472 (0.4%)	2	0/471 (0%)	0
Psychiatric symptom	0/472 (0%)	0	1/471 (0.2%)	1
Psychosis	1/472 (0.2%)	1	0/471 (0%)	0
Psychotic episode	0/472 (0%)	0	1/471 (0.2%)	1
Stress symptoms	1/472 (0.2%)	1	1/471 (0.2%)	1
Substance abuse	1/472 (0.2%)	1	1/471 (0.2%)	1
Suicidal depression	2/472 (0.4%)	2	5/471 (1.1%)	6
Suicidal ideation	29/472 (6.1%)	37	24/471 (5.1%)	37
Suicidal plans	1/472 (0.2%)	1	0/471 (0%)	0
Suicide	1/472 (0.2%)	1	0/471 (0%)	0
Suicide attempt	6/472 (1.3%)	9	2/471 (0.4%)	2
Suicide gesture	1/472 (0.2%)	1	0/471 (0%)	0
Renal and urinary disorders
Acute renal failure	0/472 (0%)	0	1/471 (0.2%)	1
Kidney stones	0/472 (0%)	0	2/471 (0.4%)	2
Membranous nephropathy	1/472 (0.2%)	1	0/471 (0%)	0
Renal failure	1/472 (0.2%)	1	0/471 (0%)	0
Ureteral calculus	0/472 (0%)	0	1/471 (0.2%)	1
Reproductive system and breast disorders
Benign prostatic hypertrophy	0/472 (0%)	0	1/471 (0.2%)	1
Enlarged prostate	0/472 (0%)	0	1/471 (0.2%)	1
Erectile dysfunction	1/472 (0.2%)	1	1/471 (0.2%)	1
Ovarian cyst NOS	1/472 (0.2%)	1	0/471 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonitis	0/472 (0%)	0	1/471 (0.2%)	1
Asthma	0/472 (0%)	0	1/471 (0.2%)	1
Asthmatic attack	0/472 (0%)	0	1/471 (0.2%)	1
Breath shortness	0/472 (0%)	0	1/471 (0.2%)	1
COPD	1/472 (0.2%)	1	1/471 (0.2%)	1
COPD exacerbation	5/472 (1.1%)	11	5/471 (1.1%)	6
Chronic obstructive airways disease exacerbated	0/472 (0%)	0	1/471 (0.2%)	2
Chronic obstructive pulmonary disease	1/472 (0.2%)	1	0/471 (0%)	0
Difficulty breathing	1/472 (0.2%)	1	0/471 (0%)	0
Emphysema	2/472 (0.4%)	2	1/471 (0.2%)	1
Hilar mass	0/472 (0%)	0	1/471 (0.2%)	1
Lung disorder	1/472 (0.2%)	1	0/471 (0%)	0
Nasal polyps	1/472 (0.2%)	1	0/471 (0%)	0
Pulmonary embolism	0/472 (0%)	0	4/471 (0.8%)	4
Short of breath	0/472 (0%)	0	1/471 (0.2%)	1
Sleep apnea	0/472 (0%)	0	2/471 (0.4%)	2
Throat lesion	1/472 (0.2%)	1	0/471 (0%)	0
Skin and subcutaneous tissue disorders
Allergic angioedema	0/472 (0%)	0	1/471 (0.2%)	1
Angioedema	1/472 (0.2%)	1	2/471 (0.4%)	2
Panniculitis	0/472 (0%)	0	1/471 (0.2%)	1
Petechial rash	0/472 (0%)	0	1/471 (0.2%)	1
Social circumstances
Alcohol use	1/472 (0.2%)	1	0/471 (0%)	0
Burglary victim	1/472 (0.2%)	1	0/471 (0%)	0
Physical assault	0/472 (0%)	0	1/471 (0.2%)	1
Treatment noncompliance	1/472 (0.2%)	1	0/471 (0%)	0
Surgical and medical procedures
Alcohol detoxification	1/472 (0.2%)	1	0/471 (0%)	0
Aortic aneurysm repair	1/472 (0.2%)	1	1/471 (0.2%)	1
Appendectomy	1/472 (0.2%)	1	1/471 (0.2%)	1
Artificial urinary sphincter implant	1/472 (0.2%)	1	0/471 (0%)	0
Atherectomy	0/472 (0%)	0	1/471 (0.2%)	1
Back surgery	0/472 (0%)	0	2/471 (0.4%)	2
Bladder tumor resection	1/472 (0.2%)	1	0/471 (0%)	0
Bowel resection	0/472 (0%)	0	1/471 (0.2%)	1
Bypass surgery	1/472 (0.2%)	1	0/471 (0%)	0
C-section	1/472 (0.2%)	1	0/471 (0%)	0
Cholecystectomy	2/472 (0.4%)	2	0/471 (0%)	0
Drug detoxification	1/472 (0.2%)	1	0/471 (0%)	0
Drug rehabilitation	1/472 (0.2%)	1	0/471 (0%)	0
Elective surgery	0/472 (0%)	0	1/471 (0.2%)	1
Foot surgery	1/472 (0.2%)	1	0/471 (0%)	0
Fusion cervical spine	0/472 (0%)	0	1/471 (0.2%)	1
Fusion of vertebra	1/472 (0.2%)	1	0/471 (0%)	0
Gallbladder operation	0/472 (0%)	0	1/471 (0.2%)	1
Gastric bypass	0/472 (0%)	0	1/471 (0.2%)	1
Gastrostomy tube insertion	1/472 (0.2%)	1	0/471 (0%)	0
Hernia repair	1/472 (0.2%)	1	0/471 (0%)	0
Hernia repair NOS	1/472 (0.2%)	1	0/471 (0%)	0
Hip replacement	0/472 (0%)	0	2/471 (0.4%)	2
Implantable defibrillator insertion	1/472 (0.2%)	1	0/471 (0%)	0
Knee operation	1/472 (0.2%)	1	2/471 (0.4%)	2
Knee total replacement	1/472 (0.2%)	1	1/471 (0.2%)	1
Lobectomy (thyroid)	0/472 (0%)	0	1/471 (0.2%)	1
Lumbar laminectomy	0/472 (0%)	0	1/471 (0.2%)	1
Lung operation	1/472 (0.2%)	1	0/471 (0%)	0
Mass excision	0/472 (0%)	0	1/471 (0.2%)	1
Penile operation	1/472 (0.2%)	1	0/471 (0%)	0
Physical therapy	0/472 (0%)	0	1/471 (0.2%)	1
Prostate transurethral resection	0/472 (0%)	0	1/471 (0.2%)	1
Prostatectomy	1/472 (0.2%)	1	0/471 (0%)	0
Rotator cuff repair	0/472 (0%)	0	2/471 (0.4%)	2
Shoulder replacement	0/472 (0%)	0	1/471 (0.2%)	1
Spinal fusion surgery	0/472 (0%)	0	1/471 (0.2%)	1
Splenectomy	0/472 (0%)	0	1/471 (0.2%)	1
Tooth extraction	0/472 (0%)	0	1/471 (0.2%)	1
Umbilical hernia repair	1/472 (0.2%)	1	0/471 (0%)	0
Uvulectomy	1/472 (0.2%)	1	0/471 (0%)	0
Wound drainage	0/472 (0%)	0	1/471 (0.2%)	1
Vascular disorders
Aneurysm of abdominal aorta	1/472 (0.2%)	1	0/471 (0%)	0
Arterial occlusive disease	1/472 (0.2%)	1	0/471 (0%)	0
Blood pressure high	2/472 (0.4%)	2	2/471 (0.4%)	2
Deep vein thrombosis leg	0/472 (0%)	0	1/471 (0.2%)	1
Hematoma	1/472 (0.2%)	1	0/471 (0%)	0
Hypertension	1/472 (0.2%)	1	1/471 (0.2%)	1
Hypotensive episode	0/472 (0%)	0	1/471 (0.2%)	1
Iliac artery stenosis	1/472 (0.2%)	1	0/471 (0%)	0
Orthostatic hypotension	1/472 (0.2%)	1	0/471 (0%)	0
Peripheral vascular disease	2/472 (0.4%)	2	2/471 (0.4%)	2
Peripheral vascular disease NOS	0/472 (0%)	0	1/471 (0.2%)	1
Popliteal artery aneurysm	1/472 (0.2%)	1	0/471 (0%)	0
Subclavian artery stenosis	0/472 (0%)	0	1/471 (0.2%)	1
Superficial femoral arterial stenosis	0/472 (0%)	0	1/471 (0.2%)	1
Thrombosis	0/472 (0%)	0	2/471 (0.4%)	2
Thrombosis arm	0/472 (0%)	0	1/471 (0.2%)	1
Thrombosis leg	1/472 (0.2%)	1	0/471 (0%)	0
Other (Not Including Serious) Adverse Events
	Integrated Care		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/472 (9.3%)		38/471 (8.1%)
Cardiac disorders
Atrial fibrillation	1/472 (0.2%)	1	0/471 (0%)	0
Ear and labyrinth disorders
Vertigo	0/472 (0%)	0	1/471 (0.2%)	1
Eye disorders
Blurry vision	0/472 (0%)	0	1/471 (0.2%)	1
Gastrointestinal disorders
Constipation	1/472 (0.2%)	1	0/471 (0%)	0
Dyspepsia	1/472 (0.2%)	2	1/471 (0.2%)	2
Flatulence	1/472 (0.2%)	1	0/471 (0%)	0
Gas	1/472 (0.2%)	1	0/471 (0%)	0
Gastric pain	0/472 (0%)	0	1/471 (0.2%)	1
Nausea	2/472 (0.4%)	2	0/471 (0%)	0
Upset stomach	1/472 (0.2%)	1	0/471 (0%)	0
General disorders
Unevaluable event	2/472 (0.4%)	2	2/471 (0.4%)	2
Chest pain	1/472 (0.2%)	1	1/471 (0.2%)	1
Flu like symptoms	0/472 (0%)	0	1/471 (0.2%)	1
Irritability	1/472 (0.2%)	1	1/471 (0.2%)	1
Investigations
Weight gain	1/472 (0.2%)	1	1/471 (0.2%)	1
Musculoskeletal and connective tissue disorders
Low back pain	1/472 (0.2%)	1	0/471 (0%)	0
Neck pain	0/472 (0%)	0	1/471 (0.2%)	1
Nervous system disorders
Headache	0/472 (0%)	0	1/471 (0.2%)	1
Tremor	1/472 (0.2%)	1	0/471 (0%)	0
Psychiatric disorders
Abnormal dreams	1/472 (0.2%)	1	0/471 (0%)	0
Abnormal thinking	0/472 (0%)	0	1/471 (0.2%)	1
Aggression	1/472 (0.2%)	1	0/471 (0%)	0
Agitated	0/472 (0%)	0	1/471 (0.2%)	1
Anger	1/472 (0.2%)	1	1/471 (0.2%)	1
Anxiety	2/472 (0.4%)	2	0/471 (0%)	0
Auditory hallucinations	1/472 (0.2%)	1	0/471 (0%)	0
Bad dreams	1/472 (0.2%)	1	0/471 (0%)	0
Behavior abnormal	1/472 (0.2%)	1	1/471 (0.2%)	1
Bizarre dreams	1/472 (0.2%)	1	1/471 (0.2%)	1
Depressed mood	1/472 (0.2%)	1	0/471 (0%)	0
Depression	0/472 (0%)	0	4/471 (0.8%)	4
Depression worsened	7/472 (1.5%)	7	3/471 (0.6%)	3
Difficulty sleeping	2/472 (0.4%)	2	0/471 (0%)	0
Dreaming excessive	0/472 (0%)	0	2/471 (0.4%)	2
Emotional distress	1/472 (0.2%)	1	0/471 (0%)	0
Frightening dreams	1/472 (0.2%)	1	0/471 (0%)	0
Homicidal ideation	0/472 (0%)	0	1/471 (0.2%)	1
Increased agitation	0/472 (0%)	0	1/471 (0.2%)	1
Lack of motivation	0/472 (0%)	0	1/471 (0.2%)	1
Mood change	2/472 (0.4%)	2	0/471 (0%)	0
Mood swings	1/472 (0.2%)	1	0/471 (0%)	0
Nervousness	1/472 (0.2%)	1	0/471 (0%)	0
Nightmares	2/472 (0.4%)	2	5/471 (1.1%)	5
Panic attack	1/472 (0.2%)	1	0/471 (0%)	0
Panic attacks	0/472 (0%)	0	1/471 (0.2%)	1
Paranoia aggravated	0/472 (0%)	0	1/471 (0.2%)	1
Sleep disturbance	0/472 (0%)	0	1/471 (0.2%)	1
Suicidal ideation	6/472 (1.3%)	7	8/471 (1.7%)	8
Suicide attempt	1/472 (0.2%)	1	0/471 (0%)	0
Violent behavior	1/472 (0.2%)	1	0/471 (0%)	0
Vivid dreams	1/472 (0.2%)	1	3/471 (0.6%)	4
Reproductive system and breast disorders
Erectile dysfunction	1/472 (0.2%)	1	0/471 (0%)	0
Skin and subcutaneous tissue disorders
Drug rash	1/472 (0.2%)	1	0/471 (0%)	0
Generalized itching	1/472 (0.2%)	1	0/471 (0%)	0
Night sweats	0/472 (0%)	0	1/471 (0.2%)	1
Pruritis	1/472 (0.2%)	1	0/471 (0%)	0
Vascular disorders
Blood pressure high	0/472 (0%)	0	1/471 (0.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.