Behavioral Activation and Medication Optimization for Perioperative Mental Health Feasibility Study
Phase: NA
Conditions: Older Adults, Anxiety, Depression, Cardiac Surgery, Orthopedic Surgery, Major Surgical Resection of a Thoracic Malignancy, Major Surgical Resection of an Abdominal Malignancy
Sponsor: Washington University School of Medicine

Protocol Title: 
Behavioral Activation and Medication Optimization for 
Perioperative Mental Health Feasibility Study 
 
 
Protocol ID# 
202101103 
 
 
NCT#: 
NCT05110690 

 
 
    
 
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BEHAVIORAL ACTIVATION AND MEDICATION OPTIMIZATION FOR 
PERIOPERATIVE MENTAL HEALTH   
FEASIBILITY STUDY 
 
 
 
PI:  
 
 
 
Michael Avidan, MBBCh, FCASA  
 
 
Professor, Anesthesiology and Surgery 
 
 
Head, Department of Anesthesiology  
Washington University School of Medicine 
660 S. Euclid Ave. 
Campus Box 8054 
St. Louis, MO 63110 
                                                PI phone:  314-273-4136 
 
          avidanm@wustl.edu   
 
 
 
Research Protocol #        
202101103 
 
Protocol v1.0 Date:    
January 29, 2021  
               v.2.0 Date:   
October 8, 2021 
 
   v.3.0 Date:   
December 22, 2021 
 
   v.4.0 Date:   
January 07, 2022 
   v.5.0 Date:   
April 11, 2022 
        v.6.0 Date:   
July 1, 2022 
 
   v.7.0 Date:   
August 1, 2022  
 
 
1 
Background and Significance 
Inadequate management of preoperative mental health disorders often contributes to poor 
postoperative outcomes [1], including increased rates of readmission, delirium, falls, and mortality 
[2-5]. However, very little work has been done to improve perioperative mental health. In particular, 
there has been limited systematic efforts that identify evidence-based behavioral and pharmacological 
strategies that were originally developed for depression and anxiety in otherwise medically well 
psychiatric patients.  A mental health intervention bundle, composed of behavioral and 
pharmacological strategies, can mitigate anxiety and depression symptoms during the perioperative 
period [6]. However, we currently lack conclusive evidence on effectiveness of such an intervention 
bundle focused on the delivery of perioperative mental health care in older surgical patients. Towards 
this end, we will develop and test an intervention bundle that encompasses: (1) behavioral activation, 
and (2) medication optimization (see more details on the intervention bundle in section 4.2). 
 
2 
Objectives 

 
 
    
 
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The study will address the following objectives: (1) demonstrate the feasibility of our study 
procedures including patient recruitment, screening and outcome measures, and feasibility of 
adapting our intervention bundle and its intervention delivery process within three older surgical 
patient populations (i.e., orthopedic, oncologic, and cardiac); (2) empirically test the effectiveness of 
our adapted perioperative mental health intervention bundle with clinically significant symptoms of 
depression and/or anxiety; and lastly (3) identify implementation strategies to ensure acceptability, 
feasibility, and adoption of our intervention bundle by patient and clinician stakeholders. Insights 
gained from this pilot study will inform the design of three clinical trials that are planned to start in 
Jan 2023. This project is led by research team members of the newly established Center for 
Perioperative Mental Health https://perioperativewellness.wustl.edu/ that strives to improve 
perioperative mental health and well-being for older adults.  
 
3 
Study Setting and Participants 
The study will be conducted at Barnes-Jewish Hospital and Washington University School of 
Medicine locations, including Siteman Cancer Center and Barnes-Jewish West County Hospital. 
Participants will include patients and caregivers. We expect to recruit and enroll up to 70 participants 
total in this study: up to 45 patients, up to 12-15 in each of 3 surgical cohorts; up to 25 caregiver 
participants.  
 
3.1 
Patient Participants  
3.1.1 Inclusion criteria 
Patients will be included if they meet all of the following eligibility criteria:  
1. Age ≥60 years on the day of surgery;   
2. Scheduled major orthopedic surgery, or major surgical resection of a thoracic or 
abdominal malignancy, or major cardiac procedure;  
3. Clinically significant depression or anxiety symptoms screened by the PHQ-ADS 
(Patient Health Questionnaire Anxiety and Depression Scale) ≥10 [7].  
3.1.2 Exclusion criteria 
Patients will be excluded from the study if they meet any of the following:  
1. Estimated life expectancy < 12 months;  
2. Unable to read, speak, and understand English;   
3. Current alcohol or other substance abuse;   
4. Severe cognitive impairment screened by the SBT (Short Blessed Test) >10;   
5. Acutely suicidal (see instruments in Appendix A).  
Data related to patient inclusion and exclusion will be gathered either via EHR chart review, and/or 
clinical PI discretion, and/or self-reported by patient during telephone screening process. Eligible 
patients will be offered the opportunity to participate in the study regardless of gender or minority 
status. Thus, the sample composition will reflect the composition of community-living older adults in 
the St. Louis area. All of our studies actively encourage the participation of minorities in the research.  
 
3.2 
Caregiver participants  

 
 
    
 
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Caregivers offer a unique perspective on a patient’s mood and health status, and can be in a position 
to help effect change, engagement in activities and potentially our intervention bundle. Patient 
caregivers will be identified by the patient as a family member or friend who cares for the patient as 
needed to support health and safety, and often have additional care-related responsibilities in the 
perioperative period. 
 
3.3 
Participant Recruitment and Screening 
We have outlined our multi-pronged approach to recruit patients, caregivers and clinicians for this 
study.  
 
3.3.1 Patient recruitment  
In all three cohorts, patients may be contacted by the study team and invited to screen if interested. 
Prospective patients will be identified by Epic workbench reports customized to limit results to those 
at least 60 years of age with an eligible surgery scheduled at BJH/WUSM. For the WUSM 
Orthopedic Surgery clinics, patients complete a PROMIS questionnaire as standard routine practice at 
appointment check-in. Given that the PROMIS scores are available for the orthopedic surgical 
patients, the EHR report will be further customized as needed based on PROMIS scores. 
 
Initial contact by research coordinator may be made by phone, or in-person if the patient is on 
campus for a clinical visit in one of the collaborating departments. We will use an information sheet 
or phone script (see Appendix A) to introduce the goals of the center and the study. Additionally, 
recruitment flyers (see Appendix B) will be utilized to invite interested patients to contact the study 
team to screen.  The IRB-approved flyers will be distributed to the waiting rooms and clinical offices 
of the clinicians seeing our target population, as well as the CPAP which many surgical patients visit 
prior to scheduled surgery. Lastly, patients can also be referred to the study by their clinician, either 
by offering a recruitment flyer to any patients who meet our inclusion criteria, or by the clinic team at 
the time of their clinic visit. Clinical teams may refer patients to the study team for screening, some 
by phone, or email to study team members, or email to cpmh@wustl.edu. Some prospective 
participants may have clinic visits at the included Departments’ satellite sites, and some orthopedic 
procedures scheduled through Washington University take place at Barnes-Jewish West County 
Hospital, where those patients may also be enrolled and have study visits.  However, the majority of 
consenting and study procedures will take place within the WUSM and BJH Medical Center Campus.   
 
 
3.3.2 Patient screening 
We will then screen the patients who are interested to proceed in the study and provide a verbal 
consent. (Appendix A) The screening checklist (also in Appendix A) will be based on our eligibility 
criteria (see criteria above). To avoid burdening patients with the full PHQ-ADS at the time of 
screening, patients will first be asked to complete the brief PHQ-4 (i.e., first 4 questions of PHQ-
ADS related to anxiety and depression) Patients who score >3 will continue with the remaining 
questions in the PHQ-ADS. Patients with a total score of PHQ-ADS ≥10, and a SBT (Short Blessed 
Test) score of < 9 will be invited to consent to participate in the study (Table 1). This will be 
completed at the time of recruitment by a trained member of the research team, and the screener can 
be collected by phone or in person per patient preference.   
 
Table 1. Scored Instruments for Screening (see details in Appendix A) 

 
 
    
 
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Screening 
Instrument 
Eligibility Criteria 
Cut-off for 
Eligibility 
Source 
PHQ-4 
Pre-screen Depr/Anx sx 
Inclusion >  3 
Self-report in screening instrument 
PHQ-ADS  
Clinically Significant Sx 
Inclusion > 10 
Self-report in screening instrument 
SBT 
Cognitive health 
Exclusion > 10 
Self-report in screening instrument 
 
 
3.3.3 Caregiver recruitment  
Patients may refer their caregivers (e.g., spouse, partner, children, friend) to contact the study team if 
interested, or if they prefer to share the caregiver’s phone number, the study team contact them by 
phone and invite them. With the patients’ consent, patients’ caregivers are also invited to participate by 
phone, or mail. They will participate in a brief REDCap survey to report any changes related to 
confusion or delirium in the patient once before surgery, and once per week for 4 weeks after surgery 
(FAM-CAM attached). Additionally, some patients’ caregivers  (up to 25) will be invited to participate 
in a semi-structured interview (see Appendix J) after the patient’s participation in the intervention has 
been completed.  
 
 
3.4 
Participant Consenting and Enrollment  
3.4.1 Patient consent  
Patients will be invited to read, discuss, review and ask any questions they may have about study 
participation with a study team member, and then complete the Informed Consent Form (Appendix 
C). The informed consent will be available either via a paper collected by mail or in person, or by 
secure REDCap link to e-consent, as per patient preference. Patients who meet all eligibility criteria 
in 3.1 and provide consent may be enrolled into the study per PI discretion. Some patients who meet 
the eligibility criteria but who may require additional clinical input before enrolling them into the 
study, will be discussed with the study team clinicians and the PI.  
 
3.4.2 Caregiver consent 
Caregivers will be invited to participate in semi-structured interviews about the intervention bundle 
that can be conducted via Zoom/Phone or in-person depending on participant convenience and 
choice. Hence, they will be consented verbally or with a written consent depending on their 
participation.  If they consent to a semi-structured interview (Appendix J). The interviews with 
study patient caregivers, will provide valuable feedback on the intervention bundle. Caregivers may 
also consent verbally to participate in the FAM-CAM confusion and delirium assessment via 
phone, mail, or email link to REDCap survey.   
 
4 
Study Design 
This is a feasibility study utilizing mixed methods. All eligible and consenting patients will receive 
the intervention bundle and will undergo a standard battery of assessments prior to the intervention 
and will be followed for approximately 3 months in the postoperative period. In conjunction with the 

 
 
    
 
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quantitative data collected, qualitative methods will be employed to evaluate acceptability, 
implementation and practicality of the intervention.   
            
4.1 
Assessments  
At enrollment, a research coordinator will administer a battery of baseline assessments (see Appendix 
D) to characterize patient participants. Patient participants will complete these baseline assessments 
after consent:    
• Demographics survey  
• Medical History of Comorbidities  
• Brief Pain survey  
• BADS (Behavioral Activation Depression Scale)  
• Brief survey of Patient Reported Falls past 3mo 
• VR-12 Quality of Life survey 
• SDM-4 (Shared Decision Making) 
• PHQ-ADS (Patient Health Questionnaire Anxiety and Depression Scale, 
collected at screening in Appendix A) 
• SBT (Short Blessed Test, collected at screening in Appendix A)    
• Review of Medication list (at initial intervention visit)   Ultra Brief Confusion 
Assessment Method (and 3D-CAM if UB-CAM is positive) or FAM-CAM, 
and/or delirium may be assessed by EHR review using the CHART-DEL [23] 
method (Appendix M).   
Anxiety and depression assessment will use the PHQ-ADS, as described above. The use of this tool 
for this population is supported by a recent meta-analysis suggesting that the PHQ9 (on which this 
tool is based) has good sensitivity and specificity in the diagnosis of depression in older adults [9]. 
Quality of Life (QoL) will be assessed using the Veterans RAND 12 Item Health Survey (VR-12) 
[10]. The questions in this patient-reported survey correspond to the QoL domains of general health 
perceptions, physical functioning, role limitations due to physical and emotional problems, bodily 
pain, energy/fatigue levels, social functioning and mental health. Cognitive function assessment will 
be performed using the Short Blessed Test (SBT) as described above. The SBT is a reliable test for 
characterizing cognitive functioning in this setting [22]. Falls data will be collected by monthly 
Patient-Reported Falls Questionnaire, which will be collected  
by phone with other assessments or via a REDCap survey which can be emailed to participants one 
time per month asking about any falls over the last month.  
 
4.2 
Perioperative Mental Health Intervention Bundle 
Our intervention bundle will be initiated prior to surgery and continue postoperatively, and will span 
for approximately 3 to 4 months across the perioperative period (including pre- and 3 month post-
operative periods). The personalized intervention bundle is comprised of behavioral activation and 
medication optimization, both facilitated by specially trained interventionists on the research team.  
 
 
4.2.1 Behavioral Activation 

 
 
    
 
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The behavioral intervention will consist of behavioral activation (BA), the basic premise of which is 
to help people with mental health problems to engage in activities that are reinforcing or meaningful 
and guided by their personal values [13]. The interventionists in this component of the intervention 
bundle, Perioperative Wellness Partners, are qualified social workers and therapists with relevant 
mental health experience, in addition to specific training to implement this intervention.  Patients will 
be asked to check with their physicians if there is any question about the safety of any physical 
activities that are included in the behavioral activation plan. Behavioral activation as the core 
intervention allows for uniformity across participants from each cohort, yet enough flexibility for the 
actual components of behavioral activation to be individually adapted based on patient preferences. 
In a recent meta-analysis, behavioral activation programs improved depression and anxiety [14], as 
well as disability in older adults [15]. In addition, BA delivered by telehealth to older adults was cost-
effective and lowered health care utilization costs over 1 year [16]. In addition to the core 
intervention of behavioral activation, study participants will be able to adapt the intervention by 
choosing activities, per their preference, with demonstrated benefit in improving depression and 
anxiety symptoms in older adults [17, 18]. BA will span across approximately 3 months 
postoperatively and will begin pre-operatively, with sessions approximately weekly or biweekly, 
depending on patient preference and health condition. For example, participants with hospital stays 
>1 week, behavioral intervention may continue weekly in the hospital setting, if the patient chooses. 
Finally, after discharge during the postoperative period, the behavioral intervention will continue for 
the remaining months/sessions. The timing, format and frequency of the behavioral activation 
sessions will be adapted and tailored based on patient preferences and needs. The behavioral 
activation process will be guided by the internal study team manual,(Appendix F) which will be 
adapted and calibrated as needed throughout this feasibility study,  along with the adaptations to the 
BA patient worksheets (see Appendix H) which the patient and perioperative wellness partners may 
use to guide these intervention sessions and activities. We will track all adaptations to BA conduct 
and content during this study for our future intervention study. 
 
4.2.2 Medication Optimization 
Medications will be reviewed and optimized, as appropriate, by our team of interventionists including 
a psychiatrist, pharmacologist, perioperative wellness partners, and pharmacists. In several clinical 
trials including thousands of older adults, we have developed and refined a process for this review 
and medication optimization, including adjusting suboptimal dosing for anti-depressants and 
discontinuing medications that are harmful for brain health (such as anticholinergics [19]). 
Medication optimization consists of a simple set of principles: reconcile patient’s medications, 
identify the patient’s likely need for, and interest in, a medication adjustment, make the adjustment, 
and assess the response to that adjustment. Benzodiazepines, non-benzodiazepine sedatives, strong 
centrally acting anticholinergics, and antihistamines may be deprescribed as they increase the risk for 
falls and delirium. We will follow the principles of shared decision-making with patients for 
medication changes, identifying DEMS (deprescribing eligible medications) which worsen functional 
recovery, impair cognitive function, and increase medical risks like falls, delirium, and bleeding  
With the patients’ consent, we will initiate communication with the prescribing provider regarding 
any changes to medications (DEMs in particular) which they have prescribed.  While the participant 
is in-hospital, the interventionist’s role will include coordinating with the hospital team to ensure that 
medication changes that were introduced preoperatively are maintained in-house and that no new 
inappropriate medications are initiated. We will give voice to patient and family concerns by helping 

 
 
    
 
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them communicate with the hospital (and subsequent transitional) provider team. After discharge, 
and up to approximately 3 months postoperatively, the interventionist will ensure that medication 
changes are reconciled during transitions of care. The interventionists will ensure the agreed-upon 
changes are implemented, or an alternative course of action is justified. The internal study team 
manual for medication optimization will be updated as needed in the feasibility study. Please see 
Medication Optimization SOP in Appendix F.   
 
4.3 
Evaluation Measures and Outcomes 
Preoperative assessments along with preoperative and postoperative surveys (assessments described 
in 4.1 above) regarding quality of life, depression, and anxiety will be obtained from all study 
participants. Study participants will be followed for approximately 3 months after their scheduled 
procedure. They will complete follow-up surveys at approximately 1 month and approximately 3 
months after surgery by either web-based survey, mail, or via a telephone interview (or in person if 
the visit coincides with a clinic visit). Collection of falls data will occur approximately monthly for 3 
months by phone with study coordinator, or REDCap, or in person. The results of follow-up surveys 
will be obtained via secure REDCap e-mail link, mail, or telephone survey. Rehospitalizations will be 
obtained from patient self-report and/or EHR at the end of study follow-up. Please see Table 2.1 for 
list of outcomes and details. 
Additional pre-operative data related to patient medical, social and surgical history, problems, 
diagnosis and medication lists will be retrieved from the patient electronic health record using the 
research data core (RDC). Post-operative data including post-operative acute diagnoses (e.g., 
complications), additional procedures, postoperative opioid use, pain scores will also be retrieved.  
 
4.3.1 Primary Feasibility Outcomes  
Reach of the study: patients who agreed to participate in the study out of total eligible to participate.  
Reach of the intervention bundle: patients who completed the interventions out of patients who 
agreed to participate in the pilot.   
 
4.3.2 Secondary Feasibilty Outcomes  
Completeness of planned RCT primary outcome data collection at specified timepoints  
 
4.3.2.1 Potential Study Primary Outcomes for Planned RCT   
Effectiveness outcomes will include the primary outcome measure of PHQ-ADS, a validated 
composite scale of depression and anxiety symptoms [7] measured at baseline, 1, and 3 months after 
surgery. The Behavioral Activation for Depression Scale, or BADS (activation subscale), is our 
primary measure of target engagement. BADS is a sensitive and pragmatic assessment of the 
mechanism of change in Behavioral Activation. Approximately three months post-operative is the 
primary endpoint.  
 
4.3.2.2 Potential Study Secondary Outcomes for Planned RCT  
The secondary outcomes will include QoL measured via the VR-12 Health Survey, and other 
perioperative outcomes of interest, nominated by our stakeholders as key outcomes of interest, 
including:  

 
 
    
 
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1. In-hospital: (i) Delirium incidence, assessed by trained research coordinators using the Ultra 
Brief and 3-D Confusion Assessment Method, [20] as in our prior work [19], and/or Delirium 
incidence may be assessed by EHR review using the CHART-DEL [23] method ;  (ii) Length of 
Stay (hospital and ICU), assessed by EHR review.  
2. Post-discharge: (i) Falls, prospectively assessed monthly falls reported by patients. (ii) All-cause 
rehospitalization out to approximately 3 months postoperative, assessed from EHR report, 
supplemented by review with patient and caregiver.  
3. Process outcomes: Shared Decision Making (modified collaboRATE) 3 item survey will be 
administered at post-end of study. CAHPS modified survey will be administered after the 
intervention is complete, as part of post-end of study surveys.  
4. Implementation-potential surveys: Acceptability of Intervention Measure, Intervention 
Appropriateness Measure, Feasibility of Intervention Measure. 
 
4.3.3 Exploratory Feasibilty Outcomes 
Impletmentation potential  
Completeness of planned RCT primary outcome data collection at specified timepoints  
 
Table 2. Feasibility study outcomes and potential study primary and secondary outcomes for 
planned RCT. Note: The surveys and questionnaires will be administered via email or research 
coordinators over the telephone. 
Outcomes  
Specific measure: description 
Source 
Timepoint 
Reach 
(Primary) 
Reach of the study: patients who agreed to 
participate in the study out of total eligible to 
participate 
Reach of the intervention bundle: patients who 
completed the interventions out of patients who 
agreed to participate in the pilot 
Electronic 
Health Record, 
Research data 
warehouse 
End of Study 
Completeness of 
planned RCT 
primary outcome 
data collection at 
specified timepoints 
(Secondary) 
Defined as a percentage of instrument or data 
fields completed for- Patient Health 
Questionnaire Anxiety and Depression Scale 
(PHQ-ADS)62: 16-item scale with components of 
the Patient Health Questionnaire-9 and 
Generalized Anxiety Disorder Scale (collected at 
baseline; 1 mo; 3 mo) 
Research data 
warehouse 
End of Study 
Implementation-
Potential 
(Exploratory) 
Acceptability, appropriateness and feasibility of 
the interventions: The Acceptability of 
Intervention Measure (AIM), the Intervention 
Appropriateness Measure (IAM), and the 
Feasibility of Intervention Measure (FIM).77 
Each survey has 4 items in a Likert scale ranging 
from completely disagree to completely agree.  
Surveys 
 
End of Study 
 

 
 
    
 
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Completeness of 
planned RCT 
secondary outcomes 
data collection at 
specified timepoints 
(Exploratory) 
We will be measuring the completeness of data 
collection for the following potential secondary 
outcomes for the planned RCT secondary 
outcomes: 
• 
Quality of Life (collected at baseline; 1 
mo; 3 mo) 
• 
In-hospital delirium incidence (collected 
at baseline; in-hospital/postoperatively) 
• 
Post-discharge falls (collected at 
baseline; 1 mo; 2 mo; 3 mo) 
• 
Medication optimized and adherence to 
medications(collected at baseline; 1 mo; 
3 mo) 
• 
Length of stay (both hospital and ICU) 
• 
All-cause rehospitalization (collected in 
the hospital/postoperatively; 1 mo; 3 
mo) 
• 
Persistent postsurgical pain (collected at 
1 mo; 3 mo) 
• 
Patient experience (collected at end of 
study) 
• 
Shared decision making (collected at end 
of study) 
Research data 
warehouse 
End of Study 
 
 
Table 2.1 Details on Potential Study Outcomes for Planned RCT  
 
Effectiveness Outcomes 
Data Source 
Description 
Data Collection 
Mechanism  
 
Time points   
(Baseline, 1, 
2, 3 month-
post-op or 
EOS) 
Primary 
(Clinical) 
Anxiety and 
Depression 
Patient 
Health 
Questionnaire 
Anxiety and 
Depression 
Scale (PHQ-
ADS)  
A validated composite 
of symptoms of 
depression and anxiety 
Patient Self-Report 
Baseline; 
1 mo and 3 mo 
Primary (Target 
Engagement 
measure) 
Anxiety and 
Depression / Target 
Engagement 
Behavioral 
Activation for 
Depression 
Scale 
(BADS) 
A validated scale 
utilized to measure 
target engagement in 
studies of geriatric 
depression 
Patient Self-Report 
Baseline; 
1mo; 2mo; 
3mo 
Secondary 
(Clinical) 
Quality of Life 
The Veterans 
RAND 12 
Item Health 
Survey (VR-
12)43 
A patient-reported 
global health measure. 
The questions in this 
survey correspond to 
the QOL domains of 
general health 
Patient Self-Report 
Baseline; 
1 mo and 3 mo 

 
 
    
 
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perceptions, physical 
functioning, role 
limitations due to 
physical and emotional 
problems, bodily pain, 
energy/fatigue levels, 
social functioning and 
mental health. 
In-hospital delirium 
incidence  
 
Ultra Brief 
CAM to 
screen for 
3D CAM, 
and if 
UBCAB 
positive, 
then 3D 
CAM 
Confusion 
Assessment 
Method44  
 
UB-CAM and 3D 
CAM are  
standardized, 
evidence-based 
interview that enables 
researchers and 
clinicians, following 
structured training, to 
reliably and 
reproducibly identify 
the four cardinal 
features of delirium. 
 
 
UB-CAM and 3D 
CAM Research 
Coordinator- 
Administered  
Baseline/pre-
op; In-
hospital: 
During post-
op hospital 
stay; up to 
twice daily 
for 3 days; if 
not in person, 
UB-CAM 
may be 
collected by 
phone.  
 
 
Family Confusion 
Assessment Method 
FAM-CAM 
The FAM-CAM is 
intended to evaluate 
for evidence of 
delirium based on 
observations from 
family members or 
caregivers. The 
instrument facilitate 
and educate caregivers 
to pick up acute 
changes in mental 
status, and the earliest 
signs of cognitive 
changes in frail or 
cognitively impaired 
older persons. 
Survey or phone 
Baseline/pre-
op; post-op, 
once every 
week for 4 
weeks. 
Post-discharge falls 
Patient 
Reported 
Falls  
A Patent Reported 
Falls survey will be 
collected monthly 
either by phone or 
REDCap link, at 
follow-up clinic 
appointments. 
Patient Self-Report 
Baseline; 
1mo; 2mo; 
3mo 
Medication list 
Data 
collection 
Appendix D; 
Appendix G 
Review of all patient 
medications, 
confirming accuracy 
of EHR med list, 
number of 
medications optimized 
and medication 
adherence 
Patient Self-Report/ 
study team member 
verifies EHR meds 
list with patient 
Baseline, 
initial 
intervention 
visit; 
approximately 
1mo; 
approximately 
3mo at end of 

 
 
    
 
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intervention. 
Length of stay (both 
hospital and ICU) 
Research 
Data Core 
Standardized reports 
on the research data 
core (RDC) warehouse 
will generate statistics 
of enrolled patients 
regarding the length of 
stay, rehospitalization, 
and related clinical 
metrics.  
EHR report 
In-hospital: at 
ICU and 
hospital 
discharge 
All-cause 
rehospitalization  
Research 
Data Core 
EHR report 
Post-op: 1 mo 
and 3 mo 
Secondary 
(Process) 
Patient experience 
Modified-
Consumer 
Assessment 
of Healthcare 
Providers and 
Systems 
(CAHPS)45 
The modified CAHPS 
asks patients about their 
experience before 
surgery, during surgery, 
and after surgery. 
Patient Self-Report 
Post-EOS  
 
 
 
 
 
 
 
 
 
 
 
 
 
Shared decision 
making  
Shared 
decision 
making 
process  
CollaboRAT
E modified  
A 3-item survey 
modified to measure 
shared decision making, 
following a encounters 
with study 
interventionists and 
perioperative wellness 
partners 
Patient Self-Report 
Post-EOS 
Implementation Outcomes 
 
Data Source 
Description 
Data Collection 
Mechanism 
 
Time points 
 
Implementation-
Potential (I) 
Acceptability 
of 
Intervention 
Measure,  
Intervention 
Appropriaten
ess Measure, 
Feasibility of 
Intervention 
Measure  
Acceptability, 
Feasibility and 
Appropriateness 4-item 
Likert scale survey 
Patient Self-Report 
Post-EOS 
In addition to these outcomes, we will also be assessing fidelity of our intervention bundle which will 
assess the extent to which an intervention bundle is carried out by our perioperative wellness partner, 
as intended and consistently across different settings, and patients. To track this, we will observe and 
take notes on the patient and the perioperative wellness partner during the behavioral intervention and 
medication optimization sessions with the patient and clinician. Observations will involve a member 
of the research team observing the wellness partner over a period of time or number of intervention 
sessions. We will capture data on patient interactions with the wellness partner, their delivery of the 
intervention bundle, any observed barriers and facilitators to the intervention adherence, acceptance 
and fit within the perioperative workflow. These observation sessions of patients and their wellness 

 
 
    
 
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partners will be selected based on a convenience sample.  If the patient agrees to audio/video 
recording, the intervention sessions will be audio recorded (or audio/video if the patient prefers to 
meet by Zoom teleconference).  The observations may be made by a member of the research team 
reviewing the recorded sessions.   
Lastly, we will also obtain various stakeholder perspectives on the intervention bundle after the 
intervention period has been completed using semi-structured interviews. We will conduct interviews 
with patients, and caregivers, and the topics of discussions will be guided by an implementation 
science framework referred to as CFIR (Consolidated Framework of Implementation Research). The 
interviews will explore the participants’ perceptions, attitudes, experiences with the intervention 
bundle, intervention bundle acceptability and detailed accounts of participants' experiences after the 
intervention has been stopped with regards to intervention sustainability and maintenance. These 
insights will inform whether the intervention bundle needs to be changed or adapted before our future 
trials (see interview guides in Appendix J). Interviews will be conducted via Zoom or telephone and 
will be digitally recorded and transcribed verbatim.  
 
5 
Data Analysis 
The quantitative data will be used to provide baseline and post-intervention comparisons on a number 
of outcome variables relevant to the intervention, with the hypothesis that performance on these 
measures will improve post intervention. These data will also be used to estimate effect sizes for 
further trials so that these are suitably powered. Quantitative data will be tabulated for descriptive 
purposes. Given the small sample size, a non-parametric approach will be used to calculate effect size 
data (r = Z/√ (N)), where Z is the standardized test-statistic from a Wilcoxon signed-rank test and N 
is the sample size, along with the associated 95% confidence interval. The r values will be calculated 
for the timepoint as compared to baseline.  
 
The observation data will be analyzed using open coding and FRAME analytic framework that helps 
track any adaptations to intervention bundle and delivery. The interview data will be analyzed using 
thematic analysis [8].  
 
Table 3. Study Calendar  
 
 
Time 0 
Baseline/ 
Time 1 
 
In-
Hospital / 
Post-Op 
1 mo 
follow up 
2 mo 
follow up 
3 mo 
follow up 
Post-
EOS 
Patient Consent 
X 
 
 
 
 
 
 
Patient Screening  
(Appendix A)  
X 
 
 
 
 
 
 
Patient Baseline surveys  
(Appendix D) 
 
 
X 
 
 
 
 
 
Caregiver Consent 
 
X 
 
 
 
 
 
X 
Patient Delirium Assessment  
(Appendix K) pt UB/ 3-D CAM ; & 
Caregiver if applicable, FAM-CAM 
 
X (pt) 
X(pt) 
twice 
daily x 3 
FAM-
CAM if 
applicable 
 
 
 

 
 
    
 
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1x weekly for 4 weeks. 
days post-
op 
 
(weekly x 
4wks) 
Patient Follow-up 1 & 3 mo Surveys 
(Appendix G) 
 
 
 
X 
 
X 
 
Patient Monthly Surveys 
(Appendix L) 
 
 
 
X 
X 
X 
 
Patient Post-EOS Surveys  
(Appendix I) 
 
 
 
 
 
 
X* 
Patient Semi-Structured Interview  
(Appendix J) 
 
 
 
 
 
 
X* 
Caregiver  
Semi-Structured Interview 
(Appendix J) 
 
 
 
 
 
 
X* 
Behavioral Activation and 
Medication Review Intervention 
Sessions 
 
 
Approximately 6-12 sessions as needed (per Pt 
preference) from Baseline, continuing for up to 
approximately 3 months post-op during study 
data collection, until EOS.  
 
*Post-End of Study (EOS) implementation surveys and semi-structured interviews will be completed approximately 2 
weeks after EOS assessment.  
 
 
6 
Patient Participant Retention  
Participant retention strategies will include flexibility in scheduling follow-up visits and coordination 
of research (both data collection and intervention) visits with the clinical visits. Remuneration for 
each data collection study visit will be provided after the final follow-up visit to encourage retention 
as well. For patients who are difficult to reach by phone, we may utilize a reminder, the Attempting to 
Reach You Letter (Appendix N) to remind them to contact either the Perioperative Wellness Partner 
or the Study Coordinator for a study session.  
 
 
7 
Protection of Human Subjects 
The study will be conducted under appropriate Washington University Institutional Review Board 
guidance, and use only IRB-approved study procedures and instruments. The study team will follow 
the protocol under the supervision of the PI, a mentor with several years of experience in the conduct 
of human volunteer studies, and co-Investigators with extensive expertise in human subject research. 
All members of the study team are IRB-approved and trained in Good Clinical Practice and Human 
Subjects Research education.   
 
8 
Data Management for Participant Privacy 
A unique patient number (UPN) will be assigned at enrollment and used wherever possible on the 
case report forms (CRF) to identify data, minimizing use of patients’ names or personal identifiers in 
data.  

 
 
    
 
Page 14 of 18 
 
All paper data will be stored under lock and key (two locked doors, e.g., office, file cabinet) and all 
electronic data will be hosted on a password-protected, firewall-secured server that is only accessible 
to the research team through password-protected departmental computers. Surveys that are completed 
electronically will be administered via the Research Electronic Data Capture (REDCap) server. All 
REDCap email correspondence will be sent using secure survey links. Similarly, interview data from 
caregivers will follow the same security and storage policies.  
 
8.1 
List of Protected Health Information collected for study 
For Patient and Caregiver Participants, the HIPAA-protected identifiers that will be collected for 
this study include: 
• Name 
• Date of birth 
• Contact information 
• Mailing address 
• Phone number 
• Electronic mail address 
• SSN for the purpose of remuneration   
For Patient Participants only, these additional HIPAA-protected identifiers will also be collected 
for study:  
• Dates of services (surgical procedure, hospitalization)  
• Medical record number 
 
9 
Potential Risks 
This study involves minimal risk to subjects. Unlikely but potential risks include errors in medication 
recommendations or medication withdrawal symptoms, and breach of confidentiality. The risk of 
medication withdrawal (i.e., from benzodiazepines) is mitigated by slowly tapering rather than 
stopping these medications. Patients who are identified as being acutely suicidal will be excluded 
from the study. Nevertheless, since the rate of completed suicide in the USA remains high (i.e., about 
twice the rate of homicide) and most Americans who commit suicide suffer from depression, all 
participants eligible to participate in this study are statistically at a relatively higher risk for suicide 
than the general population. However, the participants’ absolute risk for completing suicide during 
this brief study remains very low (i.e., about 1 in 3,000 to 10,000) and participation in the study does 
not create or increase the risk of completed suicide; rather, most experts believe that one of the most 
efficient ways to decrease suicidal risk in older depressed individuals is to treat their depression. 
Furthermore, all participants will be formally assessed frequently throughout the study. If the study 
personnel identify that a participant has become acutely suicidal, this participant will be referred to a 
mental health professional for further evaluation and treatment (see section: Procedures to Minimize 
Risks). This may lead to a clinical intervention that is lifesaving and may not have occurred had the 
participant not been participating in the study. 
 
10 Adverse Experiences  

 
 
    
 
Page 15 of 18 
 
Based on the nature of this study, which involves surveys, a cognitive test, and a behavioral 
intervention, adverse events are exceedingly unlikely. The principal investigator and study 
coordinator will monitor for breaches of confidentiality and other adverse events on an ongoing basis.  
If the PI or study coordinator becomes aware of a reportable adverse event, the event will be reported 
to HRPO according to institutional guidelines.   
 
11 Procedures to Minimize Potential Risks 
Professor Eric Lenze, MD (PI on the Center for Perioperative Mental Health; Co-I on this study) will 
manage the oversight of the interventions making medication optimization recommendations to 
reduce the risk of medication error or medication withdrawal symptoms. Algorithms for tapering 
medications that should not be abruptly discontinued will be employed. We have carried out this 
deprescribing protocol in several large RCTs and have not seen any problems occur. 
 
Suicide Risk Management: As discussed above, at each assessment point, the research staff will 
assess for passive death wish, and suicidal ideation, intent or plan when they administer the PHQ-
ADS. If a participant endorses suicidal ideation, intent, or plan, the rater will be trained to follow an 
operationalized protocol (Appendix E) that has been developed to manage high-risk participants in 
other studies of depressed participants potentially at risk for suicide. This protocol has already been 
used successfully by Dr. Lenze’s team to manage acutely suicidal patients. Briefly, the protocol 
entails a specific determination of the suicidal risk and prescribes a set of actions. If a participant is 
determined to be at high and immediate risks, the rater is instructed to stay with the participant until 
he or she has contacted a study psychiatrist (Dr. Lenze) to discuss the situation and to devise a plan. 
In case of extreme emergency, raters are instructed to call their hospital security team or 911 for 
immediate help and to initiate commitment proceedings. 
 
Patients will be encouraged to check with their physician if there is any question about the safety of 
any physical activities that are included in the behavioral activation plan. It is possible that the 
participant may feel uncomfortable completing the surveys or participating in the study sessions.  The 
study sessions and interview can be discontinued at any time, and the patient may refuse to answer 
any questions that s/he does not wish to answer. 
To minimize the risk of breach of confidentiality, we will ensure that protected health information 
will only be shared with members of the research team. Only data necessary to complete the study 
will be collected. Data will be coded with UPN wherever possible, and the master list linking names 
to UPNs will be securely accessible only to the PI, Co-Investigators, data analyst, and primary 
research coordinator.  Electronic data will be stored as detailed in section 8.   
 
12 Data and Safety Monitoring Plan 
The specific monitoring plan for this investigation is commensurate with the risks and the size and 
complexity of the studies planned. Given the nature of the protocol, the risks are likely limited to 
breach of confidentiality. Data will be monitored and protected as described in Section 8, with PI 
oversight of data management. 
 
Participation in this study does not entail any physical or medical risks that are greater than those 
ordinarily encountered in daily life. It is possible that the participant may feel uncomfortable 
completing the questionnaires. If a participant becomes upset, the PI will talk to the participant either 

 
 
    
 
Page 16 of 18 
 
at that time or will contact the participant by telephone. If any further referrals are deemed necessary 
(i.e., social work or psychiatry), these referrals will be made in collaboration with the patient’s 
primary medical team. 
 
There is also a risk of breach of confidentiality. All reasonable steps will be taken to ensure that 
patient privacy is maintained. Hard copy data (i.e. signed informed consent forms) will be maintained 
in a locked office within a locked suite. Electronic data will be stored on a Washington University 
password-protected server and never stored on a portable hard drive or laptop computer. Patient data 
will be identified by a study ID only, with a master key linking patient names with study IDs kept in a 
separate file accessible only to the Primary Investigator and Research Study Assistant. 
 
The only interventions outside the standard of care for management of the patient’s diagnosed 
condition in this study are the administration of questionnaires, a cognitive test, and medication 
optimization. We expect that the occurrence of a serious adverse event as it relates to these study 
interventions to be extremely rare. If a breach of confidentiality were to occur, it would be reported to 
QASMC and HRPO within 10 days of notification. 
 
The study principal investigator and study coordinator will monitor for breaches of confidentiality 
and other adverse events on an ongoing basis. Once the PI or study coordinator becomes aware of a 
reportable adverse event, the event will be reported to HRPO and QASMC according to institutional 
guidelines. This study does not require QASMC audit or submission of DSM reports. 
 
13 Premature Discontinuation 
Subjects will be withdrawn if the investigator decides that discontinuation is in the best interest of the 
subject, or the subject requests withdrawal from the study. As part of the informed consent process, 
patients will be notified they may choose to not participate in the study or withdraw at any time with 
no penalty, and no effect on the standard care they receive. 
 
14 Potential Benefits of the Proposed Research to Participants and Others 
Although the study is designed to improve symptoms of depression and anxiety and other outcomes 
of care, there is no guarantee that the study participants will receive any clinical benefits by 
participating in the study. This may lead to a clinical intervention that is lifesaving and may not have 
occurred had the participant not been participating in the study. Given the undertreatment of 
depression and anxiety in older adults, the minimal risks are acceptable in comparison to the potential 
benefits in improving the mental health of older adults undergoing surgery. 
 
15 Remuneration 
It will not cost the patient anything to participate in the study, and with the flexible design allowing 
for phone visits, they will not be required to make any extra study visits to the medical center (some 
visits may be concurrent with a clinic or procedure appointment).  Patients will receive remuneration 
by debit card of $25 for completion of each data collection study visit at Baseline, 1, 2, 3 month post-
op, Post-EOS data collection surveys, and semi-structured interview, up to $125 after completion of 
their participation.  
 
16 Funding 

 
 
    
 
Page 17 of 18 
 
The study is funded by the National Institute of Mental Health (NIMH) (P50 MH122351-01A1). 
                               
 
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