Messy Memories: A Mobile Application Exposure Therapy Intervention to Reduce Psychological Distress and Improve Health Behaviors Following Critical Illness
Phase: NA
Conditions: Critical Illness, Psychological Distress, Health Behavior
Sponsor: Columbia University

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STUDY TITLE: Messy Memories: A Mobile Application Exposure Therapy Intervention to 
Reduce Psychological Distress and Improve Health Behaviors Following Critical Illness 
 
IRB NUMBER: AAAU1653 
 
NCT NUMBER: NCT05849454 
 
PRINCIPAL INVESTIGATOR: Nadia Liyanage-Don, MD, MS 
 
1. Study Purpose and Rationale 
Although posttraumatic stress disorder (PTSD) has traditionally been associated with military 
combat, sexual assault, or natural disasters, a growing body of literature suggests that it also 
frequently develops in response to life-threatening medical events, particularly those requiring 
critical care.1,2 Critical illness can be an incredibly traumatic experience, often involving treatment 
in the intensive care unit (ICU), intubation or other invasive medical procedures, altered levels of 
consciousness, inability to communicate, sensory and sleep deprivation, physical pain, and 
delirium.3,4 The cumulative physical and psychological stress associated with critical illness can 
be severe enough to induce clinically-significant symptoms of PTSD,5,6 hallmarks of which include 
intrusive thoughts, persistent re-experiencing of the traumatic event, negative alterations in mood 
and cognition, increased arousal or hypervigilance, and avoidance of trauma-related stimuli.7 Up 
to 63% of critical illness survivors report subsequent PTSD symptoms, which are associated with 
physical disability, functional impairment, poor health-related quality of life, and diminished life 
course opportunities.8-12 Furthermore, patients with medically-related PTSD are more likely to 
engage in unhealthy behaviors, such as tobacco use,13,14 sedentary lifestyle,15,16 poor diet,16 and 
medication nonadherence.17-20 
There are multiple existing treatment modalities for PTSD, including pharmacotherapy, cognitive 
behavioral therapy, interpersonal therapy, stress inoculation training, and relaxation 
techniques.21 However, exposure therapy (ET) is considered the gold standard PTSD treatment,22 
supported by decades of research and recommended in the practice guidelines of organizations 
such as the Institute of Medicine23 and the National Institute for Clinical Excellence.24 Based on 
emotional processing theory, ET involves habituation, extinction, and modification of the 
pathological elements of a theoretical fear structure.25,26 Patients are repeatedly exposed to 
trauma-related stimuli in a safe clinical environment, leading to habituation of maladaptive 
emotional responses to the traumatic event and an increased sense of control and self-
competence. In turn, this reduces avoidance of trauma-related stimuli, resulting in even more 
spontaneous exposure to such stimuli and further reduction in PTSD symptoms.27,28 ET is highly 
effective for improving PTSD triggered by various forms of trauma, including combat, noncombat, 
and sexual trauma.29-32 ET also significantly reduces symptoms that often co-occur with PTSD, 
such as depression, anxiety, guilt, and anger.33,34 Several recent large-scale reviews and meta-
analyses have confirmed that ET is both safe and effective for improving PTSD symptoms in 
various patient populations, including those with complex medical comorbidities.35-37 
Less is known about the role of ET for reducing PTSD symptoms after life-threatening medical 
events. In a study of patients with PTSD related to hematopoietic stem cell transplantation for 
hematologic or lymphoid malignancy, exposure-based therapy led to a significant reduction in 
PTSD symptoms and lower odds of PTSD diagnosis at 12 months compared to an assessment-
only control.38 Among patients with HIV-induced PTSD symptoms, those enrolled in a biweekly 
ET program experienced a greater decrease in PTSD symptoms both immediately post-
intervention and at 3-month follow-up compared to those enrolled in a waitlist control.39 A study 
of patients with PTSD symptoms due to a cardiovascular event (e.g., myocardial infarction, 
coronary artery bypass graft, stroke) showed that ET was associated with an improvement in 

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PTSD symptoms compared to an education-only control group, though the study was 
underpowered to reach statistical significance.40 To our knowledge, there have been no studies 
exploring the safety, efficacy, or acceptability of ET for treating PTSD specifically induced by 
critical illness requiring intensive care unit (ICU) treatment. Furthermore, even when PTSD 
treatments are available and offered, patients often face considerable barriers to accessing such 
treatments, including financial constraints, availability of mental health providers, travel time or 
distance, lack of transportation, concerns about privacy, and perceived stigma.41-44 The avoidant 
behavior typical of PTSD makes it even more challenging for patients to seek, accept, or engage in 
effective treatment.45 
In response to these barriers, novel treatment delivery approaches have been developed in recent 
years to make therapy for PTSD more accessible and acceptable. Many of these interventions are 
grounded in ET principles, including a version of PTSD psychotherapy for primary care46 and 
strategies to reduce burnout stress in ICU nurses.47 Preliminary evidence suggests that these brief, 
flexible, self-directed interventions are effective for treating PTSD and anxiety disorders.48 
Technological solutions, such as clinical videoconferencing and mobile device applications, have 
also been used to overcome barriers to timely and effective delivery of PTSD care. For example, 
the smartphone application PTSD Coach, which offers psychoeducation about PTSD as well as 
coping skills based on cognitive behavioral therapy, was found feasible and acceptable when 
tested in a community sample of trauma survivors.49 In a subsequent randomized controlled trial, 
users of the PTSD Coach mobile application had a significant decrease in PTSD symptoms 
compared to a waitlist-control group.50 A self-directed mobile mindfulness training application 
initiated in ICU patients following hospital discharge demonstrated feasibility, acceptability, and 
usability, with similar reductions in psychological distress and physical symptoms compared to 
either a therapist-led telephone-based mindfulness program or a web-based critical illness 
education program.51 Other mobile applications have been developed and tested for treating social 
anxiety disorder,52 reducing self-injurious thoughts and behaviors,53 and lowering alcohol 
consumption among college students.54 A variety of mindfulness meditation applications, such as 
Headspace and Calm, have also been marketed to the general public with the broader aim of 
improving mental health and well-being.55 However, there is currently no mobile application 
available that directly targets stress-related concerns while following evidence-based ET 
principles.  
The purpose of the proposed pilot study is to conduct preliminary testing of a newly developed 
mobile application (Messy Memories) that specifically targets stress-related concerns to reduce 
psychological distress and improve health behaviors among survivors of critical illness. The 
Messy Memories app allows the user to self-administer exposure therapy with the goal of 
reducing psychological distress and ultimately improving health behaviors. The user is asked to 
document a traumatic or distressing memory (either in writing or via audio recording) and 
process what it felt like to re-experience the memory. Users can return to their documented 
memory as often as they like until it becomes easier to re-experience.  
The app was initially designed by researchers to target stress-related concerns in frontline 
healthcare workers after Drs. Sheila Rauch (Emory), Naomi Simon (NYU Langone Health), and 
Barbara Rothbaum (Emory) created an evidence-informed framework for health system 
response to a traumatic event based on different levels of intervention (including self-directed 
intervention). (See https://adaa.org/sites/default/files/PhasedApproachtoCovid-19.ver1.2.pdf 
for more detail.) This model was presented as a plan for addressing the increasing shortage of 
mental health resources at a time of increasing need for these resources. Drs. Sheila Rauch and 
Barbara Rothbaum are renowned experts with decades of experience in the field of PTSD 
research and treatment (see: Meet the Team | Emory School of Medicine).    

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The Messy Memories application is a self-directed exposure intervention, and an extension of 
the framework created by Drs. Rauch, Simon, and Rothbaum. Specifically, the Messy Memories 
app allows the user to self-administer exposure therapy techniques outside of the traditional 
psychotherapy context. The Messy Memories app was initially released in a written form for 
self-help, but with widespread use of smartphones, a mobile application has the potential to 
further reduce barriers and increase access to care.  
The Messy Memories app does not directly request any identifiable information from users. 
Participants will also be explicitly instructed not to provide any identifiable information when 
utilizing and responding to app prompts. The Messy Memories Study team at CUIMC will not 
share any identifiable subject data with the app developer.  
For our study, we will determine the feasibility of enrolling critical illness survivors into the 
intervention, test the ability of participants to follow the intervention protocol, assess 
participant satisfaction with the intervention, and measure changes in psychological distress 
before and after completing the intervention. We note that in order to be eligible, participants 
will indicate some level of psychological distress related to their ICU hospitalization, however 
the minimum threshold for this level of psychological distress is well below the threshold for 
PTSD.   
Aim 1: Assess the feasibility of recruiting and engaging critical illness survivors in a mobile 
application-based exposure therapy intervention (Messy Memories). Hypothesis: The 
intervention will be feasible based on recruitment, retention, and completion rates of ≥70%. 
Aim 2: Assess the acceptability of recruiting and engaging critical illness survivors in a mobile 
application-based exposure therapy intervention (Messy Memories). Hypothesis: The 
intervention will be acceptable based on participant satisfaction ratings of ≥70% and qualitative 
analysis of exit survey responses. 
Aim 3 (exploratory): Assess engagement of the mechanistic target (PTSD symptoms) by the 
mobile application-based exposure therapy intervention (Messy Memories). Hypothesis: 
Participants will report improvement in PTSD symptoms, based on pre-/post-intervention 
decrease in scores on the PTSD Checklist for the Diagnostic and Statistical Manual of Mental 
Disorders, 5th Edition (PCL-5). 
2. Study Design  
Overall approach: The proposed pilot study will conduct preliminary testing of a novel mobile 
application (Messy Memories) that uses remotely delivered exposure therapy to reduce 
psychological distress and improve health behaviors in survivors of critical illness. Specifically, 
we aim to assess the feasibility and acceptability of recruiting and engaging critical illness 
survivors in the intervention. We also aim to explore the efficacy of the intervention in engaging 
the mechanistic target (PTSD symptoms) to reduce psychological distress. The results of this 
initial pilot study will be used to make refinements to the research protocol in preparation for a 
future adequately powered randomized controlled trial testing whether the intervention can 
significantly reduce psychological distress and, in turn, improve behavioral outcomes (e.g., 
medication adherence, physical activity, dietary habits, sleep patterns, substance use) among 
survivors of critical illness. 
Eligibility:  
Patients will be included if they meet the following inclusion/exclusion criteria:  
Inclusion Criteria: 
(1) Age 18 years old or older 

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(2) Able to speak and write in English 
(3) Previously admitted to an ICU 
(4) Have internet access (e.g., Wi-Fi)  
(5) Have access to an internet-equipped smartphone device (e.g., iPhone, Android)  
(6) Meet a minimum threshold of psychological distress related to their prior critical 
illness as demonstrated by scoring ≥10 points on the PTSD Checklist for the Diagnostic 
and Statistical Manual of Mental Disorders, 5th Edition (PCL-5, see Measures section 
for a complete description).  
Exclusion Criteria: 
(1) ICU discharge occurred <30 days prior to the time of study enrollment 
(2) Score <10 points on the PCL-5 during the initial eligibility screening 
(3) Unable to comply with the protocol (either self-selected or indicating that s/he/they 
cannot complete all requested tasks) for reasons that include, but are not limited to, 
cognitive impairment (e.g., dementia), alcohol and/or substance abuse, or severe 
mental illness (e.g., schizophrenia). 
(4) Unavailable for follow-up for reasons such as terminal illness and imminent plans to 
leave the United States (as we have migrant or mobile patients due to their citizenship 
and work issues). 
 
Intervention: Messy Memories is a mobile application that allows users to self-administer 
exposure therapy techniques outside of the traditional psychotherapy context. The intervention 
was initially released in a written format for individual self-help, but with the widespread use of 
smartphones, a mobile version was developed with the potential to further reduce barriers and 
increase access to mental health care. Appendix A shows screenshots of the user view of the 
various application modules. Please note that these images are only examples of the user interface 
and do not include every screen the user might see while interacting with the app. 
 
Participants will be asked to engage with the Messy Memories application at least 3 days a week 
for at least 10 minutes each day using their own mobile smartphone device. Participants may 
proceed through the modules of the application at their own pace and may return to any module 
as many times as they desire throughout the 6-week intervention period. Mechanistic target and 
clinical symptom assessments will occur at Week 0 (baseline), Week 3 (mid-intervention), Week 
6 (end of intervention), and Week 12 (follow-up). All study procedures, including eligibility 
screening, consent process, outcome assessments, and exit surveys, will be conducted remotely 
via telephone or Zoom video conference. 
 
Modules: 
• 
Introduction: Provides a general overview of the application, offers suggestions for its use, 
describes how stress may impact mental health, and explains how processing difficult 
memories related to stress may help to improve well-being. 
• 
Memory Processing: Participants recall a difficult (“messy”) memory, which they will be 
asked to audio record, including what they did, felt, thought, smelled, saw, etc. They are 
then asked questions about what it was like to re-experience the memory, such as what 
emotions were elicited (e.g., sadness, anger, fear). Next, participants are asked to process 
what the memory means to them. They are then instructed to listen to their recording of 
the memory or re-record it as often as they like, until the memory becomes easier to re-

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experience. They respond to processing questions each time they listen to or re-record 
their prior difficult memory. 
• 
Feedback: Shows data from the participant’s engagement with the application, including 
feedback related to memory processing. 
Data collected:   
• 
Data directly provided by the participant: While using the Messy Memories application, 
participants will use affect rating sliders to directly input information related to their 
mood over the past several days, their level of distress before and after processing a 
difficult memory, and answers to questions about revisiting their difficult memory. Direct 
recordings of the participant’s “messy memory” (audio recorded) will only be available on 
the participant’s smartphone while using the app. These recordings (audio) will not be 
collected as data.    
• 
Data indirectly provided by the participant: The Messy Memories application will also 
collect data on how long and how frequently participants use the application. Specifically, 
each response to a prompt within the application will be recorded with a timestamp (date 
and time) to indicate when the participant provided a particular response. 
• 
Protected Health Information (PHI): The Messy Memories application does not collect or 
store PHI. Participants will be instructed not to record any identifiable information while 
using the app. 
Measures: 
Feasibility: To assess feasibility of the intervention, we will determine: 1) the number of 
participants that are needed to screen and consent; 2) the proportion of eligible participants who 
accept the offer to participate; 3) the proportion of consenting participants who download the 
application and initiate the intervention (i.e., log into the app at least once after the baseline visit); 
4) the proportion of consenting participants who access the Memory Processing module at least 
once; 5) the total number of times that the Memory Processing module is accessed; 6) the total 
number of times that each additional modules (i.e., Introduction, Feedback) is accessed. We will 
also describe how participants generally engage with the app (e.g., frequency and duration of 
engagement with each feature). In addition, we will assess the relative efficacy of each of our 
recruitment strategies. 
Acceptability: To assess acceptability of the intervention, participants will be asked to complete 
an exit survey via telephone interview or self-administered online. The survey will include 
questions regarding perceptions and feelings about the intervention. Participants will also be 
asked to provide qualitative feedback on the intervention (e.g., likes, dislikes, suggestions for 
improvement). 
Proctor’s Implementation Measures: Three validated measures (Acceptability of Intervention 
Measure [AIM], Feasibility of Intervention Measure [FIM], and Intervention Appropriateness 
Measure [IAM]) will be used to assess the acceptability, feasibility, and appropriateness of the 
Messy Memories intervention, respectively.56 Each measure consists of four items answered on a 
5-point scale (1 = strongly disagree, 5 = strongly agree). Average responses of ≥4 on the AIM, 
FIM, and IAM are indicative of adequate acceptability, feasibility, and appropriateness, 
respectively.56,57 
System Usability Scale (SUS): The SUS is a reliable tool for evaluating the usability of various 
products and services, including hardware, software, mobile devices, websites, and 
applications.58,59 It consists of ten items answered on a 5-point scale (1 = strongly disagree, 5 = 
strongly agree). We will use a score ≥68 to indicate adequate usability, in accordance with prior 
studies.60  

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PTSD symptoms: PTSD symptoms triggered by the prior critical illness and ICU hospitalization 
will be assessed using the PTSD Checklist for the Diagnostic and Statistical Manual of Mental 
Disorders, 5th Edition (PCL-5).61 The PCL-5 is an extensively validated self-report measure 
developed by the National Center for PTSD that corresponds to DSM-5 criteria for PTSD. Patients 
are provided a list of 20 PTSD symptoms and asked to rate how much they have been bothered by 
each symptom due to their prior critical illness and ICU hospitalization on a scale of 0 = not at all 
to 4 = extremely. We will classify participants with PCL-5 scores ≥34 as having elevated PTSD 
symptoms, which has been validated as a screening cutoff and used in prior studies of civilian 
populations.62-64 
Other psychological symptoms: In addition to PTSD symptoms, we will also assess for symptoms 
of depression, anxiety, and anxiety sensitivity. Depression will be assessed using the 8-item 
Patient Health Questionnaire (PHQ-8),65 with scores ≥10 positive for depression.66,67 Anxiety will 
be assessed using the 7-item Generalized Anxiety Disorder (GAD-7) scale,68 with scores ≥10 
positive for anxiety.69 Anxiety sensitivity will be assessed using the 16-item Anxiety Sensitivity 
Index (ASI),70 with scores ≥17 indicating high anxiety sensitivity.71 
Health behaviors: The International Physical Activity Questionnaire (IPAQ),72 will be used to 
measure the type, frequency, and intensity of daily physical activity. The Pittsburgh Sleep Quality 
Index (PSQI)73 will be used to measure total sleep duration and sleep quality. Participants will 
also be asked to report on their patterns of tobacco, alcohol, and substance/drug use. 
Post-ICU support: As part of the baseline visit, participants will be asked questions about any 
medical, psychological, and social support that they may have received after their prior ICU 
admission. Participants will also be asked about what forms of post-ICU support they think would 
be helpful for patients and their families.  
Sociodemographic and clinical characteristics: Participant sociodemographic information (e.g., 
age, sex, gender, sexual orientation, race, ethnicity, primary language, educational attainment, 
occupation, annual household income, marital/partner status, living situation, insurance status) 
will be self-reported at screening. Participants will also be asked to self-report any comorbid 
medical or psychiatric conditions, as well as provide information about their prior ICU admission 
(e.g., location, primary diagnosis, duration of hospitalization, need for intubation/mechanical 
ventilation, need for renal replacement therapy, need for central line placement). 
 
3. Statistical Procedures  
 
General approach: Given that this pilot study is, by design, not powered to test the effect of our 
intervention on study outcomes, we do not intend to publish analyses of these effects. Although 
some have used pilot studies to estimate effect sizes on primary outcomes, we agree with leaders 
in our field who argue that effect size estimates from small pilot studies are too imprecise to 
meaningfully inform effect size assumptions or power analyses for larger, later-stage studies. 
Therefore, we do not provide power calculations for the effects of our intervention on study 
outcomes. However, we will use estimates from these studies (e.g., standard deviations, attrition 
rates) to help determine appropriate sample sizes for a future study that is powered to detect 
meaningful reductions in measures of psychological distress following critical illness. 
Descriptive statistics: Categorical data will be presented as percentages and continuous data 
will be presented as means with standard deviations for normally distributed measures and as 
medians with interquartile ranges for measures that are not normally distributed. Checks of 
assumptions (e.g., normality) underlying statistical procedures will be performed and corrective 
procedures will be applied (e.g., log transformations, nonparametric tests). 

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Outcomes: The primary outcomes are feasibility and acceptability of the Messy Memories 
intervention and research procedures. Feasibility will be based on participant recruitment, 
retention, and completion rates of ≥70%. Acceptability will be based on participant satisfaction 
ratings of ≥70% and qualitative analysis of exit survey responses. The exploratory outcome is the 
ability of the Messy Memories intervention to engage the proposed mechanistic target, which will 
be based on pre-/post-intervention change in patient-reported PTSD symptoms specifically 
triggered by the prior critical illness and ICU hospitalization. 
Aim 1: Assess the feasibility of recruiting and engaging critical illness survivors in a mobile 
application-based exposure therapy intervention (Messy Memories). Hypothesis: The 
intervention will be feasible based on recruitment, retention, and completion rates of ≥70%. 
Aim 2: Assess the acceptability of recruiting and engaging critical illness survivors in a mobile 
application-based exposure therapy intervention (Messy Memories). Hypothesis: The 
intervention will be acceptable based on participant satisfaction ratings of ≥70% and qualitative 
analysis of exit survey responses. 
Statistical approach for Aims 1 & 2: We will calculate means and standard deviations (or 
medians and interquartile ranges if variables are non-normal) as well as frequencies and 
proportions to assess feasibility and acceptability outcomes. T-tests or chi-square tests will be 
used to compare the demographic and clinical characteristics of 1) eligible patients who did vs. 
did not enroll in the study and 2) consenting participants who did vs. did not complete the study. 
Free-text responses from the exit survey will be described qualitatively and used to contextualize 
our quantitative results and guide future research. 
Aim 3 (exploratory): Assess engagement of the mechanistic target (PTSD symptoms) by the 
mobile application-based exposure therapy intervention (Messy Memories). Hypothesis: 
Participants will report improvement in PTSD symptoms based on pre-/post-intervention 
decrease in scores on the PTSD Checklist for the Diagnostic and Statistical Manual of Mental 
Disorders, 5th Edition (PCL-5). 
Statistical approach for Aim 3: We will assess whether the Messy Memories intervention 
engages the mechanistic target (PTSD symptoms) by comparing pre-/post-intervention change 
in PCL-5 score using one-sample t-tests with comparison values of 0 (i.e., all null hypotheses 
entail no change in PCL-5 score). Given the exploratory nature of Aim 3, we will focus the 
interpretation of these analyses on effect sizes (Cohen’s D) rather than statistical significance to 
assess potential signals for intervention effects. 
Sample size and power estimates: Because the proposed study is a pilot trial, we did not 
conduct a formal power analysis. We aim to recruit as many participants as possible but selected 
a minimum n=30 based on pragmatics, the needs of the trial, and previous pilot studies suggesting 
that this sample size is sufficient to provide an accurate indication of the feasibility and 
acceptability of the study procedures.  
Interim analyses: Given the relatively small sample size of this study and the expected minimal 
risk of the intervention, no interim analyses are currently planned. However, if concerns arise 
related to adverse events, then an interim analysis may be conducted and the study may be 
stopped early depending on the recommendations of the IRB and/or NIA. 
Subgroup analyses: Given that this is a stage 1A/1B pilot feasibility study, we do not plan to 
conduct any pre-specified subgroup analyses. 
 
4. Study Procedures 
Provide a detailed description of which procedures are being conducted by Columbia researchers.  
You may include information about study instruments and study measures. 

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Recruitment: We aim to enroll ≥30 participants in this pilot study. Potential participants will 
be identified and recruited using several different approaches, each of which is described below. 
1. Post-ICU support groups 
We will work with providers at Vanderbilt University Medical Center, University of 
Pittsburgh Medical Center, UCLA (University of California – Los Angeles), the University 
of Michigan Medical Center, and other U.S.-based centers who host post-ICU support 
groups. Led by teams of providers (e.g., physicians, psychologists, social workers), these 
groups meet regularly via zoom (and/or in person) to provide ongoing practical and 
psychological support to critical illness survivors. Support group members have all had a 
prior ICU admission and have experienced varying degrees of psychological distress as a 
result. Support group leaders have agreed to share the study flyer with their post-ICU 
support group members. Those who are interested in participating in the study can follow 
a link or QR code on the flyer, which will direct them to the Qualtrics-based screening 
information sheet. Those who consent to screen will complete a self-administered study 
screener on Qualtrics.  
 
Dr. Liyanage-Don or another member of the study team may also offer a brief live video 
presentation to post-ICU support groups to describe the study and answer any initial 
questions the attendees may have about the study. At the presentation, Dr. Liyanage-Don 
(or a member of the study team) would share the study flyer with the group.   
 
2. Post-ICU recovery clinics/providers 
We will work with providers at Vanderbilt University Medical Center, University of 
Pittsburgh Medical Center, UCLA (University of California – Los Angeles), the University 
of Michigan Medical Center, and other U.S. based centers who provide multidisciplinary 
care to patients after an ICU admission. Clinic leaders have agreed to share the study flyer  
with their post-ICU recovery patients. Those who are interested in participating in the 
study can follow a link or QR code on flyer, which will direct them to the Qualtrics-based 
screening information sheet. Those who consent to screen will complete a self-
administered study screener on Qualtrics.  
 
3. Post-ICU patients at Columbia: Direct referrals from outpatient treating 
clinicians 
Patients may also be referred directly to the Messy Memories research team by the 
patient’s clinical care team within the ColumbiaDoctors/NYPH healthcare system. We will 
only accept referrals from providers who confirm that the patient meets the Messy 
Memories study inclusion and exclusion criteria, deem the patient appropriate for 
participation, and receive verbal approval from the patient to be contacted by research 
personnel. The treating clinician will provide patient’s first and last name and MRN so 
that a member of the research team can identify the patient in the electronic health record 
(EHR) to confirm contact information, English-speaking status and eligibility (as needed). 
The treating clinician may use an IRB-approved study brochure to introduce the study to 
their patient should they choose. Please note that this brochure, unlike the study flyer, 
does not contain any QR codes or links to a Qualtrics information sheet. Once the above 
steps have been completed, a member of the research team will contact the patient to 
discuss the study in detail. Patients who express interest in learning more about the study 
will move forward with the consent to screen, which will be conducted verbally using a 
screening information sheet. Those who consent to screen will complete a study screener 
with a member of the study team. 
 

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4. Facebook.com groups (e.g., post-ICU support groups) 
We may post information about this study on "Facebook" groups. Please note, as most 
Facebook post-ICU support groups are private groups run by an administrator team, the 
research team will send the IRB-approved flyer and recruitment language to the 
administrator or other group member who may post or share this information directly 
with the group. In cases where the groups are not private, members of the study team may 
post this language. Interested individuals may click on the link or scan the QR code to 
navigate to the Qualtrics consent to screen and screener to see if they are eligible or contact 
the study team and review the consent to screen and screener over the phone if preferred. 
 
5. CUIMC RecruitMe 
We may post the study on the "RecruitMe” website (https://recruit.cumc.columbia.edu). 
Interested individuals may click on the link to the study Qualtrics consent to screen and 
screener to see if they are eligible or contact the study team and review the consent to 
screen and screener over the phone if preferred.  
 
6. ResearchMatch 
We may post the study on “ResearchMatch” (https://www/researchmatch.org). 
ResearchMatch will provide the study team with a de-identified list of volunteers that fit 
the study eligibility criteria. The study team will send a contact message through 
ResearchMatch to the potential participants. ResearchMatch will provide the study team 
the contact information for volunteers that reply "yes" to the contact message and consent 
to their information being shared with the study team. Once contacted by the research 
team, individuals that express interest in participating in the study will be offered the 
choice of completing the consent to screen and screener over the phone or via Qualtrics. 
 
7. ClinicalTrials.gov 
Individuals who contact study staff to express interest in participating in the study after 
finding the study on ClinicalTrials.gov may also be recruited. They will be offered the 
choice of completing the consent to screen and screener over the phone or via Qualtrics. 
 
8. Sudden Cardiac Arrest Foundation (SCAF) 
The study flyer may be advertised by SCAF, a community of cardiac arrest survivors, their 
families, and other advocates. We will provide the study flyer and scripted language to 
foundation contacts who will share it with the SCAF community (e.g. through their website 
and/or via their email listserv). Interested individuals may click on the link or scan the QR 
code to navigate to the study Qualtrics consent to screen and screener to see if they are 
eligible or contact the study team and review the consent to screen and screener over the 
phone if preferred.  
 
9. PACE Study  
The PACE Study (IRB# AAAT4053) team will share a list of English-speaking former 
participants of the PACE Study, who agreed to be contacted about future study 
opportunities, with the Messy Memories research team. The list of former PACE 
participants will include their MRN, first and last name, language, and contact 
information. The Messy Memories research team will access the patient’s Epic medical 
record to confirm initial eligibility, contact information, and language. The research team 
will contact potential participants to discuss the Messy Memories study. Once contacted, 
individuals that express interest in participating in the study will be offered the choice of 
completing the consent to screen and screener over the phone or via Qualtrics. 
 

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10. Post-ICU patients at Columbia: TRAC requests refreshed by CUIMC IT on a 
monthly basis as needed 
 
Patients identified from TRAC request: 
Potential participants for this study will also be identified through a TRAC request. We 
will submit a request to TRAC to identify patients who meet the following criteria: 
• 
18 years of age or older 
• 
Preferred language: English  
• 
Discharged from an ICU at least 30 days prior 
• 
Living status: not deceased  
• 
No presence of significant cognitive impairment indicated (e.g., dementia)  
• 
No presence of significant psychiatric comorbidity indicated (e.g., psychosis)  
• 
Research Contact Status captured during initial registration: agreed to be 
contacted about research 
 
The TRAC request will reflect the following information for patients who meet these 
criteria: 
• 
MRN 
• 
First and Last Name 
• 
Date of Birth  
• 
Preferred Language  
• 
Research Contact Status 
• 
Date of ICU discharge  
• 
Date of ICU admission  
• 
ICD-10 diagnosis code(s) at ICU discharge  
• 
Patient Contact Information (phone numbers, email) 
• 
Names of providers in patient’s Care Team 
The study team will contact the patient’s provider (e.g., primary care doctor) to confirm study 
eligibility. If the provider confirms that the patient is eligible, the study team will contact the 
patient to introduce the study. The study team may access the patient’s medical record to confirm 
contact information, provider, and eligibility criteria prior to contacting the patient. Patients who 
are contacted by the study team and express interest in learning more about the study will move 
forward with the consent to screen, which will be conducted verbally using a screening 
information sheet.  Those who consent to screen will complete a study screener with a member of 
the study team.  
 
Screening: Upon granting consent to be screened, participants will be asked to complete a brief 
screening questionnaire (either online or over the phone with the study team) to determine their 
eligibility for study participation. Individuals completing the screener via Qualtrics will be asked 
to share their name and contact information so that a study team member can contact them if 
they screen eligible, if their screener is incomplete or needs clarification, or if they agree to be 
contacted about future research studies. All participants will be informed of their screening status 
upon completion of the screener. Those who do not meet study criteria will be thanked for their 
time and informed that they are not eligible for the study. Those who do meet study criteria will 
be informed that they are eligible for the study. All individuals who complete the study screener 
will be surveyed for interest in being contacted for future research studies and/or to provide 
feedback on the design of research studies. 
 

Revised 2/20/2024 
Page 11 of 19 
Potential participants will be asked to report their age (those ages 18 years or older will be eligible 
to participate) and primary language (those able to speak and write in English will be eligible to 
participate). Additional sociodemographic information (e.g., sex assigned at birth, gender 
identity, race, ethnicity, living situation, annual household income, occupation, highest level of 
education, zip code, health insurance status, marital and partner status) will be collected as part 
of screening. Potential participants will be asked to report the approximate date of their ICU 
discharge (those discharged at least 30 days prior to the time of screening will be eligible to 
participate). Potential participants will be asked to confirm that they have access to both the 
internet (e.g., Wi-Fi) and to an internet-equipped smartphone device (e.g., iPhone, Android). 
Potential participants will also be asked to complete the PCL-5 as part of the screening 
questionnaire (scores ≥10 points are required for study eligibility). Potential participants will also 
be asked whether they have any physical, psychological, or cognitive condition (e.g., severe 
dementia, severe mental illness, severe alcohol and/or substance abuse) that would preclude them 
from completing any aspect of the study protocol. 
In all cases, the screening consent process and responding to screening questions is expected to 
take approximately 25 minutes to complete.  
Consent: Individuals who are screened and found to be eligible for the study based on inclusion 
and exclusion criteria will then be invited to schedule a visit (either by phone or Zoom, depending 
upon the participant’s preference) to undergo a consent discussion for participation in the overall 
study using a verbal information sheet. On or prior to the visit, a study team member may send a 
copy of the verbal information sheet via mail or email with the patient’s permission. As part of the 
consent process, the study team member will provide a complete description of the study in clear 
and easy-to-understand language, including risks and benefits, as well as answer any questions 
that participants may have after receiving this information. If an eligible participant verbally 
consents to participate in the study, they will accrue.  
All accrued participants will receive a copy of the information sheet via email or mail. Participants 
will be asked to schedule a time to complete the baseline visit and study staff will confirm their 
mailing address to send study materials, including instructions for downloading the Messy 
Memories app, tips for using the Messy Memories app, and mental health resources including 
study phone numbers to contact study staff. Study phone messages will be checked on a regular 
basis. Study materials may also be emailed to participants if needed or requested.  
Study Visits: 
Please note that study staff may email participants to schedule/confirm study visits, send study 
materials as needed or requested, and/or email questionnaires via Qualtrics. Study staff may also 
communicate with participants via SMS text messaging using CUIMC-encrypted cell phones 
available exclusively to study staff to schedule/confirm study visits and/or answer questions 
should they arise.  
“Visit 1”/Baseline Visit (Approximately 60 Minutes): Participants will complete a brief 
baseline visit via Zoom (or over the phone if preferred). This session (guided by study staff) 
entails: 
1. completing a brief baseline assessment, which will include: 
a. details of the prior ICU admission (e.g., date, location) 
b. comorbid medical and/or psychiatric conditions 
c. psychological symptoms (PHQ-8, GAD-7, ASI) 
d. health behaviors (IPAQ, PSQI, tobacco/alcohol use) 
e. post-ICU support (see Measures for full description) 
2. downloading the Messy Memories app to their smartphone and logging in with their 
study-provided login  

Revised 2/20/2024 
Page 12 of 19 
a. Participants will be advised to reach out to the study team if they forget their login.  
3. a brief orientation to the app with suggested guidance for usage 
Participant App Usage:  Participants will be asked to use the Messy Memories app for 6 weeks 
beginning the day that all components of the Baseline Visit are complete. This date marks the start 
of the intervention. Participants will be advised of the date which marks the end of the 
intervention (6 weeks later). They will be asked to focus on their memory of their ICU experience 
for memory processing. They will be asked to use the app at least 3 days a week for at least 30 
minutes each day. They will be instructed to stop using and delete the app from their phones when 
their study participation ends.   
Post-Baseline Check-In: Participants will receive a phone call from study staff within one week 
of the baseline assessment to confirm that they are not experiencing any technical difficulties with 
the app. If a participant expresses distress related (or not related) to the app, study staff will follow 
safety protocol by sharing the IRB-approved list of resources with the participant over the phone 
and/or via email and will consult with the study PI.  
“Visit 2”/3-Week/Mid-Intervention Questionnaire (Approximately 25 minutes): 
Approximately three weeks after the start of the intervention (Baseline Visit) participants will be 
asked to complete a questionnaire by telephone or video consisting of the PCL-5, PHQ-8, GAD-7, 
ASI, IPAQ, and PSQI. If a participant expresses that they will not be available to complete the 
questionnaire by telephone or video, or if the study team is unable to reach the participant, the 
study team will send the questionnaire to the participant via Qualtrics. Those who do not complete 
the survey will remain on the study, and this task will be listed as “not completed” and included 
as part of analysis.   
6-Week/End of Intervention Call: A member of the study team will call the participant within 
one week prior to the end of the intervention to remind the participant of the date when the 
intervention ends and that they are to stop using the Messy Memories app at that time. This call 
can also be used to schedule the 6-week/Post-Intervention Questionnaire.    
“Visit 3”/6-Week/Post-Intervention Questionnaire (Approximately 40 minutes): 
Approximately six weeks after the start of the intervention (Baseline Visit) participants will be 
asked to complete another questionnaire by telephone or video consisting of the PCL-5, PHQ-8, 
GAD-7, ASI, IPAQ, PSQI, substance use measures, implementation measures (e.g., feasibility, 
acceptability, appropriateness, satisfaction), and qualitative feedback on the intervention (e.g., 
likes, dislikes, suggestions for improvement). If a participant expresses that they will not be 
available to complete the questionnaire by telephone or video, or if the study team is unable to 
reach the participant, the study team will send the questionnaire to the participant via Qualtrics. 
Those who do not complete the survey will remain on the study, and this task will be listed as “not 
completed” and included as part of analysis.   
“Visit 
4”/12-Week/Follow-Up 
Questionnaire 
(Approximately 
30 
minutes): 
Approximately six weeks after the end of the intervention, participants will be asked to complete 
one final questionnaire by phone consisting of the PCL-5, PHQ-8, GAD-7, ASI, IPAQ, PSQI, and 
substance use measures. If a participant expresses that they will not be available to complete the 
questionnaire by telephone or video, or if the study team is unable to reach the participant, the 
study team will send the questionnaire to the participant via Qualtrics. Those who do not complete 
the survey will remain on the study, and this task will be listed as “not completed” and included 
as part of analysis.   
Compensation: 
Participants will be compensated a total of $120 if they complete all components of the study in 
the form of TruCentive electronic gift cards. This compensation will be allocated in the following 
amounts:  

Revised 2/20/2024 
Page 13 of 19 
§ 
$30 for completion of all components of the Baseline Visit (completing questionnaires, 
downloading the app, and being onboarded to the app with study staff) 
§ 
$30 for completion of the 3-Week/Mid-Intervention Questionnaire  
§ 
$30 for completion of the 6-Week/Post-Intervention Questionnaire  
§ 
$30 for completion of the 12-Week/Follow-up Questionnaire  
 
Participants who complete only part of a questionnaire (50%, for example) will not receive partial 
compensation for that questionnaire. Participants may, however, skip any question(s) that they 
do not feel comfortable answering, and this will not impact their compensation for the study. 
 
All compensation will be provided via TruCentive e-gift cards sent to subjects by email, SMS text 
message or both.  Each TruCentive electronic gift card will allow participants to choose from a list 
of pre-approved businesses at which they may use each card (including Target, Amazon, 
Starbucks, Chipotle, etc.). 
 
Participants will receive instructions for utilizing TruCentive. 
 
5. Risks 
 
Study procedures (i.e., completing questionnaires such as the PCL-5, answering Messy Memories 
app questions, and, as applicable, recording and processing distressing memories of prior ICU 
experiences in the Messy Memories app) present minimal risk. Exposure treatments pose some 
risk of psychological discomfort, but participants will not be required to interact with the app any 
more than they choose to and can discontinue using the app at any time without penalty. The 
questions asked and the thoughts evoked during the course of this research study pose minimal 
risk of psychological discomfort, and participants may skip any question or questionnaire that 
they choose. Participants will be made aware of these risks and will be assured that they can 
terminate their participation in the study at any time without penalty. Mental health resources 
will be provided to all participants.  
 
A potential risk of this study is violation of participant privacy, since patient medical information 
will be used as a source of data. Special protections against this risk will be provided (see below). 
Although the Messy Memories application does not directly collect or store protected health 
information, it is possible that participants may enter personally identifiable information into the 
free text fields within the application. To mitigate against this, participants will be instructed not 
to enter any personally identifiable information into the free text fields at any time while using 
the application. In addition, direct recordings of participants' prior distressing memory (audio 
recorded) will not be stored on the Messy Memories application nor collected as study data. The 
study-provided login to access the Messy Memories app will not contain any identifiable 
information. Participants will contact the study team if they require any assistance with the study 
login.   
6. Benefits  
 
There is no direct benefit to subjects who participate in this study.  
Improved psychological symptoms and adherence to health behaviors: Participants may benefit 
from the intervention in terms of decreased psychological distress and posttraumatic stress 
disorder (PTSD) symptoms related to their prior critical illness. This may help participants 
become more adherent to their medical treatments and develop adaptive health behaviors. 
Participants may also benefit from the attention they receive from study personnel.    

Revised 2/20/2024 
Page 14 of 19 
Contributions to scientific/medical knowledge: While participants in this study may not directly 
benefit from their participation, we anticipate the results from this study will benefit future 
research seeking to reduce psychological distress and improve health behaviors after prior critical 
illness experiences. 
 
7. Alternatives 
 
The alternative is not to participate in the study. Participants will be assured that they can decide 
at any point to discontinue participation with absolutely no consequences. Additionally, the 
Principal Investigator may withdraw participants from the study after enrollment upon further 
examination of eligibility criteria and/or at their professional discretion.  
 
8. Data and Safety Monitoring 
 
As this study presents minimal risk to participants, data and safety monitoring will be conducted 
by the study staff as directed by the principal investigator.  Investigators and research staff will 
meet weekly to discuss any issues or concerns with the study, in particular, whether there were 
any unexpected complaints about the study procedures or questionnaires, or whether there were 
any breaches in data confidentiality (which will be reported to the IRB as required by policy). If 
unexpected complaints about the procedures or questionnaires are generated, then the study may 
be stopped or altered prior to recruiting the full sample.  
The Study Principal Investigator (PI), Nadia Liyanage-Don, MD, and Dr. Ian Kronish, a board-
certified general internist, will be responsible for ensuring participants’ safety. The investigators 
will be informed of unanticipated problems or unexpected serious adverse events that may be 
related to the study protocol as soon as they occur, and they will notify the Institutional Review 
Board, in compliance with policy.  
If participants incidentally disclose that they are experiencing severe symptoms related to anxiety, 
depression, psychological distress, or suicidal ideation at any point in the study the study team 
will follow a standardized safety protocol. This will include reminding participants of available 
mental health resources provided at the beginning of the study to all participants, offering a phone 
call with a study PI/MD within 24 hours, encouraging participants to stop using the Messy 
Memories app if they feel it is causing excessive distress, and encouraging participants to seek 
medical and/or psychological care with a doctor or mental health professional. All instances of 
incidentally reported severe psychological distress will be communicated to a Study PI/MD within 
24 hours. The Study PI/MD will determine next steps and follow-up with the participant as 
deemed appropriate.  
The study team will collect required demographic data to report to the NIA as required via  
CROMS (Clinical Research Operations and Management System).  
A description of the study will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This website will not include information that can identify participants. At most, the website 
will include a summary of the results.  
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