Primary Outcomes

Description: This study will examine between-group differences in clinical, behavioral, genetic, neuroanatomical, and neurophysiological variablesin individuals with SMD or DMDD and/or MDD, BD (BD, see protocol 00-M-0198) or those with anxiety (01-M-0192) (Leibenluf

Measure: This study will examine between-group differences in clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables

Time: ongoing

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Primary Outcomes

Description: Pre- to post-CBT changes in functional, connectivity and structural MRI measures of brain networks relevant for anxiety. Brain regions include the amygdala, anterior insula, dorsal anterior cingulate cortex (dACC) and ventrolateral prefrontal cortex (vlPFC). Functional activation and connectivity of these brain regions are assessed using simple computer tasks performed during MRI scanning. Tasks engage threat reactivity, self-regulatory control and the interaction of these processes. Structural connections between regions will be measured using a MRI technique that measures water diffusion in the brain.

Measure: Brain function/structure as assessed by Magnetic Resonance Imaging scans

Time: Baseline and 12-weeks

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Secondary Outcomes

Description: The Pediatric Anxiety Rating Scale (PARS) is a clinician-administered assessment to rate the severity of anxiety symptoms associated with common DSM-V anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) in children. The investigators are looking for decreases in anxiety severity ratings from pre- to post-treatment.

Measure: Pediatric Anxiety Rating Scale

Time: weeks 0, 3, 6, 9, 12

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Primary Outcomes

Description: The primary implementation outcome will be evaluated assessing the rate of ED-initiated BUP therapy with referral for ongoing MAT over the 12 month period.

Measure: Implementation (Considered the Primary Outcome)

Time: 12 months

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Description: The primary effectiveness outcome is defined as the rates of patient engagement in formal addiction treatment on the 30th day post enrollment.

Measure: Effectiveness

Time: 30 Days Post Enrollment

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Secondary Outcomes

Description: Fidelity will be measured using a critical action checklist relating to the provision of ED-initiated BUP with referral for ongoing MAT in eligible patients.

Measure: Implementation: Fidelity

Time: Baseline Period (Baseline)

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Description: Fidelity will be measured using a critical action checklist relating to the provision of ED-initiated BUP with referral for ongoing MAT in eligible patients.

Measure: Implementation: Fidelity

Time: IF Evaluation Period (18 months)

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Description: ED provider readiness and preparedness ruler score to initiate BUP and provide referral for ongoing MAT

Measure: Implementation: ED provider Readiness and Preparedness Ruler Score

Time: Pre IF (Baseline)

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Description: ED provider readiness and preparedness ruler score to initiate BUP and provide referral for ongoing MAT

Measure: Implementation: ED provider Readiness and Preparedness Ruler Score

Time: Post IF (6 months)

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Description: ED provider readiness and preparedness ruler score to initiate BUP and provide referral for ongoing MAT

Measure: Implementation: ED provider Readiness and Preparedness Ruler Score

Time: post IF Evaluation Period (12 months)

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Description: ED ORCA score relating to ED-initiated BUP with referral for ongoing MAT

Measure: Implementation: ED Organizational Readiness to Change Assessment (ORCA) Score

Time: Pre IF (Baseline)

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Description: ED ORCA score relating to ED-initiated BUP with referral for ongoing MAT

Measure: Implementation: ED Organizational Readiness to Change Assessment (ORCA) Score

Time: Post IF (6 months)

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Description: ED ORCA score relating to ED-initiated BUP with referral for ongoing MAT

Measure: Implementation: ED Organizational Readiness to Change Assessment (ORCA) Score

Time: Post IF Evaluation Period (12 months)

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Description: Community opioid treatment provider/program readiness and preparedness ruler score to continue MAT for patients with OUD who have received ED-initiated BUP

Measure: Implementation: Community Readiness and Preparedness Ruler Score

Time: Pre IF (Baseline)

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Description: Community opioid treatment provider/program readiness and preparedness ruler score to continue MAT for patients with OUD who have received ED-initiated BUP

Measure: Implementation: Community Readiness and Preparedness Ruler Score

Time: Post IF (6 months)

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Description: Community opioid treatment provider/program readiness and preparedness ruler score to continue MAT for patients with OUD who have received ED-initiated BUP

Measure: Implementation: Community Readiness and Preparedness Ruler Score

Time: post IF Evaluation Period (12 months)

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Description: Community opioid treatment provider/program ORCA score relating to receiving patients with OUD who have received ED-initiated BUP

Measure: Implementation: Community ORCA Score

Time: Pre IF (Baseline)

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Description: Community opioid treatment provider/program ORCA score relating to receiving patients with OUD who have received ED-initiated BUP

Measure: Implementation: Community ORCA Score

Time: Post IF (6 months)

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Description: Community opioid treatment provider/program ORCA score relating to receiving patients with OUD who have received ED-initiated BUP

Measure: Implementation: Community ORCA Score

Time: post IF Evaluation Period (12 months)

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Description: Self-reported days of illicit opioid use (past 7 days) as measured by Time-Line Follow-Back methods at 30 days

Measure: Effectiveness: Opioid Use

Time: 30 days post enrollment

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Description: Overdose event (past 30 days) captured by participant self-report, state medical examiner records, National Death Index and review of medical records

Measure: Effectiveness: Overdose Event

Time: 30 days post enrollment

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Description: HIV risk taking behaviors (past 30 days) as measured by HIV Risk Taking Behavior Scale

Measure: Effectiveness: HIV Risk

Time: 30 days post enrollment

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Description: All Healthcare Service Utilization Inpatient and Outpatient

Measure: Effectiveness: Healthcare Service Utilization

Time: 30 days post enrollment

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Description: Rates of illicit opioid negative urines

Measure: Effectiveness: Illicit Opioid Urine Toxicology

Time: 30 days post enrollment

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Primary Outcomes

Description: Interviewer assesses frequency in binge eating episodes

Measure: Change in occurrences of binge eating episodes using Eating Disorder Diagnostic Interview

Time: Week 8; R33 also reviews at 6-month follow-up

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Description: Interviewer assesses frequency of compensatory weight control behaviors

Measure: Change in occurrences of compensatory weight control behavior using Eating Disorder Diagnostic Interview

Time: Week 8; R33 also reviews at 6-month follow-up

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Description: Interviewer assesses change in psychosocial impairment

Measure: Change in psychosocial impairment due to eating disorder symptoms using the Clinical Impairment Assessment Questionnaire

Time: Week 8; R33 also reviews at 6-month follow-up

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Secondary Outcomes

Description: Assess if CAT produces larger pre-post reductions in reward region in response to thin models and binge food (Not collected during COVID-19 shelter-at-home order)

Measure: Change in reward region of the brain using fMRI

Time: Week 1 and Week 8

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Description: Assess if there are any changes in suicide ideation/attempts

Measure: Change in suicidal ideation/attempts using the Patient Health Questionnaire version 9 (PHQ-9)

Time: Weeks 2, 4 and 6

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Description: Assess if there are any changes in negative affect

Measure: Change in negative affect using the Positive Affect and Negative Affect Scale-Revised

Time: Weeks 2, 4, and 6

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Description: Assess if there are any changes in body dissatisfaction

Measure: Change in body dissatisfaction using the Body Dissatisfaction Scale

Time: Weeks 2, 4 and 6

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Description: Assess if there are any changes in food addiction (Only collected during R61 phase)

Measure: Change in food addiction using the Yale Food Addiction Scale version 2.0

Time: Weeks 2, 4, and 6

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Description: Assess if there are any changes in valuation of the thin beauty ideal

Measure: Change in valuation of thin ideal using the Thin Ideal Valuation Scale

Time: Weeks 2, 4, 6, and 8; R33 also reviews at 6-month follow-up

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Description: Assess if there are any changes in dietary restraint

Measure: Change in dietary restraint using the 10-item Dutch Restrained Eating Scale

Time: Week 8; R33 also reviews at 6-month follow-up

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Description: Three implicit association tasks will assess response to binge foods, thin models, and eating disorder behavior words at pre- and post-test (Not collected during COVID-19 shelter-at-home order)

Measure: Change in implicit associations of binge foods, thin models, and eating disorder behavior words

Time: Week 8; R33 also reviews at 6-month follow-up

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Primary Outcomes

Description: This system entails continuous coding of infants' attention engagement into one of 6 mutually exclusive states: unengaged, onlooking, object engaged, person-engaged, supported joint engagement, and coordinated joint engagement. Due to the importance of the construct of engagement to our PIE theory of change, the total percent of time in joint engagement (supported + coordinated) will serve as the most proximal intervention outcome (i.e., changes expected at Posttest-1). Recent studies with children with NDs have shown that the coding system is sensitive to change in joint engagement after relatively short interventions.

Measure: Change in Parent Child Engagement Coding from pretest to posttest 1

Time: Baseline, posttest 1 (6-8 weeks after pretest)

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Description: This system entails continuous coding of infants' attention engagement into one of 6 mutually exclusive states: unengaged, onlooking, object engaged, person-engaged, supported joint engagement, and coordinated joint engagement. Due to the importance of the construct of engagement to our PIE theory of change, the total percent of time in joint engagement (supported + coordinated) will serve as the most proximal intervention outcome (i.e., changes expected at Posttest-1). Recent studies with children with NDs have shown that the coding system is sensitive to change in joint engagement after relatively short interventions.

Measure: Change in Parent Child Engagement Coding from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Secondary Outcomes

Description: The MSEL is a standardized developmental assessment for children birth to 58 months, frequently used in studies of children with NDs, and comprised of 4 scales: Fine Motor, Visual Reception, Receptive Language, and Expressive Language. The investigators will administer only the Receptive and Expressive Language subscales of the MSEL at the second posttest and the first follow up assessment. To be eligible for the intervention portion of the study, children have to score at least 1 s.d. below the mean on either the Receptive or Expressive Language subscale of the MSEL. The investigators will report t scores (Mean = 50, SD = 10)and the standardized total Early Learning Composite (Mean = 100, SD = 15). Higher scores indicate greater developmental skills.

Measure: Change in Mullen Scales of Early Learning Receptive Language T-Scores from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: The MSEL is a standardized developmental assessment for children birth to 58 months, frequently used in studies of children with NDs, and comprised of 4 scales: Fine Motor, Visual Reception, Receptive Language, and Expressive Language. The investigators will administer only the Receptive and Expressive Language subscales of the MSEL at the second posttest and the first follow up assessment. To be eligible for the intervention portion of the study, children have to score at least 1 s.d. below the mean on either the Receptive or Expressive Language subscale of the MSEL. The investigators will report t scores (Mean = 50, SD = 10)and the standardized total Early Learning Composite (Mean = 100, SD = 15). Higher scores indicate greater developmental skills.

Measure: Change in Mullen Scales of Early Learning Expressive Language T-scores from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: A play-based assessment used to measure children's approach-avoidance to novel sensory toys (i.e., hyper-reactivity) and orienting responses (i.e., hypo-reactivity) across three sensory modalities (auditory, visual, tactile). The investigators will report a mean score for Hypo (range = 1-5), Hyper (range = 1-5) sensory subscales. Higher scores indicate greater sensory differences in that domain (e.g. a high hypo domain score would indicate more hyposensitive reactions to sensory stimuli seen in the child).

Measure: Change in Sensory Processing Assessment for Young Children from Pretest to Posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: A treatment response measure of social communication behaviors and other behaviors associated with autism spectrum disorder (ASD). Administration of the BOSCC involves a 12-minute video recorded interaction between an examiner and a young child using two standard sets of toys and play with bubbles. Behaviors are coded from video. Total score range is 16-80. Higher scores indicate more typical social communication skills, lower scores indicate poorer skills.

Measure: Change in The Behavioral Observation of Social Communication Change (BOSCC) from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: Designed to measure the extent to which children will follow attentional cues of the examiner. Six prompts for attention following are embedded into the larger study protocol. Items are scored dichotomously as yes "1" or no "0".Total score range is 0-6. Higher scores indicate more typical responses to bids for joint attention.

Measure: Change in The Attention Following Protocol (AF Protocol) from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: A parent report measure of children's expressive communication skills, such as vocabulary and pre-grammar abilities. The Words and Gestures (toddler) form will be used. Total words and gestures endorsed by parents will be reported. Greater words and gestures reported indicates larger expressive vocabulary.

Measure: Baseline expressive communication level: The MacArthur-Bates Communicative Development Inventory

Time: Baseline

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Description: A 43 item parent questionnaire that asks about the child's responses to various sensory stimuli in the context of functional activities and daily routines in the child's environment. It also documents strategies parents use to respond to their child's behaviors. Hyper and Hypo mean domain scores will be reported (range = 1-5). Greater domain scores indicate a greater presence of that type of sensory response.

Measure: Change in The Sensory Experiences Questionnaire version 2.1 from pretest to posttest 1

Time: Baseline, posttest 1 (6-8 weeks after pretest)

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Description: A 43 item parent questionnaire that asks about the child's responses to various sensory stimuli in the context of functional activities and daily routines in the child's environment. It also documents strategies parents use to respond to their child's behaviors. Hyper and Hypo mean domain scores will be reported (range = 1-5). Greater domain scores indicate a greater presence of that type of sensory response.

Measure: Change in The Sensory Experiences Questionnaire version 2.1 from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: The Parental Stress Scale is a brief, 18-item scale designed to assess parent stress in nonclinical or clinical populations. It has acceptable levels of internal consistency (coefficient α = .83) and test-retest reliability (r = .81 over 6 weeks). It has good concurrent validity with the widely used Parent StressIndex (r =.75), which is a longer, more intrusive measure. A total score will be reported (range = 18-90).

Measure: Baseline level of parent stress: Parental Stress Scale

Time: Baseline

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Description: RSA levels will be collected using a standard protocol while the child is seated in a high chair exposed to social and non-social stimuli.

Measure: Change in Respiratory sinus arrhythmia from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: Skin conductance levels will be collected using a standard protocol while the child is seated in a high chair exposed to social and non-social stimuli.

Measure: Change in skin conductance levels from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: Parent-child interaction videos will be coded for parent responsiveness to child prelinguistic communication cues. These are each rated on a 0-7 scale. Higher scores indicate greater responsivity from parents.

Measure: Change in Parent Responsiveness to Child Prelinguistic Communication Cues from pretest to posttest 1

Time: Baseline, posttest 1 (6-8 weeks after pretest)

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Description: Parent-child interaction videos will be coded for parent responsiveness to child prelinguistic communication cues. These are each rated on a 0-7 scale. Higher scores indicate greater responsivity from parents.

Measure: Change in Parent Responsiveness to Child Prelinguistic Communication Cues from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Description: Parent-child interaction videos will be coded for parent responsiveness to child sensory reactivity cues. These are each rated on a 0-7 scale. Higher scores indicate greater responsivity from parents.

Measure: Change in Parent Responsiveness to Child Sensory Reactivity Cues from pretest to posttest 1

Time: Baseline, posttest 1 (6-8 weeks after pretest)

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Description: Parent-child interaction videos will be coded for parent responsiveness to child sensory reactivity cues. These are each rated on a 0-7 scale. Higher scores indicate greater responsivity from parents.

Measure: Change in Parent Responsiveness to Child Sensory Reactivity Cues from pretest to posttest 2

Time: Baseline, posttest 2 (13-16 weeks after pretest)

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Primary Outcomes

Description: The CY-BOCS is a measure of obsessive compulsive symptoms and severity. The Obsession Rating Scale measures 5 domains of obsessional severity on a scale from 0 (no impairment) to 4 (extreme impairment.) The Compulsion Rating Scale measures 5 domains of compulsion severity on a scale from 0 (no impairment) to 5 (extreme impairment.) The total range of OCD severity is reported on a scale from 0-40, with a higher score indicating greater severity.

Measure: Children's Yale-Brown Obsessive-Compulsive Scale

Time: In-treatment and follow-up (6-12 months)

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Description: The PARS is a measure of anxiety symptoms and severity. The Anxiety Severity Items are 7 questions meant to assess the frequency of anxiety symptoms and associated impairment. Items are measured on a scale from 0 (none) to 5 (extreme).The total range of anxiety severity is reported on a scale from 0-35, with a higher score indicating greater severity.

Measure: Pediatric Anxiety Rating Scale

Time: In-treatment and follow-up (6-12 months)

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Secondary Outcomes

Description: The CSQ-8 measures consumer satisfaction with mental health services; satisfaction is measured using 8 items on a scale from 1 (Poor) to 4 (Excellent). Total satisfaction ranges from 8-32, with a high score indicating greater satisfaction.

Measure: Client Satisfaction Questionnaire-8

Time: In-treatment and follow-up (6-12 months)

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Description: The CGI is a clinician-rated measures of global severity and improvement. The Severity of illness scale reports the severity of current symptoms on a scale from 1 (not at all ill) to 7 (among the most extremely ill patients.) The Global Improvement Scale tracks improvement since treatment initiation on a scale from 1 (very much improved) to 7 (very much worse). The highest possible score on either scale is 7, indicating extreme severity or worse treatment outcome.

Measure: Clinical Global Impression Scales

Time: In-treatment and follow-up (6-12 months)

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Description: The CSDS measures the extent to which anxiety symptoms interfere with functioning. The Disability Scale measures the degree to which anxiety impacts school, social, and home life on a scale from 0 (Not at all) to 10 (very, very much.) Total anxiety-related impairment ranges from 0-30, with higher scores indicating greater impairment.

Measure: Child Sheehan Disability Scale

Time: In-treatment and follow-up (6-12 months)

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Description: The measure tracks both the quality and quantity of homework completed between treatment sessions. This form has been used previously by our research group in large-scale treatment trials, and has been helpful in determining barriers to homework completion.

Measure: Homework Compliance Form

Time: Up to 6 months

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Description: The Exposure Guide is a exposure therapy fidelity/quality tool completed by study therapists. This tool collects information regarding the use of specific therapeutic tools during exposures.

Measure: Exposure Guide

Time: Up to 6 months

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Description: The TASCP is a 12-item measure of therapeutic alliance between a caregiver and his/her child's therapist. This measure assesses the bond and collaboration between caregiver and therapist. Each item is rated using a scale from 0: "not true" to 4: "very much true."

Measure: Therapeutic Alliance Scales for Caregivers and Parents (TASCP)

Time: Up to 6 months

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Description: 75 The TASC-r is a 12-item measure of therapeutic alliance between a child and his/her therapist. This measure assesses the degree of affective bond between child and therapist, as well as amount of therapeutic task collaboration. Each item is rated using a scale from 0: "not true" to 4: "very much true."

Measure: Therapeutic Alliance Scales for Children-Revised (TASC-r)

Time: Up to 6 months

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Description: The PQ-LES-Q is a 13-item measure of child functioning in life that uses a 5-point ratings scale, with higher scores indicating better quality of life. This measure has both parent and child versions, assessing the same items from both child and parent perspectives. The measure assesses quality of the child's life in a variety of domains.

Measure: Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q)

Time: In-treatment and follow-up (6-12 months)

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Description: The TPA is designed to independently solicit from youth and parent the top 3 problems they feel are most important to address in treatment. This is an idiographic measure of impairment that is driven by the individual needs and desires of the consumer. Respondents rate how much each problem bothers them from 0 ("not at all") to 10 (very, very much).

Measure: Top Problems Assessment (TPA)

Time: In-treatment and follow-up (6-12 months)

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Description: The CSQ assesses parent perceptions of the extent to which caring for a child with emotional problems affects several domains, including family life and relationships, demands on time, financial strain, disruption of social life, worry, guilt, and fatigue. This is a 21-item self-report measure that calls for parents to rate the extent of strain for each item using a 0 ("not at all") to 4 ("very much") scale.

Measure: Caregiver Strain Questionnaire (CSQ)

Time: In-treatment and follow-up (6-12 months)

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Description: The BTQ-P is a 28-item measure adapted from the BTQ to assess parent perceptions of barriers to accessing treatment for their child's anxiety. The measure is completed at the outset of treatment and assesses such domains as logistic and financial barriers, stigma, and aspects of treatment. Items are rated on a 0 ("not at all true") to 2 ("mostly true") scale.

Measure: Barriers to Treatment Questionnaire - Parent Version (BTQ-P)

Time: In-treatment and follow-up (6-12 months)

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Description: The PAS-PR is a 5-item questionnaire assessing the frequency and interference associated with accommodating the child's anxiety. Each item is followed by a series of common examples to illustrate the principle of accommodation for parents. Responses for frequency include 0 (never), 1 (rarely), 2 (occasionally), 3 (often), and 4 (always). Response options for interference due to accommodation include 0 (none), 1 (mild), 2 (moderate), 3 (severe), and 4 (extreme).

Measure: Pediatric Accommodation Scale-Parent Report (PAS-PR)

Time: In-treatment and follow-up (6-12 months)

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Description: We will record reactions from caregivers and child to treatment assignment using this clinician-rated measure. It includes capturing both verbatim responses from caregivers and child, as well as asking for interviewer impressions reactions from caregivers and child to treatment group assignment following randomization. The clinician also records the likelihood that the family will remain in the study and adhere to study protocols.

Measure: Randomization Debrief

Time: Administered at baseline

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Description: This measure is a 3-item self-report questionnaire that captures parental beliefs about the efficacy about each treatment condition (office-based or home/community-based) using a scale from 1:"I expect my child will be very much improved," to 7: "I expect my child will be very much worse." The parent is also asked to select which treatment option would be best for their family. There is also a patient version of this measure used to capture patient beliefs about the efficacy about each treatment condition (office-based or home/community-based) using the same scale. The patient is asked to select which treatment option they believe would be best for them and their family. The patient version of this measure will be completed by youth 12+.

Measure: Treatment Expectancy

Time: Administered at baseline

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Description: The SRS-2 is a 65-item self-report measure administered to caregivers or teachers to assess their perception of the presence of a child's social impairment. This measure is used to evaluate children aged 4-18 years old. Items are rated on a scale from 1 ("not true") to 4 ("almost always true").

Measure: The Social Responsiveness Scale, Second Edition (SRS-2)

Time: Administered at baseline and at discharge (up to 6-months)

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Description: The ARI-P is a 7-item parent report questionnaire assessing child's irritability. The items are each given a rating of: "not true," "somewhat true" or "certainly true".

Measure: Affective Reactivity Index - Parent Version (ARI-P)

Time: In-treatment and follow-up (6-12 months)

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Description: The ARI-S is a 7-item self-report report questionnaire assessing irritability. The items are each given a rating of: "not true," "somewhat true" or "certainly true".

Measure: Affective Reactivity Index - Self Report (ARI-S)

Time: In-treatment and follow-up (6-12 months)

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Description: The Distress Intolerance Index is a 10-item self-report report questionnaire assessing the inability to tolerate negative somatic and emotional states. Items are rated on a 5-point scale from "very little" (0) to "very much".

Measure: Distress Intolerance Index

Time: In-treatment and follow-up (6-12 months)

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Description: The PAS is a 12-item questionnaire assessing the frequency of and beliefs about parental accommodation. The frequency of parental accommodation is measured on a scale from "Never/Almost Never" (0), to "Always/Almost Always" (3). The beliefs about parental accommodation are measured on a scale from "Strongly Disagree" (0), to "Strongly Agree" (3).

Measure: Parent Accommodation Scale (PAS)

Time: In-treatment and follow-up (6-12 months)

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Description: The feedback form is a 3-item self-report questionnaire that asks caregivers or child which treatment group their family was in and for open-ended feedback about their experience in the study (i.e. what did they really like, what would they change, general suggestions/ comments). All responses on this survey are received anonymously. Caregivers and children complete separate feedback forms. Children 8+ will complete the child version of this measure.

Measure: Feedback Forms - Caregiver and Child Versions

Time: Administered only at discharge, up to 6-months into study

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Description: This form captures whether the patient ended treatment before or at 6 months, as well as the reasons for discontinuation (e.g., scheduling, transportation, financial, treatment fit, symptoms) that apply. This form also gathers information about whether referrals were provided to the family upon study discharge.

Measure: End of Treatment Form

Time: Administered only at discharge, up to 6-months into study

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Description: This 7-item measure asks for participants' caregivers to discuss to whom they would like the findings of the study to be disseminated (i.e., local policy makers, educators, etc.). Additionally, it asks for information on how they would like findings to be shared (i.e., via social media, presentations, etc.) as well as caregivers to share highlights of their experience in the study.

Measure: Sharing Study Findings

Time: Administered only at discharge, up to 6-months into study

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Description: We will record the rate of session reschedules, cancellations and no-shows, along with the overall number of sessions attended. We will also document the reason why a scheduled appointment does not occur using the Treatment Cancellation Form.

Measure: Treatment Attendance

Time: Up to 6 months

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Description: This is a case record form that documents any change in patient status (e.g., drop-out and premature termination) and the reasons for such changes.

Measure: Reasons for Treatment Discontinuation form

Time: Administered only at discharge, up to 6-months into study

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Primary Outcomes

Description: The SCS is a 26-item self-report questionnaire in which respondents describe how they relate to themselves during times of distress. The SCS includes the 5 item Self-Kindness subscale (ranging from 5-25; higher scores reflect more self-kindness), the 5-item Self-Judgment subscale (ranging from 5-25; higher scores reflect more self-judgment), the 4-item Common Humanity subscale (ranging from 4-20; higher scores reflect higher levels of common humanity), the 4-item Isolation subscale (ranging from 4-20; higher scores indicate higher levels of isolation), the 4-item Mindfulness subscale (ranging from 4-20; higher scores reflect higher levels of mindfulness) and the 4-item Over-Identification subscale (ranging from 4-20). Responses are given on a 5-point scale from "1-Almost Never" to "5-Almost Always." Mean scores on the six subscales are then averaged to create an overall self-compassion score ranging from 26 to 130. Higher scores correspond to higher levels of self-compassion.

Measure: Self-Compassion Scale (SCS); Change from baseline in Self-Compassion at post-treatment (2 mo) and follow up (3mo)

Time: Baseline, 8-10 weeks, 12-14 weeks

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Description: The TRGI is a 32-item validated self-report measure assessing traumatic guilt. The TRGI has three scales - Guilt Severity, Distress, and Guilt Cognitions. In all 32 items the answers are recorded on 5-point scale (ranging from 0 - not at all true to 4 - extremely true). Eight items are reverse-scored. We will use the TRGI as one of our eligibility criteria and to monitor changes in guilt and related cognitions over time.

Measure: Trauma-Related Guilt Inventory (TRGI); Change from baseline in trauma-related guilt at post-treatment (2 mo) and follow up (3mo)

Time: Baseline, 8-10 weeks, 12-14 weeks

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Description: The ISS is a 30-item self-report measure assessing shame proneness scored on a 5-point Likert scale ranging from 0 = "never" to 4 = "almost always". The ISS yields sum scores for two subscales, self-esteem (6 items; range = 0-24 with higher scores reflecting higher levels of self-esteem) and internalized shame (24 items; range = 0-96 with higher scores reflecting higher levels of shame) and has been well-validated with research and clinical populations. The self-esteem items are interspersed to counteract a negative response set.

Measure: Internalized Shame Scale (ISS); Change from baseline in shame at post-treatment (2 mo) and follow up (3mo)

Time: Baseline, 8-10 weeks, 12-14 weeks

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Secondary Outcomes

Description: The CAPS is a semi-structured interview used to assess PTSD diagnostic criteria and severity. Respondents select up to three of the most traumatic events they have experienced, and those events are used as the basis for assessing PTSD symptoms. The CAPS assesses each of the 20 items from the DSM-5 criteria B, C, D, and E. The assessor combines information about frequency and intensity of an item into a single severity rating (0=Absent; 1=Mild/subthreshold; 2=Moderate/threshold; 3=Severe/markedly elevated; 4=Extreme/incapacitating). CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms (range = 0-40). Similarly, CAPS-5 symptom cluster severity scores are calculated by summing the individual item severity scores for symptoms corresponding to a given DSM-5 cluster: Criterion B (items 1-5); Criterion C (items 6-7); Criterion D (items 8-14); and, Criterion E (items 15-20).

Measure: Clinician Administered PTSD Scale for DSM-5; Change from baseline in PTSD symptoms at post-treatment (2 mo) and follow up (3mo)

Time: Baseline, 8-10 weeks, 12-14 weeks

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Description: The WHO-QOL BREF is a 26-item validated self-report measure that that assesses quality of life across four domains: physical (7 items, range 1-5), psychological (6 items, range 1-5), social relationships (3 items, range 1-5), and environment (8 items, range 1-5). The four domain scores denote an individual's perception of quality of life in each particular domain. The mean score of items within each domain is used to calculate the domain score. Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life). There are also two items that are examined separately: question 1 asks about an individual's overall perception of quality of life on a scale of 1 - "very poor" to 5 - "very good". Question 2 asks about an individual's overall perception of their health on a scale of 1 - "very dissatisfied" to 5 - "very satisfied". The WHO-QOL-BREF has excellent internal validity and test-retest reliability.

Measure: Quality Of Life Enjoyment & Satisfaction Questionnaire (WHO-QOL-BREF); Change from baseline in quality of life at post-treatment (2 mo) and follow up (3mo)

Time: Baseline, 8-10 weeks, 12-14 weeks

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Description: The Alcohol TLFB is a drinking assessment method that obtains estimates of daily drinking. The TLFB will be employed at all three assessment points to evaluate alcohol and other substance use during the 90 days preceding each interview. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period. The TLFB will be used at each follow-up to establish: percentage days heavy drinking, percent days abstinent, length of initial abstinence, length of use episodes, severity of relapse and current alcohol/drug use pattern. The Alcohol TLFB has been shown to have good psychometric characteristics with a variety of groups, and can generate variables that provide a wide range of information about an individual's use (e.g., pattern, variability, and magnitude of use).

Measure: Timeline Follow-back; Change from baseline in frequency of substance use at post-treatment (2 mo) and follow up (3mo)

Time: Baseline, 8-10 weeks, 12-14 weeks

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Other Outcomes

Description: Beck Scale for Suicidal Ideation (BSSI): This scale is a 19-items instrument that evaluates the presence and intensity of suicidal thoughts in a week before evaluation (19). Each item is scored based on an ordinal scale from 0 to 2 and the total score is 0 to 38 with higher score indicating more risk for suicide.

Measure: Beck Scale for Suicidal Ideation; Change from baseline in suicidal risk at post-treatment (2 mo) and follow up (3mo)

Time: Baseline, 8-10 weeks, 12-14 weeks

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Primary Outcomes

Description: the gold standard for PTSD diagnosis, a trained expert administrator scores PTSD symptom severity; range 0-80, higher score represents greater severity

Measure: Clinician Administered PTSD Symptom Scale for DSM5 (CAPS-5)

Time: week 10

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Secondary Outcomes

Description: well-validated and widely used 9-item self-report measure of depression symptom severity, range 0-27, higher score represents greater severity

Measure: Change in Patient Health Questionnaire (PHQ-9) Score

Time: week 10, and 2, 6 and 12 months later, compared to baseline

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Description: a reliable 20-item screen for PTSD, in which each item is rated on a 5-point Likert scale, range 0-80, higher score represents greater severity

Measure: Change in PTSD Checklist for DSM5 (PCL5) Score

Time: week 10, and 2, 6 and 12 months later, compared to baseline

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Description: a clinically validated 9-item assessment of sleep quality and sleep disturbances; range 0 to 21, higher score represents greater severity

Measure: Change in Pittsburgh Sleep Quality Index (PSQI) Score

Time: week 10, and 2, 6 and 12 months later, compared to baseline

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Description: a reliable 22-item self-report measure assessing functional status and post concussive symptoms, range 0-88, higher score represents greater severity

Measure: Change in Neurobehavioral Symptom Inventory (NSI) Score

Time: week 10, and 2, 6 and 12 months later, compared to baseline

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Description: a reliable 100 item self-report inventory measuring overall quality of life in 8 dimensions; range 100 to 500, higher score represents greater severity

Measure: Change in World Health Organization Quality of Life Inventory (WHOQOL-100) Score

Time: week 10, and 2, 6 and 12 months later, compared to baseline

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Other Outcomes

Description: inflammatory cytokine that increases with physical and psychological trauma, measured at the picogram per milliliter level, present in plasma at detectable levels in all individuals with the single molecule array (SIMOA) technology to be applied, but expected to decrease in response to intervention

Measure: Change in plasma tumor necrosis factor-alpha level

Time: week 10, compared to baseline

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Description: inflammatory cytokine that increases with physical and psychological trauma, measured at the picogram per milliliter level, present in plasma at detectable levels in all individuals with the SIMOA technology to be applied, but expected to decrease in response to intervention

Measure: Change in plasma interleukin-6 level

Time: week 10, compared to baseline

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Description: inflammatory cytokine that increases with physical and psychological trauma, measured at the picogram per milliliter level, present in plasma at detectable levels in all individuals with the SIMOA technology to be applied, but expected to decrease in response to intervention

Measure: Change in plasma interleukin-10 level

Time: week 10, compared to baseline

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Description: Normalized Summary Score for a battery of 7 tests to measure various aspects of cognition including memory, executive function, attention span; normed for age, with a score of 50 being average, scores greater than 50 demonstrate greater than average cognitive function, and scores lower than 50 indicating lower than average cognitive function

Measure: Change in NIH Toolbox Cognition Battery (NIH-TB) Neurocognitive Assessment Composite Score

Time: week 10, compared to baseline

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Primary Outcomes

Description: Covid-19 infection rates in cannabis users will be compared to rates in the general population. Our online questionnaire responses will compare infection rates of cannabis users in this study against the Johns Hopkins University Coronavirus Research Center data (https://coronavirus.jhu.edu).

Measure: Prevention of COVID-19

Time: Five years

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Description: Severity of persistent symptoms in cannabis users testing positive for active infection and/or antibodies will also be compared to the general population. Patients will answer the widely used FLU-PRO questionnaire, which asks about flu symptoms and severity, to capture diagnoses, symptoms, and medical interventions related to COVID-19. The data from cannabis user patients will be compared with national and international data surveys, such as the Covid Symptom Study (https://covid.joinzoe.com/us-2).

Measure: Treatment of COVID-19

Time: Five years

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Description: The primary objective is to assess the efficacy and safety of medical cannabis as medicine for treatment of chronic pain and other chronic debilitating diseases. Pain will be measured by Brief Pain Inventory (BPI) numeric scale. Change from baseline in BPI will be assessed at 3-month intervals. For prospective associations between cannabis use and outcomes, use of a lagged mixed-effects models will examine temporal associations between cannabis use and pain severity, opioid sparing, and patient satisfaction. Data will be analyzed from baseline and the annual follow-up waves.

Measure: Treatment of Symptoms

Time: Five years

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Secondary Outcomes

Description: Secondary objectives include evaluating increases or decreases in quality of life, and increases or decreases in concomitant opioid use. Satisfaction with treatment will be measured by a Visual Analog Score (VAS). Change From baseline in Satisfaction with treatment measured by (VAS) be assessed at 3-month intervals.

Measure: Cannabis Impact on Quality of Life

Time: Five years

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Description: Tertiary objectives will examine preferences for routes of administration, and preferences for THC / CBD ratios. Categorical factors will be summarized using frequencies and percentages, while continuous measure distributions will be described using means, standard deviations, and quartiles of interest.

Measure: Cannabis Route and Dosing

Time: Five years

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Description: Incidence of Treatment-Related Adverse Events will be measured by Physician Global Assessment (PGA) numeric scale. Number of participants with Treatment-Related Adverse Events will be assessed by CTCAE v4.0.

Measure: Monitoring Adverse Events

Time: Five years

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Primary Outcomes

Description: The primary outcome measure is the mean of the change on the Socialization and Communication Subscale Standard Scores on the Vineland Adaptive Behavior Scales (VABS-3). The primary endpoint is the change on this outcome measure from baseline to six months.

Measure: Change on the Socialization and Communication Subscale Standard Scores on the Vineland Behavior Scales

Time: Baseline, 6 months

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Secondary Outcomes

Description: Change in VABS-3 (Vineland Adaptive Behavior Scales) Socialization Standard Score

Measure: Change in VABS-3 Socialization Standard Score

Time: Baseline, 6 months

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Description: Change in VABS-3 (Vineland Adaptive Behavior Scales) Communication Standard Score

Measure: Change in VABS-3 Communication Standard Score

Time: Baseline, 6 months

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Description: Clinical Global Impression- Severity Scale

Measure: Change in CGI-Severity score

Time: Baseline, 6 months

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Description: Clinical Global Impression- Impression

Measure: CGI-Intervention score

Time: Baseline, 6 months

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Description: Pediatric Quality of Life Scale

Measure: Change in the Pediatric Quality of Life Scale

Time: Baseline, 6 months

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Other Outcomes

Description: Assess for infusion reactions

Measure: Incidence and severity of infusion reactions

Time: Baseline, 6 months

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Description: Assess for infections directly related to the study product infusions

Measure: Incidence and severity of product-related infections

Time: Baseline, 6 months

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Description: Assess for anti-HLA antibodies

Measure: Evidence of formation of anti-HLA antibodies

Time: Baseline, 6 months, 12 months

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Description: Assess for signs and symptoms of graft versus host disease

Measure: Incidence and severity of graft versus host disease

Time: 6 months, 12 months

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Description: Assess for study related and unexpected adverse events

Measure: Incidence and severity of unexpected adverse events related to the study product

Time: Baseline, 6 months, 12 months

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Primary Outcomes

Description: The 6-minute walk test (6MWT) will be used to measure cardiorespiratory fitness (CRF) during which individuals will be asked to walk continuously for six minutes on a flat, indoor surface around cones (separated by 100ft). The possible distance range is 400 meters to 650 meters. Higher scores reflect better outcomes (greater physical fitness).

Measure: Difference in Participant's Total Distance During 6-minute Walk

Time: Baseline and the last study visit (Up to 20 weeks)

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Secondary Outcomes

Description: Mean difference in overall minutes spent walking per week from baseline to last study visit (up to 20 minutes). This information will be obtained from the participant's Fitbit. Higher scores reflect more minutes walking.

Measure: Mean Difference in Minutes Spent Walking

Time: Baseline and the last study visit (up to 20 weeks)

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Description: Mean difference in daily steps from baseline to last study visit (up to 20 weeks). This information will be obtained from the participants Fitbit. Higher scores reflect more daily steps.

Measure: Mean Difference in Daily Steps

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in overall score from baseline to last study visit (up to 20 weeks). The UCLA Loneliness scale is a 20 item scale. Answers are on a 4 point scale with options "I often feel this way," "I sometimes feel this way," "I rarely feel this way," and "I never feel this way." Possible scores range from 20 to 80. Higher scores reflect worse outcomes (greater feelings of loneliness).

Measure: Mean Difference Overall UCLA Loneliness Scale Score

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in the overall score from baseline to last study visit (up to 20 weeks). The PANSS is a semi-structured interview using a 30-item scale to evaluate the presence, absence and severity of Positive, Negative and General Psychopathology symptoms of schizophrenia. All 30 items are rated on a 7-point scale (1 = absent; 7 = extreme). Possible scores range from 30 to 210. Higher scores reflect worse outcomes (i.e. greater symptoms of psychosis).

Measure: Mean Difference Overall PANSS Score

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in body weight change from baseline to last study visit (up to 20 weeks). Expected normal BMI ranges from 14 to 54. Higher scores reflect worse outcomes (i.e. greater body mass).

Measure: Mean Difference in Body Weight Change

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in blood pressure change from baseline to last study visit (up to 20 weeks).

Measure: Mean difference in blood pressure change

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in resting heart rate change from baseline to last study visit (up to 20 weeks). Expected normal heart rate ranges from 40 to 120. Higher scores reflect worse outcomes (poorer heart condition).

Measure: Mean Difference in Resting Heart Rate Change

Time: Baseline and the last study visit (Up to 20 weeks)

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Other Outcomes

Description: Mean difference in composite motivation score from baseline to last study visit (up to 20 weeks). The BREQ-2 is a 19 item self-report scale. Answers are on a 5 point Likert scale ranging from 0 to 4. 0 corresponds to "not true for me" and 4 corresponds to "very true for me." Possible scores range from 0 to 46. Higher scores reflect better outcomes (higher autonomous motivation to exercise).

Measure: Mean Difference in Composite Motivation Score on the Behavioral Regulation Exercise Questionnaire (BREQ-2)

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in composite score from baseline to last study visit (up to 20 weeks). The BPNE is an 11 item self-report scale. Answers are on a 5 point Likert scale ranging from "I don't agree at all" to "I completely agree." Possible scores range from 11 to 55. Higher scores reflect better outcomes (i.e. more psychological needs being met through exercise).

Measure: Mean Difference in Composite Score on the Basic Psychological Needs in Exercise Scale (BPNES)

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in composite score from baseline to last study visit (up to 20 weeks). 2. The PACES is an 18 item self-report scale. Answers are on a 7-point scale. Possible scores range from 18 to 126. Higher scores reflect better outcomes (greater enjoyment of physical activity).

Measure: Mean Difference in Composite Score on the Physical Activity Enjoyment Scale (PACES)

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in composite score from baseline to last study visit (up to 20 weeks). The BPNS is a 21 item self-report scale. Answer are on a 7-point Likert scale ranging from "not at all true" to "very true." Possible scores range from 21 to 147. Higher scores reflect better outcomes (better autonomy, competence, and relatedness).

Measure: Mean Difference in Composite Score on the Basic Psychological Needs Scale (BPNS)

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in composite score from mid-treatment to last study visit (up to 20 weeks). The Autonomy Scale is a 6 item self-report scale. Answers are made using a 7-point scale. Possible scores range from 7 to 46. Higher scores reflect better outcomes (better relationship between research participant and staff.

Measure: Mean Difference in Composite Score on the Autonomy Support Scale

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Total score at Post treatment visit only (16 weeks). The End of Study survey measures participant's satisfaction and feedback with the PACE-Life trial. The survey is a 18 item self-report scale, consisting of both Likert scale and open-ended items. Answers are made using a 5-point Likert scale. Possible scores range from 18-90. Higher scores reflect higher levels of satisfaction and enjoyment in the study.

Measure: End of Study Survey

Time: Post treatment only (16 weeks)

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Primary Outcomes

Measure: Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Volume of distribution (V) or apparent oral volume of distribution (V/F) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Elimination rate constant (ke) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Half-life (t1/2) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Absorption rate constant (ka) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: AUC (area under the curve) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Maximum concentration (Cmax) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Measure: Time to achieve maximum concentration (Tmax) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

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Primary Outcomes

Description: Thoughts and feelings about mental health impact of COVID-19

Measure: NIMH COVID Study survey - adult responses

Time: Biweekly online responses

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Secondary Outcomes

Description: Ratings on measures of mental health symptoms and distress

Measure: DSM XC and KS survey

Time: Biweekly online self report

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Primary Outcomes

Description: The 12-item version of the General Health Questionnaire (GHQ-12) is a self-reported instrument that measures symptoms of anxiety and depression. It provides cut-off points to identify people at risk of anxiety and/or depression, which differ slightly between countries

Measure: Anxiety and depressive symptoms

Time: 12 months

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Secondary Outcomes

Description: Ad hoc survey on experiences, fears, and concerns about Covid-19

Measure: Experiences, fears and concerns about the Covid-19

Time: Baseline

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Description: Ad hoc survey on experiences, fears, and concerns about Covid-19

Measure: Experiences, fears and concerns about the Covid-19

Time: 3 months

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Description: Ad hoc survey on experiences, fears, and concerns about Covid-19

Measure: Experiences, fears and concerns about the Covid-19

Time: 6 months

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Description: Ad hoc survey on experiences, fears, and concerns about Covid-19

Measure: Experiences, fears and concerns about the Covid-19

Time: 12 months

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Description: Ad hoc survey on Covid-19 training and resource prioritization

Measure: Training and resource prioritization

Time: Baseline

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Description: Ad hoc survey on Covid-19 training and resource prioritization

Measure: Training and resource prioritization

Time: 3 months

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Description: Ad hoc survey on Covid-19 training and resource prioritization

Measure: Training and resource prioritization

Time: 6 months

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Description: Ad hoc survey on Covid-19 training and resource prioritization

Measure: Training and resource prioritization

Time: 12 months

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Description: Item from the Columbia Suicide Severity Rating Scale (C-SSRS) that measures suicidal ideation with a dichotomous answer (presence/absence)

Measure: Suicide ideation (presence)

Time: Baseline

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Description: Item from the Columbia Suicide Severity Rating Scale (C-SSRS) that measures suicidal ideation with a dichotomous answer (presence/absence)

Measure: Suicide ideation (presence)

Time: 3 months

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Description: Item from the Columbia Suicide Severity Rating Scale (C-SSRS) that measures suicidal ideation with a dichotomous answer (presence/absence)

Measure: Suicide ideation (presence)

Time: 6 months

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Description: Item from the Columbia Suicide Severity Rating Scale (C-SSRS) that measures suicidal ideation with a dichotomous answer (presence/absence)

Measure: Suicide ideation (presence)

Time: 12 months

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Description: 5-point Likert item from the Columbia Suicide Severity Rating Scale (C-SSRS). Higher scores indicate higher frequency.

Measure: Suicide ideation (frequency)

Time: Baseline

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Description: 5-point Likert item from the Columbia Suicide Severity Rating Scale (C-SSRS). Higher scores indicate higher frequency.

Measure: Suicide ideation (frequency)

Time: 3 months

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Description: 5-point Likert item from the Columbia Suicide Severity Rating Scale (C-SSRS). Higher scores indicate higher frequency.

Measure: Suicide ideation (frequency)

Time: 6 months

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Description: 5-point Likert item from the Columbia Suicide Severity Rating Scale (C-SSRS). Higher scores indicate higher frequency.

Measure: Suicide ideation (frequency)

Time: 12 months

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Description: Ad hoc 3-item survey to evaluate acute stress disorder. Higher values of the 5-points Likert scales suggest higher frequency of symptoms

Measure: Acute stress symptoms

Time: Baseline

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Description: Ad hoc 3-item survey to evaluate acute stress disorder. Higher values of the 5-points Likert scales suggest higher frequency of symptoms

Measure: Acute stress symptoms

Time: 3 months

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Description: Ad hoc 3-item survey to evaluate acute stress disorder. Higher values of the 5-points Likert scales suggest higher frequency of symptoms

Measure: Acute stress symptoms

Time: 6 months

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Description: Ad hoc 3-item survey to evaluate acute stress disorder. Higher values of the 5-points Likert scales suggest higher frequency of symptoms

Measure: Acute stress symptoms

Time: 12 months

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Description: Ad hoc survey on support network. The answers to the multiple items will be adjusted so higher values indicate higher levels of psychological and social support

Measure: Psycho/social support and network

Time: Baseline

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Description: Ad hoc survey on support network. The answers to the multiple items will be adjusted so higher values indicate higher levels of psychological and social support

Measure: Psycho/social support and network

Time: 3 months

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Description: Ad hoc survey on support network. The answers to the multiple items will be adjusted so higher values indicate higher levels of psychological and social support

Measure: Psycho/social support and network

Time: 6 months

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Description: Ad hoc survey on support network. The answers to the multiple items will be adjusted so higher values indicate higher levels of psychological and social support

Measure: Psycho/social support and network

Time: 12 months

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Description: The Brief Resilience Scale (BRS) is a 6-item self-reported instrument that measures resilience. The range of scores is 6-30. Higher scores indicate higher resilience levels.

Measure: Resilience

Time: Baseline

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Description: The Brief Resilience Scale (BRS) is a 6-item self-reported instrument that measures resilience. The range of scores is 6-30. Higher scores indicate higher resilience levels.

Measure: Resilience

Time: 3 months

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Description: The Brief Resilience Scale (BRS) is a 6-item self-reported instrument that measures resilience. The range of scores is 6-30. Higher scores indicate higher resilience levels.

Measure: Resilience

Time: 6 months

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Description: The Brief Resilience Scale (BRS) is a 6-item self-reported instrument that measures resilience. The range of scores is 6-30. Higher scores indicate higher resilience levels.

Measure: Resilience

Time: 12 months

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Description: The 12-item version of the General Health Questionnaire (GHQ-12) is a self-reported instrument that measures symptoms of anxiety and depression. It provides cut-off points to identify people at risk of anxiety and/or depression, which differ slightly between countries

Measure: Anxiety and depressive symptoms

Time: Baseline

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Description: The 12-item version of the General Health Questionnaire (GHQ-12) is a self-reported instrument that measures symptoms of anxiety and depression. It provides cut-off points to identify people at risk of anxiety and/or depression, which differ slightly between countries

Measure: Anxiety and depressive symptoms

Time: 3 months

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Description: The 12-item version of the General Health Questionnaire (GHQ-12) is a self-reported instrument that measures symptoms of anxiety and depression. It provides cut-off points to identify people at risk of anxiety and/or depression, which differ slightly between countries

Measure: Anxiety and depressive symptoms

Time: 6 months

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Primary Outcomes

Measure: percentage of patients who required hospitalisation, developed severe illness (ICU admission) or died

Time: Day 28

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Secondary Outcomes

Measure: percentage of patients who required hospitalisation, developed severe illness (ICU admission) or died

Time: 3 months

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Primary Outcomes

Description: total severity score from the Impact of Event Scale-Revised (IES-R)

Measure: impact of the COVID-19 pandemic on psychiatric symptomatology

Time: through study completion, an average of 2 year

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Primary Outcomes

Description: Frequency of central or peripheral neurological or psychiatric symptoms observed in patients with COVID-19

Measure: Central or peripheral neurological symptoms or psychiatric symptoms observed in patients with Covid-19

Time: 12 months

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Secondary Outcomes

Description: Impact on neurological or psychiatric disease trajectories assessed by severity scores or subjective progression (improved, stable, impaired) during and after COVID-19 pathology in patients with pre-existing neurological and psychiatric diseases

Measure: Progression of pre-existing neurological or psychiatric pathologies

Time: 12 months

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Primary Outcomes

Description: Depression, anxiety and stress scales (DASS21). Score range: 0 (worst outcome) to 21 (best outcome)

Measure: Depression, anxiety and stress

Time: 2 weeks

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Secondary Outcomes

Description: Davidson Trauma Scale (DTS). The DTS is a 17-item, Likert-scale, self-report instrument that assesses the 17 DSM-IV symptoms of PTSD. Both a frequency and a severity score can be determined. The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). Higher scores are indicative a worse outcome.

Measure: Post-traumatic stress syndrome

Time: 2 weeks

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Description: Insomnia Severity Index. Score range: 0 (best outcome) to 28 (worst outcome)

Measure: Insomnia

Time: 2 weeks

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Description: General Self-Efficacy Scale. Score range: 10 (worst outcome) to 40 (best outcome)

Measure: Self Efficacy

Time: 2 weeks

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Primary Outcomes

Description: Number of intrusive memories of traumatic events recorded by participants in a daily pen and and paper diary.

Measure: Frequency of intrusive memories

Time: Baseline weeks 1-3, throughout the duration of the intervention phase (approximately 5 weeks), post-intervention weeks 1-2 and for 1 week 2 months post-intervention. Change is assessed from baseline to post-intervention.

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Secondary Outcomes

Description: A brief bespoke measure of concentration adapted from that used previously with refugees (Holmes et al., 2017). It has three questions about disruption to concentration from intrusive memories. A higher score on each question means a worse outcome.

Measure: Concentration

Time: Baseline, 2-weeks post-intervention and 2-months post-intervention

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Description: Developed by Woodfield Trauma Service. The measure asks how many hours the person has spent doing various activities in the past two weeks (for example, domestic chores, exercise, cultural activities). A higher score means a better outcome.

Measure: Social and Occupational Activity Tally (SOAT)

Time: Baseline, 2-weeks post-intervention and 2-months post-intervention

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Description: Four items from the Dissociative Experiences Scale II - items two, three, 14 and 20 (DES II; Carlson, & Putnam, 1993). Each item asks how often (from 0% to 100% of the time) the dissociative experience described happens to the individual. A higher score on each question means a worse outcome.

Measure: Dissociation

Time: Baseline, 2-weeks post-intervention and 2-months post-intervention

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Description: The PCL-5 (Weathers, Litz, Keane, Palmieri, Marx, & Schnurr, 2013) is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Total scores can range from 0 to 80, with higher scores meaning a worse outcome.

Measure: Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (PCL-5)

Time: Baseline and 2-weeks post-intervention

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Description: The PHQ-9 (Kroenke, Spitzer & Williams, 2001) is a nine-item self-report measure that assesses the nine DSM-IV symptoms of depression. Total scores can range from 0 to 27, with higher scores meaning a worse outcome.

Measure: Patient Health Questionnaire (PHQ-9)

Time: Baseline and 2-weeks post-intervention

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Description: The WHO DAS 2.0 (World Health Organisation, 2010) is a measure of health and disability. Total scores can range from 0 to 48, with higher scores meaning a worse outcome.

Measure: World Health Organisation Disability Assessment Schedule 2.0 (WHO DAS 2.0) 12 item version

Time: Baseline and 2-weeks post-intervention

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Other Outcomes

Description: A bespoke measure to assess adherence to self-guided practice of the intervention. It includes four questions to assess how often, and for how long, the person played Tetris after experiencing intrusive memories during the previous week.

Measure: Self-Guided Intervention Adherence Questionnaire

Time: Time Frame: Intervention sessions 2-5, 1 week post-intervention, 2 weeks post-intervention and 2 months post-intervention.

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Description: A bespoke questionnaire to gain feedback on the intervention. It includes 16 questions to assess acceptability and usefulness of the intervention with a variety of response options including yes/no, visual analogue scales and open responses.

Measure: Feedback Questionnaire

Time: 1-week post-intervention.

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Primary Outcomes

Description: Number of intrusive memories of traumatic events recorded by participants in a pen and and paper diary.

Measure: Frequency of intrusive memories

Time: Daily through study completion, an average of 3 months. Change is assessed from baseline to post-intervention.

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Secondary Outcomes

Description: A brief bespoke measure of concentration adapted from that used previously with refugees (Holmes et al., 2017). It has three questions about disruption to concentration from intrusive memories. A higher score on each question means a worse outcome.

Measure: Concentration

Time: Baseline and 2-weeks post-intervention

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Description: Developed by Woodfield Trauma Service. The measure asks how many hours the person has spent doing various activities in the past two weeks (for example, domestic chores, exercise, cultural activities). A higher score means a better outcome.

Measure: Social and Occupational Activity Tally (SOAT)

Time: Baseline and 2-weeks post-intervention

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Description: Four items from the Dissociative Experiences Scale II - items two, three, 14 and 20 (DES II; Carlson, & Putnam, 1993). Each item asks how often (from 0% to 100% of the time) the dissociative experience described happens to the individual. A higher score on each question means a worse outcome.

Measure: Dissociation

Time: Baseline and 2-weeks post-intervention

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Description: The PCL-5 (Weathers, Litz, Keane, Palmieri, Marx, & Schnurr, 2013) is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Total scores can range from 0 to 80, with higher scores meaning a worse outcome.

Measure: Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (PCL-5)

Time: Baseline and 2-weeks post-intervention

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Description: The PHQ-9 (Kroenke, Spitzer & Williams, 2001) is a nine-item self-report measure that assesses the nine DSM-IV symptoms of depression. Total scores can range from 0 to 27, with higher scores meaning a worse outcome.

Measure: Patient Health Questionnaire (PHQ-9)

Time: Baseline and 2-weeks post-intervention

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Description: The WHO DAS 2.0 (World Health Organisation, 2010) is a measure of health and disability. Total scores can range from 0 to 48, with higher scores meaning a worse outcome.

Measure: World Health Organisation Disability Assessment Schedule 2.0 (WHO DAS 2.0) 12 item version

Time: Baseline and 2-weeks post-intervention

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Other Outcomes

Description: A bespoke measure to assess adherence to self-guided practice of the intervention. It includes four questions to assess how often, and for how long, the person played Tetris after experiencing intrusive memories during the previous week.

Measure: Self-Guided Intervention Adherence Questionnaire

Time: Intervention weeks 2-5, 1 week post-intervention and 2 weeks post-intervention

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Description: A bespoke questionnaire to gain feedback on the intervention. It includes 16 questions to assess acceptability and usefulness of the intervention with a variety of response options including yes/no, visual analogue scales and open responses.

Measure: Feedback Questionnaire

Time: 1-week post-intervention.

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Primary Outcomes

Description: Professional Quality of Life Questionnaire (proQOL): min score of 10; max score of 50; higher scores mean worse outcome

Measure: Change in professional quality of life

Time: Before peer support program, through study completion (an average of 7 months)

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Secondary Outcomes

Description: Stress Risk & Resilience Self-Index: min score 0; max score of 12; higher scores mean worse outcome

Measure: Change in mental health symptoms and resilience markers

Time: Before peer support program, through study completion (an average of 7 months)

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Primary Outcomes

Description: Using Sniffin' Sticks olfactory testing pens to test smell

Measure: Smelling ability

Time: 6 months

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Primary Outcomes

Description: Diagnostic values of anosmia and ageusia for COVID-19 with questionnaire

Measure: Diagnostic values of anosmia and ageusia for COVID-19

Time: at inclusion

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Secondary Outcomes

Description: Diagnostic values of CODA (Clinical Olfactory dysfunction Assessment) score for COVID-19 : Simple, fast, semi-objective olfactory test developed for epidemic context

Measure: Diagnostic values of CODA

Time: at inclusion

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Primary Outcomes

Description: Rate of consent among informed eligible participants

Measure: Recruitment rate

Time: At inclusion

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Description: Rates of completion of intervention sessions among participants

Measure: Completion rate

Time: During and post-intervention (1 month)

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Description: Symptoms of peri-traumatic distress, min. score 0, max score 24, higher score corresponds to worse distress

Measure: Peri-traumatic distress inventory (negative emotions)

Time: Pre-post intervention (1 month after discharge/death)

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Description: Posttraumatic stress, min. score 6, max score 24, higher score corresponds to worse distress

Measure: Impact of Events Scale (6 item)

Time: 1 month post intervention

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Description: Posttraumatic stress, min. score 6, max score 24, higher score corresponds to worse distress

Measure: Impact of Events Scale (6 item)

Time: 6 months post intervention

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Description: Posttraumatic stress, min. score 6, max score 24, higher score corresponds to worse distress

Measure: Impact of Events Scale (6 item)

Time: 12/13 months post intervention

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Secondary Outcomes

Description: Prolonged Grief, scored according to diagnostic criteria for prolonged grief disorder

Measure: Prolonged Grief-13-scale

Time: 6 and 13 months

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Description: Symptoms of depression, min. score 8, max score 40, higher score corresponds to worse symptoms

Measure: PROMIS Depression (8 item scale)

Time: Baseline to 1, 6, and 12/13 months

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Description: Symptoms of anxiety, min. score 8, max score 40, higher score corresponds to worse symptoms

Measure: PROMIS Anxiety (8 item scale)

Time: Baseline to 1, 6, and 12/13 months

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Description: Perceived stress, min. score 0, max score 16, higher score corresponds to worse stress

Measure: Perceived Stress Scale (4 item)

Time: Baseline to 1, 6, and 12/13 months

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Other Outcomes

Description: Worry, min. score 3, max score 15, higher score corresponds to greater worry

Measure: Short Penn State Worry Questionnaire (3 items)

Time: Baseline to 1, 6, and 12/13 months

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Description: Brooding, min. score 5, max score 20, higher score corresponds to greater brooding/rumination

Measure: Brooding subscale of Ruminative Responses Scale

Time: Baseline to 1, 6, and 12/13 months

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Description: Intolerance of uncertainty, min score 2, max score 8, greater score indicates greater uncertainty intolerance

Measure: Intolerance of uncertainty Scale (2 item)

Time: Baseline to 1, 6, and 12/13 months

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Primary Outcomes

Description: composition, home confinement, change in the environment, personal room at home, screens with internet access, parents' current professional status, teleworking, care, family concerns related to Covid-19, parenting stress, schooling, recurrent complaints.

Measure: Interview of the parents : contextual data

Time: Baseline

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Description: related to education; related to daily family life; related to leisure, related to care (children/adolescents, parents)

Measure: Interview of the children/adolescents/ parents : Experience of the confinement in general

Time: Baseline

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Description: related to education; related to daily family life; related to leisure, related to care (children/adolescents, parents)

Measure: Interview of the children/adolescents/ parents : Experience of the confinement in general

Time: 1 month

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Description: related to education; related to daily family life; related to leisure, related to care (children/adolescents, parents)

Measure: Interview of the children/adolescents/ parents : Experience of the confinement in general

Time: 3 months

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Description: Data relating to disease and management of care. Experience of the referring caregiver.

Measure: Interview of the referring caregiver : data relating to disease and management of care

Time: 3 months

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Primary Outcomes

Description: DS1923-F5 Thermochron iButtons

Measure: Skin thermometry

Time: 6 hours

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Description: DS1923-F5 Thermochron iButtons

Measure: Hygrometry under costume

Time: 6 hours

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Description: A Polar H10 heart rate monitor (Polar Electro, Finland) will carry all items during the entire research

Measure: Heart rate

Time: 6 hours

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Description: Meteoscop - M

Measure: Air thermometry

Time: 6 hours

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Description: Meteoscop - M

Measure: Air hygrometry

Time: 6 hours

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Primary Outcomes

Measure: Neurodevelopmental Outcomes

Time: 3-4 years of age

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Primary Outcomes

Description: SARS-CoV 2 RNA PCR in semen

Measure: SARS-CoV 2 presence in semen

Time: Enrollment

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Description: SARS-CoV 2 RNA PCR in urine

Measure: SARS-CoV 2 presence in urine

Time: Enrollment

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Description: Interleukin quantitative analysis in Semen, to assess if past inflammation due to SARS-CoV 2 Infection was present

Measure: Inflammation in Semen

Time: Enrollment

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Description: Spermiogram done following WHO guidelines and criteria

Measure: Semen quantitative and qualitative analysis

Time: Enrollment

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Secondary Outcomes

Description: International Index of Erectile Function (IIEF-5) questionnaire administration. Score range from 0 to 25. Higher scores mean good erectile function

Measure: Erectile Function

Time: Enrollment

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Description: SExual Chronicle REcording Table (SECRET) questionnaire administration Questionnaire helps to assess the sexual habits of individuals

Measure: Sexual Habits

Time: Enrollment

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Description: International Prostate Symptom Score (IPSS) questionnaire administration Score range from 0 to 35. Higher scores mean worst urinary function

Measure: Urinary function

Time: Enrollment

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Description: Male Sexual Health Questionnaire Short Form (MSHQ-SF) admnistration Higher scores mean better sexual and ejaculatory function

Measure: Sexual and Ejaculatory Function

Time: Enrollment

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Primary Outcomes

Description: Generalised anxiety disorder score (GAD-7) scale. Score 0-21, with a higher score associated with greater anxiety symptoms. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. GAD-7 score at baseline will be controlled for.

Measure: Anxiety as measured by generalised anxiety disorder score (GAD-7) scale

Time: Day 14

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Secondary Outcomes

Description: The Patient Health Questionnaire (PHQ-9) is a screening tool for the identification of depressive disorders, which has been validated for use in primary care. Each of the nine items in the questionnaire is based on the DSM diagnostic criteria for clinical depression. The PHQ-9 is scored out of 27 according to severity, where score of 5-9 indicates mild depression, 10-14 moderate, 15-19 moderately severe, and 20 or above severe depression.

Measure: Depression as measured by the patient health questionnaire 9 (PHQ-9)

Time: 14 days and week 12

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Description: The Trauma screening questionnaire (TSQ) is a 10 point scale used to identify symptoms of post traumatic stress disorder (PTSD), with a score between 0 and 10, with a score of 6 or higher scored as positive.

Measure: Trauma as measured by Trauma screening questionnaire (TSQ)

Time: 12 weeks

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Description: Generalised anxiety disorder score (GAD-7) scale. Score 0-21, with a higher score associated with greater anxiety symptoms. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively. GAD-7 score at baseline will be controlled for.

Measure: Anxiety as measured by generalised anxiety disorder score (GAD-7) scale

Time: Week 12

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Other Outcomes

Description: Risk factors for psychological distress from admission with Covid-19 will be collected, these will include, age, gender, ethnicity, length of hospital stay, oxygen requirement, co-morbidites, years of education, smoking status, occupation.

Measure: Risk associated with distress

Time: Baseline analysis

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Description: Framework analysis. Qualitative feedback of patient experience. Semi structured interviews of a subset of patients will be performed to gain further insight into the patient experience. These will be analysed using a framework thematic analysis, to identify themes which will then be used to code the text.

Measure: Qualitative analysis

Time: Baseline

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Primary Outcomes

Description: Quantitative online questionnaire Survey using UniPark

Measure: Interest in digital interventions (attitudes, behavioral intentions, behavioral experiences)

Time: T1 (prior/beginning of rehab/clinic stay); T2 (end of rehab/clinic stay approx. 5 weeks after T1)

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Description: Quantitative online questionnaire Survey using UniPark

Measure: Usability and effectiveness of digital interventions

Time: T1 (prior/beginning of rehab/clinic stay); T2 (end of rehab/clinic stay approx. 5 weeks after T1)

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Description: Quantitative online questionnaire Survey using UniPark

Measure: Stressors and barriers due to Covid-19

Time: T1 (prior/beginning of rehab/clinic stay); T2 (end of rehab/clinic stay approx. 5 weeks after T1)

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Primary Outcomes

Description: Feasibility will be determined by the following measures: Able to recruit >30% of eligible patients approached Complete early EMDR intervention programme in 75% or more of trial participants randomised to intervention. Protocol adherence Assignment of causality of serious events will be assessed by the chief investigator. Events attributable to trial procedures will be reviewed by trial management board, study sponsor and the research ethics committee, in order to determine ongoing feasibility. Outcome measures completed in 75% or more of trial participants

Measure: Feasibility of recruitment, intervention adherence, incidence of treatment related adverse events and trial completion to final assessment timepoints

Time: 12 months

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Secondary Outcomes

Description: The PTSD Checklist-Civilian Version (PCL-C) is a validated, standardised self-reporting questionnaire for PTSD comprising of 17 items that correspond to key PTSD symptoms

Measure: Post-Traumatic stress disorder

Time: 6 months post-hospital discharge

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Description: Hospital Anxiety and Depression Scale (HADS) is a 14-item, self-reported measure with 7-items relating to symptoms of anxiety and 7-items relating to depression

Measure: Anxiety and depression

Time: 6 months

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Description: Montreal Cognitive Assessment (MoCA) is a validated tool, used to detect cogntive impairment

Measure: Cognitive function

Time: 6 months post-hospital discharge

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Description: EQ5D -5L comprises five quality-of-life dimensions; mobility, self-care, usual activities, pain/discomfort andanxiety/depression.

Measure: Health Related Quality of Life

Time: 6 months post-hospital discharge

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Description: WHODAS 2.0 is a generic assessment tool that produces standarised disability levels and profiles

Measure: Health and disability

Time: 6 months post-hospital discharge

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Description: Wrist worn physical activity monitoring

Measure: Physical activity

Time: 6 months post-hospital discharge

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Description: Patient generated subjective global assessment

Measure: Nutritional status

Time: 6 months post-hospital discharge

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Primary Outcomes

Measure: Change of number of days drinking

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Measure: Change of number of days drug use

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Secondary Outcomes

Measure: Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (AUDADIS-5 (AUDADIS-V)

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Measure: Short Inventory of Problems - Alcohol and Drugs (SIP-AD)

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Measure: Drug Abuse Screening Test (DAST-10)

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Measure: Brief Situational Confidence Questionnaire (BSCQ)

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Measure: Craving rating

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Description: Range from 0-100 (no pain to worst pain imaginable)

Measure: Pain rating

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Description: Total score between 0-27, higher scores indicate greater levels of depression

Measure: Patient Health Questionnaire-9 (PHQ-9)

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Description: Total score between 0-21, higher scores indicate greater levels of anxiety

Measure: General Anxiety Disorder-7 (GAD-7)

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Measure: CAIR Pandemic Impact Questionnaire (CAIR-PIQ)

Time: Difference between baseline and post-treatment (8 weeks from baseline)

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Description: Range from 8 to 32, with higher values indicating higher satisfaction

Measure: Client Satisfaction Questionnaire (CSQ)

Time: Post-treatment (8 weeks from baseline)

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Measure: Usage Rating Profile Intervention (URPI)

Time: Post-treatment (8 weeks from baseline)

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Primary Outcomes

Description: I. Primary endpoint is olfactory function assessed using the UPSIT and classified as Anosmia; Mild, moderate, and severe microsomia. assessed at the time COVID-19 diagnosis (+1 week) or at the time of registration for in hospital patients

Measure: UPSIT scores

Time: At time of diagnosis (+1 week ) post COVID 19 diagnosis or at time of recruitment into study

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Secondary Outcomes

Description: I. The changes in olfaction in patients with SARS CoV-2 infection over an initial 12 month period (at day 0, 1 month, 3 month, 6 month, 9 month and 12 month) using the UPSIT.

Measure: UPSIT scores

Time: at day 0, 1 month, 3 month, 6 month, 9 month and 12 month

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Description: Quality of Life using the validated Questionnaire of Olfactory Disorders for English speakers (eQOD)

Measure: eQOD scores

Time: at day 0, 1 month, 3 month, 6 month, 9 month and 12 month

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Description: Quality of Life using the validated SinoNasal Outcome Tool-22 (SNOT-22)

Measure: SNOT 22 scores

Time: at day 0, 1 month, 3 month, 6 month, 9 month and 12 month

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Primary Outcomes

Description: To demonstrate the benefits of a comprehensive family approach (OLAF) on the incidence of PTSD observed in 2 close referents of a patient, 6 months after leaving the intensive care unit, in the context of confinement linked to the SARS pandemic- CoV2.

Measure: incidence of PTSD observed 6 months after patient's discharge from the intensive care unit

Time: Month 6

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Secondary Outcomes

Description: The incidence of PTSD 6 months after patient's death in the intensive care unit

Measure: incidence of PTSD observed 6 months after patient's death in the intensive care unit

Time: Month 6

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Description: The incidence of PTSD 3 months after the death or discharge from the intensive care unit

Measure: PTSD incidence at month 3

Time: Month 3

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Description: The incidence of PTSD 12 months after the death or discharge from the intensive care unit

Measure: PTSD incidence at month 12

Time: Month 12

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Description: The incidence of symptoms of anxiety and / or depression 3 months after death or discharge from the intensive care unit

Measure: Symptoms incidence at month 3

Time: Month 3

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Description: The incidence of symptoms of anxiety and / or depression 6 months after death or discharge from the intensive care unit

Measure: Symptoms incidence at month 6

Time: Month 6

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Description: The incidence of symptoms of anxiety and / or depression 12 months after death or discharge from the intensive care unit

Measure: Symptoms incidence at month 12

Time: Month 12

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Description: The incidence of persistent complicated grief 3 months after death in intensive care

Measure: incidence of persistent complicated grief at month 3

Time: Month 3

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Description: The incidence of persistent complicated grief 6 months after death in intensive care

Measure: incidence of persistent complicated grief at month 6

Time: Month 6

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Description: The incidence of persistent complicated grief 12 months after death in intensive care

Measure: incidence of persistent complicated grief at month 12

Time: Month 12

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Primary Outcomes

Measure: Percentage of Participants with Adverse Events in Part 1

Time: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort)

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Measure: Percentage of Participants with Adverse Events in Part 2

Time: From randomization up to 8 weeks

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Measure: Part 2: Change in suicide risk assessed using the Columbia Suicide Severity Rating Scale (C-SSRS)

Time: From randomization up to 8 weeks

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Secondary Outcomes

Measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1

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Measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1

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Measure: Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Terminal Elimination Phase Half-Life (T1/2) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Area Under the Concentration-Time Curve from Time 0 to 12 hours (AUC(0-12h)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Area Under the Concentration-Time Curve from Time Extrapolated to Infinity (AUC (0-inf)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Apparent Clearance (CL/F) of RO6953958 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Apparent Volume of Distribution (V/F) of RO6953958 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Cumulative Amount of Unchanged Drug Excreted into the Urine (Ae) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Fraction of the Administered Drug Excreted into the Urine (Fe) of RO6953958 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Renal Clearance of the Drug from Urine (CLR) of RO6953958 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Parts 2: Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 and Day 10

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Measure: Parts 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 and Day 10

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Measure: Parts 2: Average Plasma Concentration (Cavg) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Tmax of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 and Day 10

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Measure: Part 2: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: T1/2 of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: CL/F of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: V/F of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: Ae of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: Fe of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: CLR of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: Trough Plasma Concentration (Ctrough) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Accumulation Ratio based on AUC (Rauc) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Accumulation Ratio based on Ctrough (RCtrough) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Primary Outcomes

Description: Investigators will compute the number of phone screens conducted, number of eligibility sessions completed, and number of subjects enrolled to obtain participant enrollment rates.

Measure: Feasibility via recruitment rate

Time: Screening to enrollment (Week 1)

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Description: Investigators will calculate the mean number of sessions attended and the dropout rate, recording reason for drop out, such as participants' desire to withdraw from the NET treatment vs. medical complications of pregnancy or early delivery.

Measure: Feasibility via retention rate (sessions completed/dropout rate)

Time: Week 1 (NET Session 1) to Week 6 (NET Session 6)

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Description: Investigators will calculate the mean number of follow-up questionnaires completed.

Measure: Feasibility via retention rate (completion of follow-up questionnaires)

Time: 1 Week Post-treatment (Post-treatment Evaluation), 1 Month Post-treatment (Post-treatment Evaluation), 1 Month Post-partum (Follow-up Evaluation)

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Description: Investigators will compute mean ratings of satisfaction (adapted Client Satisfaction Questionnaire).

Measure: Acceptability of the NET intervention via participant satisfaction

Time: 1 Week Post-treatment (Post-treatment evaluation)

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Description: Investigators will compute mean ratings of expectancy via feasibility and acceptability questionnaires.

Measure: Acceptability of the NET intervention via participant expectancy

Time: Week 1 (NET Session 1) , Week 2, Week 3, Week 4, Week 5, Week 6 (NET Sessions 6)

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Description: Investigators will compute mean ratings of perceived benefit via post-treatment evaluations.

Measure: Acceptability of the NET intervention via perceived benefit

Time: 1 Week Post-treatment (Post-treatment evaluation), 1 Month Post-treatment (post-treatment evaluation), 1 Month Postpartum (follow-up evaluation)

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Description: Primary outcome will include qualitative feedback regarding aspects of the NET intervention and its acceptability during pregnancy and in preparation for the transition to parenthood via a study-developed qualitative interview.

Measure: Acceptability of the NET intervention via qualitative feedback

Time: Upon study completion (up to 10 months) or upon early withdrawal from intervention

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Description: Investigators will use the Posttraumatic Check List for DSM-5 (PCL-5), a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD.

Measure: Change in Symptoms of PTSD

Time: Week 1 (NET Session 1), 1 Week Post-treatment (Post-treatment evaluation), 1 Month Post-treatment (post-treatment evaluation), 1 Month Postpartum (follow-up evaluation)

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Secondary Outcomes

Description: Investigators will use the Edinburgh Postnatal Depression Scale (EPDS), a 10-item self-report measure for depression screening in the perinatal period.

Measure: Change in Symptoms of Perinatal Depression

Time: Week 1 (NET Session 1), 1 Week Post-treatment (Post-treatment evaluation), 1 Month Post-treatment (post-treatment evaluation), 1 Month Postpartum (follow-up evaluation)

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Primary Outcomes

Description: incidence of taste and smell impairment in critically ill subjects

Measure: taste and smell impairment

Time: up to 3 months

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Primary Outcomes

Description: Daily number of admissions for acute cardio- and neurivascular conditions in France.

Measure: Daily number of admissions for acute cardio- and neurivascular conditions in France.

Time: 1 day

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Secondary Outcomes

Description: Specific mortality rate.

Measure: Specific mortality rate.

Time: 1 day

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Primary Outcomes

Description: Change in neurological symptoms domain of the survey between pre and post COVID 19 in FMD and PD patients.

Measure: Change in neurological symptoms domain of the survey between pre and post COVID 19 in FMD and PD patients.

Time: December 2021

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