Kathy is founder and Director of ICNARC and works within a team of audit, research, IT and administrative staff. ICNARC’s aim is to facilitate improvements in the organisation and practise of critical care through a broad programme of audit and research. In 2004, Kathy was awarded the Humphry Davy Medal by the Royal College of Anaesthetists as a mark of distinction for her significant contribution to critical care. More recently, Kathy completed a Harkness Fellowship in Health Care Policy in the USA (Nov 2004 to Oct 2005). Kathy is an Honorary Professor in the Department of Public Health and Policy at the London School of Hygiene and Tropical Medicine.

1. www.icnarc.org
Psychological Outcomes
following a nurse-led
Preventive Psychological Intervention
(POPPI) trial
Kathy Rowan
Chief Investigator
The views expressed today are those of the author(s) and not necessarily
those of the NHS, the NIHR or the Department of Health and Social Care.
NIHR HSDR: 12/64/124
NRES Committee South Central - Oxford B Ref: 15/SC/0287
ISRCTN Registry: 53448131
NIHR CRN portfolio ID: 18940

2. POPPI Team
Psychologists Patients
ICNARC
Clinical Trials Unit
Prof Chris Brewin* David Aaronovitch* Alvin Richards-Belle
Dr Dorothy Wade* Nicole Als Prof David Harrison*
Prof John Weinman* Margaret Harvey Dr Sheila Harvey*
Chris Whitman Nick Hudson
Clinicians Economic evaluation Paul Mouncey*
Dr David Howell* Dr Zia Sadique* Prof Kathy Rowan**
Prof Monty Mythen* Prof Richard Grieve* Jerome Wulff
Deborah Smyth*
Process evaluation
(independent)
John Welch* Lydia Emerson
** Chief Investigator
* Co-investigators

3. www.icnarc.org
Setting for POPPI trial
• High level of psychological morbidity post-ICU
- clinically important PTSD symptoms of 25%
• Acute stress and early frightening memories
(hallucinations/delusions/nightmares) in ICU
are risk factors for post-ICU traumatic stress
• CBT techniques effective in reducing these risk
factors in mental health settings -
even when delivered by trained non-experts
• Evidence suggests that addressing risk factors
early, while in ICU, looked promising
• Few NHS ICUs have regular access to
psychologists

4. www.icnarc.org
Hypothesis
• We hypothesised that:
– a preventive, complex psychological intervention
– delivered by ICU-selected, trained nurses
– commenced early
– would reduce development of patient-reported
PTSD symptom severity at six months

5. www.icnarc.org
Intervention
• Early, nurse-led, preventive
complex psychological intervention
• Three elements
– Promotion of a therapeutic ICU environment
and, for the acutely stressed
– Three stress support sessions
– Relaxation & recovery programme

6. www.icnarc.org
Intervention development
• Theoretically and empirically developed,
tested and refined for the critically ill
– drawing on theories/techniques of CBT for psychosis
• Oversight from EPAG (Expert Psychology Advisory Group)
– Prof Daniel Freeman, Prof of Clinical Psychology
– Dr Vaughan Bell, Clinical Psychologist
– Dr Dane Goodsman, Medical Education
– plus psychologists, clinicians and patients from
POPPI Team

7. www.icnarc.org
Promotion of a therapeutic environment
• An online training course for all staff
• Aimed at improving staff-patient
communication and reducing stressors
to create a more healing environment
• Final competency test
• Posters, card and slide-sets –
enabling the whole unit team to promote key
messages and help improve the environment
• Key role of educators and research team for
wider dissemination

8. www.icnarc.org
Stress support sessions for acutely stressed*
• Session one (~30 mins) –
helping patients understand and cope with stress
• Session two (~30 mins) –
managing frightening thoughts from critical care
• Session three (~30 mins)–
creating confidence and hope for a good recovery
• Ideally starting in ICU/completed in one week
by same nurse
*

9. www.icnarc.org
Relaxation and recovery programme
• On tablet between stress support sessions
• On DVD/booklet post-sessions
Relaxation
practice
Restful nature
sounds and
images
Relaxing
music
MeditationMeditation
Patient
Recovery
Stories
Calming
music

10. www.icnarc.org
POPPI nurses
• Three, ICU-selected
• Registered nurse
(at least three years experience)
• Effective communicator
(with patients, families, colleagues)
• Able to work flexibly
• Interested, motivated, organised and able to
manage a busy schedule

11. www.icnarc.org
Training
• Central POPPI nurse training (three-day)
on delivery of stress support sessions with
actors/role-playing
• Experiential learning (one-month) back in ICU
• Competency testing

12. www.icnarc.org
Design
• Multicentre, parallel-group, cluster-RCT with
integrated economic and process evaluations
Controlsites
Baseline InterventionTransition
0 17
Months (Sept 2015-Jan 2017)
Interventionsites

13. www.icnarc.org
Sites
• 24 UK NHS adult, general, critical care units
– 12 intervention/12 control
• Selected on geography, status, size, etc.
in three steps of 8 (4 control/4 intervention)
• Randomised in second month of baseline

14. www.icnarc.org
Eligibility
• Inclusion
– Age 18+ years
– Unit LOS >48 hours
– Level 3 care during first 48 hours
– RASS between +1 and -1
– GCS 15
– English-speaking and able to communicate orally
• Exclusion
– Pre-existing chronic cognitive impairment or PTSD
– Pre-existing psychotic illness
– Receiving end-of-life care
• Able to consent (with approach in ICU)

15. www.icnarc.org
Control sites
Screen
Consent
Six-month follow-up

16. www.icnarc.org
Intervention sites (intervention period)
Screen
Consent
Six-month follow-up
IPAT ≥7
IPAT
IPAT <5IPAT 5-6
Repeat IPAT
(max 3 times)
Stress support sessions
Therapeuticenvironment

17. www.icnarc.org
Six-month follow-up
• Primary outcome
– PTSD symptom severity at six months
• PTSD Symptom Scale – Self Report (PSS-SR) questionnaire
• Validated, 17 questions, range 0-51
• >18 predicts current/future PTSD
• Secondary outcomes
– Days alive/free from sedation to day 30
– Critical care LOS
– PSS-SR >18 at six months
– Depression at six months (HADS)
– Anxiety at six months (HADS)
– Quality of life at six months (EQ-5D-5L)

18. www.icnarc.org
Sample size (power calculation)
• Assumed mean of 10.3 points on PSS-SR
• Treatment effect reduction of 4.2 points
• Minimum of 1,378 patients
(including refusals/lost to follow-up)
• Anticipated 85% power

19. www.icnarc.org
Analysis principles
• Intention to treat
• Pre-specified statistical analysis plan
– Wulff et al. JICS 2018
• P<0.05 (two-sided)
• No adjustment for multiple testing
• No planned interim analysis
• Multiple imputation for missing covariates and
outcomes

20. www.icnarc.org
>26,000 patient admissions
screened during trial period
2,961 potentially eligible patients
2,048 approached for consent
1,458 consented
73% did not meet stable criteria
Of those that met stable criteria,
59% did not meet transient criteria
913 (31%) not approached for
consent (e.g. missed/other reasons)
590 (29%) declined
Results

21. www.icnarc.org
Baseline
Sites Intervention Control
Time period Baseline Intervention Baseline Intervention
Patients N 283 340 284 446
Age, years 59.5 (16.0) 60.4 (15.0) 57.2 (16.2) 57.2 (15.6)
Sex – Male N (%) 168 (59.4) 187 (55.0) 179 (63.0) 268 (60.1)
Quintile of IMD 2015 – N (%)
1 – Least deprived 41 (14.5) 57 (16.9) 57 (20.1) 95 (21.3)
5 – Most deprived 69 (24.4) 58 (17.2) 53 (18.7) 82 (18.4)
Elective surgical – N (%) 17 (6.0) 20 (5.9) 24 (8.5) 37 (8.3)
ICNARC Physiology Score 21.1 (7.0) 21.0 (7.6) 21.2 (7.1) 21.4 (7.2)
APACHE II score 16.9 (6.5) 17.7 (6.4) 16.7 (5.8) 16.9 (6.2)
Last NEWS prior to consent 3.2 (2.2) 2.8 (2.1) 3.1 (2.4) 2.8 (2.4)
STAI-6 at consent
– median (IQR)
43 (33, 57) 43 (30, 55) 43 (30, 53) 43 (33, 50)
HrQoL (thermometer) at consent
– median (IQR)
50 (35, 70) 50 (30, 70) 50 (40, 70) 50 (40, 70)

22. www.icnarc.org Promotion of a therapeutic environment

23. www.icnarc.org
Stress support sessions
• Over 80% received at least two sessions

24. www.icnarc.org
Relaxation & recovery programme
• 77% of patients reported using the tablet
computer application between sessions
• 96% of patients received the DVD and booklet
(after session two)

25. www.icnarc.org
Follow-up response rate
• 79.3% of survivors at six months
• Overall rate and characteristics of responders
consistent between intervention/control and
across periods (baseline/intervention)

26. www.icnarc.org
Approach to analysis
InterventionsitesControlsites

27. www.icnarc.org
Approach to analysis
InterventionsitesControlsites

28. www.icnarc.org
Approach to analysis
InterventionsitesControlsites

29. www.icnarc.org
Approach to analysis
InterventionsitesControlsites
Control sites
Baseline period
Intervention sites
Baseline period
Control sites
Intervention period
Intervention sites
Intervention period
Is the change in intervention sites
different from the change in control sites?
Baseline period Intervention period

30. www.icnarc.org
Primary outcome
Control sites Intervention sites
0
2
4
6
8
10
12
14
Baseline
period
Intervention
period
Baseline
period
Intervention
period

31. www.icnarc.org
Primary outcome
Control sites Intervention sites
0
2
4
6
8
10
12
14
Baseline
period
Intervention
period
Baseline
period
Intervention
period
+0.1

32. www.icnarc.org
Primary outcome
Control sites Intervention sites
0
2
4
6
8
10
12
14
Baseline
period
Intervention
period
Baseline
period
Intervention
period
+0.1 −0.3
Adjusted treatment effect (95% CI):
−0.03 (−2.58 to 2.52)
Similar results from sensitivity analyses

33. www.icnarc.org
• Days alive and free from sedation to day 30
Secondary outcomes
Control sites Intervention sites
0
5
10
15
20
25
30
Baseline
period
Intervention
period
Baseline
period
Intervention
period
Adjusted treatment effect (95% CI):
0.47 (−1.03 to 1.96)

34. www.icnarc.org
• PSS-SR threshold for prediction of current
or future PTSD (>18 points)
Secondary outcomes
Control sites Intervention sites
0
5
10
15
20
25
30
Baseline
period
Intervention
period
Baseline
period
Intervention
period
Adjusted odds ratio (95% CI):
1.32 (0.66 to 2.67)

35. www.icnarc.org
• Depression at six months
Secondary outcomes
Control sites Intervention sites
0
2
4
6
8
Baseline
period
Intervention
period
Baseline
period
Intervention
period
Adjusted treatment effect (95% CI):
−0.22 (−1.40 to 0.95)

36. www.icnarc.org
• Anxiety at six months
Secondary outcomes
Control sites Intervention sites
0
2
4
6
8
Baseline
period
Intervention
period
Baseline
period
Intervention
period
Adjusted treatment effect (95% CI):
−0.24 (−1.50 to 1.01)

37. www.icnarc.org
• Health-related quality of life at six months
Secondary outcomes
Control sites Intervention sites
0.0
0.2
0.4
0.6
0.8
1.0
Baseline
period
Intervention
period
Baseline
period
Intervention
period
Adjusted treatment effect (95% CI):
−0.007 (−0.063 to 0.076)

38. www.icnarc.org
Subgroup analyses
Subgroup
Age (years)
18-47
48-59
60-69
70-99
Gender
Female
Male
Index of Multiple Deprivation
1 (least deprived)
2
3
4
5 (most deprived)
Duration of delirium (days)
0
1-2
>2
STAI-6
20-30
31-43
44-53
54-80
Surgical status
Emergency/urgent
P-value
0.93
0.92
0.08
0.41
0.35
0.76
5 (most deprived)
Duration of delirium (days)
0
1-2
>2
STAI-6
20-30
31-43
44-53
54-80
Surgical status
Emergency/urgent
Elective/scheduled
Non-surgical
Predicted PSS-SR
a
<7
7-9
10-12
13-15
≥16
Site implementation score category
b
1 (Lowest)
2
3 (Highest)
0.41
0.35
0.76
0.08
0.49
Difference in Mean PSS-SR (95% CI)
Favors Intervention Favors Usual care
-15 -10 -5 0 5 10 15

39. www.icnarc.org
Subgroup
Age (years)
18-47
48-59
60-69
70-99
Gender
Female
Male
Index of Multiple Deprivation
1 (least deprived)
2
3
4
5 (most deprived)
Duration of delirium (days)
0
1-2
>2
STAI-6
20-30
31-43
44-53
54-80
Surgical status
Emergency/urgent
Elective/scheduled
P-value
0.93
0.92
0.08
0.41
0.35
0.76
Subgroup analyses
4
5 (most deprived)
Duration of delirium (days)
0
1-2
>2
STAI-6
20-30
31-43
44-53
54-80
Surgical status
Emergency/urgent
Elective/scheduled
Non-surgical
Predicted PSS-SR
a
<7
7-9
10-12
13-15
≥16
Site implementation score category
b
1 (Lowest)
2
3 (Highest)
0.41
0.35
0.76
0.08
0.49
Difference in Mean PSS-SR (95% CI)
Favors Intervention Favors Usual care
-15 -10 -5 0 5 10 15

40. www.icnarc.org
Cost-effectiveness plane: six months
Mean inc. costs =-755
Mean inc. QALY=0.004

41. www.icnarc.org
Summary
• POPPI intervention did not significantly reduce
PTSD symptom severity and no difference in
any secondary outcomes
• No significant variation across subgroups
• Secondary/sensitivity analyses all consistent
with primary analysis (not shown)
• Results indicate that this complex intervention
should not be adopted in its current form and
further exploratory analyses may inform future
developments in this area, given the high rates
of ongoing psychological morbidity seen