Baseline visit
The baseline visit will take place between 4 to 6 weeks after hospital discharge. Information regarding the study will be given to the patient, and informed consent will be obtained. After that, the patient will be randomized. During this first visit, demographic data, medical history, and ICU and hospitalization variables will be collected from all the included patients, regardless of their randomization arm. All patients will complete a series of questionnaires to evaluate their quality of life and the presence of anxiety, depression, or post-traumatic stress disorder. The presence of pain and its influence on the patients’ lifes will also be evaluated.
Intervention group
The intervention consists of a program that includes early patient care, therapeutic education, and psychological intervention. It will be implemented across three medical visits scheduled as follows:
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Visit 1 Intervention group, 4 to 6 weeks after hospital discharge.
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Visit 2 Intervention group, 8 weeks after hospital discharge.
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Visit 3 Intervention group, 18 weeks after hospital discharge.
Components:
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Interview and physical examination.
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Therapeutic education about the PICS, orally and in writing with specific documents delivered at the end of the visit, i.e., a PICS fact-sheet developed by the investigators and a rehabilitation manual recommended by the Follow-up and Rehabilitation Committee of the Argentine Society of Intensive Care, SATI [
14].
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Therapeutic education about pain (if the patient reports pain) which includes an explanation of pain neurophysiology, the rational use of drugs prescribed by other specialists, information about how to manage daily life activities, and the importance of pre-emptive pain management for proper rehabilitation.
A psychological intervention will be conducted if the following criterium is met: a score higher than 8 on the hospital anxiety and depression (HAD) test depression subscale (
supplement, questionnaire Q1) [
17]. The intervention protocol will consist of 7 weekly sessions lasting one and a half hours each (supplement, Table
1). The intervention in depression is based on Rehm’s model of self-control. Psychological interventions may cause adverse events resulting in worsening of patients’ clinical course (overdose, self-harm, and self-harm attempts). Therefore, the investigators will monitor any related symptom, report it as an adverse event, and refer the patient for treatment by a specialist unit.
Outcome measurements
Demographic data will be collected at baseline visit, including age, gender, body mass index, smoking habits, socioeconomic level, work status, and marital status. Barthel index and medical history will also be recorded, especially psychiatric disorders, chronic pain, opioid usage, and previous ICU admission (Supplement, Table
2).
Data regarding ICU and hospital admission will be also collected: Acute Physiology and Chronic Health disease Classification System (APACHE II) and Sequential Organ Failure Assessment Score (SOFA) severity scores, days under invasive or non-invasive mechanical ventilation, presence of sepsis [
18] (
Supplement Definition, D5), need for tracheostomy, use of vasoactive drugs, acute kidney injury (
Supplement Definition, D6) and need for renal replacement therapy, stress hyperglycaemia and hypoglycaemia (
Supplement Definition, D6, D7), corticoid use, use of neuromuscular blocking agents, days under sedation, ICU acquired weakness, delirium presence, maximum value of ferritin, d-dimer and C reactive protein, and ICU and hospital length of stay. The Mini-Mental State Exam (MMSE) test, which is a widely used test of cognitive function among the elderly that assesses orientation, attention, memory, language, and visual-spatial skills, will be evaluated before answering the questionnaires [
19].
The impact of the intervention program on health-related quality of life reported by the patient will be assessed through the European quality of life 5 dimensions/5 levels (
supplement, questionnaire Q2) [
20]. The questionnaire assesses the quality of life of study participants according to 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each scored according to a scale of 1 (no problems) to 5 (extreme problems) and generating a 5-digit code corresponding to the quality of life. The visual analog scale of the same test will also be assessed (from 0—worst imaginable health—to 100—best imaginable health). The questionnaire provides a simple descriptive profile of a respondent’s health status. Quality of life will be assessed at Baseline Visit and at 3 and 6 months after discharge.
Pain (presence and intensity) will be assessed by the Brief Pain Inventory (BPI) questionnaire (
supplement, questionnaire Q3) [
21] at the baseline visit and at 3 and 6 months after discharge. This questionnaire is a multidimensional questionnaire that evaluates pain intensity in the last 24 hours (worst, lowest, average) and current (right now). It also assesses the impact of pain on daily activities (general activity, encouragement, work, social interaction, sleep, enjoyment of life and the ability to walk). The questions are rated on a scale from 0 to 10, with 10 being the worst possible value. Subsequently, the average intensity score (BPI intensity score) and average interference score (BPI interference score) is calculated. Following IMMPACT recommendations, a clinically significant pain will be recorded if the mean intensity score (BPI intensity score) is greater than or equal to 3 [
22].
If BPI is positive for pain, pain catastrophizing will be assessed by the Pain Catastrophizing Scale (PCS) (
supplement, questionnaire Q4) [
23] and patients will also complete the
Douleur Neuropathique en 4 Questions (DN4) (
supplement, questionnaire Q5) to screen for neuropathic pain [
24]. The PCS consists of 13 questions that explore the frequency of thoughts and feelings that the interviewees have in the presence of current or anticipated pain, which are grouped into three scoring subscales (magnification, rumination and defencelessness). Each question is rated on a 5-point scale (0: not at all; 4: all the time). The maximum total score is 52 points. A score greater or equal than 30 will be considered as a clinically relevant level of catastrophizing.
The impact of the intervention program on the incidence of anxiety or depression will be assessed by the Hospital Anxiety and Depression test (HAD) (
supplement, questionnaire Q1) [
17], consisting of 14 questions, with two subscales, one for anxiety and the other for depression, with seven items each and a maximum score of 21 for each subscale. The cut-off points are as follows: 0 to 7 imply the absence of clinically relevant anxiety and depression, 8 to 10 imply de presence of symptoms that require consideration, and 11 to 21 it report the presence of relevant symptoms, with a very probable diagnosis of anxiety or depression. According to Bjelland’s review, cut-off points equal or greater that 8 will be used as abnormal anxiety or depression’s values. This test will be performed at the baseline visit and at 3 and 6 months [
25].
Finally, the incidence of post-traumatic stress disorder (PTSD) [
26] will be evaluated with the post-traumatic stress disorder checklist questionnaire (PCL-5) [
27]. It contains 20 questions that correspond to the DSM-V criteria. Participants will rate their symptoms on a scale of 0 (not at all), 1 (slightly), 2 (moderately), 3 (quite) to 4 (extremely), with a score ranging from 0 to 80. The overall severity of the symptoms can be assessed adding up the scores of each question (interval 0–80). The severity of each symptom can also be evaluated adding up the scores of the questions. DSM-5 symptom cluster severity scores can be obtained by adding up the scores for the items within a given cluster, i.e., cluster B (items 1–5), cluster C (items 6–7), cluster D (items 8–14), and cluster E (items 15–20). A provisional PTSD diagnosis can be made by treating each item rated 2 (“moderately”) or higher as a symptom endorsed, then following the DSM-5 diagnostic rule which requires at least: 1 B item (questions 1–5), 1 C item (questions 6–7), 2 D items (questions 8–14), and 2 E items (questions 15–20) (
supplement, questionnaire Q6).
For this analysis, questionnaire licensing was obtained. The validated version in Spanish was used for each of them, except for PCL-5 which, being a new questionnaire, is not yet validated in Spanish, but it has the advantage of screening PTSD according to the DSM-V criteria. The questionnaires are shown in the
supplement.