Prediction of Long-Term Physical, Mental, and Cognitive Problems Following Critical Illness: Development and External Validation of the PROSPECT Prediction Model*

OBJECTIVES: ICU survivors often suffer from long-lasting physical, mental, and cognitive health problems after hospital discharge. As several interventions that treat or prevent these problems already start during ICU stay, patients at high risk should be identified early. This study aimed to develop a model for early prediction of post-ICU health problems within 48 hours after ICU admission. DESIGN: Prospective cohort study in seven Dutch ICUs. SETTING/PATIENTS: ICU patients older than 16 years and admitted for greater than or equal to 12 hours between July 2016 and March 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes were physical problems (fatigue or ≥ 3 new physical symptoms), mental problems (anxiety, depression, or post-traumatic stress disorder), and cognitive impairment. Patient record data and questionnaire data were collected at ICU admission, and after 3 and 12 months, of 2,476 patients. Several models predicting physical, mental, or cognitive problems and a composite score at 3 and 12 months were developed using variables collected within 48 hours after ICU admission. Based on performance and clinical feasibility, a model, PROSPECT, predicting post-ICU health problems at 3 months was chosen, including the predictors of chronic obstructive pulmonary disease, admission type, expected length of ICU stay greater than or equal to 2 days, and preadmission anxiety and fatigue. Internal validation using bootstrapping on data of the largest hospital (n = 1,244) yielded a C-statistic of 0.73 (95% CI, 0.70–0.76). External validation was performed on data (n = 864) from the other six hospitals with a C-statistic of 0.77 (95% CI, 0.73–0.80). CONCLUSIONS: The developed and externally validated PROSPECT model can be used within 48 hours after ICU admission for identifying patients with an increased risk of post-ICU problems 3 months after ICU admission. Timely preventive interventions starting during ICU admission and follow-up care can prevent or mitigate post-ICU problems in these high-risk patients.


Background and objectives 3a
D;V Explain the medical context (including whether diagnostic or prognostic) and rationale for developing or validating the multivariable prediction model, including references to existing models.
3b D;V Specify the objectives, including whether the study describes the development or validation of the model or both.e-Table S3a.Outline of developed models.

Source
General post-ICU health problems were defined as symptoms in physical, mental, or cognitive domains.e-Table S3b.Legend of displayed model.Each number represents a different subtype of the models.The higher the number, the more variables are added to the model as can be seen in the column on the right.

Reference categories: low education [variable education]; medical Admission [variable
The variables included in the model, depending on the model's subtype as can be seen on the left.The numbers represent the regression coefficients of the variable.
Represents the mean value of the response variable when all predictor variables are equal to zero The performance of each model's subtype is shown here.
of data 4a D;V Describe the study design or source of data (e.g., randomized trial, cohort, or registry data), separately for the development and validation data sets, if applicable.4b D;V Specify the key study dates, including start of accrual; end of accrual; and, if applicable, end of follow-up.10e V Describe any model updating (e.g., recalibration) arising from the validation, if done.Report performance measures (with CIs) for the prediction model.Model-updating 17 V If done, report the results from any model updating (i.e., model specification, model performance).-*Items relevant only to the development of a prediction model are denoted by D, items relating solely to a validation of a prediction model are denoted by V, and items relating to both are denoted D;V.We recommend using the TRIPOD Checklist in conjunction with the TRIPOD Explanation and Elaboration document.

Table S3d .
Model P12 (prediction model for physical problems; 12 months post ICU)

Table S3e .
Model Pc (prediction model for physical problems; 3 + 12 months post ICU combined)

Table S3f .
Model M3 (prediction model for mental problems; 3 months post ICU)

Table S3g .
Model M12 (prediction model for mental problems; 12 months post ICU)

Table S3h .
Model Mc (prediction model for mental problems; 3 + 12 months post ICU combined)

Table S3j .
Model C12 (prediction model for cognitive problems; 12 months post ICU)

Table S3k .
Model Cc (prediction model for cognitive problems; 3 + 12 months post ICU combined)

Table S3l .
Model Gen3 (prediction model for general post-ICU health problems; 3 months post ICU) Checklist individual Strength -fatigue subscale (CIS); Quality of Life (QoL) measured with the EuroQol 5-Dimension 5-Level (EQ5D5L); Hospital Anxiety and Depression Scale (HADS); Acute Physiology and Chronic Health Evaluation (APACHE score), Chronic obstructive pulmonary disease (COPD).Positive score defined by a score of ≥5 on the Clinical Frailty Scale (CFS) ₫ Positive score defined by a score of >37 on the Checklist Individual Strength -fatigue subscale (CIS-8) € Positive score defined by a score of ≥ 8 on the Hospital Anxiety and Depression Scale (HADS) anxiety subscales £ Positive score defined by a score of ≥ 8 on the Hospital Anxiety and Depression Scale (HADS) depression subscales Positive score defined by a score of >37 on the Checklist Individual Strength -fatigue subscale (CIS-8) € Positive score defined by a score of ≥ 8 on the Hospital Anxiety and Depression Scale (HADS) anxiety subscales £ Positive score defined by a score of ≥ 8 on the Hospital Anxiety and Depression Scale (HADS) depression subscales ¥ Positive score defined as cognitive impairment with a score of ≥43 on the abbreviated Cognitive Failure Questionnaire (CFQ-14) Mechanical ventilation within first 24 hours of ICU admission Abbreviation: APACHE, Acute Physiology and Chronic Health Evaluation; ICU, Intensive Care Unit; IQR, Interquartile range; COPD, chronic obstructive pulmonary disease; CPR, cardiopulmonary resuscitation; QoL, quality of life; SD, standard deviation.
¥ Positive score defined as cognitive impairment with a score of ≥43 on the abbreviated Cognitive Failure Questionnaire (CFQ-14) ₭ Mechanical ventilation within first 24 hours of ICU admission Abbreviation: APACHE, Acute Physiology and Chronic Health Evaluation; ICU, Intensive Care Unit; IQR, Interquartile range; COPD, chronic obstructive pulmonary disease; CPR, cardiopulmonary resuscitation; SD, standard deviation.Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; ICU, Intensive Care Unit; IQR, Interquartile range; COPD, chronic obstructive pulmonary disease; CPR, cardiopulmonary resuscitation; SD, standard deviation.