Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: An uncontrolled before-and-after study

Background Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients. Methods A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients’ physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality. Result A total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32–0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes. Conclusion Current prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation. Trial registration Dutch Trial Registration, NTR5932.


Introduction
Background 2 Scientific background and explanation of rationale X 3 ,4 Theories used in designing behavioral interventions X 3 ,4

Participants 3
Eligibility criteria for participants, including criteria at different levels in recruitment/sampling plan (e.g., cities, clinics, subjects) X 5 Method of recruitment (e.g., referral, self-selection), including the sampling method if a systematic sampling plan was implemented X 5 Recruitment setting

X 5
Settings and locations where the data were collected X 5,6,7 Interventions 4 Details of the interventions intended for each study condition and how and when they were actually administered, specifically including: X 5,6,7 o Content: what was given? X 5,6,7 o Delivery method: how was the content given? X 5,6,7 o Unit of delivery: how were the subjects grouped during delivery? X 5,6,7 o Deliverer: who delivered the intervention? X 5,6,7 o Setting: where was the intervention delivered? X 5,6,7 o Exposure quantity and duration: how many sessions or episodes or X 5,6,7 events were intended to be delivered? How long were they intended to last? o Time span: how long was it intended to take to deliver the X 5,6,7 intervention to each unit? o Activities to increase compliance or adherence (e.g., incentives)

X 6
Objectives 5 Specific objectives and hypotheses X 4 Outcomes 6 Clearly defined primary and secondary outcome measures X 7 Methods used to collect data and any methods used to enhance the X 7,8 quality of measurements Information on validated instruments such as psychometric and biometric X 6,7,8 properties Sample Size 7 How sample size was determined and, when applicable, explanation of any X 7 interim analyses and stopping rules Assignment 8 Unit of assignment (the unit being assigned to study condition, e.g., Method individual, group, community) Method used to assign units to study conditions, including details of any restriction (e.g., blocking, stratification, minimization) Inclusion of aspects employed to help minimize potential bias induced due to non-randomization (e.g., matching) Blinding 9 Whether or not participants, those administering the interventions, and X 5 (masking) those assessing the outcomes were blinded to study condition assignment; if so, statement regarding how the blinding was accomplished and how it was assessed.
Unit of Analysis 10 Description of the smallest unit that is being analyzed to assess X 6,7,8 intervention effects (e.g., individual, group, or community) If the unit of analysis differs from the unit of assignment, the analytical method used to account for this (e.g., adjusting the standard error estimates by the design effect or using multilevel analysis) Statistical 11 Statistical methods used to compare study groups for primary methods X 7,8 Methods outcome(s), including complex methods of correlated data Statistical methods used for additional analyses, such as a subgroup X 8 analyses and adjusted analysis Methods for imputing missing data, if used X 8 Statistical software or programs used X 8

Participant flow 12
Flow of participants through each stage of the study: enrollment, X 9 assignment, allocation, and intervention exposure, follow-up, analysis (a diagram is strongly recommended) o Enrollment: the numbers of participants screened for eligibility, X 9 found to be eligible or not eligible, declined to be enrolled, and enrolled in the study o Assignment: the numbers of participants assigned to a study X 9 condition o Allocation and intervention exposure: the number of participants X 9 assigned to each study condition and the number of participants who received each intervention o Follow-up: the number of participants who completed the follow-X 9 up or did not complete the follow-up (i.e., lost to follow-up), by study condition o Analysis: the number of participants included in or excluded from X 9 the main analysis, by study condition Description of protocol deviations from study as planned, along with reasons Recruitment 13 Dates defining the periods of recruitment and follow-up X 5 Baseline Data 14 Baseline demographic and clinical characteristics of participants in each X 9,10 study condition Baseline characteristics for each study condition relevant to specific X 9,10 disease prevention research Baseline comparisons of those lost to follow-up and those retained, overall and by study condition Comparison between study population at baseline and target population of interest Baseline 15 Data on study group equivalence at baseline and statistical methods used X 9-11 equivalence to control for baseline differences Numbers 16 Number of participants (denominator) included in each analysis for each X 9,10 analyzed study condition, particularly when the denominators change for different outcomes; statement of the results in absolute numbers when feasible Indication of whether the analysis strategy was "intention to treat" or, if X 8 not, description of how non-compliers were treated in the analyses Outcomes and 17 For each primary and secondary outcome, a summary of results for each X 9-11 estimation estimation study condition, and the estimated effect size and a confidence interval to indicate the precision Inclusion of null and negative findings Inclusion of results from testing pre-specified causal pathways through which the intervention was intended to operate, if any Ancillary 18 Summary of other analyses performed, including subgroup or restricted X 11 analyses analyses, indicating which are pre-specified or exploratory Adverse events 19 Summary of all important adverse events or unintended effects in each X 9 study condition (including summary measures, effect size estimates, and confidence intervals)

Interpretation 20
Interpretation of the results, taking into account study hypotheses, X 12-14 sources of potential bias, imprecision of measures, multiplicative analyses, and other limitations or weaknesses of the study Discussion of results taking into account the mechanism by which the X 12-14 intervention was intended to work (causal pathways) or alternative mechanisms or explanations Discussion of the success of and barriers to implementing the intervention, X 12-14 fidelity of implementation Discussion of research, programmatic, or policy implications X 12-14 Generalizability 21 Generalizability (external validity) of the trial findings, taking into account the study population, the characteristics of the intervention, length of follow-up, incentives, compliance rates, specific sites/settings involved in the study, and other contextual issues Overall 22 General interpretation of the results in the context of current evidence X 12-15 Evidence and current theory