A randomized control trial comparing the management of suspected acute appendicitis using the proposed algorithm (Fig. 2) compared to the current best practice with the rate of CT utilization as the primary outcome of interest. The study has been registered at ClinicalTrials.gov (NCT 03324165).
Patients were recruited from the Acute Care Surgery Service of Singapore General Hospital (1500-bed general hospital) and Sengkang General Hospital (1000-bed general hospital). The target population consisted of patients between the ages of 16 and 80 who were admitted to the General Surgery department of either hospitals with a diagnosis of suspected appendicitis.
Patients who were pregnant and had generalized peritonitis or a palpable mass on presentation were excluded from the study. Other exclusion criteria were age less than 16 years or more than 80 years old, evidence of delirium or dementia, high risk for surgery (American Society of Anesthesiologists score of 4 and above), and immunocompromised state.
Informed consent was obtained from patients prior to formal recruitment into the study.
Patients were randomized into one of the two management arms at the point of initial assessment by the surgical team.
Intervention arm—Computation of the AS with management as per proposed algorithm (Fig. 2)
Usual care arm—Current best practice (based on the discretion of the attending surgeon)
Patients were randomized into either the intervention or usual care arm in equal numbers (n = 80). The randomization schedule was generated using standard statistical software by a statistician who was not involved in data analysis. Envelopes containing the treatment instructions were marked according to that schedule. Randomization was performed in blocks of six subjects, three for the intervention and three for the control arm, to ensure balanced groups.
The primary outcome of interest was the CT utilization rate between the intervention and usual care arm. Secondary outcomes included the percentage of missed diagnosis, negative appendectomies, length of stay in days, and overall cost of stay in dollars.
The definitions of the above outcome measures were as follows:
CT utilization—The proportion of patients with CT scans performed within each management arm
Missed diagnosis—Patients who were not diagnosed with acute appendicitis during the initial admission but were subsequently readmitted within 2 weeks of discharge due to progression of symptoms, with eventual surgery showing acute appendicitis on histology
Negative appendectomies—Patients who were operated with a pre-operative diagnosis of acute appendicitis with subsequent histology showing no features of acute appendicitis
Length of stay—Duration of total hospitalization (measured in days) from point of admission to discharge during the study follow-up period
Cost of stay—Total cost incurred by the patient in Singapore dollars during admission. This includes ward charges, medications, and costs of diagnostic procedures
Data collection and follow-up
Pre, per-, and post-treatment data were collected prospectively in a standardized data collection sheet. Study data was collected and managed using the REDCap electronic data capture tools hosted at Singapore General Hospital. REDCap (Research Electronic Data Capture) is a secure, Web-based application designed to support data capture for research studies .
Patients who were randomized to the control arm had their AS retrospectively calculated by the study coordinator to allow comparison between the various AS categories.
In patients who underwent CT evaluation, the eventual results were categorized into 1 of the following 4 categories by the attending surgeon.
Acute appendicitis diagnosed on CT scan
No acute appendicitis but alternative diagnosis for symptoms established. These alternative diagnoses include bowel pathology (colitis/enteritits, diverticulitis, colonic malignancy), urologic pathology (urinary tract infections and ureteric calculi), and gynaecologic conditions such as pelvic inflammatory disease, ruptured ovarian cysts, or ovarian torsion
No acute appendicitis without any alternative diagnosis for symptoms established
Equivocal for acute appendicitis
Patients were followed-up in person 2 weeks after discharge. Subsequent follow-up was determined based on clinical indication. Patients lost to follow-up were contacted via the phone to determine if an initial diagnosis of appendicitis had been missed. A search via the National Electronic Health Record (NEHR) database was also performed to identify patients who defaulted but re-presented at another hospital for treatment. The NEHR database captures the admission information of every person who has visited the public health care system in Singapore.
Sample size calculation
Based on our previous publication, 80% of all patients with suspected appendicitis were subjected to CT evaluation . If the algorithm had been implemented on this group of patients, the percentage of CT scans performed could have been reduced to 60%. To determine the specified difference in proportion of CT scan utilization using a one-sided chi-square test assuming 80% power and 5% type I error rate, 160 patients (80 subjects with suspected appendicitis in each study arm) were required after accounting for 10% lost to follow-up.
Study data was analyzed using appropriate summary statistics and statistical tests to address the study objectives. The distribution of baseline demographics and clinical characteristics by study arm was summarized.
The proportion of CT utilization, the primary outcome of interest, was compared between the two study arms using a one-sided chi-square test.
The CT utilization rate, stratified by the AS category, was compared between the two study arms using Fisher’s exact test. As there were relatively few patients with AS of 1, 2, and 3, these were collated into one category (AS 1 to 3) during the above analysis.
Negative appendectomy rate and proportion of missed diagnosis along with a 95% confidence interval were estimated for each study arm using simple asymptotic methods. Median length and cost of stay between the 2 study arms were compared using the Mann-Whitney U test. All statistical analysis was done using R 3.1.1 (R Core Tam 2014, Vienna, Austria), and statistical significance was taken as P value < 0.05. This study was carried out under the approval of the Centralized Institutional Review Board of the Singapore Health Services.