Abstract
Background
During the Coronavirus disease 2019 (COVID-19) pandemic, a protocol was adopted by our department on antibiotics treatment for Acute Uncomplicated Appendicitis (AUA). Our study aimed to determine the feasibility and safety of non-operative treatment (NOT), compared to upfront laparoscopic appendectomy (LA), for AUA in children during the pandemic.
Method
Our prospective comparative study was conducted from May 1, 2020 to January 31, 2021. Patient selection criteria included: age ≥5 years, abdominal pain duration ≤48 h, ultrasound (US)/Computered Tomography scan confirmation of AUA, US appendiceal diameter 6–11 mm with no features of perforation/abscess collection and no faecolith. For NOT patients, intravenous antibiotics were administered for 24–48 h followed by oral for 10-day course. Comparison was performed between patients whose parents preferred NOT to those who opted for up-front appendectomy. Primary outcomes were NOT success at index admission, early and late NOT failure rates till 27 months. Secondary outcomes were differences in complication rate, hospital length of stay (LOS) and cost between groups.
Results
77 patients were recruited: 43 (55.8%) underwent NOT while 34 (44.2%) patients opted for LA. Success of NOT at index admission was 90.7% (39/43). Overall, NOT failure rate at 27 months’ follow-up was 37.2% (16/43). Of the NOT failures, 1 appendix was normal on histology while only 1 was perforated. There were no significant differences in secondary outcomes between both groups except for LOS of late NOT failure. Cost for upfront LA was nearly thrice that of NOT.
Conclusion
Our stringent COVID protocol together with shared decision-making with parents is a safe and feasible treatment option during a crisis situation.
Level of Evidence
Treatment study, Level II.
Keywords: Antibiotics treatment, Uncomplicated appendicitis, Paediatrics, Patient choice design
1. Introduction
In January 2020, Singapore reported its first case of Coronavirus disease 2019 (COVID-19) infection. By March 2020, the World Health Organisation had declared COVID-19 a global pandemic. The disruption caused by the pandemic was manifold. Countries worldwide were faced with a sudden shortage of personal protective equipment and suitable healthcare facilities to house infected cases. Healthcare workers were being redeployed to COVID-19 specific roles. Globally, healthcare institutions were forced to shift their overall healthcare strategy in this unascertained situation. Non-essential operations were cancelled at our institution from March 2020, a scenario not dissimilar from the rest of the world [1,2].
Nonetheless, patients with emergency surgical conditions continue to present to hospitals. Acute appendicitis is one of the most common causes of abdominal pain, and is the leading cause of a surgical emergency among children [3]. In our institution alone, an average of 176 cases of appendicitis are reported annually.
The pandemic also raised additional concerns. Early reports cautioned regarding post-operative pulmonary complications resulting in high mortality in COVID-19 positive patients undergoing surgery [4]. Additionally, international and local guidelines made recommendations to avoid aerosol generating procedures such as laparoscopy to reduce the risk of spreading COVID-19 infection [5,6].
Prior to the pandemic, several studies had suggested that antibiotic treatment for acute uncomplicated appendicitis (AUA) in children is a safe and feasible alternative to surgery [[7], [8], [9], [10]]. We have always treated acute appendicitis in our institution with surgery by default, with majority of appendectomies conducted laparoscopically. Now faced with the challenge of safely deferring surgery in acute appendicitis, our institution adopted a non-operative treatment (NOT) approach as an alternative to surgery for a select groups of patients with AUA.
Under this protocol, patients with confirmed radiological findings of acute appendicitis were first assessed for their suitability of conservative management according to strict inclusion and exclusion criteria. The eventual decision for NOT versus surgery was made after taking in parental preference, incorporating patient/parent choice into the study design.
In the recent years, published literature has demonstrated the short-term efficacy and safety of conservatively managed AUA during the COVID-19 pandemic [11]. Yet, the use of antibiotics to treat AUA remains a point of contention among many, largely due to concerns over the risk of recurrence [12]. The objective of our study is to evaluate the short and long-term outcomes of NOT of AUA in children that primarily stemmed from adopting a more conservative management approach in response to the pandemic.
2. Methods
2.1. Study design and population
This was a prospective, comparative cohort study conducted with Institutional Review Board ethics approval (CIRB 2019–2040). The study enrolled eligible paediatric patients who were admitted to our hospital from 1 May 2020 to 31 January 31 2021 with AUA. During this 9-month period, all patients who required admission to our hospital were tested for COVID-19 infection by Antigen Rapid Test (ART)/Polymerase Chain Reaction (PCR) as per our institutional guidelines.
Patients were eligible for NOT of AUA upon meeting the following inclusion criteria: ≤48 h of abdominal pain, age 5 years and above to 16 years, appendiceal diameter of 6–11 mm as seen on Ultrasound (US) or Computered Tomography (CT) scan and the absence of radiological features of free pus, phlegmon, appendiceal perforation and faecolith.
Exclusion criteria for NOT included patients with generalized peritonitis on clinical examination as well as patients with a significant medical history or concurrent medical condition that may potentially place them at a higher risk for complications should NOT be offered.
Parents of eligible patients were counselled regarding both treatment options - upfront surgery versus non-operative treatment with antibiotics alone. The information provided included risk of failure of NOT, procedural details regarding of laparoscopic appendectomy under general anaesthesia, and possible post-operative complications. A joint decision on the choice of treatment were then made by both parent and patient, as well as the attending surgeon.
We collected patients’ data relating to demographics (age, gender, race), clinical symptoms on admission (abdominal pain duration, anorexia, fever, nausea/vomiting, migration of pain, constant pain), clinical signs on physical examination (localized right iliac fossa tenderness, generalized tenderness, generalized guarding, pain on percussion/hopping/coughing), laboratory tests of inflammatory markers (white blood cell (WBC) counts, neutrophil percentage, C-reactive protein (CRP) levels), radiological findings (maximum appendiceal diameter on US or CT scan), intraoperative findings at appendectomy (presence of free pus, phlegmon, perforation), and histopathology of the resected appendix specimen where applicable (presence of faecolith, perforation).
2.2. Non-operative treatment (NOT) group
For patients managed with NOT, initial intravenous (IV) antibiotics, Amoxicillin/Clavulanic acid or a combination of Ceftriaxone and Metronidazole were administered for a minimum of 24 h. The dosages used were as follows: Amoxicillin/Clavulanic acid 40 mg/kg 8 hourly, Ceftriaxone 50 mg/kg 12 hourly and Metronidazole 7.5 mg/kg 8 hourly. Patients whose clinical condition improved after receiving 24 h of IV antibiotics were discharged home with a course of oral antibiotics (Amoxicillin/Clavulanic acid or Cefalexin and Metronidazole) for 10 days. Those that were deemed clinically stable but did not show improvement were treated with an additional 24 h of IV antibiotics before being assessed again. Regular diet was allowed only after an initial 12-h period of clear liquid diet. On discharge, all patients were given a ‘diary card’ to track their home recovery. Parents were also counselled regarding worrisome symptoms to look out for, and when they should be prompted to return to hospital for review.
All patients were under active surveillance for 1-year post-discharge as per the stipulated follow-up duration of the NOT protocol. A clinic review by a surgeon was conducted at the 2-week mark after discharge. Telephone follow-ups were conducted at 3–7 days, 3 months and 1 year after discharge from hospital by a trained Advanced Nurse Practitioners (APN). A set of open-ended questions were used to screen for symptoms suggestive of a recurrence. The APN would make 3 attempts to get in touch with the patient's parents at each follow-up time-point before deeming the patient ‘lost to follow-up’. After one year of active surveillance, we continued to track the patients for re-admissions for recurrent appendicitis in our Electronic Medical Records system.
Failure of NOT during the index admission was defined as clinical deterioration (e.g., increasing abdominal pain, new onset fever), or the lack of clinical improvement (e.g., persistent fever and pain, unable to advance diet) after 48 h of antibiotics administration. Patients who experienced NOT failure were offered laparoscopic appendectomy as per our department practice.
Patients who were successfully treated by NOT during the index admission but were subsequently re-admitted with abdominal pain or fever were re-evaluated for the possibility of recurrent appendicitis as per usual clinical practice in our institution. All patients who were diagnosed with recurrent appendicitis were also offered laparoscopic appendectomy.
2.3. Laparoscopic appendectomy (LA) group
In the instances where parents preferred surgery over NOT, all these cases of AUA underwent appendectomy via laparoscopic approach as per standard departmental practice. IV antibiotics, either Amoxicillin/Clavulanic acid or Ceftriaxone and Metronidazole, were prescribed for 24 h peri-operatively. Patients were deemed fit for discharge if they were able to resume normal diet and had no early post-operative complications. The clinical decision for conversion to open surgery was left to the discretion of the operating surgeon.
2.4. Outcomes
The primary outcomes of our study were success rates of NOT during index admission, as well as the early and late failure rates of NOT. Failure of NOT was defined as a patient having to undergo appendectomy. Early or initial failure was defined as the appendectomy occurring during the index admission. Late failure was defined as appendectomy occurring after the patient has been discharged up until the point of manuscript writing which is 27 months from when the first study case was admitted.
Secondary outcomes included complications of the patient having received either treatment options (NOT or surgery). The length of hospital stays (LOS) and hospital bill for each admission between the groups would also be analysed. In the event that the patient required appendectomy post discharge from index admission, the total LOS would be computed as well.
2.5. Statistical analysis
Continuous variables were reported as mean with standard deviation (±SD) when the dataset is normally distributed or as median with interquartile range (IQR) if the dataset was skewed. Frequencies with percentage were used to describe categorical variables. Statistical comparison between the groups were made using Student's t-test, Mann–Whitney U test or Analysis Of Variance (ANOVA) test for continuous variables. Chi-Squared test were used to compare categorical variables. A p-value of <0.05 was considered as statistically significant. Statistical analysis was performed with IBM SPSS Statistics version 28 software.
3. Results
3.1. Patient demographics
A total of 157 patients with acute appendicitis were admitted to our hospital from 1 May 2020 to 31 January 31 2021. Forty-six of these 157 patients had complicated appendicitis. Of the 111 patients with AUA, 29 were found to have faecolith visualized on either US or CT scan (Fig. 1 ). A further 5 patients were excluded as they did not meet the NOT protocol criteria (Table 1 ).
Fig. 1.
Flow diagram of paediatric patients diagnosed with acute uncomplicated appendicitis (AUA); ∗CA – complicated appendicitis; ∗APP – appendicitis.
Table 1.
Summary of exclusion reason for 5 identified patients.
| Patient | Reason for Exclusion |
|---|---|
| 1 | Patient had a significant medical history (oncology) |
| 2 | Patient presented to the Emergency Department with dengue fever |
| 3 | Patient was 4 years of age at presentation |
| 4 | Patient was conservatively managed despite presenting with an abdominal pain duration of 1 week as the parents declined surgical intervention |
| 5 | Patient's parents insisted for surgery before completing 48 h of antibiotics therapy |
Of the 77 patients eligible for consideration of NOT, 43 (55.8%) of patients and parents decided for NOT, while 34 (44.2%) of them chose appendectomy (Fig. 1). Those in the appendectomy group presented with a longer median abdominal pain duration when compared to the NOT group (48 vs 24 h, p < 0.001). In addition, the mean maximum appendix diameter in the appendectomy group was significantly greater than those in the NOT group (11.0 vs 8.0 mm, p < 0.001). Apart from this, there were no significant differences in patient demographic and clinical characteristics (Table 2 ). Similarly, when the Paediatric Appendicitis Score (PAS) and Children Appendicitis Score (CAS) were tabulated for both treatment groups, there was no statistically significant difference [13,14].
Table 2.
Patient demographics and clinical characteristics.
| Antibiotics (n = 43) | Appendectomy (n = 34) | p-value | |
|---|---|---|---|
| Age (years), Mean (±SD) | 11.6 (±2.9) | 11.5 (±2.8) | 0.78 |
| Gender | |||
| Male, n (%) | 26 (60.5) | 19 (55.9) | 0.82 |
| Race | 0.30 | ||
| Chinese, n (%) | 18 (41.9) | 21 (61.8) | |
| Malay, n (%) | 9 (20.9) | 3 (8.8) | |
| Indian, n (%) | 10 (23.3) | 6 (17.6) | |
| Others, n (%) | 6 (14.0) | 4 (11.8) | |
| Clinical symptoms on admission | |||
| Abdominal pain duration (hours), Mean (±SD) | 26 (16.4) | 43 (24.0) | 0.001 |
| Anorexia, n (%) | 16 (37.2) | 14 (41.2) | 0.81 |
| Fever, n (%) | 17 (39.5) | 11 (32.4) | 0.64 |
| Nausea/Vomiting, n (%) | 29 (67.4) | 25 (73.5) | 0.62 |
| Migration of Pain, n (%) | 16 (37.2) | 16 (47.1) | 0.49 |
| Constant Pain, n (%) | 28 (65.1) | 22 (64.7) | 1.00 |
| Clinical signs on physical examination | |||
| Localised RIF Tenderness, n (%) | 39 (90.7) | 28 (82.4) | 0.32 |
| Generalised Tenderness, n (%) | 2 (4.7) | 3 (8.8) | 0.65 |
| Generalised guarding, n (%) | 9 (20.9) | 8 (23.5) | 0.65 |
| Pain on percussion/hopping/coughing, n (%) | 9 (20.9) | 10 (29.4) | 0.69 |
| Laboratory findings | |||
| WBC (109/L), Mean (±SD) | 14.79 (±3.89) | 15.23 (±5.44) | 0.68 |
| Neutrophils (%), Mean (±SD) | 76.26 (±12.26)a | 75.99 (±18.21) | 0.94 |
| CRP (mg/L), Mean (±SD)b | 22.25 (±25.02) | 25.89 (±27.64) | 0.56 |
| Imaging findings | |||
| Maximum appendix diameter (mm), Mean (±SD) | 8.0 (±1.2) | 11.0 (±2.5) | 0.001 |
| Appendicitis Scoring System | |||
| Paediatric Appendicitis Score (PAS), Mean (±SD) | 5.6 (±1.81) | 5.8 (±1.9) | 0.72 |
| Children Appendicitis Score (CAS), Mean (±SD) | 3.7 (±1.5) | 3.9 (±1.0) | 0.43 |
1 missing Neutrophil level.
5 missing CRP levels (4 patients underwent NOT while 1 patient had appendectomy).
3.2. Primary outcomes
There were 4 patients in the NOT group who experienced early/initial failure, whereas 8 patients experienced late NOT failure within 6 months of the index admission. An additional 4 patients experienced late NOT failure of up to 27 months after the index admission. As such, the initial success rate of NOT at index admission was 90.7% (39/43).
Among the failures at index admission, 3 patients were confirmed to be acute uncomplicated appendicitis and one patient had complicated appendicitis with perforation on histology.
The late recurrence rate of appendicitis at the 1-year mark after presentation was 28% (12 out of 43) whilst the overall failure of NOT at point of manuscript writing (27 months after presentation) was 37.2% (16 out of 43).
We attempted to identify possible risk factors for timing of NOT failure by performing a subgroup analysis of patients who were treated with NOT (Table 3 ). However, neither the mean duration of abdominal pain, the maximum appendiceal diameter nor laboratory inflammatory markers were found to be associated with a higher risk of early or late failure of NOT.
Table 3.
Subgroup analysis of patients who were treated with NOT.
| Successfully Treated (n = 27) | Early failure of NOT (n = 4) | Late failure of NOT (n = 12) | p-value | |
|---|---|---|---|---|
| Abdominal pain duration (hours), Mean (±SD) | 28 (18) | 30 (12) | 23 (14) | 0.63 |
| Maximum appendix diameter (mm), Mean (±SD) | 7.7 (±1.1) | 8.8 (±2.1) | 8.4 (±1.0) | 0.13 |
| Laboratory Findings | ||||
| WBC (109/L), Mean (±SD) | 14.28 (±3.69) | 17.69 (±4.79) | 14.97 (±3.97) | 0.26 |
| Neutrophils (%), Mean (±SD) | 73.39 (±12.69)a | 84.65 (±8.62) | 79.69 (±10.78) | 0.12 |
| CRP (mg/L), Mean (±SD)b | 25.68 (±27.33) | 11.38 (±12.53) | 18.74 (±22.88) | 0.50 |
1 missing Neutrophil level.
5 missing CRP levels (3 patients were successfully treated with antibiotics while 1 patient required appendectomy and 1 patient had late failure of NOT).
All 16 patients who experienced a failure of NOT underwent laparoscopic appendectomy with 3-ports access. Amongst these 16 patients, 14 had an intra-operative and histopathological diagnosis of AUA, whilst only 1 patient had progressed to perforated appendicitis in the initial failure group. For the remaining one patient, the histopathology report revealed a normal, suggesting that a negative appendectomy had been performed. The rated of negative appendectomy in our study was thus 2.3%. Surgery was offered in this patient due to the complaint of persistent abdominal pain. She was admitted 15 months and 17 months after the index admission. At each admission, she had complained of right sided abdominal pain. Inflammatory markers were either normal or mildly elevated. The appendix on US measured maximally 8.0–8.2 mm at the tip with slightly increased echogenicity in the surrounding fat adjacent to the appendiceal tip raising the possibility of early acute appendicitis. As per NOT protocol, the patient was offered surgery at the 15-month readmission. However, this was declined as the patient had upcoming school examinations. Hence, each readmission was treated with a course of antibiotics. The patient underwent elective laparoscopic appendectomy at 18 months after her index admission. Of note, there were no features of chronic appendicitis as well on the histopathology of the resected specimen. Therefore, the overall success of the NOT patient group, excluding one negative appendectomy, was 28/43 = 65.1% at 27 months of follow-up.
Our lost to follow up rate was 3 out of 27 patients (11%) at 3-month follow up and 10 out of 27 patients (37%) at 1-year follow up.
3.3. Secondary outcomes
There were no significant differences in complications between NOT and upfront laparoscopy appendectomy groups (2 vs 2; p = 0.791). Among the 2 patients managed by NOT, one experienced allergic reaction to antibiotics while the other had thrombophlebitis at intravenous plug site. For the 2 patients who underwent laparoscopic appendectomy, one experienced prolonged ileus while the other had post-operative fever.
Common complications such as wound infection, intra-abdominal collection and adhesive intestinal obstruction were not observed in any of our patients. None of the patients managed per NOT protocol experienced any complications during readmission and surgery for acute appendicitis. There were no cases that required conversion from laparoscopic to open appendectomy. There was no mortality after application of NOT. Interestingly, there were no COVID-19 infected patient with AUA within our study period – all had tested negative on a PCR test. In addition, we did not encounter any missed diagnosis of AUA during the same period. Notably, no health care worker was infected with COVID-19 by our patients.
The total hospital length of stay (LOS) for index admission was comparable between NOT and the laparoscopic appendectomy group (2.0 vs 2.5 days; p = 0.10). The hospital LOS was also not statistically longer for patients who had early failure of NOT (Table 4 ).
Table 4.
Subgroup analysis of LOS for patients treated with NOT.
| Successfully Treated (n = 27) | Early failure of Antibiotics (n = 4) | Late failure (n = 12) | Appendectomy (n = 34) | p-value | |
|---|---|---|---|---|---|
| Total Length of Stay (days), Mean ( ± SD) | 2.48 (±0.85) | 3.75 (±0.96) | 3.83 (±1.27) | 2.94 (±1.41) | 0.009 |
The inpatient hospital bill size in each treatment category was analysed (Table 5 ). The average cost per patient was lowest in the NOT group when compared to laparoscopic appendectomy; be it upfront, or for early and late recurrences (p < 0.001). Although the cost for undergoing laparoscopic appendectomy for early or late recurrence was more than that of upfront surgery, the difference was not statistically significant when post hoc analysis was performed. In Singapore, medical care is heavily subsidized by the government for all Singaporean citizens admitted to public health institutions although patients have an option to pay privatised rates for premium rooms. Nonetheless, the number of patient bill analysed was small as we only considered the inpatient bill size for patients admitted under subsidized care.
Table 5.
Cost analysis for fully subsidised patient (C class only).
| Successfully Treated (n = 15) | Early failure of Antibiotics (n = 2) | Late failure (n = 2) | Appendectomy (n = 10) | p-value | |
|---|---|---|---|---|---|
| Total cost | $834.0 (±312.9) | $2823.9 (±1114.9) | $2591.7 (±488.0) | $2230.9 (±736.1) | <0.001 |
4. Discussion
The COVID-19 pandemic made performing surgery more complicated and dangerous for the surgical and anaesthesia teams, as well as for patients who may be harbouring an undiagnosed Covid-19 infection. These concerns provided the motivation to try non-operative treatment of AUA.
Some centres worldwide have taken to extending antibiotic treatment of acute appendicitis to include patients with perforated disease without the need for an interval appendectomy [15]. However, the success rate of such cases has been shown to be lower. In our centre, we have chosen to continue treating cases of perforated appendicitis with surgery throughout the COVID-19 pandemic. This clinical decision explains the strict inclusion and exclusion criteria we have employed in rolling out the NOT protocol. This ensured that only patients with the highest chance of success were enrolled (i.e. those with a shorter duration of symptoms, of the older age group, with a smaller maximum appendiceal diameter and without faecolith) [[16], [17], [18], [19], [20], [21], [22], [23], [24]].
In our study, the complication rates were the same between the group of patients successfully treated with NOT compared with those who failed NOT during the index admission, as well as those who were readmitted for recurrent appendicitis. This can be attributed in part to the close inpatient monitoring for clinical non-improvement or worsening, as well as a robust post-discharge follow-up plan. In addition, parents were also equipped by our medical staff with adequate knowledge on when they should seek medical attention for possible recurrent appendicitis. The authors acknowledge that Singapore is a developed nation of small geographical size. This unique characteristic further supported the feasibility of implementing the NOT protocol safely as our patients typically have quick and easy access to appropriate medical care for both non-emergency and emergency conditions.
Regarding the 37% of NOT patients who were loss to follow-up, with our institution being the largest dedicated paediatric hospital in the country, it would be reasonable to assume that patients who experienced recurrent appendicitis would return to our hospital for medical attention. The converse may also be true – that those who had been lost to follow up are otherwise well.
Appendectomy is currently still considered the gold standard treatment for appendicitis. However, the NOT protocol has proven to be a safe and efficacious alternative in the face of a crisis situation such as the COVID-19 pandemic. This protocol was an interim stopgap measure that provided us some downtime for the recalibration of medical services. It is widely believed that Covid-19 pandemic will not be the last in this lifetime. Scientists have warned that the threat by zoonoses is on the rise. Should there be an infectious outbreak of similar magnitude in the future, we can confidently roll out the NOT protocol once again.
Another significant lesson learnt from our study is the concept of patient/parent-driven care and the importance of shared decision-making. Based on our previous study on parental perception of NOT vs laparoscopic appendectomy, parents who chose NOT were more averse to surgical risks and possible complications of undergoing surgery. This was especially so if the patient in question was of the younger age group. On the other hand, parents who chose upfront appendectomy preferred a definitive treatment with no risk of recurrence [25]. The 55.8% take up rate for NOT in our study concurred with the findings from our previous study. In addition, this rate may also reflect the parents’ general sense of fearfulness towards COVID-19 and the lack of confidence in a healthcare system that was being taxed during the pandemic. It is important to acknowledge patient-centred outcomes that are relevant to the patients and their family. This could include disability days for patients or parents, healthcare costs incurred as well as social-cultural beliefs. Hence, it may well be that if given a choice, patients and parents may continue to choose NOT even when the pandemic is well over.
We do acknowledge several limitations for our study design. Firstly, this was a comparative cohort study based on a stringent selection protocol and parents/surgeons shared decision design model. It had the inherent selection bias related to the role of the surgical team as well as the likely uneven distribution of patients’ characteristics between the 2 arms. Indeed, in our attempt to minimize this concern, all surgeons within the department utilized standardized counselling information. Our findings should therefore be applicable only to acute simple, non-perforated appendicitis. In addition, we only analyzed the costing incurred by the subsidized patients as they formed the majority of our patients load. The costing for private patients may be slightly varied.
5. Conclusion
Non-operative treatment with antibiotic for AUA is a safe alternative to surgery. The experience during the COVID-19 pandemic has increased our confidence in offering NOT for our patients. Embracing principles of patient-driven care may be useful even when not faced in a crisis situation. Moving forwards, the results of this study need to be replicated in a larger trial incorporating a patient/parent choice design. Five-year or even longer outcomes regarding late recurrences of appendicitis should also be evaluated.
Conflict of interest
The authors declare that there are no known conflicts of interest associated with this publication.
Funding
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
References
- 1.Al-Jabir A., Kerwan A., Nicola M., et al. Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 1. Int J Surg. 2020;79:168–179. doi: 10.1016/j.ijsu.2020.05.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Hope C., Reilly J.J., Griffiths G., et al. The impact of COVID-19 on surgical training: a systematic review. Tech Coloproctol. 2021;25:505–520. doi: 10.1007/s10151-020-02404-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Addiss D.G., Shaffer N., Fowler B.S., et al. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol. 1990;132 doi: 10.1093/oxfordjournals.aje.a115734. [DOI] [PubMed] [Google Scholar]
- 4.Bhangu A., Nepogodiev D., Glasbey J.C., et al. Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: an international cohort study. Lancet. 2020;396:27–38. doi: 10.1016/S0140-6736(20)31182-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Brat G.A., Facs M., Hersey S., et al. Protecting surgical teams during the COVID-19 outbreak: a narrative review and clinical considerations 2020. Ann Surg. 2020 doi: 10.1097/SLA.0000000000003926. 10.1097/SLA.0000000000003926. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Pryor A. SAGES recommendations regarding surgical response to Covid-19 crisis. n.d. https://www.sages/org/recommendations-surgical-response-covid-19/(accessed 22 August, 2022).
- 7.Maita S., Andersson B., Svensson J.F., et al. Nonoperative treatment for nonperforated appendicitis in children: a systematic review and meta-analysis. Pediatr Surg Int. 2020;36:261–269. doi: 10.1007/s00383-019-04610-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Podda M., Gerardi C., Cillara N., et al. Antibiotic treatment and appendectomy for uncomplicated acute appendicitis in adults and children: a systematic review and meta-analysis. Ann Surg. 2019;270:1028–1040. doi: 10.1097/SLA.0000000000003225. [DOI] [PubMed] [Google Scholar]
- 9.Georgiou R., Eaton S., Stanton M.P., et al. Efficacy and safety of nonoperative treatment for acute appendicitis: a meta-analysis. An Pediatr. 2017;139 doi: 10.1542/peds.2016-3003. [DOI] [PubMed] [Google Scholar]
- 10.Prechal D., Damirov F., Grilli M., et al. Antibiotic therapy for acute uncomplicated appendicitis: a systematic review and meta-analysis. Int J Colorectal Dis. 2019;34:963–971. doi: 10.1007/s00384-019-03296-0. [DOI] [PubMed] [Google Scholar]
- 11.Emile S.H., Hamid H.K.S., Khan S.M., et al. Rate of application and outcome of non-operative management of acute appendicitis in the setting of COVID-19: systematic review and meta-analysis. J Gastrointest Surg. 2021;25:1905–1915. doi: 10.1007/s11605-021-04988-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Patkova B., Svenningsson A., Almström M., et al. Nonoperative treatment versus appendectomy for acute nonperforated appendicitis in children: five-year follow up of a randomized controlled pilot trial. Ann Surg. 2020;271:1030–1035. doi: 10.1097/SLA.0000000000003646. [DOI] [PubMed] [Google Scholar]
- 13.Samuel M. Pediatric appendicitis score. J Pediatr Surg. 2002;37:877–881. doi: 10.1053/jpsu.2002.32893. [DOI] [PubMed] [Google Scholar]
- 14.Yap T.-L., Chen Y., Low W.W.X., et al. A new 2-step risk-stratification clinical score for suspected appendicitis in children. J Pediatr Surg. 2015;50:2051–2055. doi: 10.1016/j.jpedsurg.2015.08.028. [DOI] [PubMed] [Google Scholar]
- 15.Tanaka Y., Uchida H., Kawashima H., et al. More than one-third of successfully nonoperatively treated patients with complicated appendicitis experienced recurrent appendicitis: is interval appendectomy necessary? J Pediatr Surg. 2016;51:1957–1961. doi: 10.1016/j.jpedsurg.2016.09.017. [DOI] [PubMed] [Google Scholar]
- 16.Bech-Larsen S.J., Lalla M., Thorup J.M. The influence of age, duration of symptoms and duration of operation on outcome after appendicitis in children. Dan Med J. 2013;60:A4678. [PubMed] [Google Scholar]
- 17.Miyauchi H., Okata Y., Hatakeyama T., et al. Analysis of predictive factors for perforated appendicitis in children. Pediatr Int. 2020;62:711–715. doi: 10.1111/ped.14148. [DOI] [PubMed] [Google Scholar]
- 18.Lounis Y., Hugo J., Demarche M., et al. Influence of age on clinical presentation, diagnosis delay and outcome in pre-school children with acute appendicitis. BMC Pediatr. 2020;20 doi: 10.1186/s12887-020-02053-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Almaramhy H.H. Acute appendicitis in young children less than 5 years: review article. Ital J Pediatr. 2017;43:1–9. doi: 10.1186/s13052-017-0335-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Pogorelić Z., Domjanović J., Jukić M., et al. Acute appendicitis in children younger than five years of age: diagnostic challenge for pediatric surgeons. Surg Infect. 2020;21:239–245. doi: 10.1089/sur.2019.175. [DOI] [PubMed] [Google Scholar]
- 21.Carpenter J.L., Orth R.C., Zhang W., et al. Diagnostic performance of us for differentiating perforated from nonperforated pediatric appendicitis: a prospective cohort study. Radiology. 2017;282:835–841. doi: 10.1148/radiol.2016160175. [DOI] [PubMed] [Google Scholar]
- 22.Shindoh J., Niwa H., Kawai K., et al. Predictive factors for negative outcomes in initial non-operative management of suspected appendicitis. J Gastrointest Surg. 2010;14:309–314. doi: 10.1007/s11605-009-1094-1. [DOI] [PubMed] [Google Scholar]
- 23.Ein S.H., Langer J.C., Daneman A. Nonoperative management of pediatric ruptured appendix with inflammatory mass or abscess: presence of an appendicolith predicts recurrent appendicitis. J Pediatr Surg. 2005;40:1612–1615. doi: 10.1016/j.jpedsurg.2005.06.001. [DOI] [PubMed] [Google Scholar]
- 24.Huang L., Yin Y., Yang L., et al. Comparison of antibiotic therapy and appendectomy for acute uncomplicated appendicitis in children a meta-analysis. JAMA Pediatr. 2017;171:426–434. doi: 10.1001/jamapediatrics.2017.0057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Kyaw L., Pereira N.K., Ang C.X., et al. Parental preferences in treatment of acute uncomplicated appendicitis comparing surgery to conservative management with antibiotics and their views on research participation. Eur J Pediatr. 2020;179:735–742. doi: 10.1007/s00431-019-03555-w. [DOI] [PubMed] [Google Scholar]