Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Ceresoli (2019)

Type of study:

RCT.

Funding and conflicts of interest:

All authors declare that they have no confict of interest.

Inclusion criteria:

• Patients aged 18-65 years with first episode of uncomplicated acute appendicitis.

Exclusion criteria:

• Complicated AA;
• On-going immunodeficiency status;
• Active neoplasm or neoplasm in the last 5 years;
• Assumption of antibiotics in the previous 30 days;
• Pregnancy or delivery in the previous 6 months;
• ASA IV AND V;
• Allergy to the antibiotics established for the study.

N total at baseline:

Conservative: N = 19

Appendectomy: N = 22

Describe intervention (treatment/procedure/test):

Conservative treatment

Describe control (treatment/procedure/test):

Appendectomy

Length of follow-up:

1 year.

Loss-to-follow-up:

None.

Appendectomy rate

I: 3/19 (15.8%)*

C: 22/22 (100%)

*1 patient worsened between the 1^st and second ertapenem administration and was operated with no complications. One worsened between the 2^nd and 3^rd  administration and at operation was found to have complicated appendicitis (perforation), while the 3^rd patient worsened after the third dose of antibiotic.

Long-term negative outcomes within a year (re-intervention due to bowel occlusion or intraperitoneal abscess, bowel occlusion longer than 48 hours, intraperitoneal abscess, incisional hernia or wound dehiscence for surgical arm; recurrence of AA in the antibiotic arm).

I: 1/16 (6.2%)**

C: 5/22 (22.7%)

**1 patient experienced relapse of acute appendicitis at 30 days from the third dose of ertapenem: according to the protocol, he underwent surgery and an uneventful laparoscopic appendectomy was performed; no complications were observed. No further events or complications were observed at 1-year follow-up.

Length of hospital stay, mean (SD)

I: 4.1 (2.8)

C: 3.5 (1.3)

Length of work absence

I: 8.5 (7.9)

C: 11.4 (5.3)

Author’s conclusion:

In conclusion, the dogmatic indication to surgery in case of suspected acute appendicitis allowed saving many lives in pre-antibiotic era. However, this approach has decreased the stimulus to investigate the role of the vermiform appendix, to understand the primium movens of acute inflammation of the appendix, to reach a broad agreement on the diagnosis and on the diagnostic tools, to establish a common histopathological classification and to find a worldwide accepted definition of uncomplicated and complicated acute appendicitis. Unfortunately, the present study does not add further evidences on this intricated topic; however, it demonstrates the great difficulty in providing evidence-based answers to questions directly arising from daily surgical practice.

CODA collaborative (2020)

Type of study:

RCT.

Funding and conflicts of interest:

The CODA trial was funded by the Patient-Centered Outcomes Research Institute.

The CODA Collaborative writing committee assumes responsibility for the content of this article. The views presented in this work are solely the responsibility of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute, its board of governors, or its methodology committee. Supported by a Patient-Centered Outcomes Research Institute Award (1409-240099). Dr. Evans reports receiving advisory board fees from Tetraphase Pharmaceuticals; Dr. Moran, receiving grant support from Allergan, ContraFect, and Nabriva; Dr. Park, receiving grant support from Bristol Myers Squibb and Atox Bio; and Dr. Winchell, receiving consulting fees from Stryker. No other potential conflict of interest relevant to this article was reported.

Inclusion criteria:

• Consecutive English- or Spanish-speaking adults (≥18 years of age) in emergency departments who had appendicitis that had been confirmed on imaging were approached by research coordinators.

Exclusion criteria:

• Patients were excluded from the trial if they had septic shock, diffuse peritonitis, recurrent appendicitis, evidence of severe phlegmon on imaging (if the surgeon determined that a more extensive operation, such as ileocolectomy, was likely to be performed), walled-off abscess, free air or more than minimal free fluid, or evidence suggestive of neoplasm.

N total at baseline:

Conservative: N = 776

Appendectomy: N = 776

Describe intervention (treatment/procedure/test):

Conservative treatment.

Describe control (treatment/procedure/test):

Appendectomy.

Length of follow-up:

90 days.

Loss-to-follow-up:

I: N = 96

C: N = 114

Appendectomy rate 90 days FU

I: 196/676 (29.0%)

C: 656/656 (100%)

EQ-5D score

I: 0.92 (0.13)

C: 0.91 (0.13)

Complications*

I: 27/676 (4.0%)

C: 20/656 (3.0%)

*Complications antibiotic group:

- 1 severe antibiotic reaction

- 4 unplanned admits to ICU

- 1 acute renal failure requiring dialysis

- 1 pulmonary embolism requiring therapy

- 1 septic shock requiring pressors

- 19 hospitalizations other than for treatment of appendicitis.

Complications surgery group:

- 1 bleeding requiring transfusion

- 19 hospitalization other than for treatment of appendicitis.

Days in hospital after index treatment, number of days/number of participants (mean)

I: 421/622 (0.68)

C: 93/609 (0.15)

Long term results at 2 and 3 years follow-up.

The CODA Collaborative (2020) also reported the number of patients who underwent an appendectomy within two and three years after initial conservative treatment. The appendectomy rate within two years after initial conservative treatment of acute, uncomplicated appendicitis was 41/62 (66.1%). The appendectomy rate within three years of initial conservative treatment of acute, uncomplicated appendicitis was 5/9 (55.5%).

Author’s conclusion:

Eriksson (1995)

Type of study:

RCT.

Funding and conflicts of interest:

The authors thank Dr Gunnar Granstrom, Department of Infectious Diseases, Karolinska Institute, Danderyd Hospital, for help in designing the antibiotic treatment and Dr Anders Moberg, Depanment of Pathology, Danderyd Hospital, for pathological evaluation. This work was supported by the Danderyd Hospital, the funds of the Karolinska Institute, Swedish Hoechst AB, Pfizer AB and the Mutual Group Life Insurance Company 'Forenade Liv', Stockholm, Sweden.

Inclusion criteria:

• typical history and clinical signs, positive findings at ultrasonography and either increased WBC and CRP values, or high CRP or WBC levels on two occasions within a 4-h interval.

Exclusion criteria:

• increased abdominal pain and generalized peritonitis, and subjected to surgery (only one patient was affected and subsequent data were discounted).

N total at baseline:

Intervention: N = 20

Control: N = 20

Describe intervention (treatment/procedure/test):

Conservative treatment.

Describe control (treatment/procedure/test):

Appendectomy

Length of follow-up:

30 days.

Loss-to-follow-up:

None.

Appendectomy rate*

I: 7/20 (35%)

C: 20/20 (100%)

*Seven patients given antibiotic treatment were readmitted with recurrent appendicitis (six had phlegmonous appendicitis and one a perforated appendicitis after 15h of pain before hospitalization). Surgery occurred after a mean of 7 (range 3 to 12) months after conservative treatment.

Author’s conclusion:

The study indicates patients' interest in conservative treatment as 40 of 45 agreed to participate in the study despite being informed about the risk for recurrence.

O’Leary (2021)

Type of study:

RCT.

Funding and conflicts of interest:

The authors report no conflicts of interest.

Inclusion criteria:

• Patients aged 16 years and older with a clinical suspicion of acute appendicitis.

Exclusion criteria:

• normal preoperative imaging, normal bloods including white cell count and C-reactive protein, age < 16 years, complicated appendicitis, an episode of right iliac fossa pain in the past 1 year, inflammatory bowel disease, out of hours presentation, failure to consent, previous appendectomy, reduced mental capacity, pregnancy, breast-feeding patients, current or prior malignancy, moving to another country, deemed unsuitable by admitting consultant, significant comorbidities, patients with previous anaphylaxis to penicillin and not fluent in English.

N total at baseline:

Intervention: N = 91

Control: N = 89

Describe intervention (treatment/procedure/test):

Conservative treatment

Describe control (treatment/procedure/test):

Appendectomy

Length of follow-up:

12 months.

Loss-to-follow-up:

None.

Appendectomy rate within 1 year FU

I: 23/91 (25.3%)

C: 89/89 (100%)

Appendectomy rate later than 1 year FU

I: 29*/91 (31.9%)

C: 89/89 (100%)

*Additional 6 patients to the 23 patients with an required appendectomy within 1 year follow-up.

EQ-5D, mean (95% CI)

I: 0.439 (95% CI 0.319 to 0.560)

C: 0,876 (95% CI 0,808 to 0.945

Pain, mean (95% CI) (0-10)

I: 0.3 (95% CI 0.1 to 0.5)

C: 0.1 (95% CI 0.0 to 0.2)

Sickness days

I: 5.3 days

C: 8.9 days

Length of stay

I: 2.8 days

C: 2.3 days

Author’s conclusion:

Patients with acute, uncomplicated appendicitis treated with antibiotics only endure high recurrence rates and an inferior quality of life, when assessed prospectively. Surgery should remain the mainstay of treatment for this commonly encountered acute surgical condition.

Salminen (2015)

Type of study:

RCT.

Funding and conflicts of interest:

The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Salminen reported receiving personal fees for lectures from Merck and Roche. No other disclosures were reported.

The APPAC trial was supported by a government research grant (EVO Foundation) awarded to Turku University Hospital.

Inclusion criteria:

• Patients aged 18 to 60 years admitted to the emergency department with a clinical suspicion of uncomplicated acute appendicitis confirmed by a CT scan were enrolled in the study.

Exclusion criteria:

• Patients with complicated appendicitis, which was defined as the presence of an appendicolith, perforation, abscess, or suspicion of a tumor on the CT scan, were excluded. Other exclusion criteria were age younger than 18 years or older than 60 years, contraindications for CT (eg, pregnancy or lactating, allergy to contrast media or iodine, renal insufficiency with serum creatinine level >150 μmol/L, actively taking metformin), peritonitis, unable to cooperate and provide informed consent, and the presence of serious systemic illness.

N total at baseline:

Intervention: N = 257

Control: N = 273

Describe intervention (treatment/procedure/test):

Conservative treatment

Describe control (treatment/procedure/test):

Appendectomy.

Length of follow-up:

1 year.

Loss-to-follow-up:

I: N = 29

C: N = 57

Appendectomy rate

I: 70/256 (27.3%)

C: 272/273 (99.6%)

Complications*

I: 6/216 (2.8%) (95% CI 1.0 to 6.0)

C: 45/220 (20.5%) (95% 15.3 to 26.4)

*Overall complications, not specified.

Length of hospital stay (primary hospitalization), median (IQR)

I: 3 (3 to 3) days.

C: 3 (2 to 3) days.

Pain at discharge, median (IQR)

I: 2.0 (1 to 2)

C: 3.0 (2 to 4)

Pain at 1 week FU, median (IQR)

I: 1.0 (1 to 1)

C: 2.0 (1 to 3)

Pain at 2 months FU, median (IQR)

I: 1.0 (1 to 1)

C: 1.0 (1 to 1)

Length of sick leave, median (IQR)

I: 7.0 (7 to 12) days.

C: 19.0 (14 to 21) days.

Author’s conclusion:

Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy.Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications.

Salminen (2018)

Type of study:

RCT.

Funding:

This trial was supported by the Mary and Georg C. Ehrnrooth Foundation, a government research grant (EVO Foundation) awarded to Turku University Hospital, and a Turku University research grant.

None of the funding entities had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Conflict of interest disclosures:

All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Dr Salminen reports receipt of personal fees for lectures from Merck, Lilly, and Orion Pharma.

No other disclosures were reported.

Inclusion criteria:

• Signed informed consent;
• Age between 18 and 60 years;
• CT-scan diagnosis of uncomplicated AA.

Exclusion criteria:

• Age <18 years or >60 years;
• Pregnancy or lactating;
• Allergy to contrast media or iodine;
• Renal insufficiency, serum creatinine >150 umol/l;
• Metformine medication;
• Peritonitis;
• Inability to co-operate and give informed consent;
• Serious systemic illness;
• Complicated AA in a CT-scan: Appendicolith, perforation, periappendicular abscess or suspicion of a tumour.

N total at baseline:

Intervention: N = 257

Control: N = 273

Describe intervention (treatment/procedure/test):

Conservative treatment

Describe control (treatment/procedure/test):

Appendectomy.

Length of follow-up:

7 years.

Loss-to-follow-up:

I: N = 30

C: N = 58

Appendectomy rate between one and five years after initial conservative treatment

I: 30/81 (37.0%)

C: 273/273 (100%)

Author’s conclusion

Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late re- currence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an al- ternative to surgery for uncomplicated acute appendicitis.

Sippola (2020)

Type of study:

RCT.

Funding:

This trial was supported by the Mary and Georg C. Ehrnrooth Foundation and a government research grant awarded to Turku University Hospital.

The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Conflict of interest disclosures:

Dr Sippola reported grants from Mary and Georg C. Ehrnrooth Foundation and Turku University Hospital during the conduct of the study. Dr Salminen reported personal fees from Orion Pharma and Merck outside the submitted work. No other disclosures were reported.

Inclusion criteria:

• Signed informed consent
• Age between 18 and 60 years
• CT scan diagnosis of uncomplicated AA.

Exclusion criteria:

• Age < 18 years or > 60 years
• Pregnancy or lactating
• Allergy to contrast media or iodine
• Renal insufficiency, serum creatinine > 150 μmol/l
• Metformine medication
• Peritonitis
• Inability to co-operate and give informed consent
• Serious systemic illness
• Complicated AA in a CT scan: Appendicolith, perforation, periappendicular abscess or
• suspicion of a tumour

N total at baseline:

Intervention: N = 257

Control: N = 273

Describe intervention (treatment/procedure/test):

Conservative treatment

Describe control (treatment/procedure/test):

Appendectomy.

Length of follow-up:

7 years.

Loss-to-follow-up:

I: N = 15

C: N = 1

Appendectomy rate

I: 70/81 (86.4%)

C: 273/273 (100%)

Author’s conclusion

Long-term QOL is similar after appendectomy and antibiotic therapy for treating uncomplicated acute appendicitis. Pa- tients taking antibiotics who later underwent appendectomy were less satisfied than patients with successful antibiotic treatment or appendectomy, underlining the importance of discovering potential parameters predictive of appendicitis recurrence.

Styrud (2006)

Type of study:

RCT.

Funding and conflicts of interest:

This work was supported by research funds of the Swedish Society of Medicine, Karolinska Institutet; the Wallenius Corporation; Aventis Pharma (former Hoecht Marion Roussel). We are indebted to G. Orrebrink and O. Sta˚hlebrandt for their contributions to this study.

Inclusion criteria:

• All patients admitted for suspected acute appendicitis with a CRP level >10 mg/l in whom perforation was not suspected were asked to participate in the study.

Exclusion criteria:

• Excluded were patients with suspicion of perforation of the appendix, those unwilling to participate, patients with a C-reactive protein (CRP) level

N total at baseline:

Intervention: N = 124

Control: N = 128

Describe intervention (treatment/procedure/test):

Conservative treatment.

Describe control (treatment/procedure/test):

Appendectomy.

Length of follow-up:

1 year.

Loss-to-follow-up:

None.

Appendectomy rate

I: 16/128 (12.5%)

C: 124/124 (100%)

Complications

I: 4/128 (3.1%)

C: 17**/124 (17%)

*Complications after surgery.

**Mainly wound infections.

Length of hospital stay

I: 3.0 (1.4) days.

C: 2.6 (1.2) days.

Days of sick leave

I: 5.3 (4.1)

C: 6.0 (4.4)

Time off work
I: 8.0 (8.0)

C: 10.1 (7.6)

Author’s conclusion:

In conclusion, this study shows that acute appendicitis can be treated successfully with antibiotics with a short hospital stay, minimal sick leave, and limited duration of pain. There is a risk of recurrence, which should be compared with the rate of complications after appendectomy.

Vons (2011)

Type of study:

RCT.

Funding and conflicts of interest:

The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. CV, CB, BF, and DF had full access to all data in the study and fi nal responsibility for the decision to submit for publication. All other authors could request examination of any of the data elements.

Funding French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002.

We declare that we have no confl icts of interest.

Inclusion criteria:

• All adults examined in the emergency department and suspected to have an acute appendicitis were assessed for possible inclusion in the study.

Exclusion criteria:

• Patients were excluded if one of the following criteria were present: age less than 18 years (no upper age limit); antibiotic treatment 5 days before; allergy to β-lactam antibiotics; known intolerance to amoxicillin plus clavulanic acid (nausea, vomiting); receiving steroid or anticoagulant treatments; past history of infl ammatory bowel disease; pregnancy or a positive pregnancy test; life expectancy less than 1 year; allergy to iodine or blood creatinine 200 μmol/L or more; or inability to understand information about the protocol or to sign the consent form.

N total at baseline:

Intervention: N = 120

Control: N = 119

Describe intervention (treatment/procedure/test):

Conservative treatment.

Describe control (treatment/procedure/test):

Appendectomy.

Length of follow-up:

1 year.

Loss-to-follow-up:

Appendectomy rate

I: 39/120 (32.5%)

C: 119/119 (100%)

Author’s conclusion:

Cluster/richtlijn: GE-chirurgie; acute appendicitis

Uitgangsvraag/modules: Welke behandeling heeft de voorkeur bij volwassen patiënten met een acute simpele appendicitis?

Database(s): Ovid/Medline, Embase.com

Datum: 22 augustus 2022

Periode: 2000 - heden

Talen: Engels, Nederlands

Literatuurspecialist: Miriam van der Maten

BMI-zoekblokken: voor verschillende opdrachten wordt (deels) gebruik gemaakt van de zoekblokken van BMI-Online https://blocks.bmi-online.nl/ Bij gebruikmaking van een volledig zoekblok zal naar de betreffende link op de website worden verwezen.

Toelichting:

Voor deze vraag is gezocht op de elementen:

• Appendicitis
• Non-operatieve behandeling (bestaande uit conservatieve behandeling met (intraveneuze) antibiotica)
• Appendectomie

Het sleutelartikel van Bom (Population preference for treatment of uncomplicated appendicitis) wordt niet gevonden met de search omdat het niet geïndexeerd is als RCT of SR. Qua zoektermen zou het wel uit de search komen.

Te gebruiken voor richtlijnen tekst:

Nederlands

In de databases Embase.com en Ovid/Medline is op 22 augustus 2022 met relevante zoektermen gezocht naar systematische reviews en RCT over de behandelingsvoorkeur bij volwassenen met acute appendicitis. De literatuurzoekactie leverde 440 unieke treffers op.

Engels

On the 22^nd of August, relevant search terms were used to search for systematic reviews and RCT about the preferred treatment for adults with acute appendicitis in the databases Embase.com and Ovid/Medline. The search resulted in 440 unique hits.

EMBASE

OVID/MEDLINE

Ontdubbeld

SRs

169

166

191

RCT

199

223

249

Totaal

368

389

440

No.

Query

Results

#17

#15 OR #16

368

#16

#12 AND #14 NOT #15 = RCT

199

#15

#12 AND #13 = SR

169

#14

'randomized controlled trial'/exp OR random*:ti,ab OR (((pragmatic OR practical) NEAR/1 'clinical trial*'):ti,ab) OR ((('non inferiority' OR noninferiority OR superiority OR equivalence) NEAR/3 trial*):ti,ab) OR rct:ti,ab,kw

1947413

#13

'meta analysis'/exp OR 'meta analysis (topic)'/exp OR metaanaly*:ti,ab OR 'meta analy*':ti,ab OR metanaly*:ti,ab OR 'systematic review'/de OR 'cochrane database of systematic reviews'/jt OR prisma:ti,ab OR prospero:ti,ab OR (((systemati* OR scoping OR umbrella OR 'structured literature') NEAR/3 (review* OR overview*)):ti,ab) OR ((systemic* NEAR/1 review*):ti,ab) OR (((systemati* OR literature OR database* OR 'data base*') NEAR/10 search*):ti,ab) OR (((structured OR comprehensive* OR systemic*) NEAR/3 search*):ti,ab) OR (((literature NEAR/3 review*):ti,ab) AND (search*:ti,ab OR database*:ti,ab OR 'data base*':ti,ab)) OR (('data extraction':ti,ab OR 'data source*':ti,ab) AND 'study selection':ti,ab) OR ('search strategy':ti,ab AND 'selection criteria':ti,ab) OR ('data source*':ti,ab AND 'data synthesis':ti,ab) OR medline:ab OR pubmed:ab OR embase:ab OR cochrane:ab OR (((critical OR rapid) NEAR/2 (review* OR overview* OR synthes*)):ti) OR ((((critical* OR rapid*) NEAR/3 (review* OR overview* OR synthes*)):ab) AND (search*:ab OR database*:ab OR 'data base*':ab)) OR metasynthes*:ti,ab OR 'meta synthes*':ti,ab

733409

#12

#9 AND #10 AND #11 AND ([english]/lim OR [dutch]/lim) AND [2000-2022]/py NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) NOT (('animal experiment'/exp OR 'animal model'/exp OR 'nonhuman'/exp) NOT 'human'/exp)

1921

#11

'appendectomy'/exp/mj OR 'laparoscopy'/exp/mj OR appendectom*:ti,ab,kw OR 'surgery'/exp/mj OR 'surgery'/lnk OR surgical:ti,ab,kw OR surger*:ti,ab,kw OR operation*:ti,ab,kw OR operative:ti,ab,kw

5876084

#10

'conservative treatment'/exp/mj OR conservative:ti,ab,kw OR noninvasive:ti,ab,kw OR 'non invasive':ti,ab,kw OR nonsurg*:ti,ab,kw OR 'non surg*':ti,ab,kw OR nonoperati*:ti,ab,kw OR 'non operati*':ti,ab,kw OR 'drug therapy'/exp/mj OR 'intravenous drug administration'/exp/mj OR intravenous:ti,ab,kw OR ((drug NEAR/2 (treat* OR therap*)):ti,ab,kw) OR 'antiinfective agent'/exp/mj OR antibacterial*:ti,ab,kw OR ((anti NEAR/1 bacterial*):ti,ab,kw) OR antibiotic*:ti,ab,kw

4063348

#9

'appendicitis'/exp/mj OR appendicit*:ti,ab,kw

30103

#

Searches

Results

11

9 or 10

389

10

(6 and 8) not 9 = RCT

223

9

6 and 7 = SR

166

8

exp randomized controlled trial/ or randomized controlled trials as topic/ or random*.ti,ab. or rct?.ti,ab. or ((pragmatic or practical) adj "clinical trial*").ti,ab,kf. or ((non-inferiority or noninferiority or superiority or equivalence) adj3 trial*).ti,ab,kf.

1538779

7

meta-analysis/ or meta-analysis as topic/ or (metaanaly* or meta-analy* or metanaly*).ti,ab,kf. or systematic review/ or cochrane.jw. or (prisma or prospero).ti,ab,kf. or ((systemati* or scoping or umbrella or "structured literature") adj3 (review* or overview*)).ti,ab,kf. or (systemic* adj1 review*).ti,ab,kf. or ((systemati* or literature or database* or data-base*) adj10 search*).ti,ab,kf. or ((structured or comprehensive* or systemic*) adj3 search*).ti,ab,kf. or ((literature adj3 review*) and (search* or database* or data-base*)).ti,ab,kf. or (("data extraction" or "data source*") and "study selection").ti,ab,kf. or ("search strategy" and "selection criteria").ti,ab,kf. or ("data source*" and "data synthesis").ti,ab,kf. or (medline or pubmed or embase or cochrane).ab. or ((critical or rapid) adj2 (review* or overview* or synthes*)).ti. or (((critical* or rapid*) adj3 (review* or overview* or synthes*)) and (search* or database* or data-base*)).ab. or (metasynthes* or meta-synthes*).ti,ab,kf.

612522

6

limit 5 to ((english language or dutch) and yr="2000 -Current")

2074

5

4 not (comment/ or editorial/ or letter/ or ((exp animals/ or exp models, animal/) not humans/))

3275

4

1 and 2 and 3

3481

3

exp appendectomy/ or exp Laparoscopy/ or appendectom*.ti,ab,kf. or exp Surgical Procedures, Operative/ or exp Specialties, Surgical/ or su.fs. or (surgical or surger* or operation* or operative).ti,ab,kf.

5237182

2

exp Conservative Treatment/ or conservative.ti,ab,kf. or noninvasive.ti,ab,kf. or 'non invasive'.ti,ab,kf. or nonsurg*.ti,ab,kf. or 'non surg*'.ti,ab,kf. or nonoperati*.ti,ab,kf. or 'non operati*'.ti,ab,kf. or exp Drug Therapy/ or exp Infusions, Intravenous/ or intravenous.ti,ab,kf. or (drug adj2 (treat* or therap*)).ti,ab,kf. or exp Administration, Intravenous/ or exp Anti-Infective Agents/ or antibacterial*.ti,ab,kf. or (anti adj1 bacterial*).ti,ab,kf. or antibiotic*.ti,ab,kf.

3783876

1

exp Appendicitis/ or appendicit*.ti,ab,kf.

27045

Reference

Reason for exclusion

Ehlers (2016)

De Almeide Leite is a more recent published SR and includes the same studies.

Emile (2022)

De Almeide Leite is a more recent published SR and includes the same studies.

Di Saverio (2014)

De Almeide Leite is a more recent published SR and includes the same studies.

Findlay (2016)

De Almeide Leite is a more recent published SR and includes the same studies.

Fitzmaurice (2012)

Non-randomized study.

Fitzmaurice (2011)

Narrative review.

Harnoss (2017)

De Almeide Leite is a more recent published SR and includes the same studies.

Herrod (2022)

De Almeide Leite is a more recent published SR and includes the same studies.

Köhler (2021)

Narrative review.

Flum (2020)

Already included in SR of De Almeide Leite (2022).

Hansson (2009)

Non-randomized study.

Liu (2011)

De Almeide Leite is a more recent published SR and includes the same studies.

Mason (2012)

De Almeide Leite is a more recent published SR and includes the same studies.

Poprom (2019)

De Almeide Leite is a more recent published SR and includes the same studies.

Rollins (2016)

De Almeide Leite is a more recent published SR and includes the same studies.

Monsell (2022)

Non-randomized study.

O’Leary (2021)

Already included in SR of De Almeide Leite (2022).

Park  (2017)

Wrong comparison.

Sakran (2017)

De Almeide Leite is a more recent published SR and includes the same studies.

Sallinen (2016)

De Almeide Leite is a more recent published SR and includes the same studies.

Schumm (2020)

Wrong comparison.

Sugiura (2020)

Wrong comparison.

Varadhan (2009)

De Almeide Leite is a more recent published SR and includes the same studies.

Varadhan (2012)

De Almeide Leite is a more recent published SR and includes the same studies.

Yang (2019)

De Almeide Leite is a more recent published SR and includes the same studies.

Zagales (2022)

De Almeide Leite is a more recent published SR and includes the same studies.

Salminen (2015)

Already included in SR of De Almeide Leite (2022)

Salminen (2022)

Already included in SR of De Almeide Leite (2022)

Styrud (2006)

Already included in SR of De Almeide Leite (2022)

Talan (2017)

Already included in SR of De Almeide Leite (2022)

Talan (2022)

Wrong comparison.

Thompson (2022)

Wrong comparison.

Vons (2011)

Already included in SR of De Almeide Leite (2022)