Appendix AMethods

PubMed 1946 to June 1, 2020

Key question 1: CT diagnosis

(“Diverticulitis”[Mesh] OR “Diverticulosis, Colonic”[Mesh] OR diverticulitis [tiab] OR diverticulosis [tiab] OR diverticular [tiab] OR “Abdomen, Acute”[Mesh] OR “acute abdomen” OR ((acute or nonspecific OR non-specific OR emergen*) AND (abdome* OR abdomi*) AND pain) OR peritonitis)

AND

(“Tomography, X-Ray Computed”[Mesh] OR CT scan OR “cat scan” OR tomography OR “low dose CT” OR LDCT OR “Spiral CT”)

Key question 2: Treatment of acute diverticulitis

(“Diverticulitis”[Mesh] OR “Diverticulosis, Colonic”[Mesh] OR diverticulitis [tiab] OR diverticulosis [tiab] OR diverticular [tiab])

AND

(Hospital OR hospitals OR hospitalization OR “Hospitalization”[Mesh] OR Inpatient* OR discharge* OR outpatient OR “Ambulatory Care”[Mesh] OR antibiotic* OR “Anti-Bacterial Agents”[Mesh] OR medication* OR medical OR “Radiology, Interventional”[Mesh] OR interventional radiology)

Key question 3: Interval colonoscopy

(“Diverticulitis”[Mesh] OR “Diverticulosis, Colonic”[Mesh] OR diverticulitis [tiab] OR diverticulosis [tiab] OR diverticular [tiab])

AND

(Colonoscopy OR Colonography OR “Colonography, Computed Tomographic”[Mesh] OR “Colonoscopy”[Mesh] OR ((colon OR colorectal) AND (cancer or carcinoma or neoplasm*) AND screen*) OR ((colon OR colorectal) AND “Early Detection of Cancer”[Mesh]) OR (“Colonic Neoplasms”[Mesh] AND screen*))

Key question 4: Prevention of recurrence

(“Diverticulitis”[Mesh] OR “Diverticulosis, Colonic”[Mesh] OR “Diverticulosis, Small Intestinal” [Supplementary Concept] OR diverticulitis[tiab] OR diverticulosis[tiab] OR diverticular[tiab])

AND

(Recur* OR repet* OR repeat OR attacks OR “Elective Surgical Procedures”[Mesh] OR Mesalazine OR Mesalamine OR “Mesalamine”[Mesh] OR 5-ASA OR “5 ASA” OR Aminosalicylic Acid OR Pentacol OR “Diet Therapy”[Mesh] OR diet OR fiber OR fibre OR rifaximin OR “Probiotics”[Mesh] OR probiotic* OR balsalazide OR VSL#3 OR Lactobacillus casei OR ((surger* OR surgic* OR resect* OR operation OR operate) and elective))

Searches combined with OR

NOT

(“addresses”[pt] or “autobiography”[pt] or “bibliography”[pt] or “biography”[pt] or “case reports”[pt] or “comment”[pt] or “congresses”[pt] or “dictionary”[pt] or “directory”[pt] or “festschrift”[pt] or “government publications”[pt] or “historical article”[pt] or “interview”[pt] or “lectures”[pt] or “legal cases”[pt] or “legislation”[pt] or “news”[pt] or “newspaper article”[pt] or “patient education handout”[pt] or “periodical index”[pt] or “comment on” or (“Animals”[Mesh] NOT “Humans”[Mesh]) OR rats[tw] or cow[tw] or cows[tw] or chicken*[tw] or horse[tw] or horses[tw] or mice[tw] or mouse[tw] or bovine[tw] or sheep or ovine or murinae)

Embase 1947 to June 1, 2020

#30.

(#6 OR #28) AND ([article]/lim OR [article in press]/lim)

#29.

#6 OR #28

#28.

#8 AND #27

#27.

#9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26

#26.

‘elective surgery’/de

#25.

‘lactobacillus casei’/de

#24.

‘balsalazide’/de

#23.

‘probiotic agent’/de

#22.

‘rifaximin’/de

#21.

‘fiber’/de

#20.

‘diet therapy’/de

#19.

‘aminosalicylic acid’/de

#18.

‘mesalazine’/de

#17.

‘colonography’/de

#16.

‘colonoscopy’/de

#15.

‘interventional radiology’/de

#14.

‘drug therapy’/de

#13.

‘antibiotic agent’/de

#12.

‘ambulatory care’/de

#11.

‘outpatient’/de

#10.

‘hospital patient’/de

#9.

‘hospitalization’/de

#8.

#1 OR #2Diverticulitis

#7.

#4 AND #5 AND ([article]/lim OR [article in press]/lim)

#6.

#4 AND #5

#5.

#1 OR #2 OR #3

#4.

‘computer assisted tomography’/de

#3.

‘acute abdomen’/de

#2.

‘diverticulosis’/de

#1.

‘diverticulitis’/de

Cochrane to June 1, 2020

((Diverticulitis OR diverticulosis OR diverticular OR “acute abdomen” OR ((acute or nonspecific OR non-specific OR emergen*) AND (abdome* OR abdomi*) AND pain) OR peritonitis)

AND

(“CT scan” OR “cat scan” OR tomography)) OR (Diverticulitis OR diverticulosis OR diverticular)

CINAHL 1961 to June 1, 2020

((Diverticulitis OR diverticulosis OR diverticular OR “acute abdomen” OR ((acute or nonspecific OR non-specific OR emergen*) AND (abdome* OR abdomi*) AND pain) OR peritonitis) AND (“CT scan” OR “cat scan” OR tomography))

OR

(Diverticulitis OR diverticulosis OR diverticular)

Study Eligibility Criteria for KQ 1 (CT Imaging)

• Population(s):

  • KQ 1 (all): Adults with suspected or known diagnosis of acute colonic diverticulitis

    • Suspected diagnosis for diagnosis of acute diverticulitis
    • Known diagnosis for staging of disease
    • Exclude: Non-colonic diverticulitis (except for KQ 1d)
  • KQ 1d: Adults with acute abdominal pain who receive an abdominal CT
• Intervention:

  • CT (computed tomography) scan

    • With or without IV (intravenous), oral, or rectal contrast
• Comparators:

  • No CT scanning (as an explicit comparator)
  • MRI (magnetic resonance imaging)
  • Ultrasonography
  • Other diagnostic interventions
  • No comparator (single group studies)
• Outcomes:

  • KQ 1a: Diagnostic accuracy (from existing systematic reviews only)

    • Acute diverticulitis vs. other condition
    • Complicated vs. uncomplicated diverticulitis
    • For staging of severity
  • KQ 1b: Clinical outcomes

    • Short-term (≤1 month)

      ▪

      Time to resolution of acute diverticulitis

      ▪

      Length of hospital stay

      ▪

      Conversion to complicated diverticulitis

      ▪

      Diverticulitis-related morbidities (e.g., abscess formation) and mortality

      ▪

      Change in management (treatment decisions)

    • Medium- (>1 to <12 mo) to long-term (≥1 year)

      ▪

      Recurrent diverticulitis

      ▪

      Future episode of complicated diverticulitis

      ▪

      Diverticulitis-related morbidities (e.g., strictures) and mortality

  • KQ 1c: Harms

    • Harms of over-treatment (due to false positive findings; e.g., surgery, stress)
    • Harms of under-treatment (due to false negative findings; e.g., peritonitis, unnecessary surgery for other condition)
  • KQ 1d: Incidental findings

    • Sequelae related to incidental findings (e.g., unnecessary liver biopsy)
• Modifiers/Subgroups of interest

  • Patient characteristics (e.g., prior history of diverticulitis, age)
  • Presentation of illness (e.g., specific signs or symptoms, such as large volume ascites)
  • Other factors (e.g., complicated or uncomplicated diverticulitis, hospital setting)
• Timing

  • Any
• Setting

  • Inpatient, emergency department (or equivalent), outpatient
• Design

  • KQ 1a: For test accuracy:

    • Existing systematic reviews
  • KQ 1b, 1c, 1d: For clinical outcomes and harms:

    • Prospective
    • Retrospective only if unbiased sampling (inclusion criteria based on pre-imaging criteria only)
    • N≥100 receiving CT
    • Publication since 1990

Study Eligibility Criteria for KQ 2 (Treatment of Acute Diverticulitis)

• Population(s):

  • Adults with acute complicated or uncomplicated diverticulitis, whether first or recurrent episode

    • KQ 2a: Intervention = hospitalization: uncomplicated diverticulitis
    • KQ 2b: Intervention = antibiotics: uncomplicated or complicated diverticulitis
    • KQ 2c: Intervention = interventional radiology: complicated diverticulitis (e.g., abscess)
  • Exclude: Complicated diverticulosis, without diverticulitis (e.g., hemorrhagic diverticulosis)
  • Exclude: Symptomatic uncomplicated diverticular disease (SUDD)
  • Exclude: Meckel’s diverticula (unless concurrent acute diverticulitis)
  • Exclude: Non-colonic diverticulitis
• Interventions versus Comparators:

  • Hospitalization versus No hospitalization (for patients not requiring surgery)
  • Antibiotics versus No antibiotics or versus Alternative antibiotic regimen (for any patient)

    • Any class, route, treatment duration, or initiation time, and comparisons among these
    • Use of any antibiotics (e.g., at clinician’s discretion) or specific antibiotics
  • Interventional radiology procedure versus No procedure (conservative management; for patients with complicated diverticulitis for whom no procedure is an option)

    • Any interventional radiology procedure appropriate for the severity and type of complication
    • Exclude: Comparison of intervention radiology procedures or techniques
• Outcomes:

  • Short-term (≤30 days)

    • Resolution of diverticulitis
    • Return to normal bowel function
    • Length of hospital (or intensive care unit) stay
  • Short- and medium-term (<1 year)

    • Interventional radiology procedure for diverticulitis (avoidance) (exclude for comparisons of interventional radiology procedure with conservative management)
  • Medium- to long term (>1 month)

    • Recurrent diverticulitis
    • Opioid misuse
  • Any duration (short-, medium-, or long-term)

    • Conversion to complicated diverticulitis
    • Surgery for diverticulitis (avoidance)

      ▪

      Including colostomy (avoidance)

    • Rehospitalization for diverticulitis or complications
    • Quality of life/Functional outcomes
    • Resource use
    • Missed work, employment, school outcomes, etc.
    • Diverticulitis-related morbidities
    • Mortality, both diverticulitis-related and all-cause
  • All categorical “effectiveness” outcomes include time to outcome
  • Harms, adverse events, side effects of interventions (any time frame)

    • Hospitalization comparison:

      ▪

      Hospital-based infections and other harms

    • Antibiotics comparisons:

      ▪

      Side effects/adverse events attributable to antibiotics

      ▪

      Clostridioides difficile (C diff) infection

      ▪

      Antibiotic resistance

    • Interventional radiology comparisons:

      ▪

      Adverse events related to procedures, including bleeding and catheter infections

      ▪

      Need for second procedures or revisions

• Modifiers/Subgroups of interest:

  • Patient characteristics (e.g., prior history of diverticulitis, age)
  • Presentation or course of illness (e.g., specific symptoms)
  • Other factors (e.g., complicated or uncomplicated diverticulitis, hospital setting)
• Timing:

  • Minimum duration of follow-up = treatment duration (hospitalization, antibiotic use)
• Setting:

  • Inpatient, emergency department (or equivalent), outpatient
• Design:

  • Randomized controlled trials (all subquestions)

    • N≥10/arm
  • Nonrandomized comparative studies

    • Antibiotics (all outcomes) or hospitalization and IR comparisons (short- to medium-term outcomes; <1 year)

      ▪

      Restrict to studies that use modeling or other analytic methods to minimize selection bias (due to inherent differences between people who receive one or the other intervention), or that restrict study eligibility criteria such that comparisons being made are between patients with similar presentations.

    • Long-term outcomes, hospitalization and IR comparisons (long-term outcomes; ≥1 year)

      ▪

      Allow crude comparisons of long-term outcomes under the assumption that characteristics during acute diverticulitis that were associated with treatment decision (e.g., older patients being more likely to be hospitalized) would not have a major impact on long-term outcomes.

    • Hospitalization and antibiotics: N≥30/arm; Interventional radiology N≥10/arm
  • Single group studies

    • Only for adverse events
    • N>100
  • Longitudinal (Exclude: cross-sectional)
  • Prospective or retrospective
  • Publication since 1990
  • Exclude: Case reports (and series of case reports)

Study Eligibility Criteria for KQ 3 (Colonoscopy)

• Population(s)

  • Adults with history of (resolved) acute diverticulitis
  • Exclude: Active diverticulitis
  • Exclude: History of related condition (only), e.g., complicated diverticulosis, SUDD
  • Exclude: Meckel’s diverticula (unless concurrent acute diverticulitis)
  • Exclude: Non-colonic diverticulitis
• Interventions:

  • Elective colonoscopy (full colon)
  • Elective CT colonography
• Comparators:

  • No colon cancer screening
  • Flexible sigmoidoscopy and barium enema
  • Limited colonoscopy (e.g., left-sided)
  • Virtual colonoscopy
  • Stool guaiac testing (etc.)
  • Other colon cancer screens (e.g., DNA tests)
  • Different intervals, Different initial colonoscopy timing after acute episode
  • No comparator
• Outcomes:

  • Colorectal cancer death
  • Colorectal cancer
  • High-risk colonic premalignant lesions

    • Adenoma, high grade dysplasia
    • Adenoma ≥10 mm
    • Adenoma, villous
    • Serrated polyp
  • Tolerance, feasibility, and completion of procedure; technical adequacy
  • Harms, adverse events, and side effects of colonoscopy (e.g. perforation, bleeding)
• Modifiers/Subgroups of interest:

  • Patient characteristics (e.g., age, family history)
  • Course of illness (e.g., prior complicated vs. uncomplicated diverticulitis)
  • Alarm symptoms
  • Other factors (e.g., timing since last episode of acute diverticulitis)
• Timing:

  • Start of colorectal cancer screening after resolution of acute disease
• Setting:

  • Outpatient
• Design:

  • Randomized controlled trials

    • N≥10/arm
  • Nonrandomized comparative studies

    • No restriction based on analytic methods
    • Including comparisons with healthy (non-diverticulitis) people
    • N≥200 (total)
  • Single group studies

    • N≥200 (receiving colonoscopy or CT colonography)
  • Case-control studies

    • Including comparisons with healthy (non-diverticulitis) people
    • N≥100/arm
  • Prospective or retrospective
  • Publication since 1990
  • Exclude: Case reports (and series of case reports)

Study Eligibility Criteria for KQ 4 (Prevention of Recurrence)

• Population(s):

  • Adults with history of (resolved) acute diverticulitis
  • Exclude: Ongoing acute diverticulitis
  • Exclude: History of related condition (only), e.g., complicated diverticulosis, SUDD
  • Exclude: Meckel’s diverticula (unless concurrent acute diverticulitis)
  • Exclude: Non-colonic diverticulitis
• Interventions:

  • Pharmacological treatments

    • Any class, route, regimen, treatment duration, or initiation time
  • Non-pharmacological interventions

    • Any class/type, route/method, regimen, treatment duration, or initiation time
  • Elective surgery

    • Laparoscopic, open, robot-assisted, or any other type of colon surgery conducted as an elective (non-emergent) procedure
  • Exclude: Natural history or undefined/unspecified intervention or undefined/unspecified comparator
• Comparators:

  • Pharmacological and non-pharmacological intervention comparisons:

    • Alternative pharmacologic or non-pharmacologic intervention (or regimen)

      ▪

      Pharmacologic vs. non-pharmacologic intervention

      ▪

      Other class/type

      ▪

      Other intervention within class/type

      ▪

      Same intervention different treatment duration

      ▪

      Same intervention, different initiation time

    • No intervention

      ▪

      Placebo

      ▪

      “Usual care” (needs to be defined)

  • Elective surgery comparisons:

    • No or deferred elective surgery
    • Exclude: Comparisons with other surgical approaches or techniques
  • All:

    • Exclude: Natural history or undefined/unspecified intervention or comparator
• Outcomes:

  • Recurrent diverticulitis
  • Acute complicated diverticulitis
  • Surgery for diverticulitis (avoidance; except for elective surgery comparisons)

    • Including colostomy (avoidance)
  • Hospitalization for diverticulitis or diverticulitis-related complications (e.g., fistula, stricture)
  • Quality of life/Functional outcomes
  • All categorical “effectiveness” outcomes include time to outcome
  • Harms, adverse events, or side effects of interventions (e.g., surgical complications)

    • From single-group studies of elective surgery, only serious, major, or clinically important adverse events/complications
• Modifiers/Subgroups of interest:

  • Patient characteristics (e.g., age)
  • Course of illness (e.g., prior complicated vs. uncomplicated diverticulitis)
  • Other factors (e.g., time since last episode of diverticulitis)
• Timing:

  • No minimum duration of follow-up
  • Hospitalization, unit stay, post-hospitalization
• Setting:

  • Inpatient, emergency department (or equivalent), outpatient
• Design:

  • Randomized controlled trials

    • N≥10/arm
  • Nonrandomized comparative studies

    • Restrict to studies that use modeling or other analytic methods to minimize selection bias (due to inherent differences between people who receive one or the other intervention)
    • N≥30/arm
  • Single group studies

    • Only for adverse events
    • Elective surgery

      ▪

      N≥500

    • Other interventions

      ▪

      N≥100

  • Longitudinal (Exclude: cross-sectional)
  • Prospective or retrospective
  • Publication since 1990
  • Exclude: Case reports (and series of case reports)