Antibiotics versus topical antiseptics for chronic suppurative otitis media
Appendices
Appendix 1. Search strategies
| CENTRAL (CRS Web) | MEDLINE (Ovid) | Embase (Ovid) |
| 1 MESH DESCRIPTOR Otitis Media EXPLODE ALL AND CENTRAL:TARGET1061 | 1 exp Otitis Media/ 2 ("otitis media" or OME).ab,ti. 3 exp Tympanic Membrane Perforation/ 4 exp Tympanic Membrane/ 5 ("ear drum*" or eardrum* or tympanic).ab,ti. 6 4 or 5 7 (perforat* or hole or ruptur*).ab,ti. 8 6 and 7 9 1 or 2 or 3 or 4 or 8 10 exp Suppuration/ n 11 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or moist or wet or mucopurulen* or discomfort or pain* or earach*).ab,ti. 12 10 or 11 13 exp Chronic Disease/ 14 exp Recurrence/ 15 (chronic* or persist* or recurr* or repeat*).ab,ti. 16 13 or 14 or 15 17 9 and 12 and 16 18 ((chronic or persist*) adj3 (ear or ears or aural) adj3 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort)).ab,ti. 19 CSOM.ab,ti. 20 exp Otitis Media, Suppurative/ 21 (earach* adj6 (chronic or persist* or recurr* or repeat*)).ab,ti. 22 17 or 18 or 19 or 20 or 21 | 1 exp otitis media/ 2 ("otitis media" or OME).ab,ti. 3 exp eardrum perforation/ 4 exp eardrum/ 5 ("ear drum*" or eardrum* or tympanic).ab,ti. 6 4 or 5 7 (perforat* or hole or ruptur*).ab,ti. 8 6 and 7 9 1 or 2 or 3 or 8 10 exp suppuration/ 11 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or moist or wet or mucopurulen* or discomfort or pain* or earach*).ab,ti. 12 10 or 11 13 exp chronic disease/ 14 exp recurrent disease/ 15 (chronic* or persist* or recurr* or repeat*).ab,ti. 16 13 or 14 or 15 17 9 and 12 and 16 18 exp suppurative otitis media/ 19 CSOM.ab,ti. 20 ((chronic or persist*) adj3 (ear or ears or aural) adj3 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort or disease*)).ab,ti. 21 (earach* adj3 (chronic or persist* or recurr* or repeat*)).ab,ti. 22 17 or 18 or 19 or 20 or 21 |
| Web of Science (Web of Knowledge) | CINAHL (EBSCO) | Cochrane ENT Register (CRS Web) |
| #1 TOPIC: ("otitis media" or OME) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #2 TOPIC: (("ear drum*" or eardrum* or tympanic) AND (perforat* or hole or ruptur*)) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #3 #2 OR #1 Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #4 TOPIC: ((suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or moist or wet or mucopurulen* or discomfort or pain* or earach*) AND (chronic* or persist* or recurr* or repeat*)) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #5 #4 AND #3 Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #6 TOPIC: (((chronic or persist*) NEAR/3 (ear or ears or aural) NEAR/3 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort))) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #7 TOPIC: ((earach* NEAR/3 (chronic or persist* or recurr* or repeat*))) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #8 #7 OR #6 OR #5 Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years | S21 S17 OR S18 OR S19 OR S20 S20 TX ((chronic or persist*) N3 (ear or ears or aural) N3 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort)) S19 TX (earach* N3 (chronic or persist* or recurr* or repeat*)) S18 TX csom S17 S9 AND S12 AND S16 S16 S13 OR S14 OR S15 S15 TX chronic* or persist* or recurr* or repeat* S14 (MH "Recurrence") S13 (MH "Chronic Disease") S12 S10 OR S11 S11 TX suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or moist or wet or mucopurulen* or discomfort or pain* or earach*) S10 (MH "Suppuration+") S9 S1 OR S2 OR S3 OR S8 S8 S6 AND S7 S7 TX perforat* or hole or ruptur* S6 S4 OR S5 S5 TX "ear drum*" or eardrum* or tympanic S4 (MH "Tympanic Membrane") S3 (MH "Tympanic Membrane Perforation") S2 TX "otitis media" or OME S1 (MH "Otitis Media+") | 1 ("otitis media" or OME):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 2 (("ear drum*" or eardrum* or tympanic)):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 3 (perforat* or hole or ruptur*):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 4 #2 AND #3 AND INREGISTER 5 #4 OR #1 AND INREGISTER 6 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or discomfort or earach* or mucopurulen*):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 7 (pain):AB,TI,TO AND INREGISTER 8 #6 OR #7 AND INREGISTER 9 (chronic* or persist* or recurr* or repeat*):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 10 #5 AND #8 AND #9 AND INREGISTER 11 (csom):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 12 (((chronic* or persist* or recurr* or repeat*) and (ear or ears or aural) and (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort or disease*))):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 13 ((earach* and (chronic or persist* or recurr* or repeat*))):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 14 #10 OR #11 OR #12 OR #13 AND INREGISTER |
| ClinicalTrials.gov (CRS Web) | ICTRP (WHO Portal) | Other |
| Search 1: (chronic OR persistent OR recurrence OR recurrent) AND (suppuration OR pus OR discharge OR otorrhea or active OR mucopurulent) AND Condition: "Otitis Media" OR OME AND Study type: interventional Search 2: (chronic OR persistent OR recurrence OR recurrent) AND (earache OR "ear ache" OR "ear pain" OR "ear discharge" OR "wet ear" OR "moist ear" OR "weeping ear") AND Study type: interventional Search 3: ("ear drum" OR eardrum OR "tympanic membrane") AND (hole OR perforation OR rupture) AND Study type: interventional | otitis media AND chronic OR ear discharge OR earache OR wet ear OR weeping ear OR moist ear OR CSOM OR OME AND chronic OR tympanic membrane AND perforation OR eardrum AND hole OR eardrum AND perforation | LILACS TW:"otitis media" OR "TW:"ear discharge" OR TW:earache OR ((TW:eardrum OR TW:tympanic) AND (TW:perforation OR hole)) OR ((TW:wet OR moist OR weeping) AND TW:ear) AND: Filter: Controlled Clinical Trial IndMed otitis media OR ear discharge OR csom OR earache OR wet ear OR tympanic membrane perforation OR eardrum hole OR wet ear OR weeping ear or moist ear OR OME PakMediNet otitis media | ear discharge | csom | earache | wet ear | tympanic membrane perforation | eardrum hole | wet ear | weeping ear African Index Medicus "otitis media" OR "ear discharge" OR CSOM |
Appendix 2. Data extraction form
| REF ID: | Study title: |
| Date of extraction: | Extracted by: |
| Name and email address of correspondence authors: |
| General comments/notes (internal for discussion): |
FLOW CHART OF TRIAL:
| Intervention ( name the intervention) | Comparison ( name the intervention) | |
| No. of people screened | ||
| No. of participants randomised ‐ all | ||
| No. randomised to each group | ||
| No. receiving treatment as allocated | ||
| No. not receiving treatment as allocated ‐ Reason 1 ‐ Reason 2 | ||
| No. that dropped out1 (no follow‐up data for any outcome available) | ||
| No. excluded from analysis2 (for all outcomes) ‐ Reason 1 ‐ Reason 2 | ||
1This includes patients who withdrew and provided no data, or did not turn up for follow‐up.
2This should be the people who were excluded from all analyses (e.g. because the data could not be interpreted or the outcome was not recorded for some reason). This is the number of people who dropped out, plus the people who were excluded by the authors for some reason (e.g. non‐compliant).
INFORMATION TO GO INTO THE 'CHARACTERISTICS OF INCLUDED STUDIES' TABLE:
| Methods | X arm, double‐/single‐/non‐blinded, [multicentre] parallel‐group/cross‐over/cluster RCT, with x duration of treatment and x duration of follow‐up |
| Participants | Location: [country, rural?, no. of sites etc.] Setting of recruitment and treatment: [specialist hospital? general practice? school? state YEAR] Sample size:
Participant (baseline) characteristics:
Inclusion criteria:
Exclusion criteria: |
| Interventions | Intervention (n = x): drug name, method of administration, dose per day/frequency of administration, duration of treatment For aural toileting: who does it, methods or tools used, frequency, duration Comparator group (n = y): Concurrent treatment: Use of additional interventions (common to both treatment arms): |
| Outcomes | Outcomes of interest in the review: Primary outcomes:
Secondary outcomes
|
| Funding sources | "No information provided"/"None declared"/State source of funding |
| Declarations of interest | "No information provided"/"None declared"/State conflict |
| Notes | Clinical trial registry no: (if available) Unit of randomisation: person/ears/other (e.g. cluster‐randomised by hospital/school) [In the case of randomisation by person]: Methods for including patients with bilateral disease, for example:
|
RISK OF BIAS TABLE:
(See table 8.5d in the Cochrane Handbook for Systematic Reviews of Interventions: http://handbook.cochrane.org/).
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High/low/unclear risk | Quote: "…" Comment: |
| Allocation concealment (selection bias) | High/low/unclear risk | Quote: "…" Comment: |
| Blinding of participants and personnel (performance bias) | High/low/unclear risk | Quote: "…" Comment: |
| Blinding of outcome assessment (detection bias) | High/low/unclear risk | Quote: "…" Comment: |
| Incomplete outcome data (attrition bias) | High/low/unclear risk | Quote: "…" Comment: |
| Selective reporting (reporting bias) | High/low/unclear risk | Quote: "…" Comment: |
FINDINGS OF STUDY
CONTINUOUS OUTCOMES
| Results (continuous data table) | |||||||
| Outcome | Intervention (name the intervention) | Comparison (name the intervention) | Other summary statistics/Notes | ||||
| Mean | SD | N | Mean | SD | N | Mean difference (95% CI), P values etc. | |
| Disease‐specific health‐related quality of life (COMQ‐12, COMOT‐15, CES)1 Time point: (state) | |||||||
| Hearing: [Measurement method: include frequencies and report results separately if they are presented in the paper] Time point: [xx] | |||||||
| Comments: [If there is no information apart from (vague) narration, quote here] [If information is in the form of graphs, used this software to read it: http://arohatgi.info/WebPlotDigitizer/app/, and save a copy of your charts in a folder] | |||||||
1State the measurement method: this will be instrument name/range for patient‐reported outcomes.
DICHOTOMOUS OUTCOMES
| Results (dichotomous data table) | ||||||
| Outcome | Applicable review/ Intervention1 | Group A ‐ intervention arm | Group B – control | Other summary statistics/Notes | ||
| No. of people with events | No. of people analysed | No. of people with events | No. of people analysed | P values, RR (95% CI), OR (95% CI) | ||
| Resolution of ear discharge or 'dry ear' at 1 to 2 weeks [Measurement method or definition used: not/unclear if/otoscopically confirmed]1 Time point: [State actual time point] | ||||||
| Resolution of ear discharge or 'dry ear' at 2 to 4 weeks [Measurement method or definition used: not/unclear if/otoscopically confirmed] Time point: [xx] | ||||||
| Resolution of ear discharge or 'dry ear' after 4 weeks [Measurement method or definition used: not/unclear if/otoscopically confirmed] Time point: [xx] | ||||||
| Ear pain/discomfort/local irritation Time point: [xx] | ||||||
| Suspected ototoxicity [Measurement method or definition used] Time point: [xx] | ||||||
| Sensorineural hearing loss [Measurement method or definition used] Time point: [xx] | ||||||
| Tinnitus [Measurement method or definition used] Time point: [xx] | ||||||
| Dizziness/vertigo/balance [Measurement method or definition used] Time point: [xx] | ||||||
| Serious complications: Time point: state length of follow‐up of the trial | Note down the page number /table where info was found for ease of checking | |||||
| Otitic meningitis [How was this diagnosed?] | ||||||
| Lateral sinus thrombosis [How was this diagnosed?] | ||||||
| Cerebellar abscess [How was this diagnosed?] | ||||||
| Mastoid abscess/mastoiditis [How was this diagnosed?] | ||||||
| Postauricular fistula [How was this diagnosed?] | ||||||
| Facial palsy [How was this diagnosed?] | ||||||
| Other complications [How was this diagnosed?] | ||||||
| Death [How was this diagnosed?] | ||||||
| Multiple serious complications [How was this diagnosed?] | ||||||
| Comment/additional notes: If any calculations are needed to arrive at the data above, note this down here. | ||||||
1State briefly how this was measured in the study, especially whether there was deviation from what was expected in the protocol.
For adverse events, note down how these were collected, e.g. whether the adverse event was one of the prespecified events that the study planned to collect, when it was collected and how/who measured it (e.g. as reported by patients, during examination and whether any scoring system was used).
| Topical antibiotics with steroids | Topical antibiotics | Systemic antibiotics | Topical antiseptics | Aural toileting (ear cleaning) | |
| Topical antibiotics with steroids | Review CSOM‐4 | ||||
| Topical antibiotics | Review CSOM‐4 | Review CSOM‐1 | |||
| Systemic antibiotics | Review CSOM‐4 | Review CSOM‐3 | Review CSOM‐2 | ||
| Topical antiseptics | Review CSOM‐4 | Review CSOM‐6 | Review CSOM‐6 | Review CSOM‐5 | |
| Aural toileting | Review CSOM‐4 | Not reviewed | Not reviewed | Not reviewed | Review CSOM‐7 |
| Placebo (or no intervention) | Review CSOM‐4 | Review CSOM‐1 | Review CSOM‐2 | Review CSOM‐5 | Review CSOM‐7 |
| CSOM‐1: Topical antibiotics for chronic suppurative otitis media (Brennan‐Jones 2018a). CSOM‐2: Systemic antibiotics for chronic suppurative otitis media (Chong 2018a). CSOM‐3: Topical versus systemic antibiotics for chronic suppurative otitis media (Chong 2018b). CSOM‐4: Topical antibiotics with steroids for chronic suppurative otitis media (Brennan‐Jones 2018b). CSOM‐5: Topical antiseptics for chronic suppurative otitis media (Head 2018a). CSOM‐6: Antibiotics versus topical antiseptics for chronic suppurative otitis media (Head 2018b). CSOM‐7: Aural toilet (ear cleaning) for chronic suppurative otitis media (Bhutta 2018). | |||||
| Class of antibiotics | Examples | Route of administration |
| Quinolones | Ciprofloxacin, ofloxacin, levofloxacin | Oral, intravenous, topical |
| Aminoglycosides | Gentamicin, tobramycin | Topical or parenteral |
| Neomycin/framycetin | Only topical | |
| Cephalosporins | Ceftazidime | Parenteral |
| Penicillins | Ticarcillin plus clavulanic acid | Parenteral |
| Monobactams | Aztreonam | Parenteral |
| Antiseptic agent used aurally | Target and mechanism of action |
| Rubbing alcohol (ethanol, isopropanol) | Penetrating agents that cause loss of cellular membrane function, leading to release of intracellular components, denaturing of proteins, and inhibition of DNA, RNA, protein and peptidoglycan synthesis. |
| Povidone iodine | Highly active oxidising agents that destroy cellular activity of proteins. Disrupts oxidative phosphorylation and membrane‐associated activities. Iodine reacts with cysteine and methionine thiol groups, nucleotides and fatty acids, resulting in cell death. |
| Chlorhexidine | Membrane‐active agents that damage cell wall and outer membrane, resulting in collapse of membrane potential and intracellular leakage. Enhanced passive diffusion mediates further uptake, causing coagulation of cytosol. |
| Hydrogen peroxide | Produces hydroxyl free radicals that function as oxidants, which react with lipids, proteins and DNA. Sulfhydryl groups and double bonds are targeted in particular, thus increasing cell permeability. |
| Boric acid | It is likely that the change in the pH media of the ear canal interrupts the growth of bacteria by affecting the amino acid, which causes alteration in the three‐dimensional structure of bacterial enzymes. Extreme changes in pH cause protein denaturation. |
| Aluminium acetate/acetic acid | Acetic acid changes the pH media of the ear canal and interrupts the growth of bacteria by affecting the amino acid, which causes alteration in the three‐dimensional structure of bacterial enzymes. Extreme changes in pH cause protein denaturation. Aluminium acetate is an astringent that helps reduce itching, stinging and inflammation. |
| Sources: Gupta 2015; McDonnell 1999; Sheldon 2005. | |
