Effectiveness of iodoform-based filling materials in root canal treatment of deciduous teeth: a systematic review and meta-analysis

Figures & data

Table 1. Summary of some methodologic characteristics of the included studies.

Author and date	Age: years (average)	Number of sample participants Performing Sample calculation Gender distribution	Number of teeth (Type) Reason for treatment Number of operators (sessions and technique) Number of evaluators (blinding and calibration)	Iodoform-based filling materials (Trademark or Composition)	Noniodoform-based filling materials (Trademark or composition)	Follow-up time (months)	Clinical and/or radiographic evaluation criteria
Al-Ostwani et al., 2016 [9]	3-9.	39. Unreported sample calculation. 19 girls. 20 boys.	64 (molars). Caries. 3 operators (one session and chemical-mechanical technique). 2 evaluators (double-blinded and calibration not reported).	- Metapex (Meta Biomed / Korea). -Endoflas-CF (adding 56.5% zinc oxide, 40.6% iodoform, 1.63% barium sulfate and 1.07% calcium hydroxide, and mixed with eugenol without adding chlorophenol).	- ZOE (Fares, Damascus, Syria, License 0009). - ZOP (50% zinc oxide powder with 50% hydrolytic própolis - Syrian patent number/5918).	6 and 12.	Clinical success: Based on the presence of normal mucosa without abnormal mobility, pain, or sensitivity to percussion. Radiographic success: Associated with decrease in the size of radiolucency and the presence of bone regeneration. If the radiolucency remained stable without remarkable changes, the treatment was classified as suspected and required further observation. Treatment failure was classified into two degrees as (a) the radiolucency slightly increased in size, but it was separated from succeeding bud with adequate bone and (b) the radiolucency threatening the succeeding buds, so the tooth was extracted. Clinical and radiographic success data separated.
Calixto-Chanca et al., 2014 [37]	3-6.	48. Unreported sample calculation. 24 boys. 24 girls.	56 (molars and anterior). Unreported reason for treatment. Number of operators not reported (number of session not reported and chemical-mechanical technique). Number of evaluators not reported (blinding and calibration not reported).	Modified Guedes-Pinto paste (0.30 g of iodoform, 0.1 ml camphorated paramonochlorophenol, 0.25 ml sodium rifamycin SV, 5 mg prednisone and 0.30 mg zinc oxide).	CTZ (chloramphenicol 500 mg, tetracycline 500 mg, zinc oxide 1000 mg and a drop of eugenol).	15 days, 2 and 4.	Clinical success: Absence of espontaneous pain, change in gum color, submucosal abscess, mobility and fistula each (yes and no). Radiographic success: Periodontal ligament space (normal and widened), root resorption (physiological and pathological), interradicular area (apposition and resorption). Clinical and/or radiographic success data individual condition evaluated but not summarized.
Cassol et al., 2019 [38]	2-7.	23. Unreported sample calculation. 16 boys. 7 girls.	27. Caries and trauma. 1 operator (different number of session and chemical-mechanical technique). 2 evaluators (double-blinded and calibration realized).	Modified Guedes-Pinto paste (iodoform  + camphorated parachlorophenol  + ointment comprising 5.0 mg prednisolone acetate and 1.5 mg rifamycin).	Calen®/ZO paste (S.S. White Artigos Dentários Ltda., Rio de Janeiro,Brazil).	6,9 and 12.	Clinical success: Absence of signs or symptoms of infection, such as pain, swelling, fistula, or sensitivity to percussion. Radiographic success: Reduction in the size of the previous radiolucent area, or no new radiolucency. Clinical and radiographic success data separated.
Chen et al., 2017 [17]	5.88 (±1.27.)	155. Sample calculation. Distribution by gender not reported.	160 (molars). Caries. 1 operator (2 session and chemical-mechanical technique). 2 evaluators (double-blindedand calibration realized).	- Vitapex (Neo Dental Chemical Products Co. Ltd., Tokyo, Japan). - MPRCF® (0.21 g zinc oxide, 0.07 g eugenol, 0.18 g iodoform and 0.01 g calcium hy- droxide).	ZOE (0.42 g zinc oxide, 0.14 g eugenol).	6, 12 and 18.	Clinical success: Completely free of clinical signs and symptoms including pain, gingival abscesses, fistula openings, and abnormal mobility. Radiographic success: Abcense of pathologic external root resorption and no radiographic lesions. The radiographic examination also included resorption of excess extraradicularly extruded materials and filling material in the root canal, and direction of the succes- sor permanent molars. The overfilled material was described as non-resorbed, partly resorbed, or completely resorbed. The state of filling material in the root canal were divided into five levels: both root and filling no change; root no change but filling resorbed; root began resorption, filling resorbed at faster rate; root began re- sorption, filling resorbed at same rate (the distance from the apex in the radiograph to the bottom of the filling being less than 1 mm); root began resorption, filling resorbed at slower rate. Clinical and radiographic success data separated.
Divya et al., 2019 [36]	4-9 (6,25).	17. Unreported sample calculation. Distribution by gender not reported.	30 (molars). Caries. 1 operator (number of session not reported and chemical-mechanical technique). 1 evaluator (blinding and calibration not reported).	- Endoflas with propolis [Propolis liquid (Brazilian Green Bee Propolis Liquid Extract, Uniflora®) and Endoflas powder (Sanlor and Cia. S. En C. S., Colombia). The mixing ratio of Endoflas powder and Propolis liquid was 2:1].	- LSTR (3Mix) (Ciprofloxacin, metronidazole and minocycline) (1: 3: 3).	3, 6 and 12.	Clinical insuccess: Presence of spontaneous pain, swelling, Sinus tractand mobility and premature exfoliation. Radiographic insuccess: Whether any increase/decrease of periapical and furcation radiolucencies, deviation in the path of eruption of succedaneous teeth, internal root resorption had decreased or increased following treatment, resorption of over‐pushed material, resorption of filling material with respect to root resorption. Clinical and radiographic success data separated.
Doneria et al., 2017 [27]	4-8.	64. Unreported sample calculation. Distribution by gender not reported.	64 (molars) Caries. 1 operator (number of session not reported and chemical-mechanical technique). 1 clinical evaluator (was the operator) and 2 radiographic evaluators independent (double-blinded and calibration realized).	Vitapex (Neo dental co., Tokyo, Japan).	- ZnO‐ozonated oil [ZnO powder (DPI, Mumbai, India) (0.2 g, arsenic free) and ozonated castor oil (0.007 cc Ozonil, Ozone Forum of India, Mumbai, India)]. 3Mix‑MP modified(ornidazole tablets 500 mg (Ornida, Aristo pharmaceuticals, India), ciprofloxacin tablets 500 mg (Ciplox®, Alchemist Ltd., India), and cefaclor tablets 250 mg (DistaclorTM DT, Baroque pharmaceuticals, India)(1: 1: 1).	1, 6, 12 and 18.	Clinical success: Absence of pain, presence of healthy soft tissue, and absence of abnormal mobility. Radiographic success: included static/reduction in size of intra‐radicular radiolucency, evidence of bone regeneration/continuity of lamina dura, and the absence of internal/external resorption. The treatment was judged to be successful when both clinical and radiographic criteria were fulfilled. Clinical and radiographic success data separated.
Goel et al., 2018 [12]	4-9.	120. Sample calculation. 77 boys. 43 girls.	120 (molars) Caries. 1 operator (number of session not reported and chemical-mechanical technique). Number of evaluators not reported (blinding and calibration not reported).	Endoflas (Sanlor laboratories).	- ZOE (Prevest Denpro). - ZnO-Aloe vera (not reported). - ZnO −10% NaF (preparado na Pharmacology Lab).	3, 6, 9 and 12	Clinical success: Absence of pain and swelling, no tenderness on percussion, absence of sinus or fistula and mobility and presence of healthy soft tissue (defined as the absence of swelling, redness, or sinus tract). Radiographic success: Absence of periapical or inter- radicular pathology, absence of internal or pathological external root resorption, reduction or no change in the size of interradicular radiolucencies, presence of evidence of bone regeneration and radiographic continuity of lamina dura. Clinical and radiographic success data separated.
Goinka et al. 2020 [20]	4-9.	50. Unreported sample calculation. Distribution by gender not reported.	51 (primary second molars). Teeth with chronic infection. Number of operators not reported (number of session not reported and chemical-mechanical technique). 3 evaluators (duble-blinded and calibration not report). The result was determined by an agreement of at least two observers.	Metapex (Meta Biomed/Korea).	ZOE paste (Vishal Dentocare Pvt., Ltd., Gujarat) = ZnO -Aloe vera gel (DPI, Mumbai, India, 0.2 g arsenic free)	3, 6 and 12.	Clinical success: Presence of normal mucosa without abnormal mobility, pain, or sensitivity to percussion. Radiographic success: Decrease in the size of radiolucency and the presence of bone regeneration. If the radiolucency remained stable without remarkable changes, the treatment was classified as suspected and required further observation. Treatment failure was classified into two degrees as (a) the radiolucency slightly increased in size, but it was separated from succeeding bud with adequate bone and (b) the radiolucency threatening the succeeding buds, so the tooth was extracted. Clinical and radiographic success data separated.
Kottapalli et al., 2019 [35]	4-10.	Not reported.	30 (molars). Caries. 1 operator (1 session and chemical-mechanical technique). Number of evaluators not reported (blinding and calibration not reported).	Endoflas FS (Sanlor and Cia. S. En C. S., Colombia).	Mixture of zinc oxide powder (DPI, Mumbai, India) and nanohydroxyapatite (Sigma – Aldrich, Saint Louis, USA) with saline.	3, 6 and 12.	Clinical success: Absence of pain, tenderness on percussion, swelling and mobility. Radiographic success: Resorption of overpushed material (if any), resorption of material with the physiologic root resorption, deviated path of eruption of succedaneous teeth. Clinical and radiographic success data separated.
Moness et al., 2012 [21]	3-5.	80. Unreported sample calculation. Distribution by gender not reported.	160 (maxillary primary incisors). Caries. 1 operator (1 session and chemical-mechanical technique). Number of evaluators not reported (blinding and calibration not reported).	Zical (Zinc Oxide Eugenol, Bismuth Subcarbonate, Iodoform, Resins and Barium Sulphate, eugenol and excipients) (Prevest Denpro Limited).	- Apexcal (Calcium hydroxide, bismuth carbonate, polyethylene glycol, glycerine, water) (Ivoclar Vivadent Ag). - ZOE (El Gomhoriay)	1, 3, 6, 9 and 12.	Clinical evaluation criteria History of pain Loss of clinical crown/ coronal restoration, recurrent caries Sensitivity to percussion Signs of erythema or swelling in the surrounding gingival tissue and mucosa Presence of fistula / sinus in the surrounding gingival tissue and mucosa. Radiographic evaluation criteria Presence or absence of periapical radiolucency Presence or absence of pathological internal or external root resorption Presence or absence of widening of periodontal membrane space. Clinical and radiographic success data separated.
Mortazavi and Mesbahi, 2004 [10]	3-13.	58. Unreported sample calculation. 32 boys. 26 girls.	58 (molars and anterior). Caries and trauma. Number of operators not reported (2 sessions and chemical-mechanical technique). Number of evaluators not reported (blinding and calibration not reported).	Vitapex (Neo Dental Chemical Products Co., Ltd, Tokyo, Japan).	ZOE (Associated Dental Products Ltd).	3 and 10-16.	Clinical success: Without evidence of pain, fistula, intraoral swelling, extraoral swelling or abnormal mobility were completely free of clinical signs and symptoms at the follow-up. Radiographic success: Evidence of bone radiolucency in their preoperative radiographs demonstrated evidence of a reduction in the size of the radiolucent area at the follow-up, and without any evidence of a radiolucent area at the start of treatment showed no newly formed radiolu- cency after. Clinical and/or radiographic success data individual condition evaluated but not summarized.
Nakornchai et al., 2010 [28]	3-8.	37. Unreported sample calculation. Distribution by gender not reported.	50 (molars). Caries. Number of operators not reported (3Mix – 1session and Vitapex − 1 or 2 sessions with chemical-mechanical technique). 1 evaluator (single-blinded and calibration realized).	Vitapex (Neo Dental Chemical Products Co., Ltd, Tokyo, Japan).	3Mix-MP (met- ronidazole (FlagylÒ, Sanofi-Aventis, Thailand), ciprofloxacin (CiprobayÒ, Bayer, Germany), and minocycline (MinocinÒ, Wyeth, China) (1: 1: 1).	6 and 12.	Clinical insuccess: Absence of pain, gingival abscesses, fistula openings, or abnormal mobility were completely free of clinical signs and symptoms. Radiographic success: Static or reduced size of bifurcation ⁄ periapical radiolucency, no progression of pathologic external root resorption, no progression of internal root resorption, and no newly formed radiographic lesions. If calcified metamorphosis occurred, it was noted but not regarded as a treatment failure. Clinical and radiographic success data separated.
Ozalp et al., 2005 [14]	3-9.	76. Unreported sample calculation Distribution by gender not reported.	80 (molars). Unreported reason for treatment. 2 operators (1session or 2 session when not collaborative patient and chemical-mechanical technique). Number of evaluators not reported (single-blinded and calibration not reported).	Vitapex (Diadent Group Int. Inc., Burnaby, BC, Canada).	ZOE (Associated Dental Products Ltd., Purton, Swindon, Wiltshire, UK). Calcitur (Voco, Cuxhaven, Germany). Sealapex (Kerr, Sybron Dental Specialties, Inc, Salerno, Italy).	2, 4, 6, 8, 10, 12 and 18.	Clinical success: Absence of pain, gengival swelling, tenderness to percussion, abnormal mobility, fistula or abscess. Radiographic success: Absence of furcation or periapical radiolucency, non-continuity of lamina dura and pathologic root resorption. Clinical and radiographic success data separated.
Pandranki et al., 2018 [18]	4-9.	26. Unreported sample calculation. Distribution by gender not reported.	60 (not reported). Caries. 1 operator (number of session not reported and chemical-mechanical technique). 2 evaluators (double-blinded and calibration realized).	Endoflas (Sanlor and Cia. S. en C.S.,Colombia).	ZOE (Not reported).	3, 6, 12 and 24.	Clinical success: When tooth is asymptomatic (i.e. without pain, tenderness, abscess, and decrease or absence of mobility). Radiographic success: Reduction in the size of interradicular radiolucency or the size remaining same and also when no signs of internal or external pathological root resorption demonstrated. If the tooth was symptomatic, it was considered as clinical failure and increase in postoperative inter‐radicular radiolucency or development of new postoperative radiolucency was considered as a radiographic failure. Clinical and radiographic success data separated.
Pramila et al., 2016 [16]	4-9.	88. Unreported sample calculation. 40 girls. 48 boys.	111 (not reported). Caries. 1 operator (1 session and chemical-mechanical technique). 2 evaluators (double-blinded and calibration realized).	- RC Fill (Medensco DentalProducts, Mumbai, India). - Vitapex (Neo Dental International, Inc.).	ZOE (Pulpdent Corporation)	6, 12 and 30.	Clinical and radiographic criteria according to modified American Association of Endodontists. Clinical and radiographic success data separated.
Qadeer et al., 2016 [29]	3-8 (3.54 Dp = 1,69).	100. Sample calculation. 54 girls 46 boys	100 (primary molars). Caries. Number of operators not reported (number sessions not reported). Number of evaluators not reported (blinding and calibration not reported).	Vitapex (Not reported).	3 Mix (Not reported).	6.	Radiographic success Absence of interradicular or periapical radiolucency. Radiographic success data separated.
Reddy and Fernandes, 1996 [13]	3-8.	26. Unreported sample calculation. 15 boys. 11 girls.	30 (posterior and anterior). Caries. Number of operators not reported (2 sessions and technique filling not reported). Number of evaluators not reported (blinding and calibration not reported).	Maisto (14 g zincoxide, 42 g iodoform, 2 g thymol, 3 g camphor and 0,5 g lanolin).	ZOE (Not reported).	3-6 and 9.	Clinical success Absence of pain, tenderness, mobility and health of tissues surrounding teeth. Radiographic sucess: Resorption of excesso material, interradicular radiolucencies and bone formation. Clinical and radiographic success data separated.
Rewal et al., 2014 [11]	4-9.	50. Unreported sample calculation. 28 boys. 22 girls.	50 (molars). Unreported reason for treatment. 1 operator (1 session and chemical-mechanical technique). 1 clinical evaluator and 2 radiographic evaluators (blinding not reported and calibration realized).	Endoflas (Sanlor and Cia. S. en C.S., Cali, Colombia),	ZOE (Not reported)	3, 6 and 9.	Clinical success: Absence of pain, redness, swelling, tenderness on percussion, and sinus or fistula. Radiographic success: Reduction in the size of interradicular radiolucency or the size remaining the same. Clinical and radiographic success data separated and summarized.
Subramaniam and Gilhortra, 2011 [19]	5-9.	Not report.	45 (molars). Caries. Number of operators not reported (1 session and chemical-mechanical technique). Number of evaluators not reported (blinding and calibration not reported).	- Endoflas FS (Sanlor e Cia. S.en C.S., Cali, Colombia). -Metapex (Meta Biomed Company Ltd.).	ZOE (Not reported).	3, 6, 12 and 18.	Clinical success: No gingival swelling/inflammation/redness. No sinus opening in the oral mucosa or purulent exudate expressed from the gingival margin. No abnormal mobility other than mobility due to normal exfoliation. Absence of pain on percussion/tenderness. Radiographic success: No evidence of extensive pathologic root resorption. Reduction or no change in pre-operative pathologic interradicular and/or periapical radiolucency. No evidence of development of new post-operative pathologic radiolucency involving the succedaneous tooth germ. Clinical and radiographic success data separated.
Trairatvorakul and Chunlasikaiwan, 2008 [15]	3-7 (5.6 +-1.2).	42. Unreported sample calculation. Distribution by gender not reported.	54 (lower molars). Caries. 1 operator (1 session and chemical-mechanical technique). 2 evaluators (blinding realized and calibration not reported).	Vitapex (Neo Dental, Tokyo, Japan).	Zinc Oxide (Thailaisart Co, Saraburi, Thailand) and Eugenol (Tien Yuan Chemical Co, Singapore).	6 and 12.	Clinical success: Absence of pain, presence of healthy soft tissue (defined as the absence of swelling, redness, or sinustract) and absence of abnormal mobility. Radiographic success: Continuity of the lamina dura, reduction in the size of any pathologic inter-radicular and/ or periapical radiolucencies, or evidence of bone regeneration. Two conditions were considered to require further observation before considering treatment as a failure or success: 1) absence of change or more discontinuity of lamina dura; 2) absence of change in size of radiolucent area. Clinical and radiographic success data separated and summarized.
Zacharczuk et al., 2019 [30]	G1: 6.15 (± 1.38) and G2: 6.3 (± 1.49).	Not report. Unreported sample calculation. Distribution by gender not reported.	46 (primary molars). Teeth diagnosed with pulp necrosis. 4 operators (1 session and chemical-mechanical technique) (trained and calibrated). Number of evaluators not reported (blinding and calibration not reported).	Maisto­Capurro paste: (equal parts by volume of calcium hydroxide and iodoform, with propylene glycol as carrier).	3Mix­MP (metronidazole, ciprofloxacin, minocycline in a ratio 1:1:1 by volume). Carriers (macrogol and propylene glycol) were also used in a ratio 1:1 by volume.	1, 3, 6, 12 and 18.	Clinical success: Absence of any of the following: pain or sensitivity to percussion and palpation, swelling, fistula and non­ physiological mobility. Radiographic success: Absence of internal or external non­physiological resorption, no progression or reduction of radiolucent periapical/interradicular lesion and evidence of bone regeneration. Clinical and radiographic success data separated.

ZOE: Zinc-Oxide and Eugenol. LSTR: Lesion Sterilization and Tissue Repair Therapy.

Figure 1. Forest-plot of the clinical evaluation after 6 months in deciduous teeth.

Figure 2. Forest-plot of the clinical evaluation after 9–12 months in deciduous teeth.

Figure 3. Forest-plot of the clinical evaluation after 18–30 months in deciduous teeth.

Figure 4. Forest-plot of the radiographic evaluation after 6 months in deciduous teeth.

Figure 5. Forest-plot of the radiographic evaluation after 9–12 months in deciduous teeth.

Figure 6. Forest-plot of the radiographic evaluation after 18–30 months in deciduous teeth.

Table 2. Summary of findings in Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for clinical or radiographic evaluation at 6 months (A), 9-12 months (B) or 18-30 months (C) in deciduous teeth.

Outcomes	№ of participants (studies) Follow up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
				Risk with non-iodoform-based filling materials	Risk difference with iodoform-based filling materials
A. Iodoform-based filling materials compared to non-iodoform-based filling materials in the root canal treatment of deciduous teeth with chemical-mechanical technique and/or LSTR at 6 months.
Total: Chemical-mechanical  technique and LSTR. Event: clinical failures.  follow-up: 6 months.	974 (16 RCTs)	⨁⨁◯◯ LOW^a,b	OR 0.43 (0.19 to 0.97)	43 per 1000	24 fewer per 1000 (35 fewer to 1 fewer)
Subgroup: Chemical-  mechanical technique. Event: clinical failures.  follow-up: 6 months.	811 (12 RCTs)	⨁⨁◯◯ LOW^a,b	OR 0.37 (0.14 to 0.94)	45 per 1000	28 fewer per 1000 (38 fewer to 3 fewer)
Subgroup: LSTR. Event: clinical failures.  follow-up: 6 months.	163 (4 RCTs)	⨁◯◯◯ VERY LOW^d,e	OR 0.77 (0.14 to 4.19)	36 per 1000	8 fewer per 1000 (31 fewer to 99 more)
Total: Chemical-mechanical  technique and LSTR. Event: radiographic failures  follow-up: 6 months.	1014 (16 RCTs)	⨁◯◯◯ VERY LOW^d,e	OR 0.78 (0.43 to 1.42)	51 per 1000	11 fewer per 1000 (28 fewer to 20 more)
Subgroup: Chemical-  mechanical technique. Event: radiographic failures.  follow-up: 6 months.	731 (12 RCTs)	⨁◯◯◯ VERY LOW^a,c,d	OR 0.67 (0.32 to 1.43)	103 per 1000	32 fewer per 1000 (68 fewer to 38 more)
Subgroup: LSTR. Event: radiographic failures. Follow-up: 6 months.	283 (4 RCTs)	⨁◯◯◯ VERY LOW^d,e	OR 0.92 (0.33 to 2.59)	195 per 1000	13 fewer per 1000 (121 fewer to 190 more)
B. Iodoform-based filling materials compared to non-iodoform-based filling materials in the root canal treatment of deciduous teeth with chemical-mechanical technique and/or LSTR at 9–12 months.
Total: Chemical-mechanical  technique and LSTR. Event: clinical failures.  follow-up: 9–12 months.	1156 (18 RCTs)	⨁⨁◯◯ LOW ^a,b	OR 0.46 (0.23 to 0.93)	69 per 1000	36 fewer per 1000 (52 fewer to 5 fewer)
Subgroup: Chemical-  mechanical technique. Event: clinical failures.  follow-up: 9–12 months.	996 (14 RCTs)	⨁⨁◯◯ LOW ^a,b	OR 0.43 (0.19 to 0.97)	68 per 1000	38 fewer per 1000 (55 fewer to 2 fewer)
Subgroup: LSTR. Event: clinical failures.  follow-up: 9–12 months.	160 (4 RCTs)	⨁◯◯◯ VERY LOW ^c,d	OR 0.57 (0.15 to 2.12)	73 per 1000	30 fewer per 1000 (61 fewer to 70 more)
Total: Chemical-mechanical  technique and LSTR. Event: radiographic failures.  follow-up: 9–12 months.	1160 (18 RCTs)	⨁◯◯◯ VERY LOW ^a,b,e	OR 0.43 (0.24 to 0.75)	166 per 1000	87 fewer per 1000 (120 fewer to 36 fewer)
Subgroup: Chemical-  mechanical technique. Event: radiographic failures.  follow-up: 9–12 months.	1000 (14 RCTs)	⨁◯◯◯ VERY LOW ^a,b,e	OR 0.47 (0.23 to 0.96)	145 per 1000	71 fewer per 1000 (107 fewer to 5 fewer)
Subgroup: LSTR. Event: radiographic failures. Follow-up: 9–12 months.	160 (4 RCTs)	⨁⨁◯◯ LOW ^b,c	OR 0.34 (0.13 to 0.87)	305 per 1000	175 fewer per 1000 (251 fewer to 29 fewer)
C. Iodoform-based filling materials compared to non-iodoform-based filling materials in the root canal treatment of deciduous teeth with chemical-mechanical technique and/or LSTR at 18-30 months.
Total: Chemical-mechanical  technique and LSTR. Event: clinical failures.  follow-up: 18–30 months.	503 (7 RCTs)	⨁◯◯◯ VERY LOW ^a,d	OR 1.08 (0.58 to 2.03)	104 per 1000	7 more per 1000 (41 fewer to 86 more)
Subgroup: Chemical-  mechanical technique. Event: clinical failures.  follow-up: 18–30 months.	427 (5 RCTs)	⨁◯◯◯ VERY LOW ^a,d	OR 1.32 (0.65 to 2.67)	148 per 1000	38 more per 1000 (46 fewer to 169 more)
Subgroup: LSTR. Event: clinical failures.  follow-up: 18–30 months.	76 (2 RCTs)	⨁◯◯◯ VERY LOW ^d,f	OR 0.43 (0.09 to 2.09)	128 per 1000	69 fewer per 1000 (115 fewer to 107 more)
Total: Chemical-mechanical  technique and LSTR. Event: radiographic failures  follow-up: 18–30 months.	502 (7 RCTs)	⨁◯◯◯ VERY LOW ^a,d	OR 1.06 (0.51 to 2.21)	149 per 1000	8 more per 1000 (67 fewer to 130 more)
Subgroup: Chemical-  mechanical technique. Event: radiographic failures.  follow-up: 18–30 months.	427 (5 RCTs)	⨁◯◯◯ VERY LOW ^a,d,g	OR 1.51 (0.78 to 2.92)	137 per 1000	56 more per 1000 (27 fewer to 179 more)
Subgroup: LSTR. Event: radiographic failures. Follow-up: 18–30 months.	75 (2 RCTs)	⨁◯◯◯ VERY LOW ^d,f	OR 0.39 (0.08 to 2.00)	211 per 1000	116 fewer per 1000 (190 fewer to 137 more)

LSTR: Lesion Sterilization and Tissue Repair Therapy.

The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI); CI: Confidence interval; OR: Odds ratio.

GRADE Working Group grades of evidence:

High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.

Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.

Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Explanations:

^aMost of the included studies were judged to be at "unclear risk of bias".

^bThe optimal size effect was not achieved.

^cThere was heterogeneity that could not be explained.

^dThe optimal information sample was not met and the confidence interval crosses the threshold.

^eAll the included studies were judged to be at "unclear risk of bias".

^fThe included studies were at high and unclear risk of bias.

^gThere is inconsistency in the direction of the effect.

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