What do systematic reviews say?

Chlorhexidine mouthrinse (any concentration; 0.05% to 0.2%) used in conjunction with mechanical oral hygiene procedures vs Placebo/control mouthrinse, or no mouthrinse (mechanical oral hygiene alone); controls pooled (protocol's separate comparisons versus mechanical oral hygiene alone and versus placebo/control merged)

• Chlorhexidine mouthrinse as an adjunctive treatment for gingival health 2017 · Cochrane All outcomes
  SoF narrative row (Other adverse effects): 22 trials reported at least 1 adverse effect apart from extrinsic tooth staining and calculus formation in the chlorhexidine rinse arms. The adverse effects most commonly…
  22 studies
  GRADE not reported

Oral vs topical antibiotics

• Antibiotics for trachoma 2019 · Cochrane Headline outcomes only
  no estimate extracted
  8 studies · 1583 participants
  Low

Oral vs intra‐vaginal antifungal treatment of uncomplicated vulvovaginal candidiasis

• Oral versus intra‐vaginal imidazole and triazole anti‐fungal treatment of uncomplicated vulvovaginal candidiasis… 2020 · Cochrane Headline outcomes only
  no estimate extracted
  23 studies · 4637 participants
  High

Oral beta‐estradiol vs placebo

• Bioidentical hormones for women with vasomotor symptoms 2016 · Cochrane Headline outcomes only
  no estimate extracted
  3 studies · 433 participants
  Low

Professional oral care vs Usual oral care

• Oral care measures for preventing nursing home‐acquired pneumonia 2022 · Cochrane All outcomes
  Measured in only 1 study (834 participants), which reported no serious events and 64 non-serious events, the most common of which were oral cavity disturbances (not defined) and dental staining.
  1 study · 834 participants
  GRADE not reported

Statin plus oral contraceptive pill vs oral contraceptive pill (OCP)

• Statins for women with polycystic ovary syndrome not actively trying to conceive 2023 · Cochrane Headline outcomes only
  no estimate extracted
  2006 participants
  GRADE not reported

Extra-oral pulp extirpation at day 0 vs Intra-oral pulp extirpation at day 7

• Interventions for treating traumatised permanent front teeth: avulsed (knocked out) and replanted 2019 · Cochrane All outcomes
  Giannetti 2006 did not report this outcome; following email correspondence, authors reported no adverse effects were seen (uncertain whether formally assessed).
  1 study
  GRADE not reported

Aciclovir (oral or intravenous) for treatment vs placebo

• Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer 2009 · Cochrane All outcomes
  Adverse effects were assessed in both studies. For intravenous aciclovir the most commonly reported adverse effect was a reaction at the injection site (8 (16%) aciclovir versus 3 (7%) placebo; all patients, n = 97);…
  2 studies
  GRADE not reported

Biotene OralBalance vs control

• Oral hygiene care for critically ill patients to prevent ventilator‐associated pneumonia 2020 · Cochrane All outcomes
  Adverse effects (Stefanescu 2013): no significant difference between groups with respect to adverse events in buccal mucosa.
  1 study
  GRADE not reported

Topical treatments (benzydamine hydrochloride oral rinse) vs placebo

• Interventions for treating burning mouth syndrome 2016 · Cochrane All outcomes

  short-term (up to 3 months) · benzydamine hydrochloride
  SoF9. Adverse effects: single study narratively reported that no adverse effects occurred from benzydamine hydrochloride oral rinse; 20 participants (1 RCT); very low.
  1 study · 20 participants
  Very low

Hyperbaric oxygen therapy plus standard care (surgery, antibiotics, oral rinse) vs Standard care alone (surgery, antibiotics, oral rinse)

The review found no eligible studies for this question.

• Interventions for treating bisphosphonate‐related osteonecrosis of the jaw (BRONJ) 2016 · Cochrane All outcomes
  no estimate extracted
  0 studies
  No studies found

NSAIDs (ketorolac oral rinse; systemic celecoxib) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  over 3 months
  SoF 3, Safety of the intervention over 3 months: systemic celecoxib (1 study) - 32 intervention participants reported 56 adverse effects, 20 placebo participants reported 20; 4 grade 3 events; 2 discontinued. Ketorolac…
  2 studies
  GRADE not reported

Calcineurin inhibitors ± oral steroids vs oral steroids alone

Calcineurin inhibitors ± oral steroids may leads to lower adverse effects: acne compared with oral steroids alone (low certainty).

• Interventions for minimal change disease in adults with nephrotic syndrome 2022 · Cochrane Headline outcomes only
  RR 0.15 [0.03, 0.67]
  4 studies · 270 participants
  Low

Chlorhexidine (mouthrinse or gel), as part of oral hygiene care vs placebo or usual care

• Oral hygiene care for critically ill patients to prevent ventilator‐associated pneumonia 2020 · Cochrane All outcomes
  Adverse effects: information from 2 studies; one stated there were none, the other reported mild reversible irritation of the oral mucosa; very low certainty. There was a lack of evidence about adverse effects.
  2 studies
  Very low

Toothbrushing (with or without antiseptics), as part of oral hygiene care vs No toothbrushing (with or without antiseptics)

• Oral hygiene care for critically ill patients to prevent ventilator‐associated pneumonia 2020 · Cochrane All outcomes
  Adverse effects: information from two studies, which stated that there were none; very low certainty. There is a lack of evidence about adverse effects.
  2 studies
  Very low

Oral plus nebulised antibiotics vs oral antibiotics plus nebulised placebo

Oral plus nebulised antibiotics showed no clear difference in adverse effects of treatment compared with oral antibiotics plus nebulised placebo (low certainty).

• Interventions for the eradication of meticillin‐resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis 2022 · Cochrane Headline outcomes only
  OR 3 [0.11, 79.91]
  1 study · 29 participants
  Low

Calcineurin inhibitors ± oral steroids vs oral steroids alone

Calcineurin inhibitors ± oral steroids showed no clear difference in adverse effects: hypertension compared with oral steroids alone (low certainty).

• Interventions for minimal change disease in adults with nephrotic syndrome 2022 · Cochrane Headline outcomes only
  RR 0.86 [0.23, 3.2]
  3 studies · 219 participants
  Low

Oral azithromycin vs control

• Antibiotics for trachoma 2019 · Cochrane Headline outcomes only
  no estimate extracted
  2 studies · 3069 participants
  GRADE not reported

Oral azithromycin vs topical tetracycline

• Antibiotics for trachoma 2019 · Cochrane Headline outcomes only
  no estimate extracted
  3 studies · 6002 participants
  GRADE not reported

Oral methotrexate and oral prednisone vs prednisone or placebo

Oral methotrexate and oral prednisone showed no clear difference in primary outcome: Adverse effects compared with placebo and oral prednisone (low certainty).

• Interventions for morphea 2019 · Cochrane Headline outcomes only
  RR 1.23 [0.75, 2.04]
  1 study · 70 participants
  Low