Interventions for the management of dry mouth: non-pharmacological interventions.

BACKGROUND: Xerostomia is the subjective sensation of dry mouth. Common causes of xerostomia include adverse effects of many commonly prescribed medications, disease (e.g. Sjogren's Syndrome) and radiotherapy treatment for head and neck cancers. Non-pharmacological techniques such as acupuncture or mild electrostimulation may be used to improve symptoms. OBJECTIVES: To assess the effects of non-pharmacological interventions administered to stimulate saliva production for the relief of dry mouth. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 16th April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), MEDLINE via OVID (1948 to 16th April 2013), EMBASE via OVID (1980 to 16th April 2013), AMED via OVID (1985 to 16th April 2013), CINAHL via EBSCO (1981 to 16th April 2013), and CANCERLIT via PubMed (1950 to 16th April 2013). The metaRegister of Controlled Clinical Trials (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov) were also searched to identify ongoing and completed trials. References lists of included studies and relevant reviews were also searched. There were no restrictions on the language of publication or publication status. SELECTION CRITERIA: We included parallel group randomised controlled trials of non-pharmacological interventions to treat dry mouth, where participants had dry mouth symptoms at baseline. DATA COLLECTION AND ANALYSIS: At least two review authors assessed each of the included studies to confirm eligibility, assess risk of bias and extract data using a piloted data extraction form. We calculated mean difference (MD) and 95% confidence intervals (CI) for continuous outcomes or where different scales were used to assess an outcome, we calculated standardised mean differences (SMD) together with 95% CIs. We attempted to extract data on adverse effects of interventions. Where data were missing or unclear we attempted to contact study authors to obtain further information. MAIN RESULTS: There were nine studies (total 366 participants randomised) included in this review of non-pharmacological interventions for dry mouth which were divided into three comparisons. Eight studies were assessed at high risk of bias in at least one domain and the remaining study was at unclear risk of bias.Five small studies (total 153 participants, with dry mouth following radiotherapy treatment) compared acupuncture with placebo. Four were assessed at high risk and one at unclear risk of bias. Two trials reported outcome data for dry mouth in a form suitable for meta-analysis. The pooled estimate of these two trials (70 participants, low quality evidence) showed no difference between acupuncture and control in dry mouth symptoms (SMD -0.34, 95% CI -0.81 to 0.14, P value 0.17, I(2) = 39%) with the confidence intervals including both a possible reduction or a possible increase in dry mouth symptoms. Acupuncture was associated with more adverse effects (tiny bruises and tiredness which were mild and temporary). There was a very small increase in unstimulated whole saliva (UWS) at the end of 4 to 6 weeks of treatment (three trials, 71 participants, low quality evidence) (MD 0.02 ml/minute, 95% CI 0 to 0.04, P value 0.04, I(2) = 57%), and this benefit persisted at the 12-month follow-up evaluation (two trials, 54 participants, low quality evidence) (UWS, MD 0.06 ml/minute, 95% CI 0.01 to 0.11, P value 0.03, I(2) = 10%). For the outcome of stimulated whole saliva (SWS, three trials, 71 participants, low quality evidence) there was a benefit favouring acupuncture (MD 0.19 ml/minute, 95% CI 0.07 to 0.31, P value 0.002, I(2) = 1%) an effect which also persisted at the 12-month follow-up evaluation (SWS MD 0.28 ml/minute, 95% CI 0.09 to 0.47, P value 0.004, I(2) = 0%) (two trials, 54 participants, low quality evidence).Two small studies, both at high risk of bias, compared the use of an electrostimulation device with a placebo device in participants with Sjögren's Syndrome (total 101 participants). A further study, also at high risk of bias, compared acupuncture-like electrostimulation of different sets of points in participants who had previously been treated with radiotherapy. None of these studies reported the outcome of dry mouth. There was no difference between electrostimulation and placebo in the outcomes of UWS or SWS at the end of the 4-week treatment period in the one study (very low that provided data for these outcomes. No adverse effects were reported.A single study at high risk of bias, compared the stimulatory effect of powered versus manual toothbrushing and found no difference for the outcomes of UWS or SWS. AUTHORS' CONCLUSIONS: There is low quality evidence that acupuncture is no different from placebo acupuncture with regard to dry mouth symptoms, which is the most important outcome. This may be because there were insufficient participants included in the two trials to show a possible effect or it may be that there was some benefit due to 'placebo' acupuncture which could have biased the effect to the null. There is insufficient evidence to determine the effects of electrostimulation devices on dry mouth symptoms. It is well known that dry mouth symptoms may be problematic even when saliva production is increased, yet only two of the trials that evaluated acupuncture reported dry mouth symptoms, a worrying reporting bias. There is some low quality evidence that acupuncture results in a small increase in saliva production in patients with dry mouth following radiotherapy.There is insufficient evidence to determine the effects of electrostimulation devices on dry mouth symptoms or saliva production in patients with Sjögren's Syndrome. Reported adverse effects of acupuncture are mild and of short duration, and there were no reported adverse effects from electrostimulation.

Interventions for the management of dry mouth: non-pharmacological interventions.

BACKGROUND: Xerostomia is the subjective sensation of dry mouth. Common causes of xerostomia include adverse effects of many commonly prescribed medications, disease (e.g. Sjogren's Syndrome) and radiotherapy treatment for head and neck cancers. Non-pharmacological techniques such as acupuncture or mild electrostimulation may be used to improve symptoms. OBJECTIVES: To assess the effects of non-pharmacological interventions administered to stimulate saliva production for the relief of dry mouth. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 16th April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), MEDLINE via OVID (1948 to 16th April 2013), EMBASE via OVID (1980 to 16th April 2013), AMED via OVID (1985 to 16th April 2013), CINAHL via EBSCO (1981 to 16th April 2013), and CANCERLIT via PubMed (1950 to 16th April 2013). The metaRegister of Controlled Clinical Trials (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov) were also searched to identify ongoing and completed trials. References lists of included studies and relevant reviews were also searched. There were no restrictions on the language of publication or publication status. SELECTION CRITERIA: We included parallel group randomised controlled trials of non-pharmacological interventions to treat dry mouth, where participants had dry mouth symptoms at baseline. DATA COLLECTION AND ANALYSIS: At least two review authors assessed each of the included studies to confirm eligibility, assess risk of bias and extract data using a piloted data extraction form. We calculated mean difference (MD) and 95% confidence intervals (CI) for continuous outcomes or where different scales were used to assess an outcome, we calculated standardised mean differences (SMD) together with 95% CIs. We attempted to extract data on adverse effects of interventions. Where data were missing or unclear we attempted to contact study authors to obtain further information. MAIN RESULTS: There were nine studies (total 366 participants randomised) included in this review of non-pharmacological interventions for dry mouth which were divided into three comparisons. Eight studies were assessed at high risk of bias in at least one domain and the remaining study was at unclear risk of bias.Five small studies (total 153 participants, with dry mouth following radiotherapy treatment) compared acupuncture with placebo. Four were assessed at high risk and one at unclear risk of bias. Two trials reported outcome data for dry mouth in a form suitable for meta-analysis. The pooled estimate of these two trials (70 participants, low quality evidence) showed no difference between acupuncture and control in dry mouth symptoms (SMD -0.34, 95% CI -0.81 to 0.14, P value 0.17, I(2) = 39%) with the confidence intervals including both a possible reduction or a possible increase in dry mouth symptoms. Acupuncture was associated with more adverse effects (tiny bruises and tiredness which were mild and temporary). There was a very small increase in unstimulated whole saliva (UWS) at the end of 4 to 6 weeks of treatment (three trials, 71 participants, low quality evidence) (MD 0.02 ml/minute, 95% CI 0 to 0.04, P value 0.04, I(2) = 57%), and this benefit persisted at the 12-month follow-up evaluation (two trials, 54 participants, low quality evidence) (UWS, MD 0.06 ml/minute, 95% CI 0.01 to 0.11, P value 0.03, I(2) = 10%). For the outcome of stimulated whole saliva (SWS, three trials, 71 participants, low quality evidence) there was a benefit favouring acupuncture (MD 0.19 ml/minute, 95% CI 0.07 to 0.31, P value 0.002, I(2) = 1%) an effect which also persisted at the 12-month follow-up evaluation (SWS MD 0.28 ml/minute, 95% CI 0.09 to 0.47, P value 0.004, I(2) = 0%) (two trials, 54 participants, low quality evidence).Two small studies, both at high risk of bias, compared the use of an electrostimulation device with a placebo device in participants with Sjögren's Syndrome (total 101 participants). A further study, also at high risk of bias, compared acupuncture-like electrostimulation of different sets of points in participants who had previously been treated with radiotherapy. None of these studies reported the outcome of dry mouth. There was no difference between electrostimulation and placebo in the outcomes of UWS or SWS at the end of the 4-week treatment period in the one study (very low that provided data for these outcomes. No adverse effects were reported.A single study at high risk of bias, compared the stimulatory effect of powered versus manual toothbrushing and found no difference for the outcomes of UWS or SWS. AUTHORS' CONCLUSIONS: There is low quality evidence that acupuncture is no different from placebo acupuncture with regard to dry mouth symptoms, which is the most important outcome. This may be because there were insufficient participants included in the two trials to show a possible effect or it may be that there was some benefit due to 'placebo' acupuncture which could have biased the effect to the null. There is insufficient evidence to determine the effects of electrostimulation devices on dry mouth symptoms. It is well known that dry mouth symptoms may be problematic even when saliva production is increased, yet only two of the trials that evaluated acupuncture reported dry mouth symptoms, a worrying reporting bias. There is some low quality evidence that acupuncture results in a small increase in saliva production in patients with dry mouth following radiotherapy.There is insufficient evidence to determine the effects of electrostimulation devices on dry mouth symptoms or saliva production in patients with Sjögren's Syndrome. Reported adverse effects of acupuncture are mild and of short duration, and there were no reported adverse effects from electrostimulation.

Interventions for the management of dry mouth: topical therapies.

BACKGROUND: Xerostomia (the feeling of dry mouth) is a common symptom especially in older adults. Causes of dry mouth include medications, autoimmune disease (Sjögren's Syndrome), radiotherapy or chemotherapy for cancer, hormone disorders and infections. OBJECTIVES: To determine which topical treatments for dry mouth are effective in reducing this symptom. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (28 October 2011), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4 2011), MEDLINE via OVID (1950 to 28 October 2011), EMBASE via OVID (1980 to 28 October 2011), CINAHL via EBSCO (1980 to 28 October 2011), AMED via OVID (1985 to 28 October 2011), CANCERLIT via PubMed (1950 to 28 October 2011). SELECTION CRITERIA: We included randomised controlled trials of topical interventions such as lozenges, sprays, mouthrinses, gels, oils, chewing gum or toothpastes for the treatment of dry mouth symptom. We classified interventions into two broad categories, saliva stimulants and saliva substitutes, and these were compared with either placebo or another intervention. We included both parallel group and crossover trials. DATA COLLECTION AND ANALYSIS: Two or more review authors independently carried out data extraction and assessed risk of bias. Trial authors were contacted for additional information as required. MAIN RESULTS: Thirty-six randomised controlled trials involving 1597 participants met the inclusion criteria. Two trials compared saliva stimulants to placebo, nine trials compared saliva substitutes to placebo, five trials compared saliva stimulants directly with saliva substitutes, 18 trials directly compared two or more saliva substitutes, and two trials directly compared two or more saliva stimulants. Only one trial was at low risk of bias and 17 were at high risk of bias. Due to the range of interventions, comparisons and outcome measures in the trials, meta-analysis was possible for only a few comparisons. Oxygenated glycerol triester (OGT) saliva substitute spray shows evidence of effectiveness compared to an electrolyte spray (standardised mean difference (SMD) 0.77, 95% confidence interval (CI) 0.38 to 1.15) which corresponds to approximately a mean difference of 2 points on a 10-point visual analogue scale (VAS) for mouth dryness. Both integrated mouthcare systems (toothpaste + gel + mouthwash) and oral reservoir devices show promising results but there is insufficient evidence at present to recommend their use. Although chewing gum is associated with increased saliva production in the majority of those with residual capacity, there is no evidence that gum is more or less effective than saliva substitutes. AUTHORS' CONCLUSIONS: There is no strong evidence from this review that any topical therapy is effective for relieving the symptom of dry mouth. OGT spray is more effective than an aqueous electrolyte spray (SMD 0.77, 95% CI 0.38 to 1.15) which is approximately equivalent to a mean difference of 2 points on a 10-point VAS scale for mouth dryness. Chewing gums appear to increase saliva production in those with residual secretory capacity and may be preferred by patients, but there is no evidence that gum is better or worse than saliva substitutes. Integrated mouthcare systems and oral reservoir devices may be helpful but further research is required to confirm this. Well designed, adequately powered randomised controlled trials of topical interventions for dry mouth, which are designed and reported according to CONSORT guidelines, are required to provide evidence to guide clinical care. For many people the symptom of dry mouth is a chronic problem and trials should evaluate whether treatments are palatable, effective in reducing xerostomia, as well as the long-term effects of treatments on quality of life of those with chronic dry mouth symptoms.

Interventions for treating oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a common chronic autoimmune disease associated with cell-mediated immunological dysfunction. Symptomatic OLP is painful and complete healing is rare. OBJECTIVES: To assess the effectiveness and safety of any form of therapy for symptomatic OLP. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 26 January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 26 January 2011) and EMBASE via OVID (1980 to 26 January 2011). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: All randomised controlled clinical trials (RCTs) of therapy for symptomatic OLP which compared treatment with a placebo or between treatments or no intervention were considered in this review. DATA COLLECTION AND ANALYSIS: The titles and abstracts of all reports identified were scanned independently by two review authors. All studies meeting the inclusion criteria were assessed for risk of bias and data were extracted. For dichotomous outcomes, the estimates of effects of an intervention were expressed as risk ratios (RR) together with 95% confidence intervals. For continuous outcomes, mean differences (MD) and 95% confidence intervals were used to summarise the data for each group. The statistical unit was the patient. Meta-analyses were done only with studies of similar comparisons reporting the same outcome measures. MAIN RESULTS: 28 trials were included in this review. Pain is the primary outcome of this review because it is the indication for treatment of OLP, and therefore this review indicates as effective, only those treatments which significantly reduce pain. Although topical steroids are considered first line treatment for symptomatic OLP, we identified no RCTs that compared steroids with placebo. There is no evidence from the three trials of pimecrolimus that this treatment is better than placebo in reducing pain from OLP. There is weak evidence from two trials, at unclear and high risk of bias respectively, that aloe vera may be associated with a reduction in pain compared to placebo, but it was not possible to pool the pain data from these trials. There is weak and unreliable evidence from two small trials, at high risk of bias, that cyclosporin may reduce pain and clinical signs of OLP, but meta-analysis of these trials was not possible.There were five trials that compared steroids with calcineurin inhibitors, each evaluating a different pair of interventions. There is no evidence from these trials that there is a difference between treatment with steroids compared to calcineurin inhibitors with regard to reducing pain associated with OLP. From six trials there is no evidence that any specific steroid therapy is more or less effective at reducing pain compared to another type or dose of steroid. AUTHORS' CONCLUSIONS: Although topical steroids are considered to be first line treatment, we identified no RCTs that compared steroids with placebo in patients with symptomatic OLP. From the trials in this review there is no evidence that one steroid is any more effective than another. There is weak evidence that aloe vera may reduce the pain of OLP and improve the clinical signs of disease compared to placebo. There is weak and unreliable evidence that cyclosporin may reduce pain and clinical signs of OLP. There is no evidence that other calcineurin inhibitors reduce pain compared to either steroids or placebo. From the 28 trials included in this systematic review, the wide range of interventions compared means there is insufficient evidence to support the effectiveness of any specific treatment as being superior.

Interventions for preventing oral mucositis for patients with cancer receiving treatment.

BACKGROUND: Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). OBJECTIVES: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. SEARCH STRATEGY: Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 16 February 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 16 February 2011), EMBASE via OVID (1980 to 16 February 2011), CINAHL via EBSCO (1980 to 16 February 2011), CANCERLIT via PubMed (1950 to 16 February 2011), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 16 February 2011) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models. MAIN RESULTS: A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate. AUTHORS' CONCLUSIONS: Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.

Interventions for preventing oral mucositis for patients with cancer receiving treatment.

BACKGROUND: Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). OBJECTIVES: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. SEARCH STRATEGY: Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 1 June 2010), CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE via OVID (1950 to 1 June 2010), EMBASE via OVID (1980 to 1 June 2010), CINAHL via EBSCO (1980 to 1 June 2010), CANCERLIT via PubMed (1950 to 1 June 2010), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 1 June 2010) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models. MAIN RESULTS: A total of 131 studies with 10,514 randomised participants are now included. Nine interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These nine interventions were: allopurinol, aloe vera, amifostine, cryotherapy, glutamine (intravenous), honey, keratinocyte growth factor, laser, and polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste. AUTHORS' CONCLUSIONS: Nine interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.

Interventions for treating oral mucositis for patients with cancer receiving treatment.

BACKGROUND: Treatment of cancer is increasingly effective but associated with short and long term side effects. Oral side effects, including oral mucositis (mouth ulceration), remain a major source of illness despite the use of a variety of agents to treat them. OBJECTIVES: To assess the effectiveness of interventions for treating oral mucositis or its associated pain in patients with cancer receiving chemotherapy or radiotherapy or both. SEARCH STRATEGY: Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 1 June 2010), CENTRAL via The Cochrane Library (to Issue 2, 2010), MEDLINE via OVID (1950 to 1 June 2010), EMBASE via OVID (1980 to 1 June 2010), CINAHL via EBSCO (1980 to 1 June 2010), CANCERLIT via PubMed (1950 to 1 June 2010), OpenSIGLE (1980 to 1 June 2010) and LILACS via the Virtual Health Library (1980 to 1 June 2010) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA: All randomised controlled trials comparing agents prescribed to treat oral mucositis in people receiving chemotherapy or radiotherapy or both. Outcomes were oral mucositis, time to heal mucositis, oral pain, duration of pain control, dysphagia, systemic infection, amount of analgesia, length of hospitalisation, cost and quality of life. DATA COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and withdrawals. Risk of bias assessment was carried out on six domains. The Cochrane Collaboration statistical guidelines were followed and risk ratio (RR) values calculated using fixed-effect models (less than 3 trials in each meta-analysis). MAIN RESULTS: Thirty-two trials involving 1505 patients satisfied the inclusion criteria. Three comparisons for mucositis treatment including two or more trials were: benzydamine HCl versus placebo, sucralfate versus placebo and low level laser versus sham procedure. Only the low level laser showed a reduction in severe mucositis when compared with the sham procedure, RR 5.28 (95% confidence interval (CI) 2.30 to 12.13).Only 3 comparisons included more than one trial for pain control: patient controlled analgesia (PCA) compared to the continuous infusion method, therapist versus control, cognitive behaviour therapy versus control. There was no evidence of a difference in mean pain score between PCA and continuous infusion, however, less opiate was used per hour for PCA, mean difference 0.65 mg/hour (95% CI 0.09 to 1.20), and the duration of pain was less 1.9 days (95% CI 0.3 to 3.5). AUTHORS' CONCLUSIONS: There is weak and unreliable evidence that low level laser treatment reduces the severity of the mucositis. Less opiate is used for PCA versus continuous infusion. Further, well designed, placebo or no treatment controlled trials assessing the effectiveness of interventions investigated in this review and new interventions for treating mucositis are needed.