Treatment of periodontitis for glycaemic control in people with diabetes mellitus.

BACKGROUND: Glycaemic control is a key component in diabetes mellitus (diabetes) management. Periodontitis is the inflammation and destruction of the underlying supporting tissues of the teeth. Some studies have suggested a bidirectional relationship between glycaemic control and periodontitis.  Treatment for periodontitis involves subgingival instrumentation, which is the professional removal of plaque, calculus, and debris from below the gumline using hand or ultrasonic instruments. This is known variously as scaling and root planing, mechanical debridement, or non-surgical periodontal treatment. Subgingival instrumentation is sometimes accompanied by local or systemic antimicrobials, and occasionally by surgical intervention to cut away gum tissue when periodontitis is severe. This review is part one of an update of a review published in 2010 and first updated in 2015, and evaluates periodontal treatment versus no intervention or usual care.  OBJECTIVES: To investigate the effects of periodontal treatment on glycaemic control in people with diabetes mellitus and periodontitis. SEARCH METHODS: An information specialist searched six bibliographic databases up to 7 September 2021 and additional search methods were used to identify published, unpublished, and ongoing studies.  SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of people with type 1 or type 2 diabetes mellitus and a diagnosis of periodontitis that compared subgingival instrumentation (sometimes with surgical treatment or adjunctive antimicrobial therapy or both) to no active intervention or 'usual care' (oral hygiene instruction, education or support interventions, and/or supragingival scaling (also known as PMPR, professional mechanical plaque removal)). To be included, the RCTs had to have lasted at least 3 months and have measured HbA1c (glycated haemoglobin). DATA COLLECTION AND ANALYSIS: At least two review authors independently examined the titles and abstracts retrieved by the search, selected the included trials, extracted data from included trials, and assessed included trials for risk of bias. Where necessary and possible, we attempted to contact study authors. Our primary outcome was blood glucose levels measured as glycated (glycosylated) haemoglobin assay (HbA1c), which can be reported as a percentage of total haemoglobin or as millimoles per mole (mmol/mol). Our secondary outcomes included adverse effects, periodontal indices (bleeding on probing, clinical attachment level, gingival index, plaque index, and probing pocket depth), quality of life, cost implications, and diabetic complications. MAIN RESULTS: We included 35 studies, which randomised 3249 participants to periodontal treatment or control. All studies used a parallel-RCT design and followed up participants for between 3 and 12 months. The studies focused on people with type 2 diabetes, other than one study that included participants with type 1 or type 2 diabetes. Most studies were mixed in terms of whether metabolic control of participants at baseline was good, fair, or poor. Most studies were carried out in secondary care.  We assessed two studies as being at low risk of bias, 14 studies at high risk of bias, and the risk of bias in 19 studies was unclear. We undertook a sensitivity analysis for our primary outcome based on studies at low risk of bias and this supported the main findings. Moderate-certainty evidence from 30 studies (2443 analysed participants) showed an absolute reduction in HbA1c of 0.43% (4.7 mmol/mol) 3 to 4 months after treatment of periodontitis (95% confidence interval (CI) -0.59% to -0.28%; -6.4 mmol/mol to -3.0 mmol/mol). Similarly, after 6 months, we found an absolute reduction in HbA1c of 0.30% (3.3 mmol/mol) (95% CI -0.52% to -0.08%; -5.7 mmol/mol to -0.9 mmol/mol; 12 studies, 1457 participants), and after 12 months, an absolute reduction of 0.50% (5.4 mmol/mol) (95% CI -0.55% to -0.45%; -6.0 mmol/mol to -4.9 mmol/mol; 1 study, 264 participants). Studies that measured adverse effects generally reported that no or only mild harms occurred, and any serious adverse events were similar in intervention and control arms. However, adverse effects of periodontal treatments were not evaluated in most studies. AUTHORS' CONCLUSIONS: Our 2022 update of this review has doubled the number of included studies and participants, which has led to a change in our conclusions about the primary outcome of glycaemic control and in our level of certainty in this conclusion. We now have moderate-certainty evidence that periodontal treatment using subgingival instrumentation improves glycaemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment versus no treatment/usual care are unlikely to change the overall conclusion reached in this review.

Mobile health applications for managing atrial fibrillation for healthcare professionals and patients: a systematic review.

AIMS: A plethora of mobile health applications (m-health apps) to support healthcare are available for both patients and healthcare professionals (HCPs) but content and quality vary considerably and few have undergone formal assessment. The aim is to systematically review the literature on m-health apps for managing atrial fibrillation (AF) that examine the impact on knowledge of AF, patient and HCP behaviour, patients' quality-of-life, and user engagement. METHODS AND RESULTS: MEDLINE, EMBASE, CINAHL, and PsychInfo were searched from 1 January 2005 to 5 September 2019, with hand-searching of clinical trial registers and grey literature. Studies were eligible for inclusion if they reported changes in any of the following: (i) knowledge of AF; (ii) provider behaviour (e.g. guideline adherence); (iii) patient behaviour (e.g. medication adherence); (iv) patient quality-of-life; and (v) user engagement. Two reviewers independently assessed articles for eligibility. A narrative review was undertaken as included studies varied widely in their design, interventions, comparators, and outcomes. Seven studies were included; six m-health apps aimed at patients and one at HCPs. Mobile health apps ranged widely in design, features, and method of delivery. Four studies reported patient knowledge of AF; three demonstrated significant knowledge improvement post-intervention or compared to usual care. One study reported greater HCP adherence to oral anticoagulation guidelines after m-health app implementation. Two studies reported on patient medication adherence and quality-of-life; both showed improved quality-of-life post-intervention but only one observed increased adherence. Regarding user engagement, five studies reported patient perspectives on usability, three on acceptability, and one on feasibility; overall all m-health apps were rated positively. CONCLUSION: Mobile health apps demonstrate improvements in patient knowledge, behaviour, and quality of life. Studies formally evaluating the impact of m-health on HCP behaviour are scarce and larger-scale studies with representative patient cohorts, appropriate comparators, and longer-term assessment of the impact of m-health apps are warranted.

Interventions for treating burning mouth syndrome.

BACKGROUND: Burning mouth syndrome (BMS) is a term used for oral mucosal pain (burning pain or discomfort in the tongue, lips or entire oral cavity) without identifiable cause. General population prevalence varies from 0.1% to 3.9%. Many BMS patients indicate anxiety, depression, personality disorders and impaired quality of life (QoL). This review updates the previous versions published in 2000 and 2005. OBJECTIVES: To determine the effectiveness and safety of any intervention versus placebo for symptom relief and changes in QoL, taste, and feeling of dryness in people with BMS. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 31 December 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11) in the Cochrane Library (searched 31 December 2015), MEDLINE Ovid (1946 to 31 December 2015), and Embase Ovid (1980 to 31 December 2015). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. We placed no restrictions on the language or date of publication when searching the electronic databases SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any treatment against placebo in people with BMS. The primary outcomes were symptom relief (pain/burning) and change in QoL. Secondary outcomes included change in taste, feeling of dryness, and adverse effects. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Outcome data were analysed as short-term (up to three months) or long-term (three to six months). MAIN RESULTS: We included 23 RCTs (1121 analysed participants; 83% female). Interventions were categorised as: antidepressants and antipsychotics, anticonvulsants, benzodiazepines, cholinergics, dietary supplements, electromagnetic radiation, physical barriers, psychological therapies, and topical treatments.Only one RCT was assessed at low risk of bias overall, four RCTs' risk of bias was unclear, and 18 studies were at high risk of bias. Overall quality of the evidence for effectiveness was very low for all interventions and all outcomes.Twenty-one RCTs assessed short-term symptom relief. There is very low-quality evidence of benefit from electromagnetic radiation (one RCT, 58 participants), topical benzodiazepines (two RCTs, 111 participants), physical barriers (one RCT, 50 participants), and anticonvulsants (one RCT, 100 participants). We found insufficient/contradictory evidence regarding the effectiveness of antidepressants, cholinergics, systemic benzodiazepines, dietary supplements or topical treatments. No RCT assessing psychological therapies evaluated short-term symptom relief.Four studies assessed long-term symptom relief. There is very low-quality evidence of a benefit from psychological therapies (one RCT, 30 participants), capsaicin oral rinse (topical treatment) (one RCT, 18 participants), and topical benzodiazepines (one RCT, 66 participants). We found no evidence of a difference for dietary supplements or lactoperoxidase oral rinse. No studies assessing antidepressants, anticonvulsants, cholinergics, electromagnetic radiation or physical barriers evaluated long-term symptom relief.Short-term change in QoL was assessed by seven studies (none long-term).The quality of evidence was very low. A benefit was found for electromagnetic radiation (one RCT, 58 participants), however findings were inconclusive for antidepressants, benzodiazepines, dietary supplements and physical barriers.Secondary outcomes (change in taste and feeling of dryness) were only assessed short-term, and the findings for both were also inconclusive.With regard to adverse effects, there is very low-quality evidence that antidepressants increase dizziness and drowsiness (one RCT, 37 participants), and that alpha lipoic acid increased headache (two RCTs, 118 participants) and gastrointestinal complaints (3 RCTs, 138 participants). We found insufficient/contradictory evidence regarding adverse events for anticonvulsants or benzodiazepines. Adverse events were poorly reported or unreported for cholinergics, electromagnetic radiation, and psychological therapies. No adverse events occurred from physical barriers or topical therapy use. AUTHORS' CONCLUSIONS: Given BMS' potentially disabling nature, the need to identify effective modes of treatment for sufferers is vital. Due to the limited number of clinical trials at low risk of bias, there is insufficient evidence to support or refute the use of any interventions in managing BMS. Further clinical trials, with improved methodology and standardised outcome sets are required in order to establish which treatments are effective. Future studies are encouraged to assess the role of treatments used in other neuropathic pain conditions and psychological therapies in the treatment of BMS.

Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy.

BACKGROUND: Oral cancers are the sixth most common cancer worldwide, yet the prognosis following a diagnosis of oral cavity or oropharyngeal cancers remains poor, with approximately 50% survival at five years. Despite a sharp increase in research into molecularly targeted therapies and a rapid expansion in the number of clinical trials assessing new targeted therapies, their value for treating oral cancers is unclear. Therefore, it is important to summarise the evidence to determine the efficacy and toxicity of targeted therapies and immunotherapies for the treatment of these cancers. OBJECTIVES: To assess the effects of molecularly targeted therapies and immunotherapies, in addition to standard therapies, for the treatment of oral cavity or oropharyngeal cancers. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health Group Trials Register (to 3 February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 1), MEDLINE via Ovid (1946 to 3 February 2015) and EMBASE via Ovid (1980 to 3 February 2015). We searched the US National Institutes of Health Trials Register (clinicaltrials.gov), the World Health Organization Clinical Trials Registry Platform, the American Society of Clinical Oncology conference abstracts and the Radiation Therapy Oncology Group clinical trials protocols for ongoing trials. We placed no restrictions on the language or date of publication. SELECTION CRITERIA: We included randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared targeted therapy or immunotherapy, plus standard therapy, with standard therapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies. We attempted to contact study authors for missing data or clarification where necessary. We combined sufficiently similar studies in meta-analyses using random-effects models when there were at least four studies and fixed-effect models when fewer than four studies. We obtained or calculated a hazard ratio (HR) and 95% confidence interval (CI) for the primary outcomes where possible. For dichotomous outcomes, we reported risk ratios (RR) and 95% CIs. MAIN RESULTS: Twelve trials (2488 participants) satisfied the inclusion criteria. In the included trials, 12% of participants (298 participants) had tumours of the oral cavity and 59% (1468 participants) had oropharyngeal tumours. The remaining 29% had tumours of the larynx or hypopharynx and less than 1% had tumours at other sites.No included trial was at low risk of bias; seven had an unclear risk of bias, and five had a high risk of bias. We grouped trials by intervention type into three main comparisons: standard therapy plus epidermal growth factor receptor monoclonal antibody (EGFR mAb) therapy (follow-up period 24 to 70 months); standard therapy plus tyrosine kinase inhibitors (TKIs) (follow-up period 40 to 60 months) and standard therapy plus immunotherapy (follow-up period 24 to 70 months), all versus standard therapy alone.Moderate quality evidence showed that EGFR mAb therapy may result in 18% fewer deaths when added to standard therapy (HR of mortality 0.82; 95% CI 0.69 to 0.97; 1421 participants, three studies, 67% oropharyngeal tumours, 2% oral cavity tumours).There was also moderate quality evidence that EGFR mAb may result in 32% fewer locoregional failures when added to radiotherapy (RT) (HR 0.68; 95% CI 0.52 to 0.89; 424 participants, one study, 60% oropharyngeal tumours).A subgroup analysis separating studies by type of standard therapy (radiotherapy (RT) or chemoradiotherapy (CRT)) showed some evidence that adding EGFR mAb therapy to RT may result in a 30% reduction in the number of people whose disease progresses (HR 0.70; 95% CI 0.54 to 0.91; 424 participants, one study, 60% oropharyngeal tumours, unclear risk of bias). For the subgroup comparing EGFR mAb plus CRT with CRT alone there was insufficient evidence to determine whether adding EGFR mAb therapy to CRT impacts on progression-free survival (HR 1.08; 95% CI 0.89 to 1.32; 891 participants, one study, 70% oropharyngeal tumours, high risk of bias). The high subgroup heterogeneity meant that we were unable to pool these subgroups.There was evidence that adding cetuximab to standard therapy may result in increased skin toxicity and rash (RR 6.56; 95% CI 5.35 to 8.03; 1311 participants, two studies), but insufficient evidence to determine any difference in skin toxicity and rash in the case of nimotuzumab (RR 1.06; 95% CI 0.85 to 1.31; 92 participants, one study).There was insufficient evidence to determine whether TKIs added to standard therapy impacts on overall survival (HR 0.99; 95% CI 0.62 to 1.57; 271 participants, two studies; very low quality evidence), locoregional control (HR 0.89; 95% CI 0.53 to 1.49; 271 participants, two studies; very low quality evidence), disease-free survival (HR 1.51; 95% CI 0.61 to 3.71; 60 participants, one study; very low quality evidence) or progression-free survival (HR 0.80; 95% CI 0.51 to 1.28; 271 participants, two studies; very low quality evidence). We did find evidence of an increase in skin rash (erlotinib: RR 6.57; 95% CI 3.60 to 12.00; 191 participants, one study; lapatinib: RR 2.02; 95% CI 1.23 to 3.32; 67 participants, one study) and gastrointestinal complaints (lapatinib: RR 15.53; 95% CI 2.18 to 110.55; 67 participants, one study).We found very low quality evidence from one small trial that adding recombinant interleukin (rIL-2) to surgery may increase overall survival (HR 0.52; 95% CI 0.31 to 0.87; 201 participants, 62% oral cavity tumours, 38% oropharyngeal tumours) and there was insufficient evidence to determine whether rIL-2 impacts on adverse effects. AUTHORS' CONCLUSIONS: We found some evidence that adding EGFR mAb to standard therapy may increase overall survival, progression-free survival and locoregional control, while resulting in an increase in skin toxicity for some mAb (cetuximab).There is insufficient evidence to determine whether adding TKIs to standard therapies changes any of our primary outcomes.Very low quality evidence from a single study suggests that rIL-2 combined with surgery may increase overall survival compared with surgery alone.

Treatment of periodontal disease for glycaemic control in people with diabetes mellitus.

BACKGROUND: Glycaemic control is a key issue in the care of people with diabetes mellitus (DM). Periodontal disease is the inflammation and destruction of the underlying supporting tissues of the teeth. Some studies have suggested a bidirectional relationship between glycaemic control and periodontal disease. This review updates the previous version published in 2010. OBJECTIVES: The objective is to investigate the effect of periodontal therapy on glycaemic control in people with diabetes mellitus. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 31 December 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2014, Issue 11), MEDLINE via OVID (1946 to 31 December 2014), EMBASE via OVID (1980 to 31 December 2014), LILACS via BIREME (1982 to 31 December 2014), and CINAHL via EBSCO (1937 to 31 December 2014). ZETOC (1993 to 31 December 2014) and Web of Knowledge (1990 to 31 December 2014) were searched for conference proceedings. Additionally, two periodontology journals were handsearched for completeness, Annals of Periodontology (1996 to 2003) and Periodontology 2000 (1993 to 2003). We searched the US National Institutes of Health Trials Registry (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of people with type 1 or type 2 DM (T1DM/T2DM) with a diagnosis of periodontitis. Interventions included periodontal treatments such as mechanical debridement, surgical treatment and antimicrobial therapy. Two broad comparisons were proposed:1. periodontal therapy versus no active intervention/usual care;2. periodontal therapy versus alternative periodontal therapy. DATA COLLECTION AND ANALYSIS: For this review update, at least two review authors independently examined the titles and abstracts retrieved by the search, selected the included trials, extracted data from included trials and assessed included trials for risk of bias.Our primary outcome was blood glucose levels measured as glycated (glycosylated) haemoglobin assay (HbA1c).Our secondary outcomes included adverse effects, periodontal indices (bleeding on probing (BOP), clinical attachment level (CAL), gingival index (GI), plaque index (PI) and probing pocket depth (PPD)), cost implications and diabetic complications. MAIN RESULTS: We included 35 studies (including seven from the previous version of the review), which included 2565 participants in total. All studies used a parallel RCT design, and 33 studies (94%) only targeted T2DM patients. There was variation between studies with regards to included age groups (ages 18 to 80), duration of follow-up (3 to 12 months), use of antidiabetic therapy, and included participants' baseline HbA1c levels (from 5.5% to 13.1%).We assessed 29 studies (83%) as being at high risk of bias, two studies (6%) as being at low risk of bias, and four studies (11%) as unclear. Thirty-four of the studies provided data suitable for analysis under one or both of the two comparisons.Comparison 1: low quality evidence from 14 studies (1499 participants) comparing periodontal therapy with no active intervention/usual care demonstrated that mean HbA1c was 0.29% lower (95% confidence interval (CI) 0.48% to 0.10% lower) 3 to 4 months post-treatment, and 0.02% lower after 6 months (five studies, 826 participants; 95% CI 0.20% lower to 0.16% higher).Comparison 2: 21 studies (920 participants) compared different periodontal therapies with each other. There was only very low quality evidence for the multiple head-to-head comparisons, the majority of which were unsuitable to be pooled, and provided no clear evidence of a benefit for one periodontal intervention over another. We were able to pool the specific comparison between scaling and root planing (SRP) plus antimicrobial versus SRP and there was no consistent evidence that the addition of antimicrobials to SRP was of any benefit to delivering SRP alone (mean HbA1c 0.00% lower: 12 studies, 450 participants; 95% CI 0.22% lower to 0.22% higher) at 3-4 months post-treatment, or after 6 months (mean HbA1c 0.04% lower: five studies, 206 patients; 95% CI 0.41% lower to 0.32% higher).Less than half of the studies measured adverse effects. The evidence was insufficient to conclude whether any of the treatments were associated with harm. No other patient-reported outcomes (e.g. quality of life) were measured by the included studies, and neither were cost implications or diabetic complications.Studies showed varying degrees of success with regards to achieving periodontal health, with some showing high levels of residual inflammation following treatment. Statistically significant improvements were shown for all periodontal indices (BOP, CAL, GI, PI and PPD) at 3-4 and 6 months in comparison 1; however, this was less clear for individual comparisons within the broad category of comparison 2. AUTHORS' CONCLUSIONS: There is low quality evidence that the treatment of periodontal disease by SRP does improve glycaemic control in people with diabetes, with a mean percentage reduction in HbA1c of 0.29% at 3-4 months; however, there is insufficient evidence to demonstrate that this is maintained after 4 months.There was no evidence to support that one periodontal therapy was more effective than another in improving glycaemic control in people with diabetes mellitus.In clinical practice, ongoing professional periodontal treatment will be required to maintain clinical improvements beyond 6 months. Further research is required to determine whether adjunctive drug therapies should be used with periodontal treatment. Future RCTs should evaluate this, provide longer follow-up periods, and consider the inclusion of a third 'no treatment' control arm.Larger, well conducted and clearly reported studies are needed in order to understand the potential of periodontal treatment to improve glycaemic control among people with diabetes mellitus. In addition, it will be important in future studies that the intervention is effective in reducing periodontal inflammation and maintaining it at lowered levels throughout the period of observation.