Antibiotics in dentistry--an update.

UNLABELLED: This review article considers the changes in antibiotic usage over the past 40 years. Perhaps the most significant advance is in the prophylactic use of these drugs to reduce the effect of dentally induced bacteraemia. A greater understanding of various dental infections and, in particular, the role of bacteria in the pathogenesis of periodontal disease, has led to further interest in the indications for these drugs as adjunctive measures. Whilst new indications for the use of antibiotics become more widespread, all members of the healthcare professions need to be aware that these drugs have significant adverse effects and their misuse can lead to life-threatening infection. CLINICAL RELEVANCE: Antibiotics have revolutionized the control of infectious diseases and have a significant role in dental practice. Dentists should be fully appraised of the benefits of these drugs and when they should be prescribed. Antibiotics usage should not be a substitute for interventional procedures, such as drainage of pus or removal of sources of infection. Indications for the use of these drugs as prophylactic measures are now reducing.

The prevalence of dysplasia and malignant lip lesions in transplant patients.

BACKGROUND: Solid organ transplant patients are at an increased risk of developing lip malignancies. The role of HLA mismatch as a risk factor for such changes has only been described in skin. METHODS: Lip lesions were evaluated in 403 solid organ transplant patients (immunosuppressed for at least 3 months) and findings compared to age and sex matched, otherwise healthy patients who acted as controls. HLA typing was provided for the transplant patients. All patients provided details of smoking history, alcohol consumption, skin type, as assessed by ease of burning to sunlight, and exposure to sunlight or other forms of ultraviolet radiation. RESULTS: Lip lesions were identified in 36 transplant patients and 29 were biopsied. Fourteen of the biopsies confirmed dysplastic or malignant changes. For the control patients, one lesion was identified as dysplastic. The prevalence of dysplastic and malignant lip lesions was significantly higher (P = 0.006) in the transplant patients when compared to controls. Risk factors for dysplastic/malignant changes in the transplant group included age (P = 0.01), smoking (P = 0.033) and HLA-B mismatch (P = 0.001). Lip covering provided a significant reduction (P = 0.045) in the development of lip changes. CONCLUSION: All transplant patients should be regularly screened for lip malignancies and consulted on smoking and sunlight exposure. HLA-B mismatch does appear to make these patients more susceptible to dysplastic/malignant changes.

Is oral health a risk for malignant disease?

UNLABELLED: Poor oral health has been associated with a variety of systemic diseases. More recent evidence suggests that the extent and severity of periodontal disease and tooth loss may be associated with an increased risk of malignant disease. An association between poor oral health, smoking, increased alcohol consumption as a risk for oral cancer is well established. Associations between oral health and tooth loss with gastric, lung and pancreatic cancers are explored. Some of the associations need further evaluation before patients are warned about their periodontal health increasing the risk of malignant changes elsewhere in the body. The smoking factor may have a commonality linking oral health with an increased risk for malignant disease. CLINICAL RELEVANCE: This paper reviews the association between oral health (especially the extent and severity of periodontal disease and tooth loss) as a risk for certain malignancies.

Does periodontal treatment improve general health?

UNLABELLED: The association between periodontal disease and various systemic conditions raises the question of the impact of periodontal therapy on general health. There is increasing evidence that periodontal intervention can reduce the prevalence of an adverse pregnancy outcome, improve glycaemic control in diabetics, reduce systemic markers of inflammation, lower cholesterol levels and improve vascular endothelial function. The magnitude of the impact of periodontal therapy on these modalities needs further quantification/study. Despite such reservations, there are indications that any form of periodontal treatment may have outcomes that extend beyond improving life expectancy of the dentition. CLINICAL RELEVANCE: This article reviews the possible impact of periodontal therapy on a variety of systemic conditions and evaluates potential benefits.

Malignant disease and the delivery of dental care.

UNLABELLED: Patients diagnosed or being treated for malignant disease can neglect their dental care and be reluctant to undertake dental treatment. This article considers the dental problems that may arise in such patients and how they can be managed. Chemotherapy and its sequelae are the main challenges to the delivery of routine dental care. For such patients, it is important to liaise with their oncologists to obtain an up-to-date haematological profile and time frame for any future treatments. For all such patients, dental care may be neglected, but it is important that dental and oral health is maintained. CLINICAL RELEVANCE: This article reviews the possible impact that malignant disease and its treatment can have on the delivery of dental care. Chemotherapy-induced bone marrow depression is likely to have the most profound effect on routine dental treatment.

Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain.

BACKGROUND: There has been a trend over recent years for combining a nonsteroidal antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain management. However, therapeutic superiority of the combination of paracetamol and an NSAID over either drug alone remains controversial. We evaluated the efficacy of the combination of paracetamol and an NSAID versus either drug alone in various acute pain models. METHODS: A systematic literature search of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and PubMed covering the period from January 1988 to June 2009 was performed to identify randomized controlled trials in humans that specifically compared combinations of paracetamol with various NSAIDs versus at least 1 of these constituent drugs. Identified studies were stratified into 2 groups: paracetamol/NSAID combinations versus paracetamol or NSAIDs. We analyzed pain intensity scores and supplemental analgesic requirements as primary outcome measures. In addition, each study was graded for quality using a validated scale. RESULTS: Twenty-one human studies enrolling 1909 patients were analyzed. The NSAIDs used were ibuprofen (n = 6), diclofenac (n = 8), ketoprofen (n = 3), ketorolac (n = 1), aspirin (n = 1), tenoxicam (n = 1), and rofecoxib (n = 1). The combination of paracetamol and NSAID was more effective than paracetamol or NSAID alone in 85% and 64% of relevant studies, respectively. The pain intensity and analgesic supplementation was 35.0% +/- 10.9% and 38.8% +/- 13.1% lesser, respectively, in the positive studies for the combination versus paracetamol group, and 37.7% +/- 26.6% and 31.3% +/- 13.4% lesser, respectively, in the positive studies for the combination versus the NSAID group. No statistical difference in median quality scores was found between experimental groups. CONCLUSION: Current evidence suggests that a combination of paracetamol and an NSAID may offer superior analgesia compared with either drug alone.

Full-Mouth Disinfection.

Full-mouth disinfection is a relatively new technique for the management of patients, especially those with moderate to severe chronic periodontitis. In this paper, the technique is reviewed and efficacy evaluated. The methodology and possible outcomes are illustrated with a case report.

Drug interactions in dentistry.

UNLABELLED: An increasing number of our patients are on medication of various types. This increase in prescribed medicines also raises the significant issue of potential drug interactions between those drugs used in dental practice and those taken by the patient. This article addresses those interactions and, where appropriate, puts them into perspective and attempts to quantify the risk. Mechanisms of relevant drug interactions are also discussed. Certain categories of drugs are more likely to be involved in interactions and again these are highlighted. Drug interactions relevant to dentistry can for the most part be prevented. A careful drug history should be taken from each patient and updated on a regular basis. CLINICAL RELEVANCE: This article highlights drug interactions that can arise in dental practice and how they can be avoided and managed.

Malignant disease and dentistry.

UNLABELLED: Reports of an ageing population, increasing incidence of malignancy and improved treatments mean that dentists may have an increasing number of patients with, or who have recovered from, a malignancy. Dental professionals are expected to have an understanding of this important disease group so that appropriate dental care can be provided safely. In this first of three articles, we shall describe the important epidemiological and clinical features of the commonest malignancies in the United Kingdom. CLINICAL RELEVANCE: Dentists should understand the clinical implications of a patient with, or recovering from, a malignancy. This article gives a summary of the relevant features of the commonest malignancies.

Effect of malignant disease and treatments on oral structures.

UNLABELLED: There has been an increase in the diagnosis and treatment options for malignant diseases. In this article we provide an overview of the impact of the treatments of malignant diseases on the oral structures. Whilst some of the complications, such as oral mucositis and oral infection, are of short duration and respond once chemotherapy has been completed, other treatments have a prolonged effect. Of particular concern is the effect of bisphosphonates on bone turnover and the risk of osteonecrosis on the jaw and hormones affecting the periodontal tissues. These unwanted effects all impact upon the quality of life of many patients diagnosed with malignant disease. CLINICAL RELEVANCE: Treatments of malignant diseases can have a profound effect on oral structures and functions. All members of the dental team need to be aware of adverse effects arising from such treatments and how they can affect oral function and quality of life.

Dental treatment, antibiotic cover and infective endocarditis: a major rethink.

UNLABELLED: The NICE Guidelines on Prophylaxis against Infective Endocarditis were published early this year. In this review, consideration is given to the evidence that the Working Party evaluated in arriving at their recommendations. CLINICAL RELEVANCE: The NICE Guidelines will have a very significant impact upon clinical practice. Antibiotic cover to prevent infective endocarditis prior to dental treatment has been a confusing and contentious issue. All members of the dental team should welcome these Guidelines which will impact upon the delivery of dental care to many categories of patient.

Analgesic efficacy of the cyclooxygenase-inhibiting nitric oxide donor AZD3582 in postoperative dental pain: Comparison with naproxen and rofecoxib in two randomized, double-blind, placebo-controlled studies.

OBJECTIVE: This study assessed the analgesic efficacy of single doses of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate (AZD3582) in acute postoperative dental pain after the removal of an impacted mandibular third molar (ie, wisdom tooth). METHODS: Two randomized, placebo-controlled, double-blind studies were performed. In a dose-finding study, 242 patients were randomized to AZD3582 375, 750, 1500, or 2250 mg (n = 41, 37, 42, and 41, respectively); naproxen 500 mg (n = 39); or placebo (n = 42). In a comparator study, 282 patients were randomized to AZD3582 500 mg (n = 78) or 750 mg (n = 83), rofecoxib 50 mg (n = 80), or placebo (n = 41). Primary outcomes included time to rescue medication, time to pain relief, and mean pain intensity difference (MPID), as well as safety profile. Pain was rated on a visual analog scale. RESULTS: In the dose-finding study, 52% (126/242) were women; the mean (SD) age was 25.1 (4) years, mean weight was 69.0 kg, and the mean (SD) body mass index (BMI) was 23.7 (3) kg/m2. In the comparator study, 58% (164/282) were women; the mean (SD) age was 27 (6.4) years, mean weight was 71 kg, and mean (SD) BMI was 24.2 (3) kg/m2. In the dose-finding study, the AZD3582 750-, 1500-, and 2250-mg groups were superior to placebo in the primary variables "time to rescue medication (0-8 hours)" (hazard ratios [HRs] [95% CIs], 0.17 [0.07-0.42], P < 0.003; 0.23 [0.11-0.50], P < 0.001; and 0.15 [0.06-0.36], P < 0.001, respectively), "time to meaningful pain relief" (HRs [95% CIs], 3.42 [1.87-6.25], P < 0.003; 2.49 [1.37-4.50], P < 0.003; and 3.07 [1.70-5.55], P < 0.001, respectively), and MPID (analysis of covariance [ANCOVA] least squares mean [LSM] differences [95% CIs], 25.8 [17.3-34.4], P < 0.003; 20.4 [12.1-28.7], P < 0.003; and 29.3 [20.9-37.6], P < 0.001, respectively). AZD3582 and naproxen did not show any statistically significant differences for the 3 primary variables, except that naproxen was superior to the AZD3582 375-mg dose for the variables time to meaningful pain relief (HR difference, 0.48 [95% CI, 0.29-0.78], P < 0.004) and MPID (difference in ANCOVA LSM, -10.2, [95% CI, -18.2 to -2.2], P < 0.012). The median times to meaningful pain relief were 115 minutes for AZD3582 375 mg, 66 minutes for 750 mg, 85 minutes for 1500 mg, 81 minutes for 2250 mg, and 162 minutes for placebo (P = NS, P = 0.003, P < 0.003, and P < 0.001, respectively). The median time to first rescue medication was 144 minutes for placebo, and <50% of the subjects on any of the AZD3582 doses or naproxen took rescue medication within 8 hours after dosing. In the comparator study, AZD3582 750 mg was superior to placebo in "time to rescue medication (0-24 hours)" (HR [95% CI], 0.4 [0.3-0.6], P < 0.001), "time to confirmed perceptible pain relief" (2.1 [1.1-3.8], P = 0.02), and MPID (11.9 [4.2-19.5], P = 0.002). However, inferiority of AZD3582 to rofecoxib for MPID could not be excluded (tolerance limit of 10 mm; P = NS for noninferiority testing). The median times to confirmed perceptible pain relief were 45 minutes for AZD3582 500 mg, 40 minutes for 750 mg, and 37 minutes for rofecoxib. The median times to first rescue medication were 218 minutes for AZD3582 500 mg, 365 minutes for 750 mg, 635 minutes for rofecoxib, and 90 minutes for placebo. Overall, AZD3582 was well tolerated. However, an effect on orthostatic blood pressure could not be excluded because there seemed to be more subjects with dizziness and orthostatic blood pressure reduction who were administered AZD3582 > or =750 mg. The proportions of patients with vertigo and decreased orthostatic blood pressure each group were as follows: AZD3582 500 mg, 6%; AZD3582 750 mg, 12%; rofecoxib, 3%; and placebo, 5%. CONCLUSIONS: AZD3582 750 mg had similar analgesic efficacy as equimolar doses of naproxen, but noninferiority to rofecoxib was not demonstrated.

Modulation of oral squamous cell carcinoma incidence in rats via diet and a novel calcium channel antagonist.

An unexpected dose related increase in oral squamous cell carcinomas was observed in a standard 2-year carcinogenicity study with a novel calcium channel blocker, in which Wistar rats received daily doses of 0, 1.5, 7, 20, or 40 mg/kg of the compound mixed with a standard diet containing fibers from barley. This finding was associated with an increased incidence of severe (destructive) periodontitis and the formation of oro-nasal fistulae at the 2 highest doses. Five assays of the compound for genotoxicity were negative indicating that a genotoxic effect was highly improbable. To investigate the underlying pathogenic mechanisms a second 2-year study in the same strain of rats was initiated and the influence of the diet and/or a possible local irritancy by the drug was assessed. In this second study the compound was administered by oral gavage at daily doses of 0, 7, or 40 mg/kg (later reduced to 20 mg/kg due to systemic intolerance) to rats maintained either on the standard diet or on a low fiber diet assumed to be less aggressive in terms of inducing periodontal lesions. Dose dependent gingival overgrowth (a class-related effect) was observed in the incisor and molar teeth area of all treated groups but was independent of the diet used. No oral tumors were found in the standard diet or low fiber diet controls and all treatment groups fed the low fiber diet, whereas in the high-dose group fed the standard diet a total of 8 oral squamous cell carcinomas were detected in association with an increased incidence of severe periodontitis. These results indicate that the increased incidence of squamous cell carcinomas observed upon chronic administration of the compound is not due to a direct tumorigenic effect of the drug. Tumor formation is attributable to severe periodontal disease favored by the diet and class related gingival overgrowth.

Risk factors for gingival overgrowth in patients medicated with ciclosporin in the absence of calcium channel blockers.

OBJECTIVES: This study investigates the effect of a range of potential risk factors on the severity of gingival overgrowth in transplant patients medicated with ciclosporin in the absence of any calcium channel blockers. MATERIALS AND METHODS: One hundred dentate solid organ transplants medicated with ciclosporin (but not calcium channel blockers or phenytoin) were recruited for the study. Demographic, pharmacological and periodontal data were recorded and gingival overgrowth assessed from stone models. RESULTS: Univariate analysis identified the duration of transplant, papilla bleeding index, creatinine serum concentration, azathioprine and prednisolone dosage as risk factors for overgrowth severity. Multivariate modelling, excluding the periodontal parameters, gave a predictive model that included dosages of ciclosporin, azathioprine, prednisolone and weight (p<0.0001, adjusted-R2=19%). Adding the periodontal variables strengthened the model (p<0.0001, adjusted-R2=34.5%). CONCLUSION: The explanatory models in this study contain a number of variables that moderate inflammation (azathioprine and prednisolone) or are markers of it (papilla bleeding index). Dosage of each of the three immunosuppressants was identified as a risk factor for the severity of gingival change. This observation appears to have been masked by the effects of the calcium channel blockers in earlier studies.

The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis.

Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.