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Robin A Seymour

Publications and source records attributed to Robin A Seymour.

10 recordsLinked to original sources
PubMed2006

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.

Adolescent↗
PubMed2005

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.

Administration, Oral↗
PubMed2005

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.

Anti-Inflammatory Agents↗
PubMed2005

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.

Acute Disease↗
PubMed2004

Sedation with midazolam leads to reduced pain after dental surgery.

UNLABELLED: Our principal objective in this study was to evaluate the potential pain reducing effect of i.v. midazolam in patients undergoing oral surgery. One-hundred-twenty-five patients with impacted mandibular third molars requiring removal under local anesthetic were randomized into 2 groups. The first group (n = 64) was administered i.v. midazolam by titration until a clinical end-point of conscious sedation followed by local anesthetic before surgery; the second group (n = 61) was the control and was administered only local anesthetic before surgery. The surgery was performed in a standardized manner in both groups by the same surgeon. Outcome measures were four primary end-points: pain intensity as assessed by a 100-mm visual analogue scale and a 4-point categorized scale hourly for 8 h, time to first analgesic, total analgesic (ibuprofen) consumption over the first 48 h, and a 5-point categorical patient global assessment scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent). Throughout the 8-h investigation period, patients in the midazolam group reported significantly lower pain intensity scores than those in the control group (19.0 +/- 13.2 mm versus 28.1 +/- 12.8 mm, P < 0.05). The patients in the midazolam group also reported significantly longer time to first analgesic (165.5 +/- 56.5 min versus 202.2 +/- 79.0 min, P < 0.05), less analgesic consumption (1275 +/- 364 mg versus 1688 +/- 407 mg, P < 0.001) and better patient global assessment (3.34 +/- 0.8 versus 2.4 +/- 0.9, P < 0.001). We conclude that systemically administered midazolam is effective in reducing postoperative pain after third molar surgery. IMPLICATIONS: In this observer blinded study, we found that i.v. midazolam treatment (0.09 mg/kg) has a pain-reducing effect after third molar surgery, thus improving postoperative pain management.

Adult↗
PubMed2004

Current concepts in periodontal pathogenesis.

Periodontal research over the last 40 years has been remarkably prolific. We now understand that severe periodontitis affects approximately 10-15% of the population (representing a large number of individuals in the UK) and gingivitis and mild periodontitis affect a majority of people. Microbiological research has identified some of the key pathogens that are implicated in periodontal disease. Plaque bacteria exist in biofilms, which have evolved to protect individual organisms within the subgingival bacterial community. For this reason, root surface instrumentation (RSI) remains the cornerstone of periodontal treatment, and is necessary to disrupt the subgingival biofilm mechanically and reduce the bacterial bioburden. Although bacteria are necessary for periodontal disease to occur, a susceptible host is also required. The immune-inflammatory response that develops in the gingival and periodontal tissues in response to the chronic presence of plaque bacteria results in destruction of structural components of the periodontium leading, ultimately, to the clinical signs of periodontitis. The nature of the host response is determined primarily by genetic factors and environmental and acquired factors such as smoking. The host response is essentially protective in nature, but both under-activity (hypo-responsiveness) and over-activity (hyper-responsiveness) of aspects of the host response can result in enhanced tissue destruction. The purpose of this paper is to review current thinking in periodontics with special reference to periodontal epidemiology, microbiology, and pathogenesis.

Biofilms↗
PubMed2002

Antibiotic prophylaxis for endocarditis, prosthetic joints, and surgery.

It would seem from a review of the evidence that the need for antibiotic prophylaxis in dentistry is overstated. In simple mathematic terms, the risk for providing coverage is greater than the outcomes that could arise if coverage is withheld. In addition, there is the increasing problem of the development of resistant strains and their impact on medicine and dentistry. Yet despite these observations, the profession continues to put their patients at this greater risk. Medico-legal issues do cloud judgments in this area and many dentists err on the side of caution. The profession does require clear, uniform guidelines that are evidence-based. At present, there is still significant debate as to who is at risk from dental-induced bacteremia and what procedures require chemoprophylaxis.

Antibiotic Prophylaxis↗
PubMed2002

Oral health and heart disease.

Over the past ten years, a body of evidence has accumulated to suggest that aspects of oral health, particularly the extent and severity of periodontal disease, may be associated with an increased risk of coronary heart disease (CHD). This evidence should be seen against the background of a more general interest in the role of chronic infections in vascular disease. There have, for example, been suggestions of associations between CHD and a range of bacterial and viral agents, including H. pylori, C. pneumoniae, and cytomegalovirus, which are involved in persistent infections at various sites around the body. Reviews of the evidence for the causality of these relationships between CHD and specific organisms have been inconclusive. By comparison, periodontal disease is related to a wide and complex range of organisms rather than a single species and although the nature of the relationship is still inconclusive, the evidence for its validity still persists to some degree. A brief synopsis of the epidemiological studies to date and their outcomes is shown in Table 1.

Adult↗
PubMed1985

An evaluation of length and end-phrase of visual analogue scales in dental pain.

Visual analogue scales (VAS) of different lengths (5, 10, 15 and 20 cm) and with different end-phrases (troublesome, miserable, intense, unbearable and worst pain imaginable) were used to record pain in 50 male and 50 female patients with pulpitis or pericoronitis. All 100 patients successfully completed the questionnaire. High correlation was found between the scores on all the scales. Scales of length 10 or 15 cm had the smallest measurement error. The scale with the end-phrase 'worst pain imaginable' was found to be the best choice for comparing present pain or worst pain between different groups. Using this scale no significant difference was found between the scores of males and females or between those of patients with pulpitis and pericoronitis. This study suggests the use of 10 cm visual analogue scales with the end-phrase 'worst pain imaginable' as being the most suitable for measuring dental pain.

Adult↗