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Biomedical subjects

Philip C Fox

Publications and source records attributed to Philip C Fox.

At least 19 recordsLinked to original sources

The impact of oral disease and nonsurgical treatment on bacteremia in children.

BACKGROUND: The authors examine the role of dental disease and nonsurgical dental procedures in the incidence and duration of bacteremia in children. METHODS: The authors randomized a group of children to receive amoxicillin or a placebo before dental rehabilitation in an operating room setting. They collected eight blood draws at the following times: two minutes after intubation (draw 1); after dental restorations, pulp therapy and cleaning (draw 2); 10 minutes later (draw 3); and five draws during and after dental extractions (draws 4-8). The authors compared dental disease parameters and the type of dental procedures performed with the incidence and duration of bacteremia. RESULTS: The authors enrolled 100 children (aged 1-8 years) in the study. The incidence of bacteremia from draw 2 was 20 percent in the placebo group and 6 percent in the amoxicillin group (P = .07), and the incidence from draw 3 was 16 percent in the placebo group and zero percent in the amoxicillin group (P = .03). Subjects with higher gingival scores were more likely to have a bacteremia for draw 2 (P = .01). The authors found that subjects in the group with bacteremia for draw 3 had undergone more pulpotomies than did subjects in the group without bacteremia for draw 3 (3 +/- 2.5 standard deviation [SD] versus 1.5 +/- 1.6 SD, P = .04), while they found almost no differences for draw 2. CONCLUSIONS: This study suggests that gingival disease has an impact on bacteremia after dental restorations and prophylaxis. Although antibiotics have an impact, they do not eliminate bacteremia altogether.

Amoxicillin↗

Relationship between mucositis and changes in oral microflora during cancer chemotherapy.

It is thought that the incidence and severity of cancer chemotherapy-associated mucositis is caused in part by changes in the oral bacterial microflora. This systematic review examined the role of oral bacterial microflora changes in the development of oral mucositis during chemotherapy. Thirteen prospective clinical trials were identified, involving 300 patients with 13 different cancer diagnoses. There was great variability in patient populations, bacterial sample collection methodology, and oral sample sites. No clear pattern regarding qualitative and quantitative oral flora changes emerged among these studies. The most frequent Gram-negative species isolated during chemotherapy were from the Enterobacteriaceae family, Pseudomonas sp. and E. coli. The most common Gram-positive species isolated were Staphylococcus sp. and Streptococcus sp. Five studies assessed the role of oral flora changes in the genesis of oral mucosal changes, with no consensus among them. More detailed studies are required to understand the relationship between chemotherapy, alterations in the nature and magnitude of the oral microflora, and the presence of mucositis.

Agranulocytosis↗

Odontogenic signs and symptoms as predictors of odontogenic infection: a clinical trial.

BACKGROUND: The authors conducted a study to determine if odontogenic signs and symptoms in the emergency department predicted the development of overt odontogenic infection at a follow-up dental visit. METHODS: One hundred ninety-five patients with odontalgia, but without overt signs of infection, were enrolled in a prospective, double-blind, randomized clinical trial. Data included dental diagnosis, pain characteristics, presence of caries and restorations, presence and size of periapical radiolucencies and other diagnostic test results. RESULTS: Thirteen of 134 subjects for whom data were available had signs of infection at the follow-up visit. Subjects in the follow-up infected (FU-I) group had larger baseline radiolucencies than did subjects in the follow-up noninfected (FU-NI) group, and restorations were more prevalent for involved teeth in the FU-I group than in the FU-NI group. CONCLUSIONS: A relationship exists between radiolucency size and the presence of amalgam restorations in patients who develop clinical signs of infection. Penicillin did not appear to influence this progression. CLINICAL IMPLICATIONS: Antibiotics are not effective in preventing the development of odontogenic infection when definitive dental therapy cannot be provided for acute pain in the absence of clinical signs of infection. Although the overall risk of developing infection is low, early treatment is indicated for teeth with larger periapical radiolucencies, amalgam restorations or both.

Abscess↗

Application of microchip assay system for the measurement of C-reactive protein in human saliva.

In the last decade, saliva has been advocated as a non-invasive alternative to blood as a diagnostic fluid. However, use of saliva has been hindered by the inadequate sensitivity of current methods to detect the lower salivary concentrations of many constituents compared to serum. Furthermore, developments in the areas related to lab-on-a-chip systems for saliva-based point of care diagnostics are complicated by the high viscosity and heterogeneous properties associated with this diagnostic fluid. The biomarker C-reactive protein (CRP) is an acute phase reactant and a well-accepted indicator of inflammation. Numerous clinical studies have established elevated serum CRP as a strong, independent risk factor for the development of cardiovascular disease (CVD). CVD has also been associated with oral infections (i.e. periodontal diseases) and there is evidence that systemic CRP may be a link between the two. Clinical measurements of CRP in serum are currently performed with "high sensitivity" CRP (hsCRP) enzyme-linked immunosorbent assay (ELISA) tests that lack the sensitivity for the detection of this important biomarker in saliva. Because measurement of salivary CRP may represent a novel approach for diagnosing and monitoring chronic inflammatory disease, including CVD and periodontal diseases, the objective of this study was to apply an ultra-sensitive microchip assay system for the measurement of CRP in human saliva. Here, we describe this novel lab-on-a-chip system in its first application for the measurement of CRP in saliva and demonstrate its advantages over the traditional ELISA method. The increased sensitivity of the microchip system (10 pg ml(-1) of CRP with 1000-fold dilution of saliva sample) is attributed to its inherent increased signal to noise ratio, resulting from the higher bead surface area available for antigen/antibody interactions and the high stringency washes associated with this approach. Finally, the microchip assay system was utilized in this study to provide direct experimental evidence that chronic periodontal disease may be associated with higher levels of salivary CRP.

C-Reactive Protein↗

Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome.

OBJECTIVE: To screen for potential efficacy and assess feasibility and safety of dehydroepiandrosterone (DHEA) as a treatment for Sjögren's syndrome (SS). METHODS: A 24-week randomized, double-blinded, pilot trial of oral DHEA (200 mg/day) versus placebo was conducted. The primary comparison was to a hypothesized 20% placebo response rate. If 14 consecutive subjects on DHEA did not respond, a Phase III trial would be considered futile. A placebo group of 14 subjects was planned to verify placebo response rate and estimate sample size required for a definitive trial. Response criteria required 20% improvement in at least 2 of 3 domains. Analysis of covariance was used to adjust for baseline differences and for stratified randomization. Outcome measures included visual analog scale questionnaires for dry eye and dry mouth symptoms, lissamine green ocular dye staining and Schirmer I tests, stimulated salivary flow, IgG, and erythrocyte sedimentation rate (ESR). RESULTS: Randomization resulted in 14 DHEA and 14 placebo group subjects. At baseline, mean +/- SD for DHEA versus placebo groups were Schirmer I tests 4.5 +/- 4.5 versus 5.4 +/- 6.1 mm/5 minutes; Van Bijsterveld score 5.3 +/- 2.1 versus 5.5 +/- 2.2; unstimulated saliva 0.03 +/- 0.05 versus 0.04 +/- 0.10 ml/minute; IgG 1,699 +/- 749 versus 1,712 +/- 621 g/dl; and ESR 40 +/- 31 versus 44 +/- 28 mm/hour. Apart from changes over the trial in dry mouth symptoms, no significant differences were noted between the DHEA and placebo groups for dry eye symptoms, objective measures of ocular dryness, stimulated salivary flow; IgG, or ESR. Four DHEA and one placebo group patient dropped out because of adverse effects. Although 7 subjects met response criteria in the DHEA group, 5 met the criteria in the placebo group, and there was no significant difference between groups. CONCLUSION: DHEA showed no evidence of efficacy in SS. Without evidence for efficacy, patients with SS should avoid using unregulated DHEA supplements, since long-term adverse consequences of exposure to this hormone are unknown.

Adjuvants, Immunologic↗

Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis.

BACKGROUND: Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence-based guidelines for preventing, evaluating, and treating mucositis. METHODS: Thirty-six panelists reviewed literature published between January 1966 and May 2002. An initial meeting in January 2002 produced a preliminary draft of guidelines that was reviewed at a second meeting the same year. Thereafter, a writing committee produced a report on mucositis pathogenesis, epidemiology, and scoring (also included in this issue), as well as clinical practice guidelines. RESULTS: Panelists created recommendations from higher levels of evidence and suggestions when evidence was of a lower level and there was a consensus regarding the interpretation of the evidence by the panel. Panelists identified gaps in evidence that made it impossible to recommend or not recommend use of specific agents. CONCLUSIONS: Oral/GI mucositis is a common side effect of many anticancer therapies. Evidence-based clinical practice guidelines are presented as a benchmark for clinicians to use for routine care of appropriate patients and as a springboard to challenge clinical investigators to conduct high-quality trials geared toward areas in which data are either lacking or conflicting.

Antineoplastic Agents↗

The role of oral microbial colonization in ventilator-associated pneumonia.

The present article reviews the association between microbial colonization of the oral cavity and the lungs in critically ill patients that develop ventilator-associated pneumonia (VAP) in the intensive care unit (ICU) setting. The risk factors and microorganisms associated with VAP are presented. The role of oral colonization of VAP-associated pathogens (VAP-AP) in the development of VAP is examined. We explore the potential factors involved in oral colonization of VAP-AP, which are atypical bacteria for the oral cavity. Strategies for the prevention or moderation of oral colonization of VAP-AP have had limited success. We need a deeper understanding of the pathophysiology of VAP in order to reduce the morbidity, mortality, and cost from this common complication in ICU medicine and surgery.

Bacterial Physiological Phenomena↗

Relationship between oral bacteria and hemodialysis access infection.

OBJECTIVE: Controversy exists concerning the association between oral bacteria and infection of hemodialysis (HD) shunts. The purpose of this study was to determine the extent to which oral bacteria are associated with vascular access site infections in a group of HD patients. STUDY DESIGN: Microbial blood culture data for 87 HD patients were collected: 53 via chart review (retrospective), and 34 with newly suspected vascular access infections (prospective). The primary outcome was the nature (i.e., species) of the bacteria recovered from blood cultures of subjects with vascular access infection, specifically those bacteria considered to be oral flora. RESULTS: The predominant bacteria reported to cause HD vascular access infections were Staphylococcus (48.6%) and Enterococcus (17.6%) species. Most infections occurred in hemodialysis catheters (89%) compared with AV grafts (11%) and AV fistulas (0%). The subclavian venous access (41%) and the internal jugular venous access (38.9%) were more commonly infected than other sites. None of the bacteria identified by blood cultures were considered to be oral flora. CONCLUSION: The results suggest that oral bacteria rarely, if ever, cause vascular access infections in hemodialysis patients.

Arteriovenous Shunt, Surgical↗

Efficacy of penicillin for dental pain without overt infection.

OBJECTIVES: Dental pain is a common presenting symptom in the acute care setting. Even in the absence of overt infection, many physicians routinely prescribe antibiotics such as penicillin. The authors sought to test the hypothesis that penicillin is not necessary or beneficial in the treatment of undifferentiated dental pain without overt infection. METHODS: This prospective, randomized, double-blind, placebo-controlled trial was conducted at an urban teaching hospital with approximately 105,000 emergency department visits per year. A convenience sample of adult emergency department patients presenting with dental pain and no clinically overt infection was randomized to receive penicillin or placebo. A structured evaluation was performed at enrollment and again at a 5- to 7-day follow-up visit. The main outcome measure was evidence of overt dental infection at the 5- to 7-day follow-up visit. RESULTS: A total of 195 patients were enrolled. Ninety-eight (50%) were randomized to treatment with penicillin. A total of 125 patients (64%) were followed up. Outcome data were identified for nine additional study patients, who returned to the dental clinic or emergency department outside of the scheduled follow-up period and were included in the final analysis. Overall, 13 of 134 patients (9%) developed signs of infection: six of 64 (9%) from the penicillin group and seven of 70 (10%) from the placebo group (p = 0.90). There was no significant difference between the penicillin and placebo groups in baseline characteristics, medication compliance, or visual analog scale pain scores at enrollment. CONCLUSIONS: These data support the hypothesis that penicillin is neither necessary nor beneficial in the treatment of undifferentiated dental pain in the absence of overt infection.

Adult↗

Treatment of primary Sjögren's syndrome with low-dose human interferon alfa administered by the oromucosal route: combined phase III results.

OBJECTIVE: This study tested the safety and efficacy of human interferon (IFN) alfa for treatment of salivary hypofunction and dry mouth symptoms in primary Sjögren's syndrome patients. METHODS: Combined results are reported from 2 phase III clinical trials in which a total of 497 subjects with primary Sjögren's syndrome received 150 international units of human IFN alfa or matching placebo 3 times per day for 24 weeks by the oromucosal route. RESULTS: Subjects given IFN alfa had a significantly (P = 0.01) greater mean increase in unstimulated whole saliva (UWS) flow, compared with subjects given placebo. In IFN alfa patients, increases in UWS correlated positively and significantly with improvements noted in 7 of 8 symptoms associated with oral and ocular dryness. The coprimary endpoints of stimulated whole saliva flow and oral dryness were not significantly improved in the IFN alfa group relative to placebo. No significant differences were found between the groups with respect to overall adverse event incidence or severity. CONCLUSION: IFN alfa given at low dosage by the oromucosal route can significantly increase UWS flow in patients with primary Sjögren's syndrome, without causing significant adverse events.

Administration, Oral↗

Sex steroid hormones in primary Sjögren's syndrome.

OBJECTIVE: To investigate the relationships between concentrations of sex hormones and measures of disease activity in patients with primary Sjögren's Syndrome (pSS). METHODS: Fifty-four women were evaluated: 39 patients (age, Q1,Q3: 57.0 yrs; 46, 66) diagnosed with pSS and 15 patients (49.0 yrs; 45, 60) who did not meet diagnostic criteria for pSS. The following measures of disease activity were assessed: serological data [antinuclear antibody, rheumatoid factor, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum immunoglobulin levels (IgG, IgA, IgM), serum protein, anti-SSA, and anti-SSB], labial minor salivary gland focus score, salivary flow rates, and objective measures of eye dryness (fluorescein corneal staining and unstimulated Schirmer's I test). Spearman correlations were calculated between these indices of disease activity and serum levels of sex hormones: dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione, testosterone, dihydrotestosterone (DHT), estrone, estradiol, and sex hormone binding globulin (SHBG). RESULTS: Numerous differences were noted between cases and controls with disease activity measures. All median values of sex steroid hormones were within the range of normal for pSS cases. Positive correlations were noted between testosterone and ESR (r = 0.36, p = 0.03), testosterone and serum protein (r = 0.37, p = 0.05), and testosterone and focus score (r = 0.44, p = 0.007). Negative correlations were present between SHBG and anti-SSA (r = -0.33, p = 0.05), SHBG and anti-SSB (r = -0.43, p = 0.009), and DHT and CRP (r = -0.41, p = 0.05). No correlations were noted between estrogens and measures of pSS disease activity. CONCLUSION: Higher levels of disease activity (ESR, serum protein, and focus score) were associated with higher concentrations of testosterone. No correlation between disease activity and estrogens was found.

Androstenedione↗

Prevalence and clinical significance of lymphocytic foci in minor salivary glands of healthy volunteers.

OBJECTIVE: To determine the prevalence and severity of focal lymphocytic sialadenitis in minor salivary glands of healthy, asymptomatic individuals, in whom Sjögren's syndrome (SS) has been excluded. METHODS: Charts of 54 healthy volunteers who had salivary gland biopsies at the National Institutes of Health from January 1992 to August 1998 were reviewed. The healthy volunteers served as control subjects in various studies of salivary dysfunction. Significant medical conditions including SS were excluded. A biopsy with a focus score (FS) >1 was regarded as positive. Descriptive statistics were used to summarize the population's characteristics. RESULTS: The frequency of focal lymphocytic infiltration in the healthy volunteers was about 15% (8 of 54). None of these individuals had subjective xerostomia or dry eyes. The positive FS ranged from 2 to 6. FS did not correlate with age, smoking, serologic findings, or salivary flow in these patients. CONCLUSION: Lymphocytic infiltration in minor salivary glands is not uncommon among individuals without a history of salivary gland dysfunction. This finding is in agreement with the result of a previous autopsy survey study, indicating that focal sialadenitis may occur in the absence of SS.

Adult↗

Decision-making on the use of antimicrobial prophylaxis for dental procedures: a survey of infectious disease consultants and review.

There is debate concerning use of antibiotic prophylaxis before invasive dental procedures for patients at risk of acquiring distant site infection (DSI). We determined the opinions and practices of infectious disease consultants (IDCs) regarding antimicrobial prophylaxis to prevent DSIs that result from invasive dental procedures by conducting a survey of the 797 members of the Infectious Diseases Society of America Emerging Infections Network (477 members [60%] responded). Ninety percent of respondents closely follow the American Heart Association guidelines for antibiotic prophylaxis for patients with valvular heart disease who undergo invasive dental procedures. In contrast, few IDCs recommend prophylaxis for patients with lupus erythematosus, poorly controlled diabetes mellitus, dialysis catheters or shunts, cardiac pacemakers, or ventriculoperitoneal shunts. Twenty-five percent to forty percent of respondents recommended prophylaxis for prosthetic vascular grafts, orthopedic implants, or chemotherapy-induced neutropenia. We conclude that IDCs differ considerably in their assessment of the need for prophylaxis for patients who have noncardiac risk factors for DSI. These differences underscore the need for definitive studies to delineate appropriate candidates for antimicrobial prophylaxis in dental practice.

Antibiotic Prophylaxis↗

Treatment of xerostomia: a systematic review of therapeutic trials.

The results of the present systematic review of randomized controlled trials published in peer-reviewed journals demonstrate the presence of a wide variety of biases and the weakness of the existing literature of xerostomia treatment. The report of statistically significant efficacy on an outcome measure is only meaningful in the setting of a well-controlled, appropriately designed clinical trial. This points to the importance of evaluating the quality of the clinical trial closely when deciding if study results are applicable to a specific patient population. Future studies in the management of xerostomia will require an increased effort on the part of investigators to eliminate easily recognized flaws during the planning stages of a clinical trial. Minimizing bias in clinical studies will allow for easier interpretation and comparisons of different studies. Better clinical trial design is vital to provide maximal confidence in the efficacy of xerostomia interventions.

Acupuncture Therapy↗