Philip C. Fox

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

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.

Subjective reports of xerostomia and objective measures of salivary gland performance

This study involves collecting saliva under unstimulated and stimulated conditions and asking standardized questions of 100 patients with xerostomia. The study examines which questions are useful in identifying and predicting current major salivary gland output deficiency or dysfunction.

Oral Pilocarpine for Post-Irradiation Xerostomia in Patients with Head and Neck Cancer

BACKGROUND AND METHODS We evaluated pilocarpine hydrochloride for the treatment of radiation-induced xerostomia, a common complication of irradiation of the head and neck. A prospective, randomized, double-blind, placebo-controlled trial was undertaken to test the safety and efficacy of pilocarpine, particularly in reversing the decrease in the production of saliva and other manifestations of xerostomia. Patients received either placebo or pilocarpine (5 mg or 10 mg orally three times a day) for 12 weeks and were evaluated at base line and every 4 weeks. RESULTS We studied 207 patients who had each received > or = 4000 cGy of radiation to the head and neck. In the patients receiving the 5-mg dose of pilocarpine, oral dryness improved in 44 percent, as compared with 25 percent of the patients receiving placebo (P = 0.027). There was overall improvement in 54 percent of the 5-mg group as compared with 25 percent of the placebo group (P = 0.003), and 31 percent of the 5-mg group had improved comfort of the mouth and tongue, as compared with 10 percent of the placebo group (P = 0.002). Speaking ability improved in 33 percent of the 5-mg group as compared with 18 percent of the placebo group (P = 0.037). Saliva production was improved, but it did not correlate with symptomatic relief. There were comparable improvements in the group receiving the 10-mg dose. The primary adverse effect was sweating, in addition to other minor cholinergic effects. Six and 29 percent of the patients in the 5-mg and 10-mg groups, respectively, withdrew from the study because of adverse effects. There were no serious adverse effects related to pilocarpine. CONCLUSIONS Pilocarpine improved saliva production and relieved symptoms of xerostomia after irradiation for cancer of the head and neck, with minor side effects that were predominantly limited to sweating.

Bacteremia Associated With Toothbrushing and Dental Extraction

Background— Antibiotic prophylaxis recommendations for the prevention of infective endocarditis are based in part on studies of bacteremia from dental procedures, but toothbrushing may pose a greater threat. The purpose of this study was to compare the incidence, duration, nature, and magnitude of endocarditis-related bacteremia from single-tooth extraction and toothbrushing and to determine the impact of amoxicillin prophylaxis on single-tooth extraction. Methods and Results— In this double-blind, placebo-controlled study, 290 subjects were randomized to (1) toothbrushing, (2) single-tooth extraction with amoxicillin prophylaxis, or (3) single-tooth extraction with identical placebo. Blood was drawn for bacterial culturing and identification at 6 time points before, during, and after these interventions. The focus of our analysis was on bacterial species reported to cause infective endocarditis. We identified 98 bacterial species, 32 of which are reported to cause endocarditis. Cumulative incidence of endocarditis-related bacteria from all 6 blood draws was 23%, 33%, and 60% for the toothbrushing, extraction-amoxicillin, and extraction-placebo groups, respectively (P<0.0001). Significant differences were identified among the 3 groups at draws 2, 3, 4, and 5 (all P<0.05). Amoxicillin resulted in a significant decrease in positive cultures (P<0.0001). Conclusions— Although amoxicillin has a significant impact on bacteremia resulting from a single-tooth extraction, given the greater frequency for oral hygiene, toothbrushing may be a greater threat for individuals at risk for infective endocarditis.

MAJOR SALIVARY GLAND FUNCTION IN PATIENTS WITH RADIATION- INDUCED XEROSTOMIA: FLOW RATES AND SIALOCHEMISTRY

Radiation therapy for cancer of the head and neck region often causes salivary gland dysfunction and xerostomia. Several reports suggest that the submandibular/sublingual (SM/SL) glands may be less radiosensitive than the parotid. The purpose of this study was to evaluate differential radiation effects on the major salivary glands. Fifty patients with radiation-induced xerostomia were evaluated (33 males, 17 females; mean age 52.7). The average total tumor dose was 6034 cGy. Major salivary gland function was compared with that of 50 non-irradiated controls. Salivary flow rates included unstimulated and stimulated flows of both the parotid and SM/SL glands. Sialochemical analyses included total protein, lysozyme, lactoferrin, sodium, chloride, and potassium. All four measures of salivary flow were significantly reduced in patients as compared to controls (p = .0001). Like the parotid, submandibular/sublingual gland dysfunction appears to be radiation dose- and field-dependent. Patients in the lowest radiation dose quartile (< or = 5000 cGy) had significantly increased salivary flow compared to those in the highest dose quartile (> or = 6800 cGy; p = .025). Glands that were partially irradiated were more likely to have some residual function than fully irradiated glands (p = .003). Lactoferrin content was increased in parotid saliva of radiation patients (p = .0001). Chloride content was significantly increased also (p = .0001). The SM/SL glands are clearly dysfunctional in post-irradiation xerostomia patients compared to controls, in terms of both flow rates and sialochemistry.

Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: Successes and barriers

The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.

Incidence of Physician-Diagnosed Primary Sjögren Syndrome in Residents of Olmsted County, Minnesota

OBJECTIVES To estimate the incidence of physician-diagnosed primary Sjögren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients. PATIENTS AND METHODS We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk. RESULTS Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia. CONCLUSIONS The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.

Pilocarpine for the treatment of xerostomia associated with salivary gland dysfunction

A double-blind placebo-controlled study was conducted to evaluate the efficacy of orally administered pilocarpine in treating oral dryness caused by salivary gland hypofunction. At low dosages, pilocarpine increased the production of saliva by parotid and submandibular and/or sublingual glands and relieved the sensation of oral dryness. The quantity and composition of pilocarpine-stimulated secretions were similar to saliva produced in response to gustatory stimulation with citrate. In appropriate patients, pilocarpine is a safe, easily administered, effective therapy to relieve xerostomia by increasing natural salivary function.

Molecular Analysis of Oral and Respiratory Bacterial Species Associated with Ventilator-Associated Pneumonia

ABSTRACT Trauma intensive care unit (TICU) patients requiring mechanical respiratory support frequently develop ventilator-associated pneumonia (VAP). Oral and oropharyngeal bacteria are believed to be responsible for many cases of VAP, but definitive evidence of this relationship is lacking. Earlier studies used conventional culture-based methods for identification of bacterial pathogens, but these methods are insufficient, as some bacteria may be uncultivable or difficult to grow. The purpose of this study was to use a culture-independent molecular approach to analyze and compare the bacterial species colonizing the oral cavity and the lungs of TICU patients who developed VAP. Bacterial samples were acquired from the dorsal tongue and bronchoalveolar lavage fluid of 16 patients. Bacterial DNA was extracted, and the 16S rRNA genes were PCR amplified, cloned into Escherichia coli, and sequenced. The sequencing data revealed the following: (i) a wide diversity of bacterial species in both the oral and pulmonary sites, some of them novel; (ii) known and putative respiratory pathogens colonizing both the oral cavity and lungs of 14 patients; and (iii) a number of bacterial pathogens (e.g., Dialister pneumosintes, Haemophilus segnis, Gemella morbillorum, and Pseudomonas fluorescens) in lung samples that had not been reported previously at this site when culture-based methods were used. Our data indicate that the dorsal surface of the tongue serves as a potential reservoir for bacterial species involved in VAP. Furthermore, it is clear that the diversity of bacterial pathogens for VAP is far more complex than the current literature suggests.

Treatment of Primary Sjogren's Syndrome with Low-Dose Natural Human Interferon-alpha Administered by the Oral Mucosal Route: A Phase II Clinical Trial

The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögrens syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögrens syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events.