PREVLAR: Phase 2a Randomized Trial to Assess the Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Head and Neck Chemoradiotherapy.

PURPOSE: No Food and Drug Administration-approved intervention exists for oral mucositis (OM) from chemoradiotherapy (CRT) used to treat head and neck cancers. RRx-001 is a hypoxia-activated, cysteine-directed molecule that affects key pathways involved in OM pathogenesis. This phase 2a, multi-institutional trial was designed to assess the safety and feasibility of 3 schedules of a fixed concentration of RRx-001; a standard-of-care arm was included to identify potential signals of efficacy for further study. METHODS AND MATERIALS: This study enrolled patients with oral cavity and oropharynx squamous cell carcinoma receiving definitive or postoperative cisplatin-based CRT. Patients were randomized into 4 cohorts. In arms 1 to 3, RRx-001 was coinfused with patients' blood at differing intervals. Arm 4 was a control cohort of patients treated with CRT alone. Trained evaluators assessed OM using a standardized data collection instrument twice weekly during treatment and then until resolution. OM severity was scored centrally using World Health Organization criteria. Safety outcomes were assessed using National Cancer Institute - Common Terminology Criteriav4 benchmarks. Long-term tumor response was defined by Response evaluation criteria in solid tumors v1.1 criteria. RESULTS: Fifty-three patients were enrolled, with 46 and 45 individuals contributing safety and efficacy data, respectively. There were no severe adverse events attributed to the study drug. Across all 3 active arms, the study drug was infused fully per protocol in 86% of patients. All 3 RRx-001 treatment cohorts appeared to demonstrate a similar or lower OM duration relative to control; arm 1 had the lowest median duration of severe oral mucositis (SOM), 8.5 days versus 24 days in controls among patients who developed at least 1 day of SOM. There were no locoregional failures in any patient. CONCLUSIONS: Our results support the safety and feasibility of RRx-001 as an intervention to mitigate SOM. Additional studies are planned to confirm its efficacy.

"Meth Mouth": An Interdisciplinary Review of a Dental and Psychiatric Condition.

OBJECTIVE: Chronic methamphetamine (MA) users experience many dental problems, a condition characterized as "meth mouth." These devastating effects on dentition is the main reason why many seek professional help. Here, we discuss the effects of MA on oral health and advocate for improved collaboration between dentists and mental health providers. We also introduce a dental evaluation tool with the goal of improving the quality of care for this often-marginalized patient population. METHODS: A Medline literature search (1985-2016) was conducted with keywords "meth mouth," "methamphetamine AND oral health"; "methamphetamine AND dental"; "methamphetamine AND dentist." Results were supplemented by references gleaned from recent reviews, credible online sources, and citations of search returns. RESULTS: MA predisposes users to tooth decay. They are also more likely to have missing dentition with a linear relationship correlating the number of years of use. A constellation of dental symptoms resulting from chronic MA use has been described in literature: gingival inflammation, excessive tooth wear, decreased salivary output, and severe dental caries. With continued use, mucosal lesions may appear on the lips and the gingival tissue may recede. MA can trigger bruxism, resulting in severe wear patterns and even cracked teeth. CONCLUSIONS: Users of MA have many unmet medical and mental health needs. An interdisciplinary approach between dentists and mental health providers can improve outcomes. The dental evaluation tool described here can improve the bidirectional collaboration between mental health and dentistry. Dental professionals are in a unique position to identify users and can facilitate referral to substance abuse treatment. Likewise, mental health providers can identify, assess severity, and prompt users for medical and dental attention.

Oral Health in Electroconvulsive Therapy: A Neglected Topic.

Psychiatric medications may have serious and untoward adverse effects such as blurred vision, restlessness, agranulocytosis, muscle rigidity, and tremors. When compared to medications, electroconvulsive therapy (ECT) is becoming a more acceptable treatment due to its efficacy, tolerability, and minimal adverse effect profile. Oral trauma can be an ECT-related adverse effect. We reviewed the published literature on oral health and dental protection in patients undergoing ECT, and found that there are deficits in all guidelines on dental protection during ECT. Dental assessment and treatment before and after ECT is warranted. Given the increased risk of poor oral health in psychiatric patients, and the continued evolution of ECT as a mainstay treatment, it is important that studies be conducted to determine the optimal method of oral protection. If adequate care can be ensured, the risks of ECT-induced oral trauma will be minimized.

Update on oral fungal infections.

The incidence of oral fungal infections has increased in recent years as a result of factors such as increased number of solid organ transplantations and the widespread use of immunosuppressive drug therapies. This article reviews the diagnosis and treatment of oral fungal infections. At one time oral fungal infections were a relatively uncommon event, but with advances in health care and polypharmacy in an increasingly aging population, these infections are becoming a more routine clinical finding. The dental practitioner therefore needs to be familiar with the diagnosis and management of oral fungal infections.

Characterization of oral biopsies from a geriatric population.

A retrospective search was performed to find the histological diagnosis for all lesions recorded by an oral pathology service for patients 65 and older from 1969-2002. The search was subcategorized into two age groups and the 20 most common diagnoses from these categories were characterized by patient gender and race. Lesions then were classified into one of seven modified etiopathogenic categories. Of the 52,774 cases recorded during this time, 7,854 involved patients aged 65-84 and 393 cases involved patients 85 and older. Inflammatory lesions were the most common category of lesion in patients over the age of 65. Among patients aged 65-84, fibroma was the most common diagnosis, while squamous cell carcinoma was the most frequent diagnosis among patients 85 and older. Neoplastic lesions (epithelial dysplasia and squamous cell carcinoma) comprised 11.7% of the diagnoses among patients aged 65-84 and 18.6% of the diagnoses among patients 85 and older. These data indicate that patients 85 and older demonstrated a statistically significant increased frequency of squamous cell carcinoma compared to patients in the 65-84 age group.

Assessment of dental faculty, staff, and students on knowledge of health effects associated with tobacco use.

OBJECTIVES: This study examined the knowledge of the health effects associated with tobacco use among dental school faculty, staff, and students. METHODS: A 30-item survey instrument was pilot-tested to ensure content validity prior to implementation. A total of 724 surveys were distributed through campus mail. RESULTS: A total of 344 (47.51%) survey instruments were returned. 71.8 percent of respondents reported using tobacco sometime during their life, 21.8 percent had smoked at least one cigarette a day for the past 30 days, but only 8.4 percent considered themselves to be smokers. Of the 71.8% reported using tobacco sometime during their lifetime, 49.7 percent reported being very confident about their ability to quit using tobacco, 32.6 percent reported that it would be unlikely for their tobacco use to result in negative health effects, and 31.7 percent reported that they were not worried about negative health effects associated with tobacco use. CONCLUSIONS: This study reveals a lack of knowledge of dental school faculty, staff, and students on the negative personal health effects associated with tobacco use.

Disseminated histoplasmosis with oral manifestation.

Histoplasmosis is a fungal disease that affects humans and is caused by Histoplasma capsulatum. The presentation of the infection may be acute, chronic, or disseminated. The disseminated form has extrapulmonary manifestations which may include oral manifestations. A patient with AIDS sought treatment and he had disseminated histoplasmosis with oral manifestations. The purpose of this case report and literature review is to emphasize the role the dental team has in the diagnosis of disseminated disease when a patient presents with oral manifestations associated with the disease. This case report is clinically relevant because it is not uncommon for oral manifestations to be one of the first signs of systemic disease.

Oral fungal infections.

Candidiasis is the most common oral fungal infection diagnosed in humans. Candidiasis may result from immune system dysfunction or as a result of local or systemic medical treatment. Because oral candidiasis is generally a localized infection, topical treatment methods are the first line of therapy, especially for the pseudomembranous and erythematous variants. Patients with dental prostheses should also be advised to disinfect the prosthesis routinely during the candidal treatment period, because the prosthesis may serve as a source of reinfection. Additionally, patients should be advised that oral hygiene aids, such as toothbrushes and denture brushes, may also be contaminated and should be discarded or disinfected. A disinfecting solution of equal parts of hydrogen peroxide and water may be used. Likewise, 2% chlorhexidine gluconate solution may be used asa disinfecting solution for dental prostheses and oral hygiene aids. Occasionally the clinician encounters a more resistant form of oral candidiasis such as the hyperplastic variant or a variant that does not respond to topical therapy. Appropriate systemic therapy should be employed for the treatment of these infections. Additionally, a biopsy should be undertaken in individuals with the hyperplastic variant of Candida because there is some degree of risk for malignant transformation. Deep fungal infections should be managed in association with appropriate medical specialists to rule out other systemic involvement. The dental health care provider plays an important part in the diagnosis and management of fungal disease, and therefore clinicians should be aware of the presenting signs and symptoms or oral fungal disease.