World Workshop on Oral Medicine VI: a systematic review of the treatment of mucous membrane pemphigoid.

OBJECTIVE: To determine the efficacy and safety of interventions for mucous membrane pemphigoid (MMP). STUDY DESIGN: We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials and observational studies were included, with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. The primary outcome was lesion remission or healing; several relevant secondary outcomes were also included. RESULTS: In the final analysis, 1 RCT and 32 observational studies were included. The one included RCT with a high risk of bias in multiple domains found limited evidence that pentoxifylline, combined with corticosteroid and cyclophosphamide, was more effective than standard therapy (corticosteroid + cyclophosphamide alone) for ocular MMP. We summarize here the outcomes from 32 observational studies examining 242 patients across 19 unique treatments. Interventions that show promise include rituximab and intravenous immunoglobulin. CONCLUSIONS: This systematic review is the most recent since 2003-2009. There is still lack of high-quality research providing evidence-based MMP treatments.

World Workshop on Oral Medicine VI: a systematic review of the treatment of mucocutaneous pemphigus vulgaris.

OBJECTIVE: To determine the efficacy and safety of interventions for pemphigus vulgaris (PV). STUDY DESIGN: We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) and observational studies were conducted along with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. Primary outcomes were disease remission and mortality; several relevant secondary outcomes were also included. RESULTS: Fourteen RCTs or CCTs and 110 observational studies were included in the final analyses. RCTs or CCTs demonstrated considerable heterogeneity in outcome measures, and all had a high risk of bias for at least 1 of 8 domains. Of the studies, 96.8% (120) described the use of oral corticosteroids. Azathioprine and mycophenolate-mofetil were the most commonly cited treatments. An increasing number of studies described biologic therapies (rituximab, intravenous immunoglobulin [IVIg]). Evidence supporting recent comprehensive treatment guidelines was reviewed. CONCLUSIONS: We found persisting wide variations in treatment practice and inadequate quality of research supporting optimal PV treatment.

Report on World Workshops on Oral Medicine (WWOM) IV and V: research themes and citation impact: WWOM VI steering committee.

The first World Workshop on Oral Medicine (WWOM) was held in 1988. The portfolio has continued to expand in scope and impact over the past 26 years. Five World Workshops were conducted between 1988 and 2010, focusing on creation of systematic reviews in biomedicine and health care of importance to the international oral medicine community. WWOM VI was conducted in April 2014 and further extended this modeling. This most recent Workshop also fostered creation of the inaugural joint meeting between the American Academy of Oral Medicine and the European Association of Oral Medicine, together with The British Society for Oral Medicine and the Oral Medicine Academy of Australasia. The goal of the WWOM portfolio is to strategically enhance international oral medicine research, education, and clinical practice. To this end, this report summarizes subject areas for WWOM IV (2004) and research recommendations for WWOM V (2010), as well as citation metrics relative to publications from these two conferences. The information is designed to provide research and clinical context for key issues in oral medicine as delineated by the WWOM portfolio over the past 10 years, as well as for projected outcomes of WWOM VI over the next 12 months.

Persistent orofacial muscle pain.

The pathophysiology of persistent orofacial myalgia has been the centre of much controversy. In this article we suggest a novel descriptive term; 'persistent orofacial muscle pain' (POMP) and review current evidence that supports the hypothesis that the induction of POMP involves the interplay between a peripheral nociceptive source in muscle, a faulty central nervous system component and decreased coping ability. In this context it is widely accepted that a complex interaction of variable intrinsic and extrinsic factors act to induce POMP and dysfunction.

Local drug delivery for oral mucosal diseases: challenges and opportunities.

There are few topical formulations used for oral medicine applications most of which have been developed for the management of dermatological conditions. As such, numerous obstacles are faced when utilizing these preparations in the oral cavity, namely enzymatic degradation, taste, limited surface area, poor tissue penetration and accidental swallowing. In this review, we discuss common mucosal diseases such as oral cancer, mucositis, vesiculo-erosive conditions, infections, neuropathic pain and salivary dysfunction, which could benefit from topical delivery systems designed specifically for the oral mucosa, which are capable of sustained release. Each condition requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. Local drug delivery may provide a more targeted and efficient drug-delivery option than systemic delivery for diseases of the oral mucosa. We identify those mucosal diseases currently being treated, the challenges that must be overcome and the potential of novel therapies. Novel biological therapies such as macromolecular biological drugs, peptides and gene therapy may be of value in the treatment of many chronic oral conditions and thus in oral medicine if their delivery can be optimized.

An international survey of oral medicine practice: proceedings from the 5th World Workshop in Oral Medicine.

OBJECTIVES: (i) To define the current state of oral medicine clinical practice internationally, and (ii) to make recommendations for future modeling of the practice of oral medicine. MATERIALS AND METHODS: A survey was designed by an international panel of oral medicine experts to assess the current state of oral medicine practice internationally. The survey was sent to oral medicine experts across the world, and responses were electronically stored and analyzed using descriptive statistics. RESULTS: Two hundred respondents completed the survey representing 40 countries from six continents. The two most common settings for an oral medicine practice were in a hospital and a dental school. More than 88% of respondents considered management of oral mucosal disease, salivary dysfunction, oral manifestations of systemic diseases, and facial pain in the definition of oral medicine. CONCLUSIONS: (i) Oral medicine clinicians diagnose and manage a wide variety of orofacial conditions; (ii) There are significant differences in the definition of oral medicine clinical practice from country to country; (iii) India has the largest expansion of oral medicine services as defined by escalating numbers of clinicians within the specialty as compared with other countries; (iv) oral medicine practitioners have a wide range of professional responsibilities.

Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy.

OBJECTIVE: To identify and compare clinical and neuroimaging predictors of primary lobar intracerebral hemorrhage (ICH) recurrence, assessing their relative contributions to recurrent ICH. METHODS: Subjects were consecutive survivors of primary ICH drawn from a single-center prospective cohort study. Baseline clinical, imaging, and laboratory data were collected. Survivors were followed prospectively for recurrent ICH and intercurrent aspirin and warfarin use, including duration of exposure. Cox proportional hazards models were used to identify predictors of recurrence stratified by ICH location, with aspirin and warfarin exposures as time-dependent variables adjusting for potential confounders. RESULTS: A total of 104 primary lobar ICH survivors were enrolled. Recurrence of lobar ICH was associated with previous ICH before index event (hazard ratio [HR] 7.7, 95% confidence interval [CI] 1.4-15.7), number of lobar microbleeds (HR 2.93 with 2-4 microbleeds present, 95% CI 1.3-4.0; HR = 4.12 when >or=5 microbleeds present, 95% CI 1.6-9.3), and presence of CT-defined white matter hypodensity in the posterior region (HR 4.11, 95% CI 1.01-12.2). Although aspirin after ICH was not associated with lobar ICH recurrence in univariate analyses, in multivariate analyses adjusting for baseline clinical predictors, it independently increased the risk of ICH recurrence (HR 3.95, 95% CI 1.6-8.3, p = 0.021). CONCLUSIONS: Recurrence of lobar ICH is associated with previous microbleeds or macrobleeds and posterior CT white matter hypodensity, which may be markers of severity for underlying cerebral amyloid angiopathy. Use of an antiplatelet agent following lobar ICH may also increase recurrence risk.

Biological responses of Lumbriculus variegatus exposed to fluoranthene-spiked sediment.

Lumbriculus variegatus was used as a bioassay organism to examine the impact of the sediment-associated polycyclic aromatic hydrocarbon (PAH) fluoranthene on behavior, reproduction, and toxicokinetics. The number of worms increased between the beginning and end of the experiment at 59 microg x g(-1) fluoranthene, but at the next higher treatment (108 microg x g(-1)) the number of worms found was lower and not different from the control. Worms exposed to 95 microg x g(-1) also exhibited increased reproduction when fed a yeast-cerophyl-trout chow mixture. On a total biomass basis, only the 95 microg x g(-1) exposure with food exhibited a statistically significant increase over the nonfed control. Evaluation of reproduction at the two highest treatments was compromised by a brief aeration failure 2 days before the end of the experiment. The behavioral responses were followed as changes in biological burial rate (sediment reworking rate) of a 137Cs-labeled marker layer. The biological burial rate increased toward a plateau as the concentration increased from the control (3.9 microg x g(-1) dry weight total PAH) to 355 microg x g(-1) dry weight fluoranthene in sediment. The aeration failure had minimal impact on the determination of reworking rate because all the data for the rate determination were collected prior to the aeration failure. Uptake and elimination rates declined with increasing treatment concentration across the range of fluoranthene concentrations, 59-355 microg x g(-1) dry weight sediment. The disconnect between the increasing biological burial rates and the decreasing toxicokinetics rates with increasing exposure concentration demonstrates that the toxicokinetic processes are dominated by uptake and elimination to interstitial water. The bioaccumulation factor (concentration in the organisms on a wet weight basis divided by the concentration in sediment on a dry weight basis) ranged from 0.92 to 1.88 on day 10 and declined to a range of 0.52 to 0.99 on day 28 with the lowest value at the highest dose.

A retrospective study of the management of oral mucous membrane pemphigoid with dapsone.

OBJECTIVE: The purpose of this retrospective study was to investigate the efficacy of dapsone therapy in the management of mucous membrane pemphigoid. STUDY DESIGN: The charts of 29 patients who had been diagnosed with mucous membrane pemphigoid by means of routine histologic analysis and direct immunofluorescence were reviewed. The oral features were graded according to severity of disease from 1 to 3. Each patient was assigned to one of 4 groups according to his or her response to therapy. RESULTS: Nine patients were treated successfully with topical corticosteroids alone. Eleven patients with moderate to severe disease who were treated initially with topical steroids showed minimal improvement; after dapsone was added, 7 of the 11 had total resolution of their lesions and 4 had greater than 75% improvement. Two patients had to discontinue dapsone because of side effects. CONCLUSIONS: In this group of 20 patients with moderate to severe mucous membrane pemphigoid, the use of dapsone in combination with topical corticosteroids caused greater than 75% resolution of oral lesions in all patients studied.

Physiologically based pharmacokinetic modeling of inhaled trichloroethylene and its oxidative metabolites in B6C3F1 mice.

A physiologically based pharmacokinetic (PBPK) model for inhaled trichloroethylene (TCE) was developed for B6C3F1 mice. Submodels described four P450-mediated metabolites of TCE, which included chloral hydrate (CH), free and glucuronide-bound trichloroethanol (TCOH-f and TCOH-b), trichloroacetic acid (TCA), and dichloroacetic acid (DCA). Inhalation time course studies were carried out for calibration of the model by exposing mice to TCE vapor concentrations of either 100 or 600 ppm for 4 h. At several time points, mice were euthanized and blood, liver, kidney, lung, and fat were collected and analyzed for TCE and its oxidative metabolites. Peak blood TCE concentrations were 0.86 and 7.32 microgram/mL, respectively, in mice exposed to 100 and 600 ppm TCE. The model overpredicted the mixed venous blood and tissue concentrations of TCE for mice of both exposure groups. Fractional absorption of inhaled TCE was proposed to explain the discrepancy between the model predictions and the TCE blood time course data. When fractional absorption (53%) of inhaled TCE was incorporated into the model, a comprehensive description of the uptake, distribution, and clearance of TCE in the blood was obtained. Fractional uptake of inhaled TCE was further verified by collecting TCE in exhaled breath following a 4-h constant concentration exposure to TCE and validation was provided by testing the model against TCE blood concentrations from an independent data set. The submodels adequately simulated the distribution and clearance kinetics of CH and TCOH-f in blood and the lungs, TCOH-b in the blood, and TCA and DCA, which were respectively detected for up to 43 and 14 h postexposure in blood and livers of mice exposed to 600 ppm TCE. This is the first extensive tissue time course study of the major metabolites of TCE following an inhalation exposure to TCE and the PBPK model predictions were in good general agreement with the observed kinetics of the oxidative metabolites formed in mice exposed to TCE concentrations of 100 and 600 ppm.

Intraoral contact allergy: a literature review and case reports.

Signs and symptoms of contact allergic reactions affecting the oral mucosa may mimic other common oral disorders, making diagnosis difficult. Patients frequently seek multiple consultations and do not receive the correct diagnosis or effective management. As intraoral contact allergy may be more prevalent than previously believed, a review of this topic is warranted. This article emphasizes signs and symptoms that suggest intraoral contact allergy, and the authors discuss the allergens that most frequently affect the oral mucosa.

Comprehensive health data systems spanning the public-private divide: the Massachusetts experience.

As systems of health care delivery have evolved from claims-based fee-for-service to capitated or managed care, with its emphasis on cost-effectiveness, quality, and performance measurement, some states have begun to experiment with new ways to collect, organize, and share health information. In many cases, the drivers of these changes have been purchasers of health care, including large and small private employers and public agencies such as Medicaid. One of the results of these changes is the increased interest in the sharing of health information, between health plans and employers, and, in some instances, between private plans and public agencies such as public health. Massachusetts, which has one of the highest rates of managed care penetration in the United States, has brought together the various parties involved in the collection and utilization of health information, to craft agreements on standards and protocols that will allow the sharing of health data. While much of the activity involves business transactions between private sector health plans, the Department of Medical Assistance (Medicaid) has joined with its private sector purchasing partners in demanding cost-effective, high-quality care; it is these demands that have helped stimulate the need to reorganize previously proprietary health information systems. The activities of two public-private coalitions, the Massachusetts Healthcare Purchaser Group and the Massachusetts Health Data Consortium, have been critical in initiating and supporting the complex processes that have led to significant changes in state-based systems of health information.

When believing is seeing: the effect of scripts on eyewitness memory.

Two studies examined the conditions under which event schema or scripts produce gap-filling errors in eyewitness accounts of a robbery. In Study 1, scripts for the robbery of a convenience store were identified. Results revealed high agreement among the 120 participants concerning the sequence of actions for such a robbery. Based on the information obtained in Study 1, participants in Study 2 (N = 144) viewed one of two sequences of slides depicting a robbery of a convenience store by a lone robber. In one sequence, three central script actions were omitted and in the other, three peripheral script actions were omitted. In addition, rate of exposure was varied (2 vs. 8 sec) as was the length of the retention interval (5 min vs. 1 week). As predicted, there was a higher rate of false recognition for central as opposed to peripheral actions, and this tendency was exaggerated for the longer retention interval. The theoretical and practical implications of the findings are discussed.

Prevalence of hereditary hemochromatosis in a Massachusetts corporation: is Celtic origin a risk factor?

The prevalence of homozygous hereditary hemochromatosis (HHC) is estimated at 1:250 in Caucasian adults. Little is known about ethnic subpopulations that might be at increased risk for this disease. HLA data have suggested a Celtic origin for HHC. Screening for HHC was offered to all employees of the Massachusetts Polaroid Corporation. Participants with a transferrin saturation of >55% or >45% and an elevated serum ferritin concentration on two screenings were referred for liver biopsy. The diagnosis of HHC was based on histological criteria, quantitative hepatic iron determination, hepatic iron index, and the phlebotomy requirement for iron depletion. Participants completed a questionnaire regarding their ethnic background. Two thousand two hundred ninety-four employees were screened, and 5 cases of HHC were detected. All 5 cases involved Caucasian men, yielding a prevalence of 1:395 for the Caucasian population. Four of the 5 cases were of 100% British-Irish ancestry based on the country of origin of their grandparents. Additional analysis revealed that the majority of grandparents of all 4 individuals came from Ireland or Wales. The exact two-tailed trend test showed a significant association of HHC with Celtic background (P = .012). The estimated cost of screening per patient identified was $18,041. Polaroid Corporation has a high representation of employees of British-Irish ancestry. Our data suggest that they are at high risk for developing HHC. A significant association of HHC with Celtic ancestry was found in this subpopulation, supporting the concept of a Celtic origin for this disease.

Relationship of cytomegalovirus to salivary gland dysfunction in HIV-infected patients.

In a previous retrospective study of HIV-infected patients we detected a relationship between xerostomia and the presence of cytomegalovirus in saliva. This prospective study compares 13 patients with HIV and a complaint of xerostomia and low salivary flow rates with a control group of 7 patients with HIV without xerostomia and normal salivary flow rates. Both groups were evaluated for the presence of cytomegalovirus in saliva, peripheral blood mononuclear cells, and labial minor salivary glands. Viral cultures, polymerase chain reaction, and histopathologic examination were used to detect cytomegalovirus. Xerostomia and low salivary flow rates were associated with the presence of CMV in saliva. The virus was detected in 10 of 13 xerostomia patients and 2 of 7 controls (p = 0.05, Fisher's exact test). Cytomegalovirus was detected in the saliva of patients who did not also have it in their blood suggesting a local source of virus replication such as the salivary glands. The minor salivary glands were not a major site of cytomegalovirus. Culture was more sensitive then polymerase chain reaction in detecting salivary cytomegalovirus as a result of the presence of inhibitors to the reaction in saliva. These results suggest a link between cytomegalovirus in saliva and salivary gland dysfunction in HIV-infected patients.