Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR Dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with 3 dental practice-based research networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95% CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased 4-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment >2 years; suppuration and dental extractions were independent risk factors for ONJ.

Aging effects on oropharyngeal swallow and the role of dental care in oropharyngeal dysphagia.

Difficulty with oropharyngeal swallow requires careful diagnosis and treatment from a team of professionals including the patients' physicians and the speech-language pathologist specializing in dysphagia. The dentist can be a critical team member in prevention, early identification, and management of oropharyngeal dysphagia. This manuscript reviews the physiology of normal oropharyngeal swallow and the effects of normal aging on this physiology. Typical etiologies for oropharyngeal dysphagia are defined as is the most commonly used physiologic diagnostic procedure, the modified barium swallow (MBS). The critical role of the dentist in identifying risk of oropharyngeal dysphagia, making appropriate referrals, and improving oral hygiene to prevent aspiration pneumonia in the elderly is discussed.

Dental risk factors for osteonecrosis of the jaws: a CONDOR case-control study.

BACKGROUND: Reports of osteonecrosis of the jaw (ONJ) have associated this lesion to treatment with bisphosphonates (BPs) and dental procedures. In this study, we investigated the association of specific dental diagnoses and procedures with ONJ among patients with past BP use. METHODS: Dentists from three practice-based research networks provided ONJ cases and controls (1:3). Data gathered from patients and dental offices with two respective standard questionnaires included demographic, medical, pharmaceutical, and dental information. Diagnoses and procedures up to 3 years prior to ONJ (prior to interview for controls) were analyzed within risk strata, defined by BP use and cancer status, using interaction terms within conditional logistic regression models. RESULTS: We enrolled 191 ONJ cases and 573 controls from 119 dental offices. Among participants who had used only oral BP, extraction was the only dental risk factor for ONJ (odds ratio (OR) = 12, p = 0.01). Suppuration was also more prevalent in cases (18 %) than in controls (9 %), but not statistically significant (OR = 9, p = 0.06). Among participants who had not used either oral or IV BP (a majority of whom received radiation therapy to the head and neck), suppuration was the only dental risk factor for ONJ (prevalence = 34 % for cases and 8 % for controls; OR = 7, p = 0.01). The prevalence of extractions in this group was also higher, but not statistically significant (44 vs 10 %; OR = 3). Limited power precludes definitive findings among participants exposed to IV BP. CONCLUSIONS: Among patients taking oral BP, extraction was the only dental procedure associated with subsequent ONJ development CLINICAL RELEVANCE: Results of this study suggest that routine dental procedures are not associated with development of ONJ in patients exposed to BPs.

The PBRN initiative: transforming new technologies to improve patient care.

The NIDCR-supported Practice-based Research Network initiative presents dentistry with an unprecedented opportunity by providing a pathway for modifying and advancing the profession. It encourages practitioner participation in the transfer of science into practice for the improvement of patient care. PBRNs vary in infrastructure and design, and sustaining themselves in the long term may involve clinical trial validation by regulatory agencies. This paper discusses the PBRN concept in general and uses the New York University College of Dentistry's Practitioners Engaged in Applied Research and Learning (PEARL) Network as a model to improve patient outcomes. The PEARL Network is structured to ensure generalizability of results, data integrity, and to provide an infrastructure in which scientists can address clinical practitioner research interests. PEARL evaluates new technologies, conducts comparative effectiveness research, participates in multidisciplinary clinical studies, helps evaluate alternative models of healthcare, educates and trains future clinical faculty for academic positions, expands continuing education to include "benchmarking" as a form of continuous feedback to practitioners, adds value to dental schools' educational programs, and collaborates with the oral health care and pharmaceutical industries and medical PBRNs to advance the dental profession and further the integration of dental research and practice into contemporary healthcare (NCT00867997, NCT01268605).

An assessment of the perceived benefits and challenges of participating in a practice-based research network.

BACKGROUND: A survey was conducted to describe the benefits of and challenges to practitioner participation in the Practitioners Engaged in Applied Research and Learning (PEARL) Network, a dental practice-based research network (PBRN). The results were compared with results from medical PBRNs across different tiers of participation (based on practitioner-investigators previous involvement with PEARL research protocols). METHODS: A 39-item web-based survey addressed the benefits of PBRN participation on three levels: individual/practitioner, practice (office), and community/professional. Participants were also asked to rate challenges to participation. RESULTS: A total of 153 of 216 PEARL practitioner-investigators participated, a response rate of 71%. The majority (70%) was male, with a median of 23 years in private practice. 'Means to stay informed of new developments in my profession' was considered a 'very important' benefit for nearly three-quarters of the sample (71%). 'Opportunity to improve clinical procedures' was considered as 'very important' by 73% of respondents. In terms of benefits related to the community and profession, 65% of respondents reported 'means to directly contribute to the evidence base of dental practice' as being 'very important'. 'Disruption in practice routine/clinical practice' was considered the most important challenge to participation. CONCLUSIONS: The benefits of and challenges to participation identified did not differ across tiers of participation and were similar to benefits identified by participants in medical PBRNs. The results of this study will help facilitate the design of future PBRN protocols to encourage greater participation by the profession. Results suggest that practitioners with similar interests could be recruited to collaborative studies between medicine and dentistry.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with three dental Practice-based Research Networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95%CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased four-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment > 2 years; suppuration and dental extractions were independent risk factors for ONJ.

Adapting to changes in molecular biosciences and technologies.

Dental education, like any other educational programme in a research-intensive university environment, must be research led or at least research informed. In this context, as the research and knowledge base of dentistry lies in the biological and physical sciences, dental education must be led by advances in research in both these areas. There is no doubt that biotechnology and nanotechnology have, over the past 25 years, led research in both these areas. It is therefore logical to assume that this has also impacted on dental education. The aim of this paper is twofold; on one hand to examine the effects of biotechnology and nanotechnology and their implications for dental education and on the other to make recommendations for future developments in dental education led by research in biotechnology and nanotechnology. It is now generally accepted that dental education should be socially and culturally relevant and directed to the community it serves. In other words, there can be no universal approach and each dental school or indeed curriculum must apply the outcomes in their own social, cultural and community settings.

Effects of high-dose vitamin E supplementation on oxidative stress and microalbuminuria in young adult patients with childhood onset type 1 diabetes mellitus.

INTRODUCTION: The aim of this study was to evaluate the effects of high-dose vitamin E supplementation (1200 mg/day) on reducing both microalbuminuria (MA) and oxidative stress in patients with type 1 diabetes mellitus (T1DM) and persistent MA. METHODS: We performed a 12-month, randomized, placebo-controlled, double-blind cross-over trial in ten Caucasian young adults (7m/3f; mean age 18.87 +/- 2.91 years) with T1DM and persistent MA. At baseline and at end of the treatment period, determination of albumin excretion rate (AER) and HbA(1c) and evaluation of the oxidant/antioxidant status were performed. RESULTS: At the beginning of the study, AER and HbA(1c) were not significantly different between the vitamin E and placebo group. No differences in terms of oxidant and antioxidant status were found between the two groups. This was associated with no significantly different urinary VEGF and TGF-beta levels. After 6 months, no significant differences in AER were observed between the two groups (p = 0.59). However, plasma and LDL-vitamin E content were significantly higher in the vitamin E group compared to the placebo group (p = 0.0001 and p = 0.004, respectively). This was associated with a significantly longer lag phase (p = 0.002) and lower MDA (p = 0.049). However, no statistically significant differences were detected in terms of VEGF and TGF-beta urinary levels. CONCLUSION: These data demonstrate that high-dose vitamin E supplementation reduces markers of oxidative stress and improves antioxidant defence in young patients with T1DM. However, although it positively affects the oxidant/antioxidant status, vitamin E supplementation does not reduce AER in patients with T1DM and persistent MA.

Clinical evaluation of ferric oxalate in relieving dentine hypersensitivity.

Previous in vitro permeability and scanning electron microscopic (SEM) studies have demonstrated the effectiveness of the oxalate ion in dentine permeability reduction and effective tubule occlusion. The aim of this randomized double-blind, split mouth 4-week clinical study, therefore was to determine whether a 1-min application of ferric oxalate (Sensodyne Sealant) on exposed root dentine was effective in reducing dentine hypersensitivity (DH). Thirteen subjects [8F:5M, mean age 46.2 (s.d. 4.15) years] completed the study. The subjective response was evaluated by tactile, thermal and evaporative methods of assessment. Data were collected at baseline and post-application at +5 min and 4 weeks. Analysis was based on paired t-test (P=0.05) and Wilcoxon-Mann-Whitney tests. No statistically significant differences were noted between ferric oxalate and placebo preparations at +5 min and 4 weeks for any of the test stimuli. There was, however, a clear trend towards immediate reduction (+5 min) in DH reverting back to baseline values at 4 weeks with the exception of the Biomat Thermal Probe mean values, which maintained the reductions in DH compared with placebo. The results of the present study demonstrated that a 1-min application of ferric oxalate is both rapid and effective in reducing DH although its long-term effectiveness still needs to be determined.

A framework for risk assessment and decision-making strategies in dangerous good transportation.

The risk from dangerous goods transport by road and strategies for selecting road load/routes are faced in this paper, by developing an original site-oriented framework of general applicability at local level. A realistic evaluation of the frequency must take into account on one side inherent factors (e.g. tunnels, rail bridges, bend radii, slope, characteristics of neighborhood, etc.) on the other side factors correlated to the traffic conditions (e.g. dangerous goods trucks, etc.). Field data were collected on the selected highway, by systematic investigation, providing input data for a database reporting tendencies and intrinsic parameter/site-oriented statistics. The developed technique was applied to a pilot area, considering both the individual risk and societal risk and making reference to flammable and explosive scenarios. In this way, a risk assessment, sensitive to route features and population exposed, is proposed, so that the overall uncertainties in risk analysis can be lowered.

Occupational injuries in Italy: risk factors and long term trend (1951-98).

OBJECTIVES: Trends in the rates of total injuries and fatal accidents in the different sectors of Italian industries were explored during the period 1951-98. Causes and dynamics of injury were also studied for setting priorities for improving safety standards. METHODS: Data on occupational injuries from the National Organisation for Labour Injury Insurance were combined with data from the State Statistics Institute to highlight the interaction between the injury frequency index trend and the production cycle-that is, the evolution of industrial production throughout the years. Multiple regression with log transformed rates was adopted to model the trends of occupational fatalities for each industrial group. RESULTS: The ratios between the linked indices of injury frequency and industrial production showed a good correlation over the whole period. A general decline in injuries was found across all sectors, with values ranging from 79.86% in the energy group to 23.32% in the textile group. In analysing fatalities, the trend seemed to be more clearly decreasing than the trend of total injuries, including temporary and permanent disabilities; the fatalities showed an exponential decrease according to multiple regression, with an annual decline equal to 4.42%. CONCLUSIONS: The overall probability of industrial fatal accidents in Italy tended to decrease exponentially by year. The most effective actions in preventing injuries were directed towards fatal accidents. By analysing the rates of fatal accident in the different sectors, appropriate targets and priorities for increased strategies to prevent injuries can be suggested. The analysis of the dynamics and the material causes of injuries showed that still more consideration should be given to human and organisational factors.

Interleukin-6 production by human monocytes stimulated with Cryptococcus neoformans components.

In order to ascertain if Cryptococcus neoformans components can induce interleukin-6 (IL-6) production, we stimulated human whole blood with purified capsular products. Their potencies in stimulating IL-6 release were mannoproteins > galactoxylomannan = glucuronoxylomannan > alpha(1-3)glucan. IL-6 production was tumor necrosis factor alpha independent and required the presence of monocytes and plasma. Since IL-6 can stimulate replication of the human immunodeficiency virus in monocytic cells, these findings may be clinically relevant.

In vitro effects of lithium chloride on TNF alpha and IL-6 production by monocytes from breast cancer patients.

It is well known that lithium chloride (LiCl) is able to trigger human monocytes to release tumor necrosis factor alpha (TNF alpha). In this study we have evaluated the in vitro effect of LiCl on TNF alpha and interleukin-6 (IL-6) release by monocytes from patients affected by non-metastatic (BCa/M0) and metastatic breast cancer (BCa/M1), preincubated with autologous serum (sPt). Our data demonstrate that monocytes from cancer patients (BCa) treated with LiCl released lower amounts of TNF alpha compared to those from healthy donors (HD). Preincubation in autologous serum (sPt) impaired TNF alpha production by monocytes from BCa with LiCl. On the contrary, our data indicate that IL-6 production by monocytes treated was not impaired. Moreover, the results obtained from the same cells, preincubated in sPt and treated with LiCl, indicate that serum factors may synergize with LiCl treatment in releasing IL-6.

Amlexanox oral paste: a novel treatment that accelerates the healing of aphthous ulcers.

Five percent Amlexanox oral paste is a novel treatment for aphthous ulcers. In 3 controlled clinical studies that evaluated 1,124 immunocompetent patients with mild to moderate aphthous ulcers, 5% Amlexanox oral paste (Aphthasol) was shown to accelerate healing of these ulcers. Treatment with Aphthasol reduced the median time to ulcer healing and to complete pain resolution in a statistically significant manner. This was true both when treatment with 5% Amlexanox oral paste was compared to treatment with a vehicle and when treatment with the Amlexanox paste was compared to no treatment. Study results after 3 days comparing treatment with the paste and no treatment indicated complete healing of ulcers for 21% and 8% of patients, respectively. Complete resolution of pain after 3 days was reported for 44% and 20% of patients, respectively.

Desensitizing effect of a potassium chloride dentifrice.

Sensodyne F is a potassium chloride (KCl) and sodium monofluorphosphate (MFP) containing dentifrice currently marketed in the United Kingdom and Germany was compared to a KCl only dentifrice and to a placebo dentifrice for effectiveness in alleviating dentin hypersensitivity. This 3-cell, randomized, double-blind, parallel clinical study utilized 62 subjects for an 8-week duration of product use. The degree of hypersensitivity of the affected teeth was assessed by tactile stimulation, cold air stimulation and overall subjective patient response. The results from these three methods of assessment indicated that a KCl containing dentifrice either alone or in combination with sodium MFP were significantly more effective than the placebo dentifrice in reducing dentin hypersensitivity. The therapeutic response to the KCl dentifrices as measured by air sensitivity and tactile sensitivity was statistically significant when compared to the placebo dentifrice within 4 weeks of use. Significant improvement was seen for all parameters at the conclusion of the 8-week clinical study period. Plaque reduction was significantly reduced at 8 weeks. The results indicate that KCl is an efficacious molecule in reducing dentin hypersensitivity when used either alone or in combination with sodium MFP as measured by improved overall patient comfort.

Caries prevalence in xerostomic individuals.

Saliva, via its lubricating, cleansing, remineralizing, antibacterial, and buffering actions, is an important protective factor for both dentition and soft tissue. Xerostomia is commonly found in older individuals due to the use of medications or medical conditions, such as Sjögren's, which directly affect salivary gland function. A xerostomic subgroup (n = 60), mean age = 60, 66 per cent female) of the Nutrition and Oral Health Study (n = 370) was reexamined for caries. Unstimulated and two-per-cent citric-acid stimulated parotid and submandibular/sublingual salivary flow rates were determined. This group was matched for number of teeth, age, sex, and alcohol and smoking habits with a medication-free subgroup (n = 60). Active root and coronal caries were found to be significantly higher in the xerostomic subgroup than in a matched subgroup of medication-free individuals. The mean DFS for the xerostomic subgroup was 45.4 +/- 21.7 for coronal caries and 5.3 +/- 5.8 for root caries. The mean number of teeth was 21.8. The mean DFS in the medication-free subgroup was 36.5 +/- 22.1 for coronal caries and 3.2 +/- 3.2 for root caries. The mean DFS in the xerostomic subgroup for coronal and root caries was statistically significantly higher (p < 0.05). The odds ratio was 2.89 for coronal caries and 3.27 for root caries in the xerostomic versus the medication-free subgroup. Caries varied inversely with salivary flow rate. The difference in flow rates for those in the lowest and highest quartile for coronal caries experience (DFS) in the xerostomic subgroup was found to be statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical effectiveness of a dentifrice containing potassium chloride as a desensitizing agent.

Sensodyne F, a dentifrice currently marketed in the United Kingdom, containing potassium chloride (KCl) and sodium monofluorophosphate (MFP) was compared to a placebo dentifrice for effectiveness in alleviating dentinal hypersensitivity. This randomized, double-blind, parallel clinical study covered 12 weeks of product use by 41 subjects. Hypersensitivity levels of the affected teeth were assessed by tactile stimulation, cold air stimulation and overall subjective patient response. The results from these three methods of assessment demonstrated that the KCl/MFP dentifrice was significantly more effective than the placebo dentifrice in reducing dentinal hypersensitivity. The therapeutic response to the KCl/MFP dentifrice as measured by air sensitivity and overall subjective evaluation was statistically significant when compared to the placebo dentifrice within 4 weeks of use. Significant improvement was observed for all parameters at the conclusion of the 12-week clinical study period. Plaque reduction was significantly reduced at week 8 and continued to improve by week 12. The results indicate that KCl with sodium MFP significantly reduced dentinal hypersensitivity and improved overall patient comfort.

Bioavailability of aspirin and salicylamide following oral co-administration in human volunteers.

BC powder (I) is a commercially available analgesic containing the active ingredients aspirin and salicylamide. The kinetics of I, BC powder minus aspirin (II), and BC powder minus salicylamide (III) were evaluated in 13 volunteers. Ten minutes after administration of I, aspirin reached a maximum concentration of 12.9 micrograms/mL, while salicylamide concentration reached a peak value of 3.4 micrograms/mL. However, when III was administered, aspirin was not detected at 10 min and only reached a concentration of 0.4 microgram/mL at 2 and 6 h. Furthermore, the area under the plasma concentration versus time curve for aspirin when III was administered was sixfold less compared with treatment with I. The area under the curve for aspirin metabolites was significantly different in I versus III. After treatment with II, a delay in salicylamide peak concentration was observed. Gentisamide was not detected throughout the study. This study demonstrates that salicylamide significantly enhances plasma levels of aspirin with potential therapeutic implications.

The effect of thromboxane on contraction of canine mesenteric and lingual arteries.

Thromboxane A2 (TXA2), a potent vasoconstrictor agent, is released from platelets and smooth muscle during inflammation and trauma. TXA2 may cause lingual artery (LA) contraction, leading to lingual paresthesia. The effects of U-46619, a TxA2 mimetic, on isolated rings of canine LA and mesenteric artery (MA) were examined. U-46619 (1 nmol/L to 1 mumol/L) caused a triphasic contraction of LA and MA; a rapid, phasic contraction; a slow, sustained contraction; and, upon washout of U-46619, a maintained contraction. The MA relaxed slowly, but the LA remained contracted for at least three h after washout. Decreasing extracellular calcium ion (Ca2+o) to less than 0.1 mumol/L with 2 mmol/L EGTA relaxed MA, but not LA. EGTA (4 mmol/L) partially relaxed the maintained contraction of LA. Inhibition of protein kinase C with amphotericin B or staurosporine inhibited the phasic and sustained contractions of LA, but did not affect the maintained contraction in the presence or absence of EGTA. Thus, CA2+o was required for the initial contraction of the LA by U-46619, but did not appear to be required for the maintained contraction following washout of U-46619. The data support the conclusion that following a brief exposure to U-46619, maintained contraction of LA persists by a unique mechanism that may be independent of Ca2+ and protein kinase C. Sustained LA contraction after exposure to endogenous TXA2 during inflammation and trauma may contribute to impaired lingual blood flow and orofacial tissue injury.