Preventing Opioid Misuse with Prescription Drug Monitoring Programs: A Framework for Evaluating the Success of State Public Health Laws

The United States is in the midst of a prescription opioid overdose and misuse epidemic. Although many factors have contributed to the escalation of prescription painkiller misuse, it parallels increases in the supply and prescribing of opioids. Prominent state-level regulatory interventions, such as the establishment of prescription drug monitoring programs (“PDMPs”), recognize prescribers as opioid gatekeepers. Prescribers, who are uniquely situated to distinguish between appropriate use and misuse of opioids, are a natural target for regulation. PDMPs also target patients who seek to obtain high volumes of prescription opioids for illicit purposes. PDMP policies are widespread but heterogeneous, largely uninformed by robust evidence or a systematic assessment of best practices. Whether these programs successfully reduce opioid misuse and overdoses remains unclear. As well, PDMPs present a number of legal and ethical challenges that, along with intervention effectiveness, warrant careful policymaker consideration going forward. This Article articulates and synthesizes for the first time key criteria intended to assist state regulators in dynamically evaluating and justifying PDMPs and other public health laws. The criteria focus on the legality of the policy, approaches to measure its effectiveness, and normative considerations that should be factored into good laws. Such a framework is crucial for policymakers given the complexities and magnitude of this public health challenge, the rich arsenal of policy options from which to choose, and the slow and uncertain progress in combating prescription painkiller misuse. Concluding recommendations include implementing PDMPs with the following features: timely and complete data, strong incentives for prescriber participation, user guidelines and education, integration into clinical work flow, and robust confidentiality and privacy protections. Ongoing evaluation of programs to identify features appropriate for retention and replication is also crucial if PDMPs are to fulfill their potential to curb prescription opioid overdose and misuse

Morphometric analysis of the mandible in the Durban Metropolitan population of South Africa

Background: The identification of an individual from skeletal remains plays a vital role in forensic investigation as it is essential for the identification of the individual’s age, sex, and/or race and further analysis. Skeletal characteristics differ from one population group to another since population-specific osteometric standards exist for sex determination. Since the mandible is the largest, strongest and most durable compact facial bone, it is the best preserved after death. While sexual dimorphism of the mandible is indicated by its shape and size, morphometric analysis is more accurate in the determination of sex from the skull. The aim of this study was to evaluate the morphometric parameters of the mandible in the Durban Metropolitan population. Materials and methods: Various morphometric parameters of the mandible were measured and assessed in 265 digital panoramic radiographs aged between 16 and 30 years (n = 530). Each parameter recorded was statistically analysed using SPSS to determine if a relationship existed between the parameter, and sex and age. Results: In this study the morphometric parameters of the male mandibles were greater than that of the females. This concurred with the findings of previous studies. The length of the mandibular ramus on the right and left sides was statistically significant with sex. Conclusions: This correlated with previous studies, indicating that the length of the mandibular ramus generally has higher sexual dimorphism than any other morphometric mandibular parameter (p = 0.000). However, only the length of the right mandibular body was statistically significant when compared with sex (p = 0.040). The findings of this study may assist forensic investigators, anatomists, anthropologists and maxillo-facial surgeons.

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects

BACKGROUND: The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. METHODS: Unstimulated saliva samples were collected from 229 OSCC-free and 45 OSCC subjects and evaluated for their content of 40 common oral bacteria using checkerboard DNA-DNA hybridization. DNA counts per ml saliva were determined for each species, averaged across subjects in the 2 subject groups, and significance of differences between groups determined using the Mann-Whitney test and adjusted for multiple comparisons. Diagnostic sensitivity and specificity in detection of OSCC by levels of salivary organisms were computed and comparisons made separately between a non-matched group of 45 OSCC subjects and 229 controls and a group of 45 OSCC subjects and 45 controls matched by age, gender and smoking history. RESULTS: Counts of 3 of the 40 species tested, Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis, were elevated in the saliva of individuals with OSCC (p < 0.001). When tested as diagnostic markers the 3 species were found to predict 80% of cancer cases (sensitivity) while excluding 83% of controls (specificity) in the non-matched group. Diagnostic sensitivity and specificity in the matched group were 80% and 82% respectively. CONCLUSION: High salivary counts of C. gingivalis, P. melaninogenica and S. mitis may be diagnostic indicators of OSCC

Bases microbiológicas para a terapia periodontal

The search for the etiologic agents of periodontal diseases started in the Golden Era of medical bacteriology, when the etiologic agents of many bacterial infections were isolated and characterized. After the initial enthusiasm in establishing the infectious nature and the true agents of periodontal diseases, this concept was virtually ignored for the next four decades. Until the early 1970s treatment regimens based on the non-specific plaque hypothesis were directed towards a non-specific reduction in plaque amount. Later, the specific plaque hypothesis established the role of some microorganisms such as A. actinomycetemcomitans, P. gingivalis, T. forsythensis, T. denticola, P. intermedia and F. nucleatum in different forms of periodontal diseases. It was recently suggested that these suspected periodontal pathogens seem to not act alone and interactions between species, especially the balance between pathogenic and beneficial species affect both progression of disease and response of tissues to periodontal therapy. Nowadays it is well established that one of the goals of therapy is to control such periodontal pathogens. Among the most commonly used therapies to treat periodontal infections are scaling and root planing (SRP), supragingival plaque control and periodontal surgeries. Many studies confirmed the reduction of "red complex" species by SRP, and apically repositioned flap can lead to an additional beneficial effect in the subgingival microbiota by decreasing levels of "red" and "orange complexes" species. Furthermore, the level of plaque control maintained by the patients has been considered a crucial step in preventing recurrence of destructive periodontitis.A busca pelos agentes etiológicos das doenças periodontais iniciou na Época de Ouro da bacteriologia médica, quando os agentes de diversas infecções foram identificados. Após o entusiasmo inicial em estabelecer a natureza infecciosa da doença periodontal, este conceito foi ignorado por quatro décadas. Até o início dos anos 70, terapias baseadas na hipótese da placa não-específica focavam a redução da quantidade de placa. Posteriormente, a hipótese da placa específica determinou o papel de alguns microorganismos como A.actinomycetemcomitams, P.gingivalis, T.forsythensis, T.denticola , P.intermedia e F.nucleatum nas diferentes formas de doença periodontal. Recentemente, foi sugerido que estes patógenos periodontais não atuam isoladamente e interações entre espécies, como o equilíbrio entre bactérias patogênicas e benéficas afetam a progressão da doença e a resposta tecidual à terapia periodontal. Atualmente está bem estabelecido que um dos objetivos da terapia é o controle destes patógenos. Dentre as terapias mais freqüentemente utilizadas no tratamento da periodontite estão raspagem e alisamento radicular (RAR), controle da placa supragengival e cirurgias periodontais. Muitos estudos confirmaram a redução de espécies do "complexo vermelho" pela RAR, e mostraram que o retalho reposicionado apicalmente pode levar a um efeito benéfico adicional na microbiota subgengival pela diminuição nos níveis de espécies dos "complexos vermelho" e "laranja". Além disso, o controle de placa mantido pelos indivíduos é considerado determinante para a prevenção da recorrência de doença periodontal destrutiva

Relationships Among IL-6, TNF-α, Adipokines, Vitamin D and Chronic Periodontitis

Objectives to explore relationships among serum adipokines, vitamin D, clinical and microbial parameters of chronic periodontitis before and after treatment. Methods weight, height and smoking status were recorded for 56 patients with chronic periodontitis. Plaque, gingivitis, bleeding on probing (BOP), suppuration, pocket depth (PD) and attachment level (AL) were measured at all teeth present. Subgingival biofilm samples from each tooth were analyzed for levels of 40 bacterial species using checkerboard DNA-DNA hybridization. Serum levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), adiponectin, leptin, resistin and vitamin D were measured at baseline. Sample collection was then performed in a subset of the population 6 months post-therapy (n=17). Serum samples were analyzed using ELISA and immunoassays. Differences in clinical, microbial and serum factors among groups were sought using the Mann-Whitney test. Correlations among factors were evaluated using regression analysis. Effects of therapy were sought using the Wilcoxon signed ranks test Results There were positive correlations between adiponectin/vitamin D and between IL-6/leptin; negative correlations between IL-6/vitamin D, and leptin/vitamin D, but no associations between serum analytes and clinical or microbial parameters. Gender and BMI were associated with levels of adipokines. Periodontal therapy improved clinical and microbiological parameters, but did not influence the levels of serum analytes. Conclusions Adipokines and IL-6 levels were affected by gender and BMI. Serum analytes were not influenced by periodontal therapy

RNA-Oligonucleotide Quantification Technique (ROQT) for the Enumeration of Uncultivated Bacterial Species in Subgingival Biofilms

Approximately 35% of the species present in subgingival biofilms are as yet uncultivated, so their role in periodontal pathogenesis is unknown. The aim of the present study was to develop a high throughput method to quantify a wide range of cultivated and uncultivated taxa in subgingival biofilm samples associated with periodontal disease or health. Oligonucleotides targeting the 16S ribosomal DNA gene were designed, synthesized and labeled with digoxigenin. These probes were hybridized with the total nucleic acids of pure cultures or subgingival biofilm samples. Target species included cultivated taxa associated with periodontal health and disease, as well as uncultivated species, such as TM7 sp OT 346, Mitsuokella sp. OT 131 and Desulfobulbus sp. OT 041. Sensitivity and specificity of the probes were determined. A Universal probe was used to assess total bacterial load. Sequences complementary to the probes were used as standards for quantification. Chemiluminescent signals were visualized after film exposure or using a CCD camera. In a pilot clinical study, 266 subgingival plaque samples from eight periodontally healthy people and 11 patients with periodontitis were examined. Probes were specific and sensitivity reached 104 cells. Fusobacterium nucleatum ss polymorphum and Actinomyces gerencseriae were the most abundant cultivated taxa in clinical samples. Among uncultivated/unrecognized species, Mitsuokella sp. OT 131 and Prevotella sp. OT 306 were the most numerous. Porphyromonas gingivalis and Desulfobulbus sp. OT 041 were only detected in patients with periodontitis. Direct hybridization of total nucleic acids using oligonucleotide probes permitted the quantification of multiple cultivated and uncultivated taxa in mixed species biofilm samples

Relationships Among Gingival Crevicular Fluid Biomarkers, Clinical Parameters of Periodontal Disease, and the Subgingival Microbiota

Background The objectives were to measure the levels of gingival crevicular fluid (GCF) biomarkers and subgingival bacterial species in periodontally healthy and periodontitis subjects in order to explore relations among these biomarkers, the subgingival microbiota, and clinical parameters of periodontal disease. Material and methods Clinical periodontal parameters were measured at 6 sites per tooth in 20 periodontitis and 20 periodontally healthy subjects. GCF and subgingival plaque samples were obtained from the mesiobuccal aspect of every tooth. GCF levels of interleukin-1β (IL-1β), matrix metalloproteinase-8 (MMP-8) and IL-8 were measured using checkerboard immunoblotting and the levels of 40 bacterial taxa quantified using checkerboard DNA-DNA hybridization. A subset of “clinically healthy” (CH) sites from each group was analyzed separately. Significance of differences between groups was determined using the unpaired t-test or the Mann-Whitney test. Correlations among immunological, microbiological and clinical data were determined using the Spearman rank correlation coefficient. Results There were positive correlations among mean clinical parameters and mean levels of the 3 biomarkers and proportions of Orange and Red complex species (p\u3c0.05). CH sites from periodontitis subjects had higher levels of IL-1β and IL-8 and higher proportions of Orange and Red complex species (p\u3c0.05) than CH sites from periodontally healthy subjects. Red complex species were positively associated with the expression of all biomarkers (p\u3c0.05), while Purple and Yellow complex species had negative correlations with IL-1β and IL-8 (p\u3c0.05). Conclusions CH sites from periodontitis subjects present higher levels of GCF biomarkers and periodontal pathogens than CH sites from periodontally healthy subjects. Different microbial complexes demonstrated distinct associations with specific GCF biomarkers

Microbial Shifts During Dental Biofilm Re-Development in the Absence of Oral Hygiene in Periodontal Health and Disease

Aim to monitor microbial shifts during dental biofilm re-development Methods Supra and subgingival plaque samples were taken separately from 28 teeth in 38 healthy and 17 periodontitis subjects at baseline and immediately after tooth cleaning. Samples were taken again from 7 teeth in randomly selected quadrants during 1, 2, 4 and 7 days of no oral hygiene. Samples were analyzed using checkerboard DNA-DNA hybridization. Species counts were averaged within subjects at each time point. Significant differences in counts between healthy and periodontitis subjects were sought using the Mann-Whitney test. Results Total supra and subgingival counts were significantly higher in periodontitis on entry and reached or exceeded baseline values after day 2. Supragingival counts of Veillonella parvula, Fusobacterium nucleatum ss vincentii and Neisseria mucosa increased from 2 to 7 days. Subgingival counts were greater for Actinomyces, green and orange complex species. Significant differences between groups in supragingival counts occurred for 17 of 41 species at entry, 0 at day 7; for subgingival plaque these values were 39/41 taxa at entry, 17/41 at day 7. Conclusions Supragingival plaque re-development was similar in periodontitis and health, but subgingival species recolonization was more marked in periodontitis