Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in adolescents, adults, and older adults: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania.

BACKGROUND: A panel convened by the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania conducted systematic reviews and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after simple and surgical tooth extraction(s) and for the temporary management (ie, definitive dental treatment not immediately available) of toothache associated with pulp and periapical diseases in adolescents, adults, and older adults. TYPES OF STUDIES REVIEWED: The panel conducted 4 systematic reviews to determine the effect of opioid and nonopioid analgesics, local anesthetics, corticosteroids, and topical anesthetics on acute dental pain. The panel used the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations, Assessment, Development and Evaluation Evidence-to-Decision Framework to formulate recommendations. RESULTS: The panel formulated recommendations and good practice statements using the best available evidence. There is a beneficial net balance favoring the use of nonopioid medications compared with opioid medications. In particular, nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen likely provide superior pain relief with a more favorable safety profile than opioids. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Nonopioid medications are first-line therapy for managing acute dental pain after tooth extraction(s) and the temporary management of toothache. The use of opioids should be reserved for clinical situations when the first-line therapy is insufficient to reduce pain or there is contraindication of nonsteroidal anti-inflammatory drugs. Clinicians should avoid the routine use of just-in-case prescribing of opioids and should exert extreme caution when prescribing opioids to adolescents and young adults.

Utilizing deliberative engagement for identifying implementation strategy priorities: lessons learned from an online deliberative forum with dental professionals.

BACKGROUND: Selecting effective implementation strategies to support guideline-concordant dental care is a complex process. We are drawing on data collected during the DISGO study to reflect on barriers we encountered in implementing a deliberative engagement process for discussing implementation strategies relevant to the evidence-based guideline targeted in this intervention. The goal is to identify factors that may influence the success of deliberative engagement as a technique to involve healthcare staff in identifying priorities for implementation strategies. METHODS: We drew on online chat transcripts from the deliberative engagement forums collected during the DISGO study. The chat transcripts were automatically generated for each discussion and captured the written exchanges between participants and moderators in all participating dental clinics. Chat transcripts were analyzed following a content analysis approach. RESULTS: Our findings revealed barriers to the successful implementation of deliberative engagement in the context of the DISGO study. Participants were not familiar with the materials that had been prepared for the forum and lacked familiarity with the topic of deliberation. Participants also did not share divergent viewpoints and reinforced existing ideas rather than introducing new ideas. CONCLUSIONS: In order to ensure that obstacles that were encountered in this study are not repeated, it is important to carefully consider how staff can effectively be prepared for the deliberations. Participants must be familiar with the content of the guideline, and most questions about the content and evidence should be answered before the deliberative engagement sessions. If perspectives among staff on a guideline are homogenous, briefing materials should introduce perspectives that complement existing views among staff. It is also necessary to create an environment in which staff are comfortable introducing opinions that may not be held by the majority of colleagues. TRIAL REGISTRATION: This project is registered at ClinicalTrials.gov with ID NCT04682730. The trial was first registered on 12/18/2020. https://clinicaltrials.gov/ct2/show/NCT04682730 .

Non-invasive assessment of cultivar and sex of Cannabis sativa L. by means of hyperspectral measurement.

Cannabis sativa L. is a versatile crop attracting increasing attention for food, fiber, and medical uses. As a dioecious species, males and females are visually indistinguishable during early growth. For seed or cannabinoid production, a higher number of female plants is economically advantageous. Currently, sex determination is labor-intensive and costly. Instead, we used rapid and non-destructive hyperspectral measurement, an emerging means of assessing plant physiological status, to reliably differentiate males and females. One industrial hemp (low tetrahydrocannabinol [THC]) cultivar was pre-grown in trays before transfer to the field in control soil. Reflectance spectra were acquired from leaves during flowering and machine learning algorithms applied allowed sex classification, which was best using a radial basis function (RBF) network. Eight industrial hemp (low THC) cultivars were field grown on fertilized and control soil. Reflectance spectra were acquired from leaves at early development when the plants of all cultivars had developed between four and six leaf pairs and in three cases only flower buds were visible (start of flowering). Machine learning algorithms were applied, allowing sex classification, differentiation of cultivars and fertilizer regime, again with best results for RBF networks. Differentiating nutrient status and varietal identity is feasible with high prediction accuracy. Sex classification was error-free at flowering but less accurate (between 60% and 87%) when using spectra from leaves at early growth stages. This was influenced by both cultivar and soil conditions, reflecting developmental differences between cultivars related to nutritional status. Hyperspectral measurement combined with machine learning algorithms is valuable for non-invasive assessment of C. sativa cultivar and sex. This approach can potentially improve regulatory security and productivity of cannabis farming.

Sharing voice during deliberative engagement to improve guideline adherence in dental clinics: findings from a qualitative evaluation of an online deliberative forum discussion.

OBJECTIVES: Selecting effective implementation strategies to support guideline-concordant dental care is a complex process. For this research project, an online deliberative forum brought together staff from dental clinics to discuss the strengths and weaknesses of implementation strategies and barriers to implementation of a component of a dental (pit-and-fissure) guideline. The goal was to determine whether deliberative engagement enabled participants' sharing of promotive and prohibitive voice about implementation strategies to promote guideline-concordant care. DESIGN: Qualitative analysis of online chat transcripts of facilitated deliberations from 31 small group sessions. SETTING: Kaiser Permanente Dental (KP Dental) in the USA. PARTICIPANTS: All staff from 16 dental offices. RESULTS: The directed content analysis revealed that participants shared prohibitive and promotive voice when offering critique of the barriers and the implementation strategies suggested by the researchers. The analysis also revealed that the focus of the deliberations often was not on the aspect of the pit-and-fissure guideline intended by the research team for deliberation. CONCLUSIONS: The deliberative forum discussions were a productive venue to ask staff in dental clinics to share their perspectives on strategies to promote guideline-concordant care as well as barriers. Participants demonstrated prohibitive voice and engaged critically with the materials the research team had put together. An important limitation of the deliberation was that the discussion often centred around an aspect of the pit-and-fissure guideline that already was implemented well. To ensure a deliberation oriented towards resolving challenging aspects of the pit-and-fissure guideline, greater familiarity with the guideline would have been important, as well as more intimate knowledge of the current discrepancies in guideline-concordant care. TRIAL REGISTRATION NUMBER: This project is registered at ClinicalTrials.gov with ID NCT04682730. The trial was first registered on 18 December 2020. https://clinicaltrials.gov/ct2/show/NCT04682730.

Testing a Deliberative Democracy Engagement Intervention to Increase Guideline-Concordance Among Oral Health Providers: Results from the DISGO Cluster-Randomized, Stepped-Wedge Trial.

Background: Dental caries affects billions worldwide and in the U.S. is among the most prevalent noncommunicable diseases in both children and adults. Early in the caries process, it can be arrested by dental sealants, which are non-invasive and thus tooth sparing, however, few dentists have adopted this approach. Deliberative engagement processes enable participants to engage with diverse perspectives on a policy issue and develop and share with policy makers informed opinions about the policy issue. We examined the effects of a deliberative engagement process on the ability of oral health providers to endorse implementation interventions and to apply dental sealants. Methods: Using a stepped wedge design, 16 dental clinics were cluster randomized, and 680 providers and staff were exposed to a deliberative engagement process that included an introductory session, workbook, facilitated small group deliberative forum, and post-forum survey. Forum participants were assigned to forums to ensure diverse role representation. Mechanisms of action examined included sharing voice and diversity of opinion. Three months after each clinic's forum, the clinic manager was interviewed about implementation interventions deployed. There were 98 clinic-months in the non-intervention period and 101 clinic-months in the intervention period. Results: Compared with providers and staff in small clinics, providers and staff in medium and large clinics more strongly agreed that their clinic should adopt two of the three proposed implementation interventions targeting the first barrier and one of the two proposed implementation interventions targeting the second barrier. Compared with the non-intervention period, in the intervention period providers did not place more sealants on occlusal non-cavitated carious lesions. Survey respondents reported sharing both promotive and prohibitive voice. From the beginning to the end of the forums, most forum participants did not change their opinions about the possible implementation interventions. At the end of the forums, there was no significant within-group variability in implementation interventions endorsed. Conclusions: Deliberative engagement intervention may help clinic leadership identify implementation interventions when there is a challenging problem, a network of semi-autonomous clinics, and autonomous providers within those clinics. It remains to be determined whether there is a range of perspectives within clinics. Trial Registration: This project is registered at ClinicalTrials.gov with ID NCT04682730. The trial was first registered on 12/18/2020. https://clinicaltrials.gov/ct2/show/NCT04682730.

Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in children: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania.

BACKGROUND: A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of Pittsburgh School of Dental Medicine, and Center for Integrative Global Oral Health at the University of Pennsylvania conducted a systematic review and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after 1 or more simple and surgical tooth extractions and the temporary management of toothache (that is, when definitive dental treatment not immediately available) associated with pulp and furcation or periapical diseases in children (< 12 years). TYPES OF STUDIES REVIEWED: The authors conducted a systematic review to determine the effect of analgesics and corticosteroids in managing acute dental pain. They used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations. RESULTS: The panel formulated 7 recommendations and 5 good practice statements across conditions. There is a small beneficial net balance favoring the use of nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen compared with not providing analgesic therapy. There is no available evidence regarding the effect of corticosteroids on acute pain after surgical tooth extractions in children. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Nonopioid medications, specifically nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen alone or in combination with acetaminophen, are recommended for managing acute dental pain after 1 or more tooth extractions (that is, simple and surgical) and the temporary management of toothache in children (conditional recommendation, very low certainty). According to the US Food and Drug Administration, the use of codeine and tramadol in children for managing acute pain is contraindicated.

Strategies for developing evidence-based clinical practice guidelines to foster implementation into dental practice.

BACKGROUND: Professional and other organizations, including oral health care organizations, have been developing evidence-based clinical practice guidelines (CPGs) to help providers incorporate the best available evidence into their clinical decision making. Although the rigor of guideline development has increased over time, ongoing challenges prevent the full adoption of CPGs into clinical practices that experience variability in provider expertise and opinion, patient flow pace, and use of electronic dental records. These challenges include lack of relevant evidence, failure to keep guidelines up to date, and failure to adopt strategies aimed at overcoming the barriers preventing implementation into clinical practice. RESULTS: This article provides a brief overview of strategies that can be used to overcome common challenges to guideline adoption. Such strategies include creating evidence-based CPGs that use additional sources of evidence and methods to inform guideline development and accelerate the guideline updating and dissemination process (that is, evidence directly from clinical practice, big data, patients' values and preferences, and living guidelines) and applying implementation strategies that have been documented as improving translation of CPGs into routine clinical practice (that is, guideline implementability, implementation science, and computable guidelines). PRACTICAL IMPLICATIONS: Adopting newer strategies for developing and translating evidence into practice could lead to improvements in patient care and population health.

Study protocol: A stepped-wedge, cluster-randomized trial of the effectiveness of a deliberative loop in identifying implementation strategies for the adoption of a dental sealant guideline in dental clinics.

BACKGROUND: The American Dental Association (ADA) recommends dental providers apply dental sealants to the occlusal surfaces of permanent molars for the prevention or treatment of non-cavitated dental caries. Despite the evidence-based support for this guideline, adherence among general dentists is low, ranging from less than 5 to 38.5%. Thus, an evidence-to-practice gap exists, and it is unclear which implementation strategies would best support providers in adopting and implementing the evidence-based practice. One potential approach to selecting and tailoring implementation strategies is a deliberative loop process, a stakeholder-engaged approach to decision-making. This trial aims to test the acceptability, feasibility, and effectiveness of using a deliberative loop intervention with stakeholders (i.e., providers and staff) to enable managers to select implementation strategies that facilitate the adoption of an evidence-based dental practice. METHODS: Sixteen dental clinics within Kaiser Permanente Northwest Dental will be cluster randomized to determine the timing of receiving the intervention in this stepped-wedge trial. In the three-part deliberative loop intervention, clinic stakeholders engage in the following activities: (1) receive background information, (2) participate in facilitated small-group discussions designed to promote learning from each other's lived experiences and develop informed opinions about effective clinic-level implementation strategies, and (3) share their informed opinions with clinic leaders, who may then choose to select and deploy implementation strategies based on the stakeholders' informed opinions. The primary outcome of Reach will be defined as patient-level receipt of guideline-concordant care. Secondary outcomes will include the cost-effectiveness, acceptability, and feasibility of the deliberative loop process. Implementation strategies deployed will be catalogued over time. DISCUSSION: These results will establish the extent to which the deliberative loop process can help leaders select and tailor implementation strategies with the goal of improving guideline-concordant dental care. TRIAL REGISTRATION: This project is registered at ClinicalTrials.gov with ID NCT04682730. The trial was first registered on 12/18/2020. https://clinicaltrials.gov/ct2/show/NCT04682730.

Can the lack of HSP90alpha protein in brain normal tissue and cell lines, rationalise it as a possible therapeutic target for gliomas?

Despite studies suggesting a role for HSP90alpha in tumorigenesis, there are no reports as to its expression in normal human brain tissue. In this study, the expression of HSP90alpha was evaluated in both cell lines (3 gliomas and 2 controls) and brain tissue specimens of 10 patients (8 gliomas and 2 normal brain tissues). No HSP90alpha protein was detected in either normal cell lines or normal brain tissue. However, 8/8 glioma tissues and 3/3 glioma cell lines did express HSP90alpha. These findings provide a rationale for targeting HSP90alpha protein as a therapeutic candidate for glioma.

Telomerase subunits expression variation between biopsy samples and cell lines derived from malignant glioma.

Although scientific advances have recognised the prognostic power of telomerase activity in different cancers, as yet there has been no investigation regarding the expression variation of telomerase subunits in glioma tissues and cell lines. In this study, a recurrent anaplastic ependymoma and seven glioblastoma biopsy samples, four cell lines and four controls including two normal brain tissues were analysed for telomerase subunit expression profiles together with telomerase activity. Since telomerase activity is linked to tumourgenesis, the genes were analysed with respect to their expression variation. TEP1 was expressed in all glioma cell lines and 70% of glioblastoma tissues, in addition to the control brain tissues. Tankyrase was expressed in 85% of the glioblastoma tissues and was down-regulated in the recurrent anaplastic ependymoma tissue control cell lines. However, it was expressed in the control tissues. Dyskerin was expressed in all cell lines and tissues apart from U87-MG and NHA cells and the recurrent anaplastic ependymoma tissue. As expected, PARP1 and GAPDH showed constitutive expression throughout all cell lines and tissues since both are known to be housekeeping genes. hTERT was expressed in all glioma cell lines and tissues but was absent in the control cells and tissues. Telomerase activity was absent in IPDDC-A2 cells and 57% of the glioblastoma tissues. These results suggest that hTERT expression and not telomerase activity possibly represents a simple and reliable biological diagnostic tool.

Buried shallow fault slip from the South Napa earthquake revealed by near-field geodesy.

Earthquake-related fault slip in the upper hundreds of meters of Earth's surface has remained largely unstudied because of challenges measuring deformation in the near field of a fault rupture. We analyze centimeter-scale accuracy mobile laser scanning (MLS) data of deformed vine rows within ±300 m of the principal surface expression of the M (magnitude) 6.0 2014 South Napa earthquake. Rather than assuming surface displacement equivalence to fault slip, we invert the near-field data with a model that allows for, but does not require, the fault to be buried below the surface. The inversion maps the position on a preexisting fault plane of a slip front that terminates ~3 to 25 m below the surface coseismically and within a few hours postseismically. The lack of surface-breaching fault slip is verified by two trenches. We estimate near-surface slip ranging from ~0.5 to 1.25 m. Surface displacement can underestimate fault slip by as much as 30%. This implies that similar biases could be present in short-term geologic slip rates used in seismic hazard analyses. Along strike and downdip, we find deficits in slip: The along-strike deficit is erased after ~1 month by afterslip. We find no evidence of off-fault deformation and conclude that the downdip shallow slip deficit for this event is likely an artifact. As near-field geodetic data rapidly proliferate and will become commonplace, we suggest that analyses of near-surface fault rupture should also use more sophisticated mechanical models and subsurface geomechanical tests.

Selective Targeting to Glioma with Nucleic Acid Aptamers.

Malignant glioma is characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue; hence, diagnosis and treatment is difficult and patient survival is poor. Aptamers contribute a promising and unique technology for the in vitro imaging of live cells and tissues, with a potentially bright future in clinical diagnostics and therapeutics for malignant glioma. The binding selectivity, uptake capacity and binding target of two DNA aptamers, SA43 and SA44, were investigated in glioma cells and patient tissues. The binding assay showed that SA43 and SA44 bound with strong affinity (Kd, 21.56 ± 4.60 nM and Kd, 21.11 ± 3.30 nM respectively) to the target U87MG cells. Quantitative analysis by flow cytometry showed that the aptamers were able to actively internalise in U87MG and 1321N1 glioma cells compared to the non-cancerous and non-glioma cell types. Confocal microscopy confirmed staining in the cytoplasm, and co-localisation studies with endoplasmic reticulum, Golgi apparatus and lysosomal markers suggested internalisation and compartmentalisation within the endomembrane system. Both aptamers selectively bound to Ku 70 and Ku 80 DNA repair proteins as determined by aptoprecipitation (AP) followed by mass spectrometry analysis and confirmation by Western blot. In addition, aptohistochemical (AHC) staining on paraffin embedded, formalin fixed patient tissues revealed that the binding selectivity was significantly higher for SA43 aptamer in glioma tissues (grade I, II, III and IV) compared to the non-cancerous tissues, whereas SA44 did not show selectivity towards glioma tissues. The results indicate that SA43 aptamer can differentiate between glioma and non-cancerous cells and tissues and therefore, shows promise for histological diagnosis of glioma.

Factors predictive of post-TVT voiding dysfunction.

In this study we assessed the incidence of voiding dysfunction in women 6 months after undergoing a tension-free vaginal tape (TVT) procedure. Logistic regression was then used to look for significantly associated factors from a range of patient, urodynamic and surgical variables. From a group of 267 women we identified 22 (8%) who needed to perform daily intermittent self-catheterisation (ISC) as a result of the TVT surgery. When potential predictive factors were examined individually there were three that appeared to be associated with the need to use ISC: menopausal status,previous incontinence surgery and the centile score for average voiding flow rate (as derived from a volume--flow rate nomogram). Following multivariate logistic regression this flow rate centile score showed the strongest association with post-TVT voiding dysfunction, the likelihood of needing ISC increasing as the centile score fell. This factor has not previously been described but is readily assessed pre-operatively and may be useful in case selection for TVT.