Healthcare Challenges and Future Solutions in Dental Practice: Assessing Oral Antibiotic Resistances by Contemporary Point-Of-Care Approaches

Antibiotic resistance poses a global threat, which is being acknowledged at several levels, including research, clinical implementation, regulation, as well as by the World Health Organization. In the field of oral health, however, the issue of antibiotic resistances, as well as of accurate diagnosis, is underrepresented. Oral diseases in general were ranked third in terms of expenditures among the EU-28 member states in 2015. Yet, the diagnosis and patient management of oral infections, in particular, still depend primarily on empiric means. On the contrary, on the global scale, the field of medical infections has more readily adopted the integration of molecular-based systems in the diagnostic, patient management, and antibiotic stewardship workflows. In this perspective review, we emphasize the clinical significance of supporting in the future antibiotic resistance screening in dental practice with novel integrated and point-of-care operating tools that can greatly support the rapid, accurate, and efficient administration of oral antibioticspublishedVersio

Epidural Analgesia Provides Better Pain Management After Live Liver Donation: A Retrospective Study

Despite the increase in surgical volumes of live liver donation, there has been very little documentation of the postoperative pain experience. The primary aim of this study was to examine the difference in acute postoperative pain intensity and adverse effects between patients who received intravenous patient-controlled analgesia (IV PCA) or patient-controlled epidural analgesia (PCEA) for pain control after live liver donation surgery. A retrospective chart review was performed of 226 consecutive patients who underwent right living donor hepatic surgery at the Toronto General Hospital, Toronto, Canada. Patients who received as their primary postoperative analgesic modality IV PCA (n = 158) were compared to patients who received PCEA (n = 68). Demographic profiles for the 2 groups were similar with respect to age, sex, and body mass index at the time of surgery. For the first 3 postoperative days, pain intensity was significantly lower in patients who received epidural analgesia (P 4) was reported more frequently in the IV PCA group (P < 0.05) along with increased sedation (P < 0.05). Pruritus was reported more frequently in the PCEA group of patients compared to the IV PCA group (P < 0.05). Significant between-group differences were not found for the incidence of postoperative vomiting, the time at which patients began fluid intake, the time to initial ambulation, or the length of hospital stay. In conclusion, epidural analgesia provides better postoperative pain relief, less sedation, but more pruritus than IV PCA after live liver donation

Patient and practice level factors associated with seasonal influenza vaccine uptake among at-risk adults in England, 2011 to 2016:An age-stratified retrospective cohort study

We sought to gain insights into the determinants of seasonal influenza vaccine (SIV) uptake by conducting an age-stratified analysis (18-64 and 65+) of factors associated with SIV uptake among at-risk adults registered to English practices. Records for at-risk English adults between 2011 and 2016 were identified using the Clinical Practice Research Datalink database. SIV uptake was assessed annually. The associations of patient, practice, and seasonal characteristics with SIV uptake were assessed via cross-sectional and longitudinal analyses, using mixed-effects and general estimating equation logistic regression models. Overall SIV uptake was 35.3% and 74.0% for adults 18-64 and 65+, respectively. Relative to white patients, black patients were least likely to be vaccinated (OR18-64: 0.82 (95% CI: 0.80, 0.85); OR65+: 0.59 (95% CI: 0.56, 0.62)), while Asian patients among 18-64 year olds were most likely to be vaccinated (OR18-64: 1.10 (95% CI: 1.07, 1.13)). Females were more likely than males to be vaccinated among 18-64 year olds (OR18-64: 1.19 (95% CI: 1.18, 1.20)). Greater socioeconomic deprivation was associated with decreased odds of uptake among older patients (OR65+: 0.74 (95% CI: 0.71, 0.77)). For each additional at-risk condition, odds of uptake increased (OR18-64: 2.33 (95% CI: 2.31, 2.36); OR65+: 1.39 (95% CI: 1.38, 1.39)). Odds of uptake were highest among younger patients with diabetes (OR18-64: 4.25 (95% CI: 4.18, 4.32)) and older patients with chronic respiratory disease (OR65+: 1.60 (95% CI: 1.58, 1.63)), whereas they were lowest among morbidly obese patients of all ages (OR18-64: 0.68 (95% CI: 0.67, 0.70); OR65+: 0.97 (95% CI: 0.94, 0.99)). Prior influenza season severity and vaccine effectiveness were marginally predictive of uptake. Our age-stratified analysis uncovered SIV uptake disparities by ethnicity, sex, age, socioeconomic deprivation, and co-morbidities, warranting further attention by GPs and policymakers alike

Methods for identifying health state transitions from administrative data: the case of metastasis in prostate cancer

Introduction Health administrative data are a rich source of population-based information, useful for building state transition models for medical decision making. These models require identification of health state transitions and associated times. Indirect methods are needed to predict this information, as it is rarely available in administrative data. Objectives and Approach We considered a set of criteria to identify transitions to metastasis for prostate cancer patients in administrative data, utilizing dates of diagnostic and medical billing codes for secondary malignancy, palliative radiation therapy, chemotherapy and bone disorders or procedures. We evaluated the criteria using the true date of metastasis from medical charts of 195 patients linked to health care administrative data in Ontario, Canada. We also built a recursive partitioning tree to optimally combine these criteria and construct rules for identifying metastatic patients. For the evaluation, both misclassification and discrepancy between true and predicted dates for the true positives were considered. Results Criteria involving chemotherapy drugs or hospital visits with secondary malignancy ICD10 diagnosis gave the best results, with high sensitivity and specificity. Criteria involving bone related problems, radiation therapy or diagnosis of metastatic cancer in physician billing data were very specific but not sensitive. The criterion involving prescriptions for narcotics was sensitive but not specific. The fitted tree was parsimonious involving only two of the criteria, while improving the accuracy over individual criteria. Most criteria gave a “delayed” prediction, with criterion based on chemotherapy giving on average the smallest delay, as well as exhibiting the least variability. Criteria involving narcotics and bone related problems predicted metastasis date very prematurely, probably triggered by conditions other than prostate cancer. Conclusion/Implications Several criteria from administrative databases satisfactorily classified prostate cancer patients with metastasis. A classification tree was built and improved the results over single criteria, demonstrating the added benefits in using advanced statistical learning methods for this task. However, “transition to metastasis” dates were predicted inaccurately, often with significant delay

VectorDisk: a microfluidic platform integrating diagnostic markers for evidence-based mosquito control

Effective mosquito monitoring relies on the accurate identification and characterization of the target population. Since this process requires specialist knowledge and equipment that is not widely available, automated field-deployable systems are highly desirable. We present a centrifugal microfluidic cartridge, the VectorDisk, which integrates TaqMan PCR assays in two feasibility studies, aiming to assess multiplexing capability, specificity, and reproducibility in detecting disk-integrated vector-related assays. In the first study, pools of 10 mosquitoes were used as samples. We tested 18 disks with 27 DNA and RNA assays each, using a combination of multiple microfluidic chambers and detection wavelengths (geometric and color multiplexing) to identify mosquito and malaria parasite species as well as insecticide resistance mechanisms. In the second study, purified nucleic acids served as samples to test arboviral and malaria infective mosquito assays. Nine disks were tested with 14 assays each. No false positive results were detected on any of the disks. The coe cient of variation in reproducibility tests was <10%. The modular nature of the platform, the easy adaptation of the primer/probe panels, the cold chain independence, the rapid (2-3 h) analysis, and the assay multiplexing capacity are key features, rendering the VectorDisk a potential candidate for automated vector analysis

High-frequency phase shift measurement greatly enhances the sensitivity of QCM immunosensors

[EN] In spite of being widely used for in liquid biosensing applications, sensitivity improvement of conventional (5-20 MHz) quartz crystal microbalance (QCM) sensors remains an unsolved challenging task. With the help of a new electronic characterization approach based on phase change measurements at a constant fixed frequency, a highly sensitive and versatile high fundamental frequency (HFF) QCM immunosensor has successfully been developed and tested for its use in pesticide (carbaryl and thiabendazole) analysis. The analytical performance of several immunosensors was compared in competitive immunoassays taking carbaryl insecticide as the model analyte. The highest sensitivity was exhibited by the 100 MHz HFF-QCM carbaryl immunosensor. When results were compared with those reported for 9 MHz QCM, analytical parameters clearly showed an improvement of one order of magnitude for sensitivity (estimated as the I50 value) and two orders of magnitude for the limit of detection (LOD): 30 µg L-1 vs 0.66 µg L-1 I50 value and 11 µg L-1 vs 0.14 µg L-1 LOD, for 9 and 100 MHz, respectively. For the fungicide thiabendazole, I50 value was roughly the same as that previously reported for SPR under the same biochemical conditions, whereas LOD improved by a factor of 2. The analytical performance achieved by high frequency QCM immunosensors surpassed those of conventional QCM and SPR, closely approaching the most sensitive ELISAs. The developed 100 MHz QCM immunosensor strongly improves sensitivity in biosensing, and therefore can be considered as a very promising new analytical tool for in liquid applications where highly sensitive detection is required.We would like to acknowledge Federico Martin and Juan Antonio Buitrago for their excellent technical assistance. This work was supported by the Spanish Ministry of Economy and Competitiveness/European Regional Development Fund (ERDF) (DETECTA IPT-2012-0154-300000 project).March Iborra, MDC.; García Narbón, JV.; Sánchez, Á.; Arnau Vives, A.; Jiménez Jiménez, Y.; García, P.; Manclus Ciscar, JJ.... (2015). High-frequency phase shift measurement greatly enhances the sensitivity of QCM immunosensors. Biosensors and Bioelectronics. (65):1-8. https://doi.org/10.1016/j.bios.2014.10.001S186

Expert Guidance on Target Product Profile Development for AMR Diagnostic Tests

Diagnostics are widely considered crucial in the fight against antimicrobial resistance (AMR), which is expected to kill 10 million people annually by 2030. Nevertheless, there remains a substantial gap between the need for AMR diagnostics versus their development and implementation. To help address this problem, target product profiles (TPP) have been developed to focus developers’ attention on the key aspects of AMR diagnostic tests. However, during discussion between a multisectoral working group of 51 international experts from industry, academia and healthcare, it was noted that specific AMR-related TPPs could be extended by incorporating the interdependencies between the key characteristics associated with the development of such TPPs. Subsequently, the working group identified 46 characteristics associated with six main categories (i.e., Intended Use, Diagnostic Question, Test Description, Assay Protocol, Performance and Commercial). The interdependencies of these characteristics were then identified and mapped against each other to generate new insights for use by stakeholders. Specifically, it may not be possible for diagnostics developers to achieve all of the recommendations in every category of a TPP and this publication indicates how prioritising specific TPP characteristics during diagnostics development may influence (or not) a range of other TPP characteristics associated with the diagnostic. The use of such guidance, in conjunction with specific TPPs, could lead to more efficient AMR diagnostics development

Pregabalin reduces postoperative opioid consumption and pain for 1 week after hospital discharge, but does not affect function at 6 weeks or 3 months after total hip arthroplasty

BACKGROUND: This study examined whether a perioperative regimen of pregabalin added to celecoxib improved pain scores and functional outcomes postdischarge up to 3 months after total hip arthroplasty (primary outcome) and acute postoperative pain and adverse effects (secondary outcomes). METHODS: One hundred and eighty-four patients were enrolled in a randomized, double-blind, placebo-controlled study. Two hours before receiving a spinal anaesthetic and undergoing surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either pregabalin 150 mg p.o. or placebo p.o. After surgery, patients received pregabalin 75 mg or placebo twice daily in hospital and for 7 days after discharge. Patients also received celecoxib 200 mg every 12 h for 72 h and morphine i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, 6 weeks, and 3 months after surgery. RESULTS: There was no difference between groups in physical function or incidence and intensity of chronic pain 3 months after total hip arthroplasty. The pregabalin group used less morphine [mean (sd): 39.85 (28.1) mg] than the placebo group [54.01 (31.2) mg] in the first 24 h after surgery (P<0.01). Pain scores were significantly lower in the pregabalin group vs the placebo group on days 1-7 after hospitaldischarge, and the pregabalin group required less adjunctive opioid medication (Percocet) 1 week after hospital discharge (P<0.05). CONCLUSIONS: Perioperative administration of pregabalin did not improve pain or physical function at 6 weeks or 3 months after total hip arthroplasty. Perioperative administration of pregabalin decreased opioid consumption in hospital and reduced daily pain scores and adjunct opioid consumption for 1 week after discharge.Department of Anaesthesia at the University of Toronto (Merit Awards to H.C. and C.M.); Canadian Institute of Health Research Fellowship (to H.C.); Canada Research Chair in Health Psychology at York University (to J. Katz); Pfizer Canada (physician-initiated peer-reviewed Neuropathic Pain Competition)

The functional landscape of mouse gene expression

BACKGROUND: Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. RESULTS: We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. CONCLUSIONS: We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics

Fully automated point-of-care differential diagnosis of acute febrile illness

Background In this work, a platform was developed and tested to allow to detect a variety of candidate viral, bacterial and parasitic pathogens, for acute fever of unknown origin. The platform is based on a centrifugal microfluidic cartridge, the LabDisk (“FeverDisk” for the specific application), which integrates all necessary reagents for sample-to-answer analysis and is processed by a compact, point-of-care compatible device. Methodology/Principal findings A sample volume of 200 μL per FeverDisk was used. In situ extraction with pre-stored reagents was achieved by bind-wash-elute chemistry and magnetic particles. Enzymes for the loop-mediated isothermal amplification (LAMP) were pre-stored in lyopellet form providing stability and independence from the cold chain. The total time to result from sample inlet to read out was 2 h. The proof-of-principle was demonstrated in three small-scale feasibility studies: in Dakar, Senegal and Khartoum, Sudan we tested biobanked samples using 29 and 9 disks, respectively; in Reinfeld, Germany we tested spiked samples and analyzed the limit of detection using three bacteria simultaneously spiked in whole blood using 15 disks. Overall during the three studies, the FeverDisk detected dengue virus (different serotypes), chikungunya virus, Plasmodium falciparum, Salmonella enterica Typhi, Salmonella enterica Paratyphi A and Streptococcus pneumoniae. Conclusions/Significance The FeverDisk proved to be universally applicable as it successfully detected all different types of pathogens as single or co-infections, while it also managed to define the serotype of un-serotyped dengue samples. Thirty-eight FeverDisks at the two African sites provided 59 assay results, out of which 51 (86.4%) were confirmed with reference assay results. The results provide a promising outlook for future implementation of the platform in larger prospective clinical studies for defining its clinical sensitivity and specificity. The technology aims to provide multi-target diagnosis of the origins of fever, which will help fight lethal diseases and the incessant rise of antimicrobial resistance.Additional co-authors: Sieghard Frischmann, Konstantinos Mitsakaki