Comparison of opioid prescribing by dentists in the United States and England

Importance: The United States consumes most of the opioids worldwide despite representing a small portion of the world\u27s population. Dentists are one of the most frequent US prescribers of opioids despite data suggesting that nonopioid analgesics are similarly effective for oral pain. While oral health and dentist use are generally similar between the United States and England, it is unclear how opioid prescribing by dentists varies between the 2 countries. Objective: To compare opioid prescribing by dentists in the United States and England. Design, Setting, and Participants: Cross-sectional study of prescriptions for opioids dispensed from outpatient pharmacies and health care settings between January 1 and December 31, 2016, by dentists in the United States and England. Data were analyzed from October 2018 to January 2019. Exposures: Opioids prescribed by dentists. Main Outcomes and Measures: Proportion and prescribing rates of opioid prescriptions. Results: In 2016, the proportion of prescriptions written by US dentists that were for opioids was 37 times greater than the proportion written by English dentists. In all, 22.3% of US dental prescriptions were opioids (11.4 million prescriptions) compared with 0.6% of English dental prescriptions (28 082 prescriptions) (difference, 21.7%; 95% CI, 13.8%-32.1%; P \u3c .001). Dentists in the United States also had a higher number of opioid prescriptions per 1000 population (35.4 per 1000 US population [95% CI, 25.2-48.7 per 1000 population] vs 0.5 per 1000 England population [95% CI, 0.03-3.7 per 1000 population]) and number of opioid prescriptions per dentist (58.2 prescriptions per dentist [95% CI, 44.9-75.0 prescriptions per dentist] vs 1.2 prescriptions per dentist [95% CI, 0.2-5.6 prescriptions per dentist]). While the codeine derivative dihydrocodeine was the sole opioid prescribed by English dentists, US dentists prescribed a range of opioids containing hydrocodone (62.3%), codeine (23.2%), oxycodone (9.1%), and tramadol (4.8%). Dentists in the United States also prescribed long-acting opioids (0.06% of opioids prescribed by US dentists [6425 prescriptions]). Long-acting opioids were not prescribed by English dentists. Conclusions and Relevance: This study found that in 2016, dentists in the United States prescribed opioids with significantly greater frequency than their English counterparts. Opioids with a high potential for abuse, such as oxycodone, were frequently prescribed by US dentists but not prescribed in England. These results illustrate how 1 source of opioids differs substantially in the United States vs England. To reduce dental opioid prescribing in the United States, dentists could adopt measures similar to those used in England, including national guidelines for treating dental pain that emphasize prescribing opioids conservatively

Spectral aerosol extinction (SpEx): a new instrument for in situ ambient aerosol extinction measurements across the UV/visible wavelength range

We introduce a new instrument for the measurement of in situ ambient aerosol extinction over the 300– 700 nm wavelength range, the spectral aerosol extinction (SpEx) instrument. This measurement capability is envisioned to complement existing in situ instrumentation, allowing for simultaneous measurement of the evolution of aerosol optical, chemical, and physical characteristics in the ambient environment. In this work, a detailed description of the instrument is provided along with characterization tests performed in the laboratory. Measured spectra of NO2 and polystyrene latex spheres (PSLs) agreed well with theoretical calculations. Good agreement was also found with simultaneous aerosol extinction measurements at 450, 530, and 630 nm using CAPS PMex instruments in a series of 22 tests including nonabsorbing compounds, dusts, soot, and black and brown carbon analogs. SpEx measurements are expected to help identify the presence of ambient brown carbon due to its 300 nm lower wavelength limit compared to measurements limited to longer UV and visible wavelengths. Extinction spectra obtained with SpEx contain more information than can be conveyed by a simple power law fit (typically represented by Ångström exponents). Planned future improvements aim to lower detection limits and ruggedize the instrument for mobile operation

Impact of the NICE guideline recommending cessation of antibiotic prophylaxis for prevention of infective endocarditis: before and after study

Objective To quantify the change in prescribing of antibiotic prophylaxis before invasive dental procedures for patients at risk of infective endocarditis, and any concurrent change in the incidence of infective endocarditis, following introduction of a clinical guideline from the National Institute for Health and Clinical Excellence (NICE) in March 2008 recommending the cessation of antibiotic prophylaxis in the United Kingdom

A self-validating control system based approach to plant fault detection and diagnosis

An approach is proposed in which fault detection and diagnosis (FDD) tasks are distributed to separate FDD modules associated with each control system located throughout a plant. Intended specifically for those control systems that inherently eliminate steady state error, it is modular, steady state based, requires very little process specific information and therefore should be attractive to control systems implementers who seek economies of scale. The approach is applicable to virtually all types of process plant, whether they are open loop stable or not, have a type or class number of zero or not and so on. Based on qualitative reasoning, the approach is founded on the application of control systems theory to single and cascade control systems with integral action. This results in the derivation of cause-effect knowledge and fault isolation procedures that take into account factors like interactions between control systems, and the availability of non-control-loop-based sensors

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER