Impact of Hydrocodone Rescheduling on Dental Prescribing of Opioids.

INTRODUCTION: In the United States, dentists frequently prescribe hydrocodone. In October 2014, the US Drug Enforcement Administration rescheduled hydrocodone from controlled substance schedule III to II, introducing more restricted prescribing and dispensing regulations, which may have changed dental prescribing of opioids. OBJECTIVE: The study aim was to evaluate the impact of the hydrocodone rescheduling on dental prescribing of opioids in the United States. METHODS: This was a cross-sectional study of opioids prescribed by dentists between October 2012 and October 2016, using the IQVIA Longitudinal Prescription Dataset. Monthly dentist-based opioid prescribing rate (opioid prescription [Rx]/1,000 dentists) and monthly average opioid dosages per prescription (mean morphine milligram equivalent per day [MME/d]) were measured in the 24 mo before and after hydrocodone rescheduling in October 2014 (index or interruption). An interrupted time-series analysis was conducted using segmented ordinary least square regression models, with Newey-West standard errors to handle autocorrelation. RESULTS: Dentists prescribed 50,412,942 opioid prescriptions across the 49 mo. Hydrocodone was the most commonly prescribed opioid pre- and postindex (74.9% and 63.8%, respectively), followed by codeine (13.8% and 21.6%), oxycodone (8.1% and 9.5%), and tramadol (2.9% and 4.8%). At index, hydrocodone prescribing immediately decreased by -834.8 Rx/1,000 dentists (95% confidence interval [CI], -1,040.2 to -629.4), with increased prescribing of codeine (421.9; 95% CI, 369.7-474.0), oxycodone (85.3; 95% CI, 45.4-125.2), and tramadol (111.8; 95% CI, 101.4-122.3). The mean MME increased at index for all opioids except for hydrocodone, and dosages subsequently decreased during the postindex period. CONCLUSION: Following the rescheduling, dentist prescribing of hydrocodone declined while prescribing of nonhydrocodone opioids increased. Understanding the impact of this regulation informs strategies to ensure appropriate prescribing of opioids for dental pain. KNOWLEDGE TRANSFER STATEMENT: The study findings can be used by policy makers to make informed decisions in developing future risk mitigation strategies aimed to regulate opioid prescribing behaviors. Furthermore, dentist-specific resources and guidelines are needed subsequent to these policies in order to meet the dental population needs.

Recent trends in primary-care antidepressant prescribing to children and young people: an e-cohort study.

BACKGROUND: Concerns relating to increased use of psychotropic medication contrast with those of under-treatment and under-recognition of common mental disorders in children and young people (CYP) across developed countries. Little is known about the indications recorded for antidepressant prescribing in primary care in CYP. METHOD: This was an electronic cohort study of routinely collected primary-care data from a population of 1.9 million, Wales, UK. Poisson regression was undertaken to model adjusted counts of recorded depression symptoms, diagnoses and antidepressant prescriptions. Associated indications were explored. RESULTS: 3 58 383 registered patients aged 6-18 years between 1 January 2003 and 31 December 2013 provided a total of 19 20 338 person-years of follow-up. The adjusted incidence of antidepressant prescribing increased significantly [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The majority of new antidepressant prescriptions were for citalopram. Recorded depression diagnoses showed a steady decline (IRR = 0.72) while depression symptoms (IRR = 2.41) increased. Just over half of new antidepressant prescriptions were associated with depression (diagnosis or symptoms). Other antidepressant prescribing, largely unlicensed, was associated with diagnoses such as anxiety and pain. CONCLUSION: Antidepressant prescribing is increasing in CYP while recorded depression diagnoses decline. Unlicensed citalopram prescribing occurs outside current guidelines, despite its known toxicity in overdose. Unlicensed antidepressant prescribing is associated with a wide range of diagnoses, and while accepted practice, is often not supported by safety and efficacy studies. New strategies to implement current guidance for the management of depression in CYP are required.

Linear porokeratosis with multiple squamous cell carcinomas successfully treated by electrochemotherapy.

Porokeratosis is a clonal epidermal disorder of keratinization characterized by annular lesions with an atrophic centre and a hyperkeratotic edge. The cornoid lamella is the histopathological hallmark. Six clinical variants are recognized: porokeratosis of Mibelli; disseminated superficial porokeratosis; disseminated superficial actinic porokeratosis (DSAP); porokeratosis plantaris et palmaris disseminata; punctate porokeratosis and linear porokeratosis. Linear porokeratosis is the type most frequently associated with malignant transformation into squamous cell carcinoma (SCC). It is thought to represent a mosaic form of DSAP and has an incidence of less than 1 in 200 000; treatment options are limited. We describe a patient with systematized linear porokeratosis and multiple SCCs who was successfully treated with bleomycin electrochemotherapy (ECT), a form of intralesional chemotherapy. In view of their large number, the individual SCCs were treated with bleomycin ECT. One year post-treatment the patient remains tumour free. To our knowledge, this is the first case of multiple SCCs treated by ECT in the context of systematized linear porokeratosis. Our case highlights the challenges associated with diagnosing and managing this unusual form of porokeratosis.

Determining adsorbate configuration on alumina surfaces with (13)C nuclear magnetic resonance relaxation time analysis.

Relative strengths of surface interaction for individual carbon atoms in acyclic and cyclic hydrocarbons adsorbed on alumina surfaces are determined using chemically resolved (13)C nuclear magnetic resonance (NMR) T1 relaxation times. The ratio of relaxation times for the adsorbed atoms T1,ads to the bulk liquid relaxation time T1,bulk provides an indication of the mobility of the atom. Hence a low T1,ads/T1,bulk ratio indicates a stronger surface interaction. The carbon atoms associated with unsaturated bonds in the molecules are seen to exhibit a larger reduction in T1 on adsorption relative to the aliphatic carbons, consistent with adsorption occurring through the carbon-carbon multiple bonds. The relaxation data are interpreted in terms of proximity of individual carbon atoms to the alumina surface and adsorption conformations are inferred. Furthermore, variations of interaction strength and molecular configuration have been explored as a function of adsorbate coverage, temperature, surface pre-treatment, and in the presence of co-adsorbates. This relaxation time analysis is appropriate for studying the behaviour of hydrocarbons adsorbed on a wide range of catalyst support and supported-metal catalyst surfaces, and offers the potential to explore such systems under realistic operating conditions when multiple chemical components are present at the surface.

Recent trends in the incidence of anxiety and prescription of anxiolytics and hypnotics in children and young people: An e-cohort study.

BACKGROUND: Little is known regarding the recognition of anxiety in children and young people (CYP) in primary care. This study examined trends in the presentation, recognition and recording of anxiety and of anxiolytic and hypnotic prescriptions for CYP in primary care. METHOD: A population-based retrospective electronic cohort of individuals aged 6-18 years between 2003 and 2011 within the Secure Anonymised Information Linkage (SAIL) Databank primary care database was created. Incidence rates were calculated using person years at risk (PYAR) as a denominator accounting for deprivation, age and gender. RESULTS: We identified a cohort of 311,343 registered individuals providing a total of 1,546,489 person years of follow up. The incidence of anxiety symptoms more than tripled over the study period (Incidence Rate Ratio (IRR)=3.55, 95% CI 2.65-4.77) whilst that of diagnosis has remained stable. Anxiolytic/hypnotic prescriptions for the cohort as a whole did not change significantly over time; however there was a significant increase in anxiolytic prescriptions for the 15-18 year age group (IRR 1.62, 95% CI 1.30-2.02). LIMITATIONS: There was a lack of reliable information regarding other interventions available or received at a primary, secondary or tertiary level such as psychological treatments. CONCLUSIONS: There appears to be a preference over time for the recording of general symptoms over diagnosis for anxiety in CYP. The increase in anxiolytic prescriptions for 15-18 year olds is discrepant with current prescribing guidelines. Specific guidance is required for the assessment and management of CYP presenting with anxiety to primary care, particularly older adolescents.

Post-processing strategies in image scanning microscopy.

Image scanning microscopy (ISM) coupled with pixel reassignment offers a resolution improvement of √2 over standard widefield imaging. By scanning point-wise across the specimen and capturing an image of the fluorescent signal generated at each scan position, additional information about specimen structure is recorded and the highest accessible spatial frequency is doubled. Pixel reassignment can be achieved optically in real time or computationally a posteriori and is frequently combined with the use of a physical or digital pinhole to reject out of focus light. Here, we simulate an ISM dataset using a test image and apply standard and non-standard processing methods to address problems typically encountered in computational pixel reassignment and pinholing. We demonstrate that the predicted improvement in resolution is achieved by applying standard pixel reassignment to a simulated dataset and explore the effect of realistic displacements between the reference and true excitation positions. By identifying the position of the detected fluorescence maximum using localisation software and centring the digital pinhole on this co-ordinate before scaling around translated excitation positions, we can recover signal that would otherwise be degraded by the use of a pinhole aligned to an inaccurate excitation reference. This strategy is demonstrated using experimental data from a multiphoton ISM instrument. Finally we investigate the effect that imaging through tissue has on the positions of excitation foci at depth and observe a global scaling with respect to the applied reference grid. Using simulated and experimental data we explore the impact of a globally scaled reference on the ISM image and, by pinholing around the detected maxima, recover the signal across the whole field of view.

Is an online skin cancer toolkit an effective way to educate primary care physicians about skin cancer diagnosis and referral?

BACKGROUND: Skin disorders account for over 20% of GP consultations. Half of dermatology referrals to secondary care are for skin lesions, but only 12% of urgent skin cancer referrals are deemed appropriate. Suitably designed online learning resources may positively impact GP confidence in the recognition of skin cancer and improve patient outcomes. OBJECTIVE: This study evaluated the impact of a national, online, skin cancer recognition toolkit on GP confidence and knowledge in diagnosing skin cancers and referral behaviour to secondary care. METHODS: The toolkit, consisting of a referral decision aid, lesion recognition resource, clinical cases and a quiz, was launched in March 2012. Website usage statistics and online focus groups were used to assess the usability of the website and perceived changes in behaviour. The impact of the toolkit was assessed using national skin cancer referral data, cross-sectional questionnaires and urgent skin cancer referral data to two NHS trusts. RESULTS: The toolkit was accessed by 20% of GPs in England from 20th March to 31st October 2012; spending a mean of over 5 minutes each, with over 33% return users. A survey revealed that the toolkit improved perceptions of skin cancer training and self-reported knowledge about skin cancer referral pathways. Analysis of referral patterns did not identify an impact of the toolkit on number or appropriateness of urgent skin cancer referrals in the eight months following the launch of the website. Online focus groups confirmed the usefulness of the resource and suggested a positive influence on knowledge and referral behaviour. CONCLUSION: The skin cancer toolkit is an accessible online learning resource for improving confidence with skin cancer referral amongst GPs. Although we were unable to identify any immediate changes in skin cancer diagnoses or appropriate referral behaviours, research is required to evaluate its longer term effects on outcomes.

Reduced CD5(+) CD24(hi) CD38(hi) and interleukin-10(+) regulatory B cells in active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit increased circulating autoantibodies.

Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is B cell-dependent, although how particular B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype remains controversial, regulatory B cells (Bregs ), play a role in immunological tolerance via interleukin (IL)-10. Putative CD19(+) CD24(hi) CD38(hi) and CD19(+) CD24(hi) CD27(+) Bregs were evaluated in addition to their CD5(+) subsets in 69 patients with ANCA-associated vasculitis (AAV). B cell IL-10 was verified by flow cytometry following culture with CD40 ligand and cytosine-phosphate-guanosine (CpG) DNA. Patients with active disease had decreased levels of CD5(+) CD24(hi) CD38(hi) B cells and IL-10(+) B cells compared to patients in remission and healthy controls (HCs). As IL-10(+) and CD5(+) CD24(hi) CD38(hi) B cells normalized in remission within an individual, ANCA titres decreased. The CD5(+) subset of CD24(hi) CD38(hi) B cells decreases in active disease and rebounds during remission similarly to IL-10-producing B cells. Moreover, CD5(+) B cells are enriched in the ability to produce IL-10 compared to CD5(neg) B cells. Together these results suggest that CD5 may identify functional IL-10-producing Bregs . The malfunction of Bregs during active disease due to reduced IL-10 expression may thus permit ANCA production.

Heterogeneous interaction of SiO2 with N2O5: aerosol flow tube and single particle optical levitation-Raman spectroscopy studies.

Silica (SiO2) is an important mineral present in atmospheric mineral dust particles, and the heterogeneous reaction of N2O5 on atmospheric aerosol is one of the major pathways to remove nitrogen oxides from the atmosphere. The heterogeneous reaction of N2O5 with SiO2 has only been investigated by two studies previously, and the reported uptake coefficients differ by a factor of >10. In this work two complementary laboratory techniques were used to study the heterogeneous reaction of SiO2 particles with N2O5 at room temperature and at different relative humidities (RHs). The uptake coefficients of N2O5, γ(N2O5), were determined to be (7.2 ± 0.6) × 10(-3) (1σ) at 7% RH and (5.3 ± 0.8) × 10(-3) (1σ) at 40% RH for SiO2 particles, using the aerosol flow tube technique. We show that γ(N2O5) determined in this work can be reconciled with the two previous studies by accounting for the difference in geometric and BET derived aerosol surface areas. To probe the particle phase chemistry, individual micrometer sized SiO2 particles were optically levitated and exposed to a continuous flow of N2O5 at different RHs, and the composition of levitated particles was monitored online using Raman spectroscopy. This study represents the first investigation into the heterogeneous reactions of levitated individual SiO2 particles as a surrogate for mineral dust. Relative humidity was found to play a critical role: while no significant change of particle composition was observed by Raman spectroscopy during exposure to N2O5 at RH of <2%, increasing the RH led to the formation of nitrate species on the particle surface which could be completely removed after decreasing the RH back to <2%. This can be explained by the partitioning of HNO3 between the gas and adsorbed phases. The atmospheric implications of this work are discussed.

Optical trapping and Raman spectroscopy of solid particles.

The heterogeneous interactions of gas molecules on solid particles are crucial in many areas of science, engineering and technology. Such interactions play a critical role in atmospheric chemistry and in heterogeneous catalysis, a key technology in the energy and chemical industries. Investigating heterogeneous interactions upon single levitated particles can provide significant insight into these important processes. Various methodologies exist for levitating micron sized particles including: optical, electrical and acoustic techniques. Prior to this study, the optical levitation of solid micron scale particles has proved difficult to achieve over timescales relevant to the above applications. In this work, a new vertically configured counter propagating dual beam optical trap was optimized to levitate a range of solid particles in air. Silica (SiO2), α-alumina (Al2O3), titania (TiO2) and polystyrene were stably trapped with a high trapping efficiency (Q = 0.42). The longest stable trapping experiment was conducted continuously for 24 hours, and there are no obvious constraints on trapping time beyond this period. Therefore, the methodology described in this paper should be of major benefit to various research communities. The strength of the new technique is demonstrated by the simultaneous levitation and spectroscopic interrogation of silica particles by Raman spectroscopy. In particular, the adsorption of water upon silica was investigated under controlled relative humidity environments. Furthermore, the collision and coagulation behaviour of silica particles with microdroplets of sulphuric acid was followed using both optical imaging and Raman spectroscopy.

Accounting for the impact of conservation on human well-being.

Conservationists are increasingly engaging with the concept of human well-being to improve the design and evaluation of their interventions. Since the convening of the influential Sarkozy Commission in 2009, development researchers have been refining conceptualizations and frameworks to understand and measure human well-being and are starting to converge on a common understanding of how best to do this. In conservation, the term human well-being is in widespread use, but there is a need for guidance on operationalizing it to measure the impacts of conservation interventions on people. We present a framework for understanding human well-being, which could be particularly useful in conservation. The framework includes 3 conditions; meeting needs, pursuing goals, and experiencing a satisfactory quality of life. We outline some of the complexities involved in evaluating the well-being effects of conservation interventions, with the understanding that well-being varies between people and over time and with the priorities of the evaluator. Key challenges for research into the well-being impacts of conservation interventions include the need to build up a collection of case studies so as to draw out generalizable lessons; harness the potential of modern technology to support well-being research; and contextualize evaluations of conservation impacts on well-being spatially and temporally within the wider landscape of social change. Pathways through the smog of confusion around the term well-being exist, and existing frameworks such as the Well-being in Developing Countries approach can help conservationists negotiate the challenges of operationalizing the concept. Conservationists have the opportunity to benefit from the recent flurry of research in the development field so as to carry out more nuanced and locally relevant evaluations of the effects of their interventions on human well-being.

Safety and predictability of conscious sedation in dentistry -- a multi-centre regional audit: South and West Wales experience.

INTRODUCTION: There are no previously published reports of audits in conscious sedation from a group comprising the general dental services (GDS), community dental services (CDS) and hospital dental services (HDS). AIM: The main aim of this audit was to assess current practice within the group in relation to the safety and predictability of dental treatment undertaken with the aid of conscious sedation. METHODS: A total of nine centres collected data prospectively on 1,037 sedation episodes over the course of one year. Audit standards were locally agreed based on current evidence and local experience. They were set at a completion rate of 90% and an adverse incident rate of 2% or less. RESULTS: Based on the data collected, a completion rate of 92% and a minor adverse incident rate of 2.6% were recorded. CONCLUSIONS: The participating centres met the standards set locally for this audit. Current practice in the participating centres was found to be safe and predictable. The audit tool is being refined to improve the quality of data collection. Further research and service evaluation is recommended.