Sociodemographic and Clinical Predictors of Prescription Opioid Use in a Longitudinal Community-Based Cohort Study of Middle-Aged and Older Adults

Background: Despite declining opioid prescribing rates in the United States, the annual prevalence of prescription opioid use in adults ≥50 years old is estimated to be 40%, higher than that of younger adults (ages 18-29 years, 36%). As the American population ages, understanding factors that contribute to overall opioid use is a necessary first step in the determination and mitigation of inappropriate prescribing and opioid-related harms. Objective: Assess predictors of prescription opioid use in an adult population with a high prevalence of chronic pain. Methods: Data were from a community-based cohort of White and African American adults aged 50-90 years residing in predominantly rural Johnston County, North Carolina. Univariable and multivariable logistic regression models were used to evaluate sociodemographic and clinical factors in non-opioid users (n=795) at baseline (2006-2010) as predictors of opioid use at follow-up (2013-2015). Variables included age, sex, race, obesity (BMI≥30kg/m2), polypharmacy (5+ medications), educational attainment (<12, ≥12 years), employment (unemployed, employed/retired), insurance (uninsured, public, private), Census block group household poverty rate (<12%, 12–24%, ≥25%), depressive symptoms (Center for Epidemiologic Studies Depression Scale ≥16 or depression diagnosis), perceived social support (moderate/poor [<19], strong [≥19]; Strong Ties Measure of Social Support, range 0-20), pain sensitivity (sensitive [<4kg], normal [≥4kg] pressure pain threshold), and pain catastrophizing (high [≥15], moderate/low [<15]; Pain Catastrophizing Helplessness Subscale, range 0-25). Results: At follow-up, 13% (n=100) of participants were using prescription opioids. In univariable models, younger age, female sex, obesity, polypharmacy, unemployment, public (vs. private) health insurance, higher poverty rate, depressive symptoms, poorer perceived social support, pain catastrophizing, and elevated pain sensitivity were independently associated (p<0.05) with opioid use. In the multivariable model, younger age (60 vs. 70 years; adjusted odds ratio, 95% confidence interval=2.52, 1.08−5.88), polypharmacy (2.16, 1.24−3.77), high pain catastrophizing (2.17, 1.33−3.56), and depressive symptoms (2.00, 1.17−3.43) remained significant independent predictors. Conclusion: The simultaneous assessment of a breadth of clinical and sociodemographic factors identified polypharmacy, pain catastrophizing, and depressive symptoms as modifiable predictors of prescription opioid use. These findings support the incorporation of pharmacological review and behavioral approaches into chronic pain management strategies. Further research is warranted to track changes in these factors as prescription opioid use declines nationwide

Sociodemographic and Clinical Predictors of Prescription Opioid Use in a Longitudinal Community-Based Cohort Study of Middle-Aged and Older Adults

Background: Despite declining opioid prescribing rates in the United States, the annual prevalence of prescription opioid use in adults ≥50 years old is estimated to be 40%, higher than that of younger adults (ages 18-29 years, 36%). As the American population ages, understanding factors that contribute to overall opioid use is a necessary first step in the determination and mitigation of inappropriate prescribing and opioid-related harms. Objective: Assess predictors of prescription opioid use in an adult population with a high prevalence of chronic pain. Methods: Data were from a community-based cohort of White and African American adults aged 50-90 years residing in predominantly rural Johnston County, North Carolina. Univariable and multivariable logistic regression models were used to evaluate sociodemographic and clinical factors in non-opioid users (n=795) at baseline (2006-2010) as predictors of opioid use at follow-up (2013-2015). Variables included age, sex, race, obesity (BMI≥30kg/m2), polypharmacy (5+ medications), educational attainment (<12, ≥12 years), employment (unemployed, employed/retired), insurance (uninsured, public, private), Census block group household poverty rate (<12%, 12–24%, ≥25%), depressive symptoms (Center for Epidemiologic Studies Depression Scale ≥16 or depression diagnosis), perceived social support (moderate/poor [<19], strong [≥19]; Strong Ties Measure of Social Support, range 0-20), pain sensitivity (sensitive [<4kg], normal [≥4kg] pressure pain threshold), and pain catastrophizing (high [≥15], moderate/low [<15]; Pain Catastrophizing Helplessness Subscale, range 0-25). Results: At follow-up, 13% (n=100) of participants were using prescription opioids. In univariable models, younger age, female sex, obesity, polypharmacy, unemployment, public (vs. private) health insurance, higher poverty rate, depressive symptoms, poorer perceived social support, pain catastrophizing, and elevated pain sensitivity were independently associated (p<0.05) with opioid use. In the multivariable model, younger age (60 vs. 70 years; adjusted odds ratio, 95% confidence interval=2.52, 1.08−5.88), polypharmacy (2.16, 1.24−3.77), high pain catastrophizing (2.17, 1.33−3.56), and depressive symptoms (2.00, 1.17−3.43) remained significant independent predictors. Conclusion: The simultaneous assessment of a breadth of clinical and sociodemographic factors identified polypharmacy, pain catastrophizing, and depressive symptoms as modifiable predictors of prescription opioid use. These findings support the incorporation of pharmacological review and behavioral approaches into chronic pain management strategies. Further research is warranted to track changes in these factors as prescription opioid use declines nationwide

Chalcogenide Glass-on-Graphene Photonics

Two-dimensional (2-D) materials are of tremendous interest to integrated photonics given their singular optical characteristics spanning light emission, modulation, saturable absorption, and nonlinear optics. To harness their optical properties, these atomically thin materials are usually attached onto prefabricated devices via a transfer process. In this paper, we present a new route for 2-D material integration with planar photonics. Central to this approach is the use of chalcogenide glass, a multifunctional material which can be directly deposited and patterned on a wide variety of 2-D materials and can simultaneously function as the light guiding medium, a gate dielectric, and a passivation layer for 2-D materials. Besides claiming improved fabrication yield and throughput compared to the traditional transfer process, our technique also enables unconventional multilayer device geometries optimally designed for enhancing light-matter interactions in the 2-D layers. Capitalizing on this facile integration method, we demonstrate a series of high-performance glass-on-graphene devices including ultra-broadband on-chip polarizers, energy-efficient thermo-optic switches, as well as graphene-based mid-infrared (mid-IR) waveguide-integrated photodetectors and modulators

Evidence for Factorization in Three-body B --> D(*) K- K0 Decays

Motivated by recent experimental results, we use a factorization approach to study the three-body B --> D(*) K- K0 decay modes. Two mechanisms are proposed for kaon pair production: current-produced (from vacuum) and transition (from B meson). The Bbar0 --> D(*)+ K- K0 decay is governed solely by the current-produced mechanism. As the kaon pair can be produced only by the vector current, the matrix element can be extracted from e+ e- --> K Kbar processes via isospin relations. The decay rates obtained this way are in good agreement with experiment. Both current-produced and transition processes contribute to B- --> D(*)0 K- K0 decays. By using QCD counting rules and the measured B- --> D(*)0 K- K0 decay rates, the measured decay spectra can be understood.Comment: 17 pages, 6 figure

Immunolocalisation of P2Y receptors in the rat eye

Nucleotides present an important role in ocular physiology which has been demonstrated by recent works that indicate their involvement in many ocular processes. P2Y are important among P2 receptors since they can control tear production, corneal wound healing, aqueous humour dynamics and retinal physiology. Commercial antibodies have allowed us to investigate the distribution of P2Y receptors in the cornea, anterior and posterior chamber of the eye and retina. The P2Y1 receptor was present mainly in cornea, ciliary processes, and trabecular meshwork. The P2Y2 receptors were present in cornea, ciliary processes and retinal pigmented epithelium. P2Y4 was present in cornea, ciliary processes, photoreceptors, outer plexiform layer and ganglion cell layer. The P2Y6 presented almost an identical distribution as the P2Y4 receptor. The P2Y11 was also detectable in the retinal pigmented epithelium. The detailed distribution of the receptors clearly supports the recent findings indicating the relevant role of nucleotides in the ocular function

Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies.

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found that viral RNA concentrations peaked an average of 3.3 days (95% credible interval [CI] 2.5, 4.2) after first possible detectability at a cycle threshold value of 22.3 (95% CI 20.5, 23.9). The viral clearance phase lasted longer for symptomatic individuals (10.9 days [95% CI 7.9, 14.4]) than for asymptomatic individuals (7.8 days [95% CI 6.1, 9.7]). A second test within 2 days after an initial positive PCR test substantially improves certainty about a patient's infection stage. The effective sensitivity of a test intended to identify infectious individuals declines substantially with test turnaround time. These findings indicate that SARS-CoV-2 viral concentrations peak rapidly regardless of symptoms. Sequential tests can help reveal a patient's progress through infection stages. Frequent, rapid-turnaround testing is needed to effectively screen individuals before they become infectious

Site-Specific Labeling of Annexin V with F-18 for Apoptosis Imaging

Annexin V is useful in detecting apoptotic cells by binding to phosphatidylserine (PS) that is exposed on the outer surface of the cell membrane during apoptosis. In this study, we examined the labeling of annexin V-128, a mutated form of annexin V that has a single cysteine residue at the NH2 terminus, with the thiol-selective reagent 18F-labeling agent N-[4-[(4-[18F]fluorobenzylidene)aminooxy]butyl]maleimide ([18F]FBABM). We also examined the cell binding affinity of the 18F-labeled annexin V-128 ([18F]FAN-128). [18F]FBABM was synthesized in two-step, one-pot method modified from literature procedure. (Toyokuni et al., Bioconjugate Chem. 2003, 14, 1253−1259). The average yield of [18F]FBABM was 23 ± 4% (n = 4, decay-corrected) and the specific activity was ∼6000 Ci/mmol. The total synthesis time was ∼92 min. The critical improvement of this study was identifying and then developing a purification method to remove an impurity N-[4-[(4-dimethylaminobenzylidene)aminooxy]butyl]maleimide 4, whose presence dramatically decreased the yield of protein labeling. Conjugation of [18F]FBABM with the thiol-containing annexin V-128 gave [18F]FAN-128 in 37 ± 9% yield (n = 4, decay corrected). Erythrocyte binding assay of [18F]FAN-128 showed that this modification of annexin V-128 did not compromise its membrane binding affinity. Thus, an in vivo investigation of [18F]FAN-128 as an apoptosis imaging agent is warranted

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression

A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.No sponso