Through prescription writing, dental clinicians are a potential source of initial opioid exposure and subsequent abuse for adolescents and young adults.
To examine the association between index ...dental opioid prescriptions from dental clinicians for opioid-naive adolescents and young adults in 2015 and new persistent use and subsequent diagnoses of abuse in this population.
This retrospective cohort study examined outpatient opioid prescriptions for patients aged 16 to 25 years in the Optum Research Database in 2015. Prescriptions were linked by National Provider Identifier number to a clinician category.
Individuals were included in the index dental opioid (opioid-exposed) cohort if they filled an opioid prescription from a dental clinician in 2015, had continuous health plan coverage and no record of opioid prescriptions for 12 months before receiving the prescription, and had 12 months of health plan coverage after receiving the prescription. Two age- and sex-matched opioid-nonexposed control individuals were selected for each opioid-exposed individual and were assigned a corresponding phantom prescription date.
Receipt of an opioid prescription within 90 to 365 days, a health care encounter diagnosis associated with opioid abuse within 365 days, and all-cause mortality within 365 days of the index opioid or phantom prescription date.
Among 754 002 individuals with continuous enrollment in 2015, 97 462 patients (12.9%) received 1 or more opioid prescriptions, of whom 29 791 (30.6%) received prescriptions supplied by a dental clinician. The opioid-exposed cohort included 14 888 participants (7882 women 52.9%, 11 273 white 75.7%, with mean SD age, 21.8 2.4 years), and the randomly selected opioid-nonexposed cohort included 29 776 participants (15 764 women 52.9%, 20 078 67.4% white, with mean SD age, 21.8 2.4 years). Among the 14 888 individuals in the index dental opioid cohort, 1021 (6.9%) received another opioid prescription 90 to 365 days later compared with 30 of 29 776 (0.1%) opioid-nonexposed controls (adjusted absolute risk difference, 6.8%; 95% CI, 6.3%-7.2%), and 866 opioid-exposed individuals (5.8%) experienced 1 or more subsequent health care encounters with an opioid abuse-related diagnosis compared with 115 opioid-nonexposed controls (0.4%) (adjusted absolute risk difference, 5.3%; 95% CI, 5.0%-5.7%). There was only 1 death in each cohort.
The findings suggest that a substantial proportion of adolescents and young adults are exposed to opioids through dental clinicians. Use of these prescriptions may be associated with an increased risk of subsequent opioid use and abuse.
The gut microbiota has an important role in the gut barrier, inflammation and metabolic functions. Studies have identified a close association between the intestinal barrier and metabolic diseases, ...including obesity and type 2 diabetes (T2D). Recently, Akkermansia muciniphila has been reported as a beneficial bacterium that reduces gut barrier disruption and insulin resistance. Here we evaluated the role of A. muciniphila-derived extracellular vesicles (AmEVs) in the regulation of gut permeability. We found that there are more AmEVs in the fecal samples of healthy controls compared with those of patients with T2D. In addition, AmEV administration enhanced tight junction function, reduced body weight gain and improved glucose tolerance in high-fat diet (HFD)-induced diabetic mice. To test the direct effect of AmEVs on human epithelial cells, cultured Caco-2 cells were treated with these vesicles. AmEVs decreased the gut permeability of lipopolysaccharide-treated Caco-2 cells, whereas Escherichia coli-derived EVs had no significant effect. Interestingly, the expression of occludin was increased by AmEV treatment. Overall, these results imply that AmEVs may act as a functional moiety for controlling gut permeability and that the regulation of intestinal barrier integrity can improve metabolic functions in HFD-fed mice.
This study quantifies the wide-ranging health care costs affecting patients living with IBD, including the annualized direct and indirect costs of care for patients with IBD, the longitudinal drivers ...of these costs, and the cost of care for newly diagnosed patients.
Abstract
Background
The Crohn’s & Colitis Foundation’s Cost of Inflammatory Bowel Disease (IBD) Care Initiative seeks to quantify the wide-ranging health care costs affecting patients living with IBD. We aimed to (1) describe the annualized direct and indirect costs of care for patients with Crohn’s disease (CD) or ulcerative colitis (UC), (2) determine the longitudinal drivers of these costs, and (3) characterize the cost of care for newly diagnosed patients.
Methods
We analyzed the Optum Research Database from the years 2007 to 2016, representing commercially insured and Medicare Advantage–insured patients in the United States. Inclusion for the study was limited to those who had continuous enrollment with medical and pharmacy benefit coverage for at least 24 months (12 months before through 12 months after the index date of diagnosis). The value of patient time spent on health care was calculated as number of workplace hours lost due to health care encounters multiplied by the patients’ estimated average wage derived from the Bureau of Labor Statistics. Comparisons between IBD patients and non-IBD patients were analyzed based on demographics, health plan type, and length of follow-up. We used generalized linear models to estimate the association between total annual costs and various patient variables.
Results
There were 52,782 IBD patients (29,062 UC; 23,720 CD) included in the analysis (54.1% females). On a per-annual basis, patients with IBD incurred a greater than 3-fold higher direct cost of care compared with non-IBD controls ($22,987 vs $6956 per-member per-year paid claims) and more than twice the out-of-pocket costs ($2213 vs $979 per-year reported costs), with all-cause IBD costs rising after 2013. Patients with IBD also experienced significantly higher costs associated with time spent on health care as compared with controls. The burden of costs was most notable in the first year after initial IBD diagnosis (mean = $26,555). The study identified several key drivers of cost for IBD patients: treatment with specific therapeutics (biologics, opioids, or steroids); ED use; and health care services associated with relapsing disease, anemia, or mental health comorbidity.
Conclusion
The costs of care for IBD have increased in the last 5 years and are driven by specific therapeutics and disease features. In addition, compared with non-IBD controls, IBD patients are increasingly incurring higher costs associated with health care utilization, out-of-pocket expenditures, and workplace productivity losses. There is a pressing need for cost-effective strategies to address these burdens on patients and families affected by IBD.
Video Abstract
10.1093/ibd/izz104_video1
Video Abstract
izz104.video1
6039344358001
Ketamine's mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder ...(MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms, and healthy control subjects exhibited modest but significant increases in depressive symptoms for up to 1 day after ketamine administration. Both groups showed increased resting gamma power following ketamine. In MDD subjects, gamma power was not associated with the magnitude of the antidepressant effect. However, baseline gamma power was found to moderate the relationship between post-ketamine gamma power and antidepressant response; specifically, higher post-ketamine gamma power was associated with better response in MDD subjects with lower baseline gamma, with an inverted relationship in MDD subjects with higher baseline gamma. This relationship was observed in multiple regions involved in networks hypothesized to be involved in the pathophysiology of MDD. This finding suggests biological subtypes based on the direction of homeostatic dysregulation and has important implications for inferring ketamine's mechanism of action from studies of healthy controls alone.
Understanding the microscopic origins of electronic phases in high-transition temperature (high-Tc) superconductors is important for elucidating the mechanism of superconductivity. In the ...paramagnetic tetragonal phase of BaFe2–xTxAs2 (where T is Co or Ni) iron pnictides, an in-plane resistivity anisotropy has been observed. Here, we use inelastic neutron scattering to show that low-energy spin excitations in these materials change from fourfold symmetric to twofold symmetric at temperatures corresponding to the onset of the in-plane resistivity anisotropy. Because resistivity and spin excitation anisotropies both vanish near optimal superconductivity, we conclude that they are likely intimately connected.
We use an ultrahigh‐resolution 15‐T Fourier transform ion cyclotron resonance mass spectrometer to elucidate the compositional changes in Arctic organic aerosols collected at Ny‐Ålesund, Svalbard, in ...May 2015. The Fourier transform ion cyclotron resonance mass spectrometer analysis of airborne organic matter provided information on the molecular compositions of aerosol particles collected during the Arctic spring period. The air mass transport history, combined with satellite‐derived geographical information and chlorophyll concentration data, revealed that the molecular compositions of organic aerosols drastically differed depending on the origin of the potential source region. The protein and lignin compound populations contributed more than 70% of the total intensity of assigned molecules when the air masses mainly passed over the ocean region. Interestingly, the intensity of microbe‐derived organics (protein and carbohydrate compounds) was positively correlated with the air mass exposure to phytoplankton biomass proxied as chlorophyll. Furthermore, the intensities of lignin and unsaturated hydrocarbon compounds, typically derived from terrestrial vegetation, increased with an increase in the advection time of the air mass over the ocean domain. These results suggest that the accumulation of dissolved biogenic organics in the Arctic Ocean possibly derived from both phytoplankton and terrestrial vegetation could significantly influence the chemical properties of Arctic organic aerosols during a productive spring period. The interpretation of molecular changes in organic aerosols using an ultrahigh‐resolution mass spectrometer could provide deep insight for understanding organic aerosols in the atmosphere over the Arctic and the relationship of organic aerosols with biogeochemical processes in terms of aerosol formation and environmental changes.
Key Points
The molecular compositions of Arctic organic aerosols were identified using an ultrahigh‐resolution mass spectrometer (15T FT‐ICR MS)
The molecular characteristics of Arctic organic aerosols showed distinct differences depending on their potential source origin
The accumulation of biogenic organics in Arctic surface water could significantly influence the chemical properties of Arctic aerosols
Cytosolic proteins containing SH2 and SH3 domains, such as Crk and Crk-like (CrkL), are broadly expressed adapters that interact with a variety of proteins to fulfill key roles in signal transduction ...pathways triggered by activation of receptor and non-receptor tyrosine kinases. Crk and CrkL are similar to each other in structure and biochemical function, although they provide both distinct, as well as overlapping, biological roles during development. We developed a systematic approach to investigate Crk family functions at the cellular level by generating a conditional knock-out system for ablation of Crk and CrkL in cultured fibroblasts. The loss of both Crk and CrkL from fibroblasts resulted in reduced cell surface area and adoption of a rounded, refractile cellular phenotype. These morphological alterations were accompanied by a decrease in focal adhesion sites, reduced actin stress fibers and a collapse of microtubule structures. In addition, cells exhibited decreases in spontaneous motility and wound-healing behavior. Reduced p130Cas phosphorylation and actin levels closely followed the loss of Crk and CrkL, and stabilization of polymerized actin by jasplakinolide suppressed the morphological conversion. Ablation of Crk or CrkL alone conferred a much more modest phenotype suggesting that Crk and CrkL have overlapping functions that are critical for maintaining cell structure. The morphological alterations could be partially rescued by reintroduction of CrkII, and, to a lesser extent, CrkL. Taken together, our results suggest that Crk and CrkL have critical roles in cell structure and motility by maintaining cytoskeletal integrity.
BACKGROUND AND PURPOSE
Ginsenosides are the main constituents for the pharmacological effects of Panax ginseng. Such effects of ginsenosides including cardioprotective and anti‐platelet activities ...have shown stability and bioavailability limitations. However, information on the anti‐platelet activity of ginsenoside‐Rp1 (G‐Rp1), a stable derivative of ginsenoside‐Rg3, is scarce. We examined the ability of G‐Rp1 to modulate agonist‐induced platelet activation.
EXPERIMENTAL APPROACH
G‐Rp1 in vitro and ex vivo effects on agonist‐induced platelet‐aggregation, granule‐secretion, Ca2+i mobilization, integrin‐αIIbβ3 activation were examined. Vasodilator‐stimulated phosphoprotein (VASP) and MAPK expressions and levels of tyrosine phosphorylation of the glycoprotein VI (GPVI) signalling pathway components were also studied. G‐Rp1 effects on arteriovenous shunt thrombus formation in rats or tail bleeding time and ex vivo coagulation time in mice were determined.
KEY RESULT
G‐Rp1 markedly inhibited platelet aggregation induced by collagen, thrombin or ADP. While G‐Rp1 elevated cAMP levels, it dose‐dependently suppressed collagen‐induced ATP‐release, thromboxane secretion, p‐selectin expression, Ca2+i mobilization and αIIbβ3 activation and attenuated p38MAPK and ERK2 activation. Furthermore, G‐Rp1 inhibited tyrosine phosphorylation of multiple components (Fyn, Lyn, Syk, LAT, PI3K and PLCγ2) of the GPVI signalling pathway. G‐Rp1 inhibited in vivo thrombus formation and ex vivo platelet aggregation and ATP secretion without affecting tail bleeding time and coagulation time, respectively.
CONCLUSION AND IMPLICATIONS
G‐Rp1 inhibits collagen‐induced platelet activation and thrombus formation through modulation of early GPVI signalling events, and this effect involves VASP stimulation, and ERK2 and p38‐MAPK inhibition. These data suggest that G‐Rp1 may have therapeutic potential for the treatment of cardiovascular diseases involving aberrant platelet activation.
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