Periodontal Disease Treatment After Stroke or Transient Ischemic Attack: The PREMIERS Study, a Randomized Clinical Trial.

BACKGROUND: Patients with stroke/transient ischemic attack and periodontal disease (PD) are at increased risk for cardiovascular events. PD treatments that can improve stroke risk factors were tested if they might assist patients with cerebrovascular disease. METHODS: In this multicenter phase II trial, patients with stroke/transient ischemic attack and moderately severe PD were randomly assigned to intensive or standard PD treatment arms. The primary outcome measure was a composite of death, myocardial infarction, and recurrent stroke, as well as adverse events. Secondary outcome included changes in stroke risk factors. RESULTS: A total of 1209 patients with stroke/transient ischemic attack were screened, of whom 481 met the PD eligibility criteria; 280 patients were randomized to intensive arm (n=140) and standard arm (n=140). In 12-month period, primary outcome occurred in 11 (8%) in the intensive arm and 17 (12%) in the standard arm. The intensive arm was nonsuperior to the standard arm (hazard ratio, 0.65 [95% CI, 0.30-1.38]) with similar rates of adverse events (sepsis 2.1% versus 0.7%; dental bleeding 1.4% versus 0%; and infective endocarditis 0.7% versus 0%). Secondary-outcome improvements were noted in both arms with diastolic blood pressure and high-density lipoprotein cholesterol (P<0.05). CONCLUSIONS: In patients with recent stroke/transient ischemic attack and PD, intensive PD treatment was not superior to standard PD treatment in prevention of stroke/myocardial infarction/death. Fewer events were noted in the intensive arm and the 2 arms were comparable in the safety outcomes. Secondary-outcome measures showed a trend toward improvement, with significant changes noted in diastolic blood pressure and high-density lipoprotein in both the treatment arms.

A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke).

BACKGROUND: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. METHODS: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. RESULTS: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures. CONCLUSIONS: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337.

Radon Exposure and Incident Stroke Risk in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Little is known about the role of radon in the epidemiology of stroke among women. We therefore examined the association between home radon exposure and risk of stroke among middle-aged and older women in the United States. METHODS: We conducted a prospective cohort study of postmenopausal women aged 50-79 years at baseline (1993-1998) in the Women's Health Initiative. We measured exposures as 2-day, indoor, lowest living-level average radon concentrations in picocuries per liter (pCi/L) as estimated in 1993 by the US Geological Survey and reviewed by the Association of American State Geologists under the Indoor Radon Abatement Act. We used Cox proportional hazards models to estimate risk of incident, neurologist-adjudicated stroke during follow-up through 2020 as a hazard ratio and 95% CI, adjusting for study design and participant demographic, social, behavioral, and clinical characteristics. RESULTS: Among 158,910 women without stroke at baseline (mean age 63.2 years; 83% white), 6,979 incident strokes were identified over follow-up (mean 13.4 years). Incidence rates were 333, 343, and 349 strokes per 100,000 woman-years at radon concentrations of <2, 2-4, and >4 pCi/L, respectively. Compared with women living at concentrations <2 pCi/L, those at 2-4 and >4 pCi/L had higher covariate-adjusted risks of incident stroke: hazard ratio (95% CI) 1.06 (0.99-1.13) and 1.14 (1.05-1.22). Using nonlinear spline functions to model radon, stroke risk was significantly elevated at concentrations ranging from 2 to 4 pCi/L (p = 0.0004), that is, below the United States Environmental Protection Agency Radon Action Level for mitigation (4 pCi/L). Associations were slightly stronger for ischemic (especially cardioembolic, small vessel occlusive, and large artery atherosclerotic) than hemorrhagic stroke, but otherwise robust in sensitivity analyses. DISCUSSION: Radon exposure is associated with moderately increased stroke risk among middle-aged and older women in the United States, suggesting that promulgation of a lower Radon Action Level may help reduce the domestic impact of cerebrovascular disease on public health.

Radon Exposure, Clonal Hematopoiesis, and Stroke Susceptibility in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Studies suggest that clonal hematopoiesis of indeterminate potential (CHIP) may increase risk of hematologic malignancy and cardiovascular disease, including stroke. However, few studies have investigated plausible environmental risk factors for CHIP such as radon, despite the climate-related increases in and documented infrequency of testing for this common indoor air pollutant.The purpose of this study was to estimate the risk of CHIP related to radon, an established environmental mutagen. METHODS: We linked geocoded addresses of 10,799 Women's Health Initiative Trans-Omics for Precision Medicine (WHI TOPMed) participants to US Environmental Protection Agency-predicted, county-level, indoor average screening radon concentrations, categorized as follows: Zone 1 (>4 pCi/L), Zone 2 (2-4 pCi/L), and Zone 3 (<2 pCi/L). We defined CHIP as the presence of one or more leukemogenic driver mutations with variant allele frequency >0.02. We identified prevalent and incident ischemic and hemorrhagic strokes; subtyped ischemic stroke using Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria; and then estimated radon-related risk of CHIP as an odds ratio (OR) and 95% CI using multivariable-adjusted, design-weighted logistic regression stratified by age, race/ethnicity, smoking status, and stroke type/subtype. RESULTS: The percentages of participants with CHIP in Zones 1, 2, and 3 were 9.0%, 8.4%, and 7.7%, respectively (ptrend = 0.06). Among participants with ischemic stroke, Zones 2 and 1 were associated with higher estimated risks of CHIP relative to Zone 3: 1.39 (1.15-1.68) and 1.46 (1.15-1.87), but not among participants with hemorrhagic stroke: 0.98 (0.68-1.40) and 1.03 (0.70-1.52), or without stroke: 1.04 (0.74-1.46) and 0.95 (0.63-1.42), respectively (pinteraction = 0.03). Corresponding estimates were particularly high among TOAST-subtyped cardioembolism: 1.78 (1.30-2.47) and 1.88 (1.31-2.72), or other ischemic etiologies: 1.37 (1.06-1.78) and 1.50 (1.11-2.04), but not small vessel occlusion: 1.05 (0.74-1.49) and 1.00 (0.68-1.47), respectively (pinteraction = 0.10). Observed patterns of association among strata were insensitive to attrition weighting, ancestry adjustment, prevalent stroke exclusion, separate analysis of DNMT3A driver mutations, and substitution with 3 alternative estimates of radon exposure. DISCUSSION: The robust elevation of radon-related risk of CHIP among postmenopausal women who develop incident cardioembolic stroke is consistent with a potential role of somatic genomic mutation in this societally burdensome form of cerebrovascular disease, although the mechanism has yet to be confirmed.

Developmental trajectories of childhood obesity and risk behaviors in adolescence.

Using group-based trajectory modeling, this study examined 5156 adolescents from the child sample of the 1979 National Longitudinal Survey of Youth to identify developmental trajectories of obesity from ages 6-18 and evaluate associations of such trajectories with risk behaviors and psychosocial health in adolescence. Four distinctive obesity trajectories were identified: "Chronically Obese," "Decreasing," "Increasing," and "Non-obese." Males were overrepresented in the Chronically Obese and Increasing groups; females were overrepresented in the Decreasing group. African-Americans were overrepresented in the Chronically Obese, Increasing, and Decreasing groups; in contrast, Whites were overrepresented in the Non-obese group. Obesity trajectories were not associated with greater trends in alcohol use, marijuana use, or delinquency, but Chronically Obese adolescents showed a greater increase in cigarette smoking over time compared to other trajectories. The Increasing trajectory, representing a transition into obesity status from childhood to adolescence, was associated with poorer psychosocial health compared to other trajectories.

A Latent Class Analysis of Maternal Responsiveness and Autonomy-Granting in Early Adolescence: Prediction to Later Adolescent Sexual Risk-Taking.

The present study sought to extend empirical inquiry related to the role of parenting on adolescent sexual risk-taking by using latent class analysis (LCA) to identify patterns of adolescent-reported mother responsiveness and autonomy-granting in early adolescence and examine associations with sexual risk-taking in mid- and late-adolescence. Utilizing a sample of 12- to 14-year-old adolescents (N = 4,743) from the 1997 National Longitudinal Survey of Youth (NLSY97), results identified a four-class model of maternal responsiveness and autonomy-granting: low responsiveness/high autonomy-granting, moderate responsiveness/moderate autonomy-granting, high responsiveness/low autonomy-granting, high responsiveness/moderate autonomy-granting. Membership in the low responsiveness/high autonomy-granting class predicted greater sexual risk-taking in mid- and late-adolescence compared to all other classes, and membership in the high responsiveness/ moderate autonomy-granting class predicted lower sexual risk-taking. Gender and ethnic differences in responsiveness and autonomy-granting class membership were also found, potentially informing gender and ethnic disparities of adolescent sexual risk-taking.

Integrin alphavbeta3 is a coreceptor for human cytomegalovirus.

Human cytomegalovirus (HCMV) is a widespread opportunistic pathogen that causes birth defects in newborns and severe disease in immunocompromised individuals. The broad tropism of HCMV infection suggests that it uses multiple receptors. We recently showed that the epidermal growth factor receptor (EGFR) serves as a receptor for HCMV. Here we show that HCMV also uses integrin alphavbeta3 as a coreceptor. Upon infection, HCMV glycoproteins gB and gH independently bind to EGFR and alphavbeta3, respectively, to initiate viral entry and signaling. Alphavbeta3 then translocates to lipid rafts where it interacts with EGFR to induce coordinated signaling. The coordination between EGFR and alphavbeta3 is essential for the early events of HCMV infection, including viral entry, RhoA downregulation, stress-fiber disassembly and viral nuclear trafficking. Our findings support a model in which EGFR and alphavbeta3 work together as coreceptors for HCMV entry and signaling. This discovery is fundamental to understanding HCMV pathogenesis and developing treatment strategies targeted to viral receptors.

Developmental trajectory of sexual risk behaviors from adolescence to young adulthood.

This study examined the trajectories of sexual risk behaviors among adolescents from ages 15 to 23, and factors associated with those trajectories. The sample was 5,419 adolescents from the 1997 National Longitudinal Survey of Youth. Using group-based trajectory modeling, five distinctive trajectory groups were identified. The High group had a high and increased risk trajectory over the observed ages. The Decreased group had a risk trajectory that accelerated before age 19, but decreased afterwards. The risk trajectories of the Increased-Early and Increased-Late groups were low at age 15, but increased significantly starting at ages 16 and 18 for the groups, respectively. Participants in the Low group remained at low risk over time. Sexual risk behaviors were also positively associated with alcohol use, marijuana use, and delinquency. Results highlight the need for intervention efforts to consider developmental timing of sexual risk behaviors and their associations with other problem behaviors.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Human cytomegalovirus IE1-72 protein interacts with p53 and inhibits p53-dependent transactivation by a mechanism different from that of IE2-86 protein.

Infection of host cells with human cytomegalovirus (HCMV) induces cell cycle dysregulation. Two HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, are promiscuous transactivators that have been implicated in the dysregulatory events. Cellular p53 protein is accumulated to high levels in HCMV-infected cells, but the indicative marker of p53 transcriptional activity, p21, is markedly decreased. Both IE1-72 and IE2-86 were able to transactivate the p53 promoter and interact with p53 protein in DNA-transfected or HCMV-infected cells. HCMV UL84, a multiregulatory protein expressed in early periods of HCMV infection, also interacted with p53. HCMV IE1-72 prevented or disrupted p53 binding to p53-specific DNA sequences, while IE2-86 and/or UL84 enhanced p53 binding and induced supershift of this DNA-protein complex. Both HCMV IE1-72 and IE2-86 were able to inhibit p53-dependent transcriptional activation in plasmid-transfected cells. IE1-72, rather than IE2-86, was found to be responsible for p21 downregulation in HCMV-infected HEL cells. DNA transfection analysis using IE1-72 mutants revealed that exon 2/3 and the zinc finger region of IE1-72 are essential for IE1-72's effect on the repression of p53-dependent transcriptional activation. These data suggest that HCMV IE1-72 and/or IE2-86 transactivates the p53 promoter and induces p53 accumulation, but HCMV IE1-72 represses the p53 transactivation activity by a unique binding hindrance mechanism different from that of IE2-86. Thus, various modes of viral IE proteins and p53 interactions might result in multiple outcomes, such as stimulation of cellular DNA synthesis, cell cycle progression and cell cycle arrest, and prevention of program cell death.

The microRNA spectrum in 12 body fluids.

BACKGROUND: MicroRNAs (miRNAs) are small, noncoding RNAs that play an important role in regulating various biological processes through their interaction with cellular messenger RNAs. Extracellular miRNAs in serum, plasma, saliva, and urine have recently been shown to be associated with various pathological conditions including cancer. METHODS: With the goal of assessing the distribution of miRNAs and demonstrating the potential use of miRNAs as biomarkers, we examined the presence of miRNAs in 12 human body fluids and urine samples from women in different stages of pregnancy or patients with different urothelial cancers. Using quantitative PCR, we conducted a global survey of the miRNA distribution in these fluids. RESULTS: miRNAs were present in all fluids tested and showed distinct compositions in different fluid types. Several of the highly abundant miRNAs in these fluids were common among multiple fluid types, and some of the miRNAs were enriched in specific fluids. We also observed distinct miRNA patterns in the urine samples obtained from individuals with different physiopathological conditions. CONCLUSIONS: MicroRNAs are ubiquitous in all the body fluid types tested. Fluid type-specific miRNAs may have functional roles associated with the surrounding tissues. In addition, the changes in miRNA spectra observed in the urine samples from patients with different urothelial conditions demonstrates the potential for using concentrations of specific miRNAs in body fluids as biomarkers for detecting and monitoring various physiopathological conditions.

Contrast sensitivity visual acuity in REM sleep behavior disorder: a comparison with and without Parkinson disease.

STUDY OBJECTIVES: REM sleep behavior disorder (RBD) is characterized by dream enactment behavior and is a premotoric sign associated with parkinsonism and dementia. We previously found contrast sensitivity visual acuity (CSVA) deficiencies in earliest stages of Parkinson disease (PD), plausibly associated with alpha-synuclein deposits in the inner retinal layers. We speculated that individuals with REM sleep behavior without clinical signs of parkinsonism might also show similar deficiencies. METHODS: Twenty-three patients with RBD and 28 healthy control patients. Eleven with PD and 12 with idiopathic RBD (iRBD). Twelve patients with RBD were re-evaluated after 1 year. Evaluations consisted of CSVA SLOAN low contrast acuity charts, optical coherence topography, Unified Parkinson's Disease Rating Scale (UPDRS), and general neurologic and ophthalmologic examinations. Data analyzed between groups using a one-way analysis of variance, and a paired samples t test for returning patients. RESULTS: Participants were classified into three groups: controls (n = 28), iRBD (n = 12), and RBD+PD (n = 11). Analysis of variance revealed CSVA scores were statistically significantly different between the three groups F2, 50 = 7.037, P = .002. Longitudinal analysis of RBD group showed CSVA decreased significantly at 1 year (P = .0141). To date, PD has developed in three individuals with iRBD based on progression of their UPDRS scores. CONCLUSIONS: CSVA is reduced in individuals with RBD and declines over time. It is plausible that patients with iRBD may show early loss in dopaminergic lateral inhibition in the retina, evidenced by their progressive loss of CSVA. This may represent a global loss of dopaminergic neurons similar to PD.

Delineation of Human Carotid Plaque Features In Vivo by Exploiting Displacement Variance.

While in vivo acoustic radiation force impulse (ARFI)-induced peak displacement (PD) has been demonstrated to have high sensitivity and specificity for differentiating soft from stiff plaque components in patients with carotid plaque, the parameter exhibits poorer performance for distinguishing between plaque features with similar stiffness. To improve discrimination of carotid plaque features relative to PD, we hypothesize that signal correlation and signal-to-noise ratio (SNR) can be combined, outright or via displacement variance. Plaque feature detection by displacement variance, evaluated as the decadic logarithm of the variance of acceleration and termed "log(VoA)," was compared to that achieved by exploiting SNR, cross correlation coefficient, and ARFI-induced PD outcome metrics. Parametric images were rendered for 25 patients undergoing carotid endarterectomy, with spatially matched histology confirming plaque composition and structure. On average, across all plaques, log(VoA) was the only outcome metric with values that statistically differed between regions of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Further, log(VoA) achieved the highest contrast-to-noise ratio (CNR) for discriminating between LRNC and IPH, COL and CAL, and grouped soft (LRNC and IPH) and stiff (COL and CAL) plaque components. More specifically, relative to the previously demonstrated ARFI PD parameter, log(VoA) achieved 73% higher CNR between LRNC and IPH and 59% higher CNR between COL and CAL. These results suggest that log(VoA) enhances the differentiation of LRNC, IPH, COL, and CAL in human carotid plaques, in vivo, which is clinically relevant to improving stroke risk prediction and medical management.

Clinical application of radiophotoluminescent glass dosimeter for dose verification of prostate HDR procedure.

High dose rate brachytherapy (HDR-BT) is one of the many modalities for prostate cancer treatment. Due to the nature of HDR-BT, in vivo dosimetry is feasible and can be used to verify consistent dose delivery. In order to validate a dose verification system for HDR-BT prostate cancer treatment, a radiophotoluminescent glass dosimeter (RPLGD) was used and the measurements were compared with those from a thermoluminescent dosimeter. The RPLGD shows many advantages in HDR-BT dose measurement, such as repeatability, stability, and small effective size. These advantages make the RPLGD a superior option for use as a dosimeter in HDR-BT. The results described here show that the difference between the measured dose and the treatment planned dose is less than 5%. A Monte Carlo simulation for the dose was performed using Monte Carlo N -particle to investigate position error. This study concludes that the RPLGD is a promising and reliable dosimeter for HDR-BT in vivo dosimetry with clinically acceptable accuracy.

Strategies for improving outcomes in the acute management of ischemic stroke in rural emergency departments: a quality improvement initiative in the Stroke Belt.

BACKGROUND: The timely evaluation and initiation of treatment for acute ischemic stroke (AIS) is critical to optimal patient outcomes. However, clinical practice often falls short of guideline-established goals. Hospitals in rural regions of the USA, and notably those in the Stroke Belt, are particularly challenged to meet timing goals since the vast majority of primary stroke centers (PSCs) are concentrated in urban academic institutions. METHODS: Between May 2015 and May 2017, emergency department (ED) teams from 5 non-PSC hospitals in the Stroke Belt participated in a quality improvement (QI) initiative. The intervention included a baseline practice assessment survey, repeat audit-and-feedback cycles with patient data on AIS treatment timing, personalized Continuing Medical Education/Continuing Education-certified grand rounds sessions at each participating site with expert study faculty, targeted reinforcement of best practices, and follow-up to evaluate the benefits and limitations of the intervention. RESULTS: At the start of the initiative, clinical staff from participating EDs overestimated the proportion of patients with AIS who received alteplase within the guideline-recommended 60-minute door-to-needle window at their facility. At the end of the 6-month intervention period, significantly more patients were treated with alteplase within 60 minutes of ED arrival compared to baseline across the entire sample (1.9% of patients at baseline vs. 5.2% at 6 months; P < 0.01). Similarly, there was a trend toward a decrease in the percentage of patients whose alteplase treatment was initiated more than 60 minutes after their arrival at the ED (67.3% at baseline vs. 22.2% at 6 months). CONCLUSION: Structured QI interventions that engage ED care teams to reflect on processes related to AIS diagnosis and treatment and deploy repeat audit-and-feedback cycles with real-time patient data have the potential to support an increase in the number of patients who receive alteplase within the guideline-recommended timeframe of 60 minutes from hospital arrival.

Physician Prescribing of Opioids to Patients at Increased Risk of Overdose From Benzodiazepine Use in the United States.

Importance: Recent increases in US opioid-related deaths underscore the need to understand drivers of fatal overdose. The initial prescription of opioids represents a critical juncture because it increases the risk of future opioid use disorder and is preventable. Objective: To examine new opioid prescribing patterns in US patients at increased risk of overdose from benzodiazepine use. Design, Setting, and Participants: This study used publicly available data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from January 1, 2005, through December 31, 2015, to identify adults 20 years or older receiving new opioid prescriptions and concurrently using a benzodiazepine. Main Outcomes and Measures: Population-based rates of new opioid prescriptions stratified by use of benzodiazepines. Results: This study analyzed 13 146 visits, representing 214 million visits nationally, with a new opioid prescription. Rates of new opioid prescriptions among adults using a benzodiazepine increased from 189 to 351 per 1000 persons between 2005 and 2010 (rate difference, 162; 95% CI, 29-295; P = .02) and decreased to 172 per 1000 persons by 2015 (rate difference, -179; 95% CI, -310 to -48; P = .008). New opioid prescriptions in the general population not using benzodiazepines increased nonsignificantly from 78 to 93 per 1000 US persons between 2005 and 2010 (rate difference, 15; 95% CI, -3 to 33; P = .10) and decreased nonsignificantly to 79 per 1000 persons by 2015 (rate difference, -14; 95% CI, -38 to 11; P = .28). The likelihood of receiving a new opioid prescription during an ambulatory visit remained higher for patients concurrently using benzodiazepines compared with the general population after adjusting for demographic characteristics, comorbidities, and diagnoses associated with pain (adjusted relative risk, 1.83; 95% CI, 1.56-2.15; P < .001). Naloxone was coprescribed in less than 1% of visits when a patient concurrently used a benzodiazepine. Conclusions and Relevance: In 2010, new opioid prescriptions for US adults stopped increasing and began to decrease among higher-risk patients who used benzodiazepines. These patterns suggest that the recent increase in opioid-related deaths may be associated with factors other than physicians writing new opioid prescriptions. Nevertheless, prescribing among higher-risk patients still occurred at rates higher than rates in the general population, representing an important opportunity to improve quality of care for patients experiencing pain.

Challenges in the Anesthetic Management for a Robotic Thymectomy in a Patient With Myasthenia Gravis: A Case Report.

We describe the case of a patient with myasthenia gravis undergoing a robotic-assisted thymectomy complicated by postoperative myasthenic crisis, with a focus on the anesthetic considerations specific to this case. Because myasthenia gravis is an autoimmune disease affecting acetylcholine receptors, caution must be taken with the use of neuromuscular blockade and reversal. Utilizing a robotic-assisted surgical approach makes anesthetic management challenging given the dangers of patient movement while the robot is docked, lung isolation, extubation criteria, and postoperative disposition.

Feasibility Study on Applying Radiophotoluminescent Glass Dosimeters for CyberKnife SRS Dose Verification.

CyberKnife is one of multiple modalities for stereotactic radiosurgery (SRS). Due to the nature of CyberKnife and the characteristics of SRS, dose evaluation of the CyberKnife procedure is critical. A radiophotoluminescent glass dosimeter was used to verify the dose accuracy for the CyberKnife procedure and validate a viable dose verification system for CyberKnife treatment. A radiophotoluminescent glass dosimeter, thermoluminescent dosimeter, and Kodak EDR2 film were used to measure the lateral dose profile and percent depth dose of CyberKnife. A Monte Carlo simulation for dose verification was performed using BEAMnrc to verify the measured results. This study also used a radiophotoluminescent glass dosimeter coupled with an anthropomorphic phantom to evaluate the accuracy of the dose given by CyberKnife. Measurements from the radiophotoluminescent glass dosimeter were compared with the results of a thermoluminescent dosimeter and EDR2 film, and the differences found were less than 5%. The radiophotoluminescent glass dosimeter has some advantages in terms of dose measurements over CyberKnife, such as repeatability, stability, and small effective size. These advantages make radiophotoluminescent glass dosimeters a potential candidate dosimeter for the CyberKnife procedure. This study concludes that radiophotoluminescent glass dosimeters are a promising and reliable dosimeter for CyberKnife dose verification with clinically acceptable accuracy within 5%.

Is Obesity Associated With School Dropout? Key Developmental and Ethnic Differences.

BACKGROUND: We aimed to expand the literature on child obesity and school outcomes by examining associations between obesity and high school dropout, including the role of obesity onset and duration as well as ethnicity. METHODS: Data on 5066 children obtained between 1986 and 2010 from the child cohort of the 1979 National Longitudinal Study of Youth (NLSY79) were analyzed. Group-based trajectory analysis identified obesity trajectories from 6 to 18 years. School completion information from age 14 into young adulthood was used to calculate school dropout. Chi-square and pairwise comparison tests were used to identify significant associations between obesity trajectories and school dropout. RESULTS: Adolescents belonging to an increasing trajectory (adolescent-onset obesity) had a higher likelihood of dropping out of high school compared with those belonging to chronic, decreasing (childhood-only obesity), and nonobese trajectories. This association was particularly salient among white adolescents. CONCLUSIONS: Obesity onset during early adolescence increased risk of high school dropout. White adolescents were particularly vulnerable. Given that early adolescence is marked by significant biological and social changes, future research should seek to identify the underlying processes linking adolescent obesity and school dropout to decrease school dropout risk among this vulnerable population.