Urinary Pharmacokinetics of Immediate and Controlled Release Oxycodone and its Phase I and II Metabolites using LC-MS/MS

Abstract Oxycodone is a schedule II semi-synthetic opioid in the United States that is prescribed for its analgesic effects and has a high potential for abuse. Prescriptions for oxycodone vary based on the dosage and formulation, immediate release (IR) and controlled release (CR). Monitoring oxycodone metabolites is beneficial for forensic casework. The limited studies that involve pharmacokinetics of the urinary excretion of oxycodone metabolites leave a knowledge gap regarding the excretion of conjugated and minor metabolites, pharmacokinetic differences by formulation, and the impact of CYP2D6 activity on the metabolism and excretion of oxycodone. The objectives of this study were to compare urinary excretion of phase I and II metabolites by formulation and investigate if ratio changes over time could be used to predict the time of intake. Subjects (n=7) received a single 10 mg IR tablet of Oxycodone Actavis. A few weeks later the same subjects received a single 10 mg CR tablet of Oxycodone Actavis. During each setting, urine was collected at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 24, 48, and 72 h. Urine samples (100 µL) were diluted with 900 µL internal standard mixture and analyzed on an Acquity UPLC® I-class coupled to a Waters Xevo TQD using a previously validated method. The CYP2D6 phenotypes were categorized as poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM), and ultra-rapid metabolizers (UM). Comparisons between IR and CR were performed using two-tailed paired T-test at a significance level of p=0.05. The metabolite ratios showed a general increase over time. Four metabolite to parent ratios were used to predict the time of intake showing that predictions were best at the early time points.

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History and Current Trends in the Electronic Cigarette Retail Marketplace in the United States: 2010–2016

Nicotine & Tobacco Research ◽

10.1093/ntr/nty214 ◽

2018 ◽

Vol 22 (5) ◽

pp. 843-847 ◽

Cited By ~ 7

Author(s):

Jennifer Cantrell ◽

Jidong Huang ◽

Marisa Greenberg ◽

Jeffrey Willett ◽

Elizabeth Hair ◽

...

Keyword(s):

Tobacco Industry ◽

The United States ◽

Retail Market ◽

Current Trends ◽

Published Evidence ◽

The Us ◽

Industry Response ◽

Market Trends ◽

The Impact ◽

Over Time

Abstract Introduction The US market for electronic nicotine delivery systems (ENDS) has grown rapidly in the last decade. There is limited published evidence examining changes in the ENDS marketplace prior to the US Food and Drug Administration’s (FDA) deeming rule in 2016. This study describes US ENDS retail market trends from 2010 to 2016. Methods National data were obtained from Nielsen retail scanners for five product types: (1) disposables, (2) rechargeables, (3) cartridge replacements, (4) e-liquid bottle refills, and (5) specialty vapor products. We examined dollar sales, volume, price, brand, and flavor. Results Adjusted national sales increased from $11.6 million in 2010 to $751.2 million in 2016. The annual rate of sales growth rapidly increased before slowing through 2015. The rate of growth spiked in 2016. Market share for menthol products and other assorted flavors increased from 20% in 2010 to 52.1% by 2016. NJOY’s early market dominance shifted as tobacco industry brands entered the market and eventually captured 87.8% of share by 2016. Rechargeables and accompanying products comprised an increased proportion of total volume sold over time while disposable volume declined. Specialty vapor products appeared at retail in 2015. Conclusions Findings show strong early growth in the ENDS retail market followed by considerable slowing over time, despite a slight uptick in 2016. Trends reflect shifts to flavored products, newer generation “open-system” devices, lower prices, and tobacco industry brands. This study provides a baseline against which to compare the impact of FDA’s 2016 deeming rule and future actions on the ENDS marketplace. Implications This study uses market scanner data from US retail outlets to describe trends in the ENDS retail market from 2010 to 2016, providing a baseline against which to compare the impact of FDA’s 2016 deeming rule and future actions on the ENDS marketplace. Understanding historical market trends is valuable in assessing how future regulatory efforts and advances in ENDS technology may impact industry response and consumer uptake and use.

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Spatial and temporal trends in social vulnerability and COVID-19 incidence and death rates in the United States

PLoS ONE ◽

10.1371/journal.pone.0248702 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248702

Author(s):

Brian Neelon ◽

Fedelis Mutiso ◽

Noel T. Mueller ◽

John L. Pearce ◽

Sara E. Benjamin-Neelon

Keyword(s):

Social Vulnerability ◽

Primary Care Physicians ◽

Negative Binomial ◽

Temporal Trends ◽

The United States ◽

Social Vulnerability Index ◽

Crossover Effect ◽

Death Rates ◽

The Impact ◽

Over Time

Background Socially vulnerable communities may be at higher risk for COVID-19 outbreaks in the US. However, no prior studies examined temporal trends and differential effects of social vulnerability on COVID-19 incidence and death rates. Therefore, we examined temporal trends among counties with high and low social vulnerability to quantify disparities in trends over time. Methods We conducted a longitudinal analysis examining COVID-19 incidence and death rates from March 15 to December 31, 2020, for each US county using data from USAFacts. We classified counties using the Social Vulnerability Index (SVI), a percentile-based measure from the Centers for Disease Control and Prevention, with higher values indicating more vulnerability. Using a Bayesian hierarchical negative binomial model, we estimated daily risk ratios (RRs) comparing counties in the first (lower) and fourth (upper) SVI quartiles, adjusting for rurality, percentage in poor or fair health, percentage female, percentage of smokers, county average daily fine particulate matter (PM2.5), percentage of primary care physicians per 100,000 residents, daily temperature and precipitation, and proportion tested for COVID-19. Results At the outset of the pandemic, the most vulnerable counties had, on average, fewer cases per 100,000 than least vulnerable SVI quartile. However, on March 28, we observed a crossover effect in which the most vulnerable counties experienced higher COVID-19 incidence rates compared to the least vulnerable counties (RR = 1.05, 95% PI: 0.98, 1.12). Vulnerable counties had higher death rates starting on May 21 (RR = 1.08, 95% PI: 1.00,1.16). However, by October, this trend reversed and the most vulnerable counties had lower death rates compared to least vulnerable counties. Conclusions The impact of COVID-19 is not static but can migrate from less vulnerable counties to more vulnerable counties and back again over time.

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Bikes or Bust? Analyzing the Impact of Bicycle Infrastructure on Business Performance in San Francisco

Transportation Research Record Journal of the Transportation Research Board ◽

10.1177/0361198119850465 ◽

2019 ◽

Vol 2673 (12) ◽

pp. 277-289

Author(s):

Raleigh McCoy ◽

Joseph A. Poirier ◽

Karen Chapple

Keyword(s):

San Francisco ◽

Business Performance ◽

The United States ◽

Ordinary Least Squares ◽

Grocery Stores ◽

Least Squares Regression ◽

Mode Shift ◽

Bicycle Infrastructure ◽

The Impact ◽

Over Time

Transportation agencies at the local, state, and federal levels in the United States (U.S.) have shown a growing interest in expanding bicycle infrastructure, given its link to mode shift and safety goals. These projects, however, are far from universally accepted. Business owners have been particularly vocal opponents, claiming that bicycle infrastructure will diminish sales or fundamentally change the character of their neighborhoods. Using the case of San Francisco, this research explores the relationship between bicycle infrastructure and business performance in two ways: change in sales over time, and a comparison of sales for new and existing businesses. An ordinary least squares regression is used to model the change in sales over time, isolating the effect of location on bicycle infrastructure while controlling for characteristics of the business, corridor, and surrounding neighborhood. Through a series of t-tests, average sales for businesses that pre-date bicycle infrastructure and for those that opened after the installation of such projects are compared. Ultimately, the research suggests that location on bicycle infrastructure and changes in on-street parking supply generally did not have a significant effect on the change in sales, with a few exceptions. Businesses that sell goods for the home or auto-related goods and services saw a significant decline in sales when located on corridors with bike lanes. New and existing businesses generally had similar sales, though not across the board. New restaurants and grocery stores had significantly higher sales than their existing counterparts, suggesting bicycle infrastructure may attract more upmarket businesses in those industries.

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The Top 1 Percent in International and Historical Perspective

The Journal of Economic Perspectives ◽

10.1257/jep.27.3.3 ◽

2013 ◽

Vol 27 (3) ◽

pp. 3-20 ◽

Cited By ~ 299

Author(s):

Facundo Alvaredo ◽

Anthony B Atkinson ◽

Thomas Piketty ◽

Emmanuel Saez

Keyword(s):

United States ◽

New Technologies ◽

The United States ◽

High Income ◽

Capital Income ◽

Public Attention ◽

Income Share ◽

Top Income Shares ◽

The Impact ◽

Over Time

The top 1 percent income share has more than doubled in the United States over the last 30 years, drawing much public attention in recent years. While other English-speaking countries have also experienced sharp increases in the top 1 percent income share, many high-income countries such as Japan, France, or Germany have seen much less increase in top income shares. Hence, the explanation cannot rely solely on forces common to advanced countries, such as the impact of new technologies and globalization on the supply and demand for skills. Moreover, the explanations have to accommodate the falls in top income shares earlier in the twentieth century experienced in virtually all high-income countries. We highlight four main factors. The first is the impact of tax policy, which has varied over time and differs across countries. Top tax rates have moved in the opposite direction from top income shares. The effects of top rate cuts can operate in conjunction with other mechanisms. The second factor is a richer view of the labor market, where we contrast the standard supply-side model with one where pay is determined by bargaining and the reactions to top rate cuts may lead simply to a redistribution of surplus. Indeed, top rate cuts may lead managerial energies to be diverted to increasing their remuneration at the expense of enterprise growth and employment. The third factor is capital income. Overall, private wealth (relative to income) has followed a U-shaped path over time, particularly in Europe, where inherited wealth is, in Europe if not in the United States, making a return. The fourth, little investigated, element is the correlation between earned income and capital income, which has substantially increased in recent decades in the United States.

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Contact surveys reveal heterogeneities in age-group contributions to SARS-CoV-2 dynamics in the United States

10.1101/2021.09.25.21264082 ◽

2021 ◽

Author(s):

Taylor Chin ◽

Dennis M. Feehan ◽

Caroline O. Buckee ◽

Ayesha S. Mahmud

Keyword(s):

United States ◽

Age Groups ◽

The United States ◽

Contact Rate ◽

Age Group ◽

Contact Rates ◽

Contact Patterns ◽

Age Structured ◽

The Impact ◽

Over Time

SARS-CoV-2 is spread primarily through person-to-person contacts. Quantifying population contact rates is important for understanding the impact of physical distancing policies and for modeling COVID-19, but contact patterns have changed substantially over time due to shifting policies and behaviors. There are surprisingly few empirical estimates of age-structured contact rates in the United States both before and throughout the COVID-19 pandemic that capture these changes. Here, we use data from six waves of the Berkeley Interpersonal Contact Survey (BICS), which collected detailed contact data between March 22, 2020 and February 15, 2021 across six metropolitan designated market areas (DMA) in the United States. Contact rates were low across all six DMAs at the start of the pandemic. We find steady increases in the mean and median number of contacts across these localities over time, as well as a greater proportion of respondents reporting a high number of contacts. We also find that young adults between ages 18 and 34 reported more contacts on average compared to other age groups. The 65 and older age group consistently reported low levels of contact throughout the study period. To understand the impact of these changing contact patterns, we simulate COVID-19 dynamics in each DMA using an age-structured mechanistic model. We compare results from models that use BICS contact rate estimates versus commonly used alternative contact rate sources. We find that simulations parameterized with BICS estimates give insight into time-varying changes in relative incidence by age group that are not captured in the absence of these frequently updated estimates. We also find that simulation results based on BICS estimates closely match observed data on the age distribution of cases, and changes in these distributions over time. Together these findings highlight the role of different age groups in driving and sustaining SARS-CoV-2 transmission in the U.S. We also show the utility of repeated contact surveys in revealing heterogeneities in the epidemiology of COVID-19 across localities in the United States.

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The Impact of Liver Cirrhosis and Cholelithiasis on Phase I and II Reactions Using Antipyrine and Trimethadione as a Model Substrate.

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics ◽

10.3999/jscpt.22.635 ◽

1991 ◽

Vol 22 (3) ◽

pp. 635-639 ◽

Cited By ~ 2

Author(s):

Einosuke TANAKA ◽

Akio ISHIKAWA ◽

Hironori ETOH ◽

Shogo MISAWA ◽

Katashi FUKAO ◽

...

Keyword(s):

Liver Cirrhosis ◽

Phase I ◽

The Impact ◽

Phase I And Ii

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SEIHCRD Model for COVID-19 spread scenarios, disease predictions and estimates the basic reproduction number, case fatality rate, hospital, and ICU beds requirement

10.1101/2020.07.24.20161752 ◽

2020 ◽

Author(s):

Avaneesh Singh ◽

Manish Kumar Bajpai

Keyword(s):

Basic Reproduction Number ◽

Case Fatality Rate ◽

Reproduction Number ◽

Case Fatality ◽

The United States ◽

Fatality Rate ◽

Hospital Beds ◽

The Impact ◽

Over Time ◽

The Basic Reproduction Number

We have proposed a new mathematical method, SEIHCRD-Model that is an extension of the SEIR-Model adding hospitalized and critical twocompartments. SEIHCRD model has seven compartments: susceptible (S), exposed (E), infected (I), hospitalized (H), critical (C), recovered (R), and deceased or death (D), collectively termed SEIHCRD. We have studied COVID- 19 cases of six countries, where the impact of this disease in the highest are Brazil, India, Italy, Spain, the United Kingdom, and the United States. SEIHCRD model is estimating COVID-19 spread and forecasting under uncertainties, constrained by various observed data in the present manuscript. We have first collected the data for a specific period, then fit the model for death cases, got the values of some parameters from it, and then estimate the basic reproduction number over time, which is nearly equal to real data, infection rate, and recovery rate of COVID-19. We also compute the case fatality rate over time of COVID-19 most affected countries. SEIHCRD model computes two types of Case fatality rate one is CFR daily and the second one is total CFR. We analyze the spread and endpoint of COVID-19 based on these estimates. SEIHCRD model is time-dependent hence we estimate the date and magnitude of peaks of corresponding to the number of exposed cases, infected cases, hospitalized cases, critical cases, and the number of deceased cases of COVID-19 over time. SEIHCRD model has incorporated the social distancing parameter, different age groups analysis, number of ICU beds, number of hospital beds, and estimation of how much hospital beds and ICU beds are required in near future.

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Inequality and market concentration, when shareholding is more skewed than consumption

Oxford Review of Economic Policy ◽

10.1093/oxrep/grz011 ◽

2019 ◽

Vol 35 (3) ◽

pp. 550-563 ◽

Cited By ~ 5

Author(s):

Joshua Gans ◽

Andrew Leigh ◽

Martin Schmalz ◽

Adam Triggs

Keyword(s):

The United States ◽

Relative Distribution ◽

Consumer Expenditure ◽

Survey Of Consumer Finances ◽

Consumer Expenditure Survey ◽

Consumer Finances ◽

Equity Ownership ◽

Using Data ◽

The Impact ◽

Over Time

AbstractEconomic theory suggests that monopoly prices hurt consumers but benefit shareholders. But in a world where individuals or households can be both consumers and shareholders, the impact of market power on inequality depends in part on the relative distribution of consumption and corporate equity ownership across individuals or households. The paper calculates this distribution for the United States, using data from the Survey of Consumer Finances and the Consumer Expenditure Survey, spanning nearly three decades from 1989 to 2016. In 2016, the top 20 per cent consumed approximately as much as the bottom 60 per cent, but had 15 times as much corporate equity. Because ownership is more skewed than consumption, increased mark-ups increase inequality. Moreover, over time, corporate equity has become even more skewed relative to consumption.

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Abstract WP41: Age-Specific Differences in the Use of Endovascular Treatment and Hospital Outcomes in Patients With Acute Ischemic Stroke: A Community-Wide Perspective

Stroke ◽

10.1161/str.51.suppl_1.wp41 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Saqib A Chaudhry ◽

Iqra N Akhtar ◽

Ameer E Hassan ◽

Mohammad Rauf A Chaudhry ◽

Mohsain Gill ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

International Classification Of Diseases ◽

The United States ◽

Primary Diagnosis ◽

Limited Information ◽

Hospital Outcomes ◽

The Impact ◽

Over Time

Background: Relatively limited information is available about trends over time in the use of endovascular treatment in patients of different ages hospitalized with acute ischemic stroke and the association between use of thrombectomy treatment and hospital outcomes in age strata. We performed this analysis to evaluate trends in the utilization of endovascular treatment in acute ischemic stroke by age strata in real-world practice. Methods: We conducted this study by identifying patients admitted with a primary diagnosis of ischemic stroke in the United States from 2007 to 2016 using the Nationwide Inpatient Sample. International Classification of Diseases, ninth revision, and tenth, Clinical Modification (ICD-9-CM, ICD-10-CM) codes were used to identify patients admitted for ischemic stroke and undergoing endovascular treatment. Results: Of the 4,590,533 patients admitted with ischemic stroke, 269,922 (5.88%) received intravenous thrombolytic treatment, and 51,375 (1.12%) underwent endovascular treatment. There is almost 12-fold significant increase in the use of endovascular treatment patients admitted with acute ischemic stroke between 2007 to 2016. Patients who were 75 years and older experienced a marked increase in the receipt of endovascular treatment over time (0.12% 2007; 1.91% 2016; trend p<0.0001). We observed statistically significant improvement in outcomes including minimal disability (6.3% to 18.8%; trend p<0.0001) and in hospital mortality (25.0% to 16.5%; trend p<0.0001) in patients 75 years and older treated with endovascular treatment in study period. We observed similar trend of outcomes in each of the other age-specific groups under study (<55, 55-64 and 65-74 years). Conclusions: Our findings indicate a recent increase in the use of endovascular in middle-aged and elderly patients with acute ischemic strokes. The impact of endovascular treatment on hospital outcomes was observed in each of our age strata understudy though the magnitude of absolute and relative benefit varied according to age.

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Searching for Security, 1942–1947

Armed Guests ◽

10.1093/oso/9780190097752.003.0005 ◽

2020 ◽

pp. 106-168

Author(s):

Sebastian Schmidt

Keyword(s):

The United States ◽

Second World War ◽

The Political ◽

Us Military ◽

Military Presence ◽

The Cold War ◽

Open Question ◽

The Impact ◽

Second World ◽

Over Time

In the uncertain security climate after the conclusion of the Second World War but before the intensification of the Cold War, the major factor that shaped US strategic planning was the impact of novel destructive technologies that radically increased the speed and scale of warfare. American planners responded by seeking to enlarge the defensive perimeter of the United States beyond its territory. How to realize this and what it meant in concrete terms, however, was an open question. Over time, the wartime allies worked out a variety of arrangements premised on different rationales in light of the political difficulties associated with a foreign peacetime military presence. Where US military presences were maintained, they were predicated on temporary conditions, and none were fated to become the kind of arrangements we are familiar with today. The discussion develops case studies of American interactions with Canada, Portugal, Britain, France, Iceland, and Saudi Arabia.

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