Search

Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June-August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers. In both states, a convenience sample of persons who work in dairies was interviewed, and blood specimens were collected. Among 115 persons, eight (7%; 95% CI = 3.6%-13.1%) had serologic evidence of recent infection with A(H5) virus; all reported milking cows or cleaning the milking parlor. Among persons with serologic evidence of infection, four recalled being ill around the time cows were ill; symptoms began before or within a few days of A(H5) virus detections among cows. This finding supports the need to identify and implement strategies to prevent transmission among dairy cattle to reduce worker exposures and for education and outreach to dairy workers concerning prevention, symptoms, and where to seek medical care if the workers develop symptoms. Timely identification of infected herds can support rapid initiation of monitoring, testing, and treatment for human illness, including mild illness, among exposed dairy workers., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The COVID-19 pandemic was an unparalleled stressor that enhanced isolation. Loneliness has been identified as an epidemic by the US Surgeon General. This study aimed to: (1) characterize longitudinal trajectories of loneliness during the acute phase of the COVID-19 pandemic; (2) identify longitudinal mediators of the relationship of loneliness with anxiety and depression; and (3) examine how loneliness naturally clusters and identify factors associated with high loneliness. Two hundred and twenty-nine adults (78% female; mean age = 39.5 ± 13.8) completed an abbreviated version of the UCLA Loneliness Scale, Perceived Stress Scale, Emotion Regulation Questionnaire, State Anxiety Inventory, and Patient Health Questionnaire-8 longitudinally between April 2020 and 2021. Trajectory analyses demonstrated relatively stable loneliness over time, while anxiety and depression symptoms declined. Longitudinal analyses indicated that loneliness effects on anxiety and depression were both partially mediated by perceived stress, while emotion regulation capacity only mediated effects on anxiety. Three stable clusters of loneliness trajectories emerged (high, moderate, and low). The odds of moderate or high loneliness cluster membership were positively associated with higher perceived stress and negatively associated with greater cognitive reappraisal use. Our results demonstrate the important interconnections between loneliness and facets of mental health throughout the early phases of the pandemic and may inform targeted future interventions for loneliness work., (© 2024 John Wiley & Sons Ltd.)

Households are a primary setting for transmission of SARS-CoV-2. We examined the role of prior SARS-CoV-2 immunity on the risk of infection in household close contacts. Households in the United States with an individual who tested positive for SARS-CoV-2 during September 2021-May 2023 were enrolled if the index case's illness began ≤6 days prior. Household members had daily self-collected nasal swabs tested by RT-PCR for SARS-CoV-2. The effects of prior SARS-CoV-2 immunity (vaccination, prior infection, or hybrid immunity) on SARS-CoV-2 infection risk among household contacts were assessed by robust, clustered multivariable Poisson regression. Of 1,532 contacts (905 households), 8% had immunity from prior infection alone, 51% from vaccination alone, 29% hybrid immunity, and 11% had no prior immunity. Sixty percent of contacts tested SARS-CoV-2-positive during follow-up. The adjusted risk of SARS-CoV-2 infection was lowest among contacts with vaccination and prior infection (aRR: 0.81, 95% CI: 0.70, 0.93, compared with contacts with no prior immunity) and was lowest when the last immunizing event occurred ≤6 months before COVID-19 affected the household (aRR: 0.69, 95% CI: 0.57, 0.83). In high-transmission settings like households, immunity from COVID-19 vaccination and prior infection was synergistic in protecting household contacts from SARS-CoV-2 infection., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza., (Published by Oxford University Press on behalf of National Academy of Sciences 2024.)

The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially post the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023. More than 200 individuals who tested positive for influenza and their household contacts were enrolled within 7 days of the first illness in the household. All participants were prospectively followed for 10 days completing daily symptom diaries and collecting nasal swabs, which were tested for influenza via RT-PCR. We analyzed these data by modifying a previously published Bayesian data augmentation approach that imputes infection times of cases to obtain both intrinsic (assuming no susceptible depletion) and realized (observed within household) generation times. We assessed the robustness of the generation time estimate by varying the incubation period, and generated estimates of the proportion of transmission before symptomatic onset, infectious period, and latent period. We estimated a mean intrinsic generation time of 3.2 (95% credible interval, CrI: 2.9-3.6) days, with a realized household generation time of 2.8 (95% CrI: 2.7-3.0) days. The generation time exhibited limited sensitivity to incubation period variation. Estimates of the proportion of transmission that occurred before symptom onset, the infectious period, and the latent period were sensitive to variation in incubation periods. Our study contributes to the ongoing efforts to refine estimates of the generation time for influenza. Our estimates, derived from recent data following the COVID-19 pandemic, are consistent with previous pre-pandemic estimates, and will be incorporated into real-time Rt estimation efforts., Competing Interests: Declaration of interest • M. S. S. reports a leadership role as Associate Director of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS), paid to Trustees of Columbia University. All other authors report no potential conflicts. • N. M.B. reports grant/contracts from NIH to the University of North Carolina School of Medicine, Doris Duke Charitable Foundation, and North Carolina Collaboratory; participation on a DSMB or advisory board for the Snowball Study Technical Interchange; a leadership or fiduciary role on the American Society of Tropical Medicine and Hygiene Scientific Committee; and other financial or nonfinancial interests with the COVID-19 Equity Evidence Academy (RADx-UP CDCC) Steering Committee and North Carolina Occupational Safety and Health Education Research Center. • E. A. reports serving as a former consultant for Hillevax and Moderna, presenting a Merck-supported lecture at the Latin American Vaccine Summit, and receipt of grant/research support from Pfizer for pneumococcal pneumonia studies. • S. R. reports grant support from BioFire. • H. Q. N. reports grant/research support from CSL Seqirus, GSK, and ModernaTX, and honorarium for participating in a consultancy group for ModernaTX outside the submitted work. • S. H. M. reports grants/contracts from NIH, the American Academy of Pediatrics, and the Doris Duke Charitable Foundation. • E. S. reports grants or contracts to institution from Vanderbilt University Medical Center (originating at CDC #75D30121C11656). • H. K. T. has received research funding from the CDC. • C. G. G. reports participation on an advisory board for Merck, and receipt of grant/research support from AHRQ, CDC, US Food and Drug Administration, NIH, and Syneos Health. • All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Asymptomatic influenza virus infection occurs but may vary by factors such as age, influenza vaccination status, or influenza season. We examined the frequency of influenza virus infection and associated symptoms using data from two case-ascertained household transmission studies (conducted from 2017-2023) with prospective, systematic collection of respiratory specimens and symptoms. From the 426 influenza virus infected household contacts that met our inclusion criteria, 8% were asymptomatic, 6% had non-respiratory symptoms, 23% had acute respiratory symptoms, and 62% had influenza-like illness symptoms. Understanding the prevalence of asymptomatic and mildly symptomatic influenza cases is important for implementing effective influenza prevention strategies and enhancing the effectiveness of symptom-based surveillance systems., Competing Interests: Competing Interest Statement: EAB receives research support from CSL Seqirus unrelated to the current work. HQN receives research support unrelated to this work from CSL Seqirus, GSK, ModernaTX Inc, and honorarium for participating in a consultancy group for Moderna outside the submitted work. Dr. Grijalva has received consulting fees from Merck, and research support from SyneosHealth, NIH, FDA and AHRQ.

Background: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes from coronavirus disease 2019 (COVID-19); however, rebound after treatment has been reported. We compared symptom and viral dynamics in individuals with COVID-19 who completed N/R treatment and similar untreated individuals., Methods: We identified symptomatic participants who tested severe acute respiratory syndrome coronavirus 2-positive and were N/R eligible from a COVID-19 household transmission study. Index cases from ambulatory settings and their households contacts were enrolled. We collected daily symptoms, medication use, and respiratory specimens for quantitative polymerase chain reaction for 10 days during March 2022-May 2023. Participants who completed N/R treatment (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R treatment completion or 7 days after symptom onset if untreated., Results: Treated (n = 130) and untreated participants (n = 241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; P = .009) and VL rebound (27% vs 7%; P < .001). Average daily symptoms were lower among treated participants without symptom rebound (1.0 vs 1.6; P < .01) but not statistically lower with symptom rebound (3.0 vs 3.4; P = .5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; P < .01) but not statistically lower with VL rebound (4.8 vs 5.1; P = .7)., Conclusions: Individuals who completed N/R treatment experienced fewer symptoms and lower VL but rebound occured more often compared with untreated individuals. Providers should prescribe N/R, when indicated, and communicate rebound risk to patients., Competing Interests: Potential conflicts of interest. S. R. reports grant support from BioFire. H. Q. M. reports grant/research support from CSL Sequiris and CSK. J. G. P. reports serving as a former consultant for CSL Seqirus and receipt of grants from the National Institutes of Health (NIH) and CSL Seqirus. E. A. reports serving as a former consultant for Hillevax and Moderna, presenting a Merck-supported lecture at the Latin American Vaccine Summit, and receipt of grant/research support from Pfizer for pneumococcal pneumonia studies. C. G. G. reports being a former advisor to Merck, participation on a data and safety monitoring board (DSMB) or advisory board for Merck, and receipt of grant/research support from AHRQ, CDC, US Food and Drug Administration, NIH, and Syneos Health. N. M.B. reports grant/contracts from NIH to the University of North Carolina School of Medicine, Doris Duke Charitable Foundation, and North Carolina Collaboratory; participation on a DSMB or advisory board for the Snowball Study Technical Interchange; a leadership or fiduciary role on the American Society of Tropical Medicine and Hygiene Scientific Committee; and other financial or nonfinancial interests with the COVID-19 Equity Evidence Academy (RADx-UP CDCC) Steering Committee and North Carolina Occupational Safety and Health Education Research Center. S. H. M. reports grants/contracts from NIH, the American Academy of Pediatrics, and the Doris Duke Charitable Foundation. E. A. B. reports research support to the Marshfield Clinic Research Institute from the CDC. E. S. reports grants or contracts to institution from Vanderbilt University Medical Center (originating at CDC #75D30121C11656). S. G. reports support for attending meetings and/or travel from the Infectious Diseases Society of America for Infectious Disease Week 2022 and 2023. K. G. M., L. M., S. B.-W., and V. O. report funding to Westat via the CDC (contract 75D30121C11571). M. S. S. reports a leadership role as Associate Director of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS), paid to Trustees of Columbia University. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

As population immunity to SARS-CoV-2 evolves and new variants emerge, the role and accuracy of antigen tests remain active questions. To describe recent test performance, the detection of SARS-CoV-2 by antigen testing was compared with that by reverse transcription-polymerase chain reaction (RT-PCR) and viral culture testing during November 2022-May 2023. Participants who were enrolled in a household transmission study completed daily symptom diaries and collected two nasal swabs (tested for SARS-CoV-2 via RT-PCR, culture, and antigen tests) each day for 10 days after enrollment. Among participants with SARS-CoV-2 infection, the percentages of positive antigen, RT-PCR, and culture results were calculated each day from the onset of symptoms or, in asymptomatic persons, from the date of the first positive test result. Antigen test sensitivity was calculated using RT-PCR and viral culture as references. The peak percentage of positive antigen (59.0%) and RT-PCR (83.0%) results occurred 3 days after onset, and the peak percentage of positive culture results (52%) occurred 2 days after onset. The sensitivity of antigen tests was 47% (95% CI = 44%-50%) and 80% (95% CI = 76%-85%) using RT-PCR and culture, respectively, as references. Clinicians should be aware of the lower sensitivity of antigen testing compared with RT-PCR, which might lead to false-negative results. This finding has implications for timely initiation of SARS-CoV-2 antiviral treatment, when early diagnosis is essential; clinicians should consider RT-PCR for persons for whom antiviral treatment is recommended. Persons in the community who are at high risk for severe COVID-19 illness and eligible for antiviral treatment should seek testing from health care providers with the goal of obtaining a more sensitive diagnostic test than antigen tests (i.e., an RT-PCR test)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Edwin J. Asturias reports grant support from Pfizer, consulting fees from Hillevax and Moderna, and payment from Merck for a lecture delivered at the Latin American Vaccine Summit. Carlos G. Grijalva reports support from the Food and Drug Administration and grants from the National Institutes of Health (NIH) and Syneos Health. Son H. McLaren reports institutional support from the Respiratory Virus Transmission Network, receipt of the Ken Graff Young Investigator Award from the American Academy of Pediatrics, Section on Emergency Medicine, institutional support from the National Center for Advancing Translational Science, the National Heart, Lung, and Blood Institute, and the Doris Duke Charitable Foundation COVID-19 Fund to Retain Clinician-Scientists. Suchitra Rao reports grant support from Biofire. Melissa S. Stockwell reports institutional support from the University of Washington, Boston Children’s Hospital, Westat, and New York University, and service as the Associate Director of the American Academy of Pediatrics Pediatric Research in Office Settings Research Network (payment to the trustees of Columbia University). Huong Q. Nguyen reports research support from CSL Seqirus, GSK, and ModernaTX, and an honorarium from ModernaTX for participating in a consultancy group, outside the submitted work. No other potential conflicts of interest were disclosed.

Background: The ongoing COVID-19 pandemic has led to hundreds of millions of infections worldwide. Although differences in COVID-19 hospitalization rates between males and females have been described, many infections in the general population have been mild, and the severity of symptoms during the course of COVID-19 in non-hospitalized males and females is not well understood., Methods: We conducted a case-ascertained study to examine household transmission of SARS-CoV-2 infections in Nashville, Tennessee, between April 2020 and April 2021. Among enrolled ambulatory adult participants with laboratory-confirmed SARS-CoV-2 infections, we assessed the presence and severity of symptoms (total, systemic, and respiratory) daily using a symptoms severity questionnaire, from illness onset and throughout the 2-week follow-up period. We compared the mean daily symptom severity scores (0-3: none, mild, moderate, and severe) and change in symptoms between males and females using a multivariable linear mixed effects regression model., Results: The analysis included 223 enrolled adults with SARS-CoV-2 infection (58% females, mostly white, non-Hispanic) from 146 households with 2917 total daily symptom reports. The overall mean severity of total symptoms reported over the illness period was 1.04 and 0.90 for females and males, respectively. Mean systemic and respiratory scores were higher for females than for males ( p  < 0.001). In multivariable analyses, females reported more severe total and systemic symptoms during the illness period compared with males. However, no significant differences in reported respiratory symptoms were observed., Conclusions: Our findings indicate that among ambulatory adults with SARS-CoV-2 infections, females reported slightly higher symptom severity during their illness compared with males., Competing Interests: C.G.G. reports grants from Syneos Health, the National Institutes of Health, the Food and Drug Administration, the Agency for Health Care Research and Quality, and consultation fees from Merck. The other authors have no potential conflicts of interest to report., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Importance: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season., Objective: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US., Design, Setting, and Participants: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment., Exposures: Household contacts living with a primary case., Main Outcomes and Measures: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted., Results: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons., Conclusions and Relevance: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.

Influenza seasons typically begin in October and peak between December and February (1); however, the 2022-23 influenza season in Tennessee began in late September and was characterized by high pediatric hospitalization rates during November. This report describes a field investigation conducted in Tennessee during November 2022, following reports of increasing influenza hospitalizations. Data from surveillance networks, patient surveys, and whole genome sequencing of influenza virus specimens were analyzed to assess influenza activity and secondary illness risk. Influenza activity increased earlier than usual among all age groups, and rates of influenza-associated hospitalization among children were high in November, reaching 12.6 per 100,000 in children aged <5 years, comparable to peak levels typically seen in high-severity seasons. Circulating influenza viruses were genetically similar to vaccine components. Among persons who received testing for influenza at outpatient clinics, children were twice as likely to receive a positive influenza test result as were adults. Among household contacts exposed to someone with influenza, children were more than twice as likely to become ill compared with adults. As the influenza season continues, it is important for all persons, especially those at higher risk for severe disease, to protect themselves from influenza. To prevent influenza and severe influenza complications, all persons aged ≥6 months should get vaccinated, avoid contact with ill persons, and take influenza antivirals if recommended and prescribed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Noah Kojima reports receipt of consulting fees from Curative. Mary-Margaret A. Fill reports support from the Council of State and Territorial Epidemiologists (CSTE) to attend the CSTE annual meeting, and from Johns Hopkins University to attend the Johns Hopkins Center for Health Security Emerging Leaders in Biosecurity Summer Research Symposium; service as an external member on the University of Tennessee’s One Health Initiative Board; and participation as CSTE representative to the Advisory Committee on Immunization Practices Adult Immunization Schedules and General Best Practices work groups. Carlos G. Grijalva reports institutional support from the National Institute for Allergy and Infectious Diseases, National Institutes of Health (NIH); grant support from NIH, the Agency for Healthcare Research and Quality, the Food and Drug Administration, and Campbell Alliance/Syneos Health; consulting fees from Merck; and advisory services to Merck. William Schaffner reports serving as the medical director of the National Foundation for Infectious Diseases. Jonathan E. Schmitz reports federal, Roche, and Quantum Material Correlation grant support; consulting fees from Gene Capture, Inc.; and honoraria from Pfizer. No other potential conflicts of interest were disclosed.

We used daily real-time reverse-transcription polymerase chain reaction (RT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study, conducted April 2020-May 2021, to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration. Ct values varied across RT-PCR platforms and by participant age. Specimens collected from children and adolescents had higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms, with the lowest Ct value occurring 2-6 days after symptom onset., Competing Interests: Potential conflicts of interest. C. G. G. reports grants from Campbell Alliance/Syneos, the National Institutes of Health, the Food and Drug Administration, the Agency for Health Care Research and Quality, and Sanofi-Pasteur; and consultation fees from Pfizer, Merck, and Sanofi-Pasteur. N. B. H. reports grant support from Sanofi-Pasteur and Quidel. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Objectives: Examine age differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risk from primary cases and infection risk among household contacts and symptoms among those with SARS-CoV-2 infection., Methods: People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations., Results: The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower in primary cases age 12 to 17 years than from primary cases 18 to 49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contact pairs age ≥65 years (76%) and 5 to 11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group., Conclusions: Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: Dr Halasa reports grants from Sanofi and Quidel. Dr Grijalva reports grants from Campbell Alliance/Syneos, the National Institutes of Health, the Food and Drug Administration, the Agency for Health Care Research and Quality and Sanofi-Pasteur, and consultation fees from Pfizer, Merck, and Sanofi-Pasteur. Other authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Competing Interests: The authors report no conflicts of interest.

Individuals with substance use disorders (SUDs), including those in long-term recovery, and their loved ones are facing rapid changes to treatment and support services due to COVID-19. To assess these changes, the Addiction Policy Forum fielded a survey to their associated patient and family networks between April 27 and May 13, 2020. Individuals who reported a history of use of multiple substances were more likely to report that COVID-19 has affected their treatment and service access, and were specifically more likely to report both use of telehealth services and difficulties accessing needed services. These findings suggest that individuals with a history of using multiple substances may be at greater risk for poor outcomes due to COVID-19, even in the face of expansion of telehealth service access., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Episodic Future Thinking (EFT) reduces delay discounting (DD; preference for smaller, immediate rewards) and various maladaptive behaviors. Exploring potential personalization of EFT to optimize its ability to alter DD and demand for unhealthy reinforcers is important for the development of interventions targeting long-term improvement and maintenance of health. In this investigation, using 2 separate studies, we examined the effects of EFT with and without a health goal on rates of discounting, demand, and craving for cigarettes and fast food among cigarette smokers and obese individuals, respectively. Using data collected from Amazon Mechanical Turk (mTurk), Study 1 ( N = 189) examined the effect of EFT on DD and measures of cigarette demand and craving in cigarette smokers who were randomly assigned to 1 of 3 conditions: EFT-health goal, EFT-general, or Episodic Recent Thinking (ERT)-general. Study 2 ( N = 255), using a 2x2 factorial design, examined the effects of health goals and general EFT on DD and measures of fast food demand and craving in obese individuals who were randomly assigned to 1 of 4 conditions: EFT-health goal, EFT-general, ERT-health goal or ERT-general. Health goal EFT was not more effective than general EFT in reducing monetary discounting. However, the addition of a health goal to general EFT was significantly associated with higher effect on intensity and elasticity of demand for cigarettes and fast food compared to EFT without a health goal. These findings suggest that the amplification of future thinking through the inclusion of a health goal may promote healthy decisions and result in positive behavior changes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Aims: Amazon Mechanical Turk (MTurk) provides a crowdsourcing platform for the engagement of potential research participants with data collection instruments. This review (1) provides an introduction to the mechanics and validity of MTurk research; (2) gives examples of MTurk research; and (3) discusses current limitations and best practices in MTurk research., Methods: We review four use cases of MTurk for research relevant to addictions: (1) the development of novel measures, (2) testing interventions, (3) the collection of longitudinal use data to determine the feasibility of longer-term studies of substance use and (4) the completion of large batteries of assessments to characterize the relationships between measured constructs. We review concerns with the platform, ways of mitigating these and important information to include when presenting findings., Results: MTurk has proved to be a useful source of data for behavioral science more broadly, with specific applications to addiction science. However, it is still not appropriate for all use cases, such as population-level inference. To live up to the potential of highly transparent, reproducible science from MTurk, researchers should clearly report inclusion/exclusion criteria, data quality checks and reasons for excluding collected data, how and when data were collected and both targeted and actual participant compensation., Conclusions: Although on-line survey research is not a substitute for random sampling or clinical recruitment, the Mechanical Turk community of both participants and researchers has developed multiple tools to promote data quality, fairness and rigor. Overall, Mechanical Turk has provided a useful source of convenience samples despite its limitations and has demonstrated utility in the engagement of relevant groups for addiction science., (© 2020 Society for the Study of Addiction.)

Objective: This study aimed to determine if episodic future thinking (EFT) can decrease delay discounting (DD) among adults with prediabetes both in and out of the laboratory. DD measures how much the value of a reinforcer decreases as a function of the delay to receive it., Methods: Adults with prediabetes (n = 67) completed a three-session study. At session 1, baseline measures (including DD) were collected. At sessions 2 and 3, participants were prompted to engage in either EFT or control episodic thinking (CET) while completing DD and other measures. In addition, between the completion of sessions 2 and 3, participants engaged in EFT or CET at home and completed DD tasks remotely via smartphones or other Internet-connected devices., Results: Results showed significant -1.2759 (-20.24%) reductions in DD in the EFT group compared with a + 0.0287 (+0.46%) DD increase in the CET group (p = .0149) in the laboratory; and -0.4095 (-8.85%) reduction in DD in the EFT group compared with a + 0.2619 (+5.64%) increase in the CET group (p = .011) at home. Working memory (measured by Backwards Corsi and Digit Span) was found to moderate the effects of EFT on some measures of DD. EFT did not change measures from the food purchase task or a food ad libitum procedure., Conclusions: Results show that EFT decreases DD in and out of the laboratory and supports the further exploration of EFT as an intervention for prediabetes and related chronic diseases., Clinical Trial Registration: NCT03664726.

Introduction: The experimental tobacco marketplace (ETM) approximates real-world situations by estimating the effects of several, concurrently available products and policies on budgeted purchasing. Although the effects of increasing cigarette price on potentially less harmful substitutability are well documented, the effects of other, nuanced pricing policies remain speculative. This study used the ETM as a tool to assess the effects of two pricing policies, conventional cigarette taxation and e-liquid subsidization, on demand and substitutability., Methods: During sampling periods, participants were provided 2-day samples of 24 mg/mL e-liquid, after which ETM purchase sessions occurred. Across two ETM sessions, conventional cigarettes were taxed or e-liquid was subsidized in combination with increasing cigarette price. The other four available products were always price constant and not taxed or subsidized., Results: E-liquid functioned as a substitute for conventional cigarettes across all conditions. Increasing cigarette taxation and e-liquid subsidization increased the number of participants for which e-liquid functioned as a substitute. Cigarette taxation decreased cigarette demand, by decreasing demand intensity, and marginally increased the initial intensity of e-liquid substitution, but did not affect the functions' slopes (substitutability). E-liquid subsidization resulted in large increases in the initial intensity of e-liquid substitution, but did not affect e-liquid substitutability nor cigarette demand., Implications: 24 mg/mL e-cigarette e-liquid was the only product to significantly substitute for cigarettes in at least one condition throughout the experiment; it functioned as a significant substitute throughout all four tax and all four subsidy conditions. Increasing cigarette taxes decreased cigarette demand through decreases in demand intensity but did not affect e-cigarette substitution. Increasing e-liquid subsidies increased e-liquid initial intensity of substitution but did not affect cigarette demand., Conclusions: This study extended research on the behavioral economics of conventional cigarette demand and e-liquid substitutability in a complex marketplace. The results suggest that the most efficacious method to decrease conventional cigarette purchasing and increase e-liquid purchasing may involve greatly increasing cigarette taxes while also increasing the value of e-liquid through potentially less harmful product subsidization or differential taxation., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Reinforcer pathology is derived from the integration of two measures: (a) self-control (i.e., delay discounting), and (b) reward valuation (i.e., behavioral economic demand). Narrative theory asserts that vividly imagining oneself in a hypothetical, yet realistic, scenario can acutely alter decision making, valuation of reinforcers such as food, and how much food is consumed. The present study measured changes in reinforcer pathology for highly palatable snacks following either a negative or neutral scenario in obese individuals. Participants (N = 48), with a body mass index of 30 or greater, rated their liking of 7 calorie-dense snack items and completed discounting and purchase demand tasks for their top-rated snack. Participants then read a randomly assigned hypothetical scenario (i.e., a devastating hurricane [negative] or minor storm [neutral]), completed the tasks again, and were given ad libitum access to their top 3 ranked snack foods. Results indicated that delay discounting, demand for participants' top-rated snack food, and negative affect all increased in the hurricane group compared with the minor storm group. The hurricane group also consumed more calories, even when hunger was standardized with a preload meal bar. Consistent with reinforcer pathology, these results suggest that vivid consideration of a devastating scenario constricts the temporal window and increases demand for hedonic snack foods among obese individuals. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Delay discounting, or the process by which reinforcers lose value with delay to their receipt, has been identified as a trans-disease process underlying addiction, other disorders, and maladaptive health behaviors. Delay discounting has been identified as an endophenotype for multiple psychiatric disorders including substance use disorder, ADHD, and major depressive disorder, with this endophenotype being linked to deficits in dopaminergic and serotonergic neurotransmission. In addition, neuroanatomical and neurophysiological deficits in areas of the executive and impulsive systems have been associated with both steeper discounting and substance use disorders. Delay discounting constitutes a novel target for interventions to change health behaviors. A new theory, termed reinforcer pathology, has been developed uniting these findings and setting the stage for future research., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Delay discounting, or the preference for smaller, sooner over larger, later rewards, has been associated with alcohol use disorder and problem drinking. Episodic future thinking has been suggested as an intervention to address steep delay discounting. In the present study, we examined the effect of up to six consecutive sessions of episodic future thinking., Methods: Repeated, within-subject data were collected from current and recent problem drinkers (n = 50) over six sessions. Linear mixed-effect models were used to estimate effects of repeated sessions and manipulations. Participants completed episodic future thinking interviews at up to six sessions, in which they generated personalized future events. Participants also engaged with cues of scarcity. At each session, participants completed three delay discounting tasks under: a no-cue baseline condition, a future cue condition, and a scarcity cue condition., Results: Delay discounting in the no cue condition did not change over time. Discounting rates were reduced in the future cue condition, and these effects grew larger with repeated sessions. In the scarcity condition, discounting rates were slightly higher, with no effect of repeated sessions., Conclusions: Episodic future thinking reduced delay discounting rate while future cues were presented, and these effects grew larger with repeated sessions. This suggests that repeated episodic future thinking may cumulatively potentiate repair of excessive preference for immediate reward., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The majority of people with prediabetes transition to type 2 diabetes. Weight gain is a known predictor of increasing the risk of diabetes, but another reason may be a focus on immediate rewards and discounting of the future. Delay discounting (DD: devaluation of future consequences) is related to obesity and poor glycemic control in persons with type 2 diabetes. This study was designed to assess whether changes in DD are associated with HbA1c change beyond BMI change in individuals with prediabetes. Hierarchical regression showed changes in BMI (p = 0.008) and the $1000 DD task (p = 0.04) were associated with HbA1c change beyond demographic characteristics, with the full model accounting for 25.8% of the variance. Those with greater BMI increases and greater increases in discounting of the future showed the greatest increases in HbA1c. DD represents a novel target to prevent progression from prediabetes to type 2 diabetes.

Our understanding and effectiveness in treating addiction is not fully adequate. Therefore, perhaps developing a pragmatic theory for identifying novel determinants and potential interventions is needed. The experimental medicine approach, derived from Claude Bernard, proposes a methodology for inductive theory development and suggests interventions directed at targets closely aligned with the underlying mechanisms of the disorder. The steps of theory development under this approach are intended to (1) identify an intervention target; (2) develop assays to verify target measurement; (3) engage the target via experiment or intervention; and (4) test the degree to which target engagement produces other therapeutically useful changes in the disorder. In this article, we review these steps in detail using an example from our work. That is, shortened temporal windows (target) is frequently observed among those who are addicted. Delay discounting is an assay used to measure that target. We and others have demonstrated manipulation of the target, delay discounting, is associated with changing the drug valuation among those with addiction. We conclude with a culmination of the experimental medicine approach by proposing a recently developed hypothesis of substance use disorder, Reinforcer Pathology 2.0., Competing Interests: Conflict of InterestWarren K. Bickel also reports being a principal in HealthSim, LLC and NotifiUs LLC as well as a general partner in Red 5 Group LLC. Warren K. Bickel and Sarah E. Snider report being Principals in BEAM Diagnostics, Inc. Alexandra M. Mellis has no biomedical financial interests or potential conflicts of interests., (© Association for Behavior Analysis International 2019.)

Reinforcer pathology theory stipulates that individuals with both (a) high preference for smaller, immediate over larger, delayed rewards; and (b) high demand for unhealthy commodities are uniquely susceptible to poor health outcomes. Specifically, two behavioral economic tasks (delay discounting, assessing preference for smaller, immediate or larger, delayed rewards; and purchasing, assessing purchases of commodities over changes in price) have been independently associated with conditions such as overweight/obesity and problem substance use. In the present study, we examined possible shared neural regions involved in the processes of delay discounting and demand for snack foods in a prediabetic sample. Fifty-four participants completed both of these tasks. Conjunction between delay discounting and purchasing task results indicates substantial common neural substrates recruited during these two tasks, consistent with interpretations of executive control, interoception, and attention, in the prefrontal cortex, insula, and frontoparietal cortex (superior/middle frontal cortex and superior/inferior parietal lobules), respectively. Collectively, these results suggest possible neural substrates in which the two behavioral risk factors of reinforcer pathology may interact during real-world decision-making in prediabetes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Abstinence self-efficacy (ASE) and delay discounting predict treatment outcomes and risk of relapse. Associations between delay discounting and ASE among individuals in recovery from substance use have not been investigated. Data from 216 individuals in recovery from substance abuse recruited from The International Quit & Recovery Registry, an ongoing online data collection program used to understand addiction and how people succeed in recovery, were included in the analysis. Discounting rates were assessed using an adjusting-delay task, and ASE was assessed using the Relapse Situation Efficacy Questionnaire (RSEQ). Delay discounting was a significant predictor of ASE, even after controlling for age, gender, race, ethnicity, annual income, education level, marital status, and primary addiction. Context-specific factors of relapse included Negative Affect, Positive Affect, Restrictive Situations (to drug use), Idle Time, Social-Food Situations, Low Arousal, and Craving. A principal component analysis of RSEQ factors in the current sample revealed that self-efficacy scores were primarily unidimensional and not situation specific. The current study expands the generality of delay discounting and indicates that discounting rates predict ASE among individuals in recovery from substance use disorders. This finding supports the recent characterizations of delay discounting as a candidate behavioral marker of addiction and may serve as a basis to better identify and target subgroups that need unique or more intensive interventions to address higher risks of relapse and increase their likelihood of abstinence. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: The Experimental Tobacco Marketplace (ETM) is a digital storefront in which participants can purchase tobacco products using an account balance that reflects their typical tobacco product purchasing. The ETM is also an ideal resource to investigate the harm-reduction potential of alternative nicotine products such as e-cigarettes. In a series of experiments, we explored the effects of harm-reduction narratives that encouraged e-cigarette substitution of conventional cigarettes in the ETM. These narratives incorporated different cognitive biases in order to determine which strategy is most effective., Methods: In both experiments, participants, recruited from Amazon Mechanical Turk, read a narrative about a friend that either falls ill or faces financial difficulties and then made purchases in the ETM. Some of these narratives specifically incorporated different cognitive biases including trusting authority. Across ETM trials, the price of conventional cigarettes increased while the price of the alternative products, including e-cigarettes, remained constant., Results: Across both experiments, a general pattern emerged supporting the effectiveness of narratives in increasing e-cigarette purchasing. Importantly, from a harm-reduction perspective, this increase in e-cigarette substitution frequently corresponded with a decrease in conventional cigarette purchasing., Conclusions: Narratives can decrease conventional cigarette and increase e-cigarette purchasing in an ETM that mimics real-world marketplaces. Invoking different cognitive biases may bolster this effect. Narratives can be a valuable harm-reduction tool because they are cost-effective, can be widely disseminated, and can be personalized to individuals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Despite promising decreases in overall smoking rates, a significant proportion of the population continues to engage in this costly behavior. Substituting e-cigarettes for conventional cigarettes is an increasingly popular harm-reduction strategy. Narratives may be one method of increasing the substitutability of e-cigarettes. Participants (N = 160) were assigned to 1 of 4 narratives that described a close friend becoming ill. In the positive narrative, participants read about a friend that became ill but learned it was only the flu. In the negative narrative, the friend became ill from smoking cigarettes; in the negative regret narrative, the friend became ill from smoking cigarettes and explicitly expressed regret for having started smoking; and in the negative change narrative, the friend became ill from smoking, switched to e-cigarettes, and made a full recovery. Participants then completed an experimental tobacco marketplace (ETM) in which they could purchase conventional cigarettes and alternative nicotine products, including e-cigarettes. Across ETM trials, the price of conventional cigarettes increased while the price of the alternative products remained constant. Initial purchasing of conventional cigarettes decreased and initial purchasing of e-cigarettes increased in the negative-change group compared with the other three groups. This finding was moderated by conventional cigarette dependence and perception of e-cigarette risk but not previous e-cigarette exposure. Narratives can change conventional cigarette and e-cigarette purchasing in an ETM that mimics real-world marketplaces. Narratives can be a valuable harm-reduction tool because they are cost-effective, can be widely disseminated, and can be personalized to individuals. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Negative income shock, or the rapid reduction in financial stability, has previously been shown to increase impulsive choice for money and demand for fast food. The interplay of these conditions for obesity is called reinforcer pathology. The present work examines the impact of negative income shock on monetary and fast food discounting using a cross-commodity delay discounting task and on purchasing of fast food and an alternative commodity. An obese sample (n = 120) was recruited from Amazon Mechanical Turk and assigned to read one of two narratives: negative income shock (n = 60) or control (n = 60). Participants then completed both within- and cross-commodity discounting tasks of money and food, and purchase tasks for fast food and bottled water. The negative income shock group demonstrated greater impulsive choice across discounting tasks, as well as higher intensity of demand for fast food but not for a non-caloric control commodity (bottled water). These results suggest that negative income shock increases preference for immediate reinforcement regardless of commodity type (money or fast food), but has specific effects increasing demand for particular commodities (fast food but not an alternative). In a reinforcer pathology framework, negative income shock increasing discounting of the future while increasing demand for fast food specifically represents a high-risk state for negative health behavior in obesity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Reading experimenter-provided narratives of negative income shock has been previously demonstrated to increase impulsivity, as measured by discounting of delayed rewards. We hypothesized that writing these narratives would potentiate their effects of negative income shock on decision-making more than simply reading them. In the current study, 193 cigarette-smoking individuals from Amazon Mechanical Turk were assigned to either read an experimenter-provided narrative or self-generate a narrative describing either the negative income shock of job loss or a neutral condition of job transfer. Individuals then completed a task of delay discounting and measures of affective response to narratives, as well as rating various narrative qualities such as personal relevance and vividness. Consistent with past research, narratives of negative income shock increased delay discounting compared to control narratives. No significant differences existed in delay discounting after self-generating compared to reading experimenter-provided narratives. Positive affect was lower and negative affect was higher in response to narratives of job loss, but affect measures did not differ based on whether narratives were experimenter-provided or self-generated. All narratives were rated as equally realistic, but self-generated narratives (whether negative or neutral) were rated as more vivid and relevant than experimenter-provided narratives. These results indicate that the content of negative income shock narratives, regardless of source, consistently drives short-term choices. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

This review critically examines neurobehavioral theoretical developments in decision making in addiction in the 21st century. We specifically compare each theory reviewed to seven benchmarks of theoretical robustness, based on their ability to address: why some commodities are addictive; developmental trends in addiction; addiction-related anhedonia; self-defeating patterns of behavior in addiction; why addiction co-occurs with other unhealthy behaviors; and, finally, means for the repair of addiction. We have included only self-contained theories or hypotheses which have been developed or extended in the 21st century to address decision making in addiction. We thus review seven distinct theories of decision making in addiction: learning theories, incentive-sensitization theory, dopamine imbalance and systems models, opponent process theory, strength models of self-control failure, the competing neurobehavioral decision systems theory, and the triadic systems theory of addiction. Finally, we have directly compared the performance of each of these theories based on the aforementioned benchmarks, and highlighted key points at which several theories have coalesced., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Basic research on delay discounting, examining preference for smaller-sooner or larger-later reinforcers, has demonstrated a variety of findings of considerable generality. One of these, the magnitude effect, is the observation that individuals tend to exhibit greater preference for the immediate with smaller magnitude reinforcers. Delay discounting has also proved to be a useful marker of addiction, as demonstrated by the highly replicated finding of greater discounting rates in substance users compared to controls. However, some research on delay discounting rates in substance users, particularly research examining discounting of small-magnitude reinforcers, has not found significant differences compared to controls. Here, we hypothesize that the magnitude effect could produce ceiling effects at small magnitudes, thus obscuring differences in delay discounting between groups. We examined differences in discounting between high-risk substance users and controls over a broad range of magnitudes of monetary amounts ($0.10, $1.00, $10.00, $100.00, and $1000.00) in 116 Amazon Mechanical Turk workers. We found no significant differences in discounting rates between users and controls at the smallest reinforcer magnitudes ($0.10 and $1.00) and further found that differences became more pronounced as magnitudes increased. These results provide an understanding of a second form of the magnitude effect: That is, differences in discounting between populations can become more evident as a function of reinforcer magnitude., (© 2017 Society for the Experimental Analysis of Behavior.)

The maturing fields of behavioral- and neuro-economics provides conceptual understanding of the Competing Neurobehavioral Decision Systems theory (CNDS) and reinforcer pathology (i.e. high valuation of and excessive preference for drug reinforcers) allowing us to coherently categorize treatments into a theoretically comprehensive framework of addiction. In this chapter, we identify and clarify how existing and novel interventions can ameliorate reinforcer pathology in light of the CNDS and be leveraged to treat addiction.

Endodermal sinus (yolk sac) tumors (ESTs) are rare neoplasms that most commonly arise in the ovaries or testis. Only six cases of prostatic ESTs have been reported in the literature. We report a case of prostatic EST, the first case in which the patient had a history of previous testis cancer. Treatment included cisplatin-based chemotherapy and radical prostatectomy. Previous cases of primary ESTs and use of cisplatin-based therapy as well as metastatic tumors to the prostate are discussed., (© 2015 S. Karger AG, Basel.)

Background and Purpose: Patients with spinal neuropathy are at an increased risk for urolithiasis. Data on percutaneous nephrolithotomy (PCNL) in this population are limited. Our objective is to review our experience in managing stones with PCNL in patients with spinal neuropathy., Patients and Methods: Twenty-one patients with spinal neuropathy underwent PCNL at our institution between January 2005 and August 2011. Their medical records were reviewed retrospectively to collect data relating to stone characteristics, treatment outcomes, and complications., Results: Forty-two PCNL were performed on 26 kidneys. Five patients had bilateral stones. They were 14 (66.7%) patients with spinal cord injury, 5 (23.8%) with spina bifida, and 2 (9.5%) with other neurologic abnormalities. There were 90.5% of patients with preoperative bacteriuria and 47.6% with severe scoliosis, making positioning for PCNL challenging. Complete staghorn stones occurred in 46.2% of kidneys, and 50% of stones were struvite. Only 53.8% of kidneys were stone free after the first PCNL. The success rate increased to 80.8% after the second and 88.5% after the third PCNL. Urosepsis developed in three (14.3%) patients, necessitating admission to the intensive care unit postoperatively. Six (28.6%) patients needed blood transfusion. One patient had a pneumothorax and another had a perforation of the collecting system., Conclusions: Based on our experience, PCNL in patients with spinal neuropathy had a stone clearance rate comparable with that of the general population. These patients, however, needed multiple PCNLs to be stone free and had a higher incidence of complications (especially infectious).

Ewing sarcoma, also referred to as primitive neuroectodermal tumor (PNET), is a malignancy, histologically characterized by Homer-Wright rosettes and small round cells, that presents most commonly in bone or soft tissue in the pediatric and adolescent populations. We report the case of a patient that presents with intermittent gross hematuria, abdominal mass and elevated blood pressure. After surgical excision of the renal mass, the rare finding of a primary renal Ewing's sarcoma was discovered. After surgery the patient was additionally treated with chemotherapy. After presenting this case, we briefly discuss the unique case of isolated renal Ewing's sarcoma, including incidence and treatment.

Increased reactive oxygen species (ROS) are implicated in several vascular pathologies associated with vascular smooth muscle hypertrophy. In the current studies, we utilized transgenic (Tg) mice (Tg(p22smc)) that overexpress the p22(phox) subunit of NAD(P)H oxidase selectively in smooth muscle. These mice have a twofold increase in aortic p22(phox) expression and H(2)O(2) production and thus provide an excellent in vivo model in which to assess the effects of increased ROS generation on vascular smooth muscle cell (VSMC) function. We tested the hypothesis that overexpression of VSMC p22(phox) potentiates angiotensin II (ANG II)-induced vascular hypertrophy. Male Tg(p22smc) mice and negative littermate controls were infused with either ANG II or saline for 13 days. Baseline blood pressure was not different between control and Tg(p22smc) mice. ANG II significantly increased blood pressure in both groups, with this increase being slightly exacerbated in the Tg(p22smc) mice. Baseline aortic wall thickness and cross-sectional wall area were not different between control and Tg(p22smc) mice. Importantly, the ANG II-induced increase in both parameters was significantly greater in the Tg(p22smc) mice compared with control mice. To confirm that this potentiation of vascular hypertrophy was due to increased ROS levels, additional groups of mice were coinfused with ebselen. This treatment prevented the exacerbation of hypertrophy in Tg(p22smc) mice receiving ANG II. These data suggest that although increased availability of NAD(P)H oxidase-derived ROS is not a sufficient stimulus for hypertrophy, it does potentiate ANG II-induced vascular hypertrophy, making ROS an excellent target for intervention aimed at reducing medial thickening in vivo.