Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection

Purpose

To evaluate whether ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced magnetic resonance imaging (MRI) can detect allograft rejection in pediatric kidney transplant patients.

Procedures

The USPIO ferumoxytol has a long blood half-life and is phagocytosed by macrophages. In an IRB-approved single-center prospective clinical trial, 26 pediatric patients and adolescents (age 10–26 years) with acute allograft rejection (n = 5), non-rejecting allografts (n = 13), and normal native kidneys (n = 8) underwent multi-echo T2* fast spoiled gradient-echo (FSPGR) MRI after intravenous injection (p.i.) of 5 mg Fe/kg ferumoxytol. T2* relaxation times at 4 h p.i. (perfusion phase) and more than 20 h p.i. (macrophage phase) were compared with biopsy results. The presence of rejection was assessed using the Banff criteria, and the prevalence of macrophages on CD163 immunostains was determined based on a semi-quantitative scoring system. MRI and histology data were compared among patient groups using t tests, analysis of variance, and regression analyses with a significance threshold of p < 0.05.

Results

At 4 h p.i., mean T2* values were 6.6 ± 1.5 ms for native kidneys and 3.9 ms for one allograft undergoing acute immune rejection. Surprisingly, at 20–24 h p.i., one rejecting allograft showed significantly prolonged T2* relaxation times (37.0 ms) compared to native kidneys (6.3 ± 1.7 ms) and non-rejecting allografts (7.6 ± 0.1 ms). Likewise, three additional rejecting allografts showed significantly prolonged T2* relaxation times compared to non-rejecting allografts at later post-contrast time points, 25–97 h p.i. (p = 0.008). Histological analysis revealed edema and compressed microvessels in biopsies of rejecting allografts. Allografts with and without rejection showed insignificant differences in macrophage content on histopathology (p = 0.44).

Conclusion

After ferumoxytol administration, renal allografts undergoing acute rejection show prolonged T2* values compared to non-rejecting allografts. Since histology revealed no significant differences in macrophage content, the increasing T2* value is likely due to the combined effect of reduced perfusion and increased edema in rejecting allografts.

     

Ventricular Assist Devices: The Basics

As the cases of heart failure continue to rise, more ventricular assist devices are likely to be implanted. Providers in a variety of care environments are more likely to see patients with ventricular assist devices because they are living longer; therefore, it is necessary for providers to understand the unique care and complications related to these devices, such as thrombosis, stroke, bleeding, right-sided heart failure, ventricular dysrhythmias, and infection. The current literature regarding the complications and management of patients with these devices was reviewed and summarized, with a focus on HeartWare (HeartWare International Inc, Framingham, MA) and HeartMate II (Thoratec Corp, Pleasanton, CA).     

‘The team for both sides?’ A qualitative study of change in heart failure services at three acute NHS Trusts

Heart failure (HF) is an increasingly prevalent long‐term condition that affects around 900,000 people in the United Kingdom (National Institute for Health and Clinical Excellence). The study examined how HF services in the English National Health Service (NHS) were changing, focusing particularly on the primary/secondary care interface. The maintenance of continuity in care in the face of increasing demand and financial pressures on health and social care was a key concern. Semi‐structured interviews were conducted with 22 members of staff working in HF services in three NHS acute Trusts in the West Midlands of England. Interviews were conducted between April and December 2011 with purposively selected participants and data were analysed using the Framework Method. Four main themes emerged from the analysis: service context, capacity, the primary/secondary interface and communication across boundaries. Barriers to, and facilitators of, continuity of care for patients with HF were identified within these themes. The findings provide insights into the structure, management and work of HF services in the acute and community settings. They highlight how local systems for the management of HF patients are developing in ways which are not necessarily consistent with national policy.     

Racial/Ethnic Disparities in Cumulative Environmental Health Impacts in California: Evidence From a Statewide Environmental Justice Screening Tool (CalEnviroScreen 1.1)

Objectives. We used an environmental justice screening tool (CalEnviroScreen 1.1) to compare the distribution of environmental hazards and vulnerable populations across California communities.Methods. CalEnviroScreen 1.1 combines 17 indicators created from 2004 to 2013 publicly available data into a relative cumulative impact score. We compared cumulative impact scores across California zip codes on the basis of their location, urban or rural character, and racial/ethnic makeup. We used a concentration index to evaluate which indicators were most unequally distributed with respect to race/ethnicity and poverty.Results. The unadjusted odds of living in one of the 10% most affected zip codes were 6.2, 5.8, 1.9, 1.8, and 1.6 times greater for Hispanics, African Americans, Native Americans, Asian/Pacific Islanders, and other or multiracial individuals, respectively, than for non-Hispanic Whites. Environmental hazards were more regressively distributed with respect to race/ethnicity than poverty, with pesticide use and toxic chemical releases being the most unequal.Conclusions. Environmental health hazards disproportionately burden communities of color in California. Efforts to reduce disparities in pollution burden can use simple screening tools to prioritize areas for action.Communities of color in the United States often reside in neighborhoods with worse air quality,1 more environmental hazards,2 and fewer health-promoting environmental amenities such as parks.3 This unequal distribution of exposures may contribute to racial/ethnic health disparities in environmentally sensitive diseases such as cancer and asthma.4 Research has shown that communities of color in California experience higher cancer risk from toxic air contaminants5 and higher average levels of nitrate contamination in their drinking water6 and that they live closer to hazardous waste sites7 and traffic.8 However, less is known about the extent to which communities of color are simultaneously exposed to multiple potential sources of pollution and the implications of such coexposures for health.There is, thus, an increasing need for analytic frameworks and decision-making tools that account for exposures to multiple environmental hazards through a variety of routes. Such frameworks should also consider differential vulnerability to the health effects of those exposures, which can vary across the population because of both individual and community-level factors.9–11 For example, age and health status, including suffering from preexisting cardiovascular disease or asthma, have been shown to increase susceptibility to the adverse health effects of air pollution.12–14Several studies suggest that an individual’s educational attainment modifies the health effects of air pollution: greater effects are observed among the less educated.15,16 Poverty can hinder access to adequate nutrition and medical care to prevent and manage the health impacts of pollution. At the community level, the concentration of poverty in disadvantaged neighborhoods can lead to conditions that increase levels of chronic psychosocial stress that weaken the body’s ability to defend against external challenges.17 A cumulative impact approach that considers differential vulnerability and environmental stressors is particularly important for assessing racial/ethnic environmental health disparities because communities of color in the United States experience lower average levels of education18 and wealth19 and, for some groups, higher rates of chronic health conditions20 that increase susceptibility to environmental health hazards.Although the field is still in its infancy, several proposed methods are used to better reflect the cumulative impacts of environmental exposures and population vulnerabilities and provide assessments that can support the incorporation of equity and environmental justice goals into policymaking.21–24 The California Environmental Protection Agency first released such a method—the California Communities Environmental Health Screening Tool, or CalEnviroScreen—in April 2013, and an updated version, CalEnviroScreen 1.1, was published in September 2013.25 CalEnviroScreen is a screening tool that considers both pollution burden and population vulnerability in assessing the potential for cumulative impacts across California zip codes. It was developed following consultation with government, academic, business, and nongovernmental organizations and 12 public workshops in 7 regions of the state that resulted in more than 1000 oral and written comments on 2 preliminary drafts.26 The tool employs a model that can be adapted to different applications and as new information becomes available. For example, subsequent iterations have been developed using a finer geographic resolution and the addition of new indicators.27 It purposefully relies on publicly available data sets for transparency and relatively simple methods so that it can be understood by a general audience.We used CalEnviroScreen 1.1 to assess the extent of geographic and racial/ethnic disparities in the potential for cumulative environmental health impacts from multiple environmental hazards in California. We employed a concentration index to examine which environmental hazards are most inequitably distributed, and we considered variations to CalEnviroScreen to evaluate the sensitivity of our findings to the structure of the model.     

Hispanic Men in the United States: Acculturation and Recent Sexual Behaviors With Female Partners, 2006–2010

Objectives. We examined Hispanic men’s recent risky and protective sexual behaviors with female partners by acculturation.Methods. Using the 2006–2010 National Survey of Family Growth, we performed bivariate analyses to compare acculturation groups (Hispanic Spanish-speaking immigrants, Hispanic English-speaking immigrants, Hispanic US natives, and non-Hispanic White men) by demographics and recent sexual behaviors with women. Multivariable logistic regression models for sexual behaviors by acculturation group were adjusted for demographics.Results. Compared with Hispanic Spanish-speaking immigrants, non-Hispanic White men were less likely to report exchange of money or drugs for sex (adjusted odds ratio [AOR] = 0.3; 95% confidence interval [CI] = 0.1, 0.9), but were also less likely to report condom use at last vaginal (AOR = 0.6; 95% CI = 0.4, 0.8) and anal sex (AOR = 0.4; 95% CI = 0.3, 0.7). Hispanic US natives were less likely to report condom use at last vaginal sex than were Spanish-speaking immigrants (AOR = 0.6; 95% CI = 0.4, 0.8). English- and Spanish-speaking immigrants did not differ in risky or protective sexual behaviors.Conclusions. Our findings suggest that targeted interventions focusing on unique sexual risks and sociodemographic differences by acculturation level, particularly nativity, may be helpful for preventing sexually transmitted infections.In the United States, Hispanics are one of the subpopulations disproportionately affected by sexually transmitted infections (STIs).1 In 2010, reported cases of chlamydia were 2.7 times higher for Hispanics than for non-Hispanic Whites.1 Similarly, primary and secondary syphilis cases were 2.2 times higher for Hispanics than for non-Hispanic Whites, an increase of 9.5% since 2009.1 Reported gonorrhea rates were also 2.2 times higher for Hispanics than for non-Hispanic Whites. Regarding gender, the racial/ethnic disparity in gonorrhea rates was higher for men (48.7 per 100 000 for Hispanics vs 19.5 per 100 000 for non-Hispanic Whites) than for women (51.1 per 100 000 for Hispanics vs 26.6 per 100 000 for non-Hispanic Whites).1 Among young adult men (18–26 years), STI disparities were even greater; among Hispanic men, the prevalence of chlamydia and gonorrhea was 5.3 and 4.1 times higher than for non-Hispanic White men, respectively.2Research has shown that Hispanics face many unique challenges that increase their risks for STIs, including immigration-related challenges, living apart from their spouse or regular partner, language barriers, racism, social isolation, and limited access to health care.1,3–5 Compared with non-Hispanic Whites, Hispanics often also have higher poverty, unemployment, and high school dropout rates, and are younger.1,4,6 From 2000 to 2010, the Hispanic population in the United States increased by more than 15.2 million (an increase of 43%), contributing to half of the total population growth in the country.7 Because of the growing Hispanic population, the disproportionate burden of STIs, and the numerous barriers and challenges increasing their risk for STIs, an assessment of the sexual behaviors of Hispanics, including risk and protective behaviors, are of public health importance.An epidemiological concept known as the Hispanic paradox posits that health outcomes for Hispanics tend to be more similar to those of non-Hispanic Whites than those of non-Hispanic Blacks because of less acculturation, or “Americanization,” among Hispanics, which has been shown to be associated with lower sexual risk behaviors and better health outcomes.8–10 Some research suggests that the Hispanic paradox is variable and fluid or may not exist at all.11,12 Although many studies have examined the relationship between acculturation and sexual risk behaviors that are related to STI transmission, most of this research has focused on Hispanic women, adolescents, or men who have sex with men.13–22 Fewer studies have examined differences among Hispanic men in their sexual behaviors with female partners in terms of acculturation group. One study found that low-income, recent-immigrant Hispanic men (living in the United States less than 5 years) were more likely to commercially exchange sexual services and less likely to have a main sex partner than established immigrants (living in the United States for more than 5 years).23 Conversely, established Hispanic immigrant men were more likely to report unprotected sexual intercourse and multiple sex partners than recent immigrants.23 For protective behaviors, condom use at last sex did not significantly differ by acculturation among Hispanic men, although condom use is positively associated with acculturation for women.18,24,25 All of these studies were restricted to specific local areas.Acculturation of Hispanics has been measured in many ways—the use of a single variable, a combination of variables, or scales developed to capture the various aspects of acculturation. Complex measures of acculturation include attitudinal and behavioral factors focused on cultural values.10 More intricate scales of acculturation include heritage and mainstream scales with measures of attitude, behavior, and social relations.10,26 However, it is difficult to include comprehensive measures of acculturation in national surveys that have limited space and competing interests. Measures such as language, country of origin, nativity, and length of time in the country are considered proxy measures of acculturation.11,13,19,27–29 The most frequently used variable to measure acculturation is language of interview (English or Spanish) or the language spoken at home.3,13,14,17,19,21,22,24,27–33 Although acculturation is a multifaceted concept, research suggests that language preference may be a reliable proxy for more complex acculturation measures of Hispanics living in the United States.17For an examination of differences in Hispanic men’s sexual behaviors with female partners by level of acculturation, a national-level examination is useful given the diversity of the Hispanic population in the United States, where origin (Mexican, Puerto Rican, Cuban, Central American, etc.) differs by geography.34 Using data from a national survey, we analyzed the recent sexual behaviors of acculturation groups of Hispanic men (categorized by language of interview and nativity) and compared them with those of non-Hispanic White men. Specifically, we sought to examine differences in recent risky and protective sexual behaviors with female partners among acculturation groups using the 2006–2010 National Survey of Family Growth (NSFG).     

Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment,Learning, and Social Behavior

Background

In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today.

Objectives

The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model.

Methods

We administered vaccines to six groups of infant male rhesus macaques (n = 12–16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate.

Results

We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors.

Conclusions

This comprehensive 5-year case–control study, which closely examined the effects of pediatric vaccines on early primate development, provided no consistent evidence of neurodevelopmental deficits or aberrant behavior in vaccinated animals.

Citation

Curtis B, Liberato N, Rulien M, Morrisroe K, Kenney C, Yutuc V, Ferrier C, Marti CN, Mandell D, Burbacher TM, Sackett GP, Hewitson L. 2015. Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior. Environ Health Perspect 123:579–589; http://dx.doi.org/10.1289/ehp.1408257     

The effect of physician gender on length of patient consultations: observational findings from the UK hospital setting and synthesis with existing studies

Objectives

To investigate the effect of physician gender on consultation length in UK hospital outpatient clinics and compare this, through meta-analysis, with previous studies outside the UK.

Design

Observational data on clinic times were analysed and findings were combined in a meta-analysis with existing studies investigating the effect of physician gender on consultation length.

Setting

UK hospital practice.

Participants

A total of 174 observations of outpatient consultations with 10 hospital specialists (consultants) from different specialties in two UK hospital trusts.

Main outcome measures

Clinic times were recorded and analysis of consultation length was undertaken with physician gender as a covariate. Data were then synthesised through meta-analysis with 10 existing studies in this field.

Results

No statistically significant difference was found in the length of consultations for male and female doctors in these UK hospital settings. When pooled with existing studies, consultations with women doctors were found to be approximately two minutes longer than with men (p = 0.01).

Conclusions

Findings from this analysis of clinic consultations in the UK National Health Service do not support previous studies, which were undertaken predominantly in North America and primary care settings. Overall, meta-analysis suggests doctors’ gender may influence consultation length. Gender differences in communication should be considered in training clinicians and in overall clinical practice.