Association of Race and Ethnicity With High Longevity Deceased Donor Kidney Transplantation Under the US Kidney Allocation System.

RATIONALE & OBJECTIVE: The US Kidney Allocation System (KAS) prioritizes candidates with a≤20% estimated posttransplant survival (EPTS) to receive high-longevity kidneys defined by a≤20% Kidney Donor Profile Index (KDPI). Use of EPTS in the KAS deprioritizes candidates with older age, diabetes, and longer dialysis durations. We assessed whether this use also disadvantages race and ethnicity minority candidates, who are younger but more likely to have diabetes and longer durations of kidney failure requiring dialysis. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Adult candidates for and recipients of kidney transplantation represented in the Scientific Registry of Transplant Recipients from January 2015 through December 2020. EXPOSURE: Race and ethnicity. OUTCOME: Age-adjusted assignment to≤20% EPTS, transplantation of a≤20% KDPI kidney, and posttransplant survival in longevity-matched recipients by race and ethnicity. ANALYTIC APPROACH: Multivariable logistic regression, Fine-Gray competing risks survival analysis, and Kaplan-Meier and Cox proportional hazards methods. RESULTS: The cohort included 199,444 candidates (7% Asian, 29% Black, 19% Hispanic or Latino, and 43% White) listed for deceased donor kidney transplantation. Non-White candidates had significantly higher rates of diabetes, longer dialysis duration, and were younger than White candidates. Adjusted for age, Asian, Black, and Hispanic or Latino candidates had significantly lower odds of having a ETPS score of≤20% (odds ratio, 0.86 [95% CI, 0.81-0.91], 0.52 [95% CI, 0.50-0.54], and 0.49 [95% CI, 0.47-0.51]), and were less likely to receive a≤20% KDPI kidney (sub-hazard ratio, 0.70 [0.66-0.75], 0.89 [0.87-0.92], and 0.73 [0.71-0.76]) compared with White candidates. Among recipients with≤20% EPTS scores transplanted with a≤20% KDPI deceased donor kidney, Asian and Hispanic recipients had lower posttransplant mortality (HR, 0.45 [0.27-0.77] and 0.63 [0.47-0.86], respectively) and Black recipients had higher but not statistically significant posttransplant mortality (HR, 1.22 [0.99-1.52]) compared with White recipients. LIMITATIONS: Provider reported race and ethnicity data and 5-year post transplant follow-up period. CONCLUSIONS: The US kidney allocation system is less likely to identify race and ethnicity minority candidates as having a≤20% EPTS score, which triggers allocation of high-longevity deceased donor kidneys. These findings should inform the Organ Procurement and Transplant Network about how to remedy the race and ethnicity disparities introduced through KAS's current approach of allocating allografts with longer predicted longevity to recipients with longer estimated posttransplant survival. PLAIN-LANGUAGE SUMMARY: The US Kidney Allocation System prioritizes giving high-longevity, high-quality kidneys to patients on the waiting list who have a high estimated posttransplant survival (EPTS) score. EPTS is calculated based on the patient's age, whether the patient has diabetes, whether the patient has a history of organ transplantation, and the number of years spent on dialysis. Our analyses show that Asian, Black or African American, and Hispanic or Latino patients were less likely to receive high-longevity kidneys compared with White patients, despite having similar or better posttransplant survival outcomes.

Pharmacokinetics and Egg Residues of Meloxicam After Multiple Day Oral Dosing in Domestic Chickens.

With increased ownership of backyard poultry, veterinarians must treat these birds appropriately and take into consideration drug withdrawal times for eggs meant for consumption. Few studies have examined the pharmacokinetics or egg residues for medications commonly used in avian medicine. This study determined the pharmacokinetics of meloxicam in domestic chickens (n = 8) after oral dosing at 1 mg/kg q12h for a total of 9 doses (5 days). Additionally, the presence of meloxicam residues in eggs was determined. The terminal half-life, maximum concentration, and time to maximum concentration were 3.02 ± 1.15 hours, 7.14 ± 1.54 µg/mL, and 1.6 ± 0.52 hours, respectively. No drug was detected in yolks and whites after 8 days and 3 days, respectively. On the basis of these results, a 2-week withdrawal time should be adequate to avoid drug residues in eggs meant for consumption.

Patient engagement in clinical trial design for rare neuromuscular disorders: impact on the DELIVER and ACHIEVE clinical trials.

BACKGROUND: Engaging individuals living with disease in drug development and regulatory processes leads to more thoughtful and sensitive trial designs, drives more informative and meaningful outcomes from clinical studies, and builds trust between the public, government, and industry stakeholders. This engagement is especially important in the case of rare diseases, where affected individuals and their families face many difficulties getting information, treatment, and support. Dyne Therapeutics is developing therapeutics for people with genetically-driven muscle diseases. During the development of potential treatments for Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1), Dyne sought the opinions of individuals living with these diseases to inform its clinical trial design and to decrease the difficulties that participants and families might experience participating in them. METHODS: Dyne engaged individuals and families living with DMD and DM1 as expert partners in its clinical development programs. Dyne convened panels of affected individuals and care partners/parents of individuals living with DMD (n = 8) or DM1 (n = 18). Workshops focused on how affected individuals and their families evaluate and select clinical trials for participation, the importance, quality, and burden associated with individual trial design elements, participation considerations such as site location and the study visit design, patient privacy, the suitability and scope of travel and participant support programs, and the accessibility of content in the informed consent (or assent) forms. Dyne also engaged the DMD Community Advisory Board (CAB) to collect feedback and advice on designing optimal and meaningful clinical trials and measuring relevant outcomes. RESULTS: The issues most important to individuals living with DM1 and DMD regarding clinical trials were the ability to participate/access to the trial, perceptions of benefit and risk of trials and potential treatments, the flexibility of participation, clear communication from the sponsor, availability of information from trusted sources, and patient enrollment. In response to the patient advisory workshops and CAB feedback, Dyne refined clinical trial inclusion/exclusion criteria and clinic visit design, developed a travel service program to address the burden of clinical trial travel and enable long-distance and cross-border participation, planned for home visits when feasible, and allowed for adequate rest before clinic visit initiation and between assessments. Additionally, Dyne developed and implemented a transparent and consistent communications plan (including age-appropriate content) for trial participants and community members, and assessed and adjusted procedures to provide maximum participant comfort and lower anxiety, particularly with younger participants. CONCLUSIONS: Ongoing communication with the Duchenne CAB and with DMD and DM1 patient advisory committee members allows Dyne to stay current with disease community perspectives and feedback on the needs and preferences of those affected and has provided valuable insights into the participant experience thereby helping Dyne initiate clinical trials that better meet the needs of affected individuals and their families.

WHY IS THIS IMPORTANT?: Including the viewpoint of people living with chronic diseases when developing new therapeutics helps address their specific needs and improve their quality of life. This is very important for rare diseases, where individuals and their families face many challenges getting information, treatment, and support. WHAT DID WE DO?: Dyne Therapeutics, a company focused on developing potential medicines for rare muscle diseases, actively involved individuals living with Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1) in their drug development process. Dyne organized workshops for individuals and families living with DMD and DM1 and participated in community advisory boards to gather input from patient advocacy organization leaders. HOW DID THIS HELP?: Partnering with individuals and families living with DMD and DM1 helped Dyne improve clinical trial design and reduce the difficulties affected individuals and their families face when participating in these trials. This valuable feedback has allowed Dyne to design clinical trials to better address the needs of those living with DMD and DM1.

Graft Survival of En Bloc Deceased Donor Kidneys Transplants Compared With Single Kidney Transplants.

BACKGROUND: The US Kidney Allocation System allocates en bloc deceased donor kidney grafts from donors <18 kg in sequence A along with single kidney transplants (SKTs) from kidney donor profile index (KDPI) top 20% donors. Although en bloc grafts outperform SKT grafts holding donor weight constant, it is unclear if en bloc grafts from the smallest pediatric donors perform the same as top 20% KDPI SKTs. METHODS: Using the Scientific Registry of Transplant Recipients, we compared the donor characteristics and graft survival of en bloc grafts from the smallest donors (<8 kg) and from larger donors (≥8 kg) with SKTs by KDPI sequence for transplants performed in 2021. RESULTS: Larger donor en blocs had similar 1-y survival to sequence A SKTs estimated by the Kaplan-Meier method (96% versus 96%, P = 0.9), but the smallest donor en blocs had significantly shorter 1-y survival than those SKTs (80% versus 96%, P < 0.01). Using transplants from 2010 to 2012, the smallest donor en blocs had similar 10-y survival to sequence A SKTs (69% versus 64%, P = 0.3). CONCLUSIONS: These findings suggest that future updates of the Kidney Allocation System should include a score specific to pediatric donors to account for these differences in en bloc graft survival.

Association Between Restricted Abortion Access and Child Entries Into the Foster Care System.

Importance: The 2022 US Supreme Court decision Dobbs v Jackson Women's Health Organization overturned federal protections to abortion care, allowing many states to severely restrict or ban access to abortion. Given the implications of the Dobbs ruling, there is a need to understand the full consequences of restricted abortion access. Before 2022, many states restricted access to safe and legal abortions through Targeted Regulation of Abortion Providers (TRAP) laws, which provide a historical mode for estimating the consequences of abortion restrictions. Objective: To use TRAP law enactment as a natural experiment to quantify the association between restricted abortion access and foster care entries. Design, Setting, and Participants: In this cohort study, data on the enactment of TRAP laws and case-level data on foster care entries were used to estimate the association between restricted abortion access and foster care entries in each of the 50 US states and the District of Columbia. The sample included children conceived between January 1, 1990, and December 31, 2011, who were placed into foster care at any point between January 1, 2000, and December 31, 2020. Data analysis was performed from January 2023 to July 2023. Exposures: Restricted abortion access due to state-level TRAP laws during pregnancy. Main Outcomes and Measures: The main outcome was the number of children entering foster care in each state, measured by year of child conception. The analysis was performed using a generalized difference-in-differences design, comparing entries into foster care in states with TRAP laws to states without TRAP laws, before and after their implementation. Results: This study included 4 179 701 children who were placed into foster care during the study period, with 11 016 561 entries. More than half of the children were male (51.4%), and the mean (SD) age was 7.4 (5.2) years. There was an 11% increase in foster care placement after abortion access was restricted in states with TRAP laws, relative to states without TRAP laws (incidence rate ratio [IRR], 1.11 [95% CI, 1.01-1.23]). These laws had significant consequences for Black children (IRR, 1.15 [95% CI, 1.05-1.28]) and racial and ethnic minority children (IRR, 1.15 [95% CI, 1.02-1.30]). The increase in entries due to TRAP laws was particularly attributable to housing inadequacy (IRR, 1.21 [95% CI, 1.11-1.32]). Conclusions and Relevance: Restricted abortion access can have numerous consequences, and these findings reveal a heightened strain on the US foster care system, particularly affecting marginalized racial and ethnic communities and financially vulnerable families. These placements have been shown to have lifelong consequences for children and substantial costs for both states and the federal government. To further examine the widespread implications of the overturning of Roe v Wade, future studies should forecast the expected increase in foster care entries and estimate the expenditure needed to support these children.

Community needs, concerns, and perceptions about health research: findings from the clinical and translational science award sentinel network.

OBJECTIVES: We used results generated from the first study of the National Institutes of Health Sentinel Network to understand health concerns and perceptions of research among underrepresented groups such as women, the elderly, racial/ethnic groups, and rural populations. METHODS: Investigators at 5 Sentinel Network sites and 2 community-focused national organizations developed a common assessment tool used by community health workers to assess research perceptions, health concerns, and conditions. RESULTS: Among 5979 individuals assessed, the top 5 health concerns were hypertension, diabetes, cancer, weight, and heart problems; hypertension was the most common self-reported condition. Levels of interest in research participation ranged from 70.1% among those in the "other" racial/ethnic category to 91.0% among African Americans. Overall, African Americans were more likely than members of other racial/ethnic groups to be interested in studies requiring blood samples (82.6%), genetic samples (76.9%), or medical records (77.2%); staying overnight in a hospital (70.5%); and use of medical equipment (75.4%). CONCLUSIONS: Top health concerns were consistent across geographic areas. African Americans reported more willingness to participate in research even if it required blood samples or genetic testing.

Cellular Uptake of Gold Nanorods in Breast Cancer Cell Lines.

Nanosized materials have been proposed for a wide range of biomedical applications, given their unique characteristics. However, how these nanomaterials interact with cells and tissues, as well as how they bio-distribute in organisms, is still under investigation. Differences such as the nanoparticle size, shape, and surface chemistry affect the basic mechanisms of cellular uptake and responses, which, in turn, affects the nanoparticles' applicability for biomedical applications. Thus, it is vital to determine how a specific nanoparticle interacts with cells of interest before extensive in vivo applications are performed. Here, we delineate the uptake mechanism and localization of gold nanorods in SKBR-3 and MCF-7 breast cancer cell lines. Our results show both differences and similarities in the nanorod-cell interactions of the two cell lines. We accurately quantified the cellular uptake of gold nanorods in SKBR-3 and MCF-7 using inductively coupled plasma mass spectrometry (ICP-MS). We found that both cell types use macropinocytosis to internalize bare nanorods that aggregate and associate with the cell membrane. In addition, we were able to qualitatively track and show intracellular nanoparticle localization using transmission electron microscopy. The results of this study will be invaluable for the successful development of novel and "smart" nanodrugs based on gold nano-structural delivery vehicles, which heavily depend on their complex interactions with single cells.

The Impact of Nonpharmacological Interventions on Patient Experience, Opioid Use, and Health Care Utilization in Adult Cardiac Surgery Patients: Protocol for a Mixed Methods Study.

BACKGROUND: Despite pharmacological treatments, patients undergoing cardiac surgery experience severe anxiety and pain, which adversely affect outcomes. Previous work examining pediatric and nonsurgical adult patients has documented the effectiveness of inexpensive, nonpharmacological techniques to reduce anxiety and pain as well as health care costs and length of hospitalization. However, the impact of nonpharmacological interventions administered by a dedicated comfort coach has not been evaluated in an adult surgical setting. OBJECTIVE: This trial aims to assess whether nonpharmacological interventions administered by a trained comfort coach affect patient experience, opioid use, and health care utilization compared with usual care in adult cardiac surgery patients. This study has 3 specific aims: assess the effect of a comfort coach on patient experience, measure differences in inpatient and outpatient opioid use and postoperative health care utilization, and qualitatively evaluate the comfort coach intervention. METHODS: To address these aims, we will perform a prospective, randomized controlled trial of 154 adult cardiac surgery patients at Michigan Medicine. Opioid-naive patients undergoing first-time, elective cardiac surgery via sternotomy will be randomized to undergo targeted interventions from a comfort coach (intervention) versus usual care (control). The individualized comfort coach interventions will be administered at 6 points: preoperative outpatient clinic, preoperative care unit on the day of surgery, extubation, chest tube removal, hospital discharge, and 30-day clinic follow-up. To address aim 1, we will examine the effect of a comfort coach on perioperative anxiety, self-reported pain, functional status, and patient satisfaction through validated surveys administered at preoperative outpatient clinic, discharge, 30-day follow-up, and 90-day follow-up. For aim 2, we will record inpatient opioid use and collect postdischarge opioid use and pain-related outcomes through an 11-item questionnaire administered at the 30-day follow-up. Hospital length of stay, readmission, number of days in an extended care facility, emergency room, urgent care, and an unplanned doctor's office visit will be recorded as the primary composite endpoint defined as total days spent at home within the first 30 days after surgery. For aim 3, we will perform semistructured interviews with patients in the intervention arm to understand the comfort coach intervention through a thematic analysis. RESULTS: This trial, funded by Blue Cross Blue Shield of Michigan Foundation in 2019, is presently enrolling patients with anticipated manuscript submissions from our primary aims targeted for the end of 2020. CONCLUSIONS: Data generated from this mixed methods study will highlight effective nonpharmacological techniques and support a multidisciplinary approach to perioperative care during the adult cardiac surgery patient experience. This study's findings may serve as the foundation for a subsequent multicenter trial and broader dissemination of these techniques to other types of surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04051021; https://clinicaltrials.gov/ct2/show/NCT04051021. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21350.

Mixed S-nitrosylated polymerized bovine hemoglobin species moderate hemodynamic effects in acutely hypoxic rats.

Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being developed as a potential therapy for increasing tissue oxygenation, yet they have not reached their full potential because of unwanted hemodynamic side effects (vasoconstriction, low cardiac output, and oxygen delivery) due in part to nitric oxide (NO) scavenging by cell-free Hb. It may be possible to overcome the NO scavenging effect by coinfusing S-nitrosylated (SNO) HBOC along with unmodified HBOC. SNO-HBOC, like free Hb, may act as an NO donor in low-oxygen conditions. We hypothesized that an unaltered HBOC, polymerized bovine Hb (PBvHb), coinfused with an SNO-PBvHb, would improve hemodynamics and oxygen delivery during hypoxia. Vascular oxygen content and hemodynamics were determined after euvolemic rats were infused (3 ml) with lactated Ringer's solution, PBvHb, SNO-PBvHb, or PBvHb plus SNO-PBvHb (1:10) during normoxia or acute hypoxia (fraction of inspired oxygen = 10%, 120 min). Hemodynamic side effects resulting from PBvHb infusion (vasoconstriction, elevated pulmonary blood pressure, and reduced cardiac output) were offset by SNO-PBvHb in acute hypoxic, but not normoxic, conditions. These data support the potential use of HBOC mixed with SNO-HBOC for the treatment of conditions in which acute hypoxia is present, such as tumor oxygenation, wound healing, hemorrhagic trauma, and sickle cell and hemolytic anemia.

Patient Input to Inform the Development of Central Nervous System Outcome Measures in Myotonic Dystrophy.

Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystem, genetic disorders caused by repeat expansions on chromosome 19 (DM1) and chromosome 3 (DM2). Although the effects of DM on the skeletal, cardiac, and smooth muscles, as well as the endocrine and central nervous systems, can be disabling, there are no disease-modifying therapies for the disorder. Following a process established by the US Food and Drug Administration (FDA) in 2012 known as the Patient-Focused Drug Development (PFDD) Initiative, Myotonic (formerly the Myotonic Dystrophy Foundation) has been conducting patient- and caregiver-inclusive sessions to explore disease burden as defined by patients and caregivers, and what affected individuals want most from potential new therapies. In September 2017, at Myotonic's annual conference, a session titled "Bringing the Patient Voice to CNS-Targeting Drug Development in Myotonic Dystrophy" attracted some 350 members of the DM community. During the session, patients and caregivers described CNS disease symptoms, their impact on quality of life, and potential CNS-related targets that they considered important for drug development consideration. These included fatigue and daytime sleepiness; dysregulated sleep; cognitive deficits such as "brain fog," memory and focus impairment, learning and attention difficulties, and time management challenges; emotional/psychological/behavioral difficulties, including impulsivity, apathy, antisocial behavior, personality changes, and depression; social difficulties, including disconnection, lack of awareness, and feelings of isolation; and general anxieties about the future and potential loss of independence. Improvements in memory and lessening of "brain fog" were considered particularly important.

Learnings from Patient-Report Workshop on Disease Progression in Myotonic Dystrophy.

For researchers, pharmaceutical companies, and regulatory agencies involved in the development of treatments that slow or stop disease progression, the highly variable and unpredictable progression of symptoms in myotonic dystrophy (DM) makes it difficult to assess whether an intervention provides clinically-meaningful benefit on disease progression for patients. In evaluating the effectiveness of treatments, drug developers and regulators need to understand what triggers progression, since the presence or absence of triggers may influence symptoms in ways that could complicate the assessment of progression. To better understand disease burden and what people living with DM view as meaningful benefits, Myotonic (formerly Myotonic Dystrophy Foundation) convened a meeting based on the US Food and Drug Administration's Patient-focused Drug Development initiative, at the Myotonic Annual Conference in September 2018. Over 300 people living with DM met to share with regulators and drug developers how disease progression has affected their lives and what they would consider to be the most beneficial treatment effects of progression-targeting therapies. A panel of five adults with DM (three with DM1 and two with DM2) was asked to describe when disease symptoms took a turn for the worse, what seemed to trigger disease progression, what treatment approaches have proven useful, and what characteristics panel participants most desire in a new treatment. Audience members were then invited to share their experiences. Specific triggers of progression vary from person to person, even within a single family. Among the triggers most frequently cited by meeting participants were physical and emotional stress, lack of sleep, illness, injury, surgery, pregnancy, overdoing it, and lack of activity. Illness in general was said to trigger symptoms. Slowing or stopping disease progression is viewed by people with DM as the most important objective of therapy.

Trends in Medicare Part B Spending on Discarded Drugs, 2017-2020.

This cross-sectional study quantifies trends in discarded drug spending since the onset of mandated reporting.

Determination of Meloxicam in Egg Whites and Yolks Using Reverse Phase Chromatography.

A new method of analysis has been developed and validated for the determination of meloxicam in egg whites and yolks. Following a liquid extraction for the whites and a solid phase extraction for the yolks, samples were separated on an XBridge C18 column and quantified using ultraviolet detection at 360 nm. The mobile phase was a mixture of water with glacial acetic acid and acetonitrile, with a flow rate of 1 mL/min. The procedure produced a linear graph over the concentration range 5-1500 ng/mL with a lower limit of quantification of 5 ng/mL. Intra- and inter-assay variability was 10% or less for both the whites and yolks. The average recovery for whites was 96% and the average recovery in yolks was 97%.

Pharmacokinetics and egg residues after oral administration of a single dose of meloxicam in domestic chickens (Gallus domesticus).

OBJECTIVE To determine the pharmacokinetics of meloxicam in domestic hens and duration and quantity of drug residues in their eggs following PO administration of a single dose (1 mg of meloxicam/kg). ANIMALS 8 healthy adult White Leghorn hens. PROCEDURES Hens were administered 1 mg of meloxicam/kg PO once. A blood sample was collected immediately before and at intervals up to 48 hours after drug administration. The hens' eggs were collected for 3 weeks after drug administration. Samples of the hens' plasma, egg whites (albumen), and egg yolks were analyzed by high-performance liquid chromatography. RESULTS The half-life, maximum concentration, and time to maximum concentration of meloxicam in plasma samples were 2.8 hours, 7.21 µg/mL, and 2 hours, respectively. Following meloxicam administration, the drug was not detected after 4 days in egg whites and after 8 days in egg yolks. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that meloxicam administered at a dose of 1 mg/kg PO in chickens appears to maintain plasma concentrations equivalent to those reported to be therapeutic for humans for 12 hours. The egg residue data may be used to aid establishment of appropriate drug withdrawal time recommendations.

Patient-Centered Therapy Development for Myotonic Dystrophy: Report of the Myotonic Dystrophy Foundation-Sponsored Workshop.

Myotonic dystrophy (DM) is an autosomal dominant, repeat expansion, progressive disorder with no drug therapies. Consequently, to better define a regulatory pathway in anticipation of new treatment strategies under investigation, the Myotonic Dystrophy Foundation convened a workshop entitled "Patient-Centered Therapy Development for Myotonic Dystrophy" in September 2015. Participants included representatives from academia, industry, the patient community, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). Presenters described the symptom burden of the disease, and existing data on DM biomarkers, endpoints, natural history, and benefit-risk considerations. FDA participants helped clarify the regulatory requirements for new drug treatment approvals and DM-specific issues such as variability, slow progression, and low prevalence. Workshop attendees gained a better understanding of DM and the current status of existing data and tools to support therapeutic drug research and development.

Genes associated with antibody-dependent cell activation are overexpressed in renal biopsies from patients with antibody-mediated rejection.

INTRODUCTION: Antibody-mediated rejection (ABMR) is dependent on complement activating donor-specific anti-HLA antibodies (DSA). This is commonly detected by C4d deposition in allografts. However, recent data define a C4d negative ABMR phenotype suggesting a role for complement-independent DSA injury, antibody-dependent cellular cytotoxicity (ADCC). METHODS: Here, we established an in vitro ADCC model that identified human ADCC-activated genes using microarray analysis. We subsequently interrogated renal allograft biopsies from patients with ABMR and controls for mRNA expression of the ADCC-activated gene set. RESULTS: We identified 13 ADCC-activated genes. Six gene expression assays including 8 of the 13 genes (CCL3, CCL4/CCL4L1/CCL4L2, CD160, IFNG, NR4A3 and XCL1/XCL2) were analyzed in 127 kidney biopsies obtained from HLA-sensitized (HS), non-HS patients and control individuals. Most ADCC-activated genes showed significantly higher expression in the transplant samples compared to the controls (p<0.0005). The gene expression levels were significantly higher in HS and non-HS transplant patients who developed ABMR compared to those who did not (p=0.04-0.002). There was no difference in the gene expression levels between C4d positive and negative ABMR (p=0.26-0.99). Samples from high PRA (>80%) or positive DSA patients showed higher gene expression levels for the ADCC-activated genes compared to low PRA (<80%) and negative DSA patients (p=0.04-0.001). CONCLUSION: ADCC pathways are active in transplant patients with ABMR, and likely mediate allograft injury, providing a potential mechanism for C4d negative ABMR.

Perceived importance of activities of daily living and arthritis helplessness in rheumatoid arthritis; a prospective investigation.

OBJECTIVE: To examine the contribution of perceived importance of activities of daily living (ADL) to arthritis-specific helplessness in a sample of rheumatoid arthritis (RA) patients over a 1-year period. METHOD: Forty-two individuals from an outpatient rheumatology clinic completed measures of ADL importance, helplessness, depression, pain, and disability; the physician's assistant provided objective ratings of disability. RESULTS: Time 1 importance of ADL predicted a significant amount of variance in Time 2 arthritis helplessness after statistically controlling disease and psychological covariates. Moreover, increased perceived ADL importance predicted decreased arthritis helplessness over the 1-year period. CONCLUSIONS: Results indicate that RA patients' experience of arthritis-specific helplessness may be minimized over time when performing ADL is perceived as important. Furthermore, these findings provide preliminary evidence for one possible antecedent to increased perceptions of arthritis helplessness in individuals with RA.

Centralized research recruitment-evolving a local clinical research recruitment web application to better meet user needs.

Recruiting volunteers into clinical research remains a significant challenge for many clinical research study teams, thus the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan developed UMClinicalStudies (http://www.UMClinicalStudies.org)-a Web application that links the community to a single gateway for clinical research. UMClinicalStudies (formerly named "Engage") is an integral piece of MICHR's efforts to increase clinical research participation in order to advance medical discoveries. Despite the initial success of the application, barriers to research participation remain, including the applications accessibility for potential research volunteers and study team members. In response, new initiatives were instigated to identify user needs, in order to broaden the ability to simultaneously assist researchers in recruitment activities, while also aiding potential volunteers in the exploration of and participation in clinical research opportunities. To do this, improvements to the interface and functionality were identified and implemented for both the public and the research audiences through extensive system analysis, and through the application of human computer interactivity processes, resulting in significant improvements in usability and ultimately research volunteerism, indicating that utilizing such technology is pivotal in reaching broader audiences for clinical trial participation.

Community-based priorities for improving nutrition and physical activity in childhood.

Overweight among America's youth has prompted a large response from foundations, government, and private organizations to support programmatic interventions. The architecture for many of these programs was derived from "experts," whereas the perspective of families, and communities--those most affected and most instrumental in altering behavior--is rarely the driving force. Shaping America's Youth (SAY) was established to assess programs that target nutrition and physical activity and to promote the necessary family and community input. In a 2004 report, SAY documented how community efforts are motivated, funded, structured, and evaluated. It identified discordance between that effort and the opinions of experts. To ensure that the voices of families and communities are integrated into such local and national policies and programs, SAY initiated a unique series of 5-day-long town meetings, input from which was independently statistically analyzed. Across a range of demographics, the results indicated that participants perceive the barriers and solutions similarly. There was broad agreement that the family has primary responsibility, starting with a need to focus on improved quality and duration of family time directed at nutrition and activity. Concurrently they identified needed actions from external sources, including clear and consistent nutrition information; ready access to healthy foods; and a built environment that promotes physical activity. Rather than one-dimensional or governmental solutions, they expressed a need for community-based partnerships integrating health care, education, environment, government, and business. Although this citizen-engagement process did not identify specific actions, it defined basic steps that communities must integrate into future approaches.