CD28-Selective Inhibition Prolongs Non-Human Primate Kidney Transplant Survival.

Costimulation blockade using belatacept results in improved renal function after kidney transplant as well as decreased likelihood of death/graft loss and reduced cardiovascular risk; however, higher rates and grades of acute rejection have prevented its widespread clinical adoption. Treatment with belatacept blocks both positive (CD28) and negative (CTLA-4) T cell signaling. CD28-selective therapies may offer improved potency by blocking CD28-mediated costimulation while leaving CTLA-4 mediated coinhibitory signals intact.

Should responder analyses be conducted on continuous outcomes?

Continuous outcomes are often dichotomized to classify trial subjects as responders or nonresponders, with the difference in rates of response between treatment and control defined as the "responder effect." In this article, we caution that dichotomization of continuous interval outcomes may not be best practice. Defining clinical benefit or harm for continuous interval outcomes as the difference between the means of treatment and control, that is, the "continuous treatment effect," we examine the case where treatment and control outcomes are normally distributed and differ only in location.

Preventive Medicine Physicians' Role in Health Care Organizations' Pursuit of the Triple Aim.

Context: The Institute for Healthcare Improvement's Triple Aim is rooted in improving population health and therefore requires a focus on prevention as well as management of disease. Preventive medicine (PM) physicians are uniquely trained in clinical medicine as well as health care delivery and systems-based practice, thus potentially positioning them to lead population health and contribute to the Triple Aim.

Objective: The objectives of this study were to (1) describe PM physicians' contributions related to the Triple Aim and (2) describe PM physician satisfaction with these activities.

Implementation of Evidence-Based Recommendations for Preventive Services in the Veterans Health Administration.

Introduction: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States. To date, there has been scant research on how VHA adopts clinical preventive services guidelines and how U.S.

Alignment of Preventive Medicine Physicians' Residency Training With Professional Needs.

Preventive medicine (PM) physicians promote population-based approaches to health care with training that emphasizes public health, epidemiology, and policy. PM physicians use these skills in varied, often nonclinical, practice settings. PM career diversity challenges educators when designing residency curricula.

Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion.

The shortage of available organs remains the greatest barrier to expanding access to transplant. Despite advances in genetic editing and immunosuppression, survival in experimental models of kidney xenotransplant has generally been limited to <100 days. We found that pretransplant selection of recipients with low titers of anti-pig antibodies significantly improved survival in a pig-to-rhesus macaque kidney transplant model (6 days vs median survival time 235 days).

Screening for Intimate Partner Violence, Elder Abuse, and Abuse of Vulnerable Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Intimate partner violence (IPV), elder abuse, and abuse of vulnerable adults are common and result in adverse health outcomes.

Objective: To review the evidence on screening and interventions for IPV, elder abuse, and abuse of vulnerable adults to inform the US Preventive Services Task Force.

Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through October 4, 2017; references; experts; literature surveillance through August 1, 2018.

CD122 signaling in CD8+ memory T cells drives costimulation-independent rejection.

Interrupting T cell costimulatory signals as a strategy to control undesired immune responses, such as occur in autoimmunity or transplantation, has the potential to alleviate many of the unwanted side effects associated with current immunosuppressive therapies. Belatacept, a high-affinity version of CTLA4-Ig that blocks ligand ligation to CD28, has been approved for use in kidney transplant recipients. Despite the long-term benefits associated with its use, such as improved renal function and lower cardiovascular risk, a subset of patients treated with belatacept experience elevated rates of acute T cell-mediated rejection, tempering enthusiasm for its use.

Preventing T cell rejection of pig xenografts.

Xenotransplantation is a potential solution to the limited supply of donor organs. While early barriers to xenograft acceptance, such as hyperacute rejection, are now largely avoided through genetic engineering, the next frontier in successful xenograft survival will require prevention of T cell-mediated rejection. Most successful immunosuppressive regimens in xenotransplantation utilize T cell depletion with antibody therapy.

Pre-transplant antibody screening and anti-CD154 costimulation blockade promote long-term xenograft survival in a pig-to-primate kidney transplant model.

Xenotransplantation has the potential to alleviate the organ shortage that prevents many patients with end-stage renal disease from enjoying the benefits of kidney transplantation. Despite significant advances in other models, pig-to-primate kidney xenotransplantation has met limited success. Preformed anti-pig antibodies are an important component of the xenogeneic immune response.

Team assessment of behaviour: a high stakes assessment with potential for poor implementation and impaired validity.

Team assessment of behaviour (TAB) is the multi-source feedback assessment of professional behaviours that all UK foundation doctors must engage in twice during their two-year programme. TAB can identify the few underperforming trainees and provide feedback to consolidate the good practice of most. For optimum validity, TAB must be undertaken by a range of assessors, as specified in the national UK Foundation Programme curriculum.

Women, but not men, have prolonged QT interval if depressed after an acute coronary syndrome.

Aims: Depression is a mortality risk marker for acute coronary syndrome (ACS) patients. We hypothesized that the QT interval, a predictor for risk of sudden cardiac death, was related to depressive symptoms in ACS.

Methods And Results: We performed an analysis of admission electrocardiograms from hospitalized patients with unstable angina or non-ST elevation myocardial infarction from two prospective observational studies of depression in ACS.