Development of a Patient Preference Survey for Wearable Kidney Replacement Therapy Devices.

Background: Recent innovations have the potential to disrupt the current paradigm for kidney failure treatment. The US Food and Drug Administration is committed to incorporating valid scientific evidence about how patients weigh the benefits and risks of new devices into their decision making, but to date, premarket submission of patient preference information (PPI) has been limited for kidney devices. With input from stakeholders, we developed a survey intended to yield valid PPI, capturing how patients trade off the potential benefits and risks of wearable dialysis devices and in-center hemodialysis.

Stimulating Patient Engagement in Medical Device Development in Kidney Disease: A Report of a Kidney Health Initiative Workshop.

New technologies challenge current dialysis treatment paradigms as devices become smaller, more portable, and increasingly used outside the dialysis clinic. It is unclear how patients will view this care transition, and it will be important to consider patient and care partner perspectives during all aspects of development for novel dialysis therapies, from design and clinical trials to regulatory approval. To gain insight into this area, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology, the US Food and Drug Administration, and nearly 80 member organizations and companies dedicated to enhancing patient safety and fostering innovation in kidney disease, convened a workshop of patients, care partners, and other kidney community stakeholders.

Overcoming Barriers in Kidney Health-Forging a Platform for Innovation.

Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology.

Incorporating patient-preference evidence into regulatory decision making.

Background: Patients have a unique role in deciding what treatments should be available for them and regulatory agencies should take their preferences into account when making treatment approval decisions. This is the first study designed to obtain quantitative patient-preference evidence to inform regulatory approval decisions by the Food and Drug Administration Center for Devices and Radiological Health.

Methods: Five-hundred and forty United States adults with body mass index (BMI) ≥ 30 kg/m(2) evaluated tradeoffs among effectiveness, safety, and other attributes of weight-loss devices in a scientific survey.

Summary of FDA workshop on ischemia reperfusion injury in kidney transplantation.

The Food and Drug Administration (FDA) held an open public workshop in September 2011 to discuss the current state of science related to the effects of ischemia reperfusion injury (IRI) on outcomes in kidney transplantation. Topics included the development of IRI and delayed graft function (DGF), histology and biomarkers, donor factors, recipient factors, organ quality and organ preservation by means of cold storage solutions or machine perfusion. Various mechanisms of injury and maladaptive response to IRI were discussed as potential targets of intervention.

Summary of FDA antibody-mediated rejection workshop.

The Food and Drug Administration (FDA) held an open public workshop in June 2010 to discuss the current state of science related to antibody-mediated rejection (AMR) in kidney transplantation. Desensitization, acute AMR and chronic AMR (CAMR) were considered in the context of clinical trial design. Participants discussed experiences with HLA antibody detection and quantitation and the utility of monitoring donor-specific antibodies (DSAs) to inform the management of patients with AMR.

Health-related and specific olfaction-related quality of life in patients with chronic functional anosmia or severe hyposmia.

Objectives/hypothesis: To measure health-related and olfaction-related quality of life (QoL) in patients with permanent, severe hyposmia or functional anosmia.

Study Design: A case study in a university ENT department of patients with severe olfactory dysfunction defined by Sniffin' Sticks olfactory test kit with a score for odor threshold, discrimination, and identification (TDI) < 20 and a dysfunction lasting longer than 6 months.

Methods: Assessment of QoL by using the SF-36 Health Survey questionnaire and the Questionnaire for Olfactory Dysfunction (QOD).

U.S. Food and Drug Administration and off-label use of expandable metal biliary stents within the peripheral vasculature.

Expandable metal stents are used to maintain the patency of compromised ducts, lumens, and vessels. As medical devices, there products are regulated by the Center for Devices and Radiological Health of the U.S.

Cryopreservation and long-term liquid nitrogen storage of peripheral blood mononuclear cells for flow cytometry analysis: effects on cell subset proportions and fluorescence intensity.

The effect of cryopreservation and long-term liquid nitrogen storage on peripheral blood mononuclear cell (PBMC) subsets was prospectively analyzed using monoclonal antibodies and flow cytometry. Brief cryopreservation did not significantly alter the proportion of positively stained cells for CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells. A small but statistically significant increase in the proportion of positive cells was observed for HLA-DR+ and HLe-1+ cells.

T-cell subsets in healthy teenagers: transition to the adult phenotype.

Little is known about the normal range and variability of T-cell subsets in older children. We analyzed peripheral blood mononuclear cell subsets in 112 healthy children, ages 12-19 years (mean +/- SD: 15.4 +/- 1.

The effects of cigarette smoking on T cell subsets. A population-based survey of healthy caucasians.

To investigate the influence of cigarette smoking on mononuclear cell subsets, we determined T cell, B cell, monocyte, and HLA-DR+ subsets in a population-based, stratified, random sample of healthy Caucasians using monoclonal antibodies and flow cytometry. The study population consisted of 282 subjects 20 to 69 yr of age, including 108 smokers and 174 nonsmokers. Multivariate analysis techniques were used to assess the influence of cigarette smoking status after controlling for the effects of age and gender.

The influence of age, race, and gender on peripheral blood mononuclear-cell subsets in healthy nonsmokers.

To investigate the influence of age, race, and gender on the cellular immune system, we determined T-cell, B-cell, monocyte, natural killer (NK)-cell, and HLA-DR+-cell subsets in 266 nonsmokers from a population-based random sample of healthy adults using monoclonal antibodies and flow cytometry. Blacks had a lower total white blood-cell count than whites (P less than or equal to 0.0001), due primarily to a decrease in granulocytes.

Association of cigarette smoking with decreased numbers of circulating natural killer cells.

To investigate the relationship between cigarette smoking and the level of circulating natural killer (NK) cells, we studied 282 subjects from a population-based, stratified random sample of healthy persons. NK cells were enumerated by flow cytometry using the monoclonal antibody anti-Leu 11A. Cigarette smokers had a significantly lower proportion of NK cells than did subjects who had never smoked (5.

Molecular epidemiology of HTLV-I-associated non-Hodgkin's lymphomas in Jamaica.

As part of epidemiologic studies of human T-lymphotropic virus (HTLV)-I-associated malignancies in Jamaica, the authors evaluated 26 patients with non-Hodgkin's lymphoma for the presence of integrated HTLV-I provirus in their malignant cells. Fifteen of 26 patients had integrated provirus. All 15 also were HTLV-I antibody positive.

Long-term seropositivity for human T-lymphotropic virus type III in homosexual men without the acquired immunodeficiency syndrome: development of immunologic and clinical abnormalities. A longitudinal study.

The long-term effects of seropositivity for human T-lymphotropic virus type III (HTLV-III) on T-lymphocyte subsets and health status were evaluated in longitudinal studies of 250 initially healthy homosexual men. The relative risk of having an inverted T-lymphocyte helper-to-suppressor ratio rose from 14.3-fold among short-term seropositive subjects (less than 19 months) to 46.

Familial chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) was previously documented in a father and 4 of his 5 offspring. Follow-up studies revealed spontaneous regression of the disease in 1 patient and shifts in the clinical patterns in the other patients; the unaffected sibling developed lung adenocarcinoma. Cell surface analysis showed that 2 of these patients shared a common surface immunoglobulin profile with mu- and delta-type heavy chains and kappa-type light chains, whereas a 3d sibling with CLL had elevated mu- and kappa-chains.

Cell surface antigen expression in newborn cord blood lymphocytes infected with HTLV.

Human T cell lymphocyte lines, established from lymphoid tissues from patients with adult T cell malignancies infected with the human T cell lymphoma virus (HTLV), were used in co-culture experiments to infect newborn cord blood lymphocytes (CBL). The infected and non-infected CBL cell lines were typed for HLA alloantigen determinants and tested for cell surface antigens using selected monoclonal antibodies. Infected cord blood lymphocytes showed inappropriate expression of alloantigenic determinants of the HLA-A and -B alleles.

Amyl nitrite may alter T lymphocytes in homosexual men.

To evaluate the recent outbreak of Kaposi's sarcoma (KS) and opportunistic infections in homosexual men, clinical, virological, and immunological data on two homosexual men with KS and on fifteen healthy homosexual volunteers were collected. Both KS patients had regularly used amyl or butyl nitrite (AN); they had low helper/suppressor (H/S) T-lymphocyte ratios before chemotherapy and high titres of antibody against cytomegalovirus (CMV). Eight of the fifteen volunteers were regular AN users; seven of the eight had low H/S ratios due to larger than normal numbers of OKT8-positive suppressor cells and smaller numbers of OKT4-positive helper cells.

Deposition of immune complexes in the ovarian follicle of rabbits with experimental chronic serum sickness. I. Immunopathology.

In the present study, deposition of antigen-antibody complexes in the ovarian follicles of the rabbit is described. Forty-one rabbits were immunized with multiple daily injections of bovine serum albumin. Twenty-two rabbits developed systemic chronic serum sickness.