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1.
J Patient Saf ; 17(5): e367-e372, 2021 08 01.
Article in English | MEDLINE | ID: mdl-27642689

ABSTRACT

ABSTRACT: After a number of high-profile incidents and national reports, it has become clear that all health professionals and all medical students must be able to raise concerns about a colleague's behavior if this behavior puts patients, colleagues, or themselves at risk.Detailed evidence from medical students about their confidence to raise concerns is limited, together with examples of barriers, which impair their ability to do so. We describe a questionnaire survey of medical students in a single-center, examining self-reported confidence about raising concerns in a number of possible scenarios. Thematic analysis was applied to comments about barriers identified.Although 80% of respondents felt confident to report a patient safety issue, students were less confident around issues of probity, attitude, and conduct. This needs to be addressed to create clear mechanisms to raise concerns, as well as support for students during the process.


Subject(s)
Students, Medical , Attitude of Health Personnel , Health Personnel , Humans , Patient Safety , Surveys and Questionnaires
2.
Future Healthc J ; 6(3): 192-195, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31660525

ABSTRACT

BACKGROUND: Flipped learning is an approach in which core teaching is delivered using online material viewed prior to face-to-face learning, applying knowledge gained from online material. Core teaching in a module for third-year undergraduate medical students was based around a 1-week course comprising 32 hours of lectures. Feedback suggested that students were poorly engaged and attendance was poor. OBJECTIVES: To develop and evaluate a programme of learning for medical students using flipped learning. METHODS: Core lectures were videoed and students were advised to watch online at home in the morning prior to a case-based interactive discussion session in the afternoon. Feedback was undertaken prior to and following change in delivery; changes in Likert scale feedback were assessed. Thematic assessment of free-text feedback was undertaken. Results of in-course assessment examinations were compared prior to and following change in delivery. RESULTS: Student feedback showed a significant improvement in satisfaction with flipped learning compared to standard lectures, both in scores and free-text feedback. Results of in-course assessments did not change between the two methods of delivery. CONCLUSIONS: Flipped learning can improve student satisfaction and engagement with teaching, but our study has not demonstrated an improvement in assessment scores.

3.
Transplantation ; 102(12): 2065-2071, 2018 12.
Article in English | MEDLINE | ID: mdl-29781954

ABSTRACT

BACKGROUND: The potential for clinical trials to impact patient care may be limited if the outcomes reported vary by trial and lack direct relevance to patients. Despite the many trials conducted in kidney transplantation, premature death due to cardiovascular disease, infection, and malignancy remains high. We aimed to assess the range and consistency of outcomes reported in trials in kidney transplantation. METHODS: We searched for randomized trials conducted in kidney transplantation. We extracted the outcome measures, classified them into outcome domains, and into categories (clinical, surrogate or patient-reported outcome [PRO]). We assessed the measures used for the top 4 domains. RESULTS: Overall, 397 trials reported 12 047 outcomes measures and time points (median, 19 per trial; interquartile range, 9-42) across 106 different domains, of which 55 (52%) were surrogate, 35 (33%) clinical, and 16 (15%) PRO. The 4 most frequently reported were graft function (322 [81%] trials, 118 outcome measures), acute rejection (234 [59%], 93 measures), graft loss (215 [54%], 48 measures), and mortality (204 [51%], 51 measures). The remaining 102 domains were reported in less than 50% of trials. CONCLUSIONS: Mortality- and graft-related outcome domains were frequently reported and assessed with a multiplicity of measures. Most outcome domains were surrogate outcomes, and the reporting of relevant life-threatening complications and PRO were uncommon. Establishing core outcomes based on the shared priorities of patients/caregivers and health professionals in kidney transplantation may improve the relevance and consistency of outcome reporting in trials to better inform clinical decision making.


Subject(s)
Endpoint Determination , Kidney Transplantation , Patient Reported Outcome Measures , Randomized Controlled Trials as Topic/methods , Research Design , Endpoint Determination/standards , Humans , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Kidney Transplantation/standards , Postoperative Complications/etiology , Randomized Controlled Trials as Topic/standards , Research Design/standards , Treatment Outcome
4.
Transplantation ; 101(8): 1887-1896, 2017 08.
Article in English | MEDLINE | ID: mdl-28737661

ABSTRACT

BACKGROUND: Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. METHODS: We convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. RESULTS: Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders-inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. CONCLUSIONS: Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.


Subject(s)
Clinical Trials as Topic/standards , Consensus , Delphi Technique , Kidney Transplantation/standards , Nephrology/standards , Humans , Treatment Outcome
5.
Transplantation ; 101(8): 1875-1886, 2017 08.
Article in English | MEDLINE | ID: mdl-28738403

ABSTRACT

BACKGROUND: Inconsistencies in outcome reporting and frequent omission of patient-centered outcomes can diminish the value of trials in treatment decision making. We identified critically important outcome domains in kidney transplantation based on the shared priorities of patients/caregivers and health professionals. METHODS: In a 3-round Delphi survey, patients/caregivers and health professionals rated the importance of outcome domains for trials in kidney transplantation on a 9-point Likert scale and provided comments. During rounds 2 and 3, participants rerated the outcomes after reviewing their own score, the distribution of the respondents' scores, and comments. We calculated the median, mean, and proportion rating 7 to 9 (critically important), and analyzed comments thematically. RESULTS: One thousand eighteen participants (461 [45%] patients/caregivers and 557 [55%] health professionals) from 79 countries completed round 1, and 779 (77%) completed round 3. The top 8 outcomes that met the consensus criteria in round 3 (mean, ≥7.5; median, ≥8; proportion, >85%) in both groups were graft loss, graft function, chronic rejection, acute rejection, mortality, infection, cancer (excluding skin), and cardiovascular disease. Compared with health professionals, patients/caregivers gave higher priority to 6 outcomes (mean difference of 0.5 or more): skin cancer, surgical complications, cognition, blood pressure, depression, and ability to work. We identified 5 themes: capacity to control and inevitability, personal relevance, debilitating repercussions, gaining awareness of risks, and addressing knowledge gaps. CONCLUSIONS: Graft complications and severe comorbidities were critically important for both stakeholder groups. These stakeholder-prioritized outcomes will inform the core outcome set to improve the consistency and relevance of trials in kidney transplantation.


Subject(s)
Caregivers/standards , Clinical Trials as Topic/standards , Consensus , Delphi Technique , Health Personnel/standards , Kidney Transplantation/standards , Outcome Assessment, Health Care , Adolescent , Adult , Aged , Humans , Middle Aged , Surveys and Questionnaires , Young Adult
6.
Transplant Direct ; 2(6): e79, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27500269

ABSTRACT

BACKGROUND: Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. METHODS: This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes.

7.
J Am Heart Assoc ; 5(2)2016 Feb 18.
Article in English | MEDLINE | ID: mdl-26896478

ABSTRACT

BACKGROUND: Transplantation of allogeneic mesenchymal stromal cells (MSCs) is a promising treatment for heart failure. We have shown that epicardial placement of cell sheets markedly increases donor cell survival and augments therapeutic effects compared with the current methods. Although immune rejection of intramyocardially injected allogeneic MSCs have been suggested, allogeneic MSCs transplanted on the heart surface (virtual space) may undergo different courses. This study aimed to elucidate immunologic response against epicardially placed allogeneic MSCs, rejection or acceptance of these cells, and their therapeutic effects for heart failure. METHODS AND RESULTS: At 4 weeks after coronary artery ligation, Lewis rats underwent epicardial placement of MSC sheets from syngeneic Lewis or allogeneic Fischer 344 rats or sham treatment. At days 3 and 10 after treatment, similar ratios (≈50% and 30%, respectively) of grafted MSCs survived on the heart surface in both MSC sheet groups. By day 28, survival of syngeneic MSCs was substantially reduced (8.9%); survival of allogeneic MSCs was more extensively reduced (0.2%), suggesting allorejection. Correspondingly, allogeneic MSCs were found to have evoked an immunologic response, albeit low level, as characterized by accumulation of CD4(+) T cells and upregulation of interleukin 6. Despite this alloimmune response, the allogeneic MSC sheet achieved myocardial upregulation of reparative factors, enhanced repair of the failing myocardium, and improved cardiac function to the equivalent degree observed for the syngeneic MSC sheet. CONCLUSIONS: Allogeneic MSCs placed on the heart surface evoked an immunologic response; however, this allowed sufficient early phase donor cell survival to induce equivalent therapeutic benefits to syngeneic MSCs. Further development of this approach toward clinical application is warranted.


Subject(s)
Heart Failure/surgery , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/immunology , Myocardial Infarction/surgery , Myocardium/immunology , Regeneration , Animals , CD4-Positive T-Lymphocytes/immunology , Cell Survival , Cells, Cultured , Disease Models, Animal , Graft Rejection/immunology , Graft Survival , Heart Failure/immunology , Heart Failure/pathology , Heart Failure/physiopathology , Interleukin-6/immunology , Male , Myocardial Infarction/immunology , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardium/pathology , Rats, Inbred F344 , Rats, Inbred Lew , Recovery of Function , Stroke Volume , Time Factors , Transplantation, Homologous , Ventricular Function, Left
8.
Clin Kidney J ; 8(5): 623-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26413291

ABSTRACT

BACKGROUND: Black, Asian and minority ethnic (BAME) communities are disproportionately affected by inequalities in transplant services in the UK. There are some indications from pilot programmes that appeals for BAME organ donors may be more effectively communicated by employing grassroots, community-networking approaches, but such initiatives have not been adequately described or evaluated. METHODS: Lay individuals from BAME communities were trained as peer outreach workers. They attended a series of public events to promote knowledge of organ donation and transplantation among the public. Information was gathered from 806 evaluation forms completed by event attendees at 34 separate events. From these, 54 follow-up interviews were conducted with event attendees who completed evaluation forms, indicated that they intended to sign up to the NHS Organ Donor Register (ODR) within the next month and consented to follow-up. RESULTS: Peer outreach initiatives of the type evaluated are associated with increased numbers of BAME people registering as organ donors. A total of 8.8% of event attendees signed up to the NHS ODR. The programme was most effective with people who had previously considered becoming organ donors but who did not know how to go about it. It was less effective with people who had not previously considered it, or who were scared about signing up, or who feared family or religious disapproval. CONCLUSIONS: Peer outreach programmes with BAME communities can be an effective way of reducing inequalities by increasing the number of people on the NHS ODR and encouraging people to think about the issue.

9.
Clin Transplant ; 27(3): 359-67, 2013.
Article in English | MEDLINE | ID: mdl-23406516

ABSTRACT

BACKGROUND: The shortage of organs donated for transplantation is particularly severe among ethnic minorities. Previous work has often studied ethnic minorities in broad groups, failing to differentiate by age or country of education. We investigated the younger generation of UK-educated ethnically Indian and Pakistani students to determine their attitudes toward organ donation. METHODS: We conducted nine focus groups and eight semi-structured interviews. Participants were divided by ethnicity, gender, and medical/non-medical background. Interview transcripts were analyzed by thematic analysis. RESULTS: Six key factors influencing attitudes toward organ donation were found: religion, awareness of the importance of donation, impact of medical education, culture-specific factors, treatment of donors and their organs, and influence of family. The attitude of Islam to donation was highly relevant to Pakistani participants, more than other factors; for Indians, all six factors were similarly relevant. We found that medical education specifically had an important effect on shaping attitudes toward donation. Cultural changes suggested the younger generation may differ from their elders as they adopt British culture. Awareness of donation was universally low. CONCLUSIONS: Indian and Pakistani students are hesitant to donate organs because of multiple factors, which if addressed in a culturally relevant manner could substantially improve donation rates.


Subject(s)
Attitude , Health Knowledge, Attitudes, Practice , Organ Transplantation , Students, Medical/psychology , Tissue and Organ Procurement , Adolescent , Adult , Female , Humans , India , Male , Pakistan , Surveys and Questionnaires , United Kingdom , Universities , Young Adult
10.
Transplantation ; 95(2): 341-6, 2013 Jan 27.
Article in English | MEDLINE | ID: mdl-23197178

ABSTRACT

BACKGROUND.: Donor-specific anti-HLA antibodies (DSA) are a major cause of alloimmune injury. Transplant recipients with negative complement-dependent cytotoxic crossmatch (CDC-XM) and donor cell-based flow cytometric crossmatch (flow-XM) but low level DSA (i.e., by Luminex) have worse outcomes compared with nonsensitized patients. The aim of this study was to establish whether complement-activating ability in this low-level DSA, present before transplantation, as determined by this technique is important in dictating pathogenicity. METHODS.: We retrospectively studied 52 patients with preformed DSA detected by single-antigen flow cytometric fluorescent beads (SAFBs). Patients were transplanted using a steroid-sparing regimen consisting of alemtuzumab induction, 1 week of corticosteroids and tacrolimus monotherapy.Fifteen (29%) of 52 patients experienced antibody-mediated rejection (AMR), whereas 37 (71%) patients did not. There were no demographic differences between patients with AMR and those without. Pretransplant sera were retested using a modified (SAFB) assay, which detects the presence of the complement fragment C4d as a result of DSA-induced complement activation. RESULTS.: C4d+DSA were detected in 10 (19%) of 52 patients. Biopsy-proven AMR occurred in 7 (70%) of the 10 patients with C4d+DSA and in 8 (19%) of 42 patients with C4d-DSA. AMR-free survival was worse in patients with C4d+DSA (P<0.001). CONCLUSIONS.: The ability of preformed, low-level, DSA to trigger C4d fixation in vitro in patients with negative conventional crossmatch tests is predictive for AMR. C4d SAFB is potentially a powerful tool for risk stratification prior to transplantation and may allow identification of unacceptable donor antigens, or patients who may require enhanced immunosuppression.


Subject(s)
Antibody-Dependent Cell Cytotoxicity , Complement Activation , Graft Rejection/immunology , HLA Antigens/immunology , Histocompatibility , Isoantibodies/blood , Kidney Transplantation/immunology , Adult , Biomarkers/blood , Biopsy , Complement C4b , Disease-Free Survival , Drug Therapy, Combination , Female , Flow Cytometry , Graft Rejection/mortality , Graft Rejection/prevention & control , Graft Survival/drug effects , Histocompatibility Testing , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/mortality , Male , Middle Aged , Multivariate Analysis , Peptide Fragments , Proportional Hazards Models , Retrospective Studies , Survival Analysis , Time Factors , Treatment Outcome
11.
Transplantation ; 94(7): e42, 2012 Oct 15.
Article in English | MEDLINE | ID: mdl-23210131
12.
Transplantation ; 93(9): 860-4, 2012 May 15.
Article in English | MEDLINE | ID: mdl-22411561

ABSTRACT

Transplantation research is complex because of consent being required from several individuals, the multiplicity of sites at which donation may occur, its unpredictability, and the time constraints. It is also constrained by a tight regulatory framework, which seems to be stifling research in the United Kingdom. In this article, we recommend that (1) donor consent forms be expanded to include consent to research on organs and associated retrieved material, contemporaneously and in the future, (2) if a research intervention occurs before a recipient is identified, the organ may subsequently be offered on a "take it or leave it" basis, (3) if a research intervention occurs after a recipient is identified, that recipient has the "right of veto" on the research, (4) patients should be able to participate in more than one trial at a time, if clinically appropriate, (5) a Research Ethics Committee with specific transplantation expertise should be established, (6) the unduly onerous legal obstacles erected by the Human Tissue Act (2004) should be removed, and (7) the Organ Donor Register should be expanded to include potential donor wishes on research.


Subject(s)
Biomedical Research , Informed Consent/legislation & jurisprudence , Tissue Donors , Tissue and Organ Procurement/legislation & jurisprudence , Humans , Informed Consent/ethics , Tissue Donors/ethics , Tissue Donors/legislation & jurisprudence , Tissue Donors/supply & distribution , Tissue and Organ Procurement/ethics , United Kingdom
13.
Transplantation ; 93(4): 348-53, 2012 Feb 27.
Article in English | MEDLINE | ID: mdl-22258288

ABSTRACT

Deciding to use an organ from a donor with a primary central nervous system (CNS) tumor necessitates offsetting the risk of tumor transmission with the chances of survival if the patient waits for another offer of a transplant. Published data vary in the quoted risk of tumor transmission. We used data obtained by reviewing 246 UK recipients of organs taken from donors with CNS tumors and found no evidence of a difference in overall patient mortality for recipients of a kidney, liver, or cardiothoracic organ, compared with recipients of organs from donors without a CNS tumor. Recent publication of the UK experience of transplanting organs from CNS tumor donors found no transmission in 448 recipients of organs from 177 donors with a primary CNS tumor (Watson et al., Am J Transplant 2010; 10: 1437). This 0% transmission rate is associated with an upper 95% confidence interval limit of 1.5%. Using a series of assumptions of risk, we compared the risks of dying as a result of the transmission of a primary brain tumor with the risks of dying if not transplanted. On this basis, the use of kidneys from a donor with a primary CNS tumor provides a further 8 years of life over someone who waited for a donor who did not have a primary CNS tumor, in addition to the life years gained by the transplant itself. The benefits for the recipients of livers and cardiothoracic organs were less, but there was no disadvantage in the impact on life expectancy.


Subject(s)
Central Nervous System Neoplasms/complications , Heart Transplantation/mortality , Kidney Transplantation/mortality , Liver Transplantation/mortality , Tissue Donors , Transplantation , Humans , Life Expectancy , Outcome Assessment, Health Care , Risk Factors , Survival Rate , Tissue and Organ Procurement , Waiting Lists
14.
Int Urol Nephrol ; 44(1): 157-65, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21614509

ABSTRACT

OBJECTIVES: We surveyed the following groups of individuals concerning their attitudes towards the pathway leading up to live donor kidney transplantation (LDKT) and post-operative follow-up: kidney transplant (deceased and live donor) recipients, live kidney donors and medical and nursing staff caring for end-stage renal disease and dialysis patients. MATERIALS AND METHODS: Participants were recruited within a tertiary renal and transplant centre and invited to complete anonymized questionnaires, be involved in focus groups and undertake structured interviews. RESULTS: A total of 464 participants completed the questionnaire (36% health care professionals and 64% patients). Most perceived donor risk as small or very small (62%), and 49% stated that a potential donor should be given up to 3 months to reconsider the decision to donate. Participants were almost equally divided as to whether consensus of the donor's family is necessary (46%) or not (44%) in LDKT. Seventy-one percentage of the participants suggested that patients have a greater appreciation of a LDKT if they have been on dialysis; 58% of participants thought that donor and recipient should recuperate beside each other after surgery; 45% thought that the post-operative follow-up for the donor should last up to a year; and 83% thought that donor follow-up should include medical status and quality of life. In the interviews, participants expressed several interesting views. CONCLUSIONS: Participants believed that LDKT is safe for the donor, and the pathway to surgery and post-operative follow-up should be performed in a way that ensures lack of coercion and includes family support and an extensive post-operative follow-up.


Subject(s)
Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Kidney Failure, Chronic/surgery , Kidney Transplantation/psychology , Living Donors/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Critical Pathways , Family Relations , Female , Focus Groups , Humans , Kidney Failure, Chronic/psychology , Male , Middle Aged , Nurses/psychology , Physicians/psychology , Postoperative Care , Preoperative Care , Renal Dialysis , Surveys and Questionnaires , Time Factors , Young Adult
15.
Kidney Int ; 81(2): 170-8, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21918502

ABSTRACT

Fas ligand is a well-known inducer of apoptosis in cells expressing its receptor Fas; it also prevents autoimmunity by inducing apoptosis of activated T cells. However, Fas ligand also mediates non-apoptotic functions involving inflammatory cell migration and cytokine responses. We sought here to study the role of Fas ligand in nephrotoxic nephritis, a model of crescentic glomerulonephritis, using generalized lymphoproliferative disorder (GLD) mice on a C57BL/6 background, which have defective Fas ligand and display only mild autoimmunity. These mice were significantly protected from glomerular crescent formation, glomerular thrombosis, renal impairment, and albuminuria 15 days after the induction of glomerulonephritis in comparison with wild-type mice. There were a reduced number of apoptotic cells in the glomeruli of nephritic GLD mice but no defect in their antibody responses or splenocyte proliferation at 15 days following the induction of glomerulonephritis. Bone marrow transplantation from wild-type mice restored disease susceptibility to GLD mice; however, wild-type mice were not protected when transplanted with bone marrow from GLD mice. Mesangial cells express Fas ligand in vitro, and these cells isolated from GLD mice produced lower amounts of monocyte chemoattractive protein-1 following interleukin-1 stimulation compared with cells from wild-type mice. Thus, Fas ligand-defective mice are protected from nephrotoxic nephritis, a disease in which both circulating and intrinsic renal cells appear to have a role.


Subject(s)
Fas Ligand Protein/genetics , Fas Ligand Protein/metabolism , Glomerulonephritis/metabolism , RNA, Messenger/metabolism , Albuminuria/genetics , Animals , Apoptosis/genetics , Autoimmune Diseases/genetics , Autoimmune Diseases/metabolism , Bone Marrow Transplantation , Cells, Cultured , Chemokine CCL2/metabolism , Disease Models, Animal , Disease Susceptibility/immunology , Disease Susceptibility/metabolism , Glomerulonephritis/genetics , Glomerulonephritis/immunology , Glomerulonephritis/pathology , Immunoglobulins , Immunotoxins , Lymphoproliferative Disorders/genetics , Lymphoproliferative Disorders/metabolism , Mesangial Cells/metabolism , Mice , Mice, Inbred C57BL , Thrombosis/genetics
16.
Nephrol Dial Transplant ; 27(6): 2517-25, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22167592

ABSTRACT

BACKGROUND: There are many views regarding the initiation of the process for live donor kidney transplantation (LDKT), the motives of the donor and the appropriate ways to promote LDKT. METHODS: Health care professionals and patients were recruited in a tertiary renal and transplant centre and completed an anonymous questionnaire. They were then divided into focus groups and a structured interview was performed in order to discover the rationale behind the answers in the questionnaire. RESULTS: Four hundred and sixty-four participants completed the questionnaire. There were 168 health care professionals and 296 patients. Most of the participants (26.9%) suggested that the first approach to a potential donor should be made by the potential recipient. Participants believed that the most important motives for a kidney donor are relief as a result of the recipient's improved health after the transplant (82.5%) and altruism (80.4%). About 89.2% of participants believed that proper long-term medical follow-up of the donor is the most important factor for LDKT promotion. Fifty-five participants discussed the rationale of their answers in the focus group interview. CONCLUSIONS: In our study, participants preferred an initial approach of the donor by the recipient. The relief as a result of the recipient's improved health was suggested as a very strong motive for donation. Proper donor follow-up was considered to be paramount for the further development of LDKT.


Subject(s)
Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Kidney Failure, Chronic/surgery , Kidney Transplantation/psychology , Living Donors/psychology , Living Donors/statistics & numerical data , Physicians/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Altruism , Communication , Culture , Female , Focus Groups , Follow-Up Studies , Humans , Kidney Failure, Chronic/psychology , Male , Middle Aged , Postoperative Care , Preoperative Care , Prognosis , Surveys and Questionnaires , Time Factors , Young Adult
17.
Transplantation ; 92(7): 774-80, 2011 Oct 15.
Article in English | MEDLINE | ID: mdl-21836540

ABSTRACT

BACKGROUND: Immunosuppressive regimens for kidney transplantation which reduce the long-term burden of immunosuppression are attractive, but little data are available to judge the safety and efficacy of the different strategies used. We tested the hypothesis that the simple, cheap, regimen of alemtuzumab induction combined with tacrolimus monotherapy maintenance provided equivalent outcomes to the more commonly used combination of interleukin-2 receptor monoclonal antibody induction with tacrolimus and mycophenolate mofetil combination maintenance, both regimens using steroid withdrawal after 7 days. METHODS: One hundred twenty-three live or deceased donor renal transplant recipients were randomized 2:1 to receive alemtuzumab/tacrolimus or daclizumab/tacrolimus/mycophenolate. The primary endpoint was survival with a functioning graft at 1 year. RESULTS: Both regimens produced equivalent, excellent outcomes with the primary outcome measure of 97.6% in the alemtuzumab arm and 95.1% in the daclizumab arm at 1 year (95% confidence interval of difference 6.9% to -1.7%) and at 2 years 92.6% and 95.1%. Rejection was less frequent in the alemtuzumab arm with 1- and 2-year rejection-free survival of 91.2% and 89.9% compared with 82.3% and 82.3% in the daclizumab arm. There were no significant differences in terms of the occurrence of opportunistic infections. CONCLUSION: Alemtuzumab induction with tacrolimus maintenance monotherapy and short-course steroid use provides a simple, safe, and effective immunosuppressive regimen for renal transplantation.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neoplasm/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Tacrolimus/therapeutic use , Adult , Alemtuzumab , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Neoplasm/adverse effects , Daclizumab , Drug Therapy, Combination , Female , Graft Survival/immunology , Graft Survival/physiology , Humans , Immunoglobulin G/adverse effects , Immunoglobulin G/therapeutic use , Immunosuppressive Agents/adverse effects , Kidney Transplantation/physiology , Longitudinal Studies , Male , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Prospective Studies , Tacrolimus/adverse effects , Treatment Outcome
18.
Transplantation ; 92(2): 176-82, 2011 Jul 27.
Article in English | MEDLINE | ID: mdl-21637139

ABSTRACT

BACKGROUND: Antibody-mediated rejection (AMR) is associated with allograft loss. Identification of factors associated with poor outcome has not been extensively studied. METHODS: We retrospectively studied 469 patients who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies [DSAbs]). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P = 0.0016, 0.001, and 0.012, respectively). RESULTS: Allograft survival was inferior in the AMR group (70.2%) compared with the nonrejector group (97.0%) (P<0.001). Forty-two of 48 (87.5%) of patients with acute AMR had DSAbs. Patients with CII DSAbs at the time of AMR, whether alone or in combination with CI DSAbs had the worst allograft survival (P = 0.014). Both the mean cumulative and immunodominant mean fluorescence index were higher in those patients who subsequently lost their grafts (P<0.001). Patients with diffuse C4d staining had inferior allograft survival than those with focal C4d or no staining (P = 0.02). There was no significant difference in survival by histological grade but a trend to inferior outcomes in those with vascular involvement (P = 0.06). Those patients who met the full Banff criteria had worse survival than those with suspicion for AMR only (P = 0.04). CONCLUSION: This study identifies patients at risk of graft failure from AMR. These patients may benefit from newer therapeutic strategies including the use of eculizumab or bortezomib.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antibodies, Neoplasm/adverse effects , Antibodies/physiology , Antigens, CD/immunology , Antigens, Neoplasm/immunology , Glycoproteins/immunology , Graft Rejection/epidemiology , Graft Rejection/immunology , Kidney Transplantation/immunology , Adult , Alemtuzumab , Antibodies, Monoclonal, Humanized , CD52 Antigen , Complement C4b/metabolism , Female , Graft Rejection/diagnosis , Humans , Incidence , Male , Middle Aged , Peptide Fragments/metabolism , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , Tissue Donors
19.
Clin Transplant ; 25(3): E312-9, 2011.
Article in English | MEDLINE | ID: mdl-21362049

ABSTRACT

Development of live donor kidney transplantation (LDKT) programs has intensified debate regarding acceptability of certain donor categories and potential commercialization. Concerning these issues, we surveyed the views of medical and nursing staff caring for patients with renal failure and renal transplant recipients and donors. Participants were recruited from a tertiary transplant unit and invited to complete an anonymous questionnaire. Four hundred and sixty-four participants completed the questionnaire (42% response). One hundred and sixty-eight (36.2%) were health care professionals and 296 (63.8%) patients; 85.6% of participants were willing to donate to their children, 80.2% to siblings, 80.8% to parents, 72% to a non-blood-related relative or friend, and 15.3% to a stranger. If participants had hypothetical renal failure, they were prepared to accept a kidney from a parent (79.5%), sibling (78.7%), child (56.3%), a non-blood-related relative or friend (79.3%), or stranger (54.1%). Regarding commercialization, responders' attitudes were that the donor should not accept financial reward (29.1%), be compensated for expenses only (60.6%), or should receive a direct financial reward (10.1%). For non-directed donation, 23.5%, 55.6%, and 20.7% were not in support of reward, compensation only, and financial reward, respectively. While live kidney donation was accepted by the majority of individuals surveyed, only the minority approved of commercialization.


Subject(s)
Attitude of Health Personnel , Directed Tissue Donation/ethics , Kidney Transplantation/economics , Kidney Transplantation/ethics , Living Donors , Tissue and Organ Procurement/economics , Tissue and Organ Procurement/ethics , Adolescent , Adult , Aged , Aged, 80 and over , Data Collection , Directed Tissue Donation/legislation & jurisprudence , Female , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Surveys and Questionnaires , Young Adult
20.
Eur J Immunol ; 40(11): 3280-90, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21061447

ABSTRACT

The long-term stability of renal grafts depends on the absence of chronic rejection. As T cells play a key role in rejection processes, analyzing the T-cell repertoire may be useful for understanding graft function outcomes. We have therefore investigated the power of a new statistical tool, used to analyze the peripheral blood TCR repertoire, for determining immunological differences in a group of 229 stable renal transplant patients undergoing immunosuppression. Despite selecting the patients according to stringent criteria, the patients displayed heterogeneous T-cell repertoire usage, ranging from unbiased to highly selected TCR repertoires; a skewed TCR repertoire correlating with an increase in the CD8(+) /CD4(+) T-cell ratio. T-cell repertoire patterns were compared in patients with clinically opposing outcomes i.e. stable drug-free operationally tolerant recipients and patients with the "suspicious" form of humoral chronic rejection and were found significantly different, from polyclonal to highly selected TCR repertoires, respectively. Moreover, a selected TCR repertoire was found to positively correlate with the Banff score grade. Collectively, these data suggest that TCR repertoire categorization might be included in the calculation of a composite score for the follow-up of patients after kidney transplantation.


Subject(s)
Graft Rejection/immunology , Kidney Transplantation/immunology , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology , Adult , Aged , CD4-CD8 Ratio , Female , Follow-Up Studies , Graft Rejection/blood , Graft Rejection/pathology , Humans , Immunosuppression Therapy/methods , Kidney Transplantation/pathology , Male , Middle Aged , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Transplantation, Homologous
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