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INTRODUCTION: The human gut microbiota has the potential to modulate the outcomes of several human diseases. This effect is likely to be mediated through interaction with the host immune system. This protocol details the establishment of a biorepository of clinically annotated samples, which we will use to explore correlations between the gut microbiota and the immune system of immune-compromised patients. We aim to identify microbiome-related risk factors for adverse outcomes. METHODS AND ANALYSES: This is a protocol for the development of a biorepository of clinically annotated samples collected prospectively across three centres in Melbourne, Australia. Participants will be recruited across the following clinical streams: (1) acute leukaemia and allogeneic stem cell transplant; (2) end-stage liver disease and liver transplant; (3) patients receiving any cancer immunotherapies (eg, chimeric antigen receptor therapy); (4) deceased organ donors and (5) healthy adult controls. Participants will be asked to provide paired peripheral blood and microbiota samples (stool and saliva) at either (1) single time point for healthy controls and deceased organ donors or (2) longitudinally over multiple prespecified or event-driven time points for the remaining cohorts. Sampling of fluid from bronchoalveolar lavage and colonoscopy or biopsy of tissues undertaken during routine care will also be performed. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the relevant local ethics committee (The Royal Melbourne Hospital Human Research Ethics Committee). The results of this study will be disseminated by various scientific platforms including social media, international presentations and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12623001105639. Date registered 20 October 2023.
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Microbioma Gastrointestinal , Humanos , Australia , Interacciones Microbiota-Huesped/inmunología , Bancos de Muestras Biológicas , Estudios Prospectivos , Proyectos de Investigación , Manejo de Especímenes/métodosRESUMEN
INTRODUCTION: Subclinical rejection (SCR) refers to the presence of acute rejection without accompanying kidney allograft dysfunction. The impact of SCR on long-term graft survival remains a subject of ongoing debate. METHODS AND ANALYSIS: We will perform a systematic search of databases including MEDLINE, Embase and Cochrane Central, from January 1995 to November 2023. We will include English-language studies involving adult kidney transplant patients who investigated SCR. We will exclude studies focused on 'for-cause' biopsies. Both title, abstract screening and full-text screening will be performed by two or more reviewers. The primary outcome of this study will be death-censored allograft loss. The secondary outcome will include development of subsequent rejection. For time-dependent outcomes, we will prioritise HRs and the 95% CIs. In cases where HRs are unavailable, we will calculate risk ratios based on the recorded events. The risk of bias will be assessed using the Cochrane Collaboration's revised tool for assessing the risk of bias in randomised trials and the Newcastle-Ottawa scale for cohort studies. We will employ a random effects model. We will evaluate heterogeneity using the I2 variable. We will assess publication bias by funnel plots, Begg and Mazumdar test, and Egger's test. ETHICS AND DISSEMINATION: Ethics approval does not apply as no original data will be collected. The results will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023463536.
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Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Riñón , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Humanos , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Organ donation entails saving or transforming lives through the provision of organs, either from living donors or deceased individuals. In Jordan, low donation rates are attributed to religious misconceptions, limited education and insufficient awareness of the burden on patients with organ failure. OBJECTIVES: To investigate the attitudes of the Jordanian population towards the practicality and effectiveness of introducing an opt-out organ donation system through legislative measures, with the aim of increasing donation rates. DESIGN: This cross-sectional study used a designed self-administered questionnaire. Data were subsequently analysed using IBM SPSS software. SETTING: The study encompassed all 12 cities located in Jordan. PARTICIPANTS: Data were collected from 1146 Jordanian participants, excluding individuals under the age of 18. RESULTS: Approximately 36.6% reported organ or blood donation while 18.9% participated in awareness campaigns. Many (75.7%) perceived insufficient awareness about the importance of organ donation, and 67.1% noted a scarcity of online donor registration platforms. Only 12.0% of participants discussed organ donation with healthcare providers. As anticipated, only 9.0% were registered donors while 67.7% expressed acceptance of organ donation, with 55.3% willing to enrol in donor programmes. Religion influenced 54.2% of organ donation decisions. There are associations between agreement for a new enactment and prior organ or blood donation or discussions with healthcare providers. However, religion affected willingness to donate organs. Most importantly, refusal to be a donor after death was associated with religion, occupation and awareness levels. CONCLUSION: Despite the population's understanding and support for the concept of organ donation, the willingness towards donating their own organs is limited. To boost organ donation rates and acceptance of the new enactment, we recommend conducting educational campaigns, improving online registration platforms, enhancing healthcare provider engagement, collaborating with religious communities and advocating for supportive policies.
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Conocimientos, Actitudes y Práctica en Salud , Obtención de Tejidos y Órganos , Humanos , Estudios Transversales , Jordania , Femenino , Masculino , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven , Donantes de Tejidos/psicología , Adolescente , AncianoRESUMEN
INTRODUCTION: Patients with cirrhosis awaiting liver transplantation (LT) are often frail, and malnourished. The period of time on the waitlist provides an opportunity to improve their physical fitness. Prehabilitation appears to improve the physical fitness of patients before major surgery. Little is known about prehabilitation in patients with cirrhosis. The aim of this feasibility study will be to investigate the feasibility, safety, and effectiveness of a multimodal prehabilitation programme in this patient population. METHODS AND ANALYSIS: This is an open-label single-arm feasibility trial recruiting 25 consecutive adult patients with cirrhosis active on the LT waiting list of the McGill University Health Centre (MUHC). Individuals will be excluded based on criteria developed for the safe exercise training in patients with cirrhosis. Enrolled individuals will participate in a multimodal prehabilitation programme conducted at the PeriOperative Programme complex of the MUHC. It includes exercise training with a certified kinesiologist (aerobic and resistance training), nutritional optimisation with a registered dietician and psychological support with a nurse specialist. The exercise training programme is divided into an induction phase with three sessions per week for 4 weeks followed by a maintenance phase with one session every other week for 20 weeks. Aerobic training will be individualised based on result from cardiopulmonary exercise testing (CPET) and will include a high-intensity interval training on a cycle ergometer. Feasibility, adherence and acceptability of the intervention will be assessed. Adverse events will be reviewed before each visit. Changes in exercise capacity (6-minute walk test, CPET, liver frailty index), nutritional status and health-related quality of life will be assessed during the study. Post-transplantation outcomes will be recorded. ETHICS AND DISSEMINATION: The research ethics board of the MUHC has approved this study (2021-7646). Our findings will be submitted for presentation at national and international conferences, and for peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT05237583.
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Estudios de Factibilidad , Cirrosis Hepática , Trasplante de Hígado , Ejercicio Preoperatorio , Listas de Espera , Humanos , Trasplante de Hígado/rehabilitación , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Calidad de Vida , Aptitud Física , Adulto , Terapia por Ejercicio/métodos , Masculino , FemeninoRESUMEN
INTRODUCTION: Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4. METHODS AND ANALYSIS: BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1-5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in COL1A1 or COL1A2 can be included in the trial.Each subject receives four intravenous doses of 3×106/kg BOOST cells at 4 month intervals, with 48 (doses 1-2) or 24 (doses 3-4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally.The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover. ETHICS AND DISSEMINATION: The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482.
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Trasplante de Células Madre Mesenquimatosas , Osteogénesis Imperfecta , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Células Madre Fetales/trasplante , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas , Estudios Multicéntricos como Asunto , Osteogénesis Imperfecta/terapia , Resultado del TratamientoRESUMEN
INTRODUCTION: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk. METHODS AND ANALYSIS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation. ETHICS AND DISSEMINATION: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309). TRIAL REGISTRATION NUMBER: NCT05148715.
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Inhibidores de la Calcineurina , Funcionamiento Retardado del Injerto , Trasplante de Riñón , Donantes de Tejidos , Adulto , Femenino , Humanos , Masculino , Muerte Encefálica , Inhibidores de la Calcineurina/administración & dosificación , Inhibidores de la Calcineurina/uso terapéutico , Funcionamiento Retardado del Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Estudios Multicéntricos como Asunto , Ontario , Proyectos Piloto , Quebec , Ensayos Clínicos Controlados Aleatorios como Asunto , Tacrolimus/uso terapéutico , Tacrolimus/administración & dosificaciónRESUMEN
INTRODUCTION: Lung transplantation is the gold-standard treatment for end-stage lung disease for a small group of patients meeting strict acceptance criteria after optimal medical management has failed. Physical frailty is prevalent in lung transplant candidates and has been linked to worse outcomes both on the waiting list and postoperatively. Exercise has been proven to be beneficial in optimising exercise capacity and quality of life in lung transplant candidates, but its impact on physical frailty is unknown. This review aims to assess the effectiveness of exercise interventions in modifying physical frailty for adults awaiting lung transplantation. METHODS AND ANALYSIS: This protocol was prospectively registered on the PROSPERO database. We will search four databases plus trial registries to identify primary studies of adult candidates for lung transplantation undertaking exercise interventions and assessing outcomes pertaining to physical frailty. Studies must include at least 10 participants. Article screening will be performed by two researchers independently at each stage. Extraction will be performed by one reviewer and checked by a second. The risk of bias in studies will be assessed by two independent reviewers using tools appropriate for the research design of each study; where appropriate, we will use Cochrane Risk of Bias 2 or ROBINS-I. At each stage of the review process, discrepancies will be resolved through a consensus or consultation with a third reviewer. Meta-analyses of frailty outcomes will be performed if possible and appropriate as will prespecified subgroup and sensitivity analyses. Where we are unable to perform meta-analysis, we will conduct narrative synthesis following Synthesis without Meta-analysis guidance. The review will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. ETHICS AND DISSEMINATION: No ethical issues are predicted due to the nature of this study. Dissemination will occur via conference abstracts, professional networks, peer-reviewed journals and patient support groups. PROSPERO REGISTRATION NUMBER: CRD42022363730.
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Fragilidad , Trasplante de Pulmón , Humanos , Ejercicio Físico , Metaanálisis como Asunto , Calidad de Vida , Revisiones Sistemáticas como AsuntoRESUMEN
OBJECTIVES: This study aims to investigate factors with a significant influence on deceased organ donation rates in Organisation for Economic Co-operation and Development (OECD) countries and determine their relative importance. It seeks to provide the necessary data to facilitate the development of more efficient strategies for improving deceased organ donation rates. DESIGN: Retrospective study. SETTING: Publicly available secondary annual data. PARTICIPANTS: The study includes 36 OECD countries as panel members for data analysis. OUTCOME MEASURES: Multivariable panel data regression analysis was employed, encompassing data from 2010 to 2018 for all investigated variables in the included countries. RESULTS: The following variables had a significant influence on deceased organ donation rates: 'opt-in' system (ß=-4.734, p<0.001, ref: 'opt-out' system), only donation after brain death (DBD) donors allowed (ß=-4.049, p=0.002, ref: both DBD and donation after circulatory death (DCD) donors allowed), number of hospital beds per million population (pmp) (ß=0.002, p<0.001), total healthcare employment pmp (ß=-0.00012, p=0.012), World Giving Index (ß=0.124, p=0.008), total tax revenue as a percentage of gross domestic product (ß=0.312, p=0.009) and percentage of population aged ≥65 years (ß=0.801, p<0.001) as well as high education population in percentage (ß=0.118, p=0.017). CONCLUSIONS: Compared with the promotion of socioeconomic factors with a positive significant impact on deceased organ donation rates, the following policies have been shown to significantly increase rates of deceased organ donation, which could be further actively promoted: the adoption of an 'opt-out' system with presumed consent for deceased organ donation and the legal authorisation of both DBD and DCD for transplantation.
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Trasplante de Órganos , Obtención de Tejidos y Órganos , Humanos , Organización para la Cooperación y el Desarrollo Económico , Estudios Retrospectivos , Donantes de TejidosRESUMEN
BACKGROUND: Navigating the organ donation and transplantation system in Canada can be challenging for individuals on transplant journeys. Although it is likely that the COVID-19 pandemic has further contributed to these challenges, the experiences of individuals during the pandemic in Canada have not been well elicited. OBJECTIVE: To illuminate how the COVID-19 pandemic has impacted individuals on transplant journeys in Canada. DESIGN: Convergent parallel mixed-methods study. SETTING: Canada. PARTICIPANTS: Adult patients, caregivers, and donors on transplant journeys across Canada. DATA COLLECTION: Eight focus groups and an online survey between May and November 2021. Focus group transcripts were analysed using an inductive conventional content analysis approach. Survey data were analysed using descriptive statistics. The study was guided by individuals with lived experience of organ donation and transplantation. RESULTS: A total of 830 participants completed three COVID-19 related survey questions, with 21 participating in the focus groups. Survey results: over 50% of patients and caregivers reported that the pandemic impacted their access to their healthcare team, their mental health (60% and 65%, respectively) and their comfort going out in public (80% and 75%, respectively). Although many donors reported several factors that impacted their transplant journey, the impact appeared to be greater for patients and caregivers. Qualitative results: three themes emerged from the qualitative data that contextualise participant's experiences: compounding isolation, disruption amid uncertainty and unforeseen benefits. CONCLUSION: The COVID-19 pandemic has exacerbated many of the challenges that individuals on transplant journeys experience. It will be critical for transplant programmes to consider these factors in future care provision.
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COVID-19 , Trasplante de Órganos , Trasplantes , Adulto , Humanos , Pandemias , COVID-19/epidemiología , Canadá/epidemiologíaRESUMEN
INTRODUCTION: Ischaemic cold static storage (ICSS) is the gold standard in donor heart preservation. This ischaemic time frame renders a time constraint and risk for primary graft dysfunction. Cold oxygenated heart perfusion, known as non-ischaemic heart preservation (NIHP), theoretically limits the ischaemic time, while holding on to the known advantage of hypothermia and cardioplegia, a low metabolic rate. METHODS AND ANALYSIS: The NIHP 2019 study is an international, randomised, controlled, open, multicentre clinical trial in 15 heart transplantation centres in 8 European countries and includes 202 patients undergoing heart transplantation, allocated 1:1 to NIHP or ICSS. Enrolment is estimated to be 30 months after study initiation. The patients are followed for 12 months after transplantation.The primary objective is to evaluate the effect of NIHP on survival, allograft function and rejection episodes within the first 30 days after transplantation. The secondary objectives are to compare treatment groups with respect to survival, allograft function, cardiac biomarkers, rejection episodes, allograft vasculopathy, adverse events and adverse device effects within 12 months. ETHICS AND DISSEMINATION: This protocol was approved by the Ethics Committee (EC) for Research UZ/KU Leuven, Belgium, the coordinating EC in Germany (Bei Der LMU München), the coordinating EC in the UK (West Midlands-South Birmingham Research), the EC of Hospital Puerta de Hierro, Madrid, Spain, the EC of Göteborg, Sweden, the coordinating EC in France, the EC of Padova, Italy and the EC of the University of Vienna, Austria. This study will be conducted in accordance with current local regulations and international applicable regulatory requirements according to the principles of the Declaration of Helsinki and ISO14155:2020. Main primary and secondary outcomes will be published on modified intention-to-treat population and per-protocol population. TRIAL REGISTRATION NUMBER: NCT03991923.
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Trasplante de Corazón , Humanos , Donantes de Tejidos , Europa (Continente) , Trasplante Homólogo , Criopreservación/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
OBJECTIVE: The main objective of the study was to evaluate the influence of arterial hypertension, diabetes, dyslipidaemia, smoking, alcoholism and COPD (chronic obstructive pulmonary disease) on the viability of the extracted tissue as well as the donor. DESIGN: Observational case-control study. SETTING: Regional hospital in Northern Spain. PARTICIPANTS: 1517 corneas were registered. INTERVENTIONS: Patients' medical history was reviewed after corneal donation and evaluation. Previous medical information (age, sex and cardiovascular risk factors (CVRFs)) and data related to the donor (type of donor), the corneal tissue and its evaluation, and the viability of the implant were collected. RESULTS: A total of 1517 corneas were registered and 81.5% of the donors presented at least one CVRF. In relation to the viability of the donor, it was observed that having suffered from COPD reduced the viability of the donor (no COPD: 93.8% vs COPD: 88%; OR=0.49; 95% CI: 0.28 to 0.84) while alcohol consumption increased it (drinker or ex-drinker: 95.8% vs non-drinker: 92.5%; OR=1.84; 95% CI: 1.01 to 3.33). Regarding tissue viability, decreased viability was observed in the presence of COPD (no COPD: 72.5% vs COPD: 64; OR=0.67; 95% CI: 0.47 to 0.96) and diabetes mellitus (no diabetes: 72.9% vs diabetes: 67.2%; OR=0.76; 95% CI: 0.58 to 0.99). As regards the viability of the implant, a total of 1039 corneas (68.9%) were suitable, observing decreased viability when suffering from COPD (no COPD: 69.8% vs COPD: 60.7%; OR=0.67; 95% CI: 0.47 to 0.94) and increased when having an active smoking habit (no habit: 65.3% vs habit: 74.1%; OR=1.52; 95% CI: 1.21 to 1.91). CONCLUSIONS: Through this study, it can be concluded that in the absence of absolute exclusion criteria for donors, the assessment of how CVRF, alcoholism and COPD may affect the donor provides details about the quality of the tissue to be obtained.
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Alcoholismo , Enfermedades Cardiovasculares , Diabetes Mellitus , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Factores de Riesgo , Córnea , Factores de Riesgo de Enfermedad Cardiaca , Donantes de Tejidos , Enfermedad Pulmonar Obstructiva Crónica/epidemiologíaRESUMEN
INTRODUCTION: Shingrix, an effective adjuvanted, recombinant herpes zoster vaccine (RZV), has been available since 2018. Immunocompromised patients are known to be predisposed to vaccine failure. In-vitro testing of immunological surrogates of vaccine protection could be instrumental for monitoring vaccination success. So far, no test procedure is available for vaccine responses to RZV that could be used on a routine basis. METHODS AND ANALYSIS: This is a single-centre, three-arm, parallel, longitudinal cohort study aspiring to recruit a total of 308 patients (103 with a liver cirrhosis Child A/B, 103 after liver transplantation (both ≥50 years), 102 immunocompetent patients (60-70 years)). Blood samples will be taken at seven data collection points to determine varicella zoster virus (VZV) and glycoprotein E (gE)-specific IgG and T cell responses. The primary study outcome is to measure and compare responses after vaccination with RZV depending on the type and degree of immunosuppression using gE-specific antibody detection assays. As a secondary outcome, first, the gE-specific CD4+ T cell response of the three cohorts will be compared and, second, the gE-VZV antibody levels will be compared with the severity of possible vaccination reactions. The tertiary outcome is a potential association between VZV immune responses and clinical protection against shingles. ETHICS AND DISSEMINATION: Ethical approval was issued on 07/11/2022 by the Ethics Committee Essen, Germany (number 22-10805-BO). Findings will be published in peer-reviewed open-access journals and presented at local, national and international conferences. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (number DRKS00030683).
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Vacuna contra el Herpes Zóster , Herpes Zóster , Trasplante de Hígado , Niño , Humanos , Estudios Longitudinales , Estudios Prospectivos , Herpes Zóster/prevención & control , Herpesvirus Humano 3 , Adyuvantes Inmunológicos , Glicoproteínas , Adyuvantes Farmacéuticos , Cirrosis Hepática/cirugía , Vacunas de SubunidadRESUMEN
INTRODUCTION: Tissue transplantation can improve the quality of life of patients in a very wide range of applications. In 2021, around 900 people in Germany agreed to donate organs after death - the number of tissue donors was significantly higher. Nevertheless, there is a shortage of organs and tissues in Germany. In order to counteract this, the introduction of a presumed consent legislation has been discussed time and again. However, the debates focused on possible positive effects for organ donation, whereas potential consequences for tissue donation have so far not been considered in the political discourse or in research. Using an exploratory approach, this paper aims to contribute to closing this research gap: Multidisciplinary interviews with experts were conducted to investigate whether the presumed consent legislation is a key success factor for increasing the number of tissue donors in Germany and which other approaches might be promising. METHODS: We conducted qualitative interviews with 14 experts who worked as employees in different positions in tissue banks/networks, ophthalmologists performing corneal transplantation, medical ethicists, lawyers or scientists. These interviews were evaluated using the structuring content analysis according to Mayring. In reporting, we followed the Standards for Reporting Qualitative Research (SQRQ). RESULTS: The majority of experts did not consider presumed consent legislation to be a key factor in increasing the donation rate in Germany. Instead, an improvement of processes and structures in tissue donation was cited as the most important optimization potential. Furthermore, communication measures were postulated to create transparency about the characteristics of tissue donation as distinct from organ donation. These should address not only the general population, but also the professional groups involved in the tissue donation process. CONCLUSION: The present study indicates that the presumed consent legislation is not a success factor for increasing the number of tissue donors in Germany. It would be far more effective to improve structures and processes in order to identify the large number of potential tissue donors and to be able to conduct informed conversations with their relatives. Information measures for the general public and professionals, which clearly differentiate between tissue donation and organ donation, are also more promising than fruitless debates about the introduction of the presumed consent legislation.
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Consentimiento Presumido , Obtención de Tejidos y Órganos , Humanos , Calidad de Vida , Alemania , Donantes de TejidosRESUMEN
INTRODUCTION: Ischaemia/reperfusion injuries (IRIs) are associated with poorer survival of kidney grafts from expanded criteria donors. Preclinical studies have shown that mineralocorticoid receptor antagonists (MRAs) prevent acute and chronic post-ischaemic renal dysfunction by limiting IRI. However, data concerning the safety of MRAs in brain-dead donor patients are scarce. We seek to investigate the tolerance of MRAs on the haemodynamics in this population. METHODS AND ANALYSIS: CANREO-PMO is a randomised, controlled, single-centre, double-blind study. Brain-dead organ donors hospitalised in intensive care are randomised 1:1 after consent to receive 200 mg potassium canrenoate or its matching placebo every 6 hours until organ procurement. The primary outcome is a hierarchical composite endpoint that includes: (1) cardiocirculatory arrest, (2) the impossibility of kidney procurement, (3) the average hourly dose of norepinephrine/epinephrine between randomisation and departure to the operating room, and (4) the average hourly volume of crystalloids and/or colloids received. Thirty-six patients will be included. The secondary endpoints evaluated among the graft recipients are the: (1) vital status of the kidney graft recipients and serum creatinine level with estimated glomerular filtration rate (GFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) at 3 months after renal transplantation, (2) percentage of patients dependent on dialysis and/or with an estimated GFR <20 mL/min/1.73 m2 at 3 months, (3) vital status of the kidney graft recipients at 3 months, and (4) vital status of the kidney graft recipients and creatinine levels (in µmol/L), with the estimated GFR according to CKD-EPI (in mL/min/1.73 m2), at 1 year, 3 years and 10 years after transplantation. ETHICS AND DISSEMINATION: This trial has full ethical approval (Comité de Protection des Personnes: CPP Ouest II-ANGERS, France), and the written consent of relatives will be obtained. Results will be reported at conferences, peer-reviewed publications and using social media channels. TRIAL REGISTRATION NUMBER: NCT04714710.
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Ácido Canrenoico , Trasplante de Riñón , Antagonistas de Receptores de Mineralocorticoides , Humanos , Encéfalo , Muerte Encefálica , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/cirugía , Donantes de Tejidos , Método Doble Ciego , Daño por Reperfusión Miocárdica/prevención & controlRESUMEN
INTRODUCTION: Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but are also at risk of graft loss from rejection with underimmunosuppression. Biomarkers that predict both iRAEs and rejection while allowing individualisation of immunosuppression exposure are lacking. Although plasma viral DNA levels of torque teno virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in newly transplanted KTRs within the first year after transplant, its role for prevalent KTRs on stable immunosuppression is less clear.This study aims to determine the prognostic value of TTV levels for severe infections (defined as infections requiring hospitalisation) in prevalent KTRs on stable immunosuppression for at least 3 months and compare it against that of other commonly available biomarkers. The study also aims to explore the relationship between TTV levels and factors affecting the 'net state of immunosuppression' as well as other clinical outcomes. METHODS AND ANALYSIS: This is a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured using the TTV R-GENE kit upon recruitment when study subjects are admitted and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months. The relationship between TTV load and clinical outcomes such as severe infections will be analysed and compared against that from other common biomarkers and previously published predictive scores. ETHICS AND DISSEMINATION: The study was approved by the SingHealth Centralised Institutional Review Board (2023/2170). The results will be presented at conferences and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05836636.
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Trasplante de Riñón , Torque teno virus , Humanos , Monitorización Inmunológica , Estudios Prospectivos , Terapia de Inmunosupresión/efectos adversos , Estudios Observacionales como AsuntoRESUMEN
BACKGROUND AND AIMS: Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes. METHODS AND ANALYSIS: This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated. ETHICS AND DISSEMINATION: The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders. TRIAL REGISTRATION NUMBER: NCT05260268.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Humanos , Estudios Prospectivos , Calidad de Vida , Cumplimiento y Adherencia al TratamientoRESUMEN
OBJECTIVE: To investigate whether observable differences exist between patterns of withdrawal of life-sustaining measures (WLSM) for patients eligible for donation after circulatory death (DCD) in whom donation was attempted compared with those patients in whom no donation attempts were made. SETTING: Adult intensive care units from 20 centres in Canada, the Czech Republic and the Netherlands. DESIGN: Secondary analysis of quantitative data collected as part of a large, prospective, cohort study (the Death Prediction and Physiology after Removal of Therapy study). PARTICIPANTS: Patients ≥18 years of age who died after a controlled WLSM in an intensive care unit. Patients were classified as not DCD eligible, DCD eligible with DCD attempted or DCD eligible but DCD was not attempted. PRIMARY AND SECONDARY OUTCOME MEASURES: The process of WLSM (timing and type and, if applicable, dosages of measures withdrawn, dosages of analgesics/sedatives) was compared between groups. RESULTS: Of the 635 patients analysed, 85% had either cardiovascular support stopped or were extubated immediately on WLSM. Of the DCD eligible patients, more were immediately extubated at the initiation of WLSM when DCD was attempted compared with when DCD was not attempted (95% vs 61%, p<0.0001). Initiation of WLSM with the immediate cessation of cardiovascular measures or early extubation was associated with earlier time to death, even after adjusting for confounders (OR 2.94, 95% CI 1.39 to 6.23, at 30 min). Other than in a few patients who received propofol, analgesic and sedative dosing after WLSM between DCD attempted and DCD eligible but not attempted patients was not significantly different. All patients died. CONCLUSIONS: Patients in whom DCD is attempted may receive a different process of WLSM. This highlights the need for a standardised and transparent process for end-of-life care across the spectrum of critically ill patients and potential organ donors.
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Unidades de Cuidados Intensivos , Pacientes , Adulto , Humanos , Estudios de Cohortes , Estudios Prospectivos , Extubación Traqueal , Hipnóticos y SedantesRESUMEN
OBJECTIVES: The aim of this retrospective cross-sectional study was to assess the performance of paediatric organ donation in intensive care units following neurological determinants of death in Saudi Arabia. DESIGN: Retrospective cross-sectional study. SETTING: Paediatric intensive care units at three tertiary centres over 5 years. PARTICIPANTS: 423 paediatric deaths (<14 years) from January 2017 to December 2021. PRIMARY OUTCOME: Patients were identified as either possible, potential, eligible, approached, consented or actual donors based on organ donation definitions from the WHO, Transplantation Society and UK potential donor audit. SECONDARY OUTCOME: Secondary outcome was causative mechanisms of brain injury in possible donors. Demographics of the study cohort (age, sex, hospital length of stay (LOS), paediatric intensive care unit LOS, pre-existing comorbidities, admission type and diagnosis category) were compared between possible and non-possible donors. Demographics were also compared between patients who underwent neurological determination of death and patients who did not. RESULTS: Among the 423 paediatric deaths, 125 (29.6%) were identified as possible donors by neurological criteria (devastating brain insult with likelihood of brain death, Glasgow Coma Score of 3 and ≥2 absent brainstem reflexes). Of them, 41 (32.8%) patients were identified as potential donors (neurological determination of death examinations initiated by the treating team), while only two became actual donors. The eligible death conversion rate was 6.9%. The reporting rate to organ procurement organisation was 70.7% with a consent rate of 8.3%. The most common causes of brain insult causing death were cardiac arrest (44 of 125 patients, 35.2%), followed by traumatic brain injury and drowning (31 of 125 patients, 24.8%), and intracranial bleeding (13 of 125 patients, 11.4%). CONCLUSION: Major contributors to low actual donation rate were consent, donor identification and donor referral.
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Muerte Encefálica , Unidades de Cuidado Intensivo Pediátrico , Obtención de Tejidos y Órganos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Muerte Encefálica/diagnóstico , Estudios Transversales , Estudios Retrospectivos , Arabia Saudita/epidemiología , Centros de Atención Terciaria , Obtención de Tejidos y Órganos/estadística & datos numéricosRESUMEN
INTRODUCTION: Individuals with anorexia nervosa (AN) harbour distinct gut microbiomes compared with healthy individuals, which are sufficient to induce weight loss and anxiety-like behaviours when transplanted into germ-free mice. We hypothesise that faecal microbiome transfer (FMT) from healthy donors would help restore the gut microbiome of individuals with AN, which in turn, may aid patient recovery. METHODS: We aim to conduct an open-label pilot study in 20 females aged 16-32 years in Auckland, New Zealand who meet the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for AN and have a body mass index 13-19 kg/m2. We will recruit four healthy, lean, female donors, aged 18-32 years, who will undergo extensive clinical screening prior to stool donation. Faecal microbiota will be harvested from donors and double encapsulated in delayed release, acid-resistant capsules. All participants will receive a single course of 20 FMT capsules (five from each donor) which they can choose to take over two or four consecutive days. Stool and blood samples will be collected from participants over a period of 3 months to assess their gut microbiome profile, metabolome, levels of intestinal inflammation and nutritional status. Our primary outcome is a shift in the gut microbiome composition at 3 weeks post-FMT (Bray-Curtis dissimilarity). We will also monitor participants' body composition (whole-body dual-energy X-ray absorptiometry scans), eating disorder psychopathology, mental health and assess their views on, and tolerability of, treatment. All adverse events will be recorded and reviewed by an independent data monitoring committee. ETHICS AND DISSEMINATION: Ethics approval was provided by the Central Health and Disability Ethics Committee (Ministry of Health, New Zealand, 21/CEN/212). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences. TRIAL REGISTRATION NUMBER: ACTRN12621001504808.
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Anorexia Nerviosa , Microbioma Gastrointestinal , Microbiota , Femenino , Anorexia Nerviosa/terapia , Cápsulas , Proyectos Piloto , Humanos , Adolescente , Adulto Joven , AdultoRESUMEN
INTRODUCTION: The usage of a T-cell depleted, reduced intensity conditioning (RIC) approach to haematopoietic cell transplantation (HCT) in adult patients with acute lymphoblastic leukaemia (ALL) over 40 years of age and in first complete remission (CR) has resulted in encouraging rates of event-free and overall survival in a population of adults with high risk disease. However, relapse rates remain high-with disease progression being the major cause of treatment failure. Using different, more powerful conditioning approaches is the logical next step in examining the role of RIC allogeneic HCT in adult ALL. METHODS AND ANALYSIS: The ALL-RIC trial is a two-arm, phase II, multicentre, randomised clinical trial in adult patients with ALL in first or second CR, who are undergoing allogeneic HCT. Comparison of a novel RIC transplant conditioning regimen using reduced-dose total body irradiation (TBI), cyclophosphamide and alemtuzumab, is made against a standardised RIC approach using fludarabine, melphalan and alemtuzumab. The primary outcome of the study is disease-free survival at 3 years, defined as time from randomisation to the first of either relapse or death from any cause. Patients who are still alive and progression-free at the end of the trial will be censored at their last date known to be alive. Secondary outcomes include overall survival and non-relapse mortality. ETHICS AND DISSEMINATION: The protocol was approved by the East Midlands-Leicester Central Research Ethics committee (18/EM/0112). Initial approval was received on 12 June 2018. Current protocol version (V.6.0) approval obtained on 18 November 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: EudraCT Number: 2017-004800-23.ISRCTN99927695.