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  • Pediatric Heart Transplantation: Transitioning to Adult Care (TRANSIT): Baseline Findings
    Pediatric Cardiology. 2017;03:03

    Study Details

    Aims: To compare an intervention focussed on increasing heart transplant (HT) knowledge, self management, self-advocacy skills and enhancing support, against usual care in young adult HT recipients transferring to adult care.
    Interventions: Participants were randomised to receive either a transition program focussing on increasing HT related knowledge, self-care, self-advocacy skills, and social support, versus usual care.
    Participants: 88 HT recipients from 6 Children’s Hospitals, ready to transition to the adult program, aged ≥ 18 years.
    Outcomes: Measured outcomes included HT knowledge, self-management and self-advocacy, support, immunosuppression, adverse events and adherence.

    CET Conclusion

    Reviewer: Dr. Liset Pengel, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
    This report presents baseline data of a pilot RCT that compares a transition programme to adult care with usual care for young adults who had a heart transplant. Eighty-eight patients ≥18 years were recruited from six paediatric heart transplant centres in the US and randomised to a 3-month, 2 phase transition programme or standard transfer of care. Prior to randomisation medical records data were collected and at the last paediatric clinical visit patients completed self-report instruments. The two intervention groups showed no differences in terms of baseline and clinical characteristics or on any of the self-report instruments. The Heart Transplant Knowledge Questionnaire tested knowledge of medications, appointment keeping, healthy lifestyle, benefits and risks of heart transplantation, and transition to adult care, and showed low scores at baseline. Scores on other questionnaires showed that patients are still developing self-management skills and self-advocacy skills. Follow-up data at 3 and 6 months will show whether the transition programme is successful in improving these outcomes and skills when compared to usual care.

    Expert Review

    Reviewer: Professor Michael Burch, Great Ormond Street Hospital, London, United Kingdom.
    Conflicts of interest: No
    Clinical Impact Rating : ★★★☆☆ (3 of 5)
    This interesting study investigates young adult heart transplant patients transitioning to adult care. The data shown represents the baseline values and shows that the young adults do not have a good understanding of heart transplantation and their self-advocacy and self-management skills are incomplete. This has implications for all paediatric heart transplant programmes.

    Abstract

    Young adult solid organ transplant recipients who transfer from pediatric to adult care experience poor outcomes related to decreased adherence to the medical regimen. Our pilot trial for young adults who had heart transplant (HT) who transfer to adult care tests an intervention focused on increasing HT knowledge, self-management and self-advocacy skills, and enhancing support, as compared to usual care. We report baseline findings between groups regarding (1) patient-level outcomes and (2) components of the intervention. From 3/14 to 9/16, 88 subjects enrolled and randomized to intervention (n = 43) or usual care (n = 45) at six pediatric HT centers. Patient self-report questionnaires and medical records data were collected at baseline, and 3 and 6 months after transfer. For this report, baseline findings (at enrollment and prior to transfer to adult care) were analyzed using Chi-square and t-tests. Level of significance was p < 0.05. Baseline demographics were similar in the intervention and usual care arms: age 21.3 +/- 3.2 vs 21.5 +/- 3.3 years and female 44% vs 49%, respectively. At baseline, there were no differences between intervention and usual care for use of tacrolimus (70 vs 62%); tacrolimus level (mean +/- SD = 6.5 +/- 2.3 ng/ml vs 5.6 +/- 2.3 ng/ml); average of the within patient standard deviation of the baseline mean tacrolimus levels (1.6 vs 1.3); and adherence to the medical regimen [3.6 +/- 0.4 vs 3.5 +/- 0.5 (1 = hardly ever to 4 = all of the time)], respectively. At baseline, both groups had a modest amount of HT knowledge, were learning self-management and self-advocacy, and perceived they were adequately supported. Baseline findings indicate that transitioning HT recipients lack essential knowledge about HT and have incomplete self-management and self-advocacy skills.
  • Improved pulse wave velocity and renal function in individualized calcineurin-inhibitor treatment by immunomonitoring: the randomized controlled Calcineurin Inhibitor-Sparing (CIS) Trial
    Transplantation. 2017;26:26

    Study Details

    Aims: To compare the monitoring of cyclosporine A (CsA) using nuclear factor of activiated T-cells -regulated gene expression (NFAT-RE), versus standard CsA trough level (C0) monitoring.
    Interventions: Participants were randomly assigned to either standard monitoring (CsA dose adjusted to target a C0 of 80–150 μg/L), or NFAT-RE (CsA adjusted to target a residual NFAT-RE of 15–30%).
    Participants: 55 renal allograft recipients from a deceased or living donor ≥6 months prior to study entry, aged ≥18 years with stable renal allograft function, and receiving CsA microemulsion, mycophenolic acid with or without low-dose steroids.
    Outcomes: The primary outcome measured was the change in arterial stiffness, assessed by pulse wave velocity. Secondary outcomes included peripheral and central blood pressure, cardiac augmentation index, biopsy-proven acute rejection, graft loss or death, renal function, safety and tolerability.

    CET Conclusion

    Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
    This small but interesting RCT investigates the use of immune monitoring using NFAT-regulated gene expression (NFAT-RE) in stable kidney transplant recipients. All patients received cyclosporine and MMF with/without steroids, and control patients were monitored using standard trough cyclosporine levels. The authors demonstrate a significant improvement in pulse-wave velocity and GFR with NFAT-RE monitoring, with no obvious excess in adverse events or rejection. The small size of this study means that further evidence would be required to demonstrate safety in terms of rejection and graft survival. It appears, however, that NFAT-RE monitoring may allow minimisation of cyclosporine dose safely in these stable, low risk recipients. It is worth noting that trough cyclosporine levels in the standard monitoring arm increased over the 12-month study period, with a corresponding fall in GFR, which does raise the risk of treatment bias in a non-blinded study such as this.

    Expert Review

    Reviewer: Professor Ron Shapiro, Kidney/Pancreas Transplantation, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mt. Sinai, USA.
    Conflicts of interest: No
    Clinical Impact Rating : ★★★★★ (5 of 5)
    This is an extremely interesting trial of utilizing immunologic monitoring to manage immunosuppression in stable renal transplant recipients. Patients were randomized either to routine PK monitoring (i.e. peak and trough levels) or NFAT-regulated gene expression. Patients randomized to NFAT-regulated gene expression had reduced cardiovascular risk, as assessed by pulse wave velocity, fewer infections, and better renal function than the control group. This is a very important trial. Most immunosuppression is, at some level, an educated guess about what patients should be receiving, based on a composite of clinical and laboratory factors, but without any real immunologic monitoring data. This trial utilized immunologic monitoring to titrate immunosuppressive drug dosing. Even with a very small number of patients, the authors were able to demonstrate a benefit of immunologic monitoring. The study utilized an immunosuppressive agent, cyclosporine that is used in a very small minority of transplant recipients. This work should be repeated by other centers, with larger numbers of patients, utilizing tacrolimus-based immunosuppression. If the findings from this initial experience are replicated, this could lead to a sea change in how patients are managed after transplantation.

    Abstract

    BACKGROUND A new immune monitoring tool which assesses the expression of nuclear factor of activated T-cells (NFAT)-regulated genes measures the functional effects of cyclosporine A. This is the first prospective randomized controlled study to compare standard pharmacokinetic monitoring by cyclosporine trough levels to NFAT-regulated gene expression (NFAT-RE). METHODS Expression of the NFAT-regulated genes was determined by qRT-PCR at cyclosporine trough and peak level. Cardiovascular risk was assessed by change of pulse wave velocity from baseline to month 6. Clinical follow-up was 12 months. RESULTS In total, 55 stable kidney allograft recipients were enrolled. Mean baseline residual NFAT-regulated gene expression was 13.1 +/- 9.1 %. Patients in the NFAT-RE group showed a significant decline in pulse wave velocity from baseline to month 6 versus the standard group (-1.7 +/- 2.0 vs. 0.4 +/- 1.4 m/s, p<0.001). Infections occurred more often in the standard group compared to the immune monitoring group. No opportunistic infections occurred with NFAT-RE monitoring. At 12 months' follow-up, renal function was significantly better with NFAT-RE versus standard monitoring (Nankivell GFR 68.5 +/- 17.4 vs. 57.2 +/- 19.0 ml/min, p=0.009). CONCLUSIONS NFAT-RE as translational immune monitoring tool proved efficacious and safe in individualizing cyclosporine therapy, with the opportunity to reduce the cardiovascular risk and improve long-term renal allograft function.
  • Enhanced Recovery Open Versus Laparoscopic Left Donor Nephrectomy: a Randomized Controlled Trial
    Urology. 2017;08

    Study Details

    Aims: To evaluate the postoperative outcomes between laparoscopic donor nephrectomy (LDN) and open donor nephrectomy (ODN) within a specified Enhanced Recovery Program (ERP) for left kidney donations.
    Interventions: Participants were randomized to LDN or ODN with recovery optimized within an ERP. ODN was performed via a 12-15 cm supracostal incision above the 11th rib and an extra-pleural extra peritoneal approach was adopted. LDN was performed via a standard 4-port distribution.
    Participants: 224 left side donors who did not express a preference for either ODN or LDN.
    Outcomes: The primary outcome measured was donor recovery as evaluated by the physical fatigue domain of the Multidimensional Fatigue Inventory 20 (MFI-20). Other measured outcomes included the other domains within the MFI-20, scores of Short Form-36 health survey, pain scores, analgesic requirements, length of hospital stay, return to work, daily activities, perioperative complications and graft outcome measures.

    CET Conclusion

    Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
    This single-centre study from Egypt investigates the effect of an Enhanced Recovery Protocol (ERP) on laparoscopic and open left donor nephrectomy. Donors were randomised 1:1 to laparoscopic or open nephrectomy, and all donors underwent an enhanced recovery plan. Unfortunately, the details of the ERP are given in supplementary digital content, which is not currently available on the journal website. The authors demonstrate a significant advantage to laparoscopic nephrectomy even in the setting of ERP, with reduced physical fatigue, shorter hospital stay less pain and reduced opioid use. Warm ischaemic time did not differ between the groups. The study appears well conducted, with appropriate randomisation, although not blinded. Analysis is per protocol, excluding 2 patients who withdrew consent and underwent open nephrectomy. The results are perhaps not too surprising, given the existing evidence of the benefits of the laparoscopic approach. Without detail of the ERP used, it is not clear what the potential benefits could be – hopefully this will be added to the journal site upon full publication.

    Expert Review

    Reviewer: Professor Stuart M. Flechner, Cleveland Clinic Lerner College of Medicine, USA.
    Conflicts of interest: No
    Clinical Impact Rating : ★★★☆☆ (3 of 5)
    The authors performed a single centre prospective RCT comparing laparoscopic (110 patients) to open surgical (109 patients) donor nephrectomy. All kidneys were left, about 96% had single renal arteries, and each patient was supplemented with epidural anesthesia. A mention is made of an Enhanced Recovery Protocol (ERP) but this definition was placed in supplemental materials and not the primary paper. The primary endpoint was patient reported “fatigue,” which seems very qualitative. Clinical outcomes for both donors and recipients are reported to be quite good for either technique, and the authors concluded that "LDN was associated with less general and physical fatigue and better physical function at six weeks postoperative when compared to open surgery for left kidney donation." The findings are in line with many other reports on this topic, but this trial appears to be well designed and executed. Time for return to employment would have been helpful. Some limitations are to be noted. Firstly, although in supplemental material one, it surmises the selected donors were generally young and with a BMI <25kg/m2. Secondly, since about 20% of donors have right kidneys with anatomical features favouring their use, the centre should not leave donors with inferior kidneys just to perform a left laparoscopic nephrectomy. Thirdly, an important issue that must be highlighted for the laparoscopic cases is that the authors secured the donor renal artery using hem-o-lock clips. The manufacturer (Weck) has reported several international donor deaths from clips that dislodged and a "black box warning" from American and European regulatory agencies have restricted the use of these clips in donor nephrectomy. Such practice cannot be supported.

    Abstract

    OBJECTIVE To compare recovery outcomes between laparoscopic donor nephrectomy (LDN) and open donor nephrectomy (ODN) within a specified Enhanced Recovery Program (ERP) for left kidney donations. MATERIALS AND METHODS A phase III randomized trial was conducted between January 2013 and June 2015, eligible left side donors were randomized to laparoscopic or open donor nephrectomy in a 1:1 ratio with recovery optimized within a standardized ERP. The primary outcome was patient-reported measure of physical fatigue, as measured by the physical fatigue domain of the translated Multidimensional Fatigue Inventory 20 (MFI-20). Secondary outcomes included other donor recovery outcomes, postoperative pain scores, hospital stay, perioperative complications and graft outcomes. RESULTS A total of 224 donors (laparoscopy, n=113; open surgery, n=111) were randomly allocated. Six weeks postoperatively, physical fatigue domain scores in MFI-20 were significantly lower in the LDN group (mean: laparoscopy, 8.2 +/- 3.2 vs. open surgery, 13.05+/- 2.9) (p=0.007). Median total hospital stay was also significantly shorter in the LDN group (median: laparoscopy, 2; interquartile range [IQR], 1 to 5 vs. open surgery, 4; IQR, 2 to 9 days) (P = 0.002). LDN was associated with less pain scores and less non-opioid analgesic requirements. Warm ischemia times were not significantly different in both groups (mean: laparoscopy, 2.5 +/- 0.8 vs. open surgery, 2.2 +/- 0.6) (p=0.431). CONCLUSION Even when optimized within an ERP, LDN was associated with less general and physical fatigue and better physical function at six weeks postoperatively when compared to open surgery for left kidney donations.
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