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Transplant Trial Watch

The Transplant Trial Watch provides a monthly overview of the 10 most important new clinical trials in organ transplantation, selected and reviewed by the Peter Morris Centre for Evidence in Transplantation (Oxford University)

February 2021

Kidney


  1. The effect of mannitol on oxidation-reduction potential in patients undergoing deceased donor renal transplantation - A randomized controlled trial
    Acta anaesthesiologica Scandinavica. 2021;65(2):162-168

    Study Details

    Aims: This study aimed to investigate whether mannitol was effective in reducing overall oxidative stress in recipients of deceased donor kidney transplants.
    Interventions: Patients were randomly assigned to either the mannitol group or the placebo group.
    Participants: 34 patients undergoing deceased donor kidney transplantation.
    Outcomes: The primary endpoints were the effect of mannitol on overall static oxidative-reduction potential (sORP) and capacity of the oxidative-reduction potential (cORP). The secondary endpoint was the assessment of percentage change of sORP and cORP values from baseline.

    CET Conclusion

    Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    This is a small but well conducted double-blinded RCT in renal transplantation. 34 transplant recipients were randomised to receive a placebo infusion or 1g/Kg infusion of mannitol prior to graft reperfusion. The study size was predicated on results in partial liver resection. Serum markers for oxidative stress were measured using the RedoxSYS Diagnostic System (Aytu Bioscience Inc), which were expressed as Static Oxidative Reduction Potential and Capacity of Oxidative Reduction Potential. There was no significant difference in either of these parameters comparing mannitol to placebo. Unfortunately, the study was not powered to detect clinically relevant outcomes and they are not reported beyond the intra-operative parameters.

    Abstract

    BACKGROUND Mannitol, an osmotic diuretic, is proposed to be an oxygen radical scavenger. Mannitol is often used in renal transplantation to attenuate oxidative stress and thus to protect renal graft function. We tested the hypothesis that mannitol reduces overall oxidative stress during deceased donor renal transplantation. METHODS We randomly assigned 34 patients undergoing deceased donor renal transplantation to receive a solution of mannitol or placebo shortly before graft reperfusion until the end of surgery. We evaluated oxidative stress by measuring the static oxidative-reduction potential (sORP) and the capacity of the oxidative-reduction potential (cORP). sORP and cORP were measured preoperatively, before and within 10 minutes after graft reperfusion, and postoperatively. RESULTS 17 patients were enrolled in the mannitol group and 17 patients were enrolled in the placebo group. Mannitol had no significant effect on sORP (148.5 mV [136.2; 160.2]) as compared to placebo (143.6 mV [135.8; 163.2], p = 0.99). There was also no significant difference in cORP between the mannitol (0.22µC [0.16; 0.36]) and the placebo group (0.22 µC [0.17; 0.38], P = 0.76). CONCLUSION Mannitol showed no systemic redox scavenging effects during deceased donor renal transplantation. To evaluate the direct effect of mannitol on the renal graft further studies are needed.
  2. Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3 trial
    Lancet. 2020;396(10263):1653-1662

    Study Details

    Aims: This study aimed to determine if supplemental oxygen during hypothermic machine perfusion (HMP) led to improvements in the outcome of kidneys donated following circulatory death.
    Interventions: One kidney from each donor was randomised to either oxygenated hypothermic machine perfusion (HMPO2) or HMP without oxygenation.
    Participants: 197 kidney pairs were randomised.
    Outcomes: The primary endpoint was the estimated glomerular filtration rate (eGFR) at 12 months post-transplant. The secondary endpoints included patient survival and graft survival up at 12 months, primary non function, delayed graft function, renal function according to CKD-EPI and MDRD equations, acute rejection and safety outcomes.

    CET Conclusion

    Reviewer: Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    The well-designed, multicentre, double-blind, randomised controlled trial compared oxygenated hypothermic machine perfusion (HMP) with standard (non-oxygenated) HMP in kidney pairs from DCD donors aged 50 and over with sites in Belgium, The Netherlands and United Kingdom. Kidneys from each pair were randomised according to a computer-generated sequence. Blinding was ensured by using empty dummy oxygen bottles in the standard HMP arm and all health care professionals and transplant recipients were blinded to the allocation. The sample size calculation showed that 81 pairs were needed to provide 90% power to show an 8 ml/min/1.73m² difference in the primary outcome estimated GFR. The primary analysis, based on intention-to-treat and ony including only kidney pairs for which both grafts were functioning at 12 months, showed no significant difference in eGFR. A sensitivity analysis that accounted for failed grafts and patient death showed a significantly higher eGFR in the oxygenated group. Graft failure was significantly lower in the oxygenated HMP group as was the number of biopsy-proven rejection episodes. The authors conclude that oxygenated HMP has the potential to improve clinical outcomes and reduce health-care costs.

    Abstract

    BACKGROUND Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve the outcome of kidneys donated after circulatory death. METHODS This randomised, double-blind, paired, phase 3 trial was done in 19 European transplant centres. Kidney pairs from donors aged 50 years or older, donated after circulatory death, were eligible if both kidneys were transplanted into two different recipients. One kidney from each donor was randomly assigned using permuted blocks to oxygenated hypothermic machine perfusion (HMPO2), the other to HMP without oxygenation. Perfusion was maintained from organ retrieval to implantation. The primary outcome was 12-month estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation in pairs of donated kidneys in which both transplanted kidneys were functioning at the end of follow-up. Safety outcomes were reported for all transplanted kidneys. Intention-to-treat analyses were done. This trial is registered with the ISRCTN Registry, ISRCTN32967929, and is now closed. FINDINGS Between March 15, 2015, and April 11, 2017, 197 kidney pairs were randomised with 106 pairs transplanted into eligible recipients. 23 kidney pairs were excluded from the primary analysis because of kidney failure or patient death. Mean eGFR at 12 months was 50.5 mL/min per 1.73 m2 (SD 19.3) in the HMPO2 group versus 46.7 mL/min per 1.73m2 (17.1) in HMP (mean difference 3.7 mL/min per 1.73m2, 95% CI -1.0 to 8.4; p=0.12). Fewer severe complications (Clavien-Dindo grade IIIb or more) were reported in the HMPO2 group (46 of 417, 11%, 95% CI 8% to 14%) than in the HMP group (76 of 474, 16%, 13% to 20%; p=0.032). Graft failure was lower with HMPO2 (three [3%] of 106) compared with HMP (11 [10%] of 106; hazard ratio 0.27, 95% CI 0.07 to 0.95; p=0.028). INTERPRETATION HMPO2 of kidneys donated after circulatory death is safe and reduces post-transplant complications (grade IIIb or more). The 12-month difference in eGFR between the HMPO2 and HMP groups was not significant when both kidneys from the same donor were still functioning 1-year post-transplant, but potential beneficial effects of HMPO2 were suggested by analysis of secondary outcomes. FUNDING European Commission 7th Framework Programme.
  3. Retroperitoneoscopic Standard or Hand-Assisted Versus Laparoscopic Standard or Hand-Assisted Donor Nephrectomy: A Systematic Review and the First Network Meta-Analysis
    Journal of Clinical Medicine Research. 2020;12(11):740-746

    Study Details

    Aims: This study aimed to compare the feasibility, safety and reproducibility of four types of donor nephrectomies, including retroperitoneoscopic (RPDN), hand-assisted retroperitoneoscopic (HARDN), laparoscopic (LPDN) and hand-assisted laparoscopic donor nephrectomy (HALDN).
    Interventions: Electronic databases including the Cochrane library, MEDLINE (PubMed), EMBASE and Google Scholar were searched. Data extraction was performed independently by two authors. The risk of bias was assessed using the Newcastle-Ottawa scale (NOS).
    Participants: 8 studies were included in the review.
    Outcomes: The outcomes of interest included estimated blood loss (EBL), duration of operation, intraoperative complications, postoperative graft complications, duration of hospital stay and postoperative pain.

    CET Conclusion

    Reviewer: Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    The systematic review and network meta-analysis aimed to compare the feasibility, safety and reproducibility of four minimally invasive procedures, i.e. retroperitoneoscopic (RPDN), laparoscopic (LPDN), handassisted retroperitoneoscopic (HARDN) and hand-assisted laparoscopic donor nephrectomy (HALDN). The bibliographic search identified 97 studies of which 8 comparative studies met the inclusion criteria. Data extraction was done in duplicate by independent reviewers. The methodological quality was assessed and all studies were considered to be of high quality. Significantly more right kidneys were retrieved and the operative times was significantly shorter with RPDN and HARDN compared with LPDN and HALDN. The network meta-analysis showed that operative time of RPDN and HARDN was significantly shorter than LPDN and that RPDN retrieved more right kidneys compared with LPDN. No significant differences were found for the other outcomes including warm ischaemic time, intraoperative complications, postoperative graft complications and hospital stay. The authors conclude that each approach is safe and can be adequately applied in selected patients.

    Abstract

    Background: At the present four minimally invasive procedures namely retroperitoneoscopic (RPDN), laparoscopic (LPDN), hand-assisted retroperitoneoscopic (HARDN) and hand-assisted laparoscopic donor nephrectomy (HALDN) are used to perform donor nephrectomies. The current evidence based on retrospective studies and on pairwise only meta-analyses is inconclusive. Up to authors' best knowledge there is no so far network meta-analysis to compare all the above-mentioned procedures. Therefore, a network meta-analysis was conducted to compare the feasibility, safety and reproducibility of the four donor nephrectomies procedures. Methods: Google Scholar, EMBASE, PubMed, and Cochrane library were used for a systematic literature search. Both updated pairwise and network meta-analyses were performed. Results: Compared to LPDN there was evidence of significantly more right kidneys retrieved with RPDN; nonsignificant differences demonstrated both with HALDN and HARDN compared to LPDN. There was evidence that the operative time was significantly shorter by 77 min in RPDN compared to LPDN; on the other hand, HARDN and HALDN did not demonstrate significant differences when compared to LPDN. Conclusions: The present study demonstrates that each approach can be applied safely in adequately selected patients. Moreover, retroperitoneoscopic is reliable, safe and easily reproducible alternative of LPDN for both left and right kidneys.
  4. 5-Year outcomes of the prospective and randomized cistcert study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients
    Transplant International. 2020;[record in progress]

    Study Details

    Aims: The aim of this study was to report the 5-year outcomes of the CISTERT study, a randomised controlled trial that compared the safety and efficacy of steroid withdrawal versus replacement of cyclosporine with everolimus at 3-months post-transplant, in de novo renal transplant recipients.
    Interventions: Participants were randomised to switch to either steroid withdrawal or replace cyclosporine by everolimus at 3-months following transplantation.
    Participants: 151 de novo kidney transplant patients.
    Outcomes: The outcomes of interest included the assessment of glomerular filtration rate (GFR) at one year following transplantation, graft survival, patient survival, malignancies, infections, rejection episodes, diabetes, proteinuria and cardiovascular morbidity.

    CET Conclusion

    Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    This paper reports 5-year outcomes of the CISTERT study, which compared conversion from CNI to everolimus with steroid withdrawal strategies from 3-months post-transplant. The results are as one would expect from the two strategies – a slight improvement in GFR in patients who were able to tolerate everolimus, but with higher incidence of new-onset diabetes and rejection compared to the steroid withdrawal (and CNI continuation) arm. Graft and patient survival were excellent and similar in both arms. It is good to see investigators publishing long-term results from RCTs. As with many mTOR studies, treatment was poorly tolerated and the difference in GFR was absent in the modified intent-to-treat analysis. The study is likely underpowered as a number of patients originally randomised to everolimus failed to convert, and only 36-37% patients remained on the randomised treatment for the full 5 years of follow-up.

    Abstract

    BACKGROUND Withdrawal of either steroids or calcineurin inhibitors are two strategies to reduce treatment-related side effects and improve long-term outcomes of kidney transplantation. The Cistcert study compared the efficacy and safety of these two strategies. METHODS In this multi-center, randomized controlled trial, 151 incident kidney transplant recipients received cyclosporine (CsA), mycophenolic acid (MPA) and steroids during three months, followed by either steroid withdrawal (CsA/MPA) or replacement of cyclosporine with everolimus (EVL) (EVL/MPA/steroids). RESULTS Five-year patient (89% vs 86%; p=NS) and death-censored graft survival (95% vs 96%; p=NS) were comparable in the CsA/MPA and EVL/MPA/steroids arm respectively. 51 CrEDTA clearance was comparable in the intention-to-treat analysis, but in the on-treatment population, the EVL/MPA/steroids arm exhibited a superior 51 CrEDTA clearance at 1 and 5 years after transplantation (61.6 vs 52.4, p=0.05 and 59.1 vs 46.2mL/min/1.73 m2 , p=0.042). Numerically more and more severe rejections were observed in the EVL/MPA/steroids arm, which also experienced a higher incidence of post-transplant diabetes (26% versus 6%, p=0.0016) and infections. No significant differences were observed in cardiovascular outcomes and malignancy. CONCLUSIONS Both regimens provide an excellent long-term patient and graft survival. Regarding graft function, EVL/MPA/steroids is an attractive strategy for patients with good tolerability who remain free of rejection.
  5. PREventive effect of FENestration with and without clipping on post-kidney transplantation lymphatic complications (PREFEN): study protocol for a randomised controlled trial
    BMJ Open. 2020;10(10):e032286

    Study Details

    Aims: This protocol aims to examine the preventative effect of metal clips around the edges of a small fenestration on post-kidney transplantation lymphatic complications (PKTL).
    Interventions: Participants will be randomised to one of two groups: with small fenestration only or with small fenestration and clipping around the edges.
    Participants: Deceased donor kidney transplant reicipients.
    Outcomes: The primary outcome is the incidence of post-transplant symptomatic lymphatic complications. The secondary outcomes include estimated blood loss, duration of operation, surgical complications, length of hospital stay, postoperative complications, all-cause mortality, total perirenal fluid accumulation, serum creatinine levels, blood urea nitrogen (BUN) level, glomerural filtration rate (GFR), delayed graft function and primary non-function.

    CET Conclusion

    Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    This is the protocol for an interesting RCT in renal transplantation. Whilst there is prior existing evidence regarding prophylactic peritoneal fenestration, and even the size of fenestration, there is no evidence regarding clipping the edges of the window. The study protocol has good descriptions of the randomisation methods, blinding methods and statistical analysis. The power calculation has been done to detect a small difference in incidence (only 5%) at 6 months follow up, which may be too small to be clinically significant in the face of any potential complication, such as intestinal herniation.

    Abstract

    INTRODUCTION Peritoneal fenestration is an effective preventive method for reducing the rate of lymphatic complications in kidney transplantation (KTx). The size of the fenestration plays an important role in its effectiveness. A large peritoneal window is no longer indicated, due to herniation and difficulties in performing biopsies. Small preventive fenestration is effective but will be closed too early. The aim of this study is to evaluate whether metal clips around the edges of a small fenestration result in optimal effects with minimum fenestration size. METHODS AND ANALYSIS This trial has been initiated in July 2019 and is expected to last for 2 and a half years. All patients older than 18 years, who receive kidneys from deceased donors, will be included. The kidney recipients will be randomly allocated to either a control arm (small fenestration alone) or an intervention arm (small fenestration with clipping). All fenestrations will be round, maximum 2 cm, and close to the kidney hilum. Clipping will be performed with eight metal clips around the peritoneal window (360degree) in every 45degree in an oblique position. The primary endpoint is the incidence of symptomatic post-KTx lymphatic complications, which require interventional treatment within 6 months after KTx. Secondary endpoints are intraoperative and postoperative outcomes, including blood loss, operation time, severity grade of lymphocele/lymphorrhea and relative symptoms. ETHICS AND DISSEMINATION This protocol study received approval from the Ethics Committee of the University of Heidelberg (Registration Number S-318/2017). A Standard Protocol Items: Recommendations for Interventional Trials checklist is available for this protocol. The results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Registry (NCT03682627).
  6. Transplant social worker and donor financial assistance to increase living donor kidney transplants among African Americans: The TALKS Study, a randomized comparative effectiveness trial
    American Journal of Transplantation. 2020;[record in progress]

    Study Details

    Aims: The aim of this study was to investigate whether a transplant social worker intervention (TALK SWI) when delivered alone or in combination with living donor (LD) financial assistance was more effective in increasing LD activation events among African American transplant canditates, compared to ususal care.
    Interventions: Participants were randomised to one of three groups: the TALK SWI group, the TALK SWI plus financial assistance group, or the usual care group.
    Participants: 300 African American transplant candidates on the deceased donor kidney transplant waiting list.
    Outcomes: The primary endpoint was the assessment of LD kidney transplant donor activation events on behalf of the study participants. The secondary endpoint was the assessment of transplant canditates’ pursuit of LD transplants.

    CET Conclusion

    Reviewer: Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    The randomised controlled trial compared the incremental effectiveness of a transplant social worker intervention alone or paired with living donor financial assistance versus usual care on living donor activation events in African American candidates. 300 participants were randomised according to a computer-generated sequence with concealment of allocation. The social worker intervention addressed concerns previously identified among African American patients and families considering living donor kidney transplantation (LDKT), including medical distrust, financial concerns, and donor coercion. Most participants rated the social worker intervention as useful and 99% felt that the social worker was helpful. Only 2 out of 100 participants in the social worker paired with financial assistance group made use of the financial assistance. The intention to treat analysis showed that the overall rate of donor evaluation was low and that there were no statistically significant differences between groups over 12 months follow-up. There were also no statistically significant differences between groups for taking a step forward in LDKT pursuit.

    Abstract

    Lack of donors hinders living donor kidney transplantation (LDKT) for African Americans. We studied the effectiveness of a transplant social worker intervention (TALK SWI) alone or paired with living donor financial assistance to activate African Americans' potential living kidney donors. African Americans (N=300) on the transplant waiting list were randomly assigned to usual care; TALK SWI; or TALK SWI plus Living Donor Financial Assistance. We quantified differences in live kidney donor activation (composite rate of live donor inquiries, completed new live donor evaluations, or live kidney donation) after 12 months. Participants ' mean age was 52 years, 56% were male, and 43% had annual household income less than $40,000. Most previously pursued LDKT. Participants were highly satisfied with TALK social workers, but they rarely utilized Financial Assistance. After 12 months, few (n=39, 13%) participants had a new donor activation event [35 (12%) new donor inquiries; 17 (6%) new donor evaluations; 4 (1%) LDKT]. There were no group differences in donor activation events [subdistribution hazard ratio (95% CI): 1.09 (0.51-2.30) for TALK SWI and 0.92 (0.42-2.02) for TALK SWI plus Financial Assistance compared to Usual Care, p=0.91)]. Alternative interventions to increase LDKT for African Americans on the waiting list may be needed.
  7. To compare intraoperative goal directed fluid therapy by trans-oesophageal Doppler vis-a-vis FloTrac TM in patients undergoing living related renal transplantation-a prospective randomised controlled study
    Indian Journal of Anaesthesia. 2020;64(Suppl 4):S220-S226

    Study Details

    Aims: The aim of this study was to compare two types of intraoperative goal directed fluid therapy (GDFT) in patients undergoing living donor kidney transplantation: one based on corrected flow time (CFT), measured using trans oesophageal doppler (TED), and another based on stroke volume variation (SVV), assessed using FloTrac™ .
    Interventions: Participants were randomised to either the TED group or the FloTrac™ group.
    Participants: 60 patients undergoing living donor kidney transplantation.
    Outcomes: The primary endpoints were the assessment of total fluid and number of fluid boluses administered intraoperatively. The secondary endpoints were the assessment of allograft function as well as any postoperative complications resulting from fluid overload.

    CET Conclusion

    Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    This small single-centre study investigated the use of two different types of goal-directed fluid therapy during living donor kidney transplantation. Recipients were randomised to use of trans-oesophageal doppler or FloTrac (stroke volume variation) to guide fluid management intraoperatively. No significant differences were found in fluid volume, operative complications or post-operative outcomes between the groups. Overall, the study is well designed and reported, although it is not entirely clear why block randomization was required and the protocol was registered retrospectively. The biggest risk is of type II error due to small sample size, but from the data presented here it appears that either method of fluid management can be used effectively.

    Abstract

    Background: Optimal intra-operative fluid therapy in renal transplantation (RT) is essential to ensure adequate graft function while preventing fluid overload related complications. This RCT was to compare the intraoperative goal directed fluid therapy (GDFT) based either on corrected flow time (CFT), measured by trans oesophageal Doppler (TED) or on the stroke volume variation (SVV), by FloTrac in patients undergoing living donor RT. Methods: This prospective, randomised controlled trial (RCT) was done on 60 end stage renal disease (ESRD) patients, American Society of Anaesthesiologists(ASA) grade III-IV, age 18 to 65 years of either sex, scheduled for living donor RT under general anaesthesia. They were randomly divided into two groups: TED group (n = 30) and FloTrac TM group (n = 30) and administered GDFT, based upon CFT (TED) and SVV (FloTrac TM). The primary outcome was to compare the total fluid and number of fluid boluses administered intraoperatively, while the secondary outcomes were to compare any postoperative complications due to fluid overload and allograft function, assessed by serial serum creatinine levels up to 90 days postoperatively. Results: The mean total intra-operative fluid [3991.67 +/- 856.32 vs. 3543.33 +/- 1131.35, P = 0.089] and the amount of fluid administered per kg body weight per hour [13.32 +/- 4.67 vs. 11.82 +/- 4.76, P = 0.222] were lesser in the FloTrac compared to TED group, though not statistically significant. However, the postoperative incidence of allograft dysfunction, including rejection (P = 0.743) and acute tubular necrosis (ATN) (P = 0.999), and other complications (P = 0.643) were comparable. Conclusions: Both TED and FloTrac devices can be used effectively to guide GDFT in RT, However, lesser total fluid was required in the FloTrac group, which may lead to a lesser number of fluid-related postoperative complications.
  8. Life satisfaction and happiness in patients shielding from the COVID-19 global pandemic: A randomised controlled study of the 'mood as information' theory
    PLoS ONE [Electronic Resource]. 2020;15(12):e0243278

    Study Details

    Aims: This study aimed to examine the effects of the COVID-19 pandemic on the life satisfaction and happiness of kidney transplant patients undertaking mandatory shielding.
    Interventions: Participants were randomised to those who were to be primed with a question regarding the COVID-19 pandemic and those who were not.
    Participants: 200 kidney transplant recipients.
    Outcomes: The outcomes of interest were overall life satisfaction, momentary happiness, overall lifetime happiness and desire to change.

    CET Conclusion

    Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    This is a very interesting and well conducted RCT in renal transplantation during the COVID-19 pandemic in the UK. The study is predicated on the basis that humans desire explanations for behaviours and feelings. Telephone interviews were conducted to assess patients’ life satisfaction and happiness. 200 renal transplant recipients, who were shielding during the period of the study (May 1st- 29th 2020), were randomised to one of two groups. The first group received a “priming” introduction whereby they were asked “By the way, how’s the COVID-19 pandemic making you feel at the moment?” Both groups had the same introductory conversation apart from this one sentence and then were asked the same 4 questions about their life satisfaction. Patients who had the priming introduction gave significantly better scores for lifetime happiness, life satisfaction and momentary happiness, as well as desire for change. It seems that asking a question about the COVID-19 pandemic, that brings this negative event into the frame, resulted in a discounting effect, whereby positive changes in both momentary happiness and other components of global life satisfaction were given higher scores. This has strong implications for how and when measures of life satisfaction should be gathered.

    Abstract

    OBJECTIVES To extrapolate the 'mood as information' theory to the unique and ecologically relevant setting of the COVID-19 pandemic; the specific aim was to inform health care providers of the impact of bringing the pandemic to salience during life satisfaction evaluations, assessing whether this 'prime' results in increased or decreased reports of satisfaction which are derived unconsciously. DESIGN Prospective Randomised Interventional Study. SETTING Renal Transplant Department in a tertiary centre in the United Kingdom. PARTICIPANTS 200 Renal transplant patients aged between 20 and 88 years. Telephone interviews were undertaken between 1st May, 2020 and 29th May, 2020, at the height of 'shielding' from COVID-19. INTERVENTIONS Participants were randomised into 2 groups, with 1 group receiving a simple 'priming question' regarding the COVID pandemic and the other group having no prior contact. MAIN OUTCOME MEASUREMENTS Individuals were then asked to rate their own overall lifetime happiness; desire to change; overall life satisfaction and momentary happiness on a scale of 1 to 10 for each measure. Independent sample t-tests were used to compare results between the two groups, with a type 1 error rate below 5% considered statistically significant. RESULTS Participants' overall happiness with their life as a whole revealed that individuals who were primed with a question about COVID-19 reported increased overall happiness with their life compared to individuals who had not been primed (+0.88, 95% confidence interval 0.42 to 1.35, p = 0.0002). In addition, participants in the primed group reported less desire to change their life when compared to the non-primed group (-1.35, 95% confidence interval -2.06 to -0.65, p = 0.0002). Participants who were primed with the COVID-19 question also reported a higher overall satisfaction with their life than individuals who had not been primed (+1.01, 95% confidence interval 0.50 to 1.52, p = 0.0001). Finally, the participants who received the priming question demonstrated increased reported momentary happiness (+0.64, 95% confidence interval 0.03 to 1.24, p = 0.04). CONCLUSIONS The results demonstrated that bringing salience to the COVID-19 pandemic with a simple question leads to positive changes in both momentary happiness and other components of global life satisfaction, thereby extrapolating evidence for the application of the mood-as-information theory to more extreme life circumstances. Given the importance of patient-reported evaluations, these findings have implications for how, when and where accurate and reproducible measurements of life satisfaction should be obtained.

Various


  1. Modifying dietary patterns in cardiothoracic transplant patients to reduce cardiovascular risk: the AMEND-IT Trial
    Clinical Transplantation. 2020;[record in progress]:e14186

    Study Details

    Aims: This study aimed to evaluate the feasibility and effectiveness of modifying dietary patterns to reduce cardiovascular risk in cardiothoracic transplant patients.
    Interventions: Participants were randomised to either the Mediterranean diet group or the low-fat diet group.
    Participants: 21 lung and 20 heart transplant recipients.
    Outcomes: The primary endpoint was the assessment of the feasibility of the Mediterranean dietary intervention versus the low-fat diet intervention. The secondary endpoints were the measurement of blood pressure, body mass index (BMI), body weight, glucose regulation markers, blood lipids and prednisolone dosage.

    CET Conclusion

    Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    This is an interesting and good quality pilot study in cardiothoracic transplant recipients. Patients were randomised to a low-fat diet based on British Heart Foundation guidelines, or a “Mediterranean” diet supplemented with extra-virgin olive oil for 12 months. Both groups received a 5-hour education session, as well as attended cooking lessons with a trained chef. Those on the “Mediterranean” diet were asked to consume 40ml of olive oil per day (supplied by the study investigators). Physical activity was neither encouraged nor monitored. The report declares that 95% completed the study with good adherence to randomised diets, and this was assessed with a dietary questionnaire. After 12 months patients on the “Mediterranean” diet experienced a greater reduction in weight and in BMI but these are not statistically evaluated. The low fat group experienced a greater reduction in both diastolic and systolic blood pressure; again these are not compared with any statistical test of significance. Both groups had improved insulin resistance, total cholesterol and triglycerides. This is a pilot study for the moderation of dietary patterns in cardiothoracic transplant patients and it shows that these dietary changes are feasible and can be maintained for 12 months. A definitive study is required.

    Abstract

    Cardiovascular disease (CVD) is common after cardiothoracic transplantation. In a pilot intervention we assessed feasibility and potential effectiveness of dietary interventions to reduce CVD risk. We recruited patients from a tertiary hospital and randomly allocated them to a Mediterranean or low-fat diet for twelve months. Feasibility was measured by patient participation, retention and adherence. Changes in weight, body mass index (BMI), heart rate, blood pressure, glucose markers and blood lipids were assessed using longitudinal Generalized Estimating Equation regression models with 95% confidence intervals. Of 56 heart and 60 lung transplant recipients, 52 (45%) consented, 41 were randomised and 39 (95%) completed the study with good adherence to randomized diets. After 12 months, changes in many risk factors were seen in the Mediterranean and low-fat diet groups respectively including mean BMI (-0.5 vs. 0.0kg/m2 ), systolic/diastolic blood pressure +0.5/+0.1 vs -4.4/-3.5 mmHg; fasting glucose -0.26 vs -0.27 mmol/L; total cholesterol -0.56 vs -0.40 mmol/L. Changes in BMI and systolic/diastolic blood pressure in 49 eligible patients who did not take part were +0.7 kg/m2 and +2.5/+1.8 mmHg. Thus such dietary interventions in cardiothoracic transplant patients are feasible, and potentially beneficial. A definitive nutritional intervention study in these high-risk patients is warranted.
  2. Randomised sham-controlled double-blind trial evaluating remote ischaemic preconditioning in solid organ transplantation: a study protocol for the RIPTRANS trial
    BMJ Open. 2020;10(11):e038340

    Study Details

    Aims: This protocol aims to determine if remote ischaemic preconditioning (RIPC) leads to improvements in function and longevity of transplanted organs in brain-dead organ donors.
    Interventions: Patients will be randomly assigned to either RIPC intervention or sham-intervention.
    Participants: Brain-dead organ donors
    Outcomes: The primary endpoint is the incidence of delayed graft function of renal allografts. The secondary endpoints are short-term functional outcomes of transplanted organs, graft survival and rejection.

    CET Conclusion

    Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
    This protocol describes a randomised controlled trial designed to answer a longstanding question in transplantation: does remote ischaemic preconditioning improve outcomes following solid organ transplantation? The investigators propose a large (500 patient) multicentre, double blind sham-controlled trial, using a thigh tourniquet in deceased brain-dead donors prior to organ procurement. Primary outcome will be delayed-graft function in resulting kidney allografts, and outcome data for all transplanted organs will be collected. The study is powered to show a reduction in delayed graft function from 25% to 15% - an ambitious but clinically relevant endpoint. Of interest, donor family consent will not be sought (as approved by the local ethics committee). This may be more of a challenge in other settings where donor interventions face greater restriction.

    Abstract

    INTRODUCTION Remote ischaemic preconditioning (RIPC) using a non-invasive pneumatic tourniquet is a potential method for reducing ischaemia-reperfusion injury. RIPC has been extensively studied in animal models and cardiac surgery, but scarcely in solid organ transplantation. RIPC could be an inexpensive and simple method to improve function of transplanted organs. Accordingly, we aim to study whether RIPC performed in brain-dead organ donors improves function and longevity of transplanted organs. METHODS AND ANALYSES RIPTRANS is a multicentre, sham-controlled, parallel group, randomised superiority trial comparing RIPC intervention versus sham-intervention in brain-dead organ donors scheduled to donate at least one kidney. Recipients of the organs (kidney, liver, pancreas, heart, lungs) from a randomised donor will be included provided that they give written informed consent. The RIPC intervention is performed by inflating a thigh tourniquet to 300 mm Hg 4 times for 5 min. The intervention is done two times: first right after the declaration of brain death and second immediately before transferring the donor to the operating theatre. The sham group receives the tourniquet, but it is not inflated. The primary endpoint is delayed graft function (DGF) in kidney allografts. Secondary endpoints include short-term functional outcomes of transplanted organs, rejections and graft survival in various time points up to 20 years. We aim to show that RIPC reduces the incidence of DGF from 25% to 15%. According to this, the sample size is set to 500 kidney transplant recipients. ETHICS AND DISSEMINATION This study has been approved by Helsinki University Hospital Ethics Committee and Helsinki University Hospital's Institutional Review Board. The study protocol was be presented at the European Society of Organ Transplantation congress in Copenhagen 14-15 September 2019. The study results will be submitted to an international peer-reviewed scientific journal for publication. Trial registration number: Nct03855722.