BACKGROUND:

Non-adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to immunosuppressant therapy is a modifiable patient behaviour, and different approaches to increasing adherence have emerged, including multi-component interventions. There has been limited exploration of the effectiveness of interventions to increase adherence to immunosuppressant therapy.

OBJECTIVES:

This review aimed to look at the benefits and harms of using interventions for increasing adherence to immunosuppressant therapies in solid organ transplant recipients, including adults and children with a heart, lung, kidney, liver and pancreas transplant.

SEARCH METHODS:

We searched the Cochrane Kidney and Transplant Register of Studies up to 14 October 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

SELECTION CRITERIA:

All randomised controlled trials (RCTs), quasi-RCTs, and cluster RCTs examining interventions to increase immunosuppressant adherence following a solid organ transplant (heart, lung, kidney, liver, pancreas) were included. There were no restrictions on language or publication type.

DATA COLLECTION AND ANALYSIS:

Two authors independently screened titles and abstracts of identified records, evaluated study quality and assessed the quality of the evidence using the GRADE approach. The risk of bias was assessed using the Cochrane tool. The ABC taxonomy for measuring medication adherence provided the analysis framework, and the primary outcomes were immunosuppressant medication initiation, implementation (taking adherence, dosing adherence, timing adherence, drug holidays) and persistence. Secondary outcomes were surrogate markers of adherence, including self-reported adherence, trough concentration levels of immunosuppressant medication, acute graft rejection, graft loss, death, hospital readmission and health-related quality of life (HRQoL). Meta-analysis was conducted where possible, and narrative synthesis was carried out for the remainder of the results.

MAIN RESULTS:

Forty studies involving 3896 randomised participants (3718 adults and 178 adolescents) were included. Studies were heterogeneous in terms of the type of intervention and outcomes assessed. The majority of studies (80%) were conducted in kidney transplant recipients. Two studies examined paediatric solid organ transplant recipients. The risk of bias was generally high or unclear, leading to lower certainty in the results. Initiation of immunosuppression was not measured by the included studies. There is uncertain evidence of an association between immunosuppressant medication adherence interventions and the proportion of participants classified as adherent to taking immunosuppressant medication (4 studies, 445 participants: RR 1.09, 95% CI 0.95 to 1.20; I² = 78%). There was very marked heterogeneity in treatment effects between the four studies evaluating taking adherence, which may have been due to the different types of interventions used. There was evidence of increasing dosing adherence in the intervention group (8 studies, 713 participants: RR 1.14, 95% CI 1.03 to 1.26, I² = 61%).  There was very marked heterogeneity in treatment effects between the eight studies evaluating dosing adherence, which may have been due to the different types of interventions used. It was uncertain if an intervention to increase immunosuppressant adherence had an effect on timing adherence or drug holidays. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on persistence. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on secondary outcomes. For self-reported adherence, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants classified as medically adherent to immunosuppressant therapy (9 studies, 755 participants: RR 1.21, 95% CI 0.99 to 1.49; I² = 74%; very low certainty evidence). Similarly, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the mean adherence score on self-reported adherence measures (5 studies, 471 participants: SMD 0.65, 95% CI -0.31 to 1.60; I² = 96%; very low certainty evidence). For immunosuppressant trough concentration levels, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants who reach target immunosuppressant trough concentration levels (4 studies, 348 participants: RR 0.98, 95% CI 0.68 to 1.40; I² = 40%; very low certainty evidence). It is uncertain whether an intervention to increase adherence to immunosuppressant medication may reduce hospitalisations (5 studies, 460 participants: RR 0.67, 95% CI 0.44 to 1.02; I² = 64%; low certainty evidence). There were limited, low certainty effects on patient-reported health outcomes such as HRQoL. There was no clear evidence to determine the effect of interventions on secondary outcomes, including acute graft rejection, graft loss and death. No harms from intervention participation were reported.

AUTHORS' CONCLUSIONS:

Interventions to increase taking and dosing adherence to immunosuppressant therapy may be effective; however, our findings suggest that current evidence in support of interventions to increase adherence to immunosuppressant therapy is overall of low methodological quality, attributable to small sample sizes, and heterogeneity identified for the types of interventions. Twenty-four studies are currently ongoing or awaiting assessment (3248 proposed participants); therefore, it is possible that findings may change with the inclusion of these large ongoing studies in future updates.

INTRODUCTION:

Lay-caregivers in organ transplantation (to candidates, recipients, and donors) are essential to pre- and postoperative care, but report significant caregiving-related stressors. This review aims to summarize studies testing nonpharmacological interventions aimed at improving organ transplant caregiver-reported outcomes.

METHODS:

In accordance with PRISMA, we conducted a systematic review (searched PubMed, Embase, Cochrane Central, PsycInfo, and CINAHL, no start-date restriction through 7/1/2021). Quality of comparative studies assessed by ROBS-2 or ROBINS.

RESULTS:

Twelve studies met inclusion. Study designs, interventions, and outcomes varied. Sample sizes were small across caregivers to adults (nine studies, five with caregiver samples ns≤50) and pediatric patients (three studies, caregiver samples ns≤16). Study designs included seven single-arm interventions, two prepost with comparison cohorts, and three randomized-controlled trials. Eight studies included transplant-specific education as the intervention, an interventional component, or as the comparison group. Outcomes included transplant specific knowledge, mental health, and intervention acceptability. Of the nine prepost caregiver assessments and/or comparison groups, four studies demonstrated no statistically significant intervention effects.

CONCLUSION:

Few interventions addressing the needs of organ transplant caregivers have been empirically evaluated. Existing interventions were well-received by caregivers. Given complexities of care in transplantation, research is needed evaluating interventions using rigorous trial methodology with adequate samples.

Obesity might be associated with mortality and clinical outcomes following transplantation; however, the direction of this relationship has not been well-recognized in youth. The aim of this systematic review and meta-analysis was to investigate the association of obesity with post-transplant mortality and clinical outcomes in children and adolescents. Following a systematic search of observational studies published by December 2018 in PubMed, Scopus, Embase, and Cochrane library, 15 articles with total sample size of 50,498 patients were included in the meta-analysis. The main outcome was mortality and secondary outcomes included acute graft versus host disease (GVHD), acute rejection, and overall graft loss. The pooled data analyses showed significantly higher odds of long term mortality (OR 1.30, 95% CI 1.15-1.48, P < 0.001, I2 = 50.3%), short term mortality (OR 1.79, 95% CI 1.19-2.70, P = 0.005, I2 = 59.6%), and acute GVHD (OR 2.13, 95% CI 1.5-3.02, P < 0.001, I2 = 1.7%) in children with obesity. There were no significant differences between patients with and without obesity in terms of acute rejection (OR 1.07, 95% CI 0.98-1.16, P = 0.132, I2 = 7.5%) or overall graft loss (OR 1.04, 95% CI 0.84-1.28, P = 0.740, I2 = 51.6%). This systematic review and meta-analysis has stated higher post-transplant risk of short and long term mortality and higher risk of acute GVHD in children with obesity compared to those without obesity. Future clinical trials are required to investigate the effect of pre-transplant weight management on post-transplant outcomes to provide insights into the clinical application of these findings. This may in turn lead to establish guidelines for the management of childhood obesity in transplantations.

PURPOSE:

There are conflicting results as to the effect of inhaled nitric oxide (iNO) therapy on the risk of acute kidney injury (AKI). The aim of this study was to perform a meta-analysis to assess the updated data.

METHODS:

We systematically searched Web of Science, the Cochrane Library, Wanfang, and PubMed for relevant randomized control trials between database inception and 9/07/2020. Relative risks (RRs) with 95% confidence intervals (CIs) predicting the risk of AKI were extracted to obtain summary estimates using fixed-effects models. The Trim and Fill method was used to evaluate the sensitivity of the results and adjust for publication bias in meta-analysis.

RESULTS:

15 randomized controlled studies from 14 articles involving 1853 patients were included in the study. Analyzing the eligible studies we found: (1) iNO therapy significantly increased the risk of AKI in acute respiratory distress syndrome patients (RR 1.55, 95% CI 1.15-2.10, p = 0.004; I 2 for heterogeneity 0%; P het = 0.649). (2) The use of iNO was associated with reduced AKI risk in patients undergoing cardiac surgery (RR 0.80, 95% CI 0.64-0.99, p = 0.037; I 2 for heterogeneity 0%; P het = 0.528). (3) For organ transplantation recipients, there was no effect of iNO administration on the risk of AKI (RR 0.50, 95% CI 0.16-1.56, p = 0.233; I 2 for heterogeneity 0%; P het = 0.842). The Trim and Fill analysis showed that the overall effect of this meta-analysis was stable.

CONCLUSIONS:

The effect of iNO on AKI risk might be disease-specific. Future RCTs with larger patient populations should aim to validate our findings.

BACKGROUND:

The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID-19).

METHODS:

Systematic review and meta-analysis of data on 202 SOTR with COVID-19, published as case reports or case series. We extracted clinical, hemato-chemical, imaging, treatment, and outcome data.

RESULTS:

Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57 years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID-19 disease. Age (OR 1.07, 95% CI 1-1.11, P = .001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2-8.5, P = .013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008-0.558, P = .012) and tacrolimus continuation (OR 0.3, 95% CI 0.1-0.7, P = .013) were independent predictors of survival.

CONCLUSIONS:

Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID-19. Specifically, receiving tacrolimus could be beneficial for COVID-19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID-19 can be derived from our data.

BACKGROUND:

Efforts to ameliorate the organ shortage have predominantly focused on improving processes and interventions at multiple levels in the organ donation process, but no comprehensive review of hospital-level features contributing to organ donation exists. We undertook a systematic review of the literature to better understand current knowledge and knowledge gaps about hospital-level metrics and interventions associated with successful organ donation.

METHODS:

We searched six electronic databases (PubMed, Embase, CINAHL, Web of Science, Health Business Elite, and Google scholar) and conference abstracts for articles on hospital-level features associated with the final outcome of organ donation (PROSPERO CRD42020187080). Editorials, letters to the editor, and reviews without original data were excluded. Our main outcomes were conversion rate, donation rate, number of organs recovered, number of donors, and authorization rate.

RESULTS:

Our search yielded 2177 studies, and after a thorough assessment, 72 articles were included in this systematic review. Studies were thematically categorized into 1) Hospital-level interventions associated with metrics of organ donation; these included patient- and family-centric measures (i.e. standardized interviews, collaborative requesting and decoupling, and dedicated in-house coordinators), and donor management goals that significantly increased conversion rates by up to 64%; 2) Hospital-level multi-stage programs/policies; which increased authorization rates between 30 and 50%; and 3) Hospital characteristics and qualities; being an academic center, trauma center and larger hospital correlated with higher authorization and conversion rates. Most studies had considerable risk of bias and were of low quality.

CONCLUSIONS:

There is a lack of well-designed studies on hospital-level metrics and interventions associated with organ donation. The use of thoughtful, patient- and family-centric approaches to authorization generally is associated with more organ donors. Future work can build on what is known about the hospital role in organ donation to improve the entire organ donation process.

IMPORTANCE:

Comprehensive data on childhood mycosis fungoides (MF) is scarce.

OBJECTIVE:

To describe clinical features, immunophenotypes, various treatment options, and prognosis of MF in children and adolescents.

EVIDENCE REVIEW:

This systematic review searched MEDLINE via PubMed, Embase, Cochrane, and Scopus databases in October 2019. The search terms included mycosis fungoides, infant, children, and adolescent. No filter for the publication period was used, but studies written in a language other than English were excluded. Reference lists of the relevant articles were also searched manually. Case series and case reports were included if data on childhood MF were extractable. The Asan Medical Center database for cases of childhood MF was also searched. Patients were treated from January 1, 1990, to July 31, 2019, and were younger than 20 years at the time of diagnosis. The methodologic quality of the included studies was assessed with items from the Newcastle-Ottawa scale. Data were analyzed from December 9, 2019, to September 4, 2020.

FINDINGS:

A total of 571 unique patients were included. The mean (SD) age at diagnosis was 12.2 (4.2) years; at onset, 8.6 (4.2) years. The female-to-male ratio was 1:1.6 (350 male patients [61.3%]). Among 522 patients with data available at diagnosis, stage 1 disease constituted 478 cases (91.6%), followed by stage 2 (39 [7.5%]) and stage 4 (5 [1.0%]). Among the 567 patients with data available, the most common variant of MF was the hypopigmented form (309 [54.5%]), followed by classic MF (187 [33.0%]). The MF lesions were predominantly the CD4+ and CD8+ immunophenotype in 99 (49.5%) and 79 (39.5%) of 200 patients, respectively. Among the treatments, narrowband UV-B was the most frequently used (150 of 426 [35.2%]). Most patients were alive with the disease (185 of 279 [66.3%]); 83 of 279 (29.8%) were in complete remission; and 11 of 279 (3.9%) had died by the last follow-up. A longer time from onset to diagnosis (hazard ratio [HR], 1.24; 95% CI, 1.06-1.45), granulomatous slack skin (HR, 12.25; 95% CI, 1.99-75.26), granulomatous MF (HR, 14.59; 95% CI, 1.31-162.00), a history of organ transplant (HR, 10.15; 95% CI, 0.98-105.37), and stage 2 disease at the time of diagnosis (HR, 10.22; 95% CI, 2.94-35.50) were associated with worse outcomes.

CONCLUSIONS AND RELEVANCE:

The findings of this review suggest that there is often a significant delay until the establishment of a correct diagnosis of childhood MF, which may be detrimental to the prognosis.

INTRODUCTION:

A solid organ transplant (SOT) recipient, already taking immunosuppression, may represent the ideal candidate for vascularised composite allograft transplantation (VCA). However, concerns have been raised about the potential risk of SOT loss or the need for increased immunosuppression to sustain the VCA. This systematic review examines all published cases of SOT recipients who have received a VCA to establish associated morbidity and immunosuppression requirements.

METHODS:

A systematic review was performed in accordance with the PRISMA guidelines. The PubMed, MEDLINE and EMBASE databases were searched for original articles published between January 1997 and May 2019. Only articles relating to patients who had received both a VCA and SOT with a reported follow up of greater than six months were included.

RESULTS:

Fifteen articles were identified, including data from 39 VCAs in 37 patients. There was no increase in the number of SOT rejection episodes, complications such as post-transplant lymphoproliferative disorder or graft versus host disease, de novo donor specific HLA antibodies or short-term risks to the recipient when compared with SOT in isolation. One child required a sustained increase in their baseline immunosuppression following bilateral hand transplantation.

CONCLUSIONS:

In this small heterogeneous cohort, the addition of a VCA to a SOT does not appear to increase the short-term risks to the SOT or the patient with comparable results to SOT in isolation. However, data are often poorly reported and longer-term follow up and uniform reporting of outcomes would be beneficial to more accurately assess the safety profile of combining VCA with SOT.

PURPOSE:

We performed a systematic review of the literature to identify the ideal blood pressure (BP) target in neurologically deceased organ donors to optimize outcomes of recipient organ function and survival, and organs transplanted per donor.

SOURCE:

We searched MEDLINE and EMBASE from inception to December 2018 for studies that evaluated BP targets in neurologically deceased organ donors. A two-step review process with three independent reviewers was employed. We assessed the risk of bias and applied Grading of Recommendations Assessment, Development, and Evaluation methodology to evaluate the certainty of the evidence by outcome.

PRINCIPAL FINDINGS:

Twelve cohort studies were included in our final analysis. Seven studies showed that hypotension was associated with worse post-transplant graft function or survival, while three studies found no association between hypotension and post-transplant graft function or survival. Two other studies showed no association between hypotension and organs transplanted per donor. Overall, six of the identified studies had serious risk of bias.

CONCLUSION:

A systolic BP less 90 mmHg may be associated with graft dysfunction in kidney recipients, but this is based on very low certainty in evidence. Although an ideal and universal BP target in neurologically deceased organ donors is not clearly identifiable in the literature, this could reflect the complexity of donor hemodynamics and the need for individualized targets for different organs. Further prospective research is required to address these questions.