Measurement of health-related quality of life in pediatric organ transplantation recipients: a systematic review of the PedsQL transplant module
Quality of Life Research. 2020;[record in progress]
OBJECTIVE To collect and assess the extant empirical literature assessing disease-specific health-related quality of life (HRQOL) in pediatric transplant recipients using the PedsQL 3.0 Transplant Module (PedsQL-TM) assessment. STUDY DESIGN A systematic search and review procedure was conducted of research reporting use and results of the PedsQL-TM with samples of pediatric heart, liver, kidney, and lung transplantation. Searches were conducted in nine scholarly databases and two additional sources to identify unpublished research. Multiple reviewers screened studies meeting inclusion criteria in accordance with PRISMA guidelines. RESULTS A final sample of nine studies reported findings for the PedsQL-TM with pediatric organ transplant recipients. Most studies relied on either kidney or liver transplant recipients from single pediatric transplant centers. Factor validity of the PedsQL-TM and inter-rater reliability (IRR) between patients and parents have not been adequately determined. Internal consistency reliability was found as acceptable or excellent across multiple studies. PedsQL-TM scores were found to vary with other HRQOL issues, yet few studies examined their association with medication adherence or posttransplant health outcomes. CONCLUSIONS With the goal of enhancing and sustaining HRQOL in pediatric organ transplant recipients, the need for a psychometrically valid and reliable measure of transplant-specific HRQOL is apparent. Research on the PedsQL-TM supports the promise of this measure although future efforts should be taken to examine measurement issues such as factor validity and IRR. Assessing transplant-specific HRQOL in these patients is paramount for their care and appropriate decision-making by patients, families, and the transplant team.
Photodynamic therapy for the prevention and treatment of Actinic Keratosis/Squamous cell carcinoma in solid organ transplant recipients: A systematic review and meta-analysis
Journal of the European Academy of Dermatology & Venereology. 2020;34(2):251-259
Solid organ transplant recipients (sOTR) are at an increased risk of developing cutaneous cancers, especially squamous cell carcinoma (SCC). Photodynamic therapy (PDT) for the prevention and treatment of actinic keratosis (AK)/SCC in sOTR is increasingly prescribed given the increase in solid organ transplantations performed worldwide. PDT has added advantages of superior cosmetic outcomes and good safety profile compared to conventional surgical methods and other topical therapies. We aim to evaluate the role of PDT in the prevention and treatment of AK/SCC in sOTRs. The Cochrane Library, PubMed and Embase Database were searched. Articles reporting PDT outcomes amongst sOTR with or without AK/SCC at baseline were selected. We classified the studies into two categories: (1)PDT as prevention measure and (2)treatment of AK/SCC in sOTR. Primary outcome for the prevention category was three-year incidence of AK/SCC and complete response (CR) of lesions after PDT exposure in the treatment category. Secondary outcomes were cosmesis and adverse reaction in both categories. Pooled results were expressed as risk difference (RD) with corresponding 95% confidence interval (95% CI). Twelve out of 641 articles met our eligibility criteria, out of which 4 RCTs reported the preventive effect of AK/SCC and another 5 RCTs reported the treatment effect of PDT in sOTR. One RCT did not report absolute number of lesions at baseline/end of study for results to be pooled in the quantitative analysis. The remaining three studies were cohort studies reporting treatment and preventive effect of PDT in sOTR. PDT group had a lower incidence as a preventive measure with pooled RD of 0.14(95% CI 0.08-0.19). The CR in PDT was higher in the treatment group with a pooled RD of 0.77(95% CI 0.6-0.94) and 0.50 (95% CI 0.22-0.79) in pre-divided lesional areas and number of lesions respectively. In conclusion, PDT is efficacious for prevention and treatment of AK/SCC in sOTRs. This article is protected by copyright. All rights reserved.
Efficacy and safety of ketoconazole combined with calmodulin inhibitor in solid organ transplantation: A systematic review and meta-analysis
Journal of Clinical Pharmacy & Therapeutics. 2020;45(1):29-34
WHAT IS KNOWN AND OBJECTIVE Calcineurin inhibitors (CNIs) can significantly improve the results of solid organ transplantation regarding graft and patient survival. However, the high cost, chronic nephrotoxicity and other side effects are major challenges for the long-term use of these drugs. Ketoconazole can significantly increase the plasma concentration of CNIs by inhibiting the activity of the cytochrome P450 enzyme. The combination of ketoconazole-CNIs can reduce the cost of medication for patients by reducing the dosage of CNIs, but its safety is still controversial. Therefore, this study was designed to assess the safety and efficacy of this combination. METHODS We performed a systematic literature search in PubMed, Embase, Cochrane Library and clinicaltrials.gov for randomized controlled trials on ketoconazole and CNI (cyclosporin or tacrolimus) co-administration in solid organ transplantation. Two authors independently selected studies, assessed the risk of bias and extracted data. The meta-analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration. PROSPERO registration number: CRD42019118796. RESULTS AND DISCUSSION Five relevant trials with 326 patients were included. Compared with the controls, ketoconazole combined with CNIs can significantly reduce the dose of CNIs in patients receiving solid organ transplantation (WMD = -203.04 mg/day; 95% CI: -310.51 to -95.57, P = .0002). There was no significant difference in serum creatinine between the experimental group and the control group (WMD = -0.19 mg/mL; 95% CI: -0.52 to 0.14, P = .26). In addition, there was no significant difference in the number of rejections between the two groups (OR = 0.58; 95% CI: 0.27 to 1.22, P = .15). WHAT'S NEW AND CONCLUSION The co-administration of ketoconazole and CNIs can significantly reduce the dose of CNIs. This combination may be safely used as a CNI-sparing agent from the time of solid organ transplantation with low-dose ketoconazole, based on the findings of this review.
Heart Transplantation From Brain Dead Donors: A Systematic Review of Animal Models
Transplantation. 2020;[record in progress]
Despite advances in mechanical circulatory devices and pharmacological therapies, heart transplantation is the definitive and most effective therapy for an important proportion of qualifying patients with end-stage heart failure. However, the demand for donor hearts significantly outweighs the supply. Hearts are sourced from donors following brain death, which exposes donor hearts to substantial pathophysiological perturbations that can influence heart transplant success and recipient survival. While significant advances in recipient selection, donor and HTx recipient management, immunosuppression and pretransplant mechanical circulatory support have been achieved, primary graft dysfunction after cardiac transplantation continues to be an important cause of morbidity and mortality.Animal models, when appropriate, can guide/inform medical practice, and fill gaps in knowledge that are unattainable in clinical settings. Consequently, we performed a systematic review of existing animal models that incorporate donor brain death and subsequent heart transplantation, and assessed studies for scientific rigor and clinical relevance. Following literature screening via MEDLINE and Embase, 29 studies were assessed. Analysis of included studies identified marked heterogeneity in animal models of donor brain death coupled to heart transplantation, with few research groups worldwide identified as utilizing these models. General reporting of important determinants of heart transplant success was mixed, and assessment of posttransplant cardiac function was limited to an invasive technique (pressure-volume analysis), which is limitedly applied in clinical settings. This review highlights translational challenges between available animal models and clinical heart transplant settings that is potentially hindering advancement of this field of investigation.
Indications and outcomes of combined heart-liver transplant: A systematic review and met-analysis
Transplant Rev (Philadelphia). 2020;34(2):100517
BACKGROUND Combined heart-liver transplantation (CHLT) has become a viable option for treating concomitant heart and liver failure. However, data are lacking with respect to long-term outcomes. METHODS An electronic search was performed to identify all studies on CHLT. Following application of inclusion and exclusion criteria, a total of seven studies consisting of 99 CHLT patients were included from the original 1864 articles. RESULTS CHLT recipient mean age was 53.0years (95% CI 48.0-58.0), 67.5% of which (95% CI 56.5-76.9) were male. 65.5% (95% CI 39.0-85.0) of patients developed heart failure due to amyloidosis whereas 21.6% (95% CI 12.3-35.2) developed heart failure due to congenital causes. The most common indication for liver transplant was amyloidosis [65.5% (95% CI 39.0-85.0)] followed by liver failure due to hepatitis C [13.8% (95% CI 2.1-54.4)]. The mean intensive care unit length of stay was 8days (95% CI 5-11) with a mean length of stay of 24days (95% CI 17-31). Cardiac allograft rejection within the first year was 24.7% (95% CI 9.5-50.7), including antibody mediated [5% (95% CI 1.7-15.2)] and T-cell mediated rejection [22.7% (95% CI 8.8-47.1)]. Overall survival was 87.5% (95% CI 78.6-93.0) at 1year and 84.3% (95% CI 75.4-90.5) at 5years. CONCLUSIONS CHLT in select patients with coexisting end-stage heart and liver failure appears to offer high survival and low rejection rates.
Exploring failure of antimicrobial prophylaxis and pre-emptive therapy for transplant recipients: a systematic review
BMJ Open. 2020;10(1):e034940
OBJECTIVES Infections remain a threat for solid organ and stem cell transplant recipients. Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients; however, the failure rates of prophylaxis are not negligible. The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy. SETTING This systematic review included prospective randomised controlled trials and prospective single-arm studies. PARTICIPANTS The studies included were on prophylaxis and pre-emptive therapy of opportunistic infections in transplant recipients. Studies were included from databases MEDLINE, CENTRAL and Embase published until October first 2018. PRIMARY AND SECONDARY OUTCOME MEASURES Primary outcome measures were breakthrough infections, adverse events leading to stopping of treatment, switching medication or dose reduction. Secondary outcome measures were acquired resistance to antimicrobials, antifungals or antivirals and death. RESULTS From 3317 identified records, 30 records from 24 studies with 2851 patients were included in the systematic review. Seventeen focused on prophylactic and pre-emptive treatment of cytomegalovirus and seven studies on invasive fungal infection. The main reasons for failure of prophylaxis and pre-emptive therapy were adverse events and breakthrough infections, which were described in 54% (13 studies) and 38% (9 studies) of the included studies, respectively. In 25%, six of the studies, a detailed description of patients who experienced failure of prophylaxis or pre-emptive therapy was unclear or lacking. CONCLUSIONS Our results show that although failure is reported in the studies, the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy. Clearly reporting on patients with a negative outcome should be improved. We have provided guidance on how to detect failure early in a clinical setting in accordance to the results from this systematic review. Prospero registration number: Crd42017077606.
Biatrial vs. bicaval orthotopic heart transplantation: a systematic review and meta-analysis
Annals of Thoracic Surgery. 2020;05:05
BACKGROUND Orthotopic heart transplantation (OHT) is the gold standard treatment in end-stage heart disease. Controversy remains whether bicaval OHT is superior to biatrial OHT in both early and late outcomes. This study aimed to provide an overview of the early and late outcomes in patients who underwent a bicaval or biatrial OHT. METHODS A systematic literature search was performed for articles published before December 2017. Studies comparing adult patients undergoing biatrial OHT and bicaval OHT were included. Early outcomes were pooled in odds ratios and late outcomes were pooled in rate ratios. Late survival was visualized by a pooled Kaplan-Meier curve. RESULTS In the meta-analysis 36 publications were included, counting 3555 patients undergoing biatrial OHT and 3208 patients undergoing bicaval OHT. Early outcomes in mortality, tricuspid regurgitation, mitral regurgitation and permanent pacemaker implantation differed significantly in favor of the bicaval OHT patients. Long-term survival was significantly better in patients undergoing bicaval versus biatrial OHT [hazard ratio 1.32, 95% confidence interval (CI) (1.1 to 1.6), P=0.008]. Also, late tricuspid regurgitation was less frequently seen in the bicaval OHT patients [rate ratio 2.14, CI 95% (1.17 to 3.94), P = 0.014]. CONCLUSIONS This systematic review with meta-analysis shows that, bicaval OHT results in more favorable early and late outcomes for patients undergoing a bicaval OHT compared with biatrial OHT. Therefore, the bicaval OHT should be considered as preferable technique for OHT.
The impact of Centre's heart transplant status and volume on in-hospital outcomes following extracorporeal membrane oxygenation for refractory post-cardiotomy cardiogenic shock: a meta-analysis
BMC Cardiovascular Disorders. 2020;20(1):10
BACKGROUND Postcardiotomy cardiogenic shock (PCS) that is refractory to inotropic support remains a major concern in cardiac surgery and is almost universally fatal unless treated with mechanical support. While reported mortality rates on ECMO vary from center to center, aim of the current report is assess if the outcomes differ between centres according to volume and heart transplantation status. METHODS A systematic search was performed according to PRISMA statement using PubMed/Medline databases between 2010 and 2018. Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and heart transplantation status of the centre. Paediatric and congenital heart surgery-related studies along with those conducted in the setting of veno-venous ECMO for respiratory distress syndrome were excluded. Differences were assessed by means of subgroup meta-analysis and meta-regression. RESULTS Fifty-four studies enrolling N = 4421 ECMO patients were included. Of those, 6 series were performed in non-HTx centres (204 pts.;4.6%). Overall 30-day survival (95% Confidence Intervals) was 35.3% (32.5-38.2%) and did not statistically differ between non-HTx: 33.3% (26.8-40.4%) and HTx centres: 35.7% (32.7-38.8%); Pinteraction = 0.531. There was no impact of centre volume on survival as well: scoef = 0.0006; P = 0.833. No statistical differences were seen between HTx and non-HTx with respect to ECMO duration, limb complications, reoperations for bleeding, kidney injury and sepsis. There were however significantly less neurological complications in the HTx as compared to non-HTx centres: 11.9% vs 19.5% respectively; P = 0.009; an inverse relationship was seen for neurologic complications in centres performing more ECMOs annually scoef = - 0.0066; P = 0.031. Weaning rates and bridging to HTx and/or VADs were higher in HTx facilities. CONCLUSIONS There was no apparent difference in survival after ECMO implantation for refractory PCS according to centre's ECMO volume and transplantation status. Potentially different risk profiles of patients in these centres must be taken account for before definite conclusions are drawn.
Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: A systematic review
American Journal of Transplantation. 2020;06:06
Solid-organ transplantation (SOT) is frequently complicated by cancers, which render immunosuppression challenging. Immune checkpoint inhibitors (CPIs) have emerged as treatments for many cancers. Data are lacking regarding efficacy and rejection risk in the SOT population. We conducted a systematic literature review and analyzed 83 cases of CPI use for cancer in SOT. Two thirds of these patients received anti-PD-1/PD-L1 therapy, 15.7% received anti-CTLA-4 therapy and 10.8% received a combination. Allograft rejection occurred in 39.8% of patients, leading to end-stage organ failure in 71.0% of cases. Outcomes were similar across organs and immunotherapy regimens. The use of immunosuppressants other than steroids, time since transplantation and prior episodes of rejection were associated with the risk of rejection. The median overall survival of patients was 36 weeks. Most of the deaths were related to cancer progression. In non-kidney recipients, graft rejection was strongly associated with worse survival. At the end of the study, 19.3% of the patients were alive, free from rejection and tumor progression. This study highlights the difficult trade-off facing oncologists and transplant specialists managing transplant recipients with cancer, and the need for prospective data and novel biomarkers for identifying the patients likely to benefit from immunotherapy in the SOT setting.
Executive Functioning in Pediatric Solid Organ Transplant Recipients: A Meta-Analytic Review
BACKGROUND Examining executive functioning (EF) post-transplant has become increasingly prevalent, as EF deficits are associated with poor disease-related outcomes and psychosocial functioning. The purpose of the current meta-analysis was to compare overall and domain-specific EF between healthy youth and those with a kidney, heart, or liver transplant, and identify moderating variables related to EF differences between these two groups. METHODS A literature search of PsycINFO, Pubmed, and Medline was conducted for eligible articles published until January 2019. Twenty studies met eligibility criteria and were included in the present meta-analysis. RESULTS Results from the random effects model indicated a significant standardized mean difference in overall EF skills with transplant recipients demonstrating worse EF (g = .40, 95% CI = .29, .50) than healthy youth. Specifically, transplanted youth had worse working memory (g = .33, 95% CI = .01, .66), processing speed (g = .41, 95% CI = .19, .62), attentional control (g = .53, 95% CI = .33, .73), and metacognitive skills (g = .36, 95% CI = .18, .54). Assessment type and time since transplantation were not significant moderators. CONCLUSIONS Pediatric solid organ transplant recipients demonstrate worse overall EF skills and deficits in working memory, processing speed, attentional control, and metacognitive skills. Many children who have undergone solid organ transplantation will require additional support in medical and academic settings due to deficits in various EF domains.