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Pharmacotherapy Jan 2021Tacrolimus therapy in solid organ transplant (SOT) recipients is challenging due to its narrow therapeutic window and pharmacokinetic variability both between patients...
BACKGROUND
Tacrolimus therapy in solid organ transplant (SOT) recipients is challenging due to its narrow therapeutic window and pharmacokinetic variability both between patients and within a single patient. Intrapatient variability (IPV) of tacrolimus trough concentrations has become a novel marker of interest for predicting transplant outcomes. The purpose of this review is to evaluate the association of tacrolimus IPV with graft and patient outcomes and identify interventions to improve IPV in SOT recipients.
METHODS
A systematic review of the literature was performed using PubMed and Embase from database inception to September 20, 2020. Studies were eligible only if they evaluated an association between tacrolimus IPV and transplant outcomes. Both pediatric and adult studies were included. Measures of variability were limited to standard deviation, coefficient of variation, and time in therapeutic range.
RESULTS
Forty-four studies met the inclusion criteria. Studies were published between 2008 and 2020 and were observational in nature. Majority of data were published in adult kidney transplant recipients and identified an association with rejection, de novo donor specific antibody (dnDSA) formation, graft loss, and patient survival. Evaluation of IPV-directed interventions was limited to small preliminary studies.
CONCLUSIONS
High tacrolimus IPV has been associated with poor outcomes including acute rejection, dnDSA formation, graft loss, and patient mortality in SOT recipients. Future research should prospectively explore IPV-directed interventions to improve transplant outcomes.
Topics: Graft Survival; Heart; Humans; Immunosuppressive Agents; Kidney; Liver; Lung; Organ Transplantation; Tacrolimus
PubMed: 33131078
DOI: 10.1002/phar.2480 -
Pharmacotherapy Jan 2021The use of direct-acting oral anticoagulants (DOACs) has increased secondary to the mounting evidence for comparable efficacy and potentially superior safety to vitamin...
The use of direct-acting oral anticoagulants (DOACs) has increased secondary to the mounting evidence for comparable efficacy and potentially superior safety to vitamin K antagonists (VKAs) in the general population. However, insufficient data regarding DOAC use in solid organ transplant (SOT) recipients and numerous pharmacokinetic and pharmacodynamic considerations limit their use in this highly selected patient population. A systematic review of recent clinical evidence on the safety and efficacy of DOACs compared to VKAs in SOT recipients was conducted. Additional considerations including transplant-specific strategies for DOAC reversal and common pharmacokinetic/pharmacodynamic concerns were also reviewed. Although current evidence is limited to single-center retrospective analyses, DOACs, especially apixaban, appear to be a safe and effective alternative to VKAs for SOT recipients with stable graft function and without drug-drug interactions. Reliable data on DOAC reversal at the time of transplant surgery are lacking, and clinicians should consider idarucizumab, andexanet alfa, and other non-specific reversal agents on an individual patient basis. There is no evidence supporting deviations from the Food and Drug Administration labeling recommendations for DOAC dosing in the setting of drug-drug interactions, obesity, and renal function, especially in patients on hemodialysis.
Topics: Administration, Oral; Anticoagulants; Humans; Organ Transplantation
PubMed: 33155327
DOI: 10.1002/phar.2485 -
American Journal of Transplantation :... Oct 2021Medicine-taking among transplant recipients is a complex and ubiquitous task with significant impacts on outcomes. This study aimed to describe the perspectives and...
Medicine-taking among transplant recipients is a complex and ubiquitous task with significant impacts on outcomes. This study aimed to describe the perspectives and experiences of medicine-taking in adult solid organ transplant recipients. Electronic databases were searched to July 2020, and thematic synthesis was used to analyze the data. From 119 studies (n = 2901), we identified six themes: threats to identity and ambitions (impaired self-image, restricting goals and roles, loss of financial independence); navigating through uncertainty and distrust (lacking tangible/perceptible benefits, unprepared for side effects, isolation in decision-making); alleviating treatment burdens (establishing and mastering routines, counteracting side effects, preparing for the unexpected); gaining and seeking confidence (clarity with knowledge, reassurance through collective experiences, focusing on the future outlook); recalibrating to a new normal posttransplant (adjusting to ongoing dependence on medications, in both states of illness and health, unfulfilled expectations); and preserving graft survival (maintaining the ability to participate in life, avoiding rejection, enacting a social responsibility of giving back). Transplant recipients take medications to preserve graft function, but dependence on medications jeopardizes their sense of normality. Interventions supporting the adaptation to medicine-taking and addressing treatment burdens may improve patient satisfaction and capacities to take medications for improved outcomes.
Topics: Adult; Graft Survival; Humans; Interpersonal Relations; Organ Transplantation; Qualitative Research; Transplant Recipients
PubMed: 33866675
DOI: 10.1111/ajt.16613 -
Scientific Reports May 2016Colorectal cancer (CRC) is one of the most predominant solid carcinomas in Western countries. However, there is conflicting information on the effects of soy isoflavone... (Meta-Analysis)
Meta-Analysis Review
Colorectal cancer (CRC) is one of the most predominant solid carcinomas in Western countries. However, there is conflicting information on the effects of soy isoflavone on CRC risk. Therefore, we performed a meta-analysis to assess the association between soy isoflavone consumption and CRC risk in humans using PubMed, Embase, Web of Science, and Cochrane Library databases. A total of 17 epidemiologic studies, which consisted of thirteen case-control and four prospective cohort studies, met the inclusion criteria. Our research findings revealed that soy isoflavone consumption reduced CRC risk (relative risk, RR: 0.78, 95% CI: 0.72-0.85; I(2) = 34.1%, P = 0.024). Based on subgroup analyses, a significant protective effect was observed with soy foods/products (RR: 0.79; 95% CI: 0.69-0.89), in Asian populations (RR: 0.79; 95% CI: 0.72-0.87), and in case-control studies (RR: 0.76; 95% CI: 0.68-0.84). Therefore, soy isoflavone consumption was significantly associated with a reduced risk of CRC risk, particularly with soy foods/products, in Asian populations, and in case-control studies. However, due to the limited number of studies, other factors may affect this association.
Topics: Asia; Case-Control Studies; Clinical Trials as Topic; Colorectal Neoplasms; Female; Humans; Isoflavones; Male; Risk Assessment; Soy Foods; Glycine max
PubMed: 27170217
DOI: 10.1038/srep25939 -
Diagnostics (Basel, Switzerland) Mar 2020This systematic review aimed to investigate the influence of periodontitis on post-transplant IL-6 serum levels of solid organ transplanted patients as compared to... (Review)
Review
This systematic review aimed to investigate the influence of periodontitis on post-transplant IL-6 serum levels of solid organ transplanted patients as compared to healthy subjects. Four databases (PubMed, Scholar, EMBASE, and CENTRAL) were searched up to February 2020 (PROSPERO CRD42018107817). Case-control and cohort studies on the association of IL-6 serum levels with a periodontal status of patients after solid organ transplantation were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Random effects meta-analyses were thoroughly conducted. GRADE assessment provided quality evidence. Four case-control studies fulfilled the inclusion criteria (274 transplant recipients and 146 healthy controls), all of low risk of bias. Meta-analyses revealed significantly higher IL-6 levels in transplanted patients than healthy individuals with low-quality evidence (Mean Difference (MD): 2.55 (95% confidence interval (CI): 2.07, 3.03)). Transplanted patients with periodontitis have higher serum IL-6 levels than transplanted patients without periodontitis with moderate quality evidence (MD: 2.20 (95% CI: 1.00, 3.39)). We found low-quality evidence of higher IL-6 levels than healthy patients in patients with heart and kidney transplant. In these transplanted patients, there was moderate quality evidence that periodontitis is associated with higher IL-6 serum levels. Future research should consider the impact of such a difference in organ failure and systemic complications.
PubMed: 32230707
DOI: 10.3390/diagnostics10040184 -
The Cochrane Database of Systematic... Apr 2021A solution for increasing the number of available organs for transplantation is to encourage more individuals to register a commitment for deceased organ donation.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A solution for increasing the number of available organs for transplantation is to encourage more individuals to register a commitment for deceased organ donation. However, the percentage of the population registered for organ donation remains low in many countries.
OBJECTIVES
To evaluate the benefits and harms of various interventions used to increase deceased organ donor registration.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 11 August 2020 through contact with an Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs), cluster RCTs and quasi-RCTs of interventions to promote deceased organ donor registration. We included studies if they measured self-reported or verified donor registration, intention to donate, intention to register a decision or number of individuals signing donor cards as outcomes.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed retrieved studies and extracted data from included studies. We assessed studies for risk of bias. We obtained summary estimates of effect using a random-effects model and expressed results as risk ratios (RR) (95% confidence intervals; CI) for dichotomous outcomes and mean difference (MD; 95% CI) or standardised mean difference (SMD; 95% CI) for continuous outcomes. In multi-arm trials, data were pooled to create single pair-wise comparisons. Analyses were stratified by specific intervention setting where available.
MAIN RESULTS
Our search strategy identified 46 studies (47 primary articles, including one abstract) comprising 24 parallel RCTs, 19 cluster RCTs and 3 quasi-RCTs. Sample sizes ranged from 138 to 1,085,292 (median = 514). A total of 16 studies measured registration behaviour, 27 measured intention to register/donate and three studies measured both registration behaviour and intention to register. Interventions were delivered in a variety of different settings: schools (14 studies), driver's motor vehicle (DMV) centres (5), mail-outs (4), primary care centres (3), workplaces (1), community settings (7) and general public (12). Interventions were highly varied in terms of their content and included strategies such as educational sessions and videos, leveraging peer leaders, staff training, message framing, and priming. Most studies were rated as having high or unclear risk of bias for random sequence generation and allocation concealment and low risk for the remainder of the domains. Data from 34/46 studies (74%) were available for meta-analysis. Low certainty evidence showed organ donation registration interventions had a small overall effect on improving registration behaviour (16 studies, 1,294,065 participants: RR 1.30, 95% CI 1.19 to 1.43, I2 = 84%), intention to register/donate (dichotomous) (10 studies, 10,838 participants: RR 1.21, 95% CI 1.03 to 1.42, I2 = 91%) and intention to register/donate (continuous) (9 studies, 3572 participants: SMD 0.23, 95% CI 0.11 to 0.36, I2 = 67%). Classroom-based interventions delivered in a lecture format by individuals from the transplant community may be effective at increasing intention to register/donate (3 studies, 675 participants: RR 1.33, 95% CI 1.15 to 1.55, I² = 0%). Community interventions targeting specific ethnic groups were generally effective at increasing registration rates (k = 5, n = 4186; RR 2.14, 95% CI 1.35 to 3.40, I² = 85%), although heterogeneity was high. In particular, interventions delivered in the community by trained peer-leaders appear to be effective (3 studies, 3819 participant: RR 2.09, 95% CI 1.08 to 4.06, I² = 87%), although again, the data lacked robustness. There was some evidence that framing messages (e.g. anticipated regret) and priming individuals (e.g. reciprocity) in a certain way may increase intention to register/donate, however, few studies measured this effect on actual registration. Overall, the studies varied significantly in terms of design, setting, content and delivery. Selection bias was evident and a quarter of the studies could not be included in the meta-analysis due to incomplete outcome data reporting. No adverse events were reported.
AUTHORS' CONCLUSIONS
In our review, we identified a variety of approaches used to increase organ donor registration including school-based educational sessions and videos, leveraging peer leaders in the community, DMV staff training, targeted messaging and priming. The variability in outcome measures used and incompleteness in reporting meant that most data could not be combined for analysis. When data were combined, overall effect sizes were small in favour of intervention groups over controls, however, there was significant variability in the data. There was some evidence that leveraging peer-leaders in the community to deliver organ donation education may improve registration rates and classroom-based education from credible individuals (i.e. members of the transplant community) may improve intention to register/donate, however, there is no clear evidence favouring any particular approach. There was mixed evidence for simple, low-intensity interventions utilising message framing and priming. However, it is likely that interest in these strategies will persist due to their reach and scalability. Further research is therefore required to adequately address the question of the most effective interventions for increasing deceased organ donor registration.
Topics: Bias; Humans; Tissue Donors
PubMed: 35608942
DOI: 10.1002/14651858.CD010829.pub2 -
Experimental and Clinical... Dec 2022There is no systematic review and meta- analysis for pediatric solid-organ transplants in India. The objective of the study was to collect high-evidence data in this... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
There is no systematic review and meta- analysis for pediatric solid-organ transplants in India. The objective of the study was to collect high-evidence data in this regard.
MATERIALS AND METHODS
A systematic review and meta- analysis was performed for pediatric solid-organ transplants in India. We used the search engines of PubMed, Google Scholar, PubMed Central, Embase, and MEDLINE from beginning of data availability until April 26, 2022. Data from 2 participating centers were also used. Analyses were performed by the DerSimonian random model.
RESULTS
Of 50 000 primary searches, only 31 studies were included for analysis. In total, data for pediatric kidney (n = 1057), liver (n = 914), and heart (n = 117) were reported. For the pediatric kidney, the 1-year, 5-year, and 10-year patient survival rates were 96% (range, 93%-99%; I² = 91.17%, H² = 11.33, P < .01), 90% (range, 85%-94%; I² = 93.54%, H² = 15.47, P < .01), and 75% (range, 62%-88%; I² = 97.36%, H² = 37.82, P < .01), respectively. The 1-year, 5-year, and 10-year renal graft survival rates were 93% (range, 90%-96%; I² = 63.82, H² = 2.76, P < .01), 83% (range, 76%-89%; I² = 86.39%, H² = 7.35, P < .01), and 66% (range, 57%-75%; I² = 81.68%, H² = 5.46, P < .01), respectively. The acute rejection rate was 23% (range, 20%-27%; I² = 5.44%, H² = 1.06, P = .39). For the pediatric liver transplant, the 1-year and 5-year survival rates were 92% (range, 89%-95%; I² = 49.96%, H² = 2, P < .04) and 88% (range, 85%-90%; I² = 0; H² = 1, P = .72), respectively.
CONCLUSIONS
The outcomes of pediatric solid-organ transplants in India are comparable to those of the Western world. However, cause of graft loss and patient death is largely attributed to infections, unlike the experiences reported in the West. An effective registry is a primary pillar to expand pediatric solid- organ transplants in India.
Topics: Child; Humans; Graft Rejection; Organ Transplantation; Kidney; Liver; Lung; Graft Survival; Registries
PubMed: 36718004
DOI: 10.6002/ect.2022.0207 -
Hip & Pelvis Sep 2022There is still controversy regarding clinical outcomes following primary hip arthroplasty after solid organ transplantation (SOT). The aim of this study was to determine... (Review)
Review
There is still controversy regarding clinical outcomes following primary hip arthroplasty after solid organ transplantation (SOT). The aim of this study was to determine whether clinical outcomes after hip arthroplasty differ between previous SOT recipients and control subjects with no history of undergoing SOT. We conducted a systematic search of MEDLINE, Embase, and the Cochrane Library for studies comparing the clinical outcomes after hip arthroplasty following SOT published up to January 5, 2022. A comparison of medical and surgery-related complications, as well as the readmission rate and 90-day mortality rate between previous SOT recipients and control subjects was performed. Subgroup analyses of the SOT types, liver transplantation (LT) and kidney transplantation (KT), were also performed. Ten studies that included 3,631,861 cases of primary hip arthroplasty were included; among these, 14,996 patients had previously undergone SOT and 3,616,865 patients had not. Significantly higher incidences of cardiac complications, pneumonia, and acute kidney injury were observed in the SOT group compared with the control group. Regarding surgical complications, a higher transfusion rate was observed in the SOT group. The readmission rate and 90-day mortality rate were also significantly higher in the SOT group. A significantly higher incidence of deep vein thrombosis was observed in the KT subgroup compared with the control group. A higher risk of medical and surgical complications, as well as higher readmission and mortality rates after hip arthroplasty was observed for previous SOT recipients compared to patients with no history of SOT.
PubMed: 36299470
DOI: 10.5371/hp.2022.34.3.127 -
The Cochrane Database of Systematic... Sep 2022Non-adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Adolescent; Adult; Child; Graft Rejection; Humans; Immunosuppressive Agents; Medication Adherence; Organ Transplantation; Transplant Recipients
PubMed: 36094829
DOI: 10.1002/14651858.CD012854.pub2 -
Infection and Drug Resistance 2023Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral... (Review)
Review
Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral preparation approved for invasive mucormycosis. In recent years, population pharmacokinetic studies of ISA have been reported continuously. This paper aims to summarize the characteristics of population pharmacokinetic models of ISA in adults, and provide theoretical basis for individualized administration of ISA. We systematically searched PubMed, Embase, CNKI, Wanfang, VIP and other databases to collect population pharmacokinetic models published from the establishment of the database to March 2023. A total of 6 studies were included in this review, including healthy men and women, invasive fungal infections with malignant tumors or neutropenia, solid organ transplantation. The dose of ISA was 40-400mg for single-dose. The multiple-dose of ISA was 200mg every 8 hours for the first 48 hours and then 200mg once daily. All studies used a two-compartment model, first-order elimination. For oral formulations, except for one study that used first-order absorption, the others used Weibull absorption. Body mass index (BMI) was the most common covariable, followed by total body weight, lean body mass, race, sex, population type (healthy volunteers/patients), and creatinine clearance. These studies included several covariates, and the clearance rate (CL) was similar among populations. In the future, external validation and population pharmacokinetic studies in special populations such as patients with severe liver disease and ECMO support are needed.
PubMed: 38089964
DOI: 10.2147/IDR.S434622