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1.
Transplant Proc ; 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35918194

RESUMO

We used the Bayesian model to show the relationship between prevalence and the test's negative and positive predictive value. We used the above principle to understand the utility of biomarkers for acute rejection under different pretest probability of rejection. Given the test's sensitivity and specificity, the disease prevalence affects the predictive value of the test; the clinical decision to get any test should be considered while understanding the prevalence of disease and cost, risks, benefits of the tests, and available alternatives.

2.
JAMA Surg ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921119

RESUMO

Importance: Despite the acceptance of living-donor liver transplant (LDLT) as a lifesaving procedure for end-stage liver disease, it remains underused in the United States. Quantification of lifetime survival benefit and the Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score range at which benefit outweighs risk in LDLT is necessary to demonstrate its safety and effectiveness. Objective: To assess the survival benefit, life-years saved, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. Design, Setting, and Participants: This case-control study was a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database of 119 275 US liver transplant candidates and recipients from January 1, 2012, to September 2, 2021. Liver transplant candidates aged 18 years or older who were assigned to the wait list (N = 116 455) or received LDLT (N = 2820) were included. Patients listed for retransplant or multiorgan transplant and those with prior kidney or liver transplants were excluded. Exposures: Living-donor liver transplant vs remaining on the wait list. Main Outcomes and Measures: The primary outcome of this study was life-years saved from receiving an LDLT. Secondary outcomes included 1-year relative mortality and risk, time to equal risk, time to equal survival, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. MELD-Na score ranges from 6 to 40 and is well correlated with short-term survival. Higher MELD-Na scores (>20) are associated with an increased risk of death. Results: The mean (SD) age of the 119 275 study participants was 55.1 (11.2) years, 63% were male, 0.9% were American Indian or Alaska Native, 4.3% were Asian, 8.2% were Black or African American, 15.8% were Hispanic or Latino, 0.2% were Native Hawaiian or Other Pacific Islander, and 70.2% were White. Mortality risk and survival models confirmed a significant survival benefit for patients receiving an LDLT who had a MELD-Na score of 11 or higher (adjusted hazard ratio, 0.64 [95% CI, 0.47-0.88]; P = .006). Living-donor liver transplant recipients gained an additional 13 to 17 life-years compared with patients who never received an LDLT. Conclusions and Relevance: An LDLT is associated with a substantial survival benefit to patients with end-stage liver disease even at MELD-Na scores as low as 11. The findings of this study suggest that the life-years gained are comparable to or greater than those conferred by any other lifesaving procedure or by a deceased-donor liver transplant. This study's findings challenge current perceptions regarding when LDLT survival benefit occurs.

3.
4.
Drug Test Anal ; 14(8): 1368-1376, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35332698

RESUMO

Urine is a common matrix for screening for cannabis use. Urine assays typically measure total 11-nor-9-carboxy-Δ9 -tetrahydrocannabinol (THCCOOH) concentrations after hydrolysis cleaves the glucuronide. Urine THCCOOH concentration is adjusted by urine creatinine concentration or specific gravity, to account for variable hydration states. Therefore, we performed a population pharmacokinetic analysis of the urinary THCCOOH excretion, urinary flow rate, and creatinine excretion rate data. Urine was obtained over 168 h from six subjects who smoked low- (15.8 mg) and high-dose (33.8 mg) Δ9 -tetrahydrocannabinol (THC) cigarettes on two occasions. Samples were analyzed for THCCOOH concentration by gas chromatography-mass spectrometry (GC-MS) and volume, time, and creatinine concentration measured. A population pharmacokinetic model of the urinary clearance of THCCOOH was created from these data, and potential covariates of urine creatinine concentration and urine creatinine excretion rate were assessed. Elimination clearance of THCCOOH was estimated as 0.104 ± 0.088 L/min, and its urinary clearance was 0.0022 ± 0.0015 L/min. Total urine excretion of THCCOOH was estimated at 2.3%. Urine flow rate and urine creatinine concentrations were significantly correlated, r2 = 0.35. Creatinine excretion rate was 129.6 ± 71.0 ml/min, and the intrasubject variability was 31%-52% (SD%) during the week. Urinary creatinine excretion rate was a significant covariate for the urinary clearance of THCCOOH. Creatinine clearance is a significant covariate for urinary THCCOOH clearance. Only 2%-3% of bioavailable THC is excreted as THCCOOH and THCCOO-glucuronide via the urine. Correction of urine drug and/or metabolite concentration with urine creatinine concentration or specific gravity may be more problematic than previously appreciated.

5.
Transplantation ; 106(2): 248-256, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33966022

RESUMO

BACKGROUND: The study aims is to use the fragility index (FI) to examine the strength of evidence of randomized controlled trials (RCTs) published in the last decade on kidney transplantation. METHODS: We searched MEDLINE for studies on kidney transplantation. We included the RCTs that compared 2 groups with 1:1 randomization and reported significant P values (<0.05) for a dichotomous outcome and were published in the top 10 transplant journals. We calculated the FI; a calculation used to determine the minimum number of subjects needed to change from a nonevent to an event to make the study results nonsignificant (P ≥ 0.05). RESULTS: Fifty-seven RCTs met our inclusion criteria. The median sample size was 100 participants in each arm, the median number of events was 16 (interquartile range, 8-30) in the intervention group. Among the included trials, 79% were industry-funded, 93% involved medications, and the majority were open label. The median FI was 3 (interquartile range, 1-11). In 43% of the trials, the number of patients reported lost to follow-up was higher than or equal to the FI. Only 4% of the RCTs imputed a value for the missing dichotomous outcome. Furthermore, the median number of subjects who discontinued the trial because of adverse effects was 21, which was greater than the FI in 60% of the RCTs. CONCLUSIONS: The arbitrary classification of results into "significant" and "nonsignificant" based on P value <0.05 should perhaps be interpreted with the help of other statistical parameters and FI is one of them.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Tamanho da Amostra
6.
Clin Transplant ; 36(2): e14517, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34679190

RESUMO

The OPTN/UNOS utilizes the calculated estimated posttransplant survival (EPTS) score as the measure of post-kidney transplant survival to guide allocation of deceased donor kidney transplantation. This score does not include any metric of functional capacity. Peak oxygen uptake (VO2peak ), is an established predictor of survival among both the general and diseased populations. We assessed the association and discriminative capacity of VO2peak and that of EPTS score and all-cause mortality post-kidney transplant. Additionally, we assessed the "mortality risk" lower VO2peak conferred on those patients with low EPTS score. Among a cohort of 293 transplant recipients with at least 3-years post-transplant follow-up, the median VO2peak was 15.0 ml/Kg/min. Lower pre-transplant VO2peak and higher EPTS score conferred higher risk of post-transplant mortality. Among the cohort of "low-risk" patients (patients with EPTS score < 50) those with lower VO2peak had significantly higher risk of mortality (log rank p = 0.045). In fact, the mortality risk among those with low-EPTS (< 50) and low VO2peak  < 12 ml/Kg/min was equivalent to those with high EPTS (> 80) score. We concluded functional capacity as defined by VO2peak is an important reflection of post-transplant survival. VO2peak is able to identify those with low EPTS who have similar survival to that of high EPTS phenotype.


Assuntos
Transplante de Rim , Transplantes , Sobrevivência de Enxerto , Humanos , Rim , Transplante de Rim/efeitos adversos , Transplantados
9.
Clin Transplant ; 35(6): e14305, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33797134

RESUMO

The current American Society of Transplantation (AST) accredited transplant fellowship programs in the United States provide no structured formal training in leadership and administration which is essential for successfully running a transplant program. We conducted a survey of medical directors of active adult kidney and kidney-pancreas transplant programs in the United States about their demographics, training pathways, and roles and responsibilities. The survey was emailed to 183 medical directors, and 123 (67.2%) completed the survey. A majority of respondents were older than 50 years (61%), males (80%), and holding that position for more than 10 years (47%). Only 51% of current medical directors had taken that position after completing a one-year transplant fellowship, and 58% took on the role with no prior administrative or leadership experience. The medical directors reported spending a median 50%-75% of time in clinical responsibilities, 25%-50% of time in administration, and 0%-25% time in research. The survey also captured various administrative roles of medical directors vis-à-vis other transplant leaders. The study, designed to be the starting point of an improvement initiative of the AST, provided important insight into the demographics, training pathways, roles and responsibilities, job satisfaction, education needs, and training gaps of current medical directors.


Assuntos
Internato e Residência , Diretores Médicos , Adulto , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Humanos , Rim , Masculino , Pâncreas , Inquéritos e Questionários , Estados Unidos
10.
Transpl Int ; 34(6): 1083-1092, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33733479

RESUMO

Kidney transplantation is the preferred treatment for kidney failure; however after transplant, reduced physical function, poor self-perceptions, and unemployment are common concerns that remain. This randomized controlled trial compared the effects of a 12-month exercise rehabilitation program (intervention) to standard care alone (control) in kidney transplant recipients. The exercise intervention consisted of a 2 day/week, 60-minute personalized, one-on-one, resistance-based exercise trainings. Eighty participants completed the study (52 intervention vs. 28 control). For individuals unemployed at baseline, there was a 52.3% increase in employment compared to 13.3 % increase in the control group after 12 months (P = <0.0001). For those already employed at baseline, 100% of individuals maintained employment in both groups after 12 months (P = 0.4742). For all comers, there was a positive trend for Global Physical Health (P = 0.0034), Global Mental Health (P = 0.0064), and Physical Function (P = 0.0075), with the intervention group showing greater improvements. These findings suggest the implementation of an exercise rehabilitation program postkidney transplant can be beneficial to increase employment for individuals previously unemployed, improve self-perceived health, physical function, and mental health, overall contributing to better health outcomes in kidney transplant recipients. (Clinicaltrials.gov number: NCT02409901).


Assuntos
Transplante de Rim , Emprego , Exercício Físico , Terapia por Exercício , Humanos , Qualidade de Vida , Transplantados
11.
Transplant Proc ; 53(5): 1548-1553, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33573819

RESUMO

BACKGROUND: Recipients of ABO-incompatible (ABOI) and positive crossmatch (PXM) kidney transplants are at high risk for antibody-mediated acute rejection. Despite aggressive immunosuppression in high-risk patients, the incidence of acute rejection remains considerably higher than in other groups. No published studies have examined plasma concentrations of anti-thymocyte globulin (ATG) in patients undergoing plasma exchange. The objectives of this study were to compare plasma ATG concentrations before and after plasma exchange in ABOI and PXM kidney transplant patients to determine the amount removed. MATERIALS AND METHODS: This prospective pharmacokinetic evaluation enrolled 10 patients undergoing ABOI or PXM kidney transplant at an academic medical center. Blood and waste plasma samples from 5 patients were assayed for total and active ATG concentrations. Patient records were monitored for renal function and rejection rates in the first 6 months post-transplant. RESULTS: Total ATG concentrations decreased a mean of 59.78 ± 13.91% after each plasma exchange session, and active ATG levels decreased a mean of 56.8 ± 17.08%. Mean daily concentrations reflect a lack of expected ATG accumulation. Only 1 of 4 patients had detectable ATG concentrations after 30 days. After 6 months, the incidence of acute rejection in this sample was 44% and graft survival was 89%. CONCLUSIONS: This is the first study to show that plasma exchange removes a substantial amount of ATG in high-risk kidney transplant patients. Based on these results, we believe these high-risk patients have been traditionally underdosed.


Assuntos
Soro Antilinfocitário/sangue , Incompatibilidade de Grupos Sanguíneos/sangue , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/efeitos adversos , Troca Plasmática/estatística & dados numéricos , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Soro Antilinfocitário/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/terapia , Tipagem e Reações Cruzadas Sanguíneas , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática/métodos , Estudos Prospectivos , Adulto Jovem
12.
Transplantation ; 105(8): 1708-1717, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33093406

RESUMO

BACKGROUND: Participant withdrawal from clinical trials occurs for various reasons, predominantly adverse effects or intervention inefficacy. Because these missing participant data can have implications for the validity, reproducibility, and generalizability of study results, when conducting a systematic review, it is important to collect and appropriately analyze missing data information to assess its effects on the robustness of the study results. METHODS: In this methodologic survey of missing participant data reporting and handling in systematic reviews, we included meta-analyses that provided pooled estimates of at least 1 dichotomous intervention outcome of a randomized controlled trial performed in adult kidney transplant subjects. RESULTS: Eighty-three systematic reviews (17 Cochrane and 66 non-Cochrane reviews) met the inclusion criteria. The most common intervention was drugs (80%), with the majority involving immunosuppressant drugs 55% (n = 46), followed by surgery in 14% (n = 12). The median follow-up duration was 12 months (maximum, 240 mo). Intention-to-treat or modified intention-to-treat analysis was reported in 24% (n = 20) of the reviews (76% of Cochrane and 10% of non-Cochrane). Overall, the majority of systematic reviews did not quantify (90% [n = 60] non-Cochrane and 29% [n = 5] Cochrane) or include the reasons for missing participant data (88% [n = 58] non-Cochrane and 24% [n = 4] Cochrane). Eleven percent (n = 9) handled missing participant data, 5% (n = 4) justified the analytical method(s) used to handle it, and 2% (n = 2) performed a sensitivity analysis for it. CONCLUSIONS: Systematic reviews of kidney transplantation provide inadequate information on missing participant data and usually do not handle or discuss the associated risk of bias with it.


Assuntos
Gerenciamento de Dados , Transplante de Rim , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Humanos
15.
Transpl Infect Dis ; 23(3): e13517, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33217091

RESUMO

HIV + patients are commonly accepted for kidney transplantation. However, patients on protease inhibitor (PI)- or cobicistat (cobi)-based regimens have trouble achieving optimal tacrolimus (Tac) levels. Our study compared the ability to achieve target levels using liquid versus immediate-release capsule Tac in kidney transplant patients with HIV on PI- or cobi-based regimens. The study included four kidney transplant patients who were converted to liquid Tac due to inability to achieve acceptable drug levels on the capsule formulation. Tac trough levels were analyzed retrospectively to compare target levels before and after conversion. The individual patient time in the therapeutic range (TTR) was calculated using Rosendaal's linear interpolation method, and the difference between before and after conversion TTR was determined. In combined data, 44.63% of all Tac trough levels were within the target range after conversion to liquid Tac compared to 22.07% prior to conversion (P < .001). Furthermore, 3.31% and 7.44% of Tac trough levels were lower than 3 ng/mL or higher than 12 ng/mL, respectively, after conversion compared to 11.72% (P = .0564) and 24.14% (P < .0001) prior to conversion. The overall mean TTR was 45.1% after conversion to liquid Tac compared to 16.2% prior to conversion (P = .097). Finally, the coefficient of variation for Tac trough levels was 42.6 after conversion compared to 56.4 prior to conversion. A significantly improved ability to achieve target trough Tac levels was achieved with liquid Tac extemporaneous versus capsule formulation in kidney transplant patients with HIV taking a PI- or cobi-based regimen.


Assuntos
Infecções por HIV , Transplante de Rim , Cobicistat , Infecções por HIV/tratamento farmacológico , Humanos , Imunossupressores , Inibidores de Proteases , Estudos Retrospectivos , Tacrolimo
17.
Am J Transplant ; 20(9): 2522-2529, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32185880

RESUMO

Postoperative pain is an outcome of importance to potential living kidney donors (LKDs). We prospectively characterized the prevalence, severity, and patterns of acute or chronic postoperative pain in 193 LKDs at six transplant programs. Three pain measurements were obtained from donors on postoperative Day (POD) 1, 3, 7, 14, 21, 28, 35, 41, 49, and 56. The median pain rating total was highest on POD1 and declined from each assessment to the next until reaching a median pain-free score of 0 on POD49. In generalized linear mixed-model analysis, the mean pain score decreased at each pain assessment compared to the POD3 assessment. Pre-donation history of mood disorder (adjusted ratio of means [95% confidence interval (CI)]: 1.40 [0.99, 1.98]), reporting "severe" on any POD1 pain descriptors (adjusted ratio of means [95% CI]: 1.47 [1.12, 1.93]) and open nephrectomy (adjusted ratio of means [95% CI]: 2.61 [1.03, 6.62]) were associated with higher pain scores across time. Of the 179 LKDs who completed the final pain assessment, 74 (41%) met criteria for chronic postsurgical pain (CPSP), that is, any donation-related pain on POD56. Study findings have potential implications for LKD education, surgical consent, postdonation care, and outcome measurements.


Assuntos
Transplante de Rim , Seguimentos , Humanos , Transplante de Rim/efeitos adversos , Doadores Vivos , Nefrectomia/efeitos adversos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Prevalência
18.
Nephrol Dial Transplant ; 35(7): 1099-1112, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32191296

RESUMO

The construct of frailty was first developed in gerontology to help identify older adults with increased vulnerability when confronted with a health stressor. This article is a review of studies in which frailty has been applied to pre- and post-kidney transplantation (KT) populations. Although KT is the optimal treatment for end-stage kidney disease (ESKD), KT candidates often must overcome numerous health challenges associated with ESKD before receiving KT. After KT, the impacts of surgery and immunosuppression represent additional health stressors that disproportionately impact individuals with frailty. Frailty metrics could improve the ability to identify KT candidates and recipients at risk for adverse health outcomes and those who could potentially benefit from interventions to improve their frail status. The Physical Frailty Phenotype (PFP) is the most commonly used frailty metric in ESKD research, and KT recipients who are frail at KT (~20% of recipients) are twice as likely to die as nonfrail recipients. In addition to the PFP, many other metrics are currently used to assess pre- and post-KT vulnerability in research and clinical practice, underscoring the need for a disease-specific frailty metric that can be used to monitor KT candidates and recipients. Although frailty is an independent risk factor for post-transplant adverse outcomes, it is not factored into the current transplant program risk-adjustment equations. Future studies are needed to explore pre- and post-KT interventions to improve or prevent frailty.


Assuntos
Fragilidade/fisiopatologia , Falência Renal Crônica/cirurgia , Transplante de Rim/normas , Idoso , Humanos , Fatores de Risco
20.
Transplantation ; 104(4): 700-707, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31815910

RESUMO

Noninvasive biomarkers are needed to monitor stable patients following kidney transplantation (KT), as subclinical rejection, currently detectable only with invasive surveillance biopsies, can lead to chronic rejection and graft loss. Several biomarkers have recently been developed to detect rejection in KT recipients, using different technologies as well as varying clinical monitoring strategies defined as "context of use (COU)." The various metrics utilized to evaluate the performance of each biomarker can also vary, depending on their intended COU. As the use of molecular biomarkers in transplantation represents a new era in patient management, it is important for clinicians to better understand the process by which the incremental value of each biomarkers is evaluated to determine its potential role in clinical practice. This process includes but is not limited to an assessment of clinical validity and utility, but to define these, the clinician must first appreciate the trajectory of a biomarker from bench to bedside as well as the regulatory and other requirements needed to navigate this course successfully. This overview summarizes this process, providing a framework that can be used by clinicians as a practical guide in general, and more specifically in the context of subclinical rejection following KT. In addition, we have reviewed available as well as promising biomarkers for this purpose in terms of the clinical need, COU, assessment of biomarker performance relevant to both the need and COU, assessment of biomarker benefits and risks relevant to the COU, and the evidentiary criteria of the biomarker relevant to the COU compared with the current standard of care. We also provide an insight into the path required to make biomarkers commercially available once they have been developed and validated so that they used by clinicians outside the research context in every day clinical practice.


Assuntos
Biomarcadores/metabolismo , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Doenças Assintomáticas , Tomada de Decisão Clínica , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/terapia , Humanos , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento
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