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BACKGROUND: Adolescent and young adult (AYA) solid organ transplant (SOT) recipients experience increased rates of rejection and graft loss surrounding the time of health care transition, in part due to poor medication adherence. This study aims to examine the impact of a once-daily formulation of tacrolimus, LCP-tacrolimus (LCPT), on medication adherence for AYA SOT patients. METHODS: A retrospective descriptive analysis was performed for all patients who underwent SOT and were prescribed LCPT after the age of 12 at our single-center pediatric hospital. Medication adherence was assessed via provider documentation and the medication level variability index (MLVI). RESULTS: Twenty-nine patients were prescribed LCPT as part of their immunosuppression regimen. Twenty patients were converted to LCPT from immediate-acting (IR) tacrolimus; six patients were initiated immediately following transplant, and three patients were unable to receive LCPT due to insurance denial. There was a numeric improvement in medication adherence for converted patients when measured by provider assessment (45.0% vs. 68.4%, p = .140) and MLVI (40.0% vs. 71.4%, p = .276), though these did not reach statistical significance. There were no differences in episodes of rejection or adverse effects. LCPT prescription was not associated with decreased medication burden, and two patients transitioned back to IR tacrolimus due to increased cost. CONCLUSIONS: LCPT use did not significantly improve patient adherence; however, it resulted in numerically higher perceived and measured adherence rates. LCPT appears to be safe and effective in the management of SOT recipients; however, it may not affect pill burden and may result in a higher financial burden. Use may be considered for a select group of AYA SOT recipients.
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Rejeição de Enxerto, Imunossupressores, Adesão à Medicação, Transplante de Órgãos, Tacrolimo, Humanos, Tacrolimo/administração & dosagem, Tacrolimo/uso terapêutico, Adolescente, Estudos Retrospectivos, Masculino, Feminino, Imunossupressores/administração & dosagem, Imunossupressores/uso terapêutico, Adulto Jovem, Rejeição de Enxerto/prevenção & controle, Transplantados, Esquema de Medicação, Criança, AdultoRESUMO
OBJECTIVE: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that adversely affects solid organ transplant (SOT) recipients. Published guidelines endorse 5 to 10 mg/kg/day (trimethoprim component) trimethoprim-sulfamethoxazole (TMP-SMX) as the recommended regimen for PJP prevention, often resulting in drug-related adverse effects. We investigated the use of a low-dose TMP-SMX regimen given at 2.5 mg/kg/dose once daily every Monday, Wednesday, and Friday at a large pediatric transplantation center. METHODS: A retrospective chart review was conducted, including patients ages 0 to 21 years who underwent SOT from January 1, 2012, to May 1, 2020, and who were subsequently started on PJP prophylaxis with low-dose TMP-SMX for a minimum of 6 months. The primary end point was the incidence of breakthrough PJP infection on the low-dose TMP-SMX regimen. Secondary end points include the prevalence of adverse effects characteristic of TMP-SMX. RESULTS: A total of 234 patients were included in this study, and 6 of 234 patients (2.6%) were empirically transitioned to treatment dosing of TMP-SMX given a clinical concern for PJP, although none received a diagnosis of PJP. There were 7 patients (2.6%) who experienced hyperkalemia, 36 (13.3%) had neutropenia, and 22 (8.1%) had thrombocytopenia (all grade 4). Clinically significant serum creatinine elevations were seen in 43 of 271 patients (15.9%). Elevations of liver enzymes were seen in 16 of 271 patients (5.9%). Rash was documented in 4 of 271 patients (1.5%). CONCLUSIONS: In our patient cohort, low-dose TMP-SMX preserves the efficacy of PJP prophylaxis while providing an acceptable adverse effect profile.
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Bivalirudin has been used in increasing frequency as an alternative to unfractionated heparin (UFH) in pediatric recipients of Berlin Heart EXCOR ventricular assist devices (VAD). This single-center, retrospective review characterizes anticoagulant trends and outcomes in pediatric Berlin Heart VAD recipients implanted between September 1, 2013, and August 31, 2021, anticoagulated with either bivalirudin or UFH. Thirty-one patients were included; 65% who received bivalirudin and 35% who received UFH. The median age was 2.9 years, included 64.5% females, with 61.3% of patients diagnosed with dilated cardiomyopathy and 25.8% of patients with congenital heart disease. Therapeutic anticoagulation was achieved sooner in the bivalirudin group compared to UFH via anti-Xa monitoring (median 5.7 and 69.5 hours, respectively, p < 0.001). Bivalirudin had a greater number of therapeutic values comparatively to UFH (52% and 24%, respectively; p < 0.001) and a superior number of hours in the therapeutic range (67% and 32%, respectively; p < 0.001). Secondary outcomes were similar among the two groups, apart from greater chest tube output (UFH), more frequent events of elevated plasma-free hemoglobin (bivalirudin), and more frequent elevated inflammatory markers postimplant (bivalirudin). Prevalence of pump replacements secondary to significant clot burden and prevalence of stroke was comparable. In this patient cohort, bivalirudin demonstrated greater anticoagulation stability comparatively to UFH. Multicenter collaboration would be necessary to identify whether this further translates into improved patient outcomes.
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Anticoagulantes, Heparina, Feminino, Humanos, Criança, Pré-Escolar, Masculino, Heparina/uso terapêutico, Anticoagulantes/uso terapêutico, Resultado do Tratamento, Hirudinas, Fragmentos de Peptídeos/uso terapêutico, Estudos Retrospectivos, Proteínas Recombinantes, Antitrombinas/uso terapêuticoRESUMO
INTRODUCTION: Immune cell function assay (ICFA) and CD3 lymphocyte counts have been considered to be useful in discerning the overall intensity of immunosuppression in pediatric orthotopic heart transplant (OHT) recipients. METHODS: The aim of this retrospective analysis was to evaluate trends of ICFA and CD3 lymphocyte counts and their association with adverse outcomes post-OHT. RESULTS: A total of 381 ICFA and 493 CD3 laboratory values obtained in 78 patients within six months post-OHT were analyzed. There were 14 patients treated for biopsy-proven acute rejection, four of whom had ISHLT grade 2R/3A rejection. In patients with rejection versus those without, CD3 and ICFA values were 122 (IQR 74.5-308) cells/mm2 and 224.5 (IQR 132-343.5) ng/ml compared to 231.8 (IQR 68-421) cells/m2 and 191 (IQR 81.5-333) ng/mL (p = NS for both). Twenty-six patients had at least one detectable cytomegalovirus or Epstein-Barr virus DNAemia within the study timeframe. In patients with viremia versus those without, CD3 and ICFA values were 278.5 (IQR 68-552) cells/mm2 and 130 (IQR 48-284) ng/ml compared to 195 (IQR 74.5-402.5) cells/mm2 and 212 (IQR 89-342) ng/ml (p = NS for both). CONCLUSIONS: No association was found between these immune markers and adverse outcomes. In the absence of larger pediatric studies justifying the role of these tests in identifying elevated risk profiles post OHT, we do not recommend their routine use.
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Infecções por Vírus Epstein-Barr, Transplante de Coração, Criança, Humanos, Imunossupressores/efeitos adversos, Estudos Retrospectivos, Infecções por Vírus Epstein-Barr/diagnóstico, Infecções por Vírus Epstein-Barr/etiologia, Herpesvirus Humano 4, Contagem de Linfócitos, Transplante de Coração/efeitos adversos, Rejeição de Enxerto/diagnóstico, Rejeição de Enxerto/etiologia, TransplantadosRESUMO
Treatment outcomes associated with the use of novel COVID-19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30-day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild-moderate COVID-19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment. This IRB-approved, retrospective study included 154 SOTR with a documented positive SARS-CoV-2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR (N = 28) or sotrovimab (N = 51) experienced a lower rate of 30-day hospitalization or death as compared to those who received no specific treatment (N = 75) (p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS-CoV-2 specific agents in the treatment of SOTR with COVID-19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.
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COVID-19, Transplante de Órgãos, Humanos, COVID-19/epidemiologia, SARS-CoV-2, Estudos Retrospectivos, Transplante de Órgãos/efeitos adversos, TransplantadosRESUMO
Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.
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Tratamento Farmacológico da COVID-19, Lactamas, Leucina, Nitrilas, Prolina, Ritonavir, Transplantados, Adulto, Inibidores de Calcineurina/uso terapêutico, Ciclosporina/uso terapêutico, Rejeição de Enxerto/tratamento farmacológico, Rejeição de Enxerto/prevenção & controle, Humanos, Imunossupressores/uso terapêutico, Lactamas/uso terapêutico, Leucina/uso terapêutico, Nitrilas/uso terapêutico, Transplante de Órgãos, Prolina/uso terapêutico, Estudos Retrospectivos, Ritonavir/uso terapêutico, Sirolimo/uso terapêutico, Tacrolimo/uso terapêuticoRESUMO
Pediatric solid organ transplant (SOT) recipients are at a uniquely elevated risk for vaccine preventable illness (VPI) secondary to a multitude of factors including incomplete immunization at the time of transplant, inadequate response to vaccines with immunosuppression, waning antibody titers observed post-SOT, and uncertainty among providers on the correct immunization schedule to utilize post-SOT. Multiple guidelines are in existence from the Infectious Diseases Society of America and the American Society of Transplantation, which require use in adjunct with additional published references. We summarize the present state of SOT vaccine recommendations from relevant resources in tandem with the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices guidance utilizing both routine and rapid catch-up schedules. The purpose of this all-inclusive review is to provide improved clarity on the most optimal pre- and post-transplant vaccine management within a one-stop-shop for the immunizing clinician.
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Transplante de Órgãos, Vacinas, Criança, Humanos, Terapia de Imunossupressão, Transplantados, Vacinação, Vacinas/uso terapêuticoRESUMO
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) predisposes patients for risk of recurrent disease in allografts. METHODS: We report a case of a recipient of an unrelated living donor renal transplant and discuss considerations for utilization of ofatumumab and eplerenone in treatment for recurrent FSGS. RESULTS: The recipient was initially managed with scheduled plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab post-transplant during index hospitalization. With notable recurrence of FSGS noted on kidney transplant biopsy, she was initially treated with additional plasmapheresis sessions leading to downtrend in proteinuria. The patient was then transitioned to LDL-A pheresis, which resulted again in uptrend in proteinuria. This prompted return to scheduled plasmapheresis sessions weekly, leading again to a downtrend in proteinuria. Albumin levels remained within normal range throughout her course. Following initiation of eplerenone and ofatumumab, the patient demonstrated normalization of urine protein:creatinine ratio and remission of FSGS recurrence without need for additional apheresis. CONCLUSIONS: With notable risk of recurrence of FSGS in kidney transplants leading to allograft failure, the use of ofatumumab and eplerenone in conjunction should be considered for management to induce remission.
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Anticorpos Monoclonais Humanizados/uso terapêutico, Anti-Hipertensivos/uso terapêutico, Eplerenona/uso terapêutico, Glomerulosclerose Segmentar e Focal/tratamento farmacológico, Transplante de Rim, Adolescente, Quimioterapia Combinada, Feminino, Glomerulosclerose Segmentar e Focal/cirurgia, Humanos, Imunoglobulinas Intravenosas/uso terapêutico, Plasmaferese, RecidivaRESUMO
Ideological commitment of military personnel has been associated with mitigating trauma and protecting mental health. This pilot study assessed whether Democratic and Republican political affiliation differentially predicted probable posttraumatic stress disorder (PTSD) and symptoms of depression in 62 male Iraq and Afghanistan combat veterans. The Liberalism-Conservatism Scale, the PTSD Checklist-Military Version (PCL-M), and the Patient Health Questionnaire-9 (PHQ-9) were assessment measures. Results revealed that Democratic combat veterans had stronger liberal attitudes than Republican combat veterans (r = 0.95). Moreover, of the 50% of the entire sample higher than the cutoff score of 50 on the PCL-M, 84.8% were Democrats compared with 10.3% of Republicans. On the PHQ-9, 46.9% of Democrats compared with 3.7% of Republicans were higher than the cutoff score of 20. These initial results suggest possible mechanisms of action, including differences in shattered world view assumptions, willingness to disclose emotional concerns, and physiological reactions between Democratic and Republican combat veterans.
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Depressão/psicologia, Política, Transtornos de Estresse Pós-Traumáticos/psicologia, Veteranos/psicologia, Adulto, Campanha Afegã de 2001-, Humanos, Guerra do Iraque 2003-2011, Masculino, Projetos Piloto, Adulto JovemRESUMO
OBJECTIVES: Tracheitis is an infection of the lower respiratory tract and is defined by the US Centers for Disease Control and Prevention (CDC) based on signs and symptoms with no radiographic evidence of pneumonia. One method of treatment involves the use of tobramycin given by nebulizer. The purpose of this study was to compare the safety and efficacy of nebulized gentamicin with nebulized tobramycin. METHODS: This study was conducted in patients under 21 years of age who received greater than or equal to 1 day of gentamicin, 80 mg, or tobramycin, 300 mg, given twice a day by nebulization within the 14-month study period. The primary endpoint was amount of time until the patient no longer met the CDC definition of tracheitis. RESULTS: There were 19 patients who presented with 60 separate encounters. The average age of the patients within the gentamicin group was 7.2 and 5 years old within the tobramycin group. The average duration of time for the gentamicin treatment encounters to be free of the CDC definition of tracheitis was 3.36 days compared to 3.17 days with tobramycin. No adverse effects were observed that were attributable to aminoglycoside nebulization. CONCLUSIONS: No differences were detected between the safety and efficacy of intravenous gentamicin administered twice a day by nebulizer and that of tobramycin inhalation solution given twice daily in children without cystic fibrosis.
