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2.
Prog Transplant ; 34(1-2): 47-52, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38465633

RESUMEN

Introduction: Delayed graft function in kidney transplant is associated with an increased risk of rejection and graft loss. Use of rabbit antithymocyte globulin induction in delayed graft function has been correlated with less rejection compared to basiliximab, but optimal dosing remains unknown. Program Evaluation Aims: The purpose of this evaluation was to retrospectively assess the short-term effectiveness and tolerability of a clinical protocol that increased the net state of immunosuppression in delayed graft function kidney transplant recipients using cumulative 6 mg/kg rabbit antithymocyte globulin induction. Design: This retrospective cohort included 88 kidney transplant recipients with delayed graft function, transplanted between January 2017 and March 2021, who either received cumulative 4.5 mg/kg pre-protocol or 6 mg/kg post-protocol rabbit antithymocyte globulin. Outcomes evaluated were biopsy-proven acute rejection and incidence of graft loss, infection, and cytopenia at 6 months. Results: A significant reduction of biopsy-proven acute rejection incidence occurred post-protocol implementation (10/33, 30.3% vs 6/55, 10.9%; P = .04). Of those with rejection, significantly less post-protocol patients were classified as acute cellular rejection (9/10, 90.0% vs 2/6, 33.3%; P = .04). No death-censored graft loss was observed in either group. Rates of cytopenia and infection were similar pre- versus post-protocol implementation. Conclusion: Increasing the exposure to rabbit antithymocyte globulin and maintenance immunosuppression in delayed graft function kidney transplant recipients was tolerable and significantly reduced rejection occurrence at 6 months.


Asunto(s)
Suero Antilinfocítico , Funcionamiento Retardado del Injerto , Rechazo de Injerto , Inmunosupresores , Trasplante de Riñón , Humanos , Suero Antilinfocítico/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Rechazo de Injerto/prevención & control , Funcionamiento Retardado del Injerto/epidemiología , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Adulto , Conejos , Supervivencia de Injerto/efectos de los fármacos , Animales , Resultado del Tratamiento , Anciano
3.
Prog Transplant ; 33(3): 261-265, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37491859

RESUMEN

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may be effective in reducing body weight and hemoglobin A1c (HbA1c) post-kidney transplantation. Limited literature exists on use of these agents outside of kidney transplant. The purpose of this program evaluation was to evaluate the safety and efficacy of SGLT2i in kidney, liver, and lung transplant recipients. Methods: This was a retrospective program evaluation of adult kidney, liver, and lung transplant recipients between August 31, 2016 and July 31, 2021. Patients initiated on SGLT2i for diabetes for a minimum of 90 days with at least 1 follow-up appointment were screened for inclusion. Outcomes were compared between SGLT2i initiation to nadir values 3-12-months post-initiation. Outcomes included change in hemoglobin A1c, fasting blood glucose, actual body weight, and body mass index. Safety outcomes included adverse effects, cardiovascular events, death-censored graft loss, and all-cause mortality. Results: Forty-nine patients met inclusion criteria, (26 liver, 18 kidney, 4 lung, and 1 simultaneous liver-kidney recipient). The median time from transplant to SGLT2i initiation was 1216 days (IQR 524-2256). Glycemic and weight loss outcomes showed a statistically significant benefit from SGLT2i use. Total safety outcome incidence was minimal at 12 months. No patient experienced myocardial infarctions, graft loss, or mortality at 3-12 months. One incidence of urinary tract infection and stroke occurred each. The most common adverse effects included hypotension and hypoglycemia. Conclusion: This program evaluation demonstrated that SGLT2i can be used safely in solid organ transplant recipients. These agents can provide an additional non-insulin agent for post-transplant diabetes mellitus management in solid organ transplant.


Asunto(s)
Trasplante de Riñón , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Receptores de Trasplantes , Humanos , Peso Corporal , Hemoglobina Glucada , Hipoglucemiantes/uso terapéutico , Estudios Retrospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
4.
Prog Transplant ; 33(1): 90-94, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36503331

RESUMEN

INTRODUCTION: Limited evidence exists on the effect of isavuconazonium sulfate and posaconazole delayed release tablets on tacrolimus dose-to-concentration ratios in lung transplant recipients. PROJECT AIMS: The purpose of this evaluation was to assess the impact of novel triazoles on tacrolimus dose-to-concentration ratios. DESIGN: This retrospective review included lung transplant recipient ≥18 years of age from January 1, 2017 to October 1, 2020 who received either posaconazole delayed release tablets or isavuconazonium sulfate for. A paired analysis evaluated outcomes pre-triazole and post-triazole initiation. RESULTS: Forty-one patients met evaluation criteria for inclusion. A total of 34 of 41 patients received posaconazole delayed release tablets. Of these patients, 22 of 34 were transitioned from previous triazole to posaconazole delayed release tablets and experienced a 47% reduction in tacrolimus dose-to-concentration ratio. Twelve patients were newly initiated on posaconazole delayed release tablets and experienced a 50% reduction in tacrolimus dose-to-concentration ratios. Although not statistically significant, a 30% reduction in tacrolimus dose-to-concentration ratio was observed when transitioning to isavuconazonium sulfate from previous triazole therapy. CONCLUSION: Limited data exists to provide guidance on tacrolimus dose adjustments with initiation and conversion of novel triazoles, however, this evaluation provides more knowledge on the drug interaction with novel triazoles and tacrolimus.


Asunto(s)
Antifúngicos , Tacrolimus , Humanos , Antifúngicos/uso terapéutico , Triazoles/uso terapéutico , Comprimidos
5.
Prog Transplant ; 32(4): 357-362, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36039519

RESUMEN

Introduction: Given the negative outcomes associated with uncontrolled diabetes mellitus, non-insulin therapies with glycemic, cardiovascular, and weight-loss benefits in the general population, such as the glucagonlike peptide-1 receptor agonists (GLP1-RA) have become a more alluring therapeutic option in transplant populations. However, limited evidence exists to demonstrate its safety and efficacy in solid organ transplant. Methods: This program evaluation included adult kidney, liver, lung transplant recipients initiated on a GLP1-RA for diabetes mellitus management for a minimum of 3 months, had at least one follow-up visit after starting therapy, and had at least one hemoglobin A1c (HbA1c) level drawn between 3-12 months after GLP1-RA initiation. Outcomes were assessed at time of initiation of GLP1-RA (baseline) and 3-12 months post-initiation. Nadir values between 3-12 months were utilized to assess outcomes. Results: One-hundred eighteen patients met study inclusion criteria. Seventy-percent of patients received a kidney transplant, 19.5% received a liver transplant, and 6.8% received a lung transplant. A statistically significant difference was observed in median fasting blood glucose and HbA1c at baseline to 3-12-month nadir (P < 0.0001). A significant weight loss benefit was also observed. The rate of adverse drug reactions was low. Seven-percent of patients experienced nausea, 4.2% developed pancreatitis, and 7.1% reported having had at least one hypoglycemic event. Discussion: This is the largest study evaluating GLP1-RA in organ transplantation and demonstrates GLP1-RA is both safe and effective. Further assessment on long-term use of these agents on cardiovascular and renal outcomes is still needed.


Asunto(s)
Diabetes Mellitus Tipo 2 , Trasplante de Órganos , Adulto , Humanos , Hemoglobina Glucada/análisis , Hemoglobina Glucada/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/uso terapéutico , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico
6.
Pediatr Transplant ; 26(6): e14304, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35531710

RESUMEN

BACKGROUND: Efforts have been concentrated on improving vaccination administration during the pretransplant evaluation period. However, concern for human leukocyte antigen (HLA) sensitization subsequent to vaccination exists. METHODS: A retrospective review of pediatric kidney transplant candidates (PKTCs) ≤18 years old who had received vaccinations between February 1, 2017 and November 30, 2019 was conducted. Emergence of de novo anti-HLA antibody (HLA-Ab) 3-4 weeks postvaccinations detected by the Luminex single antigen bead assay (SAB) was evaluated. Outcomes assessed included change in the HLA-Ab mean fluorescence intensity (MFI) ≥25% from baseline, and change in preexisting HLA-Ab MFI strength, categorized as weak: 1000-2999; moderate: 3000-9999; and strong: ≥10 000. RESULTS: Sixty vaccinations were administered to 14 patients. Forty-one potential de novo HLA-Ab were detected in five patients. After additional antibody panel testing, 5/41 potential de novo HLA-Ab were determined to be HLA specific; the remaining 36 were deemed nonspecific. The 5 de novo HLA-Ab were observed in three patients and were deemed weak antibody (Ab). Median MFI showed a significant increase for nonspecific Ab, but not de novo HLA-Ab. Median MFI values were deemed transient at 7-10 week follow-up. No HLA-donor-specific Ab developed posttransplant in the patients who developed de novo HLA-Ab. CONCLUSION: Vaccination resulted in a transient increase in non-HLA-specific Ab. The majority of responses were non-HLA specific, hypothesized to be related to denatured antigens on single antigen beads. These data suggest limited clinical impact of vaccinations on the emergence of de novo HLA-Ab.


Asunto(s)
Trasplante de Riñón , Adolescente , Formación de Anticuerpos , Niño , Rechazo de Injerto/prevención & control , Antígenos HLA , Humanos , Isoanticuerpos , Vacunación
7.
Prog Transplant ; 32(1): 67-72, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34859711

RESUMEN

INTRODUCTION: Recurrent urinary tract infections remain a challenge in solid organ transplant and have a negative impact on morbidity/mortality. PROJECT AIM: The purpose of this program evaluation was to determine the impact of methenamine on recurrent urinary tract infection in kidney and liver-kidney transplant recipients. DESIGN: This retrospective review included patients > 18 years of age who received a kidney or liver-kidney transplant. Patients were divided into the following groups: (1) Methenamine therapy initiation received methenamine for ≥ 180 days or (2) Non-methenamine therapy: did not receive recurrent urinary tract infection prophylaxis. A total of 60 patients were included. RESULTS: When comparing outcomes between methenamine therapy initiation and non-methenamine therapy group, a significant reduction in the rate of recurrent urinary tract infection was reported in the methenamine therapy initiation group (0.6 vs 1.3 per 180 patient days follow-up, P = 0.0005). A significant reduction was also noted with rate of asymptomatic bacteriuria, treatment failures, bacteremia, hospitalizations due to recurrent urinary tract infection, multi-drug resistant organism isolated, and the average duration of antibiotic use. A significant difference in the time to failure of methenamine therapy initiation versus non-methenamine therapy is noted up to 180 patient-days follow-up (RR 1.56, P = 0.0019). CONCLUSION: This evaluation supported methenamine therapy for recurrent urinary tract infection in kidney and liver-kidney transplant. The most significant impact of methenamine recurrent urinary tract infection was seen in the first 30 days after initiation.


Asunto(s)
Bacteriuria , Trasplante de Riñón , Infecciones Urinarias , Femenino , Hipuratos/uso terapéutico , Humanos , Masculino , Metenamina/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/prevención & control
8.
Prog Transplant ; 32(1): 73-77, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34874192

RESUMEN

INTRODUCTION: Posttransplant diabetes mellitus (PTDM) can increase morbidity and mortality in liver transplant recipients. Although hepatitis C seropositivity is a known risk factor for PTDM, the impact of viremia versus no viremia at time of transplant is unknown. PROJECT AIMS: This program evaluation sought to compare PTDM in hepatitis C seropositive patients with and without viremia at the time of liver transplant. DESIGN: This single-center retrospective review included adult hepatitis C seropositive liver transplant recipients transplanted between January 1, 2010 to September 5, 2017 without pretransplant diabetes. Primary outcome was PTDM within 1 year. Secondary outcomes included evaluating 1-year posttransplant death-censored graft loss, mortality, and metabolic outcomes. RESULTS: Fifty-seven liver transplant recipients with hepatitis C were included, of which 53% (n = 30) were viremic at transplant. Baseline characteristics were similar between groups. Significantly more patients with pretransplant viremia developed PTDM by 1-year posttransplant compared to the patients without viremia (43% vs 11%, P = 0.01). There were no differences between groups outside of more patients with viremia requiring antihypertensives by 1-year posttransplant compared to patients without viremia (57% vs 22%, P = 0.01). CONCLUSION: Liver transplant patients with hepatitis C viremia at transplant were more likely to develop PTDM at 1 year compared to those without pretransplant viremia. This is an added consideration when deciding the timing of direct-acting antiviral (DAA) utilization in the context of liver transplant for hepatitis C seropositive patients.


Asunto(s)
Diabetes Mellitus , Hepatitis C Crónica , Hepatitis C , Trasplante de Hígado , Adulto , Antivirales/uso terapéutico , Diabetes Mellitus/epidemiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Receptores de Trasplantes , Viremia/tratamiento farmacológico , Viremia/epidemiología
9.
Handb Exp Pharmacol ; 272: 139-164, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34796380

RESUMEN

Immunosuppression in lung transplantation is an area devoid of robust clinical data. This chapter will review the history of immunosuppression in lung transplantation. Additionally, it will evaluate the three classes of induction, maintenance, and rescue immunosuppression in detail. Induction immunosuppression in lung transplantation aims to decrease incidence of lung allograft rejection, however infectious risk must be considered when determining if induction is appropriate and which agent is most favorable. Similar to other solid organ transplant patient populations, a multi-drug approach is commonly prescribed for maintenance immunosuppression to minimize single agent drug toxicities. Emphasis of this review is placed on key medication considerations including dosing, adverse effects, and drug interactions. Clinical considerations will be reviewed per drug class given available literature. Finally, acute cellular, antibody mediated, and chronic rejection are reviewed.


Asunto(s)
Rechazo de Injerto , Trasplante de Pulmón , Anticuerpos , Rechazo de Injerto/prevención & control , Humanos , Terapia de Inmunosupresión , Inmunosupresores/efectos adversos , Trasplante de Pulmón/efectos adversos
10.
Front Physiol ; 12: 746509, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34646164

RESUMEN

A limitation of simulated space radiation studies is that radiation exposure is not the only environmental challenge astronauts face during missions. Therefore, we characterized behavioral and cognitive performance of male WAG/Rij rats 3 months after sham-irradiation or total body irradiation with a simplified 5-ion mixed beam exposure in the absence or presence of simulated weightlessness using hindlimb unloading (HU) alone. Six months following behavioral and cognitive testing or 9 months following sham-irradiation or total body irradiation, plasma and brain tissues (hippocampus and cortex) were processed to determine whether the behavioral and cognitive effects were associated with long-term alterations in metabolic pathways in plasma and brain. Sham HU, but not irradiated HU, rats were impaired in spatial habituation learning. Rats irradiated with 1.5 Gy showed increased depressive-like behaviors. This was seen in the absence but not presence of HU. Thus, HU has differential effects in sham-irradiated and irradiated animals and specific behavioral measures are associated with plasma levels of distinct metabolites 6 months later. The combined effects of HU and radiation on metabolic pathways in plasma and brain illustrate the complex interaction of environmental stressors and highlights the importance of assessing these interactions.

11.
Prog Transplant ; 31(3): 236-241, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34155947

RESUMEN

The solid organ transplant community is slow to adopt the routine practice of using direct oral anticoagulants. Rivaroxaban and apixaban share common metabolic pathways with tacrolimus. This study aimed to clarify the impact of rivaroxaban/apixaban on tacrolimus troughs. Fifty solid organ transplant recipients with concomitant use of tacrolimus and rivaroxaban/apixaban were retrospectively assessed for changes in tacrolimus troughs and dose. Average dose-adjusted tacrolimus troughs and average tacrolimus total daily doses prior to and after rivaroxaban/apixaban initiation were compared. Subgroup analyses evaluating rivaroxaban and apixaban individually were performed. Rivaroxaban was prescribed to 18 recipients, and apixaban was prescribed to 32 recipients. Transplanted organs included kidney (n = 22), lung (n = 18), liver (n = 7), simultaneous pancreas and kidney (n = 1), and simultaneous kidney and liver (n = 2). The median doseadjusted tacrolimus trough and tacrolimus total daily dose prior to rivaroxaban/apixaban initiation was 2.15 ng/mL/mg (IQR 1.17, 3.37) and 4 mg (IQR 1.88, 6.25), respectively. The median dose-adjusted tacrolimus trough and tacrolimus total daily dose after rivaroxaban/apixaban initiation was 2.16 ng/mL/mg (IQR 1.24, 4.10) and 3.55 mg (IQR 1.5, 6.35), respectively. No significant difference was found between average dose-adjusted tacrolimus troughs or tacrolimus total daily doses before and after rivaroxaban/apixaban initiation or in the individual subgroup analyses for rivaroxaban/apixaban. It is unlikely that initiating rivaroxaban/apixaban affects tacrolimus troughs or requires tacrolimus dose adjustment. This study does not elucidate if tacrolimus affects rivaroxaban/apixaban pharmacokinetics or pharmacodynamics.


Asunto(s)
Rivaroxabán , Tacrolimus , Humanos , Pirazoles , Piridonas , Estudios Retrospectivos
12.
Environ Health Perspect ; 129(5): 57009, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-34009016

RESUMEN

BACKGROUND: Exposure to secondhand smoke (SHS) is a risk factor for developing sporadic forms of sporadic dementia. A human tau (htau) mouse model is available that exhibits age-dependent tau dysregulation, neurofibrillary tangles, neuronal loss, neuroinflammation, and oxidative stress starting at an early age (3-4 months) and in which tau dysregulation and neuronal loss correlate with synaptic dysfunction and cognitive decline. OBJECTIVE: The goal of this study was to assess the effects of chronic SHS exposure (10 months' exposure to ∼30 mg/m3) on behavioral and cognitive function, metabolism, and neuropathology in mice. METHODS: Wild-type (WT) and htau female and male mice were exposed to SHS (90% side stream, 10% main stream) using the SCIREQ® inExpose™ system or air control for 168 min per day, for 312 d, 7 d per week. The exposures continued during the days of behavioral and cognitive testing. In addition to behavioral and cognitive performance and neuropathology, the lungs of mice were examined for pathology and alterations in gene expression. RESULTS: Mice exposed to chronic SHS exposure showed the following genotype-dependent responses: a) lower body weights in WT, but not htau, mice; b) less spontaneous alternation in WT, but not htau, mice in the Y maze; c) faster swim speeds of WT, but not htau, mice in the water maze; d) lower activity levels of WT and htau mice in the open field; e) lower expression of brain PHF1, TTCM1, IGF1ß, and HSP90 protein levels in WT male, but not female, mice; and f) more profound effects on hippocampal metabolic pathways in WT male than female mice and more profound effects in WT than htau mice. DISCUSSION: The brain of WT mice, in particular WT male mice, might be especially susceptible to the effects of chronic SHS exposure. In WT males, independent pathways involving ascorbate, flavin adenine dinucleotide, or palmitoleic acid might contribute to the hippocampal injury following chronic SHS exposure. https://doi.org/10.1289/EHP8428.


Asunto(s)
Exposición a Riesgos Ambientales , Hipocampo , Contaminación por Humo de Tabaco , Animales , Cognición , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Hipocampo/metabolismo , Humanos , Masculino , Redes y Vías Metabólicas , Ratones , Tauopatías , Contaminación por Humo de Tabaco/efectos adversos , Contaminación por Humo de Tabaco/estadística & datos numéricos , Proteínas tau
13.
Radiat Res ; 196(1): 31-39, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33857301

RESUMEN

During space missions, astronauts experience acute and chronic low-dose-rate radiation exposures. Given the clear gap of knowledge regarding such exposures, we assessed the effects acute and chronic exposure to a mixed field of neutrons and photons and single or fractionated simulated galactic cosmic ray exposure (GCRsim) on behavioral and cognitive performance in mice. In addition, we assessed the effects of an aspirin-containing diet in the presence and absence of chronic exposure to a mixed field of neutrons and photons. In C3H male mice, there were effects of acute radiation exposure on activity levels in the open field containing objects. In addition, there were radiation-aspirin interactions for effects of chronic radiation exposure on activity levels and measures of anxiety in the open field, and on activity levels in the open field containing objects. There were also detrimental effects of aspirin and chronic radiation exposure on the ability of mice to distinguish the familiar and novel object. Finally, there were effects of acute GCRsim on activity levels in the open field containing objects. Activity levels were lower in GCRsim than sham-irradiated mice. Thus, acute and chronic irradiation to a mixture of neutrons and photons and acute and fractionated GCRsim have differential effects on behavioral and cognitive performance of C3H mice. Within the limitations of our study design, aspirin does not appear to be a suitable countermeasure for effects of chronic exposure to space radiation on cognitive performance.


Asunto(s)
Conducta Animal/efectos de la radiación , Cognición/efectos de la radiación , Radiación Cósmica , Neutrones , Fotones , Animales , Aspirina/administración & dosificación , Condicionamiento Clásico , Miedo , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H
14.
J Intensive Care Med ; 35(10): 1039-1043, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30373445

RESUMEN

PURPOSE: To compare clinical response of intermittent bolus versus continuous infusion neostigmine for acute colonic pseudo-obstruction (ACPO). Acute colonic pseudo-obstruction occurs due to reduced colonic parasympathetic activity. Neostigmine is an acetylcholinesterase inhibitor that increases frequency of smooth muscle contraction by increasing acetylcholine at autonomic nervous system synapses. Although these administration modalities have been studied separately, they have never been compared. METHODS: This retrospective study compared bolus versus continuous infusion neostigmine for ACPO. The primary outcome was initial clinical response, defined as bowel movement (BM) within 4 hours of bolus dose or 24 hours of initiation of continuous infusion. Secondary outcomes included time to BM, bowel diameter reduction at 24 hours, incidence of bradycardia, additional neostigmine requirements, and need for colonic decompression or surgical intervention. RESULTS: Seventy-five patients were included (bolus n = 37; infusion n = 38). Median total 24-hour neostigmine dose was 2.0 mg (interquartile range [IQR]: 2.0-2.6) with bolus and 9.6 mg (IQR: 6.3-9.6) with continuous infusion. Initial clinical response was similar (infusion 81.6% vs bolus 62.2%, P = .06), but continuous infusion was associated with greater bowel diameter reduction (73.7% vs 40.5%, P = .004). Bolus administration had shorter time to BM (1.4 vs 3.5 hours, P = .0478) and increased need for colonic decompression (67.6% vs 39.5%, P = .0148). Bolus dosing was associated with less bradycardia (13.5% vs 39.5%, P = 0.011), with no difference in atropine usage (10.8% vs 5.3%, P = .43). CONCLUSION: Initial clinical response was similar between groups; however, continuous infusion neostigmine was associated with greater bowel diameter reduction at 24 hours. Bolus administration resulted in less bradycardia; however, given the lack of difference in atropine use, clinical significance is unknown. This study is the first to compare bolus versus continuous infusion neostigmine for ACPO. Further studies are needed to confirm findings.


Asunto(s)
Inhibidores de la Colinesterasa/administración & dosificación , Seudoobstrucción Colónica/tratamiento farmacológico , Esquema de Medicación , Infusiones Parenterales , Neostigmina/administración & dosificación , Enfermedad Aguda , Adulto , Anciano , Bradicardia/inducido químicamente , Bradicardia/epidemiología , Seudoobstrucción Colónica/fisiopatología , Defecación/efectos de los fármacos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
16.
Pediatr Transplant ; 23(8): e13590, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31617318

RESUMEN

AMR is a major cause of graft loss after kidney transplantation. We evaluated a retrospective cohort of 13 pediatric kidney transplant patients diagnosed with active AMR. All 13 patients were treated with plasmapheresis (PP), IVIg, and rituximab. Anti-HLA DSAs were measured at the time of transplantation, AMR diagnosis, 30 days post-rejection treatment, 90 days post-rejection treatment, and 24 ± 12 months post-AMR. A total of 68 DSAs were identified from 13 patients at the time of active AMR diagnosis. The primary objective of this study was to differentiate treatment response rates between class I and class II anti-HLA DSA post-AMR treatment. Overall, DSAs were significantly reduced at 30 days, and the reduction was sustained at 90 days post-treatment, even for class II anti-HLA and strongly positive DSAs. A significant difference between class I and class II anti-HLA DSA was observed at 30 days; however, between class significance was lost at 90-day follow-up due to continued class II anti-HLA DSA treatment response. Low DSA strength was predictive of treatment response. eGFR demonstrated significant improvement 90 days after AMR diagnosis compared to the initial value at the time of AMR, and the effect was sustained for 12 months. These results suggest that the AMR treatment is effective in pediatric kidney transplant recipients with an early diagnosis of active AMR across both class I and class II anti-HLA DSAs.


Asunto(s)
Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Antígenos HLA/inmunología , Isoanticuerpos/inmunología , Trasplante de Riñón , Donantes de Tejidos , Receptores de Trasplantes , Biopsia , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Pronóstico , Estudios Retrospectivos
17.
Front Mol Biosci ; 6: 77, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31552266

RESUMEN

In this study, an untargeted metabolomics approach was used to assess the effects of proton irradiation (1 Gy of 150 MeV) on the metabolome and DNA methylation pattern in the murine hippocampus and left ventricle of the heart 22 weeks following exposure using an integrated metabolomics-DNA methylation analysis. The integrated metabolomics-DNA methylation analysis in both tissues revealed significant alterations in aminoacyl-tRNA biosynthesis, but the direction of change was tissue-dependent. Individual and total amino acid synthesis were downregulated in the left ventricle of proton-irradiated mice but were upregulated in the hippocampus of proton-irradiated mice. Amino acid tRNA synthetase methylation was mostly downregulated in the hippocampus of proton-irradiated mice, whereas no consistent methylation pattern was observed for amino acid tRNA synthetases in the left ventricle of proton-irradiated mice. Thus, proton irradiation causes long-term changes in the left ventricle and hippocampus in part through methylation-based epigenetic modifications. Integrated analysis of metabolomics and DNA methylation is a powerful approach to obtain converging evidence of pathways significantly affected. This in turn might identify biomarkers of the radiation response, help identify therapeutic targets, and assess the efficacy of mitigators directed at those targets to minimize, or even prevent detrimental long-term effects of proton irradiation on the heart and the brain.

18.
Diabetes Spectr ; 31(2): 167-176, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29773937

RESUMEN

PURPOSE: Post-transplant diabetes mellitus (PTDM) can lead to significant morbidity and cardiovascular death with a functioning graft. A paucity of literature exists regarding glycemic control in solid-organ transplant (SOT) recipients, including pharmacist management of PTDM. This study aimed to assess the impact of pharmacist interventions on diabetes management in a pharmacist-run PTDM clinic. METHODS: This was a single-center, prospective, observational study of 24 adult SOT recipients enrolled in a pilot pharmacist-managed PTDM clinic from 1 January to 30 June 2015. RESULTS: Improvements were realized in markers of glycemic control, including changes in A1C, average daily self-monitoring of blood glucose (SMBG) results, fasting SMBG results, and pre-lunch SMBG results from enrollment through at least 3 months of follow-up. Median A1C decreased significantly from 8.05% (interquartile range [IQR] 6.33-11.75) at baseline to 6.45% (IQR 6.05-7.3) at the last follow-up encounter (P = 0.0010). Average daily SMBG results decreased significantly from a median of 191 mg/dL (IQR 138-232 mg/dL) at baseline to 125 mg/dL (IQR 111-167 mg/dL) at the final encounter (P = 0.0023). Median fasting and pre-lunch SMBG results decreased significantly from 153 mg/dL (IQR 117-208 mg/dL) at baseline to 120 mg/dL (IQR 102-134 mg/dL) (P = 0.0064) and from 212 mg/dL (IQR 159-258 mg/dL) to 122 mg/dL (IQR 110-169 mg/dL) (P = 0.0161), respectively. Changes from baseline in other SMBG values, lipid levels, and BMI were not statistically significant. CONCLUSION: The results of our study demonstrate that a pharmacist-managed PTDM clinic can significantly affect glycemic control in SOT recipients.

19.
Pediatr Transplant ; 21(6)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28677269

RESUMEN

Pediatric transplant recipients commonly have deficient vaccination status at the time of transplantation. Utilizing transplant pharmacists to improve vaccination rates has not previously been described. This single-center, retrospective study evaluated the impact of transplant pharmacist interventions on the completion rate of vaccination schedules at time of kidney transplant. Patients who received pharmacist-led vaccination recommendations prior to transplant were compared to patients without pharmacist recommendations. Forty-seven pediatric patients were included: 24 intervention patients and 23 control patients. The median percentage of up-to-date vaccinations at time of transplant was significantly higher in intervention group (91%; IQR 86%-100%) vs. control group (80%; IQR 71%-80%) (P<.0001). The median change in up-to-date vaccinations from time of evaluation to time of transplant was also significantly higher in the intervention group (7.5%) compared to the control group (0%) (P<.0001). There was no difference in live vaccination rates. No patients in either group were readmitted for a vaccine-preventable disease within 6 months post-transplant. With pharmacist intervention, significantly more patients were up to date with vaccination schedules at the time of transplant. These results suggest that a transplant pharmacist may serve as a valuable resource to increase vaccination schedule compliance between time of evaluation and transplantation.


Asunto(s)
Promoción de la Salud/métodos , Trasplante de Riñón , Cooperación del Paciente/estadística & datos numéricos , Servicios Farmacéuticos , Cuidados Preoperatorios/métodos , Vacunación/estadística & datos numéricos , Adolescente , Niño , Preescolar , Protocolos Clínicos , Femenino , Promoción de la Salud/organización & administración , Humanos , Masculino , Servicios Farmacéuticos/organización & administración , Periodo Preoperatorio , Estudios Retrospectivos
20.
Hosp Pharm ; 52(4): 280-285, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28515507

RESUMEN

Background: Tech-Check-Tech (TCT) allows a pharmacy technician to perform the final check of medications prepared by another technician. The effect of a TCT program on the time required to process medications in a hospital pharmacy has not been previously reported. Objective: To evaluate the effect of implementing a TCT program on the time required to prepare, check, and deliver medications to automated medication supply systems (AMSS) located throughout an academic medical center. Methods: The primary outcome was the difference in mean total time required to process AMSS medications between pre- and post-implementation periods. Forty-five days pre-TCT implementation was compared to 45 days post implementation. To assess the effect of the TCT program on pharmacist-time allocation, median times required to verify stat and routine medication orders in the computerized physician order entry (CPOE) system were analyzed. Results: Mean total time spent processing AMSS medications was 24.16 ± 2.98 hours and 16.79 ± 2.65 hours for the pre- and post-TCT implementation periods, respectively (difference of 7.37 hours; 95% CI, 6.19-8.55 hours; p < 0.0001). Median verification times for stat medication orders were 5 (interquartile range [IQR], 2-12) minutes before and 4 (IQR, 2-9) minutes after TCT implementation (p < 0.0001). For routine orders, median verification times were 12 (IQR, 4-30) minutes before and 7 (IQR, 3-18) minutes after implementation (p < 0.0001). Conclusions: The total time required to process AMSS medications was significantly reduced after a TCT program was implemented in an academic medical center. Pharmacist medication order verification times were also significantly reduced.

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