Nonadherence to medications is a leading cause of morbidity in children and adolescents who have ... more Nonadherence to medications is a leading cause of morbidity in children and adolescents who have had a transplant, yet there are no published data about the use of different methods for detecting whether these children are taking their medications. There are also no published data about the age of transition at which a child assumes responsibility over taking the medications. This information is important if interventions to improve adherence are contemplated. We present an analysis of data obtained in the first year of the implementation of an adherence assessment protocol at a pediatric liver transplant clinic in a tertiary medical care center. Data were obtained for children and adolescents who had a liver transplant at least 1 year before the assessments took place. We used 5 adherence detection methods. The 4 subjective methods were self-reported, scaled questionnaires answered by nurses, physicians, caregivers, and patients. For the objective method, a standard deviation (SD) was calculated for tacrolimus blood levels obtained from each patient over time. A higher SD suggests increased variation among patients' blood levels and hence more erratic medication taking. We also asked the patients and caregivers who is responsible for taking the medications and what are the reasons for not taking them. The medical outcome measures were biopsy-proven rejection episodes, number of biopsies regardless of the results, number of hospital admissions, and number of in-patient days. An analysis of 81 cases (258 assessments) revealed that the only method that predicted the medical outcome variables (biopsy-proven rejection and number of biopsies) was the SD of medication blood levels. Patients', clinicians', and caregivers' reports were not predictive. Clinicians' ratings of adherence were not correlated with patients' or caregivers'. The transition of responsibility for medication taking occurred approximately at the age of 12 years. Forgetfulness was cited as the most common reason for nonadherence by patients and caregivers; medication side effects were not frequently cited. Our results indicate that clinical impression is not sufficient to determine whether children and adolescents are taking their medications after they have had a liver transplant. An objective assessment method should be used. Interventions targeting adherence should address the child's increasing role beginning in early adolescence. A clinical protocol incorporating objective assessments of adherence could potentially be implemented in other settings. It could form the basis for the evaluation of efficacy of interventions seeking to improve adherence to medications.
The Israel Medical Association Journal Imaj, Sep 1, 2011
BACKGROUND: Primary liver masses in children may require intervention because of symptoms or conc... more BACKGROUND: Primary liver masses in children may require intervention because of symptoms or concern about malignant transformation.OBJECTIVES: To review the management and outcome of benign liver masses in children.METHODS: We conducted a retrospective chart review of children with liver masses referred to our institution during the period 1997-2009.RESULTS: Benign liver masses were identified in 53 children. Sixteen of these children (30%) had hemangioma/infantile hepatic hemangioendothelioma (IHH) and 15 (28%) had focal nodular hyperplasia. The remainder had 6 cysts, 4 hamartomas, 3 nodular regenerative hyperplasia, 2 adenomas, 2 vascular malformations, and one each of polyarteritis nodosa, granuloma, hepatic hematoma, lymphangioma, and infarction. Median age at presentation was 6 years, and 30 (57%) were female. Masses were initially noticed on imaging studies performed for unrelated symptoms in 33 children (62%), laboratory abnormalities consistent with liver disease in 11 (21%), and palpable abdominal masses in 9 (17%). Diagnosis was made based on characteristic radiographic findings in 31 (58%), but histopathological examination was required for the remaining 22 (42%). Of the 53 children, 27 (51%) were under observation while 17 (32%) had masses resected. Medications targeting masses were used in 9 (17%) and liver transplantation was performed in 4 (8%). The only death (2%) occurred in a child with multifocal IHH unresponsive to medical management and prior to liver transplant availability.CONCLUSIONS: IHH and focal nodular hyperplasia were the most common lesions. The majority of benign lesions were found incidentally and diagnosed radiologically. Expectant management was sufficient in most children after diagnosis, although surgical intervention including liver transplant was occasionally necessary.
An eight-yr-old female with a history of multifocal lymphangioendotheliomatosis and thrombocytope... more An eight-yr-old female with a history of multifocal lymphangioendotheliomatosis and thrombocytopenia presented for MVT. The patient had multiple vascular lesions in the skin and stomach in infancy. Although her cutaneous lesions resolved with vincristine and methylprednisolone, her gastric lesions persisted. Eight yr later, she was diagnosed with portal hypertension and decompensating liver function despite therapy with bevacizumab, propranolol, furosemide, and spironolactone. Upon presentation, she was found to have a Kasabach-Merritt-like coagulopathy in association with multiple lesions in her GI tract and persistent gastric lesions. Although treatment with methylprednisolone and sirolimus normalized her coagulation factors and d-dimer levels, she never developed sustained improvement in her thrombocytopenia. Her liver function continued to deteriorate and she developed hepatorenal syndrome. Given better outcomes after OLT in comparison with MVT, she underwent OLT, with the plan ...
To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoent... more To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. Fifty percent (68/137) of infants had TB <2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB <2.0 group vs TB ≥2 (86% vs 20%, P < .0001). Infants with TB ≥2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of…
ABSTRACT Background: This single center, retrospective study details a hybrid strategy combining ... more ABSTRACT Background: This single center, retrospective study details a hybrid strategy combining short course antiviral prophylaxis and preemptive CMV and EBV PCR monitoring. Methods: 122 pediatric liver transplant recipients were followed for a mean of 2.4 years post transplant. All subjects received a brief course of postoperative ganciclovir, followed by monthly CMV and EBV PCRs. Ganciclovir was reinitiated with CMV viremia or disease. Immunosuppression was reduced if subjects developed a detectable EBV viral load, with initiation of ganciclovir at the discretion of the transplant team. Results: 43 CMV seronegative recipients received a seropositive graft and were considered high risk for CMV complications, and 79 subjects were routine risk. CMV viremia was detected in 34.4% of subjects and was more frequent in high risk than routine risk recipients (58.1% vs. 21.8%, p=0.0001). 12 subjects (9.8%) developed CMV disease (8 high risk vs. 4 routine risk, p=0.03). 3 subjects developed acute rejection in the 6 months following detection of CMV, but CMV was preceded by rejection in 13 subjects. 57 subjects (46.7%) developed a detectable EBV PCR viral load, and 8 (6.5%) developed post transplant lymphoproliferative disorder (PTLD). Subjects with a higher peak EBV PCR value were at greater risk for PTLD. There were no mortalities secondary to CMV or EBV. 38.5% of subjects were spared antiviral medications beyond their initial postoperative prophylaxis. Conclusions: These results suggest that a hybrid preventative approach for CMV and EBV is safe and effective but requires aggressive monitoring of immunosuppression. Patients who receive intensified immunosuppression for the treatment of acute rejection are at increased risk for CMV and may require more extended prophylaxis and closer monitoring.
The Israel Medical Association journal : IMAJ, 2011
Primary liver masses in children may require intervention because of symptoms or concern about ma... more Primary liver masses in children may require intervention because of symptoms or concern about malignant transformation. To review the management and outcome of benign liver masses in children. We conducted a retrospective chart review of children with liver masses referred to our institution during the period 1997-2009. Benign liver masses were identified in 53 children. Sixteen of these children (30%) had hemangioma/infantile hepatic hemangioendothelioma (IHH) and 15 (28%) had focal nodular hyperplasia. The remainder had 6 cysts, 4 hamartomas, 3 nodular regenerative hyperplasia, 2 adenomas, 2 vascular malformations, and one each of polyarteritis nodosa, granuloma, hepatic hematoma, lymphangioma, and infarction. Median age at presentation was 6 years, and 30 (57%) were female. Masses were initially noticed on imaging studies performed for unrelated symptoms in 33 children (62%), laboratory abnormalities consistent with liver disease in 11 (21%), and palpable abdominal masses in 9 (...
Nonadherence to treatment recommendations, especially when associated with transition to adult ca... more Nonadherence to treatment recommendations, especially when associated with transition to adult care providers, account, by some estimates, for most organ rejections and death in long-term pediatric survivors of solid organ transplantations. It is therefore imperative that providers become familiar with the issues related to those major risks and ways to address them. It is possible, and important, to routinely measure adherence to medications by using one of several available and proven methods of surveillance. There are numerous ways to improve adherence, and it is in fact possible to improve adherence and therefore outcomes in the transplant setting. The transition to adult services is a vulnerable period. The authors believe that it is possible to improve the transition process, and suggestions are presented in this review. However, solid research into interventions to improve transition is lacking. Nonadherence to medical recommendations is prevalent and leads to poor outcomes f...
Liver Kidney Microsomal type 1 (LKM1) antibody, the diagnostic marker of autoimmune hepatitis typ... more Liver Kidney Microsomal type 1 (LKM1) antibody, the diagnostic marker of autoimmune hepatitis type 2, is also found in a proportion of patients with hepatitis C virus infection (HCV). It is detected conventionally by the subjective immunofluorescence technique. Our aim was to establish a simple and objective enzyme-linked immunosorbent assay (ELISA) that measures antibodies to cytochrome P4502D6 (CYP2D6), the target
This review highlights the fact that in the current era, the focus of success in pediatric transp... more This review highlights the fact that in the current era, the focus of success in pediatric transplantation has moved from short-term to long-term patient and graft survival as well as achieving 'normality' after transplantation. Advances in surgical techniques, organ allocation, intensive care management, laboratory tests, interventional and diagnostic radiology, immunosuppressive, and antiviral drugs have allowed a larger number of pediatric liver transplant recipients to progress into adulthood. To achieve 'normality' several medical and psychosocial factors have become the target of intervention. Attaining optimal linear growth and puberty after transplant is important as is minimizing adverse events associated with immunosuppression. Special considerations are important in the adolescent transplant recipient, particularly adherence to medical recommendations. Liver transplant recipients have been reported to have below average intelligence quotient at school entry and significantly lower health-related quality of life than healthy controls and appropriate interventions need to be put in place early. Successful long-term outcomes in transplantation are contingent on successful transition from pediatric to adult healthcare services. Achieving operational tolerance remains a goal. In conclusion, this review outlines the myriad issues around pediatric transplantation that can be addressed so that the transplant recipient may experience a 'normal' quality of life.
Nonadherence to medications is a leading cause of morbidity in children and adolescents who have ... more Nonadherence to medications is a leading cause of morbidity in children and adolescents who have had a transplant, yet there are no published data about the use of different methods for detecting whether these children are taking their medications. There are also no published data about the age of transition at which a child assumes responsibility over taking the medications. This information is important if interventions to improve adherence are contemplated. We present an analysis of data obtained in the first year of the implementation of an adherence assessment protocol at a pediatric liver transplant clinic in a tertiary medical care center. Data were obtained for children and adolescents who had a liver transplant at least 1 year before the assessments took place. We used 5 adherence detection methods. The 4 subjective methods were self-reported, scaled questionnaires answered by nurses, physicians, caregivers, and patients. For the objective method, a standard deviation (SD) was calculated for tacrolimus blood levels obtained from each patient over time. A higher SD suggests increased variation among patients' blood levels and hence more erratic medication taking. We also asked the patients and caregivers who is responsible for taking the medications and what are the reasons for not taking them. The medical outcome measures were biopsy-proven rejection episodes, number of biopsies regardless of the results, number of hospital admissions, and number of in-patient days. An analysis of 81 cases (258 assessments) revealed that the only method that predicted the medical outcome variables (biopsy-proven rejection and number of biopsies) was the SD of medication blood levels. Patients', clinicians', and caregivers' reports were not predictive. Clinicians' ratings of adherence were not correlated with patients' or caregivers'. The transition of responsibility for medication taking occurred approximately at the age of 12 years. Forgetfulness was cited as the most common reason for nonadherence by patients and caregivers; medication side effects were not frequently cited. Our results indicate that clinical impression is not sufficient to determine whether children and adolescents are taking their medications after they have had a liver transplant. An objective assessment method should be used. Interventions targeting adherence should address the child's increasing role beginning in early adolescence. A clinical protocol incorporating objective assessments of adherence could potentially be implemented in other settings. It could form the basis for the evaluation of efficacy of interventions seeking to improve adherence to medications.
The Israel Medical Association Journal Imaj, Sep 1, 2011
BACKGROUND: Primary liver masses in children may require intervention because of symptoms or conc... more BACKGROUND: Primary liver masses in children may require intervention because of symptoms or concern about malignant transformation.OBJECTIVES: To review the management and outcome of benign liver masses in children.METHODS: We conducted a retrospective chart review of children with liver masses referred to our institution during the period 1997-2009.RESULTS: Benign liver masses were identified in 53 children. Sixteen of these children (30%) had hemangioma/infantile hepatic hemangioendothelioma (IHH) and 15 (28%) had focal nodular hyperplasia. The remainder had 6 cysts, 4 hamartomas, 3 nodular regenerative hyperplasia, 2 adenomas, 2 vascular malformations, and one each of polyarteritis nodosa, granuloma, hepatic hematoma, lymphangioma, and infarction. Median age at presentation was 6 years, and 30 (57%) were female. Masses were initially noticed on imaging studies performed for unrelated symptoms in 33 children (62%), laboratory abnormalities consistent with liver disease in 11 (21%), and palpable abdominal masses in 9 (17%). Diagnosis was made based on characteristic radiographic findings in 31 (58%), but histopathological examination was required for the remaining 22 (42%). Of the 53 children, 27 (51%) were under observation while 17 (32%) had masses resected. Medications targeting masses were used in 9 (17%) and liver transplantation was performed in 4 (8%). The only death (2%) occurred in a child with multifocal IHH unresponsive to medical management and prior to liver transplant availability.CONCLUSIONS: IHH and focal nodular hyperplasia were the most common lesions. The majority of benign lesions were found incidentally and diagnosed radiologically. Expectant management was sufficient in most children after diagnosis, although surgical intervention including liver transplant was occasionally necessary.
An eight-yr-old female with a history of multifocal lymphangioendotheliomatosis and thrombocytope... more An eight-yr-old female with a history of multifocal lymphangioendotheliomatosis and thrombocytopenia presented for MVT. The patient had multiple vascular lesions in the skin and stomach in infancy. Although her cutaneous lesions resolved with vincristine and methylprednisolone, her gastric lesions persisted. Eight yr later, she was diagnosed with portal hypertension and decompensating liver function despite therapy with bevacizumab, propranolol, furosemide, and spironolactone. Upon presentation, she was found to have a Kasabach-Merritt-like coagulopathy in association with multiple lesions in her GI tract and persistent gastric lesions. Although treatment with methylprednisolone and sirolimus normalized her coagulation factors and d-dimer levels, she never developed sustained improvement in her thrombocytopenia. Her liver function continued to deteriorate and she developed hepatorenal syndrome. Given better outcomes after OLT in comparison with MVT, she underwent OLT, with the plan ...
To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoent... more To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. Fifty percent (68/137) of infants had TB <2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB <2.0 group vs TB ≥2 (86% vs 20%, P < .0001). Infants with TB ≥2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of…
ABSTRACT Background: This single center, retrospective study details a hybrid strategy combining ... more ABSTRACT Background: This single center, retrospective study details a hybrid strategy combining short course antiviral prophylaxis and preemptive CMV and EBV PCR monitoring. Methods: 122 pediatric liver transplant recipients were followed for a mean of 2.4 years post transplant. All subjects received a brief course of postoperative ganciclovir, followed by monthly CMV and EBV PCRs. Ganciclovir was reinitiated with CMV viremia or disease. Immunosuppression was reduced if subjects developed a detectable EBV viral load, with initiation of ganciclovir at the discretion of the transplant team. Results: 43 CMV seronegative recipients received a seropositive graft and were considered high risk for CMV complications, and 79 subjects were routine risk. CMV viremia was detected in 34.4% of subjects and was more frequent in high risk than routine risk recipients (58.1% vs. 21.8%, p=0.0001). 12 subjects (9.8%) developed CMV disease (8 high risk vs. 4 routine risk, p=0.03). 3 subjects developed acute rejection in the 6 months following detection of CMV, but CMV was preceded by rejection in 13 subjects. 57 subjects (46.7%) developed a detectable EBV PCR viral load, and 8 (6.5%) developed post transplant lymphoproliferative disorder (PTLD). Subjects with a higher peak EBV PCR value were at greater risk for PTLD. There were no mortalities secondary to CMV or EBV. 38.5% of subjects were spared antiviral medications beyond their initial postoperative prophylaxis. Conclusions: These results suggest that a hybrid preventative approach for CMV and EBV is safe and effective but requires aggressive monitoring of immunosuppression. Patients who receive intensified immunosuppression for the treatment of acute rejection are at increased risk for CMV and may require more extended prophylaxis and closer monitoring.
The Israel Medical Association journal : IMAJ, 2011
Primary liver masses in children may require intervention because of symptoms or concern about ma... more Primary liver masses in children may require intervention because of symptoms or concern about malignant transformation. To review the management and outcome of benign liver masses in children. We conducted a retrospective chart review of children with liver masses referred to our institution during the period 1997-2009. Benign liver masses were identified in 53 children. Sixteen of these children (30%) had hemangioma/infantile hepatic hemangioendothelioma (IHH) and 15 (28%) had focal nodular hyperplasia. The remainder had 6 cysts, 4 hamartomas, 3 nodular regenerative hyperplasia, 2 adenomas, 2 vascular malformations, and one each of polyarteritis nodosa, granuloma, hepatic hematoma, lymphangioma, and infarction. Median age at presentation was 6 years, and 30 (57%) were female. Masses were initially noticed on imaging studies performed for unrelated symptoms in 33 children (62%), laboratory abnormalities consistent with liver disease in 11 (21%), and palpable abdominal masses in 9 (...
Nonadherence to treatment recommendations, especially when associated with transition to adult ca... more Nonadherence to treatment recommendations, especially when associated with transition to adult care providers, account, by some estimates, for most organ rejections and death in long-term pediatric survivors of solid organ transplantations. It is therefore imperative that providers become familiar with the issues related to those major risks and ways to address them. It is possible, and important, to routinely measure adherence to medications by using one of several available and proven methods of surveillance. There are numerous ways to improve adherence, and it is in fact possible to improve adherence and therefore outcomes in the transplant setting. The transition to adult services is a vulnerable period. The authors believe that it is possible to improve the transition process, and suggestions are presented in this review. However, solid research into interventions to improve transition is lacking. Nonadherence to medical recommendations is prevalent and leads to poor outcomes f...
Liver Kidney Microsomal type 1 (LKM1) antibody, the diagnostic marker of autoimmune hepatitis typ... more Liver Kidney Microsomal type 1 (LKM1) antibody, the diagnostic marker of autoimmune hepatitis type 2, is also found in a proportion of patients with hepatitis C virus infection (HCV). It is detected conventionally by the subjective immunofluorescence technique. Our aim was to establish a simple and objective enzyme-linked immunosorbent assay (ELISA) that measures antibodies to cytochrome P4502D6 (CYP2D6), the target
This review highlights the fact that in the current era, the focus of success in pediatric transp... more This review highlights the fact that in the current era, the focus of success in pediatric transplantation has moved from short-term to long-term patient and graft survival as well as achieving 'normality' after transplantation. Advances in surgical techniques, organ allocation, intensive care management, laboratory tests, interventional and diagnostic radiology, immunosuppressive, and antiviral drugs have allowed a larger number of pediatric liver transplant recipients to progress into adulthood. To achieve 'normality' several medical and psychosocial factors have become the target of intervention. Attaining optimal linear growth and puberty after transplant is important as is minimizing adverse events associated with immunosuppression. Special considerations are important in the adolescent transplant recipient, particularly adherence to medical recommendations. Liver transplant recipients have been reported to have below average intelligence quotient at school entry and significantly lower health-related quality of life than healthy controls and appropriate interventions need to be put in place early. Successful long-term outcomes in transplantation are contingent on successful transition from pediatric to adult healthcare services. Achieving operational tolerance remains a goal. In conclusion, this review outlines the myriad issues around pediatric transplantation that can be addressed so that the transplant recipient may experience a 'normal' quality of life.
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