Eyal Shemesh

Adherence and medical outcomes in pediatric liver transplant recipients who transition to adult services

Abstract:  Non‐adherence to medications is associated with poor medical outcomes in adolescent transplant recipients. It is unclear whether non‐adherence is further compromised when transplant recipients transition to the adult health care system. The purpose of the present study was to examine whether adherence changes during transition. We reviewed the medical records of 14 recently transitioned patients and compared their adherence and corresponding medical outcomes before and after transition. These outcomes were also compared with two cohorts of patients receiving care solely in pediatric or adult services. Medication adherence, measured through the use of standard deviations of tacrolimus blood levels, was examined for all patients. We found that adherence to tacrolimus significantly decreased after transition. After transitioning, patients furthermore exhibited poorer adherence than patients in the other two cohorts did over time. This small retrospective study suggests that the period of transition from pediatric to adult transplant clinics is a vulnerable one. Larger, prospective investigations of the transition process are necessary before recommendations are made regarding interventions.

Posttraumatic stress, nonadherence, and adverse outcome in survivors of a myocardial infarction.

Objective: Posttraumatic stress disorder (PTSD) symptoms have been reported in patients with coronary vascular disease, after the trauma of a myocardial infarction (MI). The effect of these symptoms on post-MI disease control has not been elucidated. We conducted a study that sought to determine whether PTSD symptoms post-MI are associated with increased likelihood of cardiovascular readmission and with nonadherence to treatment recommendations. Methods: Patients were recruited during a visit in a cardiology clinic 6 months post-MI and were followed for 1 year. Adherence to aspirin was measured by platelet thromboxane production (an indication of aspirins effect). Medical outcome was measured as rate of admission due to cardiovascular causes during the follow-up period. Self-report measures of PTSD (Impact of Event Scale), Depression, and Global Distress (SCL-90-R) were administered at enrollment. Results: Seventy-three patients were studied. Above-threshold PTSD symptom scores at enrollment, but not depression or global distress scores, were significant predictors of nonadherence to aspirin and of an increased likelihood of cardiovascular readmission over the course of the following year. Conclusions: PTSD symptoms predicted poor disease control in this cohort of MI survivors. The data suggest that screening MI survivors for symptoms of PTSD may be beneficial if this high-risk population is to be targeted for interventions.

A prospective study of posttraumatic stress symptoms and nonadherence in survivors of a myocardial infarction (MI)

We examined a novel hypothesis that links symptoms of MI-related posttraumatic stress disorder (PTSD) to nonadherence. According to this hypothesis, patients who are traumatized by their medical illness do not take their medications as prescribed. As a part of the avoidance dimension of PTSD, patients who are traumatized may avoid being reminded of the MI by not taking the medication. MI survivors were prospectively followed for 6 months to 1 year. Adherence was assessed by pill count of Captopril. Demographic variables, medical risk factors, PTSD, and other psychiatric symptom dimensions were evaluated during follow-up. One hundred two of 140 recruited patients completed follow-up. Nonadherence to Captopril was associated with poor medical outcome (r=.93, P=.006). Above-Threshold PTSD symptoms were associated with nonadherence to medications (P=.05). No other psychiatric symptom dimensions were independently associated with nonadherence. Nonadherence to medications predicts adverse outcome during the first year after an acute MI. Nonadherence is associated with PTSD symptoms, which may either be a marker for or a cause of nonadherence. Treatment of PTSD may prove to be a useful approach for improving adherence.

Non‐adherence in pediatric liver transplant recipients − an assessment of risk factors and natural history

Abstract: Despite the fact that non‐adherence to medical therapy is one of the major causes of late morbidity and mortality in pediatric liver transplant recipients, little is known of the risk factors involved in this behavior. Three cases of fatal non‐adherence are reported. Factors associated with non‐adherence were investigated by performing a retrospective chart review of a panel of 27 variables in an age‐matched cohort of 15 pediatric liver transplant recipients. The most striking differences between the severely non‐adherent group and the age‐matched cohort included history of substance abuse, child abuse (physical or sexual), not having two parents at home, having received public assistance, having been diagnosed with a psychiatric disorder, and history of school dropout. In addition it appeared that a pretransplant diagnosis of autoimmune hepatitis was associated with more significant medical sequelae related to non‐adherence. These findings are preliminary owing to the retrospective design of this study, but could be used as a starting point for a prospective study of this important phenomenon.

Child and parental reports of bullying in a consecutive sample of children with food allergy

OBJECTIVE: The social vulnerability that is associated with food allergy (FA) might predispose children with FA to bullying and harassment. This study sought to quantify the extent, methods, and correlates of bullying in a cohort of food-allergic children. METHODS: Patient and parent (83.6% mothers) pairs were consecutively recruited during allergy clinic visits to independently answer questionnaires. Bullying due to FA or for any cause, quality of life (QoL), and distress in both the child and parent were evaluated via questionnaires. RESULTS: Of 251 families who completed the surveys, 45.4% of the children and 36.3% of their parents indicated that the child had been bullied or harassed for any reason, and 31.5% of the children and 24.7% of the parents reported bullying specifically due to FA, frequently including threats with foods, primarily by classmates. Bullying was significantly associated with decreased QoL and increased distress in parents and children, independent of the reported severity of the allergy. A greater frequency of bullying was related to poorer QoL. Parents knew about the child-reported bullying in only 52.1% of the cases. Parental knowledge of bullying was associated with better QoL and less distress in the bullied children. CONCLUSIONS: Bullying is common in food-allergic children. It is associated with lower QoL and distress in children and their parents. Half of the bullying cases remain unknown to parents. When parents are aware of the bullying, the child’s QoL is better. It is important to proactively identify and address cases in this population.

Prospective analysis of nonadherence in autoimmune hepatitis: a common problem.

Objectives: To prospectively assess nonadherence to medications, the relationship between nonadherence and medical outcome and the relationship between a psychiatric risk factor (posttraumatic stress) and nonadherence in patients with a diagnosis of autoimmune hepatitis. Patients and Methods: Data were obtained in children with autoimmune hepatitis, who had consented to prospective monitoring of adherence, during 1 year of follow-up in our pediatric liver program. An electronic monitoring device as well as posttransplant trough blood levels of tacrolimus was used to evaluate adherence. A validated self-report questionnaire was used to assess posttraumatic stress. The medical outcome measure was the maximal alanine transaminase (ALT) for each monitored patient. Results: Of 37 pediatric patients, 34 (15 posttransplant) enrolled. Fourteen (41%) used the monitoring device as directed. Monitor readings ranged between 28% and 94% of optimal adherence (100%). No patient took the medications exactly as prescribed. Electronic monitoring device readings correlated inversely with maximal ALT (P = 0.03, r = −0.59), and were also correlated with the tacrolimus level variability as a measure of adherence (P = 0.04, r = −0.72). Posttraumatic stress disorder questionnaire scores were correlated with both measures of adherence (for electronic monitoring, P = 0.02, r = −0.70, for tacrolimus levels, P = 0.03, r = 0.62). Conclusions: Nonadherence to immunosuppressants was common in this cohort, and it correlated with higher maximal ALT. Nonadherence is therefore an important risk factor for poor outcome in patients with autoimmune hepatitis. Posttraumatic stress symptoms, which were correlated with nonadherence, may serve as a focus for adherence-improving interventions.

Evaluating non-adherence to immunosuppressant medications in pediatric liver transplant recipients.

Abstract:  Non‐adherence with recommended immunosuppressant medications is common post‐pediatric liver transplant and is the most important reason for organ rejection in long‐term survivors. However, there is currently no validated, standard method to measure adherence, with a well‐defined threshold, making it extremely difficult to evaluate interventions to improve adherence. Previous studies have suggested that the degree of fluctuation of medication blood levels over time can provide an idea about how regularly the medication is being taken. The present study, conducted at UCLA medical center, sought to identify a specific threshold value of the s.d. of individual tacrolimus blood levels in pediatric liver transplant recipients which would be associated with rejection episodes in these patients. A threshold of 3.0 has been identified in other studies, and was supported by the analysis of retrospective data from 96 subjects. However, further analysis found that a s.d. of 2.5 appeared to have a better fit with the data. These findings suggest the utility of monitoring the s.d. of routine tacrolimus blood levels in pediatric liver transplant recipients for detecting non‐adherence to immunosuppressant medication prior to clinical rejection, allowing earlier interventions.

Posttraumatic stress responses in children with life-threatening illnesses

Posttraumatic stress symptoms have been reported in response to various serious medical illnesses in adults and children. Not surprisingly, posttraumatic stress is probably more common in response to acute, life-threatening, events that are related to the illness. Emerging data suggest that children often experience life-saving medical procedures as traumatic, which puts caretakers and medical personnel in the role of perpetrators for the children. Trauma symptoms are also reported as common and severe in caregivers. Both of these issues have been previously poorly understood and should be addressed in assessment and treatment. As with other traumatic events, developmental considerations, the nature and severity of the event itself, social supports, and premorbid exposure to negative life events are also important issues to consider in developing appropriate interventions. The importance of developing prevention and treatment for PTSD in medically ill children and adults includes increased morbidity and mortality (e.g., nonadherence to medications) and psychiatric sequelae and decreased quality of life. Obstacles to systematic study of a psychiatric intervention for this group include difficulties assessing multidrug regimens and cognitive treatment effects in this group. The relative stability of social supports and the potential use of preventive measures make this an attractive population for intervention. Clinicians and researchers are encouraged to work together to develop and use uniform screening and assessment methods that will help to identify cases and facilitate the multicenter trials that are vital to increasing knowledge in this patient population.

Transitioning health care responsibility from caregivers to patient: A pilot study aiming to facilitate medication adherence during this process

Abstract:  Transition in pediatric transplant recipients consists of both a physical shift in medical care location as well as a transition in health care responsibilities from caregivers to patients. The purpose of the present study was to test the feasibility of a pilot intervention aiming to facilitate the transition in health care responsibilities from caregivers to patients while patients are still receiving pediatric services. Twenty‐two patients were enrolled in a two‐session educational protocol aiming to facilitate transition of responsibility. Patients were recruited from an outpatient transplant clinic. Ten were referred because of suspected difficulty in transitioning of care, and 12 were consecutively recruited without any specific a priori concerns. Medication adherence, measured through the use of standard deviations of tacrolimus blood levels, and ALT levels were the medical outcome measures. Complete data are available for 20 patients. Mean ALT levels improved after the follow‐up period. For referred patients, adherence and ALT levels improved. Standard deviation of tacrolimus decreased from 3.33 to 2.23, t = 2.52, p = 0.04. Mean ALT decreased from 120.33 to 63.99, t = 3.01, p = 0.01. Maximal ALT values decreased overall from 284.10 to 101.20, t = 2.61, p = 0.03. Our findings suggest that targeted education regarding transition in responsibility for adolescents’ own health care is feasible in the outpatient environment and may assist families who are facing this potentially challenging process. A randomized, controlled study with a substantial number of enrolled patients is needed to establish the efficacy of this or other approaches.

Improving adherence to medications in pediatric liver transplant recipients.

Abstract:  We describe results from a clinical program, which aimed at improving adherence to medications in children who had a liver transplant. We followed the medical outcomes of 23 children and adolescents who participated in a clinical adherence‐improvement protocol during the years 2001–2002. The protocol included identification of non‐adherent patients by examining tacrolimus blood levels and intervention by increasing the frequency of clinic visits for non‐adherent patients. In the two‐yr preintervention (1999–2000), there was no improvement in any of the outcomes. After the intervention, the number of patients with high alanine aminotransferase levels (100 and above) decreased significantly, from eight before the intervention to four afterwards. Other outcomes, including the number of rejection episodes (three before, none after) and the degree of adherence to tacrolimus, also improved, but the improvement did not reach statistical significance. Although non‐adherent patients were called to clinic more often under the protocol, the intervention did not lead to increased outpatient costs. This adherence‐‐improvement intervention appears to be promising in improving outcomes in pediatric liver transplant recipients. Larger, controlled studies are needed to establish the efficacy of this or other approaches.