Implementation of a multicomponent medication adherence promotion system is associated with a decrease in late T-cell-mediated rejection.

Poor immunosuppression adherence in pediatric recipients of liver transplant (LT) contributes to late T-cell-mediated rejection (TCMR) in ~90% of cases and increases the risk of mortality. A medication adherence promotion system (MAPS) was found to reduce late rejection in pediatric recipients of kidney transplants. Using quality improvement methodology, we adapted and implemented the MAPS in our LT clinic. Our primary outcome was population-level rates of late TCMR, measured as a monthly incident rate. Three-hundred fourteen patients undergoing LT are currently cared for at our institution. One-hundred sixty-two (52%) are females with a median age of 16 years and a median age at LT of 2 years. Preimplementation, monthly rejection rates were 0.84 rejections per 100 patient-months. After iterative implementation of MAPS over 2.3 years, monthly rejection rates decreased to 0.46 rejections per 100 patient-months, a 45% decrease in late TCMR. Implementation of MAPS was associated with a sustained 45% decrease in TCMR at a single center, suggesting that quality improvement tools may help improve clinical outcomes. MAPS may be an important tool to ensure long-term allograft health. Future studies should rigorously test MAPS across a multicenter sample.

Percutaneous Electrical Nerve Field Stimulation in Children and Adolescents With Functional Dyspepsia-Integrating a Behavioral Intervention.

OBJECTIVES: Functional dyspepsia (FD) includes postprandial distress and epigastric pain syndrome. Percutaneous electrical nerve field stimulation (PENFS) in addition to behavioral interventions (BI) has shown benefits in children with functional abdominal pain but not specifically in FD. We aimed to assess the efficacy of PENFS for treating FD and compare the outcomes with those who received the combination of PENFS + BI. MATERIALS AND METHODS: Charts of patients with FD who completed four weeks of PENFS were evaluated. A subset of patients received concurrent BI. Demographic data, medical history, and symptoms were documented. Outcomes at different time points included subjective symptom responses and validated questionnaires collected clinically (Abdominal Pain Index [API], Nausea Severity Scale [NSS], Functional Disability Inventory [FDI], Pittsburgh Sleep Quality Index [PSQI], Children's Somatic Symptoms Inventory [CSSI], Patient-Reported Outcomes Measurement Information Systems [PROMIS] Pediatric Anxiety and Depression scales). RESULT: Of 84 patients, 61% received PENFS + BI, and 39% received PENFS alone. In the entire cohort, API (p < 0.0001), NSS (p = 0.001), FDI (p = 0.001), CSSI (p < 0.0001), PSQI (p = 0.01), PROMIS anxiety (p = 0.02), and depression (p = 0.01) scores improved from baseline to three weeks and at three months. Subjective responses showed nausea improvement (p = 0.01) and a trend for improvement in abdominal pain (p = 0.07) at week three. Abdominal pain subjectively improved at week three and three months (p = 0.003 and 0.02, respectively), nausea at week three and three months (p = 0.01 and 0.04, respectively), and a trend for improvement in sleep disturbances at week three and three months (p = 0.08 and p = 0.07, respectively) in the PENFS + BI group vs PENFS alone. CONCLUSION: Abdominal pain, nausea, functioning, somatization, sleep disturbances, anxiety, and depression improved at three weeks and three months after PENFS in pediatric FD. Subjective pain and nausea improvement were greater in the PENFS + BI group than in the group with PENFS alone, suggesting an additive effect of psychologic therapy.

The Barriers Assessment Tool-A Patient-Centered Measure of Adherence Barriers in Pediatric Kidney Transplantation.

OBJECTIVE: Assessing barriers to adherence provides helpful information to clinicians. The objective of this study was to describe the clinical utility of the Barriers Assessment Tool (BAT) using clinical data for a large, midwestern U.S. pediatric kidney transplant program. METHODS: Focus group and clinical data were obtained during post-transplant medical visits. Qualitative and quantitative assessment methods were utilized to describe patient and caregiver feedback on the BAT, clinical utility, concordance between reporters, and the effect of interventions on subsequent assessment and electronically measured adherence. RESULTS: Patients were willing to discuss adherence issues with their care team. There was substantial agreement between patients and caregivers at two timepoints. If a barrier was not addressed, 89.6% (43/48) of patients and 85.9% (67/78) of caregivers reported the same BAT scores from the first to second assessment. When barriers were addressed with a clinic-based intervention, 82% of caregivers reported no adherence barriers. No significant change was found for patient-reported barriers. CONCLUSIONS: Standardized assessment of barriers to medication adherence provides actionable information to clinicians. Standardized assessment of adherence barriers may give clinicians opportunities to help patients and caregivers overcome these barriers which can decrease risk of rejection.

A Cost-effectiveness Analysis of Adherence Promotion Strategies to Improve Rejection Rates in Adolescent Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Nonadherence to medical regimens increases the risk of graft loss among adolescent and young adult recipients of kidney transplants. Interventions that improve adherence may decrease rejection rates, but their perceived costs are a barrier to clinical implementation. We developed a model to assess the cost-effectiveness of an adherence promotion strategy, the Medication Adherence Promotion System (MAPS). STUDY DESIGN: Simulation-based. Data sources included published articles indexed in Medline or referenced in bibliographies of relevant English-language articles. Data on costs and outcomes were taken from a single clinical center. SETTING & POPULATION: US adolescent patients after their first kidney transplant. INTERVENTION: Usual posttransplant care versus usual care plus MAPS. OUTCOME: Effectiveness measured in quality-adjusted life years (QALYs) and costs measured in 2020 US dollars. MODEL, PERSPECTIVE, & TIMEFRAME: Markov state transition decision model. We used a health care system perspective with a lifelong time horizon. RESULTS: In the base-case analysis, MAPS was more effective and less costly than usual care. MAPS cost $9,106 per patient less than usual care and resulted in a gain of 0.32 QALYs. In probabilistic sensitivity analyses, MAPS was cost saving 100% of the time. Extending results to a program level with 100 patients, any adherence promotion intervention similar in effectiveness to MAPS would cost less than $50,000/QALY if the start-up costs were <$2.5 million and annual costs <$188,000. Strategies with costs similar to MAPS that reduce the risk of rejection by as little as 3% would also have similar cost-effectiveness. LIMITATIONS: Estimates of components and costs for MAPS were based on a single center. CONCLUSIONS: Adherence promotion strategies with costs similar to MAPS can be cost-effective as long as they reduce rejection rates by at least 3%. This model can be applied to study the cost-effectiveness of adherence promotion strategies with varying costs and outcomes.

A Medication Adherence Promotion System to Reduce Late Kidney Allograft Rejection: A Quality Improvement Study.

RATIONALE & OBJECTIVE: Adolescent and young adult kidney transplant recipients have a high risk of rejection related to suboptimal adherence. Multicomponent interventions improve adherence in controlled trials, but clinical implementation is lacking. We describe an initiative to reduce allograft rejection using evidence-based adherence promotion strategies. STUDY DESIGN: Interrupted time series. SETTING & PARTICIPANTS: Kidney transplant recipients cared for at Cincinnati Children's Hospital ≥ 1 year after transplant and taking ≥1 immunosuppressive medication(s) from 2014 through 2017. QUALITY IMPROVEMENT ACTIVITIES: The following interventions, collectively called MAPS (Medication Adherence Promotion System), were implemented over 14 months: (1) adherence promotion training for clinical staff, 2) electronic health record-supported adherence risk screening, (3) systematic assessment of medication adherence barriers, (4) designation of specific staff to address adherence barriers, (5) shared decision-making with the patients to overcome adherence barriers, (6) follow-up evaluation to assess progress, and (7) optional electronic medication monitoring. OUTCOMES: Primary Outcome: Late acute rejection. Process measures were conducted to assess barriers, identify barriers, and perform interventions. The secondary outcomes/balancing measures were de novo donor-specific antibodies (DSA), biopsy rate, and rejections per biopsy. ANALYTICAL APPROACH: Time series analysis using statistical process control evaluated patient-days between acute rejections as well as monthly rejections per 100 patient-months before and after implementation. To control for known rejection risk factors including changes in treatment and case mix, multivariable analyses were performed. RESULTS: The monthly rejection rate fell from 1.61 rejections per 100 patient-months in the 26 months before implementation to 0.88 rejections per 100 patient-months in the 22 months after implementation. In the multivariable analysis, MAPS was associated with a 50% reduction in rejection incidence (incidence rate ratio, 0.50 [95% CI, 0.27-0.91]; P = 0.02). DSA and time since transplant (per each additional year) were also associated with rejection incidence (incidence rate ratio, 2.27 [P = 0.02] and 0.87 [P = 0.02], respectively). LIMITATIONS: Single-center study, and potential confounding by unmeasured variables. CONCLUSIONS: Clinical implementation of evidence-based adherence-promotion strategies was associated with a 50% reduction in acute rejection incidence over 2 years.

Caregiver-reported outcomes of pediatric transplantation: Changes and predictors at 6 months post-transplant.

BACKGROUND: It is widely assumed that pediatric solid organ transplantation results in better caregiver-reported outcomes, including reduced caregiver psychological distress and increased child health-related quality of life (HRQOL), yet little empirical evidence of this expectation exists. The current investigation aims to fill this gap and identify key clinical course factors predictive of caregiver-reported outcomes. METHODS: Forty-nine caregivers of children (Mage  = 10.30 years, SD = 5.43) presenting for kidney, liver, or heart transplant evaluation reported on their psychological distress levels (anxiety, depression, somatization, and global psychological stress) and their children's HRQOL at children's pretransplant evaluations and 6 months post-transplant. Clinical course factors were abstracted via medical chart review. RESULTS: Caregivers did not report significant changes in their psychological distress from pre- to post-transplant but reported significantly improved child HRQOL across most domains (ds = -.45 to -.54). Higher post-transplant caregiver global psychological distress was predicted by older child age, shorter time since diagnosis, and lower pretransplant caregiver-reported child HRQOL even after controlling for pretransplant caregiver psychological distress. Lower post-transplant child total HRQOL was predicted by more post-transplant hospitalizations even after controlling for pretransplant child total HRQOL. CONCLUSIONS: These preliminary results indicate pediatric solid organ transplantation was associated with some improved caregiver-reported outcomes, specifically children's HRQOL, but not caregivers' psychological distress. Linear regression models identify several clinical course and pretransplant factors associated with transplantation outcomes. Characterizing how caregivers view their psychological distress levels and children's HRQOL across the transplantation process could inform family-centered holistic care and support caregiver adaptation to transplantation.

Predicting acute rejection in children, adolescents, and young adults with a kidney transplant by assessing barriers to taking medication.

BACKGROUND: Nonadherence to immunosuppression is common among pediatric, adolescent, and young adult kidney transplant recipients and a leading cause of graft loss. Assessing barriers to medication adherence in clinical practice may identify patients at risk for rejection and provide therapeutic targets. METHODS: Kidney transplant patients and/or their caregivers were assessed for 14 barriers to medication adherence using the barriers assessment tool. We compared rejection rates between patients with at least one reported adherence barrier to those without reported adherence barriers using a Kaplan-Meier estimator and Cox proportional hazard models to adjust for other mediators of acute rejection at 2 years following barriers assessment. RESULTS: Ninety-eight patients were assessed for barriers to adherence. Over the 2-year observation period, 22 patients developed biopsy-proven acute rejection (BPAR). Kaplan-Meier estimates show that patients with an identified barrier to adherence were more likely to have BPAR (p = 0.02) than patients without an identified barrier in the 24 months following barriers assessment. The median time to rejection for patients who experienced acute rejection was 175.5 days (IQR 63-276 days) from the time of barriers assessment. An identified barrier to adherence remained the only statistically significant predictor of BPAR with Cox modeling (HR 2.6, p = 0.04), after accounting for age, sex, and race. CONCLUSIONS: Pediatric and adolescent kidney transplant recipients with identified adherence barriers are at increased risk for acute rejection. Barriers to adherence provide a potentially modifiable therapeutic target that can be assessed in clinic to guide targeted interventions.

The Role of Psychology in the Care of Children With Pancreatitis.

Children with acute recurrent and chronic pancreatitis experience severe abdominal pain that may be intermittent or chronic. Pain is often debilitating, causing interference with academic, social, family, and extracurricular activities that are important to youth. Disruption of these routines and the unpredictability of pain flares place children with pancreatitis at increased risk for development of anxious or depressive symptoms. Pediatric psychologists trained in cognitive-behavioral treatment are well suited to intervene on functional disability and mood disturbance, as well as teach coping skills. In an era where there is movement away from opioids, nonpharmacological strategies have an important place for pain management. In fact, positive outcomes following for children with other recurrent abdominal pain syndromes have been reported for this evidence-based intervention. In addition to pain management, pediatric psychologists can address other co-occurring behavioral and emotional problems in children with pancreatitis, such as needle phobia and poor adherence to the prescribed medical regimen.

Caregivers' Barriers to Facilitating Medication Adherence in Adolescents/Young Adults With Solid Organ Transplants: Measure Development and Validation.

OBJECTIVE: To evaluate the factor structure, validity, and reliability of the Caregiver Medication Barriers to Adherence Scale (CMBAS), which assesses caregivers' barriers to facilitating medication adherence in adolescent and young adults (AYAs) with solid organ transplants. METHODS: The sample included 93 caregivers of AYAs ages 12-22 years who received a liver, kidney, or heart transplant. Caregivers completed the CMBAS and surveys to assess its validity, including internalizing symptoms, personality traits (i.e., neuroticism, conscientiousness), and AYAs' nonadherence to immunosuppressant medications. AYA nonadherence to tacrolimus was objectively assessed via the Medication Level Variability Index (MLVI). RESULTS: Confirmatory factor analyses of the CMBAS revealed a two-factor model: Caregiver Emotional Distress and Caregiver Cognitive Burden/Responsibility. Higher CMBAS scores were related to higher levels of caregiver internalizing symptoms (rs = .28 to .30), neuroticism (r = .27), and caregiver proxy-reported immunosuppressant nonadherence (r = .27), as well as lower levels of caregiver conscientiousness (rs = -.25 to -.26). The CMBAS was not associated with the MLVI (rs = -.13 to -.16). CONCLUSIONS: The CMBAS demonstrated reliability and validity for caregivers of AYAs with solid organ transplants. Findings support the use of the CMBAS as a brief clinical screening tool to identify caregivers' barriers to facilitating AYA medication adherence.

Sleep quality is associated with psychosocial functioning and health-related quality of life in pediatric transplant recipients.

This study examined patient-reported sleep quality in a single-center cross-sectional sample of adolescents with solid organ transplants and evaluated associations between sleep quality, psychosocial functioning (ie, depression/anxiety symptoms), and HRQOL. Health disparities associated with minority race/ethnicity and socioeconomic variables were also examined. Sixty-nine adolescents (M = 16.51 years; SD = 1.63) who received a solid organ transplant (kidney: n = 25; liver: n = 24; heart: n = 20) completed self-report measures of sleep quality, psychosocial functioning, and HRQOL. Adolescent transplant recipients endorsed significantly lower levels of sleep quality (ie, falling asleep) compared with previously published norms of healthy peers (t = -3.60; P ≤ .001). Higher sleep quality was significantly associated with fewer anxiety and depressive symptoms (r = -.31 to -.40), and higher physical and psychosocial HRQOL (r = .33-.43). Adolescents from minority backgrounds had significantly worse sleep quality compared with non-Hispanic Whites. Adolescent transplant recipients, particularly those from minority backgrounds, may be at increased risk for experiencing poor sleep quality. Suboptimal sleep is a risk factor for higher levels of anxiety and depressive symptoms, as well as lower levels of physical and psychosocial HRQOL. Sleep is an important modifiable factor that, if improved, may contribute to lower anxiety/depressive symptoms and better HRQOL in adolescent transplant recipients.

A preliminary investigation of sleep quality and patient-reported outcomes in pediatric solid organ transplant candidates.

The current cross-sectional, single-center study aimed to examine sleep quality in a sample of adolescents awaiting solid organ transplantation and to explore associations between sleep quality and both health-related quality of life and barriers to adherence. Thirty adolescents between the ages of 12 and 18 years (M age = 15.26, SD = 1.89) who were awaiting transplantation participated in this study. Participants completed measures of sleep quality, health-related quality of life, and barriers to adherence. T test and correlational analyses were performed to examine study aims. Adolescents awaiting transplantation had significantly lower levels of overall sleep quality compared to published norms of healthy peers. Domains of sleep quality were positively related to emotional and psychosocial health-related quality of life. Sleep quality domains were also negatively related to adherence barriers. This study provides preliminary evidence demonstrating that sleep quality among transplant candidates is compromised, and that poor sleep quality is related to adolescents' functioning across a number of domains during the pretransplant period. Results highlight the clinical importance of assessing and targeting sleep functioning in adolescents awaiting transplantation in order to reduce the negative influence of suboptimal sleep on functioning during this vulnerable period.

In-hospital and 90-day outcomes after total pancreatectomy with islet autotransplantation for pediatric chronic and acute recurrent pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is used to treat debilitating chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) that has failed medical and endoscopic therapy. We performed a retrospective review of TPIAT patients at a free-standing children's hospital to evaluate perioperative outcomes. Twenty patients (median age 13, 65% female) underwent TPIAT (2015 through 2017). Of the 20 patients, 95% had CP and 1 patient (5%) had ARP alone. Seventy-five percent of the patients had a pancreatitis-associated genetic mutation; 40% had pancreas divisum. The median surgical time was 757 (IQR 657 to 835) minutes. Median islet equivalents per kg of body weight (IEQ/kg) were 6404 (IQR 5018 to 7554). At 90 days postoperatively vs preoperatively, significantly fewer patients were receiving parenteral nutrition (0% vs 25%, P = .006) and opioids (45% vs 75%, P = .01). Short Form 36-Item Health Survey (SF-36) physical health module scores and total scores improved (34.0 preoperatively vs 54.6 at 90 days, P = .008, and 47.1 vs 65.3, P = .007, respectively); SF-10 physical health scores also improved (13.4 vs 33.1, P = .02). Insulin requirement decreased from 0.5 unit/kg/day to 0.4 unit/kg/day between discharge and 90 days (P = .02). TPIAT is an effective option when debilitating disease persists despite maximal medical and endoscopic therapy. Opioid, parenteral nutrition, and exogenous insulin use can successfully be weaned within 90 days after TPIAT, with gains in health-related quality of life.

Barriers to Adherence in Juvenile Idiopathic Arthritis: A Multicenter Collaborative Experience and Preliminary Results.

OBJECTIVE: Nonadherence is currently an underrecognized and potentially modifiable obstacle to care in juvenile idiopathic arthritis (JIA). The purpose of our study was to design and implement a standardized approach to identifying adherence barriers for youth with JIA across 7 pediatric rheumatology clinics through the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) and to assess the frequency of adherence barriers in patients and their caregivers across treatment modalities. METHODS: An iterative process using coproduction among parents and providers of patients with JIA was used to design the Barriers Assessment Tool to screen for adherence barriers across 4 treatment modalities (i.e., oral medications, injectable medications, infusions, and physical/occupational therapy). This tool was implemented in 7 rheumatology clinics across the United States and patient responses were collected for analysis. RESULTS: Data were collected from 578 parents and 99 patients (n = 44 parent-child dyads). Seventy-seven percent (n = 444) of caregivers and 70% (n = 69) of patients reported at least 1 adherence barrier across all treatment components. The most commonly reported adherence barriers included worry about future consequences of therapy, pain, forgetting, side effects, and embarrassment related to the therapy. There was no significant difference between endorsement of barriers between parents and adolescents. CONCLUSION: Implementing a standardized tool assessing adherence barriers in the JIA population across multiple clinical settings is feasible. Systematic screening sheds light on the factors that make adherence difficult in JIA and identifies targets for future adherence interventions in clinical practice.

Predicting Health Care Utilization and Charges Using a Risk Score for Poor Adherence in Pediatric Kidney Transplant Recipients.

Pediatric kidney transplant recipients must follow a complicated regimen of timely adherence to immunosuppressant medication, routine blood work, and medical follow-up visits. Failure to adhere to the recommended regimen can result in medical complications and costly treatment. We developed a novel risk score to identify patients at risk for poor adherence behaviors and evaluated whether it would predict future health care utilization and charges. Our risk stratification score combined three simple pass/fail metrics of adherence derived directly from the electronic health record including standard deviation of immunosuppression drug levels, timely laboratory monitoring, and timely clinic visits as indicated by our clinical protocol. Risk for poor adherence was assessed over a three-month period. Linear regression was used to predict subsequent health care charges and utilization. Greater than 75% of patients had some degree of nonadherence risk during the study period, but there were no significant differences found on any outcomes for the overall score. However, when the individual components of the overall risk score were evaluated independently, patients with tacrolimus drug level standard deviation ≥2 (e.g., a marker of poor adherence) had greater health care utilization (e.g., hospitalizations) and increased total charges. Additionally, patients who did not follow up in clinic at least every 4 months had more ED visits and ED-related charges, but fewer hospitalizations. Regular clinic visits and minimizing drug level variation may deter future costly ED visits and hospitalizations.

Assessing barriers to adherence in routine clinical care for pediatric kidney transplant patients.

Patient-identified barriers to immunosuppressive medications are associated with poor adherence and negative clinical outcomes in transplant patients. Assessment of adherence barriers is not part of routine post-transplant care, and studies regarding implementing such a process in a reliable way are lacking. Using the Model for Improvement and PDSA cycles, we implemented a system to identify adherence barriers, including patient-centered design of a barriers assessment tool, identification of eligible patients, clear roles for clinic staff, and creating a culture of non-judgmental discussion around adherence. We performed time-series analysis of our process measure. Secondary analyses examined the endorsement and concordance of adherence barriers between patient-caregiver dyads. After three methods of testing, the most reliable delivery system was an EHR-integrated tablet that alerted staff of patient eligibility for assessment. Barriers were endorsed by 35% of caregivers (n=85) and 43% of patients (n=60). The most frequently patient-endorsed barriers were forgetting, poor taste, and side effects. Caregivers endorsed forgetting and side effects. Concordance between patient-caregiver dyads was fair (k=0.299). Standardized adherence barriers assessment is feasible in the clinical care of pediatric kidney transplant patients. Features necessary for success included automation, redundant systems with designated staff to identify and mitigate failures, aligned reporting structures, and reliable measurement approaches. Future studies will examine whether barriers predict clinical outcomes (eg, organ rejection, graft loss).

Transition readiness, adolescent responsibility, and executive functioning among pediatric transplant recipients: Caregivers' perspectives.

This study aimed both to evaluate caregivers' perspectives of EF and transition readiness among adolescent transplant recipients and to examine the indirect effects of adolescent responsibility and parent involvement across domains of EF. Fifty-seven caregivers of adolescent solid organ transplant recipients participated in this study and completed measures of adolescent EF, transition readiness, responsibility in healthcare behavior, and parent involvement. Bootstrapping procedures were used to test indirect effects. Caregiver report of adolescent EF was significantly related to transition readiness among transplant recipients. Significant indirect effects were found for adolescent responsibility but not parent involvement. No significant differences were found between metacognitive and behavioral regulation domains of EF in the association with transition readiness. Assessment of adolescent EF skills may help guide the development of individualized transition readiness guidelines to promote successful gains in self-management abilities as well as eventual transfer to adult medical services.

The interactive effect of parent personality and medication knowledge on adherence in children awaiting solid organ transplantation.

OBJECTIVE: The study aimed to examine parent personality factors as predictors of parent medication knowledge and parent-report of child medication adherence. METHOD: Seventy-eight parents (Mage = 37.68, 87.2% female) of children (Mage = 8.89, range: 0-20 years) undergoing evaluation for a solid organ transplant were recruited. Parents completed questionnaires about their personality, knowledge of their child's medications, and their child's level of medication adherence. RESULTS: Greater time since the child's diagnosis predicted lower levels of medication knowledge, while higher levels of Neuroticism and Extraversion predicted greater levels of medication knowledge. Greater medication knowledge predicted greater levels of medication adherence, with this effect being moderated by conscientiousness. Children of parents with low knowledge and low conscientiousness had the lowest levels of adherence. CONCLUSIONS: Parent personality is significantly related to medication knowledge and children's adherence prior to transplant. As parent personality is theoretically stable, Neuroticism (N), Extraversion (E), and Conscientiousness (C) serve as risk and protective factors that may influence medication knowledge and adherence even after transplantation. Parent medication knowledge and adherence are modifiable factors that would be appropriate targets for intervention during the pretransplant period. (PsycINFO Database Record

Glutathione content and antioxidant enzyme expression of in vivo matured sheep oocytes.

Retinoids play important roles in many diverse biological functions such as cell growth, morphogenesis, differentiation, and reproduction. Previous studies demonstrated that retinol administration to ewes, followed by natural service, resulted in embryos with improved competence to develop under standard in vitro conditions (5% CO(2) in air). Additional studies provided evidence that retinol may have some antioxidant effect by improving blastocyst development in cattle under atmospheric conditions (5% CO(2) in air). Glutathione is an important non-protein, sulphydryl compound found in oocytes and embryos, which acts to decrease oxidative stress. The purpose of the present study was to evaluate the effects of retinol administration to ewes on the content of glutathione and glutathione-related and antioxidant enzymes in in vivo matured sheep oocytes. Briefly, ewes were administered retinol or vehicle during superovulation, and after 60h the oviducts were removed and mature oocytes collected. Glutathione content did not differ significantly between oocytes collected from retinol-treated ewes (6.78+/-3.81pmol/oocyte) and control ewes (6.38+/-1.58pmol/oocyte). Transcripts encoding for manganese superoxide dismutase (Mn-SOD), copper zinc superoxide dismutase (Cu-Zn SOD), glutathione synthetase (GS), and glutathione transferase pi (GSTp) were detected in single ovine oocytes; however, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not reveal any significant differences in transcripts between oocytes from retinol-treated ewes and those from control ewes.