A systematic review of immunosuppressant adherence interventions in transplant recipients: Decoding the streetlight effect.

Non-adherence to immunosuppressant medications is an important risk factor for graft dysfunction. To evaluate the effectiveness of adherence-enhancing interventions, we reviewed adherence intervention studies in solid organ transplant recipients (all ages). Using the following databases: PsycINFO, PubMed, Scopus, and ScienceDirect, we identified 41 eligible studies. Only three non-randomized trials showed a possible positive effect on objective indicators of transplant outcomes (such as rejection, liver enzyme levels, kidney function). None of the 21 RCTs showed an improvement in transplant outcomes. Three studies showed a higher rate of adverse events in the intervention group as compared with controls, although this may be related to ascertainment bias. Improvement in adherence as measured indirectly (eg, with electronic monitoring devices) was not aligned with effects on transplant outcomes. We conclude that adherence interventions, to date, have largely been ineffective in improving transplant outcomes. To improve this track record, intervention efforts may wish to concentrate on non-adherent patients (rather than use convenience sampling, which excludes many of the patients who need the intervention), use direct measures of adherence to guide the interventions, and employ strategies that are intensive and yet engaging enough to ensure that non-adherent patients are able to participate.

The Medication Level Variability Index (MLVI) Predicts Poor Liver Transplant Outcomes: A Prospective Multi-Site Study.

Nonadherence to immunosuppressant medications is a leading cause of poor long-term outcomes in transplant recipients. The Medication Level Variability Index (MLVI) provides a vehicle for transplant outcome risk-stratification through continuous assessment of adherence. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi-site study evaluated whether MLVI predicts late acute rejection (LAR). Four hundred pediatric (1-17-year-old) liver transplant recipients were enrolled and followed for 2 years. The a-priori hypothesis was that a higher MLVI predicts LAR. Predefined secondary analyses evaluated other outcomes such as liver enzyme levels, and sensitivity analyses compared adolescents to pre-adolescents. In the primary analysis sample of 379 participants, a higher prerejection MLVI predicted LAR (mean prerejection MLVI with LAR: 2.4 [3.6 standard deviation] versus without LAR, 1.6 [1.1]; p = 0.026). Fifty-three percent of the adolescents with MLVI>2 in year 1 had LAR by the end of year 2, as compared with 6% of those with year 1 MLVI≤2. A higher MLVI was significantly associated with all secondary outcomes. MLVI, a marker of medication adherence that uses clinically derived information, predicts LAR in pediatric liver transplant recipients.

PTSD in solid organ transplant recipients: Current understanding and future implications.

PTSS are quite prevalent in transplant recipients, although full-scale PTSD may not be that common. Those symptoms have been linked to poor transplant outcomes, perhaps owing to non-adherence to medications and other recommendations, brought about by the avoidance dimension of the PTSD/PTSS construct (patients may avoid taking their medications because they serve as reminder of the emotionally traumatic event--the transplant). It is possible to treat PTSD via specific psychotherapeutic techniques, and the treatment has been shown to be safe and likely effective in other populations. Therefore, practitioners who treat transplant recipients should be familiar with the presentation and treatment of those symptoms. This manuscript provides a systematic literature review of the PTSD/PTSS presentation in the pediatric transplant setting, a synthesis of available research findings, and suggestions for current care and future research.

Mental health and quality-of-life concerns related to the burden of food allergy.

As food allergy increases, more research is devoted to its influence on patient and family mental health and quality of life (QoL). This article discusses the effects on parent and child QoL, as well as distress, while appraising the limitations of knowledge given the methods used. Topics include whether QoL and distress are affected compared with other illnesses, assessment of distress and QoL in parents compared with children, concerns about food allergy-related bullying, and the necessity for evidence-based interventions. Suggestions are offered for how to improve QoL and reduce distress on the way to better coping with food allergy.

Improving adherence to medications in pediatric liver transplant recipients.

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.

A combined dietary-physical activity intervention affects bone strength in obese children and adolescents.

Obesity has become the most common pediatric chronic disease in the modern era. Recent data suggests that unlike obese adults, obese children and adolescents may have decreased bone strength. It was the objective to prospectively examine the short term effects of a 3 month combined dietary-physical activity intervention on anthropometric measures, body composition, fitness and bone strength in obese children. Twelve obese subjects completed the 3 m intervention and were compared to 12 obese age and gender matched controls. Bone strength was measured using quantitative ultrasound measurements of bone speed of sound (SOS). There were significant differences in changes of body weight (0.01 +/- 0.7 vs. 2.3 +/- 0.6 kg, p = 0.033), BMI percentiles (- 2.8 +/- 1.1 vs. - 0.2 +/- 0.2 %, p = 0.037), body fat percent (by skinfolds, - 1.5 +/- 0.8 vs. 0.7 +/- 0.5 %, p = 0.035), and endurance time (170 +/- 42 vs. 50 +/- 27 s, p = 0.045) in the intervention vs. control subjects, respectively. In addition, we found a significant difference in the change of bone SOS between the intervention and control group subjects (21.5 +/- 21.6 vs. - 87.0 +/- 37 m/s, p = 0.023). During the critical period of bone development of childhood and adolescence, a combined dietary-physical activity intervention leads to increased bone strength in obese children. These results highlight the importance of multi-disciplinary programs for the treatment of childhood obesity and its complications.

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.

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.

A pilot study of posttraumatic stress and nonadherence in pediatric liver transplant recipients.

BACKGROUND: Symptoms of posttraumatic stress disorder (PTSD) were described in survivors of life-threatening diseases, the trauma being the experiences associated with the disease or its treatment. Their prevalence in liver transplant recipients is unknown. Based on clinical observations, we hypothesize that a significant proportion of pediatric liver transplant recipients suffers from PTSD symptoms. We further hypothesize that nonadherence (noncompliance) to medical management may, in some cases, be associated with these symptoms. Traumatized patients, according to this hypothesis, will avoid taking their medications, because these serve as painful reminders of the disease. OBJECTIVES: To determine the prevalence of PTSD symptoms in a sample of pediatric liver transplant recipients. To determine whether symptoms of PTSD are associated with nonadherence in these patients. To describe the clinical presentation of PTSD and the management of severe nonadherence in patients who suffer from this disorder. METHODS: Nineteen pediatric liver transplant recipients and their caretakers were interviewed, using the UCLA Post Traumatic Stress Disorder Reaction Index (PTSRI). Data were obtained on a few demographic parameters and perception of disease threat. Adherence was evaluated by 2 methods: 1) a clinician panel (taking into account the clinical sequelae of severe nonadherence); and 2) computation of the standard deviations (SDs) of consecutive determinations of blood levels of Tacrolimus (a higher SD means higher variability between individual measures and is therefore an indicator of nonadherence). As an illustration of the general phenomenon, we describe 3 cases of liver transplant recipients who were nonadherent and who suffered from PTSD. RESULTS: Six of 19 patients had positive scores on all 3 components of the PTSRI (PTSD patients). Three of these, and none of the others, were considered significantly nonadherent by the panel. Therefore, nonadherence was significantly associated with the existence of symptoms from all 3 domains of PTSD (Fisher's exact test) in our sample. In particular, a high avoidance score on the PTSRI was highly correlated with panel-determined nonadherence. Further, SD of medication levels were significantly higher in PTSD patients, compared with the rest of our sample. No significant differences were found in perception of disease threat or demographic variables between PTSD patients and the rest of our sample. The 3 cases that we describe became adherent to their medications when symptoms of PTSD subsided during the course of therapy. CONCLUSIONS: Clinically significant nonadherence, determined by 2 different methods, was associated with the full spectrum of PTSD symptoms in this sample. It was especially associated with a high avoidance score, which suggests that avoidance of reminders of the disease (eg, medications) may be a mechanism of nonadherence. Screening for and management of these symptoms, therefore, may improve adherence. This novel concept may be applicable to other patient populations. However, more data are needed before any definite conclusions can be drawn.

Acute diverticulitis of the small bowel: CT findings.

We present the computed tomographic (CT) findings in two cases of small bowel diverticulitis, one affecting the jejunum and the other a Meckel's diverticulum. The main CT finding was that of a mass with an air-fluid collection in contiguity with small bowel loops.

High-dose nitrates in the immediate management of unstable angina: optimal dosage, route of administration, and therapeutic goals.

Nitrates are commonly used for rapid relief of ischemia in the initial management of unstable angina. However, their optimal dosage, route of administration, and therapeutic goals have not been fully established. This study was conducted to determine the optimal dosage and mode of administration (intravenous bolus versus sublingual spray) of nitrates and the therapeutic goals of their use in the immediate management of unstable angina. In a single-center prospective trial, 72 consecutive patients with unstable angina accompanied by typical ST-segment depression on electrocardiogram were randomly assigned to receive isosorbide dinitrate either as repeated intravenous boluses or as sublingual sprays while being delivered to the hospital by a mobile intensive care unit. Optimal nitrate dosage was tailored to pain relief while monitoring mean blood pressure reduction to an optimal range (5% to 20%) without dosage restriction. The mean nitrate dosage needed for ischemia control during the first hour of treatment was 7.8 +/- 3.8 mg. Optimal blood pressure reduction was achieved by significantly more intravenously treated patients than sublingually treated patients (68% v 41%, P = .037). Intravenously treated patients also experienced a more pronounced therapeutic effect, as assessed by reduction in chest pain score (67% v 39%, P = .0004) and decrease in ST-segment depressions (57% v 27%, P = .004). These results show that higher doses of nitrates than previously recommended are required for ischemia control during the initial management of unstable angina. The use of repeated intravenous boluses is safe and more easily controlled and, therefore, more efficacious than sublingual sprays in inducing the maximal anti-ischemic effect while avoiding significant hypotension.

Home intravenous antibiotic treatment for febrile episodes in immune-compromised pediatric patients.

The purpose of this work was to assess the feasibility of home intravenous antibiotic treatment (HIAT) for febrile episodes in immune-compromised (neutropenic, splenectomized), low-risk pediatric patients. Thirty hematology-oncology patients who presented to our emergency room from January 1993 to January 1995 and who suffered from a febrile episode and were considered at low risk for septic complications were immediately discharged on HIAT. Patients were followed for at least 3 weeks after recovery. Patients and parents were retrospectively questioned about adverse effects and about their degree of satisfaction with home treatment. Patients who required hospitalization during this period were considered unresponsive to HIAT and were analyzed for causes and adverse effects. Thirteen out of 60 (22%) febrile episodes, or eight out of 42 (19%) episodes of fever and neutropenia eventually led to hospitalization. Pseudomonas species infections were associated with the highest rate of unresponsiveness (88%). A central venous catheter infection developed in two cases following HIAT (two cases out of 640 days of therapy). No other complications were identified. No infection-related morbidity was observed. Patients and parents were highly satisfied with HIAT and wanted to use it again, if necessary. Immediate discharge on HIAT for low-risk pediatric immune-compromised patients suffering from a febrile episode is feasible, safe, and well accepted by patients and families. Patients who are found to have Pseudomonas infections should probably be hospitalized. Our results are preliminary and must be confirmed by a prospective, randomized trial before definite recommendations can be made.

Colonoscopic resection of large colonic polyps--a prospective study.

Forty-five patients who were referred for surgical resection of large colonic polyps after index colonoscopy were considered for endoscopic polypectomy. Eighteen of these patients were ultimately referred for surgery. Twenty-five patients with 25 large polyps underwent endoscopic polypectomy; there were 9 females and 16 males with a mean age of 69 years. Among the polypectomy patients, polyp size was 3.0-6.0 cm, found mostly in the left colon. There were 21 pedunculated and 4 sessile polyps. Follow-up was carried out for a mean of 48 months (range, 12-171 months). Polypectomy was possible on a single attempt in 12 (48%) cases and in 13 (52%) cases by a piecemeal technique. Pathological examination revealed malignancy in 11 (44%), adenomatous polyp in 11 (44%), and inflammatory, hyperplastic and harmartoma in 1 patient each. Complications included bleeding in 3 (12%) patients and diarrhea and fever in 1 (4%). All complications were successfully treated conservatively without sequellae. Two patients were referred for surgery, 1 with invasion of the base of the polyp and 1 because of a synchronous malignant polyp. During follow-up, 8 metachronous polyps were detected. In 1 of these, a carcinoma was found and treated with endoscopic polypectomy. In conclusion, endoscopic polypectomy of large polyps is safe and can defer surgical treatment. Regular follow-up is required. Endoscopic polypectomy of large polyps should be considered before referral for surgical treatment.

Does the use of the ileocecal region in reconstructive urology cause persistent diarrhea?

The ileocecal region (ICR) is used extensively in reconstructive urological surgery. To evaluate whether resection of the ICR may cause protracted diarrhea, 50 patients undergoing ileocecal resection were studied. Fifty patients undergoing left colectomy for cancer were used as controls. No significant change in bowel habits was noted in the control group. Among patients undergoing ICR resection 42% had transient loosening of stools 2 weeks after surgery which improved within 3 months. Twelve months after surgery only 6 patients with solid stools preoperatively had loose stools, and none suffered diarrhea. In conclusion, in the patients studied after resection of the ICR diarrhea gradually resolved. More work is necessary to study other potential metabolic consequences of such resection.