Therapeutic Hypothermia in Organ Donors: Follow-up and Safety Analysis
This study aimed to assess the impact and safety of the hypothermia protocol on the longer term graft survival of the kidney (targeted) and extra-renal (non-targeted) organs.
This was a posthoc analysis of patients who had received organs from donors who were randomized to either hypothermia (34-35°C) or normothermia (36.5-37.5°C).
370 solid organ transplant donors from a previous trial.
The outcome for this posthoc analysis was one-year graft survival for kidney transplants, the targeted organ of the intervention.
Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
This article reports a post-hoc analysis of recipients receiving organs from brain dead donors who had undergone either mild hypothermia (34-35°C) or normothermia (36.5-37.5°C). The primary analysis was previously published and the intervention was considered potentially practice changing (https://www.transplantlibrary.com/article/26222557). Targeted temperatures were achieved by using external cooling devices. Follow-up data of 565 kidney, 262 liver, 94 heart, 99 lung and 25 pancreas transplants were obtained from national registries. There were no statistically significant difference in the adjusted and unadjusted 1-year kidney graft survival rates, however a subgroup analysis by donor type showed that the graft survival rate was significantly higher
in standard criteria donors undergoing hypothermia, also when adjusted for cold ischemia time. The 1-year adjusted and unadjusted graft survival rates for liver, heart, lung and pancreas transplants showed no statistically significant differences between the groups.
BACKGROUND In a recent trial, targeted mild hypothermia in brain dead organ donors significantly reduced the incidence of delayed graft function (DGF) after kidney transplantation. This trial was stopped early for efficacy. Here, we report long-term graft survival for all organs along with donor critical care endpoints. METHODS We assessed graft survival through one year of all solid organ transplanted from 370 donors who had been randomly assigned to hypothermia (34-35degreeC) or normothermia (36.5-37.5degreeC) prior to donation. Additionally, changes in standardized critical care endpoints were compared between donors in each group. RESULTS Mild hypothermia was associated with a nonsignificant improvement in one-year kidney transplant survival (95% vs. 92%, hazards ratio [HR] 0.61 [0.31-1.20], p=0.15). Mild hypothermia was associated with higher one-year graft survival in the subgroup of standard criteria donors (97% vs. 93%, HR 0.39 [0.15 -1.00], p=0.05). There were no significant differences in graft survival of extra-renal organs. There were no differences in critical care endpoints between groups. CONCLUSIONS Mild hypothermia in the donor safely reduced the rate of DGF in kidney transplant recipients without adversely affecting donor physiology or extra-renal graft survival. Kidneys from standard criteria donors who received targeted mild hypothermia had improved one-year graft survival.
Mindfulness-based stress reduction for solid organ transplant recipients: a randomized controlled trial
Alternative Therapies in Health & Medicine. 2010;16(5):30-8
CONTEXT Patients who have received solid organ transplants continue to experience a myriad of complex symptoms related to their underlying disease and to chronic immunosuppression that reduce the quality of life. Beneficial nonpharmacologic therapies to address these symptoms have not been established in the transplant population. OBJECTIVE Assess the efficacy of mindfulness-based stress reduction (MBSR) in reducing symptoms of anxiety, depression, and poor sleep in transplant patients. DESIGN, SETTING, AND PATIENTS Controlled trial with a two-staged randomization. Recipients of kidney, kidney/pancreas, liver, heart, or lung transplants were randomized to MBSR (n=72) or health education (n=66) initially or after serving in a waitlist. Mean age was 54 years (range 21-75); 55% were men, and 91% were white. INTERVENTIONS MBSR, a mindfulness meditation training program consisting of eight weekly 2.5-hour classes; health education, a peer-led active control. PRIMARY OUTCOME MEASURES Anxiety (State-Trait Anxiety Inventory), depression (Center for Epidemiologic Studies Depression Scale), and sleep quality (Pittsburgh Sleep Quality Index) scales assessed by self-report at baseline, 8 weeks, 6 months, and 1 year. RESULTS Benefits of MBSR were above and beyond those afforded by the active control. MBSR reduced anxiety and sleep symptoms (P < .02), with medium treatment effects (.51 and .56) at 1 year compared to health education in intention-to-treat analyses. Within the MBSR group, anxiety, depression, and sleep symptoms decreased and quality-of-life measures improved by 8 weeks (P < .01, all), and benefits were retained at 1 year (P < .05, all). Initial symptom reductions in the health education group were smaller and not sustained. Comparisons to the waitlist confirmed the impact of MBSR on both symptoms and quality of life, whereas health education improvements were limited to quality-of-life ratings. CONCLUSIONS MBSR reduced distressing symptoms of anxiety, depression, and poor sleep and improved quality of life. Benefits were sustained over 1 year. A health education program provided fewer benefits, and effects were not as durable. MBSR is a relatively inexpensive, safe, and effective community-based intervention.
Results of a randomized, placebo-controlled safety and efficacy study of topical diclofenac 3% gel in organ transplant patients with multiple actinic keratoses
European Journal of Dermatology. 2010;20(4):482-8
Increasing incidence rates of cutaneous malignancies, paralleling rising survival times of grafts and patients in organ transplant recipients, represents an escalating challenge for dermatologists worldwide. Especially, invasive squamous cell carcinomas (SCC) in immuno-compromised patients are characterized by significantly increased morbidity and mortality and characteristically outnumber basal cell carcinoma in this population. Effective management of actinic keratoses (AK) could help to prevent the further development of invasive SCC. Diclofenac in hyaluronic acid has previously shown to be an effective and well tolerated option for the treatment of AK in immuno-competent patients. However, its safety and efficacy in organ-transplant patients has not been evaluated in a controlled study so far. 32 organ transplant patients (kidney (+/- pancreas), liver, heart) screened at our specialized transplant dermatology outpatient clinic were found eligible and were randomized to either active treatment (24) or vehicle (8). Patients who had stable status of the transplanted graft in the 12 months prior to entering the study and ≥ 3 AK lesions in a contiguous 50 cm2 area on the face, forehead, hands or balding scalp were eligible for inclusion in the study. Treatment of AK with 3% diclofenac in 2.5% hyaluronic acid or placebo twice daily was conducted over a total of 16 weeks, followed by a final evaluation 4 weeks after last application of the study drug. Biopsies were taken from the treated areas at the final visit to verify clinical clearance. Patients were assessed for safety variables that included adverse events, local skin reactions, laboratory results, dosage of immunosuppressive medication and indication of graft rejection. A 24 months follow up was conducted after the end of treatment. 87% (n = 28/32) of the patients completed the 16 week treatment phase and presented for final evaluation 4 weeks after end of treatment. In the diclofenac 3% gel treatment group, a complete clearance of AK lesions was achieved in 41% (9/22) compared to 0% (0/6) in the vehicle group. Side effects in most of the patients included a mild erythema and a mild to moderate swelling of the areas treated. No graft rejections or trends for a deterioration of graft function were detected. No meaningful trends were observed in laboratory results. In 55% of the previously cleared patients, new AK developed in the study area after an average of 9.3 months. None of these patients developed invasive SCC in the study area within 24 months of follow-up. This study demonstrated a greater lesion clearance rate of AKs in OTRs treated with diclofenac 3% gel than with vehicle. Despite recurrent AK in 55% of the previously cleared patients, the 24 month results showed no invasive SCC in this group. This study suggests that diclofenac 3% gel is not only an efficient and well tolerated treatment for multiple AKs in OTRs but also may prevent invasive SCC in these high-risk patients.