Risk-adjusted relationship between voriconazole utilization and non-melanoma skin cancer among lung and heart/lung transplant patients.

BACKGROUND: We examined the relationship between voriconazole utilization and non-melanoma skin cancer (NMSC) development among adult lung and heart/lung transplant patients who were continuously enrolled in a large U.S. commercial health plan. METHODS: Cox proportional hazards regression models were constructed to assess both the crude and adjusted effect of voriconazole usage on NMSC development. Overall, 467 adult lung (98%) and heart/lung (2%) transplant patients (60% male) with median age of 58 years were analyzed. RESULTS: Fifty-seven (12%) patients developed NMSC over a median follow-up time of 610 days. At the crude level, patients with any (vs. none) claim for voriconazole were more likely to develop NMSC (19% vs. 12%, hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.02, 2.96, P = 0.04). However, after statistical adjustment for demographic and clinical factors, the effect was largely diminished and no longer statistically significant (HR: 1.23, 95% CI: 0.71, 2.14, P = 0.45). Results were similar when modeling average and total dose of voriconazole. Risk factors significantly related to NMSC development were being male, older age, sun exposure, history of chronic obstructive pulmonary disorder, and history of immune disorder. CONCLUSION: Results suggest that the relationship between voriconazole utilization and NMSC among lung transplant patients may be a result of confounding by indication, and that controlling for underlying patient characteristics is paramount.

A retrospective assessment of pre-treatment variables on the response to darbepoetin alfa after renal transplantation.

This retrospective review assesses the efficacy of darbepoetin alfa for treating anemia after renal transplantation. Patients were evaluated over a 12-week period, and efficacy was based on achieving hemoglobin >12 g/dL. Thirty-six patients were analyzed (53% male, 53% cadaveric allografts, median age 42.5 years). Baseline creatinine clearance ranged from approximately 15 to >100 mL/min. Most patients initiated darbepoetin alfa <3 months (50%) or >12 months (44%) after transplantation, 19% were previously receiving recombinant human erythropoietin (rHuEPO), and 47% were on concomitant ACE inhibitors. The majority of patients received either tacrolimus- (53%) or cyclosporine- (44%) based immunosuppression. Overall, 29 (81%) patients achieved the hemoglobin target with a mean time to response of 4.4 weeks. Neither the time to anemia onset, previous rHuEPO therapy, concomitant ACE inhibitor, allograft source, immunosuppressive regimen, nor degree of renal function affected the proportion of patients achieving the hemoglobin target, time to response or darbepoetin alfa dose requirement. Patients with anemia >12 months post-transplantation or on concomitant ACE inhibitors required a significantly longer duration of therapy. No adverse events associated with darbepoetin alfa therapy were detected. These results demonstrate that darbepoetin alfa is a safe and effective treatment for anemia in renal transplant recipients.

Human granulocytic ehrlichiosis in pancreas transplant recipients.

Human ehrlichioses are tick-borne infections caused by bacteria in the genus Ehrlichia of the family Rickettsiaceae. To date there have been three cases of ehrlichiosis reported in the transplant population, a human monocytic ehrlichiosis (HME) infection in a liver transplant recipient and two cases of human granulocytic ehrlichiosis (HGE) in kidney transplant recipients. We report three pancreas transplant patients who developed HGE in the last two years at a single southeastern center in the United States. All three patients had clinical, laboratory, and pathophysiologic findings on bone marrow biopsy and peripheral blood smears consistent with HGE, and responded to doxycycline therapy. In the setting of potent immunosuppression, ehrlichiosis should be considered in the differential diagnosis of transplant patients presenting with persistent fever, pancytopenia, and abnormal liver function. Patients with ehrlichiosis infection may be at risk for developing other opportunistic infections or lymphoproliferative disease.

A retrospective assessment of safety, efficacy, and pharmacoeconomics of generic azathioprine in heart-transplant recipients.

Although a generic formulation of azathioprine (AZA) has been available since 1996, safety, efficacy and pharmacoeconomic implications following conversion from Imuran (AZA) to generic AZA in heart-transplant patients remains to be determined. A retrospective, safety and efficacy assessment, in addition to a cost comparison, was performed in 30 heart-transplant patients who had been switched from Imuran to generic AZA. In heart-transplant patients converted from Imuran to generic AZA, no compromise in safety and efficacy, as measured by white blood cell (WBC) count, infections, rejections, malignancies, and hospitalizations was observed. Generic substitution of Imuran results in an annual cost savings of $318 per patient.

Preliminary experience with midodrine in kidney/pancreas transplant patients with orthostatic hypotension.

In an effort to ameliorate the problem of orthostatic hypotension in pancreas transplant patients, current medical management consists of maximizing the patient's hydration, altering antihypertensives, increasing sodium intake, initiation of fludrocortisone, compression stockings, and behavioral modifications. Despite these medical interventions, a subset of patients remains symptomatic. Midodrine (ProAmatine), an alpha-adrenergic agonist, was approved for the treatment of symptomatic orthostatic hypotension in the US. This preliminary report attempts to assess the safety and efficacy of midodrine use in kidney/pancreas (KP) or pancreas alone (PA) transplant recipients. A retrospective review was performed of 7 KP and 1 PA recipient experiencing symptomatic postural hypotension after maximizing other medical treatments. Blood pressure, serum creatinine (SrCr), and objective responses to postural hypotension were assessed at routine intervals. Pre-midodrine monitoring revealed a mean orthostatic change in systolic blood pressure from sitting to standing of 43 mmHg (range 20-100 mmHg). Patients received a mean starting midodrine dose of 18 mg/d, which was titrated to a maximum dose of 30 mg/d. Systolic blood pressure monitoring revealed a mean orthostatic change of 27 mmHg (range 0-81 mmHg) after initiation of treatment with midodrine and a mean follow-up of 3.2 months. All study patients reported improvement in symptoms of orthostatic hypotension. SrCr was not affected based upon comparison of pre-treatment and current SrCr values of 1.4 and 1.3 mg/dL, respectively. The most common side effect experienced was supine hypertension. These preliminary results suggest that midodrine is safe and effective in transplant recipients; however, the dosage should be titrated to symptomatic relief or a maximum dose of 30 mg. Careful monitoring for supine hypertension is necessary.