Timothy M. Clifford

Predictors of relapse to alcohol and illicit drugs after liver transplantation for alcoholic liver disease.

Background. Alcoholic liver disease (ALD) is a common indication for transplantation worldwide. This study identifies factors predicting posttransplant recidivism. Methods. Clinical and laboratory data were reviewed. Uni- and multivariate analyses for survival and relapse to alcohol and illicit drugs were performed. Result. Between July 1995 and November 2007, 387 patients underwent liver transplantation at our institution. Of these, 147 patients (38%) were found to have ALD. Five patients (3.4%) were excluded because of perioperative mortality. Overall survival was 96.2%, 89.6%, and 84.4% at 1, 3, and 5 years, respectively, with a median follow-up of 41.2 months. Twenty-seven patients (19%) returned to alcohol after transplantation. By univariate analysis, depression was the only significant factor affecting survival (P=0.01), whereas posttransplant relapse to alcohol trended toward significance (P=0.059). Multivariate analysis showed both factors to be independently associated with poor survival (P=0.008 and 0.017, respectively). Factors associated with relapse included less than 12 months of abstinence before transplant (P=0.019) and participation in rehabilitation (P=0.026). Multivariate analysis showed pretransplant abstinence less than 12 months as the only independent factor (P=0.037) associated with alcohol relapse after transplantation. Twenty-five patients (17.2%) had documented drug use after transplantation. Drug abuse before transplantation was the only independent predictor of drug abuse after transplantation (P=0.017). Conclusions. Excellent results can be obtained in patients undergoing liver transplantation for ALD, though depression and recidivism adversely impact survival. In our series, abstinence less than 12 months was associated with relapse to alcohol. Similarly, those with prior drug abuse are more likely to continue drug use after transplantation.

Enteral nutrition and drug administration, interactions, and complications

The enteral route has become the standard of care to deliver nutrition support for hospitalized acute care and ambulatory care patients. The same access device is increasingly being used to deliver medications, which provides cost savings but also creates new challenges. Cost savings can be negated if the concomitant administration of nutrition elicits a decrease in bioavailability due to incompatibilities that alter drug or nutrition therapy. Feeding tubes can deliver nutrients and drugs to the stomach, small bowel, or both, with optimal efficacy of medications depending on delivery to the appropriate segment of the gastrointestinal tract. Liquid preparations are often the preferred formulation for enteral administration. Obstruction of the enteral access device may occur when specialized medication formulations are altered inappropriately. Occasionally, the enteral formula should be changed to modify the content of free water, fiber, electrolytes, or vitamins that may interfere with the drug therapy. Intolerance to enteral nutrition such as abdominal distention and diarrhea may be the result of the medication, and the causative agent should be identified to improve patient comfort. This article will address optimal drug delivery via enteral access devices and possible complications associated with therapy.

Prevalent immunosuppressive strategies in liver transplantation for hepatitis C: results of a multi‐center international survey

To determine current immunosuppression regimens and strategies for acute cellular rejection in hepatitis C virus (HCV) patients after liver transplantation (LT), questionnaires were sent to 264 LT programs worldwide. Surveys from 81 programs were reviewed. In 27 centers (33.8%) the immunosuppression protocol used in HCV differed from non‐HCV patients. Tacrolimus‐based immunosuppression is utilized in 70 centers (86.42%). Triple therapy using tacrolimus, mycophenolate mofetil and steroids is the most common regimen (41%). Six programs (7.4%) use steroid‐free protocols. In nine centers (11%) steroids are discontinued within a week, 56% within 3 months, and 98% within the first year. At 75% of centers, mild rejection is treated by increasing baseline immunosuppression. Moderate rejection is treated by increasing baseline immunosuppression in 38% of centers, steroid bolus in 44%, and either in 16%. For severe rejection, 46% of centers give bolus steroid, and 16% administer antibodies. Among respondents, non‐US programs use significantly more cyclosporine than US programs (35.6% vs. 2.8%, P < 0.001). Duration of steroid therapy is significantly shorter in US programs than non‐US (10.8 vs. 29.4 weeks, P < 0.001). There is no consensus regarding the best immunosuppressive regimen and rejection treatments in HCV patients after LT. Our results reveal the most prevalent management practices in this difficult group of patients.

Risk Factors for Venous Thromboembolism in Patients with Chronic Liver Disease

BACKGROUND Pharmacologic prophylaxis for venous thromboembolism (VTE) in patients with chronic liver disease (CLD) presents a unique challenge because of coagulopathies associated with the disease. When evaluating whether these patients require VTE prophylaxis upon hospitalization, it would be advantageous if risk factors for the development of VTE in this population were known. OBJECTIVE To evaluate risk factors associated with the development of VTE in patients with CLD. METHODS A retrospective case-control study was conducted. Patients admitted to the University of Kentucky Chandler Hospital from October 2006 to July 2010 with a diagnosis of CLD and VTE were matched in a 1:3 fashion with CLD patients without VTE. The primary objective was to determine whether there were significant differences in laboratory values between the 2 groups. RESULTS During this time, 27 patients with CLD (1.0%) were diagnosed with VTE. These patients had significantly lower median aspartate aminotransferase (AST) (47 vs 70 U/L, p = 0.04), alanine transaminase (ALT) (24.5 vs 36 U/L, p = 0.02), albumin (2.1 vs 2.4 g/dL, p = 0.02) and hematocrit (Hct) (28.3% vs 32%, p = 0.03) values compared to the control patients. Patients with albumin lower than 1.9 g/dL had a 5.1 times greater risk of VTE compared to patients with albumin of 2.8 g/dL and higher (OR 5.14, 95% CI 1.05–25.2). CONCLUSIONS Patients with CLD who developed VTE had significantly lower AST, ALT, albumin, and Hct compared to those of control patients. Studies are necessary to further examine the significance of this finding.

Pharmacotherapy of Lung Transplantation An Overview

Lung transplantation has become a viable treatment therapy for end-stage lung disease patients. The most common etiologies of end-stage lung disease, which can require a transplant are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), and pulmonary fibrosis (PF). Listing criteria are institution and program specific. Approximately 1500 lung transplants were performed in 2008; and at 5 years post transplant, one-half are expected to survive. The surgery itself is associated with various complications, including surgical, infectious, and mechanical. Immunosuppression is paramount to the management of these patients, the goal being prevention of T cell activation to prevent rejection of the new organ. The patients commonly receive an induction agent with a T cell depleting antibody and high-dose corticosteroids. Maintenance immunosuppression begins immediately after the surgery, consisting of a combination of a calcineurin inhibitor, antimetabolite, and corticosteroids. Side effect profiles from the various agents will determine the choice of agents, and patients may have modifications throughout the therapy. The role of the pharmacist spans the inpatient management of acute complications to medication selection, management of maintenance immunosuppression, as well as monitoring for adverse drug reactions and drug–drug interactions. A multidisciplinary collaborative approach must be taken to ensure the best outcomes for this patient population.

Evaluation of Continuation of Stress Ulcer Prophylaxis at Hospital Discharge

Purpose Stress-related mucosal disease (SRMD) can adversely affect patient morbidity and mortality. The use of stress ulcer prophylaxis (SUP) in patients with no risk factors for clinically important bleeding, however, is contributing to health care-related adverse events, drug interactions, and costs. The objective was to determine the percentage of hospitalized patients who receive SUP without an approved indication and to evaluate the financial impact of inappropriate prescribing as well as the risk for significant drug-drug interactions. Methods A retrospective chart review was performed of hospitalized adult cardiology, family medicine, and internal medicine patients between July 1, 2006 and June 30, 2007. Prescribing of acid suppressive therapy (AST) during hospital admission and indications for SUP were evaluated. Concomitant medications, cost of therapy, and discharge medications were assessed as secondary outcomes. Results Of the 4,603 patients admitted during the study period, 418 were randomly selected for study inclusion. Approximately 53% (221/418) of the selected patients received SUP during hospital admission, 93% (206/221) of whom had no indication for prophylaxis. Of those who continued AST at discharge (14%; 31/221), 84% (26/31) had no approved indication. Overuse of SUP resulted in 77 potential drug-drug interactions and an estimated 30-day outpatient cost of

Understanding risk factors, screening, and treatment of postmenopausal osteoporosis.

37,950 for patients receiving these medications at discharge. Conclusion SUP is frequently prescribed to non–critically ill patients when the risk of SRMD is low. Use of SUP for patients who do not meet evidence-based criteria appears to contribute to increased health care expenditures, potential adverse events, and drug interactions.

Celecoxib-Induced Nephrotoxicity in a Renal Transplant Recipient

Between 30% and 50% of American women will endure a clinical fracture during their lifetime due to the loss of bone mineral density that occurs with menopausal estrogen loss. This article is part one in a two-part series on osteoporosis. Part two will appear in the August 2008 issue of ORTHOPEDICS.

Risk factors, prevention, and treatment of corticosteroid-induced osteoporosis in adults.

A 47‐year‐old renal transplant recipient came to the transplant clinic with a serum creatinine level that was elevated above her baseline value. She had been taking celecoxib for arthritic pain. She was told to discontinue the drug, and shortly after, her serum creatinine level returned to baseline. Several case reports describe nephrotoxicity with cyclooxygenase (COX)‐2 inhibitors. However, only two of these reports involved renal transplant recipients, and in both, rofecoxib was the COX‐2 inhibitor of concern. To our knowledge, this is the first case report of a renal transplant recipient who developed nephrotoxicity while taking celecoxib. The potential renal effects of COX‐2 inhibitors have received little attention, even though nonsteroidal anti‐inflammatory drugs are considered to carry the risk of nephrotoxicity in patients with comorbidities such as diabetes mellitus and hypertension. Further studies are necessary to determine the safety of COX‐2 inhibitors in transplant recipients and other patient groups that may be at heightened risk of nephrotoxicity.

Management of chronic kidney disease-mineral bone disorder.

An orthopedist can play a critical role in corticosteroid induced osteoporosis management by identifying at-risk patients and selecting appropriate prophylactic measures. This article is part two in a two-part series on osteoporosis. Part one appeared in the July 2008 issue of ORTHOPEDICS.