William E. Wade

Renal transplant patient compliance with free immunosuppressive medications.

Background. Noncompliance with immunosuppressive medications after renal transplantation is believed to be a major cause of allograft rejection and graft loss, with the impressive costs of these agents considered a significant reason for noncompliance. Our purpose was to determine the compliance rates of renal transplant patients who received their immunosuppressant therapy free of charge and evaluate their patterns of compliance. Methods. All patients who received a renal transplant and received their immunosuppressant medications at our institution for their first year posttransplant were included in the study. Compliance rate was calculated and serum immunosuppressant concentrations were obtained to validate compliance assessments. Results. Eighteen patients were included in the study. Approximately 48% of noncompliant patients were found to have subtarget drug concentrations, although only 14% of compliant patients had subtarget levels (&khgr;2=12.9, P <0.001). At 5 months posttransplant, 95% of the patients remained compliant; however, by 12 months posttransplant, only 48% of the patients remained compliant. The mean time to the first noncompliant month was 9.8 months (95% confidence intervals=8.60–11.0). Conclusions. Patients who received their immunosuppressants free of charge were generally compliant within their first year of transplantation, however, compliance tended to decrease over time. This suggests that drug cost alone does not explain noncompliant behavior. Intensive efforts to increase medication compliance before month 8 posttransplantation should be implemented.

Assessing NSAID Prescription Use as a Predisposing Factor for Gastroesophageal Reflux Disease in a Medicaid Population

AbstractPurpose. The purpose of the study was to determine the incidence of GERD associated with prescription NSAID consumption. Methods. All Georgia Medicaid patients > 25 years of age and continuously eligible for 1996, 1997, and 1998 were included in the study. Patients were excluded if they received a GERD diagnoses during 1996 and 1997. Patients were observed in 1998 and classified into GERD and control cohorts. Comorbidities, demographics, and NSAID prescription consumption were retained and modeled with logistic regression. Results. The absolute risk of developing GERD without previous NSAID consumption was 0.38. The absolute risk of developing GERD for those patients who consumed one or more NSAID prescriptions during 1996 and 1997 was 0.80. Thus, the relative risk of GERD for NSAID patients was 2.11. GERD was significantly associated with one or more NSAID prescriptions (OR = 1.82), age (OR = 1.05 for 5 year range), gender (OR = 1.31 for females), asthma (OR = 3.24), obesity (OR = 2.77), hiatal hernia (OR = 4.17), tobacco use (OR = 2.56), and alcohol (OR = 1.83). The initial NSAID prescription was responsible for the greatest marginal increase in GERD. Conclusions. Our study suggests that NSAIDs are associated with GERD especially for females, alcohol and tobacco users, and patients with asthma, hiatal hernia, or obesity.

Tapentadol Hydrochloride: A Centrally Acting Oral Analgesic

BACKGROUND Tapentadol hydrochloride is a centrally acting oral analgesic approved by the US Food and Drug Administration in November 2008 for the treatment of moderate to severe acute pain. It is available as immediate-release 50-, 75-, and 100-mg tablets. OBJECTIVE The purpose of this article is to review animal studies, pharmacokinetic studies, drug-drug interaction studies, and Phase II/III trials of tapentadol in various conditions producing moderate to severe pain. Efficacy and tolerability data from these studies are summarized. METHODS A search of MEDLINE and International Pharmaceutical Abstracts was conducted from January 2005 through June 30, 2009. Search terms included tapentadol, tapentadol hydrochloride, and (-)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride. Relevant information was extracted from the identified articles, and the reference lists of these articles were reviewed for additional pertinent publications. The manufacturer was contacted for clinical trials, abstracts, and poster presentations that were not identified by the literature search. ClinicalTrials.gov was searched to identify recently completed studies. RESULTS Tapentadol produces analgesia through a dual mechanism of action: mu-opioid-receptor activation and norepinephrine reuptake inhibition. Its efficacy has been reported in a number of animal studies, as well as in Phase II/III clinical trials. Primary pain disorders in which efficacy has been reported include dental extraction pain, pain after bunionectomy surgery, osteoarthritis pain of the knee and hip, and low back pain. Major adverse effects reported in Phase II/III trials primarily involved the gastrointestinal system (2%-66% of subjects) and the central nervous system (4%-65% of subjects). The occurrence of gastrointestinal adverse effects appeared to be less frequent in tapentadol recipients than in those receiving oxycodone. CONCLUSIONS Tapentadol appears to be a well-tolerated and effective analgesic for the treatment of moderate to severe acute pain. Although not currently approved for the management of chronic pain, tapentadol has been reported to be effective in managing pain associated with osteoarthritis and low back pain.

Cost‐benefit analysis of a clinical pharmacist‐managed medication assistance program in a renal transplant clinic

Medicare pays for 80% of the cost of immunosuppressant agents needed within the first 3 years of solid organ transplantation; however, many patients cannot afford the remaining 20%. Furthermore, many patients who are beyond 3 years post‐transplantation and have prescription coverage cannot afford the co‐payment for these medications. Other patients may not be able to afford their medications due to limited or no insurance coverage. The Medical College of Georgia (MCG) has been giving immunosuppressant medications to renal transplant patients if they cannot afford to pay for them. To assist MCG with drug cost for medications and maintain quality care for renal transplant patients, a clinical pharmacist‐managed medication assistance program was implemented to procure immunosuppressants from pharmaceutical manufacturers. 
Methods: All patients enrolled in medication assistance programs from 1 January 1998 through 31 December 1998 were included in this analysis. Medication acquisition costs with and without Medicare reimbursement and the cost of implementing the clinical pharmacist‐managed medication assistance program were used to determine the value of implementing this service. 
Results: Sixty‐one patients were enrolled in manufacturers’ assistance programs and a net cost avoidance of

A review of laxative therapies for treatment of chronic constipation in older adults

124,793 was realized for the year of the program (benefit‐to‐cost ratio of 7.5:1). Assuming that the hospital collected the maximum amount allowed for patients receiving Medicare benefits, a cost avoidance of

Persistence with Estrogen Therapy in a Postmenopausal Medicaid Population

69,233 was calculated (benefit‐to‐cost ratio of 4.16:1). 
Conclusions: A clinical pharmacist‐managed medication assistance program in a renal transplant clinic produced substantial cost savings over this 1‐year study period. For each dollar spent in pharmacists time, a minimum of

Cost/Death Averted with Venous Thromboembolism Prophylaxis in Patients Undergoing Total Knee Replacement or Knee Arthroplasty

4 was returned to the institution.

The use of aerosolized tobramycin in the treatment of a resistant pseudomonal pneumonitis

BACKGROUND Multiple studies have addressed the treatment of chronic constipation in adults in general; however, less guidance is available for treating this condition in older patients. OBJECTIVE The aim of this paper was to review the effectiveness of laxatives for chronic constipation in the elderly. METHODS Medline, Web of Science, international Pharmaceutical Abstracts, and the Cochrane database of Systematic Reviews were searched for english-language articles evaluating the treatment of chronic constipation in older individuals from the inception of the databases until October 2010. Search terms included constipation, treatment, laxative, elderly, and geriatric. Articles were excluded if the mean age was <65 years. RESULTS Thirty-one trials were identified. These studies varied widely in terms of methodology, quality, sample size, efficacy end points, and duration. Mean stool frequency was 9.08 bowel movements per week with psyllium and 8.29 per week with calcium polycarbophil (P = 0.04). docusate sodium daily, docusate sodium q12h, and docusate calcium daily for 3 weeks produced a mean stool frequency of 1.95 bowel movements per week versus 1.50 for placebo (P = NS), 2.29 versus 1.76 (P = NS), and 2.83 versus 1.75 (P<0.02), respectively. Mean stool frequency with lactulose versus placebo was 0.7 and 0.5 bowel movements per day (P<0.02). in patients receiving polyethylene glycol or lactulose, mean stool frequency was 1.3 and 0.9 bowel movements per day (P = 0.005). in a study comparing senna plus a bulking agent with lactulose, mean stool frequency was 4.5 per week for the combination product versus 2.2 per week for lactulose (P<0.001). A study comparing sodium picosulfate with senna reported a mean stool frequency of 0.71 and 0.63 per day (P value not reported). Lubiprostone was associated with 5.69 spontaneous bowel movements per week versus 3.46 per week for placebo (P = 0.001). CONCLUSIONS Higher-quality trials evaluating the treatment of constipation in older patients are needed to create a basis for more definitive recommendations in this population. The approach to older adults with constipation should be individualized.

The Expanding Role of Pharmacy and Therapeutics Committees

We evaluated rates of persistence with estrogen replacement therapy in postmenopausal Georgia Medicaid recipients adjusted for age and race. Data files for 1992–1994 were examined to estimate 3‐year conditional survival probabilities using the Kaplan‐Meier model, and 3800 subjects were identified. Over 54% of women remained compliant over 29 months, and 17% continued therapy for the entire 35 months of observation. Kaplan‐Meier predictors indicated that white women have a 70% chance of being compliant for 3 years, whereas black women have a 60% chance. Monthly discontinuation rates ranged from 1–1.5% after the second month of therapy. Younger, white women were the most likely to maintain and comply with therapy.

A cost analysis of fondaparinux versus enoxaparin in total knee arthroplasty.

Study Objective. To compare the cost‐effectiveness of warfarin or enoxaparin with no prophylaxis for prevention of venous thromboembolism in patients undergoing total knee replacement (TKR) or knee arthroplasty.