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With the reintroduction of colistimethate and polymyxin B into clinical practice, a review of their individual and comparative nephrotoxicity attributes as reported in contemporary literature was undertaken. Given variability in definitions used for acute kidney injury, a particular focus was placed on studies utilizing the Risk-Injury-Failure-Loss-End Stage Kidney Disease (RIFLE) criteria of assessment to provide for standardized comparison. Primary risk factors examined included the influence of dosing and the receipt of concomitant nephrotoxins. The typical severity and time course of renal injury that develops were also analyzed. Nephrotoxicity rates with colistimethate appear to approach 50%, and could be of lower frequency and severity with polymyxin B based on limited literature. Acute kidney injury generally appears to be mild to moderate in magnitude and reversible in nature, though as many as 20% of patients experiencing it may require renal replacement therapy of some duration. The majority of studies showed some relationship with dosing- variably reported as being associated with daily dose or cumulative exposure. Traditional nephrotoxic agents did not appear to confer additional risk individually in the majority of investigations, though receipt of multiple concurrent nephrotoxins did yield a relationship in several. Further studies will be required to better characterize the renal adverse effect profile of these agents, particularly in the case of polymyxin B., (© The Author(s) 2014.)

Objective: To compare the effectiveness of an evidence-based, systematic approach to hypertension care involving comanagement of patients by primary care physicians and clinical pharmacists versus usual care in reducing blood pressure in patients with uncontrolled hypertension., Methods: Patients in a staff model medical group with uncontrolled hypertension were randomized to either a usual care (UC) or a physician-pharmacist comanagement (PPCM) group. All physicians in the study received both group and individual education and participated in the development of an evidence-based hypertension treatment algorithm. Physicians were then given the names of their patients whose medical records documented elevated blood pressures (defined as systolic > or = 140 mm Hg and/or diastolic > or = 90 mm Hg for patients aged < 65 yrs, and systolic > or = 160 mm Hg and/or diastolic > or = 90 mm Hg for those aged > or = 65 yrs). Patients randomized to the UC group were managed by primary care physicians alone. Those randomized to the PPCM group were comanaged by their primary care physician and a clinical pharmacist, who provided patient education, made treatment recommendations, and provided follow-up. Blood pressure measurements, antihypertensive drugs, and visit costs/patient were obtained from medical records., Results: One hundred ninety-seven patients with uncontrolled hypertension participated in the study. Both PPCM and UC groups experienced significant reductions in blood pressure (systolic -22 and -11 mm Hg, respectively, p < 0.01; diastolic -7 and -8 mm Hg, respectively, p < 0.01). The reduction in systolic blood pressure was greater in the PPCM group after adjusting for differences in baseline blood pressure between the groups (p < 0.01). More patients achieved blood pressure control in the PPCM than in the UC group (60% vs 43%, p = 0.02). Average provider visit costs/patient were higher in the UC than the PPCM group ($195 vs $160, p = 0.02)., Conclusions: An evidence-based, systematic approach using physician-pharmacist comanagement for patients with uncontrolled hypertension resulted in improved blood pressure control and reduced average visit costs/patient.

Objective: To compare the cost of recombinant human erythropoietin (rHuEPO) with that of blood transfusion in the treatment of chemotherapy-induced anemia from a healthcare system perspective., Design: A decision analytic model. Baseline estimates were obtained from a review of clinical trials data and economic evaluation studies., Subjects: Secondary data analyses of patients with advanced malignancies, excluding hematologic malignancies and metastasized solid tumors., Interventions: Patients received either leukocyte-depleted packed red blood cells (PRBCs) or rHuEPO 150 units/kg s.c. three times per week for 6 months (24 wk). After 6 weeks, if rHuEPO recipients did not display a response, they received rHuEPO 300 units/kg s.c. three times weekly for the duration of therapy. If rHuEPO recipients still exhibited no response, they were given blood transfusions., Measurements and Main Results: For a treatment period of 24 weeks, approximately 64% of rHuEPO recipients responded at an average expected cost of $12971 per patient. One hundred percent of transfusion recipients responded at a cost of $481; this resulted in a cost savings of $8490. Variation of response rates for rHuEPO or PRBCs did not appreciably lower costs. Lower rHuEPO dosages and higher numbers of transfused units of PRBCs yielded approximately equivalent costs; however, these strategies may not be clinically prudent., Conclusions: From a healthcare system cost and outcome perspective, blood transfusion is the preferred strategy for chemotherapy-induced anemia. However, rHuEPO may be considered an effective blood-sparing alternative for patients with non-stem cell disorders. Future cost-effectiveness analyses are needed to assess more completely both the clinical and quality-of-life benefits rHuEPO may contribute to individual patients' lives and to society overall.

Women with large uterine leiomyomas traditionally have had just one choice for therapy--abdominal hysterectomy. Recently, gonadotropin-releasing hormone (GnRH) agonist therapy has been introduced as an option to shrink tumors before surgery. When administered preoperatively, usually for 2 months, GnRH therapy has been shown to reduce tumor size enough to permit an endoscopic myomectomy or a vaginal hysterectomy. It has also been shown to reduce blood loss associated with the tumors and increase hemoglobin levels. When assessed for its economic impact, preoperative GnRH therapy reduces both direct and indirect costs associated with a hysterectomy.

Critical pathways provide an excellent tool for promoting multidisciplinary efforts to develop optimal, cost-competitive plans for managing patient care. The pharmacy department can play a variety of roles in developing and implementing critical pathways. In advocating optimal drug selection and monitoring, pharmacists can help their institutions reduce costs while maintaining or improving quality of care.

A retrospective adverse drug reaction (ADR) reporting system has been in place at Cedars-Sinai Medical Center for 7 years. Initially, the system identified 300 to 400 ADRs per year. After adding a checklist, that number increased to 750 to 850 per year, an ADR rate of about 2% of total patient admissions. To increase the ADR reporting rate, we initiated a concurrent surveillance program in conjunction with the retrospective system. In the first year of the program, the combined systems identified 1,174 ADRs. In addition, the ADR rate per 100 patient days increased to between 0.5 and 0.7, and the ADR per admission rate increased to 4%. As a result of the more effective ADR surveillance program, the P & T Committee has additional data from which to develop guidelines and educational programs to increase ADR awareness and prevention, and thus, to improve patient outcomes.

A program is described in which physicians prospectively review orders for the use of colony-stimulating factors (CSFs) at a tertiary-care private teaching hospital. Hospital officers and administrators and the heads of medical subspecialties were presented with three options for managing the use of CSFs. Prospective review by physicians was selected, and a task force of medical subspecialists was established to develop criteria for use and to review orders. Initially, every order was prospectively reviewed, but criteria were developed under which some orders do not require physician review. CSF use is documented retrospectively by a drug-use evaluation pharmacist and reviewed for appropriateness by the physician task force. Between March and October 1991, 115 patients were given courses of CSFs, and the use of the physician review system resulted in appropriate use of the drugs for 98% of the oncology patients and 61% of the patients infected with the human immunodeficiency virus. The prospective physician reviewer system has been accepted by the medical staff at the facility and has helped to ensure appropriate use of CSFs.

The Adverse Drug Reaction program at CSMC identifies patients whose charts have been encoded with an ICD-9 code of E930 through E949, inclusively. Incidences per drug or drug category have permitted the Department of Pharmacy, acting through the Pharmacy and Therapeutics Committee, to review patient charts, identify trends and risk factors, and subsequently develop usage criteria for DUE studies. It is hoped that these activities will result in an improvement in usage of these drugs and a reduction in adverse drug reactions to them.

The incidence, pathogenesis, staging, and treatment of endometriosis are reviewed, with an emphasis on pharmacologic management of this condition. Endometriosis--the presence of ectopic endometrial tissue--can be found in 15-25% of infertile women and may be found in 1-5% of all women between menarche and menopause. Although the pathogenesis of endometriosis is uncertain, the most tenable etiologic theory is a combination of celomic metaplasia and retrograde menstruation. Staging is based on the American Fertility Society classification scheme, with stage I being the mildest and stage IV the most severe form of the disease. The management of endometriosis depends on the extent of the disease, the severity of the symptoms, the age of the patient, and the patient's desire for future fertility. Treatment modalities include expectant management, surgery, induction of a pseudopregnancy state with hormonal therapy (e.g., oral contraceptives), or induction of a pseudomenopausal state. The induction of a pseudomenopausal state with the use of oral danazol gained widespread favor in the 1970s as the treatment of choice in patients with endometriosis, but therapy is often associated with unpleasant adverse effects. Gonadotropin-releasing hormone (GnRH) agonists may provide a safe and clinically effective alternative to danazol therapy in patients with endometriosis. Results of a multicenter study comparing nafarelin with danazol for treatment of endometriosis indicated no significant differences between treatment groups with respect to improvements in disease state and symptomatology. The most common adverse effect associated with nafarelin therapy is hot flashes. The GnRH agonist nafarelin is as effective as danazol or oral contraceptives for the treatment of endometriosis and causes fewer adverse reactions. GnRH agonists may replace danazol as the treatment of choice in patients with endometriosis.

Metrizamide is a water-soluble contrast medium used as a diagnostic tool in myelography and cisternography. Despite its accepted safety, its use has been associated with generalized motor seizures, and several cases of this toxicity have been reported. Risk factors include phenothiazine ingestion, seizure history, and large doses of the contrast material. Abnormal electroencephalographic wave patterns, as well as seizure activity, are less frequent after cisternography than myelography. A case of a metrizamide-induced generalized motor seizure following cisternography is reported in a patient with none of the above risk factors. The need for a thorough medication history and the use of prophylactic anticonvulsants in selected patients is discussed.

Cefonicid is a 'second generation' cephalosporin administered intravenously or intramuscularly. It is similar to cefamandole in its superiority to first generation cephalosporins against several enterobacteriaceae as well as its activity against Haemophilus influenzae, including beta-lactamase-producing strains. Its activity against Staphylococcus aureus is similar to that of cefoxitin and inferior to cefamandole and first generation cephalosporins. It has excellent in vitro activity against Neisseria gonorrhoeae, but is inactive against Pseudomonas, Acinetobacter, Serratia, and Bacteroides fragilis. Due to high achievable plasma concentrations and a relatively long half-life, in most clinical trials cefonicid has been administered once daily. It was comparable in efficacy with cefamandole or cefazolin in the treatment of patients with urinary tract, lower respiratory tract, and soft tissue and bone infections. It has also been compared with penicillin in the treatment of uncomplicated gonorrhoea. Results from a small series of patients with endocarditis appear to indicate that cefonicid should not be used in patients with serious staphylococcal infections. Single doses of cefonicid given preoperatively appear to offer a similar degree of protection against post-surgical infection as multiple doses of other antibiotics, but further data from studies involving larger numbers of patients are needed to confirm these impressions. Patients who require prolonged antibiotic therapy, such as those with osteomyelitis being treated as outpatients after a relatively short inpatient course, could benefit from the once daily dose regimen of cefonicid.

Despite its vast utility in clinical oncology, the use of doxorubicin hydrochloride (Adriamycin) is limited by a potentially fatal cardiomyopathy. The following critical review, which examines the natural course, histopathologic effects, risk factors and monitoring indicators of this toxicity, also analyzes recent research of proposed mechanisms, including free radical formation with depletion of detoxifying enzymes, inhibition of vital enzyme systems and alterations in relative calcium concentrations. Prevention of the adverse reaction has been attempted by using such agents as alpha-tocopherol, selenium sulfide, coenzyme Q(10), sulfhydryl donors, nucleosides and razoxane, and via liposomal carriage and alternative methods of administration.

Ticlopidine is an inhibitor of platelet action that has been used in the treatment of a variety of disease states in which platelets play a prominent role. Studies in animals and man have demonstrated that ticlopidine is a potent inhibitor of platelet aggregation induced by adenosine diphosphate (ADP), and variably inhibits aggregation due to collagen, adrenaline (epinephrine), arachidonic acid, thrombin, and platelet activating factor. Inhibition of platelet aggregation is both dose- and time-related, with its onset of activity being 24 to 48 hours, its maximal activity occurring after 3 to 5 days, and its activity still being present 72 hours after a final dose. Ticlopidine also inhibits the release reaction of platelets, prolongs bleeding time, reduces plasma levels of platelet factor 4 and beta-thromboglobulin in patients in whom these proteins are elevated, and may also inhibit platelet adhesion, increase red cell filtrability and decrease whole blood viscosity. In a large number of animal models, ticlopidine markedly inhibits thrombus formation or graft occlusion. Ticlopidine is well absorbed after oral administration. It is extensively metabolised and at least one of its metabolites is pharmacologically active. Therapeutic trials in patients with chronic arterial occlusion due to thrombangitis obliterans or arteriosclerosis obliterans, post-myocardial infarction, cerebrovascular thromboembolic disease, subarachnoid haemorrhage, vascular shunts or fistulas for haemodialysis, and sickle cell disease have shown promise for the use of ticlopidine. However, trials of patients with intermittent claudication, angina pectoris, diabetes mellitus with microvascular disease, aortocoronary bypass grafts, and vascular prostheses have had conflicting results or have shown an unfavourable side effect profile. Further studies are clearly required to establish the role of ticlopidine in many of these areas, some of which are already in progress. Overall, side effects occur in 10 to 15% of patients receiving ticlopidine. The most common side effects are gastrointestinal disturbances and skin rashes. Neither of these necessarily require discontinuation of therapy in most patients. Agranulocytosis, thrombocytopenia, and cholestatic jaundice have also been reported. Bleeding is infrequent except possibly in patients receiving ticlopidine prior to some surgical procedures.