bluuebunny/crossref_metadata_2025 huggingface dataset:
Ticlopidine and Antiplatelet Therapy
Authors: Flores-Runk Patricia , Raasch Ralph H.
Published: January 2017

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical efficacy, and toxicity of ticlopidine. Comparisons with other antiplatelet agents are presented, with an emphasis on efficacy, and a recommendation is provided regarding ticlopidine's place in therapy.

DATA SOURCES:

A MEDLINE literature retrieval of English-language journal articles from 1987 to January 1993 and references identified from bibliographies of review articles and clinical trials.

STUDY SELECTION:

Randomized, blind, controlled studies of ticlopidine and other antiplatelet agents were preferentially selected.

DATA EXTRACTION:

Clinical trials were reviewed in terms of study design, efficacy results, and toxicity.

DATA SYNTHESIS:

Ticlopidine is a new antiplatelet agent with a distinct mechanism of action. In the largest trial of the drug for the prevention of stroke, it was found to be more effective than aspirin in reducing the risk of stroke or death. Clinical trials have also shown ticlopidine to decrease the rate of vascular death and myocardial infarction in patients with unstable angina, and to maintain venous graft patency after coronary artery bypass grafting. The use of ticlopidine in diabetic microangiopathy and peripheral vascular disease appears promising, but further studies are needed. Adverse reactions most commonly reported with ticlopidine are gastrointestinal complaints; the most severe reaction is transient neutropenia, which is seen in approximately 2.3 percent of patients and is severe in nearly 1 percent.

CONCLUSIONS:

Ticlopidine is a reasonable alternative for use in preventing stroke among patients unable to take aspirin or those who do not benefit from aspirin therapy. Its use as first-line therapy is limited by its high cost and the occurrence of hematologic adverse effects.
Evaluation of Pharmacoeconomic Studies: Utilization of a Checklist
Authors: Sacristán José A. , Soto Javier , Galende Ines
Published: January 2017

OBJECTIVE:

To review the fundamental concepts used in clinical economic analysis and establish a simple model to systematically evaluate the quality of pharmacoeconomic studies.

DATA SOURCES:

A MEDLINE search was used to identify pertinent pharmacoeconomic literature, including reviews.

STUDY SELECTION:

Selected literature evaluating the methodology of health economics studies was used.

CONCLUSIONS:

The number of studies presenting a pharmacoeconomic evaluation has increased progressively; however, the quality of the studies has not improved in parallel. The existence of different types of pharmacoeconomic studies does not justify their arbitrary use and the achievement of valid conclusions must be based on sound knowledge of the concepts employed, as well as on use of the most adequate tool in each instance. By evaluating pharmacoeconomic studies systematically, the more common errors (i.e., in planning the study or interpreting the results) can be detected and thus prevented. The checklist we present has 12 sections, each of which includes several subsections. After evaluating the corresponding subsections, each section is labeled as “correct”, “acceptable”, “doubtful”, “incorrect”, or “not applicable.” From this qualitative evaluation, aspects that have been dealt with correctly and those needing improvement will become apparent. Also, the checklist permits the user to verify whether the results have been correctly obtained and, therefore, whether the conclusions are valid. The use of a checklist for evaluating pharmacoeconomic studies may be useful for researchers, journal editors, and the audience when performing, receiving, reading, or accepting a clinical economic study.
Challenge to Clinical Pharmacy Practice in Malaysia
Authors: Hassan Yahaya
Published: January 2017

OBJECTIVE:

To report on the current status and future trends of clinical pharmacy practice in Malaysia.

DATA SOURCES:

Published conference reports and journal articles.

DATA EXTRACTION:

Data on areas related to clinical pharmacy practice in Malaysian hospitals were gleaned from various publications.

DATA SYNTHESIS:

Malaysia is capable of implementing clinical pharmacy services in hospitals and perhaps also in the community setting. The important factors in clinically oriented pharmacy practice include improvement of the drug-control process, development of physical and human resources, clinical pharmacy skills, and the training of practicing pharmacists. A number of Malaysian pharmacists have already developed a unit-dose drug distribution system, patient counseling, therapeutic drug monitoring, drug information, and total parenteral nutrition services.

CONCLUSIONS:

The pharmacy profession in Malaysia has many challenges ahead and it is hoped that every practicing pharmacist will be highly committed to future professional needs so that clinical pharmacy practice in Malaysia becomes a reality.
Nsaid Use and Efficacy in the Emergency Department: Single Doses of Oral Ibuprofen versus Intramuscular Ketorolac
Authors: Wright Julie M. , Price Stephen D. , Watson William A.
Published: January 2017

OBJECTIVE:

To compare the clinical efficacy of single doses of intramuscular ketorolac and oral ibuprofen in the emergency department (ED) treatment of acute pain.

DESIGN:

A retrospective analysis of data collected during a prospective survey of pain management efficacy. The design was noninterventional, and therapy was selected by the treating physician independent of the trial.

SETTING:

Urban teaching hospital adult patient emergency department.

PARTICIPANTS:

A convenience sample of ED patients in acute pain.

INTERVENTIONS:

Patients received ibuprofen 800 mg po (n=95), or ketorolac 60 mg im (n=30) as a single dose. Therapy was selected by the treating physician and was not influenced by the study. RF.8ULTS: Data collected were a 100-mm visual analog pain scale at patient arrival and discharge, verbal description of pain relief, patient demographics, pain management data, and discharge diagnosis. Baseline pain intensity was higher in patients receiving ketorolac (77 mm median) than in those receiving ibuprofen (65 mm, p=0.02). Pain relief was similar (p=0.29) with either treatment when assessed by visual analog scale or patient definition of pain relief.

CONCLUSIONS:

A single dose of either nonsteroidal antiinflammatory drug produced similar pain relief in the general ED population during clinical treatment of pain. Ketorolac should not necessarily be considered a more effective analgesic than ibuprofen in these commonly used doses.
Chronic Hemodialysis Patients. Part I: Characterization and Drug-Related Problems
Authors: Kaplan Barbara , Mason Nancy A. , Shimp Leslie A. , Ascione Frank J.
Published: January 2017

OBJECIVE:

To describe medication use in hemodialysis patients and to characterize the potential drug-related problems that may occur in this population.

DESIGN:

All patients being dialyzed during the study period who were responsible for taking their own medications and who were able to provide an accurate medication history were included in this study. A pharmacist administered a structured medication history and drug therapy review protocol known as the Focused Drug Therapy Review Program to identify potential drug-related problems. This process was modified for a hemodialysis population.

SETIING:

Outpatient hemodialysis unit at a university-affiliated hospital.

RESULTS:

Thirty patients with endstage renal disease requiring hemodialysis were enrolled in the study. On average, 10 prescription and 2 prescribed nonprescription medications were used per patient. The incidence of potential adverse effects and medication allergies or intolerances averaged 5.5 and 2.2 per patient, respectively. Twenty patients (67 percent) reported missing an average of 3.4 (range I-II) doses of medication per month. A total of 216 potential drug-related problems (encompassing both prescribing choices and patient behaviors) were identifiedby the pharmacist; the categories of drug selection and medication compliance contained the greatest number of potential problems (24 and 23 percent, respectively).

CONCLUSIONS:

Hemodialysis patients use a large number of medications, which increases the risk for adverse reactions and other drug-related problems. The types of potential drug-related problems identified are amenable to pharmacist input. Thus, such patients should be targeted for clinical pharmacy intervention.
Chronic Hemodialysis Patients. Part II: Reducing Drug-Related Problems through Application of the Focused Drug Therapy Review Program
Authors: Kaplan Barbara , Shimp Leslie A. , Mason Nancy A. , Ascione Frank J.
Published: January 2017

OBJECTIVE:

To test the value and measure the impact of a model of pharmacy practice called the Focused Drug Therapy Review Program (FDTRP)in patients with endstage renal disease on hemodialysis.

DESIGN:

A modified version of FDTRP, adapted for a hemodialysis population, was assessed for its impact on prescriber behavior. The impact was measured by examining the percentage of pharmacist therapeutic recommendations accepted and implemented by the prescriber.

SETTING:

Thirty patients at a university hospital-based outpatient hemodialysis unit participated in the study. Twenty-four patients completed the study through the implementation evaluation.

RESULTS:

The pharmacist generated 114 therapeutic recommendations and 85 informative comments regarding drug therapy. The prescriber accepted 76 percent and implemented 70 percent of the therapeutic recommendations. The prescriber considered the informative comments to be helpful, even if the information was known previously.

CONCLUSIONS:

The FDTRP has been shown to be useful in the care of chronic hemodialysis patients. In addition, the pharmacist was able to provide clinically important recommendations in a closely monitored patient population.
Hypertension and Endstage Renal Disease
Authors: Brown Thomas E.R. , Carter Barry L.
Published: January 2017

OBJECTIVE:

To review current literature regarding the development of hypertensive renal disease, its epidemiology, and its pathophysiology. This review focuses on strategies to slow or halt the progression of endstage renal disease (ESRD) in hypertension, including the role of blood pressure control, different types of antihypertensive agents, early treatment, and dietary considerations.

DATA SOURCES:

Information was retrieved from searching the MEDLINE database for articles consisting of epidemiologic studies, clinical studies, and review articles pertaining to hypertension and ESRD. Information also was obtained from the US Renal Data System annual data reports.

STUDY SELECTION:

Emphasis was placed on clinical trials in the English language addressing issues in hypertension and ESRD. Clinical trials reporting relationships between blood pressure control and ESRD, as well as those comparing different antihypertensive agents, were evaluated.

DATA EXTRACTION:

The methodology and results from clinical trials were evaluated. Studies were assessed according to the measures of renal function used, baseline data collected, degree of blood pressure control, and antihypertensive therapy.

DATA SYNTHESIS:

Clinical trials including patients with essential hypertension, diabetes mellitus, and renal insufficiency of various etiologies were evaluated. The recommendations from these evaluations were based on study design and the types of populations used (i.e., blacks vs. whites, diabetics vs. nondiabetics).

CONCLUSIONS:

Blood pressure control is currently the most important strategy to slow or halt the progression of renal insufficiency in hypertensive individuals. Whether specific antihypertensives are renal protective is still controversial, but results from clinical trials are promising.
Treating Isolated Systolic Hypertension in the Elderly
Authors: Howard Patricia A.
Published: January 2017

OBJECTIVE:

To review the prevalence, pathophysiology, vascular risk, and treatment of isolated systolic hypertension (ISH) in the elderly.

DATA SOURCE:

A MEDLINE search of the English language literature was performed to identify pertinent literature. Key search terms were hypertension, systolic, and elderly.

STUDY SELECTION:

All studies available evaluating drug therapy for ISH or hypertension in the elderly as well as review articles discussing the prevalence, pathophysiology, and treatment of ISH were selected.

SYNTHESIS:

ISH occurs commonly in the elderly and is associated with increased risk for cardiovascular and cerebrovascular disease. Although the mechanism for ISH in the elderly is not completely understood, the primary factor is believed to be a reduction in arterial compliance. Results of the Systolic Hypertension in the Elderly Program demonstrated that control of ISH using a diuretic alone or in combination with a beta-blocker significantly reduced the incidence of strokes and cardiovascular events. In this trial, drug therapy was found to be safe and generally well tolerated by the elderly. Newer antihypertensive agents such as the calcium-channel blockers and angiotensin-converting enzyme (ACE) inhibitors have also been shown to effectively lower SBP in the elderly, but the effects on long-term morbidity and mortality are not yet known.

CONCLUSIONS:

ISH is an important risk factor for vascular disease in the elderly. Accurate diagnosis and effective drug treatment can result in significant reductions in the risk of cardiovascular and cerebrovascular events. Based on the available trial data, diuretics appear to be the drugs of first choice unless there are contraindications. If combination drug therapy is required, beta-blockers should be considered although their contribution to vascular risk reduction remains less clear. Additional studies are needed to determine the long-term benefits and risks of alternative antihypertensive agents such as calcium-channel blockers and ACE inhibitors.
Pharmacoeconomic Analysis of Cefmenoxime Dual Individualization in the Treatment of Nosocomial Pneumonia
Authors: Paladino Joseph A. , Fell Robert E.
Published: January 2017

OBJECTIVE:

To determine if dual individualization of cefmenoxime dosing is cost-effective.

DESIGN:

Retrospective, pharrnacoeconomic decisionanalysis of two consecutively conductedprospective clinical studies.

PATIENTS:

Patientswithdocumentedgram-negative nosocomial pneumoniawere evaluated. Thirty-three patients received cefmenoximeat standarddosing and 28 patients received doses according to dual individualization methodology.

MAIN OUTCOME MEASURE:

Antibiotic and infection-related costs were compared between groups. The number of hospital antibiotic days and costs incurred on those days were also evaluated. A decision model was constructed to characterize differences in treatment outcome. Probabilities with in the decision tree were derived from 61 evaluable patients. Cost-effectiveness and incremental cost-effectiveness ratios were calculated. Sensitivity analysis was performed by varying out come probabilities, antibiotic prices, and hospital room costs.

RESULTS:

Antibiotic and infection-related costs (mean ± SEM) were $848 ± 78 for standard cefmenoxime dosing and $1123 ± 128 for dual individualization (p<0.05). Total hospital costs were $10 660 ± 1432 or standard dosing and $11 700 ± 1900 for dual individualization (p>0.05). Median antibiotic length of stay (ALOS) was 15.2 and 12.7 days for standard and dual individualization methodologies, respectively (p>0.05). Incremental analysis of cost effectiveness indicated that a similar reduction in length of stay for 259 dual individualization patients would save $321 808 annually.

CONCLUSIONS:

Sensitivity analysis indicates that by reducing ALOS, dual individualization could be a cost-effective method of betalactam dosing for patients with pneumonia. A prospective study should be conducted to validate these findings.
Clinical Experience with Ketorolac in Children
Authors: Buck Marcia L. , Rudis Maria
Published: January 2017

OBJECTIVE:

To describe the use of parenteral ketorolac in a large population of children, focusing on dosing patterns, efficacy, and safety.

DESIGN:

Observational, prospective study conducted over a four-month period.

SETTING:

A 122-bed children's medical center located within an academic medical center hospital.

PARTICIPANTS:

Children receiving ketorolac during their hospitalization.

MAIN OUTCOME PARAMETERS:

Indications for treatment, dose, dosing interval, use of a loading dose, length of therapy, efficacy (subjective response and use of concomitant therapy), and adverse effects (bleeding, gastrointestinal ulceration or vomiting, and renal dysfunction).

RESULTS:

Of 112 children evaluated, 110 received ketorolac for analgesia, and 2 were given ketorolac as an antipyretic. The children ranged in age from 6 months to 19 years. Doses of 0.5 mg/kg q6h were used for most children (range 0.17–1.0). The average length of therapy was 3.4 days (range 1–12). The most frequent reason for discontinuing ketorolac therapy was a change to oral therapy. Therapy was discontinued because of a lack of efficacy in only 2 children. Adverse reactions were unusual, with only 2 patients having bleeding potentially associated with ketorolac use.

CONCLUSIONS:

Ketorolac appears to be a safe and effective therapy for children when given in appropriate doses for a limited duration.
Omnibus Budget Reconciliation Act of 1990 and Voluntarism: Logistic Regression Analysis of Pharmacist Responsibility
Authors: Hansen Robert W. , Ranelli Paul L.
Published: January 2017

OBJECTIVE:

To examine the relationship between pharmacists' willingness to assume further professional responsibilities, as measured by attitudes to the Omnibus Budget Reconciliation Act of 1990 (OBRA '90) requirements, and their attitudes toward voluntarism as their responsibility to society and their level of interest in their jobs.

DESIGN:

A survey was distributed to a convenience sample of 443 pharmacists who were asked to indicate their responses on a number of items.

SETTING:

Surveys were distributed to participants in an annual pharmacy continuing education program.

PARTICIPANTS:

The response rate was 65 percent with completed surveys from 290 Florida pharmacists who were typically male (73 percent) and practicing in the community setting (39 percent) for over 25 years (33 percent).

MAIN OUTCOMES:

Questions were aimed at gathering the following information: (1) demographics; (2) attitudes concerning the benefits of the three OBRA '90 requirements: Patient counseling, prospective drug-use review (DUR), and information recording; (3) attitudes toward voluntarism; and (4) job interest.

RESULTS:

Pharmacists tended to agree that all three of the OBRA '90 mandates will be beneficial. Fifty-six percent favored the prospective DUR requirements, while 68 percent favored the patient counseling requirements and 66 percent favored the information-recording requirements. Logistic regression analysis showed that unit increases in scaled responses, indicating more favorable attitudes toward believing that voluntarism was one's responsibility, increased the odds of favoring counseling by 38.7 percent and information recording by 32.4 percent. A similar directional relationship was found for the DUR requirement. Job interest did not add to the predictive ability of the variables already in the models.

CONCLUSIONS:

This study suggests a possible association between pharmacists' attitudes toward social responsibility and their acceptance of expanded professional responsibility.
Pancreatitis during Intravenous Pentamidine Therapy in an AIDS Patient with Prior Exposure to Didanosine
Authors: Foisy Michelle M. , Slayter Kathryn L. , Hewitt Ross G. , Morse Gene D.
Published: January 2017

OBJECTIVE:

To report a case of an HIV-positive man who received sequential didanosine and pentamidine treatment and subsequently developed acute clinical pancreatitis.

CASE SUMMARY:

In June 1992 didanosine 200 mg po bid was initiated in a 30-year-old man with AIDS. After a 22-week course of didanosine, the patient was hospitalized and didanosine was discontinued on day 4. The patient then received 8 days of treatment for a presumed Pneumocystis carinii pneumonia (PCP) with pentamidine 4 mg/kg/d iv. As the patient responded clinically to therapy, he was discharged home to complete a 21-day course of pentamidine. On day 14 of therapy, the patient experienced nausea, vomiting, diarrhea, fatigue, and was hypotensive. The dosage of pentamidine was reduced by 50 percent. After receiving 18 doses of pentamidine, treatment was discontinued, as symptoms had worsened and serum amylase and lipase concentrations were elevated. The patient was hospitalized and the diagnosis of acute clinical pancreatitis was made. After a 21-day hospitalization, the patient was discharged home in fair condition on hyperalimentation.

DISCUSSION:

Potential causes of pancreatitis, including opportunistic infections, neoplasms, and drugs, are discussed. The most probable factors associated with pancreatitis in our patient are didanosine and pentamidine therapy.

CONCLUSIONS:

As our patient developed pancreatitis following sequential administration of didanosine and pentamidine, it would be prudent to monitor for signs and symptoms of pancreatitis in similar cases. In addition, didanosine should be discontinued during and for one week following treatment of PCP when pentamidine is used.
Anaphylactoid Reactions Associated with Ondansetron
Authors: Kossey Joyce L. , Kwok Karl K.
Published: January 2017

OBJECTIVE:

To describe two patients with anaphylactoid-type reactions to ondansetron.

CASE SUMMARY:

A 41-year-old man with grade III leiomyosarcoma of the right tibia was admitted to the hospital for his second dose of first-cycle neoadjuvant intraarterial cisplatin 60 mg/m2 therapy. He experienced an anaphylactoid reaction following intravenous ondansetron infusion that was confirmed on rechallenge. In a second case, premedication with intravenous ondansetron resulted in an anaphylactoid reaction in a 44-year-old woman with stage III ovarian cancer receiving her ninth course of cyclophosphamide and carboplatin. Both patients had received ondansetron previously with no adverse effects.

DISCUSSION:

Peer-reviewed journal articles and reports, obtained through a MEDLINE search, were reviewed. Information on the individual cases was obtained from the patients' medical records. Preservative changes in ondansetron infusion were examined as possible causes of the anaphylactoid reactions in our patients, but no conclusive data linking them were found.

CONCLUSIONS:

The efficacy and safety of ondansetron has led to the widespread use of this medication in the treatment of nausea and vomiting caused by cancer chemotherapy and radiation therapy. Practitioners should be made aware that acute severe anaphylactoid reactions could occur in patients who have previously received ondansetron with no adverse effects.
Flecainide Distribution, Transplacental Passage, and Accumulation in the Amniotic Fluid during the Third Trimester of Pregnancy
Authors: Bourget Philippe , Pons Jean-Claude , Delouis Christine , Fermont Laurent , Frydman René
Published: January 2017

OBJECTIVE:

To study the disposition of flecainide acetate and its transplacental passage (both into the fetus and in the amniotic fluid) during the third trimester of pregnancy.

DATA SOURCES:

Reference articles and books are identified in the text. A literature review is presented.

CASE SUMMARY:

Flecainide distribution, transplacental passage, and accumulation into the amniotic fluid were studied in a patient at term presenting with a fetal supraventricular tachycardia diagnosed at 33 4/7 weeks of gestation. The fetal tachycardia was accompanied by cardiac failure with placental anasarca and hydramnios. Flecainide 100 mg po bid was prescribed initially; by the time of delivery, the dosage had been decreased to 50 mg bid. At delivery day (39 5/7 weeks), the pharmacokinetics of total flecainide were studied at plateau.

DATA SYNTHESIS:

The concentrations of flecainide at birth in fetal and maternal blood and in amniotic fluid were 235.4, 241.2, and 6426.5 μg/L, respectively. Calculation of a fetomaternal blood accumulation ratio of 0.97 showed that, at this gestational age, flecainide penetrates the placental membrane easily without accumulation in fetal blood. In contrast, the concentration of flecainide in amniotic fluid was approximately 27-fold that measured in maternal peripheral blood. Our results suggest the following: (1) close to term, the metabolic clearance (fetal hepatic clearance) of flecainide offers a high yield and its excretion by the fetal kidney is efficient; (2) given that amniotic fluid is constantly swallowed, it seems that, in contrast to what is seen in adults (relative oral bioavailability ≥95 percent), the oral bioavailability of flecainide is possibly low in the fetus at term or close to term; under such circumstances, the drug would accumulate passively within the gestational sac; and (3) an alternative explanation is that the concentration in the fetus is, in part, the result of both transplacental crossing of the drug and reabsorption orally from the amniotic fluid.

CONCLUSIONS:

The regular therapeutic monitoring of flecainide is necessary and sufficient in the mother as the concentrations found appear to accurately reflect the degree of fetal accumulation. Because previous studies in infants and children have indicated few toxic adverse effects attributed to flecainide, it appears that the risk to a sucking infant of ingesting toxic amounts of flecainide in human breast milk is very low. Finally, the child of the patient described here has normal initial growth and development at the present time. The transplacental penetration of a drug can be considered, according to gestational age and the disorder being treated, as being of no consequence, dangerous, or desirable. Flecainide appears to fall into this last category.
Changing Perspectives of Stress Gastritis Prophylaxis
Authors: Smythe Maureen A. , Zarowitz Barbara J.
Published: January 2017

OBJECTIVE:

To present recent advances in stress gastritis prophylaxis in the critically ill and review considerations in selection of a prophylactic agent.

DATA SOURCES:

Information was obtained from MEDLINE search, reference lists from articles identified in search, and from review articles.

STUDY SELECTION:

Emphasis was placed on controlled trials conducted within the last 5 years.

DATA EXTRACTION:

All literature was assessed for methodology, results, and conclusions. Results of prospective, randomized trials, and meta-analyses are summarized.

DATA SYNTHESIS:

Histamine2-receptor antagonists, antacids, and sucralfate appear equally effective in preventing stress gastritis in the critically ill. A definitive cause–effect relationship between histamine2-receptor antagonists and increased incidence of nosocomial pneumonia has not yet been established. The indications for using a prophylactic agent and consideration in selecting an agent should include an evaluation of the following: Risk factors for gastritis including the type of intensive care patient, comparative efficacy, adverse effects, drug interactions, cost, and ease of administration. The least expensive, safest agent requiring minimal monitoring is sucralfate. Prevention of stress gastritis has never been shown to reduce morbidity or mortality significantly.

CONCLUSIONS:

Controversies still exist regarding the need to provide prophylaxis, the choice of an agent, and the relative importance of previously identified risk factors. Further well-designed studies are needed before consensus can be reached.
Effect of Calcium-Channel Blockers on Cyclosporine Clearance and Use in Renal Transplant Patients
Authors: Sketris Ingrida S. , Methot Michelle E. , Nicol David , Belitsky Philip , Knox Margot G.
Published: January 2017

OBJECTIVE:

To determine the effect of calcium-channel blockers (CCBs) on cyclosporine dose, clearance, and cost, and their effect on kidney graft function and survival in patients who underwent kidney transplant.

DESIGN:

A total of 176 adults receiving 177 transplants were studied retrospectively. Patients were stratified as follows: no CCB (n=57), diltiazem (n=13), nifedipine (n=37), and verapamil (n=70). Patients received cyclosporine 3–4 mg/kg by continuous infusion for 5 days followed by cyclosporine 10 mg/kg/d po to maintain initial whole blood concentrations of 300–400 ng/mL. Clearance of intravenously administered cyclosporine was calculated following at least 48 hours of the same dose by continuous infusion. The amount and cost of cyclosporine used during the first 10 days of oral therapy were also calculated.

RESULTS:

Patients receiving diltiazem, but not verapamil or nifedipine, had decreased clearance of intravenously administered cyclosporine compared with that of the mean control group. The mean clearance of intravenously administered cyclosporine ± SD in patients receiving no CCB was 5.1 ± 1.5 mL/min/kg, diltiazem was 3.7 ± 0.8 mL/min/kg, nifedipine was 6.4 ± 1.9 mL/min/kg, and verapamil was 5.2 ± 2.2 mL/min/kg. The amount and cost of 10 days of oral cyclosporine therapy was decreased in the verapamil group (5.7 ± 1.5 g and $257 ± 69) compared with that of the control group (6.7 ± 1.6 g and $304 ± 72) (p<0.001). There was no significant difference among the groups with respect to immediate graft function, 1-year serum creatinine concentration, or 1-year graft survival.

CONCLUSIONS:

Diltiazem decreased the clearance of intravenously administered cyclosporine. Although verapamil did not decrease the clearance of intravenously administered cyclosporine, it allowed a significant reduction in oral cyclosporine cost without apparent adverse effects on graft function. Further work is needed to determine the effect of CCBs on cyclosporine pharmacokinetics, especially with respect to their metabolism by gut and hepatic cytochrome P-450 enzymes, and their effect on patient outcome.
Evaluating the Accuracy of Citations in Drug Promotional Brochures
Authors: Keng Arlene , Coley Rebecca M.R.
Published: January 2017

OBJECTIVE:

To evaluate the accuracy of statements cited in 3 × 5 inch promotional cards for the 50 most frequently prescribed drugs.

MEASUREMENTS:

The 50 most frequently prescribed drugs were identified in the April 1992 issue of Pharmacy Times. File cards were requested from the pharmaceutical companies. References in the file card were retrieved and cited statements identified. Criteria used to evaluate reference accuracy were: type of study design, use of peer review journals, retrievability of references in area libraries, and reference documentation as no error, major error, or minor error. Referenced statements were classified as correct, incorrect, misleading, or taken from the abstract, discussion, or conclusion section of a study.

RESULTS:

Of the 50 most frequently prescribed products, 21 file cards were obtained. One hundred forty-two cited references were retrieved (average ± SD per file card 6.9 ± 8.4). Three hundred thirty-four cited statements were verified (average per file card 15.9 ± 24.7). Forty-two percent of references were human controlled trials, 17 percent not available, 11 percent review articles, 10 percent manufacturer information, 8 percent human uncontrolled, 4 percent nonhuman controlled, 3 percent retrospective, 2 percent tertiary literature, 1 percent epidemiologic studies, 1 percent prospective, and 1 percent editorial. Thirty-three percent of references were found in peer-review journals. Of all cited references, 73 percent were retrievable. Thirty-nine references were not retrievable: 24 were not held by local libraries and 15 were manufacturers' information. Eighty-five percent of references contained no errors in reference documentation. For accuracy of statements, 46.1 percent were correct, 29 percent not available, 15.3 percent misleading, 4.2 percent incorrect, and 5.4 percent were cited from the abstract, discussion, or conclusion section of the study.

CONCLUSIONS:

Most references cited in pharmaceutical promotional brochures referenced controlled studies that are retrievable. However, incorporation of more adequately controlled studies, more references from peer review journals, and careful evaluation of referenced statements by the pharmaceutical company, journals' editorial board, Food and Drug Administration, and healthcare professionals may be beneficial.
Fatal Neutropenia and Thrombocytopenia Associated with Ticlopidine
Authors: Carlson James A. , Maesner Jon E.
Published: January 2017

OBJECTIVE:

To report the first case of ticlopidine-associated neutropenia resulting in sepsis and death.

CASE SUMMARY:

An 83-year-old Filipino man was started on ticlopidine 250 mg bid. By the seventh week of therapy his absolute neutrophil count (ANC) had dropped to 2700 from 7600 × 106 cells/L. The ticlopidine was stopped. Six days later, he was admitted to the hospital. He died 18 hours later of gram-negative sepsis.

DISCUSSION:

Although ticlopidine therapy was discontinued four days after the patient's ANC was 2700 × 106 cells/L, the ANC dropped to and remained at 0 until his death eight days later. This may be associated with the patient's decreased clearance of ticlopidine given his age and impaired renal function. This is the first reported case of moderate or severe neutropenia in a nonwhite patient and the first reported case of sepsis and death caused by ticlopidine

CONCLUSIONS:

Healthcare professionals must be aware of the possibility of severe neutropenia and death caused by ticlopidine, even when the manufacturers' monitoring guidelines are followed.
Rifabutin: A Review with Emphasis on its Role in the Prevention of Disseminated Mycobacterium Avium Complex Infection
Authors: Maddix Daniel S. , Tallian Kimberly B. , Mead Paul S.
Published: January 2017

OBJECTIVE:

To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of rifabutin.

DATA SOURCES:

Pertinent literature published between 1982 and 1993 was identified via a MEDLINE search. Published proceedings of selected conferences were also reviewed.

STUDY SELECTION:

Selected basic science, microbiologic, and pharmacokinetic articles were evaluated. Because only limited data regarding rifabutin were available in the literature, all clinical trials involving the use of rifabutin in the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients were reviewed.

DATA SYNTHESIS:

Rifabutin is a rifamycin derivative that was approved recently for the prevention of disseminated MAC disease in patients with advanced HIV infection. The drug has in vitro and in vivo activity against gram-positive bacteria, gram-negative bacteria, and mycobacteria. Two prospective, randomized, double-blind, placebo-controlled, multicenter trials demonstrated that rifabutin decreased the progression to MAC bacteremia in AIDS patients by about 50 percent. Adverse effects that resulted in the discontinuation of rifabutin prophylaxis occurred in 16 percent of patients. Rifabutin induces hepatic enzymes to a lesser extent than does rifampin, but dosage adjustment of drugs that are known to interact with rifampin may be required.

CONCLUSIONS:

Rifabutin is the only drug shown to be effective in the prevention of MAC bacteremia in AIDS patients; therefore, it should be made available as a formulary agent. It may be reasonable to delay initiation of rifabutin prophylaxis until CD4 lymphocyte counts are less than 75–50/mm3.
Oxygen Transport Goals in the Resuscitation of Critically Ill Patients
Authors: Dasta Joseph F. , Erstad Brian L.
Published: January 2017

OBJECTIVE:

To discuss the limitations of conventional monitoring techniques of shock and examine more recent monitoring techniques that are used to titrate therapies to attain supranormal oxygen transport goals.

DATA SOURCES:

Review articles and investigations published since 1973.

STUDY SELECTION:

Articles were selected if they examined the monitoring or treatment of shock. Emphasis was placed on finding investigations involving humans that used innovative methods to assess and treat inadequate tissue perfusion.

DATA EXTRACTION:

Data were extracted primarily from original investigations and review articles published in or translated into English.

DATA SYNTHESIS:

The conventional monitoring of shock often fails to detect inadequate tissue perfusion, which may lead to inadequate resuscitation of patients, resulting in increased morbidity and mortality. Attainment of supranormal values for oxygen transport variables has been associated with improved outcomes, especially in patients with hypovolemic shock or septic shock. Additionally, interventions used to increase these variables to supranormal values have resulted in improved survival in high-risk preoperative patients with hypovolemic or septic shock, but not in severely ill postoperative patients with multiple complications.

CONCLUSIONS:

Efforts to increase oxygen transport variables to supranormal values cannot be recommended routinely for all critically ill patients. Preoperative patients in early stages of hypovolemic or septic shock may benefit from therapies titrated to achieve supranormal goals, but patients in later stages of illnesses may be harmed by such attempts. Questions remain regarding how quickly and how long the oxygen transport variables should be elevated. The most effective and least toxic therapeutic interventions for increasing the variables need to be determined.
Documenting Pharmaceutical Care: Creating a Standard
Authors: Canaday Bruce R. , Yarborough Peggy C.
Published: January 2017

OBJECTIVE:

To examine the need for a standardized, systematized approach to document patient pharmacotherapy, workable in all pharmacy practice settings, and to propose a model to meet the identified needs.

DATA SOURCE:

A MEDLINE search was conducted, in addition to an assessment of current practices and a review of known sources of pharmacotherapy/pharmaceutical care evaluation and documentation methodology.

CONCLUSIONS:

Pharmacy lacks a universally accepted, standardized, systematized approach to document the evaluation of a patient's pharmacotherapy. An approach is presented that distills the concepts of pharmaceutical care into a manageable documentation format and provides a customization of the medical history and physical examination/subjective-objective-assessment-plan system to meet the unique needs of pharmacy. This approach provides a convenient format for notes for all pharmacists, applicable in any practice setting. It provides a starting point for decisions on what pharmacy wants and accepts as a standard to provide continuity of pharmaceutical care to patients, uniform communication with healthcare colleagues, appropriate instruction to students, data analysis to demonstrate the value of services, and needed guidance to software vendors, medical records departments, and third-party payers.
Pharmacist-Managed, Physician-Directed Asthma Management Program Reduces Emergency Department Visits
Authors: Pauley Timothy R. , Magee Michael J. , Cury James D.
Published: January 2017

Objective:

To determine whether the number of emergency department (ED) visits for acute asthma exacerbations could be decreased by providing patients with a comprehensive program of asthma management delivered by a pharmacist and a physician.

Design:

Patients were selected from the ED and asked to attend a special asthma clinic that provided education about asthma and proper use of asthma medications, regular telephone contact between the pharmacist and patient, and an open-door clinic policy.

Setting:

A university-affiliated urban teaching hospital.

Participants:

The study population consisted of 25 asthmatic patients who were at least 18 years of age and who were seen in the ED a minimum of 3 times in a 12-month period.

Main outcome measures:

The number of visits to the ED for acute exacerbations of asthma was measured. Patients served as their own controls. The number of ED visits for asthma during the 6-month study period was compared with two 6-month periods prior to the study period for each patient.

Results:

The total number of ED visits for the 25 enrolled patients six months prior to their enrollment into the study was 92; the number of ED visits during the same months of the study in the prior year was 47. During the study period, there were only 6 ED visits for asthma exacerbations.

Conclusions:

The comprehensive asthma management program reduced the number of ED visits for acute exacerbations of asthma.
Paromomycin-Associated Pancreatitis in Hiv-Related Cryptosporidiosis
Authors: Tan Winston W. , Chapnick Edward K. , Abter Elfatih I.M. , Haddad Stephen , Zimbalist Eliot H. , Lutwick Larry I.
Published: January 2017

Objective:

To report a case of pancreatitis related to paromomycin administration.

Case summary:

A 39-year-old man with AIDS developed pancreatitis concurrent with successful treatment of intestinal cryptosporidiosis with paromomycin. The hyperamylasemia resolved with discontinuation of the agent and recurred when paromomycin treatment was reinstituted.

Discussion:

To our knowledge, this is the first reported case of pancreatitis believed to be induced by paromomycin. Although pancreatitis in HIV-infected patients has multiple causes, the nature of this case suggests the involvement of paromomycin. The mechanism of action is unclear.

Conclusions:

Pancreatitis should be considered in the differential diagnosis of abdominal pain in patients who are treated with paromomycin.
Continuous Midazolam Infusion for the Management of Morphine-Induced Myoclonus
Authors: Holdsworth Mark T. , Adams Val R. , Chavez Cathy M. , Vaughan Leslie J. , Duncan Marilyn H.
Published: January 2017

Objective:

To describe a patient with morphine-induced myoclonus treated with a continuous infusion of midazolam and continued morphine dose escalation.

Design:

Single case report.

Setting:

Delivery, monitoring, and titration of morphine and midazolam in the patient's home by a homecare agency.

Results:

The use of high dosages of morphine (i.e., 500 mg/h) produced myoclonic spasms in this patient, which in turn resulted in increasing pain. To allow for continuation of effective analgesia and to control the myoclonic spasms, an infusion of midazolam was initiated and titrated. The midazolam infusion allowed for continuation of the morphine dosage and also permitted further dosage escalation. As morphine dosages were further escalated, it was also necessary to increase the midazolam infusion to control additional myoclonic spasms.

Conclusions:

Use of a concomitant midazolam infusion with high doses of morphine appears to be safe and is an effective means of controlling morphine-induced myoclonus. If further dosage increases of morphine are necessary in this setting, increases in the midazolam infusion also may be required.
Use of Nitric Oxide Synthase Inhibitors as a Novel Treatment for Septic Shock
Authors: Wolfe Thomas A. , Dasta Joseph F.
Published: January 2017

Objective:

To review the current literature regarding the role of nitric oxide (NO) in the pathogenesis of septic shock and to describe the potential role of NO synthase (NOS) inhibitors in the treatment of septic shock.

Data sources:

A MEDLINE, Cancerlit, Biosis, Scisearch, CBAC, bibliography, and current journal search of applicable articles on the involvement of NO in mediating septic shock and the use of NOS inhibitors in septic shock was conducted. Articles that were searched included animal and human studies from January 1990 to August 1994.

Study selection:

Because of the preliminary nature of the research involving NOS inhibitors in septic shock, all available studies were evaluated.

Data synthesis:

NO appears to have a role in the mediation of the hemodynamic instability associated with septic shock. Cytokines and endotoxin stimulate synthesis of the inducible NOS, which produces large amounts of NO over an extended period of time. NO may be the key mediator in the pathogenesis of septic shock. Derivatives of the precursor to NO, l-arginine, have been used to investigate the role of NO in septic shock and as possible therapeutic agents. Comparison of study results among animal studies shows much variability. This variability may be attributable to differences in dosing regimens and models of septic shock. Data obtained from human studies are more consistent, but are limited to a few case series. Results indicate that NOS inhibitors increase blood pressure and systemic vascular resistance and decrease cardiac output. The effects of NOS inhibitors on morbidity and mortality have not been assessed because of the lack of an appropriate sample size.

Conclusions:

NO appears to play a role in septic shock; however, the use of NOS inhibitors to treat septic shock requires further studies to determine an appropriate dosing regimen and to determine the effects of these agents on morbidity and mortality.
Hantavirus Pulmonary Syndrome: The Four Corners Disease
Authors: Morrison Yvette Y. , Rathbun R. Chris
Published: January 2017

Objective:

To review the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of hantavirus infections, focusing on the recent outbreak of hantavirus pulmonary syndrome in the US.

Data sources:

A MEDLINE search (1966 to present) of English language literature pertaining to hantaviruses was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search.

Study selection and data extraction:

All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion.

Data synthesis:

Hemorrhagic fever with renal syndrome (HFRS) has long been recognized in Eurasia and is the predominant disease manifestation of hantavirus infection worldwide. Hantavirus pulmonary syndrome (HPS) recently has been described in the US and exhibits greater pulmonary involvement and mortality than HFRS. Historically, 4 hantavirus serotypes (Hantaan, Seoul, Puumala, Prospect Hill) are recognized; however, additional serotypes have been proposed as distinct serogroups, including the serotype responsible for HPS in the Four Corners area: the Four Corners virus (FCV). Phylogenetic analysis shows that FCV is most closely related to Prospect Hill virus, another hantavirus previously isolated in the US that has not yet been identified with human disease. Additional hantavirus serotypes isolated in the US may provide insight into the prevalence of hantavirus infection and disease in this country. Inhalation of aerosolized virus is the predominant mechanism of hantavirus infection. Diagnosis is based primarily on clinical findings and serologic evidence of hantavirus antibody or direct evidence in clinical tissue specimens. Limited clinical studies evaluating ribavirin as a therapeutic modality demonstrated that the agent improves clinical outcome in HFRS. However, the role of ribavirin in the treatment of HPS remains to be determined.

Conclusions:

Hantavirus infections are becoming increasingly recognized as a cause of disease worldwide. Recognition of hantavirus disease in the US suggests enzoonosis of pathogenic hantaviruses. In the absence of a well-established cure, early diagnosis is imperative so that aggressive supportive care can be initiated.