bluuebunny/crossref_metadata_2025 huggingface dataset:
Administration of Lipid-Emulsion Versus Conventional Amphotericin B in Patients with Neutropenia
Authors: Pascual Begoña , Ayestaran Ana , Montoro José B , Oliveras Juan , Estibalez Antero , Julia Antoni , Lopez Andres
Published: January 2017

Objective:

To evaluate the usefulness of a 20% lipid emulsion as a delivery system for amphotericin B (1 mg/mL) administered over 1 hour to patients with neutropenia with hematologic malignancies compared with amphotericin B (0.1 mg/mL) administered in dextrose 5% solution over the same time.

Design:

A prospective, comparative, randomized, labeled study.

Setting:

Hematology unit, pharmacy service, university general hospital.

Participants:

Twenty patients with neutropenia with hematologic malignancies and proven or suspected fungal infections, 10 in the fat emulsion group (group 1) and 10 in the dextrose 5% group (group 2).

Main Outcome Measures:

Clinical tolerance (i.e., fever, shaking chills, nausea, blood pressure, pulse rate) and biologic tolerance (i.e., urea, creatinine, sodium, potassium).

Results:

Clinical tolerance was comparable in both groups although amphotericin B in fat emulsion was better tolerated. Medication for symptoms related to the administration of amphotericin B was given in 6 cases in group 1 and in 8 cases in group 2. There was a statistically significant difference in the urea concentrations between the 2 groups (p = 0.023); there was an observed increase between the initial and the final serum urea (56.8 mg/d in group 1, 79.8 mg/dL in group 2). Statistically significant differences in creatinine serum concentrations (84.9 μmol/L in group 1, 123.8 μmol/L in group 2) (p = 0.047) were found. No differences were found in the antifungal efficacy of the treatment. However, as amphotericin B was started in the majority of cases (75%) as empiric treatment for fever unresponsive to antibiotic therapy, it is difficult to compare the efficacy of both preparations.

Conclusions:

The clinical tolerance of lipid-emulsion infusions is similar to that of conventionally administered amphotericin B therapy. Renal toxicity appears to be decreased when the drug is administered in a fat emulsion. This type of preparation permits the reduction of the volume and the time of administration for amphotericin B therapy.
Ifosfamide-Induced Nonconvulsive Status Epilepticus
Authors: Bhardwaj Ashwani , Badesha Pritam S
Published: January 2017

Objective:

To describe a patient with ifosfamide-induced nonconvulsive status epilepticus.

Case Summary:

A 71-year-old woman with a history of malignant mixed mesodermal tumor involving the uterus, cervix, and vagina was admitted because of local recurrence. After receiving 3 doses of ifosfamide/mesna, she was found to be unresponsive. Physical examination and laboratory data revealed no significant changes. An electroencephalogram was consistent with the diagnosis of nonconvulsive status epilepticus. The patient's mental status returned to baseline after treatment with intravenous phenytoin and discontinuation of ifosfamide therapy.

Discussion:

Central nervous system (CNS) toxicity has been described with ifosfamide, with most cases reported in the pediatric population. Among CNS toxicities, generalized tonic-clonic seizures have been reported in both children and adults. This represents the first report of nonconvulsive status epilepticus induced by ifosfamide.

Conclusions:

There was a temporal relationship between the onset of nonconvulsive status epilepticus and initiation of ifosfamide infusion. No other identifiable factor contributed to the unresponsiveness.
Comparative Role of Omeprazole in The Treatment of Gastroesophageal Reflux Disease
Authors: Skoutakis Vasilios A , Joe Ronald H , Hara Dimitri S
Published: January 2017

Objective:

To review gastroesophageal reflux disease (GERD) and its treatment, with emphasis on the use and place of omeprazole, a proton pump inhibitor.

Data Sources:

A compilation prepared by the National Library of Medicine's Interactive Retrieval Services (Medlars II) for the period 1987 to 1994 was used as the data source.

Study Selection:

Focus was placed on human comparative clinical studies with well-accepted measures of esophageal healing (endoscopy) and symptom resolution. Safety data were compiled from the clinical trials literature and large postmarketing data studies. Pharmacoeconomic studies selected were judged to meet the criteria of good design, presence of sensitivity testing, and statement of perspective.

Data Extraction:

Data were obtained from double-blind, controlled clinical studies. Other data were extracted from pertinent literature of good design and significant results.

Data Synthesis:

Overall, the clinical trials of omeprazole for the treatment of patients with erosive GERD demonstrate that omeprazole provides superior therapy in terms of esophageal healing symptom resolution and patient compliance when compared with histamine2-receptor antagonists (H2RAs) and antacids. In addition, studies also indicate that omeprazole is the most effective agent for the treatment of patients with GERD refractory to other treatments. Dosage adjustment is not necessary in patients with impaired renal or hepatic function or in the elderly. Finally, although the acquisition drug cost for daily treatment of patients with GERD is highest with the use of omeprazole, pharmacoeconomic studies indicate that treatment is more cost-effective with the use of omeprazole than with H2RA or antacid treatment alone or combined with nonpharmacologic approaches.

Conclusions:

Based on efficacy, safety, and cost-effectiveness, omeprazole is the drug of choice for the treatment of patients with endoscopically confirmed erosive GERD.
Anaphylactic Shock following Povidone
Authors: Garijo Ma Angeles Gonzalo , Quintana José A Durán , González Pedro Bobadilla , Asuero Pilar Máiquez
Published: January 2017

OBJECTIVE:

To report a patient with an anaphylactic reaction related to povidone administration.

CASE SUMMARY:

A 37-year-old man with a history of allergic rhinitis presented with urticaria, dyspnea, wheezing, rhinorrhea, and dysphonia 20 minutes after the intraarticular administration of mepivacaine hydrochloride and paramethasone acetate in his right knee. Two months after this episode, he was admitted for controlled provocation tests. Tests on mepivacaine were negative. The preparation of paramethasone contained the excipients benzalkonium chloride, polysorbate 80, and povidone. In vitro tests and provocation were negative with polysorbate 80 and benzalkonium chloride, but positive with povidone.

DISCUSSION:

Povidone, a mixture of synthetic polymers, is commonly used as an excipient in pharmaceutical products, an additive in food products, and a dispersant and stabilizer in hairsprays. Although it is well tolerated when used topically or parenterally, local and systemic effects have been reported. Furthermore, multiorgan involvement resulting from accumulation of the drug in the reticuloendothelial system has been described. The immunologic properties of povidone have not been explored in humans, but have been in animals. In fact, the capacity of povidone to release histamine and its immunogenicity are proportional to its molecular weight. An immunoglobulin (Ig) E-mediated hypersensitivity reaction in asthma has been reported. In our case, povidone was responsible for the syndrome. However, we cannot determine the exact mechanism. An unspecific histamine release and/or an IgE-mediated hypersensitivity could be involved.

CONCLUSIONS:

Povidone was responsible for a severe anaphylactic reaction in our patient. The possibility of an iatrogenic adverse effect caused by the excipient but not by the active ingredient should be considered in patients exhibiting similar symptoms. We believe that the excipients used in the preparation of all medicines should be disclosed.
Immune-Based Therapies for Treatment of HIV Infection
Authors: Piscitelli Stephen C , Minor James R , Saville M Wayne , Davey Richard T
Published: January 2017

OBJECTIVE:

To review the in vitro, animal, and clinical data on immune-based therapies for treatment of HIV infection.

DATA SOURCES:

An extensive MEDLINE search was performed for interleukins, interferons, immunotoxins, tumor necrosis factor (TNF)-directed agents, vaccines, and gene therapy.

STUDY SELECTION:

In vitro experiments with immune-based agents in cell lines infected with HIV were included. In addition, all human studies and case reports that used these agents in patients infected with HIV were selected. Additional literature included abstracts from international meetings on HIV and AIDS.

DATA EXTRACTION:

Data regarding activity, efficacy, and toxicity were extracted from in vitro and in vivo studies. When conflicting data were observed, both viewpoints were stated to give an unbiased analysis. Because HIV research involves multiple social, ethical, and scientific issues, perspectives on these problems were addressed, where appropriate.

DATA SYNTHESIS:

Current antiretroviral therapy is limited to shortterm responses and has minimal effect on overall survival. Because the human immune response to HIV infection is effective at keeping the virus suppressed for a number of years, a focus of HIV research has been to examine immune-based therapies for treatment of HIV infection that attempt to augment, enhance, or boost the patient's immune system. Interleukins, interferons, immunotoxins, TNF-directed therapies, vaccines, and gene therapy have been studied in patients infected with HIV. Properties shared among these therapeutic modalities include adverse effect profiles, response rates dependent on baseline immunocompetence, the potential to activate viral replication, the need for supportive care, and sensitive laboratory tests required for monitoring.

CONCLUSIONS:

Immune-based agents represent a new approach to the treatment of HIV infection. Whereas antiretrovirals only inhibit viral replication, these agents are designed to enhance the immune system of the patient. Future attempts to manage HIV infection may combine standard nucleoside analogs with immune-based therapies.
Antimicrobial Liquid Formulations: A Blind Taste Comparison of Three Brands of Penicillin VK and Three Brands of Amoxicillin
Authors: Chan Debora Schotik , Demers Denise M , Bass James W
Published: January 2017

OBJECTIVE:

To rate the perception of taste, texture, smell and aftertaste of various brands of penicillin VK and amoxicillin.

DESIGN:

Oral, liquid formulations of three brands of penicillin VK (PenVee K, V-Cillin-K, VeeTids) and three brands of amoxicillin (Amoxil, Trimox, Wymox) were evaluated for smell, texture, taste, and aftertaste by 30 volunteers in a blind study. Each category was scored on a scale of 1 to 5. The order in which the drugs were sampled was randomized for the first three groups of five participants. The order then was reversed for the remaining three groups of participants.

SETTING:

A 537-bed US Army teaching hospital.

PARTICIPANTS:

Participants included 30 healthy adult volunteers from the Departments of Pediatrics, Nursing, and Pharmacy.

MAIN OUTCOME MEASURES:

Drugs received cumulative scores in each category, as well as an overall total score ranking. The data were analyzed using one-way ANOVA for repeated measures with a post hoc Duncan's multiple range test to determine significant differences between individual means.

RESULTS:

Overall, Trimox and Amoxil scored significantly higher than the remaining drugs. Although V-Cillin-K scored highest in the smell category, its score was significantly below those of Trimox and Amoxil in the texture, taste, aftertaste, and overall categories. Overall, the three penicillin VK solutions scored lower than the three amoxicillin suspensions, with PenVee K ranking the lowest. Among the penicillin VK solutions, V-Cillin-K scored significantly higher overall than the other two penicillin VK solutions.

CONCLUSIONS:

Overall, all three amoxicillin oral, liquid suspensions that were studied scored significantly better than the three penicillin VK solutions.
Severe Hyperphosphatemia Induced by a Phosphate-Containing Oral Laxative
Authors: Filho Aldo J Peixoto , Lassman M Nathan
Published: January 2017

OBJECTIVE:

To describe a case of severe hyperphosphatemia following unintentional overdosage with an oral phosphate laxative, and raise attention to the risks of using such medications in the elderly.

CASE SUMMARY:

An 84-year-old white woman was admitted with confusion 8 hours after inadvertently ingesting 12 fluid ounces of Fleet Phospho-Soda (instead of the prescribed 1½ fluid ounces) prior to a colonoscopy. Her serum phosphate and ionized calcium concentrations were 10.3 mmol/L and 0.56 mmol/L, respectively. She was treated conservatively with oral phosphate binders and made an uneventful recovery.

DISCUSSION:

Several previous reports have described hyperphosphatemia in association with phosphate laxatives, especially in patients with renal or colonic disease. Our case again presents two important issues in the use of phosphate laxatives by the elderly: (1) the frequently overlooked underlying renal insufficiency in which, despite “normal” serum creatinine values, renal phosphate handling may be impaired; and (2) the potential for drug misuse and poor compliance in the elderly.

CONCLUSIONS:

Caution should be taken with the use of phosphate laxatives in the elderly in the face of potentially serious metabolic abnormalities that may be generated.
Technical and Interpretive Problems of Peripheral Nerve Stimulation in Monitoring Neuromuscular Blockade in the Intensive Care Unit
Authors: Rudis Maria I , Guslits Benjamin G , Zarowitz Barbara J
Published: January 2017

OBJECTIVE:

To review the literature and provide an overview of the technical and interpretive problems associated with peripheral nerve stimulation in monitoring neuromuscular blockade in the intensive care unit.

DATA SOURCES:

A computerized search on MEDLINE from 1985 through 1994 was performed to identify English-language comparative studies, abstracts, and review articles pertaining to peripheral nerve stimulation, train-of-four monitoring, and neuromuscular blockade in the critical care setting.

STUDY SELECTION AND DATA EXTRACTION:

Relevant studies in humans were selected and information was extracted on the use of peripheral nerve monitoring in the critically ill.

DATA SYNTHESIS:

Use of peripheral nerve stimulation is complicated in the intensive care unit. Problems may occur with the patient, the device, as well as operator technique, all of which may lead to errors in interpretation of the depth of paralysis. The critically ill patient has changing comorbid disease states and total body water composition, which may impair the accuracy or reproducibility of measurements. Technical problems relate to the operation of the device, electrode placement, and suboptimal delivery of the desired current. Difficulties in performing peripheral nerve stimulation and interassessor variability contribute to errors of interpretation.

CONCLUSIONS:

These difficulties compromise the precision, accuracy, and reliability of the peripheral nerve stimulator as a tool for monitoring neuromuscular blockade in the critically ill. Peripheral nerve stimulation should be used in conjunction with clinical parameters to make decisions regarding dose adjustments. Doses should be reduced as much as possible to provide the minimum depth of paralysis that is clinically appropriate. Technical directions and training programs for peripheral nerve stimulation should be developed, and designated individuals should be trained in its application. Large, prospective, controlled studies are necessary to evaluate the incidence of prolonged paralysis or motor neuropathy with administration of neuromuscular blocking agents in patients whose dose is adjusted on the basis of peripheral nerve stimulation.
Evaluation of Symptom Distress in a Bone Marrow Transplant Outpatient Environment
Authors: Lawrence Carol C , Gilbert Colleen J , Peters William P
Published: January 2017

OBJECTIVE:

To measure patient perceptions of autologous bone marrow transplantation (ABMT)-associated symptoms in the outpatient setting, assess the efficacy of the established antiemetic protocol, evaluate patient satisfaction, and report patient medication compliance.

DESIGN:

A prospective, descriptive study of patients with breast cancer who were enrolled in an outpatient ABMT program.

SETTING:

Duke University Autologous Bone Marrow Transplantation Program.

METHODS:

Patient perceptions of 12 symptoms were measured by the Symptom Distress Scale (SDS) on the day of admission to the hospital, the day of discharge to the outpatient clinic, after bone marrow reinfusion, and before patient release from the clinic. The number of retching and vomiting episodes was recorded by each patient daily. Patient satisfaction was determined by a standardized personal interview conducted prior to discharge. Patient compliance was assessed by a review of patient medication documentation.

RESULTS:

Twenty-eight patients were enrolled over 5 months. The median SDS scores for each symptom evaluated revealed that anorexia, nausea, fatigue, insomnia, and bowel problems were the most distressing symptoms patients experienced in the outpatient ABMT program. Scores for pain, negative outlook, cough, diminished concentration, and change in appearance indicated only mild distress associated with these variables. The total number of vomiting episodes ranged from 1 to 33 total episodes per patient per outpatient stay. The percentage of patients experiencing a complete antiemetic response ranged from 24% to 48% over the 4 days after chemotherapy but steadily improved thereafter to a peak of 90% 1 week later. Patient satisfaction results showed that patients preferred being out of the hospital and reported their anxiety controlled, although most had some problems with the outpatient clinic or medications required.

CONCLUSIONS:

Loss of appetite, fatigue, and insomnia have been identified as symptoms that are frequently present during the course of the outpatient ABMT program. Mild, intermittent nausea persists in the outpatient setting for up to 9 days after bone marrow transplant despite continuous combination antiemetic therapy. Patient interviews confirmed the belief that patients enjoy being out of the hospital. Medication compliance is more than 90% in this structured outpatient setting.
Polypharmacy among Nursing Home Geriatric Medicaid Recipients
Authors: Gupta Sanjay , Rappaport Harvey M , Bennett Lonnie T
Published: January 2017

OBJECTIVE:

To determine the factors that influence the number of different drugs prescribed to geriatric Medicaid recipients residing in Louisiana's intermediate care facilities I (ICFs I).

DESIGN:

Observational and cross-sectional with descriptive and analytic components.

PARTICIPANTS:

All geriatric Medicaid recipients in Louisiana ICFs I during 1994 (n= 19 932).

METHODS:

Relevant data on sex, age, race, geographic region of a recipient, number of prescribing physicians, number of pharmacies used, and the number of drugs prescribed to a recipient were extracted from the state Medicaid files. Frequencies for the seven study variables were calculated. Regression analysis was used to evaluate the influence of the six predictor variables on the number of drugs prescribed.

RESULTS:

The study population was 73.63% women, 60.07% 81 years of age and older, 70.65% white, 23.21% African-American, 6.14% other races, and 29.83% from predominantly rural north Louisiana. A total of 44.60% of the residents received prescriptions from one physician, 8.41% of the residents were single pharmacy users, and 45.65% were prescribed more than 10 drugs during the year. The regression model accounted for 20.53% of the total variation in the number of drugs prescribed to a recipient. Race, geographic region, number of prescribing physicians, and number of pharmacies used by a recipient influenced the number of drugs prescribed.

CONCLUSIONS:

To reduce the number of drugs prescribed and polypharmacy among geriatric Medicaid recipients, Louisiana's ICFs I should minimize the number of physicians and pharmacies used in this population.
Famciclovir for Treatment of Herpesvirus Infections
Authors: Luber Andrew D , Flaherty John F
Published: January 2017

OBJECTIVE:

To discuss the antiviral activity, pharmacokinetics, clinical efficacy, and adverse effect profile of famciclovir, the oral prodrug of penciclovir (PCV), and to compare these features of famciclovir with those of acyclovir in the treatment of herpesvirus infections.

DATA SOURCES:

Literature was identified by MEDLINE search, and abstracts from recent meetings were included where relevant. Data provided by the manufacturer were also used.

STUDY SELECTION:

Data regarding antiviral activity were included if accepted and widely used methods were followed. Clinical trials in which a comparison with acyclovir or placebo was performed were given the highest priority.

DATA SYNTHESIS:

In comparison with acyclovir, PCV has similar antiviral activity although its mode of action is not identical. When administered orally, famciclovir, the oral prodrug of PCV, is better absorbed than acyclovir, yielding an absolute bioavailability of PCV of 77%. The predominant route of PCV elimination is via the kidneys, with a half-life of approximately 2.5 hours. In trials comparing famciclovir with acyclovir for the treatment of herpes zoster in immunocompetent individuals, comparable results were obtained. Famciclovir is also effective as therapy for recurrent episodes of genital herpes and may prove useful for chronic suppressive therapy. The most common adverse effects of famciclovir are headache and gastrointestinal upset. The dosage of famciclovir for herpes zoster in immunocompetent individuals is 500 mg po tid for 7 days; for recurrent genital herpes a dosage of 125 mg po bid for 5 days is recommended. Dosage adjustments are necessary in patients with renal dysfunction.

CONCLUSIONS:

Given its comparable efficacy, similar adverse effect profile, and less frequent dosing schedule than acyclovir, famciclovir represents a viable alternative for treatment of herpes zoster and for episodic therapy of recurrent genital herpes in immunocompetent adults. Specific recommendations for other uses of famciclovir await the publication of recent clinical trial results.
What is the Role of Angiotensin-Converting Enzyme Inhibitors in Congestive Heart Failure and after Myocardial Infarction?
Authors: Nelson Kent M , Yeager Bryan F
Published: January 2017

OBJECTTVE:

To discuss the controversies surrounding the choice of angiotensin-converting enzyme (ACE) inhibitor, and the timing, dosage, and duration of ACE inhibitor therapy for congestive heart failure (CHF) and after myocardial infarction (MI). The beneficial effects of ACE inhibition in patients with CHF and after MI are reviewed. Human clinical trials are reviewed and their clinical implications are discussed.

DATA SOURCES:

MEDLINE searches (1985–1995) identified human clinical trials and review articles.

DATA EXTRACTION:

Landmark human clinical trials with morbidity and mortality end points were included. The validity of the study data were assessed on the basis of study methods, population characteristics, and statistical power.

DATA SYNTHESIS:

ACE inhibitors exert beneficial effects in patients with CHF by hemodynamic and neurohormonal mechanisms. The attenuation of ventricular remodeling that occurs with ACE inhibition does not fully explain the results of clinical trials in patients after MI. Routine determination of ejection fraction to guide ACE inhibitor therapy is not as important as the patient's clinical status. Clinicians should titrate the chosen ACE inhibitor on the basis of hemodynamic response to target doses used in major clinical trials. Because the beneficial effects of ACE inhibitors appear to be a class effect, choice of an agent should include cost considerations and the results of clinical trials.

CONCLUSIONS:

ACE inhibitors reduce morbidity and mortality in selected CHF and post-MI patients. Patients with symptomatic CHF benefit most from ACE inhibitor therapy, and it should be continued indefinitely. Treatment effects in asymptomatic patients are delayed. The role of ACE inhibitor therapy in preventing morbidity and mortality in asymptomatic patients with preserved ventricular function requires further study.
Nefazodone: Its Place among Antidepressants
Authors: Cyr Monica , Brown Candace S
Published: January 2017

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, adverse effects, and drug interactions of nefazodone, as well as to determine its place among currently available antidepressants.

DATA SOURCES:

A search of European and American literature using EMBASE and MEDLINE was completed. Nefazodone was the search term.

DATA SYNTHESIS:

Nefazodone is an antidepressant that blocks serotonin type 2 (5-HT2) receptors in addition to inhibiting the reuptake of serotonin and norepinephrine. In double-blind, placebo-controlled studies, nefazodone demonstrates antidepressant activity at dosages ranging from 400 to 600 mg/d. Sedation, dry mouth, nausea, and dizziness are the more common adverse effects of nefazodone. Nefazodone, an analog of trazodone, has not been associated with priapism at this time, and may have fewer sexual adverse effects than other antidepressants. More studies are needed to determine the potential role of nefazodone in treating anxiety, pain, and premenstrual syndrome.

STUDY SELECTION:

Only double-blind, placebo-controlled studies designed to establish the efficacy of nefazodone as an antidepressant were reviewed.

CONCLUSIONS:

Based on placebo-controlled, double-blind, comparative trials, nefazodone demonstrates greater efficacy than placebo, and equivalent efficacy to imipramine. Somnolence, dry mouth, nausea, dizziness, and constipation are the most common adverse effects. Nefazodone appears to have a milder adverse effect profile than the tricyclic antidepressants, causes fewer sexual dysfunctions than the serotonin selective reuptake inhibitors, and may cause less dizziness than trazodone. Nefazodone at dosages of at least 300 mg/d provides another option for the treatment of depression.
AUIC — A General Target for the Optimization of Dosing Regimens of Antibiotics?
Authors: Costa Teresa Dalla , Derendorf Hartmut
Published: January 2017

OBJECTIVE:

To present a systematic evaluation of the area under the inhibitory curve (AUIC) approach for the optimization of antibiotic dosing schedules for three major antibiotic classes (beta-lactams, quinolones, aminoglycosides). It has been proposed that an AUIC over 24 hours of at least 125 may be an applicable target parameter for the optimization of antibiotic dosing schedules across these antibiotic classes. Some limitations of this approach are presented and discussed.

METHODS:

A precise equation for the calculation of AUIC is derived. Moreover, a specific equation is derived for the situation that results in a trough concentration at the end of the dosing interval equal to the minimum inhibitory concentration (MIC). With the same three drags used for deriving the target AUIC value (tobramycin, cefmenoxime, ciprofloxacin), different dosing regimens are simulated to obtain the target AUIC of 125.

RESULTS:

Very different serum concentration profiles can result in the same AUIC. In an example for cefmenoxime, dosing regimens of 1 g q6h and 4.2 g q24h resulted in equal AUIC values of 125, whereas the respective time above MIC differed dramatically (99% of the dosing interval for q6h vs. 36% for q24h).

CONCLUSIONS:

It does not seem valid to accept the proposed breakpoint AUIC target of at least 125 as an applicable value for determining the appropriate dosing schedule of these classes of antibiotics. Based on the limitations discussed about the AUIC approach, the same conclusion also holds for any other fixed AUIC breakpoint target value.
Disposition of Foscarnet during Peritoneal Dialysis
Authors: Alexander Alicia CM , Akers Adam , Matzke Gary R. , Aweeka Francesca T. , Fraley Donald S.
Published: January 2017

OBJECTIVE:

To report the disposition of foscarnet in a patient undergoing peritoneal dialysis.

CASE SUMMARY:

A 34-year-old man with AIDS received foscarnet for the treatment of esophageal cytomegalovirus. We characterized the clearance of foscarnet in this patient during continuous cyclic peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD).

DISCUSSION:

The foscarnet half-lives during CCPD and CAPD were 41.4 and 45.8 hours, respectively. These values are significantly greater than the half-life of 4.5 hours observed in patients with normal renal function and about half that reported in anuric patients undergoing hemodialysis during the interdialytic period. The CCPD and CAPD clearances of foscarnet were 5.8 and 4.5 mL/min, respectively; the CAPD clearances of creatinine and urea nitrogen were 4.1 and 6.0 mL/min, respectively. The patient's estimated total body clearance values of foscarnet during CCPD and CAPD were 9.8 and 8.8 mL/min, respectively. Thus, CCPD and CAPD augmented the patient's residual clearance of foscarnet by 145% and 105%, respectively.

CONCLUSIONS:

Since incremental increases in residual clearance of 30% or more generally will result in clinically significant changes in a drug's serum concentration, foscarnet dosage needs to be individualized for patients receiving peritoneal dialysis.
Fatal Myocardial Infarction Potentially Induced by Paclitaxel
Authors: Hekmat Elham
Published: January 2017

OBJECTIVE:

To report a case of a fatal myocardial infarction (MI) possibly induced by paclitaxel in a patient with metastatic breast cancer.

CASE SUMMARY:

A 67-year-old African-American woman with metastatic breast cancer was treated with a paclitaxel infusion. Fifteen hours into the 24-hour continuous infusion, the patient developed tachypnea, respiratory distress, and chest pain. Paciltaxel infusion was discontinued. Electrocardiogram findings revealed ST elevation in leads 2, 3, and aVF acutely. The cardiac enzymes were abnormal and the echocardiogram changes showed severe global left ventricular dysfunction consistent with acute MI. The patient died 13 hours after stopping the paclitaxel infusion.

DISCUSSION:

Cardiac adverse effects of paclitaxel have been described in preliminary studies. Paclitaxel-induced cardiac abnormalities are usually described as asymptomatic and transient. MI secondary to paclitaxel infusion has rarely been reported. The mechanism by which paclitaxel causes cardiac abnormalities, especially myocardial damage, is not well understood. CONCLUSIONS: Myocardial damage secondary to paclitaxel infusion is a serious and life-threatening adverse effect. Caution should be exercised in all patients treated with paclitaxel until more information regarding risk factors is available.
A Practical Look at the Clinical Usefulness of the Beta-Lactam/Beta-Lactamase Inhibitor Combinations
Authors: Hart Susan M. , Bailey Elaine M.
Published: January 2017

OBJECTIVE:

To aid clinicians in developing an approach to the use of intravenous beta-lactam/beta-lactamase inhibitors on a patient-specific basis. To achieve this, the pharmacology, in vitro activity, and clinical use of the intravenous beta-lactam/beta-lactamase inhibitor combinations in the treatment of selected infections seen in hospitalized patients are discussed.

DATA IDENTIFICATION:

An English-language literature search using MEDLINE (1987–1995); Index Medicus (1987–1995); program and abstracts of the 32nd (1992), 33rd (1993), 34th (1994), and 35th (1995) Interscience Conference on Antimicrobial Agents and Chemotherapy; bibliographic reviews of review articles; and package inserts.

STUDY SELECTION:

In vitro and in vivo studies on the pharmacokinetics, microbiology, pharmacology, and clinical effectiveness of ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam were evaluated.

DATA SYNTHESIS:

Many properties of the beta-lactam/beta-lactamase inhibitor combinations are similar. Differences in dosing, susceptibilities, and clinical applications are important considerations for clinicians. Potential roles for these agents in the clinical setting include pneumonia, intraabdominal infections, and soft tissue infections. A short discussion on susceptibility data interpretation is also presented.

CONCLUSIONS:

There are important differences among the available beta-lactam/beta-lactamase inhibitor combinations, such as spectra of activity, which need to be considered in choosing an agent for a patient-specific case. These products can be useful alternatives to conventional two- to three-drug regimens in mixed infections such as foot infections in patients with diabetes and hospital-acquired intraabdominal infections.
Antithymocyte Immunoglobulin in Severe Aplastic Anemia and Bone Marrow Transplantation
Authors: Colby Christine , Stoukides Cheryl A. , Spitzer Thomas R.
Published: January 2017

OBJECTIVE:

To review antithymocyte immunoglobulin (ATG) and its current role in the treatment of severe aplastic anemia (SAA), focusing on ATG in immunosuppressive therapy compared with bone marrow transplantation (BMT).

DATA SOURCES:

A MEDLINE search (1966 to 1996) of English-language literature and human subjects pertaining to ATG and BMT therapy in SAA 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:

The hallmark of SAA is pancytopenia and bone marrow hypoplasia. Although the etiology in a majority of cases remains unknown, current data implicate an immune-mediated destruction of stem cells. ATG is a potent immunosuppressive agent and has emerged as an important therapy for patients with SAA. The exact mechanism of immunosuppressive action is not fully understood, although ATG appears to disrupt cell-mediated immune responses resulting in inhibition or altered T-cell function. Numerous trials have evaluated the use of ATG both as monotherapy and in combination with other immunosuppressive agents. Treatment with ATG in SAA has demonstrated a 40–70% response rate. Data suggest that intensive immunosuppressive therapy with ATG in combination with cyclosporine may provide the optimal immunosuppressive treatment. Questions still remain concerning complications and long-term survival of the patients. Although more than a 2-year follow-up shows a decline in mortality, a plateau in the survival curve was not achieved. BMT is a potential treatment for SAA. Although there is a high initial mortality due to treatment-related toxicities, successful marrow engraftment provides a cure for SAA. Many patients (75–90%) experience long-term survival after allogenic BMT. Age, donor availability, and severity of disease limit the number of eligible patients.

CONCLUSIONS:

Due to excellent results with BMT, it has become the therapy of choice for selected patients with SAA. For patients who are not eligible for BMT, intensive immunosuppressive therapy with ATG and cyclosporine is recommended. Further study to better understand the pathogenesis of SAA and prevent treatment-related complications is essential to provide the best care to all patients.
Conscientious Objection to Assisted Death: Can Pharmacy Address This in a Systematic Fashion?
Authors: Mullan Kenneth , Allen William L. , Brushwood David B.
Published: January 2017

OBJECTIVE:

To describe a legal structure for the accommodation of pharmacists' rights of conscience in the dispensing of drugs for pharmaceutically assisted death.

BACKGROUND:

Pharmacists have indicated that there is disagreement in the profession regarding the appropriateness of a practice known as “pharmaceutically assisted death”, in which lethal medications are prescribed for terminally ill patients who want to end their lives. Pharmacists who object to pharmaceutically assisted death may be asserting a conscientious objection that threatens to create a conflict with their employers. In addition, pharmacists who support pharmaceutically assisted death, but whose employers forbid the dispensing of medications for this purpose, may face a similar conflict. Current laws and principles of professional ethics fail to adequately address the resolution of either of these conflicts.

DISCUSSION:

We propose a system within which the pharmacy profession could accommodate the right to conscientious objection without sacrificing the quality of patient care. At the heart of our proposal is the understanding that employers must respect an employee's right to beliefs that differ from those of the employer and, correspondingly, the understanding that employees must respect the employer's duty to provide products and services to those who seek them from the employer.

CONCLUSIONS:

Pharmacy associations can adopt policies for conscientious objection and have those policies become law through action of the state legislature or the state board of pharmacy. This approach could lead to the development of a clear policy and procedure for resolving the issue of conscientious objection within the pharmacy community, making it far less likely that institutions outside pharmacy would be required to develop a solution for pharmacy.
Stability of Fosphenytoin Sodium with Intravenous Solutions in Glass Bottles, Polyvinyl Chloride Bags, and Polypropylene Syringes
Authors: Fischer James H , Cwik Michael J , Luer Mark S , Sibley Carolyn B , Deyo Kelly L
Published: January 2017

OBJECTIVE:

To determine the stability of fosphenytoin sodium admixtures with NaCl 0.9% injection and dextrose 5% (D5W) injection when stored in glass or polyvinyl chloride (PVC) containers, to evaluate the compatibility of fosphenytoin with 11 other intravenous solutions, and to determine the stability of fosphenytoin repackaged in polypropylene syringes.

METHODS:

Dilutions of fosphenytoin sodium 1, 8, and 20 mg phenytoin sodium equivalents (PE)/mL were prepared in NaCl 0.9%, D5W, and 11 other intravenous fluids. Aliquots of each solution in NaCL 0.9% or D5W were transferred to three glass bottles for storage at 25 °C and 21 PVC bags for storage at 25, 4, or −20 °C Aliquots of each admixture with the other intravenous fluids were transferred to three PVC bags and stored at 25 °C for 7 days. In addition, 63 syringes were filled with fosphenytoin sodium 50 mg PE/mL (undiluted) and stored at 25, 4, or −20 °C. Samples of each solution from the three containers were analyzed for visual compatibility, pH, and fosphenytoin concentration initially and at 0.5, 1, 2, 3, 7, 14, and 30 days during storage at 25 and 4 °C and at 1, 7, 14, and 30 days during storage at–20 °C. Following removal of containers from the freezer, additional samples were obtained after 7 days at 4 or 25 °C, and 7 days at 25 °C, and then 7 days at −20 °C.

RESULTS:

No visible precipitation or change in color or clarity was observed in any of the fosphenytoin solutions during the study. The concentration of fosphenytoin at each sampling time remained within 97–104% of initial concentration, regardless of container, concentration, intravenous admixture, or storage temperature.

CONCLUSIONS:

Fosphenytoin sodium, either undiluted in polypropylene syringes or diluted with NaCl 0.9% or D5W in PVC bags, remains stable for at least 30 days at room temperature, under refrigeration, or frozen. After removal from the freezer, fosphenytoin can be thawed, kept at 4 or 25 °C for 7 days, and then returned to the freezer for another 7 days. Admixtures of fosphenytoin sodium in various other intravenous fluids are stable for at least 7 days at room temperature.
Cost-Effectiveness of Thrombolytic Therapy for Acute Myocardial Infarction
Authors: Castillo Paul A , Palmer Cynthia S , Halpern Michael T , Hatziandreu Evi J , Gersh Bemard J
Published: January 2017

OBJECTIVE:

TO estimate the cost-effectiveness of thrombolytic therapy versus no thrombolytic therapy for patients following acute myocardial infarction, focusing on the impact of time to treatment on outcome.

METHODS:

A decision model was developed to assess the benefits, risks, and costs associated with thrombolytic therapy for treatment of acute myocardial infarction compared with standard nonthrombolytic therapy. The model used pooled data from a recent study of nine large randomized, controlled clinical trials and 12-month outcome data from a recently published meta-analysis of thrombolytic therapy trial data. Outcomes were expressed in terms of survival to hospital discharge and survival to 1 year after discharge. The risks of treatment that led to death, morbidity, or added costs were estimated. The model determined excess and marginal costs per death averted to hospital discharge and at 1 year. Results were also estimated in terms of cost per year of life saved. Sensitivity analyses included variations in time to treatment and drug cost.

RESULTS:

The marginal cost of thrombolytic therapy per death averted at 1 year was $222 344, or $14 438 per year of life saved. For patients treated within 6 hours of acute myocardial infarction, the marginal cost per death averted was $181 536 at 1 year, or $11 788 per year of life saved.

CONCLUSIONS:

Thrombolytic therapy is significantly more cost-effective than many other cardiovascular interventions and compares favorably with other forms of medical therapy. Results suggest that shortening the time to treatment has a critical impact on the cost-effectiveness of thrombolytic therapy.
Short-Term Comparison of Once- versus Twice-Daily Administration of Glimepiride in Patients with Non-Insulin-Dependent Diabetes Mellitus
Authors: Sonnenberg Gabriele E , Garg Dyal C , Weidler Donald J , Dixon Russell M , Jaber Linda A , Bowen Angela J , DeChemey G Stephen , Mullican William S , Stonesifer Larry D
Published: January 2017

OBJECTIVE:

To investigate the metabolic effects and frequency of adverse events with 6 mg of glimepiride, a new oral sulfonylurea, given both in once- and twice-daily dosages to patients with non-insulin-dependent diabetes mellitus (NIDDM).

RESEARCH DESIGN AND METHODS:

This 15-week study involved 161 subjects with NIDDM. Subjects were randomized into two groups. For 4 weeks, group 1 received glimepiride 3 mg twice daily, and group 2 received glimepiride 6 mg once daily. After a 3-week placebo-washout period, twice- and once-daily regimens were crossed over for a second 4-week treatment period. Subjects were hospitalized at the end of each placebo or active-treatment phase. Their glucose concentrations were recorded at 20 time points over a 24-hour period, and their insulin and C-peptide concentrations were recorded at 16 time points over the same period. Parameters that were calculated included fasting, 24-hour, and postprandial concentrations of glucose, insulin, and C-peptide.

RESULTS:

One hundred six patients were randomized to receive treatment; 94 completed the entire study. Existing physiologic mechanisms of glucose control were apparently unimpaired by glimepiride treatment. Insulin concentrations increased more during the postprandial glucose peaks than when subjects were fasting. Both twice- and once-daily regimens proved equally effective in reducing concentrations of fasting, postbreakfast, postlunch, and postdinner plasma glucose. Twenty-four-hour mean glucose concentrations showed a slightly greater decrease from baseline for the twice-daily regimen; the difference between the regimens was statistically significant but not clinically meaningful. The incidence of adverse events with glimepiride approximated that obtained with placebo, with both groups reporting only one adverse event, headache, in more than 5% of the subjects.

CONCLUSIONS:

Glimepiride is equally effective whether administered once or twice daily. Glimepiride seems to stimulate insulin production primarily after meals, when plasma glucose concentrations are highest, but controls blood glucose throughout the day.
Riluzole: A New Agent for Amyotrophic Lateral Sclerosis
Authors: Wagner Mary L , Landis Barbara E
Published: January 2017

OBJECTIVE:

To provide a comprehensive review of riluzole, including its mechanism of action, pharmacokinetics, adverse drug reactions, drug interactions, efficacy, and administration. A brief review of amyotrophic lateral sclerosis (ALS) is also included.

DATA SOURCES:

A computerized search of the MEDLINE database in May 1996 was used to identify publications regarding ALS, riluzole, and metabolism by CYP1A2. Manufacturer's information on riluzole was used when there was no primary literature.

DATA SYNTHESIS:

Riluzole is approximately 90% absorbed following an oral dose. Its bioavailability is 60%. Peak concentrations occur within 1–1.5 hours of administration. Riluzole extensively binds to lipoproteins and albumin. This agent primarily undergoes CYP1A2 hydroxylation and glucuronidation, after which it is eliminated by the kidneys. Clearance is reduced in native Japanese healthy subjects and may be reduced in patients with hepatic impairment. Two trials with a total of 1114 patients addressed the efficacy of riluzole in ALS. Riluzole extended the time to tracheostomy or death, and the effect was greatest with dosages of 100 mg/d or greater. No effect on patients' symptoms or global assessment was detected at 18 or 21 months. Several flaws in these trials have led to questions concerning the validity of these results. The most commonly reported adverse effects of riluzole have been transient elevation of liver enzyme concentrations (2–5 times the upper limit of normal), worsening of asthenia, nausea, vomiting, diarrhea, anorexia, dizziness, vertigo, somnolence, and mouth paresthesia. Not as commonly reported, but still very serious, is neutropenia, which occurred in 3 of 4000 patients.

CONCLUSIONS:

Although the benefits of riluzole are questionable and it is expensive, this agent may extend the time to tracheostomy or death in patients with ALS. At present, this is the only agent approved for the treatment of ALS and should be made available for these patients.
Automated Peritoneal Dialysis: New Implications for Pharmacists
Authors: Brophy Donald F , Mueller Bruce A
Published: January 2017

OBJECTIVE:

To review the new automated peritoneal dialysis (APD) modalities that are available to patients with end-stage renal disease (ESRD), and to examine their potential pharmacokinetic and drug dosing consequences.

DATA SOURCES:

A MEDLINE search (from January 1966 to June 1996) of English-language literature pertaining to peritoneal dialysis was performed. Additional references were obtained by reviewing the references of pertinent articles identified through the search. Tertiary sources were also used.

DATA EXTRACTION:

Data regarding peritoneal dialysis techniques and pharmacokinetics were extracted from the literature. Data were evaluated according to the study design, population, results, and conclusions.

DATA SYNTHESIS:

ESRD is the result of progressive chronic renal insufficiency and requires renal replacement therapy. APD is the fastest growing renal replacement therapy by percentage in the US and provides dialysis exchanges via a machine while the patient sleeps, thereby improving patient convenience, peritoneal dialysis compliance rates, and decreasing peritonitis rates. Well-designed pharmacokinetic studies involving APD have not been conducted. Consequently, no formal drug dosing recommendations are available for APD, and pharmacists must rely on established dosing guidelines for continuous ambulatory peritoneal dialysis (CAPD) when recommending dosing regimens. This article describes the new APD treatment modalities available and the potential pharmacokinetic differences between CAPD and APD.

CONCLUSIONS:

Well-designed studies are needed to fully characterize the pharmacokinetic parameters of drugs in APD. Until then, pharmacists should recommend that intraperitoneally administered drugs be given during the longest peritoneal dialysate dwell of the day and that serum concentrations of drugs with narrow therapeutic indices be monitored closely.