bluuebunny/crossref_metadata_2025 huggingface dataset:
Sedatives, Analgesics, and Paralytics in the Icu
Authors: Watling Sharon M , Dasta Joseph F , Seidl Edward C
Published: May 2017

Objective

To solicit practitioner-perceived opinions regarding current sedative/analgesic/paralytic practice including drug selection, admixture methods, and methods of assessing patient response to therapy via a survey tool; and to assess sedative/pain/paralytic drug use patterns including dosage, route, selection, and combination therapy by collecting actual drug administration data from multiple centers.

Methods

Respondents completed a survey and collected drug administration data for 5 consecutive days in the intensive care unit (ICU) in which they practiced.

Participants

One hundred thirty-eight members of the Society of Critical Care Medicine Clinical Pharmacology and Pharmacy section and the Critical Care Practice Research Network of the American College of Clinical Pharmacy agreed to participate in the study.

Results

Fifty-one percent of the participants completed surveys, and 45% returned drug administration data collection forms. Patients received sedative/pain/paralytic therapy 62% of the 5 days studied. The most frequently received drugs were opiates, followed by benzodiazepines. Intermittent intravenous injection, oral/enteral, and continuous infusion methods were used in most patients. Combination therapy was used 25% of the time, with benzodiazepine/opiate combinations used most often (46%). Administration protocols were rarely used. Paralytic agents were occasionally administered without sedative/pain therapy.

Conclusions

Patients received these agents during the majority of their ICU stay. Multicenter drug use data suggested a preference for opiate and benzodiazepine therapy. Many centers used continuous infusion therapy despite minimal pharmacokinetic/pharmacodynamic information on ICU patients. Further studies are needed to standardize end points, as well as obtain both pharmacokinetic/pharmacodynamic and stability data in ICU patients.
Factors Associated with Antihypertensive Prescribing
Authors: Nichol Michael B , Margolies Jane E , Gill Mark A
Published: May 2017

Objective

To investigate factors associated with treatment approaches to hypertension, a major risk factor for coronary heart and cerebrovascular disease and a significant healthcare problem in the US. The study reports on three cross-sectional national surveys of patient–physician encounters.

Population

Visits were selected for adults with hypertension diagnoses from the National Ambulatory Medical Care Surveys, which represent office encounters during a given year. Years of observation included 1989, 1990, and 1991.

Methods

Multiple variable logistic regression was used to identify predisposing, need, enabling, and health utilization characteristics associated with whether the visit resulted in a prescription of an antihypertensive. Additionally, the association of these visits with combination therapy is determined.

Results

For each of the 3 years, 69–75% of the encounters were associated with a prescription for drugs to treat hypertension. Prescribing is consistent with current literature demonstrating decreasing reliance on diuretics and β-blockers, and increasing reliance on calcium antagonists. Combination therapy decreased as a percentage of prescriptions in 1990 and 1991. Variables associated with receiving an antihypertensive prescription included predisposing characteristics (patient age >65 y), need characteristics (diagnosis of congestive heart failure [CHF]), and health utilization characteristics (physician specialty, previous diagnosis of hypertension). The most significant variables associated with combination therapy were predisposing characteristics (patient age >65 y), need (CHF diagnosis, diagnosis of hypertension with end organ involvement), and health utilization characteristics (physician specialty).

Conclusions

These national estimates reinforce previous regional data regarding the categories of hypertension medications used. Patient visits involving multiple diagnoses, cardiologists, or patients older than 65 years, are more likely to generate prescriptions for combination antihypertensive therapy.
Prevalence of Inhaled Corticosteroid Use among Patients with Chronic Obstructive Pulmonary Disease: A Survey
Authors: Jackevicius Cynthia A , Chapman Kenneth R
Published: May 2017

Objective

To determine the extent of inhaled corticosteroid use among patients with chronic obstructive pulmonary disease (COPD).

Design

Review of medical records.

Setting

Tertiary-care university teaching hospital.

Patients

Seventy-two consecutive patients prescribed an inhaled corticosteroid during hospitalization.

Intervention

None.

Measurements

Patient demographics, inhaled corticosteroid regimen, respiratory diagnosis, and inhaled corticosteroid use before and during hospitalization.

Results

The majority of patients (85%) were receiving their prescribed corticosteroid inhaler prior to admission. Beclomethasone dipropionate 250 μg/puff was the most commonly prescribed inhaled corticosteroid formulation accounting for 43% of the total corticosteroid inhaler orders. COPD was the most common respiratory diagnosis (43%) associated with inhaled corticosteroid use, followed by asthma (37%), COPD/asthma (13%), and no diagnosis (7%). During the study period, the proportion of all hospitalized patients with COPD who also received inhaled corticosteroid prescriptions (35%) was not significantly different from all hospitalized patients with asthma who received inhaled corticosteroid prescriptions (33%).

Conclusions

The rate of inhaled corticosteroid use far exceeds the rate expected among the general population of patients with COPD. Educational intervention is needed to encourage compliance with published guidelines for the management of COPD.
Algorithms Used in Adverse Drug Event Reports: A Comparative Study
Authors: Frick Pamela A , Cohen Louise G , Rovers John P
Published: May 2017

Objective

To determine if and how the Kramer and Karch algorithms differ in assigning a probability that a published case was actually an adverse drug event (ADE), and to determine if these algorithms could be used to assess published ADEs.

Design

Open, single-rater comparison of Karch and Kramer algorithms in 200 published ADE reports.

Main Results

The algorithms were not significantly different regarding the proportion of cases deemed definite (p = 0.5204) or probable (p = 0.2972) ADEs. The Kramer instrument was more likely to assign a possible risk of ADE (p = 0.0001), while the Karch instrument was more likely to assign a risk of unlikely (p = 0.0001). The algorithms agreed in 41% of the cases and could be used to assess published ADEs.

Conclusions

The Karch and Kramer algorithms may disagree in how they assign a probability of risk to a potential ADE. This may be due to how algorithms are applied, as well as to structural differences.
Therapeutic Monitoring: Revised Winter–Tozer Equation for Normalized Phenytoin Concentrations in Trauma and Elderly Patents with Hypoalbuminemia
Authors: Anderson Gail D , Pak Christopher , Doane Kenneth W , Griffy Kay G , Temkin Nancy R , Wilensky Alan J , Winn H Richard
Published: May 2017

Objective

To develop a revised equation reflecting the current practice of measuring unbound phenytoin at room temperature, and to evaluate the revised Winter–Tozer method of predicting normalized total phenytoin concentrations in two groups of patients with hypoalbuminemia — elderly nursing home patients and critically ill head trauma patients.

Design

Albumin, unbound phenytoin, and total phenytoin concentrations were obtained from two sources: prospectively from a group of elderly nursing home patients and by a retrospective chart review of trauma patients enrolled in a previous double-blind, placebo-controlled study.

Setting

Community nursing homes; a university-affiliated urban teaching hospital.

Participants

Elderly nursing home patients (n = 46) taking chronic phenytoin therapy and patients enrolled in a double-blind, placebo-controlled study (n = 58) evaluating the use of phenytoin to prevent posttraumatic seizures.

Main Outcome Measures

Prediction error analysis was performed by using the methods proposed by Sheiner and Beal. Bias and precision were evaluated by calculating the mean prediction error (MPE) and root mean squared error (RMSE), respectively.

Results

The Winter–Tozer equation consistently overpredicted the normalized phenytoin concentration in the elderly nursing home population (MPE = 3.2, RMSE = 5.9) and the trauma patients (MPE = 3.3, RMSE = 4.8). The equation was revised to reflect the increased protein binding of phenytoin with decreased temperature and resulted in significantly decreased bias in both groups of patients.

Conclusions

The revised equation is useful in predicting normalized phenytoin concentrations in both elderly nursing home patients and critically ill trauma patients.
Critical Care: Incidence and Risk Factors of Thrombocytopenia in Critically Ill Trauma Patients
Authors: Hanes Scott D , Quarles Deborah A , Boucher Bradley A
Published: May 2017

Objective

To determine the incidence of thrombocytopenia (<100 platelets × 103/mm3) and potential risk factors, including medications, associated with the development of thrombocytopenia in critically ill trauma patients.

Design

Prospective, observational study.

Setting

A 20-bed trauma intensive care unit (ICU) at a university hospital.

Patients

Sixty-three critically ill trauma patients without baseline thrombocytopenia admitted to the trauma ICU for at least 48 hours.

Interventions

Patients were followed for up to 14 days. Platelet counts were determined daily. The following data were collected and analyzed as potential risk factors for the development of thrombocytopenia: medications, age, sex, race, trauma score, mode and type of injury, alcohol history, units of packed red blood cells (PRBC) and platelets transfused, surgical procedures, duration of ICU stay, and the development of systemic inflammatory response syndrome or disseminated intravascular coagulation.

Results

Thrombocytopenia occurred in 26 (41%) of the patients. Among risk factors studied, nonhead injury, age, trauma score, duration of ICU stay, and the number of PRBC transfusions were significanüy associated with the development of thrombocytopenia (P < 0.05). However, nonhead injury, age, and trauma score were useful variables in predicting the development of thrombocytopenia by using multivariate analysis. Medications were not associated with the development of thrombocytopenia.

Conclusions

The type of injury sustained, the quantity of platelet-deficient transfusions, and age are the greatest risk factors associated with the development of thrombocytopenia in critically ill trauma patients. Drug-induced thrombocytopenia appears to play a minor role in the development of thrombocytopenia; therefore, medications should not be automatically discontinued or substituted when thrombocytopenia occurs.
Drug Stability: Rapid Loss of Fentanyl Citrate Admixed with Fluorouracil in Polyvinyl Chloride Containers
Authors: Xu Quanyun A , Trissel Lawrence A , Martinez Juan F
Published: May 2017

Objective

To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 μg/mL in dextrose 5% and in sodium chloride 0.9% injection.

Design

Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at −20, 4, 23, and 32 °C. Samples were removed immediately and at various times over 7 days and stored at −70 °C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC.

Results

Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23,32 °C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0–9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time.

Conclusions

When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 μg/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.
HIV: Cost of Medication Therapy in Ambulatory HIV-Infected Patients
Authors: Nykamp Diane , Barnett Candace W , Lago Maria , Parham Deborah L , Fernandez Enrique S
Published: May 2017

Objective

To examine the use and cost associated with prescribed medications as well as the use of over-the-counter medications and nontraditional therapies among ambulatory HIV-infected patients at Ryan White Title IIIb grantee centers.

Methods

Study participants (n = 223) were enrolled from eight centers across the US and Puerto Rico. Data were collected by a nurse, pharmacist, or physician through review of medical records and medication profdes. Information on the use of over-the-counter drugs and alternative therapies was obtained from the patients.

Results

Two hundred eleven (94.6%) patients received a mean ± SD of 5.3 ± 3.8 prescription medications during a consecutive 90-day period. The cost of medication was $1237.62 ± $1751.49 per patient. Patients with a diagnosis of AIDS received a greater number of prescription drugs: an average of 6.6 compared with 3.4 among HIV-positive patients and 3.5 among asymptomatic patients. Anti-retroviral agents were used by 143 (68.7%) patients. Zidovudine and stavudine had the highest cost ($611.81 ± $254.10 and $596.96 ± $352.80, respectively). Eighty-one (40.9%) patients reported the use of at least one over-the-counter product (range 0–11) and 11.8% reported use of alternative therapies.

Conclusions

This study shows the cost of drug treatment for HIV-infected patients has remained stable since the early 1990s. However, it is anticipated this will change due to the introduction of new anti-HIV agents, greater use of combination therapies, greater use of prophylactic therapies, and increased survival times.
Ambulatory Care: Medication Use Characteristics in an Ambulatory Elderly Population in Taiwan
Authors: Hsu Rou-Yee Chen , Lin Min-Shung , Chou Mei-Huei , Lin Ming-Fang
Published: May 2017

Objective

To compare prescribing patterns between the elderly and nonelderly in 1994, to disclose prescribing trends in the elderly between 1992 and 1994, to explore whether drug utilization is in agreement with disease prevalence, and to identify suboptimal prescribing by drug category for ambulatory elderly patients.

Design

Cross-sectional survey at two separate time intervals.

Setting

All public group practice centers (GPCs) in Taiwan.

Patients

Ambulatory adults who visited GPCs during 1 random week. Those 65 years or over were classified as the elderly group, and those 20-64 years were the nonelderly group.

Main Outcome Measures

Mean diagnosis, drug use, and expenditure; frequency of diagnosis; and prescribing by therapeutic category.

Results

Data on 30 777 elderly and 38 184 nonelderly patients were collected in 1994. There was widespread use of antacids. Compared with nonelderly adults, the elderly were diagnosed with more diseases (1.3 vs. 1.2, respectively; p < 0.01), received more medications (4.7 vs. 4.1, respectively; p < 0.01), and had higher drug expenditures (5.4 vs. 4.6, respectively; p < 0.01). Chronic illness was more prevalent in the elderly, which accounted for the extensive use of cardiovascular drugs (32.1%), nonsteroidal antiinflammatory drugs (25.9%), and anxiolytics (15.9%). The upward trend in the elderly from 1992 to 1994 with hypertension (18.6% vs. 20.0%) or diabetes (9.2% vs. 10.9%) did not result in more cases of cerebrovascular disease (7.1% vs. 4.9%). There was a substantial increase in use of antispasmodic and gastroprokinetic agents (4.5% to 10.7%); the use of antacids decreased (73.6% to 63.4%) in the elderly.

Conclusions

Compared with the prevalence of disease, there was extensive nonspecific use of anxiolytics and antacids. However, lessened use of antidepressants and postmenopausal hormone replacement may have an impact on morbidity and mortality and deserves particular attention.
Fixed Drug Eruption of the Penis Due to Hydroxyzine Hydrochloride
Authors: Cohen Herman Avner , Barzilai Asher , Matalon Andre , Harel Liora , Gross Samuel
Published: May 2017

Objective

To report four cases of fixed drug eruption induced by hydroxyzine hydrochloride (Otarex, Teva, Israel).

Case Summary

Four children with restlessness who were treated with hydroxyzine hydrochloride developed fixed drug eruption of the penis. Drug discontinuation was followed by complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration inhibiting factor (MIF) assay with hydroxyzine hydrochloride was positive.

Discussion

The pathogenesis of fixed drug eruption and the role of macrophage MTF assay in diagnosis is discussed.

Conclusions

A fixed drug eruption induced by hydroxyzine hydrochloride is possible, but is a rare phenomenon.
Management: Self-Directed Work Teams: Application to a Drug Information Center
Authors: Stachnik Joan M , Nunn-Thompson Cheryl L , Simon Pamela A , Seeger John D , Markind Jan E , Ross Jinnie R , Clark Toby
Published: May 2017

Objective

To describe the transition of a drug information center from a traditionally managed center to a self-directed work team responsible for service, education, research, and drug use policy development.

To adapt to economic, educational, and technologic changes, traditional management structures in healthcare organizations are being reassessed. In some instances, a team approach (using self-directed work teams [SDWTs]) is being implemented. SDWTs have the potential to provide a number of benefits to an organization, including reduced costs and greater employee motivation. The University of Illinois at Chicago Drug Information Center had functioned under a traditional management structure. For economic and professional reasons, the management structure of the center was changed to an SDWT, prompting a reevaluation of the mission and activities of the center.

Discussion

Although still in transition, the center's change to a team structure has proven to be positive. The nature of the SDWT requires greater involvement by team members in all aspects of the center's operation, adding to the experience of team members. The team structure also allows for greater freedom to pursue projects of personal interest to individual team members. A number of issues still need to be resolved, such as performance-based compensation and peer- and self-evaluations.

Conclusions

SDWTS can provide many benefits. The successful implementation of an SDWT, however, has a number of requirements, the most important of which are a commitment from management and effective communication among team members and with management.
Absolute Bioavailability of Bromfenac in Humans
Authors: Gumbhir-Shah Kavita , Cevallos William H , Decleene Sheryl A , Halstenson Charles E , Korth-Bradley Joan M
Published: May 2017

Objective

To estimate absolute bioavailability of bromfenac and to compare its pharmacokinetics after intravenous and oral administration.

Design

This was a randomized, open-label, single-dose, crossover study conducted under fasting conditions with a washout period of at least 48 hours between doses. Each subject received a 50-mg dose of bromfenac both intravenously and orally followed by collection of blood samples at specified time intervals. Bromfenac plasma concentrations were measured by using a validated HPLC method with ultraviolet detection.

Setting

The study was conducted at the Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, MN.

Subjects

The participants consisted of 12 healthy subjects between 18 and 45 years of age and within ± 15% of ideal body weight.

Results

The mean ± SD absolute bioavailability of bromfenac was 67% ± 20%.

Conclusions

The pharmacokinetic parameters of bromfenac were similar after intravenous and oral administration, suggesting that the prototype oral dosage form is optimal and that the observed intersubject variability is due to bromfenac itself, not the type of dosage form.
Effects of Age and Gender on the Pharmacokinetics of Bromfenac in Healthy Volunteers
Authors: Boni Joseph P , Decleene Sheryl A , Cevallos William H , Hicks David R , Korth-Bradley Joan M
Published: May 2017

Objective

To compare the pharmacokinetic parameters of bromfenac, a nonsteroidal antiinflammatory drug under development, in healthy volunteers of various ages and either gender, after single and multiple doses.

Design

Open-label, single- and multiple-dose, nonrandomized, parallel study.

Participants

Twenty young (18–45 y), 12 young-elderly (65–74 y), and 12 elderly (75–85 y) subjects were studied. Half of the subjects in each group were women.

Interventions

Bromfenac was given as a single 50-mg dose and then as 50-mg doses every 12 hours for 3 additional days. Twelve blood samples were collected for 12 hours after the first and last doses.

Main Outcome Measures

Bromfenac concentrations were measured by using an HPLC procedure with ultraviolet detection. Unbound bromfenac concentrations were measured by equilibrium dialysis. Pharmacokinetic analysis was performed by noncompartmental techniques.

Results

No significant differences related to gender were detected. Significant differences were observed in half-life (t1/2), AUC, clearance, and apparent volume of distribution when the elderly group was compared with the young group and in t1/2 when the elderly group was compared with the young-elderly group, although substantial overlap among groups was observed.

Conclusions

Administration of bromfenac to young-elderly or elderly subjects of either gender does not require a dosage adjustment in acute settings. Consideration should be made to titrating dosages in patients over 75 years of age who require repeated doses.
Phenytoin-Induced Thrombocytopenia
Authors: Holtzer Christopher D , Reisner-Keller Lori A
Published: May 2017

Objective

To describe a patient with severe thrombocytopenia induced by the administration of phenytoin for prevention of seizures. A review of the literature supplements this case description to alert clinicians to this potentially serious hematologic reaction.

Case Summary

A woman who had experienced two seizures was prescribed phenytoin to prevent seizure recurrence. Further evaluation revealed a tumor, which was resected, and phenytoin was continued. Thrombocytopenia was noted 15 days after initiation of phenytoin, which was replaced with phenobarbital. Platelet transfusion and administration of intravenous immune globulin were used to treat her thrombocytopenia. Platelets were within the normal range by day 8 after the operation.

Discussion

Phenytoin has been reported to induce various hematologic reactions, including thrombocytopenia. An intermediate epoxide metabolite of phenytoin is suspected as the cause of platelet destruction, which may occur via a complement-antibody reaction. Our patient experienced some confusion as a possible consequence of her thrombocytopenia, but no long-term sequelae followed.

Conclusions

Due to widespread use of phenytoin, clinicians must recognize the potential for the rare but serious adverse effect of thrombocytopenia, particularly in the neurosurgical population. Confusion, as observed in our patient, makes postoperative evaluation of central nervous system and cognitive function difficult, and can obscure the clinical presentation. At its worst extreme, disruption of platelet function may produce cerebral hemorrhage, which results in long-term functional deficits.
Digoxin–Itraconazole Interaction: Possible Mechanisms
Authors: Alderman Christopher P , Allcroft Peter D
Published: May 2017

Objective

To document a case in which the administration of itraconazole was associated with an apparent decrease in digoxin clearance, resulting in an increase in the serum digoxin concentration.

Case Summary

A man receiving digoxin for atrial fibrillation was concurrently treated with itraconazole 200 mg/d for esophageal candidiasis. The estimated urinary digoxin clearance was decreased during this combination therapy.

Discussion

Digoxin is primarily cleared by the kidneys, and the mechanism of renal clearance involves both glomerular filtration and tubular secretion. We postulate that itraconazole or a metabolite of this compound may have resulted in decreased tubular secretion of digoxin, accounting for decreased urinary digoxin clearance.

Conclusions

Monitoring of serum digoxin concentrations should be performed if patients taking digoxin are treated with itraconazole. Further investigation is necessary to elucidate the nature of the interaction between digoxin and itraconazole.
Pralidoxime Continuous Infusion in the Treatment of Organophosphate Poisoning
Authors: Tush Gretchen M , Anstead Michael I
Published: May 2017

Objective

To report a case of organophosphate poisoning treated with a continuous infusion of pralidoxime chloride.

Case Summary

A 27-year-old white man presented with extreme agitation, muscle weakness and fasciculations, and respiratory failure after ingesting an organophosphate pesticide (Dursban, active ingredients chlorpyrifos and xylene) as a suicide attempt. Atropine sulfate and pralidoxime chloride were administered intermittently, ut the patient continued to be extremely agitated and have muscle fasciculations. Subsequently, a continuous intravenous infusion of pralidoxime (8 mg/mL concentration) at 500 mg/h was initiated to help control breakthrough nicotinic symptoms. Therapy with atropine and pralidoxime was continued for approximately 72 hours. Therapy was discontinued due to the predominance of anticholinergic symptoms and the patient's increased awareness.

Discussion

Severe organophosphate poisoning with nicotinic and/or central manifestations should be treated with pralidoxime in addition to atropine. The rationale supporting the use of pralidoxime as a continuous infusion in this case includes: (1) slow absorption of organophosphate compounds following exposure to large quantities, (2) unknown quantity ingested, (3) delayed nicotinic effects from distribution of lipid-soluble organophosphate and metabolic activation of phosphorothioates such as chlorpyrifos, and (4) intensive care monitoring. There is limited documentation in the literature of continuous infusions of pralidoxime used to treat organophosphate poisoning and the stability of the admixture is unknown.

Conclusions

A continuous pralidoxime infusion successfully managed the prolonged nicotinic symptoms seen after ingestion of an organophosphate. A continuous infusion of pralidoxime may be particularly useful in cases of organophosphate poisoning when the extent of chemical exposure or quantity of chemical ingested is unknown but potentially toxic and the therapy must be symptomatically managed.
Benign Prostatic Hyperplasia: Diagnosis and Treatment Guideline
Authors: Lee Mary , Sharifi Roohollah
Published: May 2017

Objective

To critique the US Department of Health and Human Services Public Health Service, Agency for Health Care Policy and Research, Clinical Practice Guideline on Benign Prostatic Hyperplasia: Diagnosis and Treatment; and to provide an update on management and treatment of benign prostatic hyperplasia (BPH) since the Guideline was published.

Data Sources

A review of the published medical literature in MEDLINE from 1994 to April 1996, limited in focus to drug treatment of BPH, English language, and human subjects, was performed.

Study Selection

Controlled clinical studies of drug treatment for symptomatic BPH that used objective parameters (e.g., urinary flow rate, prostatic volume, voiding symptom scores) were evaluated. A single reviewer assessed each study.

Data Extraction

Study methods, inclusion and exclusion criteria, and treatment outcomes were assessed for all studies. Independent extraction was performed by a single observer.

Data Synthesis

Management of BPH is directed at ameliorating voiding symptoms. For moderate or severe BPH, medical or surgical therapy should be offered to the majority of patients. Medical therapy options include α-adrenergic antagonists and finasteride. The former offer the advantage of a more prompt onset of action (within weeks) when compared with finasteride. Finasteride produces a lower response rate and smaller improvement in voiding symptoms. Combination therapy of terazosin and finasteride has not been proven to be more effective than terazosin monotherapy.

Conclusions

When medical therapy is indicated for moderate or severe BPH, α-adrenergic antagonists exhibit a faster onset of action and produce greater improvement of voiding symptoms than does finasteride.
Toleration of Intravenous Azithromycin
Authors: Luke David R , Foulds George
Published: May 2017

Objective

To study the toleration of various infusate concentrations of single intravenous doses of azithromycin.

Design

Randomized, double-blind, two-treatment, two-period, crossover.

Setting

Clinical pharmacology unit.

Participants

Twenty-four healthy men aged 19–41 years.

Study Design

All subjects were initially randomized to receive single 1-hour intravenous infusions of azithromycin 1 g at infusate concentrations of 1, 2, or 5 mg/mL (n = 6 each) compared with placebo (n = 6). Subjects who were randomized to receive 1 mg/mL concentrations were subsequently administered 5 mg/mL concentrations at least 2 weeks later, those given 2 mg/mL were crossed over to 4 mg/mL, and those in the 5-mg/mL group were crossed over to 1 mg/mL concentrations.

Main outcome Measures

Subjects recorded intravenous infusion toleration using visual analog scales ranging from 0 (no signs or symptoms) to 10 (poor toleration) for erythema, pain, swelling, and tenderness. Vascular Doppler recordings were obtained during and after infusion cephalad to the infusion site.

Results

Infusion site reactions increased in incidence and severity with infusion concentrations of 4 and 5 mg/mL; the most frequent reactions were tenderness and erythema. There were no apparent trends in Doppler readings.

Conclusions

Single doses of azithromycin 1 g at infusate concentrations up to 2 mg/mL were well tolerated when administered over 1 hour to healthy men.
Impact of a Vancomycin Restriction Policy on Use and Cost of Vancomycin and Incidence of Vancomycin-Resistant Enterococcus
Authors: Morgan Amy S , Brennan Patrick J , Fishman Neil O
Published: May 2017

Objective

To review the appropriateness of vancomycin therapy, changes in vancomycin use, and the incidence of vancomycin-resistant Enterococcus (VRE) after implementation of a limited restriction policy requiring approval from the Infectious Diseases Approval service to continue vancomycin therapy beyond 72 hours.

Design

A prospective chart review was conducted in April 1995. Pharmacy billing data and infection control data were compared before and after policy implementation.

Setting

A 725-bed university teaching institution.

Patients

All patients receiving vancomycin during April 1995.

Main outcome Measures

Appropriateness of use was based on the Centers for Disease Control and Prevention (CDC) recommendations for prudent vancomycin use.

Results

A total of 333 courses of vancomycin therapy were reviewed. Vancomycin use was appropriate in 219 (66%) courses. Of the 114 courses that did not meet the CDC guidelines, 76 (67%) were for empiric use, 35 (31%) were for prophylactic use, and 3 (3%) were for therapeutic use. Overall, the total number of grams used decreased 9%, grams per 1000 patient-days decreased by 10, and the total number of patients exposed to vancomycin decreased 0.5%. Several services had large decreases in vancomycin use. Vancomycin expenditures decreased by $15 788 for the 7-month time period. The incidence of VRE remained unchanged, at 30% of all enterococcal isolates 2 years after policy implementation.

Conclusions

The limited restriction policy was effective in decreasing the total grams of vancomycin used. However, one-third of vancomycin therapy was inappropriate and the incidence of VRE was unchanged. A more stringent restriction policy could potentially increase appropriate use, further decrease the amount of vancomycin used, and decrease the incidence of VRE.
Evaluation of a Sparse Sampling Strategy for Determining Vancomycin Pharmacokinetics in Preterm Neonates: Application of Optimal Sampling Theory
Authors: Burstein Aaron H , Gal Peter , Forrest Alan
Published: May 2017

Objective

To use optimal sampling theory to determine the fewest vancomycin concentrations required and the appropriate sampling times to calculate vancomycin pharmacokinetic parameters in neonates.

Design

Unblinded evaluation in neonates with presumed sepsis.

Setting

Level 3 community-based neonatal intensive care unit.

Patients

Eleven neonates with presumed sepsis.

Interventions

Twelve courses of intravenous vancomycin 20 mg/kg were administered. Blood samples were collected 3 and 9 hours after initiation of a 1-hour infusion of the first dose.

Measurements and Main Results

A two-compartment model was fit to vancomycin concentrations using iterative two-stage analysis. Pharmacokinetic parameter estimates were used for determination of optimal sampling times for two-, three-, and four-sample strategies with subsequent generation of two-, three-, and four-sample concentration data for 100 cases. Relative performance of strategies was compared through calculation and comparison of D efficiency for the determined strategies. Bias (median percent error) and precision (median percent absolute error) of pharmacokinetic parameter estimates for each strategy in the 100 simulated cases were determined.

Conclusions

For estimation of total clearance and volume in the central and peripheral compartments, all strategies performed similarly with no difference in efficiency or bias and precision of estimates. Our results suggest that for clinical evaluations two appropriately timed samples (0.5 h after a 1-h infusion, trough concentration) are adequate for estimation of vancomycin clearance in neonates.
Ursodeoxycholic Acid Improves Cholestasis in Infants with Cystic Fibrosis
Authors: Scher Herschel , Bishop Warren P , Mccray Paul B
Published: May 2017

Objective

To describe two infants with cholestatic jaundice treated with ursodeoxycholic acid (UDCA).

Case Summary

Two infants with cystic fibrosis (CF)-associated hepatobiliary disease, manifesting as cholestatic jaundice and elevated liver enzymes within the first 6 weeks of life, had improved biochemical indices of liver function following treatment with UDCA 20–40 mg/kg/d.

Discussion

To our knowledge, this is the first report of UDCA treatment in infants with CF-associated cholestatic jaundice. Infants and children require treatment with increased doses of UDCA to compensate for reduced intestinal absorption of bile acid and immaturity of the enterohepatic circulation.

Conclusions

UDCA appears to be a cost-effective treatment for CF-associated hepatobiliary disease in infants and children.
Zafirlukast: The First Leukotreene-Receptor Antagonist Approved for the Treatment of Asthma
Authors: Kelloway Judy Shepard
Published: May 2017

Objective

To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of zafirlukast. Therapeutic issues regarding the use of a leukotriene-receptor antagonist as prophylactic antiinflammatory therapy for asthma are also discussed.

Data Sources

A MEDLINE search was conducted to identify pertinent literature, including preclinical trials, clinical trials, and reviews. Pharmacokinetic and dosing information were abstracted from the product labeling.

Study Selection

All available published articles describing double-blind, placebo-controlled trials of both oral and aerosol zafirlukast in patients with asthma or rhinitis were reviewed. These included single-dose studies with zafirlukast against exercise, allergen, leukotriene D4 (LTD4), and platelet-activating factor (PAF) challenges, and 6- and 13-week trials in patients with asthma. Studies describing clinical trials with long-term use or comparisons with other asthma medications as reported in abstracts are also included.

Data Extraction

Information on the safety and efficacy of zafirlukast from single- and multiple-dose studies was evaluated on the basis of statistical significance relative to placebo treatment.

Data Synthesis

Zafirlukast, a potent and selective antagonist of the cysteinyl leukotriene receptor, blocks leukotriene-mediated pathologic events in both experimental animal and clinical disease models. Zafirlukast antagonizes LTD4-, PAF-, and exercise-induced bronchoconstriction, and blocks both early- and late-phase responses following allergen provocation in patients with atopic asthma. Greater efficacy is noted following oral administration than with aerosol dosing, presumably because of the enhanced delivery of drug when ingested rather than inhaled.

Conclusions

Zafirlukast is the first orally active leukotriene-receptor antagonist approved by the Food and Drug Administration for the prophylactic and chronic treatment of asthma. Since the leukotrienes play an important role in the underlying inflammatory processes of asthma, zafirlukast represents a new antiinflammatory option available in an oral dosage form. It is clear that this agent has therapeutic activity in patients with asthma, but its effectiveness relative to other antiasthma medications still needs confirmation. Data from clinical studies support the use of zafirlukast as first-line therapy in patients with mild-to-moderate asthma. Further research is needed to establish its role as an add-on agent for patients with severe asthma, aspirin-sensitive asthma, and both allergies and asthma. In addition to having a favorable safety and efficacy profile, zafirlukast has the advantage of being an oral agent with twice-daily dosing; these attributes offer the potential for greater patient adherence to pharmacotherapy and, thereby, improved control of asthma symptoms.
Hepatitis B Vaccine: Current Issues
Authors: Zannolli Raffaella , Morgese Guido
Published: May 2017

Objective

To review two main issues concerning the hepatitis B vaccine: (1) the management of unresponsive subjects and (2) the need for routine booster doses.

Data Sources

Pertinent literature identified via MEDLINE (1980–1996) search as well as references cited in published articles.

Data Synthesis

The optimal procedure for management of subjects unresponsive to hepatitis B vaccine has not been well established. Most unresponsive subjects are not absolute nonresponders, since most of them can develop protective concentrations of antibodies to hepatitis B surface antigen (anti-HBsAg) after hepatitis B revaccination, consisting of a fourth or a fifth dose or a new complete course of immunization. In subjects who do not respond to the hepatitis B vaccine after four or more injections, the benefits of the combination of cytokines (e.g., interferon-alfa, interleukin-2 [aldesleukin]) and vaccine have not been clearly shown. There are two main opinions regarding the need for routine booster doses. Experts from the US, claiming long-term protection from immunologic memory, suggest delaying booster doses for at least a decade after vaccination in subjects with normal immune status. Furthermore, postvaccination antibody testing should be restricted only to high-risk subjects. Once a vaccinated subject has responded satisfactorily, further antibody tests are unnecessary. Only hemodialysis patients should be tested annually for adequate antibody concentrations and the booster dose administered when concentrations decline to less than 10 IU/L. Experts from Europe suggest that vaccine-induced antibody responses should be assessed in all subjects and booster doses administered at intervals, with the theory being that protection correlates with the presence of antibody. However, indications about appropriate timing for booster doses and target titers of anti-HBsAg remain controversial.

Conclusions

It is possible to obtain seroconversion in nonresponders by using variations in vaccination strategies (i.e., >3 doses, double amounts of HBsAg). Adjuvants such as interferon-alfa or aldesleukin are of limited use. The opinions of American experts regarding routine booster doses, as expressed by the statement of the Immunization Practices Advisory Committee, seem to be well defined and helpful to clinicians trying to resolve controversies for individual patients. The opinions of the European experts are not unanimous and are sometimes impractical. A consensus conference is needed.
Digoxin–Macrolide Drug Interaction
Authors: Bizjak Eric D , Mauro Vincent F
Published: May 2017

Macrolide antibiotics appear to be able to enhance the oral bioavailability of digoxin by altering the gastrointestinal flora that metabolize digoxin to less active dihydro metabolites, thus leading to increased serum digoxin concentrations and possible digoxin toxicity in select patients stabilized on digoxin therapy. This interaction may be of clinical importance in up to 10% of the population. Currently, the orally administered erythromycin, clarithromycin, and roxithromycin have been implicated. Although realistically this interaction may be encountered rarely, when it does occur, it can be of clinical significance.

Addendum

Following acceptance of this manuscript, two additional reports of a digoxin–clarithromycin drug interaction have been published. Nawarskas et al.28 described clarithromycin-induced digoxin toxicity (digoxin-induced ST segment changes, non-sustained ventricular tachycardia, and a digoxin concentration of 4.4 ng/mL) due to 3 days of clarithromycin 500 mg bid in a 78-year-old woman stabilized on oral digoxin 0.25 mg/d. Laberge and Martineau29 observed a clinical presentation suggestive of digoxin toxicity and an elevated digoxin concentration of 3.9 ng/mL in a 78-year-old man stabilized on digoxin 0.25 mg/d who had received 4 days of clarithromycin 250 mg bid.
Combination Antiviral Therapy for Cytomegalovirus Disease in Patients with AIDS
Authors: Cline Julie J , Garrett Anna D
Published: May 2017

Currently, combination therapy with ganciclovir and foscarnet should be reserved for patients with disease progression while receiving monotherapy or for those who are unresponsive to either agent alone. Although cidofovir and ganciclovir were shown to have synergistic activity against human CMV in vitro, there have been no in vivo studies to confirm this activity. Therefore, if a combination regimen is necessary to control CMV in a patient, foscarnet and ganciclovir should be used first.

There are several advantages of the combination therapy regimen. For instance, lower doses of the individual agents can be used with superior efficacy to monotherapy and similar toxicities.5,10 Also, for neurologic CMV involvement, the combination therapy may be superior to monotherapy because of the variable CSF penetration of either drug alone. In addition, combined therapy may be beneficial in treating and/or preventing drug-resistant strains of CMV.13

Even though combination therapy has evidence of superior efficacy compared with monotherapy in the treatment of CMV, several issues must be considered. First, combination therapy has longer administration times because of the infusion of multiple drugs, which may be an inconvenience. Also, even though the toxic effects are similar with both combined therapy and monotherapy, the adverse effects associated with combination therapy may be less well tolerated and may negatively affect the patient's quality of life. Finally, combination therapy is more expensive than monotherapy with ganciclovir or foscarnet alone.10 Patients should be evaluated with these issues in mind before combination therapy is initiated.
Compensation, Opportunity, and Information: A Comparative Analysis of Legislative Nonresponse in the American States
Authors: Fortunato David , Provins Tessa
Published: May 2017

We present a parsimonious framework for understanding contextual variation in legislative nonresponse. We argue that legislators’ propensity to vote is a function of their willingness and ability to be physically present in the chamber and determine the best position to take on a given proposal. From this framework, we derive four hypotheses regarding the compensation legislators receive, their opportunity to pursue work outside of the chamber, and their informational resources. Analyzing data on over seven million voting opportunities across two sessions in ninety-nine chambers, we find robust evidence that longer legislative sessions decrease nonresponse and that informational resources increase nonresponse, but no evidence that compensation influences nonresponse.
Anaplastic Ependymoma With Ganglionic Differentiation: Report of a Rare Case and Implications in Diagnosis
Authors: Rao Shilpa , Ravindra Niveditha , Sadashiva Nishanth , Indira Devi Bhagavatula , Santosh Vani
Published: May 2017

Ependymomas are glial neoplasms with rare cases exhibiting neuronal differentiation. We describe a case of spinal anaplastic ependymoma with ganglionic differentiation in a 28-year-old woman. The ganglionic component was labeled by synaptophysin, whereas the rest of the tumor showed features of an anaplastic ependymoma. Stem cell marker MELK was noted to stain both the neoplastic ependymal and ganglionic components, possibly suggesting a stem cell/progenitor origin for the tumor with subsequent divergent differentiation.
Synthesis and Optical Properties of Pentamethine Cyanine Dyes With Carboxylic Acid Moieties
Authors: Dost Tyler L , Gressel Michael T , Henary Maged
Published: May 2017

Cyanine dyes possessing carboxylic acid groups have been used in many different fields of study. The acid groups can act as handles for bioconjugation or as metal chelators. Several pentamethine cyanine dyes with propionic acid handles were synthesized and their optical properties were studied to determine their usefulness as fluorescent probes. The optical properties studies performed include the absorbance and emission maxima values as well as the calculation of quantum yield and molecular brightness levels. Molecular models were also calculated to help analyze the dyes’ behavior and were compared with similar dyes with varying alkyl chain lengths replacing the acid moieties.