bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Impact of Standardized Orders for Antimicrobial Prophylaxis Program
Authors: Frighetto Luciana , Marra Carlo A , Stiver H Grant , Bryce Elizabeth A , Jewesson Peter J
Published: June 2003

OBJECTIVE:

To assess the effect and economic impact of an intervention aimed at standardizing the timing of preoperative antimicrobial prophylaxis from the perspective of a major teaching hospital.

DESIGN:

A pre/post study design in which a random sample of 60 procedures from a 12-month period in the preintervention phase were reviewed. A comparative sample of 60 procedures during a seven-month postintervention phase was selected. For each prophylactic course, preoperative dose administration details were classified as early (>2 h prior to incision), on time (0–2 h prior), delayed (0–3 h after), or late (>3 after). To determine the economic impact of this intervention, we used a predictive decision analytic model using institutional costs and the published probabilities of inpatient surgical wound infections (SWIs) following administration of antimicrobials timed according to the above criteria. Two conditions were analyzed: (1) an interdisciplinary two-stage therapeutic interchange program involving staff education and modification of preoperative antimicrobial orders to ensure timely administration and (2) no intervention.

SETTING:

An 1100-bed tertiary care, university-affiliated institution.

PATIENTS:

120 randomly selected procedures involving inpatients who received a preoperative antibiotic.

OUTCOME MEASURES:

Differences in preoperative antimicrobial timing and cost avoidance associated with the intervention.

RESULTS:

In the preintervention phase, 68% of prophylactic courses were on time, 22% were early, and the balance were delayed or late. The incidence of on-time prophylaxis increased to 97% during the postintervention phase (p = 0.001). Operating room staff involvement in antimicrobial administration increased from 57% to 92% (p = 0.001). Based on a setup and annual intervention cost of $9100 CAN ($1 CAN = $0.68 US), an annual inpatient SWI avoidance of 51 cases, an average infection-associated extended hospital stay of four days, and an average treatment cost of $1957 CAN per inpatient SWI, we estimated that 153 hospital days were avoided and there was an annual cost avoidance of $90707 CAN ($1779 CAN saved per inpatient infection avoided) due to this intervention. Using sensitivity analyses, no plausible changes in the base case estimates altered the results of the economic model.

CONCLUSIONS:

An interdisciplinary approach to optimizing the timing of preoperative antimicrobial doses can impact positively on practice patterns and result in substantial cost avoidance. Costs incurred to implement such an intervention are small when compared with the annual cost avoidance to the institution.
Management of Complications of Bacillus Calmette–Guérin Immunotherapy in the Treatment of Bladder Cancer
Authors: Huang Tammy C
Published: June 2003

OBJECTIVE:

To evaluate the management strategies available for the complications associated with bacillus Calmette–Guérin (BCG) immunotherapy in the treatment of bladder cancer.

DATA SOURCES:

Clinical literature accessed through MEDLINE (January 1983–January 1999). Key search terms included bacillus Calmette-Guérin, BCG, and bladder cancer.

DATA SYNTHESIS:

BCG vaccine is a live-attenuated strain of Mycobacterium bovis; therefore, the risk for complications exists. An evaluation of treatment regimens was conducted, and the management strategies are presented.

CONCLUSIONS:

The complications associated with BCG immunotherapy range from local reactions to potentially fatal systemic reactions requiring long-term therapy. Therefore, healthcare practitioners need to be aware of the current treatment regimens available.
Indirect Modulation of Dopamine D2 Receptors as Potential Pharmacotherapy for Schizophrenia: II. Glutamate (Ant)Agonists
Authors: Carfagno Michelle L , Hoskins Lauren A , Pinto Marie E , Yeh Joanne C , Raffa Robert B
Published: June 2003

OBJECTIVE:

To summarize the published preclinical and clinical data that suggest the possible use of glutamate receptor agonists or antagonists as novel antipsychotic agents.

DATA SOURCES:

Primary and review articles were identified by MEDLINE search (from 1966 to December 1999) and through secondary sources.

STUDY SELECTION AND DATA EXTRACTION:

All of the articles identified from the data sources were evaluated and all information deemed relevant was included.

DATA SYNTHESIS:

The standard antipsychotic drugs, whose clinical activity correlates with affinity for dopamine D2 receptors, alleviate some of the positive symptoms of schizophrenia, but have limited impact on negative symptoms. Several lines of evidence implicate glutamate-receptor system dysfunction(s) in schizophrenia, either as causative or contributory factors. In addition, several standard antipsychotic drugs modulate glutamate or glutamate receptor activity, suggesting an alternative view of their mechanism of antipsychotic action. Preliminary studies have shown that drugs which modulate glutamate brain concentrations have positive effects in animal models of schizophrenia.

CONCLUSIONS:

A role for glutamate in the pathogenesis or pharmacotherapy of schizophrenia is suggested from anatomic (interactions between glutamatergic and dopaminergic systems in relevant brain regions), physiologic (implication of glutamate-receptor dysfunction), and pharmacologic (modulation of glutamate or glutamate receptors) evidence. Therefore, compounds that function at glutamate receptors might represent a novel approach to the treatment of the disease or to the amelioration of symptoms, either as monotherapy or as an adjunct to dopamine D2 receptor antagonists.
Elevated Free Fractions of Valproic Acid in a Heart Transplant Patient with Hypoalbuminemia
Authors: Haroldson Jeffrey A , Kramer Linda E , Wolff Denise L , Lake Kathleen D
Published: June 2003

OBJECTIVE:

To report a case demonstrating the importance of monitoring unbound valproic acid (VPA) serum concentrations in a patient with hypoalbuminemia.

CASE SUMMARY:

A 53-year-old white woman status–post heart transplantation was admitted to the hospital for declining cardiac function, possible rejection, and increased lethargy requiring intubation. An extensive workup of the patient's profound lethargy was initiated, including an evaluation of her VPA regimen. Initially, VPA dosages were adjusted based on the total serum concentration of VPA. Hypoalbuminemia compounded with increased lethargy prompted the measurement of unbound serum concentrations of VPA. The VPA dosage was then adjusted based on the unbound rather than the total VPA serum concentration; the patient eventually improved and was discharged from the hospital.

DISCUSSION:

Lethargy is a concentration-related adverse effect of VPA. The nonlinear pharmacokinetic and protein saturation characteristics of VPA may result in nonproportional elevations in unbound drug, and subsequent increases in adverse effects, when dosage adjustments are based solely on measurement of total VPA serum concentrations in patients with hypoalbuminemia.

CONCLUSIONS:

This case report suggests that appropriate monitoring of unbound drug concentrations of VPA may prevent unrecognized concentration-related adverse effects. Awareness of the pharmacokinetic relationship and adverse effects of VPA will aid clinicians in identifying the etiology of symptoms.
Levodopa Therapy and the Risk of Malignant Melanoma
Authors: Siple Jolene F , Schneider Diana C , Wanlass Wendy A , Rosenblatt Burton K
Published: June 2003

OBJECTIVE:

To evaluate the use of levodopa therapy in patients with Parkinson's disease and malignant melanoma.

DATA SOURCES:

A MEDLINE search (January 1966–September 1999) of English-language articles was conducted. Key search terms included levodopa, melanoma, and Parkinson's disease; 34 case reports were identified.

DATA SYNTHESIS:

Carbidopa/levodopa continues to be a mainstay in the treatment of Parkinson's disease. Since the late 1970s, a warning has appeared in the prescribing literature for levodopa regarding the risk of activating malignant melanoma. An evaluation was conducted of the case reports in which a causal relationship between levodopa and melanoma was suggested.

CONCLUSIONS:

There is an unlikely association between levodopa and induction or exacerbation of malignant melanoma.
Reversible Granulocytopenia in Association with Riluzole Therapy
Authors: North Will A , Khan Amir M , Yamase Harold T , Sporn Jonathan R
Published: June 2003

OBJECTIVE:

To report a case of severe neutropenia developing in association with riluzole 200 mg/d.

CASE SUMMARY:

A 63-year-old woman with amyotrophic lateral sclerosis (ALS) presented with nausea, anorexia, and fever two weeks following inadvertent dose escalation of riluzole from 100 to 200 mg/d. Granulocytopenia was diagnosed and evaluation for a possible causative infectious process was negative; riluzole was considered a possible offender. Blood counts returned to normal with discontinuation of riluzole and administration of filgramstim.

DISCUSSION:

Riluzole is a glutamate release inhibitor used in the treatment of ALS, a devastating, progressive neurodegenerative disorder affecting motor neurons. A variety of adverse effects have been described with riluzole therapy, most commonly dizziness and gastrointestinal disorders. In this patient, multiple investigations failed to reveal an infectious cause or other drug-induced cause for the granulocytopenia.

CONCLUSIONS:

Granulocytopenia has been reported as an adverse effect of riluzole but is not a complication well known to clinicians, and there are no detailed reports published in the literature. In this patient, several lines of evidence raise the possibility of a causal relationship between riluzole and granulocytopenia.
The Role of the Pharmacist in Humanitarian Aid in Bosnia-Herzegovina: The Experience of Pharmaciens Sans Frontières
Authors: Bussières Jean-François , St-Arnaud Chantal , Schunck Christine , Lamarre Diane , Jouberton François
Published: June 2003

BACKGROUND:

Founded in 1985, Pharmaciens Sans Frontières (PSF) is a nongovernmental organization of pharmacists involved in humanitarian aid. PSF relied on approximately 100 expatriates in 1998, which included 50 pharmacists distributed throughout 24 missions (i.e., 14 emergency, 7 development, 3 assessment). It is necessary to add 200–250 local staff to this group.

OBJECTIVE:

To describe PSF's mission in Bosnia-Herzegovina from 1992 to 1999 and to define the pharmacist's impact in the supply of medicines and the development of pharmaceutical care and services.

RESULTS:

In April 1992, at the beginning of Sarajevo's siege, PSF sent a small team of three volunteer pharmacists to Bosnia-Herzegovina. The objective of the emergency phase (1992–1995) was to set up a massive supply program of essential medicines and medical and biologic materials and to implement a distribution system based on existing health centers. The signing of the Dayton peace agreement and a progressive return to peace and stability marked the beginning of the postemergency phase (1995–1997). This phase pursued previous objectives of establishing a distribution network and added the implementation of logistic centers. PSF widened its involvement to medical laboratory analysis, production of medicines, disposal of expired medications sent during the conflict, and the implementation of a national center for quality control. Currently, the development phase's (1998–1999) objective is to provide adequate support for the reorganization of pharmaceutical care and services by establishing pharmacy work groups and developing and maintaining good relationships with the international community and Bosnia-Herzegovina pharmacists.

CONCLUSIONS:

Humanitarian aid is essential in major conflicts, as seen in the case of Bosnia-Herzegovina. Although it is difficult to evaluate the impact of the distribution network implemented by PSF, it allowed for a better provisioning of medications to the general population. PSF played an important role in such cases. In fact, PSF provides its pharmaceutical expertise to these embattled areas not only by offering financial support to the logistics or supplying of medications, but by offering professional support to the organization/reorganization of the pharmaceutical practice.
Malignant Primary Hypertension in Pregnancy Treated with Lisinopril
Authors: Tomlinson Antony J , Campbell James , Walker James J , Morgan Colin
Published: June 2003

OBJECTIVE:

To report a case of a patient treated with an angiotensin-converting enzyme (ACE) inhibitor with a good neonatal outcome.

CASE REPORT:

A 39-year-old African-Caribbean patient who had chronic hypertension presented at 18 weeks' gestation with acute hypertension. She was being treated for chronic hypertension with lisinopril, but had self-discontinued treatment. Attempts to control her hypertension with labetolol, nifedipine, and methyldopa were ineffective. She was therefore offered termination of pregnancy so treatment with lisinopril could be restarted. The patient elected to continue with the pregnancy in spite of the fetal risks associated with the use of an ACE inhibitor. She was delivered of a girl at 26 weeks' gestation. The baby initially had renal failure and also developed acute necrotizing enterocolitis. The renal failure improved simultaneously with the latter complication, and it is postulated that there was enteric excretion of lisinopril. The baby was discharged home on day 102 with no further complications.

DISCUSSION:

ACE inhibitors are acceptable medications to use in the first trimester of pregnancy; however, fetal malformations and neonatal complications have been associated with their use later in pregnancy, and they have a perinatal mortality rate of 97/1000. Lisinopril is excreted in urine and feces unchanged, and its half-life is prolonged in anuric neonates. Peritoneal dialysis eliminates lisinopril; however, this neonate improved after treatment for necrotizing enterocolitis and simultaneous improvement in bowel function.

CONCLUSIONS:

ACE inhibitors should not be used in pregnancy beyond the end of the first trimester. In exceptional cases, they may be indicated for the control of severe hypertension when the patient is refractory to other medications. The patient should be fully counseled about the adverse effect profile and neonatal outcome. This case report documents a successful outcome for mother and baby in these circumstances.
Oral Glutamine for the Prevention of Oral Mucositis Associated with High-Dose Paclitaxel and Melphalan for Autologous Bone Marrow Transplantation
Authors: Cockerham Michael B , Weinberger B Barry , Lerchie Susan B
Published: June 2003

OBJECTIVE:

To determine the effect of glutamine suspension on mucositis associated with the administration of high-dose preparative regimens for bone marrow transplantation.

METHODS:

We performed a retrospective analysis of 21 consecutive patients receiving high-dose paclitaxel and melphalan as the preparative regimen for autologous peripheral blood stem-cell transplantation for metastatic breast cancer between January 1997 and December 1997. Glutamine suspension was given as swish-and-swallow administration every four hours around the clock starting day −7, for a total dose of 24 g/d.

RESULTS:

The group given oral glutamine suspension demonstrated significantly fewer days of mucositis and a lower maximum grade of mucositis. The treatment group also had fewer days of parenteral morphine for pain relief. The group that did not receive glutamine required an average of 5.22 days of patient-controlled analgesia (PCA) morphine; the glutamine group did not require PCA morphine. The total days of narcotic pain relief were decreased in the glutamine group; however, this did not reach statistical significance. Qualitatively, the patients in the glutamine group had less oral ulceration and bleeding, and were able to tolerate liquids sooner than those in the nonglutamine group. Patients tolerated the glutamine suspension well.

CONCLUSIONS:

This study showed that around-the-clock administration of oral glutamine may decrease both the severity and duration of mucositis associated with high-dose bone marrow transplant preparative regimens. The decrease in severity and duration of mucositis translated into reduced parenteral narcotic use. A prospective, randomized, controlled trial is needed to determine future applications of glutamine in the support of patients undergoing high-dose chemotherapy.
Factors Associated with Successful Epoetin Alfa Therapy in Premature Infants
Authors: Reiter Pamela D , Rosenberg Adam A , Valuck Robert J
Published: June 2003

OBJECTIVE:

To determine the impact of two different recombinant human erythropoietin (epoetin alfa) dosing strategies on the number of red blood cell (RBC) transfusions, and explore relationships between specific patient and drug regimen variables with epoetin alfa therapy outcomes.

DESIGN:

Retrospective cohort study.

SETTING:

Level III university neonatal intensive care unit.

METHODS:

Infants who received epoetin alfa therapy three times weekly for more than one week were categorized into two epoetin alfa dosing strategy groups: group A (300–749 units/kg/wk) and group B (750–1200 units/kg/wk). The following patient variables were collected and their relationship to therapy outcomes (corrected reticulocyte count [%], hematocrit [%], and number of RBC transfusions after therapy was started) were evaluated using independent Student's t-test, correlation analysis, and stepwise linear regression: birth weight (kg), gestational age (weeks), postnatal age at therapy onset (days), duration of mechanical ventilation (days), number of RBC transfusions before epoetin alfa therapy, phlebotomy loss (mL/kg), epoetin alfa dosage (units/kg/dose), iron dosage (mg/kg/d), duration of therapy (days), and postconceptional age at therapy discontinuation (weeks).

RESULTS:

The charts of 44 patients were reviewed. No significant impact on outcome was attributed to overall dosing strategy (group A vs. group B). Linear regression identified postnatal age at therapy onset as a significant contributor to mean hematocrit (R2 = 0.116; p = 0.023) and postconceptional age at therapy discontinuation as a significant contributor to number of transfusions during and after epoetin alfa use (R2 = 0.118; p = 0.022). A significant positive correlation was found between weekly mean epoetin alfa dosage and mean reticulocyte count (r = 0.326; p = 0.046), mean iron dosage and mean reticulocyte count (r = 0.439; p = 0.006), and ventilator days and total number of transfusions (r = 0.606; p < 0.001). A significant negative correlation was found between number of transfusions and reticulocyte count (r = −0.367; p = 0.023).

CONCLUSIONS:

Epoetin alfa dosing strategy, as defined in our study, did not significantly affect the number of transfusions. However, postnatal age at therapy initiation, postconceptional age at therapy discontinuation, mean epoetin alfa dosage, and iron dosage correlate with specific outcomes of epoetin alfa therapy in premature infants.
Doxepin Toxicity in a Child following Topical Administration
Authors: Zell-Kanter Michele , Toerne Theodore S , Spiegel Katharina , Negrusz Adam
Published: June 2003

OBJECTIVE:

To describe a case of a child with altered mental status following the topical administration of doxepin.

CASE SUMMARY:

A five-year-old Hispanic girl was brought to the emergency department because she was difficult to arouse at school. She had recently developed a generalized eczematous rash for which she was prescribed doxepin hydrochloride 5% cream. An entire tube (30 g) of doxepin cream was applied in the 24 hours prior to presentation. The patient was responsive only to noxious stimuli, with no focal neurologic abnormalities. She was decontaminated and observed in a pediatric intensive care unit. By 18 hours after presentation, she had fully recovered and was discharged.

CONCLUSIONS:

Topical doxepin, available as a 5% cream, is indicated for the treatment of pruritus secondary to eczematous dermatoses in adults. Diminished skin integrity and the application of a massive quantity of doxepin 5% cream to a large body surface area contributed to the toxicity in this child. Since the safety and efficacy of doxepin cream has not been established in children younger than 12 years, it should be used with caution in this population.
Pharmacotherapy of Type 2 Diabetes Mellitus
Authors: Rendell Marc S , Kirchain William R
Published: June 2003

OBJECTIVE:

To review the drug treatments and some of the popular, nontraditional remedies now available for type 2 diabetes mellitus, as well as selected investigational agents; to describe each medication's place in the overall approach to treatment.

DATA SOURCES:

English-language journals, abstracts, review articles, and newspaper accounts.

DATA SYNTHESIS:

In the past five years, there has been tremendous progress in the pharmacotherapy of diabetes, particularly type 2 diabetes. Several new agents have entered the clinical arena, and many more are in the late stages of investigation leading to approval. Sulfonylureas stimulate the production and release of insulin; these drugs must be used in patients with an intact pancreas. The meglitinides are nonsulfonylurea agents that are also insulin secretagogues. Unlike the sulfonylureas, repaglinide appears to require the presence of glucose to close the adenosine triphosphate–sensitive potassium channels and induce calcium influx. Metformin reduces hepatic glucose production in some patients and increases peripheral glucose utilization, but its use is hampered by a high percentage of adverse reactions. Disaccharidase inhibitors effectively compensate for the defective early-phase insulin release by slowing the production of sugars from carbohydrates. Thiazolidinediones appear to activate peroxisome proliferator–activated receptor gamma, which is involved in the metabolism of lipids. Short-acting insulin and the role of weight-loss agents are also discussed.

CONCLUSIONS:

The availability of new options for diabetes therapy provides a chance for successful therapy in a larger number of patients. However, it is important to consider how much true benefit these new forms of treatment will have on the diabetic community. The best choice for a patient remains controversial.
Impact of the Dial Access Drug Information Service on Patient Outcome
Authors: Melnyk Paul S , Shevchuk Yvonne M , Remillard Alfred J
Published: June 2003

OBJECTIVE:

To determine the impact of a drug information service on patient outcomes.

DESIGN:

Prospective evaluation of patient-specific drug information requests.

SETTING:

Healthcare professional and consumer drug information service located at a college of pharmacy.

PARTICIPANTS:

Consumers and healthcare professionals of the province.

INTERVENTION:

Patient-specific questions received by the drug information service were reviewed and evaluated for actual patient outcome, inquirers' opinion of impact of the service with respect to patient outcome, and for objectivity and timeliness of the response. An expert panel determined whether the responses and recommendations given by the service were appropriate, determined what impact the service had on the patient, and assessed the seriousness of the inquiry.

MAIN OUTCOME MEASURE:

Classification of patient outcome by objective and subjective data based on predetermined desired outcomes.

RESULTS:

Ninety-eight and 68 patient-specific requests were received from healthcare professionals and consumers, respectively. The panel concluded that 94.9% of the healthcare requests and 98.5% of the consumer requests were answered appropriately and that the majority of the requests involved potentially serious drug-related problems. The panel also determined that 46.8% of the recommendations to healthcare professionals and 41.0% of the recommendations to consumers resulted in positive patient outcomes. The majority of the positive outcomes involved the prevention of a disease or its symptoms (professional section) and the reduction or elimination of symptoms (consumer section).

CONCLUSIONS:

The drug information service not only met its objectives of providing drug information in an accurate, objective, and timely manner, but was also able to provide positive patient outcomes.
Antimicrobial Selection for Hospitalized Patients with Presumed Community-Acquired Pneumonia: A Survey of Nonteaching US Community Hospitals
Authors: Dudas Vicky , Hopefl Alan , Jacobs Richard , Guglielmo B Joseph
Published: June 2003

OBJECTIVE:

To describe and evaluate empiric antimicrobial regimens chosen for hospitalized patients with presumed community-acquired pneumonia (CAP) in US hospitals, including compliance with the American Thoracic Society (ATS) guidelines. Secondary outcomes included length of stay (LOS) and mortality associated with the choice of therapy.

METHODS:

A nonrandomized, prospective, observational study was performed in 72 nonteaching hospitals affiliated with a national group purchasing organization. Patients with an admission diagnosis of physician-presumed CAP and an X-ray taken within 72 hours of admission were eligible for the study. Demographic, antibiotic selection, and outcomes data were collected prospectively from patient charts.

RESULTS:

3035 patients were enrolled; 2963 were eligible for analysis. Compliance with the ATS guidelines was 81% in patients with nonsevere CAP. The most common antibiotic regimen used for empiric treatment was ceftriaxone alone or in combination with a macrolide (42%). The overall mortality rate was 5.5%. The addition of a macrolide to either a second- or third-generation cephalosporin or a β-lactam/β-lactamase inhibitor was associated with decreased mortality and reduced LOS.

CONCLUSIONS:

Most hospitalized patients with CAP receive antimicrobial therapy consistent with the ATS guidelines. The addition of a macrolide may be associated with improved patient outcomes.
Urinary Incontinence
Authors: Couture Julie A , Valiquette Luc
Published: June 2003

BACKGROUND:

One of the more prevalent conditions associated with aging is urinary incontinence (UI), which may affect up to 55% of women and 34% of men older than 65 years. As a result of increasing longevity in developed nations, the proportion of UI-susceptible individuals continues to grow, presenting clinical and economic challenges to healthcare providers.

OBJECTIVE:

To assist the clinician in making informed decisions regarding UI, provide information on the wider ramifications of the disease, and provide a comprehensive overview of the condition.

DATA SOURCES:

MEDLINE (1966–December 1998) was searched for relevant publications using the following search terms: UI, UI in the elderly, treatment of UI, oxybutynin, flavoxate, vasopressin, quality of life in UI, and economic impact of UI.

DATA SYNTHESIS:

Key articles relating to the etiology, diagnosis, classification, economic burden, quality of life, and treatment of UI were retrieved, and this information formed the basis of the review.

CONCLUSIONS:

Although UI can be controlled relatively well with existing therapies, only about 50% of affected patients may actually seek care. There are a variety of therapeutic options available for the treatment of UI, although pharmacologic intervention is presently a relatively minor component of overall care; this suggests that effective drug therapy might play a more significant role in the future. The economic burden associated with the care of the incontinent patient is substantial, and in the US the direct medical cost of the disease was estimated at $25.5 billion in 1995. The disease also has a large impact on the individual UI patient, negatively affecting many parameters normally associated with a tolerable health-related quality of life.
Contribution of Multivitamins, Air, and Light in the Generation of Peroxides in Adult and Neonatal Parenteral Nutrition Solutions
Authors: Laborie Sophie , Lavoie Jean-Claude , Pineault Marjolain , Chessex Philippe
Published: June 2003

OBJECTIVE:

To compare the concentrations of peroxides between adult and neonatal total parenteral nutrition (TPN) solutions in response to protection against inducers of peroxidation such as multivitamins and exposure to light or air.

METHODS:

Peroxide concentrations were measured in freshly prepared adult and neonatal solutions of fat-free TPN in four settings: with or without an air inlet, and protected or unprotected from ambient light. An oxygen washout was performed by exposing a fat-free neonatal TPN solution to a continuous flow of nitrogen.

RESULTS:

Globally, light was the main inducer of peroxides in adult and neonatal solutions. However, in adult solutions the concentration of peroxides remained <15 μmol/L, while in neonatal solutions the peroxide concentration was as high as 300 μmol/L in ambient light. Although the oxygen washout did prevent the generation of peroxides, avoiding air inlet was not as effective as was photoprotection in decreasing the important peroxide load in the neonatal TPN solution.

CONCLUSIONS:

The higher concentration of peroxides found in neonatal solutions compared with adult solutions is explained by the differences in nutrient composition between the two solutions. Contamination of parenteral solutions by air during compounding accounts for the photoinduced generation of peroxides in TPN solutions. It is more convenient to protect TPN solutions from light exposure after the admixture of the multivitamin solution than to avoid contact with oxygen.
Combination Therapy with Interferon and Ribavirin in the Treatment of Chronic Hepatitis C Infection
Authors: Battaglia Andrea M , Hagmeyer Kathleen O
Published: June 2003

OBJECTIVE:

To review and critique the medical literature regarding the combination of interferon and ribavirin in the initial treatment of chronic hepatitis C virus (HCV) infection.

DATA SOURCES:

A MEDLINE search (January 1966–June 1999) was conducted to identify human clinical trials regarding the combination of interferon and ribavirin therapy for the initial treatment of chronic HCV. Bibliographies were reviewed for relevant literature.

STUDY SELECTION:

Clinical trials of combination interferon and ribavirin for the treatment of chronic HCV in interferon-naïve adults were reviewed.

DATA SYNTHESIS:

The combination of ribavirin and interferon in the treatment of chronic HCV has been beneficial in patients who are interferon-naïve. Patients with predictors of poor response, such as baseline cirrhosis, male gender, age >40 years, high baseline viral loads (>2 times 106 copies/mL), and genotype 1 respond better to combination treatment when compared with those who receive interferon monotherapy. Patients with genotype 1 and/or high viral loads may benefit most from 48 weeks of combination therapy; however, adverse effects are of greater concern in these patients. Monitoring can limit these complications.

CONCLUSIONS:

Combination therapy is effective in the treatment of interferon-naive patients with chronic HCV infection. Patients should be evaluated for duration of treatment with combination therapy by determination of predictors of response. Further trials are needed to more closely evaluate the duration of treatment and to determine the best patient population to receive combination therapy.
Dofetilide: A Class III-Specific Antiarrhythmic Agent
Authors: Kalus James S , Mauro Vincent F
Published: June 2003

OBJECTIVE:

To review published reports on the pharmacology and clinical use of dofetilide in the management of cardiac dysrhythmias.

DATA SOURCES:

A MEDLINE search (January 1966–June 1999) was performed using dofetilide and UK-68,798 as key words. English-language articles were identified, and the references of these articles were used to further identify pertinent articles.

STUDY SELECTION:

All acquired studies and reviews discussing the pharmacology, pharmacokinetics, chemistry, and clinical efficacy of dofetilide were reviewed.

DATA EXTRACTION:

Articles were selected based on quality of review of the pharmacology and clinical use of dofetilide. Given the paucity of data on the clinical pharmacology and use of dofetilide, most articles obtained were used, including abstracts when full reports were not available.

DATA SYNTHESIS:

Dofetilide is a relatively specific class III antiarrhythmic agent. It increases action potential duration and effective refractory period without impacting conduction velocity. These actions of dofetilide are explained by its ability to inhibit the rapid component of the delayed, outward-rectifying potassium current, thus blocking the efflux of potassium during repolarization. Introductory investigations suggest that dofetilide may be of use in treating and preventing atrial dysrhythmias such as atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. Dofetilide may also have a role in preventing ventricular tachycardia from occurring. Some data also suggest that dofetilide may improve the morbidity of heart failure patients. Currently, the most troublesome adverse effect of dofetilide is its propensity to induce ventricular proarrhythmias, especially torsade de pointes.

CONCLUSIONS:

Based on the data currently available, dofetilide should have a role in the pharmacotherapy of cardiac dysrhythmias, especially those of atrial origin. More data on its efficacy and tolerability are needed, however, to fully delineate dofetilide's role amid currently available antiarrhythmic agents.
Long-Term Patient Adherence to Antiretroviral Therapy
Authors: Ostrop Nikola J , Hallett Kristi A , Gill M John
Published: June 2003

OBJECTIVE:

To measure patient adherence to antiretroviral therapy over a two-year period and to identify factors impacting adherence.

METHODS:

In a regional HIV treatment center, 100 consecutive patients starting any new antiretroviral agent were enrolled in this study, which consisted of a one-year retrospective data review and a one-year prospective component. The tools used for evaluating adherence were the monthly prescription refill data and a patient questionnaire. Data analyzed included overall adherence, adherence to individual antiretrovirals, and change in adherence over time, as well as factors reported as influencing adherence.

RESULTS:

Greater than 80% adherence in taking prescribed doses was seen in 75% of patients during the retrospective phase of the study; adherence increased to 84% in the prospective phase. Throughout the prospective phase of the study, monthly median adherence rates were 98–100%. Suboptimal adherence secondary to pill fatigue or number of daily pills did not occur. Reported nonadherence to dietary restrictions varied among drugs. The primary cause given for poor adherence was difficulty remembering, followed by inconvenient dosing schedule and difficulty scheduling administration times around meals. At least one adherence tool was used by 61% of patients. A diagnosis of AIDS was associated with lower adherence in our patient population (p = 0.039); substance abuse and psychiatric history had no influence.

CONCLUSIONS:

Adherence to antiretroviral treatment regimens did not diminish over the two years studied. Several patients with poor adherence were identified, emphasizing the importance of addressing this issue both prior to and throughout treatment. A personalized approach by healthcare providers can optimize patient adherence to antiretroviral therapy by providing careful drug selection in addition to routine follow-up and the provision of information, feedback, and reminder systems.
Carbamazepine–Indinavir Interaction Causes Antiretroviral Therapy Failure
Authors: Hugen Patricia WH , Burger David M , Brinkman Kees , ter Hofstede Hadewych JM , Schuurman Rob , Koopmans Peter P , Hekster Yechiel A
Published: June 2003

OBJECTIVE:

To report a case of antiretroviral therapy failure caused by an interaction between carbamazepine and indinavir.

CASE SUMMARY:

A 48-year-old HIV-positive white man was treated with antiretroviral triple therapy, consisting of indinavir, zidovudine, and lamivudine. His HIV-RNA (viral load) became undetectable (<400 copies/mL) less than two months after this therapy was started; this was confirmed one month later. Shortly after the start of antiretroviral therapy, the patient developed herpes zoster, which was treated with famciclovir. Tramadol was initially prescribed for postherpetic neuralgia; however, this was substituted with carbamazepine due to insufficient analgesic effect. Indinavir plasma concentrations decreased substantially during carbamazepine therapy. Carbamazepine was stopped after 2.5 months and, two weeks later, the HIV-RNA was detectable (6 times 103 copies/mL). Resistance for lamivudine was observed in that blood sample; resistance for zidovudine might have been present, and resistance to indinavir was not detected. A few months later, a further increase of the HIV-RNA occurred (300 times 103 copies/mL), after which the therapy was switched to a new antiretroviral regimen containing nevirapine, didanosine, and stavudine.

DISCUSSION:

Physicians may prescribe carbamazepine for HIV-infected patients to treat seizures or postherpetic neuralgia, which are complications of opportunistic infections such as herpes zoster or toxoplasmosis. Carbamazepine is a potent enzyme inducer, predominantly of the CYP3A enzyme system, while HIV-protease inhibitors such as indinavir are substrates for and inhibitors of CYP3A. Therefore, an interaction between these drugs could be expected. A low dose of carbamazepine (200 mg/d) and the usual dose of indinavir (800 mg q8h) in our patient resulted in carbamazepine concentrations within the therapeutic range for epilepsy treatment; indinavir concentrations dropped substantially. The virologic, resistance, and plasma drug concentration data, as well as the chronology of events, are highly indicative of antiretroviral treatment failure due to the interaction between carbamazepine and indinavir.

CONCLUSIONS:

Concomitant use of carbamazepine and indinavir may cause failure of antiretroviral therapy due to insufficient indinavir plasma concentrations. Drugs other than carbamazepine should be considered to prevent this interaction. Amitriptyline or gabapentin are alternatives for postherpetic neuralgia; valproic acid or lamotrigine are alternatives for seizures. When alternate drug therapy is not possible, dosage adjustments, therapeutic drug monitoring, and careful clinical observation may help reduce adverse clinical consequences.
Clozapine-Associated Extrapyramidal Reaction
Authors: Elliott Ellie SR , Marken Patricia A , Ruehter Valerie L
Published: June 2003

OBJECTIVE:

To report a case of extrapyramidal reaction associated with a dosage increase of clozapine.

CASE SUMMARY:

A 44-year-old white man with a 20-year history of chronic paranoid schizophrenia was admitted to an inpatient psychiatric facility. His prior medications restarted on admission were clozapine 650 mg at bedtime, haloperidol 10 mg at bedtime, clonazepam 2 mg/d, and aspirin 325 mg/d. Two days after admission (hospital day 3), clozapine and clonazepam were discontinued, and he was prescribed haloperidol 5 mg every morning and 10 mg every evening. Stabilization occurred over the following 24 days, with progressively lower dosages of haloperidol and increasing dosages of clozapine. Haloperidol was discontinued on day 24. On day 47, the patient was agitated and making bizarre statements; thus, the morning dose of clozapine was increased by 50 mg (total 450 mg/d). On day 48 at 2200, a dystonic reaction was diagnosed; he received intramuscular diphenhydramine 50 mg, which caused the reaction to subside. At the time of the adverse reaction, he was prescribed clozapine 450 mg/d, vitamin E 400 IU three times daily, aspirin 325 mg/d, and acetaminophen, milk of magnesia, and Maalox as needed.

DISCUSSION:

Although the risk of extrapyramidal symptoms (EPS) is significantly lower with clozapine than with conventional agents, elevated clozapine blood concentrations have been reported to cause EPS; other reports have cited severe dystonias and dyskinesias on abrupt clozapine withdrawal. Considering the medications prescribed at the time and the discontinuation of haloperidol 24 days before the event, clozapine was the most likely cause of the extrapyramidal reaction.

CONCLUSIONS:

Regardless of anticipated safety associated with novel antipsychotics such as clozapine, reports of dystonic reactions must be taken into account and patients monitored appropriately.
Treatment of Hypertension in the Perioperative Patient
Authors: Erstad Brian L , Barletta Jeffrey F
Published: June 2003

OBJECTIVE:

To review studies and drug therapy relating to the treatment of hypertension in perioperative patients.

DATA SOURCES:

Articles were selected from a MEDLINE search (1966–August 1998), and several textbooks on hypertension and surgery were reviewed. In addition, bibliographies of all articles and textbook chapters were studied for articles not found in the computerized searches.

STUDY SELECTION:

Clinical studies involving hypertension in the perioperative setting were included. The initial search was limited to studies conducted in humans and published in English.

DATAEXTRACTION:

Information regarding drug therapy was reviewed and guidelines were constructed for managing surgical patients with acute blood pressure elevations.

DATA SYNTHESIS:

Although nitroprusside and nitroglycerin, with their short onset of action and duration of effect, are indicated for hypertensive emergencies, a variety of agents are available for hypertensive urgencies. An algorithm that can be used as a template for the development of intrainstitutional guidelines is provided.

CONCLUSIONS:

Due to the scarcity of comparative trials, decisions involving agents for the treatment of perioperative hypertension must often be made based on combined efficacy, toxicity, cost, and convenience considerations.
Bismuth Subgallate–Epinephrine Paste in Adenotonsillectomies
Authors: Hatton Randy C
Published: June 2003

OBJECTIVE:

To evaluate the role of bismuth subgallate–epinephrine (BSE) paste as a hemostatic in adenotonsillectomies.

DATA SOURCES:

MEDLINE (January 1966–October 1999) and Current Contents (January 1997–October 1999) were searched, using bismuth subgallate, adenoidectomy, tonsillectomy, and adenotonsillectomy as search terms. A citation search was performed using Science Citation Index (January 1977–October 1999).

DATA SYNTHESIS:

Adenotonsillectomies are common procedures; although there are few complications, hemorrhage is a concern. Bismuth subgallate has historically been used as an astringent and hemostatic. An evaluation of studies of bismuth subgallate and BSE paste was conducted.

CONCLUSIONS:

There is minimal evidence to support this practice, but data suggest that epinephrine may be the active ingredient in BSE paste. BSE paste is inexpensive, poses little risk, and may decrease postoperative bleeding; therefore, it may be a reasonable hemostatic agent.
Pharmacogenetic Screening for Susceptibility to Fetal Malformations in Women
Authors: Van Dyke Don C , Ellingrod Vicki L , Berg Mary J , Niebyl Jennifer R , Sherbondy Andrea L , Trembath Dimitri G
Published: June 2003

OBJECTIVE:

To present a review of the literature and research on the pharmacogenetics of congenital defects, with a focus on the need for predictive maternal genotype assays.

DATA SOURCE:

MEDLINE searches (January 1985–January 1999), past reference reviews, and unpublished research.

STUDY SELECTION:

Review of relevant human, animal, and basic science studies.

DATA EXTRACTION:

Data on research on polymorphisms, genotyping, cytochrome P450 enzyme systems, epoxide hydrolase, folate metabolism, metabolism of anticonvulsant medications, molecular genetics of neural tube defects, variations in drug metabolism, and environmental exposures were evaluated.

DATA SYNTHESIS:

Data synthesis includes not only a review of the literature but suggests ways such data might be used to facilitate the development of maternal genotype assays, with the goal of preventing birth defects.

CONCLUSIONS:

Individuals vary in how they metabolize drugs and handle toxic environmental exposures. In an ideal pregnancy, there is no or limited exposure to medications and environmental agents. However, in women with chronic medical conditions such as heart disease and seizures, this is often not possible. Unfortunately, no techniques have been available to identify those at risk in this population. Gene polymorphisms for a specific enzyme may result in an absence or reduction in the level of enzyme activity or in no change at all, with little effect on the structure/function of the gene product(s); they are not associated with clinical phenotypes in either the mother or the fetus. Other polymorphisms may be only markers. Thus, developing genotyping assays for women that are predictive of phenotype expression in the fetus is the key to screening for polymorphisms. As more mutations are identified and clinical, pharmacologic, biologic, and pharmacokinetic relationships are established, using these polymorphisms to develop a genotyping assay for women may become a clinical reality, possibly leading to preventive prepregnancy or prenatal treatment that may play an increasingly effective role in maternal care.
A Hypertensive Reaction Induced by Concurrent Use of Selegiline and Dopamine
Authors: Rose Lori M , Ohlinger Martin J , Mauro Vincent F
Published: June 2003

OBJECTIVE:

To describe a hypertensive reaction induced by concurrent use of selegiline and dopamine.

CASE SUMMARY:

A 75-year-old critically ill white man who was receiving selegiline 5 mg twice daily for Parkinson's disease was initiated on an intravenous dopamine infusion for decreased urine output and hypotension. Within minutes of starting the dopamine infusion, the patient's systolic blood pressure increased from 105 to 228 mm Hg. Similar reactions occurred during two subsequent rechallenges.

DISCUSSION:

Since monoamine oxidase is involved in the metabolism of catecholamines, selegiline may have affected the metabolism of the dopamine administered to the patient. Although selegiline is known to be a monoamine oxidase inhibitor specific for type B, evidence exists stating that selegiline may not be as specific as previously thought.

CONCLUSIONS:

Dopamine should be used cautiously, if at all, in patients who are chronically receiving selegiline or who have received selegiline within the prior two weeks.
Severe Thrombocytopenia Associated with Alatrofloxacin
Authors: Gales Barry J , Sulak Laurie B
Published: June 2003

OBJECTIVE:

To report the development of severe thrombocytopenia during alatrofloxacin therapy.

CASE SUMMARY:

A 54-year-old Native American woman was admitted for pneumonia after completing a 10-day course of loracarbef 200 mg po bid. On admission, the woman was hypoxic (PO2 56 mm Hg) and had a platelet count of 408 times 103/mm3. Alatrofloxacin 300 mg iv piggyback qd was initiated in the emergency department. The patient's condition gradually improved during the next three days. While preparing for discharge on hospital day 4, the patient developed epistaxis that lasted approximately three hours. Laboratory testing revealed a platelet count of 7 times 103/mm3; stable red blood cell count, hemoglobin, and hematocrit values; and a normal white blood cell count. Alatrofloxacin therapy was discontinued and azithromycin was initiated on hospital day 4. Methylprednisolone 125 mg iv piggyback every 12 hours was initiated on hospital day 5. The platelet count fell to 2 times103/mm3 on hospital day 5 and then began to rise, reaching 60 times 103/mm3 when the patient was discharged on hospital day 8.

DISCUSSION:

Numerous infectious, disease-related, environmental, and pharmacologic factors may cause thrombocytopenia. Drug-induced thrombocytopenia usually develops during the first two weeks of therapy and resolves within one week of drug discontinuation. Thrombocytopenia occurred in <1% of more than 7000 patients receiving alatrofloxacin or trovafloxacin during clinical trials.

CONCLUSIONS:

The time course of this patient's development of and recovery from thrombocytopenia suggests that it was induced by alatrofloxacin. Clinicians should monitor patients receiving alatrofloxacin or trovafloxacin for signs and symptoms of bleeding and thrombocytopenia.