bluuebunny/crossref_metadata_2025 huggingface dataset:
Do HMG-CoA Reductase Inhibitors Affect Fibrinogen?
Authors: Song Jessica C , White C Michael
Published: June 2003

OBJECTIVE:

To review commonly used fibrinogen assay methods and the evidence demonstrating an association between fibrinogen and increased risk of coronary artery disease and to review the current literature to determine and assess the impact of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on fibrinogen.

DATA SOURCES:

Primary and review articles identified from a MEDLINE search (1966–December 1999); references obtained from these publications were subsequently reviewed for additional relevant articles.

STUDY SELECTION AND DATA EXTRACTION:

All articles were evaluated, and all relevant information was included in this review.

DATA SYNTHESIS:

The Clauss method is currently the preferred method for determining plasma fibrinogen concentrations, due to its high degree of accuracy and precision. Furthermore, unlike immunologic methods, its reliability is unaffected by change in triglycerides. The effects of four HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin, pravastatin) on fibrinogen have been evaluated. Atorvastatin has been shown to induce significant increases in fibrinogen (22% increase; p < 0.05) by using the mmunonephelometric method. This method also demonstrated that lovastatin use was associated with a 24.4% increase (p < 0.0001) in plasma fibrinogen concentration. Simvastatin has been shown in multiple studies using the Clauss method to have a neutral effect on fibrinogen. The majority of studies have revealed significant decreases (7–19%) in fibrinogen following treatment with pravastatin.

CONCLUSIONS:

Future studies need to be performed evaluating the effects of HMG-CoA reductase inhibitors on fibrinogen, but using direct comparisons and clotting assay methodology.
Life-Threatening Eosinophilic Pleuropericardial Effusion Related to Vitamins B5 and H
Authors: Debourdeau Philippe M , Djezzar Samira , Estival Jean Louis F , Zammit Christine M , Richard René C , Castot Anne C
Published: June 2003

OBJECTIVE:

To report a case of eosinophilic pleuropericarditis resulting from concomitant use of vitamins B5 and H.

CASE SUMMARY:

A 76-year-old white woman was admitted to the hospital because of chest pain and dyspnea related to pleurisy and a pericardial tamponade. This patient had no history of allergy and had been taking vitamins B5 and H for two months. Blood tests performed showed an inflammatory syndrome and a high eosinophil concentration (1200–1500 cells/mm3). Pleurocentesis and pericardiotomy yielded a sterile exudative fluid with an eosinophilic infiltrate. There were no nuclear antibodies and no rheumatic factor; screenings for viruses, parasites, bacteria, and malignant tumor were negative. A myelogram, biopsy of the iliac crest bone, and concentration of immunoglobulin E were also normal. After withdrawal of the vitamins, the patient recovered and the eosinophilia disappeared.

DISCUSSION:

Prolonged hypereosinophilia has marked predilection to damage specific organs, including the heart, but pleuro-pericardial effusion is uncommon. Drug-related pleuropericarditis usually occurs without an increased eosinophil count. Other drugs responsible for eosinophilic pleuropericarditis are cephalosporins, dantrolene, propylthiouracil, and nitrofurantoin. To our knowledge, this is the first case report of pleuropericarditis related to vitamins B5 and H.

CONCLUSIONS:

This case suggests that vitamins B5 and H may cause symptomatic, life-threatening, eosinophilic pleuropericarditis. Physicians prescribing these commonly used vitamins should be aware of this potential adverse reaction.
Zolpidem for Antipsychotic-Induced Parkinsonism
Authors: Farver Debra K , Khan Mujeeb H
Published: June 2003

OBJECTIVE:

To report a case of antipsychotic-induced parkinsonism that was managed with zolpidem.

CASE SUMMARY:

A 34-year-old white man who had had antipsychotic-induced parkinsonism with symptoms of repetitive persistent gross tremors of the hands for numerous years was unresponsive to traditional antiparkinsonian medications. With the initiation of zolpidem 10 mg four × daily, the tremors decreased significantly.

DISCUSSION:

The use of zolpidem for antipsychotic-induced parkinsonian hand tremors in this patient was based on the severity of the symptoms and the lack of response to several trials of traditional medications. When zolpidem was started at 10 mg four × a day, the motor examination score on the Unified Parkinson's Disease Rating Scale decreased from 29 at baseline to a score of 9 after one month of use. After four months of zolpidem use, the patient's mental status decompensated, and clozapine was initiated. As the patient experienced excessive sedation, zolpidem was discontinued while clozapine was maintained to help with the psychosis and, potentially, the tremors. The tremors reemerged with a motor examination score of 30. Zolpidem was reinitiated at 5 mg four × daily, and the patient's tremors have been stable for two years.

CONCLUSIONS:

Further investigation is needed to study the use of nontraditional medications in patients requiring antipsychotic medications who have refractory parkinsonian symptoms.
Religion and Coping with Serious Medical Illness
Authors: Koenig Harold G , Larson David B , Larson Susan S
Published: June 2003

OBJECTIVE:

To review and discuss some of the research published in the last several decades that has addressed the role that religion plays in helping patients cope with serious medical illness.

DATA SOURCES:

Although this is not a systematic review of the literature, it provides a sampling of the studies that have examined the relationship between religious involvement, coping with illness, and health outcomes. This sampling of studies reflects the findings of a much larger systematic review of research (MEDLINE, Current Contents, Psychlit, Soclit, HealthStar, Cancerlit, CINAHL, and others) during the past century that was recently completed by the authors.

DATA EXTRACTION:

Epidemiologic studies published in the English-language literature were reviewed and discussed.

DATA SYNTHESIS:

A number of well-designed cross-sectional and prospective studies have examined the relationship between religious beliefs and activities and adaptation to physical illness in patients with general medical conditions, neurologic disorders, heart disease, renal failure, AIDS, and a host of other physical disorders. This review demonstrates the widespread use of religion in coping with medical illness and provides circumstantial evidence for the possible benefits of this lifestyle factor.

CONCLUSIONS:

When people become physically ill, many rely heavily on religious beliefs and practices to relieve stress, retain a sense of control, and maintain hope and their sense of meaning and purpose in life. Religious involvement appears to enable the sick, particularly those with serious and disabling medical illness, to cope better and experience psychological growth from their negative health experiences, rather than be defeated or overcome by them.
L-Arginine in the Management of Cardiovascular Diseases
Authors: Cheng Judy WM , Balwin Stephen N
Published: June 2003

OBJECTIVE:

To examine the role of L-arginine in the management of cardiovascular diseases.

DATA SOURCES:

A MEDLINE search (1966–April 2000) of review articles, using the search terms arginine, nitric oxide, and cardiovascular diseases, was conducted. After reviewing these articles, primary studies using the search terms arginine, hypercholesterolemia, hypertension, diabetes, smoking, ischemic heart disease, and heart failure were reviewed.

STUDY SELECTION:

English-language human studies were selected and evaluated based on quality of review.

DATA SYNTHESIS:

Small-scale studies have demonstrated that intravenous L-arginine augments endothelial function by enhancing vasodilation and reducing monocyte adhesion. Oral supplementation demonstrated similar effects as well as improvement of exercise ability in patients with cardiovascular diseases.

CONCLUSIONS:

L-arginine improves the management of multiple cardiovascular diseases. However, most published human studies are small. Before therapy can be routinely recommended, larger, well-designed studies are required to confirm its effect.
Comparison of FDA Reports of Patient Deaths Associated with Sildenafil and with Injectable Alprostadil
Authors: Cohen Jay S
Published: June 2003

BACKGROUND:

Sildenafil (Viagra) has been linked to 240 deaths (128 verified, 112 unverified) reported to the Food and Drug Administration (FDA) during 7.5 months of availability, and to 522 reported deaths after 13 months of availability. To date, no updated information about FDA-reported deaths has emerged, and no comparative analyses have been published.

OBJECTIVE:

To compare the mortality rates between sildenafil and injectable alprostadil, both of which are used exclusively for treating erectile dysfunction.

METHODS:

A comparison of the number of deaths per filled prescriptions reported to the FDA involving sildenafil and injectable alprostadil was undertaken to perhaps provide further insight into this issue. Materials included FDA statements on sildenafil adverse event reports to the FDA involving sildenafil and injectable alprostadil, and data on prescriptions filled for sildenafil and injectable alprostadil.

RESULTS:

The number of deaths per prescriptions filled reported in association with sildenafil was significantly greater (5.15–6.28 times) than in association with injectable alprostadil.

DISCUSSION:

Previous explanations for sildenafil-associated deaths have been based on the expected attrition within the population of men with erectile dysfunction and its commonly associated disorders, the physiologic stress of renewed sexual activity, and a pharmacologic effect of sildenafil. The results of this analysis may indicate that a pharmacologic effect of sildenafil is responsible for these deaths. However, other factors may also explain these findings: a greater frequency of reporting of sildenafil-associated events by physicians, a difference in the populations using these two drugs, or the number of prescriptions filled may not accurately reflect actual exposure.

CONCLUSIONS:

Further study should be undertaken to clarify the issues associated with sildenafil-related deaths. In the meantime, reasonable precautions might be considered in prescribing sildenafil, such as initiating treatment with a low test dose of sildenafil.
Psychometric Evaluation of Four HIV Disease—Specific Quality-of-Life Instruments
Authors: Davis Elizabeth Anne , Pathak Dev S
Published: June 2003

OBJECTIVE:

To provide a comparative evaluation of psychometric properties for three or more HIV disease—specific quality-of-life (QoL) instruments.

METHODS:

Four instruments were selected using the following criteria: multiple publications of instrument, focus of instrument on QoL, psychometric validation publication or comparison with previously validated questionnaire, stages of HIV/AIDS used or evaluated in the study, and inclusion of sample items or the instrument in at least one publication. The four HIV-specific QoL instruments were: HIV/AIDS-Targeted Quality of Life Instrument, Medical Outcomes Study HIV questionnaire (MOS-HIV), Functional Assessment of Human Immunodeficiency Virus Infection, and HIV Overview of Problems — Evaluation System. These instruments were evaluated using combined criteria derived from McHorney and Tarlov and Shumaker et al. The criteria include: administration, content, depth, reliability, validity, and responsiveness. A letter grade scale (A, B, C, D) was used in rating the criteria.

RESULTS:

No instrument demonstrated ideal psychometric properties. The MOS-HIV questionnaire was the only instrument that published results for seven of the eight categories. Therefore, a decision cannot be made about the best instrument to use for measuring QoL in an HIV-positive patient.

CONCLUSIONS:

Published data for these questionnaires had common limitations of sample size, study design, and population demographics. Hence, further testing of these questionnaires is recommended before use in any study to determine suitability, reliability, and validity.
Adjunctive Rifampin Therapy for Central Nervous System Staphylococcal Infections
Authors: Brackbill Marcia L , Brophy Gretchen M
Published: June 2003

OBJECTIVE:

To review the published clinical data assessing the role of adjunctive rifampin therapy for the treatment of staphylococcal central nervous system (CNS) infections.

DATA SOURCES:

A MEDLINE search (January 1966–March 2000) of English-language literature pertaining to CNS staphylococcal infections and rifampin was performed; tertiary sources were also used.

DATA EXTRACTION:

Human data and case reports were included, as no clinical trials have been published.

DATA SYNTHESIS:

Retrospective reviews of rifampin used in combination with other antibiotics for serious bacterial infections show conflicting results. Few case reports have described clinical successes with adjunctive rifampin therapy for CNS infections.

CONCLUSIONS:

The routine use of adjunctive rifampin for CNS infections cannot be justified.
Unanticipated Plasma Concentrations in Two Clozapine-Treated Patients
Authors: Alfaro Cara L , McClure Robert K , Vertrees Julia E , Benavides Ray
Published: June 2003

OBJECTIVE:

To report two cases of lower than anticipated clozapine plasma concentrations despite near maximum recommended doses of clozapine 800–900 mg/d in two medication-compliant schizophrenic inpatients.

CASE SUMMARIES:

Clozapine therapy was initiated in two male schizophrenic inpatients for treatment of psychotic symptoms refractory to other typical and atypical antipsychotics. Despite receiving adequate doses of clozapine for at least two months, these patients remained symptomatic. Therapeutic drug monitoring was used to target a clozapine plasma concentration of ≥250 ng/mL, the minimum value reported in the literature to be associated with increased clinical response. Clozapine plasma concentrations remained at 200 ng/mL in one patient despite dosage increases from 600 to 800 mg/d. In the second patient, administration of the maximum recommended dose resulted in concentrations between 200 and 250 ng/mL. Increasing the clozapine dosage to 1000 mg/d did not increase the clozapine plasma concentration. Evaluation of the ratio of clozapine plasma concentration clozapine to dose yielded lower than expected values compared with those reported in the literature.

DISCUSSION:

These two patients exhibited lower than anticipated clozapine plasma concentrations despite receiving high doses of clozapine. Several studies evaluating clozapine serum concentrations and clinical response have suggested threshold concentrations of ≥350 ng/mL, ≥370 ng/mL, or ≥420 ng/mL. The only study that randomized patients to three concentration ranges found that patients who achieved a clozapine serum concentration in a medium range (mean 251 ng/mL) responded better than patients in a low range (mean 91 ng/mL) and similar to patients in a high range (mean 396 ng/mL). However, attaining plasma concentrations in this range for these patients proved difficult. Reasons for the low concentrations are unclear and may be related to increased metabolic activity at several cytochrome P450 isoenzymes involved in the metabolism of clozapine.

CONCLUSIONS:

These cases illustrate lower than anticipated clozapine plasma concentrations despite high-dose clozapine therapy. Strategies to increase clozapine plasma concentrations in such patients might include adding a drug to partially inhibit the metabolism of clozapine. If those strategies are unacceptable based on risk assessment, patient compliance, or other reasons, clinicians may consider addition of a low-dose typical or other atypical antipsychotic drug to augment clozapine response. PharmD, Clinical Pharmacy Specialist for the National Institute of Mental Health; Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD
Rhabdomyolysis and HMG-CoA Reductase Inhibitors
Authors: Omar Mohamed A , Wilson James P , Cox Tamara S
Published: June 2003

OBJECTIVE:

To review rhabdomyolysis and discuss the role of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and their interactions with other agents in precipitating this condition, and to present case reports of statin-induced rhabdomyolysis.

DATA SOURCE:

Relevant clinical literature was accessed using MEDLINE (January 1985–October 2000). The following search terms were used: rhabdomyolysis, adverse events, drug interactions, statins, and HMG-CoA reductase inhibitors.

DISCUSSION:

Rhabdomyolysis occurs when extensive muscle damage results in the release of cellular contents into systemic circulation. Major complications include acute renal failure, cardiac abnormalities, and compartment syndrome. Treatment of rhabdomyolysis is supportive, with the primary aim of preventing renal and cardiac complications. Statin monotherapy or combination therapy may result in myopathy, which rarely progresses to rhabdomyolysis. The mechanism for drug interactions with the statins involves their property of lipid or water solubility. This characteristic determines the degree of hepatoenteric or renal metabolism of the statins. All statins except pravastatin undergo metabolism via the cytochrome P450 enzyme system. Other pharmacologic agents that are also metabolized via this pathway may interact with the statins and cause rhabdomyolysis. The risk of statin-induced rhabdomyolysis is increased significantly when statins are used concomitantly with such drugs as fibrates, cyclosporine, macrolide antibiotics, and azole antifungals.

CONCLUSIONS:

Rhabdomyolysis is a rare but clinically important adverse event of statin monotherapy or combination therapy. Thorough understanding of this condition may help prevent or minimize adverse health outcomes in patients receiving statin therapy.
Corticotropin for Acute Management of Gout
Authors: Taylor Charles T , Brooks Natalie C , Kelley Kristi W
Published: June 2003

OBJECTIVE:

To evaluate safety and efficacy of corticotropin for acute gout.

DATA SOURCES:

Clinical literature was accessed through MEDLINE (1966–August 2000). Key search terms included gout, ACTH, adrenocorticotropic hormone, and corticotropin.

DATA SYNTHESIS:

Joint pain and local signs of inflammation characterize gout. Acutely, colchicine and nonsteroidal antiinflammatory drugs (NSAIDs) are first-line therapy. Adverse effects or concomitant diseases limit therapy and necessitate alternative options. An evaluation of studies involving corticotropin was conducted.

CONCLUSIONS:

Corticotropin alone or in combination with colchicine was more rapidly effective and associated with fewer adverse effects than indomethacin. This regimen may be considered an alternative, especially for patients with medical problems in which other regimens are contraindicated.
Hepatotoxicity Associated with Carvedilol
Authors: Hagmeyer Kathleen O , Stein Jenny
Published: June 2003

OBJECTIVE:

To report a severe episode of pruritus and elevated serum transaminases in a patient who was receiving carvedilol.

CASE SUMMARY:

A 40-year-old white man who had been taking carvedilol for the treatment of cardiomyopathy presented to the emergency department with pruritus over his entire body. Laboratory tests showed elevated serum transaminases. Carvedilol was discontinued and the patient received hydroxyzine hydrochloride to relieve symptoms. Liver function test results returned to normal in three weeks. Approximately one year later the patient was started on metoprolol and within 10 days again developed pruritus. The patient was told to discontinue the metoprolol immediately. At the time the metoprolol was stopped the liver function test results were normal.

DISCUSSION:

To the best of our knowledge, the adverse reaction presented in this case report is rare. The etiology of this adverse reaction remains unknown but suggests a possible adverse reaction that may recur if the patient is switched to another β-adrenergic blocker. The liver function test abnormalities appear to return to normal on discontinuation of carvedilol.

CONCLUSIONS:

Carvedilol may cause pruritus and elevated liver function test results. This reaction may recur if the patient is changed to an alternative β-adrenergic blocker. Patients taking carvedilol should be monitored for signs and symptoms of hepatotoxicity. If elevated liver function test results are noted, carvedilol should be discontinued.
Amphotericin B — Not So Terrible
Authors: Bishara Jihad , Weinberger Miriam , Lin Annica Y , Pitlik Silvio
Published: June 2003

OBJECTIVE:

To describe a patient who developed adverse reactions to two different lipid formulations of amphotericin B: liposomal amphotericin B (AmBisome) and amphotericin B colloidal dispersion (ABCD, Amphocil), yet tolerated amphotericin B deoxycholate (Fungizone) despite renal toxicity.

CASE SUMMARY:

A 72-year-old woman with acute myelomonocytic leukemia was treated with amphotericin B deoxycholate for suspected pulmonary aspergillosis; the drug was well tolerated but resulted in renal failure. Antifungal therapy was then changed to liposomal amphotericin B. Within 10 minutes of liposomal amphotericin B infusion, the patient developed severe dyspnea, chest pain, and a feeling of imminent death. On the following day, liposomal amphotericin B was switched to amphotericin B colloidal dispersion. Again, within 10 minutes of this infusion, the patient developed fever, chills, hypotension, severe chest pain, dsypnea, and a feeling of imminent death. The patient refused any further treatment with these drugs and insisted on switching back to amphotericin B deoxycholate, which was then administered for 10 days and was well tolerated.

DISCUSSION:

Severe adverse reactions, such as anaphylaxis, cardiac toxicity, and respiratory failure, following administration of all three lipid formulations of amphotericin B have been reported. In most reported cases, switching to a different lipid formulation of amphotericin B was well tolerated. This is in contrast to our case, where a severe reaction was repeated when another lipid preparation was given, necessitating switching back to amphotericin B deoxycholate despite its nephrotoxicity.

CONCLUSIONS:

In some patients, paradoxically, lipid formulations of amphotericin B may be less tolerable than conventional amphotericin B.
Newness of Drugs and Use of HMO Services by Asthma Patients
Authors: Horn Susan D , Sharkey Phoebe D , Kelly H William , Uden Donald L
Published: June 2003

OBJECTIVE:

To define newness of drug technology and show associations between two measures of newness and health service utilization.

METHODS:

Healthcare use and changes in severity at each office visit were assessed for 1309 asthma patients from six health maintenance organizations (HMOs) during 1992. The age of each drug product, derived by subtracting its Food and Drug Administration (FDA) approval date from January 1, 1992, was used to construct two newness measures: the average age of all asthma drugs and, separately, all non-asthma drugs a patient used during the year and the percentages of a patient's asthma drugs from each of four time intervals of asthma drug breakthroughs. Service utilization variables included all primary care provider (PCP) visits, total prescription costs, emergency department (ED) visits, and hospitalizations.

RESULTS:

Using either measure of drug newness, multivariate analyses showed an association between greater use of newer asthma drugs and lower overall drug costs and fewer PCP visits. A trend was found between greater use of newer asthma drugs and fewer hospitalizations and ED visits. Newer non-asthma medications were associated with fewer ED visits.

CONCLUSIONS:

After controlling for patient and site variables, greater use of newer asthma drugs was associated with significantly lower drug costs and fewer PCP visits; associations with hospitalization rates and ED visits, although lower, were not significant.
Antimicrobial Cycling: The Future or a Fad?
Authors: Hodges Brian M , White Roger L
Published: June 2003

OBJECTIVE:

To assess the current evidence of the value of cycling of antimicrobials to control the emergence of resistance or to reverse existing resistance to antimicrobials.

DATA SOURCES:

Articles were obtained through a MEDLINE search of the English-language literature from 1966 to January 2000. Additionally, references from retrieved publications were reviewed to identify further articles.

STUDY SELECTION AND DATA EXTRACTION:

All investigations of switching between or cycling among antimicrobials were evaluated. Studies switching between or cycling among specific drugs or classes of drugs within institutional settings were included in this review.

DATA SYNTHESIS:

Studies involving cycling among different aminoglycosides suggest that, although temporary decreases in resistance can be documented, resistance usually rebounds rapidly on completion of the cycle and return to the original agent. Switching between classes of antimicrobials has produced inconsistent results and has been shown to replace resistance to one agent with resistance to another. Mathematical models using both in vitro and clinical data have suggested that, due to residual resistance in the population, cycling among drug classes is unlikely to yield long-term reductions in antimicrobial resistance, especially if a high level of antimicrobial resistance exists.

CONCLUSIONS:

Cycling among different antimicrobials to reverse resistance trends is currently not supported by published literature. Cycling to prevent the emergence of resistance may ultimately be more useful; however, no studies have evaluated this concept. Well-designed prospective studies are needed to evaluate the potential clinical value of antimicrobial cycling.
Pharmacokinetics of Morphine and its Glucuronidated Metabolites in Burn Injuries
Authors: Perreault Sylvie , Choinière Manon , Souich Patrick B du , Bellavance François , Beauregard Gilles
Published: June 2003

OBJECTIVE:

To investigate the effects of major thermal burn injury and continuous intravenous morphine infusion on the disposition of morphine and its glucuronidated metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) once a week for three weeks.

CASE SUMMARIES:

Five patients with major first-, second-, or third-degree burn injuries received long-term intravenous morphine infusion. The required dose varied greatly (from 4 to 39.5 mg/h). The steady-state concentrations of morphine, M3G, and M6G ranged from 20 to 452, 29 to 3436, and 20 to 1240 μmol/L, respectively. The systemic clearance (Cls) of morphine ranged from 14.8 to 40.3 mL/min/kg and did not change over time. The ratios of M6G and M3G to morphine were not affected by dose, even with the wide variation of intravenous dosage. Morphine kinetics appeared to be first-order. Mean recovery of morphine, M3G, and M6G in urine was 1.7 ± 1.0%, 42.0 ± 16.8%, and 11.8 ± 3.2%, respectively, and renal clearance ranged from 8 to 64, 26 to 325, and 59 to 589 mL/min, respectively. Mean pain intensity ratings at rest remained low and stable (0.7 ± 0.9 on day 7, 0.4 ± 0.3 on day 14, 0 ± 0 on day 21).

DISCUSSION:

To our knowledge, this is the first published report describing morphine, M3G, and M6G disposition in patients with major thermal burn injury. The Cls of morphine is similar to that observed in other patient populations and healthy subjects, suggesting that the presence of major burn injuries or a continuous morphine infusion over a three-week period may not contribute significantly to the variability among individuals. In these cases, the renal clearance of morphine and its glucuronides was within the range of values reported for other populations of patients and healthy subjects. Recovery of morphine and its glucuronides in urine was also similar to that in healthy individuals.

CONCLUSIONS:

These cases suggest that the effects of major burn injuries and of long-term intravenous infusion of morphine did not seem to modify morphine, M3G, and M6G disposition. Among patients with burn injuries, the severity of burns or duration of administration are not a cause of nonlinear kinetic of morphine or of morphine resistance. The morphine infusion rate was substantially variable and not directly related to its clearance, suggesting that monitoring of morphine should be focused on the clinical response.
Writing Manuscripts Describing Clinical Trials: A Guide for Pharmacotherapeutic Researchers
Authors: Pakes Gary E
Published: June 2003

Once researchers have completed a clinical trial and analyzed the data, they have a duty to make the results known to their peers by writing a manuscript suitable for publication in a biomedical journal. Before beginning any writing, those involved in the clinical drug trial first need to decide among themselves who is to be the first author and secondary authors, the readership they want to influence, and the most appropriate target journal to reach this readership. For content and formatting of the manuscript, writers need to carefully follow the instructions for authors as stipulated by the target journal. In general, a manuscript based on a clinical trial is presented sequentially in four sections: Introduction, Methods, Results, and Discussion (IMRAD). The Introduction concisely presents background information about the topic that was researched in the clinical trial, provides the study hypothesis, and describes the study rationale, purpose, and objectives. The Methods section delineates the study design, subject/patient selection process, procedures, end points, and types of analysis conducted in the clinical trial to investigate the study hypothesis. The Results section presents the findings of the clinical trial, and the Discussion section interprets the meaning of these findings, assesses how the findings answer the study hypothesis, and compares the study data with findings reported in earlier studies. Writers should select a title for the clinical trial manuscript that is fewer than 10 words and which embodies the essence of the study findings clearly and specifically without being sensationalistic. Writers should create the abstract last; the abstract should provide an overview of the manuscript and stimulate readers' interest. Overall, following the above principles in writing a manuscript based on a clinical drug trial will make the actual writing easier and more enjoyable, as well as increase the possibility of the manuscript being accepted for publication.
Cilostazol for Prevention of Thrombosis and Restenosis after Intracoronary Stenting
Authors: El-Beyrouty Claudine , Spinler Sarah A
Published: June 2003

OBJECTIVE:

To evaluate the potential use of cilostazol in intracoronary stenting.

DATA SOURCES:

Clinical literature was accessed through MEDLINE (1966–March 2001). Key search terms included cilostazol, intracoronary stenting, and coronary angioplasty. Abstracts of clinical trials presented at major cardiology professional association meetings were also reviewed.

DATA SYNTHESIS:

Intracoronary stent placement represents the fastest growing medical device implant. Complications of stent implantation include acute and subacute vessel closure, as well as late restenosis. Currently, antiplatelet agents are used for preventive therapy. Cilostazol is a vasodilating antiplatelet agent that reversibly inhibits platelet aggregation induced by many factors. In seven randomized trials comparing cilostazol with either aspirin or ticlopidine, cilostazol was found to be superior to aspirin and equivalent to ticlopidine in decreasing both cardiac events and rates of restenosis. In addition, cilostazol was found to be well tolerated, with no reports of adverse hematologic events.

CONCLUSIONS:

Although further comparative trials are required, cilostazol appears to be a safe and effective alternative to clopidogrel and glycoprotein IIb/IIIa receptor antagonists following intracoronary stent implantation.
Effects of Soy Phytoestrogens Genistein and Daidzein on Breast Cancer Growth
Authors: de Lemos Mário L
Published: June 2003

OBJECTIVE:

To determine whether genistein and daidzein, the major phytoestrogens in soy, can stimulate breast cancer growth.

DATA SYNTHESIS:

Systematic search through primary English-language literature on MEDLINE (1966–January 2001), EMBASE (1982–January 2001) and Current Contents (1998–January 2001).

DATA SOURCES:

Genistein and daidzein at low concentrations were found to stimulate breast tumor growth in in vitro and in vivo animal studies, and antagonize the antitumor effect of tamoxifen in vitro. At high concentrations, genistein inhibited tumor growth and enhanced the effect of tamoxifen in vitro.

CONCLUSIONS:

Genistein and daidzein may stimulate existing breast tumor growth and antagonize the effects of tamoxifen. Women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products.
Pharmacotherapy Consultation on Polypharmacy Patients in Ambulatory Care
Authors: Jameson John P , VanNoord Glenn R
Published: June 2003

OBJECTIVE:

To investigate actual cost and adverse effect outcomes associated with a pharmacotherapy consultation in ambulatory care patients receiving polypharmacy.

METHODS:

Patients receiving five or more chronic medications were randomized to receive pharmacotherapy consultation or usual medical care. Outcomes measured were changes in drug costs, medical costs, and drug-related symptoms six months after the consultation. Data were analyzed with unpaired Student's t-test for continuous data. χ2 Analysis was used for categorical data. Patients and physicians were surveyed about their perceptions of the consultations after the study period.

RESULTS:

Drug and medical costs did not differ before and after the consultation. More patients in the consultation group had adverse symptom scores improve by two or more points, and fewer had symptom scores worsen by two or more points than in the control group. Seventy percent of patients and 76% of physicians believed that the consult was beneficial.

CONCLUSIONS:

Polypharmacy patients are the most likely to have drug-related problems and require intervention. Of all the interventions performed in this study, 73% of the original problems were recognized only through a patient interview, suggesting that an interpersonal relationship remains critical to the provision of pharmaceutical care. Although patients and physicians see intuitive value in pharmaceutical care, pharmacists need to exert more energy in the direction of marketing the profession. Finally, there are numerous difficulties in measuring the benefits of these interventions, possibly making broad-based interventions in complicated patients too difficult to assess accurately. Future studies should focus on patients with limited, specific problems or on interventions with narrow goals.
Amphotericin B—Induced Seizures in a Patient with AIDS
Authors: Aruna Augustine S , AL-Samarrai Shatha A , AL-Humaidan Abdullah S
Published: June 2003

OBJECTIVE:

To report a case of multiple episodes of seizure activity in an AIDS patient following amphotericin B infusion.

CASE SUMMARY:

A 46-year-old African-American man experienced recurrent grand mal seizures during intravenous infusion of amphotericin B, then petit mal seizures as the infusion was stopped and the drug concentrations decreased with time. The patient's concurrent medications included didanosine, hydroxyzine, promethazine, hydrocortisone, and prochlorperazine. Despite administration of phenytoin and lorazepam, the seizures persisted and occurred only during amphotericin B administration.

DISCUSSION:

AIDS and cryptococcal meningitis, both of which the patient had, can potentially cause seizures. The patient had a history of alcohol abuse; alcohol intake as well as withdrawal can also cause seizures. Didanosine also has a potential for inducing seizures. However, these other potential causes of seizure were ruled out. The time course of events suggested that amphotericin B was the cause of the seizures in this AIDS patient.

CONCLUSIONS:

Amphotericin B seems to be the probable cause of the seizures. To date, only three cases of seizures associated with amphotericin B have been reported in the literature, but healthcare providers should be aware of the potential for this rare adverse effect.
Tacrolimus in Dermatologic Disorders
Authors: Skaehill Penny A
Published: June 2003

OBJECTIVE:

To review the data surrounding the use of tacrolimus for skin disorders.

DATA SOURCES:

Articles were obtained through a MEDLINE search of English-language literature (1990–May 2000); references of the retrieved publications were further reviewed for relevant literature.

STUDY SELECTION:

Original studies in humans regarding the use of tacrolimus for skin disorders were included.

DATA EXTRACTION:

The major outcomes extracted from the literature involved patient response to therapy and adverse effects.

DATA SYNTHESIS:

Tacrolimus offers an additional therapeutic approach to the treatment of immunologically based skin disorders. Controlled trials and case reports indicate topical tacrolimus is a safe and effective alternative treatment in patients with atopic dermatitis. Case reports document efficacy in recalcitrant pyoderma gangrenosum, mucosal lichen planus, and ichthyosis linearis circumflexa. Controlled trials and case reports indicate oral tacrolimus is effective in recalcitrant plaque psoriasis. Case reports document efficacy in recalcitrant pyoderma gangrenosum and leukocytoclastic vasculitis. The clinical utility of oral tacrolimus in skin disorders is limited due to potentially severe adverse effects such as infections, hypertension, hyperglycemia, hyperkalemia, nephrotoxicity, neurotoxicity, and increased risk of neoplasia.

CONCLUSIONS:

Most of the available data indicate short-term (3 wk to 3 mo) topical tacrolimus is a safe and effective treatment alternative for inflammatory skin disorders. Further study is needed to evaluate long-term safety and efficacy and to determine the best dosage regimen. Although oral tacrolimus has demonstrated efficacy in inflammatory skin disorders, the potential for serious adverse effects limits its utility to third-line therapy for patients who are resistant to, or intolerant of, conventional therapies.
Intravenous Itraconazole
Authors: Slain Douglas , Rogers P David , Cleary John D , Chapman Stanley W
Published: June 2003

OBJECTIVE:

To review the pharmacology, mycology, chemistry, pharmacokinetics, efficacy, safety, tolerability, dosage, administration, and economic issues of intravenous itraconazole.

DATA SOURCES:

A MEDLINE search from 1978 to June 2000 of the English-language literature and an extensive review of meeting abstracts was conducted. Due to the paucity of published information concerning the pharmacokinetics, efficacy, and safety of the intravenous formulation of intravenous itraconazole, additional information was obtained from the manufacturer.

DATA EXTRACTION:

Data from in vitro and preclinical studies, as well as Phase II and III clinical trials, were included.

DATA SYNTHESIS:

The triazole antifungal agent itraconazole is available in a cyclodextrin-based intravenous formulation. Intravenous itraconazole is indicated for the treatment of pulmonary and extrapulmonary blastomycosis; histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis; and pulmonary and extrapulmonary aspergillosis in patients who are intolerant of or who are refractory to amphotericin B. This formulation provides quicker and more consistent therapeutic concentrations than the oral formulations. Clinical data comparing the efficacy of intravenous itraconazole with that of amphotericin B are lacking.

CONCLUSIONS:

Intravenous itraconazole offers a less toxic alternative for patients with pulmonary and extrapulmonary blastomycosis, histoplasmosis, and aspergillosis who cannot receive oral medications or who are intolerant of or refractory to amphotericin B.
Topical Phenytoin Treatment of Stage II Decubitus Ulcers in the Elderly
Authors: Rhodes Richard S , Heyneman Catherine A , Culbertson Vaughn L , Wilson Susan E , Phatak Hemant M
Published: June 2003

OBJECTIVE:

To compare the healing of stage II decubitus ulcers with topically applied phenytoin sodium with two other standard topical treatment procedures in a long-term care setting; and to assess the extent of systemic absorption after topical application in the phenytoin group.

METHODS:

Forty-seven nursing home patients with stage II decubitus ulcers were chosen for this study. The patients were matched for age, gender, and size and severity of wounds, and randomly assigned to each treatment group. Clinical assessment of decubitus ulcers was performed at the beginning of treatment and at each dressing change. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Two phenytoin sodium plasma concentrations were to be obtained on all patients in the phenytoin group.

RESULTS:

Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications (p ⩽ 0.05). The mean ± SD time to healing in the phenytoin group was 35.3 ± 14.3 days compared with 51.8 ± 19.6 and 53.8 ± 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within two to seven days in all subjects. Patients in the standard treatment groups required six to 21 days to produce new granulation tissue. Serum phenytoin sodium concentrations were nondetectable. No patient withdrew from the study secondary to adverse treatment effects.

CONCLUSIONS:

Both the phenytoin and standard treatment groups showed progress over the study period. However, the phenytoin group demonstrated more rapid results in all aspects of ulcer healing.
Linear Immunoglobulin a Bullous Dermatosis Induced by Gemcitabine
Authors: Pozo Jesús del , Martínez Walter , Yebra-Pimentel María T , Almagro Manuel , Peña-Penabad Carmen , Fonseca Eduardo
Published: June 2003

OBJECTIVE:

To report a case of linear immunoglobulin (Ig) A bullous dermatosis (LABD) induced by gemcitabine.

CASE SUMMARY:

A 59-year-old man was diagnosed with squamous-cell carcinoma of the lung in T4N2M0 stage and treated with cisplatin, vinorelbine, and gemcitabine. Twenty-four hours after the administration of gemcitabine, a symmetric, bullous, herpetiform eruption appeared on his trunk and upper limbs. Histopathologic examination and direct immunofluorescence test were consistent with IgA bullous dermatosis. Cutaneous lesions resolved two weeks after the drug was withdrawn and topical steroid treatment was instituted.

DISCUSSION:

Drug-induced LABD is a variant of classic or idiopathic LABD. Vancomycin is the most frequently implicated drug, but other agents have been reported to cause LABD. According to the Naranjo probability scale, the relationship of gemcitabine treatment with cutaneous eruption in our patient is possible.

CONCLUSIONS:

We report the first case of gemcitabine-induced LABD. Clinicians should monitor patients receiving this drug for signs of LABD.
Blood Pressure Monitoring with Home Monitors versus Mercury Sphygmomanometer
Authors: Rotch Allison L , Dean Joseph O , Kendrach Michael G , Wright Stephanie Gooch , Woolley Thomas W
Published: June 2003

OBJECTIVE:

To determine the accuracy of three automatic monitors (arm, wrist, finger) for blood pressure measurement manufactured by Omron compared with a standard mercury sphygmomanometer.

PRIMARY END POINT:

Difference in the mean blood pressure readings from each monitor; the secondary end point was difference in pulse readings.

DESIGN:

A single-visit, crossover trial tested each device twice on the left arm of each participant; the average of the two readings was recorded. The pulse readings from each monitor were also recorded. ANOVA was used to compare mean blood pressure readings and pulse readings from each device.

RESULTS:

A total of 55 persons (mean age 53 y; 36 women) met inclusion criteria and completed the study. The mean systolic and diastolic readings obtained from the electronic arm unit were comparable to the mercury readings (124.4/78.02 vs. 129.45/77.87 mm Hg, respectively; p > 0.05 for both readings). The mean results obtained from the wrist and finger monitors differed significantly from those of the mercury readings (145.44/89.58 and 113.94/69.07 mm Hg, respectively; p < 0.05 for both monitors compared with control). No difference was measured in the mean pulse readings between the comparisons (p = 0.72). The absolute difference in systolic and diastolic blood pressure readings from control varied the least with the arm monitor.

CONCLUSIONS:

Compared with the mercury sphygmomanometer, the arm monitor was the most accurate in measuring blood pressure. The wrist and finger monitors resulted in statistically significant mean systolic and diastolic differences compared with the mercury sphygmomanometer.
Newer Dopamine Agonists in the Treatment of Restless Legs Syndrome
Authors: Weimerskirch Patti R , Ernst Michael E
Published: June 2003

OBJECTIVE:

To review the use of newer dopamine agonists, pramipexole and ropinirole, in the treatment of restless legs syndrome (RLS).

DATA SOURCES:

Biomedical literature was accessed through MEDLINE (1990–June 2000); key terms included restless legs syndrome, pramipexole, ropinirole, and dopamine agonists. References cited in those articles were also evaluated.

DATA SYNTHESIS:

A number of small clinical studies of short duration have examined the use of pramipexole and ropinirole in the treatment of RLS. Patients treated with either agent demonstrated marked improvement in RLS symptoms with minimal adverse effects. Recent postmarketing surveillance of the use of these drugs for Parkinson's disease reported problems with daytime somnolence; thus, patients should be counseled appropriately.

CONCLUSIONS:

Although the published trials show promising results for efficacy of pramipexole and ropinirole in the treatment of RLS, they are subject to many limitations. At present, these agents can be considered a reasonable alternative after failure of traditional therapies for RLS, such as carbidopa/levodopa. The encouraging results underscore the need for a large, double-blind study comparing pramipexole and ropinirole with traditional agents.