bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe Cellulitis/Myositis Caused by Stenotrophomonas Maltophilia
Authors: Downhour Nathan P , Petersen Eskild A , Krueger Todd S , Tangella Krishnarao V , Nix David E
Published: June 2003

OBJECTIVE:

To present a case of cellulitis/myositis due to Stenotrophomonas maltophilia in the absence of trauma and to discuss a potentially novel treatment option.

CASE SUMMARY:

A 57-year-old white man, having undergone an allogeneic bone marrow transplant, developed myositis with S. maltophilia of the left soleus muscle; there had been no trauma. Risk factors for infection included neutropenia, prolonged hospitalization and intensive care unit stay, and broad-spectrum antibiotic exposure. The affected area of muscle was resected and the patient successfully treated with trimethoprim/sulfamethoxazole (TMP/SMX), ticarcillin/clavulanate, and aztreonam.

DISCUSSION:

In severe myositis/cellulitis caused by S. maltophilia, TMP/SMX is considered the drug of choice. However, bacteriostatic agents such as TMP/SMX are less than ideal in neutropenic patients. The combination of ticarcillin/clavulanate plus aztreonam has been shown to improve activity in vitro against this organism compared with TMP/SMX. This is likely due to inhibition of the 2 β-lactamases this organism produces by clavulanate and aztreonam. In our study of clinical isolates of S. maltophilia, this combination reduced the minimum inhibitory concentration at 90% by 128-fold and was synergistic against 10 of 12 isolates tested in time—kill analysis.

CONCLUSIONS:

S. maltophilia is emerging as an important pathogen in patients with compromised immunity, leading to severe infections that are difficult to treat. Based on in vitro synergy studied, we recommend considering ticarcillin/clavulanate plus aztreonam as a potential treatment option in immunocompromised patients with S. maltophilia infection.
Brasofensine Treatment for Parkinson's Disease in Combination with Levodopa/Carbidopa
Authors: Frackiewicz Edyta J , Jhee Stanford S , Shiovitz Thomas M , Webster Jonathan , Topham Christine , Dockens Randy C , Whigan Daisy , Salazar Daniel E , Cutler Neal R
Published: June 2003

OBJECTIVE:

To investigate the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the dopamine transporter antagonist brasofensine (BMS-204756) in patients with Parkinson's disease receiving levodopa/carbidopa treatment.

METHODS:

A 4-period crossover study was performed in 8 men (mean age 66 y) with moderate Parkinson's disease (Hoehn—Yahr stage II—IV). A dose escalation study was used in which each patient was given a single oral dose of brasofensine 0.5, 1, 2, or 4 mg, which was coadministered with the patient's usual dose of levodopa/carbidopa.

RESULTS:

The maximum concentration (Cmax) values of brasofensine observed in plasma after oral administration were 0.35, 0.82, 2.14, and 3.27 ng/mL for the 0.5-, 1-, 2-, and 4-mg doses, respectively; these concentrations occurred 4 hours (time to Cmax) after administration in all cases. Exposure to brasofensine (based on AUC0-∞) increased at a rate greater than proportional to dose. Based on the motor performance subscale of the Unified Parkinson's Disease Rating Scale, no change in patient disability was observed at any dose level.

CONCLUSIONS:

Brasofensine was safe and well tolerated in the patient cohort studied at daily doses of up to 4 mg. Adverse events were generally mild in intensity, and included headache, insomnia, phlebitis, dizziness, ecchymosis, and vomiting.
Development of a Pharmacist-Managed Lipid Clinic
Authors: Cording Margaret A , Engelbrecht-Zadvorny Emily B , Pettit B Jill , Eastham John H , Sandoval Rheta
Published: June 2003

OBJECTIVE:

To describe the development of a pharmacist-managed lipid clinic within a primary care medical clinic and review its results after approximately 12 months of operation.

METHODS:

A pharmacist-managed lipid clinic was developed at Naval Medical Center San Diego. Administrative background, treatment algorithm development, operational issues, clinical activities, and barriers to the clinic are discussed. For intermediate outcomes, data from patients who had at least 1 intervention by the pharmacist and 1 follow-up lipid panel were analyzed for medication use, changes in lipid parameters, and percent reaching the low-density-lipoprotein (LDL) target goal. Modified National Cholesterol Education Program — Adult Treatment Panel II guidelines were used to determine the LDL goal.

RESULTS:

Following approximately 12 months of operation, the clinic received 204 referrals and consisted of 146 active patients. A brief study was conducted to assess clinical outcomes. Of 115 patients who were seen in the clinic and met inclusion criteria, 57% were receiving treatment with a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) and 17% were receiving fibrates; 17% of the patients were not receiving lipid-lowering medications. Relative to baseline, LDL cholesterol concentrations decreased 20%, high-density-lipoprotein cholesterol increased 11%, and triglycerides decreased 19%. Overall, LDL goals were reached in 77% of the patients. LDL goals were attained by 63%, 79%, and 93% of patients with targets of <100, <130, and <160 mg/dL, respectively. Results are compared with other studies regarding lipid goal attainment.

CONCLUSIONS:

A pharmacist-managed lipid clinic can be developed and integrated into a primary care medical clinic. Pharmacists can effectively manage lipid-lowering therapy, helping to achieve LDL goals.
Treatment of Clostridium Difficile-Associated Diarrhea
Authors: Malnick Stephen DH , Zimhony Oren
Published: June 2003

OBJECTIVE:

To review the literature related to the treatment and infection control of Clostridium difficile-associated diarrhea (CDAD).

DATA SOURCES:

A MEDLINE search (1966–August 2001) of the English literature was conducted.

DATA SYNTHESIS:

C. difficile is a leading cause of antibiotic-related diarrhea. The clinical spectrum extends from simple diarrhea to fulminant colitis. Cessation of antibiotic therapy alone is sufficient for mild cases; however, the majority of cases require oral metronidazole as the drug of choice. Vancomycin orally is reserved for patients who have failed to respond to metronidazole, are pregnant, or are severely ill. There is an important role for infection control interventions.

CONCLUSIONS:

CDAD is a common infection. Appropriate antibiotic treatment and infection control policies can prevent the spread and reduce the morbidity associated with this disease.
Flavopiridol, a Novel Cyclin-Dependent Kinase Inhibitor, in Clinical Development
Authors: Zhai Suoping , Senderowicz Adrian M , Sausville Edward A , Figg William D
Published: June 2003

OBJECTIVE:

To review preclinical and clinical information on flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs), tested as an antitumor agent.

DATA SOURCES:

Primary and review articles were identified by MEDLINE search (1990–June 2001). Abstracts from recent meetings were also used as source materials.

DATA EXTRACTION:

Flavopiridol was reviewed with regard to its mechanisms, preclinical and clinical results, pharmacokinetics, and metabolism.

DATA SYNTHESIS:

Flavopiridol is an inhibitor of several CDKs and displays unique anticancer properties. In addition to direct CDK inhibition, flavopiridol also exhibited other features such as inducing apoptosis in many cancer cell lines, decreasing cyclin D1 concentration, and inhibiting angiogenesis. Preclinical xenograft models showed significant antitumor activity for flavopiridol. The regimen using 72-hour continuous infusion every 2 weeks has been most extensively applied in clinical trials, with a 1-hour infusion currently being explored to achieve higher peak concentrations. Several Phase I and II trials have been reported, with some evidence of antitumor activity noted. Further Phase I and II trials using flavopiridol as a single agent and in combination with standard chemotherapeutic regimens and various tumor types are ongoing.

CONCLUSIONS:

Flavopiridol is the first CDK inhibitor to enter clinical trials. Several Phase I and Phase II clinical trials with different regimens (72-h or 1-h infusion) have been completed. Initial clinical trials have been intriguing, but many questions remain: What is the best regimen (≤72-h infusion)? Does optimal future development of this drug depend on the combination with other chemotherapy? What is the best combination of flavopiridol with other chemotherapy?
Surrogate End Points in Heart Failure
Authors: Lee Craig R , Adams Kirkwood F , Patterson J Herbert
Published: June 2003

OBJECTIVE:

To describe the potential utility of a true surrogate marker of heart failure outcomes, historically investigate the validity of surrogates most commonly evaluated in heart failure, and identify specific end points offering the most potential for future use.

DATA SOURCES:

A MEDLINE search (1966–June 2001) was completed to identify relevant literature. Additional references were also retrieved from selected articles. Search terms included b-type natriuretic peptide, cardiac remodeling, end-diastolic volume, heart failure, and surrogate end points.

DATA SYNTHESIS:

By definition, true surrogate end points must predict outcomes associated with disease progression and response to therapy. A validated surrogate measure of mortality would render significant utility in both heart failure drug development and clinical practice. Improvements in traditional functional markers of heart failure, including ejection fraction and exercise capacity, have produced inconsistent results in regard to mortality in a number of clinical trials. Numerous measures of cardiac remodeling and neurohormonal activation, however, have proven to be reliable predictors of disease progression and therapeutic response. These findings have contributed significantly to the current understanding of heart failure pathophysiology and approach to treatment. Specifically, measures such as left-ventricular end-diastolic volume (LVEDV) and, potentially, b-type natriuretic peptide (BNP) concentrations may correlate with disease progression and parallel the mortality reductions observed with angiotensin-converting enzyme inhibitor and β-blocker therapy.

CONCLUSIONS:

Currently, LVEDV and plasma BNP offer the greatest potential as surrogate end points in heart failure. Further investigation of these measures is required before routine implementation in drug development and clinical practice can be justified.
Prostaglandin Analog Treatment of Glaucoma and Ocular Hypertension
Authors: Alexander Christy L , Miller Sarah J , Abel Steven R
Published: June 2003

OBJECTIVE:

To review available data related to the use of prostaglandin analogs (bimatoprost, latanoprost, travoprost, unoprostone) in the management of ocular hypertension and open-angle glaucoma.

DATA SOURCES:

Primary and review articles were identified from a MEDLINE search (1966–May 2001) and requested information from product manufacturers.

STUDY SELECTION AND DATA EXTRACTION:

All available information, including that published in articles and abstracts, which was deemed relevant was included in this review. Limited data have been published to date.

DATA SYNTHESIS:

The prostaglandin analogs appear to be effective, well-tolerated agents for the reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma and ocular hypertension. This drug class offers an alternative for patients who do not achieve control with another topical antiglaucoma agent or for those with a contraindication to first-line therapy with β-adrenergic antagonists. Based on preliminary clinical data, bimatoprost, latanoprost, and travoprost appear to be at least as effective as timolol, while the effectiveness of unoprostone is similar or slightly less. Prostaglandin analogs may be used in conjunction with other antiglaucoma medications, although further studies must establish the optimal combination. Whether clinical experience will yield outcomes in favor of one of the prostaglandin analogs remains to be determined. Patients should be educated on adverse events associated with prostaglandin analogs, particularly the potential for changes in the pigmentation of the iris and eyelashes.

CONCLUSIONS:

Bimatoprost, latanoprost, and travoprost appear to be equivalent to the current standard of therapy in the topical treatment of elevated IOP. Further clinical data published in article versus abstract format is required to better assess potential differences among these 3 agents.
Pancreatitis Associated with Simvastatin Plus Fenofibrate
Authors: McDonald Kevin B , Garber Bryan G , Perreault Marc M
Published: June 2003

OBJECTIVE:

To report a case of acute necrotizing pancreatitis associated with simvastatin and fenofibrate use.

CASE SUMMARY:

A 70-year-old white man presenting with rapid onset of abdominal pain, nausea, and vomiting was diagnosed with acute pancreatitis. On bowel rest, his condition deteriorated secondary to systemic inflammatory response syndrome, and he was transferred to a tertiary hospital's intensive care unit (ICU). He had been taking fenofibrate for 1 year; 6 months prior to this admission, he had been taking simvastatin 3 days of the week and fenofibrate the other 4 days of the week. The pancreatic tissue became necrotic, requiring surgical debridement. After a hospital stay of 121 days, including multiple ICU admissions, the patient died secondary to a bowel perforation.

DISCUSSION:

Although idiopathic pancreatitis cannot be ruled out in this patient, no causes of pancreatitis were identified other than drug induced. Five cases of acute pancreatitis caused by simvastatin have been reported; no case reports were found for fenofibrate. The onset of pancreatitis relative to the duration of therapy with simvastatin supports this medication as a possible cause of the pancreatitis.

CONCLUSIONS:

Drug-induced pancreatitis is well established as an adverse effect of some medications, although most are substantiated only with case reports. Given the absence of other apparent causes, simvastatin and fenofibrate should be considered as possible causes of pancreatitis in this patient.
Inhibition of Warfarin Activity by Ribavirin
Authors: Schulman Sam
Published: June 2003

OBJECTIVE:

To report a case of inhibition of the effect of warfarin during treatment with ribavirin.

CASE SUMMARY:

A 61-year-old white man received combination treatment with interferon and ribavirin during 1 year for chronic hepatitis C. He was on permanent anticoagulant therapy with warfarin after a previous heart valve replacement. The dose of warfarin had to be increased by approximately 40% to maintain the desired level of anticoagulation.

DISCUSSION:

Interferon has previously been reported to potentiate the effect of warfarin. This is the first case published in the English-language literature describing an inhibition of the effect of warfarin by the combination of interferon and ribavirin. A rechallenge with ribavirin demonstrated that the inhibition of warfarin could be reproduced. The mechanism for this interaction is unclear. The pharmacokinetics of ribavirin and the potential pathways for interaction are discussed.

CONCLUSIONS:

During 4 weeks after starting or discontinuing treatment with ribavirin, prothrombin time may be affected in patients receiving warfarin for anticoagulation. It seems prudent to monitor warfarin therapy more frequently during those periods.
Pharmacokinetics and Tolerability of Lidocaine Patch 5% with Extended Dosing
Authors: Gammaitoni Arnold R , Davis Matthew W
Published: June 2003

OBJECTIVE:

To assess the pharmacokinetics, safety, and tolerability of lidocaine delivered via 4 lidocaine 5% patches applied for 18 h/d for 3 consecutive days in healthy volunteers.

METHODS:

A prospective, nonrandomized, open-label trial was conducted to determine the pharmacokinetics of 4 lidocaine patches 5% applied to the backs of 20 volunteers on days 1, 2, and 3. On each day, serum samples were collected prior to, during, and after patch application. Safety and tolerability assessments included skin evaluations, monitoring of clinical adverse events and vital signs, 12-lead electrocardiograms, and laboratory testing.

RESULTS:

For days 1, 2, and 3, the mean ± SD maximum concentrations were 145.1 ± 42.4, 153.0 ± 40.7, and 153.8 ± 51.4 ng/mL, respectively; the median × to peak plasma concentration were 18.0, 16.5, and 16.5 hours, respectively; the mean ± SD trough concentrations were 83.0 ± 29.0, 85.7 ± 31.1, and 77.0 ± 26.9 ng/mL, respectively; and the mean ± SD AUCs over 24 hours were 2089.2 ± 632.5, 2659.2 ± 726.8, and 2675.7 ± 819.2 ng ± h/mL, respectively. The patch was well tolerated; local skin reactions were generally minimal and self-limited.

CONCLUSIONS:

The application of 4 lidocaine patches 5% for 18 h/d for 3 consecutive days is well tolerated; steady-state plasma concentrations are achieved within 3 days. Maximum plasma concentrations of lidocaine are similar to those reported in a previous study with 3 lidocaine patches 5% applied for 12 h/d for 3 consecutive days.
High-Dose Oral Magnesium Treatment of Chronic, Intractable Erythromelalgia
Authors: Cohen Jay S
Published: June 2003

BACKGROUND:

Previous studies with magnesium have shown beneficial effects in pain syndromes and in vascular disorders (hypertension, migraines, Raynaud's phenomenon). However, results have been variable, possibly because of the limited oral doses achievable due to frequent diarrhea.

OBJECTIVE:

To describe the case of a 53-year-old white man (the author) with disabling erythromelalgia (EM) who achieved modest improvement limited by adverse effects with calcium antagonists and then obtained remission with the use of magnesium. Intolerant of several standard magnesium products, he attained high doses of magnesium by taking intravenous-grade magnesium sulfate diluted in water orally (up to 24 mL/d of MgSO4 50% = 1166 mg/d of magnesium).

METHODS:

After 12 months of continued improvement, patient 1, a board member of The Erythromelalgia Association, notified other members of the success of this therapy via an Internet communication channel. He encouraged those interested in high-dose magnesium therapy to consult their physicians and to report their results to the Association. Twelve patients responded to this request, describing several standard oral magnesium products.

RESULTS:

Overall, 8 of 13 patients (61.5%) reported improvement (1, remission; 3, major improvement; 2, moderate improvement; 2, mild improvement). Four patients (30.8%) reported no response to magnesium therapy, and 1 patient's symptoms worsened. Two patients' magnesium dose was limited because of diarrhea.

CONCLUSIONS:

Despite recent progress in understanding and treating EM, this vascular disorder remains painful and life-altering for many patients. In this informal survey, the use of high oral doses of magnesium produced good and sometimes dramatic results in 8 of 13 patients who had been unresponsive to many other treatments. These results suggest a possible role for high-dose oral magnesium in the treatment of EM and, perhaps, other vascular disorders.
Pirarubicin-Based versus Doxorubicin-Based Osteosarcoma Chemotherapy
Authors: Shinozaki Tetsuya , Watanabe Hideomi , Yanagawa Takashi , Shirakura Kenji , Takagishi Kenji
Published: June 2003

OBJECTIVE:

To conduct a retrospective evaluation of tetrahydropyranyladriamycin (PIR)-based combination chemotherapy for osteosarcomas in comparison with doxorubicin (DOX)-based regimens to determine differences in response and toxicities between DOX- and PIR-containing regimens.

METHODS:

Toxicities and response rates of the 2 anthracyclines given as combination chemotherapy were assessed in patients with osteosarcoma, with 19 patients receiving PIR-based and 11 receiving DOX-based regimens.

RESULTS:

The survival of osteosarcoma patients treated with PIR was significantly better than that with DOX (p = 0.023) based on 2-year follow-up. Adverse effects such as mucositis and diarrhea were also less pronounced in the PIR cohort.

CONCLUSIONS:

PIR-based combination chemotherapy might be a useful and safe chemotherapeutic strategy for osteosarcomas compared with DOX regimens. Further assessment is necessary to confirm the safety and efficacy of this treatment.
Management of Acute, Severe Asthma in Children
Authors: Streetman Darcie D , Bhatt-Mehta Varsha , Johnson Cary E
Published: June 2003

OBJECTIVE:

To briefly present the current options available for the treatment of acute, severe asthma in children, with a special focus on emergency department and inpatient treatment, and to describe newer therapies that may aid treatment in the future.

DATA SOURCES AND STUDY SELECTION:

A MEDLINE search (1966–May 2001) of the English-language literature pertaining to drug therapy of acute asthma was performed. Key word searches included acute asthma, albuterol, ipratropium, corticosteroids, magnesium, and theophylline. Additional articles from these sources and published national guidelines were identified. Relevant studies pertaining to current therapy of acute asthma in pediatric patients were selected; if there were minimal pediatric data, adult data were included.

DATA SYNTHESIS:

Asthma is a chronic, inflammatory disorder of the airways. Acute exacerbations can occur and are challenging to manage. Albuterol, ipratropium, and systemic corticosteroids have been shown to be effective in acute asthma exacerbations. Because some patients do not respond to maximal therapy, older therapies such as magnesium and theophylline are being reevaluated. Theophylline may have some therapeutic effect, but given its toxicity profile, it is unclear whether it offers any advantage over maximal β2-agonist therapy. There are only minimal published data evaluating the use of magnesium in pediatrics, and most are small trials or case reports. Newer therapies such as ventilation strategies with heliox and intravenous leukotriene modifiers currently being evaluated may or may not prove to be beneficial in the future.

CONCLUSIONS:

β2-agonists, ipratropium, and corticosteroids remain the most useful therapeutic agents for acute asthma exacerbations in pediatric patients. However, these agents are not ideal in all patients and, given the existing questions regarding safety and/or efficacy of available alternatives, more effective options are needed.
Amphotericin B Lipid Complex for Hansenula Anomala Pneumonia
Authors: Kane Sandra L , Dasta Joseph F , Cook Charles H
Published: June 2003

OBJECTIVE:

To document the first successful treatment of a patient with Hansenula anomala pneumonia.

CASE SUMMARY:

A healthy 32-year-old white man who underwent splenectomy and aortic repair following a motor vehicle accident developed a life-threatening infection 2 days after admission into the intensive care unit (ICU). A rare fungus, H. anomala, was isolated from his lungs, blood, and urine. Lipid complex amphotericin B (ABLC) was initiated following worsening signs of infection complicated by renal failure. The patient received ABLC for 17 days, eventually making a full recovery, allowing ICU discharge 1 month after admission.

DISCUSSION:

This case represents the first successful treatment of H. anomala pneumonia reported in the literature. H. anomala infections typically occur in immunocompromised, neonatal, or pediatric populations in extrapulmonary sites. All 6 cases of H. anomala pneumonia reported in the literature were fatal, and all preceded the availability of ABLC. This case of H. anomala pneumonia is unique because our adult patient survived possibly due to the availability of aggressive treatment.

CONCLUSIONS:

ABLC may be the agent of choice for treatment of H. anomala infections, particularly in patients with acute renal failure.
Herbal Supplement PC-Spes for Prostate Cancer
Authors: de Lemos Mário L
Published: June 2003

OBJECTIVE:

To determine the efficacy and toxicity of the herbal supplement PC-Spes in prostate cancer patients.

METHODS:

Literature search through MEDLINE (1966–October 2001), PubMed, and abstracts from the Annual Meeting of the American Society of Clinical Oncology (1995–2001).

RESULTS:

PC-Spes was associated with biochemical and clinical response in some prostate cancer patients. The mechanisms of action of PC-Spes appeared to be related to its estrogenic activity.

CONCLUSIONS:

PC-Spes is associated with some efficacy in prostate cancer patients. Due to the limited data available, it should not be used to replace standard androgen suppression therapy in androgen-dependent patients. PC-Spes may have a role for patients who have failed standard treatments for androgen-independent disease and have no history of thromboembolism or abnormal bleeding. PC-Spes has a toxicity profile similar to those of androgen suppression and estrogen therapy.
Pharmacology and Clinical Use of Bivalirudin
Authors: Sciulli Tina M , Mauro Vincent F
Published: June 2003

OBJECTIVE:

To review the primary literature describing the pharmacology and clinical uses of bivalirudin.

DATA SOURCES:

A MEDLINE search (January 1966–May 2001) was conducted that used bivalirudin, hirulog, and direct thrombin inhibitor as key words. References from retrieved articles and unpublished information acquired from the manufacturer and the Internet were also used.

STUDY SELECTION:

All acquired articles that discussed the pharmacology, pharmacokinetics, and clinical efficacy of bivalirudin were reviewed.

DATA EXTRACTION:

Articles were selected based on content regarding the pharmacology and clinical use of bivalirudin. Given the paucity of data pertaining to the clinical use of bivalirudin, most articles were used, including abstracts and communications with the manufacturer.

DATA SYNTHESIS:

Bivalirudin is a direct thrombin inhibitor that inactivates both unbound and fibrin-bound thrombin. Bivalirudin rapidly induces anticoagulation and has a relatively short duration of action. Bivalirudin displays linear kinetics and is primarily eliminated renally. Bivalirudin was proven effective in preventing postprocedural ischemic complications in patients with unstable or postinfarction angina who received percutaneous transluminal coronary angioplasty (PTCA). Yet, further investigations that include less critically ill patients and use the current clinical practice of administering glycoprotein IIb/IIIa antagonists and/or inserting intracoronary stents are needed to fully evaluate its efficacy. Bivalirudin has also induced early patency in patients with myocardial infarction in combination with streptokinase, but its use with newer thrombolytics needs to be studied. Bivalirudin has been used in patients with immunologically mediated, heparin-induced thrombocytopenia (HIT) without complications. Bleeding is the major adverse effect and occurs more commonly in patients with renal dysfunction.

CONCLUSIONS:

At present, bivalirudin is worthy of consideration in patients requiring PTCA who have HIT. Advocating the routine use of bivalirudin in patients experiencing an acute coronary syndrome or HIT is premature.
Relationship Between Patients’ Warfarin Knowledge and Anticoagulation Control
Authors: Tang Elaine Othilia YL , Lai Cemen SM , Lee Kenneth KC , Wong Raymond SM , Cheng Gregory , Chan Thomas YK
Published: June 2003

OBJECTIVE

To evaluate patients’ knowledge of warfarin and its relationship to anticoagulation control.

METHODS

From January to March 1999, 122 patients attending the warfarin clinic of the Prince of Wales Hospital in Hong Kong were interviewed. Their knowledge of warfarin therapy and adherence to medical advice were tested by 9 questions. A score (maximum 1.0) was calculated for each patient. The number of international normalized ratios (INRs) that was within the target range in the 4 most recent clinic visits was noted.

RESULTS

Fifty-six men and 66 women participated in the study (mean ± SD age 58.0 ± 13.0, duration of treatment 43.1 ± 39.8 mo). Patients’ warfarin knowledge was poor, with an overall score of 0.48 ± 0.18. Participants generally knew the colors of their warfarin tablets and took them regularly. They almost always informed their physicians and dentists of their warfarin therapy. Only 40–45% of patients knew the strengths of their warfarin tablets, the reason for taking warfarin, and its effect on the body. Their deficiencies in knowledge were even more obvious with respect to the possible consequences of under- or over-anticoagulation, drugs and medicated oils that might interact with warfarin, and management of a missed dose. Knowledge was related to age (r −0.43; p < 0.001) and duration of therapy (r 0.18; p = 0.044). Sixty patients (49.2%) had read the information booklet on warfarin and had better knowledge than those who had not (0.53 ± 0.20 vs. 0.42 ± 0.20; p < 0.001). Illiteracy was the main reason for not reading the booklet. There was a positive correlation between patients’ warfarin knowledge and the number of INR values that was within the target range in the 4 most recent clinic visits (r 0.20; p = 0.024).

CONCLUSIONS

Patients’ warfarin knowledge, a determinant of anticoagulation control, was generally poor. More attention should be given to the education of elderly and illiterate patients.
Hyperlipidemia in HIV-Positive Patients Receiving Antiretrovirals
Authors: Segarra-Newnham Marisel
Published: June 2003

OBJECTIVE:

To assess the frequency of lipid abnormalities and treatment outcomes for hyperlipidemia in HIV-positive patients receiving antiretroviral (ARV) therapy as outpatients at a Veterans Affairs HIV clinic.

METHODS:

All patients monitored for at least 3 months were reviewed. Data collected included age, most recent CD4+ cell count and viral load, ARV history, and all fasting cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) values. The ARV therapy at the time of lipid readings was classified as including protease inhibitors (PI+) or not including them (PI-). Lipid values were compared with goals per national guidelines and risk factors.

RESULTS:

Male patients (n = 101) providing 210 lipid profiles were evaluated (median 2 per patient). Median age was 51 years. Fourteen patients were diabetic, 31 were hypertensive, and 6 patients had documented coronary disease. Mean cholesterol, triglycerides, and LDL values were significantly higher in PI+ (n = 50) compared with those of PI- patients (n = 51; p < 0.05). HDL values were not different between groups. Significantly more PI+ patients had lipid concentrations above recommended goals compared with PI- patients (17 vs. 7; p = 0.04). Six patients achieved lipid goals after following a low-fat diet (4 PI+). Fifteen subjects (11 PI+) were being treated with medications. Ten patients (67%) reached lipid goals, 2 had not reached goals (13%), and 3 (20%) were undergoing medication titration.

CONCLUSIONS:

Our HIV-infected patients had significantly higher cholesterol, triglyceride, and LDL values when PI+. In contrast to other reports, the majority of patients treated for lipid abnormalities achieved treatment goals.
Toxic Epidermal Necrolysis Associated with Interleukin-2
Authors: Huerta Angel A Segura , Tordera Pablo , Cercós Ana C , Yuste Ana L , López-Tendero Pedro , Reynés Gaspar
Published: June 2003

BACKGROUND:

Metastatic renal cell carcinoma (MRCC) has been characteristically unresponsive to chemotherapy. In lieu of an effective regimen, interleukin-2 (IL-2) and interferon alfa are considered drugs of choice to treat this cancer. Subcutaneous IL-2 is safe and well tolerated, with a mortality rate <3%.

OBJECTIVE:

To report a case of cutaneous and hematologic toxicity in a patient treated with IL-2.

CASE SUMMARY:

A 67-year-old woman received radiotherapy and immunotherapy for cancer that had metastasized to the bone and lungs. IL-2 was part of the regimen. After 5 days of treatment with IL-2, the patient developed a hemorrhagic lesion that progressed to toxic epidermal necrolysis, as well as grade 4 pancytopenia. She died 10 days after treatment was begun. At the time of death, leukocytes were 0.3 × 103/mm3, platelets 10 × 103/mm3, and hemoglobin 6.8 mg/dL.

DISCUSSION:

Cutaneous IL-2 adverse effects are frequent, but generally mild and reversible. The adverse hematologic effects are usually transitory and pancytopenia is not frequent. The severity of cutaneous and hematologic toxicity experienced by our patient has rarely been reported.

CONCLUSIONS:

The use of IL-2 in bedridden patients with performance status >2 must be given on an individualized basis. If radiotherapy over extensive areas of the body is needed, the use of IL-2 must be postponed until radiotherapy is completed.
Low-Dose Ritonavir for Protease Inhibitor Pharmacokinetic Enhancement
Authors: Rathbun R Chris , Rossi Deanna R
Published: June 2003

OBJECTIVE:

To examine the use of low-dose ritonavir as a pharmacokinetic enhancer for HIV protease inhibitors.

DATA SOURCES:

Primary articles, review articles, and conference abstracts identified by MEDLINE search (1995–May 2001) and secondary sources.

DATA SYNTHESIS:

Low-dose ritonavir (100–200 mg) is increasingly being combined with HIV protease inhibitors to improve their effectiveness and allow less frequent dosing. An evaluation of the clinical evidence supporting this practice was conducted.

CONCLUSIONS:

Limited outcome data exist for low-dose ritonavir-based regimens in general. Although preliminary data appear promising, more clinical evidence is needed to determine the optimal dosing, long-term safety, and relative effectiveness of this approach. The role of these regimens in early therapy remains to be defined.
Treatment of Heparin-Induced Thrombocytopenia
Authors: Dager William E , White Richard H
Published: June 2003

OBJECTIVE:

To describe heparin-induced thrombocytopenia (HIT or HIT-2), an immune-mediated adverse reaction to heparin or low-molecular-weight heparin. Available treatment options and considerations in developing a therapy approach are discussed.

DATA SOURCES:

A search of the National Library of Medicine (1992–June 2001) was done to identify pertinent literature. Additional references were reviewed from selected articles.

STUDY SELECTION:

Articles related to laboratory recognition and treatment options of HIT, including the use of agents in selected clinical conditions, were reviewed and included.

CONCLUSIONS:

HIT is a rare but potentially severe adverse reaction to heparin that was, until recently, poorly understood and had limited treatment options. Recent advances describing the recognition and clinical manifestations of immune-mediated HIT, including recently available antithrombotic treatment options, have dramatically changed outcomes for patients having this syndrome.
New-Onset Seizure Associated with Quetiapine and Olanzapine
Authors: Hedges Dawson W , Jeppson Kreg G
Published: June 2003

OBJECTIVE:

To report a case involving a witnessed seizure in a patient receiving concurrent olanzapine and quetiapine.

CASE SUMMARY:

A 27-year-old white woman was observed to have a seizure while receiving a stable dosage of olanzapine 15 mg/d, with the addition of quetiapine 100 mg in the evening 1 day before the occurrence of the seizure. There were no known risk factors for epilepsy.

DISCUSSION:

This case reports a new-onset seizure in the context of concurrent olanzapine and quetiapine use. Interpretation is complicated by recent discontinuation of low-dose clonazepam.

CONCLUSIONS:

While uncommon, seizures can occur with non-clozapine atypical antipsychotics. Caution is indicated when using these drugs with other agents that may lower the seizure threshold.
Ototoxicity Induced by Gentamicin and Furosemide
Authors: Bates Duane E , Beaumont Steve J , Baylis Barry W
Published: June 2003

OBJECTIVE:

To present a case of ototoxicity induced by furosemide and once-daily gentamicin therapy.

CASE SUMMARY:

A 60-year-old white woman presented to the hospital with community-acquired pneumonia and urinary tract infection. The antibiotic regimen included gentamicin and, after 5 doses, the patient reported profound bilateral hearing loss. A Pure Tone Audiogram suggested moderate to moderately severe sensorineural hearing loss bilaterally. The only risk factors present included her age, elevated temperature, and the use of furosemide.

DISCUSSION:

Several risk factors may predispose a patient to developing aminoglycoside ototoxicity: the 1555 chromosomal mutation, preexisting disorders of hearing and balance, hypovolemia, bacteremia, liver and renal dysfunction, and the simultaneous administration of other ototoxic medications. The cumulative dose and duration of aminoglycoside therapy are more important than serum concentrations. Administration of an aminoglycoside followed by furosemide may increase the risk of ototoxicity. The aminoglycoside interacts with the cell membranes in the inner ear, increasing their permeability. This theoretically allows the loop diuretic to penetrate into the cells in higher concentrations, causing more severe damage.

CONCLUSIONS:

Auditory toxicity occurred after only 5 days of gentamicin therapy and 1 dose of furosemide. An aminoglycoside followed by furosemide may increase the risk for ototoxicity. Clinicians need to be aware of the synergistic potential of ototoxic medications.
Preventable Drug-Related Hospital Admissions
Authors: Winterstein Almut G , Sauer Brian C , Hepler Charles D , Poole Charles
Published: June 2003

OBJECTIVE:

To estimate the prevalence of preventable drug-related hospital admissions (PDRAs) and to explore if selected study characteristics affect prevalence estimates.

METHODS:

Keyword search of MEDLINE (1966–December 1999), International Pharmaceutical Abstracts (1970–December 1999), and hand search. Two reviewers independently selected studies published in peer-reviewed journals and extracted crude prevalence estimates and study characteristics. Trials had to specifically address consequences of drug therapy requiring hospital admission and include a quantitative preventability assessment. Stratified analysis and meta-regression were used to explore the association between study characteristics and prevalence estimates.

DATA SYNTHESIS:

Fifteen studies reported a median PDRA prevalence of 4.3% (interquartile range [IQR] 3.1–9.5%). The median preventability rate of drug-related admissions was 59% (IQR 50–73%). No evidence of publication bias related to study size could be determined. Because the individual study results were highly heterogeneous (Cochran's Q = 176, df = 14; p < 0.001), no meta-analytic summary estimate was computed. Stratified analysis suggested an association between prevalence estimates and 3 study characteristics: exclusion of first admissions (readmission studies: average PDRA prevalence of 14.0 %, estimated prevalence OR = 3.7); mean age of admissions >70 (OR = 2.1); and inclusion of “indirect” drug-related morbidity, such as omission errors or therapeutic failure (OR = 1.9). There was little evidence of other associations with prevalence estimates, such as selection of specific hospital units, exclusion/inclusion of planned admissions, country, and specified methods of PDRA case ascertainment.

CONCLUSIONS:

Drug-related morbidity is a significant healthcare problem, and a great proportion is preventable. Study methods in prevalence reports vary and should be considered when interpreting findings or planning future research.
Increased Lithium Dose Requirement in a Hyperglycemic Patient
Authors: Cyr Monica , Guia Melanie AC , Laizure S Casey
Published: June 2003

OBJECTIVE:

To report a case of apparent increased lithium clearance in a patient with persistent hyperglycemia.

METHODS:

Lithium doses, blood glucose concentrations, and lithium plasma concentrations were evaluated in a patient during a 53-day inpatient admission for exacerbation of bipolar disorder. The lithium dose required to increase the lithium plasma concentration by 0.1 mEq/L was computed from the lithium dose and corresponding lithium plasma concentration. This value was correlated with the blood glucose concentration.

RESULTS:

A plot of the lithium dose required to increase the lithium plasma concentration by 0.1 mEq/L versus the blood glucose concentration exhibited a direct linear relationship (r2 = 0.62). This plot indicates that higher lithium doses are needed during hyperglycemic states compared with euglycemic states to achieve equivalent plasma concentrations.

CONCLUSIONS:

Glycosuria associated with hyperglycemia induces an osmotic diuresis that increases the renal clearance of lithium, necessitating higher lithium doses to maintain therapeutic lithium plasma concentrations.
Herbs for Benign Prostatic Hyperplasia
Authors: Dvorkin Lana , Song Kathy Y
Published: June 2003

OBJECTIVE:

To review and evaluate the literature relative to the use of herbal therapies in the treatment of benign prostatic hyperplasia.

DATA SOURCES:

Literature was identified by MEDLINE, Embase, International Pharmaceutical Abstracts, and the International Bibliographic Information on Dietary Supplements searches and through cross-referencing of selected articles.

STUDY SELECTION/DATA EXTRACTION:

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

DATA SYNTHESIS:

A large percentage of men >50 years old begin to experience signs and symptoms of benign prostatic hyperplasia (BPH). Herbs hold promise in the treatment of BPH. Serenoa repens, Pygeum africanum, Urtica dioica radix, and Cucurbita peponis semen are some of the botanical therapies used in the treatment of BPH.

CONCLUSIONS:

There are many European studies examining efficacy, dose, and adverse effects of these plants in the treatment of BPH. However, numerous questions remain. These include issues concerning long-term beneficial and adverse effects of herbal therapy, prevention of complications, standardization of extracts, and concomitant use with “mainstream” medications. Based on the information available today, these botanical therapies can be used for treatment of a number of objective and subjective symptoms in patients with BPH, stages I and II.
Breast Enlargement Induced by D-Penicillamine
Authors: Tchebiner Joseph Z
Published: June 2003

OBJECTIVE:

To report a patient with reversible breast enlargement due to D-penicillamine treatment for scleroderma.

CASE SUMMARY:

A 55-year-old white woman developed enlarged breasts during D-penicillamine therapy for scleroderma. The enlargement regressed following discontinuation of the drug, and planned breast reduction surgery was avoided.

DISCUSSION:

D-Penicillamine has been used in the treatment of various diseases including scleroderma. Breast enlargement has been previously described as a rare adverse effect of this drug. The enlargement subsided following discontinuation of the medication.

CONCLUSIONS:

Attention is called to this rare adverse effect in an effort to avoid unnecessary diagnostic or therapeutic procedures, including surgery.
Cost Impact of Switching Histamine2-Receptor Antagonists to Nonprescription Status
Authors: Furler Michelle D , Rolnick Mark S , Lawday Kathleen S , Mak Miranda W , Einarson Thomas R
Published: June 2003

BACKGROUND:

There is a recent trend to switching medications from prescription to nonprescription status. Often, such switches are accompanied by dramatic changes in utilization due to increased availability or decreased insurance coverage. The histamine2-receptor antagonists (H2RAs) underwent such status change in the UK in 1994, the US in 1995, and Canada in 1996.

OBJECTIVE:

To examine the impact of the status change for H2RAs on the market for gastrointestinal (GI) agents in the US, UK, and Canada.

METHODS:

IMS market sales data from 1992 to 1997 were procured. All costs were converted to 1997 US dollars using the consumer price index. Per capita sales figures were determined using population data from the US Census Bureau's International Database.

RESULTS:

Overall spending on GI remedies increased in all 3 markets between 1992 and 1997; however, the contribution of prescription sales and number of prescriptions varied across the 3 countries. An increased market share for nonprescription H2RAs occurred in the US, correlating with a decline in prescription numbers for GI remedies. The opposing trend occurred in the UK, where market share of nonprescription H2RAs was minimal and use of prescription H2RAs increased. Prescription and nonprescription H2RA sales could not be differentiated for Canada.

CONCLUSIONS:

The impact of the H2RA status change varied across countries. Differences in utilization may be attributed to many factors such as differing healthcare systems, patient convenience, and physician prescribing practices. Further research is required to identify the reasons for differences in utilization and to quantify the potential clinical impact.
Stability of Furosemide in Human Albumin Solution
Authors: Elwell Rowland J , Spencer Anne P , Barnes Julie F , Wynn James E , Jones Curtis E
Published: June 2003

OBJECTIVE:

To determine the chemical stability of furosemide in human albumin solution over a 28-day period and to assess admixtures for microbiologic contamination.

METHODS:

Samples were prepared by mixing furosemide injectable solution and 25% human albumin solution in a 1:1 molar ratio. Six bulk containers were prepared and stored in the dark: 3 under refrigeration (∼4 °C) and 3 at room temperature (∼25 °C). Study samples were withdrawn from each bulk solution immediately after preparation and at predetermined intervals over the subsequent 28 days. Containers were observed for color change and precipitation against a light and dark background at each sampling interval. Total furosemide concentration was determined using HPLC. Additional vials were prepared and assessed for microbiologic growth at time points corresponding with chemical stability results.

RESULTS:

A mean of 94.5% ± 1.33% of the initial furosemide concentration remained after 48 hours at room temperature. Under refrigeration, 100.6% ± 1.02% of the initial concentration remained at 14 days. Beyond these respective time points, <90% of the initial furosemide concentration remained. No bacterial or fungal growth was observed.

CONCLUSIONS:

When combined with 25% human albumin solution and stored under darkness, furosemide is chemically stable and free of microbiologic contamination for 48 hours at room temperature and 14 days under refrigeration.
Effect of Tablet Splitting on Serum Cholesterol Concentrations
Authors: Duncan Megan C , Castle Sharon S , Streetman Daniel S
Published: June 2003

OBJECTIVE:

To evaluate the effects of tablet splitting on low-density lipoprotein (LDL) cholesterol and total cholesterol values in patients taking simvastatin and atorvastatin.

DESIGN:

A retrospective chart review of total cholesterol and LDL cholesterol values of patients instructed to split simvastatin or atorvastatin between January 1999 and November 2000.

SETTING:

Veterans Affairs Medical Center in Huntington, WV.

PATIENTS:

Patients were included if they were taking simvastatin or atorvastatin with regular lipid management and follow-up laboratory results. Patients were required to remain on the same milligram-per-day dose at least 6–8 weeks before and after tablet-splitting initiation and have cholesterol values drawn at least 6 weeks after initiation of both whole-tablet and half-tablet dosing. Patients were excluded if they had a triglyceride level >400 mg/dL or were noncompliant on the basis of pharmacy records and provider notes.

MEASUREMENT OUTCOMES:

The primary end points were changes in total cholesterol and LDL cholesterol values before and after the patient was switched to half-tablet therapy.

RESULTS:

The overall results for this review demonstrated no statistically significant increase in total cholesterol and LDL cholesterol concentrations. Total cholesterol and LDL cholesterol values actually decreased from presplitting to postsplitting, p = 0.017 and p = 0.003, respectively.

CONCLUSIONS:

The investigation showed that half-tablet dosing was as effective as whole-tablet dosing. The program will be continued as a part of quality patient care at the Huntington Veterans Affairs Medical Center.