bluuebunny/crossref_metadata_2025 huggingface dataset:
Medicine Information Help Lines: A Survey of Hospital Pharmacy-Based Services in the UK and Their Conformity with Guidelines
Authors: Raynor David K , Sharp Jane A , Rattenbury Hazel , Towler Rory J
Published: June 2003

OBJECTIVE:

To describe the prevalence and nature of hospital pharmacy–based medicine help lines for consumers in the UK and to compare service provision with published guidelines.

BACKGROUND:

Since 1992, telephone help lines for patients have proliferated in hospital pharmacies in the UK. There is no common template for such services with variations in target group, number and type of calls, and arrangements for training and audit. Data on these factors will help guide further development of such services.

METHODS:

All medicine help lines operating from hospital pharmacies in the UK were identified through the national Drug Information Pharmacists network. They were sent a piloted questionnaire covering many aspects of help line operation, including funding, method of advertisement, procedures, target group, number and nature of calls, and audit procedures.

RESULTS:

Eighty-two help lines were identified in England, Scotland, Wales, and Northern Ireland. Completed responses were received from 69 help lines (84% response rate). The pharmacy drug information center was the help line site in 57% of hospitals; all other help lines were located in the dispensary. In 55% of cases, help lines were open only to patients of the hospital. In the remainder of help lines, calls from the public were answered (although the majority of help lines only advertised to hospital patients). Calls were answered by pharmacists only in 45% of services, and additional staff training had been provided in 43%. Only 48% of services had written procedures or guidelines for operation of the help line. Forty-six percent of the services received fewer than five calls per week, 31% received between five and 10 calls per week, and 22% received 11 or more calls per week. In 59% of the sites, calls took an average of 10 minutes or less to answer; it took 11–15 minutes in 32% of the sites and >15 minutes in 9% of the sites. The most common queries related to adverse effects, dosage and administration, and interactions (including alcohol). Only 33% of help lines had any auditing or monitoring of the service in place.

CONCLUSIONS:

The increasing use of the telephone to provide services directly to consumers is reflected in the growth of hospital-based medicine help lines in the UK. The telephone route is likely to become more important as patients' needs for information about their medicines increase. However, the rate of calls is low when compared with the number of patients issued prescriptions; further research is needed to investigate the reasons for this low response. There is currently reason for concern because most help lines lack not only professional training in telephone counseling, but also proper documentation, monitoring, and audit procedures.
Homocysteine as a Risk Factor for Atherosclerosis
Authors: Temple Mary E , Luzier Aileen B , Kazierad David J
Published: June 2003

OBJECTIVE:

To review the role of homocysteine as a risk factor in the pathogenesis of atherosclerosis and to provide recommendations for the treatment of hyperhomocysteinemia.

DATA SOURCES:

A MEDLINE search using key terms such as homocysteine, atherosclerosis, folic acid, vitamin B6, and vitamin B12 was conducted for the time period 1966 through January 1999.

STUDY SELECTION:

An article was selected for inclusion in this review if it assessed the relationship and proposed mechanisms of hyperhomocysteinemia on the vasculature, physiologic changes due to hyperhomocysteinemia, and outcomes due to hyperhomocysteinemia, such as morbidity and mortality. In addition, studies that assessed the treatment outcomes of hyperhomocysteinemia were evaluated.

DATA SYNTHESIS:

Studies of patients with cerebral vascular disease reveal elevated homocysteine concentrations in 30–40% of patients compared with controls. Many studies demonstrate a correlation between elevated homocysteine concentrations, risk of myocardial infarction, and mortality. In addition, hyperhomocysteinemia and decreased folic acid concentrations have been identified in end-stage renal disease (ESRD) and type 2 diabetic patients, while both concentrations remained normal in healthy controls. Studies using folic acid 650 μg/d reduced homocysteine concentrations to within normal therapeutic range after two weeks of treatment. Studies with vitamins B6 and B12 have demonstrated that the use of either alone is ineffective, but when combined or administered with folic acid, homocysteine concentrations return to normal. All therapies must be given for the lifetime of the patient. In addition, patients must use discretion in their diet, as common beverages, such as coffee, have a strong correlation with hyperhomocysteinemia, while foods high in folic acid, vitamin B6 and vitamin B12 may reduce homocysteine concentrations. Additional prospective studies are needed to determine effects of treatment of hyperhomocysteinemia and various diets on atherosclerotic morbidity and mortality.

CONCLUSIONS:

Studies demonstrate a positive correlation between hyperhomocysteinemia and atherosclerosis. The treatment of choice for hyperhomocysteinemia is folic acid. Although the optimal dose is not known, 650 μg/d is the minimum effective dose. To date, no studies have assessed the effects on morbidity and mortality when treating high homocysteine concentrations in atherosclerotic patients.
Systemic Adverse Effects of Ophthalmic β-Blockers
Authors: Zanden Jeanne A Vander , Valuck Robert J , Bunch Cheryl L , Perlman Jay I , Anderson Carolyn , Wortman George I
Published: June 2003

OBJECTIVE:

To review published clinical information on the systemic adverse effects of ophthalmic β-blockers for the purpose of developing a pilot contraindication/warning system for active prescriptions in the Veterans Affairs dispensing database.

DATA SOURCES:

Articles were identified by searching MEDLINE (1966–October 2000) and International Pharmaceutical Abstracts (1970–October 2000).

STUDY SELECTION AND DATA EXTRACTION:

Article relevance was determined by review of titles, abstracts, and key words.

DATA SYNTHESIS:

The preponderance of the evidence suggests that ophthalmic β-blockers may be associated with bronchospasm and adverse cardiovascular effects including bradycardia. Depression and other central nervous system effects are reported less commonly. Data are inadequate to suggest that ophthalmic β-blocker use is routinely associated with adverse metabolic effects.

CONCLUSIONS:

The strongest level of evidence (grade A1) supports a contraindication for use of ophthalmic β-blockers for respiratory disease, with a moderate level of evidence (grade B1) for cardiovascular disease. Data are insufficient to support or refute contraindications for other disease states. The search technique and classification scheme described in this article provide a methodology for evaluating, grading, and applying evidence on potential adverse effects of drug therapy.
Zuclopenthixol-Associated Neutropenia and Thrombocytopenia
Authors: Hirshberg Boaz , Gural Alexander , Caraco Yoseph
Published: June 2003

OBJECTIVE:

To report a case of neutropenia and thrombocytopenia secondary to use of zuclopenthixol in a schizophrenic patient.

CASE SUMMARY:

A 66-year-old white man with chronic schizophrenia was referred to the hospital due to neutropenia and thrombocytopenia that developed shortly after initiation of zuclopenthixol therapy. Prior to zuclopenthixol administration, his white blood cell and platelet counts were 8.5 times 109 cells/L3 and 305 cells x 109/L, respectively. Progressive reduction in leukocyte and platelet counts occurred, reaching a nadir of 2.9 times 109 cells/L3 (granulocytes 18.9%) and 109 cells x 109/L, respectively. Zuclopenthixol was discontinued on admission, resulting in complete recovery within the next five days.

DISCUSSION:

Neutropenia and thrombocytopenia are well-known complications of antipsychotic drug therapy. Zuclopenthixol, a well-established antipsychotic agent, has relatively few adverse effects. The rapid decrease of white blood cell and platelet counts following the initiation of zuclopenthixol, as well as the rapid recovery, implicate zuclopenthixol as the predominant cause for neutropenia and thrombocytopenia in this patient.

CONCLUSIONS:

Although neutropenia and thrombocytopenia are rare complications of zuclopenthixol therapy, monitoring blood counts in patients receiving this agent seems to be justified.
Hydroxyurea in the Treatment of HIV-1
Authors: Gibbs Matthew A , Sorensen Suellyn J
Published: June 2003

OBJECTIVE:

To describe the role of hydroxyurea in the treatment of HIV-1.

DATA SOURCES:

Published clinical studies using hydroxyurea in HIV treatment were accessed through MEDLINE (January 1994–March 1999) and conference abstracts. All relevant studies were evaluated.

DATA SYNTHESIS:

Adherence, expense, and resistance limit the pharmacotherapeutic options in the management of patients with HIV. Hydroxyurea may be an alternative to conventional HIV treatments.

CONCLUSIONS:

Several potential advantages of adding hydroxyurea to antiretroviral treatment regimens include the drug's well-documented toxicity, convenient dosing, good tolerability and low cost, and its unique mechanism of action. Hydroxyurea may have synergistic effects that prove promising in initial and salvage therapy antiretroviral regimens. Larger, well-controlled clinical studies are needed to adequately define the role of hydroxyurea in the treatment of HIV.
Sorbitol Compared with Xylitol in Prevention of Dental Caries
Authors: Gales Mark A , Nguyen To-Mai
Published: June 2003

OBJECTIVE:

To summarize published data on the comparative efficacy of sorbitol and xylitol for prevention of dental caries.

DATA SOURCES:

Published double-blind comparative trials, using sorbitol and xylitol products, identified by MEDLINE (January 1966–December 1998) and International Pharmaceutical Abstracts (January 1970–December 1998) searches.

DATA SYNTHESIS:

Clinical trials generally used sorbitol and xylitol gums, which patients chewed three to five times daily for 20–40 months. Xylitol was superior to sorbitol in two longer, secondary dentition trials (30–63% reductions), but not in two primary dentition trials.

CONCLUSIONS:

The data suggest that xylitol-containing gums may provide superior efficacy in reducing caries rates in high-risk populations.
Interaction between Warfarin and Danshen (Salvia Miltiorrhiza)
Authors: Chan Thomas YK
Published: June 2003

OBJECTIVE:

To discuss the potential for an adverse interaction between the Chinese herb danshen, the dry root and rhizome of Salvia miltiorrhizaBge, and warfarin.

DATA SOURCES:

A MEDLINE search was performed (from January 1966 through October 2000) using the key words danshen and Salvia miltiorrhiza. All articles written in English or with an English extract were considered for review.

STUDY SELECTION AND DATA EXTRACTION:

All studies of antithrombotic effects of danshen or interaction between danshen and warfarin were evaluated. Previous case reports of an adverse interaction between danshen and warfarin were reviewed.

DATA SYNTHESIS:

Danshen is commonly used in mainland China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Danshen can affect hemostasis in several ways, including inhibition of platelet aggregation, interference with the extrinsic blood coagulation, antithrombin III—like activity, and promotion of fibrinolytic activity. Single-dose and steady-state studies in rats indicated that danshen increased the absorption rate constants, AUCs, maximum concentrations, and elimination half-lives, but decreased the clearances and apparent volume of distribution of both R- and S-warfarin. Consequently, the anticoagulant response to warfarin was exaggerated. Three cases have previously been published reporting gross overanticoagulation and bleeding complications when patients receiving chronic warfarin therapy also took danshen.

CONCLUSIONS:

Because of both pharmacokinetic and pharmacodynamic interactions, danshen should be avoided in patients taking warfarin.
Newer Antithrombotic Strategies in the Initial Management of Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Mathis A Scott
Published: June 2003

OBJECTIVE:

To review the place in therapy of currently available antithrombotic agents in the non–ST-segment elevation acute coronary syndromes, that is, unstable angina and non–Q-wave myocardial infarction (MI). Recommendations are made based on currently available data.

DATA SOURCE:

English-language clinical studies, position statements, and review articles pertaining to the management of unstable angina and non–Q-wave MI with currently available products.

STUDY SELECTION:

Selection of prospective clinical studies was limited to those focusing on the management of the non–ST-segment elevation acute coronary syndromes, unstable angina, and non–Q-wave MI.

DATA SYNTHESIS:

It has yet to be determined which combination of agents (dalteparin, enoxaparin, lepirudin, clopidogrel, ticlopidine, abciximab, eptifibatide, tirofiban) and procedural strategies most significantly reduces mortality and serious events in these patients. The relevant pathophysiology, diagnostic criteria, and risk-stratifying procedures are reviewed in context with information from clinical studies regarding currently available agents for the management of non–ST-segment elevation acute coronary syndromes.

CONCLUSIONS:

A large number of new therapeutic classes and agents are available for the treatment of unstable angina and non–Q-wave MI. Although the diagnoses of unstable angina or non–Q-wave MI identify risk, treatment decisions are often based on the presence or absence of ST-segment elevations. Limited prospective evidence delineates the proper utilization of resources to best manage these patients. Efforts should be aimed at identifying particular patients who will best benefit from recently available therapies.
Relationship between Clinical and Biologic Variables and Chloramphenicol Pharmacokinetic Parameters in Pediatric Patients with Sepsis
Authors: Goytia Gustavo Lugo , Lares-Asseff Ismael , Guillé María Gabriela Pérez , Pérez Adrián Guillé , Mejía Cynthia Larios
Published: June 2003

OBJECTIVE:

To evaluate the influence of several clinical and biologic factors on the disposition kinetics of oral chloramphenicol in pediatric patients and to determine the usefulness of this information to predict chloramphenicol serum concentrations.

STUDY DESIGN:

The clinical, biologic, and pharmacokinetic data of 30 consecutive pediatric patients diagnosed with sepsis and admitted to a tertiary care center were analyzed retrospectively. The patients were randomly assigned to a study group and a validation group. The model was developed by a three-step approach involving Bayesian estimation of pharmacokinetic parameters, selection of covariates by principal component analysis, and final selection by stepwise multiple linear regression. The model was tested in the study group and compared with a general population model using a prediction error analysis.

RESULTS:

Regression analysis revealed that weight, albumin, and white blood cell (WBC) count were the most important determinants for chloramphenicol distribution volume, whereas age, WBC count, and serum creatinine were the most important determinants for chloramphenicol clearance. The performance of the constructed population model improved significantly in terms of both bias and precision compared with the general model when tested in the validation group.

CONCLUSIONS:

Clinical and biologic factors may significantly influence chloramphenicol's disposition in pediatric patients with sepsis and therefore should be considered in programming dosage regimens.
Aerosolized Furosemide in the Treatment of Acute Respiratory Distress and Possible Bronchopulmonary Dysplasia in Preterm Neonates
Authors: Pai Vinita B , Nahata Milap C
Published: June 2003

OBJECTIVE:

To review the efficacy and safety of inhaled furosemide in the treatment of acute respiratory distress and possible bronchopulmonary dysplasia (BPD) in preterm neonates receiving ventilator and oxygen support.

DATA SOURCES:

A MEDLINE search was performed from January 1966 to December 1998 using the key words inhaled or aerosolized furosemide, BPD, preterm, neonate, and infant newborn.

STUDY SELECTION AND DATA EXTRACTION:

All clinical trials involving the use of inhaled furosemide in ventilator- and oxygen-dependent preterm neonates with acute respiratory distress and possible BPD were evaluated.

DATA SYNTHESIS:

Inhaled furosemide 1 and 2 mg/kg has improved pulmonary function in preterm neonates without significant adverse effects. However, only a single dose of inhaled furosemide was used in these trials, and pulmonary functions were monitored for only two or four hours after administration.

CONCLUSIONS:

Inhaled furosemide may be effective, but studies are needed to determine the optimal dosage regimen and long-term risks and benefits of its use in these patients.
Renal Allograft Dysfunction Associated with Rifampin–Tacrolimus Interaction
Authors: Chenhsu Rou-Yee , Loong Che-Chuan , Chou Mei-Huei , Lin Ming-Fang , Yang Wu-Chang
Published: June 2003

OBJECTIVE:

To report an interaction between tacrolimus and rifampin with subsequent adverse effects on renal allograft function.

CASE SUMMARY:

A 61-year-old Chinese man received a cadaveric renal transplant in 1991. Progressive deterioration of allograft function developed during the following six years while the patient was receiving cyclosporine and prednisolone. In January 1998, tacrolimus was substituted for cyclosporine for late biopsy-proven graft rejection, with target trough blood concentrations between 5 and 8 ng/mL. After conversion, serum creatinine fell to 2.0 mg/dL; the nadir was reached within one year. At the same time, rifampin was instituted for controlling tuberculosis and empiric fluconazole was discontinued. Twelve days later, the patient's serum creatinine concentration rose to 2.9 mg/dL and tacrolimus concentration fell to 1.5 ng/mL, along with oliguria. These findings suggested acute rejection, which was successfully reversed by steroid therapy. However, more than a tenfold increase in the tacrolimus dosage was required to maintain the same concentrations during subsequent months, accompanied by an increase in serum creatinine (from 2.0 to 2.6 mg/dL) and decrease in urine excretion. Biopsy at this time demonstrated acute rejection (Banff I), chronic allograft nephropathy (Banff II), and suspected tacrolimus nephrotoxicity. After unsuccessful methylprednisolone recycling, mycophenolate mofetil was introduced to control rejection and facilitate reduction of the tacrolimus dosage to minimize its nephrotoxicity.

CONCLUSIONS:

As a potent CYP3A4 isoenzyme inducer, rifampin coadministration caused the abrupt decrease in tacrolimus blood concentrations, leading to an approximate tenfold increase in its daily dose, which may be important to subsequent allograft dysfunctions.
Adverse Effects of Reduced-Dose d-Penicillamine in Children with Mild-to-Moderate Lead Poisoning
Authors: Shannon Michael W , Townsend Meaghan Kennedy
Published: June 2003

BACKGROUND:

Oral chelation therapy with d-penicillamine (d-PCN) has been proven to be effective in the treatment of mild-to-moderate lead poisoning. However, d-PCN is associated with a relatively high incidence of adverse effects when given in the standard dose of 25–30 mg/kg/d. Lower doses of d-PCN may reduce the rate of adverse effects without a significant reduction in the drug's efficacy.

OBJECTIVE:

To examine the incidence of rash, white blood cell and platelet count depression, and abnormal urinalysis with d-PCN when given in a dose of 15 mg/kg/d to children with blood lead concentrations <40 μg/dL.

METHODS:

Retrospective analysis of a clinical treatment course of children who received d-PCN during 1996 in the Lead and Toxicology Clinic of Children's Hospital, Boston. All children were treated under a reduced-dose d-PCN chelation protocol.

RESULTS:

During the study period, 55 children (mean age 37.4 mo) received 66 courses of d-PCN. Mean blood lead concentration before chelation was 24 μg/dL (range 15–37), with a corresponding erythrocyte protoporphyrin concentration of 42 μg/dL. After 77 days of treatment with d-PCN, blood lead concentration was reduced to mean 16 μg/dL (mean fall 35%; p = 0.005) and erythrocyte protoporphyrin was reduced to 28 μg/dL (p = 0.009). During chelation therapy, the white blood cell count fell below 5000/mm3 in seven cases (9.7%); there were no episodes of platelet counts falling below 150 000/mm3. No cases of abnormal urinalysis were reported; three episodes of rash (4.5%) were recorded. The only patients prematurely terminated from therapy were those who developed rash; in all three cases, drug eruption was an isolated occurrence, which resolved within 48 hours of diphenhydramine therapy. All adverse effects were transient and resolved during or immediately after chelation therapy.

CONCLUSIONS:

Reduced-dose d-PCN appears to maintain efficacy at reducing blood lead concentrations. Reduced-dose d-PCN also appears to be associated with a rate of adverse effects lower than previously reported; observed adverse effects appear to be benign and transient.
Stability of Suspension Formulations of Lansoprazole and Omeprazole Stored in Amber-Colored Plastic Oral Syringes
Authors: DiGiacinto Jennifer L , Olsen Keith M , Bergman Kimberly L , Hoie Eric B
Published: June 2003

OBJECTIVE:

To determine the stability of lansoprazole and omeprazole suspensions at ambient and refrigerated temperatures using HPLC.

DESIGN:

The contents of lansoprazole and omeprazole capsules were suspended in separate flasks containing sodium bicarbonate 8.4% to concentrations of 3 and 2 mg/mL, respectively. The contents of each flask were drawn into six amber-colored oral syringes, with one-half of the syringes stored at 22 °C (ambient) and the other half at 4 °C. Lansoprazole and omeprazole concentrations were determined by a stability-indicating HPLC assay at baseline and at 4, 8, 12, and 24 hours, and on days 4, 7, 14, 21, 30, 45, and 60 after mixing. Both omeprazole and lansoprazole were considered stable if they retained ≤90% of the baseline drug concentration.

RESULTS:

Omeprazole was stable for up to 14 days at 22 °C and 45 days at 4 °C. Lansoprazole was stable for eight hours at 22 °C and for 14 days at 4 °C.

CONCLUSIONS:

When compared with ambient or refrigerated storage conditions, omeprazole was stable for a longer duration than lansoprazole. Pharmacists may use these results to guide compounding and storage of proton-pump inhibitor suspensions.
Potential Interaction between Methotrexate and Omeprazole
Authors: Beorlegui Blanca , Aldaz Azucena , Ortega Ana , Aquerreta Irene , Sierrasesúmega Luis , Giráldez Joaquín
Published: June 2003

OBJECTIVE:

To report a case of delayed elimination of high-dose methotrexate (MTX) associated with concomitant omeprazole administration.

CASE SUMMARY:

Delayed MTX elimination was observed in an 11-year-old white boy who concomitantly received high-dose MTX and omeprazole. The patient's serum creatinine and liver function tests were normal during treatment and follow-up. The only medication we suspected of inhibiting MTX elimination was omeprazole 20 mg every 12 hours. Twenty-four hours after the first high-dose MTX cycle (15 g), omeprazole was discontinued. Thereafter, the patient received one high-dose MTX cycle without omeprazole every month for five months; MTX elimination was normal throughout MTX cycles 2 to 5.

DISCUSSION:

MTX is actively secreted in the distal tubules. The renal hydrogen/potassium adenosine triphosphatase (H+/K+-ATPase) pump makes the urine more acidic, by secreting hydrogen ions into the renal tubule and reabsorbing potassium ions. Active tubular secretion of MTX requires the activity of this pump because MTX is excreted with hydrogen ions. Omeprazole can inhibit renal elimination of the hydrogen ion and block the active tubular secretion of MTX. Therefore, the elimination half-life of MTX increases, which may result in potentially toxic concentrations of MTX. At a pH of approximately 5, as found in the renal tubules, pantoprazole is more slowly activated than omeprazole, reducing the incidence of unwanted reactions with sulfhydryl groups and adverse effects occurring outside of the gastric hydrogen pump.

CONCLUSIONS:

Based on the Naranjo probability scale, a probable drug interaction was observed. Omeprazole may delay MTX elimination; therefore, when prescribing MTX, an alternative to omeprazole should be considered.
Clindamycin in the Treatment of Streptococcal and Staphylococcal Toxic Shock Syndromes
Authors: Russell Nicole E , Pachorek Robert E
Published: June 2003

OBJECTIVE:

To evaluate the utility of clindamycin in the treatment of streptococcal and staphylococcal toxic shock syndromes.

DATA SOURCES:

Biomedical literature was accessed through MEDLINE (1966–December 1999). Key terms included clindamycin, streptococcal toxic shock, and staphylococcal toxic shock.

DATA SYNTHESIS:

Streptococcal and staphylococcal toxic shock syndromes are associated with a high mortality rate. β-Lactams have been considered the drug of choice for the treatment of these serious infections, with the occasional use of adjunctive clindamycin, although no clinical evidence has been published to support this latter regimen. An evaluation of the information to propose the usefulness of clindamycin was conducted.

CONCLUSIONS:

Experimental laboratory evidence suggests utility of the adjunctive use of clindamycin in streptococcal and staphylococcal infections complicated by toxin production. Research using animal models comparing clindamycin plus β-lactams with β-lactams alone for the treatment of these infections would be useful.
Increased Rate of Trazodone Prescribing with Bupropion and Selective Serotonin-Reuptake Inhibitors versus Tricyclic Antidepressants
Authors: Clark Nancy A , Alexander Bruce
Published: June 2003

OBJECTIVE:

To determine whether trazodone is prescribed significantly more often with selective serotonin-reuptake inhibitors (SSRIs) and bupropion than with tricyclic antidepressants (TCAs).

METHODS:

A retrospective analysis of Iowa City Department of Veteran's Affairs prescription records from March 1, 1995, to March 1, 1998, was performed. Antidepressants prescribed only by psychiatrists were included. Concomitant use was defined as trazodone prescribed on the same date or up to 42 days after the fill date of the primary antidepressant.

STATISTICS:

All comparisons used 2 times 2 c 2 contingency table. Significance level was set at p < 0.05.

RESULTS:

Significantly more patients were prescribed trazodone concurrently with bupropion and SSRI antidepressants than with TCAs. Trazodone was prescribed significantly more often for patients receiving an SSRI (p = 0.0001, c 2 = 14.59) or bupropion (p = 0.0295, c 2 = 4.74) than for patients receiving a TCA. There was no significant difference in trazodone use between the patients taking SSRIs or bupropion. The percent of patients that received an SSRI, bupropion, or a TCA in combination with trazodone was 27%, 23%, and 13%, respectively. Overall, 23.7% of patients received trazodone concomitantly with a primary antidepressant.

DISCUSSION:

The effects of antidepressants on sleep and on sleep scores of depression rating scales are reviewed. The clinical implications of these findings are discussed. The literature addressing the effects of antidepressants on sleep and on sleep scores of depression rating scales is summarized. Although sleep studies suggest that SSRIs may not improve sleep as well as a TCA, clinical studies do not often support these findings. Several studies report that bupropion may not improve sleep parameters as well as doxepin or trazodone. The clinical implications of these findings are discussed.

CONCLUSIONS:

We have demonstrated that our clinicians prescribe trazodone at a significantly higher rate with an SSRI or bupropion than with a TCA. The exact reason for this difference is not known. If trazodone is used during the first six weeks of an initial antidepressant treatment trial, it should be discontinued to determine whether the patient's sleep disturbance has responded to the primary antidepressant. More comparison studies among the newer antidepressants and between classes of antidepressants concerning their effects on sleep in the depressed patient need to be performed.
Extended-Release Nifedipine Bezoar Identified One Year after Discontinuation
Authors: Niezabitowski Lisa M , Nguyen Billie Nhu , Gums John G
Published: June 2003

OBJECTIVE:

To report a case of tablet impaction of nifedipine extended-release tablets (Procardia XL) discovered one year after discontinuation of the drug in a patient with peptic stricture.

DATA SOURCES:

English-language references identified via a MEDLINE search from 1966 through September 1998 and bibliographic review of pertinent articles.

DATA SYNTHESIS:

Extended-release nifedipine has been associated with the formation of medication bezoars in case reports. Bezoars are concretions of undigested material within the gastrointestinal (GI) tract. Although they can occur throughout the GI tract, bezoars are most frequently located in the stomach and, rarely, in the duodenum. We report an unusual case of tablet impaction with a gastric outlet obstruction in the duodenal area discovered one year after the patient stopped taking extended-release nifedipine.

CONCLUSIONS:

Extended-release nifedipine is associated with tablet impaction, even long after discontinuing administration. Although rare, clinicians should be aware of this potential problem when prescribing extended-release medications to patients at risk, and should consider this possible etiology when refractory epigastric pain and weight loss occur.
Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Lisinopril
Authors: Shaikh Zakir Hussain A , Taylor Harris C , Maroo Praful V , Llerena Luis A
Published: June 2003

OBJECTIVE:

To describe a case of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with lisinopril therapy.

CASE SUMMARY:

A 76-year-old white woman who was being treated with lisinopril and metoprolol for hypertension presented with headaches accompanied by nausea and a tingling sensation in her arms. Her serum sodium was 109 mEq/L, with a serum osmolality of 225 mOsm/kg, urine osmolality of 414 mOsm/kg, and spot urine sodium of 122 mEq/L. Diclofenac 75 mg qd for osteoarthritic pain and lisinopril 10 mg qd for hypertension was begun in 1990. Lisinopril was increased to 20 mg qd in August 1994 and to 20 mg bid prn in August 1996 for increasing blood pressure; metoprolol 50 mg qd was added in July 1996. A diagnosis of SIADH was postulated and further evaluation was undertaken to exclude thyroid and adrenal causes. After lisinopril was discontinued and the patient restricted to 1000 mL/d of fluid, serum sodium gradually corrected to 143 mEq/L. The patient was discharged taking metoprolol alone for her hypertension; serum sodium has remained ≥138 mEq/L through April 1999, 32 months after discharge, despite daily use of diclofenac.

DISCUSSION:

Angiotensin-converting enzyme (ACE) inhibitors in antihypertensive doses may block conversion of angiotensin I to angiotensin II in the peripheral circulation, but not in the brain. Increased circulating angiotensin I enters the brain and is converted to angiotensin II, which may stimulate thirst and release of antidiuretic hormone from the hypothalamus, eventually leading to hyponatremia.

CONCLUSIONS:

SIADH should be considered a rare, but possible, complication of therapy with lisinopril and other ACE inhibitors.
Efficacy of Colony-Stimulating Factors in Acute Leukemia
Authors: Holdsworth Mark T , Mathew Prasad
Published: June 2003

OBJECTIVE:

To evaluate the literature describing the safety and efficacy of the hematopoietic colony—stimulating factors (CSFs) for the management of treatment-related adverse effects in patients with acute leukemia.

DATA SOURCES:

A systematic MEDLINE search of the English-language literature (1995–April 2000) was performed to identify all randomized trials evaluating CSF use in acute leukemia. The following search terms were used: granulocyte colony—stimulating factor, filgrastim, granulocyte-macrophage colony—stimulating factor, sargramostim, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute nonlymphocytic leukemia, and acute myeloid leukemia. The references from relevant literature were also examined in order to identify reports not discovered in the MEDLINE search.

DATA SYNTHESIS:

Six randomized trials in pediatric ALL, nine in adult AML, and four in adult ALL have examined the safety and efficacy of the CSFs. Tw o of the pediatric trials supported a reduction in either the duration of hospitalization or in the incidence of febrile neutropenia when a CSF was employed during the consolidation or intensification phase of chemotherapy. The remaining pediatric trials failed to demonstrate a clinical benefit. In adult AML, eight of the nine trials showed a significant decrease in the time to neutrophil recovery when a CSF was used. Only one of these trials demonstrated a decrease in hospital stay and none showed a decreased incidence of infection for patients who received a CSF. Three of the four trials in adult ALL demonstrated the efficacy of a CSF in decreasing the number of days to neutrophil recovery. Only one trial demonstrated that a CSF led to a reduction in the number of hospital days. Trials in children or adults have not demonstrated that the CSFs influence the long-term outcome of patients with acute leukemia.

CONCLUSIONS:

The published studies document a decrease in the time to recovery from neutropenia when patients with acute leukemia are treated with a CSF. However, a consistent reduction in infectious complications or in the duration of hospitalization has not been demonstrated when a CSF is used for either pediatric or adult patients. Very limited data exist to support the premise that CSFs meet the criteria established by the American Society of Clinical Oncology for demonstrating the value of these agents. Further careful study focused on resource utilization and pharmacoeconomics may help to elucidate how healthcare institutions may most effectively employ CSFs to treat patients with acute leukemia.
Do Ethanol and Metronidazole Interact to Produce a Disulfiram-Like Reaction?
Authors: Williams Caroline S , Woodcock Kevin R
Published: June 2003

OBJECTIVE:

To obtain and evaluate evidence about the supposed disulfiram-like interaction between metronidazole and ethanol.

DATA SOURCES:

MEDLINE search from January 1964 to June 1999, using the terms metronidazole, ethanol, and drug reaction.

DATA SYNTHESIS:

The manufacturer's warnings include a disulfiram-like reaction between metronidazole and ethanol. However, review of reports published between 1969 and 1982 produced no convincing evidence that this reaction exists. Six case reports involving eight patients were evaluated.

CONCLUSIONS:

Four of the eight cases were serious, including one death, but the authors of all the reports presumed the metronidazole–ethanol reaction to be an established pharmacologic fact. None provided evidence that could justify their conclusions.
Treatment for Posttraumatic Stress Disorder
Authors: Cyr Monica , Farrar Merry Kathleen
Published: June 2003

OBJECTIVE:

To thoroughly and critically review the pharmacologic treatment of posttraumatic stress disorder (PTSD) and to review the symptomatology, diagnosis, epidemiology, pathophysiology, and assessment of PTSD.

DATA SOURCES:

A MEDLINE search (1966–October 1999) in the English language specifying PTSD drug treatment as the search term was used to identify articles.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified were reviewed; emphasis was given to randomized, double-blind, placebo-controlled studies.

DATA SYNTHESIS:

It appears that a five-week medication trial is necessary to assess clinical effects on PTSD symptoms. The monoamine oxidase inhibitors appear to be superior to the tricyclic antidepressants in improving reexperiencing and avoidance symptoms. Most studies used assessment tools that neglected hyperarousal symptoms; therefore, no conclusions regarding this symptom cluster can be drawn. Other pharmacotherapeutic interventions reported in open-label trials have yielded varying success.

CONCLUSIONS:

The current literature does not bear a sufficient number of double-blind, placebo-controlled studies using assessment tools that evaluate the three symptom clusters of PTSD to allow for a definite treatment modality to be formulated. Nonetheless, a treatment hierarchy appears to be in order based on the greatest number of double-blind, placebo-controlled studies evaluating antidepressants. Alternate modalities such as mood stabilizers, antipsychotics, anxiolytics, and adrenergic blockers should not be considered the mainstays of therapy.
Immunology of Varicella Immunization in the Elderly
Authors: Raeder Carla K , Hayney Mary S
Published: June 2003

OBJECTIVE:

To review the varicella-zoster virus (VZV) and herpes zoster disease and to summarize published reports on the use of the live-attenuated varicella zoster vaccine to enhance cell-mediated immunity in elderly individuals.

DATA SOURCE:

A MEDLINE search (1966–August 1999) for English-language clinical studies and review articles pertaining to VZV and the live-attenuated varicella vaccine was conducted; references obtained from these publications were subsequently reviewed for additional relevant articles.

STUDY SELECTION AND DATA EXTRACTION:

Representative clinical trials were summarized and relevant information was selected to assist in the understanding of VZV, the subsequent immune response, and the live-attenuated varicella vaccine.

DATA SYNTHESIS:

The physiologic, age-related decline in VZV cell–mediated immunity has been shown to be restored on administration of live-attenuated varicella vaccine. Various studies report serum anti-VZV antibody concentrations, and production of interferon-gamma were increased following vaccination. Concentrations subsequently returned to baseline one year after vaccination. Increase in responder cell frequency, a measure of cell-mediated immunity, has been reported to last up to four years after vaccination, at concentrations similar or superior to those observed following herpes zoster.

CONCLUSIONS:

Enhancement of cell-mediated immune response in elderly individuals through vaccination with live-attenuated varicella vaccine is a possible measure to protect this population from herpes zoster and to attenuate its complications. A summary of immunogenicity studies to identify the immune response to live-attenuated varicella vaccine in the elderly is presented. The absolute clinical significance, as well as appropriate administration guidelines of this prophylactic intervention, will become evident following forthcoming large, masked, placebo-controlled trials.
Lamotrigine for the Treatment of Bipolar Disorder
Authors: Engle Patricia M , Heck Amy M
Published: June 2003

OBJECTIVE:

To describe the available data regarding the clinical efficacy of lamotrigine for the treatment of bipolar disorder.

Anticonvulsants have emerged as alternative mood-stabilizing agents for patients with bipolar disorder who do not respond to lithium. Data regarding the efficacy of lamotrigine have been generated primarily from case reports, small open trials, and one large, randomized, placebo-controlled trial. These reports suggest that lamotrigine may be effective for the management of bipolar disorder.

CONCLUSIONS:

Although current data are limited, treatment-refractory patients with bipolar disorder may benefit from lamotrigine therapy. Several studies are currently underway to determine the appropriate role of lamotrigine in the treatment of bipolar disorder.
Antibiotic Use in a Canadian Province, 1995–1998
Authors: Carrie Anita G , Metge Colleen J , Zhanel George G
Published: June 2003

OBJECTIVE:

Antibiotics are among the most commonly used classes of agents in community practice; yet, studies of antibiotic use in this setting are scarce. Data from developed countries suggest increasing use of newer broad-spectrum agents, which has implications for the development of antibiotic resistance as well as cost of therapy. In this study, we quantified changing patterns of antibiotic use in community practice in Manitoba, Canada, from 1995 to 1998.

DESIGN:

A descriptive, population-based study of antibiotic use in Manitoba was facilitated by the Drug Programs Information Network (DPIN) of Manitoba Health; a data management system responsible for recording details of prescriptions dispensed for all Manitoba residents. Antibiotic use data, defined as numbers of prescriptions dispensed, were extracted from the DPIN from January 1, 1995, to March 31, 1998. Antibiotic use is reported as prescriptions per 1000 persons per year (Rx/1000/Yr) based on quarterly use.

RESULTS:

Penicillins (48.3%), macrolides (16.0%), and sulfonamides (12.5%) accounted for 75% of total antibiotic use; total use decreased 19.1% between 1995 and 1998. Use of the four most commonly prescribed agents decreased over the study period (amoxicillin, −17.4%; erythromycin, −29.0%; trimethoprim/sulfamethoxazole, −18.7%; penicillins G and V, −19.2%). In contrast, use of newer and/or broad-spectrum agents increased (ciprofloxacin, 21.9%; cefuroxime, 30.7%; and azithromycin/clarithromycin, 29.5%). Use of second-line agents as a percentage of total antibiotic use increased from 14.4% to 19.3% between January 1995 and March 1998 (p < 0.001).

CONCLUSIONS:

Penicillins, macrolides, and sulfonamides accounted for 75% of antibiotic use. Total antibiotic use declined over the study period; however, use of newer, broad-spectrum agents increased while use of older, narrow-spectrum agents decreased.
Billing for Cognitive Services: Understanding Québec Pharmacists' Behavior
Authors: Kröger Edeltraut , Moisan Jocelyne , Grégoire Jean-Pierre
Published: June 2003

BACKGROUND:

There is growing evidence that pharmacists' interventions to solve drug-related problems are effective and cost-saving. Since 1978, under the Québec provincial drug plan, payment for two cognitive services, the pharmaceutical opinion and the refusal to dispense a prescription, has been disbursed to community pharmacists. However, the number of claims for these services lags far behind expectations.

OBJECTIVE:

To identify factors influencing Québec community pharmacists in the billing for a pharmaceutical opinion or for a refusal to dispense.

METHODS:

Questions on predisposing, enabling, and reinforcing factors potentially related to pharmacists' behavior were included in a self-administered questionnaire sent to all 3517 community pharmacists practicing in the province of Québec during 1996. Using multivariate logistic regression, models were built to explain billing for an opinion and billing for a refusal.

RESULTS:

According to our models, the typical pharmacist who billed for opinions or refusals in Québec is <45 years of age, has attended a continuing education program on this topic, and believes that billing for interventions is important. This typical pharmacist handles a mean daily volume of 100–250 prescriptions, uses a decision-support computer program, and has sufficient technical staff assistance. This pharmacist believes that interventions can be billed rapidly and are consistently paid by the province's drug plan.

CONCLUSIONS:

In order to increase the billing of pharmaceutical care in community pharmacies, tailored educational programs should be offered to pharmacists. There is also a need to improve working conditions in pharmacies.
Macrolide Drug Interactions: An Update
Authors: Pai Manjunath P , Graci Danielle M , Amsden Guy W
Published: June 2003

OBJECTIVE:

To describe the current drug interaction profiles for the commonly used macrolides in the US and Europe, and to comment on the clinical impact of these interactions.

DATA SOURCES:

A MEDLINE search (1975–1998) was performed to identify all pertinent studies, review articles, and case reports. When appropriate information was not available in the literature, data were obtained from the product manufacturers.

STUDY SELECTION:

All available data were reviewed to provide an unbiased account of possible drug interactions.

DATA EXTRACTION:

Data for some of the interactions were not available from the literature, but were available from abstracts or company-supplied materials. Although the data were not always explicit, the best attempt was made to deliver pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied.

DATA SYNTHESIS:

Several clinically significant drug interactions have been identified since the approval of erythromycin. These interactions usually were related to the inhibition of the cytochrome P450 enzyme systems, which are responsible for the metabolism of many drugs. The decreased metabolism by the macrolides has in some instances resulted in potentially severe adverse events. The development and marketing of newer macrolides are hoped to improve the drug interaction profile associated with this class. However, this has produced variable success. Some of the newer macrolides demonstrated an interaction profile similar to that of erythromycin; others have shown improved profiles. The most success in avoiding drug interactions related to the inhibition of cytochrome P450 has been through the development of the azalide subclass, of which azithromycin is the first and only to be marketed. Azithromycin has not been demonstrated to inhibit the cytochrome P450 system in studies using a human liver microsome model, and to date has produced none of the classic drug interactions characteristic of the macrolides.

CONCLUSIONS:

Most of the available data regarding macrolide drug interactions are from studies in healthy volunteers and case reports. These data suggest that clarithromycin appears to have an interaction profile similar to that of erythromycin. Given this similarity, it is important to consider the interaction profile of clarithromycin when using erythromycin. This is especially necessary as funds for further studies of a medication available in generic form (e.g., erythromycin) are limited. Azithromycin has produced few clinically significant interactions with any agent cleared through the cytochrome P450 enzyme system. Although the available data are promising, the final test should come from studies conducted in patients who are taking potentially interacting compounds on a chronic basis.