bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Influencing the Incidence of Lamotrigine-Related Skin Rash
Authors: Wong Ian CK , Mawer George E , Sander Josemir WAS
Published: March 2004

OBJECTIVE:

To determine the incidences of serious and nonserious lamotrigine-related rash, determine the risk factors for lamotrigine-related rash, and evaluate the impact on the incidence of rash of the manufacturer's recommendation to reduce the starting dose of lamotrigine.

METHODS:

This was a retrospective case record survey at five tertiary referral epilepsy centers in the UK. The risk factors for lamotrigine-related rash were identified by logistic regression. The independent factors tested were gender, age, epilepsy type, concurrent medication, and starting dose of lamotrigine. The incidences of rash before and after the recommendation of reduction in starting dose were compared by •2 analysis.

RESULTS:

A total of 1050 patients were included. The incidences of serious and nonserious rash were 1.1% (95% CI 0.5% to 1.8%) and 7% (95% CI 5.5% to 8.6%), respectively. Females were at higher risk of developing rash than were males, with a relative risk of 1.8 (95% CI 1.2 to 2.8). The starting dose of lamotrigine was reduced in response to the manufacturer's recommendation, and there was a significant reduction (p = 0.045) in the incidence of serious rash, from 1.5% (12/805) to 0% (0/245). However, there was no reduction in the overall incidence of lamotrigine-related rash, with 63/805 (8%) before and 23/245 (9%) after the recommendation.

CONCLUSIONS:

Failure to detect a reduction in the incidence of lamotrigine-related rash since the new (reduced) recommended starting dose of lamotrigine may arise from failure to reduce the starting dose below a critical threshold level, incomplete compliance with current recommendations, or insufficient sample size. The results of this and other studies show that the starting dose of lamotrigine is a significant factor affecting the incidence of rash; furthermore, this study also shows that significant reduction in the incidence of serious rash can be achieved by reducing the starting dose. Therefore, clinicians should not deviate from the recommendations.
Health-Related Quality of Life in Primary Care Patients with Gastroesophageal Reflux Disease
Authors: Kaplan-Machlis Barbara , Spiegler Gerard E , Revicki Dennis A
Published: March 2004

OBJECTIVE:

To describe the clinical characteristics and health-related quality of life of family medicine patients with clinically diagnosed gastroesophageal reflux disease (GERD).

METHODS:

The study involved the baseline assessment of 268 patients enrolled in a randomized clinical trial comparing treatments for GERD. The study was conducted in a five-center, university-based family practice in southeastern West Virginia. Patients with a clinical diagnosis of GERD and who had not received treatment in the past 30 days were eligible; pregnant and lactating women and patients with severe renal or hepatic insufficiency were excluded.

RESULTS:

Two hundred sixty-eight patients were included in the analysis. Mean ± SD age was 44.9 ± 14.1 years; 61.2% were women and 91.4% were white. Mean ± SD body mass index was 30.3 ± 6 kg/m2, and >15.3% of patients had no insurance. One hundred seventy-four (64.9%) patients were enrolled from nonurban primary care clinics. One hundred sixty-four patients (61.2%) were prescribed at least one medication prior to study enrollment (mean ± SD 2.88 ± 1.71; range 1–9). When adjusted for age, gender, comorbidity status, and rural status, severity of GERD was associated with decreased health-related quality of life. GERD patients without comorbidity demonstrated decrements in health-related quality of life when compared with the US general population. When compared with another GERD population, the study patients reported fairly consistent GERD symptomatology and health-related quality of life.

CONCLUSIONS:

GERD symptom severity was associated with impaired health-related quality of life in a predominantly rural primary care population.
Tolterodine Use for Symptoms of Overactive Bladder
Authors: Ruscin J Mark , Morgenstern Nora E
Published: March 2004

OBJECTIVE:

To describe the pharmacology, pharmacokinetics, clinical efficacy, and safety of tolterodine for the treatment of overactive bladder.

DATA SOURCES:

Published articles and abstracts were identified from a MEDLINE search (January 1980–October 1998) using the terms tolterodine, PNU-200583E, urge incontinence, overactive bladder, detrusor instability, detrusor overactivity, and antimuscarinic. Pertinent articles written in English were considered for review. Additional articles were identified from the bibliographies of retrieved articles. Data from the Food and Drug Administration– approved product labeling and the manufacturer were also used in the absence of published data.

STUDY SELECTION AND DATA EXTRACTION:

Clinical studies of tolterodine involving human subjects were evaluated.

DATA SYNTHESIS:

Tolterodine is a competitive muscarinic receptor antagonist with relative functional selectivity for bladder muscarinic receptors. It is metabolized in the liver by CYP2D6 to an active metabolite (DD 01), which is partially responsible for its pharmacologic activity. Those who are genetically devoid of CYP2D6 will have higher concentrations of the parent compound and virtually undetectable concentrations of DD 01; however, the clinical efficacy does not appear to be altered. In dosages of 2 mg twice daily, tolterodine has shown consistent reductions in the number of micturitions per 24 hours and less consistently decreased incontinence episodes in patients with detrusor overactivity. The functional selectivity of tolterodine for bladder muscarinic receptors results in fewer systemic adverse effects, such as dry mouth, than occur with comparable nonselective antimuscarinic agents.

CONCLUSIONS:

Clinical studies have shown that the effectiveness of tolterodine for symptoms of overactive bladder is similar to that of oxybutynin. The adverse effect profiles of tolterodine and oxybutynin are similar; however, comparative clinical trials have shown significantly fewer patients taking tolterodine require dosage reductions or discontinue therapy due to antimuscarinic adverse effects such as dry mouth. Although more costly than oxybutynin, tolterodine represents a modest improvement over oxybutynin with respect to adverse effect profile, which may allow more patients with incontinence to tolerate therapeutic doses. Further research is necessary to determine whether tolterodine has clinical advantages over similar agents in patients with other muscarinic adverse effects, such as constipation or cognitive impairment.
Successful Use of Clopidogrel for Cerebrovascular Accident in a Patient with Suspected Ticlopidine-Induced Hepatotoxicity
Authors: Zeolla Mario M , Carson John J
Published: March 2004

OBJECTIVE:

To report a case of successful clopidogrel use in a patient who developed suspected ticlopidine-induced hepatotoxicity during therapy for a cerebrovascular accident.

CASE REPORT:

A 79-year-old white woman with a history of hypertension, type 2 diabetes, Alzheimer disease, and coronary artery disease started receiving ticlopidine 250 mg twice daily three days after hospital admission for a cerebrovascular accident. Medications prior to admission included quinapril, furosemide, insulin, atorvastatin, conjugated estrogen, medroxyprogesterone, donepezil, and vitamin E. The estrogen, medroxyprogesterone, and donepezil were discontinued on admission. Laboratory tests on admission revealed that total bilirubin, alkaline phosphatase, and aspartate aminotransferase (AST) were within normal limits. On day 39 of hospitalization, laboratory tests showed marked increases in alkaline phosphatase, AST, alanine aminotransferase, γ-glutamyl-transferase, and 5' nucleotidase. Physical examination revealed no signs of jaundice or hepatomegaly, and laboratory tests for viral hepatitis were negative. A presumptive diagnosis of ticlopidine-induced hepatotoxicity was made and ticlopidine was discontinued. The following day, clopidogrel 75 mg/d was initiated. Liver function tests returned to baseline over the following four months with ongoing clopidogrel therapy.

DISCUSSION:

Ticlopidine-induced hepatotoxicity is well documented in the literature. In the present case, clopidogrel, a structurally similar thienopyridine, was substituted for ticlopidine following the development of presumptive ticlopidine-induced hepatotoxicity. Serum liver enzyme concentrations returned to baseline with continued clopidogrel therapy, suggesting that clopidogrel is a suitable alternative in patients who develop ticlopidine-induced hepatotoxicity.

CONCLUSIONS:

Clopidogrel may be a suitable alternative for patients who develop ticlopidine-induced hepatotoxicity.
Economic Evaluation of Risperidone in an Outpatient Population
Authors: Hammond Constance M , Pierson Jerome F , Grande Thomas P , Munetz Mark R , Wilson Daniel R , Pathak Dev S
Published: March 2004

OBJECTIVE:

To study the impact of risperidone use on the cost of services provided to severely mentally disabled outpatients and on hospital avoidance, and to analyze patterns in the use of concomitant medications as a surrogate marker of changes in adverse effects or patient well-being.

METHODS:

The patients were 31 clients of community mental health centers who had received risperidone for at least three months and for whom there were at least three months of available data on medication use and costs prior to risperidone treatment. The actual average monthly costs of community mental health services obtained from a county mental health board were compared with service costs prior to use of risperidone, using the patients as their own controls, and compared with a control group.

RESULTS:

Compared with the pre-risperidone period, the average cost per month of providing mental health services increased by 73.7% during the risperidone treatment period. Compared with the pre-risperidone period, the average total cost of treatment (including medications) increased by 113.3% during the risperidone treatment period. The average total cost of medication increased by 422.8% during the risperidone treatment period compared with the pre-risperidone treatment period.

CONCLUSIONS:

From the perspective of the community mental health board, risperidone treatment did not reduce the cost of services provided to these clients, but substantially and significantly increased total costs, including medication.
Treatment of Wegener's Granulomatosis with Immune Globulin: CNS Involvement in an Adolescent Female
Authors: Taylor Charles T , Buring Shauna M , Taylor Kelly H
Published: March 2004

OBJECTIVE:

To describe the use of intravenous immune globulin (IVIG) to treat Wegener's granulomatosis (WG) in an adolescent female with an abnormal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG), as well as central nervous system involvement manifesting as generalized seizures.

CASE SUMMARY:

A 15-year-old white girl diagnosed with WG and receiving prednisone and cyclophosphamide was admitted with new-onset tonic–clonic seizures. The patient received phenobarbital and phenytoin to control seizures and was receiving cyclophosphamide and corticosteroids for WG. She developed cyclophosphamide-induced cystitis and was started on a four-day therapeutic course of IVIG following the discontinuation of cyclophosphamide. After 16 days of hospitalization, repeat EEG and MRI were within normal limits, and laboratory and clinical improvement was evident in at least nine of the affected organ systems including pulmonary, hematologic, renal, ocular, cutaneous, musculoskeletal, central nervous system, gastrointestinal, and genitourinary. The patient was discharged with clinical involvement of WG documented in two organ systems, hematologic and renal.

DISCUSSION:

WG is a form of vasculitis believed to develop due to an autoimmune disorder. The diagnosis is based on radiographic and histopathologic findings, as well as the presence of elevated antineutrophil cytoplasmic antibodies and a suggestive clinical presentation. The presentation is widely variable and is most commonly associated with upper-airway involvement such as sinusitis, cough, pulmonary infiltrates, and cavitary nodules. Renal involvement signifies generalized disease. Conventional treatment for WG includes cyclophosphamide and prednisone. Little information is available describing therapeutic alternatives. Cytotoxicity related to immunosuppressant regimens limits continuous treatment and may necessitate the use of alternative agents.

CONCLUSIONS:

This case describes the use of IVIG in an adolescent patient presenting with WG as a generalized, active disease with neurologic complications. IVIG may be useful in generalized, active WG complicated by intolerance to cyclophosphamide and seizures, but further study is necessary to define its role.
The Impact of Pharmaceutical Services in Community and Ambulatory Care Settings: Evidence and Recommendations for Future Research
Authors: Singhal Puneet K , Raisch Dennis W , Gupchup Gireesh V
Published: March 2004

OBJECTIVE:

TO review and evaluate research on pharmaceutical services in community and ambulatory care pharmacy settings, specifically study designs and patient outcome measures, and to provide recommendations to improve future research on pharmaceutical services in community and ambulatory care pharmacy settings.

DATA SOURCE:

English-language articles were identified by searching MEDLINE (1966-December 1998) and International Pharmaceutical Abstracts (1970-December 1998), using a combination of search terms: pharmacist services, pharmacist interventions, community pharmacy, ambulatory care, primary care, and patient outcomes. Relevant studies were selected based on article abstracts.

DATA EXTRACTION:

From each relevant study, we extracted the study objectives, sample size, study period, study design, major tasks performed by pharmacists, and economic, clinical, and humanistic outcomes (ECHO). Results were tabulated separately for research on community pharmacy and ambulatory care pharmacy settings.

RESULTS:

We identified 95 relevant studies. Of these, 21 studies were conducted in community pharmacy settings and 74 in ambulatory care settings. Ten community pharmacy studies used prospective, single group, pretest/posttest, or posttest only designs; seven used prospective two or more group comparison designs; and four used randomized, controlled designs. Nine studies on community pharmacies measured clinical outcomes, two measured humanistic outcomes, and five measured economic outcomes. Four studies measured both clinical and humanistic outcomes and one measured humanistic and economic outcomes. No study measured all three ECHO variables. Twenty-three studies in ambulatory care settings used prospective or retrospective, single group, pretest/posttest or posttest only designs; 21 used prospective or retrospective two-or-more group comparison designs; and 30 used randomized, controlled designs. Thirty-six measured clinical outcomes, five measured humanistic outcomes, and 15 measured economic outcomes. Fifteen studies measured clinical and economic outcomes and three measured clinical and humanistic outcomes.

CONCLUSIONS:

Only 21 of 95 selected studies were conducted in community pharmacy settings and measured the impact of pharmaceutical services on patient outcomes. Few studies employed adequate research designs to control threats to internal and external validity. In order to obtain a comprehensive and accurate picture of the impact of pharmaceutical services on patient outcomes, an attempt must be made to measure all three ECHO variables while employing adequate research design.
Rifapentine: Its Role in the Treatment of Tuberculosis
Authors: Temple Mary E , Nahata Milap C
Published: March 2004

OBJECTIVE:

To review the pharmacokinetics, efficacy, adverse effects, and cost of the newest antitubercular drug, rifapentine.

DATA SOURCES:

A MEDLINE search using key terms such as rifapentine, rifampin, isoniazid, Mycobacterium tuberculosis, and pyrazinamide was conducted for the time period 1966–November 1998.

STUDY SELECTION:

Animal data were used for basic information and human studies were selected for inclusion if they were randomized, controlled studies assessing efficacy, or if they were single- or multiple-dose studies assessing the pharmacokinetics of rifapentine. Background articles on the pathophysiology of tuberculosis and cost of care and noncontrolled studies assessing drug interactions were also included.

DATA SYNTHESIS:

Compared with an oral solution, the relative bioavailability of rifapentine is 70% following oral administration of tablets. Food increased bioavailability by 55%. Rifapentine accumulated significantly in human macrophages and its elimination half-life was longer than that of rifampin. Comparative studies of rifapentine and rifampin in humans during intensive- and continuation-phase treatment of tuberculosis suggest that at currently accepted doses, rifapentine was slightly less effective than rifampin. The most significant drug interaction with rifapentine involves indinavir: the maximum concentration and AUC of indinavir are reduced by 55% and 70%, respectively, when rifapentine is coadministered with indinavir. Adverse events of rifapentine may occur less frequently at the currently recommended 600-mg dose as compared with rifampin; however, the difference was not statistically significant. If only drug costs were evaluated during the six-month treatment of tuberculosis, rifapentine is more expensive than rifampin.

CONCLUSIONS:

Rifapentine can be administered twice weekly during the intensive phase of tuberculosis treatment and then once weekly during the continuation phase of treatment. This may improve patient adherence over some other treatments and possibly reduce costs of treatment by preventing development of resistant tubercular strains due to nonadherence. Rifapentine is well tolerated, with most patients experiencing adverse effects at a similar rate as rifampin. Rifapentine induces cytochrome P450 somewhat less than rifampin, although few drug interaction studies have been done with rifapentine. Its efficacy at the currently approved dosage of 600 mg may be slightly lower than that of rifampin. Studies are needed to determine if equal or greater efficacy can be achieved with higher doses of rifapentine. Rifampin is less expensive than rifapentine. Further pharmacoeconomic studies are needed to evaluate costs of relapse and failure in patients receiving these agents.
Role of Lamivudine in the Treatment of Chronic Hepatitis B Virus Infection
Authors: Hagmeyer Kathleen O , Pan Yu-Yuan
Published: March 2004

OBJECTIVE:

To examine the evidence regarding the therapeutic effectiveness of lamivudine in the treatment of chronic hepatitis B virus (HBV) infection in immunocompetent patients.

DATA SOURCES:

Using chronic hepatitis B and lamivudine as MeSH headings, MEDLINE was searched from 1966 to September 1998 for all published randomized controlled trials evaluating lamivudine in chronic HBV infection. Relevant articles from selected bibliographies were also retrieved.

STUDY SELECTION:

Only randomized, single- and double-blind trials in human HBV carriers published in the English language were included.

DATA SYNTHESIS:

Evidence from the controlled trials suggests that lamivudine has a therapeutic effect in suppressing HBV replication in immunocompetent patients. Lamivudine 100 mg/d appears to suppress HBV replication in as many as 97% of patients within two weeks after the initiation of therapy and is capable of suppressing histologic damages. However, viral suppression is effective only during the therapy; on discontinuation of lamivudine therapy, most patients return to the pretreatment condition. Viral resistance to lamivudine has been observed. Most patients with chronic HBV infection appear to tolerate 100 mg/d of lamivudine therapy.

CONCLUSIONS:

Evidence has shown that oral lamivudine 100 mg/d will produce rapid and significant suppression of viral replication in immunocompetent patients with chronic HBV infections. Treatment periods up to one year have been effective and well tolerated. The suppression of viral replication may not be sustained after cessation of lamivudine therapy, and very few patients have complete elimination of HBV during therapy. Therefore, long treatment periods may be necessary. Efficacy and tolerability of treatment beyond one year need to be investigated. Resistance to lamivudine has been reported in patients receiving therapy. A combination anti-HBV regimen using lamivudine and other agents with different mechanisms of action should be investigated to maximize the elimination of the viral infection while minimizing or preventing damage to the liver cells and tissues and the development of viral resistance.
The Impact of Estrogen Replacement Therapy and Raloxifene on Osteoporosis, Cardiovascular Disease, and Gynecologic Cancers
Authors: Umland Elena M , Rinaldi Christine , Parks Susan M , Boyce Eric G
Published: March 2004

OBJECTIVE:

To compare the clinical utility of estrogen replacement therapy (ERT) and raloxifene in osteoporosis and cardiovascular disease in postmenopausal women and to evaluate the contrasting adverse effects of these therapies.

DATA SOURCES:

A MEDLINE search was performed for January 1980 through September 1998 using the key terms raloxifene, estrogen, CVD, lipoproteins, and osteoporosis.

STUDY SELECTION AND DATA EXTRACTION:

All clinical studies assessing ERT and raloxifene in cardiovascular disease or osteoporosis were evaluated.

DATA SYNTHESIS:

ERT remains the standard for prevention and treatment of osteoporosis in women. Its use increases total bone mineral density (BMD) up to 12.1% and reduces hip fracture risk by 66–73%. It reduces low-density lipoprotein (LDL) cholesterol by 15–19% and increases high-density lipoprotein (HDL) cholesterol by 6–18%. Raloxifene, an alternative to ERT in the prevention of osteoporosis, increases total BMD by 2.2%. It reduces LDL by 6.2–14.1% and increases HDL by 1.5–5.7%. Preliminary data suggest that raloxifene has contrasting effects on gynecologic cancers compared with the increased risk posed by ERT.

CONCLUSIONS:

Clinical trials have illustrated greater effects on BMD with ERT than with raloxifene. Studies of significant duration assessing raloxifene and its fracture risk effects are lacking. ERT appears to have greater beneficial cardiovascular risk factor effects than raloxifene. Prospective, primary prevention studies evaluating overall cardiovascular risk reduction do not exist for either intervention. Raloxifene, while more costly, is an alternative that may have a lower associated risk of breast cancer compared with ERT.
Candesartan Cilexetil: An Angiotensin II Receptor Blocker
Authors: Stoukides Cheryl A , McVoy Heather J , Kaul Alan F
Published: March 2004

OBJECTIVE:

To summarize and critique the medical literature on candesartan cilexetil, an angiotensin II receptor blocker (ARB).

DATA SOURCES:

MEDLINE searches (January 1966–January 1999) and manufacturer prescribing literature were used to identify articles on candesartan cilexetil. Bibliographies were also reviewed for germane articles.

STUDY SELECTION:

Study and review articles describing the chemistry, human pharmacology, pharmacodynamics, pharmacokinetics, placebo-controlled trials, comparative trials, and clinical application of candesartan cilexetil based on the published literature and premarketing clinical trials were reviewed.

DATA EXTRACTION:

All literature on the use of candesartan cilexetil for treating hypertension and congestive heart failure were included.

DATA SYNTHESIS:

ARBs are a new class of drugs with increasing use in treating hypertension. Studies are ongoing to determine the role of these agents in preventing remodeling after myocardial infarction and in patients with congestive heart failure. Candesartan cilexetil is among the newest drugs in the class that includes losartan, irbesartan, and valsartan. Candesartan cilexetil has more than 1000 times more affinity for the angiotensin II, type AT1 receptor ARBs, and the binding affinity and competitive angiotensin II receptor antagonism is stronger than that of losartan. Clinical studies in patients with hypertension have demonstrated that candesartan cilexetil, in doses of 4–16 mg, is more effective in reducing sitting diastolic blood pressure than are placebo and losartan 50 mg. Candesartan cilexetil has demonstrated reductions in blood pressure comparable to those of enalapril, with the rate of adverse events greater in the enalapril group. Dosage adjustments are not necessary in elderly patients or in patients with mild hepatic or renal dysfunction. In diabetic patients, blood glucose, hemoglobinA1c, and serum lipids are not affected. The clinical studies demonstrated that the adverse effect profile of candesartan cilexetil was similar to that of placebo and there were no dose-dependent adverse effects.

CONCLUSIONS:

Candesartan cilexetil provides an alternative antihypertensive therapy that is well tolerated and effective in reducing blood pressure in a wide range of patients. Due to its greater binding affinity to the angiotensin II receptor, candesartan cilexetil appears to have a longer antihypertensive effect than losartan. This may be advantageous in decreasing morbidity and mortality associated with hypertension, although further studies are required to validate this potential advantage.
Methylxanthine Use in Anaphylaxis: What Does the Evidence Tell Us?
Authors: Ernst Michael E , Graber Mark A
Published: March 2004

OBJECTIVE:

To review the literature examining the use of methylxanthines in the treatment of anaphylaxis.

DATA SOURCES:

A MEDLINE search (January 1966–December 1998) was performed using the terms aminophylline, theophylline, and anaphylaxis.

STUDY SELECTION AND DATA EXTRACTION:

Articles discussing methylxanthine use in anaphylaxis were independently examined by each author. Additional information was obtained through the references of these articles. Articles not written in English were excluded.

DATA SYNTHESIS:

No human studies were identified. Limited published data were found in animal models of anaphylaxis.

CONCLUSIONS:

Safer agents with proven efficacy exist for the treatment of bronchoconstriction in anaphylaxis. Until data are available in humans, methylxanthines should not be recommended in the treatment of anaphylactic reactions.
Multidrug-Resistant Tuberculous Meningitis: Clinical Problems and Concentrations of Second-Line Antituberculous Medications
Authors: DeVincenzo John P , Berning Shaun E , Peloquin Charles A , Husson Robert N
Published: March 2004

OBJECTIVE:

To describe a case of culture-proven multidrug-resistant tuberculous (MDR-TB) meningitis, in which the patient survived long enough for clinicians to adjust antituberculous therapy to second-line therapeutic agents.

DESIGN:

Case report.

SETTING:

Tertiary care hospital.

PATIENT:

Twenty-one-month-old girl with MDR-TB meningitis.

INTERVENTIONS:

Initial standard treatment failed. Subsequent treatment with second-line therapeutic agents including ciprofloxacin, cycloserine, ethambutol, ethionamide, and rifabutin were given for approximately two years. Concentrations of these drugs were measured in serum and cerebrospinal fluid in the presence and absence of meningeal inflammation.

MAIN OUTCOME MEASURES/RESULTS:

The patient survived for approximately two years after initiation of second-line anti-TB therapy. During this treatment, she developed a ventriculo-peritoneal shunt tunnel tract infection secondary to MDR-TB.

CONCLUSIONS:

All TB meningitis isolates for which the source case antibiotic susceptibility pattern is not known should be cultured and susceptibility tested using rapid broth techniques. Measurement and subsequent adjustment of therapeutic drug concentrations may optimize therapy with second-line anti-TB drugs in TB meningitis. Better pediatric formulations and pharmacokinetic data for second-line and anti-TB therapeutic agents are needed.
Is Rectally Administered Cisapride an Effective Prokinetic Agent?
Authors: Gales Mark A , Harms Dustin W
Published: March 2004

OBJECTIVE:

To summarize the published data on the efficacy of rectally administered cisapride.

DATA SOURCES:

Published double-blind, placebo-controlled trials on rectally administered cisapride identified by MEDLINE (January 1966–December 1998) and International Pharmaceutical Abstracts (January 1970–December 1998) searches.

DATA SYNTHESIS:

Cisapride is an oral prokinetic agent that increases lower esophageal sphincter tone, accelerates gastric emptying, and increases small-bowel motility. Clinical trials of rectal cisapride have used both single- and multiple-dosing regimens. Typically, patients received one or two 30-mg suppositories (provided by the manufacturer). Rectal cisapride was effective in enhancing gastric emptying of solid or semisolid meals in healthy patients or patients with chronic gastric emptying disorders. Rectal cisapride was not effective in antagonizing the gastrointestinal effects of narcotic analgesics or promoting the return of small-bowel activity in adults with postoperative ileus. Mixed results were seen when rectal cisapride was used to promote enteral feedings in patients with persistent ileus.

CONCLUSIONS:

The use of rectal cisapride cannot be recommended at this time. Rectal cisapride was effective only in patients who could have otherwise taken either cisapride tablets or suspension but it was not effective in patients who are physically unable to swallow or restricted from ingesting anything orally following surgical procedures. Considering the varied patient populations and evaluation methods used in these studies, the lack of a commercially available cisapride suppository, and absence of studies involving extemporaneously prepared cisapride suppositories, the use of suppositories should be limited to investigational trials.
Calcium Treatment for Premenstrual Syndrome
Authors: Ward Michael W , Holimon Teresa D
Published: March 2004

OBJECTIVE:

TO evaluate the use of calcium supplementation in the treatment of premenstrual syndrome.

DATA SOURCES:

Clinical literature accessed through MEDLINE (from January 1967 to September 1999). Key search terms included calcium, PMS, and premenstrual.

DATA SYNTHESIS:

Up to 50% of women experience some form of premenstrual syndrome. An evaluation of studies focusing on calcium in the management of premenstrual symptoms was conducted.

CONCLUSIONS:

Calcium supplementation of 1200–1600 mg/d, unless contraindicated, should be considered a sound treatment option in women who experience premenstrual syndrome. The supplemental dose of calcium can be adjusted downward in the few patients who routinely consume large quantities of calcium in their diet.
Amphetamines to Counteract Opioid-Induced Sedation
Authors: Corey PJ , Heck Amy M , Weathermon Ronnie A
Published: March 2004

OBJECTIVE:

TO describe the data regarding the use of amphetamines and amphetamine derivatives to counteract opioid-induced sedation.

Sedation is a major dose-limiting adverse effect of opioid therapy for many patients. Several reports have evaluated the use of amphetamines and amphetamine derivatives, such as mazindol, dextroamphetamine, and methylphenidate, to counteract opioid-induced sedation, with limited results.

CONCLUSIONS:

General use of amphetamines for the treatment of opioid-induced sedation is not recommended. However, these agents may be effective for certain patients who experience dose-limiting sedation with opioids and have exhausted all other options available to manage this adverse effect. More research is needed to identify appropriate candidates for therapy, the preferred amphetamine, and the optimal dose.
Tolterodine–Warfarin Drug Interaction
Authors: Colucci Vincent J , Rivey Michael P
Published: March 2004

OBJECTIVE:

To report two cases of warfarin therapy in which the addition of tolterodine resulted in prolonged international normalized ratios (INRs).

CASE SUMMARY:

Two patients, each receiving warfarin for stroke prophylaxis in association with chronic atrial fibrillation, developed adverse effects after the initiation of tolterodine for urinary disorders. Other medications for concurrent medical diagnoses had remained unchanged. One patient had an episode of prostatitis, which was treated with levofloxacin immediately prior to tolterodine initiation. The warfarin dosage had remained constant for many weeks in both patients prior to and during the tolterodine trials. In each patient, the initiation of tolterodine was associated with a significant increase in the patient's INR measured 10–14 days later. Thus, tolterodine was ineffective in both patients and was discontinued one to two days before the elevated INRs were determined during routine clinic visits. INRs determined approximately two weeks after tolterodine was discontinued were similar to those obtained during the period before the use of the drug; the warfarin dosage remained unchanged. Rechallenge with tolterodine was not attempted in either patient.

DISCUSSION:

Several aspects of the reported cases support the validity of a proposed drug interaction when tolterodine is initiated in a patient stabilized on warfarin therapy. The temporal association of the course of tolterodine with an elevated INR, the return to the previous warfarin dose–INR response relationship after tolterodine discontinuation, and the absence of other causes for the elevated INR were factors found in both patients. Possible mechanisms to explain the suggested drug interaction are explored.

CONCLUSIONS:

Until further data are available, clinicians should be vigilant for a possible drug interaction when tolterodine therapy is initiated in a patient maintained on warfarin therapy.
Adverse Drug Events in Elderly Patients Receiving Home Health Services following Hospital Discharge
Authors: Gray Shelly L , Mahoney Jane E , Blough David K
Published: March 2004

OBJECTIVE:

To assess incidence, healthcare consequences, and identify risk factors for adverse drug events (ADEs) in elderly patients receiving home health services during the month following hospital discharge.

METHODS:

This was a prospective cohort study of three home health agencies in Madison, Wisconsin, and its surrounding area. The sample consisted of 256 participants aged •65 years who were hospitalized for medical illness, received home nursing after discharge, and completed the one-month interview. The main outcome measure was self-reported ADEs (possible, probable, or definite) during the month following hospital discharge.

RESULTS:

Incidence of ADEs was 20%. Fifty-two participants (20.3%) reported 64 ADEs: 23 possible, 37 probable, and four definite. The most common ADEs involved the gastrointestinal tract (31.3%) and the central nervous system (31.3%). Of 53 ADEs reported to providers, 59% of the drugs were discontinued or altered. One ADE resulted in hospitalization. In logistic regression, female gender (OR = 2.26; 95% CI 1.06 to 4.77) and the interaction between number of new medications and cognition were significantly associated with ADEs. The risk of an event increased with the number of new medications at discharge; however, risk was elevated primarily for participants with lower cognition.

CONCLUSIONS:

ADEs were common during the month following hospital discharge, were more frequent in women, and often resulted in medication changes. Individuals at particular risk were those with lower cognition who were discharged with several new medications.
Rhabdomyolysis Associated with Concomitant Use of Atorvastatin and Cyclosporine
Authors: Maltz Helene C , Balog Denise L , Cheigh Jhoong S
Published: March 2004

OBJECTIVE:

To describe a case of rhabdomyolysis in a cadaveric renal transplant (CRT) patient receiving atorvastatin and cyclosporine.

CASE SUMMARY:

A 40-year-old Asian woman with a history of systemic lupus erythematosus (SLE) presented with bilateral lower-extremity weakness and elevated concentrations of creatine kinase (CK), aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and alkaline phosphatase after two months of concomitant therapy with atorvastatin and cyclosporine. Her other medications were not known to cause rhabdomyolysis; neither was there evidence of an SLE flare. After atorvastatin was discontinued, her CK concentrations declined dramatically and her symptoms resolved.

DISCUSSION:

Rhabdomyolysis has been reported in patients treated with other 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors when used in combination with cyclosporine. Atorvastatin, a relatively new HMG-CoA reductase inhibitor, has not been reported to cause rhabdomyolysis when used concomitantly with cyclosporine. However, its pharmacologic and pharmacokinetic properties make an interaction with cyclosporine possible.

CONCLUSIONS:

Similar to other members of the HMG-CoA reductase inhibitor class, atorvastatin may interact with cyclosporine and potentially result in rhabdomyolysis. Clinicians should be aware of this possible drug interaction and carefully monitor patients receiving these two drugs concomitantly.
Desensitization to Allopurinol in a Patient with Previous Failed Desensitization
Authors: Tanna Saloni B , Barnes Julie F , Seth Shiv K
Published: March 2004

OBJECTIVE:

To describe an allopurinol desensitization that failed on the first attempt but was successful on the second attempt, resulting in the management of crippling tophaceous gout.

CASE SUMMARY:

A 64-year-old white man with a history of gouty nephropathy requiring hemodialysis developed a severe cutaneous reaction from exposure to allopurinol. The first desensitization attempt was unsuccessful, and the gouty nephropathy caused chronic cellulitus and urate microcrystal deposition on the patient's hands and feet. Continuous ambulatory peritoneal dialysis and hemodialysis were used to treat the patient's severe symptoms and increase uric acid clearance. This method, however, was ineffective. Severe tissue ischemia, requiring bilateral below-the-knee amputations, prompted the second desensitization attempt four years later. The second attempt, administered differently and with more caution, was successful and did not cause further complications.

DISCUSSION:

Allopurinol is the only agent available to effectively reduce uric acid concentrations in those who are over-producers. Hypersensitivity-type reactions have been reported with its use, and desensitization is the only viable therapeutic option. Few cases of desensitization to allopurinol have been reported in the literature. This article describes a failure and a subsequent success in desensitization to allopurinol.

CONCLUSIONS:

Although desensitization to allopurinol poses potential risks, the benefits can outweigh the risks of therapy. Desensitization requires close monitoring; if failure does occur, subsequent attempts can be successful, as this case report demonstrates.
Medication-Related Visits to the Emergency Department: A Prospective Study
Authors: Tafreshi Mohammad J , Melby Michael J , Kaback Keith R , Nord Teresa C
Published: March 2004

OBJECTIVE:

To assess the prevalence, preventability, category, and severity of drug-related problems; medications involved; common causes of preventable medication-related visits (MRVs); and cost of MRVs.

METHODS:

In this prospective, observational study of emergency department visits, patients were identified as having MRVs by use of a questionnaire. The patients or their representatives were interviewed to assess whether the emergency department visit was caused by a medication-related problem. Patient selection was consecutive. A blinded panel of pharmacists and one physician was used to assess study objectives.

RESULTS:

Of the 253 patients interviewed, 71 patients (28.1%) presenting to the emergency department had a medication-related reason for their visits. Of the 71 MRVs, 50 (70.4%) were judged to be preventable and 21 (29.6%) nonpreventable. The data showed that MRVs are most often caused by an adverse drug reaction, followed by overprescribing of the correct medication. The severity of MRVs was most often classified as moderate. The most common medications involved were cardiovascular agents. The preventable MRVs were mostly due to noncompliance issues, inappropriate prescribing, inappropriate monitoring, and lack of patient education. The average cost to the institution was approximately $1444 per preventable MRV.

CONCLUSIONS:

In our study, the prevalence of MRVs was higher than in previous studies due to the prospective nature of the study and the assistance of drug experts in identifying and classifying the incidents. Areas identified for improvement included compliance issues with patients, education of healthcare workers regarding prescribing and monitoring of medications, and patient education.
Treatment of Radiation-Induced Proctitis with Sucralfate Enemas
Authors: Melko George P , Turco Thomas F , Phelan Thomas F , Sauers Nathan M
Published: March 2004

OBJECTIVE:

To report a case of radiation-induced proctitis treated with sucralfate enemas.

CASE SUMMARY:

A 77-year-old white woman was transferred from an acute care institution to our inpatient rehabilitation unit with impaired mobility and reduced activities of daily living. Her condition was secondary to myopathy and peripheral neuropathy associated with postradiation chemotherapy and metastatic ovarian carcinoma. During her stay, she developed hematochezia and pain secondary to a diagnosis of radiation-induced proctitis. Her hemoglobin had reached a nadir of 7.3 g/dL. The patient received blood transfusions and was started on 10% w/v sucralfate retention enemas 2 g/20 mL daily for 12 consecutive days. She was symptom-free at discharge, with a stable hemoglobin of approximately 10 g/dL.

DISCUSSION:

Proctitis is a common adverse effect of radiotherapy to the lower abdomen and pelvic area. Sucralfate is an aluminum complex that acts as a local cytoprotective agent against ulceration of the gastrointestinal mucosal lining. Rectal administration of sucralfate, as described in our patient and reported in published case studies, may provide an alternative therapy for patients with radiation-induced proctitis.

CONCLUSIONS:

Sucralfate suspension enemas provide a viable treatment option in patients who are intolerant of, refractory to, or not candidates for standard therapy for radiation-induced proctitis.
The Pharmacokinetics, Safety, and Tolerance of Cefepime Administered as an Intravenous Bolus or as a Rapid Infusion
Authors: Garrelts James C , Wagner David J
Published: March 2004

OBJECTIVE:

To evaluate the pharmacokinetics, safety, and tolerability of cefepime administered as an intravenous bolus and short infusion.

METHODS:

A single-dose, pharmacokinetic study was conducted on 16 healthy men. Fifty milliliters of a 40 mg/mL solution of cefepime was administered by continuous infusion in intervals of three, five, 10, or 15 minutes. Blood was sampled three minutes through 12 hours after the end of the infusion. Analysis of cefepime was performed by reverse-phase HPLC with ultraviolet detection. Cefepime plasma concentrations versus time were evaluated by noncompartmental methods. History and physical examinations were conducted within two weeks of the start of the study, 24 hours before dosing, and at the end of the study. Assessments for adverse events were made throughout the study.

RESULTS:

Maximum concentration (Cmax) increased with decreasing time of infusion and was similar to reference values of Cmax. Pharmacokinetic characteristics of cefepime were not affected by the time of infusion and were on average: mean residence time was 2.3 hours, half-life 1.9 hours, the AUC extrapolated to infinity 239 μg•h/mL, total body clearance 142 mL/min, and steady-state volume of distribution 19 L. No serious adverse events, local tolerance at injection site, or significant laboratory abnormalities were noted.

CONCLUSIONS:

Cefepime 2 g was safely administered to healthy subjects as a rapid, single bolus, and its key pharmacokinetic parameters were consistent with those from longer infusions and other studies.
A Time–Kill Evaluation of Clarithromycin and Azithromycin against Two Extracellular Pathogens and the Development of Resistance
Authors: Burgess David S , Hastings Rhonda W , Horan Jennifer L
Published: March 2004

OBJECTIVE:

To determine the activity of clarithromycin, its metabolite (14-hydroxyclarithromycin), and azithromycin against Haemophilus influenzae and Staphylococcus aureus using time–kill methodology and to evaluate the susceptibility of the organisms following exposure to various concentrations of the azalide macrolides.

DATA SOURCES AND METHODS:

Clinical isolates of H. influenzae and S. aureus were obtained from the Clinical Microbiology Laboratory at University Hospital, San Antonio, Texas. Susceptibility testing was performed according to National Committee for Clinical Laboratory Standards guidelines. 14-Hydroxyclarithromycin was added to clarithromycin solutions used for H. influenzae. Time–kill studies were performed using antimicrobial concentrations of 0.25–8 x minimum inhibitory concentration (MIC) and an initial inoculum of ∼105 CFU/mL. Samples were plated onto solid agar at 0, 4, 8, 12, and 24 hours. At 0, 12, and 24 hours, samples were then plated onto solid agar incorporated with antibiotic. After incubating plates at 35 °C for 24 hours, colony counts were determined.

RESULTS:

The MICs of clarithromycin and clarithromycin plus 14-hydroxyclarithromycin for H. influenzae were 4 and 2 μg/mL, respectively. For S. aureus, the MIC of clarithromycin was 0.25 μg/mL, and the MIC of azithromycin for both organisms was 1 μg/mL. H. influenzae developed resistance to both macrolides within 12 hours when exposed to sub-MICs of clarithromycin plus 14-hydroxyclarithromycin. However, when exposed to concentrations less than or equal to the MIC of azithromycin, resistance was not conferred to clarithromycin. S. aureus, on the other hand, became resistant to azithromycin and less susceptible to clarithromycin following exposure to sub-MICs of either macrolide.

CONCLUSIONS:

Clarithromycin and azithromycin elicited a concentration-independent bacteriostatic effect against H. influenzae and S. aureus at concentrations at least two times the MIC. In addition, concentrations maintained above the MIC prevented changes in the susceptibility of H. influenzae and S. aureus to both macrolides.