bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of Benzodiazepines in Newborns
Authors: Ng Eugene , Klinger Gil , Shah Vibhuti , Taddio Anna 
Published: June 2003

BACKGROUND: Benzodiazepines are being used in neonatal intensive care units for sedation and control of seizures. However, anecdotal reports suggest that their use in infants may be associated with serious adverse effects (AEs). OBJECTIVE: To determine the incidence of AEs from benzodiazepine use in preterm and full-term infants. METHODS: Retrospective chart review of 63 infants who received benzodiazepines as a sedative or anticonvulsant over a 16-month period. RESULTS: Mean ± SD gestational age of the infants was 33.1 ± 6.2 weeks, and birth weight was 2.3 ± 1.2 kg. Median (range) postnatal age at commencement of drug administration was 19 (5–54) days. Forty-one infants received lorazepam, 8 received midazolam, and 14 received both. Ten (16%) of the infants had 14 documented adverse events: seizures (n = 6), hypotension (n = 5), and respiratory depression (n = 3). Using a validated adverse drug reaction probability scale, a probable association with benzodiazepine use was demonstrated in 12 of the AEs. Due to the retrospective nature of the data, a score for definite association was not attainable. Anticonvulsant administration was required for 4 of 6 infants and, in all cases of respiratory depression, ventilatory support was initiated or increased. Two cases of significant hypotension were treated with inotropes. There was no statistically significant correlation between AEs and benzodiazepine dose or concomitant use of inotropes or analgesics (morphine), although most infants had underlying medical conditions or received multiple drugs that may have predisposed them to experience AEs. CONCLUSIONS: Administration of benzodiazepines was frequently associated with AEs in full-term and preterm infants. It is possible that underlying illnesses and concomitant drug use predisposed these effects. Until the benefit-to-risk ratio is determined by further studies, judicious use of benzodiazepines is recommended in this vulnerable population.
Increased Use of Antidepressants in Canada: 1981–2000
Authors: Hemels Michiel EH , Koren Gideon , Einarson Thomas R 
Published: June 2003

OBJECTIVE: To provide a descriptive analysis of Canadian utilization (prescriptions, cost, cost per prescription) of antidepressants (ATC-code: N06A). METHODS: IMS Canada provided prescription volumes and costs from 1981 to 2000. We analyzed time trends for antidepressants in general and 4 subclasses (tricyclic antidepressants [TCAs], selective serotonin-reuptake inhibitors [SSRIs], dual action antidepressants [DAAs], and monoamine oxidase inhibitors [MAOIs]). Costs were discounted using the consumer price index, adjusting for population growth using data from Statistics Canada. RESULTS: Between 1981 and 2000, total prescriptions increased from 3.2 to 14.5 million. Market share of TCAs (23.7%) and MAOIs (2.1%) remained constant, despite the introduction of the first SSRI, fluoxetine, in 1989. SSRI prescriptions increased to 6.7 million (market share 46.3%). DAA use increased gradually after 1994 to 3.5 million prescriptions (23.9% market share) in 2000. The number of prescriptions expanded (possibly due to SSRIs) by 238%, with an increased cost of $2.7 billion. Total expenditures for antidepressants increased exponentially, from $31.4 million in 1981 to $543.4 million in 2000 (y = 4E — 130e0.1556x [R2 = 0.99]). Cost per prescription increased linearly from $9.85 in 1981 to $37.44 in 2000 (y = 1.72x + 7.92 [R2 = 0.96]). CONCLUSIONS: Utilization and costs of pharmacotherapy for depression have increased above the inflation rate and are expected to exceed $1.2 billion ($50 per prescription) in 2005. Increased costs may be due to increased availability of new products with increased safety, efficacy, and acquisition cost; increased number of users; and increasing costs.
ACE Inhibitor—Induced Bronchial Reactivity in Patients with Respiratory Dysfunction
Authors: Packard Kathleen A , Wurdeman Richard L , Arouni Amy J 
Published: June 2003

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are often associated with an increased incidence of cough and bronchial responsiveness that may cause further deterioration of patients with impaired pulmonary function. OBJECTIVE: To review the available literature on the incidence of cough and bronchial responsiveness associated with ACE-inhibitor therapy in patients with asthma, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). DATA SOURCES: Literature was accessed through MEDLINE (1985–September 2001). Key search terms included cough, bronchospasm, asthma, congestive heart failure, chronic obstructive pulmonary disease, ACE inhibitors, and angiotensin II receptor blockers. DATA SYNTHESIS: The literature reports several cases of increased bronchial responsiveness associated with ACE inhibitors. Larger, controlled studies evaluating the increased risk in patients with pulmonary dysfunction are limited. Data from these trials are summarized in this article. CONCLUSIONS: The literature shows that patients with primary airway disease such as asthma and COPD are not at an increased risk of developing cough or bronchoconstriction as a result of ACE-inhibitor therapy. Despite the ability of ACE inhibitors to improve exercise tolerance, perfusion, and gas transfer, patients with CHF may be at higher risk of developing cough than the general population. Whether this cough is attributed to ACE inhibition or increased left-ventricular dysfunction remains uncertain. If increased bronchial responsiveness does occur, angiotensin II receptor antagonists are another reasonable option.
Hospital Admissions Resulting from Preventable Adverse Drug Reactions
Authors: McDonnell Patrick J , Jacobs Michael R 
Published: June 2003

BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of hospital admissions. These events can lead to significant morbidity and mortality and financial costs. ADRs that may be preventable might be considered a form of medication error. OBJECTIVE: To assess the potential preventability of ADRs directly related to a patient's hospital admission. METHODS: A retrospective chart review of 437 ADRs occurring during an 11-month period was conducted at a university hospital. A subset of these events leading to hospital admissions was identified for further review. Those that resulted in admission were further examined to determine probability of causality, severity, and preventability. RESULTS: Over 11 months, 158 ADRs were directly related to hospital admission. The relationship of these admissions to drug exposure was determined to be probable or highly probable in 154 (97.4%) of these cases. From this group, 96 (62.3%) of these events were considered potentially preventable, with 23 (24%) considered severe to life-threatening. Characteristics associated with these ADRs included documentation of a toxic drug concentration or abnormal laboratory value (80%), inadequate monitoring of a patient's drug therapy (67%), inappropriate dose (51%), patient noncompliance (33%), drug—drug interaction (26%), contraindication to therapy (3%), and documented allergy (1%). These ADRs resulted in 595 hospital days, with an average length of stay of 6.1 days. CONCLUSIONS: ADRs leading to hospital admissions are often preventable. Approximately 25% of these events were serious to life-threatening. Most resulted from inadequate monitoring of therapy or inappropriate dosing. Patient noncompliance and drug interactions were also common causes. Multidisciplinary prevention strategies among physicians, pharmacists, other healthcare professionals, and patients focusing on communication and education should be targeted.
Extrapyramidal Symptoms with Ritonavir/Indinavir Plus Risperidone
Authors: Kelly Deborah V , Béïque Lizanne C , Bowmer M Ian 
Published: June 2003

OBJECTIVE: To report a case of suspected extrapyramidal symptoms (EPS) in a patient initiated on ritonavir and indinavir while taking risperidone for a tic disorder. CASE SUMMARY: A 35-year-old white man with AIDS received risperidone 2 mg twice daily for treatment of a Tourette's-like tic disorder. Ritonavir and indinavir were initiated, and 1 week later, he experienced significantly impaired swallowing, speaking, and breathing, and worsening of his existing tremors. Ritonavir and indinavir were discontinued. On the same day, the patient increased the risperidone dosage to 3 mg twice daily. Symptoms continued to worsen over the next 3 days. All investigations and laboratory parameters were unremarkable, and vital signs were stable. Risperidone was discontinued and clonazepam initiated. Three days later, the patient's symptoms were significantly improved. DISCUSSION: The symptoms described herein are consistent with neuroleptic-induced acute dystonia and potentially neuroleptic-induced parkinsonism. We believe this adverse effect occurred as a result of a drug interaction between ritonavir/indinavir and risperidone. Based on the pharmacokinetics of these medications, we hypothesize that inhibition of CYP2D6 and CYP3A4 by ritonavir and indinavir may have resulted in an accumulation of the active moiety of risperidone, which may explain the occurrence of EPS in this patient. CONCLUSIONS: This is the second published case report describing a suspected drug interaction with ritonavir, indinavir, and risperidone. Caution is warranted when risperidone is prescribed with ritonavir/indinavir, and possibly with other antiretrovirals that inhibit the same pathways.
Delayed Recurrent SIADH Associated with SSRIs
Authors: Arinzon Zeev H , Lehman Yehoshua A , Fidelman Zeev G , Krasnyansky Irina I 
Published: June 2003

BACKGROUND: Depression is a common problem in elderly patients and is frequently treated with selective serotonin-reuptake inhibitors (SSRIs). OBJECTIVE: To report a case of delayed recurrent hyponatremia after switching from one SSRI to another. CASE SUMMARY: An 87-year-old depressed woman began treatment with fluvoxamine. One week later, she was diagnosed with hyponatremia, most likely syndrome of inadequate antidiuretic hormone. Following discontinuation of fluvoxamine, the serum sodium concentration normalized. Later, she began treatment with paroxetine. Sixteen months after initiating paroxetine, she developed symptomatic recurrent hyponatremia. After paroxetine was discontinued, the sodium concentration normalized. DISCUSSION: In this case, unlike those previously reported, hyponatremia recurred 16 months after a different SSRI was initiated. The Naranjo probability scale indicates a probable relationship between recurrent hyponatremia and paroxetine. The mechanism of SSRI-induced hyponatremia is multifactorial. CONCLUSIONS: This case illustrates that replacement of one SSRI with another can cause delayed, recurrent hyponatremia in elderly patients. Plasma sodium concentrations must be monitored, not only in the first weeks of treatment, but throughout the full course.
Continuous Infusion of Coagulation Factor Products
Authors: Stachnik Joan M , Gabay Michael P 
Published: June 2003

OBJECTIVE: To review clinical information related to the use of continuous infusion factor products in patients with hemophilia. Specifically, case reports and open-label trials are summarized involving the use of factor VIII and recombinant factor VIIa for a variety of indications including surgical prophylaxis, acute bleeding, primary prevention, and management of inhibitors. In addition, issues surrounding the use of continuous infusion of factor products such as pharmacokinetic rationale, stability/sterility, and cost are reviewed. DATA SOURCES: Primary and review articles were identified through a MEDLINE search (1990–June 2001) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and all information deemed relevant was included in this review. DATA SYNTHESIS: Data concerning the administration of factor products are primarily detailed in open-label trials and case reports. Comparisons between intermittent bolus injections and continuous infusion of factor products are limited and primarily compare continuous infusion regimens with historical controls. The rationale behind the continuous-infusion approach is linked to the pharmacokinetics of factor products administered via this route. Pharmacokinetic data reveal that, with continuous infusion of factor products, a reduction in clearance and a maintenance of factor serum concentrations are noted. CONCLUSIONS: Administration of factor products (factor VIII and recombinant factor VIIa) via continuous infusion has produced favorable hemostatic effects compared with intermittent bolus injections. The advantages of continuous infusion include maintenance of a constant factor concentration, thereby reducing risk of bleeding from excessively low trough concentrations, and a decrease in factor consumption related to a reduction in factor clearance with constant infusion. Manufacturers recommend using reconstituted factor products either immediately or within 1–3 hours after reconstitution; however, several studies have found the products to be stable and sterile for longer periods.
Acute Renal Failure in Hospitalized Patients: Part II
Authors: Pruchnicki Maria C , Dasta Joseph F 
Published: June 2003

BACKGROUND:Acute renal failure (ARF) is a common condition in hospitalized patients. Research has been unable to identify the optimal target for therapeutic intervention; hence, effective prevention of and/or treatment for ARF remain elusive.OBJECTIVE:To examine the usefulness of current and potential pharmacologic treatments in seriously ill, hospitalized patients.DATA SOURCES:A MEDLINE search (1996–June 2002) was conducted using the search terms kidney (drug effects) and acute kidney failure (drug therapy). Bibliographies of selected articles were also examined to include all relevant investigations.STUDY SELECTION AND DATA EXTRACTION:Review articles, meta-analyses, and clinical trials describing prevention of and treatment for hospital-acquired ARF were identified. Results from prospective, controlled trials were given priority when available.CONCLUSIONS:Appropriate management of ARF includes prospective identification of at-risk patients, fluid administration, and optimal hemodynamic support. Drug treatments, including low-dose dopamine and diuretics, have demonstrated extremely limited benefits and have not been shown to improve patient outcome. Experimental agents influence cellular processes of renal dysfunction and recovery; unfortunately, relatively few drugs show promise for the future.
Additive Gastrointestinal Effects with Concomitant Use of Olestra and Orlistat
Authors: Heck Amy M , Calis Karim Anton , McDuffie Jennifer R , Carobene Suzanne E , Yanovski Jack A 
Published: June 2003

OBJECTIVE: To report a case of significant additive gastrointestinal effects with concomitant use of orlistat and an olestra-containing snack food. CASE SUMMARY: A 16-year-old African American girl with type 2 diabetes, hypercholesterolemia, and hypertension was participating in a pilot study that tested the safety and efficacy of orlistat. After 2 weeks of orlistat treatment, the patient presented to the clinic with complaints of soft, fatty/oily stools, flatus with discharge, abdominal pain, increased flatus, and fecal incontinence. On further questioning, it was determined that she was also consuming approximately 5 ounces of olestra-containing potato chips on a daily basis. The patient eliminated olestra from her diet and returned to the clinic with substantially diminished gastrointestinal adverse effects, despite continuing to take orlistat. DISCUSSION: This is the first published case describing additive gastrointestinal effects after concurrent use of orlistat and olestra. Education about the potential for serious additive gastrointestinal adverse effects is important to prevent premature and unnecessary discontinuation of orlistat therapy. Awareness of this potential interaction could be especially important for patients with underlying disease states in which severe gastrointestinal symptoms could result in significant complications. CONCLUSIONS: This case illustrates that significant gastrointestinal distress may result after olestra consumption during orlistat therapy. All patients receiving orlistat for the management of obesity should be properly educated about this potential drug—food interaction.
Kaletra (Lopinavir/Ritonavir)
Authors: Corbett Amanda H , Lim Michael L , Kashuba Angela DM 
Published: June 2003

OBJECTIVE: To review the pharmacology, virology, pharmacokinetics, efficacy, safety, and clinical use of lopinavir/ritonavir (Kaletra, Abbott Laboratories). DATA SOURCES: English-language MEDLINE and AIDSline searches were performed (1966–July 2001) using lopinavir, ABT-378, and Kaletra as key words. Abstracts from infectious diseases and HIV scientific meetings were identified. Abbott Laboratories provided additional published and unpublished information. DATA EXTRACTION: All publications, meeting abstracts, and unpublished information were reviewed and relevant items included. In vitro and preclinical studies were included as well as Phase II and III clinical trials. DATA SYNTHESIS: Lopinavir/ritonavir is a fixed-dose protease inhibitor (PI) combination used for the treatment of HIV-1 infection. Lopinavir, the active component of this combination, is extensively metabolized by CYP3A4 and produces low systemic concentrations when used alone. Ritonavir potently inhibits CYP3A4 and is used to enhance the systemic exposure of lopinavir. This combination results in lopinavir concentrations that greatly exceed those necessary in vitro to inhibit both wild-type and PI-resistant HIV isolates. In clinical trials with antiretroviral naïve and experienced patients, lopinavir/ritonavir was effective at suppressing HIV-RNA and increasing CD4+ T cell counts. Compared with other PIs, lopinavir/ritonavir may have advantages in the areas of pharmacokinetics, efficacy, and resistance. Toxicity, drug interactions, and medication adherence are important considerations surrounding its clinical use. CONCLUSIONS: Lopinavir/ritonavir is an effective option for the treatment of HIV-1-infected individuals when used in combination with other antiretroviral agents. It may be used as a component of initial therapy or salvage therapy; future studies will better define its place in therapy.
Estrogen Replacement Therapy for Alzheimer Disease in Postmenopausal Women
Authors: Owens Christopher T 
Published: June 2003

OBJECTIVE: To evaluate the clinical utility of oral conjugated equine estrogen in postmenopausal women with Alzheimer disease. DATA SOURCES: Literature was identified through MEDLINE (1997–January 2002). Key search terms included Alzheimer disease, estrogen replacement therapy, and treatment. DATA SYNTHESIS: Estrogen has been identified as a neuroprotective agent with possible application in degenerative disorders. Observational studies have demonstrated an association between estrogen replacement therapy and decreased incidence of Alzheimer disease. Two recent, controlled clinical trials have evaluated the role of oral conjugated estrogen in the treatment of Alzheimer disease. CONCLUSIONS: Clinical trials indicate that oral conjugated equine estrogen is not an effective treatment for Alzheimer disease in postmenopausal women.
Effect of Rifampin on Apparent Clearance of Everolimus
Authors: Kovarik John M , Hartmann Stefan , Figueiredo Joaquim , Rouilly Marisel , Port Andreas , Rordorf Christiane 
Published: June 2003

OBJECTIVE: To assess the influence of the CYP3A4 enzyme inducer rifampin on the pharmacokinetics of the immunosuppressant everolimus to provide guidance for their coadministration. METHODS: In this open-label, single-sequence, crossover study, 12 healthy subjects received a single oral 4-mg dose of everolimus alone and again after an 8-day pretreatment with rifampin 600 mg/d. Urinary excretion of 6β-hydroxycortisol was measured at various time points during rifampin treatment as a marker of CYP3A4 induction. RESULTS: Urine excretion of 6β-hydroxycortisol was significantly elevated during treatment with rifampin compared with prestudy, indicating enzyme induction. When everolimus was coadministered during rifampin treatment, the apparent clearance of everolimus was significantly increased, on average by 172%. This was manifested as a decrease in maximum concentration in all subjects, on average by 58% (range 14–73%). The AUC remained unaffected in 1 subject (although 6β-hydroxycortisol indicated enzyme induction) and decreased in the other 11 subjects. The average decrease in AUC in the full study population was 63% (range 0–82%). Everolimus half-life was reduced significantly, from an average of 32 hours to 24 hours. CONCLUSIONS: In everolimus-treated patients for whom rifampin is indicated, alternative agents with less enzyme induction potential than rifampin could be considered. Alternatively, the dose of everolimus could be individually titrated based on everolimus therapeutic drug monitoring during rifampin therapy.
The Use of Topiramate in Mood Stabilization
Authors: Maidment Ian D 
Published: June 2003

OBJECTIVE: To review data on the effectiveness of topiramate as a mood stabilizer. DATA SOURCES: Clinical literature accessed through MEDLINE (1985–September 2001) and the manufacturer. Key search terms included topiramate, mania, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: The traditional standard therapy for bipolar disorder has been lithium. Other mood stabilizers are increasingly being used to manage this complex disorder. Studies that used topiramate in bipolar disorders were evaluated. CONCLUSIONS: The present data from open trials suggest that topiramate may possibly possess antimanic properties. Controlled, double-blind studies are required to confirm this efficacy.
Role of Antibiotics for the Prevention of Cardiovascular Disease
Authors: Gabay Michael P , Jain Rupali 
Published: June 2003

OBJECTIVE: To evaluate the data regarding the use of antibiotic therapy for the prevention of cardiovascular events. DATA SOURCES: Pertinent literature was identified through a MEDLINE search (1966–September 2001) and through other secondary literature databases and/or bibliographies of pertinent articles. DATA SYNTHESIS: Cardiovascular disease is a common cause of morbidity and mortality among the general population, with well-defined risk factors (e.g., diabetes, hypertension, hyperlipidemia, cigarette smoking, genetic predisposition). Clinical data evaluating the association between the aforementioned risk factors and the development of atherosclerosis and subsequent cardiovascular disease are substantial; however, these risk factors may only partially explain the high prevalence of cardiovascular disease. The presence of Chlamydia pneumoniae within atherosclerotic lesions has been documented and may be an additional risk factor for the development and progression of cardiovascular disease. CONCLUSIONS: The results of primary and secondary prevention trials have shown conflicting evidence with regard to the beneficial effects of antibiotic therapy to reduce cardiovascular events. Currently, the lack of certainty in published data does not support the use of antibiotics for the prevention of cardiovascular disease. Clinicians should continue to emphasize interventions proven to reduce adverse cardiovascular events such as smoking cessation, reduction of hyperlipidemia, and control of hypertension.