bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity Management in Patients Receiving Low-Dose Aldesleukin Therapy
Authors: Sundin David J , Wolin Maurice J
Published: March 2004

OBJECTIVE:

To review the pathophysiology and subsequent treatment options for low-dose aldesleukin-induced toxicity when administered via intravenous bolus infusion, continuous intravenous infusion, or subcutaneous injection.

BACKGROUND:

The adverse events associated with high-dose aldesleukin therapy (600 000 IU per kg iv every 8 h for a maximum of 14 doses) are well documented in the literature; however, the adverse event profile of lower doses and alternative administration routes are less well described. An understanding of the adverse event profile associated with these alternative regimens can enhance management of toxicity.

DATA SOURCES:

English-language clinical studies, abstracts, and review articles pertaining to low-dose intravenous, continuous intravenous infusion, or subcutaneous injection of aldesleukin, as well as aldesleukin-induced adverse events.

STUDY SELECTION AND DATA EXTRACTION:

Relevant studies were selected that assist with understanding the pathophysiology, clinical management, diagnosis, and management of aldesleukin-induced adverse events.

CONCLUSIONS:

Aldesleukin therapy initiates a cytokine-mediated proinflammatory process resulting in a toxicity profile that is different from traditional nonbiologic chemotherapeutic agents. The frequency and severity of adverse events associated with aldesleukin administration are dependent upon dose, route, and administration schedule. In addition, most adverse reactions are self-limiting. Alleviation of aldesleukin-induced adverse effects can usually be achieved on an outpatient basis with agents such as antiemetics, antipyretics, and topical creams or lotions, as well as nonmedication interventions. Aggressive and proactive management of aldesleukin associated toxicities can help facilitate completion of therapy.
High Anion Gap Metabolic Acidosis Associated with Aminocaproic Acid
Authors: Budris William A , Roxe David M , Duvel James M
Published: March 2004

OBJECTIVE:

To report a case of high anion gap metabolic acidosis related to infusion of aminocaproic acid (ACA) that temporarily corrected during hemodialysis and resolved upon ACA discontinuation.

CASE SUMMARY:

A 65-year-old white woman with staphylococcal sepsis complicated by acute renal failure was treated with ACA to control a hemorrhagic coagulopathy. After receiving an initial 5-g bolus of ACA, she received a continuous intravenous infusion of 500 mg/h for just over 5 days, then 250 mg/h for a final 12 hours. Immediately after beginning ACA therapy, she developed a severe anion gap metabolic acidosis that briefly improved after hemodialysis. The condition resolved completely only after the discontinuation of ACA and therapy with a systemic alkalinizer.

DISCUSSION:

ACA is not among the previously identified causes of high anion gap metabolic acidosis. The temporal profile relating anion gap to ACA initiation, hemodialysis treatment, and ACA discontinuation supports causality in this case. The magnitude of increase in the anion gap appears to have been proportional to the dose of ACA.

CONCLUSIONS:

In patients with renal impairment, ACA administration may produce a dose-related, high anion gap metabolic acidosis that might be reversible during hemodialysis. Insufficient data are available, but when ACA must be used in such patients, a more conservative dosing of ACA should be coupled with close monitoring.
Rhabdomyolysis after Correction of Hyponatremia Due to Psychogenic Polydipsia Possibly Complicated by Clozapine
Authors: Wicki Jacques , Rutschmann Olivier T , Burri Haran , Vecchietti Gianluca , Desmeules Jules
Published: March 2004

OBJECTIVE:

To report a case of rhabdomyolysis related to rapid correction of hyponatremia attributable to compulsive drinking of water, possibly complicated by clozapine use.

CASE SUMMARY:

A 42-year-old white man treated with clozapine for schizophrenia was admitted for a generalized seizure. Marked hyponatremia due to psychogenic polydipsia was present. He developed a marked elevation of creatine kinase concentrations after correction of hyponatremia with hyperosmolar sodium solution, without clinical signs of rhabdomyolysis.

DISCUSSION:

Rhabdomyolysis associated with hyponatremia due to water intoxication has been reported in 17 patients to date. A possible explanation may lie within the framework of the calcium– sodium exchange across the skeletal muscle cell membrane. By increasing muscle cell permeability, clozapine treatment may possibly enhance the destruction of muscle cells.

CONCLUSIONS:

Hyponatremia due to water intoxication and concurrent use of clozapine should be considered in the differential diagnosis of rhabdomyolysis, especially in the severely psychiatrically disabled population.
Effect of a Dual-Lumen Peripheral Catheter on the Delivery of Known Incompatible Medications
Authors: Prince Randall A , Lucas Dirk S , Fox Janet L
Published: March 2004

OBJECTIVE:

To determine the degree to which a dual-lumen peripheral catheter prevented precipitation of solutions known to be incompatible due to pH during simultaneous infusion in an in vitro model.

METHODS:

An in vitro model was devised to simulate peripheral venous blood flow from an antecubital source to systemic circulation. Ondansetron was simultaneously infused with fluorouracil, aminophylline, sodium bicarbonate, and ampicillin sodium in concentrations reflective of clinical conditions into the Twin Cath 20/22 (the dual-lumen catheter used in this experiment). Study solutions were primed with the prepared drug solution and administered for 15 minutes. Phase I used Normosol-R as the diluent to gather preliminary data; phase II used human plasma. All samples were obtained immediately before the start of the infusion and at 5, 10, and 15 minutes during the infusion, and 5 minutes after the infusion. Samples were visually inspected at each time point for precipitation and analyzed in duplicate by the appropriate stability-indicating HPLC method (except for sodium bicarbonate). Compatibility was defined as no visual evidence of precipitation and no more than 15% mean change in final versus initial concentration.

RESULTS:

Phase I experiments showed immediate precipitation in Normosol-R within the venous flow. However, in phase II, because of the buffering capacity that plasma proteins add to plasma, no precipitation occurred. All the drug combinations used in this study have been reported to be incompatible at the concentrations tested; however, we detected no incompatibilities.

CONCLUSIONS:

The results of this study indicate that using a dual-lumen peripheral catheter, such as the Twin Cath, may allow solutions incompatible due to pH to be administered simultaneously.
Intravenous Azithromycin
Authors: Garey Kevin W , Amsden Guy W
Published: March 2004

OBJECTIVE:

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

DATA SOURCES:

A MEDLINE search from 1978 to May 1998 of the English-language literature and an extensive review of journals and meeting abstracts was conducted. Due to the lack of published literature concerning the efficacy, safety, and pharmacokinetics of the intravenous formulation of azithromycin, the manufacturer was also contacted and requested to supply information concerning intravenous azithromycin.

DATA EXTRACTION:

In vitro and preclinical studies were included, as well as data from Phase II and III clinical trials. Efficacy, pharmacokinetic, safety, and tolerability data were also supplemented with information from the manufacturer, due to the lack of published reports.

DATA SYNTHESIS:

Azithromycin, an azalide subclass of the macrolide antibiotics, is now available as an intravenous formulation. The intravenous form is approved for the treatment of community-acquired pneumonia caused by Chlamydia pneumoniae, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus (methicillin-sensitive), and Streptococcus pneumoniae, and for the treatment of pelvic inflammatory disease caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis in situations in which intravenous therapy is required. Its spectrum of activity, unique pharmacokinetics, and high and sustained tissue penetration allow for once-daily dosing with monotherapy in many cases. Clinical and bacteriologic response rates as well as the adverse event profile have been similar to or better than comparative agents.

CONCLUSIONS:

Azithromycin offers advantages over other agents due to its unique pharmacokinetics, high and sustained tissue penetration, and spectrum of activity. This allows for monotherapy and once-daily intravenous dosing for mild-to-moderate community-acquired pneumonia or pelvic inflammatory disease in many instances. Future research should focus on total duration of antibiotic therapy and the need, or lack thereof, for extensive oral antibiotic follow-up.
Severe Multisystemic Hypersensitivity Reaction to Carbamazepine Including Dyserythropoietic Anemia
Authors: Lombardi Sara M , Girelli Domenico G , Corrocher Roberto
Published: March 2004

OBJECTIVE:

To report a case of multisystemic hypersensitivity reaction to carbamazepine.

CASE SUMMARY:

An 81-year-old white man was admitted to our hospital because of fever, morbilliform pruritic rash, and jaundice. Fifty days before admission he had taken carbamazepine 200 mg po tid because of seizures. During the first few days following admission, a maculopapular rash progressed to generalized erythroderma with subsequent extensive skin exfoliation. After discontinuing carbamazepine the fever disappeared within 72 hours and hepatic function tests returned to normal within four days. Moreover, after admission the hemoglobin values gradually fell to 6.7 g/100 mL. A bone marrow aspirate showed hypercellularity with marked dyserythropoietic abnormalities, and the bone marrow biopsy showed large and diffused infiltration due to the presence of a low-grade small lymphocytic lymphoma. No specific therapy for the lymphoma was undertaken. The biochemical follow-up showed a total improvement of hemoglobin values. Eight months after drug discontinuation, the patient was asymptomatic; peripheral blood cell count and hemoglobin concentrations were persistently normal.

DISCUSSION:

To the best of our knowledge, this is the first published case report implicating carbamazepine as the cause of anemia associated with bone marrow hypercellularity and dyserythropoietic changes, instead of hypocellularity and reduction of erythroid precursors. An interesting point raised by our observation is the possible relation between carbamazepine intake and actual lymphoproliferative disease. The development of non-Hodgkin's lymphoma following carbamazepine treatment has been reported, with regression after the drug was discontinued. However, in our case, a bone marrow biopsy repeated eight months after drug discontinuation confirmed the diagnosis of low-grade lymphoma.

CONCLUSIONS:

This case report describes a severe multisystemic reaction, characterized by generalized erythroderma; and renal, hepatic, and bone marrow failure in a patient who started carbamazepine therapy 50 days beforehand.
Infection and Atherosclerosis — Focus on Cytomegalovirus and Chlamydia Pneumoniae
Authors: Cheng Judy WM , Rivera Nadya G
Published: March 2004

BACKGROUND AND OBJECTIVE:

Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections. This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (i.e, cytomegalovirus and Chlamydia pneumoniae) in atherogenesis, and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease.

DATA SOURCES:

English-language clinical studies, abstracts, and review articles pertaining to infectious agents and coronary atherosclerosis.

STUDY SELECTION AND DATA EXTRACTION:

Relevant seroepidemiologic and pathologic studies and animal models evaluating the role of cytomegalovirus or C. pneumoniae in coronary atherosclerosis.

DATA SYNTHESIS:

Studies evaluating the possible role of cytomegalovirus and C. pneumoniae in the pathogenesis of atherosclerosis, as well as studies examining the use of antimicrobial and antiviral agents for reduction of cardiovascular events, are reviewed and critiqued.

CONCLUSIONS:

Current data do not allow us to determine whether infection is a cause or a cofactor of atherosclerosis. These uncertainties can be resolved by larger scale seroepidemiologic, pathologic, and interventional studies. Such efforts will contribute to identifying populations that are appropriate for particular surveillance or specific interventions, such as antibiotics or antiviral therapy.
Clozapine-Induced Seizures and EEG Abnormalities in Ambulatory Psychiatric Patients
Authors: Silvestri Rosalia C , Bromfield Edward B , Khoshbin Shahram
Published: March 2004

OBJECTIVE:

To examine the seizure characteristics and electroencephalogram (EEG) abnormalities in psychiatric patients taking clozapine, given the estimate of a 10% cumulative risk of generalized seizures in this population.

DESIGN:

We reviewed all consecutive EEGs of ambulatory psychiatric patients taking clozapine performed at our laboratory during 1996 and 1997.

SETTING:

A university-affiliated urban teaching hospital.

SUBJECTS:

Twelve patients (4 F/8 M; mean age 40.1 y, range 20–63) had either presented with de novo ictal events within the first month of clozapine therapy (n = 8) or had EEGs recorded to assess seizure risk (n = 4).

RESULTS:

According to clinical history and interictal EEG findings, the patients were subdivided as follows: three patients with generalized tonic–clonic seizures, two with generalized myoclonic jerks (1 associated with simple partial seizures), two with complex partial seizures, and one with simple partial seizures. The EEGs revealed interictal epileptiform abnormalities (IEDs) in eight patients, two of whom had not had seizures. IEDs were focal or multifocal, with a predominance of left temporal foci. One patient showed a paroxysmal response to photic stimulation.

CONCLUSIONS:

Patients taking clozapine may be prone to partial seizures and focal EEG abnormalities as well as to generalized seizures and EEG abnormalities, as previously reported.
Influence of Prior ACE Inhibitor Therapy on Morbidity and Mortality following Acute Myocardial Infarction
Authors: Raggi Paolo , Dickson Natalie R , Boyne Michael , Pereira Roberto , Cooil Bruce , Wattanasuwan Norrapol , Russell Douglas C
Published: March 2004

BACKGROUND:

Angiotensin-converting enzyme inhibitor (ACE-I) therapy reduces complications of acute myocardial infarction (MI) even when the therapy is started very early after an acute event. This study sought to determine whether administration of ACE-I therapy prior to acute MI is related to subsequent patient morbidity and mortality.

METHODS:

Chart review of 318 consecutive patients admitted between September 1995 and December 1996 with a diagnosis of acute MI. Outcome data were compared between patient groups receiving ACE-I therapy prior to infarction and those who were not.

RESULTS:

Sixty-four patients (20%) were receiving prior ACE-I therapy. They experienced smaller MIs, as determined by peak creatine kinase elevation (1066 ± 134 vs. 1510 ± 95 IU; p < 0.05), and fewer Q-wave infarctions (p < 0.05) than did patients who were not receiving prior treatment. The severity of coronary artery disease, defined by an angiographic score, was similar for the two groups. Mortality rates, including patients resuscitated from ventricular fibrillation, were similar within the first 72 hours of admission (3% vs. 2%; p = NS), but patients receiving prior ACE-I therapy showed a greater long-term in-hospital mortality rate (14% vs. 5%; p < 0.05) related to more heart failure deaths. Multivariate logistic regression analysis identified age, treatment with digoxin prior to acute MI, and left ventricular ejection fraction after infarction, but not ACE-I therapy taken prior to infarction, as significant independent predictors of mortality and combined morbidity and mortality.

CONCLUSIONS:

In a group of patients experiencing an acute MI, those receiving prior ACE-I therapy were more likely to sustain fewer transmural MIs and smaller infarcts. Chronic ACE-I therapy may have cardioprotective effects during acute myocardial ischemia.
Stress Ulcer Prophylaxis in Medical ICU Patients: Annual Utilization in Relation to the Incidence of Endoscopically Proven Stress Ulceration
Authors: Devlin John W , Ben-Menachem Tamir , Ulep Sharon K , Peters Michael J , Fogel Ronald P , Zarowitz Barbara J
Published: March 2004

OBJECTIVE:

To measure changes in the proportion of medical intensive care unit (MICU) patients prescribed pharmacologic stress ulcer prophylaxis therapy over a 4-year period in relation to the incidence of stress-related ulceration detected by endoscopy at our institution.

DESIGN:

Retrospective 4-year review of pharmacy and endoscopy databases.

SETTING:

A 35-bed MICU.

PATIENTS:

Patients (n = 2941) admitted to the MICU for longer than 24 hours, between January 1, 1993, and December 31, 1996, without acute gastrointestinal hemorrhage on admission.

METHODS:

Records were reviewed to identify patients prescribed pharmacologic stress ulcer prophylaxis (>24 h of sucralfate or a histamine2-receptor antagonist [H2RA]), and patients with evidence of stress ulceration during endoscopy.

RESULTS:

The number of patients per year receiving stress ulcer prophylaxis significantly (p < 0.001) decreased between 1993 and 1996: 1993, 492/693 (71%); 1994, 478/798 (60%); 1995, 295/670 (44%); 1996, 164/780 (21%). There was no difference between years in the median duration of stress ulcer prophylaxis therapy or the proportion of patients receiving sucralfate versus H2RA therapy. There was no difference (p = 0.91) between years in the annual incidence of definite or possible stress-related ulceration: 1993, 6/693 (0.87%); 1994, 5/798 (0.63%); 1995, 6/670 (0.90%); 1996, 5/780 (0.64%).

CONCLUSIONS:

The incidence of endoscopically proven stress-related ulceration has remained unchanged over the past 4 years in our MICU despite significantly fewer patients receiving pharmacologic stress ulcer prophylaxis therapy.
Severe Neuromuscular Complications Possibly Associated with Amlodipine
Authors: Phillips Beth Bryles , Muller Barbara A
Published: March 2004

OBJECTIVE:

To document a case of severe, progressive myopathy, myalgias, arthralgias, and weakness possibly caused by amlodipine in a patient with benign essential hypertension.

CASE SUMMARY:

A 52-year-old white woman with asthma and newly diagnosed hypertension was initiated on zafirlukast therapy for asthma and amlodipine therapy for hypertension. Two months later, the patient reported severe, generalized muscle and joint pain, muscle stiffness, and weakness. The zafirlukast was discontinued without resolution of symptoms. Laboratory tests revealed an elevated C-reactive protein. The amlodipine dosage was increased. Her symptoms persisted and further laboratory tests revealed a positive anti-nuclear antibody screen, and negative single- and double-stranded DNA antibody tests. After another amlodipine dosage increase, the patient experienced a sudden onset of left-sided facial numbness, facial weakness, and a severe headache. The patient was admitted to rule out a possible cerebrovascular event or a metabolic neurologic process. Magnetic resonance imaging showed no abnormalities. The patient discontinued the amlodipine and reported complete resolution of the neurologic symptoms after 4 days. One month later, zafirlukast was reinitiated without a return of symptoms.

CONCLUSIONS:

Amlodipine was not initially suspected as a cause of these symptoms because these effects are not commonly associated with amlodipine therapy. However, due to the temporal relationship and progression of symptoms with increasing amlodipine dosage, drug-related causes were eventually explored. Review of the medical literature suggests myalgias and arthralgias may be adverse effects common to dihydropyridine calcium-channel antagonists.
Amoxicillin/Clavulanate-Associated Hepatic Failure with Progression to Stevens–Johnson Syndrome
Authors: Limauro David L , Chan-Tompkins Noreen H , Carter Russell W , Brodmerkel George J , Agrawal Radheshyam M
Published: March 2004

OBJECTIVE:

To describe a patient who developed hepatic failure, Stevens–Johnson syndrome (SJS), and died after receiving amoxicillin/clavulanate therapy.

CASE SUMMARY:

A 37-year-old white man without significant past medical history received a 10-day course of amoxicillin/clavulanate for treatment of pneumonia. Thirty-two days after starting amoxicillin/clavulanate, he developed jaundice, rash, pruritus, and increasing fatigue. On further evaluation, with the exclusion of toxicity from other drugs or diseases, the time course to development of cholestatic jaundice correlated with the use of amoxicillin/clavulanate. The patient consequently died with progressive hepatic failure, renal failure, and SJS.

DISCUSSION:

Hepatic injury has been reported with amoxicillin/clavulanate. Signs and symptoms of jaundice and pruritus may appear up to to six weeks after stopping therapy. Most cases of liver injury have been benign and reversible on discontinuation of the amoxicillin/clavulanate. Reported hepatic reactions have been mainly cholestatic, with some mixed cholestatic/hepatocellular liver function test abnormalities.

CONCLUSIONS:

Clinicians should be aware of amoxicillin/clavulanate as a drug capable of causing hepatitis with eventual systemic dysfunction. While recovery is usually complete following withdrawal of the drug, in patients with rash associated with hepatic dysfunction, renal insufficiency, or other unusual symptoms, earlier consideration of initiating systemic steroids or liver transplantation referral, in hopes of avoiding progressive systemic response, might be worthwhile.
Validation of an Electronic, Population-Based Prescription Database
Authors: Kozyrskyj Anita L , Mustard Cameron A
Published: March 2004

BACKGROUND:

The Drug Programs Information Network (DPIN), Manitoba's (Canada) new electronic prescription database, is a valuable data source for pharmacoepidemiologic research. Pharmacies are required to submit to the DPIN all prescriptions for Pharmacare, the province's drug insurance plan, but submission of prescriptions for social assistance recipients and treaty status Indians is discretionary.

OBJECTIVE:

The completeness of the DPIN prescription database was assessed to determine whether treaty status Indians and social assistance recipients were underrepresented.

DESIGN:

Prescriptions dispensed during March 13–17, 1995, in a stratified sample of Manitoba pharmacies were linked to DPIN by prescription number to determine the proportions submitted for Indian Affairs, Social Services, and Pharmacare recipients. Pharmacare records in the DPIN were compared with original pharmacy records to evaluate data accuracy.

RESULTS:

Of 2196 Indian Affairs and 1879 Social Services prescriptions dispensed in 58 pharmacies, a corresponding prescription was found in the DPIN for 79.7% (98% CI 78.0% to 81.4%) and 90.1% (98% CI 88.8% to 91.4%) of prescriptions, respectively. These proportions were significantly lower than the estimated proportion of Pharmacare prescriptions submitted (93%, 98% CI 92.4% to 93.6%). Ninety-two percent of 8012 DPIN Pharmacare prescriptions matched the original prescription on the drug name, quantity, and days' supply.

CONCLUSIONS:

This study established that the DPIN is a valid and reliable data source for studying prescription use among the majority of Manitoban residents. However, the DPIN database has differential validity and underrepresents prescriptions dispensed for the aboriginal population.
Chronic Creatine Kinase Elevation Not Associated with HMG-CoA Reductase Inhibitor Treatment
Authors: Lin Jennifer C , Ito Matthew K
Published: March 2004

OBJECTIVE:

To report a case of chronically elevated creatine kinase (CK) concentration that is possibly associated with renal insufficiency and prostatic carcinoma. The goal is to raise awareness among clinicians who monitor CK concentrations in patients receiving hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors.

CASE SUMMARY:

Because of an elevated CK concentration, a 64-year-old African-American man with a history of chronic heart disease and renal insufficiency was assessed for possible myositis relating to his treatment with HMG-CoA reductase inhibitors. However, an association between the elevated enzyme concentration and drug treatment could not be clearly established. The patient was subsequently diagnosed with prostatic cancer and underwent a radical retropubic prostatectomy. The CK enzyme concentration declined following the surgery despite continuation of the drug therapy.

DISCUSSION:

CK is relatively nonspecific because of its wide distribution in human tissues. Although several findings of elevated CK concentrations, particularly the CK-BB isoenzyme, in patients with carcinoma or chronic renal insufficiency have been documented, these may not be common knowledge among clinicians. This case report provides an example of an unusually high CK enzyme concentration that may be linked to prostatic carcinoma and renal insufficiency.

CONCLUSIONS:

It is important to be aware of different causes for CK enzyme concentration elevation, especially when it is used as a monitoring parameter during HMG-CoA reductase inhibitor treatment. In a case of persistent elevated CK enzyme concentration without evidence of myositis, renal insufficiency may be a contributing factor and malignancy must be ruled out.
Predictive Performance of Ten Equations for Estimating Creatinine Clearance in Cardiac Patients
Authors: Spinler Sarah A , Nawarskas James J , Boyce Eric G , Connors John E , Charland Scott L , Goldfarb Stanley ,   The Iohexol Cooperative Study Group
Published: March 2004

OBJECTIVE:

The predictive performance of 10 equations used to estimate creatinine clearance (Clcr) was assessed retrospectively from data collected on 420 patients.

DESIGN:

This study is a retrospective data analysis of information collected on hemodynamically stable patients awaiting coronary angiography during the Iohexol Cooperative Study.

SETTING:

The Iohexol Cooperative Study was a multicenter study that compared nephrotoxicity of high- and low-osmolar contrast media in patients undergoing coronary angiography. Data used for this analysis were preangiography 24-hour urine collections that were primarily collected in hospitalized patients.

PATIENTS:

Patients selected from the Iohexol Cooperative Study database for analysis were participants categorized into one or more of six subgroups: elderly (n = 222), hypoalbuminemic (n = 25), chronic renal insufficiency (n = 128), low serum creatinine (n = 115), obese (n = 208), and diabetic (n = 191) who had baseline urine collections of at least 24 hours.

OUTCOME MEASURES:

Predictive performance was assessed using bias, precision, slopes, and y-intercepts.

RESULTS:

The Salazar–Corcoran equation was unbiased in the entire group as well as in five of the subgroups. The Cockcroft–Gault equation was unbiased in three of the subgroups. All other equations were biased in predicting Clcr in the entire group as well as in at least four of the subgroups. Precision was generally poor. All slopes were significantly different than one and all y-intercepts were significantly different than zero (p < 0.01). Correlation coefficients were between 0.63 and 0.79 with the exceptions of the low serum creatinine subgroup (r values 0.35–0.64) and the Davis–Chandler equation (r values 0.35–0.71 across groups).

CONCLUSIONS:

Of the equations studied, Salazar–Corcoran and Cockcroft–Gault appear to be the best for predicting Clcr.
Contamination of Antibiotics Resulting in Severe Pediatric Methadone Poisoning
Authors: Lalkin Arieh , Kapur Bhushan M , Koren Gideon
Published: March 2004

OBJECTIVE:

To report an accidental contamination of antibiotic suspension by methadone that occurred in a retail Canadian pharmacy, leading to severe poisoning in a young child.

CASE SUMMARY:

A 4 1/2-year-old healthy Asian boy was prescribed amoxicillin suspension for cough and fever. Shortly after receiving the second dose of 5 mL he became drowsy and less responsive. On admission, he was arousable by deep pain, and pinpoint pupils were noted. A urine sample sent for a toxicology screen revealed the presence of methadone and its metabolite. Blood methadone concentrations were 0.23 and 0.14 mg/L, five and nine hours after the second dose of amoxicillin was given, respectively. The amoxicillin suspension was tested for methadone and was found to have a concentration of 2.4 g/L. The child gradually improved and was discharged on day 4 in good condition. The pharmacy in which the antibiotic was dispensed has been a dispensing center for a local methadone maintenance program, and methadone was accidentally mixed with the antibiotics.

DISCUSSION:

In this case, a near fatal outcome occurred when methadone was inadvertently mixed with antibiotics in a community pharmacy. A literature search revealed two previous reports of opiate toxicity in children following ingestion of oral antibiotic preparations.

CONCLUSIONS:

Prompt action is needed in Canadian pharmacies that dispense methadone in order to minimize such errors in the future. General practitioners, pediatricians, and emergency department physicians should recognize and suspect this rare cause of opiate toxicity in a child. In a patient presenting with a decreased level of consciousness and miosis, with or without respiratory depression, naloxone administration should be considered, whether or not a history of opioid ingestion is obtained.
The Use of Combination Antiretroviral Therapy in HIV-Infected Patients
Authors: Holtzer Christopher D , Roland Michelle
Published: March 2004

OBJECTIVE:

To review the published clinical trials of combination antiretroviral therapy, current guidelines about the use of combination antiretroviral therapy, information regarding the impact of adherence on treatment effect, and the effects of combination antiretroviral therapy on morbidity and mortality.

METHODS:

A MEDLINE search (January 1986–March 1998) was performed to identify all relevant articles. Selected articles and abstracts from this time period and references from these selections were included for review.

DISCUSSION:

Nucleoside analog monotherapy treatment of HIV infection is inferior to treatment with multiple antiretroviral agents. With the availability of new classes of medications (protease inhibitors, nonnucleoside reverse transcriptase inhibitors [NNRTIs], and new nucleoside analogs, combination antiretroviral therapy is now more potent and more complex than ever. The use and effects of protease inhibitors in combination with nucleoside analogs has been well documented. The use of NNRTIs and combination protease inhibitor regimens are not as well documented but may prove to be at least as efficacious as single protease inhibitor– containing regimens. Increases in CD4+ cell counts of >100 cells/mm3 and decreases in HIV RNA (viral load) of >2 log are common with these medications, with antiretroviral naive patients being more likely to have substantial responses to therapy than experienced patients.

CONCLUSIONS:

Combination antiretroviral therapy in HIV-infected patients is now the standard of care. Combination antiretroviral regimens have been shown to reduce, at least temporarily, the morbidity and mortality associated with HIV infection and AIDS. However, these regimens are quite complex for patients to adhere to successfully. While the true long-term effects of combination antiretroviral therapy are unknown, their current effects on the HIV epidemic are unquestionable.
Treatment of Medicaid Patients with Asthma: Comparison with Treatment Guidelines Using Disease-Based Drug Utilization Review Methodology
Authors: Laumann Julie M , Bjornson Darrel C
Published: March 2004

OBJECTIVE:

To compare asthma drug therapy in the Iowa Medicaid population with international treatment guideline recommendations and relate differences to patient outcomes.

METHODS:

Data on asthma drug therapy and respiratory-related medical services (clinic visits, emergency visits, hospital admissions) were abstracted from prescription claims and diagnostic codes of adult Iowa Medicaid patients with asthma (n = 1029).

RESULTS:

About two-thirds of the population received a prescription for a short-acting β2-agonist during the study period. Patients with greater daily use of short-acting β2-agonists had more clinic visits (p = 0.004), likely related to illness severity. Almost one-third (29.3%) of 58 patients receiving a prescription of salmeterol did not receive the recommended prescription of a short-acting β2-agonist inhaler in the 6-month period. About one-half of patients who should have been prescribed inhaled corticosteroids according to the international guidelines did not receive such a prescription in the 6-month study period. Increased use of inhaled corticosteroids was associated with fewer (p = 0.04) emergency visits.

CONCLUSIONS:

Suboptimal asthma treatment in the Iowa Medicaid population, especially in regard to the use of inhaled corticosteroids as preventive therapy, was evident after comparison with treatment guidelines. Increased daily use of inhaled corticosteroids was associated with positive patient outcomes in accordance with guideline recommendations. Educational efforts to improve closer adherence to international guidelines both in prescribing practices and patient compliance with medication for asthma management should be undertaken.
Drug-Induced Nightmares
Authors: Thompson Dennis F , Pierce Dana Reid
Published: March 2004

OBJECTIVE:

To compile and assess the English-language literature on drug-induced nightmares, excluding nightmares secondary to drug withdrawal or drug-associated night terrors.

DATA SOURCES:

Published articles, letters, case reports, and abstracts in English were identified by MEDLINE (1966–May 1998) searches using the search term nightmares, chemically induced. Additional articles were obtained from bibliographies of retrieved articles.

DATA EXTRACTION:

All case reports of drug-induced nightmares were evaluated using the Naranjo algorithm for causality. Clinical studies of drugs that reported nightmares as an adverse effect were assessed for frequency of occurrence.

DATA SYNTHESIS:

Nightmares, defined as nocturnal episodes of intense anxiety and fear associated with a vivid, emotionally charged dream experience, are generally classified as a parasomnia. Possible pharmacologic mechanisms for drug-induced nightmares, such as REM suppression and dopamine receptor stimulation, are reviewed. However, the vast majority of therapeutic agents implicated in causing nightmares have no obvious pharmacologic mechanism.

CONCLUSIONS:

Assessing causality with an event such as a nightmare is difficult because of the high incidence of nightmares in the healthy population. Using qualitative, quantitative, and possible pharmacologic mechanism criteria, it appears that sedative/hypnotics, β-blockers, and amphetamines are the therapeutic modalities most frequently associated with nightmares. These drug classes have a plausible pharmacologic mechanism to explain this effect. Dopamine agonists also have evidence of causality, with dopamine receptor stimulation as a possible pharmacologic mechanism.
Neuroleptic Malignant Syndrome Associated with Olanzapine
Authors: Filice Gregory A , McDougall Beth C , Ercan-Fang Nacide , Billington Charles J
Published: March 2004

OBJECTIVE:

To report a case of neuroleptic malignant syndrome (NMS) associated with the use of olanzapine.

CASE SUMMARY:

A 67-year-old white man with bipolar disorder developed nausea and vomiting. After 12 days, he became confused, delirious, and manic. His only medications were olanzapine 10 mg/d and divalproex sodium 500 mg bid. He was admitted to a hospital and treated for dehydration and mania. Olanzapine was given on 6 of the first 7 hospital days. On hospital day 6, typical NMS developed with the body temperature increasing to 39.9 °C, obtundation, rigidity, tremor, diaphoresis, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and elevated serum creatine kinase. Olanzapine was stopped after hospital day 7, and the syndrome resolved by hospital day 12.

DISCUSSION:

The patient had all of the major manifestations of NMS. There was no other likely explanation for his illness and he received no other drug likely to be associated with the syndrome. This is the first case reported in which NMS was associated with olanzapine.
Pharmacokinetics of Intraperitoneal Fluconazole during Continuous Cycling Peritoneal Dialysis
Authors: Dahl Naomi V , Foote Edward F , Searson Kathleen M , Fein Jacqueline L , Kapoian Toros , Steward Caroline A , Sherman Richard A
Published: March 2004

OBJECTIVE:

To investigate the pharmacokinetic characteristics of intraperitoneal fluconazole in patients undergoing continuous cycling peritoneal dialysis (CCPD).

DESIGN:

Prospective, nonrandomized, single-dose, open-label study.

PARTICIPANTS:

Five noninfected volunteer CCPD patients.

INTERVENTIONS:

Patients received a single dose of intraperitoneal fluconazole 200 mg during their long daytime dwell. Blood samples were collected before and 1, 3, 6, 12 (end of first dwell), 24 (after overnight cycling), 48, 72, 96, and 120 hours after dosing. Used dialysate was collected throughout the study. Unless the patient was anuric, urine was collected for the first 48 hours.

MAIN OUTCOME MEASURE:

Fluconazole concentrations were assayed by gas–liquid chromatography. Pharmacokinetic parameters were calculated using standard noncompartmental techniques.

RESULTS:

The bioavailability of intraperitoneal fluconazole was 96% ± 2% over a 12-hour dwell, absorption half-life was 2.5 ± 1.2 hours, serum elimination half-life was 71.65 ± 12.76 hours, and volume of distribution was 0.66 ± 0.13 L/kg. Peritoneal clearance was 5.96 ± 0.93 mL/min and proportional to total dialysate volume. Renal clearance was proportional to renal creatinine clearance.

CONCLUSIONS:

Current treatment guidelines for fungal peritonitis suggest fluconazole 200 mg intraperitoneally every 24 hours. Our data suggest that this dose, administered every 48 hours, is more than sufficient to maintain serum and peritoneal concentrations above the minimum inhibitory concentration for most Candida spp. Other factors, such as residual renal function and dialysis prescription, may also need to be considered.
Characterization of Rash with Indinavir in a National Patient Cohort
Authors: Gajewski Lidia K , Grimone Andrew J , Melbourne Kathleen M , Vanscoy Gordon J
Published: March 2004

OBJECTIVE:

To characterize indinavir-associated rash using systematic data collection through postmarketing surveillance in a sample of HIV/AIDS patients.

DESIGN:

HIV-infected patients identified through a medication counseling line who reported onset of a rash following initiation of indinavir therapy were included in this case series analysis. Pertinent information regarding onset, description, and management of rash; other medications initiated within two weeks of indinavir or rash onset; and medication allergy history was obtained through follow-up telephone contact. Patients were contacted weekly until the rash resolved or indinavir was discontinued.

SETTING:

Stadtlanders Drug Distribution Company, located in Pittsburgh, PA.

RESULTS:

Of the 110 patients identified and followed, 67% reported rash onset within two weeks of initiating indinavir therapy. The rash was initially localized in all 110 patients and subsequently spread to other areas of the body in 77% of the patients. The rash spread to the full body in 44% (49) of the patients. The rash was accompanied by pruritus in 86% of the patients, and the majority of patients (87%) were afebrile. Eighty-one patients received treatment with medications such as antihistamines or oral or topical corticosteroids. Fifty percent of patients receiving treatment for the rash reported that these medications were helpful in relieving rash symptoms. Fifty-nine percent of the patients continued indinavir therapy despite the occurrence of rash.

CONCLUSIONS:

Results from this study suggest that indinavir-associated rash occurs within two weeks of initiation of therapy for the majority of patients. Typically, the rash is localized with subsequent spread and is associated with pruritus. The majority of patients are able to continue indinavir therapy despite the occurrence of rash.
Therapy of Candida Infections: Susceptibility Testing, Resistance, and Therapeutic Options
Authors: Klepser Michael E , Lewis Russell E , Pfaller Michael A
Published: March 2004

OBJECTIVE:

Review the epidemiology of fungal infections, approved susceptibility testing methods, the scope of antifungal resistance, and advances in the treatment of fungal infections.

DATA SOURCES:

MEDLINE databases (from 1966 to March 1998) were searched for literature pertaining to the epidemiology and management of fungal infections.

STUDY SELECTION AND DATA EXTRACTION:

Articles were selected to assist in providing the reader an understanding of the epidemiology and management of fungal infections.

DATA SYNTHESIS:

Fungi have emerged as an important class of pathogens. Even though fungi rank as the fourth most commonly encountered nosocomial bloodstream pathogen, and are associated with the highest mortality of commonly encountered pathogens, only within the past year have methods for conducting and guidelines for interpreting in vitro susceptibility tests been approved. Under the guidance of these standards, we have begun to understand important issues regarding fungi such as the scope and mechanisms of antifungal resistance. Although there has not been a significant addition to our antifungal armamentarium since 1992, advances in antifungal therapy have been realized with the reformulation of available agents and the delineation of the pharmacodynamic characteristics of several antifungals. Additionally, several new agents, including a new class of antifungals, probably will enter into clinical use within the next 5 years.

CONCLUSIONS:

We have entered an era in which our understanding of fungi is increasing tremendously. Clinicians need to familiarize themselves with the current concepts surrounding the management of fungal infections in order to provide optimal care for their patients.
Chlamydia Pneumoniae and Coronary Heart Disease
Authors: Carlisle Steven S , Nahata Milap C
Published: March 2004

OBJECTIVE:

To review the potential association between Chlamydia pneumoniae (CP) infection and coronary artery disease (CAD), and to describe possible therapeutic interventions.

DATA SOURCES:

A MEDLINE search of literature (January 1966– January 1998) pertaining to CP infection associated with heart disease was performed. Additional literature was obtained from review of journals and reference lists of pertinent articles identified through the search.

STUDY SELECTION AND DATA EXTRACTION:

All articles involving CP and CAD were considered for possible inclusion in this review. Other selected articles involved possible links between infection and the atherosclerotic process, inflammation and inflammatory mediators in the atherosclerotic process, and isolation of CP from human tissue.

DATA SYNTHESIS:

Numerous reports have suggested an association between chronic CP and CAD. CP has been seroepidemiologically linked to CAD. The organism has also been isolated from atherosclerotic lesions. Two reports in humans and one report in animals have shown that macrolide therapy (azithromycin or roxithromycin) may decrease the risk of adverse cardiovascular events.

CONCLUSIONS:

Evidence seems to support an association between CP infection and an increased incidence of CAD. Additional and larger seroepidemiologic studies of this association need to be performed to establish a causal relationship between infection and CAD. Determination of the actual role of CP in CAD may decide the role of specific antichlamydial therapy in the management of this condition.
Quinine-Induced Hepatotoxicity
Authors: Farver Debra K , Lavin Megan N
Published: March 2004

OBJECTIVE:

To report a case of quinine-induced hepatotoxicity presenting within 24 hours following the ingestion of the first dose.

DATA SOURCES:

Case report information was obtained from the medical record, the patient, and the physicians involved in this patient's case. MEDLINE and Index Medicus were searched to obtain relevant published literature from January 1942 to May 1997 using the terms quinine, muscle cramps, liver disease, and hepatotoxicity.

CASE SUMMARY:

A 57-year-old Native American woman presented with symptoms of nausea, vomiting, generalized myalgia, headache, fever, chills, and rigor. The alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltranspeptidase concentrations were dramatically elevated. Quinine was suspected as the cause after several days of hospitalization and continued therapy. With discontinuation of the quinine, the patient's symptoms resolved within 48 hours and the liver enzyme concentrations declined within 72 hours.

CONCLUSIONS:

Documented hepatotoxicity has occurred with quinidine, the optical isomer of quinine. Limited awareness of quinine-induced hepatotoxicity may result in an unrecognized adverse effect.
Hyperlipidemia Associated with Protease Inhibitor Therapy
Authors: Echevarria Kelly L , Hardin Thomas C , Smith Jean A
Published: March 2004

OBJECTIVE:

To report a case of extreme hyperlipidemia associated with protease inhibitor–based antiretroviral therapy and review the relevant literature concerning lipid abnormalities with HIV infection and antiretroviral therapy.

CASE SUMMARY:

A 35-year-old HIV-infected man developed a serum cholesterol of 1472 mg/dL and fasting serum triglycerides of 8660 mg/dL after initiation of antiretroviral therapy consisting of ritonavir, saquinavir, nevirapine, and didanosine. All other medications had been stable during this time period and the abnormality resolved after discontinuation of antiretroviral therapy and initiation of lipid-lowering therapy. The elevated cholesterol and triglyceride concentrations did not recur when therapy was reinstituted with nelfinavir, saquinavir, nevirapine, and didanosine. The hyperlipidemia then was attributed to ritonavir.

DISCUSSION:

Lipid abnormalities are common in patients with HIV infection and usually consist of hypocholesterolemia and moderate hypertriglyceridemia. Hypercholesterolemia and hypertriglyceridemia have been reported with ritonavir and, less commonly, with other currently available protease inhibitors. Some cases of ritonavir-associated hyperlipidemia have been extreme. Although an association between hyperlipidemia and clinical consequences such as pancreatitis and atherosclerotic disease has not been well described with protease inhibitor therapy, pancreatitis is common in HIV-infected patients. It is possible that in some cases, protease inhibitor–induced hypertriglyceridemia may contribute to the development of pancreatitis.

CONCLUSIONS:

Optimal management of lipid abnormalities in HIV-infected patients is controversial. The potential benefit of reducing the incidence of pancreatitis and atherosclerotic events must be weighed against the risk of intolerance, toxicity, and drug interactions.