bluuebunny/crossref_metadata_2025 huggingface dataset:
Policy Watch: The Economics of Fuel Economy Standards
Authors: Portney Paul R , Parry Ian W.H , Gruenspecht Howard K , Harrington Winston
Published: January 2004

One of the most hotly contested of all energy policy issues involves Corporate Average Fuel Economy (or CAFE) standards for new cars and light-duty trucks. Tighter standards would reduce gasoline consumption, and hence both greenhouse gas emissions as well as this country's vulnerability to oil price shocks. But they would also increase the price of new vehicles, worsen traffic congestion and–depending on how they are phased in–possibly even reduce occupant safety. These effects are amenable to economic analysis, and we review the evidence to date bearing on this interesting and important question.
Recommendations for Further Reading
Authors: Saffran Bernard
Published: January 2004

This section will list readings that may be especially useful to teachers of undergraduate economics, as well as other articles that are of broader cultural interest. In general, the articles chosen will be expository or integrative and not focus on original research. If you write or read an appropriate article, please send a copy of the article (and possibly a few sentences describing it) to Bernard Saffran, c/o Journal of Economic Perspectives, Department of Economics, Swarthmore College, Swarthmore, PA 19081.
Comments
Authors: Pasinetti Luigi L , Fisher Franklin M , Felipe Jesus , McCombie J. S. L , Greenfield Robert L , Kaempfer William H , Lowenberg Anton D
Published: January 2004

To be considered for publication in the Comments section, letters should be relatively short—generally fewer than 1,000 words—and should be sent to the journal offices at the address appearing inside the front cover. The editors will choose which letters will be published. All published letters will be subject to editing for style and length.
Management of lateral sinus thrombosis: update and literature review
Authors: Ooi Eng Hooi , Hilton Malcolm , Hunter Garrett
Published: January 2004

The management of four cases of lateral sinus thrombosis (LST) over a four-year period at the Royal Darwin Hospital is presented in this retrospective review. The patients were aboriginal and presented with otalgia, otorrhoea and sepsis. Two cases had an associated complication of an otitic hydrocephalus and a subperiosteal abscess. Cholesteatoma was found in three cases. Computed tomography (CT) scan confirmed the LST in three cases. Three patients were anaemic and thrombocytopenic. All patients had positive blood cultures. The organismswere predominantly mixed anaerobes and Bacteroides species. Three patients were managed surgically as a two-stage procedure. One patient was managed as a single-stage procedure with a modified radical mastoidectomy. Therapeutic anticoagulation was utilized in one case. There were no deaths. The prognosis of LST is good if treatment is instituted early with broad-spectrum intravenous antibiotics and surgery. Therole of clot removal at surgery and the use of anticoagulation are discussed in this paper.
Aggressive papillary tumour of the nasopharynx followed by an aggressive papillary tumour of the middle ear. A multiple site tumour?
Authors: Karkos P. D. , Kelleher R. , Hilmi O. J. , Davis B. C.
Published: January 2004

We report the case of a 72-year-old male presenting with a papillary adenocarcinoma of the middle ear. He had had a similar tumour excised from the ipsilateral nasopharynx seven years previously with no evidence of local recurrence. We conclude that this middle ear lesion possibly represents a second tumour. No record of such a case has been reported previously in the literature. We discuss presentation and management and highlight the need for close follow-up of these patients.
Relapsing acute adult epiglottitis following hypophysectomy
Authors: Latif Sherif A. , Winter Stuart C. A. , Hoare Timothy J. , Frampton Michael C.
Published: January 2004

Adult epiglottitis is an uncommon disease that may become fatal because of sudden airway obstruction. Recurrent adult epiglottitis has been reported rarely in the literature. We present a case of relapsing epiglottitis in a patient with corticosteroid insufficiency secondary to pituitary surgery. It is the first case to highlight this infection occurring in a relapsing manner in a patient with pituitary-adrenocortical insufficiency on long-term steroid replacement therapy.
Comparison of the sensitivity of in vivo antibody production tests with in vitro PCR-based methods to detect infectious contamination of biological materials
Authors: Bootz F. , Sieber I. , Popovic D. , Tischhauser M. , Homberger F. R.
Published: January 2004

Bacteria and viruses may be transmitted to laboratory rodents by contaminated biological materials such as transplantable tumours, cell lines, sera or other biological materials. Biological materials are currently being screened using the mouse or rat antibody production (MAP/RAP) test (serological testing). We decided to test and validate an alternative assay using polymerase chain reaction (PCR/realtime PCR) technology to detect viral contamination directly in biological material. The aim of this study therefore is the validation of our new PCR assays and the comparison of PCR and the MAP test. For 8/14 viruses, conventional PCR was more sensitive and more specific than the MAP test in detecting murine viruses. For 12/14 viruses, the realtime PCR was more sensitive than the MAP test. In 2/14 cases, all three detection methods had the same sensitivity. Furthermore, PCR screening clearly conforms to the principles of the 3Rs as a replacement technique because it eliminates the need for using animals to screen for murine viruses in biological material.
Detection of Reovirus type 3 by use of fluorogenic nuclease reverse transcriptase polymerase chain reaction
Authors: Uchiyama A. , Besselsen D. G.
Published: January 2004

Reovirus type 3 (Reo-3) can infect numerous rodent species and induces the clinical syndrome 'oily skin disease' in neonatal mice, and is a common contaminant of biological materials. The reverse transcriptase polymerase chain reaction (RT–PCR) assay has proven useful for the detection of Reo-3 in rodents and contaminated biological materials. Fluorogenic nuclease reverse transcriptase polymerase chain reaction assays (fnRT–PCR) combine RT–PCR with an internal fluorogenic hybridization probe, thereby potentially enhancing specificity and eliminating post-PCR processing. Therefore, an fnRT–PCR assay specific for Reo-3 was developed by targeting primer and probe sequences to a unique region of the Reo-3 M3 gene. The fnRT–PCR detected both strains of Reo-3 (Dearing and Abney), but did not detect Reovirus types 1 or 2, other viruses in the family Reoviridae, or other RNA viruses that naturally infect rodents. The fnRT–PCR detected less than 1 fg of target template and detected viral RNA in tissues obtained from mice experimentally infected with Reo-3. The assay also displayed comparable sensitivity when compared to the mouse antibody production test commonly used to detect viral contamination of biological materials. In conclusion, this fnRT–PCR assay offers a potentially high-throughput diagnostic assay for detecting Reo-3 RNA in infected mice and contaminated biological materials.
A miniature self-inflating bag-mask ventilator for rats
Authors: Schumacher J. , Dendorfer A. , Binkowski K. , Klotz K.-F.
Published: January 2004

Respiratory depression and apnoea during anaesthesia may lead to hypoxia and myocardial ischaemia. A self-inflating miniature bag-mask device was assembled combining characteristics from the Ambu-bag and the Kuhn-system. This bag-mask device permitted ventilation during anaesthesia-induced apnoea in rats until a safe airway by tracheotomy was achieved.
Short-term effects of N'N-bis(dichloroacetyl)-1,8-octamethylenediamine (WIN 18446) on the testes, selected sperm parameters and fertility of male CBA mice
Authors: Brooks N. L. , van der Horst G.
Published: January 2004

N'N-bis(dichloroacetyl)-1,8-octamethylenediamine (WIN 18446), the most potent of the diamines and one of the least amoebicidal agents, was shown to exert a specific effect on the testes of CBA mice, while the Leydig cells were unaffected. Spermatogenesis was severely affected after a 42-day treatment period with 125 mg WIN 18446/kg body weight. Large multinucleated cells, vacuolization and the absence of sperm within the testes were evident in most seminiferous tubules. After 15 days of withdrawal of WIN 18446, there was a slight recovery of spermatogenesis and after withdrawal of 42 days a marked recovery of spermatogenesis. The normality or abnormality of this spermatogenic cycle could be evaluated using the semi-quantitative Stages program. There was a significant decrease in the diameters of seminiferous tubules of WIN 18446 treated mice, however an almost complete recovery was evident after 42 days of withdrawal of WIN 18446. A significant decrease in sperm concentration and sperm morphology was observed for the WIN 18446 treated mice. Various sperm motion parameters were assessed for the different treatment groups and compared to the control group. The female and male fertility indices were assessed and compared for the different treatment groups. Complete recovery of the above-mentioned parameters was evident after 42 days of withdrawal from WIN 18446, and this confirms its potential as a possible contraceptive for animal populations.
Selection of Atypical Antipsychotics for the Management of Schizophrenia
Authors: Sprague Denise A , Loewen Peter S , Raymond Colette B
Published: January 2004

OBJECTIVE

To review the evidence for selecting one atypical antipsychotic agent over another for management of schizophrenia.

DATA SOURCES

A literature search of MEDLINE (1966–June 2003), EMBASE (1998–June 2003), and the Cochrane Library was conducted using the following terms: schizophrenia, quetiapine, ziprasidone, olanzapine, aripiprazole, and risperidone. Bibliographies of relevant articles were hand-searched for additional references.

STUDY SELECTION AND DATA EXTRACTION

Prospective, randomized, blinded trials and meta-analyses that directly or indirectly compared ≥2 atypical antipsychotic agents in the management of schizophrenia are included in this review. Studies comparing an atypical agent with clozapine are not included.

DATA SYNTHESIS

A small number of prospective, randomized, blinded trials that compare efficacy and tolerability of olanzapine and risperidone have been published. These trials did not reveal clinically meaningful differences in efficacy but did confirm that their adverse effect profiles are slightly different (more weight gain with olanzapine and more extrapyramidal reactions with risperidone). Direct comparisons between other atypical antipsychotics are not available. Systematic reviews (indirect comparisons) of placebo-controlled or traditional antipsychotic-controlled trials suggest similar efficacy for quetiapine, olanzapine, and risperidone when placebo is the comparator and inferior efficacy of quetiapine compared to olanzapine and risperidone when haloperidol is the comparator. The few available economic analyses are difficult to interpret in light of current practice.

CONCLUSIONS

Additional randomized, blinded clinical trials directly comparing efficacy, tolerability, and cost-effectiveness are needed to confirm the proposed differences among atypical antipsychotic agents before recommendations can be made with confidence.
β-Blocker Underuse in Secondary Prevention of Myocardial Infarction
Authors: Everly Matthew J , Heaton Pamela C , Cluxton Robert J
Published: January 2004

OBJECTIVE

To review the clinical benefits of β-blockers as secondary prevention following a myocardial infarction (MI) and to address the reasons that clinicians are reluctant to use β-blockers in specific patient populations.

DATA SOURCES

MEDLINE was searched for articles published from January 1966 to October 2002. Relevant studies were identified by systematic searches of the literature for all reported studies of associations between β-blocker underuse and secondary prevention of MI. Additional studies were identified by a hand search of references of original or review articles.

STUDY SELECTION AND DATA EXTRACTION

English-language human studies were selected and analyzed.

DATA SYNTHESIS

Associations were observed in studies of β-blocker use as secondary prevention of MI. A lower rate of β-blocker treatment occurred in older patients and in patients with comorbid conditions such as diabetes, heart failure, chronic obstructive pulmonary disease, asthma, and peripheral arterial disease. In addition, underuse was attributed to the perception of high rates of adverse events associated with β-blockers. β-Blocker use as secondary prevention of an MI can lead to a 19–48% decrease in mortality and up to a 28% decrease in reinfarction rates. Nonetheless, β-blockers are significantly underused in many patient populations due to concomitant disease states. Due to their normal physiologic deterioration, the elderly are at an increased risk of low cardiac output and bradycardia when given a β-blocker; therefore, they should be started on a low dose that is then slowly titrated. In diabetic patients, β-blockers can impair glucose control leading to hypoglycemia; therefore, post-MI diabetic patients must routinely monitor their blood glucose levels. In patients with decompensated heart failure, β-blocker use can lead to further cardiac depression, but lower oral starting doses with slow titration can reduce this risk. β-Blockers can induce bronchospasm in patients with chronic obstructive pulmonary disease or asthma, but cardioselective β-blockers and appropriate use of medications such as albuterol can minimize these effects. Finally, in patients with peripheral arterial disease, with the exception of hypertensive patients with Reynaud's phenomenon, β-blockers can be used safely. The only absolute contraindications to β-blockers are severe bradycardia, preexisting sick sinus syndrome, second- and third-degree atrioventricular block, severe left ventricular dysfunction, active peripheral vascular disease with rest ischemia, or reactive airway disease so severe that airway support is required.

CONCLUSIONS

Overall, the cardiovascular benefits of β-blockers as secondary prevention of MI significantly outweigh the risks associated with their use.
Vascular Neurotoxicity Following Chemotherapy with Cisplatin, Ifosfamide, and Etoposide
Authors: Dietrich Jörg , Marienhagen Jörg , Schalke Berthold , Bogdahn Ulrich , Schlachetzki Felix
Published: January 2004

OBJECTIVE

To report a case of acute central nervous system (CNS) toxicity with multiple hemorrhages restricted to the corpus callosum associated with combination therapy of cisplatin, ifosfamide, and etoposide.

CASE SUMMARY

A 38-year-old white man with a testicular germ cell tumor received a cisplatin-based chemotherapy consisting of cisplatin 45 mg (20 mg/m 2 ), etoposide 570 mg (250 mg/m 2 ), and ifosfamide 4600 mg (2000 mg/m 2 ) given on 5 consecutive days during each course. After the first course of chemotherapy, the patient appeared to be neuropsychologically impaired with episodes of decreased alertness and features of a depressive syndrome. He became severely diminished in mental function, orientation, and psychomotor activity after a second course of treatment. In addition, he showed transient urinary incontinence. Motor and sensory deficits could not be detected. Magnetic resonance imaging demonstrated multiple hemorrhages restricted to the corpus callosum. An objective causality assessment revealed that an adverse drug reaction was probable.

DISCUSSION

Neurotoxicity has been associated with the administration of various antineoplastic agents. In particular, cisplatin and ifosfamide can cause both acute and delayed CNS toxicity. While ifosfamide neurotoxicity has been predominantly associated with neuropsychological impairment without evidence of structural abnormalities in neuroimaging studies, cisplatin has been shown to cause cerebrovascular complications. Various pathophysiologic conditions may contribute to these complications including thrombosis secondary to vascular endothelial injury or thromboembolic events. To our knowledge, as of December 2, 2003, vascular lesions restricted to the corpus callosum have not been reported as a complication of cisplatin- or ifosfamide-based chemotherapy.

CONCLUSIONS

Clinicians should be aware of the potential neurovascular adverse effects of cisplatin-based protocols. This is especially true in patients with subtle neurologic or neuropsychological symptoms. Chemotherapy-induced neurotoxicity should be considered in the differential diagnosis.
Single Versus Combined Antibiotic Therapy for Gram-Negative Infections
Authors: Klibanov Olga M , Raasch Ralph H , Rublein John C
Published: January 2004

OBJECTIVE

To evaluate the available clinical data regarding single versus combination antimicrobial therapy for treatment of gram-negative infections, focusing on the more recent data in predominantly nonneutropenic hosts. In vitro and in vivo data regarding various antimicrobial combinations are also discussed.

DATA SOURCES

Clinical trials, review articles, and meta-analyses were identified from a MEDLINE search (1960–July 2003). Special attention was given to clinical outcome trials performed since 1989. Search terms included gram-negative infections, drug synergism, Pseudomonas aeruginosa, monotherapy, combination therapy, carbapenems, β-lactams, cefepime, aminoglycosides, and fluoroquinolones.

DATA SYNTHESIS

Although most of the studies were not randomized, double-blind, or controlled, the most recent literature indicates that monotherapy with agents that are active against isolated organisms, including P. aeruginosa, may be appropriate for most patients. Efficacy outcomes, including mortality, did not significantly differ in most studies comparing single and combination therapies. Some trials suggest that combination therapy may be preferred in neutropenic patients and those with pseudomonal infections.

CONCLUSIONS

Hospitalized patients with gram-negative infections are often treated with combination antimicrobial agents; however, some of the recently available data, although limited, suggest that administration of monotherapy is a feasible alternative in certain patient populations.
Trimethoprim/Sulfamethoxazole for Treatment of Severe Staphylococcus aureus Infections
Authors: Adra May , Lawrence Kenneth R
Published: January 2004

OBJECTIVE

To evaluate the role of trimethoprim/sulfamethoxazole (TMP/SMX) as an alternative to vancomycin for the treatment of severe Staphylococcus aureus infections.

DATA SOURCES

Clinical literature was accessed through MEDLINE (1966–February 2003) and EMBASE (1980–February 2003). Key search terms included trimethoprim/sulfamethoxazole combination and Staphylococcus aureus.

DATA SYNTHESIS

An evaluation of case reports, case series, and clinical studies focusing on the use of TMP/SMX for treatment of severe S. aureus infections was conducted. The majority of the reports indicate that TMP/SMX may be effective for the treatment of infections due to low bacterial burdens of susceptible strains of S. aureus.

CONCLUSIONS

In select infections, TMP/SMX may be a useful alternative to vancomycin for treatment of severe S. aureus infections. Additional randomized studies should be conducted comparing this agent with vancomycin and linezolid.
Drug Control Authorities in China
Authors: Zhen Li Hui
Published: January 2004

OBJECTIVE

To provide an overview of China's drug control authorities.

DATA SOURCES

South Pharmaceutical Economy Institute.

DATA SYNTHESIS

China's drug control authorities include the State Food and Drug Administration (SFDA), which primarily oversees drug administration; the State Development and Reform Commission (SDRC), which is responsible for the drug price administration; and the Provincial Administration for Industry and Commerce, cooperating with the Provincial Food and Drug Administration, to regulate drug advertisements. Although the drug control authorities presented here have played important roles in drug administration and have obtained outstanding achievements in the past several years, they are also hindered by their respective problems and try to explore the solutions.

CONCLUSIONS

Other countries may confront the problems described here. It is therefore necessary to learn the current situation of drug control authorities in China, as well as the measures being taken to improve the situation. This understanding will aid countries seeking to enter China's pharmaceutical market.
Tracking Trends in Secondary Stroke Prevention Strategies
Authors: Carswell Jody L , Beard Kemberley A , Chevrette Michele M , Pardue Carol N , Hess David C , Fagan Susan C
Published: January 2004

BACKGROUND

Stroke is defined as a rapid onset of isolated neurologic dysfunction and is the leading cause of disability in adults, as well as the third-leading cause of death in the US. Nearly 600 000 cases of stroke are reported annually.

OBJECTIVE

To quantify the impact of emerging evidence on the use of secondary stroke prevention strategies in patients discharged from a specialized stroke center in 2002 compared with those discharged in 2000.

METHODS

Using a retrospective approach, data were collected on the first 100 patients cared for by the stroke service from July 1, 2000, to December 31, 2000. Using a prospective approach, the goal was to enroll 100 patients with a diagnosis of ischemic stroke and telephone the patients 1 and 3 months after discharge to determine patient adherence and persistence rate of medications. This is an interim report of the first 20 patients enrolled.

RESULTS

Both studies resulted in populations of 55% women and 45% men. The most common risk factor was hypertension, with 59% on admission in 2000 and 75% in 2002. Use of antithrombotics (98% in 2000 to 100% in 2002) and antihypertensives (67% in 2000 to 90% in 2002) was high in both studies and not significantly different. The 2 most significant changes in prescribing were increased use of statins (13% in 2000 to 50% in 2002, p = 0.0007) and combination clopidogrel and aspirin use (0% in 2000 to 20% in 2002, p = 0.001). At 3 months, 66.7% of patients were on the same antithrombotic medication as at discharge.

CONCLUSIONS

The dedicated stroke service was able to effectively translate emerging evidence and guidelines into practice and significantly change the use of prescribed medications for secondary stroke prevention.
Severe Dermatologic Reactions at Multiple Sites After Paclitaxel Administration
Authors: Beri Rakesh , Rosen Fred R , Pacini Michael J , Desai Swati R
Published: January 2004

OBJECTIVE

To report a case of a severe dermatologic reaction at the infusion site, as well as at multiple distant sites, after paclitaxel administration.

CASE SUMMARY

A 53-year-old white male with cancer of the base of the tongue was treated with paclitaxel 100 mg/m 2 infused over 3 hours and carboplatin dosed at an AUC of 6 mg/mL•min infused over 30 minutes via a peripheral vein on the left arm. After 4 doses of paclitaxel, the patient developed erythematous patches on both forearms and both thighs. The lesions on the left arm worsened into a necrotic ulcer, exposing underlying tissues. All of the lesions healed after paclitaxel was withheld from subsequent cycles. Based on the Naranjo probability scale, it is probable that paclitaxel was the causative agent for these lesions.

DISCUSSION

Most of the previously reported paclitaxel-induced dermatologic reactions occurred following extravasation. There are few reports of generalized dermatologic rashes. These rashes are thought to be due to delayed hypersensitivity either to paclitaxel or the solubilizing agents. Our patient had dermatologic toxicity at the infusion site, as well as at multiple other sites, that developed about 6 weeks after the first paclitaxel infusion.

CONCLUSIONS

Generalized dermatologic toxicity after paclitaxel administration is uncommon and seems to be immunologically mediated. This toxicity could be secondary to paclitaxel or the additives. The use of paclitaxel is increasing in various malignancies. Newer formulations are under development. Until these formulations are available, clinicians should report any dermatologic reactions in order to identify the cause of toxicity and develop safer administration technique.
Acetylcysteine Treatment for Non–Acetaminophen-Induced Acute Liver Failure
Authors: Sklar Grant E , Subramaniam Malar
Published: January 2004

OBJECTIVE

To evaluate the effectiveness of intravenous acetylcysteine in the treatment of non–acetaminophen-induced acute liver failure (ALF).

DATA SOURCES

A search of MEDLINE (1966–March 2003), International Pharmaceutical Abstracts (1970–2003), and Cochrane Library (2003, issue 3) databases was conducted, using the search terms acetylcysteine, non–acetaminophen-induced hepatic failure, liver failure, intravenous, and treatment.

DATA SYNTHESIS

All of the studies found were small and do not provide conclusive evidence that acetylcysteine benefits this subgroup of patients. Microvascular regional benefits were seen, but clinical outcomes have not been studied.

CONCLUSION

Intravenous acetylcysteine should not be used routinely for treatment of non–acetaminophen-induced ALF. Further large-scale studies are needed to evaluate clinical outcomes.
Urinary-Based Ovulation and Pregnancy: Point-of-Care Testing
Authors: Eichner Samantha F , Timpe Erin M
Published: January 2004

OBJECTIVE

To review the literature concerning ovulation prediction devices and pregnancy detection tests for home use.

DATA SOURCES

Articles were identified through searches of the MEDLINE (1966–May 2003), EMBASE (1980–May 2003), and International Pharmaceutical Abstracts (1970–May 2003) databases using the key words ovulation, ovulation detection, pregnancy test, diagnostic reagent kit, and diagnostic test. Additional references were located through review of the bibliographies of the articles found in the literature search. Searches were not limited by time restriction, language, or use of human or animal subjects.

STUDY SELECTION AND DATA EXTRACTION

Review articles, textbook chapters, and experimental and observational studies on home use ovulation and pregnancy tests were selected.

DATA SYNTHESIS

Luteinizing hormone (LH)-based ovulation tests have demonstrated accurate and superior ovulation detection when compared to basal body temperature charting, calendar calculation, salivary ferning, or observation of vaginal or cervical discharge changes. Systems using LH and estrone-3-glucuronide (E3G) have also demonstrated accurate detection of the fertile period. Literature evaluating home use of pregnancy tests has demonstrated accurate use by lay persons.

CONCLUSIONS

Urinary-based ovulation prediction and pregnancy detection tests available for use by nonprofessionals enable women and couples to take an active role in the family planning process. Numerous products are available at reasonable costs to the consumer.
HMG-CoA Reductase Inhibitors for the Prevention of Nephropathy
Authors: Maisch Nicole M , Pezzillo Kara K
Published: January 2004

OBJECTIVE

To evaluate the literature to determine whether hydroxymethylglutaryl coenzyme A reductase inhibitors are effective for the prevention of nephropathy.

DATA SOURCES

MEDLINE (1966–April 2003) and International Pharmaceutical Abstracts (1970–April 2003), as well as bibliographic searches, were conducted.

DATA SYNTHESIS

Although the statins are widely used for the prevention of coronary heart disease, non–lipid-lowering effects are also being investigated, namely their potential role in the prevention of nephropathy. Five trials of the statins used in this manner are reviewed, most of which included patients with dyslipidemias, making it difficult to determine whether the renoprotective effects were independent of the lipid-lowering effects.

CONCLUSIONS

Adequate evidence does not currently exist to support the widespread use of statins as alternatives to strategies known to prevent the progression of renal disease, but statins may be used to complement other therapies in patients with additional indications.
The Metabolic Syndrome: Pathophysiology, Clinical Relevance, and Use of Niacin
Authors: Ito Matthew K
Published: January 2004

OBJECTIVE

To review the pathophysiology and clinical relevance for using niacin to treat the metabolic syndrome.

DATA SOURCES

Primary articles were identified through a MEDLINE search (1966–January 2003), and recommendations for treatment were obtained from the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III guidelines.

STUDY SELECTION AND DATA EXTRACTION

Published studies showing the effects of the metabolic syndrome, atherogenic dyslipidemia, and niacin were evaluated and reviewed.

DATA SYNTHESIS

The metabolic syndrome is a highly prevalent condition that affects 24% of American adults and significantly increases the risk of coronary heart disease (CHD). Most patients with metabolic syndrome have atherogenic dyslipidemia characterized by elevated triglycerides, low high-density-lipoprotein cholesterol (HDL-C), and small, dense low-density-lipoprotein cholesterol (LDL-C) particles. The NCEP-ATP III identifies patients with the metabolic syndrome as candidates for intensified therapy. Lifestyle modifications and drug therapy are recommended. Niacin represents a good option for treating the triad of lipid abnormalities seen in the metabolic syndrome because it raises HDL-C, lowers triglycerides, and increases LDL-C particle size.

CONCLUSIONS

Treatment of the metabolic syndrome is recommended by NCEP-ATP III to further reduce CHD risk after the LDL-C target has been met. Prospective clinical studies are needed to define the impact of niacin and other lipid-modifying agents on CHD morbidity and mortality in patients with the metabolic syndrome.
Purified Poloxamer 188 for Sickle Cell Vaso-Occlusive Crisis
Authors: Gibbs Winter J , Hagemann Tracy M
Published: January 2004

OBJECTIVE

To review available literature on the pharmacology, pharmacokinetics, efficacy, toxicology, adverse effects, drug interactions, and dosage guidelines for purified poloxamer 188, a product in Phase III trials.

DATA SOURCES

Reviewers searched the following databases for English-language studies: MEDLINE (1966–November 2003), International Pharmaceutical Abstracts (1970–November 2003), and the Cochrane Library Database (3rd quarter 2003). Key search terms included purified poloxamer 188, Flocor, CRL-5861, poloxamer 188, RheothRx, and pluronic F-68.

STUDY SELECTION AND DATA EXTRACTION

Data on efficacy, adverse effects, and pharmacokinetics were obtained from randomized, open-label, and blinded clinical trials. Toxicology data were obtained from unpublished studies with purified poloxamer 188 and from available data on poloxamer 188 (nonpurified form).

DATA SYNTHESIS

Purified poloxamer 188 is a highly purified form of the nonionic block copolymer poloxamer 188. It lowers blood viscosity, decreases red blood cell (RBC) aggregation, and decreases friction between RBCs and vessel walls to increase microvascular blood flow and decrease cell injury. In clinical trials, purified poloxamer 188 demonstrated safety, but little efficacy for the treatment of sickle cell vaso-occlusive crisis. Increased efficacy has been shown in patients on concurrent hydroxyurea therapy and those <15 years of age.

CONCLUSIONS

Purified poloxamer 188 represents a new approach to the management of the sickle cell vaso-occlusive crisis. Children and patients on hydroxyurea may benefit most from purified poloxamer 188 therapy. Further studies are needed to confirm its efficacy and to determine whether the drug decreases sickle cell disease severity and complications.
Ethnic Differences in Antihypertensive Medication Use in the Elderly
Authors: Raji Mukaila A , Kuo Yong-Fang , Salazar Joel A , Satish Shiva , Goodwin James S
Published: January 2004

BACKGROUND

Determining the optimal treatment for hypertension in very old patients requires better understanding of interethnic differences in patterns and predictors of antihypertensive drug use in this population.

OBJECTIVE

To investigate interethnic variations in antihypertensive drug use in a triethnic sample of community-dwelling adults aged ≥77 years.

METHODS

We performed a cross-sectional study of non-Hispanic white, black, and Hispanic adults ≥77 years old residing in Galveston County, TX. In-home interviews in 1997 and 1998 assessed blood pressures and antihypertensive medication use in 281 subjects who reported having hypertension or who had a systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg.

RESULTS

Of the population evaluated, 62.9% of non-Hispanic whites, 60.2% of blacks, and 45.2% of Hispanics with hypertension were on antihypertensive medications (p < 0.027 across the ethnic groups). After adjusting for age, gender, years of education, household income, Medicaid insurance, number of physician visits, and cognitive function, Hispanic ethnicity, unlike black ethnicity, continued to be significantly associated with lower use of antihypertensive drugs compared with non-Hispanic whites (OR 0.41; 95% CI 0.19 to 0.90). Characteristics associated with the lower use of antihypertensive drugs included older age and low income in whites, poor cognition and infrequent physician visits in blacks, and lack of Medicaid insurance in Hispanics.

CONCLUSIONS

In the elderly, Hispanic ethnicity, unlike black ethnicity, is significantly associated with lower use of antihypertensive drug therapy compared with non-Hispanic white ethnicity, adjusting for relevant sociodemographic and health factors.
Ginger-Associated Overanticoagulation by Phenprocoumon
Authors: Krüth Patricia , Brosi Eberhard , Fux Richard , Mörike Klaus , Gleiter Christoph H
Published: January 2004

OBJECTIVE

To report a case of ginger–phenprocoumon interaction resulting in an elevated international normalized ratio (INR) and epistaxis.

CASE SUMMARY

A 76-year-old white European woman on long-term phenprocoumon therapy with an INR within the therapeutic range began using ginger products. Several weeks later, she developed an elevated INR up to 10 and epistaxis. The INR returned to the normal range after ginger was stopped and vitamin K1 was given.

DISCUSSION

There have been a number of investigations resulting in conflicting opinions on the effect of ginger on hemostasis, specifically, platelet inhibition. Nevertheless, based on these investigations, recommendations have been issued to refrain from ingesting ginger and other herbals like garlic or ginkgo biloba in situations where bleeding may be critical. An objective causality assessment revealed that the adverse drug event as a result of the phenprocoumon and ginger interaction was probable.

CONCLUSIONS

As of writing, this was the first case report that may support an interaction between an oral anticoagulant and ginger together with a brief review of the literature on ginger and hemostasis. As this interaction was observed only by chance, this case highlights the importance of self-control of anticoagulation with coumarins particularly for the detection of unknown interactions.
Measurement, Correlates, and Health Outcomes of Medication Adherence Among Seniors
Authors: Vik Shelly A , Maxwell Colleen J , Hogan David B
Published: January 2004

OBJECTIVE

To provide a comprehensive review of the literature on the measurement, correlates, and health outcomes of medication adherence among community-dwelling older adults.

DATA SOURCES

Searches of MEDLINE, PubMed, and International Pharmaceutical Abstracts databases for English-language literature (1966–December 2002) were conducted using one or more of the following terms: elderly, adherence/nonadherence, compliance/noncompliance, medication/drug, methodology/measurement, and hospitalization.

STUDY SELECTION AND DATA EXTRACTION

From the above search, studies of medication adherence in community-dwelling seniors were selected for review along with relevant publications from the reference lists of articles identified in the initial database search.

DATA SYNTHESIS

Although several methods are available for the assessment of adherence, accurate measurement continues to be difficult. The available evidence suggests that polypharmacy and poor patient–healthcare provider relationships (including the use of multiple providers) may be major determinants of nonadherence among older persons, with the impact of most sociodemographic factors being negligible. There is little consensus regarding other determinants of nonadherence. Relatively few high-quality investigations have examined the associations between nonadherence and subsequent health outcomes. Available data provide some support for increased health risks with nonadherence. However, interventions to improve adherence have seldom demonstrated positive effects on health outcomes.

CONCLUSIONS

There are few empirical data to support a simple systematic descriptor of the nonadherent patient. The inconsistencies across studies may be attributable, in part, to the inherent difficulties involved in the measurement of a behavioral risk factor such as nonadherence. Future research in this area would be strengthened by incorporation of detailed assessments of patient-reported reasons for nonadherence, the appropriateness of drug regimens, and the effect of nonadherence on health outcomes.
Involvement of Immunization-Certified Pharmacists with Immunization Activities
Authors: Neuhauser Melinda M , Wiley Danielle , Simpson Lynn , Garey Kevin W
Published: January 2004

BACKGROUND

Immunization certification courses allow pharmacists to directly administer vaccines to their patients. However, the demographics and level of immunization involvement of immunization-certified pharmacists compared with those noncertified are unknown.

OBJECTIVE

To document the demographics, professional activities, and job satisfaction of immunization-certified pharmacists compared with pharmacists not certified for immunization.

METHODS

In a cross-sectional pilot study, immunization-certified pharmacists were compared with noncertified pharmacists via a postal-mailed questionnaire. The questionnaire consisted of demographic and practice site characteristics, involvement in immunization services, and a job satisfaction survey.

RESULTS

Response rates were 48% (n = 101) and 36% (n = 158) for immunization-certified and noncertified pharmacists, respectively. Significantly more certified pharmacists were involved in immunizations (99% vs 24%; p < 0.001). Desire to improve the health care of the public and personal satisfaction were important factors that encouraged pharmacists to become certified to administer vaccines. Seventy-four percent of immunization-certified pharmacists directly administered the vaccines, primarily influenza (96%), pneumococcal (77%), hepatitis (55%), and diphtheria, pertussis, tetanus (19%). Adequate training, time, support from management and staff, and liability coverage were important factors that allowed pharmacists to incorporate immunizations into their practice. No significant differences in job satisfaction were observed between immunization-certified and noncertified pharmacists.

CONCLUSIONS

Immunization-certified pharmacists are using their skills to administer vaccines to patients within their communities. Efforts to increase the number of these pharmacists throughout the US should be undertaken.
Warfarin Initiation and Monitoring with Clotting Factors II, VII, and X
Authors: Trask Ashley S , Gosselin Robert C , Diaz Jaime A , Dager William E
Published: January 2004

OBJECTIVE

To report a case of a patient with antiphospholipid antibody syndrome and multiple thromboses who developed heparin-induced thrombocytopenia (HIT) and subsequent international normalized ratio (INR) prolongation possibly due to antiphospholipid antibodies.

CASE SUMMARY

A 56-year-old white woman with a history of antiphospholipid antibody syndrome and thrombosis taking chronic warfarin was admitted for gastrointestinal concerns and found to have an INR >14. Warfarin was discontinued, vitamin K was administered, and a heparin infusion was initiated. Over the next 2 days, thrombocytopenia, hypotension, tachycardia, hyponatremia, and progressive abdominal pain developed. Upon transfer to a tertiary care center, HIT was diagnosed, and a lepirudin infusion was initiated. Subsequently, a sudden elevation of the INR occurred (>14) with low prothrombin (factor II) activity. After INR values declined to 2–3, warfarin was reinitiated with dosing adjusted using factor X and II activity levels. Clotting factors II and X activities were measured to monitor long-term warfarin therapy, with no evidence of complications after 7 months.

DISCUSSION

Typically, the INR is used to assess the intensity of anticoagulation. The INR value represents the reduction of clotting factors II, VII, and X. In rare circumstances, an independent inhibitor or interfering substance can interfere with the process of measuring the INR. In such situations, an alternative approach can be direct measurement of clotting factor concentrations.

CONCLUSIONS

Factor II and/or factor X activity levels provided an alternative means for measuring the anticoagulant effects of warfarin in the presence of a significant inhibitor (antiphospholipid antibodies) that biased the INR measurements.
Acenocoumarol-Induced Henoch-Schönlein Purpura
Authors: Borrás-Blasco Joaquín , Girona Eva , Navarro-Ruiz Andrés , Matarredona Jaime , Giménez María Encarnación , Gutiérrez Ana , Enriquez Ricardo , Martinez Antonio
Published: January 2004

OBJECTIVE

To report a probable case of Henoch-Schönlein purpura associated with acenocoumarol therapy.

CASE SUMMARY

A 76-year-old white woman was prescribed acenocoumarol for chronic atrial fibrillation. Two months after starting therapy, the patient came to our hospital's emergency department because of abdominal pain associated with vomiting. Physical examination revealed multiple round, confluent, purpuric lesions with some vesicles and an area of residual pigmentation. Lesions were present predominantly on the legs and gluteus, and also on the abdomen and arms. Skin biopsy of the lesions was compatible with leukocytoclastic vasculitis with deposition of immunoglobulin A. An upper intestinal endoscopy was done and identified purpuric mucosal lesions in the fundus, body, and antrum of the stomach and the duodenal bulb. Renal function was not affected, although proteinuria (1.26 g/day) was found and microscopic hematuria was observed.

DISCUSSION

The most likely cause of the Henoch–Schönlein purpura in this case was considered to be acenocoumarol because of the close temporal relationship between exposure to the drug and onset of symptoms, as well as the rapid resolution of the symptoms and signs after acenocoumarol was discontinued. The oral anticoagulant was the only identifiable precipitant that the patient encountered before the Henoch–Schönlein purpura developed. An objective causality assessment revealed that the adverse drug event was probable.

CONCLUSIONS

This case report illustrates a probable association between Henoch–Schönlein purpura and acenocoumarol. As of December 2003, this reaction had not been previously reported. Clinicians should be aware of this potential adverse effect of a widely used drug.
Metabolic Bone Disease After Chronic Antacid Administration in an Infant
Authors: Robinson Renee F , Casavant Marcel J , Nahata Milap C , Mahan John D
Published: January 2004

OBJECTIVE

To describe a case of hypophosphatemia and metabolic bone disease (MBD) due to aluminum-containing antacids.

CASE SUMMARY

An 8-month-old white boy was brought to the emergency department due to irritability and pain with movement. Upon examination, the infant was irritable, unable to bear weight, had palpable clavicular bony lesions, point tenderness of the hips, and poor head control. The infant had lost several developmental milestones over the past 4 months (eg, ability to roll over) and had decreased appetite and minimal weight gain. Skeletal survey revealed multiple rib fractures, osteoporosis, and Ricketts. Hypophosphatemia (2.3 mg/dL; normal 3.2–6.3) and an elevated serum aluminum level (14 μg/L, normal 0–9) were noted. Past medical history was positive for gastroesophageal reflux. He had been started on ranitidine and aluminum hydroxide (1/2 teaspoonful per 6-ounce bottle) at 2 months of age. The infant's formula contained elevated aluminum levels. Further investigation showed that 1/2 tablespoonful instead of 1/2 teaspoonful of antacid had been added to each 6-ounce formula bottle for the prior 6 months; only 1 month of antacid therapy had been recommended. An objective causality assessment revealed a probable adverse drug event.

DISCUSSION

Phosphate-binding substances such as aluminum-containing antacids can bind large amounts of phosphorus, causing hypophosphatemia and MBD.

CONCLUSIONS

We report this case to increase awareness of the risk of hypophosphatemia and MBD (likely aluminum related) with use of over-the-counter aluminum-containing antacids in pediatrics, as well as the hazards of prescribing doses in “spoonful” units.
Rhabdomyolysis and Renal Failure Associated with Gemfibrozil Monotherapy
Authors: Layne Richard D , Sehbai Aasim S , Stark Linda J
Published: January 2004

OBJECTIVE

To report a case of rhabdomyolysis and acute renal failure associated with gemfibrozil monotherapy of hyperlipidemia.

CASE SUMMARY

A 30-year-old white man with hypertension, type 1 diabetes mellitus, and hyperlipidemia was hospitalized due to myalgias, nausea, and vomiting that began after he started working as a jackhammer operator 4 days previously. His medications were lisinopril, aspirin, insulin, and gemfibrozil. Creatine kinase and creatinine, which previously had been mildly elevated and normal, respectively, were markedly elevated, consistent with rhabdomyolysis with acute renal failure.

DISCUSSION

As of December 8, 2003, this is the only report of a patient with normal baseline creatinine level who developed rhabdomyolysis with acute renal failure associated with gemfibrozil monotherapy. Strenuous exertion, hypovolemia, and lisinopril use may have contributed to the severity of illness. An objective causality assessment revealed that an adverse drug reaction to gemfibrozil was possible.

CONCLUSIONS

Gemfibrozil monotherapy of hyperlipidemia may predispose to rhabdomyolysis with acute renal failure. Patients using gemfibrozil should be cautioned regarding strenuous exertion, dehydration, and the need for prompt evaluation of myalgias.