Latest Research

February 16, 2007

A summary of the "must-read" articles from the journals in that pile on your desk.

Statin Therapy Increases High-Density Lipoprotein

Disease regression associated with LDL cholesterol decrease, HDL cholesterol increase

Statin therapy induces regression of coronary atherosclerosis via both a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol (HDL-C), according to a report in the Feb. 7 issue of the Journal of the American Medical Association.

Stephen J. Nicholls, Ph.D., of The Cleveland Clinic in Ohio, and colleagues performed a post-hoc analysis of 1,455 patients from four prospective clinical trials conducted in North America, Europe and Australia, to assess the link between lipoprotein levels and coronary artery atheroma volume. Patients underwent serial intravascular ultrasonography to measure changes in coronary atheroma burden in response to statin treatment.

Statin therapy was associated with reduced LDL-C (from 124 mg/dL to 87.5 mg/dL, mean decrease 23.5 percent), increased HDL-C (from 42.5 mg/dL to 45.1 mg/dL, mean increase 7.5 percent), reduced LDL-C/HDL-C ratio (from 3.0 to 2.1, mean decrease 26.7 percent), and decreased total atheroma volume (mean 2.4 cubic mm). Significant disease regression occurred when LDL-C levels dropped substantially (to below 87.5 mg/dL during treatment) and HDL-C levels rose by at least 7.5 percent.

"This is, to our knowledge, the first time that increases in HDL-C levels have been shown to be an independent predictor of a beneficial outcome with statin therapy," the authors write.

The clinical trials referenced in the study were funded by Pfizer, AstraZeneca and Sankyo Pharma.

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Increased Mortality Seen with Post-CABG Aprotinin

Serine protease antagonist, but not lysine analogs, heightens death risk after heart surgery

Compared with the use of lysine analogs or no treatment after coronary artery bypass graft surgery, aprotinin is associated with increased mortality over the five-year postoperative period, according to a report in the Feb. 7 issue of the Journal of the American Medical Association.

Dennis Mangano, Ph.D., M.D., of the Ischemia Research and Education Foundation in San Bruno, Calif., and colleagues measured survival in 4,374 coronary artery bypass graft surgery patients from 69 medical centers, who had received aprotinin, or one of two lysine analogs (aminocaproic acid or tranexamic acid) or no postoperative antifibrinolytic medication. Survival was measured at six weeks, six months and annually for five years following surgery.

Aprotinin treatment was associated with a significantly increased mortality over five years relative to both untreated patients (hazard ratio for death, 1.48) and those who received lysine analog treatment (hazard ratios of 1.03 and 1.07 for aminocaproic acid and tranexamic acid, respectively). This heightened risk remained even after considering several disparate covariate factors, risk indices and patient profiles, and amounted to a 5 percent absolute increase in mortality for cardiac surgery patients over five years.

"Based on our data, we therefore believe that additional concern is now warranted regarding the long-term safety of aprotinin among patients undergoing coronary artery bypass surgery," the authors write.

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Genetic Mutations Linked to Postmenopausal Blood Clots

Five single nucleotide polymorphisms linked to venous thrombosis in postmenopausal women

Five single nucleotide polymorphisms, three of which have not been previously reported, have been linked to the incidence of venous thrombosis in postmenopausal women, according to a report published in the Feb. 7 Journal of the American Medical Association.

Nicholas L. Smith, Ph.D., of the University of Washington in Seattle, and colleagues compared the risk of venous thrombosis in a population-based study of 349 perimenopausal and postmenopausal women and 1,680 matched controls. The researchers evaluated the association of common genetic variation in 24 candidate genes with incident nonfatal venous thrombosis.

The tissue factor pathway inhibitor gene was the only one to have a global association with risk. Five single nucleotide polymorphisms (SNP) associations were identified across three candidate genes (factors V, XI, and protein C). Of another 22 variants across 15 genes, five confirmed previously reported associations (fibrinogen genes and protein C), two were inconsistent with earlier reports, and 15 were new discoveries.

"After accounting for multiple testing, five SNPs associated with venous thrombosis risk were identified, three of which have not been previously reported. Replication of these novel associations in other populations is necessary to corroborate these findings and identify which genetic factors may influence venous thrombosis risk in postmenopausal women," the authors conclude.

One of the authors received a speaker's honorarium from Celera Diagnostics.

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Financial Benefits of Pediatric Exclusivity Program Assessed

Blockbusters perform well, but some drugs tested at a loss, study finds

The economic return for pharmaceutical companies that conduct pediatric trials in exchange for six extra months of market exclusivity varies widely, according to a report in the Feb. 7 issue of the Journal of the American Medical Association.

Jennifer S. Li, M.D., of the Duke Clinical Research Institute in Durham, N.C., and colleagues analyzed nine drugs whose manufacturers submitted clinical data to the U.S. Food and Drug Administration under the Pediatric Exclusivity Program between 2002 and 2004. Using cash-flow estimates based on six or three months of extra patent protection, the team calculated each drug's net economic return and return-to-cost ratio.

The nine drugs address depression, hypertension, asthma and allergy, osteogenesis imperfecta, bacterial infection, gastroesophageal reflux, diabetes mellitus, refractory tumors and attention-deficit/hyperactivity disorder. Five had annual sales exceeding $1 billion. The net economic benefit for six additional months of market exclusivity ranged from -$8.9 million to $507.9 million (median $134 million); the net return-to-cost ratio ranged from -0.68 to 73.63. Three months of market exclusivity reduces the estimated economic benefit to a median $64 million.

"The Pediatric Exclusivity Program overcompensates blockbuster products for performing clinical trials in children, while other products have more modest returns on investment," write the authors, who add that "the greatest return is the benefit derived in obtaining new information relevant and applicable toward the care of children."

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Modest Quality Boost in Pay-for-Performance Hospitals

Financial incentives encourage only modest gains in composite and individual quality-of-care measures

A demonstration project funded by the Centers for Medicare and Medicaid Services suggests that pay-for-performance can improve the quality of care in hospitals from 2.6 to 4.1 percent compared with hospitals that adopt public reporting as a quality improvement measure, according to a report in the Feb. 1 New England Journal of Medicine.

Peter K. Lindenauer, M.D., of the Baystate Medical Center in Springfield, Mass., and colleagues measured changes in adherence to individual and composite quality measures over two years at 613 hospitals, including 207 facilities that participated in the pay-for-performance project.

Compared with the controls, pay-for-performance hospitals had more improvement in all composite quality measures, including care for acute myocardial infarction, heart failure and pneumonia, and in a composite of 10 measures. Baseline performance was inversely linked with improvement. Pay-for-performance hospitals in the lowest quintile of baseline performance had a 16.1 percent improvement in the composite of all 10 measures; a 1.9 percent improvement was reported for those in the highest quintile. After adjusting for differences in baseline performance and other hospital characteristics, pay for performance was associated with improvements from 2.6 to 4.1 percent.

"The Centers for Medicare and Medicaid Services may have much to gain from recognizing that pay for performance is fundamentally a social experiment likely to have only modest incremental value," an accompanying editorial concludes. "Rather than adopt a single new payment system for all of Medicare, a series of regional models could accelerate learning and allow Medicare officials to find out more about the effect of differing levels of incentives and formulas for payment."

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Mutations Cause of Distinct Myeloproliferative Disorders

Four new mutations in Janus kinase 2 gene identified in idiopathic erythrocytosis patients

Researchers have identified four new mutations in the Janus kinase 2 (JAK2) gene that can cause myeloproliferative disease, and patients with the mutations may have a distinct syndrome even though they are currently diagnosed as having polycythemia vera or idiopathic erythrocytosis. The findings are published in the Feb. 1 issue of the New England Journal of Medicine.

Anthony R. Green, F.R.C.Path., F.Med.Sci., of Cambridge Institute for Medical Research in Cambridge, U.K., and colleagues identified four somatic mutations in exon 12 of the JAK2 gene in 10 patients who had isolated erythrocytosis and distinctive bone marrow morphology. The patients were negative for V617F mutations in the JAK2 gene, which are found in approximately 95 percent of polycythemia vera patients.

When erythroid colonies are grown from blood samples, V617F-positive polycythemia vera patients have colonies that are homozygous for the mutation. The non-V617F mutation carriers had colonies that were heterozygous for the mutation. In a mouse model, three of the four exon 12 mutations caused a myeloproliferative phenotype.

"The diagnosis of individual patients with a myeloproliferative disorder can be difficult. Different centers use different diagnostic criteria, and several diagnostic tests are not widely used. A patient may therefore be given a diagnosis of polycythemia vera by one clinician and a diagnosis of idiopathic erythrocytosis by another. Our results emphasize the importance of molecular classification of these diseases," the authors conclude.

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Oils in Soaps, Shampoo Linked to Gynecomastia in Boys

Lavender and/or tea tree oil may possess endocrine-disrupting properties

Topical use of products such as soaps or shampoo that contain lavender oil and/or tea tree oil may result in prepubertal gynecomastia in boys, researchers report in the Feb. 1 issue of the New England Journal of Medicine.

Derek V. Henley, Ph.D., of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., and colleagues report on three otherwise healthy prepubertal boys with gynecomastia and normal serum concentrations of endogenous steroids. The boys, aged 4 to 10, all had used lavender-scented soap and skin lotions, shampoo or styling products that contained tea tree oil and lavender oil.

The gynecomastia subsided several months after the boys stopped using the products. The researchers tested the oils on human cell lines and demonstrated that they had estrogenic and anti-androgenic activities. Taken together, the case studies and the laboratory study confirmed that the oils were the likely cause of the prepubertal gynecomastia.

"We suggest that the medical community should be aware of the possibility of endocrine disruption and should caution patients about repeated exposure to any products containing these oils," the study authors write.

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Discussing Death with Relatives in ICU Eases Grief

Family members of terminally ill intensive care patients benefit from proactive communications style

The relatives of patients who are dying in the intensive care unit cope better with the loss if they are provided with written information on bereavement beforehand and are given more time to talk and discuss their relative's condition, according to the results of a study published in the Feb. 1 issue of the New England Journal of Medicine.

Elie Azoulay, M.D., of Hopital Saint-Louis in Paris, France, and colleagues conducted a study of the families of 126 patients dying in 22 French intensive care units. While 63 family members were given the standard end-of-life conference, the other 63 family members were given the brochure and as a result had a median 30-minute conference, compared with a median 20 minutes for the control group. The intervention group also spent nearly half of the time talking (14 minutes), versus one-quarter (five minutes) in the control group. After 90 days, 108 participants responded to a telephone interview to judge the effects of bereavement.

The intervention group had lower levels of depression and anxiety, less post-traumatic stress disorder-related symptoms and lower scores on the Impact of Event Scale compared to the control group, the report indicates.

A proactive strategy "resulted in longer meetings in which families had more opportunities to speak and to express emotions, felt more supported in making difficult decisions, experienced more relief from guilt, and were more likely to accept realistic goals of care," the authors conclude.

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Cardiovascular Disease in Women Linked to Air Pollution

In postmenopausal women, fine particulate air pollution associated with higher mortality

Over the long term, fine particulate air pollution exposure may increase the risk of cardiovascular disease and mortality in postmenopausal women, according to a study published in the Feb. 1 issue of the New England Journal of Medicine.

Joel D. Kaufman, M.D., of the University of Washington in Seattle, and colleagues conducted a study of 65,893 postmenopausal women in 36 U.S. cities. The women, who had no history of heart disease, were followed for six years, during which time exposure to air pollution was monitored. During the study, 1,816 women had at least one cardiovascular event, including coronary heart disease, cerebrovascular disease, coronary revascularization, myocardial infarction and stroke.

Women's exposure to particulate matter of less than 2.5 μm in aerodynamic diameter in the year 2000 ranged from 3.4 to 28.3 μg per cubic meter. Each 10 μg increase added 24 percent to the risk of a cardiovascular event and 76 percent to the cardiovascular disease mortality rate. Particulate exposure was also linked to a higher risk of cerebrovascular events (hazard ratio, 1.35).

"Our study confirms previous reports and indicates that the magnitude of health effects may be larger than previously recognized. These results suggest that efforts to limit long-term exposure to fine particulate pollution are warranted," the authors conclude.

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Antibody Improves Psoriasis Area and Severity

Antibody targets interleukin-12 and interleukin-23

A monoclonal antibody that neutralizes interleukin-12 and interleukin-23 significantly improves psoriasis area and severity in patients with moderate-to-severe disease compared with placebo, according to the results of a study published in the Feb. 8 issue of the New England Journal of Medicine.

Gerald G. Krueger, M.D., from the University of Utah in Salt Lake City, and colleagues randomly assigned 320 patients with moderate-to-severe plaque psoriasis to a placebo or to one of four regimens of an interleukin-12/23 monoclonal antibody for 12 weeks.

The researchers found that significantly more patients in the antibody group had an at least 75 percent improvement in psoriasis area and severity (ranging from 52 to 81 percent of patients depending on dose regimen) compared with only 2 percent of the placebo group. Adverse events and serious adverse events occurred at similar frequencies in both groups (79 versus 72 percent and 4 versus 1 percent for antibody and placebo, respectively).

"This study demonstrates the therapeutic efficacy of an interleukin-12/23 monoclonal antibody in psoriasis and provides further evidence of a role of the interleukin-12/23 p40 cytokines in the pathophysiology of psoriasis," Krueger and colleagues conclude.

The study was supported by Centocor in Malvern, Pa.

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Antibodies Impair Neutrophil Function in Lung Disease

Similar impairment observed in mice lacking cytokine

Patients with pulmonary alveolar proteinosis have impaired neutrophil function due to autoantibodies against granulocyte-macrophage-colony stimulating factor (GM-CSF), which is also observed in mice lacking the GM-CSF gene, according to a study in the Feb. 8 issue of the New England Journal of Medicine.

Bruce C. Trapnell, M.D., from Cincinnati Children's Hospital Medical Center in Ohio, and colleagues examined neutrophil function in 12 patients with pulmonary alveolar proteinosis, 61 healthy controls and 12 controls with cystic fibrosis or end-stage liver disease. They also studied neutrophil function in normal mice and mice lacking the GM-CSF gene.

The researchers found that neutrophils from patients with pulmonary alveolar proteinosis were impaired in both basal and antimicrobial functions after GM-CSF priming. This dysfunction could be reproduced in neutrophils from healthy controls after treatment with GM-CSF autoantibodies from patients with pulmonary alveolar proteinosis.

The investigators also found that mice lacking GM-CSF were impaired in basal neutrophil function but not functions after GM-CSF priming, and injecting mouse GM-CSF antibodies into normal mice produced neutrophil dysfunction.

"The antimicrobial functions of neutrophils are impaired in patients with pulmonary alveolar proteinosis, owing to the presence of GM-CSF autoantibodies," the authors conclude. "The effects of these autoantibodies show that GM-CSF is an essential regulator of neutrophil functions."

AbstractFull Text (subscription or payment may be required)Editorial

Many Doctors Say OK to Discuss Moral Qualms with Patient

While most believe they should refer patients to an alternative source of treatment, not all do

A majority of physicians believe they have the right to discuss moral or ethical objections to a treatment with a patient, 14 percent don't believe they have an obligation to inform patients of all the options and 29 percent don't think they need to refer them to an amenable physician, according to an article published in the Feb. 8 issue of the New England Journal of Medicine.

Farr A. Curlin, M.D., of the University of Chicago, and colleagues conducted a study by postal questionnaire of 1,820 randomly selected U.S. physicians, of whom 1,144 (63 percent) responded. The morally or ethically contentious scenarios the researchers posed included a request for terminal sedation for a dying patient, abortion after contraceptive failure and a request for birth control from an underage girl without parental approval.

While 63 percent of respondents said they believed physicians had a right to discuss their objections to a treatment based on ethical or moral grounds, 86 percent replied that they had the responsibility to explain all the available options to patients. Seventy-one percent believed they should refer patients to an alternative source of treatment. Those who did not report such obligations were more likely to be male and religious. Overall, 52 percent of the physicians objected to abortion for failed contraception and 42 percent had a problem with giving contraception to an adolescent without parental consent.

"If physicians' ideas translate into their practices, then 14 percent of patients -- more than 40 million Americans -- may be cared for by physicians who do not believe they are obligated to disclose information about medically available treatments they consider objectionable," the authors conclude. "In addition, 29 percent of patients -- or nearly 100 million Americans -- may be cared for by physicians who do not believe they have an obligation to refer the patient to another provider for such treatments."

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Clomiphene Helps Infertility Due to Polycystic Ovary

Drug more effective than metformin, but with higher risk of multiple pregnancy

Clomiphene is significantly more effective than metformin in treating infertility in women with polycystic ovary syndrome, but with a higher risk of multiple pregnancies, researchers report in the Feb. 8 issue of the New England Journal of Medicine.

Richard S. Legro, M.D., from Pennsylvania State University College of Medicine in Hershey, Pa., and colleagues randomized 626 infertile women with polycystic ovary syndrome to clomiphene citrate, metformin, or both, for six months or until a confirmed pregnancy.

The researchers found that clomiphene alone or combined with metformin significantly improved the live-birth rate compared with metformin alone (22.5 percent, 26.8 percent and 7.2 percent, respectively). However, the clomiphene groups had a higher rate of multiple pregnancies (6 percent, 3.1 percent and 0 percent, respectively). The conception rate for women who ovulated was significantly lower in the metformin group compared with the clomiphene groups, the report indicates.

"Aside from the low but ever-present risk of multiple pregnancy, the use of clomiphene citrate to treat infertility in women with the polycystic ovary syndrome is simple, inexpensive, generally safe and?more efficacious than the use of metformin," David S. Guzick, M.D., Ph.D., from the University of Rochester School of Medicine and Dentistry in Rochester, N.Y., writes in an accompanying editorial.

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Prenatal Test Relies on Fetal DNA in Maternal Blood

Ability to detect single nucleotide polymorphisms may lead to non-invasive test for Down syndrome

Free fetal DNA can be distinguished from maternal DNA in maternal plasma using single nucleotide polymorphisms, according to a study published online Feb. 2 in The Lancet. The technique could be used in a diagnostic test for chromosomal abnormalities such as trisomy 21.

Ravinder Dhallan, M.D., of Ravgen, Inc. in Columbia, Md., and colleagues conducted a study of blood samples taken from 60 pregnant women, calculated the proportion of free fetal DNA and used single nucleotide polymorphisms to distinguish it from maternal DNA.

Among the 60 samples there was a mean 34 percent proportion of free fetal DNA, and while 57 samples produced a normal result, three revealed abnormal DNA ratios for chromosome 13 and chromosome 21. When the same women underwent amniocentesis or when the babies were born, the non-invasive test was found to have generated one false-positive and one false-negative result, the equivalent of a 66.7 percent positive predictive value and a 98.2 percent negative predictive value.

"Our results show that single nucleotide polymorphisms can be used to distinguish fetal DNA from maternal DNA -- and to determine the copy number of fetal chromosomes -- in maternal blood samples," the authors conclude. "With further refinement, a prenatal diagnostic test based on the methods described could be a useful complement to currently available prenatal tests."

Several authors are employees and/or stockholders at Ravgen, Inc., the company that has issued a patent for the method described in this study.

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Prosthetic Function Improved by Targeted Reinnervation

Patient described control of artificial arm as intuitive

A patient who underwent targeted reinnervation gained substantially better control of her prosthetic arm, according to a report published online Feb. 2 in The Lancet.

Todd A. Kuiken, M.D., of Northwestern University in Evanston, Ill., and colleagues developed a new technique called targeted muscle reinnervation, which entails transferring residual nerves from an amputated limb to other muscle groups that then amplify the motor commands of the amputated nerve.

This technique was used to treat a woman whose left arm had been amputated at the humeral neck. She was fitted with a prosthesis that was designed to utilize the targeted muscle reinnervation sites.

When the patient thought about using her hand or elbow, she found that the prosthesis made an appropriate response, a control process that the patient described as "intuitive." When tested for motor and process skill functionality, the prosthesis significantly outperformed a conventional prosthesis.

"The denervated anterior chest skin was reinnervated by both the ulnar and median nerves; the patient felt that her hand was being touched when this chest skin was touched, with near-normal thresholds in all sensory modalities," the authors write. "Targeted reinnervation improved prosthetic function and ease of use in this patient. Targeted sensory reinnervation provides a potential pathway for meaningful sensory feedback," the authors conclude.

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Score Can Predict Stroke Risk After Transient Ischemia

Unified score more accurate than the California or ABCD scores alone

When it comes to the short-term risk of stroke after a transient ischemic attack, a new, unified score that is based on age, blood pressure, clinical features, duration and diabetes is a better predictor than two other scoring methods currently in use, according to a report in the Jan. 27 issue of The Lancet.

S. Claiborne Johnston, M.D., of the University of California San Francisco, and colleagues examined the value of the California and ABCD scores in predicting the early risk of stroke after a transient ischemic attack in four validation groups consisting of 2,893 patients. The two scores were then combined into a new unified score (ABCD-squared) for optimum prediction of two-day risk, and its predictive value was assessed in two derivation groups of 1,916 patients.

The researchers found that both scores were similar in predicting stroke risk after two days, seven days and 90 days. However, the unified score was more accurate in classifying patients' two-day risk of stroke.

"The great virtue of ABCD-squared as an aid to understanding prognosis is its simplicity and easy applicability," Walter N. Kernan, M.D., from Yale University School of Medicine in New Haven, Conn., writes in an accompanying editorial. "We should consider it now for communication and triage, but recognize that prognosis is dynamic and can be affected by clinical data and treatment."

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Study Suggests Alteplase Safe for Routine Use in Stroke

Large European study reports similar outcomes for experienced and inexperienced stroke centers

Centers with little experience using intravenous alteplase for thrombolysis after acute stroke have similar symptomatic intracerebral hemorrhage and three-month mortality rates as their more experienced counterparts, indicating that routine clinical use of the agent is safe and effective, researchers report in the Jan. 27 issue of The Lancet.

Nils Wahlgren, M.D., of the Karolinska Institute in Stockholm, Sweden, and colleagues evaluated data from the prospective, open, monitored, observational Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST). Safety and efficacy of intravenous alteplase for thrombolysis given during the first three hours of acute ischemic stroke was assessed in 6,483 patients from 285 European centers, half of which had little experience in stroke thrombolysis. The results were compared to pooled data from randomized controlled trials.

At 24 hours, 1.7 percent of patients had symptomatic intracerebral hemorrhage; at seven days, 7.3 percent of the SITS-MOST group had the same condition compared with 8.6 percent in the pooled trials. At three months, the SITS-MOST group mortality was 11.3 percent compared with 17.3 percent in the pooled trials.

"These data confirm that intravenous alteplase is safe and effective in routine clinical use when used within three hours of stroke onset, even by centers with little previous experience of thrombolytic therapy for acute stroke. The findings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centers," the authors conclude.

Some authors have consulted for or received compensation from Boehringer Ingelheim, NovoNordisk, Pfizer, Sanofi-Aventis, AstraZeneca, Lundbeck, GSK, and AGFA.

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Special Stroke Units May Have Better Outcomes

Fewer patients died or were disabled after stroke-unit treatment than conventional ward care

Acute stroke patients treated in specialized hospital stroke units have a lower risk of death or disability than patients treated in conventional wards, researchers report in the Jan. 27 issue of The Lancet.

Livia Candelise, M.D., of the Universita degli Studi di Milano, Italy, and colleagues compared outcomes of 4,936 patients hospitalized in stroke units within 48 hours of an acute stroke versus 6,636 patients treated in conventional wards in 260 Italian hospitals between 2000 and 2004.

The researchers found that 1,576 patients died in the hospital; 2,169 died within two years; 347 eluded follow-up. For all ages and clinical problems except unconsciousness, stroke-unit care was linked to significantly lower death and disability after two years compared with conventional care (odds ratio, 0.81).

"Admission to a stroke-unit ward with dedicated beds and staff within 48 hours of onset should be recommended for all patients with acute stroke," the authors write.

In an accompanying comment, Peter M. Rothwell, of the University of Oxford in the U.K., cautions that "similar observational studies of care in stroke units versus care in general medical wards in countries with more stroke units have produced conflicting results."

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Living Near Freeway Impairs Child Lung Development

Impairment independent of air quality

Children who live within 500 meters of a major freeway develop deficits in lung function by age 18 that are independent of air quality, according to a report published online Jan. 26 in The Lancet.

W. James Gauderman, Ph.D., of the University of Southern California in Los Angeles, and colleagues examined lung function annually over an eight-year period in 3,677 children, mean age 10 years, living in 12 areas in southern California, which had varying air quality and were of varied distances from traffic.

The researchers found that children living within 500 meters of a freeway had worse lung function than those living at least 1500 meters from a freeway, as assessed by the growth of forced expiratory volume in 1 second and maximum midexpiratory flow rate over the eight-year study period. Freeway exposure and air pollution independently contributed to reduced lung function growth. At 18 years of age, children living closer to a freeway had deficits in attained lung function, according to the study.

The risk of living near freeways "leads to important questions for society about the structure of the transportation system, engines, fuels, combustion and road dust in urban areas," Thomas Sandstrom, M.D., Ph.D., from University Hospital in Umea, Sweden, and Bert Brunekreef, Ph.D., from the University of Utrecht in the Netherlands, write in an accompanying editorial.

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MRI More Accurate Than CT for Diagnosing Stroke

MRI has higher sensitivity for stroke detection in emergency setting

Magnetic resonance imaging, or MRI, detects acute stroke with higher sensitivity and accuracy than the more widely used computed tomography (CT), which fails to accurately diagnose three in four acute strokes and picks up only 7 percent of ischemic stroke in patients presenting within three hours of symptom onset, researchers report in the Jan. 27 issue of The Lancet.

Steven Warach, M.D., Ph.D., from the National Institutes of Health in Bethesda, Md., and colleagues compared CT and MRI for the emergency diagnosis of 356 patients who were referred for suspected stroke, of whom 90 presented within three hours. Overall, 217 were finally diagnosed with acute stroke.

MRI and CT detected acute intracranial hemorrhage at similar frequencies, but MRI was better at detecting acute ischemic and hemorrhagic stroke and chronic hemorrhage. In patients presenting within three hours, MRI diagnosed acute ischemic stroke with an accuracy of 46 percent compared with only 7 percent for CT. In patients finally diagnosed with stroke, the sensitivity of detecting any acute stroke was 83 percent for MRI and 26 percent for CT, while the accuracy was 89 percent for MRI and 54 percent for CT.

Computerized tomography has been the preferred technique to quickly assess stroke patients, but "this mantle should now be passed to magnetic resonance imaging," Geoffrey A. Donnan, M.D., and colleagues from the University of Melbourne in Australia, write in an accompanying editorial.

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Ambulatory Strategy May Help Some Sleep Apnea Patients

Study of high-risk patients suggests the strategy can substitute for polysomnography

In patients who have a high probability of obstructive sleep apnea, an ambulatory strategy may be as effective as polysomnography at establishing a diagnosis and determining the effect of continuous positive airway pressure, or CPAP, according to the results of a study published in the Feb. 6 issue of the Annals of Internal Medicine.

Alan T. Mulgrew, M.B., of the University of British Columbia in Vancouver, Canada, and colleagues randomly assigned 68 patients to either polysomnography or ambulatory titration consisting of a combination of auto-CPAP and overnight oximetry.

After three months, the researchers found that the polysomnography and ambulatory groups had no significant differences in the median apnea-hypopnea index on CPAP (3.2 versus 2.5) or in their Epworth Sleepiness Scale scores and the Sleep Apnea Quality of Life Index. The ambulatory group, however, showed higher adherence to CPAP therapy.

"On the basis of our results, we suggest a clinical algorithm for use in patients who have a high probability of obstructive sleep apnea, with the caveat that patients who do not fulfill the criteria for high probability in the diagnostic algorithm, or who do not respond appropriately to CPAP, should undergo polysomnography," the authors state. "In the context of scarce resources, the ambulatory approach provides an opportunity to expedite care for patients most in need of urgent treatment while conserving polysomnography slots."

Respironics Inc. and ResMed Corp. provided grants for the study.

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More U.S. Patients Over Age 80 Are Starting Dialysis

But study finds that only about half of them are still alive a year after initiating treatment

Since 1996, increasing numbers of people in their 80s and 90s have initiated dialysis, but their odds of one-year survival are still only about 50 percent, according to a report published in the Feb. 6 issue of the Annals of Internal Medicine.

Manjula Kurella, M.D., M.P.H., of the University of California San Francisco, and colleagues analyzed 1996-2003 data from the U.S. Renal Data System.

The researchers found that 13,577 octogenarians and nonagenarians initiated dialysis in 2003 compared to 7,054 who did so in 1996. They also found that the one-year mortality rate was 46 percent and that one-year survival rates did not materially change between 1996 and 2003. Characteristics linked with death included older age, non-ambulatory status and more co-morbid conditions.

"Although dialysis may increase life expectancy for selected octogenarians and nonagenarians, overall survival times remain modest," the authors state. "When considering dialysis initiation among the elderly, decision making should be individualized and realistic estimates of survival should be considered along with expected quality of life and the patient's values."

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Treating Otitis Media a Trade-Off Between Cost, Relief

Cheapest option entails holding off on antibiotics for 72 hours

The range of treatment options for otitis media reflect a trade-off between cost and relief of symptoms, according to study findings published in the January/February issue of the Annals of Family Medicine.

Andrew S. Coco, M.D., of Lancaster General Hospital in Lancaster, Pa., conducted a cost-effectiveness analysis of treating children aged 6 months to 12 years for otitis media with one of four options: a seven- to 10-day course of amoxicillin, five days of amoxicillin, delayed prescription and watchful waiting.

The cheapest option was to delay prescription of antibiotics for the first 72 hours. The most effective option was an immediate seven- to 10-day course of antibiotics but this added a $56,000 incremental cost utility ratio per quality-adjusted life-year gained. The other two options were considered inferior.

Although immediate treatment with antibiotics was the most effective option, the author emphasizes the advantages of delayed prescription. "Delayed prescription, the least costly option, would not only save the health service industry considerable expense but would also promote demedicalization of a common, primarily self-limiting acute upper respiratory infection and lessen antibiotic resistance," he concludes.

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Use of Chronic Care Model Improves Diabetes Care

The model is effective and easy to incorporate in small primary practices

The Chronic Care Model, which aims to improve the way chronically ill patients are treated in primary practice, can be easily implemented and is very effective in improving outcomes in diabetic patients, according to a report published in the January/February issue of the Annals of Family Medicine.

Paul A. Nutting, M.D., of the Center for Research Strategies in Denver, and colleagues interviewed 90 clinicians, including 60 physicians, 17 nurse-practitioners and 13 physician's assistants, using a questionnaire to ascertain the extent to which they incorporated elements of the Chronic Care Model into their work. At the same time, reports on the care they received were gathered from 886 diabetic patients.

Clinicians who reported greater use of the Chronic Care Model had patients with lower hemoglobin A1c values and lower ratios of total cholesterol to high-density lipoprotein cholesterol.

"Clinicians in small independent primary care practices are able to incorporate elements of the Chronic Care Model into their practice style, often without major structural change in the practice, and this incorporation is associated with higher levels of recommended processes and better intermediate outcomes of diabetes care," the authors conclude.

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Validating Patients' Depression Cuts Drug Prescribing

A physician's behavior toward depressed patients affects the extent of antidepressant use

Physicians who discuss and validate a depressed patient's concerns are more likely to prescribe antidepressants based on symptoms rather than a patient's request for medication, according to study findings published in the January/February issue of the Annals of Family Medicine.

Ronald M. Epstein, M.D., of the University of Rochester Medical Center in Rochester, N.Y., and colleagues conducted a study among 152 primary care physicians by covertly recording conversations with patients who requested antidepressants in general, asked for a specific brand or did not request a prescription. The patients had symptoms of major depression or adjustment disorder.

When patients did not request antidepressants and physicians validated concerns, there was a higher prescribing rate for a diagnosis of major depression (35.7 versus 5.8 percent) than adjustment disorder. When discussion was limited, the patient's request affected prescribing (adjusted odds ratio for request versus no request, 43.54). In encounters characterized by discussion and validation, patient request and clinical indicators played an equal role in prescribing (adjusted odds ratio, 4.01 and 4.70, respectively).

"Although patients historically have been passive in discussions about medications, the Internet, direct-to-consumer advertising and increased patient health literacy will likely further increase patient requests," the authors conclude. "In theory, improved patient knowledge coupled with interventions that activate patients and train physicians to respond with exploration and validation might improve quality of care and outcomes for depression and other illnesses."

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Index Predicts Hip Fracture, Mortality in Older Women

Women with all four factors have a 9.5-fold greater risk of mortality

A four-item index based on age, weight, previous fracture and mobility can predict the risk of hip fracture and mortality in women aged 70 and older, according to a report in the January/February issue of the Annals of Family Medicine.

Daniel M. Albertsson, M.D., of the Kronoberg County Council in Vaxjo, Sweden, and colleagues surveyed 1,248 women, aged 70 years or older, regarding risk factors for hip fracture. The data were used to develop a four-item risk model termed the FRAMO Index, based on an age of at least 80 years, weight greater than 60 kg, having had a previous fragility fracture, and needing to use arms to rise from the sitting position. The predictive value of the index was assessed over the next two years.

The researchers found that the risk of hip fracture and mortality increased with the number of risk factors. Women with one or no risk factors had a 0.8 percent risk of hip fracture and a 3.2 percent risk of mortality, while women with two to four risk factors had risks of 5.4 percent for hip fracture and 23.7 percent mortality risk (odds ratios of 7.5 and 9.5, respectively).

"The FRAMO Index identified the majority of women who experienced hip fractures during a two-year follow-up, who might have been candidates for intensified preventive measures," Albertsson and colleagues conclude. "The FRAMO Index, based on four binary risk factors, would be practical for routine use in primary care."

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New Guidelines for Deep Vein and Pulmonary Thrombosis

American Academy of Family Physicians, American College of Physicians reviewed evidence

The American Academy of Family Physicians and the American College of Physicians have issued new guidelines for the diagnosis and treatment of lower extremity deep venous thrombosis (DVT) and pulmonary embolism, based on evidence-based reviews. The guidelines are published in the January/February issue of the Annals of Family Medicine.

The evidence was reviewed by a team led by Jodi Segal, M.D., of Johns Hopkins University. Amir Qaseem, M.D., Ph.D., of the American College of Physicians, and colleagues developed recommendations for the diagnosis of DVT and pulmonary embolism. They recommend using good clinical prediction tools such as the Wells prediction rule to determine the probability of disease, high-sensitivity D-dimer testing as a negative predictor in patients with a low probability of disease, and ultrasound and imaging studies for patients with intermediate to high disease probability.

The recommendations for management were developed by Vincenza Snow, M.D., of the American College of Physicians in Philadelphia, and colleagues. They recommend that low molecular weight heparin be initially used to treat DVT, while both low molecular weight and unfractionated heparin can be used to treat pulmonary embolism. Some patients with DVT and possibly pulmonary embolism can be safely and cost-effectively treated with low molecular weight heparin on an outpatient basis, they note.

"The importance of early diagnosis to prevent mortality and morbidity associated with venous thromboembolism cannot be overstressed," write Qaseem and colleagues. "This field is highly dynamic, however, and new evidence is emerging periodically that may change the recommendations."

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TV Drug Advertising Relies on Emotion, Not Facts

Most do not provide information on the medical condition, risk factors, or alternatives to medication

Direct-to-consumer television advertising of prescription medications, currently only allowed in the United States and New Zealand, is largely based on emotional appeals, not facts, and often does not provide information about a medical condition, risk factors, or lifestyle changes that could be an alternative, researchers report in the January/February issue of the Annals of Family Medicine.

Dominick L. Frosch, Ph.D., from the University of California Los Angeles, and colleagues analyzed 38 unique television ads representing seven of the 10 best-selling prescription drugs in 2004. The ads were shown during prime-time in the United States.

The researchers found that although most (82 percent) of the ads made some factual claims about the target condition, about three-quarters failed to provide information on the medical condition, risk factors or prevalence. None of the ads suggested making lifestyle changes instead of taking medication, although some ads suggested that lifestyle changes could be an adjunct to medication. The majority of the ads (95 percent) relied on emotional appeals such as regaining control over some aspect of life or obtaining social approval.

Noting that drug companies have announced new advertising guidelines that are "a step in the right direction, physicians, consumers and policymakers must take further action so that the facts about medicines are not lost in the advertising fog," David Kessler, M.D., and Douglas Levy, J.D., from the University of California San Francisco, write in an accompanying editorial. "As [the study authors] correctly point out, the consequences of poor judgments are quite different for drugs than they are for soap."

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U.K. Report Suggests Hair Dye Allergies on the Rise

Allergies to para-phenylenediamine increasing as more people color their hair

Hair dye allergies are on the rise largely due to growing numbers of young people who are using products containing para-phenylenediamine (PPD) and related agents, researchers report in an editorial in the Feb. 3 issue of BMJ. PPD allergies are typically marked by contact dermatitis and, in extreme cases, facial swelling.

John P. McFadden, B.M., F.R.C.P., of St. John's Institute of Dermatology in London, U.K., and colleagues report that dermatologists are noticing an increase in the frequency of positive reactions to PPD on patch tests. Surveys across the globe mirror these anecdotal reports. Specifically, a retrospective survey in London showed that the frequency of positive PPD patch tests doubled over six years. In addition, market research finds that more people are dying their hair and doing so at a younger age. Severe hair dye reactions have also been seen in children, the authors note.

Currently, PPD is allowed to comprise 6 percent of hair dye ingredients in the European Union, but no widely accepted alternatives to PPD or related chemicals exist. "Wider debate on the safety and composition of hair dye is overdue among medical and scientific communities, the public, and legislators," the researchers conclude.

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Prior Discussion of Test Results Reassures Patients

Chest pain patients who knew what a normal result was were less likely to have symptoms in future

Informing patients about the meaning of test results prior to testing increases rates of reassurance and reduces reports of recurrence of symptoms, according to a report published online Jan. 26 in BMJ.

Keith J. Petrie, Ph.D., of the University of Auckland in New Zealand, and colleagues conducted a study of 92 patients with chest pain, randomized to three groups prior to taking a diagnostic exercise stress test. While 28 patients received only standard information about the test, 30 patients received a pamphlet that explained the meaning of normal results, and 34 received the leaflet and also had a brief discussion about the test results.

The test patients completed a questionnaire to measure their level of reassurance and were surveyed a month after the test to ascertain the extent of continuing symptoms and the proportion of subjects still taking cardiac medication.

Fewer patients in the discussion group were still taking medication at one month, and the level of reassurance in this group was higher than in the other two groups. Those in the pamphlet group also reported higher levels of reassurance than the control group. Those in the discussion group reported less recurrence of symptoms after the test, as well.

"Improvements in reassurance are also likely to impact on unnecessary future investigations and patients' anxieties about their symptoms," the authors conclude.

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Caffeine Intake in Second Half of Pregnancy Appears Safe

Cutting down on caffeinated drinks does not appear to affect birth weight or length of pregnancy

Moderate intake of caffeine during the second half of pregnancy has no impact on the length of gestation or on birth weight, according to the results of a study published online Jan. 26 in BMJ.

Bodil Hammer Bech, M.D., of the University of Aarhus in Aarhus, Denmark, and colleagues conducted a randomized, double-blind, controlled trial of 1,207 pregnant women, who when recruited at less than 20 weeks' gestation drank three or more cups of coffee a day. They were then divided into two groups: 568 women who continued to drink caffeinated coffee and 629 who drank a decaffeinated version instead.

Data was available on birth weight of 1,150 liveborn singletons and the length of gestation for 1,153 liveborn singletons, and there was no significant difference in the outcome of the two caffeine-intake groups.

"Caffeine intake is associated with smoking and alcohol intake, which may influence birth weight. It is possible that a modification of caffeine intake could also influence other lifestyle factors. However, we found no difference between the groups in smoking or alcohol consumption," the authors write. They also note that the study left unanswered questions, such as the effect of caffeine intake earlier in the pregnancy and the effect of other substances in coffee. "Our results emphasize that care should be taken when extrapolating results to smokers," they add.

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Folic Acid Cuts Risk of Facial Clefts

Supplementation during early pregnancy cuts incidence by about one-third

Supplementation during early pregnancy with folic acid reduces the risk of cleft lip by about one-third, according to research published online Jan. 26 in BMJ.

Allen J. Wilcox, M.D., Ph.D., of the National Institute of Environmental Health Sciences at the National Institutes of Health in Durham, N.C., and colleagues conducted a study of 377 babies with cleft lip (with or without cleft palate), 196 with cleft palate and 763 healthy controls born in Norway from 1996 through 2001.

Women who were prescribed at least 400 μg a day of folic acid were less likely to give birth to a baby with cleft lip even when other confounding factors such as multivitamins and smoking were adjusted for. The babies of women who had diets rich in folate, and took both multivitamins and folic acid supplements, were at the lowest risk for cleft lip. However, folic acid intake had no effect on isolated cleft palate.

"If folic acid is able to prevent a major birth defect in addition to neural tube defects, this benefit should be included among the risks and benefits of fortifying foods with folic acid, a matter of ongoing controversy in many countries," the authors conclude.

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Drug Improves Outcomes in Patients Undergoing CABG

Nesiritide improves renal function and reduces hospital stay length and mortality

Nesiritide, which is identical to B-type natriuretic peptide secreted by the ventricles, improves renal function and reduces length of hospital stay and mortality in patients undergoing coronary artery bypass grafting (CABG), according to study findings published in the Feb. 13 issue of the Journal of the American College of Cardiology.

Robert M. Mentzer Jr., M.D., from Wayne State University School of Medicine in Detroit, and colleagues randomized 279 patients with an ejection fraction of 40 percent or less who were undergoing CABG using cardiopulmonary bypass to usual care plus either placebo or nesiritide. The drugs were given for 24-96 hours after inducing anesthesia.

The researchers found that nesiritide significantly improved postoperative renal function, with a lower peak increase in serum creatinine, a smaller drop in the glomerular filtration rate and a higher urine output. The drug also significantly reduced hospital stay length and six-month mortality.

The study "provides encouraging results in one subgroup of patients who might benefit from the use of nesiritide, but more comprehensive data are required before promoting routine use in this population," Israel Belenkie, M.D., from the University of Calgary in Alberta, Canada, writes in an accompanying editorial.

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Aging, Smoking Predict Aortic Stiffness

Activity of Rho-associated kinase predicted by aging, long-term smoking

Aging and long-term smoking predict the activity of Rho-associated kinase (ROCK), which is thought to play a role in atherosclerosis, and which along with age predicts aortic stiffness, researchers report in the Feb. 13 issue of the Journal of the American College of Cardiology.

Yukihito Higashi, M.D., Ph.D., from Hiroshima University in Japan, and colleagues measured the forearm blood flow response in 51 healthy men after intra-arterial infusion of sodium nitroprusside, acetylcholine, and fasudil (a ROCK inhibitor) alone or co-infused with NG-monomethyl-L-arginine (L-NMMA). Aortic stiffness was assessed by measuring the carotid-femoral pulse wave velocity (cf-PWV).

The researchers found that all three compounds alone or with L-NMMA significantly increased the forearm blood flow response in a dose-dependent fashion. Before or after co-infusion with L-NMMA, age and number of pack-years smoked were significant independent predictors of ROCK activity, and age and ROCK activity were significant independent predictors of cf-PWV. They also found a significant correlation between a marker of oxidative stress, serum malondialdehyde-modified low-density lipoprotein, and ROCK activity and cf-PWV.

"These findings suggest that aging and accumulating smoking habit, which might induce excessive oxidative stress, are involved in ROCK activity in the vasculature, leading to an increase in aortic stiffness in humans," Higashi and colleagues conclude.

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Diastolic Dysfunction Common in Many Heart Failure Cases

Patients with moderate or severe dysfunction at higher risk of poor outcomes

About two-thirds of patients with heart failure and preserved systolic function have diastolic dysfunction, and patients with moderate or severe dysfunction are at higher risk of poor outcomes, according to a study published in the Feb. 13 issue of the Journal of the American College of Cardiology.

Hans Persson, M.D., Ph.D., from the Karolinska Institute in Stockholm, Sweden, and colleagues examined the prevalence of diastolic dysfunction by Doppler echocardiography in 293 elderly patients with symptoms of heart failure and preserved systolic function (ejection fraction greater than 40 percent).

The researchers found that 67 percent of patients had diastolic dysfunction. Forty-four percent of patients had moderate or severe dysfunction, which were independent predictors of a poorer prognosis (hazard ratio 3.7 and 5.7, respectively).

"The findings from this study indicate that the current noninvasive assessment of diastolic filling is useful for risk stratification and necessary for entry diagnosis into any therapeutic trial of patients with heart failure with normal ejection fraction," Rick A. Nishimura, M.D., and Wissam Jaber, M.D., from the Mayo Clinic College of Medicine in Rochester, Minn., write in an accompanying editorial.

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C-Reactive Protein Indicator of Cardiac Function in Men

CRP is associated with decreased left ventricular function in asymptomatic men, but not women

Elevated levels of C-reactive protein are associated with decreased systolic function in men, but not women, according to a report published Jan. 19 in the Journal of the American College of Cardiology.

Joao Lima, M.D., of Johns Hopkins Medical Institutions in Baltimore, and colleagues studied the relationship between C-reactive protein and regional left ventricular function using tagged magnetic resonance imaging in 1,164 subjects without symptomatic cardiovascular disease enrolled in the Multi-Ethnic Study of Atherosclerosis.

There was a correlation between elevated C-reactive protein and decreased left ventricular function in men, as measured by peak systolic circumferential shortening strain, even after accounting for confounding variables like age, ethnicity, and traditional risk factors such as smoking status, hypertension and waist circumference. This correlation held both globally and regionally (i.e., in the left anterior descending artery, left circumflex artery and right coronary artery), but weakened when left ventricular mass was also considered. No such relationships were observed among women.

"Further studies are warranted to elucidate the interrelationship between inflammation, left ventricular mass, and gender in the development of left ventricular dysfunction and heart failure," the authors write.

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Cold Liquid Ventilation May Protect Infarcting Heart

Study in rabbits suggests total liquid ventilation may reduce damage during cardiac ischemia

Cooling the heart by total liquid ventilation with perfluorocarbon may rapidly protect heart muscle against damage during ischemia, according to a study in rabbits published in the Feb. 6 issue of the Journal of the American College of Cardiology.

Since decreased temperature is a powerful cardioprotective strategy during myocardial ischemia, James Downey, Ph.D., and colleagues from the University of South Alabama College of Medicine in Mobile, tested whether total liquid ventilation with cold perfluorocarbon can be used to rapidly cool and protect the infarcting heart in a rabbit model of acute myocardial infarction. Perfluorocarbon has excellent gas carrying capacity.

During 30 minutes of coronary artery occlusion, rabbits ventilated with cool liquid showed an average infarct involving only 4 percent of the heart compared with about 40 percent with warm liquid or gas. The heart temperature could be lowered to 32 degrees Celsius within five minutes of cold liquid perfusion.

"Liquid ventilation with perfluorocarbons has been safely used in humans in clinical trials," according to an accompanying editorial by Wilbur Lew, M.D., from the University of California San Diego. "This method may provide an opportunity to translate the benefits of cardiac hypothermia, which have been well documented in preclinical studies, to the clinical setting to limit infarct size in patients with myocardial ischemia."

Some of the authors are co-inventors on a patent application for cooling the heart by total liquid ventilation that has been submitted by Molecular Therapeutics.

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Statins May Slow Aortic Stenosis in Hypercholesterolemia

Change in both aortic valve area and velocity slowed by rosuvastatin

Rosuvastatin therapy slows the hemodynamic progression of aortic stenosis in patients with hypercholesterolemia, according to a report in the Feb. 6 issue of the Journal of the American College of Cardiology. The study is the first to show a positive effect of statin therapy on this disease process.

Nalini M. Rajamannan, M.D., of Northwestern University Feinberg School of Medicine in Chicago, and colleagues conducted an open-label, prospective study of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, on the progression of moderate to severe aortic stenosis in 121 consecutive patients. Only patients with elevated low-density lipoprotein received rosuvastatin.

During a mean follow-up of 73 weeks, patients with hypercholesterolemia who received rosuvastatin had a slower decrease in aortic valve area and a slower increase in aortic velocity than patients with normal lipid levels who were untreated. The statin group also saw an improvement in serum lipid levels.

"This is the first study to provide positive clinical evidence for the potential of targeted therapy in patients with asymptomatic aortic stenosis," the authors write. "Randomized trials will provide further evidence to define the treatment of this complex disease process, in which timing of therapy and characteristics of the valve lesion will need to be taken into account in the future treatment approaches."

Rajamannan holds a patent for use of statins in aortic stenosis but does not receive royalties for the patent.

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Drug-Eluting Stents May Be Best for Bare-Stent Restenosis

Further restenosis risk cut by 65 percent with sirolimus- or paclitaxel-coated stents

Drug-eluting stents are superior to balloon angioplasty and vascular brachytherapy for treating patients with bare-metal in-stent restenosis, according to a meta-analysis published in the Feb. 6 issue of the Journal of the American College of Cardiology.

Adnan Kastrati, M.D., of Deutsches Herzzentrum in Munich, Germany, and colleagues identified four randomized studies comparing sirolimus- or paclitaxel-eluting stents to standard treatment, consisting of balloon angioplasty or vascular brachytherapy, in 1,230 patients with bare-metal in-stent restenosis.

Altogether, the risks for target lesion revascularization and angiographic restenosis were both found to be about 65 percent lower in patients receiving drug-eluting stents compared with either standard treatment. No difference was noted for composite risk of death or myocardial infarction.

"Patients who develop in-stent restenosis after implantation of bare-metal stents carry a high risk for recurrence," the authors write. They recommend that drug-eluting stents "should be considered as first-line treatment for patients with bare-metal in-stent restenosis."

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Prepared jointly by the editors of Medical Economics and HealthDay's Physicians' Briefing (www.physicianbriefing.com