Latest Research

May 18, 2007

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

Relatives of Blacks with Early Lung Cancer Also at Risk

Risk over twofold for black case relatives compared to whites and 13-fold higher than black control families

First-degree relatives of black Americans diagnosed with early-onset lung cancer are more likely to develop head and neck, lung and other tobacco-related cancers themselves compared with relatives of white Americans with lung cancer, according to a report in the May issue of Chest.

Michele L. Cote, Ph.D., of Wayne State University School of Medicine in Detroit, and colleagues measured the incidence of head and neck cancer and other tobacco-related cancers in 3,556 case relatives, which included mothers, fathers and siblings, of 673 patients diagnosed with lung cancer before age 50, and compared the rates to age-, race-, and sex-matched control subjects.

The investigators found that case relatives of black Americans were 2.44-fold more likely to have head and neck cancers and 1.86-fold more likely to have any tobacco-related cancers than white case relatives. When compared to black control relatives, the risk for head and neck cancers increased to 13.42-fold and all tobacco-related cancers to 3.77-fold.

"These results can be used to counsel family members of patients with early-onset lung cancer, and suggest target populations for preventive strategies, including smoking cessation and appropriate screening," the authors conclude.

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Statin Use May Cut Lung Cancer Risk by 55 Percent

Study of veterans shows protective effect even among smokers

Statins may cut the risk of lung cancer by as much as 55 percent, according to the results of a study of U.S. veterans published in the May issue of Chest.

Vikas Khurana, M.D., of the Overton Brooks VA Medical Center in Shreveport, La., and colleagues conducted a retrospective, case-control study of 483,733 patients from eight states to determine if statin use affected the diagnosis of lung cancer.

Of the initial cohort, 163,662 patients (33.8 percent) were receiving statin therapy and 7,280 (1.5 percent) had lung cancer. Taking a statin for more than six months was associated with a 55 percent reduction in the odds of developing lung cancer across all age groups, races and body mass indexes. The protective effect even held in smokers. Exactly how statins may affect cancer risk is not known, but several studies have pointed toward beneficial effects.

Many questions remain but "these results are encouraging and strengthen the hypothesis that statins may be useful for lung cancer chemoprevention," Jhanelle Gray, M.D., of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and colleagues write in an accompanying editorial.

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Higher Rates of 'Sarcoid-Like' Lung Disease Post 9/11

NYC firefighters exposed to World Trade Center dust at risk

Rates of "sarcoid-like" granulomatous pulmonary disease spiked among New York City Fire Department rescue workers after Sept. 11, 2001, according to a new study in the May issue of Chest.

David Prezant, M.D., of the New York City Fire Department, Office of Medical Affairs in Brooklyn, and colleagues report on 26 FDNY rescue worker patients presenting with World Trade Center-"sarcoid-like" granulomatous pulmonary disease (WTC-SLGPD) in the five years after Sept. 11, 2001.

Incidence rates were 86/100,000 exposed workers in the first year after exposure and averaged 22/100,000 exposed workers in the ensuing four years. By contrast, the incidence rate was 15/100,000 workers during the 15 years before the WTC disaster. Eighteen of the 26 patients had asthma and eight of 21 patients who underwent challenge testing had airway hyperreactivity, which was not seen in dust-exposed workers with sarcoidosis prior to Sept. 11, 2001.

"This new information about the early onset of WTC-SLGPD and its association with asthma/airway hyperreactivity has important public health consequences for disease prevention, early detection and treatment following environmental/occupational exposures," the authors conclude.

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Guidelines Support Pulmonary Rehab for Lung Disease

Pulmonary rehabilitation aids chronic lung disease patients

Pulmonary rehabilitation benefits patients with chronic obstructive pulmonary disease and other lung diseases, according to new guidelines issued by the American College of Chest Physicians and the American Association of Cardiovascular and Pulmonary Rehabilitation that appear in the May issue of the journal Chest.

Andrew L. Ries, M.D., of the University of California San Diego, and colleagues conducted a systematic, evidence-based literature review on the benefits of pulmonary rehabilitation for patients with chronic lung diseases.

The resulting new guidelines state that lower and upper extremity exercise training leads to improvements in dyspnea and health-related quality outcomes in chronic lung disease patients. Pulmonary rehabilitation reduces health care utilization costs and number of days spent in the hospital. While there is not enough data to determine how pulmonary rehabilitation affects survival, it is cost-effective.

The current body of evidence does not support inspiratory muscle training, anabolic drugs or nutritional supplements in pulmonary rehabilitation. There is evidence backing the use of supplemental oxygen therapy for patients with severe hypoxemia at rest or with exercise, the guidelines state.

"There is substantial new evidence that pulmonary rehabilitation is beneficial for patients with chronic obstructive pulmonary disease and other chronic lung diseases," the guideline authors state.

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Lower Aspirin Doses Curb Heart Disease

A 30-mg daily dose curbs heart disease, but most U.S. aspirin prescriptions exceed 81 mg

Although higher aspirin doses are commonly prescribed, 30 milligrams a day work to prevent cardiovascular disease, researchers report in the May 9 issue of the Journal of the American Medical Association.

Charles Campbell, M.D., of the University of Kentucky in Lexington, and colleagues reviewed English-language studies involving aspirin dosage through February 2007.

The researchers found that while 1,300-mg/day aspirin doses are approved for use, 30-mg daily doses can completely prevent the formation of platelet thromboxane. Sixty percent of U.S. aspirin prescriptions are for 81-mg/day; 35 percent are for 325 mg/day.

Studies also show that doses exceeding 75 to 81 daily milligrams do not work better than lower doses. Moreover, higher doses involve more bleeding, mainly due to toxicity to the gastrointestinal tract.

"Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/day in the setting of cardiovascular disease prevention," the authors write. "Higher dosages, which may be commonly prescribed, do not better prevent events, but are associated with increased risks of gastrointestinal bleeding."

Several of the study authors have taken speaking, consulting or research fees from drug companies.

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Angioplasty Cuts Cardiac Risk in Silent Ischemia Patients

Percutaneous coronary intervention more effective over long term than drug therapy

Patients with silent ischemia have a lower risk of major cardiac events after myocardial infarction if they undergo percutaneous coronary intervention rather than have intensive drug therapy, according to the results of a study published in the May 9 issue of the Journal of the American Medical Association.

Paul Erne, M.D., of Kantonsspital Luzern in Switzerland, and colleagues conducted a randomized, controlled trial of 201 patients at three public hospitals in Switzerland. All had recently had a myocardial infarction and underwent stress imaging to verify silent ischemia and one- or two-vessel coronary artery disease. The patients either received intensive anti-ischemic drug therapy or angioplasty.

The study cohort was followed up for a mean of 10.2 years, during which time there were 27 major adverse cardiac events in the angioplasty group and 67 in the anti-ischemic drug group. At final follow-up, 28.9 percent of the drug therapy group had ischemia, versus 11.6 percent of the percutaneous coronary intervention group.

"This is the first, to our knowledge, long-term outcome study of an invasive therapy compared with an intensive anti-ischemic drug therapy in asymptomatic patients with silent ischemia after a recent myocardial infarction," the authors write. "Our findings argue for an ischemic-targeted approach to percutaneous coronary intervention among asymptomatic survivors of myocardial infarction."

The study was supported by grants from Hoechst Pharma, Merck Pharma, and Pfizer.

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Hepatitis C Raises Non-Hodgkin Lymphoma Risk

Risk of Waldenstrom macroglobulinemia is tripled

Infection with hepatitis C raises the risk of developing non-Hodgkin lymphoma by 20 to 30 percent, and also triples the risk of Waldenstrom macroglobulinemia, researchers report in the May 9 issue of the Journal of the American Medical Association.

Thomas P. Giordano, M.D., of Baylor College of Medicine in Houston, and colleagues conducted a study of 146,394 hepatitis C patients who had made at least two visits to U.S. Veterans Affairs health centers with a positive diagnosis for hepatitis C, and 572,293 controls without hepatitis C.

Among the study cohort, there were 1,359 cases of non-Hodgkin lymphoma, 165 cases of Waldenstrom macroglobulinemia and 551 cases of cryoglobulinemia, all of which were more likely among those with hepatitis C. There was no increase in the risk of other hematological malignancies or thyroid cancer.

"Although the clinical significance of these findings is unknown, it is possible that screening of individuals infected with hepatitis C could identify early-stage lymphoproliferative conditions suitable for early intervention strategies, including chemoprevention trials on premalignant disease. Future epidemiological and pathophysiological studies are needed to further explore the relationship between hepatitis C virus and non-Hodgkin lymphoma," the authors conclude.

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Off-Label Use of Drug-Eluting Stents Widespread

Compared with on-label use, adverse events are more frequent

Off-label use of drug-eluting stents is widespread and results in more adverse outcomes than on-label use, according to the results of two studies published in the May 9 issue of the Journal of the American Medical Association.

Nirat Beohar, M.D., of Northwestern University Feinberg School of Medicine in Chicago, and colleagues analyzed data on 5,541 patients who received drug-eluting stents, including 2,588 (47 percent) who received them for untested or off-label reasons. Although in-hospital mortality was similar for patients with on-label and off-label indications, 30-day and one-year outcomes were significantly worse in the latter group.

When Htut K. Win, M.D., of Baylor College of Medicine in Houston, and colleagues analyzed data on 3,323 patients, of whom 1,817 received stents for off-label indications, one-year adverse events were greater in the off-label group than in the on-label group. In particular, off-label patients accounted for most of the subsequent cases of stent thrombosis.

An accompanying editorial advises physicians to treat limited approval data with caution. "Clinicians must take advantage of all the information sources available (randomized controlled trials, observational studies and clinical vigilance) in making clinical decisions. Moreover, it is essential to harness the power of this disparate information by working toward common data standards," the editorialists write.

The study was supported by Cordis Corp.

AbstractFull Text (subscription or payment may be required)AbstractFull Text (subscription or payment may be required)Editorial

Newer Heart Failure Drug No Better Than Other in Study

Comparison of levosimendan and dobutamine shows no difference in mortality rates

In patients with decompensated heart failure, treatment with levosimendan has no benefit in terms of increased survival compared with dobutamine treatment, according to the results of a study published in the May 2 issue of the Journal of the American Medical Association.

Alexandre Mebazaa, M.D., Ph.D., of the Universite Paris Diderot and Hospital Lariboisiere in Paris, France, and colleagues randomly assigned 1,327 patients to receive either intravenous levosimendan or intravenous dobutamine.

Although the researchers observed an initial reduction in plasma B-type natriuretic peptide level in the levosimendan group, they found no significant group differences in 180-day all-cause mortality: 173 (26 percent) deaths occurred in the levosimendan group and 185 (28 percent) deaths in the dobutamine group. They also found that there were no significant group differences in all-cause mortality at 31 days, number of days alive and out of the hospital, patient global assessment, patient assessment of dyspnea at 24 hours, and cardiovascular death at 180 days.

"These findings may be related to the short duration of treatment in the trial, a selective effect of levosimendan in specific subgroups, or the lack of a true difference between the two drugs," the authors conclude. "Further studies are needed to distinguish between these possibilities."

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MicroRNA Expression May Identify Pancreatic Cancer

Expression patterns distinguish cancer from chronic pancreatitis and may help predict survival

Distinct microRNA expression patterns in tissue samples may help distinguish pancreatic cancer from chronic pancreatitis and predict which cancer patients are likely to be long- or short-term survivors, researchers report in the May 2 issue of the Journal of the American Medical Association.

Mark Bloomston, M.D., of Ohio State University in Columbus, and colleagues harvested and analyzed RNA from resected pancreatic cancers and benign adjacent pancreatic tissue in 65 patients and from chronic pancreatitis specimens in 42 patients.

The researchers found that the overexpression of 15 microRNAs and eight underexpressed microRNAs differentiated pancreatic cancer from chronic pancreatitis with 93 percent accuracy. They also found that a subgroup of six microRNAs in cancer patients with node-positive disease differentiated long-term (more than 24 months) and short-term (less than 24 months) survivors. The authors also report that high expression of miR-196a-2 was associated with poor median survival (14.3 months versus 26.5 months).

"This is just the beginning in the continuum connecting discovery to clinical application," state the authors of an accompanying editorial. "To advance these seminal observations into patient management requires proceeding through development and regulatory approval and establishing the evidence basis for clinical practice."

AbstractFull Text (subscription or payment may be required)Editorial

Less Mortality Due to Acute Coronary Syndrome

Improved management credited for lower rates of death and new cardiovascular events

Better management of patients with acute coronary syndrome has led to significant reductions in the rates of new heart failure and death, as well as in rates of stroke and myocardial infarction at six months, according to a report in the May 2 issue of the Journal of the American Medical Association.

Keith A.A. Fox, M.B., Ch.B., F.R.C.P., of the University of Edinburgh in Scotland, and colleagues studied of 44,372 patients who were enrolled in the Global Registry of Acute Coronary Events (GRACE) study and followed-up between July 1999 and December 2006.

Over the study period, the researchers found that the use of pharmacological medications and primary percutaneous coronary intervention increased in ST-segment elevation myocardial infarction (STEMI) and non-STEMI patients. In both groups, the rates of heart failure and pulmonary edema declined. In STEMI patients, decreases were seen in hospital deaths (18 percent), cardiogenic shock (24 percent) and six-month stroke and myocardial infarction rates (0.8 percent and 2.8 percent, respectively). In non-STEMI patients, decreases were seen in hospital deaths, and six-month death and stroke rates.

"This study population is the first demonstration of significant reductions observed in hospital rates of new heart failure in acute coronary syndrome patients, over time, and of reductions in mortality," the authors conclude.

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Euthanasia Rates Fell in Netherlands After Legalization

May be due to increased use of palliative sedation

The rates of euthanasia and physician-assisted suicide have fallen in the Netherlands since euthanasia was legalized in 2002, possibly due to wider use of interventions such as palliative sedation, according to study findings published in the May 10 issue of the New England Journal of Medicine.

Agnes van der Heide, M.D., Ph.D., from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues examined the rates of euthanasia and physician-assisted suicide in the Netherlands in 2005 by analyzing the results of questionnaires mailed to physicians. There were 5,342 completed responses. The rates were compared with data from 2001, before the Netherlands legalized euthanasia.

Euthanasia fell from 2.6 percent of all deaths in 2001 to 1.7 percent in 2005, while physician-assisted suicide also fell from 0.2 percent in 2001 to 0.1 percent in 2005. The researchers found that 0.4 percent of deaths occurred without an explicit request from the patient. The use of continuous deep sedation increased from 5.6 percent of deaths in 2001 to 7.1 percent in 2005. Neuromuscular relaxants or barbiturates were used in 73.9 percent of cases and opioids in 16.2 percent of cases.

"The Dutch Euthanasia Act was followed by a modest decrease in the rates of euthanasia and physician-assisted suicide," the authors write. "The decrease may have resulted from the increased application of other end-of-life care interventions, such as palliative sedation."

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Oral HPV Infection Increases Risk of Oropharyngeal Cancer

HPV-16 most strongly associated

Oral infection with human papillomavirus (HPV), particularly HPV-16, increases the risk of developing oropharyngeal cancer, researchers report in the May 10 issue of the New England Journal of Medicine.

Maura L. Gillison, M.D., Ph.D., from Johns Hopkins University in Baltimore, and colleagues examined the role of HPV infection in 100 patients (14 women and 86 men) with newly diagnosed oropharyngeal cancer and 200 control patients without cancer.

The researchers found a higher risk of oropharyngeal cancer in patients with 26 or more vaginal-sex partners in their lifetime (odds ratio 3.1) or six or more oral-sex partners in their lifetime (OR, 3.4). Oral HPV infection increased the risk of oropharyngeal cancer (OR, 14.6 for HPV-16; OR, 12.3 for any of 37 HPV types). HPV-16 DNA was found in 72 percent of tumor specimens and 64 percent of cancer patients were seropositive for HPV-16 proteins. Seropositivity for the HPV-16 L1 capsid protein increased the risk of oropharyngeal cancer regardless of alcohol and tobacco use.

"Oral HPV infection is strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use," Gillison and colleagues conclude.

AbstractFull Text (subscription or payment may be required)Editorial

HPV Vaccine Protects Against Anogenital, Cervical Lesions

Vaccine is 98 percent effective in women not previously exposed to HPV-16 and -18

The vaccine against four subtypes of human papillomavirus (HPV) is highly effective in preventing anogenital diseases and high-grade cervical lesions in teenage girls and young women, according to two studies published in the May 10 issue of the New England Journal of Medicine.

Suzanne M. Garland, M.D., from Royal Women's Hospital in Carlton, Victoria, Australia, and colleagues randomized 5,455 women, aged 16 to 24, to three doses of placebo or a quadrivalent vaccine against HPV-6, -11, -16 and -18. After an average follow-up of three years, the vaccine completely protected against genital warts and cancers of the cervix, vagina and vulva associated with the vaccine subtypes. In the intention-to-treat analysis, the vaccine reduced the rate of vulvar or vaginal perianal lesions by 34 percent and the rate of cervical lesions by 20 percent, regardless of causal HPV type.

Laura A. Koutsky, Ph.D., from the University of Washington in Seattle, and colleagues randomized 12,167 women, aged 15 to 26, to three doses of placebo or the same quadrivalent vaccine. After an average follow-up of three years, the vaccine efficacy was 98 percent against cervical cancer, intraepithelial neoplasia grade 2 or 3 and adenocarcinoma in situ related to HPV-16 or -18 in women who had not been previously exposed to the viruses. The vaccine efficacy was 17 percent for all high-grade cervical lesions in the intention-to-treat group (exposed and unexposed women).

"Investigators in these trials have hit their mark soundly: the vaccine showed significant efficacy against anogenital and cervical lesions related to vaccine type in women with no evidence of previous exposure to vaccine-specific types; the vaccine also appeared to be safe," according to an editorial.

Both studies were funded by Merck Research Laboratories.

Abstract - Koutsky Full Text (subscription or payment may be required)Abstract - GarlandFull Text (subscription or payment may be required)Editorial

Early Surgery for Undescended Testicle Reduces Cancer Risk

Risk reduced by half if surgery done before age 13

Early surgery for undescended testis reduces the risk of developing testicular cancer, with the risk reduced by about half if done before 13 years of age, according to study findings published in the May 3 issue of the New England Journal of Medicine.

Andreas Pettersson, M.D., from Karolinska University Hospital in Stockholm, Sweden, and colleagues examined the risk of testicular cancer based on age at treatment for undescended testis in 16,983 men who underwent orchiopexy for undescended testis in Sweden.

After a follow-up of 209,984 person-years, the researchers identified 56 cases of testicular cancer. Compared with the general Swedish population, men who underwent surgery before 13 years of age had a relative risk of testicular cancer of 2.23 versus a relative risk of 5.40 for men treated after 13 years of age.

"In summary, our results indicate that age at orchiopexy has an effect on the risk of testicular cancer in boys with an undescended testicle; the risk among those treated at 13 years of age or older was twice the risk among those who were treated at younger ages," Pettersson and colleagues conclude.

AbstractFull Text

Type 1 Diabetes Not Associated with Cognitive Decline

Average 18-year follow-up study shows no decline after conventional or intensive treatment

Type 1 diabetes is not associated with long-term cognitive decline, according to an 18-year follow-up study of patients enrolled in the Diabetes Control and Complications Trial. The findings are published in the May 3 issue of the New England Journal of Medicine.

Alan Jacobson, M.D., of Harvard Medical School in Boston, and colleagues in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study group conducted a battery of cognitive tests on 1,144 patients with type 1 diabetes at baseline and during a mean follow-up of 18 years.

Over the extended follow-up period, 40 percent of patients reported having at least one hypoglycemic coma or seizure. No changes in cognitive decline were noted in either of the treatment groups (intensive versus conventional treatment). Higher glycated hemoglobin was associated with declines in motor speed and psychomotor efficiency compared to lower glycated hemoglobin.

Hypoglycemic events that are controlled with intensive diabetes therapy do not appear to have long-term adverse effects on cognitive function, the authors write. "This conclusion lends further support to the use of intensive diabetes therapy to reduce the long-term risks of retinopathic, nephropathic, neuropathic and cardiovascular complications in type 1 diabetes."

Some of the authors report receiving lecture or consulting fees, or are advisory board members of Pfizer, Amylin, GlaxoSmithKline or Eli Lilly.

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Once-A-Year Infusion Cuts Fracture Risk in Osteoporosis

Annual infusion of zoledronic acid associated with 41 percent lower risk of hip fracture compared with placebo

In postmenopausal women with osteoporosis, a yearly dose of zoledronic acid considerably reduces fracture risk in the vertebrae and hip compared with placebo, according to study findings published in the May 3 issue of the New England Journal of Medicine.

Dennis M. Black, Ph.D., from the University of California San Francisco, and colleagues randomized 7,765 postmenopausal women with osteoporosis to a yearly intravenous infusion of either placebo or 5 mg of zoledronic acid over a three-year period.

The researchers found that zoledronic acid was associated with a 70 percent reduced risk of morphometric vertebral fracture and 41 percent lower risk of hip fracture. The drug also reduced the risk of non-vertebral fractures, clinical fractures and clinical vertebral fractures, and improved bone mineral density and bone metabolism markers. Adverse events were similar in the two groups, although there were significantly more cases of serious atrial fibrillation in the zoledronic acid group.

"Although a direct comparison with other treatments cannot be made in the absence of head-to-head studies of fracture outcome, the magnitude of effect appears to be at least similar to and possibly better than (in the case of vertebral fractures) that reported for other interventions," Juliet Compston, M.D., from the University of Cambridge School of Clinical Medicine in the United Kingdom, writes in an accompanying editorial.

The study was supported by Novartis Pharma, which markets the drug under the name Reclast.

AbstractFull TextEditorial

Medicare Spending Rises Despite Relative-Value Program

Study shows physician services up 50 percent since program started

Medicare spending continues to rise despite implementation of a resource-based relative-value scale in 1992, which was intended to redistribute Medicare payments to physicians based on relative costs rather than prevailing charges, researchers report in the May 3 issue of the New England Journal of Medicine.

Stephanie Maxwell, Ph.D., from the Urban Institute in Washington, D.C., and colleagues analyzed national Medicare data on physicians' services and American Medical Association files on relative-value units (RVU). The RVU is based on the amount of physicians' work, practice expenses and liability costs for a given service.

The investigators found that both the amount of physicians' work and total RVUs per Medicare beneficiary grew by around 50 percent from 1992 to 2002, largely attributed to change in quantity and mix of services. New service codes drove the growth of major procedures, and the quantity and mix of existing services drove imaging RVUs. Total RVU for cardiology and dermatology grew by over 100 percent.

Despite increased fee schedules for evaluation and management services, and decreased fee schedules for imaging and other major procedures, the share of Medicare spending for primary care has remained the same because of quantity changes, according to an accompanying editorial by Joseph Newhouse, Ph.D., of Harvard Medical School in Boston. "With no easy fix in sight, Medicare spending on physicians will probably remain a thorny issue."

AbstractFull TextEditorial

Streptokinase Improves Microvascular Function

However, does not improve long-term left ventricular size or function

Locally administered streptokinase given immediately after percutaneous coronary intervention (PCI) improves microvascular function but not left ventricular size or function, according to the results of a study published in the May 3 issue of the New England Journal of Medicine.

Murat Sezer, M.D., and colleagues from Istanbul University in Turkey randomized 41 patients undergoing primary PCI to intracoronary streptokinase (250 kU) or no further treatment. Both groups received a standard drug regimen including aspirin and clopidogrel. Cardiac catheterization was repeated two days after PCI and microvascular function was assessed.

The researchers found that microvascular function improved in the streptokinase group, including coronary flow reserve, index of microvascular resistance, collateral-flow index, mean coronary wedge pressure, systolic coronary wedge pressure, and diastolic deceleration time. However, after six months, both groups had similar left ventricular size and function.

"In conclusion, in our pilot evaluation, primary PCI followed by the administration of low-dose intracoronary streptokinase immediately after the procedure was associated with improved microvascular perfusion, but not with long-term improvement in ventricular size or function, as compared with primary PCI alone," Sezer and colleagues conclude.

AbstractFull TextEditorial

Less Sun Exposure Is Key to Skin Cancer Prevention

Complete avoidance or wearing protective clothing seen as preferable to sunscreen use

Avoiding direct sunlight and wearing clothes that prevent harmful ultraviolet rays from reaching the skin are more effective strategies than sunscreen application to reduce the risk of photoaging and skin cancer, according to a review article published online May 3 in The Lancet.

Stephan Lautenschlager, M.D., of Triemli Hospital in Zurich, Switzerland, and colleagues conducted a Medline search for 1990-2006 articles published in English, French and German with the keywords "sunscreen," "photoprotection" and "sun protection" and identified 200 most-cited articles.

The researchers found that the most effective prevention strategies were completely avoiding sun exposure and seeking shade when sunlight is most intense, followed by wearing hats and protective clothing, and using topical sunscreens.

Nevertheless, "sunscreens will be used by many as the predominant mode of sun protection for various societal reasons (e.g., healthiness of a tan, relaxation in the sun)," the authors write. "Sunscreens should not be abused in an attempt to increase time in the sun to a maximum."

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Abstinence from Cocaine May Resolve Cardiomyopathy

Symptoms, left-ventricular ejection fraction improve in patient after a year of abstinence

Cardiomyopathy associated with cocaine abuse may resolve after an extended period of abstinence, according to a case report published in the May 5 issue of The Lancet.

Valerio Zaca, of the University of Siena in Italy, and colleagues report the case of a 31-year-old man who presented to the emergency department with fatigue, dyspnea and chest pain, and admitted to longstanding cocaine use. Chest x-ray and transthoracic echocardiography showed cardiomegaly, bilateral pulmonary congestion, an 80-mm left-ventricular end-diastolic diameter, and a left-ventricular ejection fraction (LVEF) of 20 percent.

The patient was discharged on a regimen of carvedilol, ramipril, furosemide, potassium canrenoate and warfarin, in addition to drug abuse counseling. Drug tests showed the patient likely abstained from drug use and about a year after discharge the patient was asymptomatic and showed no signs of cardiomegaly or chest congestion. In addition, left-ventricular diameter reduced to 57 mm and LVEF increased to 50 percent.

"The observation of cardiovascular complications associated with cocaine use has become progressively more frequent," the authors write. "A history of cocaine use should be considered when assessing previously healthy young patients with heart disease."

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Colorectal Cancer Drugs Cause Magnesium Loss

Serum magnesium declined in 97 percent of patients treated with epidermal growth factor receptor-targeting antibodies

Almost all colorectal cancer patients treated with epidermal growth factor receptor-targeting antibodies such as cetuximab (Erbitux) experience magnesium loss, according to study findings published in the May issue of The Lancet Oncology.

Sabine Tejpar, M.D., of the University Hospital Gasthuisberg in Leuven, Belgium, and colleagues studied magnesium concentrations in 98 colorectal cancer patients who underwent treatment with epidermal growth factor receptor-targeting antibodies (cetuximab, matuzumab or panitumumab) with or without combined chemotherapy.

Serum magnesium concentrations declined in 95 patients (97 percent), and those treated with epidermal growth factor receptor-targeting treatment had levels significantly lower than the 16 control patients treated with chemotherapy alone.

"Our study was important because it shows that magnesium wasting will occur in all patients," said Tejpar, in a statement. "Hypomagnesemia was thought to be restricted to an undefined subset of patients," she added.

In an accompanying editorial, Marwan Fakih, M.D., of the Roswell Park Cancer Institute in Buffalo, N.Y., adds that patients at high risk could be identified early based on age, baseline magnesium concentrations and duration of treatment. "While age might be a predisposing factor, patient pharmacogenomics are probably an important factor in deciding the patient's susceptibility to this toxicity," he writes.

AbstractFull Text (subscription or payment may be required)Editorial

U.K. Stroke Mortality Hasn't Dropped in Patients Over 75

Due to aging population, absolute number of cases might increase in the future

Despite the general downward trend in intracerebral hemorrhagic stroke mortality, the incidence has not dropped in patients over 75 with the greater use of antithrombotic drugs, according to the results of a U.K. study published online May 1 in The Lancet Neurology.

Peter M. Rothwell, F.R.C.P., of the University of Oxford in Oxford, U.K., and colleagues analyzed data on incidence of intracerebral hemorrhagic stroke in patients older and younger than age 75. They looked at two studies, one conducted from 1981 to 1986 and the other from 2002 to 2006.

The studies revealed a substantial decline in stroke in patients under age 75 over the past 20 years, due to a decline in the average blood pressure. However, in patients over 75, the proportion of cases did not radically change across two decades, while the use of antithrombotic drugs increased from 4 percent of patients in 1981-1986 to 40 percent by the 2002-2006 study.

"These trends, along with the expected increase in prevalence of amyloid angiopathy with the aging population, suggest that, in contrast to projections based on mortality data below age 75 years, absolute number of cases of intracerebral hemorrhage might increase in future," the authors conclude.

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Piperazines Are New, Potentially Dangerous Party Drugs

'Pep pills' are available in U.K. shops and online

Physicians should be aware of the potential side effects of a new type of party drug containing 1-benzylpiperazine because commercially available urine toxicology screening kits may not detect it, according to a case report published in the April 28 issue of The Lancet.

David M. Wood, M.D., of Guy's and St. Thomas' Poisons Unit in London, U.K., and colleagues report on the case of an 18-year-old woman who was admitted to hospital after she collapsed and had a seizure in a nightclub where she had taken five tablets she believed to be Ecstasy or amphetamines. Upon hospitalization she was agitated, had sinus tachycardia and dilated pupils as well as low blood pressure and body temperature.

She was treated with intravenous benzodiazepines and was discharged after 12 hours by which time she was asymptomatic. The only recreational drug found in the woman's blood was 1-benzylpiperazine. Screening for piperazines, other drugs and alcohol came up negative.

"All patients with strongly suspected or reported ingestion of 1-benzylpiperazine should have an initial baseline ECG, to seek features of cardiotoxicity. They should be observed for up to eight hours after ingestion, because the onset of seizures can be delayed," the authors advise. "Further management can require the advice of a clinical toxicologist."

Full Text (subscription or payment may be required)Editorial

New Candida Drug Efficacious for Invasive Infections

Fewer ill-effects seen with micafungin than with liposomal amphotericin B

A new treatment for invasive candidosis and candidemia is as effective as liposomal amphotericin B but with fewer side effects, including fewer kidney function problems, researchers report online April 26 in The Lancet.

Ernst-Rudiger Kuse, M.D., of the Klinik fur Viszeral und Transplantationschirurgie in Hannover, Germany, and colleagues compared results for 264 candidemia and invasive candidosis patients randomly treated with 100 milligrams daily of micafungin versus 267 patients given 3 milligrams per kilogram daily of liposomal amphotericin B.

After sorting cases according to neutropenia status at baseline, the researchers found a 0.7 percent difference in proportions. They also found that the two drugs' effectiveness did not depend on catheter status, number of blood neutrophils, main infection site or other variables and adverse events were fewer with micafungin.

"Micafungin was as effective as -- and caused fewer adverse events than -- liposomal amphotericin B as first-line treatment of candidemia and invasive candidosis," the authors write.

The study was funded by Astellas Pharma GmbH.

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Socioeconomic Status Health Gap Increases with Age

Those in lower occupational grades age faster

The health-related gap between low-income and high-income patients tends to widen with age, with individuals in lower occupational grades aging faster, according to the results of a study published online April 27 in BMJ.

Tarani Chandola, D.Phil., and colleagues from University College London in the United Kingdom examined self-reported physical and mental health over time based on occupational grade in 10,308 office-based British civil servants aged 35 to 55 years at baseline.

After an average follow-up of 18 years, the researchers found that physical health declined in all groups but declined faster among individuals in lower occupational grades. A 70-year-old individual in a high-grade position had the average physical health of an individual eight years younger in a low-grade position, while the gap was only 4.5 years in mid-life. Mental health improved over time but improved more slowly in individuals in the lower grades.

"Social inequalities in self-reported health increase in early old age," Chandola and colleagues conclude. "People from lower occupational grades age faster in terms of a quicker deterioration in physical health compared with people from higher grades."

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Older Children Can Perform CPR

Younger children can still learn principles of chest compression

Children as young as 13 years old can adequately perform chest compressions for cardiopulmonary resuscitation, and younger children can still learn the principles of chest compression, according to a report published online April 27 in BMJ.

Michael Colquhoun, Sc.D., and colleagues from Cardiff University in the United Kingdom examined the ability of 157 children aged 9 to 14 years (divided into age groups 9-10, 11-12, and 13-14 years) to perform effective chest compressions for three minutes on a mannequin. The children had been taught basic life support skills in a single 20-minute session.

The researchers found that none of the youngest children, 19 percent of children aged 11-12 years, and 45 percent of the oldest children were able to perform chest compressions to the recommended depth of 38-51 mm. The oldest children were able to perform compressions as well as has been reported for adults. All children were able to place their hands in the correct position. Compression depth was significantly associated with age and weight, the report indicates.

"The children's ability to achieve an adequate depth of chest compression depended on their age and weight," Colquhoun and colleagues conclude. "Young children who are not yet physically able to compress the chest can learn the principles of chest compression as well as older children."

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Aspirin Does Not Improve Cognition in Elderly Women

May reduce risk of decline in category fluency

Long-term low-dose aspirin does not improve overall cognition in elderly women, although it may reduce the risk of decline in category fluency, according to a report published online April 27 in BMJ.

Jae Hee Kang, Sc.D., and colleagues from Brigham and Women's Hospital in Boston, randomized 6,377 women at least 65 years old to low-dose aspirin (100 mg every other day) or placebo for a mean of 9.6 years. Cognitive function was assessed by tests for general cognition, verbal memory and category fluency, a total of three times every two years over the telephone.

The researchers found that cognitive function was similar in the two groups at the initial assessment. The mean decline in global cognitive score (average performance across all tests), the risk of substantial cognitive decline and verbal memory were also similar in the two groups. However, the aspirin group had a lower risk of decline in category fluency (relative risk 0.80).

"Long-term use of low-dose aspirin does not provide overall benefits for cognition among generally healthy women aged 65 or more," Kang and colleagues conclude.

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Device Allows Diagnosis for Unexplained Palpitations

More cost-effective than conventional treatment

An implantable loop recorder allows a diagnosis to be made and is more cost-effective than conventional treatment for patients with unexplained heart palpitations, according to the results of a study published online April 30 in the Journal of the American College of Cardiology.

Antonio Raviele, M.D., from Umberto I Hospital in Venice, Italy, and colleagues studied 50 patients with unexplained, infrequent and sustained (one or fewer episodes a month for under one minute) heart palpitations. About half were randomized to implantation with an implantable loop recorder with monitoring for one year, while the remainder received conventional treatment.

The researchers found that a diagnosis was obtained in 73 percent of patients receiving the implantable loop recorder compared with only 21 percent of patients receiving conventional treatment. Although the initial cost of the implantable loop recorder was higher, the cost per diagnosis was less than half the cost of the conventional treatment group.

"In subjects without severe heart disease and with infrequent palpitations, implantable loop recorder is a safe and more cost-effective diagnostic approach than conventional strategy," Raviele and colleagues conclude.

The study was partially funded by Medtronic.

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Peptide Predicts Mortality Risk After Heart Failure

Risk higher regardless of systolic function and other variables

A high level of B-type natriuretic peptide after heart failure predicts a higher risk of death, regardless of systolic function and other variables, according to study findings published online April 30 in the Journal of the American College of Cardiology.

Gregg C. Fonarow, M.D., from the University of California Los Angeles, and colleagues measured the levels of B-type natriuretic peptide, or BNP, in 48,629 patients hospitalized for acute decompensated heart failure within 24 hours of presentation. The risk of mortality was determined based on BNP quartile: Q1 (less than 430 pg/mL), Q2 (430-839 pg/mL), Q3 (840 to 1,729 pg/mL) and Q4 (1,730 pg/mL or more).

The researchers found that in-hospital mortality increased from the lowest to highest quartile, ranging from 1.9 to 6 percent. BNP quartile independently predicted mortality regardless of whether left ventricular systolic function was preserved and even after adjusting for variables such as age, gender and systolic blood pressure, with an adjusted odds ratio of 2.23 comparing the highest and lowest quartiles.

"An elevated admission BNP level is a significant predictor of in-hospital mortality in acute decompensated heart failure with either reduced or preserved systolic function, independent of other clinical and laboratory variables," Fonarow and colleagues conclude.

The study was funded by Scios, Inc. of Mountain View, Calif.

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Genes Linked to Cognitive Decline Post Heart Surgery

Variants of two inflammatory genes reduce risk of cognitive decline

Variants of two genes involved in inflammation reduce the risk of cognitive decline after coronary artery bypass graft surgery, according to a report published online April 30 in the Journal of the American College of Cardiology.

Joseph P. Mathew, M.D., from Duke University Medical Center in Durham, N.C., and colleagues genotyped 513 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass with a panel of 37 single-nucleotide polymorphisms (SNPs). Cognitive deficit was tested six weeks later.

The researchers found a reduced risk of postoperative cognitive deficit in patients with minor frequency alleles of the C-reactive protein 1059G/C SNP (odds ratio 0.37) and the SELP 1087G/A SNP (OR, 0.51). This translated into a reduction in absolute risk of 20.6 percent and 15.2 percent, respectively. Platelet activation and levels of C-reactive protein were significantly lower in these patients, the study notes.

"The results suggest a contribution of P-selectin and C-reactive protein genes in modulating susceptibility to cognitive decline after cardiac surgery, with potential implications for identifying populations at risk who might benefit from targeted perioperative anti-inflammatory strategies," Mathew and colleagues conclude.

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Coronary Artery Calcium Scores Predict Mortality

Ten-year survival drops from 99.4 percent to 87.8 percent with a score over 999

Coronary artery calcium scores can predict 10-year mortality rates in patients without heart disease symptoms, researchers report in the May 8 issue of the Journal of the American College of Cardiology.

Matthew J. Budoff, M.D., of the Harbor-UCLA Los Angeles Biomedical Research Institute in Torrance, Calif., and colleagues assessed 25,253 asymptomatic individuals who were referred by their physician for testing. The investigators looked at the predictive power of the coronary artery calcium scores as determined by electron beam tomography.

Risk factor-adjusted 10-year survival varied with coronary artery calcium scores, from 99.4 percent for a score of zero, to 87.8 percent for a score greater than 999. Relative risk also varied, from 2.56 (score 1-10) to 62.58 (score greater than 999). About 44 percent of patients had a score of 0; 14 percent had 1-10; 20 percent had 11-100; 13 percent had 101-400; 6 percent had 401-1,000; and 4 percent were over 1,000.

"Our study shows that coronary artery calcium provides independent and incremental prognostic information in addition to traditional risk factors in the prediction of all-cause mortality," the authors write.

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White Blood Cell Count Linked to Cardiovascular Mortality

Longitudinal study shows white blood cell counts falling since 1958

White blood cells counts have fallen since the late 1950s in parallel with a decrease in overall mortality, according to a report published in the May 8 issue of the Journal of the American College of Cardiology. The researchers found an almost linear association between white blood cell count and cardiovascular mortality, but no association with cancer mortality.

Carmelinda Ruggiero, M.D., of the National Institute on Aging in Baltimore, and colleagues studied 2,803 participants in the Baltimore Longitudinal Study of Aging over a median of 13 years for women or 22 years for men. Between 1958 and 2002, the researchers assessed mortality and white blood cell counts every two years.

A downward trend in white blood cell count was observed between 1958 and 2002, coinciding with an overall decrease in mortality, and independent of age, gender and other variables. The mortality rate was lowest (13.7/1000 person-years) for individuals with a white blood cell count between 3,501 and 6000, and highest (30.2/1000 person-years) for individuals with a white blood cell count greater 10,000. Cell count was almost linearly related to the risk of cardiovascular mortality, but relatively unrelated to the risk of cancer mortality. The adjusted hazard ratio for cell counts between 6,001 and 10,000 and greater than 10,000 were 1.28 and 1.62, respectively. Neutrophil count was strongly associated with mortality.

"Our study suggests that differential white blood cell counts should be systematically screened and factored in the cardiovascular risk profile and ultimately considered in clinical decisions concerning prescription of preventive interventions," the authors conclude.

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Implantable Defibrillator Leads Often Fail in First 10 Years

One in five leads fail; higher failure in females, younger patients

The failure rate of implantable cardioverter-defibrillator leads is as high as 20 percent after 10 years, with high failure rates in females and in younger patients, according to a report published online April 30 in Circulation: Journal of the American Heart Association. The most common problems are insulation defects and lead fractures.

Thomas Kleemann, M.D., and colleagues from Herzzentrum Ludwigshafen in Germany examined the annual lead failure rate in 990 patients who had received an implantable cardioverter-defibrillator between 1992 and 2005.

After a median follow-up of 934 days, the researchers found that 15 percent of leads failed. The annual failure rate increased with time, reaching 20 percent at 10 years. Lead defects were more likely to occur in newer leads than older models (5-year survival, 80 percent and 93 percent, respectively). Failures were more common in female and younger patients, and those with multiple lead implantations. About half of defects were insulation defects (56 percent), followed by lead fractures (12 percent), loss of ventricular capture (11 percent), abnormal lead impedance (10 percent), and sensing failure (10 percent).

"This is somewhat surprising," said Kleemann, in a statement. "The older leads used polyurethane as an insulator and they had defect problems. So a change was made to silicone in 1997. But it seems that the silicone-coated wires have problems even earlier."

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