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Multivitamins in Pregnancy Ward Off Low Birth Weight

2009-06-08T22:36:00.000-07:00

LITTLE FALLS, N.J., June 8 -- Multivitamin supplementation during pregnancy may improve a baby's birth weight more than iron-folic acid supplementation alone, a meta-analysis showed.

In an analysis of 13 studies, women who received a multivitamin had a 17% greater reduction in the risk of having a baby with low birth weight (RR 0.83, 95% CI 0.74 to 0.93), Prakesh Shah, M.D., of Mount Sinai Hospital in Toronto, and colleagues reported in the June 9 Canadian Medical Association Journal.

The number needed to benefit was 50 (95% CI 33 to 100).

The World Health Organization recommends iron-folic acid supplementation alone for all pregnant women, but this strategy "needs to be challenged in light of the evidence from our review," according to the researchers.

They said their findings indicate that multivitamin supplementation could prevent about 1.5 million babies worldwide from being born with low birth weight each year.

Dr. Shah and colleagues identified 13 high-quality randomized or quasi-randomized (group assignments by identifiers such as date of birth or day of the week) trials evaluating the effect of multivitamin supplementation at any time during pregnancy. These included four cluster-randomized trials.

The multivitamins used in the various studies contained eight to 28 micronutrients.

For the prevention of low birth weight (less than 2,500 grams), multivitamins yielded a benefit against both iron-folic acid supplementation and placebo (RR 0.81, 95% CI 0.73 to 0.91).

Overall birth weight was significantly higher in the multivitamin group than in the iron-folic acid group (difference 54 g), but there was no significant difference compared with placebo.

There were no significant differences between the three study groups in the risk of preterm birth, small-for-gestational-age birth, or gestational age.

The researchers noted that the meta-analysis was limited by variability among the studies in terms of the timing and duration of supplementation, the composition of the micronutrients, and the characteristics of the study populations.

But they said "the practice in most developed countries of giving multivitamins along with iron and folic acid to pregnant women needs to be adopted in developing countries."

They acknowledged the difficulty in determining which components of the multivitamins were responsible for the beneficial effects.

"Therefore," they said, "it is not unreasonable to recommend a composite of micronutrients for supplementation because it would be impossible to identify and target individual deficiencies in every pregnant woman."

In an accompanying editorial, Zulfiqar Bhutta, M.B.B.S., Ph.D., and Batool Azra Haider, M.B.B.S., of the Aga Khan University in Karachi, Pakistan, urged caution when interpreting the results.

Drs. Bhutta and Haider had previously concluded that there was not enough evidence to justify replacing iron-folic acid supplementation with a multivitamin strategy.

They said the authors of the current meta-analysis should arguably have adjusted for the cluster-randomized trials.

In addition, they said, Dr. Shah and colleagues did not stratify the results by maternal nutritional status and stature and omitted several outcomes such as perinatal mortality.

Considering these limitations, though, "if proven effective and safe in representative healthcare systems, multimicronutrient supplementation should replace iron-folic acid supplementation in susceptible populations."

The study was funded by a Knowledge Synthesis/Translation grant from the Canadian Institutes of Health Research.

Neither the study authors nor the editorialists reported any conflicts of interest.

Primary source: Canadian Medical Association Journal
Source reference:
Shah P, et al "Effects of prenatal multimicronutrient supplementation on pregnancy outcomes: a meta-analysis" CMAJ 2009; 180: E99-E108.

Additional source: Canadian Medical Association Journal
Source reference:
Bhutta Z, Haider B "Prenatal micronutrient supplementation: Are we there yet?" CMAJ 2009; 180: 1188-89.

ASE: Mixed Results with Stress Echo in Menopausal Women

2009-06-08T22:35:00.002-07:00

coronary atherosclerosis in women in early menopause but poor specificity and no correlation with lab parameters, preliminary data from an ongoing study showed.

As verified by coronary angiography, contrast stress echocardiography had a sensitivity of 80% for coronary disease, but specificity was less than half that, Sharon Mulvagh, M.D., of the Mayo Clinic in Rochester, Minn., reported at the American Society of Echocardiography meeting.

Newer laboratory tests for coronary disease, such as high-sensitivity C-reactive protein (hs-CRP) and brain natriuretic peptide (BNP), had no correlation with contrast stress echo, nor did coronary calcification.

Predictors of a positive echo test were body mass index, family history of premature coronary artery disease (CAD), and a positive stress ECG.

"This is the first large prospective trial of early or recently menopausal women at low to intermediate risk for coronary artery disease undergoing contrast stress echo, stress ECG, electron-beam computed tomography, and novel serologies," said Dr. Mulvagh. "Contrast stress echo detected angiographically significant CAD twice as often as stress ECG, but was less specific.

"These are the preliminary results, and data from two- and five-year follow-up are pending," she added.

Little progress has been made in the development of diagnostic strategies for women in early menopause who have cardiovascular risk factors and chest pain. But technologic advances in contrast stress echo have improved image quality, visualization of wall segments, and diagnostic confidence, said Dr. Mulvagh.

Whether contrast echo enhanced the utility of other indicators of CAD had not been carefully studied, she said.

So, the Stress Echo in Menopausal Women at risk for Coronary Artery Disease Trial (SMART) was designed to address some of the unanswered questions about the role of contrast stress echo in evaluating early menopausal women.

SMART has a twofold primary objective: (1) Determine the prognostic value of contrast stress echo for predicting coronary events; (2) Explore the relationship between wall motion abnormalities identified by contrast stress echo and stress ECG, coronary calcium score, and novel serum biomarkers.

The secondary objective is to evaluate the diagnostic accuracy of contrast stress echo and stress ECG in a subset of SMART participants undergoing clinically indicated coronary angiography.

Investigators at Mayo campuses in Rochester, Scottsdale, Ariz., and Jacksonville, Fla., enrolled 400 perimenopausal, early menopausal, and surgically menopausal women referred for contrast stress echo. All were judged to have a low to moderate likelihood of CAD.

Ultimately, 389 patients underwent a contrast stress echo -- 366 had exercise tests and 23 had dobutamine assessments. Patients also had assessment of BNP, atrial natriuretic peptide (ANP), endothelin, and hs-CRP. A subset of patients had quantification of coronary calcification by electron beam CT.

Patients were monitored continuously by 12-lead ECG during contrast stress echo evaluation. An abnormal stress echo result was defined as new or worsening of wall motion abnormalities during peak stress. An abnormal ECG was defined as 1 mm or greater horizontal or downsloping ST-segment depression or ST-segment elevation for at least 80 milliseconds.

The mean age of the study group was 54.4, the mean BMI was 31.5, and 95.5% of the women were white. A quarter of the women were current or former smokers, 16.5% were diabetic, 60% had a family history of CAD, 63% were hypertensive, 80% were dyslipidemic, and 57% were obese.

Dr. Mulvagh reported that 42 women (11.5%) had abnormal contrast stress echo tests. Additionally, 22 participants (6%) had positive ECG tests, and 23 (6.2%) had indeterminate or inadequate ECG results.

Stress ECG had poor correlation with a positive contrast stress echo result. Of the 42 patients who had positive echo tests, only seven (16.7%) were positive by stress ECG.

Of 308 women who had measurement of hs-CRP, 72 had values less than 1 mg/dL (low risk), 113 had values of 1.0 to 3.0 mg/dL (average risk), and 123 had values greater than 3.0 mg/dL (high risk). Neither a positive nor a negative contrast stress echo result correlated with hs-CRP values associated with the tests.

ANP and endothelin levels also had no correlation with contrast stress echo results. The only statistically significant association involved BNP, which increased during peak wall motion score index (WMSI) (P<0.001),>

A subset of 124 patients had EBCT assessment of coronary calcium. Values did not correlate with contrast stress echo results. Of the 124, 14 had abnormal contrast stress echo tests, and their coronary calcium score averaged 37.3. In the remaining 110 patients with normal contrast stress echo tests, the coronary calcium score averaged 48.4.

A subset of 48 patients had coronary angiography for suspected CAD. Compared with angiography, contrast stress echo had a sensitivity of 80% but a specificity of 37%, resulting in an overall accuracy of 46%. Stress ECG had a 40% sensitivity, 79% specificity, and overall accuracy of 71%.

In a multivariate analysis, only conventional CAD risk factors correlated with as positive contrast stress echo test (BMI, diabetes, family history of premature CAD, and positive stress ECG).

The patients will continue to be followed for five years, and an interim analysis will be performed after two years, Dr. Mulvagh said.

The authors reported no potential conflicts of interest.

Primary source: American Society of Echocardiography
Source reference:
Abdelmoneim S, et al "Initial results from the 'Stress echo in Menopausal women at risk for coronary ARTery Disease (SMART) Trial:' An outcomes study evaluating the diagnostic and prognostic value of noninvasive testing for cardiovascular disease" J Am Soc Echocardiogr 2009; 22(5): Abstract P1-57.

ADA: GLP-1 Competitors and Early Screening Take Center Stage

2009-06-08T22:35:00.001-07:00

NEW ORLEANS, June 8 -- A head-to-head trial of two GLP-1 analogs and the possibility of predicting a diabetes diagnosis five years before the patient exhibits standard clinical markers are the focus of this exclusive MedPage Today InFocus discussion.

Sue Kirkman, M.D., vice president of clinical affairs for the American Diabetes Association, examines the results of those two studies with staff writer Kristina Fiore.

The beauty of the trial comparing liraglutide and exenatide, Dr. Kirkman said, is that two drugs in a relatively new class of drugs are being compared to each other rather than to one of the well-established treatments.

Dr. Kirkman also touches on the potential implications for very early screening in diabetes based on findings from the Whitehall study.

ADA: Glucose Metabolism Measures Can Forecast Diabetes Years Ahead

2009-06-08T22:34:00.000-07:00

NEW ORLEANS, June 8 -- Insulin sensitivity, beta-cell function, and blood glucose may provide telltale signs of impending type 2 diabetes up to five years before onset, researchers affirmed.

The traditional marker for diabetes and prediabetes diagnosis -- fasting blood glucose -- shot up in the three years prior to diabetes onset, Adam G. Tabák, M.D., of University College London, and colleagues found in a 13-year study of British civil servants.

But beta-cell function abnormalities emerged three to four years before onset and insulin sensitivity fell sharply over the five years before diagnosis, they reported here at the American Diabetes Association meeting and simultaneously online in The Lancet.

These biomarker trajectories, determined at regular check-ups over time, could improve the accuracy of risk prediction models to allow for earlier prevention efforts, the researchers said.

The models typically use only the most recent blood glucose measurements, with prevention then focusing on patients who meet glucose-based prediabetes criteria, they noted,

However, waiting to intervene until prediabetes may be too late, since they are "already on the steep part of the glucose trajectory," the researchers said.

"We hypothesize that prevention would be more effective before this unstable period, but more research is needed," they said.

"If a person could be kept on the linear part of the fasting glucose (or postload glucose) trajectory, the onset of diabetes might be substantially delayed," they said.

The results provide "unique longitudinal data illuminating what had long been suspected from cross-sectional data," said David R. Matthews, M.D., and Jonathan C. Levy, M.D., both of the Oxford Centre for Diabetes at the University of Oxford in Oxford, England, in an accompanying editorial.

Although they expressed skepticism that the results could be used for earlier screening because the predictions would have poor sensitivity and specificity, they said beta-cell function and insulin resistance could be valuable additions to risk prediction.

"We know that we have proven advice and therapies that we can give," they said. "Now the hunt has to be intensified for the pathology that causes the decompensation that precipitates diabetes."

M. Sue Kirkman, M.D., ADA vice-president of clinical affairs, agreed that the findings might not be immediately applicable to clinical practice.

A trial to compare early screening versus usual screening practice would be required, she said.

Dr. Tabák's group examined the Whitehall II study for a "high-resolution" look at changing glucose metabolism over time in 6,538 British civil servants (71% male, 91% white) without baseline diabetes who were followed with repeated serum glucose measurements and oral glucose tolerance tests.

Over up to 13 years of follow-up (median 9.7 years), 505 participants were diagnosed with diabetes.

Among those who did not develop the disease, metabolic changes were fairly gradual.

Insulin secretion changed little. Modest, linear rises occurred in fasting glucose (mean 0.004 mmol/L per year) and slight falls for insulin sensitivity -- a decline of about 15% over 13 years, which Drs. Matthews and Levy called "doubtless the effect of progressive inactivity and middle-age spread."

For incident diabetes cases, fasting plasma glucose also declined linearly until three years before diagnosis, although with a 0.028-mmol/L-per-year steeper slope than seen in nondiabetics.

But the last three years leading up to diagnosis showed a rapid drop in fasting glucose levels following a quadratic trajectory.

For postload glucose levels, the rate of increase up until six years prior to the end of follow-up was not significantly different between study participants who would go on to develop incident diabetes and those who would not.

Again, though, diabetes cases showed 1.5-fold higher postload glucose concentrations that rose in a cubic trajectory during the six years before diagnosis to the end of follow-up. In the two years before diagnosis, cases had a rapid increase in glucose concentrations from 7.60 to 11.90 mmol/L.

Insulin sensitivity declined identically between groups (1.11% per year) until five years before diagnosis. After that point, the slope was an absolute 2.76% steeper among diabetes cases to reach 86.7% by the end of the 13-year follow-up.

Beta-cell function measured by calculated insulin secretion averaged 10.4% higher in individuals who would develop diabetes up until the four years prior to diagnosis, which the editorialists explained as a compensatory effort to "maintain normoglycemia in a prevailing climate of insulin resistance."

Then roughly three years before diabetes onset, beta-cell function revealed "a further last-ditch increase" with a quadratic increase before crashing to 62.4% of normal.

Sensitivity analyses, including body mass index adjustment, had little impact on difference in trajectory of metabolic changes between groups.

Although the largely white, male study population could limit generalizability, Dr. Kirkman noted that the findings match those of other studies, such as beta-cell results in a study of Pima Indians.

The researchers said their findings supported a multistage model of diabetes development with a long compensatory period, then a stable adaptation, and finally "a transient unstable period with a rapid rise of glucose to overt diabetes."

The Whitehall II study was supported by the Medical Research Council, Economic and Social Research Council, British Heart Foundation, Health and Safety Executive, and U.K. Department of Health, the National Heart Lung and Blood Institute, National Institute on Aging, Agency for Health Care Policy Research, and The John D. and Catherine T. MacArthur Foundation.

The researchers reported no conflicts of interest.

Drs. Matthews and Levy reported no conflicts of interest.

Dr. Kirkman reported no conflicts of interest.

Primary source: The Lancet
Source reference:
Tabák AG, et al "Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study" Lancet 2009.

Additional source: The Lancet
Source reference:
Matthews DR, Levy JC "Impending type 2 diabetes" Lancet 2009.

Kennedy Releases Healthcare Reform Draft Bill

2009-06-08T22:31:00.000-07:00

WASHINGTON, June 8 -- A new draft of a healthcare reform bill from the Senate Health, Education, Labor and Pensions (HELP) Committee proposes reimbursing physicians at rates similar to those in Medicare as part of a public insurance plan option.

Not surprisingly, the bill would create a new government-sponsored insurance program -- which has been the most divisive component of healthcare reform.

While the bill offers few specifics of its "affordable access plan," such as who would be eligible, it does propose to reimburse physicians and hospitals at Medicare rates, plus an additional 10%.

The 170-page draft bill, written by HELP Chairman Sen. Edward Kennedy (D-Mass.), is a working draft, complete with committee notes and blank spots where pertinent details would be filled in. But it is a concrete proposal from one of the two committees responsible for healthcare reform.

Kennedy has not been working full time in Washington since he was diagnosed with malignant glioma in his left parietal lobe almost 13 months ago, but he has been working remotely to make good on his longtime promise of healthcare reform. (See Kennedy Diagnosed with Glioma)

The other committee of jurisdiction is the Senate Finance Committee, which has said it would mark up a bill in the next few weeks but hasn't unveiled a draft so far.

Kennedy's bill would require all individuals to have insurance and would require all employers to provider insurance or else pay their employees to purchase a plan elsewhere.

While President Barack Obama and Sen. Max Baucus (D-Mont.), chairman of the Senate Finance Committee, have endorsed an employer-mandate, they have largely stayed away from promoting an individual mandate -- something that was not politically popular during the failed reform efforts in the 1990s.

Under the bill, the government would provide credits to help eligible businesses pay for covering their employees, and certain small businesses and employees would be exempt.

Kennedy's bill would also establish an insurance exchange, called the "Affordable Health Benefits Gateway," which would be modeled after the "Connector" in Massachusetts.

The Gateway would be a state-run, one-stop shop for insurance-seekers to compare the benefits and costs of "qualified" insurance plans.

A new "Medical Advisory Council" would decide what services are "essential healthcare benefits" that all health plans would be required to cover.

The council would issue payment recommendations each year for medical and surgical care, mental health services, maternity care, and other specific services. They would take effect automatically unless rejected by Congress.

The bill would drastically change how insurance companies operate by requiring them to account for exactly what policy-holders' premiums paid for, and to provide a partial rebate to patients from portions of their premiums that didn't go toward paying for the medical expenses.

In affect, the bill would put a cap on insurance company profits.

The bill would also require plans to provide a bare minimum of basic services, provide coverage to dependents through age 26, and make it illegal for insurance plans to deny coverage based on pre-existing conditions -- something insurance groups have already pledged to do. (See Health Insurers Back Coverage for All Regardless of Current Health)

It would also require insurers to cover preventive medical services, including all recommended immunizations, and prohibit private insurers from setting annual or lifetime limits on benefits.

The bill would also:

Expand Medicaid to cover those with incomes up to 150% of the federal poverty level, and help defray costs for states that have already expanded their Medicaid programs
Establish an insurance plan for people with disabilities to help cover the costs of receiving community-based care

The draft bill does not contain any cost figures. The Senate Finance Committee's plan is expected to focus more heavily on cost estimates.

Tight Glucose Control Lowers Risk of MI, But Not Stroke or Mortality

2009-05-23T22:38:00.000-07:00

LITTLE FALLS, N.J., May 22 -- Researchers attempting to clarify the debate over intense glucose control through meta-analysis concluded that it does reduce cardiovascular risk among type 2 diabetes patients, but not overall mortality.

Their meta-analysis of five studies found that the approach reduces the risk of nonfatal myocardial infarction by 17%, and coronary heart disease events by 15%, according to Kaushik K. Ray, M.D., of Strangeways Research Lab in Cambridge, England, and colleagues.

But the treatment had no effect on stroke or all-cause mortality, the group reported in the May 23 issue of The Lancet.

"Intensive glucose-lowering treatment has cardiovascular benefit compared with standard treatment for individuals with type 2 diabetes," the researchers concluded. But it appears considerably less significant than controlling blood pressure and cholesterol, they said.

There have been conflicting reports on the effectiveness of intensive glucose control in reducing macrovascular events and all-cause mortality in patients with type 2 diabetes. But the researchers said many trials have been underpowered to show clinical benefit.

So they conducted a meta-analysis of five prospective trials -- including ADVANCE and ACCORD -- involving a total of 33,040 patients.

Over 163,000 person-years of follow-up, there were 1,497 nonfatal myocardial infarction events, 2,318 coronary heart disease events, 1,127 fatal and nonfatal stroke events, and 2,892 deaths from any cause.

The researchers found that there were 2.3 fewer myocardial infarctions and 2.9 fewer coronary heart disease events for every 200 patients on intensive glucose control treatment for five years.

That translates to a number-needed-to-treat of 87 and 69, respectively.

"This benefit is much more modest than is that from a per-mmol/L reduction in LDL cholesterol or from a 4-mm Hg lower blood pressure," the researchers said.

Intensive glycemic control resulted in a 17% reduction in events of nonfatal myocardial infarction (OR 0.83, 95% CI 0.75 to 0.93) and a 15% reduction in coronary heart disease events (OR 0.85, 95% CI 0.77 to 0.93).

There was no significant effect on stroke or all-cause mortality.

Additionally, almost twice as many patients on intensive glycemic control had a hypoglycemic episode as those on standard treatment.

Therefore, a practical clinical approach "might be to reduce HbA1c concentration steadily with care taken to avoid severe hypoglycemia," the researchers said.

Those on intensive control also gained more weight -- an average of 2.5 kg more than those on standard treatment.

The meta-analysis was limited by the methodological rigor of the assessed studies, as well as the possibility of publication bias. Also, the researchers could not assess the effects of intensive glycemic control among different patient subgroups.

An additional limitation was the inability to assess different treatment regimens.

Still, they concluded that their "quantitative analysis of randomized controlled trials provides reliable large-scale evidence of a consistent beneficial effect of intensive treatment on nonfatal myocardial infarction and coronary heart disease, without increased risk of all-cause mortality."

In an accompanying editorial, Theodore Mazzone, M.D., of the University of Illinois at Chicago, said the findings suggest a need for additional clinical trial data about the effect of controlling blood sugar on coronary heart disease risk in patients with type 2 diabetes.

Dr. Mazzone said that intensive glucose-control efforts "might need to be started sooner after onset of diabetes, and extended follow-up could be required."

He noted that tight glucose control does not have as great an impact as blood pressure and cholesterol control. But he said that given an "urgent need to address residual risk of coronary heart disease in a rapidly expanding population with type 2 diabetes, it is premature to conclude that glucose control has no part to play."

Some of the researchers reported receiving honoraria from Novartis, Merck, GlaxoSmithKline, Merck, and Novo Nordisk.

Primary source: The Lancet
Source reference:
Ray KK, et al "Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomized controlled trials" Lancet 2009; 373: 765-72.

Additional source: The Lancet
Source reference:
Mazzone T "Hyperglycemia and coronary heart disease: the meta picture" Lancet 2009; 373: 1737-38.

* Medical News: Breast Cancer

2009-05-23T22:36:00.000-07:00

Breast Cancer Risk Factors Vary by Tumor Subtype
RIDGEWOOD, N.J., May 22 -- Risk factors for the development of invasive breast cancer vary depending on whether the tumor is luminal A, luminal B, triple negative, orWomen with the luminal B breast cancer subtype, for instance, were likely to be younger at diagnosis than those with luminal A (OR before age 50 of 1.83, 95% CI 1.32 to 2.55, P=0.0001), Marilyn L. Kwan, Ph.D., of Kaiser Permanente in Oakland, Calif., and colleagues reported online in Breast Cancer Research.

Luminal B patients also were less likely to use hormone replacement therapy (OR 0.66, 95% CI 0.46 to 0.94) and oral contraceptives (OR 0.73, 95% CI 0.55 to 0.96), or to consume alcohol (OR 0.74, 95% CI 0.56 to 0.98), the investigators found.

Luminal A tumors are estrogen receptor and/or progesterone receptor positive and human epidermal growth factor receptor 2 (Her2) negative. Luminal B tumors are estrogen receptor and/or progesterone receptor positive, as well as Her2 positive.

These two subtypes have been associated with improved prognoses compared with the subtypes referred to as Her2 overexpressing and "triple negative" (basal-like in 70% of cases).

Her2-overexpressing tumors are estrogen receptor and progesterone receptor negative but Her2 positive, and triple negative tumors, as the name implies, are negative for all three, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor in the majority of cases.

Previous studies have examined associations between breast cancer risk factors, race, and hormone receptor status, but few studies have investigated the relationship between risk factors and molecular subtypes.

To address this, the researchers examined data from two large, prospective breast cancer survivorship studies, the Life After Cancer Epidemiology (LACE) Study and the Pathways Study.

LACE involved 2,280 women diagnosed with early-stage invasive breast cancer between 1997 and 2000, recruited primarily from the Kaiser Permanente Northern California Cancer Registry and the Utah Cancer Registry.

Patients were 18 to 70 years old, had completed treatment other than adjuvant hormonal therapy, and were free of recurrence.

The Pathways Study is an ongoing prospective cohort study that began recruiting in January 2006 and currently includes 2,212 women.

Patients in this study were at least 21 years old at the time of diagnosis, have primary invasive breast cancer of any stage, and no prior history of any cancer.

The current analysis includes all patients in LACE and the first 723 women in the Pathways Study whose cancers corresponded with those in LACE (stage I ≥ 1 cm, II, or IIIA) and for whom molecular subtype data were available.

Demographically, the pool of cohorts was relatively heterogeneous.

Among the 2,544 cases of invasive breast cancers included in the study:

* 1,868 (73%) were classified as luminal A
* 294 (12%) were luminal B
* 288 (11% were triple negative
* 94 (4%) were Her2-overexpressing

Compared with luminal A cases, triple negative cases tended to be younger, (OR before age 50 of 2.78, 95% CI 1.99 to 3.90, P
Her2-overexpressing cases were more likely to be younger than luminal A cases (P=0.03) and less likely to use HRT (OR 0.49, 95% CI 0.26 to 0.79).

Women with the Her2-overexpressing subtype also were more likely to be Hispanic (OR 2.19, 95% CI 1.16 to 4.13) or Asian (OR 2.02, 95% CI 1.05 to 3.88).

Premenopausal women with the triple-negative subtype were more likely to be overweight (OR 1.82, 95% CI 1.03 to 3.24) or obese (OR 1.97, 95% CI 1.03 to 3.77).

Women with the triple-negative subtype and parity of three or more also were more likely to have not breastfed their children (OR 1.68, 95% CI 1.00 to 2.81).

The "significant heterogeneity of associations by tumor subtype . . . lend[s] further support to the growing evidence base that breast cancer is a heterogeneous disease defined by estrogen receptor, progesterone receptor, and Her2 expression with distinct etiologic pathways and prognoses," the researchers concluded.

They cited study limitations that include the small number of Her2-overexpressing tumors, the case-case comparison design, and the fact that the associations reported are all in reference to risk of having the luminal A subtype "and should not be extended to risk of having invasive breast cancer."

Triple negative cases could not be further classified as basal-like or unclassified due to absence of data on CK 5/6 and EGFR markers.

These findings suggest that "public health programs aimed towards achieving a healthy weight and promoting breastfeeding might reduce the number of poor prognostic triple negative tumors among all breast cancer cases, especially the high-risk African American group," they concluded.

The LACE Study was funded by the National Cancer Institute, the Utah Cancer Registry, and the State of Utah Department of Health.

The Pathways Study was funded by the National Cancer Institute, the Department of Defense, and the American Cancer Society.

The authors declared that they have no competing interests.

Primary source: Breast Cancer Research
Source reference:
Kwan M, et al "Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors" Breast Cancer Res 2009: 11:R31.

* Medical News: Washington Watch

2009-05-23T22:34:00.000-07:00

Health Reform Expensive, But So Is Failure to Act

WASHINGTON, May 22 -- As the Senate Finance Committee prepares a national healthcare reform bill, a new report from the Urban Institute estimates that employer costs will double by 2019 if Congress fails to act.

In addition, up to 20 million people would likely join the ranks of the uninsured -- bringing the total number to 65.7 million -- according to the researchers' worst-case scenario.

Even under the most optimistic estimate, 57 million people would be uninsured by 2019 without reform, the authors said.

"The single most amazing thing is how similar the scenarios are," Len Nichols of the New America Foundation, said at a Thursday discussion of the study hosted by the Urban Institute and the Robert Wood Johnson Foundation.

Nichols, who was not involved in the study, said the bleak data on the cost of inaction prove that reform is necessary from an economic standpoint.

The researchers used a simulation model based on national survey data and economic analyses of individual and business behavior to examine how insurance plans are likely to change in the next decade.

They modeled three different scenarios if health reform is not enacted.

In the worst-case scenario, they projected slow growth in incomes and continuing high growth rates for healthcare costs. The intermediate scenario predicts a faster growth in incomes than healthcare costs, while the best-case scenario counts on growth in employment and income, with a decline in healthcare costs.

"We spend a lot of time talking about the social reasons to enact reform, but this study really makes the economic rationale," said another panelist, Karen Ignagni, president and CEO of America's Health Insurance Plans (AHIP).

The study predicted that if reform isn't enacted, the amount individuals and families spend on health insurance premiums and out-of-pocket medical expenses would increase under all three scenarios.

In the worst case, individual and family spending on healthcare costs would increase by 32% in 2019. In the best-case scenario, it would increase by 29%.

Individual and family increases would be lower than those for the government and employers because the model predicts that insurance premiums would grow faster than incomes, leading more people to drop private coverage.

Uninsured people would have no premium payments, and those on Medicaid would have little or no out-of-pocket costs, the researchers said.

The study also found if the healthcare system is unchanged, by 2019 spending on Medicaid and the Children's Health Insurance Program would grow from it s current level of $251 billion to $520 billion in the worst-case scenario: a 107% increase. In the best-case scenario, spending on the public programs would increase 61%.

The model projects that uncompensated care payments would more than double by 2019, (to $107 billion to $141 billion, depending on the scenario). The health system currently spends $62 billion providing medical care for those with no coverage.

While healthcare reform will be expensive, particularly early on, so is the cost of doing nothing, the Urban Institute researchers argued.

"The costs of health reform are likely to be high and require new money, but we're going to require new money anyway," said lead author John Holahan, Ph.D., director of the Urban Institute's Health Policy Center.

Still, reform would at least solve some underlying problems, such as reducing the number of uninsured and containing costs in the long run, Dr. Holahan said.

At a Thursday morning briefing for reporters, Sen. Max Baucus (D-Mont.) said if the healthcare system stays as is, most employees would be spending half of their income on health expenses within the next seven or eight years.

Primary source: The Urban Institute
Source reference:
"Health Reform: The Cost of Failure"

APA: American Psychiatric Association Annual Meeting

2009-05-23T22:33:00.000-07:00

APA: Personality Traits Predict Satisfaction with Knee Replacement
SAN FRANCISCO, May 22 -- A patient's personality may have as much to do with his satisfaction after knee replacement surgery as the clinical outcome, small study shows. Patients who reported being satisfied with knee replacement despite residual pain and stiffness six months later were more likely to score highly on such traits as extroversion and openness to new experiences, compared with dissatisfied patients or satisfied patients who had no physical complications, according to Raymond J. Walls, M.D., an orthopedic surgeon at Cappagh National Orthopedic Hospital in Dublin.

The study also found that patients with higher body mass index were more likely to find the six-month outcome satisfactory despite continuing symptoms.

In a poster presentation here at the American Psychiatric Association meeting, Dr. Walls said the findings could help inform the counseling provided to patients before surgery.

Dr. Walls and his colleagues contacted all patients undergoing total knee arthroplasty at the hospital from January to June 2007 -- 121 in all.

Of these, 110 agreed to complete the Ten-Item Personality Inventory, a brief personality-trait questionnaire administered by telephone.

Five types of traits were assessed: extroversion, agreeableness, conscientiousness, emotional stability, and openness to experiences.

Patients' records were reviewed for scores on the WOMAC osteoarthritis index and Short Form-36 evaluation, conducted in all patients pre-operatively and six months after surgery.

At the six-month mark, 74 patients were satisfied and had no complications, 21 were satisfied with complications, and 15 were unsatisfied, Dr. Walls reported.

Mean body mass index among satisfied patients with complications was 33.1 (SD 6.5), compared with 29.1 (SD 4.2) for unsatisfied patients. The difference was significant at P<0.05.

All three groups showed significant improvement in mean WOMAC scores relative to baseline, with a trend toward higher six-month scores (reflecting greater symptom severity) in the unsatisfied patients than in both satisfied groups.

But only the satisfied groups showed significant improvement from baseline in Short Form-36 scores.

The personality trait analysis showed no differences among groups in agreeableness, conscientiousness, or emotional stability.

But the mean scores on openness were about 3.7 among unsatisfied patients, 4.2 for those satisfied with no complications, and 4.8 for patients satisfied with complications (P<0.05).

There was also a strong but statistically insignificant trend toward greater extroversion in the satisfied-with-complications group compared with the other groups.

Dr. Walls said orthopedic surgeons would do well to take these findings into account when counseling patients prior to surgery.

He said the personality questionnaire used in the study was simple enough to perform routinely.

Patients with personality traits that might increase the risk of dissatisfaction may benefit from extra counseling about realistic expectations from knee replacement surgery, Dr. Walls said.

David Baron, D.O., chairman of the psychiatry department at Temple University in Philadelphia, said patient psychology is very important in their perceptions of outcomes after major surgery.

Pain and mobility outcomes are just one factor in satisfaction following orthopedic procedures, he said. "Maybe they had a good result but were very nervous throughout, and the doctor was cold and didn't really explain things," he said.

Doctors need to understand what the patient wants from the procedure, including the interactions with the physician as well as the clinical outcomes," Dr. Baron said.

But he questioned whether a formal personality inventory was needed.

"Good surgeons already kind of do this," he said.

Dr. Baron said some patients may actually be turned off by a formal screen, joking that some may respond with, "You're my orthopod, what are you, my shrink now?"

Instead, he said, medical school should include psychiatrist-led training on patient counseling.

"They will be better physicians, regardless of their specialty, if they develop these skills in sitting down and getting a sense of where the patient is at, and what do I need to attend to, beyond their medical or orthopedic [need]," Dr. Baron said.

No external funding for the study was reported.

Dr. Walls reported that he had no potential conflicts of interest.

Dr. Baron reported that he had no potential conflicts of interest.

Primary source: American Psychiatric Association
Source reference:
Church H, et al "Do personality traits affect subjective outcomes following total knee arthroplasty?" APA 2009; Abstract NR5-080.

ICD: International Congress of Dermatology Meeting

2009-05-23T22:24:00.000-07:00

ICD: Silica Spheres Enhance Acne Drug
PRAGUE, May 22 -- Silica-encapsulated benzoyl peroxide improved acne more with less skin irritation than a conventional form of the medication, according to results of a randomized clinical trial. Two different strengths of silica-encapsulated drug significantly reduced lesion counts compared with nonencapsulated therapy, Daniela Mavor, of Sol Gel Technologies in Ness Ziona, Israel, reported at the International Congress of Dermatology.

Differences in efficacy and tolerability emerged early and persisted through the study.

"As early as week two, we noted a reduction of acne lesions, which was significantly superior to leading commercial products," Stanley Shapiro, Ph.D., also of Sol Gel, said in a statement. "At week four, a 75% improvement was achieved.

"Throughout the study, the high-strength acne kits were significantly better tolerated than the two commercial products," he said.

Benzoyl peroxide is an established therapy for acne, but the compound often causes burning and irritation that ranges from mild to severe.

Sol Gel Technologies has developed a proprietary delivery vehicle consisting of silica microspheres that form a barrier between the skin and the medication inside the spheres.

The microencapsulating process also leads to a continuous release of the active ingredient, Mavor and colleagues explained in a poster presentation.

Investigators evaluated the safety and efficacy of silica-encapsulated benzoyl peroxide in a clinical trial involving 78 patients, ages 16 to 35, with mild or moderate acne vulgaris.

Disease activity required included at least three comedones (noninflammatory lesions), six or more papules or pustules (inflammatory lesions), no more than 25 lesions of either type, and fewer than four nodulocystic acne lesions.

The patients were randomized to one of four treatment groups: 4% or 7% silica-encapsulated benzoyl peroxide, or a 2.5% or 7% commercially available, nonencapsulated formulation of the acne medication.

Study participants were asked to apply assigned medication twice daily for four weeks. Medication came in a kit that included a cleanser, a toner, and a lotion, applied in sequence according to instructions.

The primary outcome measures were change in number, type, and severity of lesions; safety and tolerability; and change in images obtained at each clinic visit.

By week two, the 7% silica-encapsulated treatment had reduced the total lesion count significantly more than either of the two conventional therapies. The percent reduction from baseline also was significantly greater with the high-dose encapsulated formulation (P=0.016 to P=0.033).

Over the four weeks of the study, the 7% encapsulated formulation led to significantly more improvement compared with the two nonencapsulated formulations (P=0.010, P=0.021).

By Investigator Global Assessment, patients using either strength of encapsulated benzoyl peroxide improved by 40% to 50% from week one to week two. In contrast, little change was noted in patients assigned to the conventional acne therapy.

At weeks three and four, patients using the 4% silica-encapsulated formulation had 75% and 82% improvement, respectively, compared with weeks two and three, Mavor reported.

Patients in the 7% silica-encapsulated arm had improvement of 56% and 75% at weeks three and four, respectively.

A combination of physician- and patient-assessed tolerance showed no difference among the four groups after one week.

By week two, both silica-encapsulated formulations were associated with lower cumulative irritation scores. At weeks three and four, differences between groups reached statistical significance for the encapsulated formulations (P<0.008 for all comparisons).

The lowest dropout rate (5.3%) was noted for patients on 7% silica encapsulated BPO treatment. The highest dropout rate (35.7%) was noted for patients on 2.5% commercial treatment.

The study was funded by Sol Gel Technologies.

Investigators in the study included employees of Sol Gel Technologies.

Primary source: International Congress of Dermatology
Source reference:
Mavor D, et al "Improved efficacy and safety of anti-acne kits based on silica-encapsulated benzoyl-peroxide (BPO)" ICD 2009; Abstract P006.

IL-21 Seen as Critical to Immune System Antiviral Response

2009-05-14T21:27:00.000-07:00

WHEELING, W.Va., May 14 -- Mice lacking the gene for interleukin-21 were unable to halt a normally controllable viral infection, indicating that the cytokine is critical to the immune response, researchers said.

Action Points

Explain to interested patients that some chronic viral infections, including HIV, appear to disable parts of the immune system involved in antiviral responses.

Explain that this study was performed in mice and that it is uncertain to what extent the findings apply to humans.

Note that the findings have no immediate clinical implications but may lead to new treatments in the future.

CD8-positive cytotoxic T cells, known to be vital in suppressing viral infections, were effectively silenced in the IL-21 knockout mice, although CD4-positive cells still functioned normally, Allan Zajac, Ph.D., and colleagues at the University of Alabama at Birmingham reported online in Sciencexpress.

With the CD8-positive cells rendered helpless, lymphocytic choriomeningitis virus (LCMV) ran rampant in the IL-21 knockout animals, whereas normal mice were able to bring the infection under control.

But when the knockout mice were treated with exogenous IL-21, their CD8-positive cells regained signs of normal function and LCMV infections were cut short.

The researchers also found that mice engineered to carry one copy of the gene for IL-21, instead of the normal two copies, produced CD8-positive cells that showed some activity but significantly less than normal.

"Interleukin-21 served as the key messenger between the T cells, whereas before we didn't know exactly how the two types of cells communicated with each other," Dr. Zajac said in a press release.

The findings may help explain why CD8-positive T cells are induced in some viral infections -- including HIV and hepatitis C -- but then fail to act effectively, the researchers said.

It has been known that in the absence of the CD4-positive cells, CD8-positive cells lack some or all of their full functionality.

CD4-positive cells are believed to be the main source of IL-21, which promotes a wide range of immune activities.

Consequently, Dr. Zajac and colleagues guessed that it could be a messenger molecule between the two cell types.

In their experiments, mice with normal IL-21 genes cleared LCMV infections within 50-75 days, whereas viral titers in blood of IL-21 knockout mice remained high for the full 150 days of monitoring, with no animals showing clearance.

In mice with one copy of the IL-21 gene, about half the animals showed LCMV clearance after 75 days, but others showed persistent high viral titers.

Examination of CD8-positive cells from the full knockouts in vitro "revealed severe functional exhaustion," the researchers wrote.

Whereas interferon-gamma, IL-2, and tumor necrosis factor-alpha production was robust in CD8-positive cells taken from normal mice, cells from the knockouts were unable to produce significant levels of these cytokines.

The researchers also determined that induction of CD4-positive cells was reduced significantly during the early stages of LCMV infection.

"Collectively, our findings provide new insights into the determinants of the functional quality of CD8-positive T-cell responses and the role of IL-21 in ensuring the successful control of infection," Dr. Zajac and colleagues wrote.

The impairment of initial CD4-positive T cell responses initially "could be a general feature of infections that elicit nonprotective adaptive immune responses," they added.

Such infections include hepatitis B and C as well as HIV, they said.

The researchers suggested that it might be possible to develop therapies to modulate IL-21 directly or to boost the numbers or activity of cells that produce the cytokine.

The study was funded by the National Institutes of Health.

Potential conflicts of interest were not reported.

Primary source: Sciencexpress
Source reference:
Yi J, et al "A vital role for interleukin-21 in the control of a chronic viral infection" Sciencexpress 2009; DOI: 10.1126/science.1175194.

Pfizer Offers Year of Free Meds to Unemployed

2009-05-14T21:25:00.000-07:00

WHEELING, W.Va., May 14 -- Drug giant Pfizer said unemployed people who have been taking its branded products could receive them free for up to a year in a new program -- with some exceptions.

The program, called MAINTAIN, will provide access to more than 70 Pfizer drugs including atorvastatin (Lipitor), celecoxib (Celebrex), pregabalin (Lyrica), and sildenafil (Viagra).

But the program excludes biologics, most cancer drugs, and other of Pfizer's most expensive products.

Individuals who became unemployed after Jan. 1 of this year are eligible for the program and may sign up through Dec. 31.

Other eligibility requirements include having taken the branded Pfizer drug for at least three months prior to losing a job, having no other prescription drug coverage, and being able to attest to financial hardship.

Income prior to becoming unemployed is not a factor, Pfizer said. But participants who regain employment or prescription drug coverage will have to start paying again.

A stock analyst quoted by the Associated Press pointed out that the program is likely to prevent some current Pfizer drug customers from switching to generic equivalents.

The company said it was taking signups today, although the program would not be fully operational until July 1.

Pfizer said signups and additional information on the MAINTAIN program would be available at Pfizer Helpful Answers or by calling 866-706-2400 toll-free.

Related source:

Pfizer announcement

ASCO: HPV Infection Linked to Better Outcome in Oropharyngeal Cancer

2009-05-14T21:24:00.000-07:00

TORONTO, May 14 -- Patients with oropharyngeal cancer had a 50% lower five-year mortality risk when they also had human papillomavirus (HPV) infection, according to data from a randomized clinical trial.

Action Points

Explain to patients that a type of viral infection improved survival in patients with cancer of the oropharynx.

The findings came from a retrospective review of data, and the effect of HPV status on survival was not a principal outcome.

Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

HPV-positive patients had a two-year overall survival of 88% compared with 66% for HPV-negative patients (P<0.001),>

The difference between groups increased with follow-up. HPV infection also was associated with a reduced risk of locoregional recurrence and second cancers, Dr. Gillison reported at a press briefing in advance of the American Society of Clinical Oncology annual meeting.

Cancer of the oropharynx arises from two principal causes: chronic use of tobacco and alcohol or HPV infection. Previous studies had suggested that HPV status of a patient's tumor might have prognostic implications.

"HPV-positive patients have important associations with other favorable prognostic factors," said Dr. Gillison. "They tend to be younger; they have smaller tumors; they present with better performance status. Therefore, improvement in survival for this patient population may be explained by these factors and not by HPV."

To explore the role of HPV status in survival of oropharyngeal cancer, Dr. Gillison and colleagues reviewed data from a randomized clinical trial conducted by the Radiation Therapy Oncology Group.

Its principal objective was to compare standard chemotherapy with an investigational regimen.

The trial involved 721 patients. Of those, 60% had cancer of the oropharynx and 64% were HPV positive.

The two-year results demonstrated a clear survival advantage associated with HPV infection. Follow-up to five years revealed an overall survival of >75% in HPV-positive patients versus <50%>

The difference remained largely unchanged in an analysis that accounted for other factors, including treatment assignment.

"HPV-positive patients had less than half the risk of dying from their cancer at five years than HPV-negative patients, after considering the effects of other important factors," said Dr. Gillison.

"HPV-positive patients similarly had about half the risk of tumor progression or death, due in part to lower recurrence rates in the radiation field but not lower distant metastases."

As a result of the findings, RTOG and the Eastern Cooperative Oncology Group will begin to stratify all clinical trials by HPV status and possibly design trials specifically for HPV-positive or negative patients, she added.

Dr. Gillison reported no competing interests.

Primary source: American Society of Clinical Oncology
Source reference:
Gillison ML, et al "Human papillomavirus and survival of patients with oropharynx cancer" ASCO 2009.

ASCO: Ginger Eases Chemo-Related Nausea

2009-05-14T21:23:00.000-07:00

TORONTO, May 14 -- Half a teaspoon of ground ginger a day can significantly reduce the nausea associated with chemotherapy, researchers found.

Action Points

Explain to interested patients that ginger is widely used as a folk remedy for upset stomach and diarrhea.

Note that this randomized controlled trial found it was effective, in combination with standard antiemetic drugs, in controlling nausea during chemotherapy.

In a large randomized trial, the spice reduced nausea by 40% when taken along with standard antinausea medications, according to Julie Ryan, Ph.D., of the University of Rochester Medical Center in Rochester, N.Y.

Dr. Ryan told reporters that patients in the study took the spice in capsules, but it should "theoretically" also work in cookies or soft drinks -- as long as the ginger flavor isn't artificial.

The spice -- usually in the form of ginger tea or ginger ale -- is widely used as a folk remedy for upset stomach and diarrhea.

Dr. Ryan's study -- discussed during a curtain-raiser press conference for the annual meeting of the American Society for Clinical Oncology -- is to be presented in Orlando later this month.

Dr. Ryan and her colleagues enrolled 644 cancer patients, most of whom had breast cancer, in their study.

After the patients reported nausea during early cycles of chemotherapy, they were randomized to get either ginger or placebo, along with standard 5-HT3 receptor antagonist antiemetics, such as ondansetron (Zofran) and granisetron (Kytril).

Participants were divided into four arms -- those getting placebo capsules and those getting 0.5, 1.0, and 1.5 grams of ginger.

The ginger was started three days before the beginning of a chemotherapy cycle, and the antiemetics were begun in the first day of each cycle, Dr. Ryan said.

Four times a day during chemotherapy, she said, patients recorded their feelings of nausea on a seven-point scale, ranging from no nausea to extremely nauseated.

Dr. Ryan said average nausea scores were high on all four arms on the morning of the first day of a chemo cycle, but dropped significantly (at P=0.003) for the three ginger arms during the day.

The lower nausea scores were maintained for subsequent days of the cycle, she said.

Dr. Ryan said the two lower doses of the spice appeared to be more effective than the 1.5-gram dose. A gram, she said, is equivalent to about half a teaspoon of ground ginger, dried or fresh.

The research is "an interesting and rigorous study in the field of complementary medicine," said Douglas Blayney, M.D., of the University of Michigan Comprehensive Cancer Center in Ann Arbor and the society's president-elect.

He added that the study result is "an important step forward in improving quality of care for the 70% of patients who undergo chemotherapy and experience nausea and vomiting."

The study was supported by the National Cancer Institute.

Dr. Ryan did not report any conflicts.

Primary source: ASCO 2009

NSAID, COX-2 Use Discouraged for Geriatric Pain

2009-05-14T21:18:00.000-07:00

SAN FRANCISCO, May 14 -- Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors should be virtually eliminated as analgesics in older adults' medicine cabinets under updated geriatric pain management guidelines.

Although the American Geriatrics Society once recommended these agents before consideration of opioids for patients 75 and older with persistent pain, it now calls this strategy too risky.

Persistent pain is common among seniors, Bruce Ferrell, M.D., of the University of California Los Angeles, and colleagues noted in the guidelines.

The document was released at the AGS meeting ahead of publication in the August issue of the Journal of the American Geriatrics Society.

Action Points

Explain to interested patients that NSAIDs and COX-2 inhibitors carry cardiovascular and gastrointestinal risks when used at analgesic doses.

Caution patients that aspirin taken for cardioprotection -- while also an NSAID -- is used at much lower doses than when taken for analgesia.

If ignored or incorrectly treated, pain may cause falls, functional impairment, disruptions in sleep, depression and anxiety, and increased healthcare costs, they said.

However, the cardiovascular risk and gastrointestinal toxicity of NSAIDs usually outweigh the benefits of using them, the guidelines panel said.

They recommended use of NSAIDs and COX-2s only "rarely" and "with extreme caution" in highly selected individuals, such as those for whom safer therapies have failed.

For most seniors, acetaminophen (Tylenol, Excedrin) should be considered as "initial and ongoing pharmacotherapy in the treatment of persistent pain, particularly musculoskeletal pain," they said. They noted that the presence of hepatic insufficiency and/or chronic alcohol use are relative contraindications.

Opioids may be safer than long-term NSAID therapy and should be considered for all patients with moderate-severe or quality-of-life-impacting pain, they added.

Breakthrough pain with opioids should be anticipated and treated with short-acting, immediate-release opioids.

The guidelines noted the potential for opioid-associated adverse effects, which they said clinicians should anticipate and assess along with assessment of safe and responsible use of these powerful analgesics.

For those older patients who do take an NSAID or a COX-2 inhibitor plus aspirin, the panel made the following recommendations:

Use of a proton pump inhibitor or misoprostol (Cytotec) for gastrointestinal protection
Routine assessment of gastrointestinal and renal toxicity, hypertension, heart failure, and other drug-drug and drug-disease interactions
Use of no more than one NSAID or COX-2 inhibitor for pain control
Patients taking aspirin for cardioprophylaxis should not use ibuprofen (Advil, Motrin)

The update also made recommendations for the use of adjuvant painkillers and other drugs for older persons with recalcitrant pain. These included:

All patients with fibromyalgia are candidates for adjuvant analgesics, while those with neuropathic pain are candidates for a trial of these adjuvant agents.
Avoid tertiary tricyclic antidepressants because of elevated risk of adverse effects, such as anticholinergic effects and cognitive impairment.
Reserve long-term systemic corticosteroids for patients with pain-associated inflammatory disorders -- not osteoarthritis -- or metastatic bone pain.
Patients with regional or localized pain may be candidates for topical lidocaine, menthol, or capsaicin treatment.

The AGS guideline revision was based on review of the literature since the last update in 2002 and consensus among the panel of experts in geriatric pain management, pharmacology, rheumatology, neurology, nursing, palliative care, and geriatric clinical practice.

The recommendations focused on treatment of adults 75 and older, who require different pain management than younger people because of complex clinical manifestations, a high rate of concurrent illnesses, and higher potential for medication-related side effects.

However, the panel cautioned that these guidelines are no substitute for keeping abreast of new developments in pain management or for critical thinking, sound judgment, clinical experience, and "an open-minded approach to the unique individual circumstances of each clinical encounter."

Dr. Ferrell reported no conflicts of interest.

His coauthors made disclosures of relationships with Endo Pharmaceuticals, Pfizer, Eli Lilly, GlaxoSmithKline, King Pharmaceuticals, AlPharma, Cephalon, PriCara, Abbot Labs, Alkermes, Ameritox, Ortho-McNeil-Janssen Pharmaceuticals, Wyeth Pharmaceuticals, NeuroAdjuvants, Purdue Pharma, Johnson & Johnson, Novartis, XL Health, Roche, Merck, Smart E-Records, American Academy of CME, UCB Pharma, Healthcare Quality Informatics, and the International Longevity Center.

Primary source: Journal of the American Geriatrics Society
Source reference:
Ickowicz E, et al "Pharmacological management of persistent pain in older persons" J Am Geriatr Soc 2009.

SID: Actinic Keratoses Have Cyclic Nature

2009-05-11T11:11:00.000-07:00

MONTREAL, May 8 -- Actinic keratoses are dynamic lesions with intermittent expression in subjects with even extensive damage, according to an 11-month study of their natural course.

Action Points

Explain to interested patients that thick, scaly, or crusty patches of skin known as actinic keratoses are often precursors of nonmelanoma skin cancer.

Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

"At any one time, less than half of the lesions are present clinically," said Craig Elmets, M.D., who reported his findings here at the Society for Investigative Dermatology meeting.

The frequent regression and recurrence of lesions has implications for the treatment of actinic keratoses (AK), which are precursors to squamous cell carcinomas, said Dr. Elmets, of the University of Alabama in Birmingham.

"In patients with extensive actinic damage, peel treatment may be a very good approach to treating these lesions," Dr. Elmets said. "If one is going to treat individual lesions, then they need to be treated very aggressively because at any one time only a minority of the AK are present."

Dr. Elmets and colleagues followed AK lesions in 26 individuals with extensive actinic damage. At baseline, the study participants had between 10 and 40 actinic lesions and at least one prior histological diagnosis of an AK or nonmelanoma skin cancer.

Mapping of the lesions was done at baseline and again at three, six, nine, and 11 months. The lesions were also biopsied at both baseline and the end of the study.

"If a lesion that had been selected for biopsy was no longer present clinically, the site where it had been was still biopsied," Dr. Elmets explained.

At baseline, there was a total number of 610 AKs in the study group (mean 23.5 per individual), and this number was not significantly different at the end of the study, despite the development of 973 new lesions over the 11-month period.

About 40% of the lesions present at baseline had regressed by month 11, and nearly 200 of the lesions that were present at baseline regressed and then recurred, Dr. Elmets said. "A total of 51 of the lesions regressed twice."

Using a histologic grading scheme that was based on a cervical dysplasia model, he noted little progression in severity of lesions in terms of proliferation, atypia, or both.

"The histologic appearance seems to accurately correlate with the clinical appearance, and over the course of 11 months there was little evidence of histologic progression," he said.

AK lesions have strong predictive value for individuals who will eventually develop basal cell or squamous cell carcinomas," Dr. Elmets said, "but until now their natural history has not been well understood."

ASH: Resistant Hypertension Yields to Experimental Darusentan

2009-05-11T11:08:00.000-07:00

SAN FRANCISCO, May 11 -- The novel endothelin receptor antagonist darusentan nearly doubled the blood pressure control rate compared with placebo in patients previously unable to reach treatment goals, researchers said here.

Action Points

Caution patients that darusentan is not FDA approved for treatment of hypertension or any other indication.

Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In a phase III trial, darusentan also reduced 24-hour systolic pressure by about 8 mm Hg and diastolic pressure by about 7 mm Hg compared with placebo, Michael A. Weber, M.D., of the SUNY Downstate Medical College in Brooklyn, N.Y., reported at the American Society of Hypertension meeting.

This agent could be a "magic bullet" for these difficult-to-treat patients, commented George Bakris, M.D., of the University of Chicago, who moderated a press conference at which the findings were presented.

Another endothelin antagonist, bosentan (Tracleer) is approved in the U.S. for treatment of pulmonary arterial hypertension.

"We need to see further data with this," Dr. Bakris said, noting that a second phase III trial in resistant hypertension is still underway.

"If the data is as robust there as it is here, I don't think there's any question that you could move forward," such as testing it for use in nonrefractory hypertension, Dr. Bakris said.

The DAR-311 trial included 379 patients not at their systolic blood pressure goal (140 mm Hg or 130 mm Hg for those with diabetes or chronic kidney disease) despite antihypertensive therapy with at least three drugs from different classes, including a diuretic, at full or maximally tolerated doses.

Previous therapy included an ACE inhibitor or angiotensin-receptor blocker for 95% to 99% of participants, a calcium channel blocker for 69% to 79%, and a beta-blocker for 62% to 68%.

Participants were randomized to placebo or 50, 100, or 300 mg of darusentan on top of their existing drug regimen for 14 weeks.

At the end of this period, all three dose groups showed greater blood pressure results than placebo.

For the primary endpoint of change in blood pressure from baseline to week 14, the results were:

8.6 mm Hg lower systolic pressure and 5.3 lower diastolic pressure with placebo
16.5 mm Hg lower systolic pressure and 10.1 mm Hg lower diastolic pressure with 50 mg darusentan (both P<0.001>
18.1 mm Hg lower systolic pressure and 9.9 mm Hg lower diastolic pressure with 100 mg darusentan (both P<0.001>
18.1 mm Hg lower systolic pressure and 10.7 mm Hg lower diastolic pressure with 300 mg darusentan (both P<0.001>

Ambulatory blood pressure showed the same significant improvements with all three darusentan doses compared with placebo (P<0.001),>P<0.001>

Heart rate changes were not significantly different across groups, but there was a possible signal for increased cardiovascular adverse events with the experimental agent.

There was one sudden cardiac death in the placebo group whereas in the darusentan groups combined there were two MIs in patients with a prior history of coronary artery disease, one recurrence of heart failure in a patient with a history of heart failure -- Dr. Weber said inclusion of that patient in the trial was a protocol violation -- and two cases of heart failure with preserved left ventricular ejection fraction responsive to diuretic therapy.

"To my mind these latter patients are just evidence of fluid retention, not evidence of a real cardiac effect," Dr. Weber said. "There's no reason to anticipate that there would be any cardiovascular safety issue."

Edema was the most common adverse effect with the drug, as expected, at 15% to 24% compared with 10% among placebo-treated patients. Most cases were mild to moderate in severity.

Patients treated with darusentan were also more likely to experience decreases in hemoglobin (0.19, 0.92, 0.93, and 1.08 g/dL in the placebo, darusentan 50, darusentan 100, and darusentan 300 groups, respectively).

The drug did not affect white blood cell or platelet counts or appear to cause liver injury, although one patient each in the two higher dose groups had elevated liver enzymes as did one in the placebo group.

The study was supported by Gilead Sciences.

Dr. Weber reported being on the speakers' bureau for Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Forest Pharmaceuticals, GlaxoSmithKline, Novartis, and sanofi-aventis and serving as a consultant for Boehringer-Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Forest Pharmaceuticals, GlaxoSmithKline, Gilead, Novartis, and Takeda Pharmaceuticals.

Dr. Bakris reported conflicts for Abbott, GlaxoSmithKline, Novartis, Merck, Gilead, Pharmacopoeia, NicOx, Daiichi Sankyo, Forest, Walgreens, Takeda, and the Juvenile Diabetes Research Foundation.

Three other co-authors were employees of Gilead Sciences.

Primary source: American Society of Hypertension
Source reference:
Weber M, et al "Fixed doses of darusentan as compared to placebo in treatment-resistant hypertension" ASH 2009; Abstract LB-OR-06.

SID: Cardiovascular Mortality Risk Debated in Severe Psoriasis

2009-05-11T11:07:00.000-07:00

ONTREAL, May 11 -- Mortality rates over nearly 30 years were significantly increased in patients with severe psoriasis compared with rates in the general population, results of two studies showed.

Action Points

Explain to interested patients that although death rates were higher in psoriasis patients in both studies presented, one study showed an increase in cardiovascular deaths and the other didn't.

Note that these studies were published as abstracts and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

But the studies differ on whether cardiovascular mortality is increased, according to the researchers who reported on them at the annual meeting of the Society for Investigative Dermatology.

"In patients with extremely severe psoriasis, there is an increased risk of death from noncardiovascular, but not cardiovascular causes," said Robert Stern, M.D., of Harvard and Beth Israel Deaconess Medical Center.

His findings are in direct contrast to those of another study presented in the same session, and conflict with a growing body of evidence.

"Severe psoriasis may be an independent risk factor for cardiovascular mortality," said Rahat Azfar, M.D., of the University of Pennsylvania, whose study showed a 50% increase in cardiovascular deaths in this patient population.

"Dr. Stern's study results need to be interpreted with extreme caution due to the inherent bias in his study design," warned Joel Gelfand, M.D., M.S.C.E., also of the University of Pennsylvania, and an investigator on the study reported by Dr. Azfar.

Numerous studies, dating back to the 1970s, have shown that patients with psoriasis, particularly severe disease, have an increased cardiovascular risk, said Dr. Gelfand in an interview.

His group has also shown that psoriasis is associated with an increased risk of myocardial infarction (MI) and stroke, independent of traditional cardiovascular risk factors for these events.

"Previous studies of cardiovascular mortality have not controlled for traditional cardiovascular risk factors, as our work has done," commented Dr. Azfar.

Dr. Azfar and colleagues examined records from the U.K.'s General Practice Research Database from 1987 through 2002. The cohort consisted of more than 3,000 patients with severe psoriasis matched to more than 14,000 controls.

Compared with controls, patients with severe psoriasis had a significantly increased risk of all-cause mortality (odds ratio [OR] 1.78), Dr. Azfar said.

After controlling for traditional cardiovascular risk factors including stroke, transient ischemic attack, diabetes, hypertension, hyperlipidemia, age, gender, body mass index, and smoking, the psoriasis patients had a clinically significant increased risk of cardiovascular death (hazard ratio [HR] 1.55).

This risk was modified by age, with patients 40 and younger being at greater risk (HR 2.65) than those between 41 and 60 (HR 1.90).

This translated to an excess risk of 5.78 cardiovascular deaths per 10,000 person years at age 40, and 58.9 per 10,000 person years at age 60, Dr. Azfar said.

"Patients with psoriasis, especially if disease is severe, should be counseled about managing traditional cardiovascular risk factors as part of their routine care," she concluded.

Dr. Stern agreed that cardiovascular risk factors are important in patients with severe psoriasis, but his data suggest that they are no more important than other risk factors.

"A lot of people with psoriasis are scared by some of the new data. They say 'I have severe psoriasis, so that means I am more likely to die from a heart attack.' But our data showed that liver disease and nonmelanoma skin cancer accounted for more than half the approximately 70 excess deaths we observed in our cohort," he said.

His prospective study followed 1,376 patients from the PUVA cohort study for 28 years, from 1976 to 2004.

The patients were from 16 tertiary care academic centers across the U.S., with a disease severity ranging from mild to extreme severity. They underwent 22 cycles of interviews.

Comparing the observed and expected mortality rates among patients and controls, Dr. Stern and colleagues found an increased all-cause mortality rate (HR 1.51) among only those patients with the most severe psoriasis, defined as a body surface involvement (BSA) of 43 to 100%.

When cause of death was examined in this extremely severe disease group, noncardiovascular reasons explained the increased risk (HR 1.74), and there was a nonsignificant increase in the rate of cardiovascular deaths compared to controls (HR 1.29), Dr. Stern said.

"If you are a psoriasis patient, don't think about your psoriasis killing you, or giving you a heart attack. Think about all the other things that you need to do to stay healthy," Dr. Stern said in an interview.

Dr. Stern's study design compares apples to oranges, commented Dr. Gelfand.

"Patients who participate in psoriasis clinical trials at tertiary care medical centers may be healthier, better educated, and have better access to medical care than the general U.S. population," he noted.

"Our study used the epidemiological gold standard design -- in that it was population-based and, in effect, compared apples to apples," Dr. Gelfand said.

Dr. Stern explained that, among the noncardiovascular causes of death in his study, liver disease and nonmelanoma skin cancer conferred "a substantially significant increased risk."

"Those two types of mortality probably reflect our population, which got a fair amount of PUVA therapy and subsequent UV therapy, which increases the risk of those tumors. The liver disease probably stems from the fact that alcohol use seems to be more prevalent among people with psoriasis, and also our cohort had a very high level of exposure to methotrexate."

Exposure to PUVA therapy might also be an explanation for the lack of increased cardiovascular mortality in Dr. Stern's psoriasis group, suggested James Krueger, M.D., Ph.D., from New York's The Rockefeller University, during the question period.

"PUVA is one of the best treatments we have to suppress skin inflammation and it may actually modify the natural history of inflammation, both in the skin and systemically, so I think this might even suggest that PUVA treatment alters the cardiovascular risk of this disease," Dr. Krueger said.

Dr. Azfar's study was funded by funded by the National Institutes of Health and a grant from Centocor.

Dr. Azfar declared no conflicts of interest.

Dr. Stern made no statement on funding and declared no conflicts of interest.

SID: Melanoma in U.S. Shows Steady Increase

2009-05-11T11:02:00.000-07:00

MONTREAL, May 11 -- The incidence of melanoma in the U.S. increased rapidly over a 12-year period -- across socioeconomic lines and for all tumor thicknesses -- according to a study reported here.

Action Points

Explain to interested patients that malignant melanoma is the most dangerous form of skin cancer and is believed to result from exposure to ultraviolet light.

Explain that UV exposure also contributes to premature aging of the skin, and the most common source of UV is the sun.

Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

During the study period from 1992 to 2004, the incidence of all thicknesses of melanoma increased from 18.2 per 100,000 to 26.3 per 100,000 (95% CI 25.7 to 27.0) -- an annual increase of 3.1% (P<0.001),>

A total of 70,596 new cases was reported over the period.

"This has implications for preventive screening and primary care," Eleni Linos, M.D., Ph.D., of Stanford University Medical Center, told colleagues at the Society for Investigative Dermatology meeting here.

"We believe this represents a genuine increase in melanoma cases, not just a sign of better screening," she said in an interview.

Her study, published in the Journal of Investigative Dermatology, examined data from the Surveillance Epidemiology and End Results (SEER) registry between 1992 and 2004. (See: Reports of Increases in Melanoma Incidence Are Real).

The research focused only on non-Hispanic white subjects, in whom 90% of melanomas occur, said Dr. Linos.

Melanoma affects both sexes, but during the period of the study, cases involving women outnumbered those in men by a 3:2 margin.

The steepest increase and highest overall incidence occurred in men ages 65 years and older, with the rate rising from 73 to 126 new cases per 100,000 (CI 120.2 to 132.4). Among women the rate was 51 per 100,000 (CI 50.8 (47.5 to 54.2).

Among those younger than 65 years, incidence rates were 18.8 cases per 100,000 in men (CI 18.0 to 19.6) and 17.9 cases among women (CI 17.1 to 18.7).

Fortunately, the increase in overall incidence was not matched by an increase in mortality, which rose by 0.4% annually, with a 2% annual rise in older men.

"The vast majority of melanomas that are diagnosed are thin, and that is why we have not seen such a dramatic increase in mortality rates," Dr. Linos explained.

Researchers examined melanoma trends according to socioeconomic status to determine whether the findings could be explained by better screening in those with higher brackets, and by higher mortality rates in those with lower socioeconomic status.

Similarly, tumor thickness was examined to determine whether the increased incidence could be explained by more diagnoses of thin, clinically insignificant tumors.

"We found parallel increases across all socioeconomic groups and thicknesses, representing a true increase in clinically significant tumors," she said.

Dr. Linos reported no conflicts of interest.

ECO: Physical Activity May Be Driven by Biological Regulator

2009-05-07T20:54:00.000-07:00

LITTLE FALLS, N.J., May 7 -- More physical education programming in school won't necessarily increase a child's total physical activity levels, researchers said.

Action Points

Explain that kids who went to schools with more time devoted to physical activity had no difference in total activity levels compared with their peers who went to schools with fewer hours dedicated to physical education.

Explain that the findings suggest that the body may regulate physical activity similar to the way it regulates other factors such as appetite.

Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In fact, kids in schools that devoted extensive time to physical activity showed no difference in total activity levels compared with peers in schools with fewer phys ed classes, Terence J. Wilkin, M.D., and colleagues reported at the European Congress on Obesity in Amsterdam.

The finding suggests that the body may regulate physical activity much the way it regulates appetite.

"Environmental opportunity does not control physical activity," Dr. Wilkin said. "What we're looking at is a brain control of physical activity. If a child is imposed upon to undertake physical activity at one time of day, then they will down-regulate at another in order to meet a set point."

Dr. Wilkin said there is debate about what controls physical activity. Some researchers say it is environmental -- the more green space or parental encouragement that a child has to exercise, the higher his or her physical activity levels will be.

But Dr. Wilkin and colleagues said biological mechanisms may be at work.

"Nature is most unlikely to leave physical activity to chance because it's the only modifiable component of energy expenditure that you have available. Over evolution, energy conservation would have been absolutely crucial to survival of the species," Dr Wilkin said.

"So it's likely that nature will have built in a control of physical activity and this study is all about establishing whether or not you can see that control working."

To test the hypothesis, researchers conducted a prospective study of 206 children ages 7 to 11 from three schools that offered very different amounts of physical education -- average of 9.2, 2.4, and 1.7 hours/week, respectively.

The children wore accelerometers to measure total daily physical activity, only taking them off while they slept. Each child did this for one week during each of four consecutive school terms.

The researchers found that children in the school with the highest levels of physical education programming had about 40% more in-school activity than the other two schools (P<0.001).>

But there were no significant differences in total weekly physical activity between the children in the three schools.

"Those children who've had the opportunity during the course of the day to exercise wilt when it comes to the evening," Dr. Wilkin said. "Those who didn't have the opportunity voluntarily recorded very large amounts of activity."

Even after adjustment for rainfall and daylight hours, the results remained the same.

"This doesn't mean that more activity is not good for you, because more activity is good for you," Dr. Wilkin said. "It raises the question of how do you engineer the situation that will create more activity."

Although engineering environmental factors such as physical activity in school is the "intuitive thing to do," Dr. Wilkin said, it may have only limited effects.

The researchers aren't sure of the exact mechanism by which the body regulates activity, but Dr. Wilkin said the existence of this "activity-stat, like thermostat" is highly likely.

"Thryroid function, adrenal function, potassium levels, sodium levels are constant because they're constantly being monitored and constantly being adjusted," Dr. Wilkin said. "I believe the same thing is happening with activity. How, I don't know."

The study was supported by Bright Future Trust, Child Growth Foundation, Nestle, Kirby Laing Foundation, London Law Trust, and the EarlyBird Diabetes Trust.

The researchers reported no conflicts of interest.

Primary source: European Congress on Obesity
Source reference:
Mallam K, et al "Impact of physical education on the body composition and metabolic health of primary school children" ECO 2009; Abstract 920.

FDA Requires New Warnings for Testosterone Gels

2009-05-07T20:53:00.000-07:00

WHEELING, W.Va., May 7 -- To prevent children from accidental exposure to the products, two testosterone gels will now be required to carry a boxed warning, the FDA announced.

The two products -- AndroGel 1% and Testim 1% -- have been linked to eight confirmed cases of virilization of children 9 months to 5 years of age. The children came into skin-to-skin contact with adults who were using the products, the agency said today.

Both agents are approved for men who produce low levels of testosterone or none at all.

Current labels on the gels instruct users to apply it to the shoulders or upper arms. AndroGel is also approved for application to the abdomen. The instructions also tell users to wash their hands after application and to cover the treated area with clothing.

The secondary exposures to children appeared to occur because users fail to follow these instructions, said Dianne Murphy, M.D., director of the FDA's Office of Pediatric Therapeutics, at a press briefing.

Of the fully reviewed cases, children developed inappropriate enlargement of the genitalia (penis or clitoris), pubic hair, advanced bone age, increased libido, and/or aggressive behavior, the agency found.

In most cases, these effects regressed when the children were no longer exposed to the gels. However, in a few cases, enlarged genitalia did not fully return to age-appropriate size and bone age remained modestly greater than the child's chronological age.

The effects led to surgery in one child due to misdiagnosis of the actual cause.

Dr. Murphy said more than a dozen other cases were still under review.

The boxed warning will give additional information about the risk of secondary exposure and the steps that should be taken to reduce this risk.

These steps include:

Adults who use testosterone gels should wash their hands with soap and warm water after every application.
Adults should cover the application site with clothing once the gel has dried.
Adults should wash the application site thoroughly with soap and warm water before any skin-to-skin contact with another person is anticipated.
Children and women should avoid contact with testosterone application sites on the skin of men who use these products.
Adults should note that use of any similar, but unapproved, products from the marketplace -- including the Internet -- that can result in the same serious adverse effects should be avoided.

Dr. Murphy said 1.4 million prescriptions for AndroGel and 370,000 for Testim were filled in 2007.

Women received 25,000 of the AndroGel prescriptions, she added.

FDA officials declined to comment specifically on why women would use the gels, but Mark Hirsch, M.D., of the agency's reproductive and urologic drugs division, noted that some people believe testosterone products can enhance female libido.

Dr. Murphy said small children were especially sensitive to the gels because their ratio of skin surface area to volume or weight is much higher than in adults.

Dialysis Patients Take the Most Pills

2009-05-07T20:51:00.000-07:00

SAN FRANCISCO, May 7 -- At an average of 19 pills a day, dialysis patients may have the highest pill burden seen in any chronic disease.

The high number of phosphate binders and other drugs taken daily by dialysis patients may impact their quality of life, said researchers led by Rajnish Mehrotra, M.D., of the University of California Los Angeles.

A quarter of the 233 chronic dialysis patients in their study took at least 25 pills each day, the investigators reported online in the Clinical Journal of the American Society of Nephrology.

One patient downed 70 a day, Dr. Mehrotra said.

Although pill burden is best known as an issue in HIV/AIDS treatment because of the dozens of tablets patients had to take in early regimens, most regimens now include fewer than 20 pills a day.

Action Points

Explain to interested patients that pill burden is a measure of the number of total pills prescribed to be taken daily rather than the number of separate medications.

Note that the study could not eliminate potential confounding nor draw a causal link between pill burden and quality of life.

The average for diabetes mellitus is two to four pills a day and for congestive heart failure is 10 to 11, the researchers noted.

Dialysis patients have a high burden of coexisting diseases that require medication, but the single largest contributor to pill burden in the study was phosphate binders, the researchers noted.

The patients in the cross-sectional study done at three university-affiliated dialysis units across the country took a mean of 11 different medications, including two parenteral drugs on average.

Phosphate binders accounted for 49% of the daily pill burden, which exceeded 10 in 91% of the dialysis patients, 20 in 47%, and more than 30 in 17%.

Higher total pill burden was independently associated with lower health-related quality of life on the physical subscale of the SF 36 questionnaire in the multivariate analysis (P<0.001).>

Other significant factors in physical health-related quality of life were greater comorbidity and lower serum albumin.

Surprisingly, the psychological effect of pill burden did not appear to be significant. The mental component of health-related quality of life did not correlate with pill burden in either the univariate or multivariate analyses.

The only mental health-related quality of life predictors were lower serum phosphorus level and shorter duration on dialysis (P<0.01).>

"It is tempting for us to speculate that a high pill burden makes people feel worse because they have all the attendant side effects of medication," Dr. Mehrotra said.

But he noted that in this type of study confounding can never be eliminated with certainty, and the lack of effect on the mental health component suggested that pill burden might have been a surrogate for more severe disease.

However, it's likely that the association reflects both reasons, Dr. Mehrotra said.

Overall median medication adherence was 72%, but only 38% of patients were fully adherent to the prescribed phosphate binder therapy.

Both total pill burden and phosphate binder pill burden were linked to lower adherence (P=0.03 and P=0.003, respectively) with a threshold of 12 for phosphate binders.

However, taking more phosphate binders was not linked to lower serum phosphate levels.

"It appears reasonable to conclude that reducing pill burden may improve patient adherence," the investigators said, although they acknowledged that the study could not determine whether that would be the case.

Since frequency of phosphate binders cannot be reduced, choosing an agent that requires fewer pills may be prudent, as would attention to causes of out-of-range phosphate levels, such as diet, Dr. Mehrotra said.

The study was funded by a grant from Shire Pharmaceuticals, the makers of the phosphate binder lanthanum carbonate.

Dr. Mehrotra reported grant support and honoraria from Shire Pharmaceuticals as well as conflicts of interest with Amgen, Baxter Health Care, and Novartis.

Primary source: Clinical Journal of the American Society of Nephrology
Source reference:
Chiu Y-W, et al "Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients" Clin J Am Soc Nephrol 2009.

First Clues in H1N1 Outbreak Came in March

2009-05-07T20:44:00.000-07:00

in the current H1N1 (swine) flu outbreak was a 10-year-old asthmatic boy in San Diego County, Calif., who developed fever, cough, and vomiting on March 30.

Two days later, he was treated for his symptoms in an urgent-care clinic and physicians took a nasopharyngeal swab, according to Fatimah Dawood, M.D., of the CDC and colleagues.

That sample, together with one taken from a nine-year-old California girl about the same time, was the first clue that a novel triple-reassortant influenza A virus was circulating, Dr. Dawood and colleagues reported online in the New England Journal of Medicine.

Action Points

Explain to interested patients that this package of research and commentary provides details about the current outbreak of H1N1 (swine) flu, as well as historical information about similar viruses.

Their paper is part of a five-paper package of research and commentary published by the journal.

The H1N1 strain -- swine-origin influenza A (H1N1) virus, or S-OIV for short -- was quickly shown to have novel genetics, including genes from triple-reassortant swine influenza viruses that were known to circulate among swine herds in North America and two genes (encoding the neuraminidase and matrix proteins) that were similar to those seen in Eurasian pigs.

"This particular genetic combination of influenza virus segments had not been seen before in the U.S. or elsewhere," the researchers said.

Triple-reassortant swine flu viruses -- with elements of human, bird, and pig flu -- are not unknown, according to Lyn Finelli, Dr.P.H., of the CDC and colleagues.

Such chimeric strains emerged in pig herds in the U.S. in the late 1990s and caused at least 11 cases of human disease from December 2005 through February 2009, Dr. Finelli and colleagues said in another paper in the journal.

The median age of the 11 patients was 10 and four had underlying health conditions. Nine had been exposed to pigs, five through direct contact and four through visits to a location where pigs were kept.

In another patient, human-to-human transmission was suspected.

Among the 10 patients with known clinical symptoms, all reported cough, 90% reported fever, 60% reported headache, and 30% reported diarrhea. Four patients had complete blood counts, with leukopenia in two, lymphopenia in one, and thrombocytopenia in another.

Four patients were hospitalized and two had mechanical ventilation. Four patients were given oseltamivir (Tamiflu), and all 11 recovered from their illness.

Dr. Dawood and colleagues -- dealing with a much larger outbreak -- described some of the clinical characteristics of the 642 confirmed cases reported up to May 5, 2009:

Patients ranged in age from three months to 81 years and 60% were 18 or younger.
Of patients with available data, 18% had recently traveled to Mexico and 16% were identified from school outbreaks.
The most common symptoms were fever (94%), cough (92%), and sore throat (66%) -- similar to those seen in seasonal flu -- but 25% of patients had diarrhea, and 25% had vomiting, which are not typical of seasonal flu.
Of the 399 patients for whom hospitalization status was known, 36 (9%) required inpatient care. Of 22 inpatients with available data, 12 had characteristics that conferred an increased risk of severe seasonal influenza, 11 had pneumonia, eight were admitted to an intensive care unit, four had respiratory failure, and 2 died.

One implication of the symptoms is that clinicians should be aware of the possibility of a gastrointestinal route of transmission, Dr. Dawood told reporters.

As of May 5, the researchers said, 18 of the 22 inpatients (82%) had recovered from acute illness but two patients -- a previously healthy 23-month-old child and a previously healthy 30-year-old woman -- remained critically ill with respiratory failure.

A 22-month-old child with neonatal myasthenia gravis and a 33-year-old woman who was pregnant when she became ill died, the researchers said.

The current epidemic virus "is only the latest influenza virus, not the last," according to Robert Belshe, M.D., of Saint Louis University in St. Louis, Mo.

Writing in an accompanying editorial, Dr. Belshe said the outbreak demonstrates the need for increased financial support for surveillance, public health efforts, and vaccine development.

He argued that the outbreak "brings out the best and worst of contemporary society."

One on hand, he said, the genetics of the virus were identified rapidly, the information was widely disseminated, and public health activities were heightened.

On the other, "inflammatory political posturing has occurred that illustrates the need for effective communication by physicians and scientists to the public."

The publication of the papers comes as the World Health Organization continues to warn that the H1N1 strain could reach pandemic status.

As the H1N1 (swine) flu outbreak continues to spread, a central question is what happens as the southern hemisphere enters its winter months, an official of the agency said.

If the virus becomes established in the southern hemisphere -- triggering a change to the full pandemic level -- as many as two billion people could become infected, according to Keiji Fukuda, M.D., the agency's assistant director-general for health, security, and environment.

"If you look at past pandemics, it would be a reasonable estimate to say perhaps a third of the world's population would get infected with the virus," he told reporters.

Even if most cases are mild, Dr. Fukuda told reporters, "that's a lot of people to get infected" and some will certainly have severe disease and die.

There could be a "very large numbers of people who could develop pneumonia, require respirators, and who could die," he said.

But he wouldn't speculate on how many might die if the virus outbreak becomes a pandemic.

"It's very premature to make those kinds of projections," he said, especially since much is still unknown about the H1N1 virus and how it behaves, both clinically and epidemiologically.

Dr. Fukuda said that the WHO is very concerned about what will happen in the south, where conditions are very different than they are in North America and Europe.

Among other worries, he said, many areas of the southern hemisphere have populations that are especially vulnerable to infections -- those suffering from malnutrition, in wars zones, with an underlying health issue such as HIV.

Even when the seasonal flu strikes, he said, those populations are often severely affected.

Dr. Dawood and colleagues did not report study support or any potential conflicts.

Dr. Finelli and colleagues did not report study support or any potential conflicts.

Dr. Belshe reported serving as a consultant or speaker for MedImmune and Novartis.

Primary source: New England Journal of Medicine
Source reference:
Dawood FS, et al "Emergence of a novel swine-origin influenza A (H1N1) virus in humans" N Engl J Med 2009; 361.

Additional source: New England Journal of Medicine
Source reference:
Shinde V, et al "Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009" N Engl J Med 2009; 361.

Additional source: New England Journal of Medicine
Source reference:
Belshe R "Implications of the emergence of a novel H1 influenza virus" N Engl J Med 2009; 361

School Kids 'Wagging' Breakfast Are Missing Healthy Brain Fuel

2009-03-24T23:06:00.000-07:00

The national MBF Healthwatch survey has revealed that a disturbing number of children 'wag' breakfast claiming there is 'no time' to eat, they are 'too tired' or 'can't be bothered' having a meal before going to school.

The survey found that 22% of parents interviewed said their children skip breakfast on three to five school days of each week, and a further 20% skip breakfast on one or two school days.

The remaining 58% of parents said their school aged children always ate breakfast before school.

Bupa* Chief Medical Officer Dr Christine Bennett said, "It is disturbing to find that 42% of children are sent to school on one or more days on an empty stomach because it sends a clear message at an early age that breakfast isn't important.

"Wagging breakfast is the healthy lifestyle equivalent of driving your car on an empty petrol tank - it inevitably runs out when you most need it.

"Research shows that skipping breakfast results in reduced learning, reduced attention and poor food choices for the rest of the day. Children who skip breakfast are more likely to be overweight which in the long term can lead to the development of chronic health issues.

"Children who miss out on breakfast are also less likely to get the recommended intake of dairy, fruit and vegetables," she said.

Asked why their children missed out on breakfast before school, just over half (51.6%) of parents said there was no time because of the pressures of being late for school or work or because of sleeping in.

"Parents should encourage their children to eat breakfast. Storing a few simple ingredients in the cupboard or fridge or organising breakfast the night before can help in the morning rush. Healthy shakes and cereal bars are great for eating on the way to school. Toast, yoghurt and fruit are also quick, easy options," Dr Bennett said.

Viewed nationally, the MBF Healthwatch survey showed that children missed breakfast at an average rate of 1.2 days a week - Tasmanian children were least likely to miss breakfast at 0.6 while Queensland and Western Australia had the worst record for breakfast 'wagging' at 1.4 and 1.5 days respectively.

"With many competing demands, we know that Australian families live in a 'time poor' society but the importance of making time for children to enjoy a healthy breakfast before going to school cannot be overstated," Dr Bennett said. "It can be the start of a lifetime of healthy eating habits," she said.

Notes:

The MBF Healthwatch survey was conducted by research consultancy TNS Healthcare. For more information on the MBF Healthwatch Survey, please visit: http://www.mbf.com.au/wellness

*Bupa Australia cares for its customers under the brands MBF, HBA, Mutual Community, ClearView and Bupa Care Services.

Source: Matt Allison
Research Australia

Alpha-Waves Precede Blunders, New Study Finds

2009-03-24T23:05:00.000-07:00

A distinct alpha-wave pattern occurs in two brain regions just before subjects make mistakes on attention-demanding tests, according to a new study by researchers from the University of California, Davis, and the Donders Institute

From spilling a cup of coffee to failing to notice a stop sign, everyone makes an occasional error due to lack of attention. Now a team led by a researcher at the University of California, Davis, in collaboration with the Donders Institute in the Netherlands, has found a distinct electric signature in the brain which predicts that such an error is about to be made.

The discovery could prove useful in a variety of applications, from developing monitoring devices that alert air traffic control operators that their attention is flagging, to devising new strategies to help children cope with attention deficit hyperactivity disorder (ADHD). The work will be posted online on March 23 by the journal Human Brain Mapping as part of a special issue highlighting innovations in electromagnetic brain imaging that will be published in May.

How the brain responds to mistakes has been the subject of numerous studies, said Ali Mazaheri, a research fellow at the UC Davis Center for Mind and Brain. "But what I was looking for was the state the brain is in before a mistake is made," he said, "because that's what can tell us what produces the error."

Working with colleagues at the Donders Institute for Brain, Cognition and Behavior at Radboud University, where he was a Ph.D student at the time, Mazaheri recruited 14 students into his study. While they took an attention-demanding test, Mazaheri recorded their brain activity using MEG - magnetoencephalography - a non-invasive brain-wave recording technique similar to, but more sensitive than electroencephalography (EEG), the technique commonly used in hospitals to detect seizures.

The test, known as the "sustained attention response task," was developed in the 1990s to evaluate brain damage, ADHD and other neurological disorders. As participants sit at a computer for an hour, a random number from 1 to 9 flashes onto the screen every two seconds. The object is to tap a button as soon as any number except 5 appears.

The test is so monotonous, Mazaheri said, that even when a 5 showed up, his subjects spontaneously hit the button an average of 40 percent of the time.

By analyzing the recorded MEG data, the research team found that about a second before these errors were committed, brain waves in two regions were stronger than when the subjects correctly refrained from hitting the button. In the back of the head (the occipital region), alpha wave activity was about 25 percent stronger, and in the middle region, the sensorimotor cortex, there was a corresponding increase in the brain's mu wave activity.

"The alpha and mu rhythms are what happen when the brain runs on idle," Mazaheri explained. "Say you're sitting in a room and you close your eyes. That causes a huge alpha rhythm to rev up in the back of your head. But the second you open your eyes, it drops dramatically, because now you're looking at things and your neurons have visual input to process."

The team also found that errors triggered immediate changes in wave activity in the front region of the brain, which appeared to drive down alpha activity in the rear region, "It looks as if the brain is saying, 'Pay attention!' and then reducing the likelihood of another mistake," Mazaheri said.

It shouldn't take too many years to incorporate these findings into practical applications, Mazaheri said. For example, a wireless EEG could be deployed at an air traffic controller's station to trigger an alert when it senses that alpha activity is beginning to regularly exceed a certain level.

It could also provide new therapies for children with ADHD, he said. "Instead of watching behavior - which is an imprecise measure of attention - we can monitor these alpha waves, which tell us that attention is waning. And that can help us design therapies as well as evaluate the efficacy of various treatments, whether it's training or drugs."

Notes:

Collaborating in the study were Ingrid Nieuwenhuis, Hanneke van Dijk and principal investigator Ole Jensen, all at the Donders Institute.

Support for this work was provided by the framework of the Netherlands Organization for Scientific Research (NWO) and BrainGain Smart Mix Programme of the Netherlands Ministry of Economic Affairs. Ali Mazaheri is currently funded by a Rubicon grant From NWO.

About UC Davis

For 100 years, UC Davis has engaged in teaching, research and public service that matter to California and transform the world. Located close to the state capital, UC Davis has 31,000 students, an annual research budget that exceeds $500 million, a comprehensive health system and 13 specialized research centers. The university offers interdisciplinary graduate study and more than 100 undergraduate majors in four colleges - Agricultural and Environmental Sciences, Biological Sciences, Engineering, and Letters and Science - and advanced degrees from five professional schools: Education, Law, Management, Medicine, and Veterinary Medicine. The UC Davis School of Medicine and UC Davis Medical Center are located on the Sacramento campus near downtown.

Source: Liese Greensfelder
University of California - Davis

Research provides new perspective on the way kids think

2009-03-24T23:02:00.001-07:00

For parents who have found themselves repeating the same warnings or directions to their toddler over and over to no avail, new research from the University of Colorado at Boulder offers them an answer as to why their toddlers don't listen to their advice: they're just storing it away for later.

Scientists -- and many parents -- have long believed that children's brains operate like those of little adults. The thinking was that over time kids learn things like proactively planning for and understanding how actions in the present affect them in the future. But the new study suggests that this is not the case.

"The good news is what we're saying to our kids doesn't go in one ear and out the other, like people might have thought," said CU-Boulder psychology Professor Yuko Munakata, who conducted the study with CU doctoral student Christopher Chatham and Michael Frank of Brown University. "It also doesn't go in and then get put into action like it does with adults. But rather it goes in and gets stored away for later."

A paper on their study titled "Pupillometric and Behavioral Markers of a Developmental Shift in the Temporal Dynamics of Cognitive Control" will appear in the Proceedings of the National Academy of Sciences the week of March 23.

"I went into this study expecting a completely different set of findings," said Munakata. "There is a lot of work in the field of cognitive development that focuses on how kids are basically little versions of adults trying to do the same things adults do, but they're just not as good at it yet. What we show here is they are doing something completely different."

During the study, the CU-Boulder researchers used a computer game designed for children, and a technique known as pupillometry -- a process that measures the diameter of the pupil of the eye to determine the mental effort of the child -- to study the cognitive abilities of 3-and-a-half-year-olds and 8-year-olds.

The computer game involved teaching children simple rules about two cartoon characters -- Blue from Blue's Clues and SpongeBob Squarepants -- and their preferences for different objects. In the directions for the game, children were told that Blue likes watermelon, so they were to press the happy face on the computer screen only when they saw Blue followed by a watermelon. When SpongeBob appeared, they were told to press the sad face on the screen.

"The older kids found this sequence easy, because they can anticipate the answer before the object appears," Chatham said. "But preschoolers fail to anticipate in this way. Instead, they slow down and exert mental effort after being presented with the watermelon, as if they're thinking back to the character they had seen only after the fact."

Using pupillometry to determine the time at which children exerted mental effort, the speed of their responses for each type of sequence and the relative accuracy of those responses, the researchers found that children neither plan for the future nor live completely in the present. Instead, they call up the past as they need it.

"For example, let's say it's cold outside and you tell your 3-year-old to go get his jacket out of his bedroom and get ready to go outside. You might expect the child to plan for the future, think 'OK it's cold outside so the jacket will keep me warm,' " said Chatham. "But what we suggest is that this isn't what goes on in a 3-year-old's brain. Rather, they run outside, discover that it is cold, and then retrieve the memory of where their jacket is, and then they go get it."

Munakata doesn't claim to be a parental expert, but she does think their new study has relevance to parents' daily interactions with their toddlers.

"If you just repeat something again and again that requires your young child to prepare for something in advance, that is not likely to be effective," Munakata said. "What would be more effective would be to somehow try to trigger this reactive function. So don't do something that requires them to plan ahead in their mind, but rather try to highlight the conflict that they are going to face. Perhaps you could say something like 'I know you don't want to take your coat now, but when you're standing in the yard shivering later, remember that you can get your coat from your bedroom."

Munakata said the findings have broader implications for research in the field of cognitive development.

"Further study could help people figure out why kids are doing poorly or well in different educational settings," she said.

http://www.colorado.edu/

Childhood soy consumption may reduce breast cancer among Asian women

2009-03-24T23:00:00.000-07:00

American women who ate higher amounts of soy during childhood had a 58 percent reduced risk of breast cancer, according to a study published in Cancer Epidemiology, Biomarkers and Prevention , a journal of the American Association for Cancer Research.

"Historically, breast cancer incidence rates have been four to seven times higher among white women in the U.S. than in women in China or Japan. However, when Asian women migrate to the U.S., their breast cancer risk rises over several generations and reaches that of U.S. white women, suggesting that modifiable factors, rather than genetics, are responsible for the international differences. These lifestyle or environmental factors remain elusive; our study was designed to identify them," said Regina Ziegler, Ph.D., M.P.H., a senior investigator in the NCI Division of Cancer Epidemiology and Genetics (DCEG).

The current study focused on women of Chinese, Japanese and Filipino descent who were living in San Francisco, Oakland, Los Angeles or Hawaii. Researchers interviewed 597 women with breast cancer and 966 healthy women. If the women had mothers living in the United States, researchers interviewed those mothers to determine the frequency of soy consumption in childhood.

Researchers divided soy intake into thirds and compared the highest and lowest groups. High intake of soy in childhood was associated with a 58 percent reduction in breast cancer. A high level of soy intake in the adolescent and adult years was associated with a 20 to 25 percent reduction. The childhood relationship held in all three races and all three study sites, and in women with and without a family history of breast cancer. "Since the effects of childhood soy intake could not be explained by measures other than Asian lifestyle during childhood or adult life, early soy intake might itself be protective," said the study's lead investigator, Larissa Korde, M.D., M.P.H., a staff clinician at the NCI's Clinical Genetics Branch.

"Childhood soy intake was significantly associated with reduced breast cancer risk in our study, suggesting that the timing of soy intake may be especially critical," said Korde. The underlying mechanism is not known. Korde said her study suggests that early soy intake may have a biological role in breast cancer prevention. "Soy isoflavones have estrogenic properties that may cause changes in breast tissue. Animal models suggest that ingestion of soy may result in earlier maturation of breast tissue and increased resistance to carcinogens."

As provocative as the findings are, Ziegler cautioned that it would be premature to recommend changes in childhood diet. "This is the first study to evaluate childhood soy intake and subsequent breast cancer risk, and this one result is not enough for a public health recommendation," she said. "The findings need to be replicated through additional research."

http://www.aacr.org/

Drinkers Beware: Face Flushing Sign of Cancer Risk

2009-03-24T22:59:00.000-07:00

(Ivanhoe Newswire) -- If your face gets flushed when you drink alcohol, you could be in danger of developing esophageal cancer.

Researchers said facial flushing after drinking is predominately caused by an inherited deficiency in an enzyme called aldehyde dehydrogenase 2, or ALDH2. There is growing evidence that ALDH2-deficient people are at a much higher risk of esophageal cancer, specifically squamous cell carcinoma, from alcohol consumption than those individuals with fully active ALDH-2.

Doctors from the National Institute on Alcohol Abuse and Alcoholism, the National Institutes of Health and the Kurihama Alcohol Center in Japan are trying to spread the word that people who experience facial flushing after drinking should reduce their alcohol consumption and be screened for endoscopic cancer.

There are about 540 million ALDH-2-deficient patients in the world, so even a small percent reduction in esophageal cancers due to a reduction in alcohol drinking would translate into a substantial number of lives saved, researchers said.

Esophageal cancer is one of the deadliest cancers, with five-year survival rates of 15.6 percent in the United States, 12.3 percent in Europe and 31.6 percent in Japan. Nearly one third of East Asians experience facial flushing, nausea and an increased heart rate after drinking alcohol.

SOURCE: PLoS Medicine, March 2009

Genetic Clues to Treating Schizophrenia

2009-03-24T22:56:00.000-07:00

(Ivanhoe Newswire) -- Scientists discovered a gene that may control the way some people who suffer from mental illnesses such as schizophrenia and bipolar disorder respond to medications.

Researchers at Scotland's University of Edinburgh also identified seven proteins that are important to the development of mental illnesses, and they said they hope their discovery will help doctors create new medicines to target these proteins.

Using existing data from the landmark Human Genome Project, the researchers analyzed variations of a gene called DISC1 and found that it affects a number of other genes that current medications are designed to target. They said by identifying those patients in whom DISC1 may be a root cause of illness, they may be able to target the patients for whom these drugs would be most effective.

"We know that disorders such as schizophrenia have a genetic element and that this specific gene, DISC1, is important to that process," lead author William Hennah of the Finland Institute for Molecular Medicine was quoted as saying. "This research helps us to understand exactly how it affects brain development and provides clues about how to solve problems where that process goes wrong."

SOURCE: Public Library of Science One, 2009

Scientists Find Link Between Vertigo And Osteoporosis

2009-03-24T22:53:00.000-07:00

Scientists in Korea found that people with osteoporosis, a disease that lowers bone density and increases risk of fracture, are also more likely to have vertigo, a dizziness disorder caused by problems in the inner ear.

The study was the work of Dr Ji Soo Kim, of Seoul National University College of Medicine in Korea, and colleagues, and is published in the 24 March issue of the journal Neurology.

For the study, Kim and colleagues examined 209 people with benign positional vertigo (BPV) for which there was no known cause and compared them with 202 people with no history of dizziness (the controls).

BPV can sometimes result from ear surgery or head trauma and is thought to be when crystals of calcium carbonate become loose and move around in the tubes of the inner ear that help people to balance.

For the osteoporosis data, the researchers used the bone mineral density measures of front and back lumbar spine and femur of the participants.

After adjusting for age, sex, alcohol, smoking, and hyperphosphatemia (a condition that can also lower calcium levels), the results showed that people with low bone density, or osteoporosis, were three times more likely to have vertigo than people with normal bone density.

They also showed that people with osteopenia, the stage before osteoporosis, were twice as likely to have vertigo as people with normal bone density.

The results showed gender differences in that 25 per cent of women with vertigo were more likely to have osteoporosis compared with only 9 per cent of women who did not have vertigo. For men, 12 per cent of those with vertigo had osteoporosis compared with 6 per cent without vertigo.

The researchers concluded that:

"Osteopenia/osteoporosis may be associated with idiopathic benign positional vertigo (BPV). The effectiveness of measuring bone mineral densitometry and restoring normal calcium metabolism for preventing recurrences of BPV requires further validation."

Kim said in a press statement that:

"These findings suggest a problem with calcium metabolism in people with vertigo."

"Women most often have their first case of vertigo in their 50s, when they are also having a drop in bone mass due to loss of estrogen," added Kim, explaining that "estrogen is one of the main hormones that influence calcium and bone metabolism."

So far, no one has discovered whether estrogen plays a role in vertigo, and since men also get vertigo, Kim suggests other factors must also be involved.

Sources: Journal abstract, American Academy of Neurology .

Written by: Catharine Paddock, PhD

ImVisioN Therapeutics Reports Positive Phase I Clinical Results For Treatment Of Cat Dander Allergy

2009-03-22T12:09:00.000-07:00

ImVisioN Therapeutics AG, a biopharmaceutical company pioneering intralymphatic immunotherapy (ILIT™), today announced that it has obtained positive Phase I clinical results for its lead product, IVN201 (Cat-MAT), an immunotherapeutic product for the treatment of cat dander allergy.

The study was conducted from August 2008 to March 2009 in a total of 20 patients with allergy to cat dander. The results demonstrated an excellent safety profile and exceptional tolerability in allergic patients. In addition, the IVN201 program showed the first signs of efficacy as measured by several clinical parameters. The double-blind, placebo-controlled clinical study was conducted at the University Hospital in Zurich, Switzerland.

Based on these results, ImVisioN plans to close a Series B Financing Round by mid-2009, which will be used to fund Phase II clinical studies of Cat-MAT and to start clinical trials with Birch-MAT to treat birch pollen allergy and Mite-MAT to treat house dust-mite allergy, respectively.

Martin Steiner, Chief Executive Officer and Co-Founder of ImVisioN, said: "We are delighted to report that the results of our first human clinical study with IVN201 have demonstrated an outstanding safety profile together with immunological effects and indications of clinical efficacy. These results are remarkable for a first-in-man clinical study and we are now very keen to begin a subsequent Phase II trial with a larger number of patients."

About ImVisioN Therapeutics

ImVisioN Therapeutics is a private biotechnology company headquartered in Switzerland. The Company is the pioneer in intralymphatic immunotherapy (ILIT™), a proprietary technology for the delivery of immunotherapy in the treatment of allergies. ILIT is clinically proven and has been shown to be a safer, more efficacious and more convenient means of delivering allergy therapeutics. By combining ILIT with another proprietary technology, Modular Antigen Transporter (MAT), ImVisioN leverages the potential of ILIT for the development of drugs that use allergens safely for specific and highly effective antigen presentation. ImVisioN's lead product is for the treatment of cat dander allergy and the Company has programs addressing birch pollen and house dust mite allergy. The Company's proprietary technology platforms are applicable to further allergy targets, which may be addressed in future.

Intralymphatic immunotherapy (ILIT™)

ImVisioN is the pioneer of intralymphatic immunotherapy (ILIT), a clinically proven proprietary technology for the safe and effective delivery of allergy immunotherapy. Traditional allergen specific immunotherapy can cure severe allergies but involves multiple physician consultations (50 to 80 visits for subcutaneous injection) over a prolonged period of time and the risk of severe reactions to the treatment. Intralymphatic immunotherapy (ILIT) can achieve a cure within as little as 3 injections due to the efficient processing within the cells of the immune system located predominantly in the lymph nodes. ILIT is expected to have several advantages over other treatment alternatives:

- Improved safety profile
- Rapid therapeutic effect
- Improved patient compliance (reduced number of injections)

ILIT was recently demonstrated to be safe and efficacious in a clinical setting comparing it to traditional (subcutaneous) immunotherapy with grass pollen extract. Patients receiving ILIT had significantly fewer adverse events and achieved cure of allergy much faster (3 months as opposed to 1 year) and with substantially reduced amounts of the allergen (3,000 units as opposed to 4,000,000 units) than with traditional allergy immunotherapy.

IVN201 against cat dander allergy

ImVisioN's lead product, IVN201, is a safe, efficacious alternative developed using the proprietary MAT technology for intralymphatic immunotherapy. The therapy uses the molecule Fel d1 (the major cat dander allergen) for the allergen module of the MAT molecule. Fel d1 is a potent allergen with more than 80% of cat allergy patients being sensitized to it.

Clinical Trial Exploring Use Of Cardiac Device In New Groups Of Heart Failure Patients Completes Enrollment Phase

2009-03-22T12:06:00.000-07:00

Medtronic, Inc. (NYSE: MDT) announces completion of the enrollment phase of 1,800 patients in the RAFT clinical trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial), which is studying the impact of cardiac resynchronization therapy in mildly symptomatic heart failure patients, or those at risk of worsening heart failure, but not currently indicated under medical guidelines to receive treatment with the device.

"This study is important to guide therapy for heart failure patients with milder heart failure symptoms who have a dilated heart and poor heart function. These patients have a tendency to develop worsening symptoms, to require hospitalization, and they may die prematurely. This study will determine if cardiac resynchronization therapy, when used earlier in the disease, can delay or prevent the progression of heart failure," said Anthony Tang, M.D., RAFT Nominated Principal Investigator and Adjunct Professor of Medicine, University of Ottawa.

More than 22 million people worldwide - including 500,000 Canadians and 5 million Americans - have heart failure, a condition in which the heart cannot adequately pump blood to the body. Cardiac resynchronization therapy is a proven treatment for some patients with moderate to severe heart failure (New York Heart Association, or NYHA Class III and ambulatory Class IV) that improves the heart's pumping efficiency, may help to reduce heart failure symptoms as well as hospitalizations, and may improve quality of life and reduce mortality. The RAFT trial is one of several clinical trials underway to determine whether patients with mild or fewer symptoms (NYHA Class II) also may benefit from cardiac resynchronization therapy.

"Medtronic-sponsored research has demonstrated the utility of cardiac device therapy in heart failure patients," said Marshall Stanton, M.D., vice president of clinical research for the Cardiac Rhythm Disease Management business at Medtronic. "The aim of these efforts is to ensure more heart failure patients who could benefit from our therapies are able to receive them."

About RAFT

A double-blinded, randomized, controlled trial, RAFT is led by the University of Ottawa Heart Institute and jointly supported by a peer reviewed grant from Medtronic and the Canadian Institutes of Health Research (CIHR). It involves 1,800 patients with mild to moderate heart failure (NYHA Class II and III), left ventricular ejection fraction (LVEF, a measure of the heart's pumping effectiveness) less than or equal to 30 percent and QRS duration of greater than or equal to 120 milliseconds. Patients in the control group received either a single or dual chamber ICD; patients in the "experimental" arm received a cardiac resynchronization therapy-defibrillator. The primary outcome is a composite of total mortality and heart failure hospitalization; secondary outcomes include total mortality, cardiovascular mortality, sudden arrhythmic death, health related quality of life, and cost economics. Patients will be followed for a minimum of 18 months.

About Heart Failure and Cardiac Resynchronization Therapy

- Heart failure is a major economic burden, with the high incidence of hospitalizations as a major cost driver. Estimates place the cost of treating Canadian patients with moderate to severe heart failure at up to $2.3 billion CAD annually1. In the United States, it costs $34.5 billion annually2.

- Chronic heart failure occurs when the heart is unable to pump enough blood to sustain adequate circulation in the body's tissues.

- The initial manifestation in heart failure is a decrease in blood output from the left ventricle. In many cases, this decrease in pumping output is accompanied by errant impulses from the heart's electrical system. These can result in accelerated rhythms that adversely affect the heart's ability to pump blood and are potentially lethal.

- Cardiac resynchronization therapy uses an implantable device to improve the pumping efficiency of the heart and increase blood flow to the body.

- Cardiac resynchronization therapy is intended to complement standard drug therapy, and dietary and lifestyle modifications.

- Some heart failure patients may also be at risk for sudden cardiac death and are eligible to receive an implantable-cardioverter defibrillator (ICD), a device that uses electrical impulses to stop fatal heart rhythms, or a combination cardiac resynchronization therapy defibrillator. Recent studies have shown that ICD therapy significantly reduces death from sudden cardiac arrest in patients with heart failure and poor heart pumping function.

Caution: Similar studies to RAFT, using CRT devices in this patient population, are being conducted in the United States. The use of CRT devices is limited by federal (or United States) law for this indication.

About Medtronic

Medtronic, Inc. , headquartered in Minneapolis, is the global leader in medical technology - alleviating pain, restoring health, and extending life for millions of people around the world.

Any forward-looking statements are subject to risks and uncertainties such as those described in Medtronic's Annual Report on Form 10-K for the year ended April 25, 2008. Actual results may differ materially from anticipated results.

1 J.D. Bentkover et al. New technologies and potential cost savings related to morbidity and mortality reduction in Class III/IV heart failure patients in Canada. International Journal of Cardiology; 88(2003) 33-41.

2Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics - 2008 update: a report from the Ame

tional Journal of Cardiology; 88(2003) 33-41.

2Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics - 2008 update: a report from the Ame

Genzyme Receives Positive Opinion For European Approval Of Renvela For Patients With Kidney Disease

2009-03-22T12:03:00.000-07:00

Genzyme Corporation (Nasdaq: GENZ) announced that the European Medicines Agency's Committee for Human Medicinal Products (CHMP) has adopted a positive opinion for the marketing authorization of the new phosphate binder Renvela® (sevelamer carbonate) for use in patients with chronic kidney disease (CKD), including patients not on dialysis, with serum phosphorous levels > 1.78 mmol/L (5.5 mg/dL).

Genzyme's filing in Europe for Renvela includes both tablet and powder formulations for the control of serum phosphorus in adult hyperphosphatemic CKD patients. The CHMP opinion will be forwarded to the European Commission, which will make a final decision on the authorization. The European Commission generally follows the advice of the CHMP, but is not obligated to do so. A decision from the European Commission is expected at the end of May.

"Upon approval this will represent a significant addition to the treatment options available to nephrologists," said Professor Markus Ketteler, Professor of Medicine and Clinical Nephrologist, Klinikum Coburg, Academic Teaching Hospital of the University of Würzburg, Germany. "Physicians will hopefully soon have an approved non-absorbed, calcium-free phosphate binder to use with hyperphosphatemic patients, regardless of their dialysis status, with the added flexibility of a powder formulation."

"We are delighted with this positive opinion," said John P. Butler, President, Cardiometabolic & Renal, at Genzyme. "If confirmed by the European Commission, this will be the first phosphate binder for patients not on dialysis approved through the centralized procedure. This is an acknowledgement of the value Renvela is expected to bring to patients with CKD."

Renvela is a next-generation version of renagel® (sevelamer hydrochloride), a calcium-free, metal-free, non-absorbed phosphate binder, and has the added benefit of a carbonate buffer. In a clinical study comparing Renvela to Renagel, both drugs controlled serum phosphorus equally to within recommended KDOQI1 range.

In the United States, Genzyme launched Renvela in its tablet formulation for patients with CKD on dialysis in March 2008. The company is also seeking FDA approvals of the powder formulation and for the treatment of hyperphosphatemic CKD patients not on dialysis.

Elevated serum phosphorus levels are common in patients with CKD because phosphorus is not easily filtered by the diseased kidneys and therefore builds up in the body. This can lead to calcification of tissues, and increased risk of cardiovascular mortality. Controlling serum phosphorus is therefore an important element in the care of patients with CKD.

About Renvela and Renagel

Renvela (sevelamer carbonate) and Renagel (sevelamer hydrochloride) are currently the only phosphate binders available that do not contain either calcium or a metal. Sevelamer, the active moiety in both Renagel and Renvela, has an established safety profile and is not systematically absorbed. It is used by more than 350,000 patients worldwide.

Renvela and Renagel are indicated for the control of serum phosphorus in patients with chronic kidney disease (CKD) on dialysis. Sevelamer is contraindicated in patients with hypophosphatemia or bowel obstruction. Caution should be exercised in patients with dysphagia, swallowing disorders, severe gastrointestinal (GI) motility disorders including severe constipation or major GI tract surgery. Common adverse events reported with sevelamer include vomiting, nausea, diarrhea, dyspepsia, abdominal pain, and constipation. Other events reported include pruritus, rash, fecal impaction, and intestinal obstruction. Drug-drug interactions may occur with some medications and should be taken into consideration when instructing patients how to take sevelamer. Patients should be informed to take sevelamer with meals and to adhere to their prescribed diets.

About Genzyme

One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 11,000 employees in locations spanning the globe and 2008 revenues of $4.6 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation.

With many established products and services helping patients in nearly 90 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune disease, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.

This press release contains forward-looking statements regarding Genzyme's future business plans and strategies, including without limitation: the anticipated receipt of marketing authorization for Renvela from the European Commission and the expected timing thereof; and the potential receipt of FDA approval of the powder formulation of Renvela and for use in CKD patients not on dialysis. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those forecasted. These risks and uncertainties include, among others: whether the European Commission approves Renvela and the actual timing of the decision; whether the FDA approves the powder formulation of Renvela; whether the FDA approves the use of Renvela in CKD patients not on dialysis; and the risks and uncertainties described in Genzyme's SEC reports filed under the Securities Exchange Act of 1934, including the factors discussed under the caption "Risk Factors" in Genzyme's Annual Report on Form 10-K for the period ended December 31, 2008. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of today's date and Genzyme undertakes no obligation to update or revise the statements.

Genzyme®, Renvela® and Renagel® are registered trademarks of Genzyme Corporation or its subsidiaries. All rights reserved.

Genzyme's press releases and other company information are available at genzime.com and by calling Genzyme's investor information line at 1-800-905-4369 within the United States or 1-678-999-4572 outside the United States.

1 The National Kidney Foundation's 2003 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for Bone Metabolism and Disease in CKD recommend sevelamer as a first-line treatment option to control phosphorus.

Source
Genzyme

2009-03-20T06:21:00.001-07:00

comming soon