LONDON, June 29 -- Bolstering the GI tract with a mix of disease-fighting microbes significantly reduced the occurrence of diarrhea associated with antibiotics and Clostridium difficile, according to investigators here.
Hospitalized patients who consumed a probiotic milkshake twice a day during antibiotic therapy had 75% fewer episodes of diarrhea they reported online in BMJ.
The drink, containing Lactobacillus casei, L. bulgaricus, and Streptococcus thermophilus, also kept the GI tracts clear of diarrhea-causing C. difficile, said research dietitian Mary Hickson, M.D., of Imperial College and Hammersmith Hospital, and colleagues, on the basis of a placebo-controlled trial.
Diarrhea complicates antibiotic therapy in 5% to 25% of patients, she noted. C. difficile causes 15% to 25% of the antibiotic-related cases of diarrhea, mostly affecting older patients.
Probiotics have demonstrated a beneficial effect in various gastrointestinal disorders, including diarrhea related to infection and antibiotic use, Dr. Hickson and her colleagues wrote. Lactobacilli, bifidobacteria, and Streptococcus species all have been evaluated for prevention and treatment of diarrhea. Several reviews have supported the benefits of probiotics.
The investigators evaluated the effects of a probiotic supplement in 135 hospital patients on antibiotic therapy. The patients' mean age was 74 years, and at admission all were free of diarrhea and of conditions that might cause diarrhea.
The patients were randomized to probiotic therapy or matching placebo. Twice daily during antibiotic therapy and for one week afterward all patients consumed a 100 mL milkshake. Patients randomized to active therapy received a supplement containing L. casei, L. bulgaricus, and S. thermophilus.
The primary outcome was occurrence of antibiotic-associated diarrhea. The secondary outcome was diarrhea associated with the presence of C. difficile toxin.
Of 57 evaluable patients assigned to probiotic therapy, seven (12%) developed diarrhea during antibiotic treatment compared with 19 of 56 (34%) in the placebo group. The difference translated into an odds ratio of 0.25, reflecting a 75% reduction in diarrhea incidence (P=0.007). None of the patients in the probiotic group had diarrhea associated with C. difficile, but nine of 53 (17%) in the placebo group did (P=0.001).
The probiotic supplement efficiently prevented diarrhea associated with antibiotic use and the presence of C. difficile, as indicated by the number needed to treat to prevent a single case of diarrhea. For antibiotic use the number needed to treat was five, and the probiotic supplement prevented a case of C. difficile-associated diarrhea for every six patients treated.
A cost analysis showed that the amount to prevent one case of antibiotic-associated diarrhea would be in the range of $100 and prevention of a single case of diarrhea related to C. difficile would cost about $120.
Dr. Hickson and colleagues concluded that probiotic therapy "has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50." The further stated their belief that the results are generalizable to any population of older hospitalized patients.
The study was supported by the Healthcare Foundation and Hammersmith Hospital Trustees and Danone Vitapole. Dr. Hickson and some of her co-investigators disclosed that they had received travel funds from Danone Vitapole to attend an international conference on probiotics.Additional source: BMJSource reference: Hickson M, et al. "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial." BMJ. 2007;epub.
Saturday, June 30, 2007
Atypical Hyperplasia Risks Grow with the Number of Sites
ROCHESTER, Minn., June 29 -- Women with atypical hyperplasia in three or more places in the breast have a sharply increased risk of developing breast cancer, researchers here said.
Atypical hyperplasia -- also known as atypia -- is well known to increase the risk of breast cancer by about four times that faced by women who don't have the condition, according to Amy Degnim, M.D., of the Mayo Clinic.
But, as she and her colleagues reported in the July 1 issue of the Journal of Clinical Oncology, when atypia is seen in several places in the breast, the risk doubles to eight times.
Other factors tending to increase the risk are younger age at diagnosis and the presence of calcifications, the researchers said.
Their findings come from an analysis of 331 women with atypia -- members of the 9,376-strong Mayo Benign Breast Disease Cohort, who had breast biopsies from 1967 through 1991.
Followed for an average of 13.7 years, 66 developed breast cancer, the researchers reported. Compared to the general population, that works out to a risk ratio of 3.88, with a 95% confidence interval from 3.0 to 4.94 -- in close accord with previous estimates.
But the researchers also found:
Family history did not appear to make a difference; the risks were much the same whether the women had a strong, weak, or negative family history of breast cancer.
Women diagnosed at a younger age had significantly higher risk ratios compared to age-matched expected rates - 6.76 for those diagnosed younger than 45, 5.10 for those diagnosed from 45 through 55, and 2.87 for those diagnosed at an older age. The trend was significant at P=0.01.
The risks increased with the number of foci of atypia - 2.33 for a single focus, 5.26 for two foci, and 7.97 for three or more. The trend was significant at P<0.001.
A small number of women - 38 -- had both three or more foci and calcifications and their risk was 10.4 times that of the general population.
The analysis also showed that the relative risk of breast cancer for the group was elevated for several years, with 20-year and 25-year cumulative risks of 21% and 29%, respectively.
When the participants were stratified on the basis of the number of foci, the 25-year cumulative risks were 18% for a single focus, 45% for two foci, and 49% for three or more.
The value of the findings to clinicians lies in the ability to stratify risk, Dr. Degnim said.
"We can have more informed discussions with our patients regarding their personal risk," she said. "This will help us to have individualized discussions regarding how aggressively to pursue risk-reduction treatments."
The most commonly used tool to predict risk in women with atypia is the so-called Gail model, Dr. Degnim said, which used such factors as age at onset of menses, age at birth of first child, number of previous breast biopsies, presence of atypia, and number of close relatives with breast cancer.
But that model may not be accurate, she said, because the current study suggests that family history plays little or no role.
The research was supported by the Department of Defense, the Susan G. Komen Breast Cancer Foundation, the Breast Cancer Research Foundation, and the Fred C. and Katherine B. Andersen Foundation. The authors said they had no potential conflicts. Primary source: Journal of Clinical OncologySource reference: Degnim AC et al. "Stratification of Breast Cancer Risk in Women with Atypia: a Mayo Cohort Study." J Clin Oncol 2007;25:2671-77.
Atypical hyperplasia -- also known as atypia -- is well known to increase the risk of breast cancer by about four times that faced by women who don't have the condition, according to Amy Degnim, M.D., of the Mayo Clinic.
But, as she and her colleagues reported in the July 1 issue of the Journal of Clinical Oncology, when atypia is seen in several places in the breast, the risk doubles to eight times.
Other factors tending to increase the risk are younger age at diagnosis and the presence of calcifications, the researchers said.
Their findings come from an analysis of 331 women with atypia -- members of the 9,376-strong Mayo Benign Breast Disease Cohort, who had breast biopsies from 1967 through 1991.
Followed for an average of 13.7 years, 66 developed breast cancer, the researchers reported. Compared to the general population, that works out to a risk ratio of 3.88, with a 95% confidence interval from 3.0 to 4.94 -- in close accord with previous estimates.
But the researchers also found:
Family history did not appear to make a difference; the risks were much the same whether the women had a strong, weak, or negative family history of breast cancer.
Women diagnosed at a younger age had significantly higher risk ratios compared to age-matched expected rates - 6.76 for those diagnosed younger than 45, 5.10 for those diagnosed from 45 through 55, and 2.87 for those diagnosed at an older age. The trend was significant at P=0.01.
The risks increased with the number of foci of atypia - 2.33 for a single focus, 5.26 for two foci, and 7.97 for three or more. The trend was significant at P<0.001.
A small number of women - 38 -- had both three or more foci and calcifications and their risk was 10.4 times that of the general population.
The analysis also showed that the relative risk of breast cancer for the group was elevated for several years, with 20-year and 25-year cumulative risks of 21% and 29%, respectively.
When the participants were stratified on the basis of the number of foci, the 25-year cumulative risks were 18% for a single focus, 45% for two foci, and 49% for three or more.
The value of the findings to clinicians lies in the ability to stratify risk, Dr. Degnim said.
"We can have more informed discussions with our patients regarding their personal risk," she said. "This will help us to have individualized discussions regarding how aggressively to pursue risk-reduction treatments."
The most commonly used tool to predict risk in women with atypia is the so-called Gail model, Dr. Degnim said, which used such factors as age at onset of menses, age at birth of first child, number of previous breast biopsies, presence of atypia, and number of close relatives with breast cancer.
But that model may not be accurate, she said, because the current study suggests that family history plays little or no role.
The research was supported by the Department of Defense, the Susan G. Komen Breast Cancer Foundation, the Breast Cancer Research Foundation, and the Fred C. and Katherine B. Andersen Foundation. The authors said they had no potential conflicts. Primary source: Journal of Clinical OncologySource reference: Degnim AC et al. "Stratification of Breast Cancer Risk in Women with Atypia: a Mayo Cohort Study." J Clin Oncol 2007;25:2671-77.
Commission on Veterans’ Care Recommends Measures to Improve Treatment at Home
By JACQUELINE PALANK
WASHINGTON, June 29 — The presidential commission investigating problems in health care for military personnel wounded in Iraq and Afghanistan held its final hearing Friday, and focused on problems with moving patients through various stages of aid, from Defense Department hospitals to those run by the Veterans Administration or private health care, to home care and to jobs.
Today’s veterans are more likely than those of previous conflicts to suffer from “polytrauma,” including burns, brain injury and shrapnel from explosives, members of the commission said, making their treatment more complicated.
The health care system should also take into account the strain that puts on family members, commissioners said, and should make more use of contractors who can help in out-patient care.
The commission, led by Donna E. Shalala, a Democrat and former secretary of health and human services, and Bob Dole, the Republican presidential nominee in 1996, was established in March after articles in The Washington Post described poor conditions at the Walter Reed Army Medical Center here.
“We’re very solution-driven,” Ms. Shalala said of the panel. “We will not be issuing a report that points fingers.”
Because today’s wounds are different and the families of the veterans are different — many are older, with homes and spouses to return to — more veterans should be allowed to return home for treatment, commissioners said.
Returning patients to their homes can relieve the strain on some families, said commissioners, who reported that some relatives must now leave their homes and jobs to assist with their service members’ treatment in distant hospitals run by the Departments of Defense or Veterans Affairs. But caring for injuries at home requires support from the V.A., they said, and support offered now is often insufficient.
Another consideration is that the patients’ physical wounds are also accompanied by post-traumatic stress disorder, commissioners said.
The hearing on Friday was the commission’s seventh, and several members of Congress who have introduced legislation on veterans care came to testify. Mr. Dole and Ms. Shalala asked if they would include the commission’s recommendations in pending legislation.
“We would welcome suggestions, absolutely,” said Senator Carl Levin, Democrat of Michigan and chairman of the Senate Armed Services committee.
Mr. Levin said the Senate’s veterans bill, which is scheduled for the floor, seeks to improve medical record sharing between the military and the Department of Veterans Affairs as well as address discrepancies in the disability ratings each department uses to determine how much in benefits a service member is paid each month.
Representative Steve Buyer, Republican of Indiana and the ranking member of the House Veterans’ Affairs Committee, said he was concerned that the departments did not adequately use private contractors to provide outpatient treatment, which could allow patients to receive care at home rather than have to travel to a veterans hospital.
“If we’re patient-centric, we should allow the transition of that patient to occur,” Mr. Buyer said.
Ms. Shalala said, “This is a different war in which we have people who have families and they want to go home.”
WASHINGTON, June 29 — The presidential commission investigating problems in health care for military personnel wounded in Iraq and Afghanistan held its final hearing Friday, and focused on problems with moving patients through various stages of aid, from Defense Department hospitals to those run by the Veterans Administration or private health care, to home care and to jobs.
Today’s veterans are more likely than those of previous conflicts to suffer from “polytrauma,” including burns, brain injury and shrapnel from explosives, members of the commission said, making their treatment more complicated.
The health care system should also take into account the strain that puts on family members, commissioners said, and should make more use of contractors who can help in out-patient care.
The commission, led by Donna E. Shalala, a Democrat and former secretary of health and human services, and Bob Dole, the Republican presidential nominee in 1996, was established in March after articles in The Washington Post described poor conditions at the Walter Reed Army Medical Center here.
“We’re very solution-driven,” Ms. Shalala said of the panel. “We will not be issuing a report that points fingers.”
Because today’s wounds are different and the families of the veterans are different — many are older, with homes and spouses to return to — more veterans should be allowed to return home for treatment, commissioners said.
Returning patients to their homes can relieve the strain on some families, said commissioners, who reported that some relatives must now leave their homes and jobs to assist with their service members’ treatment in distant hospitals run by the Departments of Defense or Veterans Affairs. But caring for injuries at home requires support from the V.A., they said, and support offered now is often insufficient.
Another consideration is that the patients’ physical wounds are also accompanied by post-traumatic stress disorder, commissioners said.
The hearing on Friday was the commission’s seventh, and several members of Congress who have introduced legislation on veterans care came to testify. Mr. Dole and Ms. Shalala asked if they would include the commission’s recommendations in pending legislation.
“We would welcome suggestions, absolutely,” said Senator Carl Levin, Democrat of Michigan and chairman of the Senate Armed Services committee.
Mr. Levin said the Senate’s veterans bill, which is scheduled for the floor, seeks to improve medical record sharing between the military and the Department of Veterans Affairs as well as address discrepancies in the disability ratings each department uses to determine how much in benefits a service member is paid each month.
Representative Steve Buyer, Republican of Indiana and the ranking member of the House Veterans’ Affairs Committee, said he was concerned that the departments did not adequately use private contractors to provide outpatient treatment, which could allow patients to receive care at home rather than have to travel to a veterans hospital.
“If we’re patient-centric, we should allow the transition of that patient to occur,” Mr. Buyer said.
Ms. Shalala said, “This is a different war in which we have people who have families and they want to go home.”
Old Drugs In, New Ones Out
By ANDREW POLLACK
CAMBRIDGE, Mass. — Can an antipsychotic drug from the 1950s be paired with a 1980s antibiotic to shrink 21st-century tumors? Might an anticlotting drug help a steroid relieve arthritis? How about a cholesterol treatment and a pain reliever teaming up to tame diabetes?
Alexis Borisy, the pharmaceutical industry’s master matchmaker, is betting they can. And if he is right, he may have found a cheap and quick way to develop a new cornucopia of medicines.
Mr. Borisy is the 35-year-old co-founder and chief executive of CombinatoRx, a biotechnology company dedicated to the proposition that two old generic drugs can together make a powerful new medicine, often for an entirely different disease.
It is too early to tell if Mr. Borisy will succeed and, indeed, one of his company’s drugs failed in a clinical trial this week.
But with drug makers big and small struggling to fill their product pipelines, other biotechnology companies are also betting that pairing old drugs can be a better business than inventing new ones from scratch — which can take years and cost hundreds of millions of dollars, with no guarantee of success.
For example, Pozen, based in Chapel Hill, N.C., is developing combination drugs in partnerships with the pharmaceutical giants GlaxoSmithKline and AstraZeneca.
Orexigen Therapeutics of San Diego, recently went public based on the prospects for two combination drugs it is developing to treat obesity. And privately held Celator Pharmaceuticals of Princeton, N.J., has raised more than $40 million from venture capitalists to combine old cancer drugs in a new way.
“We think if we prove this concept clinically we have an almost unlimited pipeline,” said Andrew S. Janoff, the chief executive of Celator.
Helping propel the trend is the growing supply of drugs that have lost patent protection, providing a lode of material to test for newfound potential.
Information technology also plays a key role for CombinatoRx (which is pronounced com-bin-a-TOR-ics, as in the mathematics field that deals with combinations). The company relies on the latest robotic drug-screening technology and software to test several thousand pairs of medicines a day.
At its laboratory here, researchers and robots systematically pair about 2,000 generic drugs with one another, with 2 million different combinations possible. Each is tested on human cells. If a drug pair inhibits the cells’ production of inflammatory proteins, for example, that might be reason to explore whether the combination might work against arthritis.
Mr. Borisy describes it as a “dumb, brute-force, empirical approach” that assumes current knowledge of disease is too limited to predict in advance what combinations might work. The company does, though, give priority to testing pairs it believes have the best chance of working.
Eight of the company’s randomly arranged marriages, including drugs for cancer, arthritis and diabetes, have moved into clinical trials — an unusually high number for a company that is only seven years old. Other companies are taking more calculated approaches. Orexigen, in creating its obesity drug Contrave, took a treatment used for drug and alcohol addiction and combined it with an antidepressant sometimes used to help people quit smoking.
Meanwhile, Celator is focusing on drugs that are already used together to treat cancer. But while doctors now generally use the maximum tolerable dose of each drug, Celator says the ratio of the drugs is what matters more. So the company is developing combination products meant to deliver optimal ratios of the drugs to tumors.
Besides being quicker or cheaper to develop than single new drugs, combinations might also be more effective. Scientists have long known that the biochemical pathways involved in disease are complex, with numerous alternate routes. Trying to interfere with disease by blocking a single point can be like trying to keep traffic from reaching downtown Manhattan by closing a single intersection.
That is why doctors routinely use two or more drugs to treat people with cancer, heart disease, H.I.V. infection and other diseases.
But only more recently have pharmaceutical companies decided to do the combination themselves as a way to increase their profit.
Successful combination drugs already on the market include Advair from GlaxoSmithKline, which pairs two asthma drugs, and Vytorin, which combines cholesterol-lowering drugs from Merck and Schering-Plough that work in different ways.
When they work, combination drugs mean fewer pills to swallow, making it easier for patients to complete a course of treatment — and, as a result, for companies to hit sales targets.
Combination drugs can also let a weaker-selling medication ride the coattails of a stronger drug, or partly shield a product that has lost patent protection from generic competition. One of the ingredients in Vytorin, for instance, is Merck’s Zocor, which has gone off patent.
But for companies like CombinatoRx, which do not have any drugs of their own, finding value in off-patent products is the whole point.
Mr. Borisy, who dropped out of a Harvard chemistry doctoral program to become a drug industry consultant, started CombinatoRx in 2000 with three researchers from his former Harvard laboratory.
The company’s approach to drug research has attracted considerable attention, including Mr. Borisy being named 2003 “innovator of the year” among people under 35 by the Massachusetts Institute of Technology’s magazine Technology Review. The company has raised nearly $200 million from investors, including $44 million from its initial public offering in November 2005.
Several disease foundations have paid CombinatoRx to try to find combinations for treating their specialties. And Angiotech Pharmaceuticals, the company that supplies the drug used in Boston Scientific’s drug-coated stent for coronary arteries, has found combinations it hopes to use in future stents.
“They were far ahead of anyone else, and the way they were doing it we thought was just elegant,” said Dr. Rui Avelar, the chief medical officer for Angiotech.
For all the company’s promise and attention, though, it is far from clear that any of CombinatoRx’s drugs will reach the market. Three of the eight drugs that made it to clinical trials have since been dropped — including one on Thursday — because they did not work well enough in people, despite their effectiveness in the cell-based laboratory tests.
Those cold clinical realities have helped pull the company’s shares to the $6 range, below the initial public offering price of $7 and well under a high of almost $14 in early 2006.
Currently, the company’s lead drug is a treatment for rheumatoid arthritis and osteoarthritis that combines prednisolone, a steroid, and dipyridamole, a blood anticoagulant.
Steroids are used to treat arthritis, but they have undesirable side effects. Adding an anticoagulant seems somehow to amplify the steroid’s desirable effects, allowing use of a very low dose with greatly reduced side effects, Mr. Borisy said. The drug has shown promise in early clinical trials.
Combinations of existing drugs can enter clinical trials more quickly than totally new medicines because much is already known about their toxicity and how they behave in the body.
But some industry executives say the combinations risk encountering regulatory problems downstream. They say the Food and Drug Administration must be persuaded that a combination offers a real benefit to patients and is not just a commercial gimmick, because each additional drug a patient uses can raise the risk of safety problems, in part from interactions between the drugs.
Another risk for companies as they mine drugs no longer protected by patents is that other companies might try to sell similar combinations. While the combinations themselves can be patented, legal challenges could arise if the combination is deemed too obvious. Mr. Borisy says he is not worried because “our patents are so obviously non-obvious.”
Another business risk is that even if a combination pill is protected by patents, doctors might prescribe the two ingredients separately, especially if that would save the patient money.
Pozen, for instance, is developing a combination of the generic pain reliever naproxen with AstraZeneca’s popular heartburn remedy Nexium. The idea is that Nexium will protect the stomach from naproxen’s potentially ulcer-causing side effects. But many physicians are already prescribing an antacid pill along with a pain killer — and using generic stomach drugs rather than Nexium.
William L. Hodges, chief financial officer of Pozen, contends that his company’s combination pill will be more effective than two drugs taken separately. In the Pozen pill, he says, the naproxen is not released until Nexium has already lowered the stomach’s acidity.
Assuming companies like Pozen and CombinatoRx can surmount the challenges of two-drug combinations, the next question is whether three drugs might be even better. The answer appears to be yes, but developing trio drugs would be even more difficult.
For a triple combination, the F.D.A. might want evidence that the trio is better than not only the individual parts but also better than any of the possible pairs. Showing that would require huge and costly clinical trials.
But Mr. Borisy says his researchers and robots will be up to the task. “We’re going to get to that,” he said, “each step in time.”
CAMBRIDGE, Mass. — Can an antipsychotic drug from the 1950s be paired with a 1980s antibiotic to shrink 21st-century tumors? Might an anticlotting drug help a steroid relieve arthritis? How about a cholesterol treatment and a pain reliever teaming up to tame diabetes?
Alexis Borisy, the pharmaceutical industry’s master matchmaker, is betting they can. And if he is right, he may have found a cheap and quick way to develop a new cornucopia of medicines.
Mr. Borisy is the 35-year-old co-founder and chief executive of CombinatoRx, a biotechnology company dedicated to the proposition that two old generic drugs can together make a powerful new medicine, often for an entirely different disease.
It is too early to tell if Mr. Borisy will succeed and, indeed, one of his company’s drugs failed in a clinical trial this week.
But with drug makers big and small struggling to fill their product pipelines, other biotechnology companies are also betting that pairing old drugs can be a better business than inventing new ones from scratch — which can take years and cost hundreds of millions of dollars, with no guarantee of success.
For example, Pozen, based in Chapel Hill, N.C., is developing combination drugs in partnerships with the pharmaceutical giants GlaxoSmithKline and AstraZeneca.
Orexigen Therapeutics of San Diego, recently went public based on the prospects for two combination drugs it is developing to treat obesity. And privately held Celator Pharmaceuticals of Princeton, N.J., has raised more than $40 million from venture capitalists to combine old cancer drugs in a new way.
“We think if we prove this concept clinically we have an almost unlimited pipeline,” said Andrew S. Janoff, the chief executive of Celator.
Helping propel the trend is the growing supply of drugs that have lost patent protection, providing a lode of material to test for newfound potential.
Information technology also plays a key role for CombinatoRx (which is pronounced com-bin-a-TOR-ics, as in the mathematics field that deals with combinations). The company relies on the latest robotic drug-screening technology and software to test several thousand pairs of medicines a day.
At its laboratory here, researchers and robots systematically pair about 2,000 generic drugs with one another, with 2 million different combinations possible. Each is tested on human cells. If a drug pair inhibits the cells’ production of inflammatory proteins, for example, that might be reason to explore whether the combination might work against arthritis.
Mr. Borisy describes it as a “dumb, brute-force, empirical approach” that assumes current knowledge of disease is too limited to predict in advance what combinations might work. The company does, though, give priority to testing pairs it believes have the best chance of working.
Eight of the company’s randomly arranged marriages, including drugs for cancer, arthritis and diabetes, have moved into clinical trials — an unusually high number for a company that is only seven years old. Other companies are taking more calculated approaches. Orexigen, in creating its obesity drug Contrave, took a treatment used for drug and alcohol addiction and combined it with an antidepressant sometimes used to help people quit smoking.
Meanwhile, Celator is focusing on drugs that are already used together to treat cancer. But while doctors now generally use the maximum tolerable dose of each drug, Celator says the ratio of the drugs is what matters more. So the company is developing combination products meant to deliver optimal ratios of the drugs to tumors.
Besides being quicker or cheaper to develop than single new drugs, combinations might also be more effective. Scientists have long known that the biochemical pathways involved in disease are complex, with numerous alternate routes. Trying to interfere with disease by blocking a single point can be like trying to keep traffic from reaching downtown Manhattan by closing a single intersection.
That is why doctors routinely use two or more drugs to treat people with cancer, heart disease, H.I.V. infection and other diseases.
But only more recently have pharmaceutical companies decided to do the combination themselves as a way to increase their profit.
Successful combination drugs already on the market include Advair from GlaxoSmithKline, which pairs two asthma drugs, and Vytorin, which combines cholesterol-lowering drugs from Merck and Schering-Plough that work in different ways.
When they work, combination drugs mean fewer pills to swallow, making it easier for patients to complete a course of treatment — and, as a result, for companies to hit sales targets.
Combination drugs can also let a weaker-selling medication ride the coattails of a stronger drug, or partly shield a product that has lost patent protection from generic competition. One of the ingredients in Vytorin, for instance, is Merck’s Zocor, which has gone off patent.
But for companies like CombinatoRx, which do not have any drugs of their own, finding value in off-patent products is the whole point.
Mr. Borisy, who dropped out of a Harvard chemistry doctoral program to become a drug industry consultant, started CombinatoRx in 2000 with three researchers from his former Harvard laboratory.
The company’s approach to drug research has attracted considerable attention, including Mr. Borisy being named 2003 “innovator of the year” among people under 35 by the Massachusetts Institute of Technology’s magazine Technology Review. The company has raised nearly $200 million from investors, including $44 million from its initial public offering in November 2005.
Several disease foundations have paid CombinatoRx to try to find combinations for treating their specialties. And Angiotech Pharmaceuticals, the company that supplies the drug used in Boston Scientific’s drug-coated stent for coronary arteries, has found combinations it hopes to use in future stents.
“They were far ahead of anyone else, and the way they were doing it we thought was just elegant,” said Dr. Rui Avelar, the chief medical officer for Angiotech.
For all the company’s promise and attention, though, it is far from clear that any of CombinatoRx’s drugs will reach the market. Three of the eight drugs that made it to clinical trials have since been dropped — including one on Thursday — because they did not work well enough in people, despite their effectiveness in the cell-based laboratory tests.
Those cold clinical realities have helped pull the company’s shares to the $6 range, below the initial public offering price of $7 and well under a high of almost $14 in early 2006.
Currently, the company’s lead drug is a treatment for rheumatoid arthritis and osteoarthritis that combines prednisolone, a steroid, and dipyridamole, a blood anticoagulant.
Steroids are used to treat arthritis, but they have undesirable side effects. Adding an anticoagulant seems somehow to amplify the steroid’s desirable effects, allowing use of a very low dose with greatly reduced side effects, Mr. Borisy said. The drug has shown promise in early clinical trials.
Combinations of existing drugs can enter clinical trials more quickly than totally new medicines because much is already known about their toxicity and how they behave in the body.
But some industry executives say the combinations risk encountering regulatory problems downstream. They say the Food and Drug Administration must be persuaded that a combination offers a real benefit to patients and is not just a commercial gimmick, because each additional drug a patient uses can raise the risk of safety problems, in part from interactions between the drugs.
Another risk for companies as they mine drugs no longer protected by patents is that other companies might try to sell similar combinations. While the combinations themselves can be patented, legal challenges could arise if the combination is deemed too obvious. Mr. Borisy says he is not worried because “our patents are so obviously non-obvious.”
Another business risk is that even if a combination pill is protected by patents, doctors might prescribe the two ingredients separately, especially if that would save the patient money.
Pozen, for instance, is developing a combination of the generic pain reliever naproxen with AstraZeneca’s popular heartburn remedy Nexium. The idea is that Nexium will protect the stomach from naproxen’s potentially ulcer-causing side effects. But many physicians are already prescribing an antacid pill along with a pain killer — and using generic stomach drugs rather than Nexium.
William L. Hodges, chief financial officer of Pozen, contends that his company’s combination pill will be more effective than two drugs taken separately. In the Pozen pill, he says, the naproxen is not released until Nexium has already lowered the stomach’s acidity.
Assuming companies like Pozen and CombinatoRx can surmount the challenges of two-drug combinations, the next question is whether three drugs might be even better. The answer appears to be yes, but developing trio drugs would be even more difficult.
For a triple combination, the F.D.A. might want evidence that the trio is better than not only the individual parts but also better than any of the possible pairs. Showing that would require huge and costly clinical trials.
But Mr. Borisy says his researchers and robots will be up to the task. “We’re going to get to that,” he said, “each step in time.”
Disability, the Insurance That Is Often Sadly Overlooked
By HILLARY CHURA
It took just 17 days for Cindy Wrenn to realize that her disability insurance premium was not just another drain on her checking account. One-third of American workers are likely to be disabled for an extended period, and she became one of them when she had a stroke and brain aneurysm at age 28.
Mrs. Wrenn signed up for her long-term disability insurance policy in February 2002, as a supplement to the one she had through her job as a licensed title agent. After her medical emergency, the policies paid 70 percent of her salary for the six months it took her to get back to work full time.
“We thought we were too young to have an illness and were pretty secure in our jobs,” said Mrs. Wrenn, of Knoxville, Md. “It wasn’t an outrageous premium, so we did it. Because of disability insurance, we got to follow through with the purchase of our house, and that is where we are living today.”
Disability insurance provides partial income replacement so that if someone becomes disabled, they need not dive into savings, sell a home or radically change how they live. Working people are more likely to become disabled than they are to die prematurely, even though twice as many people have life insurance as have disability coverage, according to industry statistics.
According to the Department of Housing and Urban Development, illness is a major factor in home foreclosures.
About one-third of 20-year-old workers today will become disabled before they hit retirement age at 67, according to the Social Security Administration. And the primary cause of disability is chronic disease — cardiovascular, musculoskeletal problems and cancer are leading diagnoses — rather than work-related mishaps or nonworkplace accidents, according to a 2007 study for the Life and Health Insurance Foundation for Education, a nonprofit organization that informs the public about insurance needs.
While job-related expenses decrease if someone cannot work, other expenses can soar, especially if homes must be altered to accommodate a disability, said Craig Sampson, a lawyer in Richmond, Va. He bought disability insurance in 1999 when he was self-employed. He pays about $800 a year for $30,000 in coverage.
“Being disabled, you can go down the financial tubes fairly quickly,” he said. “Not only do you have regular living expenses you are unable to meet, but you have other expenses and all the uncovered medical bills. There’s a lot of stuff health insurance doesn’t cover.”
Tammy Brown of Bradford, Ark., signed up for short-term and long-term disability insurance after she started working for Wal-Mart Stores when she was 17. Fifteen years later, in December 2004, when she was 32, she learned that she had amyotrophic lateral sclerosis, or Lou Gehrig’s disease, and was told she had two to five years to live. She took the summer of 2005 off to spend time with her children, then 6 and 9, and received short-term disability. She went back to work in a wheelchair for about a year, then left on long-term disability in 2006. She receives about half of her salary now.
“Without disability, we would’ve lost our home, our vehicle,” Mrs. Brown, now 34, said. “We probably would’ve had to move in with my in-laws.”
The family bought a handicapped-accessible van and installed a handicapped lavatory complete with roll-in shower and rails around the toilet as well as two ramps to the house and a lift to help move Mrs. Brown around the home. Now unable to use her hands or arms to any degree or walk, she needs 24-hour care, either from relatives or someone they pay.
“As I look back on it, I don’t know what we’d have done without it,” Mrs. Brown said. “I never thought I’d ever use it. I thought I’d be working at Wal-Mart until I was 60 or 70.”
There are two major types of disability insurance. Short-term coverage, often offered by employers, covers the first part of a disability and may provide income for a week up to a year or two, depending on the policy.
Long-term insurance starts after short-term coverage ends and helps replace income for a predetermined period, usually two or five years or when the disabled person retires. It can be offered through work — though usually not free —as well as through private policies.
Even those with a policy through work should consider buying private coverage, as an employer’s policy may be bare-bones, could take a while to begin and will not continue when the employee changes jobs. It may also exclude pre-existing health problems.
About 42 percent of full-time workers have no short- or long-term disability, according to Michael Fradkin, vice president for disability product management for the Metropolitan Life Insurance Company. Specialists agree that if you can afford only one type of disability insurance, buy long-term coverage since being without an income for several months would be a burden but being without an income ever again could be devastating.
Because independent disability insurance tends to be expensive — and becomes more so as people age — specialists urge workers to buy it as soon as they start working so they can lock in lower rates. Besides, young workers often have not yet developed health problems that will hinder coverage later.
Mr. Fradkin said many employers offer disability policies, but some have been shifting costs to employees. At the same time, insurers are changing policies to make benefits less generous. They also are becoming more selective in who is granted a private policy.
The policy should replace at least 60 percent of take-home salary and ideally up to 80 percent, if that level of coverage is affordable. Disability insurance will not cover the whole salary for fear that there would be no incentive to work if the entire paycheck could be collected for staying home.
Before purchasing an individual long-term disability policy, it is best to figure out monthly expenses as well as any income from employers, investments or the government. Realize, however, that Social Security payments tend to be minimal, have a five-month waiting period and apply only if someone cannot do any job. Payouts through work policies are subject to taxes, while benefits through independent coverage are tax free.
Bruce Block, a disability specialist with Jenkins Block & Associates in Baltimore, said few people really understood their coverage. Plans vary. Some pay if someone is unable to work in her own professions; others pay if a person cannot do any job, Mr. Block said. Some offer a combination. Others provide coverage for only a few years, some until Social Security begins.
Premiums vary depending on age, sex, income, health, whether a person smokes, what type of job they have and the exclusions they accept. Generally a young nonsmoking accountant who would not need a payout for two years would pay a smaller premium than a chain-smoking construction worker who would want immediate disbursements.
Cara J. Lovenson, an insurance broker and employee benefits consultant in New York City, said she recently sold a policy to a 45-year-old man in relatively good health who is paid about $200,000 a year. She said the policy cost him about $2,800 a year, covered 80 percent of his salary and started payments after 90 days.
Mrs. Wrenn said that when she and her husband, Matthew, discuss ways to cut expenses, dropping their disability is never an option.
“I’ll never let it go,” Mrs. Wrenn said, “well, not until I retire.”
It took just 17 days for Cindy Wrenn to realize that her disability insurance premium was not just another drain on her checking account. One-third of American workers are likely to be disabled for an extended period, and she became one of them when she had a stroke and brain aneurysm at age 28.
Mrs. Wrenn signed up for her long-term disability insurance policy in February 2002, as a supplement to the one she had through her job as a licensed title agent. After her medical emergency, the policies paid 70 percent of her salary for the six months it took her to get back to work full time.
“We thought we were too young to have an illness and were pretty secure in our jobs,” said Mrs. Wrenn, of Knoxville, Md. “It wasn’t an outrageous premium, so we did it. Because of disability insurance, we got to follow through with the purchase of our house, and that is where we are living today.”
Disability insurance provides partial income replacement so that if someone becomes disabled, they need not dive into savings, sell a home or radically change how they live. Working people are more likely to become disabled than they are to die prematurely, even though twice as many people have life insurance as have disability coverage, according to industry statistics.
According to the Department of Housing and Urban Development, illness is a major factor in home foreclosures.
About one-third of 20-year-old workers today will become disabled before they hit retirement age at 67, according to the Social Security Administration. And the primary cause of disability is chronic disease — cardiovascular, musculoskeletal problems and cancer are leading diagnoses — rather than work-related mishaps or nonworkplace accidents, according to a 2007 study for the Life and Health Insurance Foundation for Education, a nonprofit organization that informs the public about insurance needs.
While job-related expenses decrease if someone cannot work, other expenses can soar, especially if homes must be altered to accommodate a disability, said Craig Sampson, a lawyer in Richmond, Va. He bought disability insurance in 1999 when he was self-employed. He pays about $800 a year for $30,000 in coverage.
“Being disabled, you can go down the financial tubes fairly quickly,” he said. “Not only do you have regular living expenses you are unable to meet, but you have other expenses and all the uncovered medical bills. There’s a lot of stuff health insurance doesn’t cover.”
Tammy Brown of Bradford, Ark., signed up for short-term and long-term disability insurance after she started working for Wal-Mart Stores when she was 17. Fifteen years later, in December 2004, when she was 32, she learned that she had amyotrophic lateral sclerosis, or Lou Gehrig’s disease, and was told she had two to five years to live. She took the summer of 2005 off to spend time with her children, then 6 and 9, and received short-term disability. She went back to work in a wheelchair for about a year, then left on long-term disability in 2006. She receives about half of her salary now.
“Without disability, we would’ve lost our home, our vehicle,” Mrs. Brown, now 34, said. “We probably would’ve had to move in with my in-laws.”
The family bought a handicapped-accessible van and installed a handicapped lavatory complete with roll-in shower and rails around the toilet as well as two ramps to the house and a lift to help move Mrs. Brown around the home. Now unable to use her hands or arms to any degree or walk, she needs 24-hour care, either from relatives or someone they pay.
“As I look back on it, I don’t know what we’d have done without it,” Mrs. Brown said. “I never thought I’d ever use it. I thought I’d be working at Wal-Mart until I was 60 or 70.”
There are two major types of disability insurance. Short-term coverage, often offered by employers, covers the first part of a disability and may provide income for a week up to a year or two, depending on the policy.
Long-term insurance starts after short-term coverage ends and helps replace income for a predetermined period, usually two or five years or when the disabled person retires. It can be offered through work — though usually not free —as well as through private policies.
Even those with a policy through work should consider buying private coverage, as an employer’s policy may be bare-bones, could take a while to begin and will not continue when the employee changes jobs. It may also exclude pre-existing health problems.
About 42 percent of full-time workers have no short- or long-term disability, according to Michael Fradkin, vice president for disability product management for the Metropolitan Life Insurance Company. Specialists agree that if you can afford only one type of disability insurance, buy long-term coverage since being without an income for several months would be a burden but being without an income ever again could be devastating.
Because independent disability insurance tends to be expensive — and becomes more so as people age — specialists urge workers to buy it as soon as they start working so they can lock in lower rates. Besides, young workers often have not yet developed health problems that will hinder coverage later.
Mr. Fradkin said many employers offer disability policies, but some have been shifting costs to employees. At the same time, insurers are changing policies to make benefits less generous. They also are becoming more selective in who is granted a private policy.
The policy should replace at least 60 percent of take-home salary and ideally up to 80 percent, if that level of coverage is affordable. Disability insurance will not cover the whole salary for fear that there would be no incentive to work if the entire paycheck could be collected for staying home.
Before purchasing an individual long-term disability policy, it is best to figure out monthly expenses as well as any income from employers, investments or the government. Realize, however, that Social Security payments tend to be minimal, have a five-month waiting period and apply only if someone cannot do any job. Payouts through work policies are subject to taxes, while benefits through independent coverage are tax free.
Bruce Block, a disability specialist with Jenkins Block & Associates in Baltimore, said few people really understood their coverage. Plans vary. Some pay if someone is unable to work in her own professions; others pay if a person cannot do any job, Mr. Block said. Some offer a combination. Others provide coverage for only a few years, some until Social Security begins.
Premiums vary depending on age, sex, income, health, whether a person smokes, what type of job they have and the exclusions they accept. Generally a young nonsmoking accountant who would not need a payout for two years would pay a smaller premium than a chain-smoking construction worker who would want immediate disbursements.
Cara J. Lovenson, an insurance broker and employee benefits consultant in New York City, said she recently sold a policy to a 45-year-old man in relatively good health who is paid about $200,000 a year. She said the policy cost him about $2,800 a year, covered 80 percent of his salary and started payments after 90 days.
Mrs. Wrenn said that when she and her husband, Matthew, discuss ways to cut expenses, dropping their disability is never an option.
“I’ll never let it go,” Mrs. Wrenn said, “well, not until I retire.”
Symptomatic Early Neurosyphilis a Risk in HIV-Infected Men
HIV-infected homosexual men with syphilis have about a 2% risk for developing symptomatic early neurosyphilis, according to a CDC study.
The estimate, published in MMWR, was based on a review of 49 cases. Neurosyphilis was the only sign of syphilis in half the patients, and about one-third had persistent symptoms 6 months after treatment.
An editorial note recommends that physicians be alert for neurosyphilis when treating HIV-infected people with cranial nerve dysfunction or other unexplained neurologic symptoms.
The estimate, published in MMWR, was based on a review of 49 cases. Neurosyphilis was the only sign of syphilis in half the patients, and about one-third had persistent symptoms 6 months after treatment.
An editorial note recommends that physicians be alert for neurosyphilis when treating HIV-infected people with cranial nerve dysfunction or other unexplained neurologic symptoms.
Sanofi pulls obesity drug application in U.S.
By Ben Hirschler, European Pharmaceuticals CorrespondentFri Jun 29, 1:07 PM ET
Sanofi-Aventis SA is withdrawing its application to sell obesity drug rimonabant -- its biggest new drug hope -- in the United States, the French drugmaker said on Friday.
The move comes two weeks after a U.S. advisory panel said the medicine should not be approved in the world's largest drugs market because it may increase suicidal thinking and depression.
Sanofi said it would work towards resubmitting the medicine, known by the brand names Acomplia and Zimulti, at a future date and would undertake necessary discussions with the Food and Drug Administration (FDA) on required modifications to its file.
Industry analysts said the decision was a fresh setback for the hoped-for blockbuster, which is also facing an extended safety review in Europe, where it has been on the market since last year.
Paul Diggle of Nomura Code Securities said the drug might yet have a future in the United States as a niche treatment for diabetes but as a weight-loss treatment it appeared "fatally wounded."
Others said the world's third-biggest drugmaker was acting proactively to save face and avoid outright rejection from the
FDA.
Shaojing Tong, an analyst with Mehta Partners in New York, said the medicine could still be approved if it fares well in a large trial underway that may provide a better picture of its risks and benefits -- but this would delay approval until 2011.
"This trial is longer than earlier studies and metabolic benefits from raising HDL (good) cholesterol and lowering triglycerides could be reflected" in terms of patient health benefits, Tong said.
The drug is the first in a new class of drugs that switch off the same brain circuits that make people hungry when they smoke cannabis.
EU DECISION IN JULY
European regulators said they were still reviewing the latest safety data on the medicine and would only come to a final decision on the product next month.
"The review is expected to be finalized at the July CHMP (Committee for Medicinal Products for Human Use) meeting," a spokeswoman for the European Medicines Agency said.
The EU watchdog had initially said it was likely to give a view this month. Sanofi said it was submitting an update of safety data on the medicine to the CHMP.
Shares in Sanofi, which plunged on the U.S. panel decision earlier in June, gave up earlier gains to end 0.6 percent down on the day at 60.10 euros in Paris.
Acomplia is currently not recommended for European patients with major depression, due to its potential psychiatric side effects, and industry analysts believe further restrictions on its use are now very possible.
"I don't think it will be withdrawn in Europe but I think the label is going to get tougher," Nomura's Diggle said. "There is no way that people's forecasts are not going to come down even further."
Paris-based Sanofi has in the past trumpeted Acomplia as potential mega blockbuster, with sales of $3 billion a year or more. But actual take-up of the medicine in those markets where it is available has been slow, partly because of lack of reimbursement.
Worldwide sales of Acomplia in the first quarter of 2007 totaled just 15 million euros ($20.17 million), down from 20 million in the fourth quarter of 2006.
It is currently approved in 42 countries and marketed in 20 to treat obesity and overweight patients with associated cardiovascular risk factors.
(Additional reporting by Ransdell Pierson in New York)
Sanofi-Aventis SA is withdrawing its application to sell obesity drug rimonabant -- its biggest new drug hope -- in the United States, the French drugmaker said on Friday.
The move comes two weeks after a U.S. advisory panel said the medicine should not be approved in the world's largest drugs market because it may increase suicidal thinking and depression.
Sanofi said it would work towards resubmitting the medicine, known by the brand names Acomplia and Zimulti, at a future date and would undertake necessary discussions with the Food and Drug Administration (FDA) on required modifications to its file.
Industry analysts said the decision was a fresh setback for the hoped-for blockbuster, which is also facing an extended safety review in Europe, where it has been on the market since last year.
Paul Diggle of Nomura Code Securities said the drug might yet have a future in the United States as a niche treatment for diabetes but as a weight-loss treatment it appeared "fatally wounded."
Others said the world's third-biggest drugmaker was acting proactively to save face and avoid outright rejection from the
FDA.
Shaojing Tong, an analyst with Mehta Partners in New York, said the medicine could still be approved if it fares well in a large trial underway that may provide a better picture of its risks and benefits -- but this would delay approval until 2011.
"This trial is longer than earlier studies and metabolic benefits from raising HDL (good) cholesterol and lowering triglycerides could be reflected" in terms of patient health benefits, Tong said.
The drug is the first in a new class of drugs that switch off the same brain circuits that make people hungry when they smoke cannabis.
EU DECISION IN JULY
European regulators said they were still reviewing the latest safety data on the medicine and would only come to a final decision on the product next month.
"The review is expected to be finalized at the July CHMP (Committee for Medicinal Products for Human Use) meeting," a spokeswoman for the European Medicines Agency said.
The EU watchdog had initially said it was likely to give a view this month. Sanofi said it was submitting an update of safety data on the medicine to the CHMP.
Shares in Sanofi, which plunged on the U.S. panel decision earlier in June, gave up earlier gains to end 0.6 percent down on the day at 60.10 euros in Paris.
Acomplia is currently not recommended for European patients with major depression, due to its potential psychiatric side effects, and industry analysts believe further restrictions on its use are now very possible.
"I don't think it will be withdrawn in Europe but I think the label is going to get tougher," Nomura's Diggle said. "There is no way that people's forecasts are not going to come down even further."
Paris-based Sanofi has in the past trumpeted Acomplia as potential mega blockbuster, with sales of $3 billion a year or more. But actual take-up of the medicine in those markets where it is available has been slow, partly because of lack of reimbursement.
Worldwide sales of Acomplia in the first quarter of 2007 totaled just 15 million euros ($20.17 million), down from 20 million in the fourth quarter of 2006.
It is currently approved in 42 countries and marketed in 20 to treat obesity and overweight patients with associated cardiovascular risk factors.
(Additional reporting by Ransdell Pierson in New York)
U.S. hospital, doctor visits balloon, survey finds
By Maggie Fox, Health and Science EditorFri Jun 29, 5:12 PM ET
Hospital and doctor visits in the United States have surged by 20 percent in the past five years and the most commonly prescribed medications are antidepressants, according to statistics published on Friday.
The survey by the U.S. Centers for Disease Control and Prevention also found most people who visited emergency rooms had private health insurance, although the uninsured were twice as likely to use emergency services as people with insurance.
The report estimates that 1.2 billion visits were made to hospitals, emergency rooms and physicians' offices in 2005.
"It was only a few years ago that we released that the total number of visits had reached 1 billion. And now we are up to 1.2 billion," Catharine Burt of the CDC's National Center for Health Statistics said in a telephone interview.
"That's a 20 percent increase in the just the last five years -- a huge number," said Burt. "I can tell you that the number of hospitals and physicians has not increased 20 percent."
The reason is clear -- Americans are getting older. "When you reach 50 things start going wrong, just little by little, and you keep going back to the doctors," Burt said.
The baby boom generation -- born between 1946 and 1964 -- are now prime users of the medical system.
Burt's team surveyed 352 hospitals and about 1,200 physicians throughout 2005 for the study.
OLDER AND DEPRESSED
Of 2.4 billion drugs mentioned in patients' medical records in 2005, 118 million were antidepressants, Burt found. High blood pressure drugs followed, with 113 million and arthritis or headache drugs were mentioned in 110 million.
"These are visits. These aren't people," she said. People taking antidepressants may need more frequent doctor visits.
The report also shed light on the controversial issue of emergency room visits. Many health care experts are worried that the 43 million people who lack health insurance in the United States must rely on emergency rooms for care -- not the best way to prevent serious conditions.
The survey suggests this is true. "People with no insurance are twice as likely to use the emergency department as the privately insured," Burt said.
Nearly 28 percent of all doctors visits by uninsured people are to emergency rooms, compared to 6.6 percent of visits made by people with insurance.
The report found that 46 million of the visits made to ERs in 2005 were by people with insurance, compared to 19 million by people without insurance.
"With 315,000 people visiting emergency departments every day, the alarm bells are sounding and policymakers should heed the alert and respond," said Dr. Brian Keaton, president of the American College of Emergency Physicians, which is pressing for a national commission on access to emergency medical services.
The CDC report is available on the Internet at http://www.cdc.gov/nchs/data/ad/ad388.pdf.
Hospital and doctor visits in the United States have surged by 20 percent in the past five years and the most commonly prescribed medications are antidepressants, according to statistics published on Friday.
The survey by the U.S. Centers for Disease Control and Prevention also found most people who visited emergency rooms had private health insurance, although the uninsured were twice as likely to use emergency services as people with insurance.
The report estimates that 1.2 billion visits were made to hospitals, emergency rooms and physicians' offices in 2005.
"It was only a few years ago that we released that the total number of visits had reached 1 billion. And now we are up to 1.2 billion," Catharine Burt of the CDC's National Center for Health Statistics said in a telephone interview.
"That's a 20 percent increase in the just the last five years -- a huge number," said Burt. "I can tell you that the number of hospitals and physicians has not increased 20 percent."
The reason is clear -- Americans are getting older. "When you reach 50 things start going wrong, just little by little, and you keep going back to the doctors," Burt said.
The baby boom generation -- born between 1946 and 1964 -- are now prime users of the medical system.
Burt's team surveyed 352 hospitals and about 1,200 physicians throughout 2005 for the study.
OLDER AND DEPRESSED
Of 2.4 billion drugs mentioned in patients' medical records in 2005, 118 million were antidepressants, Burt found. High blood pressure drugs followed, with 113 million and arthritis or headache drugs were mentioned in 110 million.
"These are visits. These aren't people," she said. People taking antidepressants may need more frequent doctor visits.
The report also shed light on the controversial issue of emergency room visits. Many health care experts are worried that the 43 million people who lack health insurance in the United States must rely on emergency rooms for care -- not the best way to prevent serious conditions.
The survey suggests this is true. "People with no insurance are twice as likely to use the emergency department as the privately insured," Burt said.
Nearly 28 percent of all doctors visits by uninsured people are to emergency rooms, compared to 6.6 percent of visits made by people with insurance.
The report found that 46 million of the visits made to ERs in 2005 were by people with insurance, compared to 19 million by people without insurance.
"With 315,000 people visiting emergency departments every day, the alarm bells are sounding and policymakers should heed the alert and respond," said Dr. Brian Keaton, president of the American College of Emergency Physicians, which is pressing for a national commission on access to emergency medical services.
The CDC report is available on the Internet at http://www.cdc.gov/nchs/data/ad/ad388.pdf.
Clodronate does not improve breast cancer survival
By Will Boggs, MDFri Jun 29, 5:41 PM ET
Treatment with clodronate does not improve survival in women with early or advanced breast cancer, according to the results of a meta-analysis of published studies.
"There is no definitive data to support the use of clodronate at this point in time for the purpose of improving breast cancer survival," Dr. Tam Cam Ha from the National Cancer Centre, Singapore, told Reuters Health. "This reaffirms the current status of knowledge and current practice guidelines, as clodronate isn't routinely prescribed for the purposes of improving survival," the researcher added.
Clodronate is a member of a class of drugs called bisphosphonates, which are used to treat the bone-thinning disease osteoporosis.
In the British Journal of Cancer, Dr. Ha and Dr. H. Li note that bisphosphonates in some trials have apparently prolonged survival in breast cancer patients while other results have been negative. The researchers therefore pooled results from 13 trials to examine the effect of oral clodronate (1,600 milligrams daily for 2 or 3 years) on survival in women with breast cancer.
In women with early breast cancer, there was no difference in overall survival or in the time it took the breast tumor to spread to the bone or other sites between patients who received clodronate in addition to standard treatment and those who did not.
Similarly, in women with advanced breast cancer, clodronate did not change the overall survival or the appearance of bone metastasis.
"We wouldn't really argue against or for the use of this agent in breast cancer patients based on this study," Dr. Ha said. Currently, big multicenter trials are investigating this, the researcher noted, and the results of one of the trials will be available in the near future and that may provide more evidence on this subject.
SOURCE: British Journal of Cancer, June 18, 2007.
Treatment with clodronate does not improve survival in women with early or advanced breast cancer, according to the results of a meta-analysis of published studies.
"There is no definitive data to support the use of clodronate at this point in time for the purpose of improving breast cancer survival," Dr. Tam Cam Ha from the National Cancer Centre, Singapore, told Reuters Health. "This reaffirms the current status of knowledge and current practice guidelines, as clodronate isn't routinely prescribed for the purposes of improving survival," the researcher added.
Clodronate is a member of a class of drugs called bisphosphonates, which are used to treat the bone-thinning disease osteoporosis.
In the British Journal of Cancer, Dr. Ha and Dr. H. Li note that bisphosphonates in some trials have apparently prolonged survival in breast cancer patients while other results have been negative. The researchers therefore pooled results from 13 trials to examine the effect of oral clodronate (1,600 milligrams daily for 2 or 3 years) on survival in women with breast cancer.
In women with early breast cancer, there was no difference in overall survival or in the time it took the breast tumor to spread to the bone or other sites between patients who received clodronate in addition to standard treatment and those who did not.
Similarly, in women with advanced breast cancer, clodronate did not change the overall survival or the appearance of bone metastasis.
"We wouldn't really argue against or for the use of this agent in breast cancer patients based on this study," Dr. Ha said. Currently, big multicenter trials are investigating this, the researcher noted, and the results of one of the trials will be available in the near future and that may provide more evidence on this subject.
SOURCE: British Journal of Cancer, June 18, 2007.
Surgeons Push for Less Invasive Lung Cancer Procedures
FRIDAY, June 29 (HealthDay News) - Less invasive lung surgery should become the first option for cancer patients, U.S. experts say.
The procedure, called thoracoscopic lobectomy, "should be considered the standard of care for patients with early-stage lung cancers," Dr. Michael Reed, an assistant professor of surgery at the University of Cincinnati (UC) and a minimally invasive thoracic surgeon at University Hospital, said in a prepared statement. "But few surgeons offer the procedure because it's difficult and requires a lot of additional training."
Only an estimated 10 percent of all lung cancer operations nationwide are minimally invasive procedures. However, these procedures result in faster recovery time and less pain for patients, Reed said.
Thoracoscopic lobectomy is a minimally invasive lung surgery that uses several small incisions instead of a major chest incision that requires rib-spreading. Only a handful of academic medical centers, including UC, are actively training surgeons to perform the procedure.
"The key to implementing this program into our practice was having a dedicated team of extensively trained thoracic surgeons with expertise in both open and minimally invasive, video-guided techniques," Dr. Sandra Starnes said in a prepared statement. "This isn't a procedure you can perform confidently after just a few cases -- mentorship and expertise are key."
The Cincinnati team has trained two cardiothoracic surgery fellows and more than a dozen community thoracic surgeons to perform minimally invasive lung surgery.
To assess how the training program affected the rate of minimally invasive lobectomies at UC, Reed and Starnes conducted a four-year review of surgical cases at University Hospital and the Cincinnati Department of Veterans Affairs Medical Center.
They found that the number of minimally invasive lobectomies performed by UC surgeons has increased by about 57 percent over four years.
Prior to the implementation of the training program, only about 18 percent of lobectomies were performed with minimally invasive procedures. Now, Reed estimated, 75 percent of lobectomies at University Hospital employ minimally invasive techniques.
"We've shown that with a predetermined, step-by-step plan -- guided by a highly experienced minimally invasive thoracic surgeon -- thoracoscopic lobectomy can be integrated safely into thoracic surgical training programs," Reed said.
These findings were to be presented June 29 at the Western Thoracic Surgical Association's annual meeting in Santa Ana Pueblo, N.M.
More information
The National Cancer Institute has more about lung cancer treatment.
The procedure, called thoracoscopic lobectomy, "should be considered the standard of care for patients with early-stage lung cancers," Dr. Michael Reed, an assistant professor of surgery at the University of Cincinnati (UC) and a minimally invasive thoracic surgeon at University Hospital, said in a prepared statement. "But few surgeons offer the procedure because it's difficult and requires a lot of additional training."
Only an estimated 10 percent of all lung cancer operations nationwide are minimally invasive procedures. However, these procedures result in faster recovery time and less pain for patients, Reed said.
Thoracoscopic lobectomy is a minimally invasive lung surgery that uses several small incisions instead of a major chest incision that requires rib-spreading. Only a handful of academic medical centers, including UC, are actively training surgeons to perform the procedure.
"The key to implementing this program into our practice was having a dedicated team of extensively trained thoracic surgeons with expertise in both open and minimally invasive, video-guided techniques," Dr. Sandra Starnes said in a prepared statement. "This isn't a procedure you can perform confidently after just a few cases -- mentorship and expertise are key."
The Cincinnati team has trained two cardiothoracic surgery fellows and more than a dozen community thoracic surgeons to perform minimally invasive lung surgery.
To assess how the training program affected the rate of minimally invasive lobectomies at UC, Reed and Starnes conducted a four-year review of surgical cases at University Hospital and the Cincinnati Department of Veterans Affairs Medical Center.
They found that the number of minimally invasive lobectomies performed by UC surgeons has increased by about 57 percent over four years.
Prior to the implementation of the training program, only about 18 percent of lobectomies were performed with minimally invasive procedures. Now, Reed estimated, 75 percent of lobectomies at University Hospital employ minimally invasive techniques.
"We've shown that with a predetermined, step-by-step plan -- guided by a highly experienced minimally invasive thoracic surgeon -- thoracoscopic lobectomy can be integrated safely into thoracic surgical training programs," Reed said.
These findings were to be presented June 29 at the Western Thoracic Surgical Association's annual meeting in Santa Ana Pueblo, N.M.
More information
The National Cancer Institute has more about lung cancer treatment.
Friday, June 29, 2007
Inpatients With MRSA Much More Common Than Suspected
SAN FRANCISCO, June 28 -- The rate of methicillin-resistant Staphylococcus aureus in U.S. hospital patients is now nearly 5% -- dramatically higher than previously thought, according to a nationwide survey of healthcare facilities.
In a one-day snapshot of infection rates conducted late last year, 46 of every 1,000 patients harbored MRSA, according to the Association for Professionals in Infection and Epidemiology (APIC). This is eight to 11 times higher than earlier estimates.
Of those MRSA patients, the survey found, 34 of every 1,000 were infected while 12 of every 1,000 were simply colonized and -- while they did not yet have active disease -- could potentially have transmitted the organism.
The survey "presents a grim picture," according to principal investigator William Jarvis, M.D., of Jason and Jarvis Associates, a private consulting firm in healthcare epidemiology.
"The findings argue for immediate, aggressive efforts to detect and prevent transmission of MRSA," Dr. Jarvis said.
The survey results, released here at APIC's annual meeting, includes data from 1,237 healthcare facilities in 50 states, each of which was asked to provide a "snapshot" of all MRSA cases in the hospital during a single day.
The survey included almost all types of healthcare facilities, including acute, cancer, cardiac, pediatric, rehabilitation, and long-term care. County, public, and private facilities were included and sizes ranged from fewer than 100 beds to more than 300.
The snapshots found 8,654 MRSA cases, including both community-acquired MRSA and healthcare-associated MRSA, in a total of 187,058 inpatients.
The survey also found:
54% of MRSA cases were in men.
67% were on the medical service of their respective hospitals.
81% of cases were detected by clinical cultures and the remainder by active surveillance cultures.
77% were detected less than 48 hours after admission.
37% only had skin and soft tissue infections, which are most commonly seen with community-acquired MRSA, and the rest had infections of the lungs, bloodstream, and urinary tract.
Fewer than 30% of isolates were susceptible to clindamycin (Cleocin) and fewer than 20% were susceptible to levofloxacin (Levaquin).
Because 81% of cases were detected only after clinical manifestations of disease, the association said, it is likely that a "significant number" of patients have the potential to transmit MRSA to healthcare workers or other patients.
"This survey is a wake up-call for healthcare facilities," APIC president Denise Murphy, R.N., said, "because the transmission of MRSA is preventable."
"The scope of this public health threat demands commitment and participation from every hospital, at all levels of the facility," said Murphy, who is a senior safety officer at Barnes-Jewish Hospital in St. Louis.
According to the CDC, MRSA infections accounted for 2% of the total number of staph infections in 1974, but by 1995 it was 22% and in 2004 it was 63%.
The agency last year issued new recommendations for managing MRSA and other drug-pathogens in hospitals that urged "judicious use" of antibiotics, frequent hand washing, and active surveillance.
The survey was financed by APIC.Additional source: Association for Professionals in Infection Control & EpidemiologySource reference: "National Prevalence Study of Methicillin-Resistant Staphylococcus aureus (MRSA) in U.S. Healthcare Facilities"
In a one-day snapshot of infection rates conducted late last year, 46 of every 1,000 patients harbored MRSA, according to the Association for Professionals in Infection and Epidemiology (APIC). This is eight to 11 times higher than earlier estimates.
Of those MRSA patients, the survey found, 34 of every 1,000 were infected while 12 of every 1,000 were simply colonized and -- while they did not yet have active disease -- could potentially have transmitted the organism.
The survey "presents a grim picture," according to principal investigator William Jarvis, M.D., of Jason and Jarvis Associates, a private consulting firm in healthcare epidemiology.
"The findings argue for immediate, aggressive efforts to detect and prevent transmission of MRSA," Dr. Jarvis said.
The survey results, released here at APIC's annual meeting, includes data from 1,237 healthcare facilities in 50 states, each of which was asked to provide a "snapshot" of all MRSA cases in the hospital during a single day.
The survey included almost all types of healthcare facilities, including acute, cancer, cardiac, pediatric, rehabilitation, and long-term care. County, public, and private facilities were included and sizes ranged from fewer than 100 beds to more than 300.
The snapshots found 8,654 MRSA cases, including both community-acquired MRSA and healthcare-associated MRSA, in a total of 187,058 inpatients.
The survey also found:
54% of MRSA cases were in men.
67% were on the medical service of their respective hospitals.
81% of cases were detected by clinical cultures and the remainder by active surveillance cultures.
77% were detected less than 48 hours after admission.
37% only had skin and soft tissue infections, which are most commonly seen with community-acquired MRSA, and the rest had infections of the lungs, bloodstream, and urinary tract.
Fewer than 30% of isolates were susceptible to clindamycin (Cleocin) and fewer than 20% were susceptible to levofloxacin (Levaquin).
Because 81% of cases were detected only after clinical manifestations of disease, the association said, it is likely that a "significant number" of patients have the potential to transmit MRSA to healthcare workers or other patients.
"This survey is a wake up-call for healthcare facilities," APIC president Denise Murphy, R.N., said, "because the transmission of MRSA is preventable."
"The scope of this public health threat demands commitment and participation from every hospital, at all levels of the facility," said Murphy, who is a senior safety officer at Barnes-Jewish Hospital in St. Louis.
According to the CDC, MRSA infections accounted for 2% of the total number of staph infections in 1974, but by 1995 it was 22% and in 2004 it was 63%.
The agency last year issued new recommendations for managing MRSA and other drug-pathogens in hospitals that urged "judicious use" of antibiotics, frequent hand washing, and active surveillance.
The survey was financed by APIC.Additional source: Association for Professionals in Infection Control & EpidemiologySource reference: "National Prevalence Study of Methicillin-Resistant Staphylococcus aureus (MRSA) in U.S. Healthcare Facilities"
ADA: Self Glucose Monitoring Found Unneeded Ritual for Many Type 2 Diabetes
CHICAGO, June 28 -- Those daily glucose-monitoring finger sticks may be overkill for many patients with type 2 diabetes, reported investigators here.
In a one-year study, glycosylated hemoglobin levels were similar among patients whose only glucose monitoring testing was an HbA1c every three months compared with patients who followed one of two frequent self-monitoring regimens, reported Andrew J. Farmer, M.D., of the University of Oxford in England, and colleagues in British and U.S. centers.
Results were no better for patients who followed an intensive self-monitoring regimen than those who followed a less-demanding one, Dr. Farmer said in a late-breaking studies session at the American Diabetes Association meeting.
"Patients, clinicians and policy-makers will need to look at the results to reach decisions about appropriate use of self-monitoring of blood glucose technology," he said. "The results of this trial will add to the evidence available to make the decisions."
He cautioned, however, that all patients with type 1 diabetes, and patients with type 2 who require insulin injections, should adhere to self-monitoring guidelines, as tight glycemic control with insulin, plus lifestyle interventions, have been conclusively shown to reduce the occurrence of microvascular and macrovascular complications of diabetes.
John Buse, M.D., Ph.D., of the University of North Carolina at Chapel Hill, the president of the ADA, commented that he had no major quibble with Dr. Farmer's results. His own research, he said, had found that self monitoring was not as beneficial as had been anticipated, and he suspects that "a lot of glucose self-monitoring in the U.S. is not cost-effective. A lot of patients check more frequently that they should."
Self-monitoring can be useful for newly diagnosed type 2 patients to determine the proper dose of drugs, but the U.S. medical system, as opposed to the British system, works against frequent visits to a physician for HbA1c testing, Dr. Buse pointed out.
Self-monitoring is a good tool, Dr. Buse said, and it can work. Yet he cites the practice of many patients who check their blood one or more or times a day and don't write the readings down, or who keep them faithfully but don't report them to their doctors.
"How useful it is depends on how you use it," he added.
Dr. Farmer said previous studies of self-monitoring of blood glucose have been multifactorial, confounding the relative contributions of self-monitoring or other interventions on risk-factor reduction in patients with non-insulin dependent diabetes.
The Oxford investigators designed a trial to see whether standard care, self-monitoring of blood glucose alone, or self monitoring in combination with diabetes education (aimed at incorporating HbA1c results into self-care could) have an effect on overall glycemic control in patients who do not require exogenous insulin.
They recruited 453 adults with type 2 diabetes from 48 family practices. The mean patient age was 65.7 years, and 57% of the participants were male. They were randomly assigned to either:
Standard care with HbA1c testing once every three months.
Self-monitoring of blood glucose at least six times per week, with the results recorded in a self-care log that was shared with a research nurse every three months, and with instruction to call their doctors if glucose levels fell outside of established parameters; or
Self-monitoring at least six times a week, after individual training, with phone and clinic follow-up to interpret and apply the results of testing to enhance motivation, goal-setting, dietary maintenance, physical activity, and drug regimens.
The primary study outcome was HbA1c at one year, adjusted for baseline values.
A total of 57 patients (13%) were lost to follow-up at one year. The loss of patients was distributed even across the three groups, and the analysis was by intention-to-treat.
The authors found that two-thirds of patients who followed the less-intensive self-monitoring regimen and half of those following the more intensive plan had monitored their blood glucose levels at least twice per week over the past 12 months.
The mean HbA1c at baseline was similar across the three groups at 7.5%, above the less than 7% value recommended by the American Diabetes Association., and at one year there were still no significant differences among the groups. The mean difference in HbA1c between controls and patients in the less-intensive monitoring groups was 0.14% in favor of monitoring, and between controls and the hard-core self monitors, the mean difference was 0.17%, also in favor of monitoring. These differences were not statistically significant, however (P=0.12).
"A difference of -0.5% or more would generally be needed for a therapy to be considered clinically effective, and we powered the study to be able to see a difference that large if it existed, but we did not get it," said Dr. Farmer.
The study was funded by the Health Technology Assessment Programme, which is part of the United Kingdom National Institute for Health Research. Author conflicts of interest were not available. Primary source: American Diabetes Association 2007 Scientific SessionsSource reference: Farmer AJ et al. "Self-blood glucose monitoring yields no significant improved in non-insulin users with type 2 diabetes." Presented June 26.
In a one-year study, glycosylated hemoglobin levels were similar among patients whose only glucose monitoring testing was an HbA1c every three months compared with patients who followed one of two frequent self-monitoring regimens, reported Andrew J. Farmer, M.D., of the University of Oxford in England, and colleagues in British and U.S. centers.
Results were no better for patients who followed an intensive self-monitoring regimen than those who followed a less-demanding one, Dr. Farmer said in a late-breaking studies session at the American Diabetes Association meeting.
"Patients, clinicians and policy-makers will need to look at the results to reach decisions about appropriate use of self-monitoring of blood glucose technology," he said. "The results of this trial will add to the evidence available to make the decisions."
He cautioned, however, that all patients with type 1 diabetes, and patients with type 2 who require insulin injections, should adhere to self-monitoring guidelines, as tight glycemic control with insulin, plus lifestyle interventions, have been conclusively shown to reduce the occurrence of microvascular and macrovascular complications of diabetes.
John Buse, M.D., Ph.D., of the University of North Carolina at Chapel Hill, the president of the ADA, commented that he had no major quibble with Dr. Farmer's results. His own research, he said, had found that self monitoring was not as beneficial as had been anticipated, and he suspects that "a lot of glucose self-monitoring in the U.S. is not cost-effective. A lot of patients check more frequently that they should."
Self-monitoring can be useful for newly diagnosed type 2 patients to determine the proper dose of drugs, but the U.S. medical system, as opposed to the British system, works against frequent visits to a physician for HbA1c testing, Dr. Buse pointed out.
Self-monitoring is a good tool, Dr. Buse said, and it can work. Yet he cites the practice of many patients who check their blood one or more or times a day and don't write the readings down, or who keep them faithfully but don't report them to their doctors.
"How useful it is depends on how you use it," he added.
Dr. Farmer said previous studies of self-monitoring of blood glucose have been multifactorial, confounding the relative contributions of self-monitoring or other interventions on risk-factor reduction in patients with non-insulin dependent diabetes.
The Oxford investigators designed a trial to see whether standard care, self-monitoring of blood glucose alone, or self monitoring in combination with diabetes education (aimed at incorporating HbA1c results into self-care could) have an effect on overall glycemic control in patients who do not require exogenous insulin.
They recruited 453 adults with type 2 diabetes from 48 family practices. The mean patient age was 65.7 years, and 57% of the participants were male. They were randomly assigned to either:
Standard care with HbA1c testing once every three months.
Self-monitoring of blood glucose at least six times per week, with the results recorded in a self-care log that was shared with a research nurse every three months, and with instruction to call their doctors if glucose levels fell outside of established parameters; or
Self-monitoring at least six times a week, after individual training, with phone and clinic follow-up to interpret and apply the results of testing to enhance motivation, goal-setting, dietary maintenance, physical activity, and drug regimens.
The primary study outcome was HbA1c at one year, adjusted for baseline values.
A total of 57 patients (13%) were lost to follow-up at one year. The loss of patients was distributed even across the three groups, and the analysis was by intention-to-treat.
The authors found that two-thirds of patients who followed the less-intensive self-monitoring regimen and half of those following the more intensive plan had monitored their blood glucose levels at least twice per week over the past 12 months.
The mean HbA1c at baseline was similar across the three groups at 7.5%, above the less than 7% value recommended by the American Diabetes Association., and at one year there were still no significant differences among the groups. The mean difference in HbA1c between controls and patients in the less-intensive monitoring groups was 0.14% in favor of monitoring, and between controls and the hard-core self monitors, the mean difference was 0.17%, also in favor of monitoring. These differences were not statistically significant, however (P=0.12).
"A difference of -0.5% or more would generally be needed for a therapy to be considered clinically effective, and we powered the study to be able to see a difference that large if it existed, but we did not get it," said Dr. Farmer.
The study was funded by the Health Technology Assessment Programme, which is part of the United Kingdom National Institute for Health Research. Author conflicts of interest were not available. Primary source: American Diabetes Association 2007 Scientific SessionsSource reference: Farmer AJ et al. "Self-blood glucose monitoring yields no significant improved in non-insulin users with type 2 diabetes." Presented June 26.
Cell Therapy Key to Staunching Stress Incontinence
INNSBRUCK, Austria, June 28 -- A novel treatment to relieve stress incontinence in women, strengthening the urinary rhabdosphincter with cultured autologous tissue, has panned out.
A year after the procedure, 38 of the 42 women who underwent the procedure were completely continent, according to Hannes Strasser, M.D. of the University of Innsbruck.
He and colleagues used autologous muscle and connective tissue cells -- extracted, grown in culture, and re-implanted - and found the approach safe and effective, they reported in the June 30 issue of The Lancet. In contrast, only two of 21 women in a control group given standard collagen injections were continent.
Other outcome measures, including the thickness and contractility of the rhabdosphincter, also improved significantly (P<0.0001), the researchers said
A estimated 165,000 women a year in the U.S. have surgery for stress incontinence.
The findings "can be seen as the beginning of a new era in urogynecology," said Giacomo Novara, M.D., of the University of Padua and Walter Artibani, M.D., of the IRCCS Instituto Oncologico Veneto, both in Padua, Italy, in an accompanying commentary.
Drs. Novara and Artibani said the urological community has been waiting for the results since 2003, when preliminary observations of the procedure were reported.
The results of the current randomized controlled trial are "impressive, both in terms of efficacy and tolerability of the new procedure," they said, although larger multicenter studies, with longer follow-up, should be performed.
Dr. Strasser and colleagues enrolled 63 women with stress incontinence and randomized them in a two-to-one fashion to either endoscopic injections of collagen into the periurethral tissue or to the experimental procedure.
The 42 women in the experimental arm, ages 36 to 84, had a muscle biopsy and blood sample taken, which were then taken to one of two centers in Austria certified to produce myoblasts and fibroblasts. Several of the authors have financial connections with the two centers.
After six to eight weeks of culture, the myoblasts were injected into the rhabdosphincter in 15 to 18 portions at two different levels in the middle third of the urethra, using an ultrasound transducer so the physicians could visualize the organs.
At the same time, the fibroblasts (with a small amount of collagen) were injected into the urethral submucosa in 25 to 30 places.
Because the two procedures were different, the study was not fully blinded, the researchers said, but the randomization was blinded, and those who collected and analyzed data did not know which women were in which group.
A year after the procedure, the researchers found:
90% of the women who got the experimental procedure were continent, compared with 9.5% of those who got collagen injections. The difference was significant at P<0.0001.
On average, the rhabdosphincter of the treated women was a millimeter thicker than those in the control group - 3.38 versus 2.32 mm.
Contractility of the rhabdosphincter was also better - 1.56 mm versus 0.67.
There was no significant difference in the thickness of the urethra.
Dr. Strasser and colleagues said that after a median follow-up of three years no severe side-effects or scars have been reported in any of the 63 volunteers, and postoperative results have not changed. They added that long-term post-operative data are needed and more studies are needed before the procedure can be established as a standard incontinence treatment.
Dr. Strasser and co-author Rainer Marksteiner, Ph.D., are co-owners of Innovacell Biotechnologie, while co-author Martin Fussenegger, M.D. is an owner of IGOR The companies run certified facilities where the autologous cells were grown. Eva Margreiter, Ph.M., is an employee of Innovacell. The study was supported by a grant from the Medical University Innsbruck. Primary source: The LancetSource reference: Strasser S et al. "Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial." Lancet 2007; 369: 2179-86 Additional source: The LancetSource reference: Giacomo Novara and Walter Artibani. "Myoblasts and fibroblasts in stress urinary incontinence." Lancet 2007; 369: 2139-40.
A year after the procedure, 38 of the 42 women who underwent the procedure were completely continent, according to Hannes Strasser, M.D. of the University of Innsbruck.
He and colleagues used autologous muscle and connective tissue cells -- extracted, grown in culture, and re-implanted - and found the approach safe and effective, they reported in the June 30 issue of The Lancet. In contrast, only two of 21 women in a control group given standard collagen injections were continent.
Other outcome measures, including the thickness and contractility of the rhabdosphincter, also improved significantly (P<0.0001), the researchers said
A estimated 165,000 women a year in the U.S. have surgery for stress incontinence.
The findings "can be seen as the beginning of a new era in urogynecology," said Giacomo Novara, M.D., of the University of Padua and Walter Artibani, M.D., of the IRCCS Instituto Oncologico Veneto, both in Padua, Italy, in an accompanying commentary.
Drs. Novara and Artibani said the urological community has been waiting for the results since 2003, when preliminary observations of the procedure were reported.
The results of the current randomized controlled trial are "impressive, both in terms of efficacy and tolerability of the new procedure," they said, although larger multicenter studies, with longer follow-up, should be performed.
Dr. Strasser and colleagues enrolled 63 women with stress incontinence and randomized them in a two-to-one fashion to either endoscopic injections of collagen into the periurethral tissue or to the experimental procedure.
The 42 women in the experimental arm, ages 36 to 84, had a muscle biopsy and blood sample taken, which were then taken to one of two centers in Austria certified to produce myoblasts and fibroblasts. Several of the authors have financial connections with the two centers.
After six to eight weeks of culture, the myoblasts were injected into the rhabdosphincter in 15 to 18 portions at two different levels in the middle third of the urethra, using an ultrasound transducer so the physicians could visualize the organs.
At the same time, the fibroblasts (with a small amount of collagen) were injected into the urethral submucosa in 25 to 30 places.
Because the two procedures were different, the study was not fully blinded, the researchers said, but the randomization was blinded, and those who collected and analyzed data did not know which women were in which group.
A year after the procedure, the researchers found:
90% of the women who got the experimental procedure were continent, compared with 9.5% of those who got collagen injections. The difference was significant at P<0.0001.
On average, the rhabdosphincter of the treated women was a millimeter thicker than those in the control group - 3.38 versus 2.32 mm.
Contractility of the rhabdosphincter was also better - 1.56 mm versus 0.67.
There was no significant difference in the thickness of the urethra.
Dr. Strasser and colleagues said that after a median follow-up of three years no severe side-effects or scars have been reported in any of the 63 volunteers, and postoperative results have not changed. They added that long-term post-operative data are needed and more studies are needed before the procedure can be established as a standard incontinence treatment.
Dr. Strasser and co-author Rainer Marksteiner, Ph.D., are co-owners of Innovacell Biotechnologie, while co-author Martin Fussenegger, M.D. is an owner of IGOR The companies run certified facilities where the autologous cells were grown. Eva Margreiter, Ph.M., is an employee of Innovacell. The study was supported by a grant from the Medical University Innsbruck. Primary source: The LancetSource reference: Strasser S et al. "Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial." Lancet 2007; 369: 2179-86 Additional source: The LancetSource reference: Giacomo Novara and Walter Artibani. "Myoblasts and fibroblasts in stress urinary incontinence." Lancet 2007; 369: 2139-40.
Nissen Responds to Rosiglitazone Debate at ADA Meeting
June 28, 2007 (Chicago, IL) – Dr Steven Nissen (Cleveland Clinic, OH) arrived to a packed auditorium to tell the audience what he knew about rosiglitazone (Avandia, GlaxoSmithKline), when he knew it, and what he believes needs to be done next. Although he has been much in the spotlight in the past month, his audience this time, instead of politicians on Capitol Hill, was a house full of doctors and researchers in a hastily added panel discussion at the American Diabetes Association (ADA) 2007 Scientific Sessions in Chicago, IL.
Discussing the cardiovascular safety of a drug that has shaken up the cardiovascular and diabetic communities, Nissen outlined his rationale for performing and publishing a meta-analysis that linked the popular diabetes drug to increased cardiovascular events. Speaking during the panel discussion, Nissen defended his decision to put the results of his analysis into the scientific realm, despite the expected tumult the findings would generate, as well as the confusion that might ensue among patients taking the drug.
"We didn't call for the withdrawal of the drug, and we didn't call for regulatory action," said Nissen. "We simply said that we want you and others who treat these patients to be aware of the findings. There was a lot of criticism--should this have been published or shouldn't it--but let me say to you the alternative to us was unacceptable. The alternative would be to keep the scientific community in the dark, to not tell you that a pooled analysis of all these data showed a pretty substantial increase in the risk of the most serious complication of diabetes."
Some audience members weren't having anything of this argument, however, and one in particular said publishing the results was irresponsible, mainly because patient dropouts in ongoing rosiglitazone trials would be a natural consequence. The failure of those trials, he said, would fall squarely on Nissen's shoulders.
Data snooping on quite a big scale
The meta-analysis in question, published in the May 21, 2007 issue of New England Journal of Medicine (Nissen SE and Wolski K. N Engl J Med 2007; 356:2457-71), and reported by heartwire at that time, suggested that rosiglitazone increased the risk of MI 43% and might also increase the risk of cardiovascular death, an end point that met only borderline statistical significance. Nissen noted that GlakoSmithKline, the maker of rosiglitazone, as well as the Food and Drug Administration conducted similar meta-analyses, and both of these showed an increase in ischemic events.
Like all meta-analyses, Nissen said there are weaknesses to his study. He did not have access to patient-level data, and the cardiovascular events, which were not adjudicated, were not the primary end point in any of the 42 trials included in the meta-analysis.
"This is an important weakness," said Nissen. "We're always on firmer ground when we have prospective, adjudicated, carefully collected end points. These end points were primarily collected as serious adverse events." Despite these limitations, however, "patients and providers should consider the potential for serious cardiovascular effects of treatment with rosiglitazone for type 2 diabetes."
Dr Philip Home (Newcastle University, Newcastle upon Tyne, UK), who spoke during the panel discussion, said he believes the meta-analysis should have been published, as did all panel members, including Drs David Nathan (Harvard University Medical School, Boston, MA), Barry Goldstein (Thomas Jefferson University, Philadelphia, PA), and John Buse (University of North Carolina Medical School, Chapel Hill). However, Home said study was "data snooping on quite a big scale" and that the results should be used only to generate future studies.
Home, who is the lead author of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, pointed out that an interim analysis of this trial, conducted in light of the recent rosiglitazone concerns and published online June 5, 2007 in the New England Journal of Medicine, showed no statistically significant differences in the overall risk of hospitalization or death from cardiovascular causes. The RECORD study, he noted, is specifically designed to examine cardiovascular events, unlike the trials included in the meta-analysis. The results, he said, suggest that rosiglitazone should continue to have a role in glucose-lowering therapy and that studies like Nissen's meta-analysis, while important for raising awareness, form a "a poor basis for making decisions."
While it is important to wait for cardiovascular-end-point trials before making regulatory decisions, Nissen lamented the fact that in the eight years since the approval of rosiglitazone no definitive end-point trials have been published, despite the signal of increased risk of ischemic events observed in the earliest studies. The RECORD study, said Nissen, is too flawed to answer the question of whether or not rosiglitazone increases cardiovascular risk.
Half-baked editorial with an axe to grind
One of the biggest criticisms leveled by Home, as well by other audience members, was aimed squarely at last month's editorial accompanying Nissen's meta-analysis. Written by Drs Bruce Psaty (University of Washington, Seattle) and Curt Furberg (Wake Forest University, Winston-Salem, NC), the editorialists shared Nissen's concerns, but Home called it a "half-baked editorial with an axe to grind."
In a later discussion with Dr Richard Kahn, the chief scientific and medical officer of the ADA, when asked if they would start a patient on rosiglitazone, Nathan, Goldstein, and Buse said they would not, at least not until the cardiovascular issues were settled. They would be reluctant to take a well-controlled patient off the drug, however, but might switch if the patient failed to reach glycemic targets with the drug. Nathan reminded the audience that rosiglitazone, at this time, is intended for glycemic control to prevent microvascular and neurologic complications, not for the prevention of cardiovascular disease.
Discussing the cardiovascular safety of a drug that has shaken up the cardiovascular and diabetic communities, Nissen outlined his rationale for performing and publishing a meta-analysis that linked the popular diabetes drug to increased cardiovascular events. Speaking during the panel discussion, Nissen defended his decision to put the results of his analysis into the scientific realm, despite the expected tumult the findings would generate, as well as the confusion that might ensue among patients taking the drug.
"We didn't call for the withdrawal of the drug, and we didn't call for regulatory action," said Nissen. "We simply said that we want you and others who treat these patients to be aware of the findings. There was a lot of criticism--should this have been published or shouldn't it--but let me say to you the alternative to us was unacceptable. The alternative would be to keep the scientific community in the dark, to not tell you that a pooled analysis of all these data showed a pretty substantial increase in the risk of the most serious complication of diabetes."
Some audience members weren't having anything of this argument, however, and one in particular said publishing the results was irresponsible, mainly because patient dropouts in ongoing rosiglitazone trials would be a natural consequence. The failure of those trials, he said, would fall squarely on Nissen's shoulders.
Data snooping on quite a big scale
The meta-analysis in question, published in the May 21, 2007 issue of New England Journal of Medicine (Nissen SE and Wolski K. N Engl J Med 2007; 356:2457-71), and reported by heartwire at that time, suggested that rosiglitazone increased the risk of MI 43% and might also increase the risk of cardiovascular death, an end point that met only borderline statistical significance. Nissen noted that GlakoSmithKline, the maker of rosiglitazone, as well as the Food and Drug Administration conducted similar meta-analyses, and both of these showed an increase in ischemic events.
Like all meta-analyses, Nissen said there are weaknesses to his study. He did not have access to patient-level data, and the cardiovascular events, which were not adjudicated, were not the primary end point in any of the 42 trials included in the meta-analysis.
"This is an important weakness," said Nissen. "We're always on firmer ground when we have prospective, adjudicated, carefully collected end points. These end points were primarily collected as serious adverse events." Despite these limitations, however, "patients and providers should consider the potential for serious cardiovascular effects of treatment with rosiglitazone for type 2 diabetes."
Dr Philip Home (Newcastle University, Newcastle upon Tyne, UK), who spoke during the panel discussion, said he believes the meta-analysis should have been published, as did all panel members, including Drs David Nathan (Harvard University Medical School, Boston, MA), Barry Goldstein (Thomas Jefferson University, Philadelphia, PA), and John Buse (University of North Carolina Medical School, Chapel Hill). However, Home said study was "data snooping on quite a big scale" and that the results should be used only to generate future studies.
Home, who is the lead author of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, pointed out that an interim analysis of this trial, conducted in light of the recent rosiglitazone concerns and published online June 5, 2007 in the New England Journal of Medicine, showed no statistically significant differences in the overall risk of hospitalization or death from cardiovascular causes. The RECORD study, he noted, is specifically designed to examine cardiovascular events, unlike the trials included in the meta-analysis. The results, he said, suggest that rosiglitazone should continue to have a role in glucose-lowering therapy and that studies like Nissen's meta-analysis, while important for raising awareness, form a "a poor basis for making decisions."
While it is important to wait for cardiovascular-end-point trials before making regulatory decisions, Nissen lamented the fact that in the eight years since the approval of rosiglitazone no definitive end-point trials have been published, despite the signal of increased risk of ischemic events observed in the earliest studies. The RECORD study, said Nissen, is too flawed to answer the question of whether or not rosiglitazone increases cardiovascular risk.
Half-baked editorial with an axe to grind
One of the biggest criticisms leveled by Home, as well by other audience members, was aimed squarely at last month's editorial accompanying Nissen's meta-analysis. Written by Drs Bruce Psaty (University of Washington, Seattle) and Curt Furberg (Wake Forest University, Winston-Salem, NC), the editorialists shared Nissen's concerns, but Home called it a "half-baked editorial with an axe to grind."
In a later discussion with Dr Richard Kahn, the chief scientific and medical officer of the ADA, when asked if they would start a patient on rosiglitazone, Nathan, Goldstein, and Buse said they would not, at least not until the cardiovascular issues were settled. They would be reluctant to take a well-controlled patient off the drug, however, but might switch if the patient failed to reach glycemic targets with the drug. Nathan reminded the audience that rosiglitazone, at this time, is intended for glycemic control to prevent microvascular and neurologic complications, not for the prevention of cardiovascular disease.
Exercise Training in Ambulatory Stroke Survivors Has Benefits
By Megan Rauscher
NEW YORK (Reuters Health) Jun 28 - For stroke survivors who have completed rehab and are ambulatory, exercise training is feasible and improves physical functioning and aspects of mental health, an exploratory study conducted in the UK shows.
"There was also strong anecdotal evidence of social benefits," first author Dr. Gillian E. Mead of the University of Edinburgh told Reuters Health.
The study involved 66 independently ambulatory stroke patients with a mean age of 72 without significant dysphasia, confusion, or medical contraindications to exercise training. All of them had completed their rehabilitation and had been discharged from the hospital.
They were randomized to a 12-week program of exercise training, which included both endurance and resistance training, held three times a week, or to relaxation sessions focusing on "attention control."
According to a report of the study in the June issue of the Journal of the American Geriatrics Society, stroke patients tolerated the exercise training well, with high rates of attendance at exercise classes and individual exercises.
Compared with a non-exercise attention control intervention, exercise training led to "greater improvements in physical function and physical fitness," Dr. Mead said.
Specifically, at 3 months, the exercisers performed significantly better than the non-exercisers on the timed up-and-go test, walking economy and the role-physical item on the Short Form Health Survey-36.
At 7 months, however, only role-physical function remained significantly better in the exercise group, "suggesting that benefits of exercise training are lost after the exercise sessions cease," the authors write.
"This work," Dr. Mead said, "justifies the provision of exercise classes in the community for stroke patients, and further larger multicenter trials to investigate whether exercise training can reduce disability and to explore its cost-effectiveness."
J Am Geriatr Soc 2007;55:892-899.
NEW YORK (Reuters Health) Jun 28 - For stroke survivors who have completed rehab and are ambulatory, exercise training is feasible and improves physical functioning and aspects of mental health, an exploratory study conducted in the UK shows.
"There was also strong anecdotal evidence of social benefits," first author Dr. Gillian E. Mead of the University of Edinburgh told Reuters Health.
The study involved 66 independently ambulatory stroke patients with a mean age of 72 without significant dysphasia, confusion, or medical contraindications to exercise training. All of them had completed their rehabilitation and had been discharged from the hospital.
They were randomized to a 12-week program of exercise training, which included both endurance and resistance training, held three times a week, or to relaxation sessions focusing on "attention control."
According to a report of the study in the June issue of the Journal of the American Geriatrics Society, stroke patients tolerated the exercise training well, with high rates of attendance at exercise classes and individual exercises.
Compared with a non-exercise attention control intervention, exercise training led to "greater improvements in physical function and physical fitness," Dr. Mead said.
Specifically, at 3 months, the exercisers performed significantly better than the non-exercisers on the timed up-and-go test, walking economy and the role-physical item on the Short Form Health Survey-36.
At 7 months, however, only role-physical function remained significantly better in the exercise group, "suggesting that benefits of exercise training are lost after the exercise sessions cease," the authors write.
"This work," Dr. Mead said, "justifies the provision of exercise classes in the community for stroke patients, and further larger multicenter trials to investigate whether exercise training can reduce disability and to explore its cost-effectiveness."
J Am Geriatr Soc 2007;55:892-899.
Disclosure of Medical Errors to Patients Reviewed
A review in the current New England Journal of Medicine examines the current thinking on disclosure to patients of harmful medical errors.
After describing the evolution of "an environment ripe for change" on disclosure, the review:
-- describes the National Quality Forum's safe-practice guideline on disclosure as a "core component of high-quality health care";
-- discusses disclosure laws that have been proposed or enacted, as well as concerns about the ability of regulators to audit or enforce them; and
-- considers the status of current programs and likely future developments, including the likelihood that some organizations "will move the involved clinicians to the periphery and will rely on rapid-response teams to conduct disclosures."
It concludes that "within a decade, full and frank disclosure of these events to patients is likely to be the norm rather than the exception."
After describing the evolution of "an environment ripe for change" on disclosure, the review:
-- describes the National Quality Forum's safe-practice guideline on disclosure as a "core component of high-quality health care";
-- discusses disclosure laws that have been proposed or enacted, as well as concerns about the ability of regulators to audit or enforce them; and
-- considers the status of current programs and likely future developments, including the likelihood that some organizations "will move the involved clinicians to the periphery and will rely on rapid-response teams to conduct disclosures."
It concludes that "within a decade, full and frank disclosure of these events to patients is likely to be the norm rather than the exception."
Overweight elderly don't have higher death rates
After the age of 80, carrying a few extra pounds may not subtract years from your lifespan, a new study from Japan shows.
Among a group of 80-year-olds followed for four years, the researchers found that underweight individuals were more likely to die from cancer, heart disease or pneumonia than normal-weight or overweight people. "Overweight status was associated with longevity and underweight with short life," Dr. Yutaka Takata and colleagues from Kyushu Dental College in Kitakyushu City conclude.
While being overweight has been tied to a greater risk of heart disease, studies have also found that being underweight with heart disease may carry an increased risk of morbidity and mortality, Takata and his team note.
To better understand the controversial relationship between body mass index (BMI) and mortality from heart disease, as well as all-cause mortality, the researchers looked at men and women who were 80-years-old.
Fifty-two were underweight, with an average BMI of 17.2; another 468 were normal-weight, with BMIs averaging 21.8; and 155 were overweight, with an average BMI of 27.3. Just five people in the study were obese (with a BMI of 30 or greater), so they were included in the overweight group. People with BMIs between 18.5 and 25 are considered normal weight, while individuals with BMIs of 25 or greater are classified as overweight.
Mortality rates from heart disease, pneumonia and cancer for normal-weight and overweight individuals weren't significantly different, the researchers found. But underweight men and women were nearly four times as likely to die from any cause compared with as overweight individuals, and nearly 18 times more likely to die from cancer. Heart disease mortality in the underweight group was almost four times greater than among normal-weight individuals.
Other studies have found a protective effect of extra pounds among older individuals, Takata and his colleagues note; for example, among elderly US men, the lowest mortality is seen among men with BMIs of 26 and among women with BMIs of 29.6. While Takata and his colleagues attempted to control for the effects of illness, it is still possible that existing disease accounted for some of the increased mortality risk seen among the underweight individuals, they note.
"It is likely that only mild obesity (but not severe obesity) or overweight status in older people and in patients with heart disease may be associated with a lower mortality rate from any disease, as well as with lower mortality from cardiovascular disease," the researchers conclude.
SOURCE: Journal of the American Geriatrics Society, June 2007.
Among a group of 80-year-olds followed for four years, the researchers found that underweight individuals were more likely to die from cancer, heart disease or pneumonia than normal-weight or overweight people. "Overweight status was associated with longevity and underweight with short life," Dr. Yutaka Takata and colleagues from Kyushu Dental College in Kitakyushu City conclude.
While being overweight has been tied to a greater risk of heart disease, studies have also found that being underweight with heart disease may carry an increased risk of morbidity and mortality, Takata and his team note.
To better understand the controversial relationship between body mass index (BMI) and mortality from heart disease, as well as all-cause mortality, the researchers looked at men and women who were 80-years-old.
Fifty-two were underweight, with an average BMI of 17.2; another 468 were normal-weight, with BMIs averaging 21.8; and 155 were overweight, with an average BMI of 27.3. Just five people in the study were obese (with a BMI of 30 or greater), so they were included in the overweight group. People with BMIs between 18.5 and 25 are considered normal weight, while individuals with BMIs of 25 or greater are classified as overweight.
Mortality rates from heart disease, pneumonia and cancer for normal-weight and overweight individuals weren't significantly different, the researchers found. But underweight men and women were nearly four times as likely to die from any cause compared with as overweight individuals, and nearly 18 times more likely to die from cancer. Heart disease mortality in the underweight group was almost four times greater than among normal-weight individuals.
Other studies have found a protective effect of extra pounds among older individuals, Takata and his colleagues note; for example, among elderly US men, the lowest mortality is seen among men with BMIs of 26 and among women with BMIs of 29.6. While Takata and his colleagues attempted to control for the effects of illness, it is still possible that existing disease accounted for some of the increased mortality risk seen among the underweight individuals, they note.
"It is likely that only mild obesity (but not severe obesity) or overweight status in older people and in patients with heart disease may be associated with a lower mortality rate from any disease, as well as with lower mortality from cardiovascular disease," the researchers conclude.
SOURCE: Journal of the American Geriatrics Society, June 2007.
U.S. tracks serious form of syphilis in gay men
By Will DunhamThu Jun 28, 6:03 PM ET
A particularly serious form of the sexually transmitted bacterial disease syphilis has been detected in gay and bisexual U.S. men infected with the AIDS virus, federal health officials reported on Thursday.
The U.S. Centers for Disease Control and Prevention tracked 49 HIV-infected gay and bisexual men who had "symptomatic early neurosyphilis" from January 2002 to June 2004 in four cities -- Los Angeles, San Diego, Chicago, New York.
The CDC cited the report as further evidence that gay and bisexual men, many also infected with HIV, are the driving force behind increases in U.S. syphilis cases this decade.
The findings also indicate that these men are engaging in the same risky, unprotected sex that can spread the human immunodeficiency virus, which causes AIDS.
"These are primarily infections that people are probably getting because they're not using condoms," Dr. Thomas Peterman of the CDC's Division of STD Prevention, an author of the report.
In some instances, the men involved have the attitude that they do not need safe-sex practices because they already are infected with HIV, Peterman said.
Since dropping to the lowest level on record in 2000, the U.S. rate of syphilis has risen steadily. Gay and bisexual men accounted for 7 percent of syphilis cases in 2000, but more than 60 percent in 2005, CDC officials have said.
Symptomatic early neurosyphilis is a rare manifestation of syphilis usually occurring within the first year of infection.
Ordinary syphilis is readily curable with antibiotics in its early stages. Neurosyphilis can lead to blindness or stroke, Peterman said.
"There are a number of studies that continue to show that there are some HIV-infected and some uninfected men who have sex with men who continue to have large numbers of (sexual) partners and anonymous sex. This is one of the consequences of that," Peterman said.
Of the 49 HIV-positive gay and bisexual men with symptomatic early neurosyphilis, 63 percent were non-Hispanic whites, 18 were non-Hispanic blacks and 14 percent were Hispanic. Their average age was 38.
"I think the bigger message is that we need to get control of syphilis. And control of syphilis would require safe-sex behavior, reducing the number of partners, and using condoms with those partners," Peterman said.
"And for men who have sex with men, it means getting tested for HIV and other STDs at least once a year," Peterman added.
Syphilis, like many other sexually transmitted diseases, raises the likelihood of infection by or transmission of HIV.
A particularly serious form of the sexually transmitted bacterial disease syphilis has been detected in gay and bisexual U.S. men infected with the AIDS virus, federal health officials reported on Thursday.
The U.S. Centers for Disease Control and Prevention tracked 49 HIV-infected gay and bisexual men who had "symptomatic early neurosyphilis" from January 2002 to June 2004 in four cities -- Los Angeles, San Diego, Chicago, New York.
The CDC cited the report as further evidence that gay and bisexual men, many also infected with HIV, are the driving force behind increases in U.S. syphilis cases this decade.
The findings also indicate that these men are engaging in the same risky, unprotected sex that can spread the human immunodeficiency virus, which causes AIDS.
"These are primarily infections that people are probably getting because they're not using condoms," Dr. Thomas Peterman of the CDC's Division of STD Prevention, an author of the report.
In some instances, the men involved have the attitude that they do not need safe-sex practices because they already are infected with HIV, Peterman said.
Since dropping to the lowest level on record in 2000, the U.S. rate of syphilis has risen steadily. Gay and bisexual men accounted for 7 percent of syphilis cases in 2000, but more than 60 percent in 2005, CDC officials have said.
Symptomatic early neurosyphilis is a rare manifestation of syphilis usually occurring within the first year of infection.
Ordinary syphilis is readily curable with antibiotics in its early stages. Neurosyphilis can lead to blindness or stroke, Peterman said.
"There are a number of studies that continue to show that there are some HIV-infected and some uninfected men who have sex with men who continue to have large numbers of (sexual) partners and anonymous sex. This is one of the consequences of that," Peterman said.
Of the 49 HIV-positive gay and bisexual men with symptomatic early neurosyphilis, 63 percent were non-Hispanic whites, 18 were non-Hispanic blacks and 14 percent were Hispanic. Their average age was 38.
"I think the bigger message is that we need to get control of syphilis. And control of syphilis would require safe-sex behavior, reducing the number of partners, and using condoms with those partners," Peterman said.
"And for men who have sex with men, it means getting tested for HIV and other STDs at least once a year," Peterman added.
Syphilis, like many other sexually transmitted diseases, raises the likelihood of infection by or transmission of HIV.
Breast Cancer Survival May Run in Families
THURSDAY, June 28 (HealthDay News) -- Women can look to their mothers and sisters to help determine their chances of survival from breast cancer, new research suggests.
This Swedish study, published in the online issue of Breast Cancer Research, found that if a woman succumbs to breast cancer, her daughters or sisters have a 60 percent increased risk of dying from the disease if they develop it.
Led by Mikael Hartman from the Karolinska Institute in Stockholm. a team of researchers used Sweden's Multi-Generation Register to identify 2,787 mother-daughter pairs and 831 sister pairs of women who were diagnosed with breast cancer between 1961 and 2001.
The researchers found that daughters of mothers who survived breast cancer after five years had a 91 percent chance of surviving the disease, compared with an 87 percent chance for daughters of mothers who died within five years.
The same went for sisters. Having a sister who died of breast cancer within five years gave a 70 percent chance of survival, compared with an 88 percent chance of survival for those who had a sister who survived for five years.
Overall, the daughters and the sisters of a woman who died within five years were 60 percent to 70 percent more likely of dying from the disease within five years if they developed it.
These findings are "relevant to women with newly diagnosed breast cancer" and to those treating them, Hartman said in a prepared statement.
Future research is needed to determine what inherited factors may play a role in survival.
More information
The National Cancer Institute has more about breast cancer.
This Swedish study, published in the online issue of Breast Cancer Research, found that if a woman succumbs to breast cancer, her daughters or sisters have a 60 percent increased risk of dying from the disease if they develop it.
Led by Mikael Hartman from the Karolinska Institute in Stockholm. a team of researchers used Sweden's Multi-Generation Register to identify 2,787 mother-daughter pairs and 831 sister pairs of women who were diagnosed with breast cancer between 1961 and 2001.
The researchers found that daughters of mothers who survived breast cancer after five years had a 91 percent chance of surviving the disease, compared with an 87 percent chance for daughters of mothers who died within five years.
The same went for sisters. Having a sister who died of breast cancer within five years gave a 70 percent chance of survival, compared with an 88 percent chance of survival for those who had a sister who survived for five years.
Overall, the daughters and the sisters of a woman who died within five years were 60 percent to 70 percent more likely of dying from the disease within five years if they developed it.
These findings are "relevant to women with newly diagnosed breast cancer" and to those treating them, Hartman said in a prepared statement.
Future research is needed to determine what inherited factors may play a role in survival.
More information
The National Cancer Institute has more about breast cancer.
WHO: Air travelers should exercise legs
By FRANK JORDANS, Associated Press WriterThu Jun 28, 11:08 PM ET
The World Health Organization recommended Friday that passengers on long flights exercise their legs and resist taking sleeping pills to reduce the risk of potentially fatal blood clots.
Although the danger of developing deep vein thrombosis — normally in the form of a blood clot in the calves — is small, it increases if people are immobile for long periods in cramped conditions, the U.N. agency said in a report. Some people are also predisposed to the condition for genetic or lifestyle reasons.
WHO based its recommendations on research done by scientists in Britain, Switzerland and the Netherlands after the death in 2000 of a British woman after a long flight from Australia.
Emma Christofferson, 28, died from a pulmonary embolism, which occurs when a blood clot in the extremities breaks away and travels to the lungs. The condition can be treated if detected in time.
WHO said studies showed the risk of developing blood clots during any form of travel longer than four hours was 1 in 6,000 among the general population. That would translate into one case for every 15 fully booked jumbo jets.
"The risk to an individual stepping on a plane is tiny," Patrick Kesteven, a British doctor involved in the 24-page report, told The Associated Press.
"The problem is, vast numbers of people step on planes, and so it's a tiny risk multiplied by a huge denominator, so that in terms of a public health issue it's a highly significant problem," he said.
The Geneva-based International Air Transport Association said some 2.2 billion journeys are made by plane every year, though it was unable to say how many are long-haul.
Association spokesman Anthony Council said many airlines inform passengers of the risk of blood clots. "The advice that we give to passengers is that if you're in one of those at-risk groups you should speak to your physician before traveling," he told the AP.
Shanthi Mendis, a WHO expert on the issue, said the risks vary depending on a person's condition and how they behave, but added that the most important factor was immobility.
By getting up for a short walk, or doing exercises to contract the calf muscles every hour, passengers can greatly reduce the risk of blood clots, she said.
People also should not take sedatives or drink large amounts of alcohol because that would make them more likely to be immobile for long periods of time.
Other factors that can affect a person's chances of developing blood clots are obesity, genetic conditions, age, use of oral contraceptives, and being shorter than 5-foot-4 or taller than 6-foot-4. The theory is that short people are less mobile because their feet dangle and taller people because they are more cramped.
Mendis said research was needed to determine the precise impact of these risk factors, but one study had shown that women who take birth control pills are 10 times more likely to develop blood clots during long-distance travel than the average person.
WHO said that while the danger of blood clots is the same whether people travel long-distance by train, car or plane, those in high-risk groups were more likely to develop clots on flights.
"For people with high risk, some other factor in aircraft travel may be playing a role," Mendis said, adding more research was need to determine the reason.
Symptoms of blood clots include pain or cramps in the calves, and swelling of the leg, Mendis said.
The World Health Organization recommended Friday that passengers on long flights exercise their legs and resist taking sleeping pills to reduce the risk of potentially fatal blood clots.
Although the danger of developing deep vein thrombosis — normally in the form of a blood clot in the calves — is small, it increases if people are immobile for long periods in cramped conditions, the U.N. agency said in a report. Some people are also predisposed to the condition for genetic or lifestyle reasons.
WHO based its recommendations on research done by scientists in Britain, Switzerland and the Netherlands after the death in 2000 of a British woman after a long flight from Australia.
Emma Christofferson, 28, died from a pulmonary embolism, which occurs when a blood clot in the extremities breaks away and travels to the lungs. The condition can be treated if detected in time.
WHO said studies showed the risk of developing blood clots during any form of travel longer than four hours was 1 in 6,000 among the general population. That would translate into one case for every 15 fully booked jumbo jets.
"The risk to an individual stepping on a plane is tiny," Patrick Kesteven, a British doctor involved in the 24-page report, told The Associated Press.
"The problem is, vast numbers of people step on planes, and so it's a tiny risk multiplied by a huge denominator, so that in terms of a public health issue it's a highly significant problem," he said.
The Geneva-based International Air Transport Association said some 2.2 billion journeys are made by plane every year, though it was unable to say how many are long-haul.
Association spokesman Anthony Council said many airlines inform passengers of the risk of blood clots. "The advice that we give to passengers is that if you're in one of those at-risk groups you should speak to your physician before traveling," he told the AP.
Shanthi Mendis, a WHO expert on the issue, said the risks vary depending on a person's condition and how they behave, but added that the most important factor was immobility.
By getting up for a short walk, or doing exercises to contract the calf muscles every hour, passengers can greatly reduce the risk of blood clots, she said.
People also should not take sedatives or drink large amounts of alcohol because that would make them more likely to be immobile for long periods of time.
Other factors that can affect a person's chances of developing blood clots are obesity, genetic conditions, age, use of oral contraceptives, and being shorter than 5-foot-4 or taller than 6-foot-4. The theory is that short people are less mobile because their feet dangle and taller people because they are more cramped.
Mendis said research was needed to determine the precise impact of these risk factors, but one study had shown that women who take birth control pills are 10 times more likely to develop blood clots during long-distance travel than the average person.
WHO said that while the danger of blood clots is the same whether people travel long-distance by train, car or plane, those in high-risk groups were more likely to develop clots on flights.
"For people with high risk, some other factor in aircraft travel may be playing a role," Mendis said, adding more research was need to determine the reason.
Symptoms of blood clots include pain or cramps in the calves, and swelling of the leg, Mendis said.
Thursday, June 28, 2007
ADA: Diabetes Yardstick Gets New Look
CHICAGO, June 27 -- Now that physicians are growing familiar with glycosylated hemoglobin percentages, average glucose levels are rising to the fore, investigators here reported.
The new standard, which involves more of a technical than clinical change, involves a more accurate calculation of HbA1c in the lab, but reporting of results as both HbA1c and an average glucose level, said David Nathan, M.D., of Harvard.
The technical change has already been performed behind the scenes, with clinical labs and manufacturers calibrating their equipment to the new standards, Dr. Nathan and colleagues reported at the American Diabetes Association meeting here.
Dr. Nathan presented preliminary results of an international study looking at whether the new HbA1c standard can be accurately and consistently translated into average glucose.
"It sounds technical and somewhat dry, but from the point of view of diabetes management, this is something that has been absolutely dominating our interest and attention -- clinical chemists, clinical pathologists, and clinicians, and investigators -- for a couple of years now," Dr. Nathan said.
There was concern among physicians that patients would be confused by the new measurement, which would effectively change an HbA1c of less than 7% (the current ADA standard) from an "A" to a "C-," Dr. Nathan said.
To prevent that confusion, the world's leading diabetes organizations -- the ADA, European Association for the Study of Diabetes, and International Diabetes Federation -- agreed on a means for translating the new measurement into a uniform reference number.
The reference number can then be translated into the familiar HbA1c values using simple mathematic formulas, and into the average blood glucose number, which may be an easier number to grasp for patients who are accustomed to daily finger sticks and blood glucose monitoring, Dr. Nathan said.
"We hope that we will have converted the hemoglobin A1c into an easily translatable value that has actually has more significance for patients," Dr. Nathan said.
The International A1c-AG study was conducted at 10 centers in the North America, Europe, and Africa, in an attempt to determine, as accurately as possible, the relationship between average blood glucose levels and HbA1c.
The study has recruited almost 650 of its goal of 700 volunteers (300 patients with type 1, 300 with type 2, and 100 without diabetes).
The patients' HbA1Cs are measured in a central laboratory in Holland using the new reference standard monthly for four months, with patients using a combination of continuous glucose monitoring for two to three days for each of the four months, plus frequent finger sticks equivalent to daily self-monitoring.
The results of the first 250 volunteers who have completed the study showed that there was a close correlation between HbA1c values at three months and average blood glucose during the same period, Dr. Nathan reported.
"The relationship appears to be the same for those with type 1 and type 2 and for men and women," Dr. Nathan said.
The investigators hope to present final results of the study at a meeting of the European Association for the Study of Diabetes in Amsterdam this September.
Details on study funding and author conflicts of interest were not available.Primary source: American Diabetes Association 2007 Scientific SessionsSource reference: Nathan D. "Relationship Between Average Blood Glucose and A1c," presented at a symposium June 25.
The new standard, which involves more of a technical than clinical change, involves a more accurate calculation of HbA1c in the lab, but reporting of results as both HbA1c and an average glucose level, said David Nathan, M.D., of Harvard.
The technical change has already been performed behind the scenes, with clinical labs and manufacturers calibrating their equipment to the new standards, Dr. Nathan and colleagues reported at the American Diabetes Association meeting here.
Dr. Nathan presented preliminary results of an international study looking at whether the new HbA1c standard can be accurately and consistently translated into average glucose.
"It sounds technical and somewhat dry, but from the point of view of diabetes management, this is something that has been absolutely dominating our interest and attention -- clinical chemists, clinical pathologists, and clinicians, and investigators -- for a couple of years now," Dr. Nathan said.
There was concern among physicians that patients would be confused by the new measurement, which would effectively change an HbA1c of less than 7% (the current ADA standard) from an "A" to a "C-," Dr. Nathan said.
To prevent that confusion, the world's leading diabetes organizations -- the ADA, European Association for the Study of Diabetes, and International Diabetes Federation -- agreed on a means for translating the new measurement into a uniform reference number.
The reference number can then be translated into the familiar HbA1c values using simple mathematic formulas, and into the average blood glucose number, which may be an easier number to grasp for patients who are accustomed to daily finger sticks and blood glucose monitoring, Dr. Nathan said.
"We hope that we will have converted the hemoglobin A1c into an easily translatable value that has actually has more significance for patients," Dr. Nathan said.
The International A1c-AG study was conducted at 10 centers in the North America, Europe, and Africa, in an attempt to determine, as accurately as possible, the relationship between average blood glucose levels and HbA1c.
The study has recruited almost 650 of its goal of 700 volunteers (300 patients with type 1, 300 with type 2, and 100 without diabetes).
The patients' HbA1Cs are measured in a central laboratory in Holland using the new reference standard monthly for four months, with patients using a combination of continuous glucose monitoring for two to three days for each of the four months, plus frequent finger sticks equivalent to daily self-monitoring.
The results of the first 250 volunteers who have completed the study showed that there was a close correlation between HbA1c values at three months and average blood glucose during the same period, Dr. Nathan reported.
"The relationship appears to be the same for those with type 1 and type 2 and for men and women," Dr. Nathan said.
The investigators hope to present final results of the study at a meeting of the European Association for the Study of Diabetes in Amsterdam this September.
Details on study funding and author conflicts of interest were not available.Primary source: American Diabetes Association 2007 Scientific SessionsSource reference: Nathan D. "Relationship Between Average Blood Glucose and A1c," presented at a symposium June 25.
ADA: Fibrates and Statins Keep Diabetic Neuropathy at Bay
CHICAGO, June 27 -- Statins can cut the risk of peripheral neuropathy from type 2 diabetes by a third, and fibrates can do it by nearly half, reported Australian investigators here.
Among nearly 1,300 patients with type 2 diabetes who were part of a longitudinal study, statins were associated with reduced risk of peripheral sensory neuropathy by 35%, and fibrates by 45%, said Timothy Davis, M.D., Ph.D., of the University of Western Australia, in Perth.
The reduced risk associated with the two lipid-lowering classes should be considered comparable, because of the wide confidence intervals involved, said Dr. Davis at the American Diabetes Association meeting here.
Dr. Davis and colleagues conducted a cross-sectional study of 1,294 patients enrolled in the Fremantle Diabetes Study, a five-year prospective study, and also evaluated 531 patients in the study who had attended six comprehensive annual assessments.
They defined neuropathy as a score greater than two out of eight on the clinical portion of the Michigan Neuropathy Screening Instrument, which, according to Dr. Davis, is among the most sensitive and specific of the clinical screening tools.
The mean age of the patients in the cross-sectional sample was 64.1+11.3 years and 48.8% were men. The median duration since diagnosis was 4.0 (range 1.0-9.0) years, and 30.9% of the patients had peripheral neuropathy.
In all, 3.5% of the patients used fibrates -- gemfibrozil (Lopid) at study outset, and later fenofibrate (Lofibra) -- and 6.8% used statins, including atorvastatin (Lipitor), simvastatin (Zocor), and pravastatin (Pravachol).
The authors found that in logistic regression analyses, many different factors were independently and positively associated (P<0.03) with prevalent peripheral neuropathy at baseline. These factors included sociodemographics, older age, longer diabetes duration, central adiposity, increasing height, higher fasting plasma glucose, systolic blood pressure, ratio of urinary albumin to creatinine, and ethnic-racial background.
In contrast, the use of fibrate therapy was negatively associated with neuropathy (odds ratio 0.30 (95% confidence interval, 0.10-0.86, (P=0.025).
Among the patients in the longitudinal substudy, the use of fibrates increased to 10.4% over five years, and the use of statins grew to 36.5%. Among these patients, the time to new peripheral neuropathy was associated with longer use of both fibrates (hazard ratio 0.52, 95% CI, 0.27-0.98) and statins (hazard ratio 0.65, 95% CI, 0.46-0.93), and both associations were significant (P<0.042).
Neither study funding nor author conflicts of interest were disclosed.Primary source: American Diabetes Association 2007 Scientific SessionsSource reference: Davis T et al. "Lipid-lowering Therapy Protects Against Peripheral Sensory Neuropathy in Type 2 Diabetes." Abstract 0004 , presented June 22.
Among nearly 1,300 patients with type 2 diabetes who were part of a longitudinal study, statins were associated with reduced risk of peripheral sensory neuropathy by 35%, and fibrates by 45%, said Timothy Davis, M.D., Ph.D., of the University of Western Australia, in Perth.
The reduced risk associated with the two lipid-lowering classes should be considered comparable, because of the wide confidence intervals involved, said Dr. Davis at the American Diabetes Association meeting here.
Dr. Davis and colleagues conducted a cross-sectional study of 1,294 patients enrolled in the Fremantle Diabetes Study, a five-year prospective study, and also evaluated 531 patients in the study who had attended six comprehensive annual assessments.
They defined neuropathy as a score greater than two out of eight on the clinical portion of the Michigan Neuropathy Screening Instrument, which, according to Dr. Davis, is among the most sensitive and specific of the clinical screening tools.
The mean age of the patients in the cross-sectional sample was 64.1+11.3 years and 48.8% were men. The median duration since diagnosis was 4.0 (range 1.0-9.0) years, and 30.9% of the patients had peripheral neuropathy.
In all, 3.5% of the patients used fibrates -- gemfibrozil (Lopid) at study outset, and later fenofibrate (Lofibra) -- and 6.8% used statins, including atorvastatin (Lipitor), simvastatin (Zocor), and pravastatin (Pravachol).
The authors found that in logistic regression analyses, many different factors were independently and positively associated (P<0.03) with prevalent peripheral neuropathy at baseline. These factors included sociodemographics, older age, longer diabetes duration, central adiposity, increasing height, higher fasting plasma glucose, systolic blood pressure, ratio of urinary albumin to creatinine, and ethnic-racial background.
In contrast, the use of fibrate therapy was negatively associated with neuropathy (odds ratio 0.30 (95% confidence interval, 0.10-0.86, (P=0.025).
Among the patients in the longitudinal substudy, the use of fibrates increased to 10.4% over five years, and the use of statins grew to 36.5%. Among these patients, the time to new peripheral neuropathy was associated with longer use of both fibrates (hazard ratio 0.52, 95% CI, 0.27-0.98) and statins (hazard ratio 0.65, 95% CI, 0.46-0.93), and both associations were significant (P<0.042).
Neither study funding nor author conflicts of interest were disclosed.Primary source: American Diabetes Association 2007 Scientific SessionsSource reference: Davis T et al. "Lipid-lowering Therapy Protects Against Peripheral Sensory Neuropathy in Type 2 Diabetes." Abstract 0004 , presented June 22.
ADA: Neuropathy Most Likely to Strike in Type 2 Diabetes
CHICAGO, June 27 -- Painful neuropathy is more common in patients with type 2 diabetes than in those with type 1, possibly, researchers suggest, because of a link with the metabolic syndrome.
In an observational study, painful diabetic polyneuropathy was three times more common among type 2 patients than type 1 patients (17.9% versus 5.8%), reported Ides M. Colin, M.D., Ph.D., of CHR-S. Joseph Medical Center in Mons, Belgium, and colleagues.
This type of neuropathy was independently associated with three components of the metabolic syndrome-obesity, low HDL cholesterol, and high triglyceride levels -- they said at the American Diabetes Association meeting here.
"The higher prevalence of diabetic polyneuropathy in type 2 diabetic patients could be due to the involvement of metabolic syndrome-associated disturbances," they wrote.
Because the epidemiology of painful diabetic polyneuropathy had not been well characterized, the researchers conducted a cross-sectional study that included 1,111 patients at 40 Belgian diabetes clinics; 344 had type 1diabetes and 767 had type 2.
The researchers tested for neuropathy in patients' feet using a monofilament for sensory perception and a device called the Neuropen for pain sensation. Participants also completed a questionnaire on characteristics of the pain sensation.
Nearly half of the patients overall complained of pain on the visual analog scale. Patients with type 2 diabetes reported it more frequently than did those with type 1 (53.6% versus 34.9%).
The occurrence of diabetic polyneuropathy was significantly higher among type 2 diabetes patients than type 1 patients (50.8% versus 25.6%, P=0.0007).
The prevalence of painful diabetic polyneuropathy showed the same significant difference (17.9% versus 5.6%).
Factors associated with higher diabetic neuropathy in a multivariate analysis were male gender (P=0.02), increasing age (P<0.0001), type 2 diabetes (P=0.02), increasing duration of the disease (P=0.0006), and HDL cholesterol at or below 40 mg/dL for men or 50 mg/dL for women (P<0.0001).
The strongest predictors of neuropathy in a bivariate analysis were foot problems (odds ratio 10.5, P<0.0001) and low HDL cholesterol (OR 2.14, P<0.0001).
Independent predictors of painful diabetic neuropathy were:
Low HDL cholesterol (OR 2.17, 95% confidence interval 1.38 to 3.41, P=0.0008).
Triglyceride levels at or above 150 mg/dL (OR 1.76, 95% CI 1.13 to 2.75, P=0.01).
Obesity (OR 1.62, 95% CI 1.05 to 2.49, P=0.03).
Nephropathy (OR 1.69, 95% CI 1.10 to 2.59, P=0.02).
Age (OR 1.47 per decade, 95% CI 1.20 to 1.81, P=0.0003).
Diabetes duration (OR 1.14 per five years, 95% 1.02 to 1.28, P=0.02).
The researchers concluded that neuropathy and painful neuropathy are mainly associated with type 2 diabetes, potentially via the metabolic syndrome, which encompassed the majority of the strong predictors found.
In an observational study, painful diabetic polyneuropathy was three times more common among type 2 patients than type 1 patients (17.9% versus 5.8%), reported Ides M. Colin, M.D., Ph.D., of CHR-S. Joseph Medical Center in Mons, Belgium, and colleagues.
This type of neuropathy was independently associated with three components of the metabolic syndrome-obesity, low HDL cholesterol, and high triglyceride levels -- they said at the American Diabetes Association meeting here.
"The higher prevalence of diabetic polyneuropathy in type 2 diabetic patients could be due to the involvement of metabolic syndrome-associated disturbances," they wrote.
Because the epidemiology of painful diabetic polyneuropathy had not been well characterized, the researchers conducted a cross-sectional study that included 1,111 patients at 40 Belgian diabetes clinics; 344 had type 1diabetes and 767 had type 2.
The researchers tested for neuropathy in patients' feet using a monofilament for sensory perception and a device called the Neuropen for pain sensation. Participants also completed a questionnaire on characteristics of the pain sensation.
Nearly half of the patients overall complained of pain on the visual analog scale. Patients with type 2 diabetes reported it more frequently than did those with type 1 (53.6% versus 34.9%).
The occurrence of diabetic polyneuropathy was significantly higher among type 2 diabetes patients than type 1 patients (50.8% versus 25.6%, P=0.0007).
The prevalence of painful diabetic polyneuropathy showed the same significant difference (17.9% versus 5.6%).
Factors associated with higher diabetic neuropathy in a multivariate analysis were male gender (P=0.02), increasing age (P<0.0001), type 2 diabetes (P=0.02), increasing duration of the disease (P=0.0006), and HDL cholesterol at or below 40 mg/dL for men or 50 mg/dL for women (P<0.0001).
The strongest predictors of neuropathy in a bivariate analysis were foot problems (odds ratio 10.5, P<0.0001) and low HDL cholesterol (OR 2.14, P<0.0001).
Independent predictors of painful diabetic neuropathy were:
Low HDL cholesterol (OR 2.17, 95% confidence interval 1.38 to 3.41, P=0.0008).
Triglyceride levels at or above 150 mg/dL (OR 1.76, 95% CI 1.13 to 2.75, P=0.01).
Obesity (OR 1.62, 95% CI 1.05 to 2.49, P=0.03).
Nephropathy (OR 1.69, 95% CI 1.10 to 2.59, P=0.02).
Age (OR 1.47 per decade, 95% CI 1.20 to 1.81, P=0.0003).
Diabetes duration (OR 1.14 per five years, 95% 1.02 to 1.28, P=0.02).
The researchers concluded that neuropathy and painful neuropathy are mainly associated with type 2 diabetes, potentially via the metabolic syndrome, which encompassed the majority of the strong predictors found.
Hepatitis C Positivity May Increase Risk for End-Stage Renal Disease
June 27, 2007 — Patients aged 18 to 70 years who have positive findings for hepatitis C virus are at an increased risk of developing end-stage renal disease, according to the results of a retrospective cohort study published in the June 25 issue of the Archives of Internal Medicine.
"Infection with chronic hepatitis C virus (HCV) has been linked to glomerulonephritis," write Judith I. Tsui, MD, from the University of California, San Francisco, and colleagues. "We undertook this study to determine whether having a positive HCV test result was associated with an increased risk for developing treated end-stage renal disease (ESRD)."
Using data from Medicare, the Department of Veterans Affairs (VA), and the US Renal Data System, the investigators performed a retrospective cohort study of 474,369 adult veterans with serum creatinine levels measurements between October 1, 2000, and September 30, 2001, and HCV antibody testing within 1 year of creatinine testing. Follow-up for the outcome of treated ESRD, defined as the onset of long-term dialysis or renal transplantation, continued through October 1, 2004. The relative risk for ESRD associated with HCV, after adjustment for other covariates (age, sex, race/ethnicity, and comorbidities), was determined with Cox proportional hazards models.
Findings from HCV antibody testing were positive in 52,874 (11.1%) of 474,369 patients. Patients with positive HCV test findings were more likely to develop ESRD, with a rate of 4.26 per 1000 person-years (95% confidence interval [CI], 3.97 - 4.57) for HCV-seropositive patients vs 3.05 (95% CI, 2.96 - 3.14) for HCV-seronegative patients.
For patients aged 18 to 70 years in whom estimated glomerular filtration rate was 30 mL/minute/1.73 m2 or greater, HCV seropositivity was associated with more than twice the risk of developing ESRD (adjusted hazard rate, 2.80; 95% CI, 2.43 - 3.23).
Study limitations include lack of generalizability to nonveteran populations; analysis being based on results of HCV antibody testing rather than HCV RNA testing; possibly reduced accuracy of the Modification of Diet in Renal Disease equation used to estimate glomerular filtration rate in patients with HCV; lack of data on proteinuria or albuminuria; use of International Classification of Diseases, Ninth Revision, codes for comorbidity diagnoses, when they are often insensitive and do not provide information on severity or control of the disease condition; possible unknown confounders; and short duration of follow-up.
"In this large national cohort of adult veterans, patients younger than 70 years with HCV seropositivity were at increased risk for developing ESRD treated with dialysis or transplantation," the authors write. "Our findings raise the question of whether current guidelines recommending that patients with ESRD and severe CKD [chronic kidney disease] be screened for HCV be expanded to include patients with moderate CKD and whether patients with HCV should routinely be screened for CKD. Future studies should investigate whether treatment eradicating HCV alters the risk for renal disease and whether existing treatments to delay the progression of CKD are effective in persons with chronic HCV."
The National Center for Research Resources of the National Institutes of Health and the National Institute on Aging supported this study. The authors have disclosed no relevant financial relationships.
Arch Intern Med. 2007;167:1271-1276.
"Infection with chronic hepatitis C virus (HCV) has been linked to glomerulonephritis," write Judith I. Tsui, MD, from the University of California, San Francisco, and colleagues. "We undertook this study to determine whether having a positive HCV test result was associated with an increased risk for developing treated end-stage renal disease (ESRD)."
Using data from Medicare, the Department of Veterans Affairs (VA), and the US Renal Data System, the investigators performed a retrospective cohort study of 474,369 adult veterans with serum creatinine levels measurements between October 1, 2000, and September 30, 2001, and HCV antibody testing within 1 year of creatinine testing. Follow-up for the outcome of treated ESRD, defined as the onset of long-term dialysis or renal transplantation, continued through October 1, 2004. The relative risk for ESRD associated with HCV, after adjustment for other covariates (age, sex, race/ethnicity, and comorbidities), was determined with Cox proportional hazards models.
Findings from HCV antibody testing were positive in 52,874 (11.1%) of 474,369 patients. Patients with positive HCV test findings were more likely to develop ESRD, with a rate of 4.26 per 1000 person-years (95% confidence interval [CI], 3.97 - 4.57) for HCV-seropositive patients vs 3.05 (95% CI, 2.96 - 3.14) for HCV-seronegative patients.
For patients aged 18 to 70 years in whom estimated glomerular filtration rate was 30 mL/minute/1.73 m2 or greater, HCV seropositivity was associated with more than twice the risk of developing ESRD (adjusted hazard rate, 2.80; 95% CI, 2.43 - 3.23).
Study limitations include lack of generalizability to nonveteran populations; analysis being based on results of HCV antibody testing rather than HCV RNA testing; possibly reduced accuracy of the Modification of Diet in Renal Disease equation used to estimate glomerular filtration rate in patients with HCV; lack of data on proteinuria or albuminuria; use of International Classification of Diseases, Ninth Revision, codes for comorbidity diagnoses, when they are often insensitive and do not provide information on severity or control of the disease condition; possible unknown confounders; and short duration of follow-up.
"In this large national cohort of adult veterans, patients younger than 70 years with HCV seropositivity were at increased risk for developing ESRD treated with dialysis or transplantation," the authors write. "Our findings raise the question of whether current guidelines recommending that patients with ESRD and severe CKD [chronic kidney disease] be screened for HCV be expanded to include patients with moderate CKD and whether patients with HCV should routinely be screened for CKD. Future studies should investigate whether treatment eradicating HCV alters the risk for renal disease and whether existing treatments to delay the progression of CKD are effective in persons with chronic HCV."
The National Center for Research Resources of the National Institutes of Health and the National Institute on Aging supported this study. The authors have disclosed no relevant financial relationships.
Arch Intern Med. 2007;167:1271-1276.
Coffee Drinking, but Not Smoking, Linked to Protective Effect in Late-Onset Blepharospasm
June 27, 2007 — Coffee drinking, but not cigarette smoking, may have a protective effect in primary late-onset blepharospasm, a rare type of dystonia.
Investigators at the University of Bari in Italy found individuals who drank 1 to 2 cups of coffee per day were less likely to develop the condition than those who drank less than this amount. Furthermore, there was a delay in the age of onset of the condition associated with coffee consumption — 1.7 years for each additional cup per day.
However, unlike studies of Parkinson's disease, which have linked smoking to a decreased risk for the disease, as well as in a previous study of blepharospasm, the Italian team found no significant protective effect of blepharospasm related to cigarette smoking.
"The protective effect of cigarette smoking and coffee in Parkinson's disease is well established. However, like Parkinson's, blepharospasm arises from the extrapyramidal system. In addition, there is a scarcity of information on the etiology of PD [Parkinson's disease] so we wanted to look at these lifestyle habits to see whether lifetime coffee and cigarette used influenced blepharospasm risk," principal investigator Giovanni Defazio, MD, of the University of Bari told Medscape.
The study is published in the June 19 Online First issue of the Journal of Neurology, Neurosurgery, and Psychiatry.
Smoking Conferred No Protective Effect
In this retrospective, case-control, multicenter study, the 2 lifestyle habits, coffee drinking and cigarette smoking, were examined in 166 patients with primary late-onset blepharospasm, 187 healthy population control subjects (patients' relatives), and 228 hospital control patients with primary hemifacial spasm all from 5 hospital-based movement disorder clinics in Italy.
The lifetime coffee consumption and smoking habits were determined for all participants by an expert interviewer who was not blinded to the case/control status but was unaware of the study hypothesis. All study subjects were asked about their coffee and smoking habits up to the reference age. This was the age of onset of dystonia or hemifacial spasm for case patients and hospital control patients.
A reference age was calculated for the population control subjects based on the duration of the spasms in the hospital control patients.
Study participants were also asked to estimate how many cups of coffee they drank and/or packs of cigarettes they smoked per day. Demographic and clinical information was also collected.
The investigators found that individuals with blepharospasm reported a significantly lower mean number of cups of coffee per day than hospital control patients and population control subjects, whereas there was no significant relationship with the amount smoked per day and a reduced risk for blepharospasm.
Delayed Disease Onset
"We found patients with blepharospasm drank coffee less often than controls, which suggests a strong protective effect. The other important result was the observation that for every additional cup of coffee consumed per day there was a delay in the age of onset of blepharospasm. So the higher the number of cups per day, the greater the delay in onset of the disease," he said.
According to Dr. Defazio, prevalence estimates of blepharospasm are uncertain. Available studies, he said, are biased because of a number of methodologic problems and likely provide an underestimation. However, he said, the most relevant research showed a prevalence of about 133 per 1 million population. Dystonia in general, he added, affects approximately 1000 per million population.
The protective effect associated with coffee is most likely caffeine, said Dr. DeFazio.
"The association of caffeine and BSP [blepharospasm] may be biologically plausible given the pro-dopaminergic activity exerted by caffeine through an antagonistic action on adenosine receptors. This has been called into play to explain the observed protective effect on the development of PD," the authors write.
As a result, said Dr. Defazio, adenosine receptor antagonists may effectively alleviate blepharospasm symptoms.
The team's next research steps, said Dr. Defazio, will be to determine whether coffee consumption has any protective effect in other forms of dystonia such as writer's cramp and cervical dystonia, because although these conditions differ in their clinical presentations, it is likely they have a common etiology.
"I believe our data may have implications for the understanding of the etiology and treatment of primary BSP and that future studies seeking additional environmental or genetic factors for dystonia should take the effect of coffee into account," he said.
J Neurol Neurosurg Psychiatry. Published online June 19, 2007.
Investigators at the University of Bari in Italy found individuals who drank 1 to 2 cups of coffee per day were less likely to develop the condition than those who drank less than this amount. Furthermore, there was a delay in the age of onset of the condition associated with coffee consumption — 1.7 years for each additional cup per day.
However, unlike studies of Parkinson's disease, which have linked smoking to a decreased risk for the disease, as well as in a previous study of blepharospasm, the Italian team found no significant protective effect of blepharospasm related to cigarette smoking.
"The protective effect of cigarette smoking and coffee in Parkinson's disease is well established. However, like Parkinson's, blepharospasm arises from the extrapyramidal system. In addition, there is a scarcity of information on the etiology of PD [Parkinson's disease] so we wanted to look at these lifestyle habits to see whether lifetime coffee and cigarette used influenced blepharospasm risk," principal investigator Giovanni Defazio, MD, of the University of Bari told Medscape.
The study is published in the June 19 Online First issue of the Journal of Neurology, Neurosurgery, and Psychiatry.
Smoking Conferred No Protective Effect
In this retrospective, case-control, multicenter study, the 2 lifestyle habits, coffee drinking and cigarette smoking, were examined in 166 patients with primary late-onset blepharospasm, 187 healthy population control subjects (patients' relatives), and 228 hospital control patients with primary hemifacial spasm all from 5 hospital-based movement disorder clinics in Italy.
The lifetime coffee consumption and smoking habits were determined for all participants by an expert interviewer who was not blinded to the case/control status but was unaware of the study hypothesis. All study subjects were asked about their coffee and smoking habits up to the reference age. This was the age of onset of dystonia or hemifacial spasm for case patients and hospital control patients.
A reference age was calculated for the population control subjects based on the duration of the spasms in the hospital control patients.
Study participants were also asked to estimate how many cups of coffee they drank and/or packs of cigarettes they smoked per day. Demographic and clinical information was also collected.
The investigators found that individuals with blepharospasm reported a significantly lower mean number of cups of coffee per day than hospital control patients and population control subjects, whereas there was no significant relationship with the amount smoked per day and a reduced risk for blepharospasm.
Delayed Disease Onset
"We found patients with blepharospasm drank coffee less often than controls, which suggests a strong protective effect. The other important result was the observation that for every additional cup of coffee consumed per day there was a delay in the age of onset of blepharospasm. So the higher the number of cups per day, the greater the delay in onset of the disease," he said.
According to Dr. Defazio, prevalence estimates of blepharospasm are uncertain. Available studies, he said, are biased because of a number of methodologic problems and likely provide an underestimation. However, he said, the most relevant research showed a prevalence of about 133 per 1 million population. Dystonia in general, he added, affects approximately 1000 per million population.
The protective effect associated with coffee is most likely caffeine, said Dr. DeFazio.
"The association of caffeine and BSP [blepharospasm] may be biologically plausible given the pro-dopaminergic activity exerted by caffeine through an antagonistic action on adenosine receptors. This has been called into play to explain the observed protective effect on the development of PD," the authors write.
As a result, said Dr. Defazio, adenosine receptor antagonists may effectively alleviate blepharospasm symptoms.
The team's next research steps, said Dr. Defazio, will be to determine whether coffee consumption has any protective effect in other forms of dystonia such as writer's cramp and cervical dystonia, because although these conditions differ in their clinical presentations, it is likely they have a common etiology.
"I believe our data may have implications for the understanding of the etiology and treatment of primary BSP and that future studies seeking additional environmental or genetic factors for dystonia should take the effect of coffee into account," he said.
J Neurol Neurosurg Psychiatry. Published online June 19, 2007.
FDA Gives Go-Ahead to Once-Daily Valsartan-Amlodipine Combination Pill for Hypertension
June 27, 2007 — The US Food and Drug Administration (FDA) has given the commercial go-ahead to a once-daily medication for hypertension (Exforge, Novartis) that combines the angiotensin receptor blocker (ARB) valsartan with amlodipine, a calcium-channel blocker, Novartis announced.
The approval indication isn't for first-line therapy, according to Novartis; rather, it's for patients with hypertension not controlled by ARB or calcium-channel-blocker monotherapy and for those with dose-limiting side effects on either valsartan or amlodipine. Exforge was approved by regulators in the European Union in January 2007.
http://www.pharma.us.novartis.com/newsroom/pressReleases/releaseDetail.jsp?PRID=2025
http://www.fda.gov/cder/whatsnew.htm
http://www.fda.gov/cder/foi/label/2007/021990lbl.pdf
The approval indication isn't for first-line therapy, according to Novartis; rather, it's for patients with hypertension not controlled by ARB or calcium-channel-blocker monotherapy and for those with dose-limiting side effects on either valsartan or amlodipine. Exforge was approved by regulators in the European Union in January 2007.
http://www.pharma.us.novartis.com/newsroom/pressReleases/releaseDetail.jsp?PRID=2025
http://www.fda.gov/cder/whatsnew.htm
http://www.fda.gov/cder/foi/label/2007/021990lbl.pdf
Telmisartan Staves Off Overt Diabetic Nephropathy
NEW YORK (Reuters Health) Jun 27 - The angiotensin receptor blocker (ARB) telmisartan may prevent the transition from incipient to overt nephropathy in patients with type 2 diabetes, according to a report in the June Diabetes Care.
Previous research has demonstrated long-term renoprotection with ARBs in Caucasians, the authors explain, but this is the first such study in Japanese patients with type 2 diabetes.
Dr. Hirofumi Makino from Okayama University Graduate School of Medicine, Japan and colleagues in the INNOVATION Study Group evaluated the efficacy of telmisartan in preventing transition from microalbuminuria to overt diabetic nephropathy in 527 Japanese patients ranging in age from 30 to 74 years.
During a mean follow-up of 1.3 years, transition rates to overt nephropathy were significantly lower with telmisartan 40 mg (22.6%) and telmisartan 80 mg (16.7%) than with placebo (49.9%), the authors report.
Differences were similar among normotensive patients, the results indicate.
Microalbuminuria remission at final observation was markedly higher among patients treated with telmisartan 40 mg (12.8%) and telmisartan 80 mg (21.2%) than among placebo-treated patients (1.2%), the researchers note.
"Overall," the investigators conclude, "telmisartan reduced transition from incipient to overt nephropathy and induced remission of albuminuria in Japanese type 2 diabetic patients."
Diabetes Care 2007;30:1577-1578.
Previous research has demonstrated long-term renoprotection with ARBs in Caucasians, the authors explain, but this is the first such study in Japanese patients with type 2 diabetes.
Dr. Hirofumi Makino from Okayama University Graduate School of Medicine, Japan and colleagues in the INNOVATION Study Group evaluated the efficacy of telmisartan in preventing transition from microalbuminuria to overt diabetic nephropathy in 527 Japanese patients ranging in age from 30 to 74 years.
During a mean follow-up of 1.3 years, transition rates to overt nephropathy were significantly lower with telmisartan 40 mg (22.6%) and telmisartan 80 mg (16.7%) than with placebo (49.9%), the authors report.
Differences were similar among normotensive patients, the results indicate.
Microalbuminuria remission at final observation was markedly higher among patients treated with telmisartan 40 mg (12.8%) and telmisartan 80 mg (21.2%) than among placebo-treated patients (1.2%), the researchers note.
"Overall," the investigators conclude, "telmisartan reduced transition from incipient to overt nephropathy and induced remission of albuminuria in Japanese type 2 diabetic patients."
Diabetes Care 2007;30:1577-1578.
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