NEW YORK (Reuters) – A task force advising the U.S. government on Monday recommended against routine use of the prostate-cancer screening test called PSA, or prostate specific antigen, for lack of a discernible health benefit.

Like a draft proposal last October, the U.S. Preventive Services Task Force gave PSA screening a D, for “don’t recommend” in healthy men.

The reaction was fast and furious. Screening advocates warned that the recommendation will cost lives, but critics of PSA testing said thousands of men will be spared impotence and incontinence as a result of needless cancer treatment.

A D means there is “moderate or high certainty” that a procedure has no net benefit or that harms outweigh benefits. It is a downgrade from the panel’s last PSA recommendation, in 2008, which said the evidence was insufficient to assess the procedure’s risks and benefits, although PSA screening for men 75 and older was not recommended.

Now, however, “there is convincing evidence that the number of men who avoid dying of prostate cancer because of screening after 10 to 14 years is, at best, very small,” the task force said in the May 22 issue of the Annals of Internal Medicine. Doctors, therefore, should discourage it.

The recommendation does not preclude men from asking for PSA screening, or doctors from offering it. But it could affect whether insurers, including the government’s Medicare program, cover the test’s $60 to $80 cost.

The only other screening method is the old-fashioned digital rectal exam, which cannot detect small, early cancers. Neither the exam nor PSA can distinguish slow-growing from aggressive cancers.

About one in six American men will be diagnosed with prostate cancer during his life; 2.8 percent, or a projected 28,000 this year, will die of it. Many cases pose no risk even without treatment. Research has shown that between one-quarter and one-third of 60-something men have prostate cancer, often without knowing it. Three-quarters of men older than 85 years have prostate cancer but few die of it.

PSA, a blood test, is a poor screening tool because PSA levels can rise for reasons unrelated to cancer, including age and prostate enlargement. Yet an elevated PSA level can trigger a biopsy to check for cancer.

Most biopsies show no cancer, which means the PSA was a false positive. But prostate biopsies that detect cancer do so based on research from the 1840s, explained Dr. Otis Brawley, chief medical officer of the American Cancer Society.

“As many as 70 percent of these lesions are cancer only by this antiquated definition and not in behavior,” he said. That is, they are indolent or inert and will not threaten a man’s health or life.

Radiation oncologist Anthony D’Amico of Dana-Farber Cancer Institute in Boston acknowledges that PSA screening causes overdiagnosis, “but if you get rid of the PSA test, men will suffer and die of prostate cancer,” he said.

“I’m shocked that they would let people die in order to avoid incontinence and erectile dysfunction, which can be corrected.”

CONFLICTING STUDIES

The task force analyzed 64 studies, but focused on two, both published in 2009 and updated this year.

The U.S. study compared 76,685 men aged 55 to 74. About half were assigned to receive annual PSA screening and half to “usual care,” which sometimes included a PSA test. The study found no evidence that PSA screening saved lives after 13 years.

The European study was similar, with about half of 162,243 men aged 55 to 69 getting regular PSA tests and half not. But for every 1,055 men who were screened every one to four years, there was one fewer death from prostate cancer after 11 years compared to men in the unscreened group. That is the basis for the task force’s conclusion that PSA screening for a decade will prevent at most one man in 1,000 from dying of prostate cancer.

The trials themselves were imperfect, polarizing the debate even further.

The American trial was marred by the fact that some men in the “unscreened, usual care” group did receive PSA tests. Such so-called crossovers can weaken a trial’s conclusions.

“With the rate of screening in the ‘unscreened arm’ matching that in the ‘screened’ arm, you can never measure a difference” in the death rates “even if one exists,” said D’Amico.

The trial scientists disagreed, saying the crossovers were statistically equivalent to having fewer people in the trial, said biostatistician Paul Pinsky of the National Cancer Institute, a member of the study team. “But there was twice as much screening in the intervention arm, and we did not find a mortality benefit.”

The European study is actually seven studies, each from one country. In five, the results mimicked the American findings: no statistically significant reduction in deaths from prostate cancer among screened men. But studies from Sweden and the Netherlands showed benefits.

The European scientists and their supporters argued that the Swedish trial in particular was strong enough to stand on its own as evidence that PSA screening saves lives.

Perhaps the greatest problem with the European study is that the screened men diagnosed with prostate cancer generally received top-of-the-line care from academic physicians. If the unscreened men developed prostate cancer, they received less specialized, less aggressive care. “That means this was a trial not only of PSA screening but also of aggressive vs. non-aggressive treatment,” said Brawley.

WEIGHING HARMS

Against the tiny benefit of PSA testing, the task force weighed its harms. At least 15 percent of PSA tests will trigger a biopsy, after which up to one-third of men experience pain, fever, bleeding, infection, difficulty urinating, or other problems requiring medical attention, studies show.

If a biopsy finds seemingly malignant cells, as happens to 120 in 1,000 screened men, about 90 percent of men opt for surgery, radiation or hormone-deprivation therapy. Up to five men in 1,000 opting for surgery will die within a month of the operation; 10 to 70 more will have serious cardiovascular complications such as a stroke or heart attack.

After radiotherapy and surgery, 200 to 300 of 1,000 men suffer incontinence, impotence or both. Hormone-deprivation therapy causes erectile dysfunction in about 400 of 1,000 men.

“When you stack up those harms, the tiny or zero benefits do not outweigh the risk,” said task force co-chair Dr. Michael LeFevre of the University of Missouri Medical School. Because PSA tests cannot distinguish between aggressive and indolent cancer, said ACS’s Brawley, “men are rendered impotent and put in diapers, and for what?” he asked. “They never really had cancer in the first place.”

The task force is not saying no man of any age under any circumstances should undergo PSA screening. “A D recommendation does not preclude discussions between clinicians and patients to promote informed decision making that supports personal values and preferences,” it said. The recommendation is against routine screening.

“Our recommendation should not preclude a physician offering a PSA test or a man requesting it,” said co-chair LeFevre. He would be glad to provide the test for his patients, he said, if the decision were based on a clear understanding of the possible benefits and harms. ACS’s Brawley agrees that “a fully-informed man who wants to be screened in his doctor’s office should be screened.” Only if physicians are prepared to explain all this, including that PSA screening misses just as many cancers as it finds, said the task force, can men make an informed choice.

Experts on both sides do agree that mass free screenings offered by hundreds of urology clinics and hospitals should end. “There is minimal discussion of risks and benefits; a pamphlet isn’t going to do it,” said D’Amico. “But a lot of fear gets invoked.”

(Reporting By Sharon Begley; Editing by Michele Gershberg and Cynthia Osterman)

LONDON (Reuters) – Low-quality and fake anti-malarial drugs flooding into markets in Asia and Africa are driving drug resistance and threatening gains made in the fight against the disease in the past decade, according to a study by global health experts.

The study found around 36 percent of anti-malarial drugs analyzed in southeast Asia were fake, while a third of samples in sub-Saharan Africa failed chemical testing because they contained either too much or not enough active ingredient.

The researchers said the problem might be even bigger.

The emergence of resistance to artemisinin drugs – currently the most effective treatment for malaria – along the Thailand-Cambodia border – has already been documented.

“Despite a dramatic rise in reports of poor-quality anti- malarial drugs over the past decade, the issue is much greater than it seems,” Gaurvika Nayyar, of the Fogarty International Center at the U.S. National Institutes of Health, wrote in a study in the Lancet Infectious Diseases journal.

“Most cases are probably unreported, reported to the wrong agencies, or kept confidential by pharmaceutical companies.”

More than 3 billion people worldwide are at risk of malaria, a mosquito-borne parasitic disease which kills around 650,000 people a year, most of them babies and children in Africa.

Nayyar said many of the deaths caused by the disease could be avoided “if drugs available to patients were efficacious, high quality, and used correctly.”

The World Health Organisation (WHO) estimates that while less than 1 percent of medicines available in developed countries are likely to be counterfeit, globally, the figure is around 10 percent.

The United Nations agency estimates that as much as a third of all medicines in some developing countries is fake.

As well as putting patients at risk, counterfeit drugs are a constant bane for companies like GlaxoSmithkline, Sanofi and other international drugmakers.

Nayyar’s team analyzed data from both published and unpublished studies that looked at chemical analyses and the packaging of malaria medicines in sub-Saharan Africa and southeast Asia where the malaria risk is highest.

Data from seven countries in southeast Asia – including from analysis of 1,437 samples of seven different malaria drugs – showed that more than a third of them failed chemical testing, nearly half were wrongly packaged, and about a third were bogus.

Analysis of data from 21 countries in sub-Saharan Africa including more than 2,500 drug samples, showed similar results, with more than a third failing chemical testing and around one fifth turning out to be fake.

(Editing by Robin Pomeroy)

(Reuters) – The University of Notre Dame and dozens of other Catholic institutions sued President Barack Obama’s administration on Monday to block a government regulation that requires employers to provide health insurance coverage for contraceptives to employees.

The regulation, which is part of the president’s healthcare reform law, has sparked a nasty fight between the administration and the Roman Catholic Church, which opposes artificial contraception.

Some 43 Catholic groups including Notre Dame, Catholic University of America and the Archdiocese of New York filed 12 different suits across the country.

The organizations accuse the federal government of forcing them to support contraception, sterilization and birth control in violation of their religious beliefs or face steep fines.

The original law exempted churches and other houses of worship from covering contraception on the basis of religious objections. But it did not carve out an exception for religious nonprofits, such as hospitals, charities and schools, sparking an outcry from church leaders.

As a compromise, Obama scaled back the controversial healthcare rule in February, announcing that insurance companies would cover the cost of the birth control for religious employers. But the complaints filed on Monday said the accommodation did not go far enough.

“In order to safeguard their religious freedoms, religious employers must plead with the government for a determination that they are sufficiently ‘religious,’” Notre Dame said in its lawsuit, filed in Indiana federal court.

Under the revised mandate, religious organizations can only qualify for the exemption if their purpose is to spread their religious beliefs. They must also primarily employ and serve people with the same religious values.

Such government scrutiny violates the separation between church and state, the suits claim. Notre Dame’s complaint said it was unclear whether the school could qualify for the exemption, given its commitment to employ and serve people of all faiths.

Jane Belford, chancellor of the Archdiocese of Washington which joined one suit, said the groups aimed to challenge the government’s redefinition of religion.

“While this mandate paid lip service to the rights of conscience and religious liberty, it created a definition that was so narrow, even the work of Mother Theresa would not have qualified as religious,” Belford said.

The Department of Health and Human Services declined to comment on the litigation.

The U.S. Conference of Catholic Bishops, although it did not join any of the suits, praised the individual dioceses, charities and schools for defending religious liberty.

At least 11 other lawsuits have previously been filed against the contraceptive mandate, according to comments that the U.S. Conference of Catholic Bishops submitted to the Department of Health and Human Services on May 15. The submission included a warning about Monday’s lawsuits: “Absent prompt congressional attention to this infringement on fundamental civil liberties, we believe the only remaining recourse … is in the courts.”

Jennifer Dalven, a lawyer at the American Civil Liberties Union, said the mandate was not new. Twenty-eight states have laws requiring insurers to cover birth control to the same extent as other medications.

“The lawsuits make it seem like taking a job is the same as joining a church. But organizations that participate in the public sphere are supposed to abide by public rules,” Dalven said.

The suits were filed around the country, including in the District of Columbia, New York, Mississippi and Texas, according to Jones Day.

(Reporting By Terry Baynes; Editing by Greg McCune and Eric Walsh)

NEW YORK (Reuters) – A task force advising the U.S. government on Monday recommended against routine use of the prostate-cancer screening test called PSA, or prostate specific antigen, for lack of a discernible health benefit.

Like a draft proposal last October, the U.S. Preventive Services Task Force gave PSA screening a D, for “don’t recommend” in healthy men.

The reaction was fast and furious. Screening advocates warned that the recommendation will cost lives, but critics of PSA testing said thousands of men will be spared impotence and incontinence as a result of needless cancer treatment.

A D means there is “moderate or high certainty” that a procedure has no net benefit or that harms outweigh benefits. It is a downgrade from the panel’s last PSA recommendation, in 2008, which said the evidence was insufficient to assess the procedure’s risks and benefits, although PSA screening for men 75 and older was not recommended.

Now, however, “there is convincing evidence that the number of men who avoid dying of prostate cancer because of screening after 10 to 14 years is, at best, very small,” the task force said in the May 22 issue of the Annals of Internal Medicine. Doctors, therefore, should discourage it.

The recommendation does not preclude men from asking for PSA screening, or doctors from offering it. But it could affect whether insurers, including the government’s Medicare program, cover the test’s $60 to $80 cost.

The only other screening method is the old-fashioned digital rectal exam, which cannot detect small, early cancers. Neither the exam nor PSA can distinguish slow-growing from aggressive cancers.

About one in six American men will be diagnosed with prostate cancer during his life; 2.8 percent, or a projected 28,000 this year, will die of it. Many cases pose no risk even without treatment. Research has shown that between one-quarter and one-third of 60-something men have prostate cancer, often without knowing it. Three-quarters of men older than 85 years have prostate cancer but few die of it.

PSA, a blood test, is a poor screening tool because PSA levels can rise for reasons unrelated to cancer, including age and prostate enlargement. Yet an elevated PSA level can trigger a biopsy to check for cancer.

Most biopsies show no cancer, which means the PSA was a false positive. But prostate biopsies that detect cancer do so based on research from the 1840s, explained Dr. Otis Brawley, chief medical officer of the American Cancer Society.

“As many as 70 percent of these lesions are cancer only by this antiquated definition and not in behavior,” he said. That is, they are indolent or inert and will not threaten a man’s health or life.

Radiation oncologist Anthony D’Amico of Dana-Farber Cancer Institute in Boston acknowledges that PSA screening causes overdiagnosis, “but if you get rid of the PSA test, men will suffer and die of prostate cancer,” he said.

“I’m shocked that they would let people die in order to avoid incontinence and erectile dysfunction, which can be corrected.”

CONFLICTING STUDIES

The task force analyzed 64 studies, but focused on two, both published in 2009 and updated this year.

The U.S. study compared 76,685 men aged 55 to 74. About half were assigned to receive annual PSA screening and half to “usual care,” which sometimes included a PSA test. The study found no evidence that PSA screening saved lives after 13 years.

The European study was similar, with about half of 162,243 men aged 55 to 69 getting regular PSA tests and half not. But for every 1,055 men who were screened every one to four years, there was one fewer death from prostate cancer after 11 years compared to men in the unscreened group. That is the basis for the task force’s conclusion that PSA screening for a decade will prevent at most one man in 1,000 from dying of prostate cancer.

The trials themselves were imperfect, polarizing the debate even further.

The American trial was marred by the fact that some men in the “unscreened, usual care” group did receive PSA tests. Such so-called crossovers can weaken a trial’s conclusions.

“With the rate of screening in the ‘unscreened arm’ matching that in the ‘screened’ arm, you can never measure a difference” in the death rates “even if one exists,” said D’Amico.

The trial scientists disagreed, saying the crossovers were statistically equivalent to having fewer people in the trial, said biostatistician Paul Pinsky of the National Cancer Institute, a member of the study team. “But there was twice as much screening in the intervention arm, and we did not find a mortality benefit.”

The European study is actually seven studies, each from one country. In five, the results mimicked the American findings: no statistically significant reduction in deaths from prostate cancer among screened men. But studies from Sweden and the Netherlands showed benefits.

The European scientists and their supporters argued that the Swedish trial in particular was strong enough to stand on its own as evidence that PSA screening saves lives.

Perhaps the greatest problem with the European study is that the screened men diagnosed with prostate cancer generally received top-of-the-line care from academic physicians. If the unscreened men developed prostate cancer, they received less specialized, less aggressive care. “That means this was a trial not only of PSA screening but also of aggressive vs. non-aggressive treatment,” said Brawley.

WEIGHING HARMS

Against the tiny benefit of PSA testing, the task force weighed its harms. At least 15 percent of PSA tests will trigger a biopsy, after which up to one-third of men experience pain, fever, bleeding, infection, difficulty urinating, or other problems requiring medical attention, studies show.

If a biopsy finds seemingly malignant cells, as happens to 120 in 1,000 screened men, about 90 percent of men opt for surgery, radiation or hormone-deprivation therapy. Up to five men in 1,000 opting for surgery will die within a month of the operation; 10 to 70 more will have serious cardiovascular complications such as a stroke or heart attack.

After radiotherapy and surgery, 200 to 300 of 1,000 men suffer incontinence, impotence or both. Hormone-deprivation therapy causes erectile dysfunction in about 400 of 1,000 men.

“When you stack up those harms, the tiny or zero benefits do not outweigh the risk,” said task force co-chair Dr. Michael LeFevre of the University of Missouri Medical School. Because PSA tests cannot distinguish between aggressive and indolent cancer, said ACS’s Brawley, “men are rendered impotent and put in diapers, and for what?” he asked. “They never really had cancer in the first place.”

The task force is not saying no man of any age under any circumstances should undergo PSA screening. “A D recommendation does not preclude discussions between clinicians and patients to promote informed decision making that supports personal values and preferences,” it said. The recommendation is against routine screening.

“Our recommendation should not preclude a physician offering a PSA test or a man requesting it,” said co-chair LeFevre. He would be glad to provide the test for his patients, he said, if the decision were based on a clear understanding of the possible benefits and harms. ACS’s Brawley agrees that “a fully-informed man who wants to be screened in his doctor’s office should be screened.” Only if physicians are prepared to explain all this, including that PSA screening misses just as many cancers as it finds, said the task force, can men make an informed choice.

Experts on both sides do agree that mass free screenings offered by hundreds of urology clinics and hospitals should end. “There is minimal discussion of risks and benefits; a pamphlet isn’t going to do it,” said D’Amico. “But a lot of fear gets invoked.”

(Reporting By Sharon Begley; Editing by Michele Gershberg and Cynthia Osterman)

NEW YORK (Reuters Health) – A small study suggests surgeons in training are still tired enough to raise their risk of making significant errors, despite new guidelines limiting their work hours.

Researchers found that orthopedic surgical residents at two Boston-area hospitals were averaging five and a half hours of sleep a night, and so fatigued during waking hours that a quarter of the time their “impairment” was equivalent to being legally drunk.

The study was conducted in 2010 and throughout most of 2011, and while it was underway rules limiting the work hours of the novice surgeons were enacted by a graduate medical education body. But they may not be enough, researchers agreed.

“I think that this study suggests that it’s more than just regulatory changes,” said Dr. Frank McCormick, of the Harvard Combined Orthopaedic Residency Program in Boston and lead author of the new study.

McCormick and his colleagues focused on identifying when during a resident’s waking hours they were most impaired by fatigue.

Knowing when surgical residents are most likely to be dangerously tired, the group explains in the Archives of Surgery, may help to target interventions that could prevent medical mistakes.

For their study, McCormick and his fellow researchers analyzed information collected from 27 orthopedic residents at Massachusetts General Hospital and Brigham And Women’s Hospital.

At the outset, each resident was asked about his or her sleep and exercise habits and use of sedatives, alcohol and other stimulants.

The residents also kept daily sleep and work logs for two weeks while they wore a special “actigraphy” wristwatch that recorded movements to gauge the person’s activity level.

Overall, residents got an average of 5.3 hours of sleep per day — though the amount of sleep each resident got ranged widely, from 2.8 hours to 7.8 hours.

Based on the activity recordings, the researchers also determined that — compared to data on a group of well-rested residents — the study participants were only functioning at about 70 percent of their mental effectiveness during 27 percent of the time they were awake.

According to the researchers, 70 percent mental effectiveness is equivalent to having a 0.08 blood alcohol level, which is considered legally drunk in most states.

Based on that level of fatigue, McCormick and colleagues calculated the residents had a 22 percent greater risk of causing a medical error than alert, well rested doctors.

“Fatigue was higher than we expected, especially within specific subgroups,” said McCormick.

For nearly half their waking hours — 48 percent — the residents were mentally fatigued, but functioning above the 70 percent level.

In general, night-shift workers were worse off than the day-shift workers.

Residents working nights slept on average about 5.1 hours a day and functioned at less than 70 percent of their mental effectiveness 32 percent of their time awake.

Residents on day shifts slept about 5.7 hours and functioned at or below 70 percent effectiveness 17 percent of the time.

Day shift residents had a projected 19 percent increase in their risk of making a medical error, while night shift residents had a 24 percent increased risk.

McCormick cautioned, however, that these risks of medical error are only predictions based on fatigue level. The researchers did not assess how many medical errors were actually caused by tired surgical residents in the study.

As a result, “It’s difficult to actually quantify the amount of medical error that we’re preventing,” he told Reuters Health.

The study had other limitations as well, the authors note. Only 40 percent of the orthopedic residents at the two hospitals completed the study. And the researchers are not sure to what degree their findings can be applied to other types of medical residents.

In the same journal, Dr. Thomas Tracy Jr. of Hasbro Children’s Hospital and Brown University in Providence, R.I. wrote in an editorial that discovering surgical residents are fatigued during certain periods “is not startling” but its pervasiveness is “a finding we simply cannot avoid and may have paid lip service to in the past.”

Last July, the Accreditation Council for Graduate Medical Education, the body that oversees resident training, enacted new rules stating that first-year residents should work no more than 16 hours straight. The rules did not impact more experienced residents, however. They are allowed to work 28-hour shifts.

The Institute of Medicine estimates the rules would cost close to $1.7 billion dollars to implement — costs stemming mostly from hiring additional staff.

McCormick suggested targeting tired residents for preventive interventions may be more cost effective, and he said there have already been changes at the hospitals involved in the study.

“We’re currently switching around our schedule, eliminating our night flow and continuing to monitor fatigue,” he told Reuters Health.

SOURCE: bit.ly/Js9sYe Archives of Surgery, online May 21, 2012.