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Drug studies paid for by the pharmaceutical industry are more likely to publish favorable results than those funded by sources with no financial interest in the findings, a new review has found.

Children’s Hospital Boston researchers reviewed 546 drug trials that were conducted between 2000 and 2006 and listed with ClinicalTrials.gov, a Web-based U.S. government registry of clinical trials. The studies included five types of drugs: cholesterol-lowering medicines, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators.

The drug industry-funded studies reported positive findings about the drug in question 85 percent of the time, compared with 50 percent for government-funded trials and 72 percent for those funded by nonprofit or nonfederal organizations, according to the report published in the Aug. 3 issue of the journal Annals of Internal Medicine.

The researchers also found nonprofit/nonfederal trials that received drug-maker contributions were more likely to report positive findings than those with no links to the industry — 85 percent versus 61 percent.

Only 32 percent of industry-funded trials published results within two years of clinical trial completion, compared with 54 percent of government-funded studies and 56 percent of nonprofit/nonfederal trials, the authors of the review pointed out.

The researchers called for more public disclosure at the start of clinical trials in order to reduce the possibility of bias in their findings.

“While we cannot specifically point to which factors contribute to the association between funding source and positive result reporting, our findings speak to the need for more disclosure of all elements of a study,” team leader Dr. Florence Bourgeois, division of emergency medicine, said in a Children’s Hospital Boston news release.

“Publication bias is likely a contributing factor, but there may be many more, including biases in study design, patient selection, data analysis and results reporting,” she added.

SOURCE: Children’s Hospital Boston.

New research provides more evidence of a link between depression and extra pounds around the waist, although it’s not exactly clear how they’re connected.

The study raises the possibility that depression causes people to put on extra pounds around the belly. The opposite doesn’t appear to be the case: researchers found that overweight people aren’t more likely to become depressed than their normal-weight peers.

These findings come from researchers at the University of Alabama at Birmingham, who examined data from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a 20-year longitudinal study of more than 5,100 men and women aged 18-30. (Longitudinal studies look for a link between cause and effect by observing a group of individuals at regular intervals over a long period of time).

Among other things, the researchers wanted to figure out if depressed people were more likely to have larger waist circumferences and a higher BMI, and how that changed over time.

They found that over a 15-year period, all the subjects put on some pounds, but those who were depressed gained weight faster.

“Those who started out reporting high levels of depression gained weight at a faster rate than others in the study, but starting out overweight did not lead to changes in depression,” said study co-author Belinda Needham, an assistant professor of sociology, in a university press release.

Since the stress hormone cortisol is related to depression and abdominal obesity, Needham speculated that elevated levels might explain why depressed people tend to gain more belly fat.

“Our study is important because if you are interested in controlling obesity, and ultimately eliminating the risk of obesity-related diseases, then it makes sense to treat people’s depression,” Needham said. “It’s another reason to take depression seriously and not to think about it just in terms of mental health, but to also think about the physical consequences of mental health problems.”

The study appears in the June issue of the American Journal of Public Health.

Long linked to physical ailments such as asthma, heart disease and lung cancer, secondhand smoke may now be tied to an increase in mental woes, new research suggests.

Prolonged exposure to another’s noxious tobacco fumes could up the odds for psychological distress, depression, schizophrenia and delirium, British researchers say.

“In the U.S., an estimated 60 percent of non-smokers have biological evidence of exposure to passive smoke. Thus, in order to improve mental and physical health, people should be made aware of these harmful effects,” said lead researcher, Mark Hamer, from the Department of Epidemiology and Public Health at University College London.

“Exposure to passive smoke was associated with higher levels of psychological distress and greater risk of future psychiatric illness,” he said.

The report is published in the June 7 online edition of the Archives of General Psychiatry.

For the study, Hamer’s team collected data on over 5,500 non-smokers and nearly 2,600 smokers. None of these people had any history of mental illness at the start of the study, the researchers noted. In addition, the researchers measured levels of cotinine in saliva, which indicates an individual’s level of exposure to tobacco smoke.

Over six years of follow-up, 14.5 percent of the individuals were found to be suffering from psychological distress. People who did not smoke, but who were exposed to high levels of secondhand smoke, were almost 50 percent more likely to suffer from psychological distress than those not exposed, the researchers found.

In addition, during the six-year follow-up period, 41 of the participants were admitted to psychiatric hospitals for problems such as depression, schizophrenia, delirium or other psychiatric problems. Those with high exposure to secondhand smoke were nearly three times as likely to be admitted versus people unexposed to the fumes, the study authors found.

Stanton A. Glantz, a professor of medicine and director of the Center for Tobacco Control Research and Education at the University of California, San Francisco, commented that “this is an important and well-done study that shows that secondhand smoke is even more dangerous than we previous thought.”

Dr. Norman H. Edelman, a scientific consultant for the American Lung Association, agreed that “this is a very well done, potentially important study.”

Edelman said, “It’s not just that people with psychiatric symptoms tend to smoke more or be around those who smoke more, it may be that the exposure to smoke adds to their symptoms.”

However, another expert questions the validity of the findings. While smoke may make one more susceptible to mental problems, people predisposed to mental health woes may find themselves in smoky environments more often.

Dr. Ted Schettler, the science director of the Science and Environmental Health Network, reasoned that, perhaps “nicotine is associated with an increased likelihood of psychological problems.”

But, he added, “On the other hand, you can easily imagine that people who are in stressful life circumstances are also finding themselves in more smoke-filled environments. I don’t know that you can separate it out.”

SOURCES: Mark Hamer, Ph.D., department of epidemiology and public health, University College London; Stanton A. Glantz, Ph.D., professor, medicine, and director, Center for Tobacco Control Research and Education, University of California, San Francisco; Norman H. Edelman, M.D., scientific consultant, American Lung Association; Ted Schettler, M.D., science director, Science and Environmental Health Network.

Two immune system molecules could form the basis of a new test to quickly detect whether tuberculosis is dormant or active and infectious, U.S. researchers said on Sunday.

“A rapid test that could tell the difference between latent and active tuberculosis would be a major step forward,” said Dr. Jason Stout of Duke University Medical Center who presented his findings at the American Thoracic Society meeting in New Orleans.

Doctors could more quickly treat active infections, helping to limit the spread of the disease, Stout said.

Current blood tests can distinguish between people who are infected with TB and those who are not but they cannot tell whether an infection is active or dormant. It takes a culture test that grows the TB bacilli to show if it is active or not, and that can take weeks.

Stout and colleagues collected blood samples from 71 people with active TB, latent TB or no infection at all.

They added a bit of TB bacteria to the blood samples to stimulate an immune response, then measured the activity of 25 immune signaling chemicals called cytokines to try to identify a pattern that could be used as a signature of active TB infection.

“We found that a pattern of two cytokines, called MCP-1 and IL-15, was reasonably good at differentiating between persons sick with TB and persons infected but not sick,” Stout said.

A third cytokine called IP-10 also showed promise at sorting between people who are infected and those who are not.

Stout said other studies have pointed to these three cytokines individually as possible TB markers, but his is the first to put all three together as a possible TB test.

“These findings could lead to earlier diagnosis of active tuberculosis, which could be beneficial for both the sick person and others around her or him who might be spared from infection,” Stout said in a statement.

Tuberculosis killed 1.8 million people in 2008, or nearly 5,000 people a day. It is caused by the Mycobacterium tuberculosis bacteria. More than 2 billion people, or about a third of the world’s population, are thought to be infected.

It is not only a scourge in poor countries but also in the West, where it has flared anew in the last 20 years because of AIDS, which weakens the immune system.

TB can be cured with antibiotics, but they need to be taken daily for months to be effective. Because people often skip doses, multiple drug resistant forms are spreading and the World Health Organization says the hard-to-treat infection is spreading.

(Reporting by Julie Steenhuysen; Editing by Anthony Boadle)

Something in dark chocolate seems to help protect the heart, and now researchers say they have identified the molecular mechanism by which a compound found in cocoa can guard against the damage of a stroke.

The compound, a flavanol called epicatechin, triggers two built-in protective pathways in the brain, according to a report published online last week in the Journal of Cerebral Blood Flow & Metabolism. The research team was led by Sylvain Dore, an associate professor of anesthesiology and critical care medicine and pharmacology and molecular sciences at John Hopkins University School of Medicine in Baltimore.

Animal studies raise the possibility that epicatechin may someday be used to treat strokes in humans, since its protective effect can be seen more than three hours after a stroke. Existing stroke treatments typically have a shorter window of activity.

While the cardioprotective effect of dark chocolate seen in several human studies appears to open the possibility that eating lots of chocolate is healthy, “I prefer to focus on cocoa,” Dore said. “Cocoa is not like chocolate, which is high in saturated fat and calories. Cocoa can be part of a healthy diet, combined with fruits and vegetables.”

It was a study of the cocoa-drinking Kuna Indians, living on islands off the coast of Panama, that led researchers to study epicatechin. An unusually low incidence of stroke and other cardiovascular disease in that population could not be explained by genetic studies, and eventually was attributed to consumption of a very bitter cocoa drink.

Studies by a number of scientists, including Dr. Norman K. Hollenberg of Harvard Medical School, identified epicatechin as the protective ingredient in dark chocolate and cocoa.

The latest research looked at the mechanism of protection in mice who were induced to have strokes. “We gave different doses of epicatechin in mice 90 minutes before a stroke and found that it reduced infarct [stroke damage] size,” Dore explained. “When we gave epicatechin after a stroke, it had a protective effect up to 3.5 hours later, but not after six hours.”

Detailed studies showed that the flavanol activated two well-known pathways that shield nerve cells in the brain from damage, the Nrf2 and heme oxygenase pathways, Dore said. Epicatechin had no protective effect in mice bred to lack those pathways.

The possibility of using epicatechin to limit human stroke damage is distant, Dore said. “We have to be very careful,” he said. “There are a lot of steps before going to human trials, potential risks and side effects. We need more work and more funding.”

Dore’s long-term plan calls for studies of epicatechin metabolites and derivatives, in cardiac disease as well as stroke. “At this point, we are using only the pure compound,” he said.

Dr. Martin Lajous, a doctoral candidate at the Harvard School of Public Health who took part in one study that showed a reduced incidence of stroke in people who ate dark chocolate regularly, agreed with Dore in saying that eating a lot of chocolate is not a healthy dietary move.

Not all chocolate is created equal, Lajous said. “That’s why we did the study in France, where they eat dark chocolate that is rich in flavanols,” he said. “Chocolate comes with a lot of calories. I would talk about small amounts of dark chocolate rather than chocolate in general.”

And the protective mechanism by which chocolate might prevent stroke isn’t yet clear, Lajous added. The main effect appears to be the lowering of blood pressure, he said. “Flavanols are hypothesized to affect relaxation of smooth vascular muscle, such as the endothelial lining of blood vessels,” Lajous said.

SOURCES: Sylvain Dore, Ph.D., associate professor, anesthesiology, critical care medicine, pharmacology and molecular sciences, Johns Hopkins University School of Medicine, Baltimore; Martin Lajous, M.D., doctoral candidate, Harvard School of Public Health, Boston;

Using magnets to stimulate the brain may ease depression in people who have not found relief from antidepressants, new research has found.

“We have settled a fundamental question about [transcranial magnetic stimulation, or TMS] therapy, which is: ‘Does it work?’” said the study’s lead author, Dr. Mark George, a professor of psychiatry, radiology and neuroscience at the Medical University of South Carolina. “The answer is ‘yes.’”

The researchers administered the magnet therapy to half of a group of 190 adults who had been depressed for at least three months, but not longer than five years, and who had taken medication for depression but were not helped. The others were given a sham treatment — simulated magnet therapy that was mostly indistinguishable from the real thing, the researchers said.

After three weeks, about 14 percent of those receiving magnet therapy were no longer depressed, compared with 5 percent who were getting the fake treatment.

The researchers continued the magnet treatment for three more weeks for those who were still depressed and also offered the real treatment to participants who’d gotten the sham treatment.

After that period, about 30 percent were no longer depressed, the researchers said.

“In a rigorous, industry-free multisite trial with a convincing sham, we found unambiguously that TMS worked better than the sham. It’s watershed,” George stated.

The findings are published in the May issue of Archives of General Psychiatry.

Psychiatrists have been interested in the possibilities of treating depression with magnet therapy for more than a decade, the experts said. Magnets are believed to work by creating electrical currents in the nerve cells in the left prefrontal cortex, a region of the brain involved with regulating mood. The current may jump-start the area, which has been shown to be underactive in people who are depressed, George said.

But testing magnet therapy has been difficult. “Double-blind” studies, in which neither the researchers nor participants know who is getting the real treatment and who is getting the fake, have been difficult to carry out.

The current study overcame that by creating an elaborate sham. During magnet therapy, participants were painlessly zapped by a pulsing electromagnetic coil 3,000 times over 37 minutes. The current created a head-tapping sensation that some people said reminded them of a woodpecker, George said.

The coil, which is aimed at the brain area to be stimulated, creates a magnetic field that passes through the skin and skull, inducing an electrical current in the brain.

Participants receiving the sham treatment felt the same head-tapping, but a metal insert below the magnet blocked the magnetic field from entering the brain while electrodes on the scalp delivered the tapping sensation.

Using electrical current to treat brain disorders has been around in some form since the 1940s and 1950s, said Tony Tang, an adjunct professor in the psychology department at Northwestern University. However, electroconvulsive, or electroshock, therapy can induce seizures, and some studies showed it might cause memory loss and brain damage. Though effective in some people, electric shock was viewed with suspicion by the public, and today is used only as a last resort, Tang said.

Magnet therapy is essentially a much gentler, less invasive form of electric shock therapy, Tang said.

“Transcranial magnet therapy is one of the most exciting new developments in our field,” Tang said. “There are new drugs coming out every year, but they are all fairly similar to each other, and we don’t see much difference in efficacy. With TMS, the mechanism is completely different. It’s a very, very safe and gentle, noninvasive way to do electric shock therapy.”

In 2008, the U.S. Food and Drug Administration approved the marketing of a device used for magnet therapy to treat depression that is considered mildly resistant to treatment, according to background information on the study provided by the U.S. National Institute of Mental Health, which funded the study.

The next step, the researchers said, is to fine-tune the treatment to determine if higher levels of magnetic stimulation or changing the location of the magnetic coil might be even more effective or if magnet therapy might work best in conjunction with medications.

In the study, the only significant side effects were headaches and mild discomfort at the stimulation site. Most participants remained depression-free for several months after treatment stopped, according to the study.

SOURCES: Mark George, M.D., professor, psychiatry, radiology and neuroscience, and director, Brain Stimulation Laboratory, Medical University of South Carolina, Charleston, S.C.; Tony Tang, Ph.D., adjunct professor, department of psychology, Northwestern University, Evanston, Ill.

Adding the antiviral drug telaprevir to a second-round treatment for hepatitis cures about half the people who were not helped in the first round, new research shows.

“This is the first large study in patients who had not responded to standard treatment,” said Dr. John G. McHutchison, associate director of the Duke Clinical Research Institute and lead author of a report in the April 8 issue of the New England Journal of Medicine.

The study is one of the last steps in a series of trials designed to get approval for the use of the drug in clinical practice. Approval of the drug will bring encouragement to people whose hepatitis C infection had not been cured by the existing treatments, McHutchison said.

“There has been no alternative for people who have been treated and have not responded,” he added. “So it holds great promise for them, that potentially something will be available in the future that can cure half of them.”

About 4 million Americans are infected with hepatitis C, a virus that is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplantation. It is usually transmitted by infected blood, most often by using a contaminated needle.

Standard treatment for hepatitis C is a 48-week course of two drugs, peginterferon alpha and ribavirin, which cures about 40 percent to 50 percent of patients but is accompanied by side effects, such as a severe rash, that makes many discontinue the treatment. Previous studies have shown a substantial improvement in cure rates when telaprevir is added to the standard therapy.

Until now, the only recourse for those who were not helped by the first round of treatment was a second round of the same therapy. The newly reported trial, sponsored by Vertex Pharmaceuticals, the maker of telaprevir, included 453 people who had not responded to a first round of treatment. All had the most common, and most difficult to treat, form of the virus, genotype 1.

Just over half, 52 percent, of those who had telaprevir added to the two-drug regimen in the second round were virus-free after six months, compared to 14 percent of those who had a second round of the two-drug treatment.

But the therapy was not problem-free, McHutchison noted. “There were also more side effects, rashes and anemia,” he said. “Also, the rate of discontinuation was higher as well.”

Still, the high cure rate speaks for itself, McHutchison added. Data from the various trials probably will be submitted to the U.S. Food and Drug Administration later this year, he said.

Telaprevir is a protease inhibitor, which works by blocking reproduction of the hepatitis C virus. It is not the only protease inhibitor being tested against hepatitis C, McHutchison said. Another such drug, boceprevir, appears to be running close to telaprevir in the race for regulatory approval. It is being developed by Merck, which acquired it when it bought Schering-Plough.

If and when they are approved, both protease inhibitors probably will be used for first-line treatment of hepatitis C, McHutchison said.

“Having more options for the patient is what it is all about,” he explained.

A number of other protease inhibitors now are in various stages of testing, added Dr. Ira Jacobson, a professor of medicine at Weill Cornell Medical College in New York City and a member of the research team that did the telaprevir study. Jacobson has also been involved in development of boceprevir.

A new era in treatment of hepatitis C will begin when a first protease inhibitor is approved, Jacobson said. “The hope in the medical community is that the regulatory agencies will see fit to approve it for all populations,” he added.

Challenging established medical wisdom about blood pressure and stroke, new British research suggests that extremely variable blood pressure, and not just high blood pressure, can greatly increase a person’s risk of stroke.

“Some people have very stable hypertension, in which case simple hypertension is all that matters, but variability and episodic hypertension is very common and matters much more than mean blood pressure in some patients,” said Dr. Peter Rothwell, a professor of neurology at the University of Oxford and lead author of four papers in the March 13 issues of The Lancet and The Lancet Neurology.

One paper looked at high blood pressure and blood pressure variability in four groups of 2,000 people, each of who had minor strokes called transient ischemic attacks (TIAs), or “mini-strokes.” These are warning signs of stroke risk.

They found that people with the greatest variation in systolic blood pressure (the higher of the 120/80 readings) over seven visits to their doctor were six times more likely to have a major stroke. People with the highest blood pressure readings were 15 times more likely to have a stroke.

“Under-diagnosis and under-treatment of hypertension is a major, seemingly intractable problem in all health-care systems,” Rothwell said. “The new research shows that part of the problem is likely to have been under-recognition of the impact of variability in blood pressure on diagnosis in routine clinical practice in primary care. It shows that doctors have to make diagnoses on the basis of blood pressure measurements that vary substantially from visit to visit.”

The message for doctors is that they have to change the way they view high blood pressure, he said.

“All current clinical guidelines encourage doctors to ignore variability and occasional high readings and to rely exclusively on the average blood pressure from multiple visits or 24-hour monitoring,” Rothwell said. “The new research shows that increased variability in blood pressure, a high maximum blood pressure and episodic hypertension are associated with high risks of stroke and other vascular events, and emphasize that any comfort taken from the fact blood pressure is sometimes normal is false.”

Other papers by Rothwell and his colleagues indicated that doctors should consider blood pressure variability when they choose among the many drugs now prescribed to control high blood pressure. A meta-analysis of 389 controlled trials found that effects on blood pressure variability explained why some classes of blood pressure drugs were more effective than others in preventing stroke. Another paper looked at the greater effectiveness of calcium channel blockers and thiazide diuretics vs. beta blockers in reducing stroke risk.

The result: “Calcium channel blockers and thiazide diuretics reduce [blood pressure] variability and beta blockers increase it,” Rothwell concluded.

He called for development of new drugs that would stabilize and lower blood pressure at the same time. “Drugs that reduced variability without reducing average blood pressure should still prevent stroke and would be likely to be helpful in patients who cannot tolerate reductions in their average blood pressure,” Rothwell theorized.

Variability can easily be measured when people visit their doctors, although “the fact that many people now monitor their blood pressure at home will be helpful in identifying variability,” he said.

“I think these findings are very important and very compelling, and may revolutionize how we treat blood pressure in the future,” said Dr. Philip B. Gorelick, director of the Center for Stroke Research at the University of Illinois, and a leading American expert on blood pressure and stroke. “They provide a very important foundation for change in future treatment.”

Rothwell’s findings already are starting to affect Gorelick’s practice, he said.

“First, we may begin to screen patients with blood pressure measurements for variability to see if we can select for classes of drugs that reduce variability,” Gorelick said. “And we can certainly adopt an at-home program to detect blood pressure variability, although within-visit variability seems to be a more important factor.”

The findings may also affect the choice of the first drugs prescribed for blood pressure control, he said. “We would consider calcium channel blockers and diuretics for initial use,” Gorelick said.

SOURCES: Peter Rothwell, M.D., Ph.D., professor, neurology, University of Oxford, England; Philip B. Gorelick, M.D., professor, neurology, and director, Center for Stroke Research, Chicago; 2010, The Lancet, The Lancet Neurology

Intensive care patients are less likely to die if they’re looked after by a multidisciplinary health care team that includes doctors, nurses, respiratory therapists, clinical pharmacists and others, says a new study.

Researchers analyzed data from more than 107,000 patients admitted to intensive care units at 112 acute care hospitals in the United States between 2004 and 2006. The risk of death was lower among patients in ICUs where a multidisciplinary team conducted daily rounds.

The lowest risk of death was among patients at the 22 (19.6 percent) hospitals that had a trained intensivist physician who consulted on or managed all ICU cases as well as daily rounds conducted by a multidisciplinary care team.

Care by a multidisciplinary team may reduce the risk of death among ICU patients for a number of reasons, said Michelle M. Kim, of the University of Pennsylvania in Philadelphia, and colleagues.

“Multidisciplinary rounds may facilitate implementation of best clinical practices, such as evidence-based treatments for acute lung injury, sepsis and prevention of ICU complications,” they wrote. “Pharmacist participation on rounds is associated with fewer adverse drug events and alone may be associated with lower mortality among ICU patients. Multidisciplinary rounds may also improve communication between health care providers.”

The findings may influence how hospitals look after ICU patients, who are often at high risk of death from conditions such as sepsis and acute lung injury.

“Based on these results and expert opinion voiced in consensus guidelines, it is reasonable for hospitals to implement routine multidisciplinary rounds when staffing capabilities allow,” Kim and colleagues wrote. “Our study shows that hospitals without the ability to implement high-intensity physician staffing can still achieve significant mortality reductions by implementing a multidisciplinary, team-based approach.”

The study appears issue of the journal Archives of Internal Medicine.

SOURCE: JAMA/Archives journals, news release

U.S. researchers have discovered a distinct pattern of brain activity in people with post traumatic stress disorder that may give doctors an objective way to test for it, they said on Wednesday.

Using a brain imaging device called magnetoencephalography, which measures how the brain processes information, a team at the University of Minnesota and the Minneapolis VA Medical Center found differences in brain activity between people with PTSD and healthy people.

Having a test for PTSD could speed treatment and simplify insurance coverage, said Dr. Apostolos Georgopoulos of the University of Minnesota, whose study appears in the Journal of Neural Engineering.

PTSD, an anxiety disorder sometimes caused by wartime trauma, can cause flashbacks, nightmares, anger or edginess.

It currently is considered a “soft disorder,” Georgopoulos said in a telephone interview.

“The thinking is people can suffer from it, but there is no biological marker.”

Georgopoulos and colleagues studied 74 U.S. veterans with PTSD and 250 people with no mental health problems.

They scanned the brains of study participants looking for a signal that might distinguish a PTSD patient from a healthy volunteer.

Georgopoulos said current imaging techniques, including magnetic resonance imaging or MRI and functional MRI, look at brain activity indirectly. To get a direct measure, they used a highly sensitive magnetoencephalography or MEG devices, which measure the magnetic fields produced by electrical activity in the brain.

“What you get out of it is a signal that directly comes from brain activity,” Georgopoulos said.

The scanner has 248 sensors that record the interactions in the brain on a millisecond by millisecond basis, much faster than current methods such as the functional magnetic resonance imaging or fMRI.

These measurements allowed the team to spot biomarkers or signals in the brain scans of those who had PTSD.

When they compared brain scans from PTSD and healthy volunteers, they could accurately pick out the PTSD patients 90 percent of the time.

“What you have in this disorder is a functional disruption of brain activity. This is what we pick up in an extremely highly accurate way,” Georgopoulos said.

The team is now looking to confirm the findings in a study of 500 patients with PTSD and 500 healthy volunteers.

A study last year by the Rand Corp research organization estimates that about 18.5 percent of the U.S. troops sent to Iraq and Afghanistan show signs of either PTSD or depression, conditions linked closely with substance abuse.

(Editing by Cynthia Osterman)

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