Category: Drugs and Disease

The effect was seen most strongly with colon, gastrointestinal tumors, researchers report

SOURCES: Andrew Chan, M.D., M.P.H., Massachusetts General Hospital, Boston; Ernest Hawk, M.D., M.P.H., vice president, division of cancer prevention and population sciences, University of Texas MD Anderson Cancer Center, Houston; Eric Jacobs, Ph.D., strategic director, pharmacoepidemiology, American Cancer Society; March 3, 2016, JAMA Oncology, online

 

 

 

 

 

A small case study released today by the Centers for Disease Control and Prevention (CDC) supports the agency’s suspicion that when pregnant women contract the Zika virus there is higher risk for adverse outcomes for the fetus, including microcephaly.

That risk appears especially associated with a Zika infection in the first trimester of pregnancy.

The discouraging news came on the same day that the CDC issued a new travel alert recommending that pregnant women not go to the Summer Olympics in Brazil, which is experiencing surges in both Zika infections and infants with microcephaly. The agency also announced that it is establishing a special registry for pregnant women in the United States who contract the virus to better understand this public health threat.

In the latest edition of the agency’s Morbidity and Mortality Weekly Report (MMWR), CDC investigators outline the cases of nine pregnant women who became infected with the Zika virus after traveling to an area of active transmission. None of them died or were hospitalized. One woman who experienced Zika symptoms in her third trimester delivered a healthy infant, as did a woman whose symptoms appeared in the second trimester. The pregnancy of another woman with second-trimester symptoms is continuing.

For six women who reported Zika symptoms in their first trimester, the outcomes were mostly grim. Two of them miscarried, two aborted their pregnancies, and another delivered an infant with microcephaly. The sixth woman has yet to deliver her child.

One woman chose to end her pregnancy after an ultrasound suggested the absence of the corpus callosum, ventriculomegaly, and brain atrophy at the 20-week mark. A follow-up fetal MRI revealed severe brain atrophy. Reverse transcription polymerase chain reaction testing detected the RNA of Zika virus in the woman’s amniotic fluid.

The MMWR article did not provide details about the other woman who had an abortion, or the health status of her fetus. Denise Jamieson, MD, MPH, a member of the agency’s Zika response team, said at a news conference today that there was no additional information on the second terminated pregnancy. Dr Jamieson coleads a section of the team focused on pregnancy and birth defects.

The results of the case study, small as it was, were surprising, she said.

“We did not expect to see these brain abnormalities in this small case series of US pregnant travellers,” Dr Jamieson said. “It is…greater than what we would have expected.”

CDC Director Tom Frieden, MD, MPH, reiterated at the news conference that although the Zika virus is strongly suspected of causing microcephaly, based on a growing body of evidence, “there’s no definite proof that it’s the sole cause.” The CDC and public health authorities in Brazil are conducting larger studies into the relationship, but the results could be months away.

The CDC hopes to glean insights from a voluntary registry it is launching on pregnant women here who contract the Zika virus. The CDC will collect data from public health agencies and individual clinicians.

Sexual Transmission of Virus More Common Than Once Believed

Another study published today in MMWR confirmed that the Zika virus spreads through sexual relations, and does so more commonly than once believed.

The article reported on 14 cases of suspected sexual transmission. In each one, a man who had traveled to an area of active virus transmission developed symptoms within 2 weeks of his female sexual partner becoming ill. Study findings moved some of the cases beyond the realm of mere suspicion.

According to the MMWR article, lab tests confirmed Zika infections in two of the women, while four others had probably contracted the virus. The CDC eliminated the cases of two women based on additional information. The investigation into the six remaining cases continues.

“We did not…anticipate that we would see this many sexually transmitted cases of Zika,” Dr Frieden said at today’s news conference.

After a separate case of sexually transmitted Zika — not included in the MMWR study — surfaced in Texas earlier this month, the CDC advised men who have a pregnant partner to use a condom or practice abstinence for the duration of the pregnancy if they have visited, or live in, a Zika zone.

“Today’s report underscores that recommendation,” Dr Frieden said.

A Cloud Over the Summer Olympics

Concern about the suspected link between the Zika virus and microcephaly prompted the CDC last month to recommend that pregnant women postpone visiting areas of active virus transmission, which include most of Latin America and the Caribbean. In a significant expansion of its travel guidance, the agency today recommended that pregnant women consider not attending the Summer Olympics in Rio de Janeiro, Brazil, scheduled for August 5 through August 21, or the Paralympic Games, scheduled for September 7 through September 18.

If pregnant women decide to go, anyway, they should consult their clinician first and, along with their partner, strictly follow steps to avoid mosquito bites, such as applying mosquito spray and wearing long-sleeve shirts and long pants, according to the CDC.

The agency encourages women who are trying to become pregnant to talk to their clinician about the risks for a Zika virus infection and precautions against mosquito bites before traveling to the Summer Olympics.

The CDC also urges precautions for sexual relations. If men travel to the Olympics, and they have a pregnant partner, they should abstain from vaginal, anal, or oral sex, or else use condoms for the duration of the pregnancy.

The CDC travel alert included other recommendations for Olympic goers, such as getting up to date on routine vaccines, traveling with a companion for safety’s sake, and only during the day; and steering clear of food sold by street vendors.

Women with asthma may take longer to get pregnant and have a lower pregnancy rate than those without the lung disease, new research suggests.

The study included 245 women, aged 23 to 45, who had unexplained fertility problems and were undergoing fertility treatment. Ninety-six of the women had been diagnosed with asthma.

The women were followed until they had a successful pregnancy, stopped treatment or the study ended. The median time for women without asthma to get pregnant was about 32 months compared to more than 55 months for those with asthma. Median means half took more time to conceive; half, less.

About 60 percent of women without asthma got pregnant, compared with just under 40 percent of those with asthma, the findings showed. The gap between the two groups increased with age, according to the study published Feb. 12 in the European Respiratory Journal.

The trial finding adds new weight to evidence suggesting a link between asthma and fertility, lead author Dr. Elisabeth Juul Gade said in a journal news release. Gade is with the department of respiratory medicine at Bispebjerg University Hospital in Copenhagen, Denmark.

“We have seen here that asthma seems to have a negative influence on fertility as it increases time to pregnancy and even more so with age,” she said. “We do not yet know the causal relationship; it may be complex with different types of asthma, psychological well-being, asthma medication and hormones all playing a role.”

Gade said doctors should encourage women with asthma to become pregnant at an earlier age and step up their asthma treatment before conceiving.

“Patient education is also of paramount importance as adherence to treatment may be enhanced if patients are informed of this link,” Gade said in the news release.

While the study found an association between asthma and difficulty conceiving, it did not prove cause-and-effect.

People with respiratory allergies, asthma and the skin condition eczema may be less likely to develop glioma brain cancer, a new study suggests.

The international team of researchers looked at more than 4,500 glioma patients and almost 4,200 people without brain cancer. The investigators found that a history of respiratory allergies, asthma and eczema was associated with a reduced risk for glioma.

People with respiratory allergies or eczema were 30 percent less likely to develop the deadly brain cancer than those without such conditions, the study found.

Although the study found an association between allergic conditions and a lower risk of gliomas, it wasn’t designed to prove a cause-and-effect relationship between those factors.

The study was released online Feb. 5 in the journal Cancer Epidemiology, Biomarkers & Prevention.

“Many other studies have shown this relationship,” study author Melissa Bondy, associate director for cancer prevention and population science at Baylor College of Medicine’s Cancer Center, said in a college news release.

“We sought to verify this relationship in the largest study to date so that we could provide a scientific consensus statement on the topic. We feel it’s now time for the next steps to be taken in this research area,” she added.

And, that next step is figuring out the mechanism behind the association, Bondy said.

Glioma is the term used to describe tumors arising from the gluey or supportive tissue of the brain, according to the American Brain Tumor Association. Just over one-quarter of all brain tumors and 80 percent of all malignant brain tumors are gliomas.

– A new type of treatment called proton radiotherapy is as effective as standard photon (X-ray) radiation therapy in treating a common type of brain tumor in children, a new study reports.

And the new therapy causes fewer long-term side effects, the researchers said.

“Proton radiotherapy is still not widely available in the U.S. or around the world, but it is increasingly recognized for its potential to reduce the side effects of treatment, particularly in the pediatric population,” study author Dr. Torunn Yock said in a news release from Massachusetts General Hospital.

“At experienced centers, proton therapy has a proven track record of treatment success and safety,” added Yock. She is an associate professor of radiation oncology at Harvard Medical School in Boston.

In photon radiotherapy, a dose of radiation is delivered all along the X-ray beam as it passes through the patient’s body. But in proton therapy, the radiation dose is focused on the target area. This means little or no radiation reaches healthy tissue in front or behind the tumor, the study authors explained.

The new study included 59 children with medulloblastoma — a tumor that occurs in the cerebellum at the base of the brain. The patients were aged 3 to 21, and all received proton radiotherapy at Mass General in Boston between 2003 and 2009.

The patients had already had surgery to remove as much of the tumor as possible. They also all had chemotherapy before, during and after proton therapy, the researchers said.

Of the 59 patients, 12 died from their tumor during the study period and one died from a traumatic brain injury, the researchers reported. Survival and tumor recurrence rates were similar to those that have been reported for photon radiotherapy.

Significant hearing loss occurred in 12 percent of patients three years after proton therapy, and in 16 percent after five years. Previous research shows that significant hearing loss occurs in about 25 percent of patients who receive photon radiotherapy, the researchers said.

The effects of proton therapy on thinking (cognitive) ability were less severe than what has been reported with photon radiotherapy, according to the study authors.

The patients in the study had no heart, lung, digestive, seizures or secondary tumor side effects, all of which can occur with photon radiotherapy, the researchers said in the news release.

Seven years after treatment, hormone level deficits were seen in 63 percent of the study patients, which is similar to that seen with photon radiotherapy, the study authors said.

The study was published online Jan. 29 in The Lancet Oncology.

“Our results indicate that proton therapy maintains excellent cure rates in pediatric medulloblastoma while reducing long-term side effects,” Yock said in the news release.

“While we are currently investigating quality of life differences between proton and photon treatment, I truly believe that — particularly for the youngest children — the ability to offer them proton therapy can make a big difference in their lives,” she concluded.

Infants whose mothers were obese before pregnancy appear to have an increased risk of death, according to a new study.

But even though the researchers found that pre-pregnancy obesity was related to worse outcomes for infants, it’s important to note that the study wasn’t designed to prove a cause-and-effect relationship.

Still, the study’s lead author, Eugene Declercq of Boston University School of Public Health, said, “There is a need for more open, honest discussions about avoiding the possible risks of maternal obesity on infant health.”

For the study, researchers reviewed data from more than 6 million newborns. The babies were born in 38 states between 2012 and 2013.

Infants born to obese women were twice as likely to die from preterm birth-related causes than those born to normal-weight women, the investigators found.

Infants born to obese women were also more likely to die from birth defects and sudden infant death, the study showed. And, the more obese the mother, the greater the risk of infant death.

Even if obese women adhered to weight-gain guidelines during pregnancy, it had little effect on infant death risk, the study authors said.

The study highlights the need to address obesity before pregnancy, and for more research into what increases the risk of death in infants born to obese women, said Declercq, a professor of community health sciences at Boston University School of Public Health.

“The findings suggest that primary care clinicians, ob-gyns and midwives need to have conversations about weight as part of well-woman care, and when women are contemplating getting pregnant,” he said in a university news release.

Taking antidepressants during the second or third trimester of pregnancy may increase the risk of having a child with autism spectrum disorder, according to a study of Canadian mothers and children published Monday in JAMA Pediatrics.

But scientists not involved in the research say the results are hard to interpret and don’t settle the long-running debate about whether expectant mothers with depression should take antidepressants.

“This study doesn’t answer the question,” says Bryan King, program director of the autism center at Seattle Children’s Hospital and a professor of psychiatry and behavioral sciences at the University of Washington. “My biggest concern is that it will be over-interpreted,” says King, who wrote an editorial that accompanied the study.

“It kind of leaves you more confused,” says Alan Brown, a professor of psychiatry and epidemiology at Columbia University who studies risk factors for autism. “Mothers shouldn’t get super worried about it,” he says.

One reason it’s confusing is that there’s strong evidence that mothers with depression are more likely than other women to have a child with autism, whether or not they take antidepressants during pregnancy. King and Brown say that makes it very hard to disentangle the effects of depression itself from those of the drugs used to treat it.

Earlier this year, a study of several thousand U.S. children found that prenatal antidepressant exposure did not increase the risk of autism spectrum disorder. In 2013, a study of nearly 670,000 Danish children also found no association between prenatal exposure to antidepressant medication and autism spectrum disorder.

But a 2013 study of more than 4,400 Swedish children concluded that in utero exposure did increase the risk that a child would develop autism. And a 2011 study of about 300 children with autism in California concluded that antidepressants “may modestly increase the risk” of an autism spectrum disorder.

The Canadian study looked at more than 145,000 children born in Quebec from 1998 to 2009. It found that children whose mothers took antidepressants during the second or third trimester of pregnancy were 87 percent more likely to be diagnosed with autism spectrum disorder.

The study tried to account for depression’s effect on risk by identifying mothers with a history of psychiatric disorders. It also compared mothers who stopped taking antidepressants during the first trimester with mothers who continued taking the medications.

Those steps allowed the team to conclude that the 87 percent increase was “above and beyond” the risk posed by depression itself, says Anick Berard, the study’s senior author and an epidemiologist and biostatistician at the University of Montreal. Berard has done other studies that linked antidepressants to birth defects and has worked as a consultant for plaintiffs who are suing companies that make antidepressants.

Other scientists aren’t so sure that Berard’s study truly shows a risk associated with antidepressant use. Mothers who kept taking antidepressants may have had more severe depression, they say. Also, they say, the increase in risk was so small that it might have been a chance finding.

An 87 percent increase “sounds very concerning,” King says. But the figure is based on just 31 children who developed autism after being exposed to antidepressants. And many of these children would have developed autism anyway, he says.

The absolute risk numbers are small, Berard says. But she says a secondary analysis showed that the risk was highest for women who took drugs called SSRIs, which affect serotonin levels. And serotonin plays an important role in brain development, she says. The number of women using only other types of antidepressants was very small, so it was impossible to draw conclusions about their safety.

“We have to be vigilant even if the risk is small,” Berard says. “Maybe we should rethink our treatment process.”

King responds that untreated depression can result in poor nutrition, sleep problems and stress, all of which can affect the health of a developing fetus. So pregnant women who are concerned about taking antidepressants should consult with their doctor before taking any action, he says.

Better information about the risks of antidepressants and other factors may emerge from a large, ongoing study of children born in Finland, says Brown, who is the study’s principal investigator. Those results may be available in the next few years.

High-dose vitamin D appears safe for people with multiple sclerosis, and it may help quiet the immune system hyperactivity that marks the disease, a small clinical trial finds.

The study, published online Dec. 30 in Neurology, bolsters evidence that vitamin D might benefit people with MS.

But clinical trials are still underway to answer the big question: Does taking vitamin D improve MS symptoms and alter the course of the disease?

The current study shows only that high doses — 10,400 IU a day — reduce the proportion of certain immune-system cells that have been implicated in the MS disease process.

“I’m not going to make any claims beyond that,” said senior researcher Dr. Peter Calabresi, a professor of neurology at Johns Hopkins University in Baltimore.

“We don’t have enough data here to guide clinical practice,” he stressed.

Bruce Bebo, executive vice president of research for the National Multiple Sclerosis Society, echoed that caution.

“This study was not designed to look at efficacy against MS. It was too small and too short to do that,” said Bebo, whose group helped fund the research.

Still, Bebo added, the findings are important for other reasons. For one, he said, “they give us some hints about the mechanisms that explain the higher MS risk associated with low vitamin D.”

MS is caused by an abnormal immune system attack on the protective sheath surrounding nerve fibers in the brain and spine. That leads to symptoms such as muscle weakness, numbness, vision problems, and difficulty with balance and coordination.

Typically, MS symptoms flare up periodically, followed by periods of remission. Over time, the disease can cause worsening problems with walking and mobility.

The precise cause of MS is unknown, but researchers believe it involves a combination of genetic vulnerability and certain environmental triggers. Inadequate vitamin D — a nutrient needed for normal immune function — is considered one of the suspects.

That’s partly based on studies showing an association between blood levels of vitamin D and the risk of developing MS. But there is also more-direct evidence, Bebo said. For example, research has shown that vitamin D can reduce the effects of an MS-like disease in lab mice.

The new findings suggest it may alter immune system activity in people with MS, too, Bebo said.

According to Calabresi, the results underscore another point: High doses of vitamin D are probably necessary.

His team tested two doses in 40 adults with MS. Over six months, one group took 10,400 IU of vitamin D a day — about 17 times the amount that the U.S. government recommends for healthy adults (600 IU a day); the other group took 800 IU a day.

In the end, only the high-dose group showed changes in their immune system activity. The largest effect, Calabresi said, was a reduction in cells that produce an inflammatory protein called interleukin-17.

However, the study looked only at certain aspects of immune function. And MS is a “complicated disease immunologically,” Calabresi noted.

He said it will be interesting to see whether vitamin D has additional immune system effects in people with MS, or possibly other autoimmune diseases.

Several clinical trials are now testing vitamin D against MS, including a U.S. study that’s still recruiting patients. The trials are using doses ranging from 5,000 to 10,000 IU a day, Calabresi said.

Without those trial results, he said, it’s too early to recommend that people with MS take vitamin D.

But, he added, since adequate vitamin D is important for overall health, people may want to be tested for deficiency in the nutrient.

With vitamin D supplements readily available, Calabresi also recognized that some people with MS will probably start taking it even in the absence of proof.

He encouraged them to use vitamin D only under medical supervision.

In this study, high doses appeared safe over six months. But, Calabresi said, high blood levels of vitamin D can send blood calcium concentrations soaring, which can cause kidney stones or other problems, such as poor appetite, weakness and constipation.

Bebo agreed. “Always speak to your [doctor] about any medications or supplements that you’re thinking of taking,” he said.

Nitrates are commonly prescribed for heart failure patients, but a new study finds they don’t improve quality of life or everyday activity levels as intended.

The drugs are prescribed to relieve chest pain so patients whose hearts still contract normally might feel comfortable enough to increase their daily activities. Now, new research suggests the opposite is true.

“Nitrates tended to reduce daily activity and significantly reduce active hours per day,” said lead researcher Dr. Margaret Redfield, a professor of medicine at the Mayo Clinic in Rochester, Minn.

Moreover, nitrates did not improve exercise capacity or symptoms of heart failure, such as shortness of breath and weakness when walking. She said symptoms tended to be worse among those taking the drugs.

“This study should change practice,” Redfield said. “Long-acting nitrates should not be used for symptom relief in heart failure.”

The report was published Dec. 10 in the New England Journal of Medicine.

For the study, Redfield’s team randomly assigned 110 heart failure patients to six weeks of daily treatment with an increasing dose of isosorbide mononitrate — from 30 milligrams (mg) to 120 mg — or to take a placebo.

The patients suffered from heart failure with so-called preserved ejection fraction, which affects about half of heart failure patients.

According to the American Heart Association, this condition means that the heart muscle contracts normally but the lower chambers of the heart — the ventricles — don’t relax as they should when being filled with blood or when they pump blood out.

This reduces the amount of blood entering the ventricles. Although the heart pumps out all the blood in the ventricles, it isn’t enough blood to meet the body’s needs.

Six weeks into the study, the groups switched medication regimens, and the trial continued for another six weeks, according to the report.

Patients wore accelerometers to measure daily activity levels. The researchers found that patients receiving the 120-mg dose of isosorbide mononitrate tended to have reduced daily activity and a significant decrease in the hours of daily activity, compared with those receiving the dummy drug.

Moreover, daily activity was reduced among patients receiving the nitrate regardless of dose, compared with the placebo. And as the dose of isosorbide mononitrate increased, activity levels decreased while remaining steady among those taking the placebo, the investigators found.

Also, no significant difference between the groups was seen in distance walked within six minutes or in quality-of-life scores. And there was no difference in blood levels of a biological indicator that is used to diagnose the extent of heart failure.

Dr. Gregg Fonarow, a professor of cardiology at the University of California, Los Angeles, said this study highlights the critical need to identify new therapies that can improve outcomes for this common, costly and deadly condition.

“Despite close to 3 million men and women having heart failure, there have not been any medications that have been demonstrated to reduce the risk of hospitalization or death,” Fonarow said.

“Use of nitrates as a treatment for heart failure in this patient population does not appear to provide a benefit,” he said.

– A small study suggests there may be a link between levels of omega-3 fatty acids and bipolar disorder.

Researchers compared 27 people with bipolar disorder and 31 people without the mental illness. Those with bipolar disorder had lower levels of certain omega-3 fatty acids that can cross the blood-brain barrier, the study authors found.

Omega-3 fatty acids play an important role in communication between brain cells, and fatty acids are a major player in the immune and inflammatory systems, the researchers said.

“Omega-3 and omega-6 fatty acids can shift the balance of inflammation, which we think is important in bipolar disorder,” study leader Erika Saunders, an associate professor and chairwoman of psychiatry at Penn State College of Medicine in College Park, Pa., said in a school news release.

Foods such as fish, vegetable oils, nuts, flax seeds and flaxseed oil, as well as leafy vegetables, are rich in omega-3 fatty acids. The study found no difference in reported consumption of these foods between the two groups of participants.

The researchers said they don’t know if that’s because only certain foods were included in the survey or because people couldn’t accurately recall what they had eaten.

They are now looking at whether increasing the amount of fatty acids in bipolar patients’ diets may benefit them.

“We are actively pursuing the next step in this line of inquiry, to get to the point where we know what changes in diets are going to help people with bipolar disorder so they can have another option beyond the medications that are currently available,” Saunder said.

Previous research has found that omega-3 supplements provided no benefit for people with bipolar disorder, the researchers added.

The study was published recently in the journal Bipolar Disorders.