U.S. study of nine pregnant travelers raises new worries about Zika

A scientist shows a picture of Aedes aegypti mosquitoes inside the International Atomic Energy Agency's (IAEA) insect pest control laboratory in Seibersdorf, Austria, February 10, 2016. REUTERS/Leonhard Foeger
A scientist shows a picture of Aedes aegypti mosquitoes inside the International Atomic Energy Agency’s (IAEA) insect pest control laboratory in Seibersdorf, Austria, February 10, 2016.

Reuters/Leonhard Foeger


A study of nine pregnant women from the United States who traveled to countries where the Zika virus was circulating shows a greater-than-expected number of fetal infections and brain abnormalities, U.S. health officials said on Friday.

Two of the women had miscarriages, two had abortions, two had apparently healthy children, and one child was born with severe microcephaly, the U.S. Centers for Disease Control and Prevention said.

Doctors are still following the two remaining pregnancies, which so far appear to be progressing without complications, the CDC said.

“We did not expect to see these brain abnormalities in this small case series of U.S. pregnant travelers,” said Dr. Denise Jamieson, a birth defects expert serving on CDC’s Zika Virus Response Team.

She said it was “greater than we would have expected.”

Brazil is investigating thousands of cases of babies born with abnormally small heads thought to be linked with Zika, a mosquito-borne virus circulating in Latin America and the Caribbean.

In the nine U.S. cases, Zika virus infection during pregnancy was associated with a range of outcomes, including early pregnancy losses, congenital microcephaly, and apparently healthy infants, the CDC said. Microcephaly is a birth defect associated with undersized heads and developmental problems.

More information will be available in the future from a new CDC registry for U.S. pregnant women with confirmed Zika virus infection and their infants.

An analysis of some cases showed the virus had crossed the placenta and affected the fetuses.

In one, a woman traveled to a Zika-affected area when she was five weeks pregnant. Antibody testing confirmed a recent

Zika infection. The mother miscarried at eight weeks, and an analysis of the fetus detected Zika virus.

“Our lab identified Zika in the placental tissues. That is suggestive that Zika may have caused the miscarriage,” CDC Director Dr. Thomas Frieden told reporters on a conference call. But he cautioned that 10 percent to 20 percent of all pregnancies end up in miscarriage, so it was not certain that Zika was to blame.

In another case, a woman in her 30s had traveled to a Zika-affected area when she was about 12 weeks pregnant. Shortly after her return, she developed a fever, eye pain, body aches and a rash. Testing confirmed a recent Zika infection.

The woman got a routine ultrasound at about 20 weeks gestation, and doctors noted that the fetus was missing its corpus callosum, tissue that connects both halves of the brain. It also had fluid in the brain and there was evidence the brain had shrunk in size. The Zika virus was detected in the amniotic fluid. The woman chose to abort the fetus.

In another case, a woman who had lived in Brazil gave birth to an infant with severe microcephaly. The CDC did not release details on where the baby was born. In January, a CDC spokesman confirmed that a U.S. woman who had lived in Brazil gave birth to a microcephalic baby in Hawaii.

“It’s more evidence to me that this association is continuing to look stronger and stronger,” said Dr. Richard Beigi, president of The Infectious Diseases Society for Obstetrics and Gynecology, who had seen the reports.

“We want to be cautious because it’s a small group of women, but from what I saw, it is suggestive that the effects look to be more severe in the early part of pregnancy,” said Beigi, an obstetrician at the University of Pittsburgh Medical Center.

The CDC is also investigating another 10 cases of Zika infection in pregnant travelers. On Jan. 15, the CDC issued an advisory telling pregnant women to consider postponing travel to areas with active transmission of Zika virus.

On the conference call, the CDC said it has developed a diagnostic test that it plans to distribute to U.S. public health laboratories to speed the diagnosis of Zika, which currently takes about a week.

It is not yet clear that Zika virus actually causes microcephaly in babies, but experts say the evidence of a link is growing.

Brazil has confirmed more than 580 cases of microcephaly, and considers most of them to be related to Zika infections in the mothers. Brazil is investigating an additional 4,100 suspected cases of microcephaly.

The CDC said it has deployed 25 staff to help with the investigation. That was in addition to the 50 CDC staff members in Brazil studying dengue, a related virus.

(Reporting by Julie Steenhuysen; Editing by David Gregorio)


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U.S. study of nine pregnant travelers raises new worries about Zika

A scientist shows a picture of Aedes aegypti mosquitoes inside the International Atomic Energy Agency's (IAEA) insect pest control laboratory in Seibersdorf, Austria, February 10, 2016. REUTERS/Leonhard Foeger
A scientist shows a picture of Aedes aegypti mosquitoes inside the International Atomic Energy Agency’s (IAEA) insect pest control laboratory in Seibersdorf, Austria, February 10, 2016.

Reuters/Leonhard Foeger


A study of nine pregnant women from the United States who traveled to countries where the Zika virus was circulating shows a greater-than-expected number of fetal infections and brain abnormalities, U.S. health officials said on Friday.

Two of the women had miscarriages, two had abortions, two had apparently healthy children, and one child was born with severe microcephaly, the U.S. Centers for Disease Control and Prevention said.

Doctors are still following the two remaining pregnancies, which so far appear to be progressing without complications, the CDC said.

“We did not expect to see these brain abnormalities in this small case series of U.S. pregnant travelers,” said Dr. Denise Jamieson, a birth defects expert serving on CDC’s Zika Virus Response Team.

She said it was “greater than we would have expected.”

Brazil is investigating thousands of cases of babies born with abnormally small heads thought to be linked with Zika, a mosquito-borne virus circulating in Latin America and the Caribbean.

In the nine U.S. cases, Zika virus infection during pregnancy was associated with a range of outcomes, including early pregnancy losses, congenital microcephaly, and apparently healthy infants, the CDC said. Microcephaly is a birth defect associated with undersized heads and developmental problems.

More information will be available in the future from a new CDC registry for U.S. pregnant women with confirmed Zika virus infection and their infants.

An analysis of some cases showed the virus had crossed the placenta and affected the fetuses.

In one, a woman traveled to a Zika-affected area when she was five weeks pregnant. Antibody testing confirmed a recent

Zika infection. The mother miscarried at eight weeks, and an analysis of the fetus detected Zika virus.

“Our lab identified Zika in the placental tissues. That is suggestive that Zika may have caused the miscarriage,” CDC Director Dr. Thomas Frieden told reporters on a conference call. But he cautioned that 10 percent to 20 percent of all pregnancies end up in miscarriage, so it was not certain that Zika was to blame.

In another case, a woman in her 30s had traveled to a Zika-affected area when she was about 12 weeks pregnant. Shortly after her return, she developed a fever, eye pain, body aches and a rash. Testing confirmed a recent Zika infection.

The woman got a routine ultrasound at about 20 weeks gestation, and doctors noted that the fetus was missing its corpus callosum, tissue that connects both halves of the brain. It also had fluid in the brain and there was evidence the brain had shrunk in size. The Zika virus was detected in the amniotic fluid. The woman chose to abort the fetus.

In another case, a woman who had lived in Brazil gave birth to an infant with severe microcephaly. The CDC did not release details on where the baby was born. In January, a CDC spokesman confirmed that a U.S. woman who had lived in Brazil gave birth to a microcephalic baby in Hawaii.

“It’s more evidence to me that this association is continuing to look stronger and stronger,” said Dr. Richard Beigi, president of The Infectious Diseases Society for Obstetrics and Gynecology, who had seen the reports.

“We want to be cautious because it’s a small group of women, but from what I saw, it is suggestive that the effects look to be more severe in the early part of pregnancy,” said Beigi, an obstetrician at the University of Pittsburgh Medical Center.

The CDC is also investigating another 10 cases of Zika infection in pregnant travelers. On Jan. 15, the CDC issued an advisory telling pregnant women to consider postponing travel to areas with active transmission of Zika virus.

On the conference call, the CDC said it has developed a diagnostic test that it plans to distribute to U.S. public health laboratories to speed the diagnosis of Zika, which currently takes about a week.

It is not yet clear that Zika virus actually causes microcephaly in babies, but experts say the evidence of a link is growing.

Brazil has confirmed more than 580 cases of microcephaly, and considers most of them to be related to Zika infections in the mothers. Brazil is investigating an additional 4,100 suspected cases of microcephaly.

The CDC said it has deployed 25 staff to help with the investigation. That was in addition to the 50 CDC staff members in Brazil studying dengue, a related virus.

(Reporting by Julie Steenhuysen; Editing by David Gregorio)


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U.S. study of nine pregnant travelers raises new worries about Zika

A scientist shows a picture of Aedes aegypti mosquitoes inside the International Atomic Energy Agency's (IAEA) insect pest control laboratory in Seibersdorf, Austria, February 10, 2016. REUTERS/Leonhard Foeger
A scientist shows a picture of Aedes aegypti mosquitoes inside the International Atomic Energy Agency’s (IAEA) insect pest control laboratory in Seibersdorf, Austria, February 10, 2016.

Reuters/Leonhard Foeger


A study of nine pregnant women from the United States who traveled to countries where the Zika virus was circulating shows a greater-than-expected number of fetal infections and brain abnormalities, U.S. health officials said on Friday.

Two of the women had miscarriages, two had abortions, two had apparently healthy children, and one child was born with severe microcephaly, the U.S. Centers for Disease Control and Prevention said.

Doctors are still following the two remaining pregnancies, which so far appear to be progressing without complications, the CDC said.

“We did not expect to see these brain abnormalities in this small case series of U.S. pregnant travelers,” said Dr. Denise Jamieson, a birth defects expert serving on CDC’s Zika Virus Response Team.

She said it was “greater than we would have expected.”

Brazil is investigating thousands of cases of babies born with abnormally small heads thought to be linked with Zika, a mosquito-borne virus circulating in Latin America and the Caribbean.

In the nine U.S. cases, Zika virus infection during pregnancy was associated with a range of outcomes, including early pregnancy losses, congenital microcephaly, and apparently healthy infants, the CDC said. Microcephaly is a birth defect associated with undersized heads and developmental problems.

More information will be available in the future from a new CDC registry for U.S. pregnant women with confirmed Zika virus infection and their infants.

An analysis of some cases showed the virus had crossed the placenta and affected the fetuses.

In one, a woman traveled to a Zika-affected area when she was five weeks pregnant. Antibody testing confirmed a recent

Zika infection. The mother miscarried at eight weeks, and an analysis of the fetus detected Zika virus.

“Our lab identified Zika in the placental tissues. That is suggestive that Zika may have caused the miscarriage,” CDC Director Dr. Thomas Frieden told reporters on a conference call. But he cautioned that 10 percent to 20 percent of all pregnancies end up in miscarriage, so it was not certain that Zika was to blame.

In another case, a woman in her 30s had traveled to a Zika-affected area when she was about 12 weeks pregnant. Shortly after her return, she developed a fever, eye pain, body aches and a rash. Testing confirmed a recent Zika infection.

The woman got a routine ultrasound at about 20 weeks gestation, and doctors noted that the fetus was missing its corpus callosum, tissue that connects both halves of the brain. It also had fluid in the brain and there was evidence the brain had shrunk in size. The Zika virus was detected in the amniotic fluid. The woman chose to abort the fetus.

In another case, a woman who had lived in Brazil gave birth to an infant with severe microcephaly. The CDC did not release details on where the baby was born. In January, a CDC spokesman confirmed that a U.S. woman who had lived in Brazil gave birth to a microcephalic baby in Hawaii.

“It’s more evidence to me that this association is continuing to look stronger and stronger,” said Dr. Richard Beigi, president of The Infectious Diseases Society for Obstetrics and Gynecology, who had seen the reports.

“We want to be cautious because it’s a small group of women, but from what I saw, it is suggestive that the effects look to be more severe in the early part of pregnancy,” said Beigi, an obstetrician at the University of Pittsburgh Medical Center.

The CDC is also investigating another 10 cases of Zika infection in pregnant travelers. On Jan. 15, the CDC issued an advisory telling pregnant women to consider postponing travel to areas with active transmission of Zika virus.

On the conference call, the CDC said it has developed a diagnostic test that it plans to distribute to U.S. public health laboratories to speed the diagnosis of Zika, which currently takes about a week.

It is not yet clear that Zika virus actually causes microcephaly in babies, but experts say the evidence of a link is growing.

Brazil has confirmed more than 580 cases of microcephaly, and considers most of them to be related to Zika infections in the mothers. Brazil is investigating an additional 4,100 suspected cases of microcephaly.

The CDC said it has deployed 25 staff to help with the investigation. That was in addition to the 50 CDC staff members in Brazil studying dengue, a related virus.

(Reporting by Julie Steenhuysen; Editing by David Gregorio)


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Febuxostat for Gout With Renal Failure Appears Feasible

Action Points

  • Patients with gout with moderate-to-severe renal impairment treated with febuxostat (Uloric) achieved their target serum urate levels (<6 mg/dL) without worsening of renal function, in a 95-patient, placebo-controlled, proof-of-concept trial.
  • Note that > 70% of patients with gout have impairments in kidney function, and the use of urate-lowering therapies, like allopurinol, can be challenging and is a common reason for persistent hyperuricemia.

A year’s treatment with febuxostat (Uloric) helped patients with gout and moderate-to-severe renal impairment to achieve their target serum urate levels without further worsening of renal function, a proof-of-concept study found.

Among patients who were randomized to febuxostat, 30 mg twice daily, 68.8% had serum urate levels below 6 mg/dL at 12 months, as did 45.2% of those given 40 or 80 mg once daily compared with none of the patients receiving placebo (P<0.001), according to Kenneth G. Saag, MD, of the University of Alabama at Birmingham, and colleagues.

And for the serum creatinine, the 12-month change from baseline did not differ significantly from placebo, with the least squares mean difference in serum creatinine being -0.10 (95% CI -0.37 to 0.17, P=0.459) mg/dL in the 30 mg group and 0.04 (95% CI -0.23 to 0.30, P=0.789) mg/dL in the 40/80 mg group, the researchers reported in Arthritis & Rheumatology.

“The most important finding of the study is that febuxostat, when used in the standard manner (40 mg daily, increased to 80 mg daily if needed to get the serum urate below 6 mg/dL in patients without tophi) was effective in reaching the target urate in most patients with moderate-to-severe renal failure,” said Michael Pillinger, MD, of NYU Langone Medical Center in New York City, who was not involved in the study.

Gout and the Kidney

More than 70% of patients with gout have impairments in kidney function, and the use of urate-lowering therapies can be challenging in these patients and is a common reason for persistent hyperuricemia. Allopurinol can be used in patients with renal impairment, but must be carefully titrated.

“However, most clinicians either eschew use of this agent entirely in chronic kidney disease patients or do not adequately titrate it to achieve target serum uric acid,” Saag and colleagues wrote.

“Febuxostat is a slightly different story,” said Pillinger. “Its metabolism is more complex and depends much less on the kidney, so that offhand it might seem to be a better bet in patients with kidney disease. In fact, based on a relatively limited amount of data, the FDA approved febuxostat for use in patients with mild-moderate renal insufficiency (estimated glomerular filtration rate down to 30), without dose adjustment,” he told MedPage Today.

Long-term studies with both allopurinol and febuxostat have shown that maintaining the serum uric acid below the target of 6 mg/dL can help stabilize renal function among patients whose baseline impairment was in the mild-to-moderate range, but patients with more severe impairment were not included in those studies.

“Thus, the urate-lowering efficacy, safety, and impact on renal function of treatment with febuxostat have not been explored in patients with gout and severe renal impairment,” the researchers wrote.

Treatment Challenges With Renal Disease

Multiple difficulties exist in treating gout in patients with suboptimal kidney function, according to Pillinger.

One of these difficulties is “that certain medications we use to lower urate simply don’t work in these people,” he told MedPage Today. Those medications, which lower urate by acting on the kidney, include probenecid and losartan — not first-line drugs for most patients, but important second-line drugs that don’t work when the estimated glomerular filtration rate is 50 or below.

“The next difficulty is that physicians have long had safety concerns about the drugs that do work in patients with suboptimal kidney function and that constitute our typical first-line agents — the xanthine oxidase inhibitors allopurinol and febuxostat,” he said.

“We have relatively few data in using them in patients with moderate renal failure, and extremely few data in using them in patients with severe renal failure. Allopurinol has gotten a particularly bad rap in this regard, since it can cause a rare hypersensitivity syndrome that can be fatal, and some of the data (but not all by any means) suggested that the risk of this is increased in renal failure patients,” Pillinger explained.

The active metabolites of allopurinol are renally excreted, so using this drug in patients with kidney failure probably could result in overdosage unless there is dosage adjustment, but whether this contributes to the hypersensitivity is less clear, he noted.

What the Study Found

Therefore, to assess the effects of febuxostat treatment on renal function in patients whose estimated glomerular filtration rate was between 15 and 50 mL/min/1.73 m2, Saag and colleagues enrolled 95 patients whose mean age was 66 and whose mean serum urate level at baseline was 10.5 mg/dL.

Renal function was considered seriously impaired in 37.5% and moderately impaired in 62.5%. Serum creatinine was below 2 mg/dL in 38.5%, between 2 and 2.5 mg/dL in 30.2%, and above 2.5 in 31.3%.

Most were white men, and the majority had hypertension and hyperlipidemia. Almost half also had diabetes.

By 6 months, 65.6% of patients in the febuxostat 30 mg group were below the serum urate target of 6 mg/dL, as were 51.6% of those in the 40/80 mg group, but none of the patients in the placebo group (P<0.001).

As with the serum creatinine, the 12-month change from baseline in estimated glomerular filtration rate did not differ significantly versus placebo for either dosage group, with a least squares mean difference of 2.38 mL/min/1.73 m2 (95% CI -0.97 to 5.73, P=0.162) in the 30 mg group and 1.19 (95% CI -2.18 to 4.57, P=0.485) in the 40/80 mg group.

However, when 12-month glomerular filtration rate was assessed according to baseline function, a small though nonsignificant benefit was seen for the 30 mg treatment among those considered moderately impaired.

Serious adverse events were reported by 15.6%, 25%, and 21.9% of patients in the 30 mg, 40/80 mg, and placebo groups, respectively. Most of these events involved worsening of renal function, and most were considered unrelated to the treatment. One patient in the 30 mg group had an alanine transaminase elevation greater than three times the upper limit of normal.

Five patients (one in the 40/80 mg group and four the placebo group) discontinued the treatment because of renal events.

Overall, 15.6% of patients in the 30 mg group withdrew because of any adverse event, as did 9.4% of the 40/80 mg group and 28.1% of the placebo group.

There were two cardiovascular deaths, one in the 40/80 mg group and one in the placebo group. Both of these were attributed to myocardial infarctions in patients who had multiple cardiovascular comorbidities. There also was one nonfatal myocardial infarction and one nonfatal stroke in the placebo group.

“To our knowledge, this prospective study is the first of its kind to evaluate the impact of urate-lowering therapy in subjects with gout and moderate-to-severe renal impairment. Our results justify implementation of a larger clinical trial in this patient population,” Saag and colleagues stated.

Limitations of the study included the small sample and short duration, and the fact that more patients with severe renal impairment had been randomized to the placebo group, possibly introducing bias.

Implications for Treatment

“The study reinforces that for patients with moderate and particularly with severe kidney disease, febuxostat may often be our best current option — at least, it appears to be safe and effective,” Pillinger said.

Allopurinol should always be considered, according to the guidelines of the American College of Rheumatology (ACR), but many clinicians remain reluctant to use it at the required doses, he noted.

Early recommendations for allopurinol use in the context of kidney disease suggested dose adjustment that resulted in patients being undertreated. However, “more recent studies have led to a different recommendation from the ACR — essentially that allopurinol can be used in patients with kidney failure, and should not be dose adjusted to the renal function itself, but instead to a target level of serum urate less than 6 mg/dL, and that the dose titration should be done slowly and carefully,” he said.

“Nonetheless, many physicians remain concerned and are quite reluctant to push the allopurinol dose much beyond what seems to have become the community standard, 300 mg daily, in such patients,” he added.

Furthermore, “we should note that although the ACR recommends using allopurinol if needed in patients with renal failure, there is no FDA approval for this usage and there are relatively few data on allopurinol safety beyond the 300 mg dose up to the FDA approved maximum of 800 mg daily,” Pillinger pointed out.

However, the potential benefits of febuxostat need to be weighed against its significantly higher cost compared with allopurinol.

Nonetheless, “given that gout patients with moderate-to-severe kidney disease commonly have worse gout and higher serum urate than those who have no or only mild kidney disease, and given the importance of urate lowering in these particular gout patients, Saag’s data supporting the use of febuxostat in such patients are both helpful and reassuring,” Pillinger concluded.

The study was funded by Takeda.

The authors disclosed financial relationships with Takeda, Ardea, Crealta, Merck, AstraZeneca, , BioCryst, CymaBay, and Regeneron. Three are employees of Takeda.

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Are Women the Key to Unlocking Alzheimer's?

Are Women the Key to Unlocking Alzheimer’s?

Latest Alzheimers News

By Brenda Goodman, MA
WebMD Health News

Reviewed by Michael W. Smith, MD

Feb. 25, 2016 — Alzheimer’s disease hit the Schafferman siblings hard. Audrey was the first. She was diagnosed at age 65, about 3 years before her younger brother Gene. Audrey died in 2007. Gene would follow 5 years later.

Gene’s daughter, Donna Shore, recalls that the disease looked a lot different in her father than it did in her aunt.

“It seemed like Aunt Audrey went a lot faster than my father did,” says Shore, 58, of Littlestown, PA. She took care of Gene. He was so spry and vibrant that he was able to continue his favorite hobby — dancing — until just a year before his death. The nursing home staff called him “Gene, Gene, the Dancing Machine.”

Shore is especially grateful that her dad never forgot who she was, calling her by her nickname, Sparky, right up until his death.

Audrey’s loss, by contrast, seemed crueler. The unfailingly kind and loving mother and grandmother became paranoid. She accused her daughters of stealing her glasses and her social security checks — when she could remember who her children were.

“I would have to go to the bathroom and cry, because I wasn’t used to my mother talking to me that way,” says Robin Broyles, 62, of Baltimore, MD.

When Audrey began sneaking out of the house and started confusing a closet for the bathroom, the family made the wrenching decision to put her in a nursing home. She died 18 months later.

Though the experience of the disease is highly individual, researchers think what happened in the Schafferman family may be part of a larger pattern, one that puts women in the epicenter of the Alzheimer’s epidemic.

Studies show that by age 65, women have about twice the risk of getting the condition. About 1 in 6 women will get Alzheimer’s after age 65, compared to about 1 in 11 men. About two-thirds of people in the U.S. with the disease are women.

Not only are women more likely to get Alzheimer’s than men, but recent studies suggest the disease does its work more swiftly in women, causing them to decline faster — and farther — than men do, at least in the beginning.

Alzheimer’s in Women: What’s the Risk?

It’s long been thought that the main reason for women’s increased risk was age. Women simply live longer than men do, and Alzheimer’s is a disease of aging. The longer you live, the more likely you are to get it.

But researchers say age alone doesn’t entirely explain the extra risk.

In a recent study, researchers at Duke University looked back at the medical histories — documented by written tests and brain scans — of almost 400 women and men enrolled in a long-running study of brain function. All the study participants were showing early changes in memory and thinking that often, but not always, progress to Alzheimer’s disease.

What the researchers found was striking. Women with early memory changes declined about twice as fast as men did, and they ended up worse off, too.

“Our findings suggest that men and women at risk for Alzheimer’s may be having two very different experiences,” says Katherine Lin, a senior at Duke and lead researcher of the study.

Lin says it’s possible there’s something unique to women’s biology or life experiences that makes them more vulnerable to the disease than men.

“Uncovering those factors should be a high priority for future research,” she says.

The Alzheimer’s Association, a national nonprofit advocacy group, agrees.

In May 2015, the association launched the Women’s Alzheimer’s Research Initiative, or WARI, which will focus on funding studies to tease out what those as-yet-unknown risks may be.

They plan to announce the first round of study grants this spring. It won’t be an easy task, as they have to pick just six to eight projects out of more than 120 applications from 17 countries. Each project will get $250,000 in research funding.

“It’s not just that women are living to be older. There’s something else going on in terms of the biology, the environment, for women compared to men that may make them at greater risk, or if they have some symptoms, change the progression,” says Kristine Yaffe, MD, a professor of psychiatry, neurology and epidemiology at the University of California, San Francisco.

Roberta Diaz Brinton, PhD, is a neuroscientist at the University of Southern California and a leading voice for studying the disease in women. She finds it puzzling that most Alzheimer’s research has been gender-blind, when women are in the majority of people with the disease.

“With AIDS, the AIDS research community did not look across the entire spectrum of everyone who was having sexual intercourse,” Brinton says. Instead, researchers focused on gay men having unprotected sex. “Focus on the people who have the biology,” she says.

New Clues in Women

One of the biggest risk factors for Alzheimer’s disease — in men or women — is a gene that carries instructions for a protein called apolipoprotein E, which ferries cholesterol and beta-amyloid in and out of cells. Beta-amyloid are sticky fragments of proteins that build up in the brains of people who have Alzheimer’s disease.

Inheriting just one copy of the APOE4 gene results in a two to four times greater risk of Alzheimer’s disease. Inheriting two copies raises the risk nearly 15 times.

That higher risk doesn’t appear to be shared equally by men and women. A 2014 study of more than 8,000 people found that APOE4 had a stronger effect in women. For healthy men, having one copy of the gene only slightly increased the risk of memory problems compared to other men. For women, a single copy nearly doubled their risk of the brain changes and eventual Alzheimer’s compared to other women.

Other studies have questioned whether lifestyle factors and experiences particular to women may be playing a role. Women are more likely than men to get depression, which increases the risk for Alzheimer’s disease.

Education, it turns out, has a powerful connection with brain health. The more education a person has, the lower their risk for getting Alzheimer’s, leading researchers to wonder whether knowledge and learning may build the brain up, almost like a muscle, making it harder for the disease to wear it away. Historically, women haven’t been as well-educated as men.

Exercise protects the brain from Alzheimer’s, and studies have shown that at least in the past, women haven’t been as physically active over the course of their lives as men are.

Even surgery is riskier for women.

A little confusion can be normal after general anesthesia, and most people recover from the experience with no lasting problems. But some people never quite recover, and older adults are known to be particularly vulnerable to long-term effects after surgery.

Researchers at Oregon Health & Science University found that men and women who’d been put to sleep for surgery did worse on tests of thinking and memory compared to similar adults who didn’t have surgery. But the declines were bigger and more rapid for women. Women also had more brain shrinkage on MRI scans after anesthesia than men did.

The more procedures a person had, the bigger the brain problems after surgery. And it didn’t seem to matter what anesthesia drug doctors used.

Hormones: Help or Harm?

Another major puzzle about Alzheimer’s has been the role of hormones, and whether hormone replacement therapy hurts or helps a woman’s memory as she ages.

Estrogen plays a large role in brain health. It boosts levels of a chemical that helps nerve cells talk to each other.

It also plays a role in how the brain uses the sugar glucose, its main fuel.

During the period just before menopause, when estrogen levels naturally start to fall, many women complain of problems with foggy thinking and scattered attention.

So doctors wondered whether giving hormones back to women might keep their memory sharp.

But in a large, government-funded study, use of estrogen and progesterone after menopause was found to increase the risk for Alzheimer’s and other kinds of dementia. In taking a closer look at the results, though, researchers saw that most of the women in the study were getting hormones when they were well past menopause, long after the body had stopped making them naturally.

That made doctors wonder if giving the hormones closer to the time when the body had stopped making them naturally, around age 50 instead of 65, might make a difference, an idea called “the timing hypothesis.”

Several studies have now checked out that theory and come up empty.

“I’m pretty confident that the data suggest no effect. No evidence of benefit or harm. If a woman is thinking about hormone therapy for whatever reason, there are a lot of things to consider in that decision, but whether or not it’s going to make someone a little smarter or a little duller, I don’t think there’s much of an effect there,” says Victor Henderson, MD, a professor of health research and policy and neurology at Stanford.

But researchers haven’t given up on the hope that estrogen might help protect some women’s brains.

“Now, I think, the question has become more refined over time. Is there even a subset of individuals we should focus on in the critical-window period, and if so, who would that subset be?” says Sarah Janicki, MD, a neurologist at Columbia University.

Personalized medicine may make it possible. Janicki led a study that looked at the genes that tell the body how to make estrogen receptors. Estrogen receptors are docking sites on cells all over the body — including cells in the brain — that recognize and respond to estrogen. She found that four gene changes to those receptors were linked to a nearly doubled risk of getting Alzheimer’s.

She says figuring out why could help target women who might benefit or be harmed from hormone therapy. And because men also have estrogen receptors on their brain cells, her research could eventually help them, too.

Menopause isn’t the only time in a woman’s life when her brain goes through big changes. Pregnancy also has an impact.

During pregnancy, a woman’s brain and her baby’s get bombarded with a chemical called allopregnanolone, a brain hormone. It spurs the growth of the baby’s new brain cells and protects them from harm. In Mom, researchers think it may reduce stress.

In mice bred to have a model of Alzheimer’s disease, allopregnanolone sparked the growth of new brain cells and bulked up the brain’s white matter — the connections that help brain cells communicate. It also reduced the amount of beta-amyloid — those sticky protein pieces — that clog the brains of Alzheimer’s patients. And it reversed the memory and thinking changes linked to the disease, so that Alzheimer’s mice treated with allopregnanolone performed the same on memory and thinking tests as normal mice.

It’s important to note that mice aren’t people. Drugs that look promising in animals often do little or nothing for humans.

But Brinton thinks allopregnanolone has promise. She’s testing the drug in people to determine the best dose and to try to get some clues about which patients could benefit from the medication. She won’t know if it helps their memory or thinking for 2 to 3 more years, she says.

Another drug that has shown promise, at least for some patients, is leuprolide, or Lupron. It’s already FDA-approved to treat endometriosis and shrink uterine fibroids.

In one study of more than 100 women with Alzheimer’s, those who took a weekly injection of the drug, along with the Alzheimer’s medication Aricept, saw almost no changes in their memory over the course of a year compared to women who took Aricept alone.

Lupron helps lower levels of follicle-stimulating hormone and luteinizing hormone, chemical signals that surge during menopause and stay high.

Craig Atwood, PhD, an associate professor of geriatrics at the University of Wisconsin School of Medicine, says the treatment helps the brain because it brings haywire hormones back into balance.

Atwood says they are looking at whether the elevated hormones are driving Alzheimer’s disease. Suppressing them may prevent women from aging as rapidly.

But he admits that’s just a guess. Right now, they really don’t understand how the drug might be working or what it might be doing in combination with Aricept.

Atwood and his co-researchers hope to raise more money for a larger clinical trial, one that would test the treatment in men and women.

Families Wait, and Hope

While science churns slowly on, Audrey Schafferman’s family is still struggling to cope without her.

When Audrey was 17, she married a man named Dennis Rose. After each child and grandchild was born, Audrey would proudly say, “It looks like the Roses!”

After Audrey’s death in 2007, Jaime Stone and some of her other grandchildren formed a team to raise money for research into the disease. They walk under the name Audrey’s Little Roses in the annual Walk to End Alzheimer’s, sponsored by the Alzheimer’s Association.

It’s the best way they know to honor the matriarch who took so much with her when she left them.

“We used to be a really, really, really close family. But here in the last couple of years, nobody really wants to get together,” Stone says.

Her grandmother, she says, was the glue that held them all together. “It’s been difficult.”

SOURCES: Donna Shore, Alzheimer’s caregiver, Littlestown, PA. Robin Broyles, Alzheimer’s caregiver, Baltimore, MD. Katherine Lin, senior, Duke University, Chapel Hill, North Carolina. Roberta Diaz Brinton, PhD, Professor, Pharmacology and Pharmaceutical Sciences, Biomedical Engineering and Neurology, University of Southern California, Los Angeles, CA. Mary Sano, PhD, director, Alzheimer’s Disease Research, The Mount Sinai School of Medicine, New York, NY. Kristine Yaffe, MD, professor, departments of psychiatry, neurology and epidemiology, the University of California at Berkeley, Berkeley, CA. Katie Schenning, MD, anesthesiologist, Oregon Health and Science University, Portland, OR.Sarah Janicki, MD, neurologist, Columbia University, New York, N.Y.Craig Atwood, PhD, associate professor, geriatrics, The University of Wisconsin School of Medicine, Madison, WI.Victor Henderson, MD, professor, health research and policy and neurology, Stanford University, Stanford, CA. Jaime Stone, granddaughter, Audrey Schafferman Rose. Annals of Neurology, April 2014. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, September 2015. Alzheimer’s Association: “2014 Alzheimer’s Disease Facts and Figures. “News briefing, Alzheimer’s Association International Conference 2015.

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Alzheimer's Risk: Do You Want to Know?

Alzheimer’s Risk: Do You Want to Know?

Latest Alzheimers News

By Matt McMillen
WebMD Health News

Reviewed by Arefa Cassoobhoy, MD, MPH

Feb. 25, 2016 — If a test could tell whether you’ll get Alzheimer’s disease someday, would you want to know? And if so, what would you do with that knowledge?

These questions are becoming more and more important as researchers close in on tools to predict your risk of Alzheimer’s disease decades before symptoms start to appear.

“Primary care physicians, in the disease’s early stages, [eventually] could be able to say, ‘It looks like there’s a problem here’ through a blood test, a saliva test, or by looking at the retina,” says Dean Hartley, PhD, director of science initiatives for the Alzheimer’s Association. “But there’s no medical test now. It’s all in the research stage.”

For now, only genetic tests are available to the general public. They can spot genes linked to a higher risk of Alzheimer’s, such as the ApoE4 gene. But genetic tests aren’t conclusive. Not everyone whose test result says they have ApoE4 will get Alzheimer’s, and many people who don’t have that gene will get the disease.

And if you have the gene, there isn’t much you can do yet, aside from making lifestyle changes that may be preventive. “You can get the ApoE4 test at your doctor’s office, but I and many of my colleagues rarely offer it, because we don’t have any treatments to offer if we determine that patients are at higher risk,” says Alzheimer’s researcher Liana Apostolova, MD, a professor at the Indiana University School of Medicine.

Also, knowing your risk could come with a price. Seven years ago, Jamie Tyrone learned unexpectedly that she had two copies of the ApoE4 gene.

“I went into a deep, dark hole,” says Tyrone, 55, a former nurse who lives in San Diego. “This information was very anxiety-provoking, to the point that I was diagnosed with PTSD [post-traumatic stress disorder]. Knowing has done me harm.”

Tyrone says Alzheimer’s was not on her radar when she was tested for a variety of genetic disorders as part of a research study. Being unprepared for the news, she says, made her anxiety worse.

Eventually she learned to cope. She started to take better care of herself, exercising and improving her diet, meditating and doing brain-twisting puzzles purported to strengthen memory and focus. And she became involved with research into the disease. She founded B.A.B.E.S., Beating Alzheimer’s By Embracing Science, a non-profit that supports research into the disease and encourages people to get involved.

Tyrone wants others to learn from her experience.

“I’m choosing to heal by talking about it,” she says. “I don’t want people to go through what I went through.”

New Ways to Detect Alzheimer’s Disease

The biggest advance toward the early prediction of Alzheimer’s, Hartley says, is using PET scans to show the buildup of beta amyloid plaques in the brain. The plaques are a risk factor for the disease, and in the past they could be seen only during an autopsy.

“This is an opportunity to see into the live brain,” Hartley says.

The FDA has approved PET amyloid imaging for use in some clinical trials and to help diagnose dementia patients, but not to predict the development of the disease — at least not yet.

“PET imaging with amyloid will be the first way of approaching prediction,” Apostolova says. MRI will also be useful, she says, as will PET imaging for tau proteins, another sign of disease.

But, she continues, amyloid PET scans are expensive, not readily available, and they expose patients to radiation.

“What if there’s another way to get at the answer of who’s at risk?” she asks.

Research Apostolova led while at UCLA resulted in a simple blood test that picks up biomarkers — or proteins in the blood — linked to Alzheimer’s. Along with other tests, it one day may help predict the disease. She published her early findings in January in the journal Neurology.

Researchers are studying several other new tests:

  • A saliva test that identifies biomarkers linked to Alzheimer’s disease.
  • A combination of cognitive tests, MRI scans, and analysis of proteins found in cerebrospinal fluid — fluid in the brain and spinal cord that can predict mild cognitive impairment, or thinking problems, 5 years before symptoms become apparent.
  • Measurements of the protein neurogranin, a potential Alzheimer’s biomarker found in fluid in the brain and spinal cord.
  • Tests that uncover the deterioration of your sense of smell may indicate Alzheimer’s.
  • Eye exams that can measure beta amyloid buildup.

All of these tests remain experimental, and their effectiveness remains to be seen.

“Saliva tests, blood tests, and things like that are not ready for prime time,” Hartley says.

Knowing Your Risk

If you do learn your risk of Alzheimer’s — through a genetic test or, eventually, through one of these still-experimental tests — what can you do with that knowledge? And how would it affect you? After all, with no viable treatments available to slow, stop, or prevent the disease — only drugs that may improve symptoms in some people for a short time — there’s little doctors can offer you.

“Some people would want to know so they can plan things out, such as long-term care insurance and end-of-life decisions, while others would not want to know,” says David Salmon, PhD, of the Shiley-Marcos Alzheimer’s Disease Research Center at the University of California, San Diego. “It’s a personal decision. It’s hard to say what the best advice would be.”

Salmon’s research suggests that knowing you’re at risk can have bad consequences. You’re more likely to rate your memory worse and do worse on a memory test than someone with the same risk who is unaware.

“We don’t think it’s depression, but we didn’t measure anxiety and stress, so we don’t know if the disclosure increased anxiety and that it’s the anxiety that causes you to have memory problems,” Salmon says.

But other research suggests that knowing your genetic risk does not up your chances of depression, anxiety, or distress. Jason Karlawish, MD, an Alzheimer’s expert and medical ethicist at the University of Pennsylvania, has studied middle-age adults with a family history of Alzheimer’s.

If people get their mood and well-being assessed before they get tested, “they have minimal problems with mood and well-being after learning the results,” Karlawish says. “We don’t have data from persons who are older and plausibly closer in age of onset to AD.”

Karlawish is involved in a study of an experimental Alzheimer’s drug known as solanezumab. The drug, made by Eli Lilly, targets amyloid plaques and may delay the onset of cognitive decline. It is now being tested on people who don’t have Alzheimer’s symptoms but whose PET scans have shown the presence of such plaques, a potential early warning sign of the disease.

It’s among several meds that may prevent or slow Alzheimer’s from getting worse that are being studied in people long before they show symptoms.

Karlawish’s previous research suggests that that knowledge may motivate people to change their lifestyles. That’s what Tyrone eventually began to do. She has improved her diet and her exercise habits, she’s at work on a book about her experiences, and she’s become involved in Alzheimer’s research, such as studies into new medication. That’s something she highly recommends — as does Karlawish — for people who know they’re at risk.

“Yes, it’s partially selfish, because you’re getting something as well as giving something,” she says. “You’re at the forefront of cutting-edge research.”

But if you don’t yet know? “I would ask them, why do you really want to know this information? And can you make changes without knowing that information?” Tyrone asks. “It may be anxiety provoking. Is it really healthy to know this information or is not healthy? What are you going to do with it?”

SOURCES: Liana Apostolova, MD, Barbara and Peer Baekgaard Professor in Alzheimer’s Disease Research, Indiana University, Bloomington, IN. Dean Hartley, PhD, director of science initiatives, Alzheimer’s Association, Chicago, IL. Jason Karlawish, MD, professor of medicine, medical ethics & health policy, University of Pennsylvania, Philadelphia, PA. David Salmon, PhD, professor in residence, UC San Diego School of Medicine, San Diego, CA. Jamie Tyrone, CEO and founder of Beating Alzheimer’s by Embracing Science, San Diego, CA.

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Obesity linked to 'worse memory'

Obesity linked to ‘worse memory’

By James Gallagher
Health editor, BBC News website
  • 26 February 2016
  • From the section Health

Obese childImage copyright
Thinkstock

People who are obese have a worse memory than their thinner friends, a small study shows.

Tests on 50 people showed being overweight was linked to worse “episodic memory” or the ability to remember past experiences.

The study in the Quarterly Journal of Experimental Psychology argues that a less vivid memory of recent meals may lead to overeating.

However, other aspects of memory – such as general knowledge – were unaffected.

Tests on rats have previously shown that with burgeoning waistlines come poorer performances in memory tests, but the evidence in humans has been mixed.

The latest experiments looked at episodic memory – the video tape in your mind – that remembers the smell of a cup of coffee or the feel of holding someone’s hand.

Fifty people with a Body Mass Index (BMI) ranging from 18 (healthy) to 51 (very obese) took part in a memory test – a bit like doing a treasure hunt on your own.

They had to “hide” objects at different times and on different scenes displayed on a computer screen.

They were later asked to recall what they had hidden, when and where.

The results showed obese people’s scores were 15% lower than thinner people.

Image copyright
Thinkstock

Image caption

What did I have for tea?

Dr Lucy Cheke, from the University of Cambridge, told the BBC News website: “The suggestion we’re making is that a higher BMI is having some reduction on the vividness of memory, but they’re not drawing blanks and having amnesia.

“But if they have a less strong memory of a recent meal, with a less strong impact in the mind, then they may have less ability to regulate how much they eat later on.”

Hunger hormones play a huge role in how much we eat, but it is already recognised that our minds have a key role too.

People watching TV while they have their dinner have been shown to eat more or feel hungrier sooner.

And those with amnesia will have repeated meals in a short period of time.

Dr Cheke concluded: “It is too early to talk in terms of advice, but we are certainly beginning to observe the mechanisms that obesity perpetuates itself.

“Concentrating on your food has been a message for a long time, but that may be a bit harder if you’re overweight.

“Hopefully knowing what’s going on will help us to develop ways of helping people.”

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Neurological patient care 'lacking'

Neurological care in England criticised by MPs’ report

  • 26 February 2016
  • From the section Health

Image of brain in skullImage copyright
Science Photo Library

Health services for people with neurological conditions in England are not good enough, says a report from a committee of MPs.

It criticises poorly co-ordinated local services, patchy hospital care and long delays in diagnosing conditions like Parkinson’s disease and epilepsy.

More than four million people have a neurological condition but few have a care plan, the report says.

The Department of Health said it would consider the recommendations.

The MPs say their report should be taken as a wake-up call, to improve services for what can be devastating or even fatal conditions.

They describe the impact of disparities, for example, in epilepsy care: in south-west Lincolnshire nearly nine out of 10 patients were seizure-free for 12 months, while in Hull and north Manchester it was fewer than five out of 10.

The report recommends that NHS England find a way of tackling the problem of variation in services and explain how it will offer everyone with a long-term condition a personalised care plan.

It also urges NHS England to make better use of the 650 consultant neurologists in England, as well as other specialist nurses, to improve access to care for patients.

Meg Hiller MP, chair of the Public Accounts Committee, said: “Strong, consistent leadership and accountability are crucial if patients are to see sustained improvements to services and more effective use of the resources available.”

She added: “This must start with improvements in planning, co-ordination and the use of data and we will be holding the Department and NHS England to account for this in the months and indeed years ahead.”

Although some progress has been made since a previous report in 2012 made recommendations aimed at improving neurological services in England, the report said changes have “not yet led to improvements in services and outcomes for patients”.

The committee says it is concerned that neurological conditions are “not a priority” for the Department of Health and NHS England.

Arlene Wilkie, chief executive of the Neurological Alliance, said neurology services need urgent attention.

‘Latest technology’

“We urge NHS England and the Department of Health to act quickly to ensure that everyone living with a neurological condition receives a high-quality, accessible service.”

She also said she was pleased that the committee agreed that cutting the role of national clinical director for adult neurology would be a mistake.

A Department of Health spokesman said it was committed to giving patients with neurological conditions the very best care, regardless of where they lived.

“We spend over £3bn every year on neurological services, we have set up a new children’s national epilepsy service and we are making sure patients with progressive neurological diseases can access the latest technology to help them communicate.

“But we know that more can be done and, along with NHS England, we will consider these recommendations and respond in due course.”

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Swedish industry wants European medicines agency if UK quits EU


Sweden should become the new home of the European Medicines Agency (EMA) if Britons vote to leave the European Union in a June referendum, according to the head of the Swedish pharmaceutical association.

The agency, which approves medicines for all EU countries, has been based in London since it started in 1995. However, a so-called Brexit would leave Europe’s equivalent of the U.S. Food and Drug Administration outside the bloc and could force a move.

Shifting to Sweden would make sense, given the country’s scientific strength and the leading role Swedish experts already play in European drug regulation, said Anders Blanck, director general of the LIF group representing research-based drugmakers.

“If the referendum in the UK results in a ‘no’ to the EU, the government should immediately launch an intensive lobbying campaign to make Sweden the new host country for the EMA,” Blanck wrote in the latest newsletter of the LIF trade group.

“My advice is to already now begin planning for how such lobbying could be done. We in the pharmaceutical industry would gladly help with full force … an EMA in Sweden would be a major boost for the entire life science field.”

Sweden’s claims to eminence in the pharmaceutical and healthcare arena include the fact that it is home to the Karolinska Institute, which awards the Nobel prize in medicine.

It has also seen significant investment recently by multinational groups such as AstraZeneca and GE Healthcare.

The EMA and the European Commission have both declined to comment on what would happen to the agency in the event of a Brexit, but Blanck said the medicines watchdog and its 600 staff would have no choice but to leave London.

Many pharmaceutical executives also see a move as inevitable and they fear that a British “Out” vote would disrupt healthcare regulation in the world’s biggest trading bloc.

Concerns about the EMA contributed to a decision by the European Federation of Pharmaceutical Industries and Associations this week to warn against Britain leaving the EU.

(Editing by Mark Potter)


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Teen mental health risk increases with food insecurity


(Reuters Health) – Adolescents living in households with limited or uncertain availability of nutritious food are more than twice as likely as other kids to have emotional problems or conduct problems, according to a new study.

“These findings add to our growing understanding of food insecurity and its implications, and demonstrate that food insecurity is an independent risk factor for mental health problems among adolescents,” said lead author Dr. Elizabeth Poole-Di Salvo of Weill Cornell Medical Center in New York.

“According to the most recent data, food insecurity affects nearly 20 percent of U.S. households with children under the age of 18 years,” Poole-Di Salvo told Reuters Health by email.

The researchers used data from a 2007 study of about 8,600 kids ages 12 to 16 years. In most cases a parent, usually the teen’s mother, was interviewed by phone.

The parents answered questions about economically-based difficulties in meeting food needs over the past 12 months and completed a 25-item measure of their child’s emotional symptoms conduct problems, hyperactivity, peer problems and social fit.

According to the results in Academic Pediatrics, 10 percent of kids in the sample lived in food insecure households, and 11 percent had parent-reported problems with mental health.

Factors like the teens’ grade level, poverty status, household income below the poverty threshold, unmarried parents, level of parent education, poor parent health, parent depression, unsafe school and unsafe neighborhood were all associated with both food insecurity and mental health risk.

But after adjusting for these and other factors, teens with food insecurity were 2.3 times as likely to have parent-reported mental health problems compared to those without food insecurity.

Almost 29 percent of teens with food insecurity had mental health problems, researchers found, compared to 9 percent of other kids. This pattern held across subtypes of mental health issues – for instance, more than 26 percent of kids with food insecurity had conduct problems, compared to more than 11 percent of other kids. Similarly, 22 percent of food insecure kids had hyperactivity compared to 11 percent of other kids, and 20 percent of food insecure kids had peer problems compared to less than 9 percent of other kids.

Having access to free or reduced-price school lunch programs did not change these results, the researchers note.

“While we cannot infer causality from this study, we suspect that exposure to food insecurity during adolescence, a period of rapid brain growth and development, may lead to suboptimal nutrition as well as increased psychological stress for the family and adolescent, and may adversely impact adolescent mental health,” Poole-Di Salvo said.

Teens dealing with food insecurity may be experiencing stress from the uncertainty of not knowing where their next meal is coming from, from being hungry or from deficiencies in specific nutrients, added senior study author Dr. Ruth E. K. Stein of Albert Einstein College of Medicine and The Children’s Hospital at Montefiore in Bronx, New York.

“We cannot definitively rule out that mental health problems also cause household food insecurity, but that seems less likely, especially since we controlled for stressful life events and maternal mental health,” Stein told Reuters Health by email.

Adults and children alike feel health-related results from the most severe economic stress, said Christian Gregory, an economist specializing in diet, safety and health economics at the U.S. Department of Agriculture Economic Research Service who was not part of the new study.

“As someone who really knows well the literature and research about the Supplemental Nutrition Assistance Program (SNAP), our primary policy intervention against food insecurity, giving people access to food or resources to food is really important” Gregory told Reuters Health by phone.

“Early identification of risk factors for both food insecurity and mental health problems are critical, and pediatricians can be instrumental in connecting families to available resources in their communities,” Poole-Di Salvo said.

SOURCE: bit.ly/1Q57USl Academic Pediatrics, Jan.-Feb. 2016.


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