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Children born to women who take folic acid in late pregnancy are at increased risk for asthma, Australian researchers say.

The University of Adelaide study included more than 500 women whose diet and supplements were assessed during pregnancy. The women’s children were checked for asthma at age 3.5 years and at 5.5 years. Asthma was found in 11.6 percent of children at 3.5 years and in 11.8 percent of children at 5.5 years.

“In our study, supplemental folic acid in late pregnancy was associated with an increased risk of asthma in children, but there was no evidence to suggest any adverse effects if supplements were taken in early pregnancy,” Michael Davies, an associate professor at the university’s Robinson Institute, said in a news release from the school.

The researchers also said they found no association between asthma and dietary folate, which is found in green, leafy vegetables, certain fruits and nuts.

Pregnant women are advised to take a supplemental dose of 400 micrograms of folic acid per day in the month before and during the first trimester of pregnancy to reduce the risk of neural tube birth defects.

“Our study supports these guidelines, as we found no increased risk of asthma if folic acid supplements were taken in pre- or early pregnancy,” Davies said. “However, these guidelines may need to be expanded to include recommendations about avoiding use of high-dose supplemental folic acid in late pregnancy.”

PUVA Photochemotherapy
“PUVA” is a term applied to a group of therapeutic techniques that use psoralens – a group of photosensitizing compounds – to sensitize cells to the effects of UVA light. Psoralens are available as oral or topical medications that patients must use before being exposed to UVA light, or in a bath formula that patients soak in prior to UVA exposure (this form of PUVA is not as widely used). Two large, multicenter studies have demonstrated the efficacy of PUVA in the treatment of psoriasis, and Dr. Pariser noted that PUVA treatment often leads to the clearing of psoriasis typically within 24 treatments with remissions lasting between three and six months.

“The introduction of PUVA for the treatment of psoriasis was a major advance for patients with severe psoriasis, as it offered them an outpatient therapy rather than other treatments that required hospitalization,” said Dr. Pariser. “However, studies show that high cumulative exposure to oral PUVA is associated with an increase in the risk of non-melanoma skin cancer, particularly squamous cell carcinoma, which is why dermatologists often reserve PUVA for psoriasis patients who have not responded favorably to other treatments.”

In an effort to minimize the total dosage of PUVA, dermatologists often combine PUVA treatments with other therapies (such as retinoids) or in rotation with other treatments. In addition to the increased risk of skin cancer and skin aging with long-term use, other common side effects of PUVA include redness, itching, dryness, irregular pigmentation, nausea and vomiting. PUVA also is not recommended for use in children or in patients with certain medical conditions, which is why dermatologists closely evaluate patients before PUVA is considered as a treatment option for psoriasis.

Targeted Phototherapy (Excimer Laser)
With the introduction of the 308 nm monochromatic xenon-chloride laser for psoriasis in 1997, the use of phototherapy to treat localized lesions became more practical and more widely available. Excimer lasers selectively target affected lesions without treating unaffected skin – therefore minimizing the potential risk of exposing uninvolved skin to UV radiation. Another advantage is that because only the affected areas are treated, higher doses can be administered in fewer treatment sessions.

Although numerous studies have demonstrated that treatment with the excimer laser can clear psoriasis, there is limited information about the duration of remission and the recommended dosage and scheduling of therapy. Dr. Pariser explained that most patients experience long-term improvement following treatment with the excimer laser, and currently the dose of energy delivered is guided by the patients’ skin type and thickness of the psoriasis plaques.

“Typically, patients receive treatment with the excimer laser two to three times a week, with a minimum of 48 hours between treatments,” said Dr. Pariser. “Side effects are minimal and are limited to the treatment area, with redness, burning and darkening of the skin being the most common. There have been cases where blistering has occurred with the use of higher doses of energy, but for the most part treatments are well-tolerated – even in children.”

Patient Considerations for UV Light Therapy
Like all treatments for psoriasis, some patients make better candidates for UV light therapy than others. Dr. Pariser added that before UV light therapy is considered, all patients must have a complete history and physical examination and be made aware of the potential long-term risks of this treatment.

“Patients with a known history of lupus (a chronic inflammatory disease) or xeroderma pigmentosum (a genetic disease characterized by extraordinary sensitivity to sunlight) should not be treated with phototherapy,” said Dr. Pariser. “In addition, patients with atypical nevi, multiple non-melanoma skin cancers, multiple risk factors for melanoma, a history of melanoma, a history of photosensitivity disorder, or who are taking photosensitizing medications or are immunosuppressed as a result of organ transplantation should be screened carefully before starting UV light therapy.”

Recommended dosing guidelines for both BB-UVB and NB-UVB vary by skin type, with light-skinned patients receiving much smaller initial and incremental doses of UV light than darker-skinned patients.

“For the right patients and with close monitoring by a dermatologist, UV light therapy can be a safe and effective treatment for psoriasis patients who might not have responded well to other traditional therapies or for various reasons might not be good candidates for systemic medications,” said Dr. Pariser. “Dermatologists can recommend the best treatment plan for patients with mild to severe psoriasis, helping them improve their condition and overall quality of life.”

Types of UVB Therapy
One type of phototherapy that has been used successfully to treat psoriasis for more than 75 years is broadband (BB)-UVB therapy. As its name implies, BB-UVB is used to treat a large area of psoriasis by exposing the affected skin to a specific wavelength of UVB light.

A newer form of UVB therapy introduced in the United States in the 1990s that is commonly used to treat psoriasis is narrowband (NB)-UVB therapy. With this therapy, narrower bands of UVB wavelengths are administered to the affected skin, and studies have shown NB-UVB therapy to be more effective in clearing psoriasis than BB-UVB.

“Studies have shown that psoriasis patients treated with NB-UVB therapy had better results than those treated with BB-UVB, including more rapid clearing and better remission rates,” said Dr. Pariser. “While both therapies are generally well-tolerated, patients must be educated as to the potential long-term side effects of UVB – including an increased risk of skin cancer and premature aging – and protect their eyes by using goggles to decrease the risk of UVB-related cataracts that could form from prolonged exposure.”

Other minor side effects of BB-UVB therapy include redness, itching, burning and stinging. Burning also is a possible side effect of NB-UVB, and Dr. Pariser noted that, although not commonly reported, there have been instances of skin blistering after exposure to NB-UVB. In addition, neither BB-UVB nor NB-UVB therapy are known to cause birth defects or disrupt a pregnancy and can be prescribed to women during pregnancy or while attempting to conceive.

Studies examining the use of and long-term safety of UVB therapy in children are limited, but Dr. Pariser explained that this therapy could be considered as a second option in selected children whose psoriasis does not respond to topical therapy as long as the light therapy is closely monitored by a dermatologist.

In some cases, UVB therapy is effective when used by itself to clear psoriasis, but dermatologists commonly use this therapy in combination with topical or systemic medications. Dr. Pariser emphasized that the decision to use combination therapy should be made on a case-by-case basis and should be tailored to meet individual patients’ needs.

Based on an extensive review of the highest-quality scientific literature on psoriasis and the opinion of recognized psoriasis experts, the American Academy of Dermatology (Academy) has released new guidelines of care for the management and treatment of psoriasis with ultraviolet (UV) light therapy, also known as phototherapy. Recommendations for the use of the most common forms of UV light therapy, as stand-alone treatments or in conjunction with other therapies, were outlined, including patient considerations.

Published online in the Journal of the American Academy of Dermatology, this is the Academy’s fifth of six sections of the guidelines of care for psoriasis, with four previously published sections focusing on general recommendations for the treatment of psoriasis and psoriatic arthritis, as well as the use of biologics, topical and systemic therapies.

“Although treatment options for psoriasis have expanded considerably in recent years, UV light therapy remains an important treatment option for many psoriasis patients,” said dermatologist David M. Pariser, MD, FAAD, president of the Academy. “Over the years, phototherapy has been shown to effectively clear psoriasis, and it is a cost-effective therapy that generally does not suppress the body’s immune response like traditional and biologic systemic therapies. However, because this therapy delivers UV light to the skin (a known carcinogen), patients need to be closely monitored by their dermatologists for the potential risk of skin cancer.”

Psoriasis is a chronic skin condition that usually develops before age 35 and is characterized by thick, red, scaly patches that itch and bleed. Nearly 7 million Americans are living with this skin condition. Both genetic and environmental factors contribute to causing the disease. Research has determined that psoriasis is linked to multiple genes, but it is not completely understood how it is inherited. However, there are at least nine locations on different chromosomes that are associated with psoriasis but researchers have not identified the specific genes that are linked to the genetic transmission of the disease.

Elders who work crossword puzzles, play cards, partake in artistic and organizational activities, and attend movie or theater productions may halve their risk for dementia, report researchers from France.

Over 4 years, dementia risk was 50 percent lower among community-living elders who reported such mentally stimulating activities at least twice weekly versus less than once weekly, Dr. Tasnime Akbaraly, at INSERM, France’s public health research agency, in Montpellier, and colleagues report.

Their study, in the journal Neurology, followed 5,698 men and women, 65 years and older, who were free of dementia at the outset. During follow-up, 161 of these elders developed dementia.

Mind-stimulating leisure time pursuits, like crossword puzzles, were found to be significantly associated with a reduced risk of dementia and Alzheimer’s disease over the 4-year follow up period.

By contrast, Akbaraly’s team observed no protective effect from physical, passive, and social leisure activities such as doing odd jobs, gardening, walking, watching television, listening to the radio, or visiting with friends.

These observations were independent of education level, occupation, and brain functioning at the beginning of the study, Akbaraly told Reuters Health in an email correspondence.

The associations also remained strong after allowing for gender, age, marital status and health-related history, such as blood vessel disease, depressive symptoms, and physical functioning.

The reduced risk of dementia observed in elders regularly partaking in mentally stimulating activities was also independent of physical, social, and passive forms of leisure activities.

These findings agree with previously published reports that mentally stimulating leisure activities may help protect from dementia, the investigators note.

Patients with acute myeloid leukemia (AML), take note: A new standard of care is emerging — at least for those younger than 50, or between 60 and 65.

That’s the take-home message of a pair of studies published Wednesday in the New England Journal of Medicine. Two research teams — the U.S.-based Eastern Cooperative Oncology Group (ECOG) and a team of scientists in the Netherlands, Belgium, Germany and Switzerland — studied almost 1,500 patients and independently reported higher rates of complete remission and overall survival in those who received high doses of the chemo drug daunorubicin, compared to those who receive the standard dose.

Though those benefits were mostly limited to specific subsets of patients — those younger than 50 or between 60 and 65, who had so-called “favorable” or “intermediate” genetic profiles — they also came without any apparent increase in serious side effects.

In essence, said Dr. Hugo Fernandez of the Moffitt Cancer Center and Research Institute in Tampa, Fla., the lead author on the U.S. study, the data suggest that oncologists have nothing to lose in using the high-dose regimen, 90 mg per square meter of body surface area compared to a standard 45 mg per square meter. That’s because AML must be treated aggressively, yet it can take days for genetic analyses to come back from the lab.

“The bottom line is survival,” Fernandez said. “We achieved it without great cost to the patients, and without any new fancy drugs, either. This wasn’t reinventing the wheel; it was using the drugs optimally. We finally got the right dose.”

In an editorial accompanying the two studies, Drs. Herve Dombret and Claude Gardin from Paris, wrote, “Do we have a new standard of care in AML? The lack of an increase in toxic effects and the benefit in overall survival strongly argue for incorporating high-dose daunorubicin into the initial treatment of younger patients with AML, at least for those with favorable- and intermediate-risk cytogenetic profiles, unless an increased rate of toxic effects is feared when high-dose daunorubicin is used in association with new agents, such as FLT3 inhibitors, currently in ongoing trials.”

According to the Leukemia & Lymphoma Society, 13,290 Americans were “expected to be diagnosed” with AML last year. Half of all AML patients are older than 65.

Treatment usually includes a so-called “7+3″ induction regimen, in which patients are given cytarabine for seven days and daunorubicin (or a related drug, such as idarubicin) for three. The daunorubicin is typically administered at 45 mg per square meter of body surface area, yet anecdotal evidence suggested higher doses might be more effective, Fernandez said.

The two research teams set out to determine whether that was actually the case — in patients younger than age 60 in the ECOG trial, or older than age 60 in the European trial.

Rates of complete remission and overall survival improved in both studies. Yet the effects were most pronounced when the researchers focused on specific subgroups, rather than the entire study population.

For instance, in the ECOG study overall, complete remission rates jumped from 57.3 percent for the standard treatment group, to 70.6 percent for the high-dose group, while median survival improved from 15.7 months to 23.7. For those patients younger than 50, survival improved from a median of 19 months, to 34.3 months. But no benefit was seen for patients 50 or older.

Similarly, survival improved from 20.7 to 34.3 months for patients with “favorable” or “intermediate” genetic profiles, but no benefit at all was observed in patients with an “unfavorable” profile.

In the European trial, overall complete remission rates rose in the high-dose group from 54 percent to 64 percent, with no overall improvement in two-year overall survival. Yet when looking only at patients aged 60 to 65, remission improved from 51 percent to 73 percent, while two-year survival improved from 23 percent to 38 percent.

“I think the take-home message is that the outcomes seem to be sufficiently improved, at least in patients less than 50, and aged 60 and 65, that this is a reasonable standard of care,” said Dr. Michael Millenson, director of the hematology service at the Fox Chase Cancer Center in Philadelphia. He added, “Since we don’t necessarily have all the cytogenetic information back when we have to make a decision about dosing, I think the reassuring thing is that there didn’t seem to be excessive toxic side effects.”

Dr. Anthony Stein, of the City of Hope in Duarte, Calif., who sees “at least two new AML patients per week,” uses idarubicin rather than daunorubicin. But, he said, “based on these two papers, it didn’t look like using the higher dose led to more toxicity, so if I were going to use daunorubicin, I would use the higher dose.”

Dr. Barton Kamen, chief medical officer at the Leukemia & Lymphoma Society, said the studies highlight the heterogeneity of AML and the power of “personalized medicine” — as well as the need for more research.

“To me the tagline is, AML is lots of different diseases,” Kamen said. “And we need to know as much as we can of the patient and the disease to treat them. This is a spectacular example of that.”

“But,” he added, “they still have a lot of work to do.”

Kamen doesn’t advocate giving high-dose daunorubicin to all patients, only those who are likely to benefit. “There are short- and long-term side effects we don’t know yet,” he said. Of particular concern, daunorubicin can damage the heart.

Indeed, Fernandez noted there are “nay-sayers” in the oncology community who suggest that, five or six years down the road, patients might be better off had they received the lower dose. “But my retort is, with the high dose, they are more likely to be alive.”