“There is emerging evidence on the widespread tissue effects of vitamin D,” write Faustino R. Pérez-Lópeza, MD, PhD, from the Department of Obstetrics and Gynecology, Universidad de Zaragoza, Spain, and colleagues. “Epidemiological and prospective studies have related vitamin D deficiency with not only osteoporosis but also cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospective studies are lacking.”

Based on a literature review and the consensus of expert opinion, the position statement panel concluded that the leading natural source of vitamin D is sunlight exposure stimulating synthesis in the skin. Dietary sources, which are not as significant as cutaneous synthesis, include animal-based foods such as fatty fish, eggs, and milk.

Measurement of serum 25-hydroxyvitamin D [25(OH)D] levels allows determination of vitamin D status, with optimal levels ranging from 30 to 90 ng/mL (75 – 225 nmol/L). However, different countries vary in their recommendations concerning optimal vitamin D levels. Factors affecting vitamin D levels include season of the year (lower in the winter), latitude, altitude, air pollution, skin pigmentation, use of sunscreens, and skin coverage by clothing.

Obesity; malabsorption syndromes; use of anticonvulsants, antiretrovirals, or various other medications, skin aging, little sun exposure, and living in residential care facilities have been associated with low serum 25(OH)D levels.

The recommended daily allowance of vitamin D is 600 IU/day, but this should increase to 800 IU/day in those patients at least 71 years of age. Postmenopausal women can generally achieve healthy levels of vitamin D though exposure without sunscreens to regular midday sunlight for 15 minutes, 3 to 4 times a week. Ingestion of vitamin D–fortified foods does not necessarily provide sufficient amounts.

When supplementation is needed, either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) may be appropriate. Depending on the dose used and the presence of renal disease or other comorbidities, monitoring may be indicated.

Specific summary recommendations include the following:

• Clinicians should recognize that vitamin D deficiency and insufficiency are widespread, affecting up to 70% of European populations (including those living in sunny regions).
• Healthy postmenopausal women may achieve adequate serum concentrations of vitamin D through either sun exposure (15 minutes per day, 3 – 4 times a week) or supplementation with 800 to 1000 IU/day.
• To achieve adequate levels, women with low serum 25(OH)D may need doses ranging from 4000 to 10,000 IU/day.
• Specific tailored doses of vitamin D supplements are needed for women with morbid obesity, both before and after gastrointestinal bypass surgery, malabsorption syndromes, and/or hepatic or renal diseases.
• Adequate amounts of vitamin D and specific bone-conserving therapies are indicated for women with vitamin D deficiency, osteoporosis, and/or previous incidental fractures. If there are no associated risk factors for low serum vitamin D levels, doses should be from 800 to 1200 IU/day.

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The population-based, retrospective birth-cohort study showed that children in Cape Cod who were exposed to drinking water contaminated with PCE, which was used to line municipal water pipes, had almost a 2-fold increased risk for bipolar disorder compared with the general population.

The study was published online January 20 in Environmental Health.

Used widely in industry and to dry clean clothes, PCE is a well-known neurotoxin, Ann Aschengrau, ScD, and colleagues from Boston University School of Public Health in Massachusetts note in their report.

PCE readily crosses the blood-brain barrier and has a high affinity for the lipophilic tissues in the central nervous system. The exact mechanisms for its neurotoxic effects remain unclear but include peroxidation of cell membrane lipids, alterations in the fatty acid profile of the brain, and loss of myelin and interactions with neuronal receptors.

Exposure to PCE has been shown to cause mood changes, anxiety, and depression in people who work with it. To date, the long-term effect of this chemical on children exposed to PCE has been less clear, although there is some evidence that children of people who work in the dry cleaning industry have an increased risk for schizophrenia.

To investigate further, the Boston team studied individuals born between 1969 and 1983 to married women who lived in towns in Cape Cod, Massachusetts, that had vinyl-lined asbestos-cement water pipes.

Dose Response

These pipes were installed by public water companies from the late 1960s through early 1980 to solve alkalinity problems in dead-end sections of their distribution systems. The liner was applied by spraying a mixture of vinyl resin and PCE. More than a decade elapsed before officials discovered that large quantities of PCE were leaching into the public water supplies.

Surveys conducted in 1980 found that drinking water supplies in Cape Cod had PCE levels ranging from 1.5 to 7750 μ/L. Because replacing the pipes was prohibitively expensive, systematic flushing and bleeding were used to reduce levels below 40 μ/L, which was the maximum recommended level at the time. The maximum contaminant level for PCE is now set at 5 μ/L.

The Cape Cod cohort included 1512 individuals. The participants included 831 persons with both prenatal and early childhood exposure to PCE and 547 persons who had not been exposed. Participants provided information on mental illnesses, demographic and medical characteristics, other sources of solvent exposure, and places of residence from the time of their birth through 1990.

PCE exposure from the vinyl-liner water distribution pipes was assessed using water distribution system modeling software that incorporated a leaching and transport algorithm, the authors explain.

The researchers did not see any meaningful increase in the risk for depression with prenatal and childhood PCE exposure (risk ratio [RR], 1.1; 95% confidence interval [CI], 0.9 – 1.4). This finding was “both surprising and maybe reassuring,” Dr. Aschengrau told Medscape Medical News, given that earlier research in PCE-exposed adults suggested an increased risk for depressive disorders.

However, the researchers did find that individuals with any exposure during gestation and early childhood were at increased risk for bipolar disorder (RR, 1.8; 95% CI, 0.9 – 3.5) and PTSD (RR, 1.5; 95% CI, 0.9 – 2.5). Further increases in risk were observed for bipolar disorder (RR, 2.7; 95% CI, 1.3 – 5.6) and PTSD (RR,1.7; 95% CI, 0.9 – 3.2) among persons with the highest exposure levels.

The risk of schizophrenia was also elevated among exposed individuals (RR, 2.1; 95% CI, 0.2 – 20.0), but the number of cases was too small to draw reliable conclusions, the authors note.

“Risk Remains Real”

The researchers note, however, that a study published in 2007 in Schizophrenia Research found a 3.4-fold increased risk for schizophrenia (95% CI, 1.3 – 9.2) among the offspring of parents who worked as dry cleaners. Adjusting for confounding factors did not appreciably alter the finding.

Mary Perrin, DrPH, assistant professor of psychiatry and environmental medicine from the New York University Langone Medical Center in New York City, worked on that study. Medscape Medical News asked her for her thoughts on the Cape Cod study.

“No one epidemiological study is going to prove anything. You have to build evidence, and my personal opinion is that it’s another brick in the wall showing that we really need tighter regulation of these substances in the environment. The animal literature is quite clear on this,” said Dr. Perrin.

She added that the Cape Cod study is “methodologically a good study. The authors articulated the limitations of the study, which you can’t ignore, and did not overstate the results, which are very interesting.”

Dr. Aschengrau and colleagues say the limitations of their study include the possibility of exposure misclassification and a lack of data on water consumption and bathing habits; self-reported mental illness data; and possible residual confounding as a result of missing data on several risk factors for mental illness.

The low response rate is another limitation. It is possible that individuals with mental illnesses preferentially ignored requests to participate, the investigators note. This would have reduced the number of cases in the final sample. However, available evidence suggests that this did not introduce selection bias, the authors say.

Dr. Aschengrau also noted that it is not possible to calculate the exact amount of PCE the participants in the study were exposed to.

“Levels of PCE were recorded as high as 1550 times the currently recommended safe limit. While the water companies flushed the pipes to address this problem, people are still being exposed to PCE in the dry cleaning and textile industries and from consumer products, and so the potential for an increased risk of illness remains real,” she said.

Dr. Aschengrau and her colleagues added that independent investigations of similarly exposed populations are needed to corroborate their findings.

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An internal investigation revealed that some blister packs “may contain an inexact count of inert or active ingredient tablets and that the tablets may be out of sequence,” Pfizer said in a press release.

The company says the cause was identified and corrected immediately.

Pfizer manufactures the tablets, which are commercialized by Akrimax Rx Products and labeled under the Akrimax Pharmaceuticals brand. The oral contraceptive is distributed nationwide.

“As a result of this packaging error, the daily regimen for these oral contraceptives may be incorrect and could leave women without adequate contraception, and at risk for unintended pregnancy,” Pfizer warned.

The packaging defects in themselves do not pose any immediate health risk, but women who may have taken the contraceptive “should begin using a non-hormonal form of contraception immediately,” notify their physician, and return the product to the pharmacy from which they obtained it, the company advises.

Recalled lot numbers are listed in the Pfizer press release, which is available on the FDA Web site.

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“People who had diet soda every day experienced a 61% higher risk of vascular events than those who reported drinking no soda,” lead investigator Hannah Gardener, ScD, an epidemiologist from the University of Miami Miller School of Medicine in Florida, told reporters attending a news conference here at the International Stroke Conference.

The risk persisted after controlling for metabolic syndrome, peripheral vascular disease, and cardiac disease history (relative risk, 1.48; 95% confidence interval, 1.03 – 2.12).

“This is the first report of this association,” said American Stroke Association national spokesperson Larry Goldstein, MD. “I think that it’s always good to do things in moderation. People should look at this information and consider it in the context of their other risk factors.”

The researchers looked at more than 2500 people from the multiethnic Northern Manhattan Study. Participants were asked to report how much and what kind of soda they drank.

During an average follow-up of 9.3 years, 559 vascular events occurred, including ischemic and hemorrhagic stroke.

The researchers also observed a marginally significant increased risk for vascular events among those who consumed diet soda daily and regular soda once or more a month (adjusted relative risk, 1.74; 95% confidence interval, 0.96 – 3.16).

As reported by Medscape Medical News, previous studies have suggested a link between diet soda consumption and the risk for metabolic syndrome and diabetes. But this is the first time diet drinks have been associated with vascular events.

“This is an observational study and not a prospective randomized trial,” Dr. Goldstein, from the Duke Stroke Center, in Durham, North Carolina, pointed out. “This is an association and not yet a proven causal relationship.”

The investigators acknowledge that additional studies are needed. The potential mechanisms for the association between diet soda and vascular events remain unknown.

What should clinicians advise patients on the basis of the information we have today? Steven Greenberg, MD, from Harvard Medical School in Boston, Massachusetts, suggests that patients start by concentrating on a healthy diet and regular exercise. “Once the metabolic syndrome is under control and any risk of diabetes, then we can consider cutting back on soda consumption.” Dr. Greenberg is the vice chair of the International Stroke Conference Committee, and during an interview he suggested that patients shouldn’t rush to eliminate diet drinks.

“I do think this is a wake-up call, though,” he said, “and we need to start paying closer attention.”

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Extreme weather and smoking may also increase the skin damage associated with ultraviolent (UV) radiation, the study suggests.

Michelle Garay, MS, of Johnson & Johnson Consumer Companies in Skillman, N.J., and colleagues presented the findings at the annual meeting of the American Academy of Dermatology (AAD).

It’s well known that repeated exposure to ultraviolet radiation from the sun or tanning beds can cause wrinkles and other skin damage and even lead to skin cancer. But researchers wanted to see if exposure to pollution and other environmental factors, such as extreme temperatures, would further aggravate damage from UV rays.

Testing for Sun Damage

The researchers placed skin cells in a variety of special chambers mimicking different environmental conditions, including:

• UV radiation alone.
• UV radiation plus cigarette smoke.
• UV radiation plus heat reaching 104 degrees Fahrenheit.
• UV radiation plus temperatures dropping below freezing.
• UV radiation plus high winds.
• UV radiation plus ozone.

Then the researchers measured key chemicals associated with premature aging of the skin due to sun damage.

Levels of all the chemicals were higher in skin cells placed in chambers that included a second environmental stressor than in the chamber with UV radiation alone.

Past AAD president Darrell S. Rigel, MD, clinical professor of dermatology at New York University Medical Center in New York City, says that while preliminary, the work generates new hypotheses that deserve testing.

“I don’t think anyone has ever looked at this before,” he tells WebMD.

The AAD already advises people to use extra sun protection near water, snow, and sand as they reflect the damaging rays of the sun that can increase your chance of sunburn, Rigel says. “It could be that people who live in polluted areas also need extra sun protection, though that remains to be tested.”

These findings were presented at a medical conference. They should be considered preliminary as they have not yet undergone the “peer review” process, in which outside experts scrutinize the data prior to publication in a medical journal.

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In the study, which included 30 000 deaths over nine years of follow-up, subjects with the highest consumption of fiber were 22% less likely to die than those with the lowest consumption, Dr Yikung Park (National Cancer Institute, Rockville, MD) and colleagues report online February 14, 2011 in the Archives of Internal Medicine. “Prior studies have focused on the relationship between fiber intake and Cardiovascular Disease (CVD), but few have examined the link between dietary fiber and mortality,” Park told heartwire . “Our analysis adds to the literature and suggests dietary fiber intake is also associated with decreased likelihood of death.”

In an accompanying commentary, Drs Lawrence de Koning and Frank B Hu (Harvard School of Public Health, Boston, MA) say the “careful control for confounding” performed by Park et al “enhances the validity of these findings and supports the hypothesis that dietary fiber is important for longevity.”

Park and colleagues agree: “The 2010 dietary guidelines for Americans recommend choosing fiber-rich fruits, vegetables, and whole grains frequently and consuming 14 g [of dietary fiber per] 1000 calories. A diet rich in dietary fiber from whole plant foods may provide significant health benefits,” they say. (The 2011 dietary guidelines have just been released.)

Benefit Comes From Whole Grains

The researchers examined dietary-fiber intake in relation to mortality from specific causes in the National Institutes of Health (NIH)-AARP Diet and Health prospective cohort study. Diet was assessed at baseline using a food-frequency questionnaire, and cause of death was identified using the National Death Index Plus.

During an average of nine years follow-up, there were 20 126 deaths among men and 11 330 among women. Fiber intake was associated with a significantly lowered risk of total death among both sexes, with a multivariate-adjusted relative risk comparing the highest quintile of fiber consumption with the lowest of 0.78 (p<0.001) in both men and women. Eating fiber also lowered the risk of death from cardiovascular, infectious, and respiratory diseases by 24% to 56% in men and by 34% to 59% in women.

An inverse association between fiber intake and cancer death was observed in men, but not in women. Deaths from specific cancers were not presented, “which makes it difficult to evaluate the benefits of fiber on specific sites of cancer,” say de Koning and Hu in their commentary.

And specifically, dietary fiber from grains, but not from other sources, was significantly inversely related to total and cause-specific death in both genders, they note, so “fiber isolates probably do not provide the same benefits as intact, whole grains,” they observe.

Do Whole Grains Act to Reduce Inflammation? Further Research Needed

The editorialists add that the finding of a strong inverse association between fiber intake and cardiovascular death “supports decades of research indicating that dietary fiber protects against cardiovascular disease and its risk factors,” including lowering blood pressure and reducing cholesterol.

Park and colleagues agree, noting that their findings for cardiovascular death are in agreement with several previous studies, including a pooled analysis in which the risk of CVD death fell by about 19% per 10-g/day increment of fiber intake.

But de Koning and Hu say that the “most striking finding” of the new study “is an inverse association between fiber intake and death from infectious and respiratory diseases”; this was “the strongest association observed by Park and colleagues, [who] suggest the benefit of dietary fiber is attributable to antioxidant and anti-inflammatory properties of whole-grain components,” they note.

“The hypothesis that whole grains reduce disease severity and respiratory and infectious disease mortality via reduced inflammation is intriguing,” they add, but “requires testing in randomized trials.”

Park et al concur: “Further studies are needed to replicate our finding on the association between dietary fiber intake and risk of death from infectious and respiratory disease. And more studies are needed to understand the role of fiber in reducing inflammation and the mechanisms by which it protects against disease and risk of death,” they conclude.

Reprinted from MedScape

For a quick list of high fiber foods, visit our companion website, Strive to Simplify, to read Eating Fiber Reduces Cardiovascular Disease.

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Her mother, Christine Brouwer, is convinced that environmental toxins played a role in her daughter’s brain cancer.

The case was highlighted during a teleconference sponsored by the Safer Chemicals, Healthy Families coalition. During the broadcast, experts drew attention to the increase in childhood cancers in recent decades, and the parallel increase in the use of new and mostly untested chemicals during the same time period.

Aside from Ms. Brouwer, the panel included Richard Clapp, DSc, MPH, professor emeritus of environmental health at Boston University School of Public Health, and Sean Palfrey, MD, professor of clinical pediatrics and public health at Boston University, Massachusetts.

“I will most likely never know what caused my daughter’s cancer, but researchers are finding more and more links between the hazardous substances in our homes and workplaces and cancer and other diseases,” Ms. Brouwer told the meeting.

After the 2008 death of her daughter, she founded Mira’s Movement, an advocacy organization.

During the teleconference, Dr. Clapp pointed out that the incidence of childhood cancers, especially leukemias and brain cancer, has been on the rise for more than 20 years. Ms. Brouwer noted that during the past decade, 7 new pediatric brain tumor histologies have been identified. She suggested that there is a link to synthetic chemicals and other environmental pollutants, the use of which has risen so dramatically in recent years that they are now ubiquitous.

According to Safer Chemicals, Healthy Families, approximately 80,000 chemicals have been produced in the United States to create commonly used products — including known carcinogens such as asbestos, formaldehyde, lead, cadmium, trichloroethylene, and vinyl chloride — with virtually no government oversight.

Childhood Cancers on the Rise

“The incidence of childhood cancers has unequivocally been going up for the last 20 years, at about a 1% increase per year,” said Dr. Clapp during the teleconference.

Fortunately, mortality from childhood cancer has been decreasing during this same time period, he reported.

He also noted that “we know a lot more than we did in 1975 about the things that cause cancer in both children and adults, and it’s clear that at least one component of the cause is environmental chemical exposure.”

“It’s not in every child for every cancer, but certainly some portion of childhood cancers can be traced back to damage done at the cellular level by chemicals that are carcinogens,” said Dr. Clapp.

Dr. Clapp also noted that in the past year, the International Agency for Research on Cancer reviewed more than 900 substances or kinds of exposures and identified about 107 that are known to cause cancer in humans. “When I first started looking at this, which was in about 1975, there were only about a dozen things known to cause cancer in humans,” he said.

Dr. Clapp pointed to examples of chlorinated solvents, such as trichloroethylene and carbon tetrachloride, that have entered community water supplies and have been implicated in the childhood cancer clusters found in Woburn, Massachusetts, and Tom’s River, New Jersey.

TSCA Overhaul

Last year, the President’s Cancer Panel provided evidence that exposure to toxic chemicals is an important and underrecognized risk factor for cancer, and recommended that the government take immediate action to reverse this trend. As reported by Medscape Medical News at that time, the panel noted that it was “particularly concerned to find that the true burden of environmentally induced cancer has been grossly underestimated.”

However, there was a decidedly mixed reaction to that report, with some hailing it as a landmark document and others concerned that it overstates the risks.

This law is the most egregious example of ineffective regulation of chemical contaminants.
The report from the President’s Cancer Panel emphasized the need for legislation that will shift the burden of proof from the government to industry, and require manufacturers to prove the safety of new and existing chemicals. In particular, the Panel called for an overhaul of the 1976 Toxic Substances Control Act (TSCA), stating that this law is “the most egregious example of ineffective regulation of chemical contaminants.”

The Safer Chemicals, Healthy Families coalition fully supports the need for updated legislation. It points out that in the 34 years since the TSCA was enacted, the Environmental Protection Agency has been able to require testing on just 200 of the more than 80,000 chemicals produced and used in the United States.

Present in Body Fluids

A number of substances are known to be related to the development of cancer, explained Dr. Palfrey. These include tobacco, ionizing radiation, asbestos, magnetic fields, pesticides, industrial solvents, and some viruses.

In normal circumstances, the body has learned to protect itself from toxins in one way or another, he said. But in the current situation, a huge number of new chemicals are entering the environment that the body has never been exposed to.

“Our bodies don’t know how to detoxify themselves or to prevent these chemicals from being absorbed,” Dr. Palfrey said during the teleconference. “Unfortunately, we may end up storing them.”

When this happens in pregnant women, the stored chemicals can be released and circulated in the fetal blood and breast milk. “What we’re finding is a multigenerational problem; if mom is exposed, it may get into the fetus.”

We are not doing what we should to protect our children.
Dr. Palfrey noted that the concern is that many of these substances being released into the environment are largely untested in adults or in children, who are even more vulnerable. “People like me have been tested to see if we have some of these compounds in our blood and urine — and sure enough we do,” he said.

The blood from umbilical cords has also been tested, and it has been found to contain many of these compounds, Dr. Palfrey added. “We are not doing what we should to protect our children, despite the fact that we may be very concerned about this issue.”

Legislation on the Horizon?

Ms. Brouwer pointed out that the United States lags behind other parts of the world. In Europe, for example, more stringent measures have been adopted. “If companies want to sell certain products, they need to demonstrate they are safe for the intended consumer,” she said. “The burden of proof lies with the company that stands to make the profit, rather than with the government. Why is our country’s priority the freedom to make a profit rather than freedom from disease?”

She pointed out that the government can be slow to implement policy changes so as not to impede industry without the necessary proof. Tobacco is one such example.

Most would admit that it was about 30 years too late.
“It took many years for stronger statements to be made about the potential harm of tobacco,” she said. “Now tobacco awareness and attempts to prevent lung cancer are a given. But most would admit that it was about 30 years too late.”

However, new legislation directed at environmental contaminants is on the horizon. In a bipartisan effort, Sen. Barbara Boxer (D-California), chair of the Environment and Public Works Committee, introduced legislation with Sen. Mike Crapo (R-Idaho) that would assist communities in determining links between cancer clusters, birth defects and other diseases, and contaminants in the surrounding environment.

In a statement, Sen. Crapo noted that “as a 2-time cancer survivor, I know that cancer can come from many sources. This legislation may provide the answers to questions that many families face when confronting disease, and it’s important that we find ways to help Americans fully understand disease clusters.”

The legislation, designated S.76, is designed to strengthen federal agency coordination and accountability when investigating these potential “clusters” of disease; to increase assistance to areas affected by potential disease clusters; and to authorize federal agencies to form partnerships with states and academic institutions to investigate and help address disease clusters.

Reprinted from Medscape.com

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“Propoxyphene, also called Darvon and Darvocet, is the worst drug in history,” Ulf Jonasson, doctor of public health, from the Nordic School in Gothenburg, Sweden, told Medscape Medical News. The researcher played a role in the decision to stop the pain reliever in the United Kingdom, Sweden, and later in the entire European Union.

“No single drug has ever caused so many deaths,” Dr. Jonasson said.

Clinicians are now prescribing analgesic alternatives to propoxyphene.

Propoxyphene was banned in the United Kingdom 5 years ago because of its risk for suicide. It was taken off the market in Europe in 2009 over concerns about fatal overdoses and now in the United States for arrhythmias.

“I agree that propoxyphene is among the worst drugs in history,” Eduardo Fraifeld, MD, president of the American Academy of Pain Medicine, said in an interview. “I’m surprised it stayed on the market so long. It’s addictive, in my experience not very effective, and toxic.”

“I’d probably add Demerol to the list too,” Dr. Fraifeld said. “It’s toxic and sedating, and my personal opinion is it should not be used at all.”

Also known as pethidine, Demerol was the first synthetic opioid synthesized in 1932 as a possible antispasmodic agent. Its analgesic properties were recognized later. For much of the 20th century, pethidine has been the opioid of choice for many physicians treating acute and chronic severe pain.

“The writing has been on the wall for both of these drugs,” Dr. Fraifeld said. “With adverse events, prescription abuse increasing, and questionable effectiveness, this isn’t innocuous.”

Burden on Prescribers and Patients

A growing number of products are entering the US market, Dr. Fraifeld noted. “It’s unrealistic to expect regulators to be able to closely track every single one.” Prescribers and patients must therefore pay close attention to any emerging side effects, he said. “Unfortunately, clinicians are not using adverse event reporting systems adequately,” Dr. Fraifeld added. “I think it’s fair to say that many physicians have no idea how to even use the system, and this is a problem.”

Propoxyphene was first developed by Eli Lilly and later sold to Xanodyne Pharmaceuticals, which marketed the drug under the brand names Darvon and Darvocet.

Since 1978, the FDA has received 2 requests to remove propoxyphene from the market. In January 2009, an advisory committee voted 14 to 12 against the continued marketing of propoxyphene products. At that time, the committee called for additional information about the drug’s cardiac effects.

In terms of benefit to risk ratio, “I would say, little ‘b’, big ‘r’ for this drug. And that’s unsettling,” committee member Ruth Day, PhD, from Duke University in Durham, North Carolina, who voted to remove propoxyphene, said at the time.

The drug is a narcotic opioid. “It looks like it offers placebo benefits with opioid risks,” added committee member Sean Hennessey, PhD, an epidemiologist from the University of Pennsylvania in Philadelphia.

Later in 2009, the FDA decided to allow continued marketing of propoxyphene, but with a new boxed warning added to the drug label alerting of the risk for fatal overdose.

That came to an end in November 2010, when regulators disclosed new study results, combined with epidemiologic data, and medical examiner reports prompting the drug’s market removal.

New study results showed propoxyphene puts patients at risk for potentially serious or even fatal heart rhythm abnormalities.

Should FDA Have Acted Sooner?

Gerald Dal Pan, MD, director of the Office of Surveillance and Epidemiology, said in November that regulators did not feel there was sufficient evidence earlier. “The new information on the effects of the electrical activity on the heart was the final piece to the puzzle,” he said.

“Long-time users of the drug need to know that these changes to the heart’s electrical activity are not cumulative,” Dr. Dal Pan added. “Once patients stop taking propoxyphene, the risk will go away.”

Although most say they are glad to see propoxyphene finally off the market, there are those who found it useful. “In 20 years, I can’t recall a single problem,” cardiologist Melissa Walton-Shirley, MD, from TJ Samson Community Hospital in Glasgow, Kentucky, told Medscape Medical News. “I was not a huge prescriber of propoxyphene meds, preferring other options, but when I did, it was Darvocet N-100.”

Dr. Shirley is forum moderator for theheart.org. She questioned the regulatory action in a recent blog. “The FDA decided to withdraw the medication after 53 years on the market but provided little in the way of data to help us understand its decision, undermining the confidence of the lay public in the FDA, the prescribers, and the pharmacists who have served them for their entire adult lives.”

Dr. Fraifeld said he had a very small number of patients in his practice taking propoxyphene. “I never liked the drug but had some patients I had inherited from other practices who were taking propoxyphene and were reluctant to change when I suggested it. I’ve prescribed alternatives, such as acetaminophen or other opioids, and everyone has transitioned quite well.”

Table. Analgesic Alternatives to Propoxyphene

Analgesic Adverse Events
Acetaminophen Hepatotoxicity, serious allergic reactions
Aspirin Gastrointestinal bleeding, tinnitus, hypersensitivity, and asthma
Nonsteroidal anti-inflammatory drugs Gastrointestinal bleeding, serious cardiovascular events, renal injury, liver injury, serious skin reactions
Tramadol Respiratory depression, seizures, nausea, vomiting, serotonin syndrome
Codeine in combination with acetaminophen Respiratory depression, constipation, sedation, nausea, vomiting, hepatotoxicity, serious skin reactions
Hydrocodone in combination with acetaminophen Respiratory depression, nausea, vomiting, constipation, sedation, addiction, hepatotoxicity, serious skin reactions
Schedule II opioids Respiratory depression, central nervous system depression, sedation, nausea, vomiting, constipation, addiction

“It’s so important that we don’t become complacent and continue to closely monitor patients,” Dr. Fraifeld said. “It can be tough because chronic pain patients are often complaining, and some of their concerns may get overlooked. We have to stop, pay attention, and, if something seems off, we have to take a look because we never know what could be the next propoxyphene.”

Reprinted from Medscape.com

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“More and more studies indicate a prevalence of CD of more than 1% in both adults and children. This should be compared with lower prevalence figures [from] 20 to 30 years ago,” Jonas Ludvigsson, MD, from the Department of Medicine, Epidemiology Unit, at the Karolinska Institute and Orebro University Hospital, Sweden, and an expert in CD, noted in an email to Medscape Medical News.

“The reason for this increase is mutlifactorial, but there is probably a true underlying increase. This has been shown when old sera have been analyzed with modern techniques, (eg, in Finland),” Dr. Ludvigsson pointed out.

Mayo Clinic Research Confirms Rise in CD

Researchers at the Mayo Clinic also report an increase in CD, according to an article in the summer issue of the Mayo Clinic’s research magazine Discovery’s Edge. Joseph Murray, MD, and colleagues analyzed stored blood samples, taken from Air Force recruits in the early 1950s, for gluten antibodies. They assumed that 1% would be positive, mirroring today’s rate. That assumption was wrong — the number of positive results was far smaller, indicating that CD was “rare,” Dr. Murray noted in the article.

This led him and his colleagues to compare those results with 2 more recently collected sets from Olmsted County, Minnesota. Their findings suggest that CD is roughly 4 times more common now than in the 1950s.

“This tells us that whatever has happened with CD has happened since 1950,” Dr. Murray said. “This increase has affected young and old people. It suggests something has happened in a pervasive fashion from the environmental perspective,” he added.

Excess Mortality Seen With CD and Latent CD

Recent research by Dr. Ludvigsson’s team (JAMA. 2009;302:1171-1178) and others supports the concept of “latent CD” or “gluten sensitivity.” Latent CD, defined in the Journal of the American Medical Association study by Dr. Ludvigsson’s team as having normal small intestinal mucosa but positive CD serology, is something that is estimated to occur in at least 1 in 1000 individuals.

Dr. Ludvigsson’s team has also reported evidence that in 1 year, 10 of 1000 individuals with CD will die compared with an expected 7 in 1000 without the disease.

“Not only is the mortality raised in patients with [CD] but also in those individuals with latent [CD],” Dr. Ludvigsson noted in a statement from the United European Gastroenterology Federation.

However, in comments to Medscape Medical News, he emphasized that “although patients with CD are at increased risk of a number of disorders, and at increased risk of death, the absolute risk increase is very small.”

A Tricky Disease

CD remains a “tricky disease,” Dr. Ludvigsson said. “It can be asymptomatic; have so-called traditional symptoms such as diarrhea, weight loss, failure to grow (in children), fatigue, and malnutrition; and have nontraditional symptoms such as osteoporosis, depression, adverse pregnancy outcome; and increased risks of both malignancy and death.”

The onset of certain autoimmune disorders including autoimmune liver disease, thyroid disease, type 1 diabetes, and Addison’s disease can actually signal CD, he noted. “This means that clinicians should consider CD in a number of symptoms and disorders.”

CD Often Undetected; Cause Unknown

CD often goes undetected, although the percentage of undetected cases varies between countries, Dr. Ludvigsson noted. “In most countries, at least two thirds of individuals with CD have not received a diagnosis by a doctor.” The reason for the high percentage of undetected disease is that the disease can be difficult to diagnose, and “it is sometimes almost asymptomatic,” he added.

Detection Methods Are Improving

Over the years, Dr. Ludvigsson told Medscape Medical News, “we have improved existing means to diagnose CD. Antibody tests are becoming better and better, although a positive antibody test should be confirmed with a small intestinal biopsy before the diagnosis is certain. Transient increases in CD antibody levels occur. In the future, I expect microscopy in the very small intestine to become a tool for diagnosis.”

Alternatives to the Gluten-Free Diet?

At this time, Dr. Ludvigsson said, the gluten-free diet remains the cornerstone of treatment for CD. However, “in the future, alternative treatment strategies may be available. The recent discovery of the structure of transglutaminase 2 may help in designing inhibitors of transglutaminase 2 to treat CD,” he said. “Another potential treatment strategy is to ingest enzymes that digest gluten, thereby increasing the safe threshold for gluten intake.

“There is also ongoing research on the topic of decreasing the bowel’s permeability to gluten, Dr. Ludvigsson told Medscape Medical News. He added, however, that the safety of this approach is unclear, as “a decreased permeability here might mean that the body cannot absorb other needed substances.

“Finally, agricultural research may mean that we can modify the gluten structure in wheat produce a kind of wheat that will not illicit an immune response in patients with CD,” the researcher noted.

Counseling CD Patients Is Important

Although evidence is scarce, said Dr. Ludvigsson, “most researchers believe that a gluten-free diet will reduce the risk of complications/comorbidity in CD, and it is important for the doctor to underline this for the patients. In patients with CD who do not become better on a gluten-free diet, the most common reason is probably that the patients do not eat a strictly gluten-free diet,” he said.

Dr. Murray advocates greater vigilance in CD patients. “It’s not enough to say, ‘You’ve got CD, be gluten-free, goodbye,’ ” he said. “CD requires medical follow-up.”

This October, at the United European Gastroenterology Week in Barcelona, Spain, Dr. Ludvigsson will be 1 of 8 researchers to receive the Association of National European and Mediterranean Societies of Gastroenterology and United European Gastroenterology Federation Rising Stars award.

Source: MedScape

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High total intakes of vitamins B6 and B12 are associated with a lower risk for depressive symptoms over time in community-residing older adults, according to the results of a cohort study reported online June 2 in the American Journal of Clinical Nutrition.

“B-vitamin deficiencies have been associated with depression,” write Kimberly A. Skarupski, from Rush University Medical Center in Chicago, Illinois, and colleagues. “We examined whether dietary intakes of vitamins B-6, folate, or vitamin B-12 were predictive of depressive symptoms over an average of 7.2 y in a community-based population of older adults.”

The Chicago Health and Aging project is an ongoing, population-based study in adults at least 65 years old. A sample of 3503 adults from this cohort, of whom 59% were African American, completed a food frequency questionnaire for dietary assessment. The 10-item version of the Center for Epidemiologic Studies Depression scale was used to determine incident depression, defined as 4 or more depressive symptoms. The association between vitamin intake and depression was examined with logistic regression models using generalized estimating equations.

After adjustment for age, sex, race, education, income, and use of antidepressant medications, higher total vitamin intakes including supplements were associated with a lower risk for incident depression during follow-up for up to 12 years. Odds of depressive symptoms were 2% lower per year for each additional 10 mg of vitamin B6 and an additional 10 μg of vitamin B12. Further adjustment for smoking, alcohol intake, widowhood, caregiver status, cognitive function, physical disability, and medical conditions did not abolish these associations. Food intakes of these vitamins or folate were not associated with depressive symptoms.

“Our results support the hypotheses that high total intakes of vitamins B-6 and B-12 are protective of depressive symptoms over time in community-residing older adults,” the study authors write.

“In the assessment and treatment of depressive symptoms in older adults, clinicians and other healthcare professionals should be mindful of the patient’s nutritional status in general, and whether there are vitamin insufficiencies in these nutrients before treatment,” the study authors conclude.

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