APA: Diagnostic and Treatment Considerations in Light of Atypical Depression

TORONTO, May 24 ??” Atypical depression affects up to about 40% of depressed patients. It differs from typical depression in symptoms, sleep characteristics, age of onset, and response to treatment.

Atypical depression is defined as being characterized by mood reactivity and at least two of these symptoms: hyperphagia, hypersomnia, leaden paralysis, or rejection sensitivity. Patients may be more functionally impaired than those with non-atypical depression.

Speaking at a symposium titled “Atypical Depression: Merging Evidence and Public Policy,” held during the American Psychiatric Association meeting, authorities on the subject reviewed the neurobiology, symptomatology, and management of the illness, including future directions and characteristics of a new drug formulation.

Charles Nemeroff, M.D., Ph.D., presented a detailed view of the neurobiology of the disease with a view toward understanding its unique pathophysiology and how to develop rational treatments. Dr. Nemeroff is professor and chairman of the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine in Atlanta.

He said the underpinnings of depression are complex, including genetic factors, hormonal abnormalities, alterations in neurotransmitter systems and neural circuits, early life trauma, and recent stressors. He attributed about a third of the etiology to genetic factors and two-thirds to environmental ones. This is just the opposite of bipolar disorder.

Evidence indicates disturbances in the three major monoamine neurotransmitter systems: serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE), and dopamine (DA). The hypothalamic-pituitary-adrenal axis also is involved, based on findings of a relative deficiency of corticotropin-releasing factor. Someday, anticipating being able to measure specific neurotransmitter disturbances, Dr. Nemeroff said, “I hope we get to the point where we can say in a given patient, ‘Here’s what your problem is… and this is the prescription that we’re going to write for you,’ …instead of the incessant trial and error that we partake in every day in our practices.”

Already, a relative 5-HT deficiency is known to be linked to depression. Low levels of its major metabolite are found in the cerebrospinal fluid (CSF) of affected patients, and there is a compensatory increase in the density of 5-HT2 receptors on platelets and in tissue. Furthermore, from a scientific and practical standpoint, all 5-HT reuptake inhibitors (e.g., selective serotonin reuptake inhibitors, SSRIs) are effective antidepressants.

Dr. Nemeroff then showed histochemical and neuroimaging evidence for the localization of the serotonin system in the brain. He showed that the dorsal raphe serotonin neurons are the source of the bulk of serotonin in the human central nervous system, sending about 70% of their product forward.

He said the biggest recent development in the field was the discovery of polymorphism in the serotonin transporter. Two forms of the gene exist: a short form (s, resulting from a 44 base pair deletion in the promoter region) and a long form (l). Therefore, people may be homozygous for either form or heterozygous with one copy of each gene in their cells. Heterozygotes or people homozygous for the short form have reduced numbers of transporter sites.

Imaging studies have shown that these patients had exaggerated amygdala responses when they were shown scary faces while in a scanner, suggesting a mechanism for their relatively excessive fearfulness, neuroticism, and anxiety. Furthermore, adult subjects with the s/s or s/l genotype were more susceptible to later depression in a gene dose-dependent fashion if they had experienced childhood abuse. “Turn[ing] this on its head, if you have the l/l allele, you are immune to the consequences of child abuse,” Dr. Nemeroff concluded. “This is the ultimate resilience gene. It protects you.”

He discussed the NE system and showed that these neurons arise mainly from the locus coeruleus. In depressed patients, a decrease in a major metabolite of NE occurs in the urine, plasma, and CSF. Other NE metabolite levels are decreased in plasma as well, compared with healthy people. Compensatory elevations in ??-adrenoreceptors occur on lymphocytes, and there is decreased epinephrine-induced platelet aggregation.

The final neurotransmitter system that Dr. Nemeroff discussed was DA, which he views as central to depression. “Dopamine is the pleasure neurotransmitter, and what else is depression except a disease in which patients have an inability to experience pleasure?” he asked. “Anhedonia is the cardinal feature of depression.”

Evidence for the pathophysiological involvement of the DA system in depression comes from imaging, postmortem, and biological fluid studies. Furthermore, antidepressants such as monamine oxidase inhibitors (MAOIs) affect DA neuronal circuits. Dr. Nemeroff showed postmortem evidence for dopaminergic abnormalities in amygdaloid nuclei in major depression, as well as lower dopamine transporter binding potential in the striatum of depressed people compared to healthy individuals. He said that up to now, the DA system has not been addressed in depression except by the use of SSRIs intended to inhibit serotonin reuptake from the synapse.

He concluded by showing that negative mood, the primary symptom of depression, resides in the anterior cingulate of the cortex. Imaging shows “clearly altered activity” in this area. The abnormality is reversed in patients who respond to antidepressants but not in non-responders.

Dr. Nemeroff predicted that modern molecular neurobiology and genetics will transform clinical practice within the next five years. “You’ll be able to order imaging tests and genomic tests that will guide you in predicting what the best treatment will be for your patients, be it pharmacotherapy, psychotherapy, and which type of each,” he said.

Phenomenology of Atypical Depression

According to DSM-IV, atypical depression requires the absence of melancholic or catatonic features, the presence of mood reactivity, plus at least two more features: increase in appetite or weight gain, hypersomnia, leaden paralysis, or long-standing interpersonal rejection sensitivity.

However, Hans-J??rgen M?¶ller, M.D., professor and chairman of psychiatry at Ludwig-Maximilians University in Munich, Germany, said this definition and its clinical significance have come into question.

Mood reactivity does not always appear to be central to the diagnosis and the lack of interdependency of accessory features have been cited as a reason not to consider atypical depression a true syndromal construct. A lack of consensus about symptom patterns adds to the clinical conundrum. Dr. M?¶ller, therefore, sought to integrate established and emerging definitions of atypical depression to help the audience develop strategies for diagnosis and treatment selection for this historically “treatment-resistant” form of depression.

He summarized cohort study results and concluded that mood reactivity was not significantly associated with other atypical symptoms and that it may not be specific for atypical depression or even a prominent and exclusive criterion. Therefore, he (along with other authors) questioned the diagnostic value of mood reactivity.

This situation makes comparisons of studies of atypical depression difficult because of varying definitional criteria and sampling methods. He also noted that ICD-10 has no operational criteria for atypical depression. In addition the Hamilton Rating Scale for Depression (HAM-D), the most frequently used one, does not refer to atypical symptoms and may underrate the condition. Dr. M?¶ller said the Inventory for Depressive Symptomatology-Clinician (IDS-C) may be a better alternative rating scale. Finally, reversal of vegetative symptoms (e.g., hypersomnia, hyperphagia, weight gain) and the relative mildness of symptoms and psychiatric comorbidity may lead to under diagnosis, as may the prominence in DSM-IV of the criterion of mood reactivity, which may not always be present.

A number of studies have revealed neurobiological differences between typical and atypical depression, most notably the lack of response to psychopharmacotherapy among atypical depression patients, but in a manner different from typical depressive patients. While atypical patients have lower responses to tricyclic antidepressants, MAOIs have better efficacy in this form of depression.

Dr. M?¶ller suggested that ICD-10 criteria for atypical depression should be modified according to the DSM-IV, and he said more professional education is needed to enhance recognition of the features of atypical depression.

Evidence-Based Management of Atypical Depression

Most studies on atypical depression have focused on younger patients. But late-onset disease is particularly troublesome as this patient population has less favorable responses to treatment and is more likely to develop resistance to medications. Because of its generally chronic course, atypical depression patients often require long term treatment. Besides pharmacotherapy, cognitive behavior therapy has been used successfully although evidence for its efficacy has been lacking.

Justine Kent, M.D., an adjunct assistant professor of psychiatry at Columbia College of Physicians and Surgeons in New York and vice-president and medical director at Comprehensive NeuroScience, Inc. in White Plains, N.Y., reviewed some pharmacologic and behavioral approaches to the management of atypical depression.

She began with a discussion of cognitive therapy (CT). In a study of 27 patients meeting the Columbia criteria for atypical depression, 56% responded to CT. Non-responders were given pharmacotherapy, to which 63% responded. She concluded that there may be subpopulations among atypical depression patients who respond better to one form of therapy or another.

In another study both CT and Nardil (phenelzine), an MAOI, produced similar positive results on HAM-D scores at 10 weeks when compared with placebo. Therefore, CT can be a viable alternative to drugs for some patients, and the two modalities may effectively treat differing populations of patients with atypical depression.

MAOIs have long been considered the gold standard in the treatment of atypical depression based on numerous efficacy studies. But because of the “tyramine effect,” in which a build up of tyramine from inhibition of monoamine oxidase in the gut can cause hypertensive crisis and other untoward effects, MAOI use has required inconvenient dietary restrictions.

More modern antidepressants include SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and, still in development, gepirone. Alternative or “nutriceutical” treatments include chromium picolinate and St. John’s wort. Among the tricyclic antidepressants, imipramine is the best studied but has been shown to be less effective than the MAOI Nardil in several placebo-controlled trials in atypical depression. In typical depression, imipramine has been shown to be effective.

Moclobemide, a reversible MAOI, was shown to have superior efficacy compared to fluoxetine in a controlled trial. One study found no difference between Prozac (fluoxetine) and Nardil.

Gepirone is a 5-HT1A partial agonist. When dosed at 30 to 120 mg/day in a randomized, placebo controlled trial of 60 patients, the response rate for the intent-to-treat sample was 62% for gepirone and 20% for placebo (P

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An Onion a Day May Repel Pancreatic Cancer

NUTHETAL, Germany, Oct. 4 — An onion a day may help fend off pancreatic cancer, researchers here said.

Apples, on the other hand, may not, Ute N?¶thlings, Ph.D., of the German Institute of Human Nutrition Potsdam-Rehbruecke, and colleagues in California and Hawaii, reported in the October issue of the American Journal of Epidemiology.

The finding comes from the Multiethnic Cohort Study, which collected baseline data — including dietary information — on more than 215,000 people ages 45 to 75 from 1993 through 1996 in California and Hawaii, said Dr. N?¶thlings and colleagues.

For this analysis, the researchers looked at possible links between flavonols — a class of polyphenols found in fruits and vegetables and thought to have cancer-fighting properties — and the risk of pancreatic cancer.

Data were available on 183,518 participants, Dr. N?¶thlings and colleagues reported. Among those, during eight years of follow-up, there were 529 cases of exocrine pancreatic cancer.

Dr. N?¶thlings and colleagues examined consumption of three flavonols — quercetin, most abundant in onions and apples; kaempferol, found in spinach and some cabbages; and myricetin, found mostly in red onions and berries — as well as the total flavonol intake.

The bottom line was that total flavonol consumption was associated with a lower risk of pancreatic cancer: When the researchers compared the lowest quintile of total intake to the highest, the relative risk was 0.77, and the trend was significant at P=0.046.

But some foods appeared to be better than others, the researchers said.

Onions and black tea appeared to show “modest inverse associations” with pancreatic cancer, although the trends were not significant (P=0.056 and P=0.07, respectively), the researchers said.

Apples and green, herbal, or other teas, on the other hand, showed no such associations.

A Cox regression analysis showed that kaempferol was associated with a significant reduction in cancer risk. When the lowest and highest quintile were compared, the relative risk reduction was 0.78, and the trend was significant at P=0.017.

Neither quercetin nor myricetin was associated with a reduced risk in the overall cohort.

On the other hand, among smokers total consumption and each of the flavonols individually was associated with reduced risk. When the lowest and highest quintiles were compared:

Total consumption was associated with a relative risk reduction of 0.41, and the trend was significant at P=0.002.
Quercetin consumption was associated with a relative risk reduction of 0.55, and the trend was significant at P=0.008.
Kaempferol was associated with a relative risk reduction of 0.27, and the trend was significant at P<0.0008.
And myricetin was associated with a relative risk reduction of 0.55, and the trend was significant at P=0.044.

“The effect was largest in smokers, presumably because they are at increased pancreatic cancer risk already,” Dr. N?¶thlings said at the American Association for Cancer Research meeting in April, where some of the data was presented.

Smoking is the only established risk factor for pancreatic cancer, Dr. N?¶thlings said.

The study is limited because “some degree of measurement error in the estimation of flavonol intake was certainly present,” the researchers said. But the questionnaire used was designed to capture a range of foods and mixed dishes, which may reduce the error, they added.

Dr. N?¶thlings and colleagues said similar studies are needed in other groups and regions of the world to confirm the findings.

The study was supported by the National Cancer Institute. The authors of the original publication have reported that they have no conflicts of interest.

Primary source: American Journal of Epidemiology

Source reference:

N?¶thlings U et al. “Flavonols and Pancreatic Cancer Risk: The Multiethnic Cohort Study.” Am J Epidemiology 2007; 166 (8): 924-31.

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APSS: Poor Sleep and Insomnia May Lead to Impaired Nutrition

MINNEAPOLIS, June 13 — Poor sleepers may be too tired during the day to eat properly, according to researchers here.

Yet by increasing the amount of sleep time — or at least the amount of time in bed before getting up — there may be a reduction in caloric intake, researchers reported at the Associated Professional Sleep Societies meeting.

“Persons with sleep complaints such as insomnia are less likely to eat at home,” said psychologist Mindy Engle-Friedman, Ph.D., of Baruch College of the City University of New York. “These meals outside the home may require less effort and may be less healthful than meals prepared at home.”

“Over time, persons with sleep complaints may have weight or health problems related to their nutrition,” she said.

She studied the sleep and diet of 21 healthy undergraduates — 12 men and nine women — for seven days. She said the differences between those eating at home and those who ate more in restaurants reached statistical significance (P

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U.S. Obesity Numbers Continue to Swell

Americans are still getting fatter, according to a new report issued by two public health groups.

In the past year, obesity rates rose in 16 states and fell in none, according to the eighth annual “F As In Fat” report, prepared jointly by the Trust for America’s Health and the Robert Wood Johnson Foundation.

Twelve states now have obesity rates of 30% or more, led by Mississippi at 34.4%, the report says. That’s up from a single state over 30% four years ago.

On the other hand, only 11 states and the District of Columbia had rates under 25%, down from 19 three years ago.

Only one state remains below 20%, the report says — Colorado is at 19.8%.

“There was a clear tipping point in our national weight gain over the last twenty years,” according to Jeff Levi, PhD, executive director of the Trust for America’s Health.

The swollen numbers are having an effect on the health of Americans, with marked increases in diabetes and hypertension, the report says.

“We can’t afford to ignore the impact obesity has on our health and corresponding health care spending,” Levi said in a statement.

The report is issued yearly by the two groups, but this is the first time it has looked at trends in obesity, according to a news release accompanying the report.

Among the findings: In 1991, no state had more than 15% of its people classed as obese, with a body mass index of 30 or more. In 2011, 38 states have obesity rates higher than 25% percent – more than one out of three. Since 1995, obesity rates have doubled in seven states and increased by at least 90% in another 10. Nine of the top 10 states in obesity rates are in the South – in order after Mississippi, they are Alabama, West Virginia, Tennessee, Louisiana, Kentucky, Oklahoma, South Carolina, and Arkansas. Michigan is number 10 on the obesity scale.

It’s a “debilitating and costly epidemic,” said Risa Lavizzo-Mourey, MD, president and CEO of the Robert Wood Johnson Foundation.

The information in the report “should spur us all” to develop ways to reverse the growing problem, Lavizzo-Mourey said in a statement.

Aside from the state-by-state data, the report also found ethnic, racial and socioeconomic variations in obesity: Among adult blacks, obesity rates were higher than 40% in 15 states, higher than 35% in 35, and higher than 30% in 42 states and the District of Columbia. Among Latinos, rates were above 35% in four states and 30% or more in 23. At the same time, adult obesity rates among whites were higher than 30% in only four states and nowhere higher than 32.1%. Nearly 33% of those who didn’t finish high school are obese, but only 21.5% of those who graduated from college or technical college. Among those who earned less than $15,000 a year, more than 33% were obese, compared with 24.6% of those who earned at least $50,000 annually.

Among other things, the report urges more money for obesity prevention, tough standards for school lunches and other foods sold to children outside of school meal programs, and implementation of strategies to increase physical activity.

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BES: Cell-Level Responses Altered in GH-Normal Undersize Kids

MANCHESTER, England — Children born small who remain undersized despite normal growth hormone levels show an unusual pattern of responsiveness to insulin-like growth factor-1 (IGF-1) and growth hormone, a researcher said here.

Lab studies indicated that cell proliferation in response to IGF-1 was reduced and turnover was higher than normal in cells taken from children born small for their gestational age who fail to catch up, said Imogen Butcher, a doctoral candidate at the University of Manchester here.

In a poster presentation at the Society for Endocrinology meeting, also held here, Butcher said the findings were among the first clues as to why children may show marked growth deficits even though they produce growth-related hormones in normal quantities.

Many children are undersized at birth relative to the norm for their gestational age but, normally, “about 90% catch up” within a few years, Butcher said.

However, about 1,500 of those born annually in Great Britain remain small, more than two standard deviations less than the mean. For a 5-year-old, Butcher explained, that would mean being the size of a toddler.

In many of these children, no endocrine abnormality can be found.

As a dissertation project, Butcher has been conducting in vitro experiments with fibroblasts from these children and from those of age-matched growth-normal children to identify alterations in signaling associated with growth related hormones.

She found that, under basal and GH stimulated conditions, proliferation in SGA cells was comparable to controls, whereas response to IGF-1 over five days was significantly reduced to about two-thirds the rate of cells from normal children (P<0.001). However, when treated with a combination of GH and IGF-1 SGA, cells grew at a similar rate to controls.

Moreover, growth rates with the hormone combination in cells from undersized children were much greater than for either hormone alone.

Another difference between cells from the two groups of children was that apoptosis was higher in those from the undersized group. About 35% of cells from those children were undergoing apoptosis when placed in serum starving medium, compared with 30% of those from normal children (P<0.001).

Because apoptosis is an indicator of cell turnover, which occurs naturally, the finding indicated that this process is speeded up significantly in the growth-deficient group.

Butcher also found that treating these stressed cells with growth hormone or IGF-1 reduced apoptosis rates. But those rates still remained higher in the cells from undersized children compared with the control cells, she said.

Finally, Butcher examined the effects of the two hormones on intracellular signaling molecules, including Stat5b, Akt, and MAPK, known to mediate cellular responses to these growth factors.

Stat5b activation in response to growth hormone was diminished in the cells from undersized children, she discovered.

In contrast, IGF-1 activated Akt to a stronger degree in the cells from growth-deficient children relative to the normal cells.

Butcher said the findings did not entirely clear up the mystery of why growth remains impaired in these children. But the finding that co-treatment with IGF-1 and growth hormone “rescues” cell growth, at least in vitro, suggests that a similar approach might be helpful clinically.

Recombinant versions of both hormones are available commercially. Some forms of growth hormone (Genotropin, Norditropin) are FDA approved for children born small for gestational age whose growth does not catch up. IGF-1 (Increlex) is approved only for children deficient in IGF-1 or in those deficient in growth hormone who also have neutralizing antibodies against it.

The study was funded by Novo Nordisk.

Other than the research funding, Butcher reported no potential conflicts of interest.

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Sputum Guidance Increases Rate of TB Detection

LONDON, June 8 — Women in developing countries are less likely than men to test positive for tuberculosis because they don’t know how to expectorate sputum properly.

In a pragmatic randomized trial in Rawalpindi, Pakistan, a few minutes of instruction in proper expectoration techniques increased the proportion of women who were smear-positive for TB by 63%, according to Mishal Sameer Khan, M.Sc., of the London School of Hygiene and Tropical Medicine here.

Sputum-submission guidance also increased the proportion of men who tested positive, but the difference from the control group wasn’t significant, Khan and colleagues reported in the June 9 issue of The Lancet.

(American TB experts said that patients in the U.S. also may need instruction in how to raise secretions from the lower respiratory tract. Too often, said one authority, they provide saliva instead.)

The researchers enrolled 3,055 men and women suspected of having TB who came to Rawalpindi’s Federal Tuberculosis Center for tests in 2005 from May through July.

Of those, 771 men and 749 women were randomly assigned to get a two-minute set of instructions on how to give a proper sputum sample and then were asked to provide a spot sample and an early-morning specimen taken upon awakening.

Patients in the control group were asked for the two samples only.

The instruction session explained the difference between sputum and saliva, emphasized the need for sputum, demonstrated the proper technique for spitting up sputum (three deep breaths, followed by a deep cough), and told patients to fill at least a quarter of the container.

The study found that:

Instructed women were more likely to test smear-positive than were women in the control group. The risk ratio was 1.63, with a 95% confidence interval from 1.19 to 2.22, which was significant at P=0.002.
13% of women in the instructed group, compared to 8% of those in the control group, were smear-positive.
Instructions were also associated with a significantly lower rate of saliva submission in the spot samples and significantly more women returning with an early-morning specimen (at P=0.003 and P=0.02, respectively).

There were no significant differences among the men, Khan and colleagues reported, although the rate of smear-positive samples tended to be higher among the instructed men than controls (11.7% versus 9.9%).

Overall, the intervention led to 49 additional cases being detected, the researchers said, with a cost of $2 per additional case.

The researchers noted that the intervention is cheap and easy to implement and therefore should be useful in resource-limited settings. They added that the large sample size and the real-world nature of the patient group imply that the results should generalize easily.

“Sputum-submission guidance is probably beneficial in settings where patients, particularly women, have little knowledge about tuberculosis and where saliva submission rates are high,” they said.

The quality of the study is high, according to Bachti Alisjahbana, M.D., of Hasan Sadikin Hospital in Bandung, Indonesia and Reinout van Crevel, M.D., of Radboud University Nijmegen Medical Center in the Netherlands.

“Developing countries see too few studies, such as Khan’s, that provide scientific evidence for decisions in health-service provision,” they said in an accompanying editorial.

Combining sputum instruction with other interventions, such as the education of health professionals or more sensitive diagnostic methods, “might further improve the diagnosis of tuberculosis,” they concluded.

The research was supported by the British Department for International Development. The authors reported they had no conflicts in interest. Also Drs. Alisjahbana and van Crevel said they had no conflicts.

Primary source: The Lancet

Source reference:
Khan MS et al. “Improvement of tuberculosis case detection and reduction of discrepancies between men and women by simple sputum-submission instructions: a pragmatic randomized controlled trial.” Lancet 2007; 369: 1955-60.

Additional source: The Lancet

Source reference:
Alisjahbana B and van Crevel R. “Improved diagnosis of tuberculosis by better sputum quality.” Lancet 2007; 369:1908-09.

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Virus Unlikely to Advance Deadly Lung Disease: Study

Most patients struggling with a progressive and fatal form of lung disease called idiopathic pulmonary fibrosis do not risk a worsening of their condition as a result of exposure to a viral infection, new research indicates.

The finding contradicts prior investigations that had suggested viral infections might rapidly advance disease in patients diagnosed with idiopathic pulmonary fibrosis (IPF).

“The results of this study suggest that the majority of cases of acute exacerbation of IPF are not due to viral infection,” study author Dr. Harold Collard, director of the Interstitial Lung Disease Program at the University of California, San Francisco (UCSF), said in a news release from the American Thoracic Society.

Collard and colleagues from the United States, Korea and Japan report their observations online in advance of publication in an upcoming print issue of the American Journal of Respiratory and Critical Care Medicine.

The authors noted that IPF is characterized by the thickening and scarring of the lungs, and most often affects men and women in their 50s, 60s and 70s.

The stiffening of lung tissue that occurs in those with the disease ultimately compromises respiratory function. In some cases, the ongoing and debilitating process unfolds slowly. However, in others, a more aggressive process takes hold in the form of an “acute” phase with more rapid consequences.

To see whether or not a viral infection might trigger the onset of this acute process, between 2006 and 2009, Collard’s team focused on 43 patients from two health facilities, all of whom had already been diagnosed with the harsher and speedier form of the disease. For comparison, 69 patients from a different medical center were also included, all of whom were diagnosed with either the slower-moving (“stable”) form of IPF or, alternatively, an acute lung injury.

After collecting lung fluid and blood samples from all of the patients, the investigators performed a series of high-tech DNA tests to look for signs of viral infection.

The results: while no evidence of viral infection was found in the “stable” IPF patients, only four of the “acute” IPF patients were infected with a tell-tale common respiratory virus.

“The presence of respiratory viral infections in these four IPF patients suggests that a small minority of acute exacerbations of IPF may be caused by occult infection with common respiratory viruses,” said Collard, who is also an assistant clinical professor of medicine at UCSF.

Unexpectedly, however, the authors also found that about one-quarter of both the acute IPF group and the acute lung infection group were infected with a common, typically symptomless virus known as the torque teno virus, or TTV. The virus was not found among any of the stable IPF patients.

The team cautioned that more research is needed to determine in what way TTV infection (which is usually associated with hepatitis) might be linked to IPF.

More information

For more on idiopathic pulmonary fibrosis, visit the U.S. National Heart, Lung and Blood Institute.

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IDSA: Younger Docs Less Sold on Value of Vaccines

BOSTON — The value of childhood vaccination is less apparent to younger doctors than to their older counterparts, a researcher said here.
In a cross-sectional survey of 551 healthcare providers, more recent graduates were less likely to think that vaccines were efficacious, according to Saad Omer, MBBS, PhD, of Emory University in Atlanta.
They were also more likely to have doubts about the safety of some vaccines, Omer told reporters at the annual meeting of the Infectious Diseases Society of America.
Overall, however, the physicians who took part in the survey remained highly supportive of childhood vaccines, Omer told MedPage Today, with nearly 90% agreeing that vaccines are getting better and safer.

“What we picked up were relative differences – relative, subtle, but important differences,” he said.

The findings are significant because doctors are one of the most powerful influences on parental decisions about vaccination, he said.

They signal “a potentially important change in immunization beliefs in the new generation of providers, compared with their older counterparts,” he and co-author Michelle Mergler, MHS, of Johns Hopkins Bloomberg School of Public Health, argued in their poster presentation.

“For a long time, we’ve suspected this kind of thing,” commented Bruce Gellin, MD, director of the National Vaccine Program Office in Washington, who was not involved in the study but who moderated a press conference at which some details were presented.

“As familiarity with the disease goes away, they’re only hearing about the vaccine and don’t often link up with what the vaccines are designed to do,” Gellin said. “In some ways this mimics the situation in society at large, where young parents are not familiar with these diseases.”

“This tells us where we need to focus our efforts,” he added.

The researchers questioned healthcare providers identified by a cohort of parents in Colorado, Massachusetts, Missouri, and Washington whose children were either fully vaccinated or exempt from one or more school immunization requirements.

All told, 84.3% of the doctors answered the questionnaire, which asked for their views on the risk of a range of vaccine-preventable diseases, including polio and influenza, and their opinions on the efficacy and safety of vaccines against them.

The researchers stratified the participants into five-year blocks, depending on the year they graduated from medical school, and used logistic regression methods to look for associations between beliefs and time since beginning practice.

They found: Most doctors – 81.2% — agreed that vaccines are one of the safest forms of medicine ever developed, and 89.1% thought that they were getting both safer and more effective. In both cases, each increase of five years in the year of graduation was associated with 20% decrease in the odds of a doctor believing the statements were true. (The odds ratio was 0.80 for both, with 95% confidence intervals from 0.7 to 0.9 and 0.7 to 1.0, respectively.) Each increase of five years in the year of graduation was also associated with a significant 18% reduction in the odds that a doctor would believe in high vaccine efficacy overall. Although there was a similar reduction in the belief in safety, it did not reach significance overall. However, younger doctors were significantly more likely to question the safety of vaccines against polio (both inactivated and oral), varicella, and measles/mumps/rubella.

In one way, Omer said, the finding may be a result of the very success of vaccination programs. “With such a low burden of disease, the efficacy and real or perceived side effects of vaccines may be the most significant factors contributing to vaccination behaviors,” he and Mergler argued.

The researchers did not report external support for the study. They said they had no disclosures.

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Obese Account for Greatest Jump in Healthcare Costs

LITTLE FALLS, N.J., July 9 — Healthcare spending on obese patients in the U.S. has ballooned, growing more than 80% over a five-year period, researchers have found.

Spending on the heaviest members of the population rose to $303.1 billion in 2006 from $166.7 billion in 2001 — an 82% increase, according to a statistical brief from the Agency for Healthcare Research & Quality.

That figure compares with a 36% increase in total expenditures for patients who were merely overweight and a 25% increase for normal-weight patients.

The increase in spending on healthcare for overweight and obese Americans tracks the general rise in obesity in the U.S., as the number of obese jumped to 58.9 million from 48.2 million over the study period, according to Marie Stagnitti, MPA, a senior statistician with the AHRQ, and author of the brief.

As a result, in 2006 overweight and obese adults represented 27.2% of the U.S. population, up from 23.6% in 2001. Conversely, the proportion of normal-weight individuals decreased from 39% to 36%.

“Obese adults were associated with over half of the growth in healthcare spending between 2001 and 2006, and that’s a remarkable figure,” said Ken Thorpe, PhD, chair of health policy at Emory University, who was not involved in the study.

“Also, there are more people who are clinically obese . . . so it’s really a combination of both” elements that is driving spending, he told MedPage Today.

Dr. Thorpe said that over time, more obese patients are being diagnosed with more chronic health problems, including diabetes, cholesterol, and heart disease, which also drives spending.

The data confirm that observation, as the AHRQ report revealed that obese patients continuously had the highest proportion of chronic conditions — 57.1% in 2001 compared with 59.7% in 2006.

When it comes to total healthcare expenditures, the obese accounted for 35.3% of the bill in 2006, up from 28.1% in 2001.

Normal-weight patients have accounted for less of the bill, dropping from 35% to 30.3% over the study period.

But while obese and overweight patients may account for a larger share of the healthcare dollar, even fit Americans faced higher healthcare costs during the five years studied.

The average annual healthcare expenditure for the obese population increased to $5,148 from $3,458 over five years and jumped to $3,636 from $2,792 for the overweight population.

Normal-weight patients spent an average of $3,315 in 2006 compared with from $2,607 in 2001.

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Abstinence-Only Programs May Withhold Valuable Health Information

NEW YORK, Jan. 6-Abstinence-only education programs are not turning out to be a panacea for the problems inherent in adolescent and premarital sex.

Indeed, they may deprive adolescents and young adults of critical sexual health information that could protect them from potentially life-threatening sexually transmitted diseases, researchers here reported in a literature review in the January issue of Journal of Adolescent Health.

The review suggested that while abstinence-only programs may offer some benefit, young people remain misinformed about contracting sexually transmitted diseases (STDs) through sexual activities other than intercourse, like oral sex or manual stimulation.

Another problem is that many teens simply fail to remain abstinent, added John Santelli, M.D., MPH, professor and chair of the department of clinical population and family health at Columbia University here.

The review he and his colleagues published showed that for women, the median age of first intercourse was 17.4 years while the median age at first marriage was 25.3 years. For men, those figures were 17.7 years and 27.1 years, respectively.

The evidence they found showed that more than 800,000 adolescents become pregnant every year, with 80% of these pregnancies being unintended.

Data in 2000 showed than there were 18.9 million sexually transmitted infections, and almost half of these occurred among individuals under age 25. Their review also showed that 50% of new HIV infections occur among people under age 25, with 25% of these infections occurring among young people ages 22 and under.

In many communities, abstinence-only programs are “replacing comprehensive sexuality education,” the authors wrote. Abstinence should be encouraged, they said, but not to the exclusion of important sexual health information.

“Abstinence is a very healthy choice for teenagers,” Dr. Santelli said, “but sex education for teenagers needs to give teenagers all the facts, all the medically accurate information they need to protect themselves.”

Dr. Santelli and colleagues went on to say that it was unethical for misinformation to be distributed or withheld from adolescents.

“An oncologist who presented only the benefits of chemotherapy and only the risks from radiation therapy would be denounced as failing in his or her obligations to the patient,” they wrote. The same holds true for health care professionals who do not provide all the necessary information available for young people to protect themselves from HIV, other STDs, and pregnancy, they said.

Abstinence-only sex education programs have been increasing in popularity, and federal funding for these programs has jumped significantly over the past decade, from $60 million in 1998 to $168 in 2005.

Yet the review by Dr. Santelli and colleagues showed that 90% of parents of middle- and high school-aged children supported sex education in school, compared with only 7% who thought sex education did not belong in schools. Only 15% of the parents said they wanted an abstinence — only form of sex education, the authors reported.

Dr. Santelli and his team conducted their literature review by searching Medline and Google Scholar for reports about abstinence-only education. They also tracked newspaper reports and internet list serves that covered the issue between January 2004 and July 2005 to read about the latest studies or reports.

Included in their evaluation were looks at current policies, adolescent pregnancy rates, and the impact of abstinence-only programs on sexually active youth, including homosexual adolescents.

Polls have shown that 99% of parents of middle- and high school-aged children support providing information on STDs and 95% supported teaching young people that sexual intercourse should be postponed into adulthood. Eighty-six percent of the parents supported having their children learn about how and where to obtain contraception.

Dr. Santelli also noted that in these polls, parents and adolescents “do not see education that stresses abstinence while also providing information about contraception as a mixed message.”

While parents appear supportive of teaching their children both abstinence and ways to protect against STDs and pregnancy, current government policies appear to suggest that there is no room for sexual health information in abstinence-only education. They also noted that many faith-based organizations are receiving increased funding to promote an abstinence-only message.

Their review indicated, for example, that contraceptive methods should not be discussed and that contraceptive failure rates should be emphasized in abstinence-only programs. “Three states, including, most recently, Maine, have refused federal abstinence-only education funding given federal restrictions on providing information about contraception,” Dr. Santelli and colleagues wrote.

Further analysis showed that data from the 2000 School Health Policies and Programs Study showed that only 21% of junior high school teachers and 55% of high school teachers taught the correct use of condoms.

When looking at gay, lesbian, bisexual, transgender, and questioning youth (those who are unsure of their sexual orientation), the authors asserted that abstinence-only education was “unlikely to meet the health needs” of this population because abstinence-only programs focus heavily on no sex until marriage and ignore homosexuality. This could lead to increased risk of infection among these youngsters, the investigators said.

The research team also looked at last year’s virginity pledge debate. A Yale study based on the National Longitudinal Study of Adolescent Health and published in the April 2005 issue of this same journal suggested that virginity pledges, which are heavily promoted in abstinence-only programs, failed to protect young people from STDs.

A few months later, the Heritage Foundation criticized the conclusions of that study citing serious flaws in the Yale researchers’ analysis.

“Schools and health care providers should encourage abstinence as an important option for adolescents,” the researchers concluded. “However, ‘abstinence-only’ as a basis for health policy and programs should be abandoned.”

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