Trial Confirms Efficacy of HPV Vaccine, Shows Cross-Protection

End-of-trial results from a trial testing Cervarix, a vaccine against human papillomavirus (HPV) types 16 and 18, showed that the vaccine continued to provide substantial protection against cervical precancers 4 years after vaccination. Cervarix provided almost complete protection in young women who had no evidence of exposure to HPV at the time of vaccination. The vaccine provided less protection for the total vaccinated cohort and was less effective with increasing age at vaccination. These findings reflect the vaccine’s lack of effectiveness against infections acquired before vaccination.

The vaccine also partially protected women against four types of HPV that are not targeted by the vaccine. (Although HPV-16 and -18 cause about 70 percent of cervical cancers worldwide, as many as 15 HPV types can cause cancer.) These results from the PATRICIA trial (Papilloma Trial against Cancer in Young Adults) were published online November 9 in Lancet Oncology in two separate papers, available here and here.

The PATRICIA trial enrolled 18,644 young women between the ages of 15 and 25 from 14 countries. The participants were randomly assigned to receive either three doses of Cervarix or three doses of a hepatitis A vaccine as a control. Results from the interim analysis, published in July 2009, showed that the vaccine greatly reduced the risk of grade 2 cervical intraepithelial neoplasias and higher (CIN2+).

The new analysis shows that, 4 years after vaccination, Cervarix provided complete protection against grade 3 cervical intraepithelial neoplasias or higher (CIN3+) associated with HPV-16 and -18 among women who had no evidence of exposure to HPV. The vaccine provided strong protection against CIN3+ caused by other HPV types in this same group of women. Among the total cohort of women who received at least one dose of Cervarix, some of whom may have had prior exposure to HPV, the vaccine provided some protection. (See the table below.)

Cervarix Vaccine Efficacy among Women Who Received at Least One Dose of Cervarix

Women with no evidence of HPV exposure at baseline Women who may have had prior exposure to HPV
Against CIN3+ associated with HPV-16 and -18 100 percent 45.7 percent
Against all CIN3+, regardless of HPV type 93.2 percent 45.6 percent
Against all adenocarcinoma in situ 100 percent 76.9 percent

The vaccine provided cross-protection against HPV-33, HPV-31, HPV-45, and HPV-51, all cancer-causing types of the virus. The researchers speculate that the observed cross-protection may be due either to the vaccine adjuvant (a substance that stimulates the immune system) or to similarities among proteins found on the surfaces of different HPV types.

In an accompanying editorial, Drs. Mark Schiffman and Sholom Wacholder of NCI’s Division of Cancer Epidemiology and Genetics, who were involved with the NCI Costa Rica HPV vaccine trial, noted the importance of the PATRICIA trial results. They also stated that “the practical aspects of vaccine uptake are now the most important issue in HPV vaccine research from a public health perspective.” To increase vaccine uptake in the developing world, where 90 percent of cervical cancer cases occur, next-generation HPV vaccines will need to be less expensive, provide protection in a single dose, and/or be stable without refrigeration, they explained.


Survey of Oncologists Suggests Lack of Progress in Cancer Pain Management

Results of a national survey show that U.S. medical oncologists receive inadequate training in cancer pain management and perceive numerous barriers to managing pain optimally in their patients. The results of the survey, conducted by Dr. Brenda Breuer and her colleagues at Beth Israel Medical Center in New York, were published online November 15 in the Journal of Clinical Oncology (JCO).

The survey, which was modeled in part after a 1990 survey conducted by the Eastern Cooperative Oncology Group (ECOG), “demonstrated disturbingly little progress” in attitudes and practices related to pain management among medical oncologists over the last 20 years, according to an accompanying editorial. Yet during this time, guidelines for managing cancer pain have been developed and disseminated, continuing medical education on the subject has become common, and access to pain specialists has increased, the study authors noted.

Dr. Breuer and her colleagues mailed the anonymous survey to a randomly selected, geographically representative sample of 2,000 medical oncologists, and 610 usable surveys (32 percent) were returned.

In the survey, oncologists gave their medical specialty good marks (a median rating of 7 on a scale of 0 to 10) for relieving cancer pain but rated their peers as more conservative than themselves in prescribing opioid drugs to manage pain. And although most respondents agreed with the basic principles of pain management, their responses to two challenging clinical scenarios presented in the survey suggest that a majority of oncologists are deficient in knowledge about opioids, the study authors reported.

As in the 1990 survey, “oncologists continue to perceive that the most significant barriers to adequate pain management are poor pain assessment, patient reluctance to report pain, and patient reluctance to take analgesics,” Dr. Breuer and her co-authors wrote. Furthermore, “poor ratings of pain management training [during medical school and residency] have barely changed” in the two decades since the 1990 ECOG survey.

“There is a worldwide outcry for adequate cancer pain management, yet the skills of many oncologists remain inadequate in this domain,” commented the authors of the editorial, Dr. Jamie H. Von Roenn of Northwestern University, who was also the lead author of the ECOG survey, and Dr. Charles von Gunten of the Institute of Palliative Medicine at San Diego Hospice. “If we are to provide patients the care they deserve, we must not just integrate training in pain management into every fellowship program, we must expect oncologists to practice what they learn.”


Nephrocalcinosis and urolithiasis in children

The incidence of adult urolithiasis has increased significantly in industrialized countries over the past decades. Sound incidence rates are not available for children, nor are they known for nephrocalcinosis, which can appear as a single entity or together with urolithiasis. In contrast to the adult kidney stone patient, where environmental factors are the main cause, genetic and/or metabolic disorders are the main reason for childhood nephrocalcinosis and urolithiasis. While hypercalciuria is considered to be the most frequent risk factor, several other metabolic disorders such as hypocitraturia or hyperoxaluria, as well as a variety of renal tubular diseases, e.g., Dent’s disease or renal tubular acidosis, have to be ruled out by urine and/or blood analysis. Associated symptoms such as growth retardation, intestinal absorption, or bone demineralization should be evaluated for diagnostic and therapeutic purposes. Preterm infants are a special risk population with a high incidence of nephrocalcinosis arising from immature kidney, medication, and hypocitraturia. In children, concise evaluation will reveal an underlying pathomechanism in >75% of patients. Early treatment reducing urinary saturation of the soluble by increasing fluid intake and by providing crystallization inhibitors, as well as disease-specific medication, are mandatory to prevent recurrent kidney stones and/or progressive nephrocalcinosis, and consequently deterioration of renal function.

source:Kidney International


Artificial Hips: Newer Might Not Be Better

Jury Still Out on Which Implants Are Safest and Most Durable.
womans hip

Traditional hip implants might be safer and last longer than some new ones, an FDA-funded study finds.

It’s among the first studies to compare outcomes in people who got different kinds of artificial hip implants with different materials.

When researchers evaluated total hip-replacement data from studies and national registries, they found no advantage for the newer metal-on-metal or ceramic-on-ceramic devices, compared with traditional metal-on-polyethylene or ceramic-on-polyethylene ones.

The available evidence suggests that traditional hip replacement devices work as well as newer, costlier implants and might last longer than at least some newer artificial hips.

The researchers conclude that manufacturers of the newer implants cannot claim that their devices are better than traditional ones.

But others feel that more research is needed to draw any strong conclusions.

All-Metal Implants Under Fire

More than 270,000 hip replacements are performed in the United States, and that number is projected to double over the next decade.

The surgery is very effective for improving mobility, but many patients need an additional operation within 10 to 15 years to replace worn out, damaged, or displaced parts.

The hope has been that the newer hip replacement devices would last longer than traditional implants.

All-metal implants have been especially popular with orthopedic surgeons in the U.S. since the introduction of a new generation of the devices in the late 1990s, but their use has declined sharply over the past year or so as concerns about their safety and durability have emerged.

Last May, FDA officials expressed concerns that the metal-on-metal implants may make people sick by releasing toxic metal ions into the bloodstream. The agency ordered 21 manufacturers that market the devices to study the issue.

In August, two all-metal implants were voluntarily removed from the market by manufacturer Johnson & Johnson following complaints that the devices failed years earlier than expected in many patients.

And in September, a British hip replacement registry found more widespread evidence of early failure for the metal-on-metal devices.

‘Many Metal-on-Metal Implants Working Well’

Joshua J. Jacobs, MD, second vice president of the American Academy of Orthopaedic Surgeons, says while some metal-on-metal hip replacement devices do appear to be prone to early failure, others probably are not.

“As of now, most metal-on-metal devices that have been implanted in the United States are working well,” he tells WebMD.

But he adds that people who have them should not ignore pain, swelling, or numbness around the area of the implant.

“It is important to seek the advice of an orthopedic surgeon without delay just in case a problem is brewing,” he says.

In the new research review, published online in the journal BMJ, researcher Art Sedrakyan, MD, PhD, of New York’s Weill Cornell Medical College and colleagues looked at 18 studies including more than 3,000 patients as well as outcomes from 830,000 hip replacement surgeries reported to various national registries.

The three largest national surgical registries showed evidence of higher rates of early implant failure associated with metal-on-metal devices, compared to metal-on-polyethylene implants.

One study showed fewer repeat surgeries for device failure for ceramic-on-ceramic implants, but the national registries data did not support this finding.

Sedrakyan tells WebMD that larger studies with longer follow-up times will be needed to determine the differences between the various devices.

Jacobs says the fact that the researchers had to consider all metal-on-metal, ceramic-on-ceramic, and polyethylene-containing devices together limited the findings.

“By necessity, this analysis was done by class, but it is important to recognize that within these broader classes some devices are performing better than others,” he says.


Most Americans With HIV Don’t Have Infection Under Control

Medications Can Help Suppress the Virus, but Many Don’t Take Them.
hi virus invading cell

Nearly three-quarters of Americans with HIV don’t have their infection under control. That’s in large part because they may not know they have HIV or because they aren’t taking drugs that suppress the virus, according to a new study from the CDC.

The study is published in the Morbidity and Mortality Weekly Report. It is being released in advance of World AIDS Day, Thursday, Dec. 1.

The report reveals that 1.2 million people in the U.S. are living with HIV, but only 28% take drugs to keep the amount of the virus in their bodies low.

A low “viral load” helps people with HIV stay healthy and reduces the chance they’ll transmit the virus to others. Untreated HIV infection can lead to AIDS.

The virus can be suppressed by antiretroviral drugs, sometimes for decades.

But the study’s authors say that one in five people who are infected with HIV do not know it. Of those who are aware of their HIV-positive status, slightly more than half receive ongoing treatment.

Testing and Treatment for HIV Lags in U.S.

“The HIV crisis in America is far from over,” Jonathan Mermin, MD, director of the Division of HIV/AIDS Prevention at the CDC in Atlanta, said in a news briefing.

“Closing the gaps in testing, care, and treatment will all be essential to slowing or reversing the U.S. AIDS epidemic,” he says.

Many people drop out of treatment because they struggle to afford health insurance or medication, or because they have mental health or substance abuse problems that make it difficult for them to take care of themselves, Mermin says.

The good news is that regular medical care and antiretroviral drugs work for most people with HIV.

More than three-quarters of those on regular drug regimens had suppressed the amount of virus circulating in their blood.

A previous study has shown that when people with HIV start treatment early and keep their viral loads low, they are 96% less likely to infect their partners.

“Treatment for HIV can prevent spread of HIV to others,” says CDC Director Thomas Frieden, MD, MPH.

“We have substantial work ahead to fully realize the potential benefit of treatment in the U.S.,” he says.

Racial Gaps in HIV

The study also found racial differences in HIV care.

Compared to whites, African-Americans and Hispanics were less likely to get antiretroviral drugs, and even if they were prescribed the medications, were less likely to achieve low viral loads.

The report also found that many people who are HIV-positive do not get information about how to prevent the spread of the disease to others.

Only about half of heterosexual men and women with HIV are counseled about precautions they should take to keep from infecting others, while only 39% of gay men with HIV get that information.

To help stem the tide of new infections, the CDC also launched a new awareness campaign aimed at gay and bisexual African-American men, who account for nearly one-quarter of all new HIV infections in this country.

The campaign, “Testing Makes Us Stronger,” will encourage these men to learn their HIV status.

“The need for this new campaign could not be clearer,” says Kevin Fenton, MD, director of the National Center for HIV/AIDS, Viral Hepatitis, STD and Tuberculosis Prevention, at the CDC.

He points to a recent 21-city study that found that nearly two-thirds of gay and bisexual African-American men who tested positive for HIV did not know they were infected.

The CDC recommends that all Americans be tested for HIV at least once during their lifetimes.

Those at high risk, such as those who have more than one sex partner, inject drugs, or are men who have sex with men, should be tested more frequently — at least once a year.


Low Vitamin D Levels Linked to Active Tuberculosis

Seasonal declines in mean vitamin D levels were followed by seasonal increases in TB notifications.

Extended sun exposure was a major component of the pre-antibiotic era treatment of tuberculosis (TB) in sanitariums, based on Nobel Prize–winning work showing that cutaneous TB responds to light therapy. Now, a cross-sectional study in Cape Town, South Africa, once again points to a role for vitamin D in TB.

Investigators measured vitamin D levels in 370 adults with latent or active TB between April 2005 and January 2010; about half of the participants were HIV positive. Vitamin D deficiency was highly prevalent, with 63% of the study population having serum 25-hydroxyvitamin D levels <50 nmol/L. Patients with active TB had significantly lower mean vitamin D levels than those with latent TB, with the association appearing even stronger for HIV-positive than for HIV-negative individuals. Vitamin D levels varied substantially by season — and TB notifications followed suit. The reporting of new TB cases was lowest in the months that immediately followed seasonal summer peaks in vitamin D levels — and highest in the months that followed seasonal troughs.

Comment: The authors acknowledge that, given the study design, they cannot exclude the possibility that the observed association is due to active TB lowering vitamin D levels. However, the study results are supported by in vitro work showing that the antimicrobial activity of macrophages is dependent on vitamin D. Clinical trials on the potential of vitamin D to prevent and treat TB seem warranted.

source:Journal Watch Infectious Diseases

The unusual γ-ray burst GRB 101225A from a helium star/neutron star merger at redshift 0.33

Long γ-ray bursts (GRBs) are the most dramatic examples of massive stellar deaths, often associated with supernovae1. They release ultra-relativistic jets, which produce non-thermal emission through synchrotron radiation as they interact with the surrounding medium2. Here we report observations of the unusual GRB 101225A. Its γ-ray emission was exceptionally long-lived and was followed by a bright X-ray transient with a hot thermal component and an unusual optical counterpart. During the first 10 days, the optical emission evolved as an expanding, cooling black body, after which an additional component, consistent with a faint supernova, emerged. We estimate its redshift to be z = 0.33 by fitting the spectral-energy distribution and light curve of the optical emission with a GRB-supernova template. Deep optical observations may have revealed a faint, unresolved host galaxy. Our proposed progenitor is a merger of a helium star with a neutron star that underwent a common envelope phase, expelling its hydrogen envelope. The resulting explosion created a GRB-like jet which became thermalized by interacting with the dense, previously ejected material, thus creating the observed black body, until finally the emission from the supernova dominated. An alternative explanation is a minor body falling onto a neutron star in the Galaxy.


Mutations causing syndromic autism define an axis of synaptic pathophysiology

Tuberous sclerosis complex and fragile X syndrome are genetic diseases characterized by intellectual disability and autism. Because both syndromes are caused by mutations in genes that regulate protein synthesis in neurons, it has been hypothesized that excessive protein synthesis is one core pathophysiological mechanism of intellectual disability and autism. Using electrophysiological and biochemical assays of neuronal protein synthesis in the hippocampus of Tsc2+/− and Fmr1−/y mice, here we show that synaptic dysfunction caused by these mutations actually falls at opposite ends of a physiological spectrum. Synaptic, biochemical and cognitive defects in these mutants are corrected by treatments that modulate metabotropic glutamate receptor 5 in opposite directions, and deficits in the mutants disappear when the mice are bred to carry both mutations. Thus, normal synaptic plasticity and cognition occur within an optimal range of metabotropic glutamate-receptor-mediated protein synthesis, and deviations in either direction can lead to shared behavioural impairments.



Self-formation of functional adenohypophysis in three-dimensional culture

The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke’s pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke’s-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions.


Men Don’t Always Think About Sex

Just Sometimes — and the Same Goes for Women, Too


thinking man

Men do think about sex more often than women overall, but not all the time — and the gap is not as wide as you might think, a new study finds.

“The absolute number of sexual thoughts is dramatically less than the urban legend that men think about sex every seven seconds,” says study researcher Terri Fisher, PhD, professor of psychology at The Ohio State University at Mansfield.

She isn’t sure where that seven-second figure originated. However, it has persisted. So she decided to investigate by asking college students to track their thoughts of sex.

Men had as many as 388 sexual thoughts per day, although the typical man had 19 a day. The typical woman had 10, although at least one woman had 140 per day. That’s a far cry from the every-seven-second finding, which would translate to more than 8,000 times during 16 waking hours.

In Fisher’s study, the men also had more frequent thoughts about two other biological needs, food and sleep, than women did — but again, not by much.

There were also plenty of women in the study who thought about all of the above — some of them a lot.

The study is due to be published in TheJournal of Sex Research.

Tracking Thoughts of Sex, Food, Sleep

Fisher asked the men and women to answer questions about eating, sleeping, and sexual behaviors. The eating and sleeping questions were meant to mask the focus on sexuality.

She assigned the men and women to one of three groups. One group kept track of thoughts of food; another, thoughts of sleep. The largest group, 163 people, tracked their thoughts about sex.

They clicked a golf tally counter when a thought occurred. At the end of the day, they wrote down the total. They kept track for a week.

”The more comfortable they were with their sexuality, the more likely they were to have sexual thoughts and record them,” Fisher tells WebMD.

Comfort with their sexuality was a stronger driver than gender, she found.

Food for Thought

“While men were thinking more about sex, they were also thinking more about food and sleep,” Fisher says.

Typically, men thought about food nearly 18 times a day, and about sleep nearly 11. Women typically thought about food about 15 times a day, and sleep nearly 9 times.

When it came to thinking about sex, ”the men were hugely different from one another,” Fisher says. “The variation was quite large.”

Hopefully, she says, the study will show there is a broad range in how often men and women think about sex — and that it is not just men who have frequent thoughts of sex.  “Some women thought about sex much more than men,” she tells WebMD.

The study may help both men and women understand that there is a broad range of ”normal,” she says.

Thinking About Sex: Perspective

“This is the best study to date looking at frequency of sexual thought,” says Janet Hyde, PhD, professor of psychology at the University of Wisconsin, Madison. She reviewed the study but was not involved in it.

Keeping track of thoughts as they occur, instead of recalling them later, helps boost accuracy, she tells WebMD.

“And it shows it’s not nearly as big a difference [between men and women] as we thought it was,” she says.

The study, she says, “goes a long way toward overturning the stereotype about men being hypersexual and women not being interested in sex.”