Parallel imaging and integrated surface coils improve spatial resolution and field of view, improving detection of brain lesions.

The white spots are brain lesions, by Reed Miller, March 31, 2010 (Bonn, Germany) — Magnetic resonance brain imaging following transfemoral aortic-valve implantation (TAVI) detects many emboli that would otherwise probably go undetected, results of a small study published in the April 6, 2010 issue of the Journal of the American College of Cardiology show [1].

The study “raises awareness of potential cerebral embolism, which most often stays clinically silent. This end point is a sensitive surrogate parameter for future neuroprotective approaches,” Dr Alexander Ghanem (University of Bonn, Germany), the study’s lead investigator, told heartwire .

In the study, the incidence of clinically silent cerebral embolic lesions on MRI images after TAVI was high, but the incidence of persistent neurological impairment was low, Ghanem and colleagues found. The risk of neurological or renal damage from emboli could change the risk/benefit ratio of TAVI in lower-surgical-risk patients. As reported in heartwire, both the CoreValve and Edwards Sapien TAVI devices are already marketed and widely used in Europe. Even though a TAVI device has yet to be FDA-approved for patients with high surgical risk, some surgeons and interventionalists are contemplating using this approach instead of surgery for lower-risk patients.

Ghanem and colleagues enrolled 30 patients undergoing a TAVI procedure to implant a CoreValve (Medtronic, Minneapolis, MN) aortic-valve prosthesis. A total of 22 patients completed the full evaluation with cerebral diffusion-weighted-MRI scans before, directly after, and three months after TAVI. The researchers assessed focal neurological impairment with the National Institutes of Health Stroke Scale (NIHSS) and serum concentration of neuron-specific enolase (NSE), which quantifies the volume of brain tissue affected by a neurological ischemic event.

Only three patients had new symptoms of neurological impairment following the TAVI, and only one (3.6%) showed a permanent neurological impairment. However, 16 patients had at least one lesion in the scan after the TAVI that was not apparent in the MRI before the TAVI. There were a total of 75 such new lesions in these 16 patients. The most any one patient had was 19. About 41% of these lesions were in patients who had shown lacunar defects and old infarcts in the baseline scan. Of those 75 new lesions, 59 were in the supratentorial region, which contains the cerebrum, and 16 were in the infratentorial region, which contains the cerebellum. About two-thirds of the supratentorial lesions (67.8%) were located on the left side. Three of the 16 patients with a post-TAVI lesion also showed infarcted tissue in the area around that lesion in the follow-up scan at three months.

Post-TAVI embolism demonstrated no significant association with calculated mortality using the EuroScore or the Society of Thoracic Surgeons score, and no statistically significant correlation to Society of Thoracic Surgeons score for permanent stroke.

Although patients with and without embolic events had no differences in their baseline characteristic, the relatively small size of the study prohibits multivariate analysis for independent risk factors of cerebral embolism, Ghanem said. However, he pointed out that the study showed that emboli were more likely to appear on scans of patients who had prior cerebral events and cerebrovascular disease, and patients with embolic events showed a nonstatistically significant tendency to have a worse renal function. A recent study in Quebec found the incidence of acute renal injury following TAVI for severe aortic stenosis was under 12% of patients, which compares favorably with the renal-injury rate with aortic surgery in that population.

The presence of many clinically silent emboli suggests that further studies of embolic risks with TAVI should be conducted, Ghanem said. He suggests further research on the long-term neurological outcomes of TAVI patients, including a comparison of neurocognitive outcomes, such as dementia and delirium, in patients undergoing conventional valve replacement or conservative treatment vs TAVI. Future studies should also evaluate the benefits of neuroprotective approaches such as embolic deflection or embolic protection.

Diagnostic Imaging and Biomarkers in Cardiology

Cardiac ultrasound (also known as echocardiogram procedure) and ECG are the workhorses of cardiac diagnosis, but ECG or ECHO results alone are inadequate cardiovascular biomarkers. More recent diagnostic imaging tools include cardiac angiography; magnetic resonance angiography (MRI angiography); computed tomography angiography (CT angiography); nuclear cardiac stress test; and serum biomarkers, including B-type natriuretic peptide (BNP) and C-reactive protein (CRP). Research is ongoing to determine which are the most accurate predictors of cardiovascular risk and disease.

Harvard Medical School, March 31, 2010  —  Migraines are notorious for causing pain. But what triggers them? How can they be prevented? And what are the best treatments? Here are answers to five questions that will help clear up a few misunderstandings and provide some useful information along the way.

  1. What exactly is a migraine?


The “classic” migraine is preceded by aura, which typically consists of strange visual disturbances — zigzagging lines, flashing lights, and, occasionally, temporary vision loss. Numbness and tingling affecting one side of the lips, tongue, face, and the hand on the same side may also occur. But only about a third of migraine sufferers experience aura, and fewer still with every attack.

The migraine headache, with or without aura, often — but not always — produces pain that usually begins (and sometimes stays) on one side of the head. A migraine headache also often has a pulsating quality to it. Many people experience nausea, extreme sensitivity to light or sound, or both.

It’s also possible to confuse other sorts of headaches with migraines. Migraines can cause nasal congestion and a runny nose, so they’re sometimes mistaken for sinus headaches. And the regular headache that most of us have experienced can have some of the features of a migrainous one, such as unilateral pain and nausea.

In short, arriving at a definition and diagnosis for migraine is complicated. Yet a simple headache diary — keeping track of headaches and factors that might have provoked them — can be very helpful in making a diagnosis.

  1. What causes a migraine?


One prevailing theory is that migraines are caused by rapid waves of brain cell activity crossing the cortex, the thin outer layer of brain tissue, followed by periods of no activity. The name for this phenomenon is cortical spreading depression.

Cortical spreading depression makes sense as a cause of aura, but researchers have also linked it to headache. Proponents cite experimental evidence that suggests it sets off inflammatory and other processes that stimulate pain receptors on the trigeminal nerves. This “neurogenic” inflammation and the release of other factors make the receptors — and the parts of the brain that receive their signals — increasingly sensitive, so migraine becomes more likely.

Some leading researchers have expressed doubt about whether migraines start with cortical spreading depression. Experimental drugs that inhibit cortical spreading depression have shown a preventive effect on aura, but not on migraine headache.

So, say some researchers, migraines are best explained as beginning lower in the brain, in the brainstem, which controls basic functions, such as respiration and responses to pain, and modulates many others, including incoming sensory information. The theory is that if certain areas of the brainstem aren’t working properly or are easily excited, they’re capable of starting cascades of neurological events, including cortical spreading depression, that account for migraine’s multiple symptoms.

  1. What triggers a migraine?


There are too many triggers to list them all here. Many migraine sufferers are sensitive to strong sensory inputs like bright lights, loud noises, and strong smells. Lack of sleep is a trigger, but so is sleeping too much, and waking up from a sound sleep because of a headache is a distinctive characteristic of migraine. Many women have menstrual migraines associated with a drop in estrogen levels. Alcohol and certain foods can start a migraine.

One of the most common triggers, stress, is one of the hardest to control. Interestingly, migraines tend to start not during moments of great stress but later on, as people wind down.

  1. How can migraines be prevented?


If you are prone to migraines, there are many steps to take to prevent or diminish the attacks:

Identify triggers so you can avoid them. That can take some time and real detective work.

Keep to a regular, stress-reducing schedule that includes a full night’s rest, balanced meals, and exercise.

Wearing blue- or green-tinted glasses can help fend off an attack in people with light sensitivity.

Try medications, such as beta blockers, tricyclic antidepressants, and anticonvulsants. All have side effects, so they should be taken at low doses and only if migraines are frequent.

  1. How can they be stopped?


Migraine sufferers can cut an attack short with one of the triptan drugs, a class that includes eletriptan (Relpax), sumatriptan (Imitrex), and zolmitriptan (Zomig). The triptan drugs seem to work by inhibiting pain signaling in the brainstem. They also constrict blood vessels, so people with a history of cardiovascular disease (heart attack, stroke, uncontrolled hypertension) are usually advised not to take them.

Pain relievers like ibuprofen (Advil, Motrin) and naproxen (Aleve) can halt a mild attack, but rebound headaches may develop if they’re taken too often. Rebound headache occurs after the body gets used to having a medication in its system; when it’s not there, headaches happen. Migraines can quickly snowball into more serious pain, so it’s important to treat the headache early, regardless of the medication.

— Peter Zimetbaum, M.D.

Harvard Heart Letter Editorial Board

Robotic op: The latest version of the da Vinci robot, a $2.5 million technology, allows two surgeons to operate together.  Credit: Emily Singer/Technology Review



Robot-driven procedures are popular, but surgeons say the technology isn’t evolving quickly enough

MIT Technology Review, March 31, 2010, by Emily Singer  —  An eight-year-old girl lies in an operating room in Children’s Hospital Boston, propped up on one side, ready for surgery. She had been complaining of pains in her side, and a scan revealed a blockage in her left kidney.

In most hospitals, she’d get a six-inch slice down her abdominal wall, giving surgeons access to her kidney during open surgery, and would then spend four to five days recovering in the hospital. But this Monday morning she is about to undergo a robotic surgical procedure. In about three hours, she’ll leave the operating room with a one-inch incision covered by a regular Band-Aid. She’ll most likely return home the next day.

Surgeon Hiep Nguyen, a specialist in pediatric urology and robotic surgery, says the da Vinci robot has greatly expanded the complexity of the minimally invasive surgeries he can perform. It offers three-dimensional vision and articulated tips on the surgical tools that go inside the patient, which allows for smaller, finer movements than traditional laparoscopy. At a recent talk in Boston, Nguyen described complex reconstructive surgeries–fashioning a urethra from an appendix, for example–that just a few years ago would have required open surgery.

But after the talk, rather than expressing wonder or hope over these new surgical possibilities, many of the surgeons, scientists, and engineers in the audience focused on their frustration with the technology. The group had varying concerns–if and when the robot will outperform traditional laparoscopy; the learning curve associated with the technology; whether it allows less experienced surgeons to perform more complex surgeries. But everyone agreed on two points. The technology isn’t advancing fast enough or dropping in price quickly enough. “The system is very expensive because only one company makes it now,” says Nguyen. “We need more competition to drive down price.”

The da Vinci robot is made by California-based Intuitive Surgical, the only big player in the robotic surgery arena (some other companies make robotic systems for eye and brain surgery). The company, founded in 1995, adapted technology originally developed for long-distance surgery–an application quickly abandoned–and created a broad patent portfolio around robotic surgery. It bought up early competitors, garnering Food and Drug Administration approval for its surgical system in 2000. And that’s largely where things have stood for the last decade.

“People have been disappointed in how slowly the robot is evolving,” says Jon Einarsson, a gynecological surgeon at Brigham and Women’s hospital in Boston. “There hasn’t been a lot of evolution or improvement in the articulation at the tip of the instrument.” Some innovations that Einersson would like to see are haptics–a sense of touch that can be translated from the robotic instruments to the surgeon–and a way to incorporate data from magnetic resonance imaging.

Some surgeons and engineers argue that a much smaller and cheaper device could provide the same visual advantages and flexibility, but that no one has been able to move this forward. “The da Vinci robot looks like it was designed to make automobiles–it’s great big clunky gear,” says Kirby Vosburgh, an engineer with the Center for Integration of Medicine and Innovative Technology (CIMIT), in Boston, who previously designed medical technology for General Electric.

Although Intuitive’s robotic surgery technology has grown in popularity, especially among gynecological and urological surgeons, it has also come under increasing scrutiny. While it seems beneficial for the complex pediatric surgeries that Nguyen specializes in, it’s not yet clear whether the robot improves outcomes for simpler surgeries that can be performed using more traditional laparoscopic procedures, such as hysterectomies. Other potential benefits of robotic surgery are more subtle and difficult to assess–whether it helps surgeons by making the procedure less physically demanding, or allows less experienced surgeons to do more complex surgeries. For example, Nguyen says only a few highly skilled surgeons could perform today’s surgery laparoscopically.

Nguyen talked Children’s Hospital into buying the latest version six months ago–for $2.5 million–after his analysis showed that the shorter hospital stays after robotic procedures would make up for the cost over time. (He receives no funding from Intuitive.) But he agrees that Intuitive’s monopoly has stalled the field. “People are afraid to challenge Intuitive because they are such a big company,” says Nguyen. “But now we’re starting to see a rebellion from physicians on the price, especially in the context of the discussion on how to cut down costs. That will motivate more people to consider coming into the market.”

Dennis Fowler, one of the surgeons in the audience at Nguyen’s talk, has experienced this first-hand. His team developed a snake-like laparoscopic tool with two cameras, which provides stereoscopic vision like the da Vinci. But he says his tool doesn’t require the large viewing console that Intuitive’s does. “We learned after we developed the camera that Intuitive had 286 patent claims related to this type of device,” says Fowler, a pioneer in laparoscopic surgeries who recently moved from Columbia University to CIMIT. “That’s the major impediment. Right now it’s an academic endeavor.”

With funding from the National Institutes of Health, Fowler and collaborators are now working on adding grippers and cutters to the device. The tools are cleverly built into the same laparoscopic cord as the camera, making the assembly resemble a Swiss Army knife. This design would reduce the number of incisions required during surgery. Once inside the body, the device unfolds like a flower. But the device is still early in development; they have built a prototype, and Fowler is now applying for a grant to test it in animals.

It’s too early to say how Fowler’s robot would perform in comparison to the da Vinci or other robotic technologies, but “even the initial prototype has numerous advantages,” Fowler says. “It will be less invasive, with one incision instead of three or four; it is vastly smaller; it will cost a small fraction of what da Vinci costs; and it will be much easier to maintain.”

Andrew Shurtleff for The New York Times

“All of a sudden I feel like I can think about my child’s future without worrying.” — April Kohrherr with Griffin, right

The New York Times, March 31, 2010, by Tara Parker-Pope  —  More than a week after President Obama signed the sweeping new health care law, which will eventually provide insurance coverage for 32 million uninsured Americans, many of us are still scratching our heads. What just happened? And how and when will we start feeling its effect?

In the long term, the legislation will require most Americans to obtain health insurance. It will also offer federal subsidies to lower premiums and significantly expand eligibility for Medicaid.

The changes will mean that 94 percent of legal residents not covered by Medicare will have health insurance, up from 83 percent now, according to the Congressional Budget Office.

While the biggest changes will not take effect until 2014, some important provisions will begin as early as June, while others will kick in by the end of the year. These include significant new restrictions on the insurance industry and new protections for consumers who already have health insurance. There are also perks for Medicare recipients and help for young adults. And in just 90 days there will be new coverage for people who have lost health insurance and can’t qualify for an individual policy.

“The basic thrust of this law is that all of these nooks and crannies, all these gaps where private insurance has left you without any option, those are going to be taken away,” said DeAnn Friedholm, the campaign director of health reform for Consumers Union, the nonprofit publisher of Consumer Reports. “It’s complicated, but it does establish a very key, important policy that you’re going to have options, regardless of your health situation or your employment situation.”

Some of the specific details will be outlined in the coming weeks by the Health and Human Services department. However, here are answers to some commonly asked questions about the health care changes coming within the next year.

Q. I don’t have health insurance. How soon will the new law help me?

The answer depends on your age and reasons for not having insurance. If you haven’t had insurance for six months, and you can’t afford or don’t qualify for insurance because of a pre-existing medical problem, you may be eligible for a new federal “high risk” pool to be offered by the end of June.

The cost of the monthly premiums hasn’t been announced, but the rates are to be based on a “standard population,” suggesting they will be based on a healthier group than typically used to calculate premiums for high-risk plans. On average, an enrollee won’t pay more than 35 percent of covered benefits, and annual out-of-pocket costs won’t be more than $5,950 for individuals and $11,900 for families. In addition, there are no lifetime limits — meaning the policy won’t be canceled if someone requires expensive medical treatment

Q. How many people can sign up for the new plan?

Until national health officials specify the premium costs and exactly what will or will not be covered, nobody knows how many people can sign up. The $5 billion set aside by Congress must last until 2014, when other options become available. By comparison, 35 states already spend a combined total of $2 billion annually on high-risk insurance pools that cover 200,000 people.

Q. How is the new federal pool different from what is already offered by state high-risk pools or Medicaid?

The federal plan is expected to offer more-affordable coverage than the existing state plans and will not impose the same income restrictions as Medicaid. State plans also typically impose high deductibles and premiums (some charge as much as $1,200 a month), and up to 12-month waiting periods before covering pre-existing health problems.

The experience of April and Steve Kohrherr of Afton, Va., shows how existing public plans fall short for many families. Their oldest son, Griffin, 6, has hemophilia, a severe bleeding disorder. His care, which has included brain surgery for a life-threatening bleed as well as twice-weekly infusions with a clotting drug, totals $500,000 or more a year.

The high cost of Griffin’s care would disqualify him from most state plans. Adding Griffin to the small group plan at the restaurant where Mr. Kohrherr works would have increased premiums for all the workers, making it unaffordable for everyone. Griffin now is covered by Medicaid, but he will lose the benefit if his family’s income exceeds about $40,000. Ms. Kohrherr works part time, but goes without insurance because the family of four cannot afford the $200 monthly cost to add her to her husband’s policy.

“If anybody was in my shoes and held their kid who was close to death, and if they had to worry about insurance at that moment, then they would never have been against this bill,” Ms. Kohrherr said. “All of the sudden I feel like I can think about my child’s future without worrying.”

Q. How will the law affect children with pre-existing conditions?

Beginning in September, the new law is expected to stop insurance companies from rejecting children or excluding coverage because of pre-existing medical problems. That’s what happened to Diane Knight, 52, of Orem, Utah, when she tried to get health insurance for her 17-year-old daughter.

Although Ms. Knight and her husband had family insurance in the past, they lost it when they left their jobs to start a small business. When they discovered that they were unable to get new insurance because both had a past cancer diagnosis, they sought an individual policy just for their daughter. But she was rejected, too, because she had used expensive prescription acne cream when she was younger and the insurance company did not want to pay for that in the future.

“To deny a perfectly healthy 17-year-old girl, and then for the rest of her life she has to say, ‘Yes I’ve been denied health insurance’ — that’s unacceptable,” said Ms. Knight, who returned to teaching public school to obtain insurance for her family. “I’m a conservative Republican, but I have lived the nightmare of health insurance.”

Since the law passed, insurers have argued that it uses vague language and does not require them to provide insurance to all children right away. Legislative experts say that the intent of Congress was clear and that the federal government will probably write the rules to reflect this, which may lead the industry to take the battle to court.

Q. Will Medicare recipients receive any immediate benefits?

This year Medicare recipients with high drug costs will get a rebate of up to $250. And in 2011, the plan will pick up a larger share of brand-name drug costs. In addition, Medicare recipients won’t be charged co-pays or deductibles for preventive care like immunizations and cholesterol screening.

The drug rebate is the first step in a 10-year plan to close the “doughnut hole,” the gap that occurs because Medicare Part D stops reimbursing for prescriptions after the first $2,830 in costs a year. The retiree must then pay all drug costs until they reach $6,440, at which point Part D pays again.

Rosale Bertrand, a 69-year-old Medicare recipient in Salt Lake City, says that early in the year, her 10 prescriptions for diabetes, high blood pressure, asthma, ulcers and chronic depression cost her about $200 a month because Part D covers much of the cost. But the doughnut hole starts in late March or April, and she must spend $600 a month until Part D kicks in again in the fall, she says.

To maintain her prescriptions, Ms. Bertrand has twice borrowed against her home and has maxed out her credit cards. Under the new law, she will save about $250 this year and about $540 next year. “It’s a start,” she said. “I was very relieved anything good could come out of it.”

Q. Will young, healthy adults who don’t have insurance be helped by the reforms?

Starting in September, adult children younger than 26 can be added to their parent’s health policy. Some plans already extend coverage to adult dependents as long as they are full-time students. Although Health and Human Services still must announce the exact eligibility requirements, Congress deleted a restriction related to marital status.

“We may see a loosening of requirements around who qualifies as a dependent child,” said Jennifer Tolbert, associate director of the Commission on Medicaid and the Uninsured for the Kaiser Family Foundation. “When they removed the requirement that a dependent child didn’t have to be unmarried, that was a signal to say, ‘We want this to a apply to a larger group.’ ”

The provision will offer some relief to Sarah Lynch, 25, of Austin, Tex., who was kicked off her parents’ plan at 23 when her course work dropped to just two classes in her final semester. Ms. Lynch has paid about $460 a month to extend coverage under a provision known as Cobra, but that plan expires in June. She has been unable to find full-time work with benefits, and her application for private insurance was rejected without explanation. The new law will give her about six months of insurance coverage on her parents’ plan before she turns 26. “It gives me a little more time to find a job with benefits,” she said.

Q. What are the immediate benefits for people who already have insurance?

Beginning in September, insurance companies will no longer be able to rescind a policy once someone gets sick, nor can they impose lifetime limits on coverage.

Today, honest mistakes on a lengthy insurance application — like forgetting to disclose a parent’s high blood pressure — could be grounds for losing your insurance.

Under the new rules, companies generally can’t rescind a policy for a minor application error. “The law takes away the incentive for insurance companies to look for application mistakes,” said Marian Mulkey, senior program officer with the California HealthCare Foundation. “There have been some egregious examples of someone getting cancer triggering a review of years of health history that seems very targeted and punitive.”

Patricia Sevchuk of Ewing, N.J., said her daughter Laura scrupulously paid her Cobra premiums while being treated for late-stage breast cancer. But more than a month after she died in 2008, the insurance company notified her husband that as much as $400,000 would no longer be covered because the medical bills had exceeded a $1 million lifetime cap. Although one oncologist waived her fees after hearing about the family’s plight, other creditors have demanded payment, and bankruptcy remains a possibility.

“There isn’t a day that goes by that I don’t think about her and what she went through,” Mrs. Sevchuk said. “To know that as much as we tried to save her, all it did was cause more anguish to the people who were left — her husband and her daughter. It’s heartbreaking.”

Q. Won’t all these changes increase my health care premiums?

How the changes will affect existing insurance costs is a source of fierce debate. Over all, the Congressional Budget Office has said that by 2016, the provisions in the new law will result in little if any increase in premiums for people with employer-sponsored plans. People with nongroup plans (those not offered by employers) may see increases, but more than half the enrollees in nongroup plans will qualify for federal subsidies, lowering costs for middle- and moderate-income families on average by about 60 percent, the C.B.O. said.

Beginning in September, insurance firms will face new limits on administrative costs and executive compensation. Violations will trigger rebates to consumers. In addition, the overhaul package includes additional money for states to review unreasonable increases in insurance rates.

“Middle- and moderate-income families will have tremendous help in the pocketbook as a result of federal subsidies that will significantly lower the out-of-pocket burden,” said Ron Pollack, executive director of the consumer health group Families USA. “And there is now a process where the federal government as well as states will review premium increases to determine their reasonableness.”

Q. Will small-business owners notice any immediate benefits?

This year tax credits as high as 35 percent of premiums will be available to many small businesses that offer health coverage to employees. Dale B. Cole Jr., co-owner and chief financial officer of Consolidated Trailers in Baltimore, said that he did not yet know how the legislation would affect him but that he hoped it would ease his costs and allow him to shop around for better coverage.

“We’ve used mirrors and smoke to try to get the premiums to where they’re bearable,” he said. “We went from a full plan with a small deductible and great prescription coverage to a plan now that is basically a high-deductible plan. It ain’t much.”

Sharp Rise in HPV-Related Oropharyngeal Carcinoma — A Legacy of the “Sexual Revolution”?,, by Zosia Chustecka, March 31, 2010 — The incidence of oropharyngeal carcinoma related to human papillomavirus (HPV) has been increasing in recent years, and there is speculation that this is the result of the “sexual revolution” of the 1960s.

This increase in the incidence of HPV-related oropharyngeal cancer has important public health implications, British experts warn in an editorial published online March 25 in the British Medical Journal.

HPV-related oropharyngeal carcinoma appears to be a new and distinct disease entity, with better survival than the classic non-HPV-related disease, they point out.

“These patients are typically younger and employed, and — because outcomes seem to be more favorable than for patients with non-HPV-related carcinoma — they will live longer with the functional and psychological sequelae of their treatment. Consequently, they need prolonged support from health, social, and other services, and may require help returning to work,” write the authors, headed by Hisham Mehanna, BMedSc, MB ChB, FRCS, director of the Institute of Head and Neck Studies and Education at University Hospital in Coventry, United Kingdom.

However, currently, there is no good evidence to support managing patients with HPV-related head and neck cancer differently from those whose tumors are not HPV-related, the researchers write.

Clinicians should not change their current treatment policies.

Several studies are being planned to evaluate different treatment options, and Dr. Mehanna and colleagues urge clinicians to offer all patients with oropharyngeal cancer the opportunity to enroll in a clinical trial. However, until data from those trials are available, “we suggest that clinicians should not change their current treatment policies.”

Maura Gillison, MD, PhD, professor of medicine, epidemiology, and otolaryngology at Ohio State University in Columbus, who was approached for independent comment, told Medscape Oncology that she agrees.

Currently, patients should be treated the same, whether they are HPV positive or negative, she said, but they should be “strongly encouraged” to participate in trials.

Increase Linked to Sexual Behavior?

As evidence for the increasing incidence of HPV-related oropharyngeal carcinoma, the researchers cite several studies. One of these, conducted in Stockholm, Sweden, found a progressive proportional increase in HPV detected in biopsies taken to diagnose oropharyngeal cancer, from 23.3% in the 1970s, to 29% in the 1980s, 57% in the 1990s, 68% in 2000 to 2002, 77% in 2003 to 2205, and 93% in 2006 and 2007 (Int J Cancer. 2009:125:362-366).

One reason for this increase could be the sexual transmission of HPV, primarily through orogenital intercourse, Dr. Mehanna and colleagues write.

They also cite a recently published pooled analysis of 8 multinational studies conducted by the International Head and Neck Cancer Epidemiology (INHANCE) consortium (Int J Epidemiol. 2010;39:166-181). Using pooled data, this group compared 5642 patients with head and neck cancer and 6069 control subjects, and found that the risk of developing oropharyngeal carcinoma was associated with a history of 6 or more lifetime sexual partners, 4 or more lifetime oral sex partners, and — for men — an earlier age at first sexual intercourse.

The association between HPV-related oropharyngeal cancers and sexual behavior — having several sexual partners, and with oral sex and “French kissing” — has been reported in previous studies. Last year, American experts highlighting the increase in HPV-related oropharyngeal cancer suggested an association with an increase in the practice of oral sex among white, younger Americans, as reported previously by Medscape Oncology.

Dr. Gillison told Medscape Oncology that “it is clear that the strongest behavioral risk for [HPV-related oropharyngeal cancer] is the lifetime number of oral sex partners.”

“However, there are no data to specifically link the increase in disease incidence to changes in oral sexual behaviors over time,” she added, pointing out that sexual-behavior surveys in the United States did not collect this type of information before the 1990s.

“This is something that I have looked at carefully,” Dr. Gillison said, and she believes that the available data suggest that the sharp increase in HPV-related oropharyngeal cancer is a result of the sexual revolution of the 1960s.

Legacy of the Sexual Revolution

“Our own work, using the [Surveillance, Epidemiology, and End Results] database, shows a strong cohort effect, which means the greatest determinant of risk in any age group is the year that you were born,” Dr. Gillison reported.

“These cohort effects are largely driven by societal changes, and they tend to affect people first who are younger, because they are the people leading the behavioral changes,” she explained.

During the 1960s, teenagers and young adults were more active sexually than previous generations, and having multiple sexual partners became more acceptable. “The more sexual partners you have, the greater the risk of contracting any sexually transmitted disease, including HPV,” Dr. Gillison pointed out.

The time lag between an oral HPV infection and the development of HPV-related oropharyngeal cancer is between 15 and 30 years, and the age at which this cancer is usually diagnosed is 50 years or more.

So the increase in this cancer that was seen in the 1990s and the 2000s is likely to be the result of young people participating in increased sexual activity in the 1960s and 1970s, Dr. Gillison suggested.

“We saw a really sharp climb in the incidence in 2000,” Dr. Gillison noted. “So you have to think: What were these people [now 50 or more years old] doing 20 to 30 years ago?”

Dr. Mehanna told Medscape Oncology that he “totally agrees.”

The time frame fits.

The time line of the sudden increase in these cancers seen in the past decade and the 20 to 30 years that it takes for HPV-related cancer to develop points to changes in sexual behaviors that began in the 1960s and 1970s, he said. “The time frame fits,” he said, although he added that “this is conjecture.”

However, there are many points that are backed up with data. “What we know for sure is that HPV causes oropharyngeal cancer, and we understand the molecular mechanisms involved, so we know how it causes it,” Dr. Mehanna explained. “We also know that patients who have HPV-related oropharyngeal cancers are more likely to have had 6 or more sexual partners or 4 or more oral sex partners,” he said, and men are more likely to have started having sex at an earlier age. This [fits] with data for cervical cancer, also caused by HPV, which is more likely in women who become sexually active at an earlier age, he noted.

Rethink on HPV Vaccination?

Because a vaccine against HPV is already marketed for use in girls and young women to prevent cervical cancer, and was recently approved for use in boys to prevent genital warts, there has been speculation about whether this vaccine will also protect against HPV-related oropharyngeal cancer.

Dr. Gillison points out that there is no scientific evidence, as yet, to show that HPV vaccination does protect against HPV-related orophageal cancer. “It ought to,” she explained, because this cancer is mainly associated with HPV type 16, and this is one of the virus types that the vaccines contain. “But science can be surprising, and things don’t always work out as we expect,” she warned. She pointed out that the oral cavity is very different from the genital area, and the differences in mucosal surfaces and in the antibodies in saliva and genital secretions might alter the response to vaccination.

“Whether the currently available HPV vaccines have the potential to prevent oral HPV infections that lead to cancer, and thereby reverse the current upward incidence trends documented now in the United States, the United Kingdom, and Sweden, is an important and unanswered question,” Dr. Gillison commented.

“Unfortunately, the studies designed to evaluate this question that were slated to start next month in young men have recently been cancelled by the pharmaceutical sponsors,” she added.

In their editorial, Dr. Mehanna and colleagues suggest that the recent rapid rise in HPV-related oropharyngeal carcinoma might alter some of the cost-effectiveness considerations about this vaccine and, in particular, its use in boys before they become sexually active.

The HPV vaccination of boys was judged to be not cost-effective in a recent analysis (BMJ 2009;339:b3884), but this decision was made on the basis of old data, Dr. Mehanna explained to Medscape Oncology. The data in that cost-effectiveness study only go up to 2003, but there has been a considerable increase — a doubling, in fact — since then, he said. There are data from 2009 that suggest that about 70% of oropharyngeal cancer is HPV-positive, compared with about 35% in 2003, he noted.

Hence, that study underestimated the incidence of HPV-related oropharyngeal cancer, Dr. Mehanna said, and a new cost-effectiveness analysis needs to be carried out to take these new incidence data into account. “It may well turn out to be cost-effective,” he added.

Dr. Mehanna is director of the Institute of Head and Neck Studies and Education, which does contract work for GlaxoSmithKline. One of his coauthors, Terence Jones, from the Liverpool CR-UK Cancer Centre, School of Cancer Studies, Division of Surgery and Oncology, in the United Kingdom, is involved in a clinical trial in patients with HPV-related oropharyngeal carcinoma with a therapeutic vaccine that the manufacturer (Advaxis) is providing free of charge.

BMJ. 2010;340:c1439. Abstract, by Nancy Fowler Larson, March 31, 2010 — Patients with knee osteorarthritis (OA) who engage in physical activity, take pain medication, or start using aids such as shoe inserts within 6 months of diagnosis experience measurable improvements, according to a study published online March 30 in Arthritis Care & Research.

Investigators launched their research from the results of a previous pilot study. The earlier exploration showed that community-based pharmacists could accurately identify OA in undiagnosed patients using a simple survey. As described by the study authors, pharmacists are readily available healthcare professionals in most developed countries, and when they assist in management of chronic diseases, patient outcomes improve.

“The objectives of this longitudinal study were to describe the participants’ lifestyle intervention as well as use of health services, and products following diagnosis, and to assess the health-related quality of life (HRQOL) of community pharmacy clients with recently diagnosed knee OA,” write Kelly A. Gindrod, PharmD, MSc, research scientist, University of British Columbia, Vancouver, Canada, and colleagues.

In 2005, pharmacists in 27 locations in Edmonton, Alberta, Canada, and Vancouver asked clients who reported knee pain, aching, and discomfort during the previous year to complete a questionnaire. The 194 patients subsequently diagnosed with OA were mostly overweight (43%) or obese (24%) white women with an average age of 63 years. They did not have previously diagnosed OA.

At intervals of 1, 3, and 6 months, participants completed follow-up questionnaires. They reported on their exercise, analgesic use, other treatments, and natural supplement intake and provided the source of advice for these interventions. The investigators evaluated HRQOL at baseline and during each follow-up period with tools that included the complete Western Ontario and McMaster Universities Osteoarthritis Index, Paper Adaptive Test, and Medical Outcomes Study Short Form 36 health survey.

Investigators Are Concerned About Self-Medication

By their 6-month assessment, 93% of subjects had seen their family physician about their OA. The majority had made lifestyle changes, as follows:

  • 75% were participating in aerobic, strength, or endurance exercises such as walking or biking;
  • 33% were using activity aids including acupuncture, knee tape, braces, or shoe inserts;
  • 52% had begun prescription or nonprescription analgesic therapy, with 50% using nonsteroidal anti-inflammatory drugs and approximately 25% taking acetaminophen; and
  • 36% had started using natural supplements, either glucosamine or a glucosamine/chondroitin combination.

More than half of the subjects reported making these lifestyle changes without the advice of a physician. At the 6-month mark, participants reported improvements in their HRQOL, including:

  • a mean change of 2.12 from baseline (95% confidence interval [CI], 0.64 – 3.60; P = .001) in the Medical Outcomes Study Short Form 36 physical component summary;
  • an average modification of 2.05 (95% CI, 0.27 – 3.83; P = .024) in Medical Outcomes Study Short Form 36 bodily pain domain scores — a 47% improvement;
  • a mean alteration in the Paper Adaptive Test of 3.09 for pain and discomfort (95% CI, 1.75 – 4.42) and 2.96 for usual daily activities (95% CI, 1.56 – 4.36; P < .001 for both) — a gain of 63% and 58%, respectively; and
  • an average change of −1.91 for Western Ontario and McMaster Universities Osteoarthritis Index total, pain, and function scores (95% CI, −2.72 to −1.10; P < .001 for all).

Of concern to investigators was the greater number of patients who used nonsteroidal anti-inflammatory drugs before trying acetaminophen, the recommended treatment for relief from knee OA pain.

“Furthermore, the decision to try analgesic therapy was often made on their own or on the advice of family and friends, suggesting that many may choose to disregard the advice of health professionals in favor of their own preferences of well-being,” the authors write.

Three limitations were stated by the investigators: there was no control group; subjects self-reported their lifestyle changes, which can result in inaccuracies; and researchers did not investigate participants’ previous exercise habits, analgesic use, or other lifestyle factors.

Calling the study “tremendously good news,” Patience White, MD, MA, chief public health officer, Arthritis Foundation, told Medscape Rheumatology that the findings demonstrate the importance of patients taking initiative. She recommended that further study rely less on self-reporting and explore a bigger picture.

“It would be very interesting to find out where people were in the beginning, and to test how they were in follow-up,” Dr. White said.

Although she is heartened that the study patients felt better after subscribing to lifestyle changes, Dr. White noted that greater physician involvement is critical in prescribing appropriate exercise.

“You don’t want somebody with early OA to immediately run out and do a marathon,” Dr. White said. “The message in this article is healthcare professionals probably ought to be talking about this more.”

Merck Frosst Canada supported the study. The study authors and Dr. White have disclosed no relevant financial relationships.

Arthr Care Res. Published online March 30, 2010.

A nod to the arts……………

It’s official: William Shakespeare has a new play out! After 300 years of debate and investigation, a play called Double Falsehood has finally been added to the Shakespeare cannon.

Lewis Theobold first presented the text as an adaptation of a lost Shakespeare play in the 18th century. For years the play was dismissed as a hoax, but experts from Arden have now concluded that Shakespeare did in fact write the play.

Like Shakespeare’s other plays written towards the end of his career, it is believed that Double Falsehood was written in collaboration with fellow playwright John Fletcher – it is already established that Henry VIII and The Two Noble Kingsman were written with Fletcher.

This month, Arden have published Double Falsehood for the first time as a Shakespeare play … Looks like I better start updating all references to “Shakespeare’s 37 plays” on this website.