A living will is a legal document that enables you to specify your preferences about end-of-life care at a time when you are clear of mind and perfectly able to do so. The document usually covers things like whether you want breathing machines and tube feedings to be used to prolong your life if you have a terminal illness, whether you want providers to attempt resuscitation in the event you are terminally ill and stop breathing, and so on.

The living will avoids confusion because your family members and caregivers will know how you feel about such situations even if you can’t express your feelings at the time they actually happen.

The Case For Living Wills: The vast majority of health care providers, especially those who frequently care for patients with terminal illness, feel quite strongly that their patients should complete a living will, no matter how uncomfortable that process may be.

Numerous scientific studies support this position. For example, in an April 2010 study in the New England Journal of Medicine, scientists found that nearly 30% of all elderly Americans did in fact encounter situations near the end of their lives when these documents would have helped assure they received the care they wanted.

Shortly before that study was published, a  separate study showed that advance care planning improved “end-of-life care and patient and family satisfaction, and reduced stress, anxiety and depression in surviving relatives.”

And before that one appeared, a third one revealed that “end-of-life discussions between doctor and patient helped ensure that one got the care one wanted,” and therefore “protected patient autonomy.”

Recent Political History of the Living Will: These and other studies support the Obama administration’s longstanding efforts to pay physicians for time spent helping Medicare patients develop living wills and other forms of advance directives.

During the epic health reform debate of 2009-2010, House Democrats attempted to include provisions authorizing such payments in the evolving legislation. However, the effort fell prey to scurrilous attacks by Sarah Palin, House Minority leader John Boehner and others. Memorably, Palin said the provisions allowed the government to create “death panels,” of all things. For his part, Boehner claimed the provisions would “start us down a treacherous path toward government-encouraged euthanasia.” (more…)

Last month, scientists reported that Truvada, Gilead’s once-a-day pill that is normally used to treat HIV infection, can be used to prevent HIV infection as well.

The report appeared in the New England Journal of Medicine. In the study, nearly 2,500 HIV-negative gay and bisexual men were randomized to receive either Truvada or a placebo. Study participants who received the anti-retroviral pill were 44% less likely to become HIV-positive during the 15 month follow-up than folks in the control group. The risk reduction was 73% among men who managed to take the pill every day or nearly every day.

The study results “represent a major advance in HIV research,” Kevin Fenton, the CDC’s HIV/AIDS czar told the Wall Street Journal. Even President Obama was moved to comment that the study, and those like it “could mark the beginning of a new era in HIV prevention.”

Truvada contains 2 drugs produced by Gilead: tenofovir and emtricitabine. Both drugs are reverse transcriptase inhibitors, which block replication of the AIDS virus in the human body. Normally, Truvada is combined with 2 other drugs to create a cocktail for the treatment of AIDS. This is the first time Truvada has been tested for its ability to prevent infection in the first place.

Gay and bisexual men comprise nearly half of the one million-or-so people who are HIV positive in this country. They are 44 times more likely to be HIV positive than other men.

Despite the apparently good news about Truvada, many public health officials raised concerns that people would not take the drug every day or fail to use condoms in a mistaken belief that the drug is, by itself, enough to prevent HIV infection. There were good reasons for this concern. Men in the study whose adherence to the once-a-day regimen was less than 90% experienced only a 21% reduction in infection risk.

It’s also not clear that Truvada will be similarly effective in IV-drug abusers or heterosexuals, since HIV enters the body via different routes in these people. Studies of Truvada’s prophylactic efficacy in these groups are underway.

The CDC plans to release guidelines for using Truvada to prevent HIV/AIDs in the near future. The drug hasn’t been approved for this purpose by the FDA, but physicians can prescribe drugs for off-label uses if they want.

By the way, Truvada costs just under $1,000 per month in the US. Also of note, the scientists responsible for the so-called Prep trial covered here are continuing to follow enrollees to look for drug resistance and long-term side effects. It’s something to keep in mind as the dust settles on this exciting finding.

Aortic Stenosis (AS) is a condition caused by progressive narrowing of the valve that governs blood flow from the heart to the brain and most other internal organs. About 1.5 million Americans have AS, one-fifth of whom have a severe form that is life-threatening.

Traditionally, the treatment for severe AS involves open heart surgery, an expensive procedure that is associated with its own risks and contraindicated in frail, elderly folks…just the kinds of people that develop the condition in the first place.

Now, scientists have shown that a relatively non-invasive treatment for severe AS may obviate the need for open-heart surgery.

The new approach involves attaching a replacement valve to a catheter, and then threading it through blood vessels to a place where it can serve the role of the malfunctioning valve. 

The replacement valve is produced from cow tissue and is housed within a metal frame. 

A study of the new device was published 2 weeks ago in the New England Journal of Medicine. In the study, a group of elderly patients received the catheter-placed device while others received various other non-surgical interventions.

The one-year mortality rate for people that received the replacement-valve was 31%. This was lower than the 51% mortality observed in controls. Of note, the study also revealed a higher incidence of early strokes (5% vs. 1%) in patients who received the new device. The increased stroke risk was nevertheless deemed “an acceptable price to pay” by Craig Smith, a study co-author.

The study was funded by Edwards Lifesciences, the same company that designed the valve. Several authors have financial ties to the company. Catheter-delivered valves “should be the new standard of care” for patients with severe AS that can’t tolerate open-heart surgery, they concluded. 

Edwards hopes to gain FDA approval for its device in 2011.

Rejection of the donor organ is a frequent and sometimes life-threatening complication of heart transplantation. It is best handled if caught early, and since early rejection is typically asymptomatic, physicians had heretofore been required to perform regular biopsies to screen for rejection of the transplanted heart.

The biopsy is expensive and not without risk however, so scientists have long searched for a non-invasive alternative to diagnose rejection.

That search may have yielded results. In a presentation at last month’s meeting of the International Society for Heart & Lung Transplantation, Michael Pham and colleagues from Stanford University showed that a genetic test reduced the need for biopsies in selected patients.

The gene test is known as Allomap. It is marketed by XDx and has been used on 7,000 transplant recipients so far. It costs about $3,000, or 25-40% less than the biopsy.

The study by Pham’s team included 602 transplant recipients. It showed that Allomap was as effective as routine biopsies in preventing serious episodes of transplant rejection like heart failure, the need for a re-transplant or death.

The study was limited to patients who were at low risk for rejection and had undergone the procedure at least 6 months prior to enrollment. Nineteen months after randomization, 14.5% of patients that were followed with the genetic test and 15.3% of those followed with routine biopsies suffered a major complication.

“You’re not going to harm patients by reducing the number of biopsies,” Pham told the Wall Street Journal.

Pham noted that his team’s findings could not be extrapolated to patients that had received a transplant within the last 6 months or to those at high risk for rejection.

The study appears in the New England Journal of Medicine.

The results of a large study of Avodart for the prevention of prostate cancer have revealed an altogether unexpected finding: the drug increases the risk for heart failure. Avodart is typically used to treat urinary symptoms caused by an enlarged prostate gland. Heart failure had not been noted when men use it for this purpose.

The study appears in the New England Journal of Medicine. It included 6,700 men that were between the ages of 50-75 and that had high PSA levels (PSA is a prostate cancer screening test) but no actual prostate cancer as revealed by a recent biopsy. Subjects were randomized to receive either Avodart or a placebo, and were re-biopsied after 4 years.

The new biopsies revealed cancer in 25% of subjects taking placebo, and 20% of those taking Avodart. Those findings match the cancer-preventing performance Merck’s Proscar, another urinary drug sold generically as finasteride, but the finasteride patients showed no signs of heart failure.

Heart failure developed in 30 men taking Avodart, compared with 16 men who received placebo.

Subset analyses showed that patients who developed heart failure tended to be taking other drugs which are known to precipitate heart failure, according to Glaxo spokesperson Sarah Alspach. The higher incidence of heart failure in the Avodart study “is unexpected and inconsistent” with previous research, she told AOLnews.

Last year, an expert panel recommended that men who are screened regularly for prostate cancer should consider taking Proscar or Avodart. It’s unclear whether the panel will revisit those recommendations in light of the new findings.

Both drugs cost about $3 per pill. To prevent one new case of cancer, 71 men would have to take Proscar for 7 years.

Prostate cancer is the most common non-skin cancer in US males. Roughly 192,000 new cases and 27,000 deaths were attributed to prostate cancer last year.

For the second time this year, a clinical trial has shown that the cholesterol-lowering drug Zetia does not prevent heart disease.  

The first trial appeared last January. That trial compared Vytorin—a blockbuster drug that combines  the active ingredient in Zetia with a generic cholesterol-buster known as simvastatin—against simvastatin alone in patients with a genetic condition causing them to have very high levels of LDL (bad) cholesterol and premature cardiovascular disease.

In that trial, Vytorin reduced LDL cholesterol levels much more than simvastatin alone but surprisingly, atherosclerotic plaques actually grew faster in the coronary arteries of the patients taking Vytorin.

The news was greeted with a precipitous fall in prescription volume for both Zetia and Vytorin.

The second study was published last week in the New England Journal of Medicine. This study compared Zetia to Niaspan, a drug that raises blood levels of HDL (good) cholesterol.

In the second study, Allen Taylor of the Walter Reed Army Medical Center and colleagues enrolled 363 people with coronary artery disease that had been taking statins for many years. 

Taylor’s group found that Niaspan shrank carotid artery plaques by 2%, but Zetia had no such effect, even though it effectively reduced cholesterol levels (as it did in the first trial). In addition, patients who received Niaspan sustained 2 heart attacks or heart-related deaths during the study, while 9 patients receiving Zetia suffered that outcome, a significant difference.

Zetia “should be better for the arteries and it wasn’t,” Taylor told reporters covering last month’s American Heart Association meetings. “The drug wasn’t operating as you would expect.”

Officials at Merck, which co-markets Vytorin, said the study wasn’t large enough to draw firm conclusions and that larger trials of a similar nature are underway. Stay tuned.

Fourteen years ago, Harvard researchers revealed that insurance companies were big-time investors in tobacco companies. The seemingly hypocritical position prompted outrage and calls for them to divest.

But when the same scientists recently re-examined the matter, they found the industry had failed to kick the habit.

By reviewing SEC filings and news reports from 2008, J. Wesley Boyd and colleagues determined that US, UK and Canadian-based insurance companies owned at least $4.4 billion worth of stock in companies whose subsidiaries produce cigarettes, cigars, chewing tobacco and related products.

“Despite calls upon the insurance industry to get out of the tobacco business by physicians and others, insurers continue to put their profits above people’s health,” Boyd told Medical News Today. “It’s clear their top priority is making money, not safeguarding people’s well-being.”

The World Health Organization estimates that tobacco products contribute to 5.4 million deaths per year worldwide.

New Jersey-based Prudential Financial Inc., which markets life and disability insurance, has holdings in tobacco firms like Reynolds American and Philip Morris, that total $264 million.
 
These numbers are dwarfed by Toronto-based Sun Life which sells health, disability, life and long-term care insurance. It owns just north of $1 billion in tobacco company stock.

Meanwhile, London-based Prudential Plc, which offers disability, health and long-term care insurance, holds $1.38 billion in British American Tobacco and other such companies.

“Insurance firms have figured out ways to profit from both… investing in tobacco (and) selling life or health insurance. (They) exclude smokers from coverage or, more commonly, charge them higher premiums. Insurers profit - and smokers lose - twice over,” wrote the authors.

Boyd’s group first reported on the matter in a 1995 Lancet article.

For years, physicians have debated when to start therapy for HIV-infected patients. Starting it early might delay, perhaps indefinitely, progression from a quiescent carrier state to the full blown syndrome, but it exposes patients to unpleasant, sometimes life-threatening side effects.

A study by Mari Kitahata and colleagues may have settled the argument in favor of early drug treatment.

The scientists tracked survival in 17,517 asymptomatic HIV-infected patients who started antiretroviral therapy at different points in the course of their disease, as determined by serum CD4 cell counts.

About a quarter of the subjects began therapy when their CD4 counts were in the 351- 500 range, and the remainder started therapy only after counts dropped to 350 or less.

The mortality risk was 69% higher in the latter group. These findings were confirmed in a second, separate cohort.

The write-up appears in the New England Journal of Medicine.

“This has been one of the most important questions in the last decade: what the optimal timing is for starting therapy,” Kitahata told the New York Times.

“Our study provides evidence that patients would live longer if antiretroviral treatment was begun when their CD4 count was above 350,” added Kitahata, who is director of clinical epidemiology at the Center for AIDS and STDs at the University of Washington.

National guidelines recommend beginning therapy in asymptomatic patients when CD4 counts drop below 350.

Women who took valproate during pregnancy had children with lower IQ scores than those who used a different antiseizure medication, according to scientists at Emory University.

Valproate, available generically or under the brand name Depakote, is the second-most-popular drug for the treatment of epilepsy.

Earlier studies had shown it to cause developmental delays and malformations in the offspring of pregnant women.

To reach these conclusions, Kimford Meador and colleagues recruited 303 pregnant women that took drugs to control epilepsy from 25 medical centers in the US and the UK between 1999 and 2004.

They performed cognitive assessments on 258 2- and 3-year-olds born to these mothers, 53 of which had taken valproate.

They found that kids whose moms had taken valproate while pregnant had a mean IQ of 92. Kids that had been exposed to lamotrigine, phenytoin and carbamazepine in utero had mean IQs of 101, 99 and 98, respectively.

Overall, there was a strong correlation between the IQs of kids and their mothers, but this relation was not present in the offspring of mothers taking valproate.

The write-up appears in the New England Journal of Medicine.

Valproate is also widely prescribed for migraines, pain and psychiatric disorders although people taking the drug for these indications were not enrolled in the study.

The study authors warned against using valproate as first-line therapy for seizure control in women of childbearing age.

“If I (use another drug) and the patient has a breakthrough seizures, I can switch the patient to valproate,” said Meador reasoned for the New York Times. But “If I put the patient on valproate as a first choice and the baby has cognitive impairment or a malformation, I can’t repair that.”

Just 6 years after scientists decoded the human genome, a line of research derived from the breakthrough known as personal genomic medicine is increasingly perceived to be an expensive bear with an uncertain future, according to commentaries in the New England Journal of Medicine.

Since the heralded announcement in 2003, geneticists have undertaken hundreds of genomewide association studies designed to compare the DNA of healthy people with those of patients having specific diseases.

The hope was to pinpoint a handful of culprit genes and by association, biochemical processes that could become targets for disease-modifying drugs, immune therapy or what have you.

But the studies appear capable of explaining just a fraction of the genetic component underlying complex diseases like cancer, schizophrenia and diabetes.

The problem, it seems, has been the assumption that such conditions were promoted by variations in a small number of genes, say 10. Instead, thousands of genes appear to be involved, with multiple variations at each locus exerting myriad effects on other genes and their variants.  

The snafu represents a setback for personal genomics companies that hoped to inform customers about their risk for these diseases.

“With few exceptions, what the genomics companies are doing right now is recreational genomics,” Duke University geneticist David Goldstein told the New York Times. “The information has little or…no clinical relevance.”

In his NEJM piece, Goldstein therefore recommends a strategic shift in genomics research towards decoding the entire DNA of patients with certain diseases.

But Peter Kraft and David Hunter of the Harvard School of Public Health, publishing in the same issue, remain optimistic about genomewide association studies.

“There will be more common variants to find,” Hunter told the Times. “It would be unfortunate if we gave up now.”