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As ‘Abortion Pill’ Turns 15, Debate Rages On

By Marie McCullough, The Philadelphia Inquirer (TNS)

Fifteen years after its approval in the United States, the drug mifepristone is used in nearly a quarter of all abortions, a proportion that has grown steadily even as the national abortion rate has fallen to a historic low.

Federal data also show that mifepristone has accelerated the shift toward early pregnancy terminations — before 10 weeks — when it is safest and has the most public acceptance. Maker Danco Laboratories says more than 2 million women have used its “early option pill.”

The impact, however, has not fit the predictions of either side in the nation’s bitter abortion divide. Mifepristone has not made abortion more common or endangered women’s health, as opponents said it would. It has done little to make abortion more accessible or part of private medical practices, as supporters hoped.

What mifepristone has done is open another front in the political battle over abortion rights. Supporters have worked to enable mifepristone to be prescribed by nonphysicians such as nurse practitioners, and remotely through “telemedicine” technology, while abortion opponents have worked to block such measures.

A few states, notably Texas, have put up high barriers to medication abortion — although legal challenges have removed or delayed most of the measures. For example, these states require doctors to stick to the outdated prescribing regimen proposed by Danco 15 years ago and approved by the U.S. Food and Drug Administration, which limits mifepristone use to no later than seven weeks of pregnancy. The simpler, lower-dose regimen used through nine weeks is recommended by medical groups and the World Health Organization.

“It’s clear that the anti-abortion movement has targeted this technology for restrictions,” said Daniel Grossman, an obstetrician-gynecologist at the University of California, San Francisco, who studies abortion access.

Cheryl Sullenger, senior policy adviser with Operation Rescue, countered with the anti-abortion view: Medication abortion is risky, painful, and involves insufficient medical supervision.

“I think it’s a moneymaking scheme for the abortionist, an opportunity to make a lot of money with a little effort,” she said.

The divide over abortion is as deep as ever. Planned Parenthood, a main provider of medication abortions, is facing Republican congressional challenges to its federal funding. Anti-abortion activists have accused the group of improprieties in donating fetal tissue for medical research, which Planned Parenthood vigorously denies.

Medication abortion actually involves mifepristone, developed in the 1980s by the French company Roussel-Uclaf, plus a second drug, misoprostol.

The mifepristone pill, taken by the patient at the abortion clinic, triggers bleeding by blocking a hormone needed to sustain pregnancy. Up to 48 hours later at home, she takes misoprostol to cause uterine contractions and ensure expulsion of the grape-sized fetus. An ultrasound or blood test two weeks later confirms the abortion.

The process feels like a heavy menstrual period, said Dayle Steinberg, president and chief executive of Planned Parenthood of Southeastern Pennsylvania.

“Most women experience strong cramps, and it takes longer than a surgical abortion,” she said.

The method has been well-studied by researchers, the FDA, and the Centers for Disease Control and Prevention:

Surgery is needed to complete about 5 percent of medication abortions. About 0.2 percent of patients suffer serious complications such as hemorrhage. There have been 14 deaths among women taking the drugs, one since 2011, and none that the FDA could definitely link to the abortion drugs.

Very early termination — through six weeks — has risen from 19 percent of all abortions in 1998, to more than a third now. The increase was greatest in the two years after mifepristone’s approval, suggesting it fueled the trend.

Medication abortion requires minimal medical equipment. A study found 193 of the nation’s abortion facilities (17 percent) offered only this option in 2011. The cost of an abortion through 12 weeks, whether surgical or medication, averages $500.

Exactly how many private physicians provide the abortion pill is unclear, but there are not many.

In 2011, 286 doctors’ offices did some type of abortion, and the total number of procedures was about 14,000 — 1 percent of the nation’s one million abortions, according to the Guttmacher Institute, a research center that supports abortion rights. Danco says 7 percent of its mifepristone sales last year were to private physicians.

“There are many reasons why private doctors may not offer it,” said Beverly Winikoff, a public health physician who worked to get mifepristone licensed and approved. “There are many building leases that prohibit them from performing abortions. Or their partners don’t want them to. Or they fear the political situation. Why should they take on that monster problem? In that sense, I have to say the anti-choice people have kind of won because people have to be so terrified all the time.”

Because abortion access remains a problem — 35 percent of women of childbearing age live in counties with no providers — some activists want to expand telemedicine.

Here’s how it works where it is now permitted: The patient goes to an abortion clinic, where a nurse does the usual work-up, which includes taking a medical history and doing an ultrasound to verify that she is less than 10 weeks pregnant.

Then the patient is connected via videoconference with a doctor in a distant location. After reviewing her records and answering questions, the doctor remotely opens a drawer in front of the patient containing two pills. The patient takes the mifepristone while the doctor and nurse observe, goes home with misoprostol, and returns in two weeks.

This option is now available in only two states — Iowa and Minnesota.

The FDA-approved but outdated abortion-pill regimen has also been the subject of legal fights in at least five states, even though physicians have discretion to prescribe approved drugs in “off-label” ways. Danco, a privately held, one-product company in New York, is “very aware” of this issue, said spokeswoman Abigail Long.

“But it costs money to change the label. We are a small company, so we have to think carefully about it. It would cost a little over $1 million,” she said.

“At the appropriate time, we’ll have a discussion with the FDA about it.”

(c)2015 The Philadelphia Inquirer. Distributed by Tribune Content Agency, LLC.

(Photo from Flickr Commons/World Can’t Wait)

Two More Studies Say FDA Is Bad At Regulating Medical Devices

By Marie McCullough, The Philadelphia Inquirer

Two new studies add to a mountain of evidence that the U.S. Food and Drug Administration has done a poor job of making sure medical devices are safe.

The studies, in the current issue of JAMA Internal Medicine, are accompanied by commentaries that point out that the agency recognizes the need for change and is in the midst of improving the device approval system.

But critics say the FDA has an inherent conflict because of its dual role of protecting public health and encouraging medical innovation.

One of the new studies focuses on the device approval pathway known as 510(k). Created in 1976, the process allows diagnostic tests, surgical machines, heart valves, and other potentially risky devices to be cleared for marketing by submitting scientific evidence that they are equivalent to a “predicate” product already on the market. In contrast, new drugs are required to show safety and effectiveness in clinical tests.

The Institute of Medicine, an influential federal advisory panel, and advocacy groups such as Public Citizen have issued reports in recent years calling for the replacement of the 510(k) system.

For their study, researchers from the National Center for Health Research chose 50 recently marketed implantable devices — including hip replacements and bladder slings — from about 400 per year that the FDA approves under 510(k). Using an FDA database, they found that just eight of the 50 devices had filed scientific data to support their claim of being like an existing product, and only 31 of 1,105 predicate devices had done so.

“Despite the legal requirement that scientific evidence of substantial equivalence be publicly available … such information is lacking for most implanted medical devices cleared between 2008 and 2012, as well as for their predicates,” the authors concluded.

The other study, led by researchers from the Pew Charitable Trusts, focused on an FDA program that monitors the safety of high-risk medical devices such as heart stents and defibrillators. While these go through more stringent approval processes than lower-risk devices, serious problems may not show up until the devices are widely used. In recent years, for example, multiple companies have recalled defective defibrillator wiring that was placed in hundreds of thousands of patients.

The researchers found that the FDA ordered 223 post-approval studies of 158 high-risk medical devices from 2005 through 2011. However, most of the studies were too small to evaluate safety, and companies were not penalized for study delays.

When the studies revealed problems, the FDA took little or no action: It ordered only one device removed from the market, and required labeling changes for 31 products. Labeling is basically the instructions for the physician.

“One device label was changed to include the high rates of heart attacks and deaths at five years,” said Joshua Rising, a Pew researcher and study author.

While label changes may prompt physicians to add stronger warnings to the consent documents that patients have to sign, the value of labeling in ensuring safety is controversial.

“Label changes aren’t going to do anything to protect anybody,” said Noorchashm. “It’s just another layer of informed consent.”

Since December, cardiac surgeon Hooman Noorchashm of Thomas Jefferson University in Philadelphia, has waged an aggressive media and lobbying campaign to get the FDA to ban a gynecological surgery device that can spread undetected cancer.

Gynecological power morcellators device enables hysterectomies or fibroid removal to be done through tiny abdominal incisions. But in as many as one in 350 cases, the procedure spreads and worsens a rare, aggressive uterine cancer that presurgical tests can’t detect.

Anesthesiologist Amy Reed, Noorchashm’s wife and the mother of their five children, has been fighting advanced leiomyosarcoma since she underwent morcellation almost a year ago.

The FDA in April issued an unusual safety advisory to discourage physicians from using the device, and in July the agency held a hearing to decide what more to do.

But it hasn’t taken further action. (The main morcellator manufacturer has suspended sales, and the device has been disavowed by many doctors and a big health insurer.

“The FDA does not have patient safety as its primary directive,” Noorchashm said. “It wants to get innovative products to market quickly.”

Photo: Thirteen of Clubs via Flickr

Consensus Grows That Bed Rest Could Hurt Pregnant Women

By Marie McCullough, The Philadelphia Inquirer

For much of his 20-year career as a maternal-fetal medicine specialist, Anthony J. Sciscione has been criticizing something obstetricians routinely prescribe to try to prevent premature birth: bed rest.

Studies consistently show that pregnant women who lay around for hours at a time, day after day, are just as likely to deliver too early as women who carry on with their normal activities.

Now, Sciscione and like-minded iconoclasts are hammering the mounting evidence that activity restriction during pregnancy is not just unhelpful, but harmful.

Last year, for example, University of North Carolina obstetrician-gynecologist Christina McCall published a paper that concluded bed rest is “unethical.”

“Since then, it’s gotten a lot of notoriety,” said Sciscione, who directs maternal-fetal medicine at Christiana Care Health System in Wilmington, Delaware.

The latest sign of a shift came last month, when the Society for Maternal-Fetal Medicine issued a new guideline and patient handout written with Sciscione’s help.

Citing the many ways that immobility is physically, mentally, and economically risky, the society for obstetricians who specialize in high-risk births recommended “against the routine use of activity restriction or bed rest during pregnancy for any” therapeutic purpose.

Each year, research suggests, about 18 percent of pregnant women in the United States are placed on bed rest — although the definition ranges from resting for an hour several times a day to uninterrupted confinement except for bathroom breaks.

This does not mean that specialists have faith in bed rest. A 2009 survey found that while 71 percent would prescribe it for women in preterm labor and 87 percent for premature rupture of membranes (the woman’s “water breaks”), most said they expected little or no benefit.

And in 2012, when the American College of Obstetricians and Gynecologists issued the only other United States guidelines, it said bed rest should not be routinely used because it hasn’t been shown to work.

So why do doctors persist in prescribing it?

Mostly because they have little else to offer. Despite all the advances in medicine, the underlying causes of preterm labor and delivery remain mysterious. The only thing proven to reduce the chance of preterm birth — and only in women with certain risk factors — is supplementation with the hormone progesterone.

The problem is that prolonged inactivity is not benign. The new guidelines, and an article reviewing the medical literature that Sciscione published, cite the growing list of documented dangers:

— Lack of weight-bearing activity results in loss of muscle mass, bone mass, blood plasma volume, and cardiovascular conditioning. Measurable harm can occur after only a few days. After giving birth, one study found, 71 percent of women had trouble with stairs, and 14 percent needed help walking.

— Despite burning up fewer calories, restricted women typically lose weight, probably because of muscle loss. Their babies also have lower birth weights compared with unrestricted women. And while most studies found bed rest makes no difference in rates of birth before 37 weeks, one study found it was more common with bed rest.

— Higher rates of gestational diabetes and life-threatening blood clots in the lungs and legs are linked to bed rest.

— Depression and anxiety are far more common when stuck in bed. Women who have to take prolonged leaves from work worry about lost income and possible job loss.

The emotional toll on the rest of the family “is also high,” Sciscione says. One study found children were frightened or confused about the health of their mothers and unborn siblings.

Photo: The Jordan Collective via Flickr

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Researchers ‘Edit’ Genes To Make Cells Resist HIV

By Marie McCullough, The Philadelphia Inquirer

PHILADELPHIA — University of Pennsylvania researchers have snipped out a single gene in patients’ immune cells to make them partly resistant to infection with HIV, the virus that causes AIDS.

The study, in this week’s New England Journal of Medicine, bolsters hope for controlling HIV without daily antiviral drugs — a so-called functional cure.

But even more important, as the first paper to report the modification of an exact spot in human DNA, it marks the arrival of the age of gene editing.

The researchers’ editing tool, developed by Sangamo BioSciences of Richmond, Calif., was made of natural proteins that recognize specific DNA sequences. These “zinc finger nucleases” can be used like molecular scissors to introduce intentional genetic mutations.

Until now, gene therapy has relied on disabled viruses to carry and dump genes somewhat randomly into a cell’s DNA.

“The ability to edit the human genome has been a prayer ever since we first understood that genes control biology,” said Sangamo CEO Edward Lanphier, who founded the company in 1995. “But we’ve moved beyond the concept of gene replacement, which was the idea behind gene therapy. Gene editing is much safer and more effective.”

Eminent AIDS researcher Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said, “I think this is an important step in the right direction, not only for HIV, but for other diseases.”

Indeed, Sangamo is working on zinc finger-based approaches to treat and possibly cure hemophilia, Huntington’s disease and sickle-cell anemia — diseases caused by a single defective gene. The firm also supplies ready-made and custom-made zinc finger proteins to scientists around the world.

“And further progress can be expected,” wrote Stanford University researchers Mark A. Kay and Bruce D. Walker in an editorial accompanying the Penn study. “In the past few years there has been an explosion in new ‘genome editing’ technology.”

The Penn study — led by gene-therapy pioneer Carl June and underwritten with federal and Sangamo funding — built on the observation that some people are naturally invulnerable to HIV infection because of genetic variations. When they do get infected, their progression to AIDS is unusually slow.

One such gene variant keeps T cells — the disease-fighting blood cells that HIV attacks — from making a receptor, a sort of doorway, that HIV uses to break in. About 10 percent of Caucasians have inherited one copy of this gene variant, making them resistant to HIV infection. About 1 percent have two copies — one from each parent — making these fortunate few immune to HIV.

To artificially confer this invulnerability, June’s team removed T cells from 12 HIV-infected patients who were taking standard antiviral drugs and used zinc fingers to delete the doorway receptor gene. The modified T cells were coaxed to multiply, then each patient received a transfusion of roughly 10 billion.

Zinc finger editing is not perfect — at least, not yet — so only about 20 percent of the modified cells actually lacked the doorway receptor gene.

To see whether these modified cells might be fighting HIV, the researchers interrupted standard drug therapies for three months in six patients with healthy T cell counts. (The other six patients had suboptimal T cell counts despite standard drugs, so their treatment was not interrupted.)

Blood levels of HIV decreased in four of the patients who suspended treatment, falling to an undetectable level in one man.

A single patient had a serious complication, but it was a reaction to the transfusion, not the cells.

Some of the modified T cells were found to concentrate in the patients’ guts, where HIV builds a stockpile. Current drugs reduce the ability of HIV to reproduce but can’t completely eliminate it from the body because of this reservoir.

“We believe the only effective way to functionally cure HIV is to get the immune system to reduce the reservoir,” Lanphier said.

AFP Photo/Spencer Platt