Stanford Study Shows Opiates' Side Effects Rooted In Patients' Genetics | Biocompare.com

Genetics play a significant role in determining which patients will suffer the most from the disturbing side effects of opiates, commonly prescribed painkillers for severe to moderate pain, according to a new Stanford University School of Medicine study, which pinpoints nausea, slowed breathing and potential for addiction as heritable traits.

"One of the most hated side effects of these opiates, nausea, is strongly inherited," said Martin Angst, MD, professor of anesthesia and one of two principal investigators for the new study, which explores individual variations in the response to opiate use. The study will be published online June 20 in Anesthesiology. Genetics also play a likely role in determining which patients will suffer from itchiness and sedation associated with the use of these powerful medications, which include morphine, methadone and oxycodone.

"The study is a significant step forward in efforts to understand the basis of individual variability in response to opioids and to eventually personalize opioid treatment plans for patients," said Angst, director of the Stanford Human Pain Research Laboratory. "Our findings strongly encourage the use of downstream molecular genetics to identify patients who are more likely or less likely to benefit from these drugs — to help make decisions on how aggressive you want to be with treatment, how carefully you monitor patients and whether certain patients are suitable candidates for prolonged treatment."

Treatment with opiates, also known as narcotics, is tricky because of this variability in drug response. Certain patients may require 10 times the amount of these painkillers to get the same level of pain relief as others. In fact, in some patients the occurrence of side effects may prevent the use of opioids for effectively alleviating pain. Side effects such as nausea or sedation can be debilitating to some, while nonexistent for others. Similarly, some patients can take medications for months with little addiction potential, while others are at risk within weeks.

Millions of U.S. patients are prescribed opiates for pain each year. A better understanding of the potential risk of side effects motivated the researchers to explore individual variation in pairs of identical and fraternal twins, Angst said. The study was prompted by past genetic studies in animals that have shown a strong genetic component in the response to opiates.

"We rely heavily on narcotics as the cornerstone medication for the relief of pain," said Angst. "Yet we don't know the answers to fundamental questions, such as why some people 'like' narcotics more than others — drug liking and disliking could be key in determining addiction potential."

Researchers recruited 121 twin pairs for the randomized, double-blinded and placebo-controlled study. Pain sensitivity and analgesic response were measured by applying a heat probe and by immersing a hand in ice-cold water, both before and during an infusion of the opiate alfentanil, a short-acting painkiller prescribed by anesthesiologists. The team also compared individual variations in levels of sedation, mental acuity, respiratory depression, nausea, itch, and drug-liking/disliking — a surrogate measure of addiction potential — between identical twins, non-identical twins and non-related subjects. This provided an estimate of the extent to which variations in responses to opiates are inherited. For example, the finding that identical twins are more similar in their responses to opiates than non-identical twins suggested inheritance plays a significant role.

Heritability was found to account for 30 percent of the variability for respiratory depression, 59 percent of the variability for nausea and 36 percent for drug disliking. Additionally, up to 38 percent for itchiness, 32 percent for dizziness and 26 percent for drug-liking could be due to heritable factors. An earlier study published by the same researchers in the March issue of Pain reported that genetics accounted for 60 percent of the variability in the effectiveness of opiates in relieving pain.

"Since side effects are common among patients who use opioid medications, it will be beneficial to use such research to help at-risk patients avoid serious, life-threatening complications," said David Clark, MD, PhD, professor of anesthesia and the other principal investigator for the study.

http://www.biocompare.com/Life-Science-News/115587-Stanford-Study-Shows-Opiates-Side-Effects-Rooted-In-Patients-Genetics/

U.S. Hospitals Adding Palliative Care Teams at a Feverish Pace | Healthland | TIME.com

Fighting stage-four ovarian cancer, Carol Delzatto has had more doctor appointments than she cares to count. But this day, she is beaming as Dr. Pamela Sutton comes into sight, greeting her patient and calling her beautiful. Delzatto looks forward to her monthly meeting with the palliative care doctor, where she won't be pricked and won't be rushed, just listened to and offered help.

Hospitals across the country have been adding programs in palliative care — which focuses on treating pain, minimizing side effects, coordinating care among doctors and ensuring the concerns of patients and their families are addressed — at a feverish pace. The field has expanded so rapidly that a majority of American hospitals now have palliative programs, to the delight of patients who say they've finally found relief and a sympathetic ear.

Palliative care has its roots in the 1970s, but was slow to grow. Several pieces of research helped to advance the cause, though, showing widespread untreated pain in hospitals and nursing homes and the positive impact palliative programs had on such patients.

"She's not writing. She is just looking at me and listening and feeling," said Delzatto, 67, during her visit to Broward General Medical Center, where Sutton helped start the palliative care program more than a decade ago.

Dr. Diane Meier of Mount Sinai Medical Center in New York, who directs the Center to Advance Palliative Care, says one of the discipline's greatest benefits is that it looks at the patient as a whole.

"Patients see a different person for every single part of their body or every problem. The patient as a whole person gets lost," said Meier, who won a MacArthur fellowship for her palliative work. "The patient is a person, not a problem list, not a list of different organ systems with different problems, not a list of different diseases. So we end up serving in a quarterback role for the entire medical system."

In 2000, there were 658 palliative programs in hospitals, according to the Center to Advance Palliative Care, representing about one-quarter of American hospitals. By 2009, about 63 percent of hospitals had palliative teams, with a total of 1,568 programs recorded. The field is expected to continue growing as awareness and acceptance spreads, just in time to help baby boomers — the 78 million Americans born between 1946 and 1964 — as they move toward old age and begin developing more serious and life-threatening illnesses.

Though the programs and their scope vary widely, a common scenario might look like this: A patient is diagnosed with lung cancer, and a palliative care team's assistance is enlisted from the start, working alongside oncologists and other specialists. The palliative team may include doctors and nurses as well as a social worker and chaplain. Together, they coordinate care among the many medical professionals, have long consults with the patients and their families to answer questions, and may preventively prescribe medications for likely side effects of treatment, from pain to constipation to nausea.

The palliative team has a clear vision of the patients' goals and personal philosophies and, depending on these factors, might help steer them away from treatments that are determined to be more painful than they're worth. Though palliative doctors share some similarities with hospice doctors in this regard, their goal is still to cure, and their patients are not considered to be at the end of their lives, they are simply facing a serious illness.

Besides cancer, their help is commonly employed for treatment of heart and liver failure, HIV and AIDS, emphysema, sickle cell anemia, chronic obstructive pulmonary disease and a wide variety of other illnesses.

Palliative teams are sometimes met with doubt by both patients and their medical colleagues. Dr. Timothy Quill, a palliative care doctor at the University of Rochester Medical Center and president of the American Academy of Hospice and Palliative Medicine, concedes that patient recognition of what palliative care is remains relatively low and that resistance to the field remains among doctors untrained in the field.

Aside from misconceptions about palliative care being non-curative pain relief for patients destined to die, specialists may find a palliative team helps a patient reach a treatment decision that doesn't offer the most payment. Quill offers an example of a heart failure patient who may be considering getting a ventricular assist device.

"The economic incentives clearly favor doing aggressive medical interventions like this," Quill said. "Palliative care, it's all conversation. And conversation is not compensated in the same way that doing procedures is in our system right now."

Meier says resistance to palliative care tends to be generational, with many younger doctors embracing the field. Research on the subject has also helped prove its worth, particularly a 2010 study published in the New England Journal of Medicine.

That widely publicized report looked at terminal lung cancer patients and found patients who received palliative care as soon as they were diagnosed were in less pain, happier and more mobile than those who didn't receive such care, and the patients ultimately lived nearly three months longer.

Even with such scientific backing, and generally rave reviews from patients, even palliative care's most ardent backers admit it would not have spread as it has without showing cost savings to hospitals. Because a result of palliative care is shorter hospital stays, it can cut costs since many insurance plans pay a flat reimbursement for a treatment, not for the length of stay.

If a bed is freed up sooner, that means another paying customer can occupy it.

"By itself, better outcomes for patients would not be enough," Meier said. "In our society and current way of life, it is impossible to introduce any innovation whether it's surgery or drugs or any innovation if you can't show that it doesn't increase costs."

Broward General's adult and pediatric palliative teams saw more than 1,300 patients last year, but so far administrators have had trouble quantifying what the precise financial impact has been. Sutton and her colleagues have little doubt their work has resulted in fewer hospitalizations and shorter stays, but have found it hard to pinpoint the savings.

Sutton is focused this day on Delzatto, asking her about her sleep and bathroom patterns, and addressing her pain by writing prescriptions. Before seeing Sutton, the patient said she was suffering so greatly she was barely able to move. Now, she's able again to live fairly normally, browsing garage sales with a neighbor and walking the mall with her husband.

"The oncologists are focusing on chemo, the patients are focusing on cure and I think the conversations about comfort aren't happening," Sutton said.

Much of the appointment, Sutton just sits and listens, to Delzatto talking about her Mother's Day celebration, her new Kindle Fire and how she hopes to be able to go on a cruise later this year. And she hears Delzatto credit her with making her life livable again.

"They need more of you," she said.

http://healthland.time.com/2012/06/04/u-s-hospitals-adding-palliative-care-teams-at-a-feverish-pace/?

Painkillers Add Costs and Delays to Workplace Injuries - NYTimes.com

Workplace insurers are accustomed to making billions of dollars in payments each year, with the biggest sums going to employees hurt in major accidents, like those mangled by machines or crushed in building collapses.

Now they are dealing with another big and fast-growing cost — payouts to workers with routine injuries who have been treated with strong painkillers, including many who do not return to work for months, if ever.

Workplace insurers spend an estimated $1.4 billion annually on narcotic painkillers, or opioids. But they are also finding that the medications, if used too early in treatment, too frequently or for too long, can drive up associated disability payouts and medical expenses by delaying an employee's return to work.

Workers who received high doses of opioid painkillers to treat injuries like back strain stayed out of work three times longer than those with similar injuries who took lower doses, a 2008 study of claims by the California Workers Compensation Institute found. When medical care and disability payments are combined, the cost of a workplace injury is nine times higher when a strong narcotic like OxyContin is used than when a narcotic is not used, according to a 2010 analysis by Accident Fund Holdings, an insurer that operates in 18 states.

"What we see is an association between the greater use of opioids and delayed recovery from workplace injuries," said Alex Swedlow, the head of research at the California Workers Compensation Institute.

The use of narcotics to treat occupational injuries is part of a broader problem involving what many experts say is the excessive use of drugs like OxyContin, Percocet and Duragesic. But workplace injuries are drawing particular interest because the drugs are widely prescribed to treat common problems like back pain, even though there is little evidence that they provide long-term benefits.

Along with causing drowsiness and lethargy, high doses of opioids can lead to addiction, and they can have other serious side effects, including fatal overdoses.

Between 2001 and 2008, narcotics prescriptions as a share of all drugs used to treat workplace injuries jumped 63 percent, according to insurance industry data. Costs have also soared.

In California, for example, workplace insurers spent $252 million on opioids in 2010, a figure that represented about 30 percent of all prescription costs; in 2002, opioids accounted for 15 percent of drug expenditures.

As a result, states are struggling to find ways to reverse the trend, and some of them have issued new pain treatment guidelines, or are expected to do so soon. These states include New York, Colorado, Texas and Washington. Insurers are also trying to influence how physicians prescribe the drugs.

Doctors in four states — Louisiana, Massachusetts, New York and Pennsylvania — appear to be the biggest prescribers of the drugs for workers' injuries, according to a review of data from 17 states by the Workers Compensation Research Institute, a group in Cambridge, Mass.

Painkiller-related costs are also hitting taxpayers, who underwrite coverage for public employees like police officers and firefighters, experts say. In February, one major underwriter, the American International Group, said that it would no longer sell backup coverage to workplace insurers, citing rising pain treatment expenses as one reason.

There is little question that strong pain medications can help some patients return to work and remain productive. But injured workers who are put on high doses of the drugs can develop chronic pain and face years of difficult treatments. It is not clear how, or if, the drugs are involved in the process, but when pain becomes chronic, the cost of a commonplace injury can equal a crippling one, experts said.

"Some of these claims look like someone who fell down an elevator shaft and had multiple injuries," said Dr. Edward J. Bernacki, the director of the division of occupational and environmental medicine at Johns Hopkins University in Baltimore.

For decades, workers' compensation plans, which vary by state, have been plagued by problems like lengthy legal battles over an injury's financial value. But it is in recent years that opioid painkillers have emerged as a major driver of costs, experts said.

Accident Fund Holdings examined its claims and found that the cost of a typical workplace injury — the sum of an employee's medical expenses and lost wage payments — was about $13,000. But when a worker was prescribed a short-acting painkiller like Percocet, that cost tripled to $39,000 and tripled again to $117,000 when a stronger longer-acting opioid like OxyContin was prescribed, said Jeffrey Austin White, an executive with the insurer, which is based in Lansing, Mich.

In a sense, insurers are experiencing the consequences of their own policies. During the last decade, they readily reimbursed doctors for prescribing painkillers while eliminating payments for treatments that did not rely on drugs, like therapy.

Those policies may "have created a monster," said Dr. Bernyce M. Peplowski, the medical director of the State Compensation Insurance Fund of California, a quasi-public agency.

For patients, such policies had consequences.

Dr. Eugenio Martinez, a physician in the Boston area who specializes in rehabilitative medicine, said one patient, a former waitress who hurt her back five years ago in a fall, recently won a court fight to force her insurer to pay for physical therapy. The insurer had cut off those payments five years ago after a few sessions, and the woman, now disabled, had no option but to take strong painkillers, Dr. Martinez said. "It certainly did not help that she was cut off," he said.

Nationwide, data suggests that a vast majority of narcotic drugs used to treat occupational injuries are prescribed by a tiny percentage of doctors who treat injured workers; in California, for example, that figure is just 3 percent. Also, the bulk of such prescriptions go to a relatively small percentage of injured workers, including those who might be addicted to the drugs or those who sell them, experts said.

Several companies, like Accident Fund Holdings and Liberty Mutual, have set up programs in which pain experts contact doctors identified as high prescribers to discuss their practices. The State Compensation Insurance Fund of California has also instituted a policy that requires approval for a doctor to prescribe an opioid for over 60 days.

Insurers say they are making progress in reducing overuse of the drugs. But their ability to influence physicians is limited because workers' compensation plans can allow employees to see any doctor. So several states have or will soon adopt new pain treatment guidelines for doctors who treat workers.

In New York, one proposal would require a doctor to refer a patient who is not improving to a pain specialist when an opioid dose exceeds a certain level, said Dr. Elain Sobol Berger, the associate medical director of the state's workers' compensation board. Washington State has already adopted such a policy.

Dr. Sobol Berger added that the New York rules, which are expected to be proposed this year, will also emphasize nondrug treatments for pain. "We know that there is a significant problem with the management of chronic pain and the use of opioids," she said.

Some insurers, like the California state fund, have also started paying for alternative approaches like specialized psychotherapy or are trying to get addicted workers into treatment. Other companies are also checking on long-disabled workers.

Mark Kulakowski, a 57-year-old former warehouse worker from Peabody, Mass., injured his back more than three decades ago while lifting a box. He has not worked since 1995. Since his injury, he has taken narcotic painkillers and has had a long list of failed treatments.

Recently, his insurer, Liberty Mutual, sought to have a nurse accompany him to his next doctor's appointment, a suggestion he welcomed if it could lead to taking fewer painkillers.

"It just drains everything out of you," he said.

http://www.nytimes.com/2012/06/03/health/painkillers-add-costs-and-delays-to-workplace-injuries.html