The Normal Hematocrit Trial, conducted in the mid-1990s, was the largest study ever to compare the use of epoetin, a drug that stimulates blood production, to treat dialysis patients, who suffer from anemia, or a below-normal red blood cell count, called hematocrit. In healthy individuals, 39 to 45 percent of their blood is comprised of red blood cells. Severe anemia, a hematocrit below 25 percent, can stress heart function, cause marked fatigue, and require blood transfusions.

Most dialysis patients need some epoetin or a similar drug to avoid severe anemia, and the higher the desired hematocrit, the higher the dose required. The study aimed to compare the effects of standard epoetin doses, which maintain patients’ hematocrit around 30 percent, and much higher doses, to raise hematocrit to normal (42 percent). The trial was stopped early in May 1996, just 29 months after it began, because of a trend toward increased deaths and heart attacks in the patients given the higher doses of epoetin. This was the first outcomes trial to show epoetin might be harmful. An editorial accompanying the August 1998 publication of the study in the New England Journal of Medicine, described how, “disappointingly,” there was a trend toward more deaths in the higher dosage group, but argued that the study still supported the recommendations of the National Kidney Foundation’s guidelines, published in the year before, that sufficient epoetin be used to maintain hematocrit between 33 and 36 percent—the upper half of the US Food and Drug Administration’s recommendation at that time—to reduce transfusions, improve quality of life, and possibly reduce deaths.

In March 2012, 14 years later, I published my own analysis of the trial based on Amgen’s clinical trial report, which I obtained through a Freedom of Information Act request. The results were dramatically different.

In 1998, although the risk of death and heart attack was significantly greater among patients receiving the higher doses of epoetin, the NEJM editors reportedly accepted Amgen’s position that the statistics should be adjusted because the company and the trials’ leaders terminated the trial early based on the recommendation of the data safety monitoring board. Therefore the trial results were reported as showing only a trend toward—and not solid evidence for—increased harm. The 1998 paper did not report the unadjusted statistics, or state that the statistical rules employed required the p value to reach 0.00088 to be considered significant, a much high bar than the traditional 0.05. This was also not appreciated by most experts.

According to the 1998 NEJM publication, the only definitive risk from higher epoetin doses was an increased risk of clotting the fistula from which blood is taken to perform hemodialysis, a common and less severe problem. And the higher dose group benefited by receiving fewer transfusions and enjoying higher measures of the “physical function” component of quality of life.

Thus, while the 1998 NEJM publication discouraged high epoetin doses to target hematocrit to 42 percent because of a trend toward increased risks, it also identified clear benefits of exceeding a hematocrit target of 30 percent—fewer transfusions and better quality of life. Epoetin use had already started to increase following the release of National Kidney Foundation’s 1997 KDOQI anemia guidelines, which incidentally, were funded by Amgen. After the NEJMpaper was published, epoetin use in dialysis patients exploded, becoming a $2.5 billion a year market in the US alone.

By 2006, new KDOQI guidelines, again supported by Amgen, recommended all dialysis and kidney disease patients should receive doses of epoetin to maintain a hematocrit of 33 to 39 percent based on quality of life improvements—citing as evidence the Normal Hematocrit Trial and some smaller trials.

The results of my own analysis, on the other hand, published this March in Kidney International, showed that the quality of life scores had not improved in the higher dosing arm. The results I found in the Amgen report, filed with the FDA in 1996, showed that bigger epoetin doses to target higher hematocrit did not improve the physical function quality of life component at all, and had significantly increased the risk of death, heart attack, other thrombotic events, and hospitalizations.

The only benefit from higher epoetin doses was reduced transfusions, though the benefit was minor: one needed to treat 10 patients for 14 months at an additional epoetin cost of about $200,000 to avoid one person being transfused. Increased hospitalizations would further increase the total cost of higher epoetin doses.

The strikingly different results were because the 1998 NEJM publication had replaced the predefined outcomes and analyses with statistical adjustments and post hoc assessments, including replacing the total lack of effect of higher doses on physical function scores with the observation that patients with higher physical function scores had higher hematocrit, presumably because healthier patients respond better to epoetin. The wording was sufficiently unclear that even the KDOQI anemia guidelines misread the quality of life results as indicating that higher doses of epoetin to target higher hematocrit had caused an improvement in quality of life, when in fact, the trial results showed no improvement.

The academic authors of the 1998 publication state there was no intent to mislead, claiming the NEJM editors removed from drafts all the adverse results that I reported in 2012. They also state the 1998 publication clearly discouraged targeting hematocrit to 42 percent. What the 1998 publication did not do, however, was make clear, as my report does, that higher epoetin doses carry great risks, while the only benefit was a meager reduction in transfusion risk at great monetary cost.

Of course, even if there was no intentional deception, the effect was to force experts to say targeting hematocrit to about 42 percent using higher epoetin doses improved quality of life and reduced transfusions, and prevented them from saying such management significantly increased deaths, cardiac events, thrombotic events, and hospitalizations. Amgen controlled the debate, and by 2012 had made $37 billion from epoetin sales in the United States alone.

And if the intent was not to mislead, why not just publish subsequent articles clarifying the results, especially the quality of life results? The anemia workgroups that developed the KDOQI guidelines included one of the 1998 NEJM authors. Why not notify the KDOQI organization and other workgroup members that they were misreading the 1998 NEJM results? I cannot imagine what Amgen would have done if they had intended to mislead.

I waited 1,260 days to receive the trial report from the FDA. Two weeks before receiving the report, on June 24, 2011, the FDA released a safety warning and new label advice for use of epoetin in chronic kidney disease. It withdrew the previous recommended dose and hematocrit target of 30-36 percent. The new label states that there is no known safe dose of epoetin, no proven safe hematocrit target, and when using epoetin in dialysis patients, decrease or stop the epoetin when hematocrit exceeds 33 percent. The label now reports the Normal Hematocrit Trial’s hazard ratio and confidence intervals for death and heart attack and all-cause death as significantly higher in the higher hematocrit arm, just as I reported them earlier this year.

Finally, as strange as it seems, I am now the sole author of the publication on the predefined primary and secondary results of the largest outcomes trial of epoetin in dialysis patients, and I didn’t even participate in the trial. Perhaps the FDA will make the epoetin label cite my paper.

Daniel Coyne is a Professor of Medicine at Washington University School of Medicine in St. Louis, Missouri.

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KANSAS CITY, Kan., May 14, 2012 /PRNewswire via COMTEX/ -- With the predominance of male athletes featured on television and covered in the media year-round, most Americans are familiar with some of the most common injuries sustained by men in various sports. As the 2012 Summer Games approaches, female athletes will have additional opportunities to be featured, but are their potential injury risks the same as their male counterparts?

"Women are more likely to have a different set of injuries because of the types of sports they play or due to inherent differences in anatomy or muscle control and responses," says Dr. Kim Templeton, an orthopedic surgeon at The University of Kansas Hospital and Professor of Orthopedic Surgery in the University School of Medicine. "Women can help reduce their potential for an injury by understanding these differences and attempting to modify those factors that can be addressed, such as relative weakness of some muscles or avoiding positions that place them at higher risk for injury."

Dr. Templeton, who is senior editor and co-author of the upcoming book "Women's Sports Injuries," lists the following injuries as most common for female athletes.

ACL Tears: The anterior cruciate ligament (ACL) is a tight band of tissue that binds together the bones in the knee to keep the joint stable. While men typically tear this ligament as a result of direct contact, women are more likely to tear it due to the positions in which they land. This injury is common among female soccer and basketball players, the latter primarily due to the way they inherently land from a jump. When landing with their hips and knees straight, this forces the knee to straighten beyond its natural range, causing the ACL to pull apart. One way to help prevent this injury is to build up strong hamstrings, which will take pressure off the ACL. Another strategy is to learn different landing techniques, especially those where the hips and knees are bent.

Concussions: Concussions occur more frequently in women than in men, for those sports played by both genders. As with the other sports-related injuries, there are probably several factors that lead to this, including weaker neck muscles in women to absorb impact and stabilize the head, differences in inherent preparation for contact around the head and a greater difference between the size of the head and the size of the ball for sports such as soccer. Responses to concussions also differ between the sexes, with men and women showing different areas of deficits in the short and long term after the injury. The first concussion increases the risk of sustaining a second concussion. Athletes, families and coaches need to be aware of the signs and symptoms of concussions. Athletes need to be kept out of practice and competition until these signs and symptoms are resolved.

"Runners Knee" or Anterior Knee Pain Syndrome: This is caused by irritation of the cartilage on the undersurface of the kneecap and is more common in women due to the alignment of the pelvis and legs and also due to inherent, relative differences in muscle strength. To avoid runner's knee, use proper running shoes with adequate support. In addition, focus on strengthening the quadriceps, the muscles in front of the thigh that straighten your knee and control your knee cap. For women, it is also important to strengthen the muscles that turn your hip out, as this will help with the positioning of the knee cap during activities.

Stress Fractures: They are small cracks in a bone, often developed from overuse and/or low bone mass. Stress fractures occur when bone is not allowed the time necessary to recuperate from the impact of sports activities, especially if athletes rapidly increase their training or change running surfaces. Stress fractures are also more common in women with low bone mass, as it does not respond and strengthen as quickly in response to increasing activities levels, as normal bone. Stress fractures can likely be prevented by gradually increasing activity, building strong, sturdy calves that absorb the shock around your bones, wearing well-cushioned sports shoe that are in good condition and developing healthy bone habits (e.g., taking in enough calories to support the athlete's level of activity, adequate calcium and vitamin D intake).

Sprained Ankle: Ankle sprains occur more commonly in female than male basketball players. These can be caused by simply rolling your ankle - whether by landing wrong on an uneven surface or due to increased friction between your shoes and the playing surface. Differences between men and women in terms of this injury are most likely due to differences in how the pelvis and legs are aligned, as well as differences in how loose ligaments are. Strengthening and balancing exercises can help avoid a sprained ankle. These exercises are especially important for those athletes who have had a prior ankle sprain, as this places them at higher risk of an addition ankle injury. For those with prior injuries, examine the position in which the sprain occurred and focus on maneuvers that avoid that movement.

Meniscus Tears: The meniscus is a rubbery, c-shaped disc that cushions your knee. The two menisci in each knee help keep your knee steady by balancing your weight across the knee. To help prevent meniscus tears, work on stretching and strengthening your legs.

If an injury does occur, Dr. Templeton recommends discussing this with your health care professional. For minor injuries of the legs, the commonly used RICE (Rest, Ice, Compression, and Elevation) protocol may be all that is needed. Continued pain after a few days suggests a follow-up with your local doctor. More significant injuries will need additional evaluation and treatment.

Rest. Take a break from the activity that caused the injury. Your doctor may recommend that you use crutches to avoid putting weight on your leg.

Ice. Use cold packs for 20 minutes at a time, several times a day. Do not apply ice directly to the skin.

Compression. To prevent additional swelling, wear an elastic compression bandage (not too tight, more compression isn't necessarily better).

Elevation. To reduce swelling, recline when you rest, and put your leg up higher than your heart.

The University of Kansas Hospital is the region's premier academic medical center, providing a full range of care. The hospital is affiliated with the University of Kansas Schools of Medicine, Nursing and Health Professions, and their various leading edge research projects. The constantly growing facility contains 576 staffed beds (plus 24 bassinets) and serves nearly 27,000 inpatients annually. The University of Kansas Hospital's comprehensive heart program is ranked 39th in the nation by U.S. News & World Report and is housed in the state of the art Center for Advanced Heart Care. Other U.S. News & World Report nationally ranked programs include Pulmonology, Ear Nose & Throat, Gastroenterology, Nephrology (kidney) and Cancer. The cancer program is part of The University of Kansas Cancer Center, based in the region's largest outpatient cancer facility, the Richard and Annette Bloch Cancer Care Pavilion, located in Westwood, Kansas, 1 ½ miles from the main hospital. The hospital has received Magnet nursing designation, reflecting the quality of care throughout the hospital, an honor awarded to only 6.6 percent of the hospitals nationwide. The hospital also houses the region's only burn center and the area's only nationally accredited Level I Trauma Center. For more information, visit www.kumed.com .

SOURCE The University of Kansas Hospital

Copyright (C) 2012 PR Newswire. All rights reserved

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LAWRENCE, Mass.,—NxStage Medical, Inc. commented on findings of the Chronic Disease Research Group (CDRG) study showing that patients receiving daily, or more frequent, home hemodialysis(HHD) with the NxStage System One are more likely to receive a kidney transplant when compared with conventional thrice-weekly dialysis, particularly in patients not on the transplant waitlist at initiation of daily HHD.

The study, "Transplant Rates in Frequent Hemodialysis and Matched Thrice-Weekly Hemodialysis Patients," was presented on Thursday, May 10 at the National Kidney Foundation (NKF) Spring Clinical Meeting in Washington, D.C.

The CDRG retrospective cohort study compared cumulative incidence of transplant in 1,873 daily HHD patients using the NxStage System One from 2005 to 2007 and a matched cohort of 9,365 thrice-weekly, in-center hemodialysis patients from the United States Renal Data System (USRDS) database. The study was designed using a unique, rigorous matching process with 17 covariates that could impact transplantation incidence, including demographics, comorbidity and socioeconomic status. Specifically, findings showed:

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CORBIN — By Jeff Noble / Staff writer

As a long-haul trucker, Rick McKiddy’s travels took him on many paths. Strong, muscular and with a big-hearted personality to match, he delivered the goods, and made a good living for his family.

But when his doctor delivered the news eight years ago that his kidneys were failing, the big friendly bear of a man was crushed.

It would lead to a path of exhausting treatments, a kidney transplant in 2007 — which his body rejected more than a year later, more treatments, and now, waiting for a donor for a second transplant.

The past eight years haven’t been the best for Rick McKiddy, his wife Kristy McKiddy, who works at Corbin Elementary School, and their two sons — 10-year-old Logan McKiddy, and 6-year-old Rex Allen McKiddy. The medical expenses have drained them of their once comfortable life, much like the dialysis treatments have drained Rick McKiddy of his energy.

But it hasn’t drained their spirits.

“If anything, it’s made us stronger. Closer. You don’t take days for granted anymore,” Rick McKiddy said.

He joined his wife and their sons after school, after he had spent four-and-a-half hours at a Corbin dialysis clinic for treatments earlier in the day.

“I do it on Mondays, Wednesdays and Fridays. It’s not really painful. It just drains your body. Your blood pressure goes down. I don’t have much energy,” Rick McKiddy added.

His trail to a successful and healthy life took a sharp detour in 2004, during that doctor’s visit.

“They found elevated levels of creatine in his body. The doctor told him that if he didn’t start treatments and have a kidney transplant, he wouldn’t live to see 30. He was 27 at the time,” Kristy McKiddy said.

Rick McKiddy recalled that day when time froze for him.

“It was hard to take when I heard the news. It was hard to swallow. We were devastated. I did a few more runs, and ultimately had to quit work when I began dialysis treatments.”

The road to a transplant contained quite a few bumps for the family. Rick McKiddy had no medical insurance or benefits. Kristy McKiddy became the breadwinner. They also learned their son Logan is a Type 1 diabetic, and is insulin-dependent.

“Raising children and working one job was hard. We have a lot of medical expenses because of the treatments and medications. We lost cars, we lost homes, we lost everything, but we never lost hope. Never,” noted Kristy McKiddy.

Part of that hope came from a strong support group from the McKiddy’s church, Blessed Hope Baptist Church in Rockholds. Another part came from the family’s hearts, and minds. “We always look on the positive side. Always. You always try to keep a smile on your face,” Rick McKiddy pointed out.

It was that strength and resilience that led them to Rick McKiddy’s first kidney transplant about five years ago at the University of Kentucky Medical Center in Lexington.

The doctors found a donor for Rick McKiddy. It was one of his wife’s kidneys.

After the transplant, Rick McKiddy spent the next 15 months on dialysis treatments. The transplanted kidney ultimately failed, due to rejection by his body.

“At UK the doctors tried a couple of treatments, beginning in July of last year. Nothing worked. So in September they told us there was nothing they could do. Rick would need a second transplant,” Kristy McKiddy said.

This time, Kristy McKiddy’s sister hopes to be the kidney donor. But according to her, the doctors at UK told the family since her husband’s body rejected her kidney, he would also reject her sister’s kidney. To make matters worse, this February, while continuing dialysis treatments, Rick McKiddy had 95 percent blockage in his main artery.

Kristy McKiddy said, “Dialysis is hard on your heart. We felt time was running out. So we investigated and found out about paired organ donation, a trade program for kidneys. My sister wants to do this. She’ll be put on a list, and they’ll try to find a perfect recipient for her kidney. In exchange, Rick will hopefully find a better match for his kidney. UK doesn’t offer this program, but they do in Baltimore, Maryland and in Indianapolis, at Indiana University Hospital. We decided to go to Indiana. And we prayed earnestly that God will put us in the right direction.”

“As a result of those decisions, everything lately has been full-throttle, wide open. And we started fund-raising, to help with the  expenses,” said Rick McKiddy.

The “Transplant Hope for Rick” 2-Mile Run/Walk will be held Saturday starting at 6 p.m. at the Corbin High School track, behind the school. All the proceeds will go to the Rick McKiddy Medical Fund, which will help with the kidney transplant expenses. While pre-registration has ended, you can still register for the walk/run by getting a registration form by emailing Kristy McKiddy at This e-mail address is being protected from spambots. You need JavaScript enabled to view it . You can also pick up a form at Corbin Elementary School, or from Michael Howard, at his insurance agency in Williamsburg. Those registering can also get a free T-shirt at the event, on a first-come, first-served basis.

Since announcing the event, Kristy McKiddy said an outpouring of support has beat a path to the McKiddy’s door.

“When the word got out about this run/walk that we needed 20 sponsors for the T-shirts, we got over 50 sponsors. We’ve also had several donations from people who wanted to help us out, but wanted to remain anonymous. We’re a strong family, but we’re also a very emotional family. Through it all, through the bumps and smooth spots, we have been blessed,” Kristy said as her eyes misted.

Rick McKiddy put it this way: “We don’t want people to feel sorry for us. There’s others who have it rougher. It’s humbling for us to see this show of support. We’re very appreciative of what people have done for us. We’re never gonna give up, that’s for sure. We’ll keep on truckin.”

Their son Logan then entered the room and asked his Mom and Dad a question.

“Can we go to Washington D.C. one day? That’s where the White House is.”

“One day,” Kristy McKiddy smiled as she answered her son. “One day.”

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