MMWR 2/7/08:

CDC is investigating an outbreak of acute allergic-type reactions among patients who have undergone hemodialysis since November 19, 2007. The majority of reactions have occurred among adult hemodialysis patients, with onset within minutes of initiating a hemodialysis session. Although the cause of the outbreak is unknown and remains under investigation, the majority of reactions occurred in patients who received intravenous heparin produced by Baxter Healthcare Corporation (Deerfield, Illinois). Baxter voluntarily recalled nine lots of heparin multidose vials after learning of these adverse events among patients who received heparin during dialysis. This report describes the ongoing investigation.

CDC was first notified on January 7, 2008, by the Missouri Department of Health and Senior Services (MDHSS) of allergic-type reactions among pediatric hemodialysis patients that occurred beginning November 19, 2007, at a pediatric hospital. The reactions had been reported to MDHSS by a health-care provider at the hospital. The symptoms occurred within minutes of dialysis initiation and included facial swelling, tachycardia, hypotension, urticaria, and nausea. A total of eight episodes of acute allergic-type reactions have been identified as occurring among four patients at the pediatric hospital during November 19, 2007–January 15, 2008. These reactions were reviewed by a clinical allergist and were determined to be consistent with anaphylactic or anaphylactoid reaction.

Upon learning of the initial cluster, CDC solicited reports of similar allergic-type reactions among hemodialysis patients nationally through nephrology e-mail lists and public health notifications. In response to these case-finding measures, CDC was contacted on January 9, 2008, by a dialysis supply company that had received reports during the previous 2-week period of approximately 50 similar reactions among adult hemodialysis patients at dialysis facilities in six states. A second supply company reported learning of similar reactions from dialysis facilities as early as December 10, 2007. CDC alerted the Food and Drug Administration (FDA) to these nationwide reports of allergic-type reactions on January 9, 2008, and has been collaborating with FDA on the investigation.

As part of the investigation, CDC has created a working case definition for these reactions. A confirmed case of acute allergic-type reaction has been defined as an episode of anaphylactic or anaphylactoid reaction characterized by angioedema (particularly swelling of lips/mouth, tongue, throat, or eyelids) or urticaria. A probable case has been defined as an episode that includes at least two of the following signs and symptoms: 1) generalized or localized sensations of warmth; 2) numbness or tingling of the extremities; 3) difficulty swallowing; 4) shortness of breath, audible wheezing, or chest tightness; 5) low blood pressure/tachycardia; or 6) nausea or vomiting.

Of the episodes reported as of January 30, CDC has identified 65 confirmed or probable cases among 53 hemodialysis patients that occurred during November 19, 2007–January 21, 2008, at 19 dialysis facilities in 12 states. CDC currently is investigating an additional 36 possible cases. Most reactions resolved after interruption of the dialysis session or treatment with diphenhydramine or steroids at the facility. Other than the eight episodes reported by MDHSS, all cases have occurred among adults.

One common factor among the cases being investigated was receipt of heparin (1,000 units/mL) from 30-mL or 10-mL vials manufactured by Baxter. Intravenous heparin is administered during most hemodialysis sessions to prevent clotting of the access and dialysis circuit. In 61 (94%) of the 65 cases, the affected patient received Baxter heparin during hemodialysis. Dialyzers from four different companies were being used when the reactions occurred. The most commonly used dialyzers, manufactured by Fresenius Medical Care (Waltham, Massachusetts), were being used in 26 (40%) of the episodes. Other exposures have not been ruled out as potential causes of the reactions, and CDC is conducting additional epidemiologic studies to examine those exposures.

On January 17, 2008, Baxter announced a voluntary recall of nine lots of heparin, based on reports the company had received (1). All nine lots were produced at a single plant; eight of the nine lots were produced during September–November 2007. Despite the January 17 recall, an additional reaction occurred on January 21, 2008, after a hemodialysis patient was administered Baxter heparin from one of the recalled lots. CDC has found indications of delays in removing the recalled lots of heparin from distribution, which might result in continued exposures. In addition, these reactions might not be limited to hemodialysis settings. One cardiac-care facility has reported seven allergic-type reactions among cardiac patients who received heparin from lots that were later recalled. CDC and state health departments are investigating these reactions.

Reported by: G Turabelidze, MD, Missouri Dept of Health and Senior Svcs; A Elward, MD, Washington Univ School of Medicine; M Jones, BJC Healthcare, St. Louis, Missouri. PR Patel, MD, M Arduino, DrPH, C Gould, MD, N Shehab, PharmD, K Sunkavalli, MPH, Div of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases; S Schillie, MD, D Blossom, MD, A Kallen, MD, J Jaeger, MD, EIS officers, CDC.

Editorial Note:

The temporal and geographic distribution of these reactions in a discrete population of patients suggests common exposure to a health-care product with wide distribution in the United States. Previous clusters of acute allergic-type reactions among hemodialysis patients have been attributed to certain types of dialyzer membranes, ethylene oxide (used by the manufacturer as a sterilant), angiotensin-converting enzyme inhibitors, and the reuse of dialyzers (2,3). However, based on preliminary findings, these previously recognized causes of allergic-type reactions in dialysis patients are unlikely to explain this outbreak. Heparin is a biologic product rarely associated with anaphylactic reactions (4).

CDC is conducting additional case-finding activities and epidemiologic studies to define the scope of the outbreak and is exploring options for laboratory testing to further characterize these reactions. Health-care providers should 1) immediately discontinue use of and segregate the recalled lots of heparin, 2) report medication reactions to MedWatch, the online FDA reporting system for adverse medication events,* and 3) report to their state or local health departments any acute allergic-type reactions that have occurred since November 2007 in patients receiving hemodialysis or intravenous medication infusion. Health departments are asked to report reactions to CDC by telephone (404-639-4514 or 404-639-4273) or e-mail (dblossom@cdc.gov or ppatel@cdc.gov).

References

1. Baxter Healthcare Corporation. Urgent product recall. Rockville, MD: Food and Drug Administration; 2008. Available at http://www.fda.gov/medwatch/safety/2008/heparin_recall_01-17-2008.pdf.
2. Arduino MJ. CDC investigations of noninfectious outbreaks of adverse events in hemodialysis facilities, 1979–1999. Semin Dial 2000;13: 86–91.
3. CDC. Epidemiologic notes and reports of acute allergic reactions associated with reprocessed hemodialyzers—Virginia, 1989. MMWR 1989;38:873–4.
4. Berkun Y, Haviv YS, Schwartz LB, Shalit M. Heparin-induced recurrent anaphylaxis. Clin Exp Allergy 2004;34:1916–8.

AMA News Release, 2/5/08:  New research on medical liability reforms continues to show that caps on non-economic damages are effective, lowering medical liability premiums, resulting in an increased supply of physicians to care for patients. A new analysis of independent research summarized by the American Medical Association (AMA) provides an update on the positive impact of caps on non-economic damages on the broken medical liability system.In states without reforms, many physicians are forced to make difficult practice decisions to limit the care they provide simply because they can’t afford to pay sky-high medical liability premiums driven-up by escalating jury awards. Regardless of the case’s merit, runaway jury awards for non-economic damages can reach millions of dollars, driving up premiums and putting access to care at risk for patients. The AMA supports caps on the non-economic damages of jury awards, and unlimited payments for economic damages, to help stabilize the broken system for patients and physicians while preserving patient access to the judicial system.

“For many patients, access to care is put in jeopardy because premiums for many physician specialties remain at or near all-time highs,” said AMA Immediate-Past President William G. Plested III, MD. “Premium rates have largely stabilized, however they remain at the highest levels in history. For example, liability premiums for obstetrician-gynecologists in New Jersey have more than doubled since 2000 to $171,000, forcing many physicians to stop delivering babies.”

The AMA’s current review of recent literature, “The Impact of Liability Pressure and Caps on Damages on the Healthcare Market: An Update of Recent Literature” (PDF, 78KB), summarizes the most recent research on the impact of medical liability reforms. Research shows that caps on non-economic damages are associated with lower premium levels of at least 17 percent, depending on the specialty. Research also shows that placing a quarter-million dollar cap on non-economic damages in states that don’t have effective reforms could result in premium savings of $1.4 billion nationwide.

“Medical liability reforms do work,” said Dr. Plested. “After placing a cap on non-economic damages more than three decades ago, the medical liability climate in California remains stable with premiums in check. In 2003, Texas enacted reforms and now patients benefit from an increase of physicians.”

Caps on non-economic damages are also associated with increased physician supply, particularly in rural counties, resulting in more physicians to care for patients. Research shows that the number of physicians in high-risk specialties, such as obstetrics and gynecology, is four to seven percent higher in states with caps.

“Medical liability reform remains a top priority for the AMA, and the thousands of physicians who have had to curtail their practices because they have been negatively impacted by the broken liability system. The fight for reforms is now largely in the states, and the AMA will continue to aggressively advocate so that no patient is prevented from being treated by a physician because of the broken liability system,” said Dr. Plested.

MedPage Today, 2/7/08:  2/7, Phend) reported that in the ICU, “Intensive insulin therapy…may starve critically injured brains and potentially lead to further damage,” according to a study presented at the Society of Critical Care Medicine meeting in Honolulu, Hawaii. Mauro Oddo, M.D., of Columbia University in New York, and colleagues found that “‘[b]rain energy crisis’ was 23 percent more likely with each 1 mmol/L decrease in systemic glucose and 10 percent more likely with each 1 unit/L increase of insulin infusion.” The researchers added that “[t]hese episodes of low brain glucose levels and high levels of metabolic distress markers were associated with greater mortality risk and poorer outcome among neuro-ICU patients.”

(2/8, Marchione) reports that according to findings published in today’s issue of BMJ, “acupuncture might improve the odds of conceiving if done right before or after embryos are placed in the womb.” Lead author Eric Manheimer, M.S., a researcher at the University of Maryland School of Medicine, and colleagues, conducted a meta-analysis of “results from seven studies on 1,366 women in the United States, Germany, Australia, and Denmark who are having in vitro fertilization, or IVF.” Participants “were randomly assigned to receive IVF alone, IVF with acupuncture within a day of embryo transfer, or IVF plus sham acupuncture, in which needles were placed too shallowly, or in spots not thought to matter.” The revealed that “three of the studies [considered] acupuncture beneficial,” another “three found a trend toward benefit, and one found no benefit.”

        By combining the study results, the researchers discovered “a 65 percent increase in pregnancy, and an 87 percent increase in the continuity of the pregnancy,” AHN (2/8, Duerme) adds. The results also showed a “ninety-one percent increase” in live births.

        The analysis indicated that “in studies where pregnancy rates were high, the benefit of acupuncture was small and non-significant,” HealthDay (2/8, Reinberg) reports. Manheimer noted that while “[a]cupuncture may be useful adjuvant treatment in the IVF process,” he believes “there needs to be more studies to confirm these findings, because they are still preliminary.”

        Nevertheless, the authors concluded that even if the likelihood of success with acupuncture were small, “an acupuncture cointervention may still be cost effective, considering the negligible costs of two to four sessions of acupuncture, relative to the high costs of in vitro fertilization,” Medscape (2/8, Barclay) adds.

        The BBC (2/8) reports that Professor Edzard Ernst, Ph.D., a leading researcher into alternative treatments from the Peninsula Medical School in Plymouth, England, advised caution regarding the findings, because “much of the observed effect could be due to a placebo response,” he said.

In continuing coverage from a previous briefing, the New York Times (2/8, C3, Saul) reports that the U.S. House Energy and Commerce Committee, which is “investigating the Lipitor (atorvastatin) advertising campaign featuring Robert Jarvik, M.D., wants information about payments to people who might have served as stunt doubles for the doctor in televised ads.” On Thursday, letters from Reps. John Dingell (D-Mich.) and Bart Stupak (D-Mich.) were mailed to “nine advertising firms thought to be involved in Dr. Jarvik’s advertising campaign for” the drug. The letters said that the aforementioned committee and its “subcommittee on oversight and investigations were investigating ‘false and misleading statements, and the use of celebrity endorsements of prescription medications in direct-to-consumer advertising.’” The Times notes that earlier this week, it had reported that “Dr. Jarvik does not row, and that a Seattle rowing enthusiast and professional photographer…had served as a stunt double in” one ad for the drug.

        According to an article on the ABC (2/7, Owens, et al.) website, “a contract uncovered in the probe has revealed Jarvik was guaranteed $1.35 million for appearing in the advertisements.” The Wall Street Journal’s (2/7, Goldstein) Health Blog also covered the story.

Hello All,

I just wanted to let all of you know that the Ruffing Care Center south of Tiffin has evacuated all of their patients to our facility this morning.

We were notified about 4 am. We have received 36 patients and now have our entire 3^rd floor occupied. Everything went very well and everyone was moved in by 8:30 am. Not to bad considering they’re about 15 miles away.

I’m not sure how long they will be here but we’re pretty sure that it will be at least over the weekend. The McCutchenville fire chief wants to make sure that the health dept. gives the ok, etc.

We’re set with everything for now but I did want to give all of you a heads up.

Kathy, if you want to let the group know  I’ll let you call that one.                                                              

Thanks,

Duane

Duane E. Kimmet

Plant Operations Director, Safety/Security Officer

St. Francis Health Care Centre

401 N. Broadway, Green Springs, OH 44836

419-639-6022

On the lighter side, a study conducted as part of a Clemson University program to get undergraduate students involved in scientific research confirms what many ICPs would have suspected: double-dipping transfers bacteria into the dip bowl.

The study, which will be published later this year in the Journal of Food Safety, was inspired by an episode of the “Seinfeld” show in which George Costanza is confronted at a funeral reception after dipping the same chip twice into the dip.

Turns out the objecting character was right. On average, the students found that three to six double dips transferred about 10,000 bacteria from the eater’s mouth to the remaining dip, reported The New York Times.

FDA issued an early communication about an ongoing safety review regarding Botox and Botox Cosmetic. FDA has received reports of systemic adverse reactions including respiratory compromise and death following the use of botulinum toxins types A and B for both FDA-approved and unapproved uses. The reactions reported are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for cerebral palsy-associated limb spasticity. Use of botulinum toxins for treatment of limb spasticity (severe arm and leg muscle spasms) in children or adults is not an approved use in the U.S. See the FDA’s “Early Communication about an Ongoing Safety Review” for Agency recommendations and additional information for healthcare professionals.

Read the complete 2008 MedWatch Safety Summary including a link to the FDA’s Early Communication about an Ongoing Safety Review regarding this issue at:  http://www.fda.gov/medwatch/safety/2008/safety08.htm#botox