Archive for December, 2006

Pharmacists Make a Difference in Diabetes Control

ASHEVILLE, N.C. — In an office behind the Hershey’s candy rack at a Kerr Drug here, Stuart Rohrbaugh shifts in his chair as his pharmacist stares at a dangerously high blood sugar reading from last month.

“I think that was the day a buddy of mine brought over his home-brew beer,” stammers Mr. Rohrbaugh, whose diabetes was diagnosed six years ago.

Silently, the pharmacist lifts her eyes, sending Mr. Rohrbaugh’s gaze to the floor.

“I know, I know,” he says.

Mr. Rohrbaugh, 37, learned relatively late in life that he had Type 1 diabetes, a malfunction of the immune system that usually surfaces in childhood. There are hundreds in Asheville with that type, and even more with the more prevalent Type 2, which often hits as a consequence of obesity or age.

And so in this town of 75,000, where people like to use sugar in their coffee and in their iced tea, and as a term of endearment, Mr. Rohrbaugh and the others face the formidable challenge of either managing their diabetes or suffering its potential ravages: blindness, organ failure, stroke.

In trying to meet that challenge, the kind of polite browbeating that Mr. Rohrbaugh faced at his local pharmacy seems to be paying off.

For the past 10 years, the city of Asheville has given free diabetes medicines and supplies to municipal workers who have the disease if they agree to monthly counseling from specially trained pharmacists. The results, city officials say, have been dramatic: Within months of enrolling in the program, almost twice as many have their blood sugar levels under control. In addition, the city’s health plan has saved more than $2,000 in medical costs per patient each year.

There are at least 21 million diabetics in the United States, and health officials have begun to despair of combating the disease because it involves getting people to do something much more difficult than taking their medicine or having surgery: altering their daily behavior, like their eating and exercise habits.

But amid this gloom, Asheville’s public health experiment is something of a ray of hope, an example, however modest, of the kind of house-to-house, block-to-block battle that can win results and save lives in the face of a disease that has resisted quick-fix solutions.

Indeed, in recent years, about 40 other employers across the country — private companies or municipalities — have adopted versions of the program.

“We get a four-to-one return on investment,” said Barry Bunting, pharmacy director at Mission Hospitals, which runs the program in Asheville for about 450 city and hospital employees. For every dollar spent on medicines or counseling about diet, exercise and lifestyle, he said, the city saves $4 by preventing emergency room visits, dialysis, amputations or other common complications of diabetes.

During the first five years of the program, participants took an average of six sick days from work a year, half the number of previous years. Within three years of enrolling in the program, patients had halved their chances of going blind or needing dialysis or an amputation, a founder of the program said.

“When you have to answer to someone each month, you think twice before eating what you shouldn’t,” said George Ledford, 69, who joined the program five years ago.

The fifth deadliest disease in the nation, diabetes costs more than $130 billion per year in medical expenses and lost productivity in the workplace. While there is no cure, patients can delay or prevent complications by using medications properly and adjusting their diet and exercise routines.

But the efforts to help people change their lifestyles are complicated by a health care system in which insurers typically do not reimburse doctors for the kinds of counseling and monitoring that might keep patients on track.

So the Asheville experiment has enlisted pharmacists in its model. They serve as coach, clinician and cheerleader for patients, and they earn a fee for each session.

“Once you have a sense of what motivates them, you set little goals each visit and then build on them,” said Dana K. Arrington, a clinical pharmacist at Kerr Drug who sees at least one diabetes patient a day.

“This month, get on the treadmill once a week for 15 minutes. Next month, we write down each time you take your pills. Then switch from whole to skim milk. It’s a slow process if you want it to stick.”

While diabetics have often shown significant improvements in controlling their blood sugar soon after taking diabetes education classes, they typically relapse within three months, according to a study released in March 2003 by the Journal of the American Pharmaceutical Association. The report was co-written by Carole W. Cranor, a pharmacoeconomist who was then at the University of North Carolina, Chapel Hill.

What makes the Asheville Project unusual, the study found, is that at the end of the first year of the program, half the participants had their blood sugar under control. That number increased to two-thirds of the original group at the end of the program’s third year.

“Asheville had unusually long-term successes because of the distinct role played by pharmacists, who have at least five years of academic training and who are more rooted and accessible in communities than doctors,” said Ms. Cranor, who is now a clinical pharmacist at Dorothea Dix Hospital in Raleigh, N.C.

Aside from Asheville’s successes, the popularity of the program is being driven by pharmaceutical companies.

GlaxoSmithKline and Sanofi-Aventis, which make diabetes drugs, have jointly given about a million dollars in the past five years to the American Pharmacists Association Foundation, a nonprofit research group, to help promote and replicate the program, said Dan Garrett, one of the founders of the Asheville Project and a director at the foundation.

Diabetics frequently fail to take their medications consistently, studies show, so these drugmakers stand to profit from better patient compliance. None of the employers or cities that adopt the program are obligated to buy from these companies, though.

The frequency of consultations is the reason the Asheville Project has shown such long-term benefits, Mr. Garrett said.

For patients struggling to adjust their daily habits, it is the little questions — those too small and too numerous to justify an appointment with a doctor—that make the disease so difficult to manage and pharmacists’ involvement so invaluable, patients said.

When Mr. Ledford kept getting sores on his feet, a common diabetes complication, his pharmacist ventured into the aisles to help him find a lotion that worked. When Mr. Ledford’s blood sugar levels spiked mysteriously, the pharmacist questioned him about any changes in his routine. “The new cup I was using for my cornflakes was the wrong size,” recounted Mr. Ledford, explaining that this mistake in figuring his carbohydrate consumption was throwing off his insulin dosage calculations.

Despite his occasional lapses, Mr. Rohrbaugh said that without frequent feedback from his pharmacist and the program’s nutritionist, he would never have been able to learn how to count his carbohydrates, drop the necessary 20 pounds and administer his insulin. “I also was struggling to afford it all,” said Mr. Rohrbaugh, a worker in city planning who was paying more than $300 per month for medicines and supplies before joining the program two years ago.

John Miall, one of the founders of the Asheville program, who recently retired as the city’s director of risk management, said that within its first year the average annual health care cost for diabetic employees dropped to $3,554 from $6,127.

“Do the math,” he said. “If just one employee is kept off dialysis, that is a $100,000 net savings for the year. That pays for a heck of a lot of preventative medicine and supplies.”

Source: NY Times, 12/30/06

In 2007, Suspect Cyanide Poisoning? Think CYANOKIT!

EMD Pharmaceuticals and Dey, LP, U.S. Affiliates of Merck KGaA of Darmstadt, Germany, jointly announced on Dec. 18 that the U.S. Food and Drug Administration (FDA) has approved Cyanokit(R) (hydroxocobalamin for injection), for the treatment of known or suspected cyanide poisoning.EMD Pharmaceuticals completed the submission of a New Drug Application (NDA) for Cyanokit(R) (hydroxocobalamin for injection) to the FDA in June of 2006. Dey, LP is located in Napa, CA and will market Cyanokit in the US market. Dey, LP expects Cyanokit to be available early in 2007.

Cyanokit’s unique mechanism of action makes possible its use in a pre- hospital or hospital setting. It is the first cyanide antidote to be approved in the United States in several decades.

In the U.S., cyanide poisoning is primarily caused by smoke inhalation during closed space structural fires. Additional causes may include accidental or intentional ingestion or exposure during industrial accidents or a terrorist attack involving cyanide.

“We are very pleased with the FDA’s decision to approve Cyanokit,” said Christy Taylor, Senior Vice President of Marketing, Sales and Business Development for Dey, LP. “Treating cyanide poisoning as soon as possible after exposure is critical to survival. Emergency responders will now have a way to treat people for cyanide poisoning immediately at the scene of a fire, accident or other emergency as well as in the emergency department of a hospital. We anticipate that the availability of Cyanokit will have a significant impact on the survival of those who are affected by cyanide poisoning.”

Cyanokit Exhibited Positive Safety, Efficacy Profiles

The FDA approval is supported by efficacy studies in animals and safety studies in healthy adults. These studies demonstrated that Cyanokit is safe and effective in treating cyanide poisoning from smoke inhalation and other causes.

At the American College of Emergency Physicians 2005 Research Forum, investigators Frederic Baud, MD, Medical and Toxicological Critical Care Department, Lariboisiere Hospital, Paris, France and Stephen W. Borron, MD, FACEP of The University of Texas Health Science Center at San Antonio presented the results of several studies including a prospective open-label study(1) carried out in 69 subjects who had been exposed to smoke inhalation from fires. Subjects were over 15 years of age, presented with soot in the mouth or nose and expectoration, and had altered neurological status. The median Cyanokit dose was 5.0 g with a range from 4.0 to 15.0 g.

Fifty of 69 patients, or 73 percent of subjects, survived following treatment with Cyanokit and supportive care. Of the 19 subjects who did not survive, 13 subjects were in initial cardiac arrest at the scene.

Of the 42 subjects with pretreatment cyanide levels considered to be potentially toxic, 28 (67 percent) survived. Of the 19 subjects whose pretreatment cyanide levels were considered potentially lethal, 11 (58 percent) survived. Of the 50 subjects who survived, 9 subjects (18 percent) experienced long-term neurologic effects from cyanide poisoning at hospital discharge.

A study of 136 healthy adult subjects(2) also was conducted to assess the safety, tolerability, and pharmacokinetics of Cyanokit.

Side effects observed with Cyanokit were generally transient and self-limiting. The most frequently occurring adverse reactions were

1) injection site reactions;

2) skin rash;

3) chromaturia (urine discoloration), which was reported in all subjects receiving 5.0 g Cyanokit or greater; and

4) erythema (skin redness), which occurred in most subjects receiving 5.0 g Cyanokit or greater.

5) Elevations in blood pressure were observed in some subjects, generally returning to normal within a few hours after administration.

People with known hypersensitivity to hydroxocobalamin and /or Vitamin B12 should not be administered Cyanokit.

“These results show that Cyanokit is safe and effective in treating cyanide poisoning, even in patients with potentially lethal concentrations of cyanide in the blood,” says Dr. Stephen W. Borron, one of medical advisors to the safety study. “In addition, the side effects experienced by patients were modest and temporary; no severe adverse events related to Cyanokit treatment were observed. These characteristics of a cyanide antidote are very important in an emergent situation requiring rapid, life-saving treatment.”

Smoke Inhalation and Cyanide Poisoning

Fire smoke is a common source of cyanide exposure. Cyanide may be produced by the pyrolysis (incomplete burning) of common synthetic or plastic materials as well as from natural materials such as wood, paper and silk. Cyanide is increasingly recognized as a common and dangerous component of fire smoke, adding to the effects of carbon monoxide as a fire smoke toxicant. In fact, cyanide poisoning and carbon monoxide poisoning most often occur together during a fire. Prompt recognition and treatment of cyanide poisoning with an antidote can save lives.

Cyanokit has been used in France for over 10 years in both pre-hospital and hospital settings to treat cyanide poisoning resulting from smoke inhalation, ingestion and other causes. Although recognized in Europe for many years, only recently has the risk of cyanide exposure in fire smoke gained recognition in the U.S. The U.S. maintains one of the highest fire- related death rates of industrialized countries even though the number of fires has steadily decreased over the past two decades. Smoke inhalation is responsible for up to 80 percent of U.S. fire-related injuries and deaths. According to the United States Fire Administration (USFA), in 2004, the most recent year for which statistics are available:

 * 3,900 civilians and 117 firefighters lost their lives in fires, with an additional 17,785 civilians injured as the result of fire     
* Of all civilian fire-related deaths, 83 percent of them occurred in residences     
* An estimated 20,800 residential structure fires are attributed to mattresses, pillows, and bedding materials, 
all of which are highly likely to contain synthetic materials that release hydrogen cyanide when they smolder

Cyanide is highly toxic by all routes of exposure and may result in rapid onset of serious effects on the nervous, cardiovascular, and respiratory systems, leading to death within minutes to hours. Exposure to lower concentrations of cyanide may produce headache, confusion, nausea, and vomiting followed in some cases by coma and death. The presence and extent of cyanide poisoning are often initially unknown.

There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and/or signs and symptoms of cyanide intoxication. If clinical suspicion of cyanide poisoning is high, Cyanokit should be administered without delay.

About Cyanokit

The active ingredient in Cyanokit, hydroxocobalamin, is a precursor of vitamin B12. Hydroxocobalamin works by binding directly to the cyanide ions, creating cyanocobalamin, a natural form of vitamin B12, which is excreted in the urine. Advantages of this approach are that methemoglobin is not produced and the oxygen-carrying capacity of the victim’s blood is not lowered. Therefore, Cyanokit is suitable for use in smoke inhalation victims. The most common side effects seen in clinical trials of hydroxocobalamin are: injection site redness; temporary discoloration of the skin, urine and mucous membranes; and transient elevations in blood pressure.

The initial dose of Cyanokit for adults is 5.0 g, (2 vials) administered by intravenous infusion. Depending upon the severity of the poisoning and the clinical response, a second dose of 5.0 g may be administered up to a total dose of 10.0 g.

Cyanokit has been approved for marketing in France (marketed under the same name by Merck Sante s.a.s.) since 1996 for the treatment of cyanide poisoning.

For full prescribing information, please contact 1-800-429-7751 or visit www.dey.com.

About EMD Pharmaceuticals, Inc.

A U.S. Affiliate of Merck KGaA of Darmstadt, Germany, EMD Pharmaceuticals is a specialty pharmaceutical company with a focus on clinical development, regulatory affairs, and business development in support of providing targeted therapies for cancer treatment and other specialty areas, including central nervous system disorders and cyanide poisoning. EMD is headquartered in Durham, N.C. Additional information about EMD is available at www.emdpharmaceuticals.com.

About Dey, LP.

A U.S. Affiliate of Merck KGaA of Darmstadt, Germany, DEY, L.P. develops, manufactures, and markets innovative airway, allergy and emergency medications that save and improve lives. The Company puts “patients first” through integrated healthcare delivery solutions, and facilitates efficient, cost- effective partnerships with its customers. DEY is committed to investing in its employees and the communities in which they live. Additional information about Dey, LP is available at www.dey.com.

(1) Borron SW

Patterns of Errors Contributing to Trauma Mortality: Lessons Learned From 2594 Deaths

by Russell L. Gruen, MD, PhD; Gregory J. Jurkovich, MD; etal.

Abstract 

Objective: To identify patterns of errors contributing to inpatient trauma deaths.
Methods: All inpatient trauma deaths at a high-volume level I trauma center from 1996 to 2004 inclusive were audited. Data were collected with daily trauma registry chart abstraction, weekly morbidity and mortality reports, hospital quality assurance reports, and annual trauma registry analyses of risk of death using TRISS and HARM methodology. Deaths that met criteria for low to medium probability of mortality or those with quality of care concerns were analyzed for errors and then subjected to 3-stage peer review at weekly departmental, monthly hospital, and annual regional forums. Patterns of errors were constructed from the compiled longitudinal data.
Results: In 9 years, there were 44,401 trauma patient admissions and 2594 deaths (5.8%), of which 601 met low to medium mortality risks. Sixty-four patients (0.14% admissions, 2.47% deaths) had recognized errors in care that contributed to their death. Important error patterns included: failure to successfully intubate, secure or protect an airway (16%), delayed operative or angiographic control of acute abdominal/pelvic hemorrhage (16%), delayed intervention for ongoing intrathoracic hemorrhage (9%), inadequate DVT or gastrointestinal prophylaxis (9%), lengthy initial operative procedures rather than damage control surgery in unstable patients (8%), over-resuscitation with fluids (5%), and complications of feeding tubes (5%). Resulting data-directed institutional and regional trauma system policy changes have demonstrably reduced the incidence of associated error-related deaths.
Conclusions: Preventable deaths will occur even in mature trauma systems. This review has identified error patterns that are likely common in all trauma systems, and for which policy interventions can be effectively targeted.

CDC: What To Do For Travellers Concerned About Possible Polonium Exposure

Background Information Concerning Polonium-210
The general population is exposed to small amounts of polonium on a regular basis; the average amount of polonium-210 in the human body is approximately 1.0×10-9 curie. Because tobacco leaves are known to concentrate polonium-210, users of tobacco products are likely to have higher levels of polonium in their bodies. Polonium-210 decays by emitting alpha particles, and the largest part of the alpha dose is delivered over the first 100 days following a single administration.

Polonium-210 is considered to be one of the most hazardous radioactive materials known, but it must be inhaled or ingested to exert its toxic effects. Between 50% and 90% of ingested polonium promptly appears in the gastrointestinal (GI) tract; from there it leaves the body in the feces. The retained fraction enters the bloodstream where it concentrates in the soft tissues, particularly the spleen and kidneys. Approximately 45% of ingested polonium gets deposited in the spleen, kidneys, and liver; 10% is deposited in the bone marrow and the remainder is distributed throughout the body. Within the bloodstream, polonium combines with the globin portion of hemoglobin.

The whole-body biological half-life of polonium-210 is approximately 40 days. The biological half-life in the spleen and kidney is approximately 60-70 days.

Clinical Guidance Recommendations
Time to onset of symptoms is sooner and the severity of prodromal symptoms is worse, the higher the dose of radiation. This is true for both external radiation exposure and internal contamination. However, acute radiation syndrome (http://www.bt.cdc.gov/radiation/arsphysicianfactsheet.asp ) caused by internal contamination with polonium may be delayed in onset compared with ARS caused by an external radiation exposure. For this reason, CDC provides the following recommendations for clinicians providing care to individuals who present with health concerns after recent travel to locations known to be environmentally contaminated with polonium-210 residues:

  • Conduct a complete history and physical examination
  • Obtain a Complete Blood Count (CBC) with differential
  • Collect a 24-hour urine sample to assay for the presence of polonium-210*

These above should be conducted regardless of an individual’s physical findings or the length of time that has passed since their coming into contact with the contaminated environment.

Asymptomatic individuals presenting for care who have recently traveled to locations known to be environmentally contaminated with polonium-210 should have a 24-hour urine collection as a screen for internal contamination. The presence of polonium-210 in the urine (in excess of background) is strongly suggestive of internal contamination. CDC recommends that individuals identified as having levels of polonium-210 in excess of background should be carefully monitored for the development of signs and symptoms of ARS.

Individuals who subsequently experience adverse health effects (e.g., fever, vomiting, diarrhea, hair loss, unusual bleeding) should be considered more likely to have developed the acute radiation syndrome. They should be admitted to the hospital to receive appropriate additional laboratory testing and medical care. Individuals who do not develop adverse health effects likely have received a much lower (or insignificant) internal dose of radiation. Those individuals not developing ARS but who are identified as having an elevated body burden of polonium still require long-term follow-up for cancer.

*For information on laboratories capable of testing for Po-210, contact your state health department, which will work with your state radiation control program office to identify an appropriate facility.

Source: CDC, 12/7/06

Ultrasound Aids Jugular Vein Catheterization

NEW YORK (Reuters Health) Dec 01 - Emergency department use of real-time ultrasonographic guidance of internal jugular vein catheterization reduces complications and improves success rates, according to Australian researchers.

Compared to a blind approach, lead investigator Dr. Julie Leung told Reuters Health, “real-time ultrasound guided placement of lines is clearly more successful and safer.” Furthermore, “the technique is easily learned.”

To evaluate the approach, Dr. Leung and colleagues at St. Vincent’s Hospital, Sydney conducted a study in 130 patients in whom central venous access was required.

They were randomized to internal jugular vein catheterization using ultrasonography or the traditional landmark technique. Operators were emergency physicians or postgraduate trainees. Before participation, all spent a minimum of 2 hours in educational session covering the procedures.

Cannulation using ultrasound was successful in 61 of 65 patients (93.9%) compared with 51 of the 65 (78.5%) who had placement with the landmark approach. The first attempt was successful in 82.0% of the ultrasonography patients and 70.6% of the landmark group.

Mean times to venipuncture and successful insertion were similar in both groups. However, there were only 3 complications (4.6%) in the ultrasonography group compared with 11 (16.9%) in landmark patients.

Given the success of the approach, the researchers conclude that in emergency departments with the appropriate equipment, “ultrasonographically-guided insertion of internal jugular vein catheters should become the standard of care.”

Ann Emerg Med 2006;48:540-547.