Innovations in Healthcare

IT’S 11 MINUTES to 8 o’clock, and the sun is still climbing over the Potomac River just outside the Gaylord National Resort & Convention Center in National Harbor, Md. Day two of SHM’s annual meeting is about to begin.

Hospitalists file into a cavernous ballroom as the day kicks off with a panel discussion on healthcare reform and a speech by that rarest of breed: a popular hospital CEO. The back of the room fills quickly, but front and center, second row—that’s the seat for Nasim Afsarmanesh, MD, director of quality for HM and neurosurgery at Ronald Reagan UCLA Medical Center in Los Angeles.

“If I’m not in the front, I zone out,” she admits.

Dr. Afsarmanesh (who often adds a hyphen to her surname— Afsar-manesh—to help others pronounce it) knows herself and she knows how to plan ahead, from taking notes on her mini-laptop to knowing when to sit up front. And this day in her life is no different. Her schedule is a 12-hour dervish, yet it’s a simple roadmap of how to navigate HM10 and its scores of sessions, speeches, and seminars.

Innovator at Heart

Dr. Afsarmanesh did her residency in 2007 at UCLA. She stayed on to take a faculty position and is now assistant clinical professor of internal medicine (IM) and neurosurgery. Her days are split about 35% clinical practice, 40% on neurology quality issues, and 25% on hospital QI projects. In her free time, she’s an SHM activist and the incoming chair of its Hospital Quality and Patient Safety (HQPS) Committee.

“I get to be an innovator,” she boasts as she picks up a Danish, a chocolate pastry, and a cup of tea following two hours of listening to others talk. “I love that. You can’t really be an innovator when you’re [purely] practicing clinical medicine.”

Innovation requires preparation, though. Dr. Afsarmanesh spends countless hours creating PowerPoint presentations, so she hit a new feature at this year’s meeting: a limited-seating workshop on drawing up effective slides. The presentation is helpful, but she’s partially distracted. “Look up healthcare from talk,” she types as a note to herself for later. She follows that with “Look up Levy’s talk” (a nod to Paul Levy, the well-liked CEO of Beth Israel Deaconess in Boston).

Facial Recognition

The distraction ratchets up as she’s already looking forward to introducing herself to the editorial board of the Journal of Hospital Medicine, where she serves as an assistant editor. There are a few people she’d like to meet in person, so she gracefully sneaks out the side door a few minutes before noon. Handshakes, a box lunch, and a chat with 40 other journal editors ensue for the next hour.

“You can meet people you talk on the phone with for several years,” she says. “You can put a face to the name. That’s important.”

Hobnobbing at a board meeting is only a brief respite, however, before it’s back to professional development. At 1:15, there’s a 60-minute lesson on how to improve care from the patient perspective. Dr. Afsarmanesh, again, is distracted. She’s a first-time presenter in a few minutes, part of a four-woman panel on building a QI educational curriculum for medical students, residents, fellows, faculty, and other healthcare providers.

She scrolls through slides, rehearsing her thoughts. She wonders whether her PowerPoint presentation would have made the grade at this morning’s session.

She is smart enough not to judge her performance too soon—someone in an audience once reached out to her a year later—as she knows the impact of a training session is more than the round of applause at its end.

“You hope that you generate a discussion more than the traditional didactics,” she says. “These meetings are meant to start a discussion and, hopefully, create a network and a community where people can continue to [share ideas and learn from each other]. … I hope that along with some of the content that people take away, the bigger thing is those connections that they make.”

Work Never Ends

It’s 4:30 p.m. and Dr. Afsarmanesh still has a sales pitch to rehearse. This time, it’s self-promotion for her soon-to-begin poster presentation: “The ABCs of Hospitalized Patients: A Multi-Disciplinary Checklist for Improving Quality of Patient Care."

After umpteen repetitions of her spiel, the presentation doesn’t win a prize, but, once again, she showcases her attention to detail: A stack of 8.5”x 11” versions of her poster are available for handouts, a feature few others in the competition have.

Some 12 hours into her tour of this massive convention center, the day is coming to a close. But not before SHM CEO Larry Wellikson, MD, SFHM, drops by to say hello.

He points out how strong her research is. Unfortunately, he uses a pen in the process.

“Don’t poke a hole in my poster,” she jokes.

Moments later, it’s back to working the line queued up at her poster. “Hi, would you like to hear about my poster?” HM2010

Richard Quinn is a freelance writer based in New Jersey.

IT’S 11 MINUTES to 8 o’clock, and the sun is still climbing over the Potomac River just outside the Gaylord National Resort & Convention Center in National Harbor, Md. Day two of SHM’s annual meeting is about to begin.

Hospitalists file into a cavernous ballroom as the day kicks off with a panel discussion on healthcare reform and a speech by that rarest of breed: a popular hospital CEO. The back of the room fills quickly, but front and center, second row—that’s the seat for Nasim Afsarmanesh, MD, director of quality for HM and neurosurgery at Ronald Reagan UCLA Medical Center in Los Angeles.

“If I’m not in the front, I zone out,” she admits.

Dr. Afsarmanesh (who often adds a hyphen to her surname— Afsar-manesh—to help others pronounce it) knows herself and she knows how to plan ahead, from taking notes on her mini-laptop to knowing when to sit up front. And this day in her life is no different. Her schedule is a 12-hour dervish, yet it’s a simple roadmap of how to navigate HM10 and its scores of sessions, speeches, and seminars.

Innovator at Heart

Dr. Afsarmanesh did her residency in 2007 at UCLA. She stayed on to take a faculty position and is now assistant clinical professor of internal medicine (IM) and neurosurgery. Her days are split about 35% clinical practice, 40% on neurology quality issues, and 25% on hospital QI projects. In her free time, she’s an SHM activist and the incoming chair of its Hospital Quality and Patient Safety (HQPS) Committee.

“I get to be an innovator,” she boasts as she picks up a Danish, a chocolate pastry, and a cup of tea following two hours of listening to others talk. “I love that. You can’t really be an innovator when you’re [purely] practicing clinical medicine.”

Innovation requires preparation, though. Dr. Afsarmanesh spends countless hours creating PowerPoint presentations, so she hit a new feature at this year’s meeting: a limited-seating workshop on drawing up effective slides. The presentation is helpful, but she’s partially distracted. “Look up healthcare from talk,” she types as a note to herself for later. She follows that with “Look up Levy’s talk” (a nod to Paul Levy, the well-liked CEO of Beth Israel Deaconess in Boston).

Facial Recognition

The distraction ratchets up as she’s already looking forward to introducing herself to the editorial board of the Journal of Hospital Medicine, where she serves as an assistant editor. There are a few people she’d like to meet in person, so she gracefully sneaks out the side door a few minutes before noon. Handshakes, a box lunch, and a chat with 40 other journal editors ensue for the next hour.

“You can meet people you talk on the phone with for several years,” she says. “You can put a face to the name. That’s important.”

Hobnobbing at a board meeting is only a brief respite, however, before it’s back to professional development. At 1:15, there’s a 60-minute lesson on how to improve care from the patient perspective. Dr. Afsarmanesh, again, is distracted. She’s a first-time presenter in a few minutes, part of a four-woman panel on building a QI educational curriculum for medical students, residents, fellows, faculty, and other healthcare providers.

She scrolls through slides, rehearsing her thoughts. She wonders whether her PowerPoint presentation would have made the grade at this morning’s session.

She is smart enough not to judge her performance too soon—someone in an audience once reached out to her a year later—as she knows the impact of a training session is more than the round of applause at its end.

“You hope that you generate a discussion more than the traditional didactics,” she says. “These meetings are meant to start a discussion and, hopefully, create a network and a community where people can continue to [share ideas and learn from each other]. … I hope that along with some of the content that people take away, the bigger thing is those connections that they make.”

Work Never Ends

It’s 4:30 p.m. and Dr. Afsarmanesh still has a sales pitch to rehearse. This time, it’s self-promotion for her soon-to-begin poster presentation: “The ABCs of Hospitalized Patients: A Multi-Disciplinary Checklist for Improving Quality of Patient Care."

After umpteen repetitions of her spiel, the presentation doesn’t win a prize, but, once again, she showcases her attention to detail: A stack of 8.5”x 11” versions of her poster are available for handouts, a feature few others in the competition have.

Some 12 hours into her tour of this massive convention center, the day is coming to a close. But not before SHM CEO Larry Wellikson, MD, SFHM, drops by to say hello.

He points out how strong her research is. Unfortunately, he uses a pen in the process.

“Don’t poke a hole in my poster,” she jokes.

Moments later, it’s back to working the line queued up at her poster. “Hi, would you like to hear about my poster?” HM2010

Richard Quinn is a freelance writer based in New Jersey.

IT’S 11 MINUTES to 8 o’clock, and the sun is still climbing over the Potomac River just outside the Gaylord National Resort & Convention Center in National Harbor, Md. Day two of SHM’s annual meeting is about to begin.

Hospitalists file into a cavernous ballroom as the day kicks off with a panel discussion on healthcare reform and a speech by that rarest of breed: a popular hospital CEO. The back of the room fills quickly, but front and center, second row—that’s the seat for Nasim Afsarmanesh, MD, director of quality for HM and neurosurgery at Ronald Reagan UCLA Medical Center in Los Angeles.

“If I’m not in the front, I zone out,” she admits.

Dr. Afsarmanesh (who often adds a hyphen to her surname— Afsar-manesh—to help others pronounce it) knows herself and she knows how to plan ahead, from taking notes on her mini-laptop to knowing when to sit up front. And this day in her life is no different. Her schedule is a 12-hour dervish, yet it’s a simple roadmap of how to navigate HM10 and its scores of sessions, speeches, and seminars.

Innovator at Heart

Dr. Afsarmanesh did her residency in 2007 at UCLA. She stayed on to take a faculty position and is now assistant clinical professor of internal medicine (IM) and neurosurgery. Her days are split about 35% clinical practice, 40% on neurology quality issues, and 25% on hospital QI projects. In her free time, she’s an SHM activist and the incoming chair of its Hospital Quality and Patient Safety (HQPS) Committee.

“I get to be an innovator,” she boasts as she picks up a Danish, a chocolate pastry, and a cup of tea following two hours of listening to others talk. “I love that. You can’t really be an innovator when you’re [purely] practicing clinical medicine.”

Innovation requires preparation, though. Dr. Afsarmanesh spends countless hours creating PowerPoint presentations, so she hit a new feature at this year’s meeting: a limited-seating workshop on drawing up effective slides. The presentation is helpful, but she’s partially distracted. “Look up healthcare from talk,” she types as a note to herself for later. She follows that with “Look up Levy’s talk” (a nod to Paul Levy, the well-liked CEO of Beth Israel Deaconess in Boston).

Facial Recognition

The distraction ratchets up as she’s already looking forward to introducing herself to the editorial board of the Journal of Hospital Medicine, where she serves as an assistant editor. There are a few people she’d like to meet in person, so she gracefully sneaks out the side door a few minutes before noon. Handshakes, a box lunch, and a chat with 40 other journal editors ensue for the next hour.

“You can meet people you talk on the phone with for several years,” she says. “You can put a face to the name. That’s important.”

Hobnobbing at a board meeting is only a brief respite, however, before it’s back to professional development. At 1:15, there’s a 60-minute lesson on how to improve care from the patient perspective. Dr. Afsarmanesh, again, is distracted. She’s a first-time presenter in a few minutes, part of a four-woman panel on building a QI educational curriculum for medical students, residents, fellows, faculty, and other healthcare providers.

She scrolls through slides, rehearsing her thoughts. She wonders whether her PowerPoint presentation would have made the grade at this morning’s session.

She is smart enough not to judge her performance too soon—someone in an audience once reached out to her a year later—as she knows the impact of a training session is more than the round of applause at its end.

“You hope that you generate a discussion more than the traditional didactics,” she says. “These meetings are meant to start a discussion and, hopefully, create a network and a community where people can continue to [share ideas and learn from each other]. … I hope that along with some of the content that people take away, the bigger thing is those connections that they make.”

Work Never Ends

It’s 4:30 p.m. and Dr. Afsarmanesh still has a sales pitch to rehearse. This time, it’s self-promotion for her soon-to-begin poster presentation: “The ABCs of Hospitalized Patients: A Multi-Disciplinary Checklist for Improving Quality of Patient Care."

After umpteen repetitions of her spiel, the presentation doesn’t win a prize, but, once again, she showcases her attention to detail: A stack of 8.5”x 11” versions of her poster are available for handouts, a feature few others in the competition have.

Some 12 hours into her tour of this massive convention center, the day is coming to a close. But not before SHM CEO Larry Wellikson, MD, SFHM, drops by to say hello.

He points out how strong her research is. Unfortunately, he uses a pen in the process.

“Don’t poke a hole in my poster,” she jokes.

Moments later, it’s back to working the line queued up at her poster. “Hi, would you like to hear about my poster?” HM2010

Richard Quinn is a freelance writer based in New Jersey.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.

Thousands of Michigan residents will have a better chance of avoiding readmission to the hospital thanks to a groundbreaking new collaboration between three of the state’s healthcare leaders.

Based on SHM’s Project BOOST (Better Outcomes for Older Adults through Safe Transitions) model, the collaborative program will be managed by the University of Michigan in collaboration with Blue Cross Blue Shield of Michigan. The Michigan Blues provide and administer health benefits to 4.7 million Michigan residents.

Project BOOST helps hospitals reduce readmission rates by providing them with proven resources and expert mentoring to optimize the discharge transition process, enhance patient and family education practices, and improve the flow of information between inpatient and outpatient providers. Project BOOST was developed through a grant from the John A. Hartford Foundation. Earlier in the year, the program recruited 15 Michigan sites to participate. Training begins in May.

Each improvement team will be assigned a mentor to coach them through the process of planning, implementing, and evaluating Project BOOST at their site. Program participants will receive face-to-face training, monthly coaching sessions with their mentors, and a comprehensive toolkit to implement Project BOOST. Sites also participate in an online peer learning and collaboration network.

“This kind of innovative, targeted program benefits both the patient and the healthcare provider by establishing better communication between all parties,” says Scott Flanders, MD, FHM, associate professor and director of hospital medicine at the University of Michigan in Ann Arbor, and SHM president.

To Flanders, it’s no coincidence that hospitalists are taking the lead in improving hospital discharges. “Readmissions are a pervasive but preventable problem,” he says. “Hospitalists are uniquely positioned to provide leadership within the hospital, to promote positive, system-based changes that improve patient satisfaction, and promote collaboration between hospitalists and primary-care physicians.”

In addition to being preventable, readmissions are costly, draining the resources, time, and energy of the patient, PCPs, and hospitals. Research in the April 2009 New England Journal of Medicine indicates that 20% of hospitalized patients are readmitted to the hospital within a month of their discharge.1 Nationally, readmissions cost Medicare $17.4 billion each year.1

Collaborative Partnerships

Prior to the program’s launch in Michigan, SHM recruited and mentored Project BOOST sites independently. However, like many productive relationships in a hospital, Project BOOST in Michigan depends on collaboration between experts.

“Blue Cross Blue Shield of Michigan is confident that this project, like our other Value Partnership programs that focus on robust, statewide, data-driven quality-improvement (QI) partnerships, will have a positive impact on thousands of Michigan lives,” says David Share, MD, MPH, BCBS Michigan’s senior associate medical director of Healthcare Quality. “We look forward to helping hospitals, physicians, and patients work together to assure smooth transitions between inpatient and outpatient care, and to reduce readmissions and improve the patient experience.”

For University of Michigan hospitalist Christopher Kim, MD, MBA, FHM, Project BOOST is a chance to work with a diverse set of groups. “We are grateful for the opportunity to work with not just Blue Cross Blue Shield of Michigan, but also with the other physician organizations across our state to implement and share best-practice ideas in transitions of care,” says Kim, director of the statewide collaborative program on transitions of care.

Results and Reports

Having launched six pilot sites just two years ago, adding 24 additional sites in 2009, Project BOOST is still a relatively young QI program, which makes reliable quantitative data about its effectiveness tough to come by. The expansion into Michigan gives SHM and others the prospect of programwide measurement of how Project BOOST affects discharge and reduces readmissions.

“This is a tremendous opportunity to improve patient safety, reduce readmissions, and study the impact of Project BOOST interventions through patient-level data,” says Mark Williams, MD, FHM, Journal of Hospital Medicine editor, principal investigator for Project BOOST, and former SHM president. “We’re thrilled to be working with the state’s healthcare leaders to implement this critical program.”

Nonetheless, in the absence of comprehensive data, the early reports from Project BOOST sites are promising. At Piedmont Hospital in the Atlanta area, the rate of readmission among patients under the age of 70 participating in BOOST is 8.5%, compared with 25.5% among nonparticipants. The readmission rate among BOOST participants at Piedmont over the age of 70 was 22%, compared with 26% of nonparticipants. When SSM St. Mary’s Medical Center in St. Louis implemented BOOST at its 33-bed hospitalist unit, 30-day readmissions dropped to 7% from 12% within three months.

Patient satisfaction rates also increased markedly, to 68% from 52%. And in 2009, the University of Pennsylvania Health System awarded its annual Operational Quality and Safety Award to the Project BOOST implementation team at the hospital.

BOOST’s Reach Expands

Project BOOST leaders are planning an aggressive expansion in the near future. In addition to the potential for new program sites, SHM has made materials available to hospitalists through the Project BOOST Resource Room at SHM’s newly redesigned Web site (see “The New Face of HospitalMedicine.org,” p. 12), www.hospitalmedicine.org/boost.

In addition to free resources, new BOOST materials are for sale through SHM’s online store. The Project BOOST Implementation Guide—available electronically for free through the resource room—is now available for sale as a hard copy. The online store also features a new Project BOOST instructional DVD for hospitalists, “Using Teach Back to Improve Communication with Patients.” TH

Brendon Shank is a freelance writer based in Philadelphia.

Reference

1. Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med. 2009;360(14): 1418-1428.

Chapter Updates

The Historic Main Street Trolley in Memphis, Tenn.

Memphis

The Memphis chapter held its quarterly meeting Feb. 4 at Erling Jensen in Memphis, Tenn. Dr. William Edmonson of the North Mississippi Medical Center in Tupelo, Miss., discussed “Updates on COPD.” Boehringer Engelheim sponsored the dinner meeting, which was attended by hospitalists and physicians in the area as well as hospital nurses and administration.

Milwaukee/Southeast Wisconsin

The Milwaukee/Southeast Wisconsin chapter’s Feb. 27 meeting in the Columbia Hospital Auditorium brought together hospitalists, nurse practitioners, pharmacists, and others from the Milwaukee area. Attendees were able to obtain CME credit on topics including acute coronary syndrome, hyponatremia, and sepsis. The meeting highlight was a presentation from Dr. Alpesh Amin, interim chair of the Department of Medicine at the University of California at Irvine. Dr. Amin discussed how to start up a local SHM chapter. Sponsorship from CME University helped make the chapter’s first HM symposium a success.

Nebraska Area

Lincoln HM group Bryan LGH hosted the Nebraska Area chapter quarterly meeting Feb. 23. Dr. Tamer Mahrous gave an overview of coding issues for hospitalists. A copy of the presentation will be sent to all of the chapter members.

The chapter elected officers to serve terms through 2012. They include: Dr. Eric Rice, president; Russ Cowles, vice president; Alissa Clough, secretary; and Jay Snow, officer at large.

Several additional items were discussed, including topics for upcoming meetings, how the chapter can best take advantage of opportunities at HM10, the possibility of launching a chapter newsletter, and organizational issues.

Thousands of Michigan residents will have a better chance of avoiding readmission to the hospital thanks to a groundbreaking new collaboration between three of the state’s healthcare leaders.

Based on SHM’s Project BOOST (Better Outcomes for Older Adults through Safe Transitions) model, the collaborative program will be managed by the University of Michigan in collaboration with Blue Cross Blue Shield of Michigan. The Michigan Blues provide and administer health benefits to 4.7 million Michigan residents.

Project BOOST helps hospitals reduce readmission rates by providing them with proven resources and expert mentoring to optimize the discharge transition process, enhance patient and family education practices, and improve the flow of information between inpatient and outpatient providers. Project BOOST was developed through a grant from the John A. Hartford Foundation. Earlier in the year, the program recruited 15 Michigan sites to participate. Training begins in May.

Each improvement team will be assigned a mentor to coach them through the process of planning, implementing, and evaluating Project BOOST at their site. Program participants will receive face-to-face training, monthly coaching sessions with their mentors, and a comprehensive toolkit to implement Project BOOST. Sites also participate in an online peer learning and collaboration network.

“This kind of innovative, targeted program benefits both the patient and the healthcare provider by establishing better communication between all parties,” says Scott Flanders, MD, FHM, associate professor and director of hospital medicine at the University of Michigan in Ann Arbor, and SHM president.

To Flanders, it’s no coincidence that hospitalists are taking the lead in improving hospital discharges. “Readmissions are a pervasive but preventable problem,” he says. “Hospitalists are uniquely positioned to provide leadership within the hospital, to promote positive, system-based changes that improve patient satisfaction, and promote collaboration between hospitalists and primary-care physicians.”

In addition to being preventable, readmissions are costly, draining the resources, time, and energy of the patient, PCPs, and hospitals. Research in the April 2009 New England Journal of Medicine indicates that 20% of hospitalized patients are readmitted to the hospital within a month of their discharge.1 Nationally, readmissions cost Medicare $17.4 billion each year.1

Collaborative Partnerships

Prior to the program’s launch in Michigan, SHM recruited and mentored Project BOOST sites independently. However, like many productive relationships in a hospital, Project BOOST in Michigan depends on collaboration between experts.

“Blue Cross Blue Shield of Michigan is confident that this project, like our other Value Partnership programs that focus on robust, statewide, data-driven quality-improvement (QI) partnerships, will have a positive impact on thousands of Michigan lives,” says David Share, MD, MPH, BCBS Michigan’s senior associate medical director of Healthcare Quality. “We look forward to helping hospitals, physicians, and patients work together to assure smooth transitions between inpatient and outpatient care, and to reduce readmissions and improve the patient experience.”

For University of Michigan hospitalist Christopher Kim, MD, MBA, FHM, Project BOOST is a chance to work with a diverse set of groups. “We are grateful for the opportunity to work with not just Blue Cross Blue Shield of Michigan, but also with the other physician organizations across our state to implement and share best-practice ideas in transitions of care,” says Kim, director of the statewide collaborative program on transitions of care.

Results and Reports

Having launched six pilot sites just two years ago, adding 24 additional sites in 2009, Project BOOST is still a relatively young QI program, which makes reliable quantitative data about its effectiveness tough to come by. The expansion into Michigan gives SHM and others the prospect of programwide measurement of how Project BOOST affects discharge and reduces readmissions.

“This is a tremendous opportunity to improve patient safety, reduce readmissions, and study the impact of Project BOOST interventions through patient-level data,” says Mark Williams, MD, FHM, Journal of Hospital Medicine editor, principal investigator for Project BOOST, and former SHM president. “We’re thrilled to be working with the state’s healthcare leaders to implement this critical program.”

Nonetheless, in the absence of comprehensive data, the early reports from Project BOOST sites are promising. At Piedmont Hospital in the Atlanta area, the rate of readmission among patients under the age of 70 participating in BOOST is 8.5%, compared with 25.5% among nonparticipants. The readmission rate among BOOST participants at Piedmont over the age of 70 was 22%, compared with 26% of nonparticipants. When SSM St. Mary’s Medical Center in St. Louis implemented BOOST at its 33-bed hospitalist unit, 30-day readmissions dropped to 7% from 12% within three months.

Patient satisfaction rates also increased markedly, to 68% from 52%. And in 2009, the University of Pennsylvania Health System awarded its annual Operational Quality and Safety Award to the Project BOOST implementation team at the hospital.

BOOST’s Reach Expands

Project BOOST leaders are planning an aggressive expansion in the near future. In addition to the potential for new program sites, SHM has made materials available to hospitalists through the Project BOOST Resource Room at SHM’s newly redesigned Web site (see “The New Face of HospitalMedicine.org,” p. 12), www.hospitalmedicine.org/boost.

In addition to free resources, new BOOST materials are for sale through SHM’s online store. The Project BOOST Implementation Guide—available electronically for free through the resource room—is now available for sale as a hard copy. The online store also features a new Project BOOST instructional DVD for hospitalists, “Using Teach Back to Improve Communication with Patients.” TH

Brendon Shank is a freelance writer based in Philadelphia.

Reference

1. Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med. 2009;360(14): 1418-1428.

Chapter Updates

The Historic Main Street Trolley in Memphis, Tenn.

Memphis

The Memphis chapter held its quarterly meeting Feb. 4 at Erling Jensen in Memphis, Tenn. Dr. William Edmonson of the North Mississippi Medical Center in Tupelo, Miss., discussed “Updates on COPD.” Boehringer Engelheim sponsored the dinner meeting, which was attended by hospitalists and physicians in the area as well as hospital nurses and administration.

Milwaukee/Southeast Wisconsin

The Milwaukee/Southeast Wisconsin chapter’s Feb. 27 meeting in the Columbia Hospital Auditorium brought together hospitalists, nurse practitioners, pharmacists, and others from the Milwaukee area. Attendees were able to obtain CME credit on topics including acute coronary syndrome, hyponatremia, and sepsis. The meeting highlight was a presentation from Dr. Alpesh Amin, interim chair of the Department of Medicine at the University of California at Irvine. Dr. Amin discussed how to start up a local SHM chapter. Sponsorship from CME University helped make the chapter’s first HM symposium a success.

Nebraska Area

Lincoln HM group Bryan LGH hosted the Nebraska Area chapter quarterly meeting Feb. 23. Dr. Tamer Mahrous gave an overview of coding issues for hospitalists. A copy of the presentation will be sent to all of the chapter members.

The chapter elected officers to serve terms through 2012. They include: Dr. Eric Rice, president; Russ Cowles, vice president; Alissa Clough, secretary; and Jay Snow, officer at large.

Several additional items were discussed, including topics for upcoming meetings, how the chapter can best take advantage of opportunities at HM10, the possibility of launching a chapter newsletter, and organizational issues.

Thousands of Michigan residents will have a better chance of avoiding readmission to the hospital thanks to a groundbreaking new collaboration between three of the state’s healthcare leaders.

Based on SHM’s Project BOOST (Better Outcomes for Older Adults through Safe Transitions) model, the collaborative program will be managed by the University of Michigan in collaboration with Blue Cross Blue Shield of Michigan. The Michigan Blues provide and administer health benefits to 4.7 million Michigan residents.

Project BOOST helps hospitals reduce readmission rates by providing them with proven resources and expert mentoring to optimize the discharge transition process, enhance patient and family education practices, and improve the flow of information between inpatient and outpatient providers. Project BOOST was developed through a grant from the John A. Hartford Foundation. Earlier in the year, the program recruited 15 Michigan sites to participate. Training begins in May.

Each improvement team will be assigned a mentor to coach them through the process of planning, implementing, and evaluating Project BOOST at their site. Program participants will receive face-to-face training, monthly coaching sessions with their mentors, and a comprehensive toolkit to implement Project BOOST. Sites also participate in an online peer learning and collaboration network.

“This kind of innovative, targeted program benefits both the patient and the healthcare provider by establishing better communication between all parties,” says Scott Flanders, MD, FHM, associate professor and director of hospital medicine at the University of Michigan in Ann Arbor, and SHM president.

To Flanders, it’s no coincidence that hospitalists are taking the lead in improving hospital discharges. “Readmissions are a pervasive but preventable problem,” he says. “Hospitalists are uniquely positioned to provide leadership within the hospital, to promote positive, system-based changes that improve patient satisfaction, and promote collaboration between hospitalists and primary-care physicians.”

In addition to being preventable, readmissions are costly, draining the resources, time, and energy of the patient, PCPs, and hospitals. Research in the April 2009 New England Journal of Medicine indicates that 20% of hospitalized patients are readmitted to the hospital within a month of their discharge.1 Nationally, readmissions cost Medicare $17.4 billion each year.1

Collaborative Partnerships

Prior to the program’s launch in Michigan, SHM recruited and mentored Project BOOST sites independently. However, like many productive relationships in a hospital, Project BOOST in Michigan depends on collaboration between experts.

“Blue Cross Blue Shield of Michigan is confident that this project, like our other Value Partnership programs that focus on robust, statewide, data-driven quality-improvement (QI) partnerships, will have a positive impact on thousands of Michigan lives,” says David Share, MD, MPH, BCBS Michigan’s senior associate medical director of Healthcare Quality. “We look forward to helping hospitals, physicians, and patients work together to assure smooth transitions between inpatient and outpatient care, and to reduce readmissions and improve the patient experience.”

For University of Michigan hospitalist Christopher Kim, MD, MBA, FHM, Project BOOST is a chance to work with a diverse set of groups. “We are grateful for the opportunity to work with not just Blue Cross Blue Shield of Michigan, but also with the other physician organizations across our state to implement and share best-practice ideas in transitions of care,” says Kim, director of the statewide collaborative program on transitions of care.

Results and Reports

Having launched six pilot sites just two years ago, adding 24 additional sites in 2009, Project BOOST is still a relatively young QI program, which makes reliable quantitative data about its effectiveness tough to come by. The expansion into Michigan gives SHM and others the prospect of programwide measurement of how Project BOOST affects discharge and reduces readmissions.

“This is a tremendous opportunity to improve patient safety, reduce readmissions, and study the impact of Project BOOST interventions through patient-level data,” says Mark Williams, MD, FHM, Journal of Hospital Medicine editor, principal investigator for Project BOOST, and former SHM president. “We’re thrilled to be working with the state’s healthcare leaders to implement this critical program.”

Nonetheless, in the absence of comprehensive data, the early reports from Project BOOST sites are promising. At Piedmont Hospital in the Atlanta area, the rate of readmission among patients under the age of 70 participating in BOOST is 8.5%, compared with 25.5% among nonparticipants. The readmission rate among BOOST participants at Piedmont over the age of 70 was 22%, compared with 26% of nonparticipants. When SSM St. Mary’s Medical Center in St. Louis implemented BOOST at its 33-bed hospitalist unit, 30-day readmissions dropped to 7% from 12% within three months.

Patient satisfaction rates also increased markedly, to 68% from 52%. And in 2009, the University of Pennsylvania Health System awarded its annual Operational Quality and Safety Award to the Project BOOST implementation team at the hospital.

BOOST’s Reach Expands

Project BOOST leaders are planning an aggressive expansion in the near future. In addition to the potential for new program sites, SHM has made materials available to hospitalists through the Project BOOST Resource Room at SHM’s newly redesigned Web site (see “The New Face of HospitalMedicine.org,” p. 12), www.hospitalmedicine.org/boost.

In addition to free resources, new BOOST materials are for sale through SHM’s online store. The Project BOOST Implementation Guide—available electronically for free through the resource room—is now available for sale as a hard copy. The online store also features a new Project BOOST instructional DVD for hospitalists, “Using Teach Back to Improve Communication with Patients.” TH

Brendon Shank is a freelance writer based in Philadelphia.

Reference

1. Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med. 2009;360(14): 1418-1428.

Chapter Updates

The Historic Main Street Trolley in Memphis, Tenn.

Memphis

The Memphis chapter held its quarterly meeting Feb. 4 at Erling Jensen in Memphis, Tenn. Dr. William Edmonson of the North Mississippi Medical Center in Tupelo, Miss., discussed “Updates on COPD.” Boehringer Engelheim sponsored the dinner meeting, which was attended by hospitalists and physicians in the area as well as hospital nurses and administration.

Milwaukee/Southeast Wisconsin

The Milwaukee/Southeast Wisconsin chapter’s Feb. 27 meeting in the Columbia Hospital Auditorium brought together hospitalists, nurse practitioners, pharmacists, and others from the Milwaukee area. Attendees were able to obtain CME credit on topics including acute coronary syndrome, hyponatremia, and sepsis. The meeting highlight was a presentation from Dr. Alpesh Amin, interim chair of the Department of Medicine at the University of California at Irvine. Dr. Amin discussed how to start up a local SHM chapter. Sponsorship from CME University helped make the chapter’s first HM symposium a success.

Nebraska Area

Lincoln HM group Bryan LGH hosted the Nebraska Area chapter quarterly meeting Feb. 23. Dr. Tamer Mahrous gave an overview of coding issues for hospitalists. A copy of the presentation will be sent to all of the chapter members.

The chapter elected officers to serve terms through 2012. They include: Dr. Eric Rice, president; Russ Cowles, vice president; Alissa Clough, secretary; and Jay Snow, officer at large.

Several additional items were discussed, including topics for upcoming meetings, how the chapter can best take advantage of opportunities at HM10, the possibility of launching a chapter newsletter, and organizational issues.

New Generics

• Donepezil orally disintegrating tablets (generic Aricept ODT)1
• Nizatadine oral solution (generic Axid oral solution), 15mg/mL.2 It is available in peppermint flavor.

New Drugs, Indications, and Dosage Forms

• Clonidine ER tablets and suspension (Clonidine ER suspension and Clonidine ER tablets) have been approved by the FDA.3
• Estradiol 10 mcg vaginal (Vagifem) low-dose tablets have been approved by the FDA for treating atrophic vaginitis due to menopause.4
• Olanzapine (Zyprexa) has been approved by the FDA to treat schizophrenia and manic or mixed episodes associated with bipolar I disorder in patients aged 13 to 17 years old.5 Prescribers must consider the potential for weight gain and hyperlipidemia, as well as other long-term risks that might occur in adolescents compared with adult patients.
• Olanzapine injection (Zyprexa Relprevv) has been approved by the FDA for treating schizophrenia in adults.6 A risk-evaluation and mitigation strategy (REMS) will be implemented with this agent. It is a long-acting, intramuscular depot injection given every two to four weeks, depending on the dose.7
• Quetiapine extended-release (Zyprexa) has been approved by the FDA as add-on therapy to antidepressants in managing adults with major depressive disorder.8 AstraZeneca, the drug manufacturer, also is seeking approval for a monotherapy indication to manage depression in the acute and maintenance phases.
• Sildenafil intravenous (Revatio IV) has been approved by the FDA for treating pulmonary arterial hypertension for patients who are temporarily unable to take the oral medication.9 The injection is administered as a single-dose of 10 mg up to three times daily. According to the manufacturer, this is bioequivalent to 20 mg three times a day for the oral formulation.
• Tiotropium bromide inhalation powder (Spiriva HandiHaler) has been approved by the FDA for reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD).10

Pipeline

• Approval is pending for Aztreonam lysine inhaled (Cayston) for the treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis.11 The FDA’s Anti-Infectives Drugs Advisory Committee voted 15-2 in favor of the drug’s safety and effectiveness, and 17-0 in favor of a regimen of 75 mg three times a day. The FDA usually approves drugs recommended by its panels.
• Darapladib, a selective and orally active LpPLA2 inhibitor, has begun Phase 3 clinical trials in the management of acute coronary syndrome (ACS).12 The study will include 11,500 male and female patients from 40 countries. It is a double-blind, randomized, placebo-controlled clinical efficacy trial of the long-term use of darapladib when added to standard of care. The study will test whether darapladib affects the chances of having a cardiovascular event, such as a myocardial infarction or a stroke, when treatment is started within 30 days after an ACS.
• Denosumab has received a positive opinion from the European Union for treating osteoporosis in postmenopausal women at increased risk of fractures, and also for treating bone loss in men with prostate cancer who are at increased risk of fractures.13 In the U.S., approval by the FDA is pending for management of osteoporosis in postmenopausal women.14 The FDA’s reproductive health advisory committee, which evaluated the agent, voted 12-1 to require the drug to carry a REMS.
• Ocrelizumab, a Phase 3 humanized anti-CD20 monoclonal antibody for treating rheumatoid arthritis (RA), recently reported positive results when given in combination with methotrexate (MTX) in an international, randomized, multicenter, double-blind trial.15 Ocrelizumab or placebo administered by intravenous infusion on days one and 15 met the primary endpoint of improving the signs and symptoms of RA in patients with an inadequate response to MTX.
• A response to an FDA complete response letter dated May 2009 was expected for rivaroxaban, an oral, direct Factor Xa inhibitor for preventing DVT and pulmonary embolism in patients undergoing hip or knee surgery. Complete review of rivaroxaban data was deferred by its manufacturers until February.16,17
• The FDA is considering a new indication for rosuvastatin (Crestor), following recommendations of the Endocrinologic and Metabolic Drugs Advisory Committee on Dec. 15, 2009.18

Safety Information

Pay attention to two agents manufactured by AstraZeneca: Dexlansoprazole (Kapidex), a new formulation of the proton-pump inhibitor lansoprazole, and bicalutamide (Casodex), which is used in combination with a hormone treatment for prostate cancer, have had medication mixups. The agent names look alike and sound alike when written and verbalized. Both written and verbal prescriptions have been dispensed in error. Bicalutamide is available as 50-mg tablets; dexlansoprazole is available as 30-mg and 60-mg capsules. TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. Walsh S. FDA Approves Generic Aricept to Treat Dementia Related to Alzheimer’s Disease. U.S. Food and Drug Administration Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm194173.htm. Accessed Dec. 28, 2009.
2. Amenal Receives FDA Approval For Nizatidine Oral Solution, the First Oral Solution for Axid in the Market. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/173591.php. Accessed Dec. 28, 2009.
3. Clonidine ER Suspension and Clonidine ER Tablets approved. Monthly Prescribing Reference Web site. Available at: www.empr.com/clonidine-er-suspension-and-clonidine-er-tablets-approved/article/159148/. Accessed Dec. 28, 2009.
4. FDA Approves Mcg Dose of Vagifem For the Treatment of Atrophic Vaginitis Due to Menopause. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/172804.php. Accessed Dec. 28, 2009.
5. Todoruk M. Eli Lilly’s Zyprexa approved in US for adolescents. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=B5699B38AADB46AF85E7B34F508DB943&logRowId=340534. Accessed Dec. 28, 2009.
6. Dennis M. FDA approves Eli Lilly’s long-acting Zyprexa injection. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=30C504823E42425FA0C3B9BB8490D5AA&logRowId=341775. Accessed Dec. 28, 2009.
7. Gever J. FDA Approves Long-Acting Olanzapine. MedPage Today Web site. Available at: www.medpagetoday.com/ProductAlert/Prescriptions/17539. Accessed Dec. 28, 2009.
8. Dennis M. FDA approves AstraZeneca’s Seroquel XR as add-on therapy; requires more data as monotherapy. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=0530A906ABCB44B5A32EC05E148E0220&logRowId=340531. Accessed Dec. 28, 2009.
9. Petrochko C. FDA Approves IV Sildenafil for Hypertension. MedPage Today Web site. Available at: www.medpagetoday.com/ProductAlert/Prescriptions/17296. Accessed Dec. 28, 2009.
10. FDA Approves Spiriva HandiHaler for the Reduction of COPD Exacerbations. Pfizer Web site. Available at: mediaroom.pfizer.com/portal/site/pfizer/?ndmViewId=news_view&newsId=20091217006384&newsLang=en. Accessed Dec. 28, 2009.
11. Leuty R. Gilead wins panel OK for cystic fibrosis drug. San Francisco Business Times Web site. Available at: sanfrancisco.bizjournals.com/sanfrancisco/stories/2009/12/07/daily59.html?surround=etf&ana=e_article. Accessed Dec. 28, 2009.
12. GSK initiates second pivotal Phase III trial for investigational cardiovascular medication Darapladib. GlaxoSmithKline Web site. Available at: www.gsk.com/media/pressreleases/2009/2009_pressrelease_10141.htm. Accessed Dec. 29, 2009.
13. Todoruk M. EU panel issues positive opinion for Amgen’s Prolia. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=A9F30DD044A14893899DF7D880FB8AB0&logRowId=342650. Accessed Dec. 29, 2009.
14. Walker EP. FDA Panel Backs Denosumab for Osteoporosis, But Not Osteopenia. MedPage Web site. Available at: www.medpagetoday.com/Endocrinology/Osteoporosis/15530. Accessed Dec. 29, 2009.
15. Phase 3 study of ocrelizumab for rheumatoid arthritis (RA). Monthly Prescribing Reference Web site. Available at: www.empr.com/phase-3-study-of-ocrelizumab-for-rheumatoid-arthritis-ra/article/159474/. Accessed Dec. 29, 2009.
16. Phase III EINSTEIN-Extension Study of Bayer’s Rivaroxaban Shows Significant Benefit in the Prevention of Secondary Symptomatic VTE. Bayer Web site. Available at: www.bayer.com/en/News-Detail.aspx?id=12554. Accessed Dec. 20, 2009.
17. Todoruk M. Bayer, Johnson & Johnson provide update on Xarelto complete response to FDA. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=8F8AEC62E7DB46C3809C1E77A8384F30&logRowId=340535. Accessed Dec. 29, 2009.
18. O’Riordan M. FDA advisory panel votes in favor of broadened rosuvastatin indication. TheHeart.org Web site. Available at: www.theheart.org/article/1035155/print.do. Accessed Dec. 29, 2009.
19. Kapidex-Casodex confusion. Institute for Safe Medication Practices Web site. Available at: www.ismp.org/newsletters/ambulatory/archives/200907_1.asp. Accessed Dec. 28, 2009.

New Generics

• Donepezil orally disintegrating tablets (generic Aricept ODT)1
• Nizatadine oral solution (generic Axid oral solution), 15mg/mL.2 It is available in peppermint flavor.

New Drugs, Indications, and Dosage Forms

• Clonidine ER tablets and suspension (Clonidine ER suspension and Clonidine ER tablets) have been approved by the FDA.3
• Estradiol 10 mcg vaginal (Vagifem) low-dose tablets have been approved by the FDA for treating atrophic vaginitis due to menopause.4
• Olanzapine (Zyprexa) has been approved by the FDA to treat schizophrenia and manic or mixed episodes associated with bipolar I disorder in patients aged 13 to 17 years old.5 Prescribers must consider the potential for weight gain and hyperlipidemia, as well as other long-term risks that might occur in adolescents compared with adult patients.
• Olanzapine injection (Zyprexa Relprevv) has been approved by the FDA for treating schizophrenia in adults.6 A risk-evaluation and mitigation strategy (REMS) will be implemented with this agent. It is a long-acting, intramuscular depot injection given every two to four weeks, depending on the dose.7
• Quetiapine extended-release (Zyprexa) has been approved by the FDA as add-on therapy to antidepressants in managing adults with major depressive disorder.8 AstraZeneca, the drug manufacturer, also is seeking approval for a monotherapy indication to manage depression in the acute and maintenance phases.
• Sildenafil intravenous (Revatio IV) has been approved by the FDA for treating pulmonary arterial hypertension for patients who are temporarily unable to take the oral medication.9 The injection is administered as a single-dose of 10 mg up to three times daily. According to the manufacturer, this is bioequivalent to 20 mg three times a day for the oral formulation.
• Tiotropium bromide inhalation powder (Spiriva HandiHaler) has been approved by the FDA for reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD).10

Pipeline

• Approval is pending for Aztreonam lysine inhaled (Cayston) for the treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis.11 The FDA’s Anti-Infectives Drugs Advisory Committee voted 15-2 in favor of the drug’s safety and effectiveness, and 17-0 in favor of a regimen of 75 mg three times a day. The FDA usually approves drugs recommended by its panels.
• Darapladib, a selective and orally active LpPLA2 inhibitor, has begun Phase 3 clinical trials in the management of acute coronary syndrome (ACS).12 The study will include 11,500 male and female patients from 40 countries. It is a double-blind, randomized, placebo-controlled clinical efficacy trial of the long-term use of darapladib when added to standard of care. The study will test whether darapladib affects the chances of having a cardiovascular event, such as a myocardial infarction or a stroke, when treatment is started within 30 days after an ACS.
• Denosumab has received a positive opinion from the European Union for treating osteoporosis in postmenopausal women at increased risk of fractures, and also for treating bone loss in men with prostate cancer who are at increased risk of fractures.13 In the U.S., approval by the FDA is pending for management of osteoporosis in postmenopausal women.14 The FDA’s reproductive health advisory committee, which evaluated the agent, voted 12-1 to require the drug to carry a REMS.
• Ocrelizumab, a Phase 3 humanized anti-CD20 monoclonal antibody for treating rheumatoid arthritis (RA), recently reported positive results when given in combination with methotrexate (MTX) in an international, randomized, multicenter, double-blind trial.15 Ocrelizumab or placebo administered by intravenous infusion on days one and 15 met the primary endpoint of improving the signs and symptoms of RA in patients with an inadequate response to MTX.
• A response to an FDA complete response letter dated May 2009 was expected for rivaroxaban, an oral, direct Factor Xa inhibitor for preventing DVT and pulmonary embolism in patients undergoing hip or knee surgery. Complete review of rivaroxaban data was deferred by its manufacturers until February.16,17
• The FDA is considering a new indication for rosuvastatin (Crestor), following recommendations of the Endocrinologic and Metabolic Drugs Advisory Committee on Dec. 15, 2009.18

Safety Information

Pay attention to two agents manufactured by AstraZeneca: Dexlansoprazole (Kapidex), a new formulation of the proton-pump inhibitor lansoprazole, and bicalutamide (Casodex), which is used in combination with a hormone treatment for prostate cancer, have had medication mixups. The agent names look alike and sound alike when written and verbalized. Both written and verbal prescriptions have been dispensed in error. Bicalutamide is available as 50-mg tablets; dexlansoprazole is available as 30-mg and 60-mg capsules. TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. Walsh S. FDA Approves Generic Aricept to Treat Dementia Related to Alzheimer’s Disease. U.S. Food and Drug Administration Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm194173.htm. Accessed Dec. 28, 2009.
2. Amenal Receives FDA Approval For Nizatidine Oral Solution, the First Oral Solution for Axid in the Market. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/173591.php. Accessed Dec. 28, 2009.
3. Clonidine ER Suspension and Clonidine ER Tablets approved. Monthly Prescribing Reference Web site. Available at: www.empr.com/clonidine-er-suspension-and-clonidine-er-tablets-approved/article/159148/. Accessed Dec. 28, 2009.
4. FDA Approves Mcg Dose of Vagifem For the Treatment of Atrophic Vaginitis Due to Menopause. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/172804.php. Accessed Dec. 28, 2009.
5. Todoruk M. Eli Lilly’s Zyprexa approved in US for adolescents. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=B5699B38AADB46AF85E7B34F508DB943&logRowId=340534. Accessed Dec. 28, 2009.
6. Dennis M. FDA approves Eli Lilly’s long-acting Zyprexa injection. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=30C504823E42425FA0C3B9BB8490D5AA&logRowId=341775. Accessed Dec. 28, 2009.
7. Gever J. FDA Approves Long-Acting Olanzapine. MedPage Today Web site. Available at: www.medpagetoday.com/ProductAlert/Prescriptions/17539. Accessed Dec. 28, 2009.
8. Dennis M. FDA approves AstraZeneca’s Seroquel XR as add-on therapy; requires more data as monotherapy. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=0530A906ABCB44B5A32EC05E148E0220&logRowId=340531. Accessed Dec. 28, 2009.
9. Petrochko C. FDA Approves IV Sildenafil for Hypertension. MedPage Today Web site. Available at: www.medpagetoday.com/ProductAlert/Prescriptions/17296. Accessed Dec. 28, 2009.
10. FDA Approves Spiriva HandiHaler for the Reduction of COPD Exacerbations. Pfizer Web site. Available at: mediaroom.pfizer.com/portal/site/pfizer/?ndmViewId=news_view&newsId=20091217006384&newsLang=en. Accessed Dec. 28, 2009.
11. Leuty R. Gilead wins panel OK for cystic fibrosis drug. San Francisco Business Times Web site. Available at: sanfrancisco.bizjournals.com/sanfrancisco/stories/2009/12/07/daily59.html?surround=etf&ana=e_article. Accessed Dec. 28, 2009.
12. GSK initiates second pivotal Phase III trial for investigational cardiovascular medication Darapladib. GlaxoSmithKline Web site. Available at: www.gsk.com/media/pressreleases/2009/2009_pressrelease_10141.htm. Accessed Dec. 29, 2009.
13. Todoruk M. EU panel issues positive opinion for Amgen’s Prolia. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=A9F30DD044A14893899DF7D880FB8AB0&logRowId=342650. Accessed Dec. 29, 2009.
14. Walker EP. FDA Panel Backs Denosumab for Osteoporosis, But Not Osteopenia. MedPage Web site. Available at: www.medpagetoday.com/Endocrinology/Osteoporosis/15530. Accessed Dec. 29, 2009.
15. Phase 3 study of ocrelizumab for rheumatoid arthritis (RA). Monthly Prescribing Reference Web site. Available at: www.empr.com/phase-3-study-of-ocrelizumab-for-rheumatoid-arthritis-ra/article/159474/. Accessed Dec. 29, 2009.
16. Phase III EINSTEIN-Extension Study of Bayer’s Rivaroxaban Shows Significant Benefit in the Prevention of Secondary Symptomatic VTE. Bayer Web site. Available at: www.bayer.com/en/News-Detail.aspx?id=12554. Accessed Dec. 20, 2009.
17. Todoruk M. Bayer, Johnson & Johnson provide update on Xarelto complete response to FDA. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=8F8AEC62E7DB46C3809C1E77A8384F30&logRowId=340535. Accessed Dec. 29, 2009.
18. O’Riordan M. FDA advisory panel votes in favor of broadened rosuvastatin indication. TheHeart.org Web site. Available at: www.theheart.org/article/1035155/print.do. Accessed Dec. 29, 2009.
19. Kapidex-Casodex confusion. Institute for Safe Medication Practices Web site. Available at: www.ismp.org/newsletters/ambulatory/archives/200907_1.asp. Accessed Dec. 28, 2009.

New Generics

• Donepezil orally disintegrating tablets (generic Aricept ODT)1
• Nizatadine oral solution (generic Axid oral solution), 15mg/mL.2 It is available in peppermint flavor.

New Drugs, Indications, and Dosage Forms

• Clonidine ER tablets and suspension (Clonidine ER suspension and Clonidine ER tablets) have been approved by the FDA.3
• Estradiol 10 mcg vaginal (Vagifem) low-dose tablets have been approved by the FDA for treating atrophic vaginitis due to menopause.4
• Olanzapine (Zyprexa) has been approved by the FDA to treat schizophrenia and manic or mixed episodes associated with bipolar I disorder in patients aged 13 to 17 years old.5 Prescribers must consider the potential for weight gain and hyperlipidemia, as well as other long-term risks that might occur in adolescents compared with adult patients.
• Olanzapine injection (Zyprexa Relprevv) has been approved by the FDA for treating schizophrenia in adults.6 A risk-evaluation and mitigation strategy (REMS) will be implemented with this agent. It is a long-acting, intramuscular depot injection given every two to four weeks, depending on the dose.7
• Quetiapine extended-release (Zyprexa) has been approved by the FDA as add-on therapy to antidepressants in managing adults with major depressive disorder.8 AstraZeneca, the drug manufacturer, also is seeking approval for a monotherapy indication to manage depression in the acute and maintenance phases.
• Sildenafil intravenous (Revatio IV) has been approved by the FDA for treating pulmonary arterial hypertension for patients who are temporarily unable to take the oral medication.9 The injection is administered as a single-dose of 10 mg up to three times daily. According to the manufacturer, this is bioequivalent to 20 mg three times a day for the oral formulation.
• Tiotropium bromide inhalation powder (Spiriva HandiHaler) has been approved by the FDA for reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD).10

Pipeline

• Approval is pending for Aztreonam lysine inhaled (Cayston) for the treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis.11 The FDA’s Anti-Infectives Drugs Advisory Committee voted 15-2 in favor of the drug’s safety and effectiveness, and 17-0 in favor of a regimen of 75 mg three times a day. The FDA usually approves drugs recommended by its panels.
• Darapladib, a selective and orally active LpPLA2 inhibitor, has begun Phase 3 clinical trials in the management of acute coronary syndrome (ACS).12 The study will include 11,500 male and female patients from 40 countries. It is a double-blind, randomized, placebo-controlled clinical efficacy trial of the long-term use of darapladib when added to standard of care. The study will test whether darapladib affects the chances of having a cardiovascular event, such as a myocardial infarction or a stroke, when treatment is started within 30 days after an ACS.
• Denosumab has received a positive opinion from the European Union for treating osteoporosis in postmenopausal women at increased risk of fractures, and also for treating bone loss in men with prostate cancer who are at increased risk of fractures.13 In the U.S., approval by the FDA is pending for management of osteoporosis in postmenopausal women.14 The FDA’s reproductive health advisory committee, which evaluated the agent, voted 12-1 to require the drug to carry a REMS.
• Ocrelizumab, a Phase 3 humanized anti-CD20 monoclonal antibody for treating rheumatoid arthritis (RA), recently reported positive results when given in combination with methotrexate (MTX) in an international, randomized, multicenter, double-blind trial.15 Ocrelizumab or placebo administered by intravenous infusion on days one and 15 met the primary endpoint of improving the signs and symptoms of RA in patients with an inadequate response to MTX.
• A response to an FDA complete response letter dated May 2009 was expected for rivaroxaban, an oral, direct Factor Xa inhibitor for preventing DVT and pulmonary embolism in patients undergoing hip or knee surgery. Complete review of rivaroxaban data was deferred by its manufacturers until February.16,17
• The FDA is considering a new indication for rosuvastatin (Crestor), following recommendations of the Endocrinologic and Metabolic Drugs Advisory Committee on Dec. 15, 2009.18

Safety Information

Pay attention to two agents manufactured by AstraZeneca: Dexlansoprazole (Kapidex), a new formulation of the proton-pump inhibitor lansoprazole, and bicalutamide (Casodex), which is used in combination with a hormone treatment for prostate cancer, have had medication mixups. The agent names look alike and sound alike when written and verbalized. Both written and verbal prescriptions have been dispensed in error. Bicalutamide is available as 50-mg tablets; dexlansoprazole is available as 30-mg and 60-mg capsules. TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. Walsh S. FDA Approves Generic Aricept to Treat Dementia Related to Alzheimer’s Disease. U.S. Food and Drug Administration Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm194173.htm. Accessed Dec. 28, 2009.
2. Amenal Receives FDA Approval For Nizatidine Oral Solution, the First Oral Solution for Axid in the Market. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/173591.php. Accessed Dec. 28, 2009.
3. Clonidine ER Suspension and Clonidine ER Tablets approved. Monthly Prescribing Reference Web site. Available at: www.empr.com/clonidine-er-suspension-and-clonidine-er-tablets-approved/article/159148/. Accessed Dec. 28, 2009.
4. FDA Approves Mcg Dose of Vagifem For the Treatment of Atrophic Vaginitis Due to Menopause. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/172804.php. Accessed Dec. 28, 2009.
5. Todoruk M. Eli Lilly’s Zyprexa approved in US for adolescents. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=B5699B38AADB46AF85E7B34F508DB943&logRowId=340534. Accessed Dec. 28, 2009.
6. Dennis M. FDA approves Eli Lilly’s long-acting Zyprexa injection. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=30C504823E42425FA0C3B9BB8490D5AA&logRowId=341775. Accessed Dec. 28, 2009.
7. Gever J. FDA Approves Long-Acting Olanzapine. MedPage Today Web site. Available at: www.medpagetoday.com/ProductAlert/Prescriptions/17539. Accessed Dec. 28, 2009.
8. Dennis M. FDA approves AstraZeneca’s Seroquel XR as add-on therapy; requires more data as monotherapy. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=0530A906ABCB44B5A32EC05E148E0220&logRowId=340531. Accessed Dec. 28, 2009.
9. Petrochko C. FDA Approves IV Sildenafil for Hypertension. MedPage Today Web site. Available at: www.medpagetoday.com/ProductAlert/Prescriptions/17296. Accessed Dec. 28, 2009.
10. FDA Approves Spiriva HandiHaler for the Reduction of COPD Exacerbations. Pfizer Web site. Available at: mediaroom.pfizer.com/portal/site/pfizer/?ndmViewId=news_view&newsId=20091217006384&newsLang=en. Accessed Dec. 28, 2009.
11. Leuty R. Gilead wins panel OK for cystic fibrosis drug. San Francisco Business Times Web site. Available at: sanfrancisco.bizjournals.com/sanfrancisco/stories/2009/12/07/daily59.html?surround=etf&ana=e_article. Accessed Dec. 28, 2009.
12. GSK initiates second pivotal Phase III trial for investigational cardiovascular medication Darapladib. GlaxoSmithKline Web site. Available at: www.gsk.com/media/pressreleases/2009/2009_pressrelease_10141.htm. Accessed Dec. 29, 2009.
13. Todoruk M. EU panel issues positive opinion for Amgen’s Prolia. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=A9F30DD044A14893899DF7D880FB8AB0&logRowId=342650. Accessed Dec. 29, 2009.
14. Walker EP. FDA Panel Backs Denosumab for Osteoporosis, But Not Osteopenia. MedPage Web site. Available at: www.medpagetoday.com/Endocrinology/Osteoporosis/15530. Accessed Dec. 29, 2009.
15. Phase 3 study of ocrelizumab for rheumatoid arthritis (RA). Monthly Prescribing Reference Web site. Available at: www.empr.com/phase-3-study-of-ocrelizumab-for-rheumatoid-arthritis-ra/article/159474/. Accessed Dec. 29, 2009.
16. Phase III EINSTEIN-Extension Study of Bayer’s Rivaroxaban Shows Significant Benefit in the Prevention of Secondary Symptomatic VTE. Bayer Web site. Available at: www.bayer.com/en/News-Detail.aspx?id=12554. Accessed Dec. 20, 2009.
17. Todoruk M. Bayer, Johnson & Johnson provide update on Xarelto complete response to FDA. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=8F8AEC62E7DB46C3809C1E77A8384F30&logRowId=340535. Accessed Dec. 29, 2009.
18. O’Riordan M. FDA advisory panel votes in favor of broadened rosuvastatin indication. TheHeart.org Web site. Available at: www.theheart.org/article/1035155/print.do. Accessed Dec. 29, 2009.
19. Kapidex-Casodex confusion. Institute for Safe Medication Practices Web site. Available at: www.ismp.org/newsletters/ambulatory/archives/200907_1.asp. Accessed Dec. 28, 2009.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Statins and postoperative cardiac outcomes
• Cardiac resynchronization therapy in patients with mild CHF symptoms
• Oral direct thrombin inhibitor versus warfarin for stroke prevention in atrial fibrillation
• Association of fatigue and medical error
• Effects of chronic inhaled steroid and beta-agonist use in COPD
• Dialysis and functional status in nursing home patients
• Outcomes with different insulin-dosing regimens
• Understanding of disease severity and outcomes in advanced dementia

Fluvastatin Improves Postoperative Cardiac Outcomes in Patients Undergoing Vascular Surgery

Clinical question: Does perioperative fluvastatin decrease adverse cardiac events after vascular surgery?

Background: Patients with atherosclerotic vascular disease who undergo vascular surgery are at high risk for postoperative cardiac events. Studies in nonsurgical populations have shown the beneficial effects of statin therapy on cardiac outcomes. However, no placebo-controlled trials have addressed the effect of statins on postoperative cardiac outcomes.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Single large academic medical center in the Netherlands.

Synopsis: The study looked at 497 statin-naïve patients 40 years or older undergoing non-cardiac vascular surgery. The patients were randomized to 80 mg of extended-release fluvastatin versus placebo; all patients received a beta-blocker. Therapy began preoperatively (median of 37 days) and continued for at least 30 days after surgery. Outcomes were assessed at 30 days post-surgery.

Postoperative myocardial infarction (MI) was significantly less common in the fluvastatin group than with placebo (10.8% vs. 19%, hazard ratio (HR) 0.55, P=0.01). In addition, the treatment group had a lower frequency of death from cardiovascular causes (4.8% vs. 10.1%, HR 0.47, P=0.03). Statin therapy was not associated with an increased rate of adverse events.

Notably, all of the patients enrolled in this study were high-risk patients undergoing high-risk (vascular) surgery. Patients already on statins were excluded.

Further studies are needed to determine whether the findings can be extrapolated to other populations, including nonvascular surgery patients.

Bottom line: Perioperative statin therapy resulted in a significant decrease in postoperative MI and death within 30 days of vascular surgery.

Citation: Schouten O, Boersma E, Hoeks SE, et al. Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med. 2009;361(10):980-989.

Cardiac Resynchronization Therapy with Implantable Cardioverter Defibrillator Placement Decreases Heart Failure

Clinical question: Does cardiac resynchronization therapy (CRT) with biventricular pacing decrease cardiac events in patients with reduced ejection fraction (EF) and wide QRS complex but only mild cardiac symptoms?

Background: In patients with severely reduced EF, implantable cardioverter defibrillators (ICDs) have been shown to improve survival. Meanwhile, CRT decreases heart-failure-related hospitalizations for patients with advanced heart-failure symptoms, EF less than 35%, and intraventricular conduction delay. It is not as clear whether patients with less-severe symptoms benefit from CRT.

Study design: Randomized, controlled trial.

Setting: 110 medical centers in the U.S., Canada, and Europe.

Synopsis: This Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study randomly assigned 1,820 adults with EF less than 30%, New York Health Association Class I or II congestive heart failure, and in sinus rhythm with QRS greater than 130 msec to receive ICD with CRT or ICD alone. The primary endpoint was all-cause mortality or nonfatal heart-failure events. Average followup was 2.4 years.

A 34% reduction in the primary endpoint was found in the ICD-CRT group when compared with the ICD-only group, primarily due to a 41% reduction in heart-failure events. In a subgroup analysis, women and patients with QRS greater than 150 msec experienced particular benefit. Echocardiography one year after device implantation demonstrated significant reductions in left ventricular end-systolic and end-diastolic volume, and a significant increase in EF with ICD-CRT versus ICD-only (P<0.001).

Bottom line: Compared with ICD alone, CRT in combination with ICD prevented heart-failure events in relatively asymptomatic heart-failure patients with low EF and prolonged QRS.

Citation: Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329-1338.

Dabigatran Is Not Inferior to Warfarin in Atrial Fibrillation

Clinical question: Is dabigatran, an oral thrombin inhibitor, an effective and safe alternative to warfarin in patients with atrial fibrillation?

Background: Warfarin reduces the risk of stroke among patients with atrial fibrillation (AF) but requires frequent laboratory monitoring. Dabigatran is an oral direct thrombin inhibitor given in fixed dosages without laboratory monitoring.

Study design: Randomized, multicenter, open-label, noninferiority trial.

Setting: 951 clinical centers in 44 countries.

Synopsis: More than 18,000 patients 65 and older with AF and at least one stroke risk factor were enrolled. The average CHADS2 score was 2.1. Patients were randomized to receive fixed doses of dabigatran (110 mg or 150 mg, twice daily) or warfarin adjusted to an INR of 2.0-3.0. The primary outcomes were a) stroke or systemic embolism and b) major hemorrhage. Median followup was two years.

The annual rates of stroke or systemic embolism for both doses of dabigatran were noninferior to warfarin (P<0.001); higher-dose dabigatran was statistically superior to warfarin (relative risk (RR)=0.66, P<0.001). The annual rate of major hemorrhage was lowest in the lower-dose dabigatran group (RR=0.80, P=0.003 compared with warfarin); the higher-dose dabigatran and warfarin groups had equivalent rates of major bleeding. No increased risk of liver function abnormalities was noted.

Bottom line: Dabigatran appears to be an effective and safe alternative to warfarin in AF patients. If the drug were to be FDA-approved, appropriate patient selection and cost will need to be established.

Citation: Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.

Resident Fatigue and Distress Contribute to Perceived Medical Errors

Clinical question: Do resident fatigue and distress contribute to medical errors?

Background: In recent years, such measures as work-hour limitations have been implemented to decrease resident fatigue and, it is presumed, medical errors. However, few studies address the relationship between residents’ well-being and self-reported medical errors.

Study design: Prospective six-year longitudinal cohort study.

Setting: Single academic medical center.

Synopsis: The authors had 380 internal-medicine residents complete quarterly surveys to assess fatigue, quality of life, burnout, symptoms of depression, and frequency of perceived medical errors. In a univariate analysis, fatigue/sleepiness, burnout, depression, and overall quality of life measures correlated significantly with self-reported major medical errors. Fatigue/sleepiness and measures of distress additively increased the risk of self-reported errors. Increases in one or both domains were estimated to increase the risk of self-reported errors by as much as 15% to 28%.

The authors studied only self-reported medical errors. It is difficult to know whether these errors directly affected patient outcomes. Additionally, results of this single-site study might not be able to be generalized.

Bottom line: Fatigue and distress contribute to self-perceived medical errors among residents.

Citation: West CP, Tan AD, Habermann TM, Sloan JA, Shanafelt TD. Association of resident fatigue and distress with perceived medical errors. JAMA. 2009;302(12):1294-1300.

Inhaled Corticosteroids Decrease Inflammation in Moderate to Severe COPD

Clinical question: Does long-term inhaled corticosteroid therapy, with and without long-acting beta-agonists, decrease airway inflammation and improve lung function in patients with moderate to severe chronic obstructive pulmonary disease (COPD)?

Background: Guideline-recommended treatment of COPD with inhaled corticosteroids and long-acting beta-agonists improves symptoms and exacerbation rates; little is known about the impact of these therapies on inflammation and long-term lung function.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Two university medical centers in the Netherlands.

Synopsis: One hundred one steroid-naïve patients, ages 45 to 75 who were current or former smokers with moderate to severe COPD, were randomized to one of four regimens: 1) fluticasone for six months, then placebo for 24 months; 2) fluticasone for 30 months; 3) fluticasone and salmeterol for 30 months; or 4) placebo for 30 months. The primary outcome was inflammatory cell counts in bronchial biopsies/induced sputum. Secondary outcomes included postbronchodilator spirometry, methacholine hyperresponsiveness, and self-reported symptoms and health status. Patients with asthma were excluded.

Short-term fluticasone therapy decreased inflammation and improved forced expiratory volume in one second (FEV1). Long-term therapy also decreased the rate of FEV1 decline, reduced dyspnea, and improved health status. Discontinuation of therapy at six months led to inflammation relapse with worsened symptoms and increased rate of FEV1 decline. The addition of long-acting beta-agonists did not provide additional anti-inflammatory benefits, but it did improve FEV1 and dyspnea at six months.

Additional studies are needed to further define clinical outcomes and assess the cost benefit of these therapies.

Bottom line: Inhaled corticosteroids decrease inflammation in steroid-naïve patients with moderate to severe COPD and might decrease the rate of lung function decline. Long-acting beta-agonists do not offer additional anti-inflammatory benefit.

Citation: Lapperre TS, Snoeck-Stroband JB, Gosman MM, et al. Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2009;151(8):517-527.

Initiation of Dialysis Does Not Help Maintain Functional Status in Elderly

Clinical question: Is functional status in the elderly maintained over time after initiating long-term dialysis?

Background: Quality-of-life maintenance often is used as a goal when initiating long-term dialysis in elderly patients with end-stage renal disease. More elderly patients are being offered long-term dialysis treatment. Little is known about the functional status of elderly patients on long-term dialysis.

Study design: Retrospective cohort study.

Setting: U.S. nursing homes.

Synopsis: By cross-linking data from two population-based administrative datasets, this study identified 3,702 nursing home patients (mean 73.4 years) who had started long-term dialysis and whose functional status had been assessed. Activities of daily living assessments before and at three-month intervals after dialysis initiation were compared to see if functional status was maintained.

Within three months of starting dialysis, 61% of patients had a decline in functional status or had died. By one year, only 1 in 8 patients had maintained their pre-dialysis functional status.

Decline in functional status cannot be attributed solely to dialysis because study patients were not compared to patients with chronic kidney disease who were not dialyzed. In addition, these results might not apply to all elderly patients on dialysis, as the functional status of elderly nursing home patients might differ significantly from those living at home.

Bottom line: Functional status is not maintained in most elderly nursing home patients in the first 12 months after long-term dialysis is initiated. Elderly patients considering dialysis treatment should be aware that dialysis might not help maintain functional status and quality of life.

Citation: Kurella Tamura MK, Covinsky KE, Chertow GM, Yaffe C, Landefeld CS, McCulloch CE. Functional status of elderly adults before and after initiation of dialysis. N Engl J Med. 2009;361(16):1539-1547.

Adding Basal Insulin to Oral Agents in Type 2 Diabetes Might Offer Best Glycemic Control

Clinical question: When added to oral diabetic agents, which insulin regimen (biphasic, prandial or basal) best achieves glycemic control in patients with Type 2 diabetes?

Background: Most patients with Type 2 diabetes mellitus (DM2) require insulin when oral agents provide suboptimal glycemic control. Little is known about which insulin regimen is most effective.

Study design: Three-year, open-label, multicenter trial.

Setting: Fifty-eight clinical centers in the United Kingdom and Ireland.

Synopsis: The authors randomized 708 insulin-naïve DM2 patients (median age 62 years) with HgbA1c 7% to 10% on maximum-dose metformin or sulfonylurea to one of three regimens: biphasic insulin twice daily; prandial insulin three times daily; or basal insulin once daily. Outcomes were HgbA1c, hypoglycemia rates, and weight gain. Sulfonylureas were replaced by another insulin if glycemic control was unacceptable.

The patients were mostly Caucasian and overweight. At three years of followup, median HgbA1c was similar in all groups (7.1% biphasic, 6.8% prandial, 6.9% basal); however, more patients who received prandial or basal insulin achieved HgbA1c less than 6.5% (45% and 43%, respectively) than in the biphasic group (32%).

Hypoglycemia was significantly less frequent in the basal insulin group (1.7 per patient per year versus 3.0 and 5.5 with biphasic and prandial, respectively). Patients gained weight in all groups; the greatest gain was with prandial insulin. At three years, there were no significant between-group differences in blood pressure, cholesterol, albuminuria, or quality of life.

Bottom line: Adding insulin to oral diabetic regimens improves glycemic control. Basal or prandial insulin regimens achieve glycemic targets more frequently than biphasic dosing.

Citation: Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747.

Advanced Dementia Is a Terminal Illness with High Morbidity and Mortality

Clinical question: Does understanding the expected clinical course of advanced dementia influence end-of-life decisions by proxy decision-makers?

Background: Advanced dementia is a leading cause of death in the United States, but the clinical course of advanced dementia has not been described in a rigorous, prospective manner. The lack of information might cause risk to be underestimated, and patients might receive suboptimal palliative care.

Study design: Multicenter prospective cohort study.

Setting: Twenty-two nursing homes in a single U.S. city.

Synopsis: The survey examined 323 nursing home residents with advanced dementia. The patients were clinically assessed at baseline and quarterly for 18 months through chart reviews, nursing interviews, and physical examinations. Additionally, their proxies were surveyed regarding their understanding of the subjects’ prognoses.

During the survey period, 41.1% of patients developed pneumonia, 52.6% of patients experienced a febrile episode, and 85.8% of patients developed an eating problem; cumulative all-cause mortality was 54.8%. Adjusted for age, sex, and disease duration, the six-month mortality rate for subjects who had pneumonia was 46.7%; a febrile episode, 44.5%; and an eating problem, 38.6%.

Distressing symptoms, including dyspnea (46.0%) and pain (39.1%), were common. In the last three months of life, 40.7% of subjects underwent at least one burdensome intervention (defined as hospitalization, ED visit, parenteral therapy, or tube feeding).

Subjects whose proxies reported an understanding of the poor prognosis and expected clinical complications of advanced dementia underwent significantly fewer burdensome interventions (adjusted odds ratio 0.12).

Bottom line: Advanced dementia is associated with frequent complications, including infections and eating problems, with high six-month mortality and significant associated morbidity. Patients whose healthcare proxies have a good understanding of the expected clinical course and prognosis receive less-aggressive end-of-life care.

Citation: Mitchell SL, Teno JM, Kiely DK, et al. The clinical course of advanced dementia. N Engl J Med. 2009;361(16):1529-1538. TH

PEDIATRIC HM LITerature

By Mark Shen, MD

Antibiotic Prophylaxis Might Prevent Recurrent UTIs

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Does antibiotic prophylaxis prevent future episodes of urinary tract infections?

Background: Recurrent urinary tract infections (UTI) in children might be associated with renal scarring and subsequent clinical consequences associated with long-term morbidity. Historically, antibiotic prophylaxis has been recommended for children who might have risk factors for recurrent infection, most commonly vesicoureteral reflux. However, scars may be present in the absence of known risk factors and upon first UTI. The efficacy of antibiotic prophylaxis in preventing recurrent UTIs is unclear.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Four centers in Australia.

Synopsis: The study looked at 576 children under the age of 18 with a history of at least one symptomatic UTI. The patients were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX) or placebo for 12 months. Children with vesicoureteral reflux were included, but those with known neurologic, skeletal, or urologic predispositions were excluded.

Thirteen percent of patients in the antibiotic group developed a UTI compared with 19% of patients in the placebo group (P=0.02). The authors calculate that at 12 months, 14 patients would need to be treated to prevent one UTI.

This study was unable to enroll the planned number of children but remained adequately powered to show a reduction in the primary outcome (rate of symptomatic UTI). However, a significant number of patients (approximately 28%) in each arm stopped taking the medication, the majority for undisclosed reasons. Despite an intention-to-treat analysis, this degree of dropout raises questions about the true effect size. Additionally, this study does not answer the more important clinical question regarding the effect of prophylaxis on potential future renal damage, specifically in children with vesicoureteral reflux.

Bottom line: Antibiotic prophylaxis might be modestly effective in preventing recurrent UTIs.

Citation: Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-1759.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Statins and postoperative cardiac outcomes
• Cardiac resynchronization therapy in patients with mild CHF symptoms
• Oral direct thrombin inhibitor versus warfarin for stroke prevention in atrial fibrillation
• Association of fatigue and medical error
• Effects of chronic inhaled steroid and beta-agonist use in COPD
• Dialysis and functional status in nursing home patients
• Outcomes with different insulin-dosing regimens
• Understanding of disease severity and outcomes in advanced dementia

Fluvastatin Improves Postoperative Cardiac Outcomes in Patients Undergoing Vascular Surgery

Clinical question: Does perioperative fluvastatin decrease adverse cardiac events after vascular surgery?

Background: Patients with atherosclerotic vascular disease who undergo vascular surgery are at high risk for postoperative cardiac events. Studies in nonsurgical populations have shown the beneficial effects of statin therapy on cardiac outcomes. However, no placebo-controlled trials have addressed the effect of statins on postoperative cardiac outcomes.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Single large academic medical center in the Netherlands.

Synopsis: The study looked at 497 statin-naïve patients 40 years or older undergoing non-cardiac vascular surgery. The patients were randomized to 80 mg of extended-release fluvastatin versus placebo; all patients received a beta-blocker. Therapy began preoperatively (median of 37 days) and continued for at least 30 days after surgery. Outcomes were assessed at 30 days post-surgery.

Postoperative myocardial infarction (MI) was significantly less common in the fluvastatin group than with placebo (10.8% vs. 19%, hazard ratio (HR) 0.55, P=0.01). In addition, the treatment group had a lower frequency of death from cardiovascular causes (4.8% vs. 10.1%, HR 0.47, P=0.03). Statin therapy was not associated with an increased rate of adverse events.

Notably, all of the patients enrolled in this study were high-risk patients undergoing high-risk (vascular) surgery. Patients already on statins were excluded.

Further studies are needed to determine whether the findings can be extrapolated to other populations, including nonvascular surgery patients.

Bottom line: Perioperative statin therapy resulted in a significant decrease in postoperative MI and death within 30 days of vascular surgery.

Citation: Schouten O, Boersma E, Hoeks SE, et al. Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med. 2009;361(10):980-989.

Cardiac Resynchronization Therapy with Implantable Cardioverter Defibrillator Placement Decreases Heart Failure

Clinical question: Does cardiac resynchronization therapy (CRT) with biventricular pacing decrease cardiac events in patients with reduced ejection fraction (EF) and wide QRS complex but only mild cardiac symptoms?

Background: In patients with severely reduced EF, implantable cardioverter defibrillators (ICDs) have been shown to improve survival. Meanwhile, CRT decreases heart-failure-related hospitalizations for patients with advanced heart-failure symptoms, EF less than 35%, and intraventricular conduction delay. It is not as clear whether patients with less-severe symptoms benefit from CRT.

Study design: Randomized, controlled trial.

Setting: 110 medical centers in the U.S., Canada, and Europe.

Synopsis: This Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study randomly assigned 1,820 adults with EF less than 30%, New York Health Association Class I or II congestive heart failure, and in sinus rhythm with QRS greater than 130 msec to receive ICD with CRT or ICD alone. The primary endpoint was all-cause mortality or nonfatal heart-failure events. Average followup was 2.4 years.

A 34% reduction in the primary endpoint was found in the ICD-CRT group when compared with the ICD-only group, primarily due to a 41% reduction in heart-failure events. In a subgroup analysis, women and patients with QRS greater than 150 msec experienced particular benefit. Echocardiography one year after device implantation demonstrated significant reductions in left ventricular end-systolic and end-diastolic volume, and a significant increase in EF with ICD-CRT versus ICD-only (P<0.001).

Bottom line: Compared with ICD alone, CRT in combination with ICD prevented heart-failure events in relatively asymptomatic heart-failure patients with low EF and prolonged QRS.

Citation: Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329-1338.

Dabigatran Is Not Inferior to Warfarin in Atrial Fibrillation

Clinical question: Is dabigatran, an oral thrombin inhibitor, an effective and safe alternative to warfarin in patients with atrial fibrillation?

Background: Warfarin reduces the risk of stroke among patients with atrial fibrillation (AF) but requires frequent laboratory monitoring. Dabigatran is an oral direct thrombin inhibitor given in fixed dosages without laboratory monitoring.

Study design: Randomized, multicenter, open-label, noninferiority trial.

Setting: 951 clinical centers in 44 countries.

Synopsis: More than 18,000 patients 65 and older with AF and at least one stroke risk factor were enrolled. The average CHADS2 score was 2.1. Patients were randomized to receive fixed doses of dabigatran (110 mg or 150 mg, twice daily) or warfarin adjusted to an INR of 2.0-3.0. The primary outcomes were a) stroke or systemic embolism and b) major hemorrhage. Median followup was two years.

The annual rates of stroke or systemic embolism for both doses of dabigatran were noninferior to warfarin (P<0.001); higher-dose dabigatran was statistically superior to warfarin (relative risk (RR)=0.66, P<0.001). The annual rate of major hemorrhage was lowest in the lower-dose dabigatran group (RR=0.80, P=0.003 compared with warfarin); the higher-dose dabigatran and warfarin groups had equivalent rates of major bleeding. No increased risk of liver function abnormalities was noted.

Bottom line: Dabigatran appears to be an effective and safe alternative to warfarin in AF patients. If the drug were to be FDA-approved, appropriate patient selection and cost will need to be established.

Citation: Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.

Resident Fatigue and Distress Contribute to Perceived Medical Errors

Clinical question: Do resident fatigue and distress contribute to medical errors?

Background: In recent years, such measures as work-hour limitations have been implemented to decrease resident fatigue and, it is presumed, medical errors. However, few studies address the relationship between residents’ well-being and self-reported medical errors.

Study design: Prospective six-year longitudinal cohort study.

Setting: Single academic medical center.

Synopsis: The authors had 380 internal-medicine residents complete quarterly surveys to assess fatigue, quality of life, burnout, symptoms of depression, and frequency of perceived medical errors. In a univariate analysis, fatigue/sleepiness, burnout, depression, and overall quality of life measures correlated significantly with self-reported major medical errors. Fatigue/sleepiness and measures of distress additively increased the risk of self-reported errors. Increases in one or both domains were estimated to increase the risk of self-reported errors by as much as 15% to 28%.

The authors studied only self-reported medical errors. It is difficult to know whether these errors directly affected patient outcomes. Additionally, results of this single-site study might not be able to be generalized.

Bottom line: Fatigue and distress contribute to self-perceived medical errors among residents.

Citation: West CP, Tan AD, Habermann TM, Sloan JA, Shanafelt TD. Association of resident fatigue and distress with perceived medical errors. JAMA. 2009;302(12):1294-1300.

Inhaled Corticosteroids Decrease Inflammation in Moderate to Severe COPD

Clinical question: Does long-term inhaled corticosteroid therapy, with and without long-acting beta-agonists, decrease airway inflammation and improve lung function in patients with moderate to severe chronic obstructive pulmonary disease (COPD)?

Background: Guideline-recommended treatment of COPD with inhaled corticosteroids and long-acting beta-agonists improves symptoms and exacerbation rates; little is known about the impact of these therapies on inflammation and long-term lung function.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Two university medical centers in the Netherlands.

Synopsis: One hundred one steroid-naïve patients, ages 45 to 75 who were current or former smokers with moderate to severe COPD, were randomized to one of four regimens: 1) fluticasone for six months, then placebo for 24 months; 2) fluticasone for 30 months; 3) fluticasone and salmeterol for 30 months; or 4) placebo for 30 months. The primary outcome was inflammatory cell counts in bronchial biopsies/induced sputum. Secondary outcomes included postbronchodilator spirometry, methacholine hyperresponsiveness, and self-reported symptoms and health status. Patients with asthma were excluded.

Short-term fluticasone therapy decreased inflammation and improved forced expiratory volume in one second (FEV1). Long-term therapy also decreased the rate of FEV1 decline, reduced dyspnea, and improved health status. Discontinuation of therapy at six months led to inflammation relapse with worsened symptoms and increased rate of FEV1 decline. The addition of long-acting beta-agonists did not provide additional anti-inflammatory benefits, but it did improve FEV1 and dyspnea at six months.

Additional studies are needed to further define clinical outcomes and assess the cost benefit of these therapies.

Bottom line: Inhaled corticosteroids decrease inflammation in steroid-naïve patients with moderate to severe COPD and might decrease the rate of lung function decline. Long-acting beta-agonists do not offer additional anti-inflammatory benefit.

Citation: Lapperre TS, Snoeck-Stroband JB, Gosman MM, et al. Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2009;151(8):517-527.

Initiation of Dialysis Does Not Help Maintain Functional Status in Elderly

Clinical question: Is functional status in the elderly maintained over time after initiating long-term dialysis?

Background: Quality-of-life maintenance often is used as a goal when initiating long-term dialysis in elderly patients with end-stage renal disease. More elderly patients are being offered long-term dialysis treatment. Little is known about the functional status of elderly patients on long-term dialysis.

Study design: Retrospective cohort study.

Setting: U.S. nursing homes.

Synopsis: By cross-linking data from two population-based administrative datasets, this study identified 3,702 nursing home patients (mean 73.4 years) who had started long-term dialysis and whose functional status had been assessed. Activities of daily living assessments before and at three-month intervals after dialysis initiation were compared to see if functional status was maintained.

Within three months of starting dialysis, 61% of patients had a decline in functional status or had died. By one year, only 1 in 8 patients had maintained their pre-dialysis functional status.

Decline in functional status cannot be attributed solely to dialysis because study patients were not compared to patients with chronic kidney disease who were not dialyzed. In addition, these results might not apply to all elderly patients on dialysis, as the functional status of elderly nursing home patients might differ significantly from those living at home.

Bottom line: Functional status is not maintained in most elderly nursing home patients in the first 12 months after long-term dialysis is initiated. Elderly patients considering dialysis treatment should be aware that dialysis might not help maintain functional status and quality of life.

Citation: Kurella Tamura MK, Covinsky KE, Chertow GM, Yaffe C, Landefeld CS, McCulloch CE. Functional status of elderly adults before and after initiation of dialysis. N Engl J Med. 2009;361(16):1539-1547.

Adding Basal Insulin to Oral Agents in Type 2 Diabetes Might Offer Best Glycemic Control

Clinical question: When added to oral diabetic agents, which insulin regimen (biphasic, prandial or basal) best achieves glycemic control in patients with Type 2 diabetes?

Background: Most patients with Type 2 diabetes mellitus (DM2) require insulin when oral agents provide suboptimal glycemic control. Little is known about which insulin regimen is most effective.

Study design: Three-year, open-label, multicenter trial.

Setting: Fifty-eight clinical centers in the United Kingdom and Ireland.

Synopsis: The authors randomized 708 insulin-naïve DM2 patients (median age 62 years) with HgbA1c 7% to 10% on maximum-dose metformin or sulfonylurea to one of three regimens: biphasic insulin twice daily; prandial insulin three times daily; or basal insulin once daily. Outcomes were HgbA1c, hypoglycemia rates, and weight gain. Sulfonylureas were replaced by another insulin if glycemic control was unacceptable.

The patients were mostly Caucasian and overweight. At three years of followup, median HgbA1c was similar in all groups (7.1% biphasic, 6.8% prandial, 6.9% basal); however, more patients who received prandial or basal insulin achieved HgbA1c less than 6.5% (45% and 43%, respectively) than in the biphasic group (32%).

Hypoglycemia was significantly less frequent in the basal insulin group (1.7 per patient per year versus 3.0 and 5.5 with biphasic and prandial, respectively). Patients gained weight in all groups; the greatest gain was with prandial insulin. At three years, there were no significant between-group differences in blood pressure, cholesterol, albuminuria, or quality of life.

Bottom line: Adding insulin to oral diabetic regimens improves glycemic control. Basal or prandial insulin regimens achieve glycemic targets more frequently than biphasic dosing.

Citation: Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747.

Advanced Dementia Is a Terminal Illness with High Morbidity and Mortality

Clinical question: Does understanding the expected clinical course of advanced dementia influence end-of-life decisions by proxy decision-makers?

Background: Advanced dementia is a leading cause of death in the United States, but the clinical course of advanced dementia has not been described in a rigorous, prospective manner. The lack of information might cause risk to be underestimated, and patients might receive suboptimal palliative care.

Study design: Multicenter prospective cohort study.

Setting: Twenty-two nursing homes in a single U.S. city.

Synopsis: The survey examined 323 nursing home residents with advanced dementia. The patients were clinically assessed at baseline and quarterly for 18 months through chart reviews, nursing interviews, and physical examinations. Additionally, their proxies were surveyed regarding their understanding of the subjects’ prognoses.

During the survey period, 41.1% of patients developed pneumonia, 52.6% of patients experienced a febrile episode, and 85.8% of patients developed an eating problem; cumulative all-cause mortality was 54.8%. Adjusted for age, sex, and disease duration, the six-month mortality rate for subjects who had pneumonia was 46.7%; a febrile episode, 44.5%; and an eating problem, 38.6%.

Distressing symptoms, including dyspnea (46.0%) and pain (39.1%), were common. In the last three months of life, 40.7% of subjects underwent at least one burdensome intervention (defined as hospitalization, ED visit, parenteral therapy, or tube feeding).

Subjects whose proxies reported an understanding of the poor prognosis and expected clinical complications of advanced dementia underwent significantly fewer burdensome interventions (adjusted odds ratio 0.12).

Bottom line: Advanced dementia is associated with frequent complications, including infections and eating problems, with high six-month mortality and significant associated morbidity. Patients whose healthcare proxies have a good understanding of the expected clinical course and prognosis receive less-aggressive end-of-life care.

Citation: Mitchell SL, Teno JM, Kiely DK, et al. The clinical course of advanced dementia. N Engl J Med. 2009;361(16):1529-1538. TH

PEDIATRIC HM LITerature

By Mark Shen, MD

Antibiotic Prophylaxis Might Prevent Recurrent UTIs

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Does antibiotic prophylaxis prevent future episodes of urinary tract infections?

Background: Recurrent urinary tract infections (UTI) in children might be associated with renal scarring and subsequent clinical consequences associated with long-term morbidity. Historically, antibiotic prophylaxis has been recommended for children who might have risk factors for recurrent infection, most commonly vesicoureteral reflux. However, scars may be present in the absence of known risk factors and upon first UTI. The efficacy of antibiotic prophylaxis in preventing recurrent UTIs is unclear.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Four centers in Australia.

Synopsis: The study looked at 576 children under the age of 18 with a history of at least one symptomatic UTI. The patients were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX) or placebo for 12 months. Children with vesicoureteral reflux were included, but those with known neurologic, skeletal, or urologic predispositions were excluded.

Thirteen percent of patients in the antibiotic group developed a UTI compared with 19% of patients in the placebo group (P=0.02). The authors calculate that at 12 months, 14 patients would need to be treated to prevent one UTI.

This study was unable to enroll the planned number of children but remained adequately powered to show a reduction in the primary outcome (rate of symptomatic UTI). However, a significant number of patients (approximately 28%) in each arm stopped taking the medication, the majority for undisclosed reasons. Despite an intention-to-treat analysis, this degree of dropout raises questions about the true effect size. Additionally, this study does not answer the more important clinical question regarding the effect of prophylaxis on potential future renal damage, specifically in children with vesicoureteral reflux.

Bottom line: Antibiotic prophylaxis might be modestly effective in preventing recurrent UTIs.

Citation: Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-1759.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Statins and postoperative cardiac outcomes
• Cardiac resynchronization therapy in patients with mild CHF symptoms
• Oral direct thrombin inhibitor versus warfarin for stroke prevention in atrial fibrillation
• Association of fatigue and medical error
• Effects of chronic inhaled steroid and beta-agonist use in COPD
• Dialysis and functional status in nursing home patients
• Outcomes with different insulin-dosing regimens
• Understanding of disease severity and outcomes in advanced dementia

Fluvastatin Improves Postoperative Cardiac Outcomes in Patients Undergoing Vascular Surgery

Clinical question: Does perioperative fluvastatin decrease adverse cardiac events after vascular surgery?

Background: Patients with atherosclerotic vascular disease who undergo vascular surgery are at high risk for postoperative cardiac events. Studies in nonsurgical populations have shown the beneficial effects of statin therapy on cardiac outcomes. However, no placebo-controlled trials have addressed the effect of statins on postoperative cardiac outcomes.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Single large academic medical center in the Netherlands.

Synopsis: The study looked at 497 statin-naïve patients 40 years or older undergoing non-cardiac vascular surgery. The patients were randomized to 80 mg of extended-release fluvastatin versus placebo; all patients received a beta-blocker. Therapy began preoperatively (median of 37 days) and continued for at least 30 days after surgery. Outcomes were assessed at 30 days post-surgery.

Postoperative myocardial infarction (MI) was significantly less common in the fluvastatin group than with placebo (10.8% vs. 19%, hazard ratio (HR) 0.55, P=0.01). In addition, the treatment group had a lower frequency of death from cardiovascular causes (4.8% vs. 10.1%, HR 0.47, P=0.03). Statin therapy was not associated with an increased rate of adverse events.

Notably, all of the patients enrolled in this study were high-risk patients undergoing high-risk (vascular) surgery. Patients already on statins were excluded.

Further studies are needed to determine whether the findings can be extrapolated to other populations, including nonvascular surgery patients.

Bottom line: Perioperative statin therapy resulted in a significant decrease in postoperative MI and death within 30 days of vascular surgery.

Citation: Schouten O, Boersma E, Hoeks SE, et al. Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med. 2009;361(10):980-989.

Cardiac Resynchronization Therapy with Implantable Cardioverter Defibrillator Placement Decreases Heart Failure

Clinical question: Does cardiac resynchronization therapy (CRT) with biventricular pacing decrease cardiac events in patients with reduced ejection fraction (EF) and wide QRS complex but only mild cardiac symptoms?

Background: In patients with severely reduced EF, implantable cardioverter defibrillators (ICDs) have been shown to improve survival. Meanwhile, CRT decreases heart-failure-related hospitalizations for patients with advanced heart-failure symptoms, EF less than 35%, and intraventricular conduction delay. It is not as clear whether patients with less-severe symptoms benefit from CRT.

Study design: Randomized, controlled trial.

Setting: 110 medical centers in the U.S., Canada, and Europe.

Synopsis: This Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study randomly assigned 1,820 adults with EF less than 30%, New York Health Association Class I or II congestive heart failure, and in sinus rhythm with QRS greater than 130 msec to receive ICD with CRT or ICD alone. The primary endpoint was all-cause mortality or nonfatal heart-failure events. Average followup was 2.4 years.

A 34% reduction in the primary endpoint was found in the ICD-CRT group when compared with the ICD-only group, primarily due to a 41% reduction in heart-failure events. In a subgroup analysis, women and patients with QRS greater than 150 msec experienced particular benefit. Echocardiography one year after device implantation demonstrated significant reductions in left ventricular end-systolic and end-diastolic volume, and a significant increase in EF with ICD-CRT versus ICD-only (P<0.001).

Bottom line: Compared with ICD alone, CRT in combination with ICD prevented heart-failure events in relatively asymptomatic heart-failure patients with low EF and prolonged QRS.

Citation: Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329-1338.

Dabigatran Is Not Inferior to Warfarin in Atrial Fibrillation

Clinical question: Is dabigatran, an oral thrombin inhibitor, an effective and safe alternative to warfarin in patients with atrial fibrillation?

Background: Warfarin reduces the risk of stroke among patients with atrial fibrillation (AF) but requires frequent laboratory monitoring. Dabigatran is an oral direct thrombin inhibitor given in fixed dosages without laboratory monitoring.

Study design: Randomized, multicenter, open-label, noninferiority trial.

Setting: 951 clinical centers in 44 countries.

Synopsis: More than 18,000 patients 65 and older with AF and at least one stroke risk factor were enrolled. The average CHADS2 score was 2.1. Patients were randomized to receive fixed doses of dabigatran (110 mg or 150 mg, twice daily) or warfarin adjusted to an INR of 2.0-3.0. The primary outcomes were a) stroke or systemic embolism and b) major hemorrhage. Median followup was two years.

The annual rates of stroke or systemic embolism for both doses of dabigatran were noninferior to warfarin (P<0.001); higher-dose dabigatran was statistically superior to warfarin (relative risk (RR)=0.66, P<0.001). The annual rate of major hemorrhage was lowest in the lower-dose dabigatran group (RR=0.80, P=0.003 compared with warfarin); the higher-dose dabigatran and warfarin groups had equivalent rates of major bleeding. No increased risk of liver function abnormalities was noted.

Bottom line: Dabigatran appears to be an effective and safe alternative to warfarin in AF patients. If the drug were to be FDA-approved, appropriate patient selection and cost will need to be established.

Citation: Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.

Resident Fatigue and Distress Contribute to Perceived Medical Errors

Clinical question: Do resident fatigue and distress contribute to medical errors?

Background: In recent years, such measures as work-hour limitations have been implemented to decrease resident fatigue and, it is presumed, medical errors. However, few studies address the relationship between residents’ well-being and self-reported medical errors.

Study design: Prospective six-year longitudinal cohort study.

Setting: Single academic medical center.

Synopsis: The authors had 380 internal-medicine residents complete quarterly surveys to assess fatigue, quality of life, burnout, symptoms of depression, and frequency of perceived medical errors. In a univariate analysis, fatigue/sleepiness, burnout, depression, and overall quality of life measures correlated significantly with self-reported major medical errors. Fatigue/sleepiness and measures of distress additively increased the risk of self-reported errors. Increases in one or both domains were estimated to increase the risk of self-reported errors by as much as 15% to 28%.

The authors studied only self-reported medical errors. It is difficult to know whether these errors directly affected patient outcomes. Additionally, results of this single-site study might not be able to be generalized.

Bottom line: Fatigue and distress contribute to self-perceived medical errors among residents.

Citation: West CP, Tan AD, Habermann TM, Sloan JA, Shanafelt TD. Association of resident fatigue and distress with perceived medical errors. JAMA. 2009;302(12):1294-1300.

Inhaled Corticosteroids Decrease Inflammation in Moderate to Severe COPD

Clinical question: Does long-term inhaled corticosteroid therapy, with and without long-acting beta-agonists, decrease airway inflammation and improve lung function in patients with moderate to severe chronic obstructive pulmonary disease (COPD)?

Background: Guideline-recommended treatment of COPD with inhaled corticosteroids and long-acting beta-agonists improves symptoms and exacerbation rates; little is known about the impact of these therapies on inflammation and long-term lung function.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Two university medical centers in the Netherlands.

Synopsis: One hundred one steroid-naïve patients, ages 45 to 75 who were current or former smokers with moderate to severe COPD, were randomized to one of four regimens: 1) fluticasone for six months, then placebo for 24 months; 2) fluticasone for 30 months; 3) fluticasone and salmeterol for 30 months; or 4) placebo for 30 months. The primary outcome was inflammatory cell counts in bronchial biopsies/induced sputum. Secondary outcomes included postbronchodilator spirometry, methacholine hyperresponsiveness, and self-reported symptoms and health status. Patients with asthma were excluded.

Short-term fluticasone therapy decreased inflammation and improved forced expiratory volume in one second (FEV1). Long-term therapy also decreased the rate of FEV1 decline, reduced dyspnea, and improved health status. Discontinuation of therapy at six months led to inflammation relapse with worsened symptoms and increased rate of FEV1 decline. The addition of long-acting beta-agonists did not provide additional anti-inflammatory benefits, but it did improve FEV1 and dyspnea at six months.

Additional studies are needed to further define clinical outcomes and assess the cost benefit of these therapies.

Bottom line: Inhaled corticosteroids decrease inflammation in steroid-naïve patients with moderate to severe COPD and might decrease the rate of lung function decline. Long-acting beta-agonists do not offer additional anti-inflammatory benefit.

Citation: Lapperre TS, Snoeck-Stroband JB, Gosman MM, et al. Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2009;151(8):517-527.

Initiation of Dialysis Does Not Help Maintain Functional Status in Elderly

Clinical question: Is functional status in the elderly maintained over time after initiating long-term dialysis?

Background: Quality-of-life maintenance often is used as a goal when initiating long-term dialysis in elderly patients with end-stage renal disease. More elderly patients are being offered long-term dialysis treatment. Little is known about the functional status of elderly patients on long-term dialysis.

Study design: Retrospective cohort study.

Setting: U.S. nursing homes.

Synopsis: By cross-linking data from two population-based administrative datasets, this study identified 3,702 nursing home patients (mean 73.4 years) who had started long-term dialysis and whose functional status had been assessed. Activities of daily living assessments before and at three-month intervals after dialysis initiation were compared to see if functional status was maintained.

Within three months of starting dialysis, 61% of patients had a decline in functional status or had died. By one year, only 1 in 8 patients had maintained their pre-dialysis functional status.

Decline in functional status cannot be attributed solely to dialysis because study patients were not compared to patients with chronic kidney disease who were not dialyzed. In addition, these results might not apply to all elderly patients on dialysis, as the functional status of elderly nursing home patients might differ significantly from those living at home.

Bottom line: Functional status is not maintained in most elderly nursing home patients in the first 12 months after long-term dialysis is initiated. Elderly patients considering dialysis treatment should be aware that dialysis might not help maintain functional status and quality of life.

Citation: Kurella Tamura MK, Covinsky KE, Chertow GM, Yaffe C, Landefeld CS, McCulloch CE. Functional status of elderly adults before and after initiation of dialysis. N Engl J Med. 2009;361(16):1539-1547.

Adding Basal Insulin to Oral Agents in Type 2 Diabetes Might Offer Best Glycemic Control

Clinical question: When added to oral diabetic agents, which insulin regimen (biphasic, prandial or basal) best achieves glycemic control in patients with Type 2 diabetes?

Background: Most patients with Type 2 diabetes mellitus (DM2) require insulin when oral agents provide suboptimal glycemic control. Little is known about which insulin regimen is most effective.

Study design: Three-year, open-label, multicenter trial.

Setting: Fifty-eight clinical centers in the United Kingdom and Ireland.

Synopsis: The authors randomized 708 insulin-naïve DM2 patients (median age 62 years) with HgbA1c 7% to 10% on maximum-dose metformin or sulfonylurea to one of three regimens: biphasic insulin twice daily; prandial insulin three times daily; or basal insulin once daily. Outcomes were HgbA1c, hypoglycemia rates, and weight gain. Sulfonylureas were replaced by another insulin if glycemic control was unacceptable.

The patients were mostly Caucasian and overweight. At three years of followup, median HgbA1c was similar in all groups (7.1% biphasic, 6.8% prandial, 6.9% basal); however, more patients who received prandial or basal insulin achieved HgbA1c less than 6.5% (45% and 43%, respectively) than in the biphasic group (32%).

Hypoglycemia was significantly less frequent in the basal insulin group (1.7 per patient per year versus 3.0 and 5.5 with biphasic and prandial, respectively). Patients gained weight in all groups; the greatest gain was with prandial insulin. At three years, there were no significant between-group differences in blood pressure, cholesterol, albuminuria, or quality of life.

Bottom line: Adding insulin to oral diabetic regimens improves glycemic control. Basal or prandial insulin regimens achieve glycemic targets more frequently than biphasic dosing.

Citation: Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747.

Advanced Dementia Is a Terminal Illness with High Morbidity and Mortality

Clinical question: Does understanding the expected clinical course of advanced dementia influence end-of-life decisions by proxy decision-makers?

Background: Advanced dementia is a leading cause of death in the United States, but the clinical course of advanced dementia has not been described in a rigorous, prospective manner. The lack of information might cause risk to be underestimated, and patients might receive suboptimal palliative care.

Study design: Multicenter prospective cohort study.

Setting: Twenty-two nursing homes in a single U.S. city.

Synopsis: The survey examined 323 nursing home residents with advanced dementia. The patients were clinically assessed at baseline and quarterly for 18 months through chart reviews, nursing interviews, and physical examinations. Additionally, their proxies were surveyed regarding their understanding of the subjects’ prognoses.

During the survey period, 41.1% of patients developed pneumonia, 52.6% of patients experienced a febrile episode, and 85.8% of patients developed an eating problem; cumulative all-cause mortality was 54.8%. Adjusted for age, sex, and disease duration, the six-month mortality rate for subjects who had pneumonia was 46.7%; a febrile episode, 44.5%; and an eating problem, 38.6%.

Distressing symptoms, including dyspnea (46.0%) and pain (39.1%), were common. In the last three months of life, 40.7% of subjects underwent at least one burdensome intervention (defined as hospitalization, ED visit, parenteral therapy, or tube feeding).

Subjects whose proxies reported an understanding of the poor prognosis and expected clinical complications of advanced dementia underwent significantly fewer burdensome interventions (adjusted odds ratio 0.12).

Bottom line: Advanced dementia is associated with frequent complications, including infections and eating problems, with high six-month mortality and significant associated morbidity. Patients whose healthcare proxies have a good understanding of the expected clinical course and prognosis receive less-aggressive end-of-life care.

Citation: Mitchell SL, Teno JM, Kiely DK, et al. The clinical course of advanced dementia. N Engl J Med. 2009;361(16):1529-1538. TH

PEDIATRIC HM LITerature

By Mark Shen, MD

Antibiotic Prophylaxis Might Prevent Recurrent UTIs

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Does antibiotic prophylaxis prevent future episodes of urinary tract infections?

Background: Recurrent urinary tract infections (UTI) in children might be associated with renal scarring and subsequent clinical consequences associated with long-term morbidity. Historically, antibiotic prophylaxis has been recommended for children who might have risk factors for recurrent infection, most commonly vesicoureteral reflux. However, scars may be present in the absence of known risk factors and upon first UTI. The efficacy of antibiotic prophylaxis in preventing recurrent UTIs is unclear.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Four centers in Australia.

Synopsis: The study looked at 576 children under the age of 18 with a history of at least one symptomatic UTI. The patients were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX) or placebo for 12 months. Children with vesicoureteral reflux were included, but those with known neurologic, skeletal, or urologic predispositions were excluded.

Thirteen percent of patients in the antibiotic group developed a UTI compared with 19% of patients in the placebo group (P=0.02). The authors calculate that at 12 months, 14 patients would need to be treated to prevent one UTI.

This study was unable to enroll the planned number of children but remained adequately powered to show a reduction in the primary outcome (rate of symptomatic UTI). However, a significant number of patients (approximately 28%) in each arm stopped taking the medication, the majority for undisclosed reasons. Despite an intention-to-treat analysis, this degree of dropout raises questions about the true effect size. Additionally, this study does not answer the more important clinical question regarding the effect of prophylaxis on potential future renal damage, specifically in children with vesicoureteral reflux.

Bottom line: Antibiotic prophylaxis might be modestly effective in preventing recurrent UTIs.

Citation: Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-1759.

Three U.S. medical centers have been recognized for innovative approaches to preventing DVT and its potentially fatal complications, which include pulmonary embolism (PE). Central to each of the DVT prevention strategies is a risk assessment tool that is easy to use, built directly into routine care, and linked directly to guideline-recommended choices for prophylaxis.

The University of California at San Diego (UCSD) Medical Center, Johns Hopkins Hospital in Baltimore, and the Veterans Affairs (VA) Medical Center in Washington, D.C., each received the first DVTeamCare Hospital Award. The North American Thrombosis Forum (NATF), in conjunction with pharmaceutical company Eisai Inc., recognized each center’s accomplishment based upon an evaluation by an independent panel of expert judges.

Having DVT prevention protocols such as these in place allows hospitalists to provide better care with less effort by leaving hospitalists free to focus on more complicated patient-care issues.

—Gregory A. Maynard, MD, FHM, hospital medicine division chief, University of California at San Diego

The award reflects NATF’s goal of enhancing thrombosis education, prevention, diagnosis, and treatment to improve patient outcomes, says NATF Executive Director Ilene Sussman, PhD. Dr. Sussman notes that DVT affects more than 600,000 Americans annually, kills more than 100,000, and is one of the leading causes of preventable deaths in hospitals. Preventable DVT-related complication is on Medicare’s list of “never events,” for which hospitals will no longer be reimbursed.

UCSD, representing medical centers with more than 200 beds, imbedded its VTE prevention protocol into admission, transfer, and perioperative order sets across all medical and surgical services, says Gregory A. Maynard, MD, FHM, hospital medicine division chief. The protocol flags three levels of DVT risk, notes possible contraindications for a particular kind of patient, and presents a set of options for guideline-recommended prophylaxis. The protocol can be paper- or computer-based. Prompting concurrent intervention is a central component of UCSD’s implementation strategy, “identifying in real-time patients who are not receiving the right DVT prophylaxis and having a front-line nurse or pharmacist intervene appropriately,” Dr. Maynard explains.

The percent of UCSD’s patients on adequate prophylaxis rose to more than 98% in the past two years, up from about 50% before the intervention, while preventable VTE dropped by 85%—about 50 fewer cases per year in a hospital with fewer than 300 beds. “Having DVT prevention protocols such as these in place allows hospitalists to provide better care with less effort by leaving hospitalists free to focus on more complicated patient-care issues,” Dr. Maynard says.

UCSD has partnered with SHM to develop DVT prevention toolkits and mentored collaboratives, with which hospitalists can take the lead on QI projects at their local institutions. SHM’s online VTE Implementation Guide is available at www.hospitalmedicine.org/ResourceRoomRedesign/RR_VTE/VTE_Home.cfm.

Dr. Streiff

Johns Hopkins Hospital, representing medical centers with more than 200 beds, developed a mandatory computer-based decision-support system to facilitate specialty-specific risk-factor assessment and the application of risk-appropriate VTE prophylaxis, says Michael Streiff, MD, FACP, director of Johns Hopkins’ Anticoagulation Management Service and Outpatient Clinic, and a member of its Evidence-Based Practice Center. Before a physician can issue any orders—medications, lab tests, nursing instructions, etc.—using a physician transfer order set, the computerized order-entry system automatically guides them through a concise set of questions about a patient’s DVT risk factors, contraindications for blood thinners, and guideline-recommended prophylaxis choices, Dr. Streiff says.

Dr. Streiff

Since implementing the system, the percent of patients being DVT-risk-stratified within 24 hours of hospital admission rose to more than 90%, and nearly 9 in 10 of the appropriate patients are now receiving risk-appropriate, American College of Chest Physicians-approved DVT prophylaxis, up from about 26% before the intervention, Dr. Streiff notes.

The VA Medical Center in Washington, D.C., representing medical centers with fewer than 200 beds, participated in a mentorship collaborative with UCSD’s Dr. Maynard and designed a seven-step process that walks providers through an evidence-based risk-factor assessment to determine appropriate thromboprophylactic therapy, says Divya Shroff, MD, associate chief of staff, Informatics. The guideline-driven steps are integrated into the VA’s computerized patient medical record system and take no more than 60 seconds to follow, says pharmacy practice resident Jovonne H. Jones, PharmD. The steps include:

• Assess patient DVT risk level;
• Educate patient about the order;
• Identify contraindications, if any;
• Choose prophylaxis drug or device;
• Accept order for drug or device;
• Check if additional prophylactic method is needed; and
• Accept the final order.

Jovonne Jones

After the intervention, the rate at which patients receive appropriate prophylaxis upon admission more than doubled. Twenty VA medical centers around the country are in the process of implementing the system, Jones says.

The award-winning protocols will be presented at an NATF-hosted program April 9 at Harvard Medical School. The protocols and implementation plans will be made available at www.DVTeamCareAward.com to help other hospitals enhance their efforts to prevent DVT. TH

Chris Guadagnino is a freelance medical writer based in Philadelphia.

Three U.S. medical centers have been recognized for innovative approaches to preventing DVT and its potentially fatal complications, which include pulmonary embolism (PE). Central to each of the DVT prevention strategies is a risk assessment tool that is easy to use, built directly into routine care, and linked directly to guideline-recommended choices for prophylaxis.

The University of California at San Diego (UCSD) Medical Center, Johns Hopkins Hospital in Baltimore, and the Veterans Affairs (VA) Medical Center in Washington, D.C., each received the first DVTeamCare Hospital Award. The North American Thrombosis Forum (NATF), in conjunction with pharmaceutical company Eisai Inc., recognized each center’s accomplishment based upon an evaluation by an independent panel of expert judges.

Having DVT prevention protocols such as these in place allows hospitalists to provide better care with less effort by leaving hospitalists free to focus on more complicated patient-care issues.

—Gregory A. Maynard, MD, FHM, hospital medicine division chief, University of California at San Diego

The award reflects NATF’s goal of enhancing thrombosis education, prevention, diagnosis, and treatment to improve patient outcomes, says NATF Executive Director Ilene Sussman, PhD. Dr. Sussman notes that DVT affects more than 600,000 Americans annually, kills more than 100,000, and is one of the leading causes of preventable deaths in hospitals. Preventable DVT-related complication is on Medicare’s list of “never events,” for which hospitals will no longer be reimbursed.

UCSD, representing medical centers with more than 200 beds, imbedded its VTE prevention protocol into admission, transfer, and perioperative order sets across all medical and surgical services, says Gregory A. Maynard, MD, FHM, hospital medicine division chief. The protocol flags three levels of DVT risk, notes possible contraindications for a particular kind of patient, and presents a set of options for guideline-recommended prophylaxis. The protocol can be paper- or computer-based. Prompting concurrent intervention is a central component of UCSD’s implementation strategy, “identifying in real-time patients who are not receiving the right DVT prophylaxis and having a front-line nurse or pharmacist intervene appropriately,” Dr. Maynard explains.

The percent of UCSD’s patients on adequate prophylaxis rose to more than 98% in the past two years, up from about 50% before the intervention, while preventable VTE dropped by 85%—about 50 fewer cases per year in a hospital with fewer than 300 beds. “Having DVT prevention protocols such as these in place allows hospitalists to provide better care with less effort by leaving hospitalists free to focus on more complicated patient-care issues,” Dr. Maynard says.

UCSD has partnered with SHM to develop DVT prevention toolkits and mentored collaboratives, with which hospitalists can take the lead on QI projects at their local institutions. SHM’s online VTE Implementation Guide is available at www.hospitalmedicine.org/ResourceRoomRedesign/RR_VTE/VTE_Home.cfm.

Dr. Streiff

Johns Hopkins Hospital, representing medical centers with more than 200 beds, developed a mandatory computer-based decision-support system to facilitate specialty-specific risk-factor assessment and the application of risk-appropriate VTE prophylaxis, says Michael Streiff, MD, FACP, director of Johns Hopkins’ Anticoagulation Management Service and Outpatient Clinic, and a member of its Evidence-Based Practice Center. Before a physician can issue any orders—medications, lab tests, nursing instructions, etc.—using a physician transfer order set, the computerized order-entry system automatically guides them through a concise set of questions about a patient’s DVT risk factors, contraindications for blood thinners, and guideline-recommended prophylaxis choices, Dr. Streiff says.

Dr. Streiff

Since implementing the system, the percent of patients being DVT-risk-stratified within 24 hours of hospital admission rose to more than 90%, and nearly 9 in 10 of the appropriate patients are now receiving risk-appropriate, American College of Chest Physicians-approved DVT prophylaxis, up from about 26% before the intervention, Dr. Streiff notes.

The VA Medical Center in Washington, D.C., representing medical centers with fewer than 200 beds, participated in a mentorship collaborative with UCSD’s Dr. Maynard and designed a seven-step process that walks providers through an evidence-based risk-factor assessment to determine appropriate thromboprophylactic therapy, says Divya Shroff, MD, associate chief of staff, Informatics. The guideline-driven steps are integrated into the VA’s computerized patient medical record system and take no more than 60 seconds to follow, says pharmacy practice resident Jovonne H. Jones, PharmD. The steps include:

• Assess patient DVT risk level;
• Educate patient about the order;
• Identify contraindications, if any;
• Choose prophylaxis drug or device;
• Accept order for drug or device;
• Check if additional prophylactic method is needed; and
• Accept the final order.

Jovonne Jones

After the intervention, the rate at which patients receive appropriate prophylaxis upon admission more than doubled. Twenty VA medical centers around the country are in the process of implementing the system, Jones says.

The award-winning protocols will be presented at an NATF-hosted program April 9 at Harvard Medical School. The protocols and implementation plans will be made available at www.DVTeamCareAward.com to help other hospitals enhance their efforts to prevent DVT. TH

Chris Guadagnino is a freelance medical writer based in Philadelphia.

Three U.S. medical centers have been recognized for innovative approaches to preventing DVT and its potentially fatal complications, which include pulmonary embolism (PE). Central to each of the DVT prevention strategies is a risk assessment tool that is easy to use, built directly into routine care, and linked directly to guideline-recommended choices for prophylaxis.

The University of California at San Diego (UCSD) Medical Center, Johns Hopkins Hospital in Baltimore, and the Veterans Affairs (VA) Medical Center in Washington, D.C., each received the first DVTeamCare Hospital Award. The North American Thrombosis Forum (NATF), in conjunction with pharmaceutical company Eisai Inc., recognized each center’s accomplishment based upon an evaluation by an independent panel of expert judges.

Having DVT prevention protocols such as these in place allows hospitalists to provide better care with less effort by leaving hospitalists free to focus on more complicated patient-care issues.

—Gregory A. Maynard, MD, FHM, hospital medicine division chief, University of California at San Diego

The award reflects NATF’s goal of enhancing thrombosis education, prevention, diagnosis, and treatment to improve patient outcomes, says NATF Executive Director Ilene Sussman, PhD. Dr. Sussman notes that DVT affects more than 600,000 Americans annually, kills more than 100,000, and is one of the leading causes of preventable deaths in hospitals. Preventable DVT-related complication is on Medicare’s list of “never events,” for which hospitals will no longer be reimbursed.

UCSD, representing medical centers with more than 200 beds, imbedded its VTE prevention protocol into admission, transfer, and perioperative order sets across all medical and surgical services, says Gregory A. Maynard, MD, FHM, hospital medicine division chief. The protocol flags three levels of DVT risk, notes possible contraindications for a particular kind of patient, and presents a set of options for guideline-recommended prophylaxis. The protocol can be paper- or computer-based. Prompting concurrent intervention is a central component of UCSD’s implementation strategy, “identifying in real-time patients who are not receiving the right DVT prophylaxis and having a front-line nurse or pharmacist intervene appropriately,” Dr. Maynard explains.

The percent of UCSD’s patients on adequate prophylaxis rose to more than 98% in the past two years, up from about 50% before the intervention, while preventable VTE dropped by 85%—about 50 fewer cases per year in a hospital with fewer than 300 beds. “Having DVT prevention protocols such as these in place allows hospitalists to provide better care with less effort by leaving hospitalists free to focus on more complicated patient-care issues,” Dr. Maynard says.

UCSD has partnered with SHM to develop DVT prevention toolkits and mentored collaboratives, with which hospitalists can take the lead on QI projects at their local institutions. SHM’s online VTE Implementation Guide is available at www.hospitalmedicine.org/ResourceRoomRedesign/RR_VTE/VTE_Home.cfm.

Dr. Streiff

Johns Hopkins Hospital, representing medical centers with more than 200 beds, developed a mandatory computer-based decision-support system to facilitate specialty-specific risk-factor assessment and the application of risk-appropriate VTE prophylaxis, says Michael Streiff, MD, FACP, director of Johns Hopkins’ Anticoagulation Management Service and Outpatient Clinic, and a member of its Evidence-Based Practice Center. Before a physician can issue any orders—medications, lab tests, nursing instructions, etc.—using a physician transfer order set, the computerized order-entry system automatically guides them through a concise set of questions about a patient’s DVT risk factors, contraindications for blood thinners, and guideline-recommended prophylaxis choices, Dr. Streiff says.

Dr. Streiff

Since implementing the system, the percent of patients being DVT-risk-stratified within 24 hours of hospital admission rose to more than 90%, and nearly 9 in 10 of the appropriate patients are now receiving risk-appropriate, American College of Chest Physicians-approved DVT prophylaxis, up from about 26% before the intervention, Dr. Streiff notes.

The VA Medical Center in Washington, D.C., representing medical centers with fewer than 200 beds, participated in a mentorship collaborative with UCSD’s Dr. Maynard and designed a seven-step process that walks providers through an evidence-based risk-factor assessment to determine appropriate thromboprophylactic therapy, says Divya Shroff, MD, associate chief of staff, Informatics. The guideline-driven steps are integrated into the VA’s computerized patient medical record system and take no more than 60 seconds to follow, says pharmacy practice resident Jovonne H. Jones, PharmD. The steps include:

• Assess patient DVT risk level;
• Educate patient about the order;
• Identify contraindications, if any;
• Choose prophylaxis drug or device;
• Accept order for drug or device;
• Check if additional prophylactic method is needed; and
• Accept the final order.

Jovonne Jones

After the intervention, the rate at which patients receive appropriate prophylaxis upon admission more than doubled. Twenty VA medical centers around the country are in the process of implementing the system, Jones says.

The award-winning protocols will be presented at an NATF-hosted program April 9 at Harvard Medical School. The protocols and implementation plans will be made available at www.DVTeamCareAward.com to help other hospitals enhance their efforts to prevent DVT. TH

Chris Guadagnino is a freelance medical writer based in Philadelphia.

Scott Flanders, MD, FHM

The growth of our medical specialty is old news. Yes, we now number about 30,000; yes, we now manage the medical care of 50% of hospitalized Medicare patients; yes, hospitalists are in two-thirds of U.S. hospitals. I could go on and on. But recently, I have observed a different type of growth altogether. It is the growth of stability.

In the recent history of HM, the focus was on the increasing number of hospitals that had hospitalists, the growth of SHM’s membership, the growth of our annual meeting, and the ever-increasing number of doctors who, at least when surveyed, called themselves hospitalists. It all looked so impressive.

Many of you know, however, that when you lifted up the hood of our field, it was not always as it seemed. HM actually was a bit unstable. Some doctors who called themselves hospitalists were, in reality, biding time until they moved on to a “real job” or went off to do a fellowship. Multiple groups competed for patients within any given hospital, and also competed for doctors. There were numerous jobs available for any given hospitalist, and, as a result, some groups had substantial turnover despite growth in numbers. In these programs, the group photo from one year to the next had an entirely new set of faces.

Instability did not just affect rank-and-file hospitalists; it also existed within programmatic leadership and entire programs. Annually in many hospitals, the hospitalists had to convince administration that the hospital needed hospitalists and that they were worthy of support. Unfortunately, it was not always successful, so some programs vanished.

Five years ago in Michigan, we were working to create a multihospital safety consortium. We had several participating institutions, all with hospitalist programs. One day, my secretary complained that every time she sent an e-mail to the consortium listserv, a handful would bounce back and indicate a handful of e-mail addresses no longer were in service, or note that an individual had “left the program.” Some of them were HM program directors. Follow-up calls showed that the program had a new director or had folded. In some cases, however, they were just too busy figuring out how to survive instead of focus on safety issues.

Fortunately, that all appears to be changing.

From Unknown to Accepted to Counted On

I have seen the change in my own institution. We, of course, continue to negotiate with hospital administration, but it is no longer about whether we should continue the program or not. Negotiations now center on line items in the budget, how much space we need, where we anticipate future growth, and what quality and safety initiatives we’re working on.

I like to think that the HM program is important infrastructure. Just as you can’t imagine a hospital without an ED or an ICU, the same holds true for the HM program.

Perhaps an even better analogy could be found in technologic innovation. Back when Al Gore invented the Internet, having an Internet connection at home was viewed as a luxury. Now, it nearly is a necessity. Just like HM programs! (OK, maybe that was a stretch.)

There also is stability within the faculty ranks. Many of our faculty have been here for years and plan to stay. Turnover has decreased dramatically. This is not unique to our program, but anecdotally is happening everywhere. In fact, we are in the process of launching additional multihospital HM-based safety projects and collaboratives. And when I reach out to programs to ask them to participate, the directors of these programs are the same ones when I last checked. If they have moved on, it has been to assume a local leadership role. The group photos also show all the same old faces, plus a few new ones. There really has been some stabilization in the field.

New Paradigm Here to Stay

The factors behind this newfound stability are numerous. Among them is the recognized importance of a well-managed HM program. In many institutions, the alternatives to hospitalists (primary-care physicians, surgeons managing all post-operative care, specialists admitting their own patients, etc.) have left the building. There is no going back, and there is no “plan B” if HM programs fold.

The recognition by prospective hospitalists—residents and students—that HM is a viable career path has increased interest in the field, and, in turn, has given many programs more choices among qualified applicants. Hospitalists currently employed in a reasonably functioning program are less likely to jump ship every year looking for something slightly better. And I expect the current economic climate has been a factor as well. As hospitals see operating margins erode, plans for infrastructure growth are delayed, funding for new programs shrinks, and hospitalist groups are asked to do more with less. In other words, they are not hiring as many new hospitalists.

In some sense, the perceived slowing in the growth of hospitalists might be concerning. I see it a different way. Slowing growth in overall numbers allows programs and the field to stabilize a bit, and this growth in stability creates enormous opportunity. Programs formerly struggling to survive can begin to innovate. We’ve seen that in Michigan, as the interest among hospitalist programs that want to participate in QI collaborations has grown. And when we hear what some programs are working on, it’s an impressive list of high-impact projects.

Hospitalists are taking ownership of care transitions, prevention of hospital-acquired complications, and disease-based QI initiatives centered on patients with heart failure, COPD, and diabetes.

Nationally, we have seen hospitalist programs coming together to successfully compete for federal research grants or foundation support targeting important national healthcare priorities. If the current healthcare reform legislation passes, it will better position HM to lead the transformation of healthcare in U.S. hospitals.

My big hope is that 10 to 20 years from now, HM is better known for its second phase of growth. Right now, we are more famous for our rapid growth and, to some extent, our impact on efficiency of care. Efficiency clearly is important; dollars saved from waste can be better put to use improving quality. But I want the field to be judged by our ability to innovate, improve the quality of hospital-care delivery, and to generate new knowledge that advances the care of all patients. Those accomplishments will have a more lasting impact on healthcare.

The stabilization of HM is making all of this possible. Our population expects and deserves great things from the nation’s fastest-growing “specialty,” and I am optimistic we will not let them down. TH

Dr. Flanders is president of SHM.

Scott Flanders, MD, FHM

The growth of our medical specialty is old news. Yes, we now number about 30,000; yes, we now manage the medical care of 50% of hospitalized Medicare patients; yes, hospitalists are in two-thirds of U.S. hospitals. I could go on and on. But recently, I have observed a different type of growth altogether. It is the growth of stability.

In the recent history of HM, the focus was on the increasing number of hospitals that had hospitalists, the growth of SHM’s membership, the growth of our annual meeting, and the ever-increasing number of doctors who, at least when surveyed, called themselves hospitalists. It all looked so impressive.

Many of you know, however, that when you lifted up the hood of our field, it was not always as it seemed. HM actually was a bit unstable. Some doctors who called themselves hospitalists were, in reality, biding time until they moved on to a “real job” or went off to do a fellowship. Multiple groups competed for patients within any given hospital, and also competed for doctors. There were numerous jobs available for any given hospitalist, and, as a result, some groups had substantial turnover despite growth in numbers. In these programs, the group photo from one year to the next had an entirely new set of faces.

Instability did not just affect rank-and-file hospitalists; it also existed within programmatic leadership and entire programs. Annually in many hospitals, the hospitalists had to convince administration that the hospital needed hospitalists and that they were worthy of support. Unfortunately, it was not always successful, so some programs vanished.

Five years ago in Michigan, we were working to create a multihospital safety consortium. We had several participating institutions, all with hospitalist programs. One day, my secretary complained that every time she sent an e-mail to the consortium listserv, a handful would bounce back and indicate a handful of e-mail addresses no longer were in service, or note that an individual had “left the program.” Some of them were HM program directors. Follow-up calls showed that the program had a new director or had folded. In some cases, however, they were just too busy figuring out how to survive instead of focus on safety issues.

Fortunately, that all appears to be changing.

From Unknown to Accepted to Counted On

I have seen the change in my own institution. We, of course, continue to negotiate with hospital administration, but it is no longer about whether we should continue the program or not. Negotiations now center on line items in the budget, how much space we need, where we anticipate future growth, and what quality and safety initiatives we’re working on.

I like to think that the HM program is important infrastructure. Just as you can’t imagine a hospital without an ED or an ICU, the same holds true for the HM program.

Perhaps an even better analogy could be found in technologic innovation. Back when Al Gore invented the Internet, having an Internet connection at home was viewed as a luxury. Now, it nearly is a necessity. Just like HM programs! (OK, maybe that was a stretch.)

There also is stability within the faculty ranks. Many of our faculty have been here for years and plan to stay. Turnover has decreased dramatically. This is not unique to our program, but anecdotally is happening everywhere. In fact, we are in the process of launching additional multihospital HM-based safety projects and collaboratives. And when I reach out to programs to ask them to participate, the directors of these programs are the same ones when I last checked. If they have moved on, it has been to assume a local leadership role. The group photos also show all the same old faces, plus a few new ones. There really has been some stabilization in the field.

New Paradigm Here to Stay

The factors behind this newfound stability are numerous. Among them is the recognized importance of a well-managed HM program. In many institutions, the alternatives to hospitalists (primary-care physicians, surgeons managing all post-operative care, specialists admitting their own patients, etc.) have left the building. There is no going back, and there is no “plan B” if HM programs fold.

The recognition by prospective hospitalists—residents and students—that HM is a viable career path has increased interest in the field, and, in turn, has given many programs more choices among qualified applicants. Hospitalists currently employed in a reasonably functioning program are less likely to jump ship every year looking for something slightly better. And I expect the current economic climate has been a factor as well. As hospitals see operating margins erode, plans for infrastructure growth are delayed, funding for new programs shrinks, and hospitalist groups are asked to do more with less. In other words, they are not hiring as many new hospitalists.

In some sense, the perceived slowing in the growth of hospitalists might be concerning. I see it a different way. Slowing growth in overall numbers allows programs and the field to stabilize a bit, and this growth in stability creates enormous opportunity. Programs formerly struggling to survive can begin to innovate. We’ve seen that in Michigan, as the interest among hospitalist programs that want to participate in QI collaborations has grown. And when we hear what some programs are working on, it’s an impressive list of high-impact projects.

Hospitalists are taking ownership of care transitions, prevention of hospital-acquired complications, and disease-based QI initiatives centered on patients with heart failure, COPD, and diabetes.

Nationally, we have seen hospitalist programs coming together to successfully compete for federal research grants or foundation support targeting important national healthcare priorities. If the current healthcare reform legislation passes, it will better position HM to lead the transformation of healthcare in U.S. hospitals.

My big hope is that 10 to 20 years from now, HM is better known for its second phase of growth. Right now, we are more famous for our rapid growth and, to some extent, our impact on efficiency of care. Efficiency clearly is important; dollars saved from waste can be better put to use improving quality. But I want the field to be judged by our ability to innovate, improve the quality of hospital-care delivery, and to generate new knowledge that advances the care of all patients. Those accomplishments will have a more lasting impact on healthcare.

The stabilization of HM is making all of this possible. Our population expects and deserves great things from the nation’s fastest-growing “specialty,” and I am optimistic we will not let them down. TH

Dr. Flanders is president of SHM.

Scott Flanders, MD, FHM

The growth of our medical specialty is old news. Yes, we now number about 30,000; yes, we now manage the medical care of 50% of hospitalized Medicare patients; yes, hospitalists are in two-thirds of U.S. hospitals. I could go on and on. But recently, I have observed a different type of growth altogether. It is the growth of stability.

In the recent history of HM, the focus was on the increasing number of hospitals that had hospitalists, the growth of SHM’s membership, the growth of our annual meeting, and the ever-increasing number of doctors who, at least when surveyed, called themselves hospitalists. It all looked so impressive.

Many of you know, however, that when you lifted up the hood of our field, it was not always as it seemed. HM actually was a bit unstable. Some doctors who called themselves hospitalists were, in reality, biding time until they moved on to a “real job” or went off to do a fellowship. Multiple groups competed for patients within any given hospital, and also competed for doctors. There were numerous jobs available for any given hospitalist, and, as a result, some groups had substantial turnover despite growth in numbers. In these programs, the group photo from one year to the next had an entirely new set of faces.

Instability did not just affect rank-and-file hospitalists; it also existed within programmatic leadership and entire programs. Annually in many hospitals, the hospitalists had to convince administration that the hospital needed hospitalists and that they were worthy of support. Unfortunately, it was not always successful, so some programs vanished.

Five years ago in Michigan, we were working to create a multihospital safety consortium. We had several participating institutions, all with hospitalist programs. One day, my secretary complained that every time she sent an e-mail to the consortium listserv, a handful would bounce back and indicate a handful of e-mail addresses no longer were in service, or note that an individual had “left the program.” Some of them were HM program directors. Follow-up calls showed that the program had a new director or had folded. In some cases, however, they were just too busy figuring out how to survive instead of focus on safety issues.

Fortunately, that all appears to be changing.

From Unknown to Accepted to Counted On

I have seen the change in my own institution. We, of course, continue to negotiate with hospital administration, but it is no longer about whether we should continue the program or not. Negotiations now center on line items in the budget, how much space we need, where we anticipate future growth, and what quality and safety initiatives we’re working on.

I like to think that the HM program is important infrastructure. Just as you can’t imagine a hospital without an ED or an ICU, the same holds true for the HM program.

Perhaps an even better analogy could be found in technologic innovation. Back when Al Gore invented the Internet, having an Internet connection at home was viewed as a luxury. Now, it nearly is a necessity. Just like HM programs! (OK, maybe that was a stretch.)

There also is stability within the faculty ranks. Many of our faculty have been here for years and plan to stay. Turnover has decreased dramatically. This is not unique to our program, but anecdotally is happening everywhere. In fact, we are in the process of launching additional multihospital HM-based safety projects and collaboratives. And when I reach out to programs to ask them to participate, the directors of these programs are the same ones when I last checked. If they have moved on, it has been to assume a local leadership role. The group photos also show all the same old faces, plus a few new ones. There really has been some stabilization in the field.

New Paradigm Here to Stay

The factors behind this newfound stability are numerous. Among them is the recognized importance of a well-managed HM program. In many institutions, the alternatives to hospitalists (primary-care physicians, surgeons managing all post-operative care, specialists admitting their own patients, etc.) have left the building. There is no going back, and there is no “plan B” if HM programs fold.

The recognition by prospective hospitalists—residents and students—that HM is a viable career path has increased interest in the field, and, in turn, has given many programs more choices among qualified applicants. Hospitalists currently employed in a reasonably functioning program are less likely to jump ship every year looking for something slightly better. And I expect the current economic climate has been a factor as well. As hospitals see operating margins erode, plans for infrastructure growth are delayed, funding for new programs shrinks, and hospitalist groups are asked to do more with less. In other words, they are not hiring as many new hospitalists.

In some sense, the perceived slowing in the growth of hospitalists might be concerning. I see it a different way. Slowing growth in overall numbers allows programs and the field to stabilize a bit, and this growth in stability creates enormous opportunity. Programs formerly struggling to survive can begin to innovate. We’ve seen that in Michigan, as the interest among hospitalist programs that want to participate in QI collaborations has grown. And when we hear what some programs are working on, it’s an impressive list of high-impact projects.

Hospitalists are taking ownership of care transitions, prevention of hospital-acquired complications, and disease-based QI initiatives centered on patients with heart failure, COPD, and diabetes.

Nationally, we have seen hospitalist programs coming together to successfully compete for federal research grants or foundation support targeting important national healthcare priorities. If the current healthcare reform legislation passes, it will better position HM to lead the transformation of healthcare in U.S. hospitals.

My big hope is that 10 to 20 years from now, HM is better known for its second phase of growth. Right now, we are more famous for our rapid growth and, to some extent, our impact on efficiency of care. Efficiency clearly is important; dollars saved from waste can be better put to use improving quality. But I want the field to be judged by our ability to innovate, improve the quality of hospital-care delivery, and to generate new knowledge that advances the care of all patients. Those accomplishments will have a more lasting impact on healthcare.

The stabilization of HM is making all of this possible. Our population expects and deserves great things from the nation’s fastest-growing “specialty,” and I am optimistic we will not let them down. TH

Dr. Flanders is president of SHM.

New Generics

• Fentanyl citrate troche/lozenge (generic Actiq) transmucosal lollipop1,2
• Perindopril erbumine (generic Aceon) tablets3

New Drugs, Indications, Label Changes, and Dosage Forms

• Capsaicin 8% patch (Qutenza) has been approved by the U.S. Food and Drug Administration (FDA) as a prescription medication to treat pain associated with post-herpetic neuralgia.4 The patch is a higher concentration than over-the-counter (OTC) products. The most common side effects in clinical trials were pain, swelling, itching, redness, and bumps at the application site, as well as blood pressure increases.5 Patch placement requires the use of a topical anesthetic and additional pain relief (ice or opioid pain relievers). Therefore, patch placement must be performed by a healthcare professional. Once the patch is applied, the patient must be observed for at least an hour, as there could be a significant increase in blood pressure.
• Diclofenac sodium topical (Pennsaid) has been approved by the FDA as a topical treatment to manage knee osteoarthritis.6 The transdermal carrier dimethylsulfoxide (DMSO) is utilized to deliver active diclofenac sodium through the skin to the pain site.7
• Exenatide injection (Byetta) has been approved by the FDA as monotherapy for treating patients with Type 2 diabetes mellitus, along with diet and exercise.8
• Human papilloma virus (HPV) vaccine (Gardasil) has been approved by the FDA for preventing condyloma acuminata due to HPV types 6 and 11 in males ages 9 to 26.9 The makers hope that this vaccine will decrease the need to treat genital warts. Clinical studies showed that in males not infected with HPV at the beginning of the study, the vaccine was close to 90% effective in preventing genital warts caused by infection of HPV types 6 and 11. The manufacturer plans to obtain additional safety and effectiveness information in this patient population.
• Lansoprazole 24HR (Prevacid OTC) 15-mg delayed-release capsules are available for treating frequent heartburn.10 The capsules will be available by prescription in both the 15-mg and 30-mg dosage strengths.
• Metoclopramide HCl orally disintegrating tablet (Metozolv ODT) has been approved by the FDA for treating both acute and recurrent diabetic gastroparesis and for the short-term management (four to 12 weeks) of adults with documented symptomatic gastroesophageal reflux disease who do not respond to conventional therapy.11
• Peramivir intravenous will be made available by the Centers for Disease Control (CDC) as an emergency treatment for children and adult patients who develop H1N1 influenza and are nonresponsive to oral or inhaled antiviral therapies.12
• Rosuvastatin (Crestor) has been approved by the FDA for treating heterozygous familial cholesterolemia in children ages 10-17.13
• Telmisartan 80-mg tablets (Micardis) have been approved by the FDA for risk reduction of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years and older who are at high risk for major cardiovascular events, or who are not able to take angiotensin-converting enzyme inhibitors.14
• Telmisartan/amlodipine tablets (Twynsta) have been approved by the FDA as a new combination for treating hypertension, either alone or in combination with other antihypertensive agents. This combination is not indicated for cardiovascular risk reduction. The tablets are available in the following strengths of telmisartan/amlodipine, respectively: 40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg, and 80 mg/10 mg.
• Tranexamic acid (Lysteda) has been approved by the FDA for the treatment of menorrhagia.15 This is the first nonhormonal, oral therapeutic agent approved to treat this condition.16

Pipeline

• Indacaterol is being investigated as a once-daily bronchodilator for treating adults with chronic obstructive pulmonary disease (COPD).17 Novartis has received a complete response letter from the FDA requesting additional data on the dosing of the agent. The company is working with the FDA to resolve these issues.
• Rituximab injection (Rituxan) is approved for treating moderate to severe rheumatoid arthritis after patients have been treated with methotrexate, as well as non-Hodgkin’s lymphoma.18 Genentech/Biogen is attempting to expand rituximab use to treat patients earlier in the course of their disease. The FDA recently rejected this application, citing the rare but serious safety risk of developing progressive multifocal leukoencephalopathy.

Safety Information

Use of omeprazole and clopidogrel combination therapy should be avoided, according to new data from the FDA.18 Current data suggest that clopidogrel’s antiplatelet effect may be hindered by 50% with concomitant omeprazole therapy. Omeprazole blocks the conversion of clopidogrel to its active, antiplatelet form, thus significantly decreasing its effectiveness. It is not known if other proton-pump inhibitors interfere with clopidogrel’s effectiveness. Other drugs that should not be used with clopidogrel include esomeprazole (Nexium), cimetidine (Tagamet and Tagamet HB), fluconazole (Diflucan), ketoconazole (Nizoral), voriconazole (VFEND), etravirine (Intelence), felbamate (Felbatol), fluoxetine (Prozac, Sarafem, and Symbyax), fluvoxamine (Luvox), and ticlopidine (Ticlid). TH

Michele B. Kaufman is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

• Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA Web site. Available at: www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=077312&TABLE1=OB_Rx. Accessed Nov. 19, 2009.
• Covidien gets approval of generic pain drug. Forbes.com Web site. Available at: http://www.forbes.com/feeds/ap/2009/10/30/business-health-care-us-covidien-actiq_7069457.html. Accessed Nov. 19, 2009.
• Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA Web site. Available at: www.accessdata.fda.gov/scripts/cder/ob/default.cfm Accessed Nov. 19, 2009.
• Riley K. FDA Approves New Drug Treatment for Long-Term Pain Relief after Shingles Attacks. FDA Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191003.htm. Accessed Nov. 19, 2009.
• Qutenza Approved for Post-Shingles Nerve Pain. U.S. News and World Report Web site. Available at: health.usnews.com/articles/health/healthday/2009/11/17/qutenza-approved-for-post-shingles-nerve-pain.html. Accessed Nov. 19, 2009.
• Nuvo shares surge on FDA pain cream approval. Reuters Web site. Available at: www.reuters.com/article/email/idUSN0543459820091105. Accessed Nov. 19, 2009.
• Pennsaid. Nuvo Web site. Available at: www.nuvoresearch.com/pipeline/pennsaid.asp. Accessed Nov. 19, 2009.
• BYETTA Approved For Expanded Use As First-Line Treatment For Type 2 Diabetes. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/169396.php. Accessed Nov. 19, 2009.
• Burgess S. FDA Approves New Indication for Gardasil to Prevent Genital Warts in Men and Boys. FDA Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm187003.htm Accessed Nov. 19, 2009.
• Prevacid 24hr available over-the-counter. Monthly Prescribing Reference Web site. Available at: www.empr.com/prevacid-24hr-available-over-the-counter/article/157592/. Accessed Nov. 19, 2009.
• FDA Approves New Salix Product Exclusively in Catalent’s Zydis Fast Dissolve Technology. Catalent Web site. Available at: www.catalent.com/about-us/news/45. Accessed Nov. 19, 2009.
• Peramivir to be Used for Special Swine Flu Cases. Pharmaceutical-Technology.com Web site. Available at: www.pharmaceutical-technology.com/News/News68102.html. Accessed Nov. 19, 2009.
• Dennis M. AstraZeneca’s Crestor approved in US for paediatric use; Vimovo filed in Europe. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=41E54BF434C54C8E903A9EB4EF0839AA&logRowId=332380. Accessed Nov. 19, 2009.
• FDA Approves New Use for Micardis in Cardiovascular Risk Reduction and Twynsta as New Combination Treatment for High Blood Pressure. Boehringer Ingelheim Web site. Available at: us.boehringer-ingelheim.com/newsroom/2009/files/micardis_twynsta_approve_10-19-09.pdf. Accessed Nov. 19, 2009.
• Todoruk M. FDA approves Xanodyne’s Lysteda for menorrhaegia. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=8FCB424A8E7147A08CEC9BFCD8A450D2&logRowId=337054. Accessed Nov. 19, 2009.
• Xanodyne announces FDA approval of Lysteda for treatment of women with heavy menstrual bleeding. Xanodyne Web site. Available at: www.xanodyne.com/newsroom_details.asp?NewsId=61. Accessed Nov. 19, 2009.
• Todoruk M. FDA requests additional data for Novartis’ COPD drug indacaterol. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=B426F5ED30AB43A89338DAD0124168A7&logRowId=332718. Accessed Nov. 19, 2009.
• Genentech and Biogen Idec Receive a Complete Response from FDA for Earlier Use of Rituxan for Rheumatoid Arthritis. Genentech Web site. Available at: www.gene.com/gene/news/press-releases/display.do?method=detail&id=12407. Accessed Nov. 19, 2009.
• Walsh S. FDA Announces New Warning on Plavix: Avoid Use with Prilosec/Prilosec OTC. FDA Web site. Available at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191169.htm. Accessed Nov. 19, 2009.

New Generics

• Fentanyl citrate troche/lozenge (generic Actiq) transmucosal lollipop1,2
• Perindopril erbumine (generic Aceon) tablets3

New Drugs, Indications, Label Changes, and Dosage Forms

• Capsaicin 8% patch (Qutenza) has been approved by the U.S. Food and Drug Administration (FDA) as a prescription medication to treat pain associated with post-herpetic neuralgia.4 The patch is a higher concentration than over-the-counter (OTC) products. The most common side effects in clinical trials were pain, swelling, itching, redness, and bumps at the application site, as well as blood pressure increases.5 Patch placement requires the use of a topical anesthetic and additional pain relief (ice or opioid pain relievers). Therefore, patch placement must be performed by a healthcare professional. Once the patch is applied, the patient must be observed for at least an hour, as there could be a significant increase in blood pressure.
• Diclofenac sodium topical (Pennsaid) has been approved by the FDA as a topical treatment to manage knee osteoarthritis.6 The transdermal carrier dimethylsulfoxide (DMSO) is utilized to deliver active diclofenac sodium through the skin to the pain site.7
• Exenatide injection (Byetta) has been approved by the FDA as monotherapy for treating patients with Type 2 diabetes mellitus, along with diet and exercise.8
• Human papilloma virus (HPV) vaccine (Gardasil) has been approved by the FDA for preventing condyloma acuminata due to HPV types 6 and 11 in males ages 9 to 26.9 The makers hope that this vaccine will decrease the need to treat genital warts. Clinical studies showed that in males not infected with HPV at the beginning of the study, the vaccine was close to 90% effective in preventing genital warts caused by infection of HPV types 6 and 11. The manufacturer plans to obtain additional safety and effectiveness information in this patient population.
• Lansoprazole 24HR (Prevacid OTC) 15-mg delayed-release capsules are available for treating frequent heartburn.10 The capsules will be available by prescription in both the 15-mg and 30-mg dosage strengths.
• Metoclopramide HCl orally disintegrating tablet (Metozolv ODT) has been approved by the FDA for treating both acute and recurrent diabetic gastroparesis and for the short-term management (four to 12 weeks) of adults with documented symptomatic gastroesophageal reflux disease who do not respond to conventional therapy.11
• Peramivir intravenous will be made available by the Centers for Disease Control (CDC) as an emergency treatment for children and adult patients who develop H1N1 influenza and are nonresponsive to oral or inhaled antiviral therapies.12
• Rosuvastatin (Crestor) has been approved by the FDA for treating heterozygous familial cholesterolemia in children ages 10-17.13
• Telmisartan 80-mg tablets (Micardis) have been approved by the FDA for risk reduction of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years and older who are at high risk for major cardiovascular events, or who are not able to take angiotensin-converting enzyme inhibitors.14
• Telmisartan/amlodipine tablets (Twynsta) have been approved by the FDA as a new combination for treating hypertension, either alone or in combination with other antihypertensive agents. This combination is not indicated for cardiovascular risk reduction. The tablets are available in the following strengths of telmisartan/amlodipine, respectively: 40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg, and 80 mg/10 mg.
• Tranexamic acid (Lysteda) has been approved by the FDA for the treatment of menorrhagia.15 This is the first nonhormonal, oral therapeutic agent approved to treat this condition.16

Pipeline

• Indacaterol is being investigated as a once-daily bronchodilator for treating adults with chronic obstructive pulmonary disease (COPD).17 Novartis has received a complete response letter from the FDA requesting additional data on the dosing of the agent. The company is working with the FDA to resolve these issues.
• Rituximab injection (Rituxan) is approved for treating moderate to severe rheumatoid arthritis after patients have been treated with methotrexate, as well as non-Hodgkin’s lymphoma.18 Genentech/Biogen is attempting to expand rituximab use to treat patients earlier in the course of their disease. The FDA recently rejected this application, citing the rare but serious safety risk of developing progressive multifocal leukoencephalopathy.

Safety Information

Use of omeprazole and clopidogrel combination therapy should be avoided, according to new data from the FDA.18 Current data suggest that clopidogrel’s antiplatelet effect may be hindered by 50% with concomitant omeprazole therapy. Omeprazole blocks the conversion of clopidogrel to its active, antiplatelet form, thus significantly decreasing its effectiveness. It is not known if other proton-pump inhibitors interfere with clopidogrel’s effectiveness. Other drugs that should not be used with clopidogrel include esomeprazole (Nexium), cimetidine (Tagamet and Tagamet HB), fluconazole (Diflucan), ketoconazole (Nizoral), voriconazole (VFEND), etravirine (Intelence), felbamate (Felbatol), fluoxetine (Prozac, Sarafem, and Symbyax), fluvoxamine (Luvox), and ticlopidine (Ticlid). TH

Michele B. Kaufman is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

• Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA Web site. Available at: www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=077312&TABLE1=OB_Rx. Accessed Nov. 19, 2009.
• Covidien gets approval of generic pain drug. Forbes.com Web site. Available at: http://www.forbes.com/feeds/ap/2009/10/30/business-health-care-us-covidien-actiq_7069457.html. Accessed Nov. 19, 2009.
• Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA Web site. Available at: www.accessdata.fda.gov/scripts/cder/ob/default.cfm Accessed Nov. 19, 2009.
• Riley K. FDA Approves New Drug Treatment for Long-Term Pain Relief after Shingles Attacks. FDA Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191003.htm. Accessed Nov. 19, 2009.
• Qutenza Approved for Post-Shingles Nerve Pain. U.S. News and World Report Web site. Available at: health.usnews.com/articles/health/healthday/2009/11/17/qutenza-approved-for-post-shingles-nerve-pain.html. Accessed Nov. 19, 2009.
• Nuvo shares surge on FDA pain cream approval. Reuters Web site. Available at: www.reuters.com/article/email/idUSN0543459820091105. Accessed Nov. 19, 2009.
• Pennsaid. Nuvo Web site. Available at: www.nuvoresearch.com/pipeline/pennsaid.asp. Accessed Nov. 19, 2009.
• BYETTA Approved For Expanded Use As First-Line Treatment For Type 2 Diabetes. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/169396.php. Accessed Nov. 19, 2009.
• Burgess S. FDA Approves New Indication for Gardasil to Prevent Genital Warts in Men and Boys. FDA Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm187003.htm Accessed Nov. 19, 2009.
• Prevacid 24hr available over-the-counter. Monthly Prescribing Reference Web site. Available at: www.empr.com/prevacid-24hr-available-over-the-counter/article/157592/. Accessed Nov. 19, 2009.
• FDA Approves New Salix Product Exclusively in Catalent’s Zydis Fast Dissolve Technology. Catalent Web site. Available at: www.catalent.com/about-us/news/45. Accessed Nov. 19, 2009.
• Peramivir to be Used for Special Swine Flu Cases. Pharmaceutical-Technology.com Web site. Available at: www.pharmaceutical-technology.com/News/News68102.html. Accessed Nov. 19, 2009.
• Dennis M. AstraZeneca’s Crestor approved in US for paediatric use; Vimovo filed in Europe. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=41E54BF434C54C8E903A9EB4EF0839AA&logRowId=332380. Accessed Nov. 19, 2009.
• FDA Approves New Use for Micardis in Cardiovascular Risk Reduction and Twynsta as New Combination Treatment for High Blood Pressure. Boehringer Ingelheim Web site. Available at: us.boehringer-ingelheim.com/newsroom/2009/files/micardis_twynsta_approve_10-19-09.pdf. Accessed Nov. 19, 2009.
• Todoruk M. FDA approves Xanodyne’s Lysteda for menorrhaegia. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=8FCB424A8E7147A08CEC9BFCD8A450D2&logRowId=337054. Accessed Nov. 19, 2009.
• Xanodyne announces FDA approval of Lysteda for treatment of women with heavy menstrual bleeding. Xanodyne Web site. Available at: www.xanodyne.com/newsroom_details.asp?NewsId=61. Accessed Nov. 19, 2009.
• Todoruk M. FDA requests additional data for Novartis’ COPD drug indacaterol. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=B426F5ED30AB43A89338DAD0124168A7&logRowId=332718. Accessed Nov. 19, 2009.
• Genentech and Biogen Idec Receive a Complete Response from FDA for Earlier Use of Rituxan for Rheumatoid Arthritis. Genentech Web site. Available at: www.gene.com/gene/news/press-releases/display.do?method=detail&id=12407. Accessed Nov. 19, 2009.
• Walsh S. FDA Announces New Warning on Plavix: Avoid Use with Prilosec/Prilosec OTC. FDA Web site. Available at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191169.htm. Accessed Nov. 19, 2009.

New Generics

• Fentanyl citrate troche/lozenge (generic Actiq) transmucosal lollipop1,2
• Perindopril erbumine (generic Aceon) tablets3

New Drugs, Indications, Label Changes, and Dosage Forms

• Capsaicin 8% patch (Qutenza) has been approved by the U.S. Food and Drug Administration (FDA) as a prescription medication to treat pain associated with post-herpetic neuralgia.4 The patch is a higher concentration than over-the-counter (OTC) products. The most common side effects in clinical trials were pain, swelling, itching, redness, and bumps at the application site, as well as blood pressure increases.5 Patch placement requires the use of a topical anesthetic and additional pain relief (ice or opioid pain relievers). Therefore, patch placement must be performed by a healthcare professional. Once the patch is applied, the patient must be observed for at least an hour, as there could be a significant increase in blood pressure.
• Diclofenac sodium topical (Pennsaid) has been approved by the FDA as a topical treatment to manage knee osteoarthritis.6 The transdermal carrier dimethylsulfoxide (DMSO) is utilized to deliver active diclofenac sodium through the skin to the pain site.7
• Exenatide injection (Byetta) has been approved by the FDA as monotherapy for treating patients with Type 2 diabetes mellitus, along with diet and exercise.8
• Human papilloma virus (HPV) vaccine (Gardasil) has been approved by the FDA for preventing condyloma acuminata due to HPV types 6 and 11 in males ages 9 to 26.9 The makers hope that this vaccine will decrease the need to treat genital warts. Clinical studies showed that in males not infected with HPV at the beginning of the study, the vaccine was close to 90% effective in preventing genital warts caused by infection of HPV types 6 and 11. The manufacturer plans to obtain additional safety and effectiveness information in this patient population.
• Lansoprazole 24HR (Prevacid OTC) 15-mg delayed-release capsules are available for treating frequent heartburn.10 The capsules will be available by prescription in both the 15-mg and 30-mg dosage strengths.
• Metoclopramide HCl orally disintegrating tablet (Metozolv ODT) has been approved by the FDA for treating both acute and recurrent diabetic gastroparesis and for the short-term management (four to 12 weeks) of adults with documented symptomatic gastroesophageal reflux disease who do not respond to conventional therapy.11
• Peramivir intravenous will be made available by the Centers for Disease Control (CDC) as an emergency treatment for children and adult patients who develop H1N1 influenza and are nonresponsive to oral or inhaled antiviral therapies.12
• Rosuvastatin (Crestor) has been approved by the FDA for treating heterozygous familial cholesterolemia in children ages 10-17.13
• Telmisartan 80-mg tablets (Micardis) have been approved by the FDA for risk reduction of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years and older who are at high risk for major cardiovascular events, or who are not able to take angiotensin-converting enzyme inhibitors.14
• Telmisartan/amlodipine tablets (Twynsta) have been approved by the FDA as a new combination for treating hypertension, either alone or in combination with other antihypertensive agents. This combination is not indicated for cardiovascular risk reduction. The tablets are available in the following strengths of telmisartan/amlodipine, respectively: 40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg, and 80 mg/10 mg.
• Tranexamic acid (Lysteda) has been approved by the FDA for the treatment of menorrhagia.15 This is the first nonhormonal, oral therapeutic agent approved to treat this condition.16

Pipeline

• Indacaterol is being investigated as a once-daily bronchodilator for treating adults with chronic obstructive pulmonary disease (COPD).17 Novartis has received a complete response letter from the FDA requesting additional data on the dosing of the agent. The company is working with the FDA to resolve these issues.
• Rituximab injection (Rituxan) is approved for treating moderate to severe rheumatoid arthritis after patients have been treated with methotrexate, as well as non-Hodgkin’s lymphoma.18 Genentech/Biogen is attempting to expand rituximab use to treat patients earlier in the course of their disease. The FDA recently rejected this application, citing the rare but serious safety risk of developing progressive multifocal leukoencephalopathy.

Safety Information

Use of omeprazole and clopidogrel combination therapy should be avoided, according to new data from the FDA.18 Current data suggest that clopidogrel’s antiplatelet effect may be hindered by 50% with concomitant omeprazole therapy. Omeprazole blocks the conversion of clopidogrel to its active, antiplatelet form, thus significantly decreasing its effectiveness. It is not known if other proton-pump inhibitors interfere with clopidogrel’s effectiveness. Other drugs that should not be used with clopidogrel include esomeprazole (Nexium), cimetidine (Tagamet and Tagamet HB), fluconazole (Diflucan), ketoconazole (Nizoral), voriconazole (VFEND), etravirine (Intelence), felbamate (Felbatol), fluoxetine (Prozac, Sarafem, and Symbyax), fluvoxamine (Luvox), and ticlopidine (Ticlid). TH

Michele B. Kaufman is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

• Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA Web site. Available at: www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=077312&TABLE1=OB_Rx. Accessed Nov. 19, 2009.
• Covidien gets approval of generic pain drug. Forbes.com Web site. Available at: http://www.forbes.com/feeds/ap/2009/10/30/business-health-care-us-covidien-actiq_7069457.html. Accessed Nov. 19, 2009.
• Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA Web site. Available at: www.accessdata.fda.gov/scripts/cder/ob/default.cfm Accessed Nov. 19, 2009.
• Riley K. FDA Approves New Drug Treatment for Long-Term Pain Relief after Shingles Attacks. FDA Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191003.htm. Accessed Nov. 19, 2009.
• Qutenza Approved for Post-Shingles Nerve Pain. U.S. News and World Report Web site. Available at: health.usnews.com/articles/health/healthday/2009/11/17/qutenza-approved-for-post-shingles-nerve-pain.html. Accessed Nov. 19, 2009.
• Nuvo shares surge on FDA pain cream approval. Reuters Web site. Available at: www.reuters.com/article/email/idUSN0543459820091105. Accessed Nov. 19, 2009.
• Pennsaid. Nuvo Web site. Available at: www.nuvoresearch.com/pipeline/pennsaid.asp. Accessed Nov. 19, 2009.
• BYETTA Approved For Expanded Use As First-Line Treatment For Type 2 Diabetes. Medical News Today Web site. Available at: www.medicalnewstoday.com/articles/169396.php. Accessed Nov. 19, 2009.
• Burgess S. FDA Approves New Indication for Gardasil to Prevent Genital Warts in Men and Boys. FDA Web site. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm187003.htm Accessed Nov. 19, 2009.
• Prevacid 24hr available over-the-counter. Monthly Prescribing Reference Web site. Available at: www.empr.com/prevacid-24hr-available-over-the-counter/article/157592/. Accessed Nov. 19, 2009.
• FDA Approves New Salix Product Exclusively in Catalent’s Zydis Fast Dissolve Technology. Catalent Web site. Available at: www.catalent.com/about-us/news/45. Accessed Nov. 19, 2009.
• Peramivir to be Used for Special Swine Flu Cases. Pharmaceutical-Technology.com Web site. Available at: www.pharmaceutical-technology.com/News/News68102.html. Accessed Nov. 19, 2009.
• Dennis M. AstraZeneca’s Crestor approved in US for paediatric use; Vimovo filed in Europe. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=41E54BF434C54C8E903A9EB4EF0839AA&logRowId=332380. Accessed Nov. 19, 2009.
• FDA Approves New Use for Micardis in Cardiovascular Risk Reduction and Twynsta as New Combination Treatment for High Blood Pressure. Boehringer Ingelheim Web site. Available at: us.boehringer-ingelheim.com/newsroom/2009/files/micardis_twynsta_approve_10-19-09.pdf. Accessed Nov. 19, 2009.
• Todoruk M. FDA approves Xanodyne’s Lysteda for menorrhaegia. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=8FCB424A8E7147A08CEC9BFCD8A450D2&logRowId=337054. Accessed Nov. 19, 2009.
• Xanodyne announces FDA approval of Lysteda for treatment of women with heavy menstrual bleeding. Xanodyne Web site. Available at: www.xanodyne.com/newsroom_details.asp?NewsId=61. Accessed Nov. 19, 2009.
• Todoruk M. FDA requests additional data for Novartis’ COPD drug indacaterol. FirstWord Web site. Available at: www.firstwordplus.com/Fws.do?articleid=B426F5ED30AB43A89338DAD0124168A7&logRowId=332718. Accessed Nov. 19, 2009.
• Genentech and Biogen Idec Receive a Complete Response from FDA for Earlier Use of Rituxan for Rheumatoid Arthritis. Genentech Web site. Available at: www.gene.com/gene/news/press-releases/display.do?method=detail&id=12407. Accessed Nov. 19, 2009.
• Walsh S. FDA Announces New Warning on Plavix: Avoid Use with Prilosec/Prilosec OTC. FDA Web site. Available at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191169.htm. Accessed Nov. 19, 2009.