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NIOSH Adds to Hazardous-Drugs List
Afatinib, axitinib, and belinostat head the list of 34 additions to the updated National Institute for Occupational Safety and Health (NIOSH) List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings. The list is “an important resource as well as a tool to raise awareness among workers about the hazards of some drugs,” said NIOSH Director John Howard, MD, “enabling workers to take the necessary steps to protect themselves from exposure while doing their job.”
The list includes drugs used for cancer chemotherapy, antiviral drugs, hormones, and bioengineered drugs. The 3 main categories are antineoplastic drugs (including those with manufacturer’s safe-handling guidance [MSHG]), nonantineoplastic drugs that meet ≥ 1 of the NIOSH criteria for hazardous drugs (including those with MSHG), and nonantineoplastic drugs that primarily have adverse reproductive effects.
NIOSH estimates that 8 million U.S. health care workers are potentially exposed to hazardous drugs in the workplace. Some drugs defined as hazardous may not pose a significant risk of direct occupational exposure until the formulations are altered (as when coated tablets are crushed). Other hazards include, for example, skin contact with or inhalation of dust as uncoated tablets are counted. Five of the newly added drugs have safe-handling recommendations.
NIOSH says “no single approach can cover the diverse potential occupational exposures to the drugs” and notes that safe-handling precautions can vary with the activity and formulation of the drug. Still, the list also provides general guidance for “possible scenarios” that might be encountered in health care settings where hazardous drugs are handled. It addresses situations such as receiving, unpacking, and placing drugs in storage; administering an intact tablet or capsule from a unit-dose package; cutting, crushing, or manipulating tablets or capsules; and compounding oral liquid drugs or topical drugs.
The new report also provides health care organizations with guidance on generating their own list of hazardous drugs. Hazardous drug evaluation is “a continual process,” NIOSH says, advising that every facility must assess each new drug that enters its workplace and when appropriate reassess its list of hazardous drugs as new toxicologic data become available.
The list of hazardous drugs is updated periodically at http://www.cdc.gov/niosh/topics/hazdrug/.
Afatinib, axitinib, and belinostat head the list of 34 additions to the updated National Institute for Occupational Safety and Health (NIOSH) List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings. The list is “an important resource as well as a tool to raise awareness among workers about the hazards of some drugs,” said NIOSH Director John Howard, MD, “enabling workers to take the necessary steps to protect themselves from exposure while doing their job.”
The list includes drugs used for cancer chemotherapy, antiviral drugs, hormones, and bioengineered drugs. The 3 main categories are antineoplastic drugs (including those with manufacturer’s safe-handling guidance [MSHG]), nonantineoplastic drugs that meet ≥ 1 of the NIOSH criteria for hazardous drugs (including those with MSHG), and nonantineoplastic drugs that primarily have adverse reproductive effects.
NIOSH estimates that 8 million U.S. health care workers are potentially exposed to hazardous drugs in the workplace. Some drugs defined as hazardous may not pose a significant risk of direct occupational exposure until the formulations are altered (as when coated tablets are crushed). Other hazards include, for example, skin contact with or inhalation of dust as uncoated tablets are counted. Five of the newly added drugs have safe-handling recommendations.
NIOSH says “no single approach can cover the diverse potential occupational exposures to the drugs” and notes that safe-handling precautions can vary with the activity and formulation of the drug. Still, the list also provides general guidance for “possible scenarios” that might be encountered in health care settings where hazardous drugs are handled. It addresses situations such as receiving, unpacking, and placing drugs in storage; administering an intact tablet or capsule from a unit-dose package; cutting, crushing, or manipulating tablets or capsules; and compounding oral liquid drugs or topical drugs.
The new report also provides health care organizations with guidance on generating their own list of hazardous drugs. Hazardous drug evaluation is “a continual process,” NIOSH says, advising that every facility must assess each new drug that enters its workplace and when appropriate reassess its list of hazardous drugs as new toxicologic data become available.
The list of hazardous drugs is updated periodically at http://www.cdc.gov/niosh/topics/hazdrug/.
Afatinib, axitinib, and belinostat head the list of 34 additions to the updated National Institute for Occupational Safety and Health (NIOSH) List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings. The list is “an important resource as well as a tool to raise awareness among workers about the hazards of some drugs,” said NIOSH Director John Howard, MD, “enabling workers to take the necessary steps to protect themselves from exposure while doing their job.”
The list includes drugs used for cancer chemotherapy, antiviral drugs, hormones, and bioengineered drugs. The 3 main categories are antineoplastic drugs (including those with manufacturer’s safe-handling guidance [MSHG]), nonantineoplastic drugs that meet ≥ 1 of the NIOSH criteria for hazardous drugs (including those with MSHG), and nonantineoplastic drugs that primarily have adverse reproductive effects.
NIOSH estimates that 8 million U.S. health care workers are potentially exposed to hazardous drugs in the workplace. Some drugs defined as hazardous may not pose a significant risk of direct occupational exposure until the formulations are altered (as when coated tablets are crushed). Other hazards include, for example, skin contact with or inhalation of dust as uncoated tablets are counted. Five of the newly added drugs have safe-handling recommendations.
NIOSH says “no single approach can cover the diverse potential occupational exposures to the drugs” and notes that safe-handling precautions can vary with the activity and formulation of the drug. Still, the list also provides general guidance for “possible scenarios” that might be encountered in health care settings where hazardous drugs are handled. It addresses situations such as receiving, unpacking, and placing drugs in storage; administering an intact tablet or capsule from a unit-dose package; cutting, crushing, or manipulating tablets or capsules; and compounding oral liquid drugs or topical drugs.
The new report also provides health care organizations with guidance on generating their own list of hazardous drugs. Hazardous drug evaluation is “a continual process,” NIOSH says, advising that every facility must assess each new drug that enters its workplace and when appropriate reassess its list of hazardous drugs as new toxicologic data become available.
The list of hazardous drugs is updated periodically at http://www.cdc.gov/niosh/topics/hazdrug/.
Letters to the Editor: Benefit of self-administered vaginal lidocaine gel in IUD placement
“BENEFIT OF SELF-ADMINISTERED VAGINAL LIDOCAINE GEL IN IUD PLACEMENT"
ANDREW M. KAUNITZ, MD (COMMENTARY; DECEMBER 2016)
Use anesthesia for in-office GYN procedures
The recent article by Dr. Kaunitz on the use of self-administered lidocaine gel prior to intrauterine device (IUD) placement was excellent. Having been known as the “lidocaine queen” in the Department of ObGyn at the Mayo Clinic, I feel strongly that gynecologic office procedures should always involve some form of anesthesia, whether with topical lidocaine, intracervical lidocaine, or paracervical block. Such anesthesia often makes the procedure a “nonevent” for the patient. While Dr. Kaunitz describes the use of a fine-toothed tenaculum, I have found that after administration of lidocaine gel, an Allis clamp applied superficially to the cervix provides sufficient traction, is often not detected by the patient, and does not leave any holes. It is unusual for it to slip off.
It is important to teach residents that it is not necessary for women to “tolerate” pain to have good health. I use the above techniques for endometrial biopsy and cervical biopsy as well—there is never a reason for a woman’s biopsy to be done without anesthesia.
Ingrid Carlson, MD
Ponte Vedra, Florida
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
“BENEFIT OF SELF-ADMINISTERED VAGINAL LIDOCAINE GEL IN IUD PLACEMENT"
ANDREW M. KAUNITZ, MD (COMMENTARY; DECEMBER 2016)
Use anesthesia for in-office GYN procedures
The recent article by Dr. Kaunitz on the use of self-administered lidocaine gel prior to intrauterine device (IUD) placement was excellent. Having been known as the “lidocaine queen” in the Department of ObGyn at the Mayo Clinic, I feel strongly that gynecologic office procedures should always involve some form of anesthesia, whether with topical lidocaine, intracervical lidocaine, or paracervical block. Such anesthesia often makes the procedure a “nonevent” for the patient. While Dr. Kaunitz describes the use of a fine-toothed tenaculum, I have found that after administration of lidocaine gel, an Allis clamp applied superficially to the cervix provides sufficient traction, is often not detected by the patient, and does not leave any holes. It is unusual for it to slip off.
It is important to teach residents that it is not necessary for women to “tolerate” pain to have good health. I use the above techniques for endometrial biopsy and cervical biopsy as well—there is never a reason for a woman’s biopsy to be done without anesthesia.
Ingrid Carlson, MD
Ponte Vedra, Florida
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
“BENEFIT OF SELF-ADMINISTERED VAGINAL LIDOCAINE GEL IN IUD PLACEMENT"
ANDREW M. KAUNITZ, MD (COMMENTARY; DECEMBER 2016)
Use anesthesia for in-office GYN procedures
The recent article by Dr. Kaunitz on the use of self-administered lidocaine gel prior to intrauterine device (IUD) placement was excellent. Having been known as the “lidocaine queen” in the Department of ObGyn at the Mayo Clinic, I feel strongly that gynecologic office procedures should always involve some form of anesthesia, whether with topical lidocaine, intracervical lidocaine, or paracervical block. Such anesthesia often makes the procedure a “nonevent” for the patient. While Dr. Kaunitz describes the use of a fine-toothed tenaculum, I have found that after administration of lidocaine gel, an Allis clamp applied superficially to the cervix provides sufficient traction, is often not detected by the patient, and does not leave any holes. It is unusual for it to slip off.
It is important to teach residents that it is not necessary for women to “tolerate” pain to have good health. I use the above techniques for endometrial biopsy and cervical biopsy as well—there is never a reason for a woman’s biopsy to be done without anesthesia.
Ingrid Carlson, MD
Ponte Vedra, Florida
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Letters to the Editor: Avoid uterine vessels when injecting vasopressin
“DO YOU UTILIZE VASOPRESSIN IN YOUR DIFFICULT CESAREAN DELIVERY SURGERIES?”
ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2016)
Avoid uterine vessels when injecting vasopressin
Thank you for your recent editorial discussing using vasopressin in difficult cesarean deliveries. I am very interested in using vasopressin for our placenta previa cases.
I reviewed the Kato et al article that Dr. Barbieri referenced, and the authors note a risk of injecting vasopressin into a vessel.1 If you are injecting into the placental bed, how can you confirm you are not in a vessel? (When you withdraw, you will get some blood regardless.)
Sara Garmel, MD
Dearborn, Michigan
REFERENCE
- Kato S, Tanabe A, Kanki K, et al. Local injection of vasopressin reduces the blood loss during cesarean section in placenta previa. J Obstet Gynaecol Res. 2014;40(5):1249–1256.
Dr. Barbieri responds
I agree with Dr. Garmel that we should avoid the intravascular injection of vasopressin. As I noted in the editorial, “I prefer to inject vasopressin in the subserosa of the uterus rather than inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.” Subserosal injection creates a depot bleb of vasopressin that is absorbed over a few minutes. You can visualize the reduced blood flow to the uterus following vasopressin injection because the uterus blanches and the diameter of the uterine vessels decreases significantly.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
“DO YOU UTILIZE VASOPRESSIN IN YOUR DIFFICULT CESAREAN DELIVERY SURGERIES?”
ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2016)
Avoid uterine vessels when injecting vasopressin
Thank you for your recent editorial discussing using vasopressin in difficult cesarean deliveries. I am very interested in using vasopressin for our placenta previa cases.
I reviewed the Kato et al article that Dr. Barbieri referenced, and the authors note a risk of injecting vasopressin into a vessel.1 If you are injecting into the placental bed, how can you confirm you are not in a vessel? (When you withdraw, you will get some blood regardless.)
Sara Garmel, MD
Dearborn, Michigan
REFERENCE
- Kato S, Tanabe A, Kanki K, et al. Local injection of vasopressin reduces the blood loss during cesarean section in placenta previa. J Obstet Gynaecol Res. 2014;40(5):1249–1256.
Dr. Barbieri responds
I agree with Dr. Garmel that we should avoid the intravascular injection of vasopressin. As I noted in the editorial, “I prefer to inject vasopressin in the subserosa of the uterus rather than inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.” Subserosal injection creates a depot bleb of vasopressin that is absorbed over a few minutes. You can visualize the reduced blood flow to the uterus following vasopressin injection because the uterus blanches and the diameter of the uterine vessels decreases significantly.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
“DO YOU UTILIZE VASOPRESSIN IN YOUR DIFFICULT CESAREAN DELIVERY SURGERIES?”
ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2016)
Avoid uterine vessels when injecting vasopressin
Thank you for your recent editorial discussing using vasopressin in difficult cesarean deliveries. I am very interested in using vasopressin for our placenta previa cases.
I reviewed the Kato et al article that Dr. Barbieri referenced, and the authors note a risk of injecting vasopressin into a vessel.1 If you are injecting into the placental bed, how can you confirm you are not in a vessel? (When you withdraw, you will get some blood regardless.)
Sara Garmel, MD
Dearborn, Michigan
REFERENCE
- Kato S, Tanabe A, Kanki K, et al. Local injection of vasopressin reduces the blood loss during cesarean section in placenta previa. J Obstet Gynaecol Res. 2014;40(5):1249–1256.
Dr. Barbieri responds
I agree with Dr. Garmel that we should avoid the intravascular injection of vasopressin. As I noted in the editorial, “I prefer to inject vasopressin in the subserosa of the uterus rather than inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.” Subserosal injection creates a depot bleb of vasopressin that is absorbed over a few minutes. You can visualize the reduced blood flow to the uterus following vasopressin injection because the uterus blanches and the diameter of the uterine vessels decreases significantly.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Letters to the Editor: Patient with a breast mass: Why did she pursue litigation?
“PATIENT WITH A BREAST MASS: WHY DID SHE PURSUE LITIGATION?”
JOSEPH S. SANFILIPPO, MD, MBA, AND STEVEN R. SMITH, JD (WHAT'S THE VERDICT?; DECEMBER 2016)
Clear communication is often key to avoiding litigation
Thank you for the article concerning the patient who commenced action for delay in diagnosis of her breast lesion. In my opinion the gynecologist lost control of the situation because of inadequate communication with the patient either on his or her part and/or on the part of the staff.
J. S. Calabrese, MD, JD
Buffalo, New York
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
“PATIENT WITH A BREAST MASS: WHY DID SHE PURSUE LITIGATION?”
JOSEPH S. SANFILIPPO, MD, MBA, AND STEVEN R. SMITH, JD (WHAT'S THE VERDICT?; DECEMBER 2016)
Clear communication is often key to avoiding litigation
Thank you for the article concerning the patient who commenced action for delay in diagnosis of her breast lesion. In my opinion the gynecologist lost control of the situation because of inadequate communication with the patient either on his or her part and/or on the part of the staff.
J. S. Calabrese, MD, JD
Buffalo, New York
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
“PATIENT WITH A BREAST MASS: WHY DID SHE PURSUE LITIGATION?”
JOSEPH S. SANFILIPPO, MD, MBA, AND STEVEN R. SMITH, JD (WHAT'S THE VERDICT?; DECEMBER 2016)
Clear communication is often key to avoiding litigation
Thank you for the article concerning the patient who commenced action for delay in diagnosis of her breast lesion. In my opinion the gynecologist lost control of the situation because of inadequate communication with the patient either on his or her part and/or on the part of the staff.
J. S. Calabrese, MD, JD
Buffalo, New York
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Chest Pain Numbs Holiday Cheer
ANSWER
The correct interpretation includes normal sinus rhythm and right atrial enlargement. The latter is suggested by tall P waves in leads II, III, and aVF (typically ≥ 2.5 mm), which may be caused by pressure or volume overload of the right atrium or by conditions causing pulmonary hypertension.
Given this patient’s presentation of right-side chest pain with a history of COPD, smoking, palpable left saphenous vein, and right atrial enlargement, a chest CT was performed. It confirmed the suspicion of a pulmonary embolus.
ANSWER
The correct interpretation includes normal sinus rhythm and right atrial enlargement. The latter is suggested by tall P waves in leads II, III, and aVF (typically ≥ 2.5 mm), which may be caused by pressure or volume overload of the right atrium or by conditions causing pulmonary hypertension.
Given this patient’s presentation of right-side chest pain with a history of COPD, smoking, palpable left saphenous vein, and right atrial enlargement, a chest CT was performed. It confirmed the suspicion of a pulmonary embolus.
ANSWER
The correct interpretation includes normal sinus rhythm and right atrial enlargement. The latter is suggested by tall P waves in leads II, III, and aVF (typically ≥ 2.5 mm), which may be caused by pressure or volume overload of the right atrium or by conditions causing pulmonary hypertension.
Given this patient’s presentation of right-side chest pain with a history of COPD, smoking, palpable left saphenous vein, and right atrial enlargement, a chest CT was performed. It confirmed the suspicion of a pulmonary embolus.
A 64-year-old woman presents with nondescript pain throughout her right chest. One week ago, she developed aching in both lower extremities, worse in the left leg than in the right. Two days ago, she noticed a tender area on her lower left leg that “feels like a hard rope.” She denies constitutional symptoms and changes in bowel or bladder habits.
Initial history-taking produces only the vague response that she’s “had my share of medical problems” through the years. A review of the electronic medical record reveals a history of chronic obstructive pulmonary disease (COPD), tobacco use, and recurrent community-acquired pneumonia—as well as a pattern of missed appointments. Her most recent visit was five years ago.
On further questioning, the patient informs you that she was shocked for a rapid heartbeat in the past year, following a weekend of binge-drinking on a cruise. She also reveals that she has increased her per-day cigarette habit from one to 2.5 packs to “deal with the stress of the holidays.” However, she reports no changes in her respiratory status or her “usual” productive morning cough. She denies shortness of breath, as well as any history of hypertension, diabetes, thyroid disorder, or cardiac-related chest pain.
The patient has been divorced for 11 years. Her job keeps her on the road between eight and 10 hours a day. She drinks alcohol on the weekend—anywhere from one six-pack to an entire case of beer. She began smoking at age 13 and hasn’t stopped since, refusing any offers of smoking cessation. She tried marijuana a few years ago but “didn’t like” how it made her feel. She denies using illicit or prescription drugs.
Family history reveals that the patient’s parents and both sets of grandparents were chronic smokers. Her paternal grandfather died of complications from emphysema, her maternal grandfather of asbestosis, and both grandmothers of strokes. Her parents are alive and reside in an assisted living facility. Her mother is being treated for colon cancer, and her father has had two myocardial infarctions. She had one brother who died in a motorcycle accident at age 15.
Her height is 69 in and her weight, 142 lb. Vital signs include a blood pressure of 152/94 mm Hg; pulse, 90 beats/min; respiratory rate, 16 breaths/min-1; and temperature, 97.2°F.
On physical exam, the patient appears older than her stated age but is in no distress. The HEENT exam is significant for corrective lenses, stained teeth, and leukoplakia on the oral mucosa. Neck veins are elevated, with a prominent A wave present. There is no thyromegaly or carotid bruits. The lungs reveal coarse rhonchi bilaterally in all lung fields, with no significant changes with coughing. The cardiac rate is regular with no evidence of a murmur or rub. Peripheral pulses are strong and equal bilaterally in both upper and lower extremities. The abdominal exam shows no evidence of organomegaly or masses, and the abdominal aorta is easily palpable. There is no edema in the lower extremities; however, a palpable cord is present along the entire length of the left greater saphenous vein. The neurologic exam is grossly intact without focal signs.
In addition to routine laboratory specimens, a chest x-ray and ECG are obtained. The ECG shows a ventricular rate of 96 beats/min; PR interval, 126 ms; QRS duration, 80 ms; QT/QTc interval, 384/485 ms; P axis, 79°; R axis, 18°; and T axis, 63°. What is your interpretation of this ECG?
Statins May Reduce the Risk of Alzheimer’s Disease
Statins may lower the risk of developing Alzheimer’s disease, but the decrease in risk varies across statin molecules, and by gender, race, and ethnicity, according to research published online ahead of print December 12 in JAMA Neurology.
None of the statins assessed in the study affected the risk of developing Alzheimer’s disease among black men, said Julie M. Zissimopoulos, PhD, Vice Dean for Academic Affairs and Assistant Professor in the Sol Price School of Public Policy at the University of Southern California in Los Angeles, and her associates.
Several studies have suggested that statins exert a protective effect against Alzheimer’s disease, but they have had insufficient follow-up times, lacked minorities, and removed hyperlipidemic participants. For these reasons, Dr. Zissimopoulos and her colleagues analyzed medical and pharmacy data for a large, diverse sample of Medicare beneficiaries.
The researchers examined 399,979 adults aged 65 and older who initiated statin therapy during a two-year period. Beneficiaries were followed for approximately seven years. The mean interval between statin exposure and Alzheimer’s disease diagnosis was 5.4 years.
The study population included 310,240 non-Hispanic whites, 32,658 Hispanics, 32,278 non-Hispanic blacks, and 24,803 participants of Asian, Native American, other, or unknown race or ethnicity. The investigators confined their analysis to the four most commonly prescribed statins: simvastatin, atorvastatin, pravastatin, and rosuvastatin.
Overall, 1.72% of women and 1.32% of men were diagnosed as having Alzheimer’s disease during each year of follow-up. Study participants who were exposed to higher statin levels during the two-year exposure period were 10% less likely to receive a diagnosis of Alzheimer’s disease during follow-up, compared with those exposed to lower levels of statins. High exposure to statins reduced the risk of Alzheimer’s disease among women of all races (hazard ratio [HR], 0.85) and men of all races (HR, 0.88).
This association, however, varied across gender, race, and ethnicity. Statins decreased the risk of Alzheimer’s disease the most among Hispanic men (HR, 0.71), followed by black women (HR, 0.82), white women (HR, 0.86), and white men (HR, 0.89), but they did not decrease the risk of Alzheimer’s disease among black men, said Dr. Zissimopoulos. Simvastatin significantly decreased the risk of Alzheimer’s disease among white, Hispanic, and black women, compared with other subgroups, and atorvastatin significantly decreased the risk among white women, Hispanic women, and Hispanic men. Pravastatin and rosuvastatin decreased the risk of Alzheimer’s disease significantly among white women only.
These findings suggest that “certain patients facing multiple, otherwise equal statin alternatives for hyperlipidemia treatment, may reduce Alzheimer’s risk by using a particular statin. The right statin type for the right person at the right time may provide a relatively inexpensive means to lessen the burden of Alzheimer’s disease,” the investigators said.
This study was supported by the National Institute on Aging, the University of Southern California Zumberge Research Fund, and the Schaeffer-Amgen Fellowship Program.
—Mary Ann Moon
Suggested Reading
Zissimopoulos JM, Barthold D, Brinton RD, Joyce G. Sex and race differences in the association between statin use and the incidence of Alzheimer disease. JAMA Neurol. 2016 Dec 12 [Epub ahead of print].
Statins may lower the risk of developing Alzheimer’s disease, but the decrease in risk varies across statin molecules, and by gender, race, and ethnicity, according to research published online ahead of print December 12 in JAMA Neurology.
None of the statins assessed in the study affected the risk of developing Alzheimer’s disease among black men, said Julie M. Zissimopoulos, PhD, Vice Dean for Academic Affairs and Assistant Professor in the Sol Price School of Public Policy at the University of Southern California in Los Angeles, and her associates.
Several studies have suggested that statins exert a protective effect against Alzheimer’s disease, but they have had insufficient follow-up times, lacked minorities, and removed hyperlipidemic participants. For these reasons, Dr. Zissimopoulos and her colleagues analyzed medical and pharmacy data for a large, diverse sample of Medicare beneficiaries.
The researchers examined 399,979 adults aged 65 and older who initiated statin therapy during a two-year period. Beneficiaries were followed for approximately seven years. The mean interval between statin exposure and Alzheimer’s disease diagnosis was 5.4 years.
The study population included 310,240 non-Hispanic whites, 32,658 Hispanics, 32,278 non-Hispanic blacks, and 24,803 participants of Asian, Native American, other, or unknown race or ethnicity. The investigators confined their analysis to the four most commonly prescribed statins: simvastatin, atorvastatin, pravastatin, and rosuvastatin.
Overall, 1.72% of women and 1.32% of men were diagnosed as having Alzheimer’s disease during each year of follow-up. Study participants who were exposed to higher statin levels during the two-year exposure period were 10% less likely to receive a diagnosis of Alzheimer’s disease during follow-up, compared with those exposed to lower levels of statins. High exposure to statins reduced the risk of Alzheimer’s disease among women of all races (hazard ratio [HR], 0.85) and men of all races (HR, 0.88).
This association, however, varied across gender, race, and ethnicity. Statins decreased the risk of Alzheimer’s disease the most among Hispanic men (HR, 0.71), followed by black women (HR, 0.82), white women (HR, 0.86), and white men (HR, 0.89), but they did not decrease the risk of Alzheimer’s disease among black men, said Dr. Zissimopoulos. Simvastatin significantly decreased the risk of Alzheimer’s disease among white, Hispanic, and black women, compared with other subgroups, and atorvastatin significantly decreased the risk among white women, Hispanic women, and Hispanic men. Pravastatin and rosuvastatin decreased the risk of Alzheimer’s disease significantly among white women only.
These findings suggest that “certain patients facing multiple, otherwise equal statin alternatives for hyperlipidemia treatment, may reduce Alzheimer’s risk by using a particular statin. The right statin type for the right person at the right time may provide a relatively inexpensive means to lessen the burden of Alzheimer’s disease,” the investigators said.
This study was supported by the National Institute on Aging, the University of Southern California Zumberge Research Fund, and the Schaeffer-Amgen Fellowship Program.
—Mary Ann Moon
Suggested Reading
Zissimopoulos JM, Barthold D, Brinton RD, Joyce G. Sex and race differences in the association between statin use and the incidence of Alzheimer disease. JAMA Neurol. 2016 Dec 12 [Epub ahead of print].
Statins may lower the risk of developing Alzheimer’s disease, but the decrease in risk varies across statin molecules, and by gender, race, and ethnicity, according to research published online ahead of print December 12 in JAMA Neurology.
None of the statins assessed in the study affected the risk of developing Alzheimer’s disease among black men, said Julie M. Zissimopoulos, PhD, Vice Dean for Academic Affairs and Assistant Professor in the Sol Price School of Public Policy at the University of Southern California in Los Angeles, and her associates.
Several studies have suggested that statins exert a protective effect against Alzheimer’s disease, but they have had insufficient follow-up times, lacked minorities, and removed hyperlipidemic participants. For these reasons, Dr. Zissimopoulos and her colleagues analyzed medical and pharmacy data for a large, diverse sample of Medicare beneficiaries.
The researchers examined 399,979 adults aged 65 and older who initiated statin therapy during a two-year period. Beneficiaries were followed for approximately seven years. The mean interval between statin exposure and Alzheimer’s disease diagnosis was 5.4 years.
The study population included 310,240 non-Hispanic whites, 32,658 Hispanics, 32,278 non-Hispanic blacks, and 24,803 participants of Asian, Native American, other, or unknown race or ethnicity. The investigators confined their analysis to the four most commonly prescribed statins: simvastatin, atorvastatin, pravastatin, and rosuvastatin.
Overall, 1.72% of women and 1.32% of men were diagnosed as having Alzheimer’s disease during each year of follow-up. Study participants who were exposed to higher statin levels during the two-year exposure period were 10% less likely to receive a diagnosis of Alzheimer’s disease during follow-up, compared with those exposed to lower levels of statins. High exposure to statins reduced the risk of Alzheimer’s disease among women of all races (hazard ratio [HR], 0.85) and men of all races (HR, 0.88).
This association, however, varied across gender, race, and ethnicity. Statins decreased the risk of Alzheimer’s disease the most among Hispanic men (HR, 0.71), followed by black women (HR, 0.82), white women (HR, 0.86), and white men (HR, 0.89), but they did not decrease the risk of Alzheimer’s disease among black men, said Dr. Zissimopoulos. Simvastatin significantly decreased the risk of Alzheimer’s disease among white, Hispanic, and black women, compared with other subgroups, and atorvastatin significantly decreased the risk among white women, Hispanic women, and Hispanic men. Pravastatin and rosuvastatin decreased the risk of Alzheimer’s disease significantly among white women only.
These findings suggest that “certain patients facing multiple, otherwise equal statin alternatives for hyperlipidemia treatment, may reduce Alzheimer’s risk by using a particular statin. The right statin type for the right person at the right time may provide a relatively inexpensive means to lessen the burden of Alzheimer’s disease,” the investigators said.
This study was supported by the National Institute on Aging, the University of Southern California Zumberge Research Fund, and the Schaeffer-Amgen Fellowship Program.
—Mary Ann Moon
Suggested Reading
Zissimopoulos JM, Barthold D, Brinton RD, Joyce G. Sex and race differences in the association between statin use and the incidence of Alzheimer disease. JAMA Neurol. 2016 Dec 12 [Epub ahead of print].
Point/Counterpoint: Is limb salvage always best in diabetes?
Salvage limbs at all costs
Aggressive limb salvage in people with diabetes leads to an overall reduction in cost not only economically, but also from the patient’s perspective. The vast majority of diabetic patients with critical ischemia are actually good candidates for limb salvage. Tragically, many of these patients are never referred for evaluation for limb salvage because of misconceptions about the pathophysiology of the disease.
An argument against limb salvage is that primary amputation prevents or shortens the course of wound care and enables patients to become ambulatory, albeit with a prosthesis, faster. However, in the modern era of vascular surgery, revascularization can be performed successfully with minimal mortality and excellent rates of limb salvage, especially when it’s done within a team-based approach.
The mortality in primary amputation is shockingly high, anywhere from 5% to 23% higher than revascularization alone, and the major complication rate of amputation associated with diabetes is also unacceptably high – up to 37%. This is in contrast to a 17% rate in major nonamputation vascular surgery and 1%-5% in endovascular procedures (BMC Nephrol. 2005;6:3).
We can’t ignore the economic burden this places on the country. In 2014, primary amputations cost the health care system $11 billion annually, and that is expected to grow to more than $25 billion in the next several years, according to the SAGE Group. It’s important to keep in mind that Medicare covers over 80% of this cost.
A number of studies have shown that conservative management with wound care and amputation is more cost effective than primary amputation in ambulatory, independent adults. Data can be difficult to interpret because of different recording strategies for all the costs associated with amputation, but a single-institution study concluded that revascularization costs almost $5,280 more than expectant management, but $33,900 less than primary amputation alone (Cardiovasc Surg. 1999;7;62-9).
We must also consider the costs of revision after primary amputation; above-the-knee amputation has a 12% in-hospital revision rate, and below-the-knee amputation about 20%. Endovascular interventions, on the other hand, have a 1%-9% in-hospital revision rate, and only 2%-4% of these patients will go on to require an amputation during the same admission (Eur J Vasc Endovasc Surg. 2006;32:484-90; Arch Phys Med Rehabil. 2005;86:480-6).This does not include the costs of those complications as well as other indirect costs of amputation, such as nursing home care and living situation modification (Int J Behav Med. 2016;23:714-21; Pak J Med Sci. 2014; 30:1044-9). They quickly add up to that $25 billion.
The proponents of primary amputation tell us that it leads to quicker recovery time and an earlier time to ambulation. However, only 47% of patients will actually ambulate after amputation, in contrast to 97% who will ambulate after limb salvage as a primary procedure. In a nonambulatory cohort, 21% of those patients go on to regain functional status that was lost prior to surgery (J Vasc Surg. 1997;25;287-95).
Many question if our success with vascular surgery over the past few decades can translate to helping the most difficult subset of patients. An Italian study reported on a cohort of diabetic vs. nondiabetic patients and determined both groups have similar amputation-free rates after infrainguinal arterial reconstruction for critical limb ischemia, with excellent primary and secondary patency rates and a limb salvage rate of 88% at 5 years (J Vasc Surg. 2014;59:708-19). This tells us that we do have the skill set necessary to save these limbs.
A multidisciplinary limb preservation team is paramount to the success of any limb salvage program. A revascularization team should be in place which uses early intervention to achieve the highest limb salvage rates possible. Wound care needs to be an integrated part of it. Advanced podiatric reconstructive surgery also is key because this can provide complex foot reconstructions and help ambulatory patients return home.
Dr. Trissa A. Babrowski is an assistant professor of surgery, specializing in vascular surgery and endovascular therapy, at the University of Chicago Heart and Vascular Center. She had no financial relationships to disclose.
Primary amputation can be OK
I am not an amputationalist. I do practice limb salvage. In fact I’m probably the most aggressive limb salvage surgeon in my hospital. But primary amputation is a completely acceptable option for a selected group of patients with diabetes. We should not try to do limb salvage “at all costs.”
I do not find this to be a contradictory position. In fact, I think it adds credence to my support of limb salvage that I think primary amputation can be OK. In all honesty, there are very few things in life that should be done at all costs.
A study out of Loma Linda University involving patients with CLI compared primary amputation vs. revascularization; 43% of patients had a primary amputation (Ann Vasc Surg. 2007;21:458-63). A multivariate analysis showed that patients with major tissue loss, end-stage renal disease (ESRD), diabetes and nonambulatory status were more likely to undergo primary amputation rather than revascularization.
While major tissue loss (Rutherford category 6) is certainly an indication for primary amputation, ambulatory status can represent a gray area in determining the best course. ESRD and diabetes are much more nonspecific factors; probably more than 10% of the patients that we see with CLI have ESRD. Also, 50%-70% of these patients with CLI, and in some series even higher percentages, have diabetes. Thus, these factors by themselves do not assist us in determining which patients potentially should be offered primary amputation vs. revascularization.
In general, we know that we can get good results in limb bypass or revascularization in patients with CLI: The PREVENT III multicenter trial, with the use of the vein as the conduit, showed 1-year limb salvage rates of 88% in these high-risk patients (J Vasc Surg. 2006;43:742-51). However, one of the major risk factors that adversely affected outcome was ESRD.
We know that ESRD is a significant predictor of lowering our chances of saving a limb successfully. Knowing the cost of multiple continued episodes of revascularization in these patients prior to proceeding with an amputation, it’s intuitive that these patients would benefit from a more precise process in their treatment from the beginning. A number of papers have concluded that a primary amputation may be the preferred approach in patients with ESRD.
Can we preoperatively predict which patients with CLI will fail operative revascularization? Data from the New England Vascular Quality Initiative identified eight variables associated with failure of revascularization, among them age younger than 59, ESRD, diabetes, CLI, conduit requiring venovenostomy, tarsal target, and nursing home residence (Ann Vasc Surg. 2010;24:57-68). The presence of three or more risk factors has a 27.7% risk of limb loss and/or graft thrombosis within 1 year.
Postponing amputation is a major cost issue. Direct costs of bypass for critical limb ischemia were $3.6 billion in 2004 (J Vasc Surg. 2011;54:1021-31), and we know that a functional outcome can be problematic in this patient group. Factors associated with a poor functional outcome include dementia, dependent-living situation preoperatively and nonambulatory status.
Unfortunately, there are not a lot of data that deal with quality of life outcomes for patients with CLI who have undergone bypass. Using a point system comprised of dialysis (4 points), tissue loss (3 points), age above 75 (2 points), hematocrit less than or equal to 30 (2 points), and coronary artery disease (1 point), a follow-up study of patients in the PREVENT III trial found that a high-risk group (greater than or equal to 8 points) had an amputation-free survival of only 45% (J Vasc Surg. 2009;50:769-75). Again, these results do not justify the effort and costs of limb salvage in this high-risk patient group.
We should consider the following options carefully in selecting a cost-effective patient-focused approach in patients with CLI: wound care, primary amputation, bypass revascularization, or endovascular revascularization. I would argue that the vascular surgeon who is qualified as an expert in all of the above is best positioned to select an appropriate plan of treatment based upon the patient’s risk factors, wound factors, ambulatory ability, pattern of disease, severity of ischemia, and living status.
Thus, upon presentation, a patient with CLI should undergo confirmatory tests and optimize his or her risk factors. The vascular surgeon then has the option, in discussion with the patient and family, to pursue an appropriate treatment plan inclusive of primary amputation – not one of limb salvage “at all costs.”
Primary amputation should be used in situations where there is dementia and nonambulatory status, and in patients who are poor candidates for revascularization because of high risk of failure and limited life expectancy. The recently developed WIfI (wound, ischemia, and foot infection) classification can also be utilized, as stage 4 WIfI classification is associated with high risk of limb loss – 38%-40% at 1 year.
Primary amputation is an option that can result in better care overall, and it is a cost-effective approach for a selected group of patients. We should not try to do limb salvage at all cost. Primary amputation, in selected patients, is OK.
Dr. Timothy J. Nypaver is head of vascular surgery at Henry Ford Hospital, Detroit. He had no financial relationships to disclose.
Salvage limbs at all costs
Aggressive limb salvage in people with diabetes leads to an overall reduction in cost not only economically, but also from the patient’s perspective. The vast majority of diabetic patients with critical ischemia are actually good candidates for limb salvage. Tragically, many of these patients are never referred for evaluation for limb salvage because of misconceptions about the pathophysiology of the disease.
An argument against limb salvage is that primary amputation prevents or shortens the course of wound care and enables patients to become ambulatory, albeit with a prosthesis, faster. However, in the modern era of vascular surgery, revascularization can be performed successfully with minimal mortality and excellent rates of limb salvage, especially when it’s done within a team-based approach.
The mortality in primary amputation is shockingly high, anywhere from 5% to 23% higher than revascularization alone, and the major complication rate of amputation associated with diabetes is also unacceptably high – up to 37%. This is in contrast to a 17% rate in major nonamputation vascular surgery and 1%-5% in endovascular procedures (BMC Nephrol. 2005;6:3).
We can’t ignore the economic burden this places on the country. In 2014, primary amputations cost the health care system $11 billion annually, and that is expected to grow to more than $25 billion in the next several years, according to the SAGE Group. It’s important to keep in mind that Medicare covers over 80% of this cost.
A number of studies have shown that conservative management with wound care and amputation is more cost effective than primary amputation in ambulatory, independent adults. Data can be difficult to interpret because of different recording strategies for all the costs associated with amputation, but a single-institution study concluded that revascularization costs almost $5,280 more than expectant management, but $33,900 less than primary amputation alone (Cardiovasc Surg. 1999;7;62-9).
We must also consider the costs of revision after primary amputation; above-the-knee amputation has a 12% in-hospital revision rate, and below-the-knee amputation about 20%. Endovascular interventions, on the other hand, have a 1%-9% in-hospital revision rate, and only 2%-4% of these patients will go on to require an amputation during the same admission (Eur J Vasc Endovasc Surg. 2006;32:484-90; Arch Phys Med Rehabil. 2005;86:480-6).This does not include the costs of those complications as well as other indirect costs of amputation, such as nursing home care and living situation modification (Int J Behav Med. 2016;23:714-21; Pak J Med Sci. 2014; 30:1044-9). They quickly add up to that $25 billion.
The proponents of primary amputation tell us that it leads to quicker recovery time and an earlier time to ambulation. However, only 47% of patients will actually ambulate after amputation, in contrast to 97% who will ambulate after limb salvage as a primary procedure. In a nonambulatory cohort, 21% of those patients go on to regain functional status that was lost prior to surgery (J Vasc Surg. 1997;25;287-95).
Many question if our success with vascular surgery over the past few decades can translate to helping the most difficult subset of patients. An Italian study reported on a cohort of diabetic vs. nondiabetic patients and determined both groups have similar amputation-free rates after infrainguinal arterial reconstruction for critical limb ischemia, with excellent primary and secondary patency rates and a limb salvage rate of 88% at 5 years (J Vasc Surg. 2014;59:708-19). This tells us that we do have the skill set necessary to save these limbs.
A multidisciplinary limb preservation team is paramount to the success of any limb salvage program. A revascularization team should be in place which uses early intervention to achieve the highest limb salvage rates possible. Wound care needs to be an integrated part of it. Advanced podiatric reconstructive surgery also is key because this can provide complex foot reconstructions and help ambulatory patients return home.
Dr. Trissa A. Babrowski is an assistant professor of surgery, specializing in vascular surgery and endovascular therapy, at the University of Chicago Heart and Vascular Center. She had no financial relationships to disclose.
Primary amputation can be OK
I am not an amputationalist. I do practice limb salvage. In fact I’m probably the most aggressive limb salvage surgeon in my hospital. But primary amputation is a completely acceptable option for a selected group of patients with diabetes. We should not try to do limb salvage “at all costs.”
I do not find this to be a contradictory position. In fact, I think it adds credence to my support of limb salvage that I think primary amputation can be OK. In all honesty, there are very few things in life that should be done at all costs.
A study out of Loma Linda University involving patients with CLI compared primary amputation vs. revascularization; 43% of patients had a primary amputation (Ann Vasc Surg. 2007;21:458-63). A multivariate analysis showed that patients with major tissue loss, end-stage renal disease (ESRD), diabetes and nonambulatory status were more likely to undergo primary amputation rather than revascularization.
While major tissue loss (Rutherford category 6) is certainly an indication for primary amputation, ambulatory status can represent a gray area in determining the best course. ESRD and diabetes are much more nonspecific factors; probably more than 10% of the patients that we see with CLI have ESRD. Also, 50%-70% of these patients with CLI, and in some series even higher percentages, have diabetes. Thus, these factors by themselves do not assist us in determining which patients potentially should be offered primary amputation vs. revascularization.
In general, we know that we can get good results in limb bypass or revascularization in patients with CLI: The PREVENT III multicenter trial, with the use of the vein as the conduit, showed 1-year limb salvage rates of 88% in these high-risk patients (J Vasc Surg. 2006;43:742-51). However, one of the major risk factors that adversely affected outcome was ESRD.
We know that ESRD is a significant predictor of lowering our chances of saving a limb successfully. Knowing the cost of multiple continued episodes of revascularization in these patients prior to proceeding with an amputation, it’s intuitive that these patients would benefit from a more precise process in their treatment from the beginning. A number of papers have concluded that a primary amputation may be the preferred approach in patients with ESRD.
Can we preoperatively predict which patients with CLI will fail operative revascularization? Data from the New England Vascular Quality Initiative identified eight variables associated with failure of revascularization, among them age younger than 59, ESRD, diabetes, CLI, conduit requiring venovenostomy, tarsal target, and nursing home residence (Ann Vasc Surg. 2010;24:57-68). The presence of three or more risk factors has a 27.7% risk of limb loss and/or graft thrombosis within 1 year.
Postponing amputation is a major cost issue. Direct costs of bypass for critical limb ischemia were $3.6 billion in 2004 (J Vasc Surg. 2011;54:1021-31), and we know that a functional outcome can be problematic in this patient group. Factors associated with a poor functional outcome include dementia, dependent-living situation preoperatively and nonambulatory status.
Unfortunately, there are not a lot of data that deal with quality of life outcomes for patients with CLI who have undergone bypass. Using a point system comprised of dialysis (4 points), tissue loss (3 points), age above 75 (2 points), hematocrit less than or equal to 30 (2 points), and coronary artery disease (1 point), a follow-up study of patients in the PREVENT III trial found that a high-risk group (greater than or equal to 8 points) had an amputation-free survival of only 45% (J Vasc Surg. 2009;50:769-75). Again, these results do not justify the effort and costs of limb salvage in this high-risk patient group.
We should consider the following options carefully in selecting a cost-effective patient-focused approach in patients with CLI: wound care, primary amputation, bypass revascularization, or endovascular revascularization. I would argue that the vascular surgeon who is qualified as an expert in all of the above is best positioned to select an appropriate plan of treatment based upon the patient’s risk factors, wound factors, ambulatory ability, pattern of disease, severity of ischemia, and living status.
Thus, upon presentation, a patient with CLI should undergo confirmatory tests and optimize his or her risk factors. The vascular surgeon then has the option, in discussion with the patient and family, to pursue an appropriate treatment plan inclusive of primary amputation – not one of limb salvage “at all costs.”
Primary amputation should be used in situations where there is dementia and nonambulatory status, and in patients who are poor candidates for revascularization because of high risk of failure and limited life expectancy. The recently developed WIfI (wound, ischemia, and foot infection) classification can also be utilized, as stage 4 WIfI classification is associated with high risk of limb loss – 38%-40% at 1 year.
Primary amputation is an option that can result in better care overall, and it is a cost-effective approach for a selected group of patients. We should not try to do limb salvage at all cost. Primary amputation, in selected patients, is OK.
Dr. Timothy J. Nypaver is head of vascular surgery at Henry Ford Hospital, Detroit. He had no financial relationships to disclose.
Salvage limbs at all costs
Aggressive limb salvage in people with diabetes leads to an overall reduction in cost not only economically, but also from the patient’s perspective. The vast majority of diabetic patients with critical ischemia are actually good candidates for limb salvage. Tragically, many of these patients are never referred for evaluation for limb salvage because of misconceptions about the pathophysiology of the disease.
An argument against limb salvage is that primary amputation prevents or shortens the course of wound care and enables patients to become ambulatory, albeit with a prosthesis, faster. However, in the modern era of vascular surgery, revascularization can be performed successfully with minimal mortality and excellent rates of limb salvage, especially when it’s done within a team-based approach.
The mortality in primary amputation is shockingly high, anywhere from 5% to 23% higher than revascularization alone, and the major complication rate of amputation associated with diabetes is also unacceptably high – up to 37%. This is in contrast to a 17% rate in major nonamputation vascular surgery and 1%-5% in endovascular procedures (BMC Nephrol. 2005;6:3).
We can’t ignore the economic burden this places on the country. In 2014, primary amputations cost the health care system $11 billion annually, and that is expected to grow to more than $25 billion in the next several years, according to the SAGE Group. It’s important to keep in mind that Medicare covers over 80% of this cost.
A number of studies have shown that conservative management with wound care and amputation is more cost effective than primary amputation in ambulatory, independent adults. Data can be difficult to interpret because of different recording strategies for all the costs associated with amputation, but a single-institution study concluded that revascularization costs almost $5,280 more than expectant management, but $33,900 less than primary amputation alone (Cardiovasc Surg. 1999;7;62-9).
We must also consider the costs of revision after primary amputation; above-the-knee amputation has a 12% in-hospital revision rate, and below-the-knee amputation about 20%. Endovascular interventions, on the other hand, have a 1%-9% in-hospital revision rate, and only 2%-4% of these patients will go on to require an amputation during the same admission (Eur J Vasc Endovasc Surg. 2006;32:484-90; Arch Phys Med Rehabil. 2005;86:480-6).This does not include the costs of those complications as well as other indirect costs of amputation, such as nursing home care and living situation modification (Int J Behav Med. 2016;23:714-21; Pak J Med Sci. 2014; 30:1044-9). They quickly add up to that $25 billion.
The proponents of primary amputation tell us that it leads to quicker recovery time and an earlier time to ambulation. However, only 47% of patients will actually ambulate after amputation, in contrast to 97% who will ambulate after limb salvage as a primary procedure. In a nonambulatory cohort, 21% of those patients go on to regain functional status that was lost prior to surgery (J Vasc Surg. 1997;25;287-95).
Many question if our success with vascular surgery over the past few decades can translate to helping the most difficult subset of patients. An Italian study reported on a cohort of diabetic vs. nondiabetic patients and determined both groups have similar amputation-free rates after infrainguinal arterial reconstruction for critical limb ischemia, with excellent primary and secondary patency rates and a limb salvage rate of 88% at 5 years (J Vasc Surg. 2014;59:708-19). This tells us that we do have the skill set necessary to save these limbs.
A multidisciplinary limb preservation team is paramount to the success of any limb salvage program. A revascularization team should be in place which uses early intervention to achieve the highest limb salvage rates possible. Wound care needs to be an integrated part of it. Advanced podiatric reconstructive surgery also is key because this can provide complex foot reconstructions and help ambulatory patients return home.
Dr. Trissa A. Babrowski is an assistant professor of surgery, specializing in vascular surgery and endovascular therapy, at the University of Chicago Heart and Vascular Center. She had no financial relationships to disclose.
Primary amputation can be OK
I am not an amputationalist. I do practice limb salvage. In fact I’m probably the most aggressive limb salvage surgeon in my hospital. But primary amputation is a completely acceptable option for a selected group of patients with diabetes. We should not try to do limb salvage “at all costs.”
I do not find this to be a contradictory position. In fact, I think it adds credence to my support of limb salvage that I think primary amputation can be OK. In all honesty, there are very few things in life that should be done at all costs.
A study out of Loma Linda University involving patients with CLI compared primary amputation vs. revascularization; 43% of patients had a primary amputation (Ann Vasc Surg. 2007;21:458-63). A multivariate analysis showed that patients with major tissue loss, end-stage renal disease (ESRD), diabetes and nonambulatory status were more likely to undergo primary amputation rather than revascularization.
While major tissue loss (Rutherford category 6) is certainly an indication for primary amputation, ambulatory status can represent a gray area in determining the best course. ESRD and diabetes are much more nonspecific factors; probably more than 10% of the patients that we see with CLI have ESRD. Also, 50%-70% of these patients with CLI, and in some series even higher percentages, have diabetes. Thus, these factors by themselves do not assist us in determining which patients potentially should be offered primary amputation vs. revascularization.
In general, we know that we can get good results in limb bypass or revascularization in patients with CLI: The PREVENT III multicenter trial, with the use of the vein as the conduit, showed 1-year limb salvage rates of 88% in these high-risk patients (J Vasc Surg. 2006;43:742-51). However, one of the major risk factors that adversely affected outcome was ESRD.
We know that ESRD is a significant predictor of lowering our chances of saving a limb successfully. Knowing the cost of multiple continued episodes of revascularization in these patients prior to proceeding with an amputation, it’s intuitive that these patients would benefit from a more precise process in their treatment from the beginning. A number of papers have concluded that a primary amputation may be the preferred approach in patients with ESRD.
Can we preoperatively predict which patients with CLI will fail operative revascularization? Data from the New England Vascular Quality Initiative identified eight variables associated with failure of revascularization, among them age younger than 59, ESRD, diabetes, CLI, conduit requiring venovenostomy, tarsal target, and nursing home residence (Ann Vasc Surg. 2010;24:57-68). The presence of three or more risk factors has a 27.7% risk of limb loss and/or graft thrombosis within 1 year.
Postponing amputation is a major cost issue. Direct costs of bypass for critical limb ischemia were $3.6 billion in 2004 (J Vasc Surg. 2011;54:1021-31), and we know that a functional outcome can be problematic in this patient group. Factors associated with a poor functional outcome include dementia, dependent-living situation preoperatively and nonambulatory status.
Unfortunately, there are not a lot of data that deal with quality of life outcomes for patients with CLI who have undergone bypass. Using a point system comprised of dialysis (4 points), tissue loss (3 points), age above 75 (2 points), hematocrit less than or equal to 30 (2 points), and coronary artery disease (1 point), a follow-up study of patients in the PREVENT III trial found that a high-risk group (greater than or equal to 8 points) had an amputation-free survival of only 45% (J Vasc Surg. 2009;50:769-75). Again, these results do not justify the effort and costs of limb salvage in this high-risk patient group.
We should consider the following options carefully in selecting a cost-effective patient-focused approach in patients with CLI: wound care, primary amputation, bypass revascularization, or endovascular revascularization. I would argue that the vascular surgeon who is qualified as an expert in all of the above is best positioned to select an appropriate plan of treatment based upon the patient’s risk factors, wound factors, ambulatory ability, pattern of disease, severity of ischemia, and living status.
Thus, upon presentation, a patient with CLI should undergo confirmatory tests and optimize his or her risk factors. The vascular surgeon then has the option, in discussion with the patient and family, to pursue an appropriate treatment plan inclusive of primary amputation – not one of limb salvage “at all costs.”
Primary amputation should be used in situations where there is dementia and nonambulatory status, and in patients who are poor candidates for revascularization because of high risk of failure and limited life expectancy. The recently developed WIfI (wound, ischemia, and foot infection) classification can also be utilized, as stage 4 WIfI classification is associated with high risk of limb loss – 38%-40% at 1 year.
Primary amputation is an option that can result in better care overall, and it is a cost-effective approach for a selected group of patients. We should not try to do limb salvage at all cost. Primary amputation, in selected patients, is OK.
Dr. Timothy J. Nypaver is head of vascular surgery at Henry Ford Hospital, Detroit. He had no financial relationships to disclose.
Depression in pediatric bipolar disorder
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Vedolizumab effective at treating UC in wide range of patients
When treating patients for ulcerative colitis (UC), clinicians should consider using vedolizumab, because the drug has been found to be both safe and highly effective in patients who have never received tumor necrosis factor (TNF)–antagonist treatment and those who have but did not benefit from it, according to a study published in the February issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.08.044).
“Approximately 50% of patients with UC do not respond to induction therapy with TNF antagonists or lose response over time such that after 1 year of treatment, clinical remission is observed in only 17%-34% of patients,” explained the authors of the report, led by Brian G. Feagan, MD, of the University of Western Ontario in London. “Furthermore, the risk of serious infection (with immunosuppressants in general, and TNF antagonists specifically) is an important concern [so] alternative approaches to treatment are needed.”
For this study, Dr. Feagan and his colleagues turned to the GEMINI 1 trial, which evaluated vedolizumab in patients with moderate and severe UC via a multicenter, phase III, randomized, placebo-controlled trial. This study produced data on 374 subjects who had been randomized into cohorts receiving either vedolizumab intravenously or a placebo. However, this number was deemed too low, so a further 521 patients were enrolled for an open-label study and randomized in the same 3:2 ratio as the previous study. The former study was called Cohort 1 and the latter called Cohort 2.
“Eligible patients had UC for [at least] 6 months before enrollment, MCS [Mayo Clinic scores for disease activity] from 6 to 12, and endoscopic subscores of [at least] 2 within 7 days before the first dose of study drug, and evidence of disease extending [at least] 15 cm proximal to the rectum,” the authors explained.
Vedolizumab was administered at baseline, with follow-up evaluations at 2, 4, and 6 weeks. Subjects who experienced a clinical response – defined as an MCS reduction of at least 3 points and 30%, along with at least a 1-point reduction in rectal bleeding and an absolute rectal bleeding subscore of either 0 or 1 – were re-randomized into cohorts that received the drug every 4 weeks or every 8 weeks, for a period of up to 46 weeks. The total length of the study was, therefore, 52 weeks; for patients that were re-randomized, follow-up evaluations took place every 4 weeks.
A total of 464 patients who were enrolled and completed the study were naive to TNF antagonists, while 367 had previously been treated with TNF antagonists unsuccessfully. At 6-week follow-up, 53.1% of naive subjects receiving vedolizumab had achieved clinical response, versus 26.3% of naive subjects on placebo (absolute difference, 26.4%; 95% confidence interval, 12.4-40.4). Similarly, those with previous TNF antagonist exposure who were given vedolizumab had a 39.0% clinical response rate, versus 20.6% of those on placebo (AD, 18.1%; 95% CI, 2.8-33.5).
At week 52, naive subjects on vedolizumab continued to have far higher rates of clinical response than did those on placebo, with 46.9% and 19.0%, respectively (AD, 28.0%; 95% CI, 14.9-41.1). For those with previous TNF antagonist exposure, the disparity between vedolizumab and placebo was similarly profound: 36.1% versus 5.3%, respectively (AD, 29.5%; 95% CI, 12.8-46.1).
Adverse event rates between naive and previously exposed patients were not significantly different, according to the findings. In naive patients, 74% of those on vedolizumab experienced an adverse event, and 9% experienced a serious adverse event. For those on placebo, those rates were 75% and 16%, respectively. For patients who had previously been on a TNF antagonist, subjects on vedolizumab had an 88% rate of adverse events and a 17% rate of serious adverse events, compared with 84% and 11%, respectively, for those on placebo.
“It is notable that, in maintenance, the absolute remission rates were substantially lower in the TNF failure population for both vedolizumab-treated and placebo-treated patients,” the investigators noted, positing that “The relatively low placebo response rate in the TNF-failure group could be attributed to the presence of a greater proportion of patients with more refractory disease and poor prognostic factors, such as pancolitis and long disease duration.”
The study was funded by Millennium Pharmaceuticals. Dr. Feagan disclosed serving as a consultant and receiving financial support for research from Millennium and other companies. No other coauthors reported relevant financial disclosures.
When treating patients for ulcerative colitis (UC), clinicians should consider using vedolizumab, because the drug has been found to be both safe and highly effective in patients who have never received tumor necrosis factor (TNF)–antagonist treatment and those who have but did not benefit from it, according to a study published in the February issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.08.044).
“Approximately 50% of patients with UC do not respond to induction therapy with TNF antagonists or lose response over time such that after 1 year of treatment, clinical remission is observed in only 17%-34% of patients,” explained the authors of the report, led by Brian G. Feagan, MD, of the University of Western Ontario in London. “Furthermore, the risk of serious infection (with immunosuppressants in general, and TNF antagonists specifically) is an important concern [so] alternative approaches to treatment are needed.”
For this study, Dr. Feagan and his colleagues turned to the GEMINI 1 trial, which evaluated vedolizumab in patients with moderate and severe UC via a multicenter, phase III, randomized, placebo-controlled trial. This study produced data on 374 subjects who had been randomized into cohorts receiving either vedolizumab intravenously or a placebo. However, this number was deemed too low, so a further 521 patients were enrolled for an open-label study and randomized in the same 3:2 ratio as the previous study. The former study was called Cohort 1 and the latter called Cohort 2.
“Eligible patients had UC for [at least] 6 months before enrollment, MCS [Mayo Clinic scores for disease activity] from 6 to 12, and endoscopic subscores of [at least] 2 within 7 days before the first dose of study drug, and evidence of disease extending [at least] 15 cm proximal to the rectum,” the authors explained.
Vedolizumab was administered at baseline, with follow-up evaluations at 2, 4, and 6 weeks. Subjects who experienced a clinical response – defined as an MCS reduction of at least 3 points and 30%, along with at least a 1-point reduction in rectal bleeding and an absolute rectal bleeding subscore of either 0 or 1 – were re-randomized into cohorts that received the drug every 4 weeks or every 8 weeks, for a period of up to 46 weeks. The total length of the study was, therefore, 52 weeks; for patients that were re-randomized, follow-up evaluations took place every 4 weeks.
A total of 464 patients who were enrolled and completed the study were naive to TNF antagonists, while 367 had previously been treated with TNF antagonists unsuccessfully. At 6-week follow-up, 53.1% of naive subjects receiving vedolizumab had achieved clinical response, versus 26.3% of naive subjects on placebo (absolute difference, 26.4%; 95% confidence interval, 12.4-40.4). Similarly, those with previous TNF antagonist exposure who were given vedolizumab had a 39.0% clinical response rate, versus 20.6% of those on placebo (AD, 18.1%; 95% CI, 2.8-33.5).
At week 52, naive subjects on vedolizumab continued to have far higher rates of clinical response than did those on placebo, with 46.9% and 19.0%, respectively (AD, 28.0%; 95% CI, 14.9-41.1). For those with previous TNF antagonist exposure, the disparity between vedolizumab and placebo was similarly profound: 36.1% versus 5.3%, respectively (AD, 29.5%; 95% CI, 12.8-46.1).
Adverse event rates between naive and previously exposed patients were not significantly different, according to the findings. In naive patients, 74% of those on vedolizumab experienced an adverse event, and 9% experienced a serious adverse event. For those on placebo, those rates were 75% and 16%, respectively. For patients who had previously been on a TNF antagonist, subjects on vedolizumab had an 88% rate of adverse events and a 17% rate of serious adverse events, compared with 84% and 11%, respectively, for those on placebo.
“It is notable that, in maintenance, the absolute remission rates were substantially lower in the TNF failure population for both vedolizumab-treated and placebo-treated patients,” the investigators noted, positing that “The relatively low placebo response rate in the TNF-failure group could be attributed to the presence of a greater proportion of patients with more refractory disease and poor prognostic factors, such as pancolitis and long disease duration.”
The study was funded by Millennium Pharmaceuticals. Dr. Feagan disclosed serving as a consultant and receiving financial support for research from Millennium and other companies. No other coauthors reported relevant financial disclosures.
When treating patients for ulcerative colitis (UC), clinicians should consider using vedolizumab, because the drug has been found to be both safe and highly effective in patients who have never received tumor necrosis factor (TNF)–antagonist treatment and those who have but did not benefit from it, according to a study published in the February issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.08.044).
“Approximately 50% of patients with UC do not respond to induction therapy with TNF antagonists or lose response over time such that after 1 year of treatment, clinical remission is observed in only 17%-34% of patients,” explained the authors of the report, led by Brian G. Feagan, MD, of the University of Western Ontario in London. “Furthermore, the risk of serious infection (with immunosuppressants in general, and TNF antagonists specifically) is an important concern [so] alternative approaches to treatment are needed.”
For this study, Dr. Feagan and his colleagues turned to the GEMINI 1 trial, which evaluated vedolizumab in patients with moderate and severe UC via a multicenter, phase III, randomized, placebo-controlled trial. This study produced data on 374 subjects who had been randomized into cohorts receiving either vedolizumab intravenously or a placebo. However, this number was deemed too low, so a further 521 patients were enrolled for an open-label study and randomized in the same 3:2 ratio as the previous study. The former study was called Cohort 1 and the latter called Cohort 2.
“Eligible patients had UC for [at least] 6 months before enrollment, MCS [Mayo Clinic scores for disease activity] from 6 to 12, and endoscopic subscores of [at least] 2 within 7 days before the first dose of study drug, and evidence of disease extending [at least] 15 cm proximal to the rectum,” the authors explained.
Vedolizumab was administered at baseline, with follow-up evaluations at 2, 4, and 6 weeks. Subjects who experienced a clinical response – defined as an MCS reduction of at least 3 points and 30%, along with at least a 1-point reduction in rectal bleeding and an absolute rectal bleeding subscore of either 0 or 1 – were re-randomized into cohorts that received the drug every 4 weeks or every 8 weeks, for a period of up to 46 weeks. The total length of the study was, therefore, 52 weeks; for patients that were re-randomized, follow-up evaluations took place every 4 weeks.
A total of 464 patients who were enrolled and completed the study were naive to TNF antagonists, while 367 had previously been treated with TNF antagonists unsuccessfully. At 6-week follow-up, 53.1% of naive subjects receiving vedolizumab had achieved clinical response, versus 26.3% of naive subjects on placebo (absolute difference, 26.4%; 95% confidence interval, 12.4-40.4). Similarly, those with previous TNF antagonist exposure who were given vedolizumab had a 39.0% clinical response rate, versus 20.6% of those on placebo (AD, 18.1%; 95% CI, 2.8-33.5).
At week 52, naive subjects on vedolizumab continued to have far higher rates of clinical response than did those on placebo, with 46.9% and 19.0%, respectively (AD, 28.0%; 95% CI, 14.9-41.1). For those with previous TNF antagonist exposure, the disparity between vedolizumab and placebo was similarly profound: 36.1% versus 5.3%, respectively (AD, 29.5%; 95% CI, 12.8-46.1).
Adverse event rates between naive and previously exposed patients were not significantly different, according to the findings. In naive patients, 74% of those on vedolizumab experienced an adverse event, and 9% experienced a serious adverse event. For those on placebo, those rates were 75% and 16%, respectively. For patients who had previously been on a TNF antagonist, subjects on vedolizumab had an 88% rate of adverse events and a 17% rate of serious adverse events, compared with 84% and 11%, respectively, for those on placebo.
“It is notable that, in maintenance, the absolute remission rates were substantially lower in the TNF failure population for both vedolizumab-treated and placebo-treated patients,” the investigators noted, positing that “The relatively low placebo response rate in the TNF-failure group could be attributed to the presence of a greater proportion of patients with more refractory disease and poor prognostic factors, such as pancolitis and long disease duration.”
The study was funded by Millennium Pharmaceuticals. Dr. Feagan disclosed serving as a consultant and receiving financial support for research from Millennium and other companies. No other coauthors reported relevant financial disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point:
Major finding: Response to vedolizumab in patients new to TNF antagonists was 53.1%, versus 26.3% in the placebo cohort; patients who failed TNF antagonist treatment previously had a 39.0% response rate to vedolizumab, versus 20.6% on placebo.
Data source: Post-hoc cohort analysis of 831 UC patients from the GEMINI 1 study population.
Disclosures: Funding provided by Millennium Pharmaceuticals. Dr. Feagan disclosed potential conflicts of interest.
What Are Safe and Efficacious Therapies for Restless Legs Syndrome in Adults?
The American Academy of Neurology (AAN) has published evidence-based recommendations for management of restless legs syndrome (RLS) in adults. The practice guideline was published online ahead of print November 16, 2016, in Neurology. The practice guideline addresses the question: What are safe and effective therapies, including both pharmacologic and nonpharmacologic approaches, for the symptoms and clinical consequences (eg, disturbed sleep, periodic limb movements in sleep, depression/anxiety, and decreased quality of life) of RLS in adults.
“When addressing RLS, clinicians and patients must first determine whether symptoms require treatment, the setting in which this practice guideline is relevant,” said John W. Winkelman, MD, PhD, and colleagues. Dr. Winkelman is an Associate Professor of Psychiatry at Harvard Medical School and Medical Director of the Sleep Health Center of Brigham and Women’s Hospital in Boston.
“Treatment should be considered if RLS symptoms interfere with sleep or daytime function to an important degree,” the guideline authors said. “Before determining the best treatment, it is important to first ensure there are no contributing factors to RLS symptoms (eg, iron deficiency or serotonergic antidepressants). The guidelines advise clinicians to consider prescribing a pharmacologic agent to reduce RLS symptoms in patients with moderate to severe primary RLS. There is strong (Level A) evidence for use of pramipexole, rotigotine, cabergoline, and gabapentin enacarbil; moderate evidence (Level B) supports ropinirole, pregabalin, and IV ferric carboxymaltose; and weak evidence (Level C) supports levodopa. When considering efficacy alone, clinicians may prefer cabergoline. It is rarely used in clinical practice for RLS, however, because it is associated with a risk of cardiac valvulopathy. Clinicians are also advised to consider the augmentation risks associated with dopaminergic agents.
For patients with periodic limb movement disorder, there is strong (Level A) evidence supporting ropinirole. Moderate evidence (Level B) supports pramipexole, rotigotine, cabergoline, and pregabalin; and weak evidence (Level C) supporting levodopa. The authors note insufficient evidence (Level U) for gabapentin enacarbil and ferric carboxymaltose. With regard to objective sleep measures (eg, total sleep time, sleep efficiency, sleep latency, wake after sleep onset) there is moderate evidence (Level B) supporting ropinirole, gabapentin, encarbil, and pregabalin. However, there is insufficient evidence (Level U) supporting pamipexole, rotigotine, cabergoline, or levodopa.
For subjective sleep measures, cabergoline and gabapentin enacarbil have Level A evidence; ropinirole, pramipexole, rotigotine, and pregabalin have Level B evidence; and levodopa and prolonged-release oxycodone/naloxone, and vibratory stimulation have Level C evidence. Insufficient evidence (Level U) exists for ferric carboxymaltose and iron sucrose.When patients with RLS fail to respond to other treatments, clinicians are advised to consider prescribing prolonged-release oxycodone/naloxone (Level C) or to consider nonpharmacologic options, including pneumatic compression (Level B), infrared spectroscopy or transcranial magnetic stimulation (Level C), and vibrating pads (Level C).
For iron-deficient patients with RLS (ferritin levels ≤ 75 µg/L), clinicians are advised to prescribe ferrous sulfate with vitamin C. In patients on hemodialysis with secondary RLS, clinicians are advised to prescribe vitamin C and E supplementation (Level B), ropinirole, levodopa, or exercise (Level C).
—Erica Tricarico
Suggested Reading
Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: treatment of restless legs syndrome in adults: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016 Nov 16 [Epub ahead of print].
The American Academy of Neurology (AAN) has published evidence-based recommendations for management of restless legs syndrome (RLS) in adults. The practice guideline was published online ahead of print November 16, 2016, in Neurology. The practice guideline addresses the question: What are safe and effective therapies, including both pharmacologic and nonpharmacologic approaches, for the symptoms and clinical consequences (eg, disturbed sleep, periodic limb movements in sleep, depression/anxiety, and decreased quality of life) of RLS in adults.
“When addressing RLS, clinicians and patients must first determine whether symptoms require treatment, the setting in which this practice guideline is relevant,” said John W. Winkelman, MD, PhD, and colleagues. Dr. Winkelman is an Associate Professor of Psychiatry at Harvard Medical School and Medical Director of the Sleep Health Center of Brigham and Women’s Hospital in Boston.
“Treatment should be considered if RLS symptoms interfere with sleep or daytime function to an important degree,” the guideline authors said. “Before determining the best treatment, it is important to first ensure there are no contributing factors to RLS symptoms (eg, iron deficiency or serotonergic antidepressants). The guidelines advise clinicians to consider prescribing a pharmacologic agent to reduce RLS symptoms in patients with moderate to severe primary RLS. There is strong (Level A) evidence for use of pramipexole, rotigotine, cabergoline, and gabapentin enacarbil; moderate evidence (Level B) supports ropinirole, pregabalin, and IV ferric carboxymaltose; and weak evidence (Level C) supports levodopa. When considering efficacy alone, clinicians may prefer cabergoline. It is rarely used in clinical practice for RLS, however, because it is associated with a risk of cardiac valvulopathy. Clinicians are also advised to consider the augmentation risks associated with dopaminergic agents.
For patients with periodic limb movement disorder, there is strong (Level A) evidence supporting ropinirole. Moderate evidence (Level B) supports pramipexole, rotigotine, cabergoline, and pregabalin; and weak evidence (Level C) supporting levodopa. The authors note insufficient evidence (Level U) for gabapentin enacarbil and ferric carboxymaltose. With regard to objective sleep measures (eg, total sleep time, sleep efficiency, sleep latency, wake after sleep onset) there is moderate evidence (Level B) supporting ropinirole, gabapentin, encarbil, and pregabalin. However, there is insufficient evidence (Level U) supporting pamipexole, rotigotine, cabergoline, or levodopa.
For subjective sleep measures, cabergoline and gabapentin enacarbil have Level A evidence; ropinirole, pramipexole, rotigotine, and pregabalin have Level B evidence; and levodopa and prolonged-release oxycodone/naloxone, and vibratory stimulation have Level C evidence. Insufficient evidence (Level U) exists for ferric carboxymaltose and iron sucrose.When patients with RLS fail to respond to other treatments, clinicians are advised to consider prescribing prolonged-release oxycodone/naloxone (Level C) or to consider nonpharmacologic options, including pneumatic compression (Level B), infrared spectroscopy or transcranial magnetic stimulation (Level C), and vibrating pads (Level C).
For iron-deficient patients with RLS (ferritin levels ≤ 75 µg/L), clinicians are advised to prescribe ferrous sulfate with vitamin C. In patients on hemodialysis with secondary RLS, clinicians are advised to prescribe vitamin C and E supplementation (Level B), ropinirole, levodopa, or exercise (Level C).
—Erica Tricarico
Suggested Reading
Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: treatment of restless legs syndrome in adults: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016 Nov 16 [Epub ahead of print].
The American Academy of Neurology (AAN) has published evidence-based recommendations for management of restless legs syndrome (RLS) in adults. The practice guideline was published online ahead of print November 16, 2016, in Neurology. The practice guideline addresses the question: What are safe and effective therapies, including both pharmacologic and nonpharmacologic approaches, for the symptoms and clinical consequences (eg, disturbed sleep, periodic limb movements in sleep, depression/anxiety, and decreased quality of life) of RLS in adults.
“When addressing RLS, clinicians and patients must first determine whether symptoms require treatment, the setting in which this practice guideline is relevant,” said John W. Winkelman, MD, PhD, and colleagues. Dr. Winkelman is an Associate Professor of Psychiatry at Harvard Medical School and Medical Director of the Sleep Health Center of Brigham and Women’s Hospital in Boston.
“Treatment should be considered if RLS symptoms interfere with sleep or daytime function to an important degree,” the guideline authors said. “Before determining the best treatment, it is important to first ensure there are no contributing factors to RLS symptoms (eg, iron deficiency or serotonergic antidepressants). The guidelines advise clinicians to consider prescribing a pharmacologic agent to reduce RLS symptoms in patients with moderate to severe primary RLS. There is strong (Level A) evidence for use of pramipexole, rotigotine, cabergoline, and gabapentin enacarbil; moderate evidence (Level B) supports ropinirole, pregabalin, and IV ferric carboxymaltose; and weak evidence (Level C) supports levodopa. When considering efficacy alone, clinicians may prefer cabergoline. It is rarely used in clinical practice for RLS, however, because it is associated with a risk of cardiac valvulopathy. Clinicians are also advised to consider the augmentation risks associated with dopaminergic agents.
For patients with periodic limb movement disorder, there is strong (Level A) evidence supporting ropinirole. Moderate evidence (Level B) supports pramipexole, rotigotine, cabergoline, and pregabalin; and weak evidence (Level C) supporting levodopa. The authors note insufficient evidence (Level U) for gabapentin enacarbil and ferric carboxymaltose. With regard to objective sleep measures (eg, total sleep time, sleep efficiency, sleep latency, wake after sleep onset) there is moderate evidence (Level B) supporting ropinirole, gabapentin, encarbil, and pregabalin. However, there is insufficient evidence (Level U) supporting pamipexole, rotigotine, cabergoline, or levodopa.
For subjective sleep measures, cabergoline and gabapentin enacarbil have Level A evidence; ropinirole, pramipexole, rotigotine, and pregabalin have Level B evidence; and levodopa and prolonged-release oxycodone/naloxone, and vibratory stimulation have Level C evidence. Insufficient evidence (Level U) exists for ferric carboxymaltose and iron sucrose.When patients with RLS fail to respond to other treatments, clinicians are advised to consider prescribing prolonged-release oxycodone/naloxone (Level C) or to consider nonpharmacologic options, including pneumatic compression (Level B), infrared spectroscopy or transcranial magnetic stimulation (Level C), and vibrating pads (Level C).
For iron-deficient patients with RLS (ferritin levels ≤ 75 µg/L), clinicians are advised to prescribe ferrous sulfate with vitamin C. In patients on hemodialysis with secondary RLS, clinicians are advised to prescribe vitamin C and E supplementation (Level B), ropinirole, levodopa, or exercise (Level C).
—Erica Tricarico
Suggested Reading
Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: treatment of restless legs syndrome in adults: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016 Nov 16 [Epub ahead of print].
