Facebook, Twitter, Instagram, Snapchat, YouTube, blogs, webpages, Google+, LinkedIn. What do all of these social media outlets have in common? Each can get physicians in trouble under the Health Insurance Portability and Accountability Act (HIPAA), state privacy laws, and state medical laws, to name a few. It seems that all too often, news outlets are reporting data breaches generated in the medical community, many of which arise out of physicians’ use of social media, and most of which could have been avoided.

Physicians should be aware of the intersection of social media—both for personal and professional use—and HIPAA and state laws. Even an inadvertent, seemingly innocuous disclosure of a patient’s protected health information (PHI) through social media can be problematic.

PHI is defined under HIPAA, in part, as health information that (i) is created or received by a physician, (ii) relates to the health or condition of an individual, (iii) identifies the individual (or with respect to which there is a reasonable basis to believe the information can be used to identify the individual), and (iv) is transmitted by or maintained in electronic media, or transmitted or maintained in another form or medium. Under HIPAA, a physician may use and disclose PHI for “treatment, payment, or healthcare operations.” Generally, using or disclosing PHI through social media does not qualify as treatment, payment, or healthcare operations. If a physician were to use or disclose a patient’s PHI without permission, this would be a violation of HIPAA—and likely state law as well.

In order to use or disclose a patient’s PHI without obtaining the patient’s consent, a physician must de-identify the information so that the information does not identify the patient and there is no reasonable basis to believe that the information can be used to identify the patient. One option under HIPAA is to retain an expert to determine “that the risk is very small that the information could be used, alone or in combination with other reasonably available information, by an anticipated recipient to identify an individual who is the subject of the information.” Alternatively, and more commonly, a physician seeking to use or disclose patient PHI can remove the following identifiers from the PHI:

1. Names;
2. Geographic information;
3. Dates (e.g. birth date, admission date, discharge date, date of death);
4. Telephone numbers;
5. Fax numbers;
6. E-mail addresses;
7. Social Security numbers;
8. Medical record numbers;
9. Health plan beneficiary numbers;
10. Account numbers;
11. Certificate/license numbers;
12. Vehicle identifiers and serial numbers, including license plate numbers;
13. Device identifiers and serial numbers;
14. URLs;
15. IP address numbers;
16. Biometric identifiers (e.g. finger and voice prints);
17. Full-face photographic images and any comparable images; and
18. Other unique identifying numbers, characteristics, or codes.

Identifier #18 is the most difficult to comply with in light of the significant amount of personal information available on the Internet, particularly through search engines like Google. Inputting even a small amount of information into a search engine will generate relevant “hits” that make it increasingly difficult to comply with the de-identification standards under HIPAA. Even if the first 17 identifiers are carefully removed, the broadness of #18 can turn a seemingly harmless post on social media into a patient privacy violation.

Do not let the following examples be you:

Example 1: An ED physician in Rhode Island was fired, lost her hospital medical staff privileges, and was reprimanded by the Rhode Island Board of Medical Licensure and Discipline for posting information about a trauma patient on her personal Facebook page. According to the Rhode Island Board of Medical Licensure and Discipline, “[She] did not use patient names and had no intention to reveal any confidential patient information. However, because of the nature of one person’s injury … the patient was identified by unauthorized third parties. As soon as it was brought to [her] attention that this had occurred, [she] deleted her Facebook account.” Despite the physician leaving out all information she thought might make the patient identifiable, she apparently did not omit enough.

Example 2: An OB-GYN in St. Louis took to Facebook to complain about her frustration with a patient: “So I have a patient who has chosen to either no-show or be late (sometimes hours) for all of her prenatal visits, ultrasounds, and NSTs. She is now 3 hours late for her induction. May I show up late to her delivery?” Another physician then commented on this post: “If it’s elective, it’d be canceled!” The OB-GYN at issue then responded: “Here is the explanation why I have put up with it/not cancelled induction: prior stillbirth.”

Although the OB-GYN did not reveal the patient’s name, controversy erupted after someone posted a screenshot of the post and response comments to the hospital’s Facebook page. The hospital issued a statement indicating that its privacy compliance staff did not find the posting to be a breach of privacy, but the hospital added it would use this opportunity to educate its staff about the appropriate use of social media. Many believe this physician got off too easy.

The penalties for patient privacy violations (or even alleged patient privacy violations) are multifaceted. Not only can the federal government impose civil and criminal sanctions under HIPAA on the physician and his/her affiliated parties (e.g. physician’s employer), but states can also impose penalties. State-imposed penalties for patient privacy violations vary from state to state. Additionally, the patient may sue the violating physician and his/her affiliated parties for privacy violations. Although HIPAA does not afford patients the right to bring a private cause of action against a physician, state law often does grant patients such a right. Also, state medical boards often have the right to impose penalties, monetary and non-monetary, on a physician for privacy violations. These can include suspension or termination of medical licensure.

Recent reports indicate that people who “like,” “share,” “re-tweet,” or comment on inappropriate social media posts are also getting reprimanded. Finally, the reputational harm associated with an inappropriate post on social media is immeasurable, especially in light of the availability of information on the Internet. Unfortunately, when the physicians described above enter their names in a search engine, they do not see their professional accomplishments and prestigious educations; instead, their top hits are news articles reporting on their inappropriate posts.

Post with caution.

Steven M. Harris, Esq., is a nationally recognized healthcare attorney and a member of the law firm McDonald Hopkins LLC in Chicago. Write to him at sharris@mcdonaldhopkins.com.

Facebook, Twitter, Instagram, Snapchat, YouTube, blogs, webpages, Google+, LinkedIn. What do all of these social media outlets have in common? Each can get physicians in trouble under the Health Insurance Portability and Accountability Act (HIPAA), state privacy laws, and state medical laws, to name a few. It seems that all too often, news outlets are reporting data breaches generated in the medical community, many of which arise out of physicians’ use of social media, and most of which could have been avoided.

Physicians should be aware of the intersection of social media—both for personal and professional use—and HIPAA and state laws. Even an inadvertent, seemingly innocuous disclosure of a patient’s protected health information (PHI) through social media can be problematic.

PHI is defined under HIPAA, in part, as health information that (i) is created or received by a physician, (ii) relates to the health or condition of an individual, (iii) identifies the individual (or with respect to which there is a reasonable basis to believe the information can be used to identify the individual), and (iv) is transmitted by or maintained in electronic media, or transmitted or maintained in another form or medium. Under HIPAA, a physician may use and disclose PHI for “treatment, payment, or healthcare operations.” Generally, using or disclosing PHI through social media does not qualify as treatment, payment, or healthcare operations. If a physician were to use or disclose a patient’s PHI without permission, this would be a violation of HIPAA—and likely state law as well.

In order to use or disclose a patient’s PHI without obtaining the patient’s consent, a physician must de-identify the information so that the information does not identify the patient and there is no reasonable basis to believe that the information can be used to identify the patient. One option under HIPAA is to retain an expert to determine “that the risk is very small that the information could be used, alone or in combination with other reasonably available information, by an anticipated recipient to identify an individual who is the subject of the information.” Alternatively, and more commonly, a physician seeking to use or disclose patient PHI can remove the following identifiers from the PHI:

1. Names;
2. Geographic information;
3. Dates (e.g. birth date, admission date, discharge date, date of death);
4. Telephone numbers;
5. Fax numbers;
6. E-mail addresses;
7. Social Security numbers;
8. Medical record numbers;
9. Health plan beneficiary numbers;
10. Account numbers;
11. Certificate/license numbers;
12. Vehicle identifiers and serial numbers, including license plate numbers;
13. Device identifiers and serial numbers;
14. URLs;
15. IP address numbers;
16. Biometric identifiers (e.g. finger and voice prints);
17. Full-face photographic images and any comparable images; and
18. Other unique identifying numbers, characteristics, or codes.

Identifier #18 is the most difficult to comply with in light of the significant amount of personal information available on the Internet, particularly through search engines like Google. Inputting even a small amount of information into a search engine will generate relevant “hits” that make it increasingly difficult to comply with the de-identification standards under HIPAA. Even if the first 17 identifiers are carefully removed, the broadness of #18 can turn a seemingly harmless post on social media into a patient privacy violation.

Do not let the following examples be you:

Example 1: An ED physician in Rhode Island was fired, lost her hospital medical staff privileges, and was reprimanded by the Rhode Island Board of Medical Licensure and Discipline for posting information about a trauma patient on her personal Facebook page. According to the Rhode Island Board of Medical Licensure and Discipline, “[She] did not use patient names and had no intention to reveal any confidential patient information. However, because of the nature of one person’s injury … the patient was identified by unauthorized third parties. As soon as it was brought to [her] attention that this had occurred, [she] deleted her Facebook account.” Despite the physician leaving out all information she thought might make the patient identifiable, she apparently did not omit enough.

Example 2: An OB-GYN in St. Louis took to Facebook to complain about her frustration with a patient: “So I have a patient who has chosen to either no-show or be late (sometimes hours) for all of her prenatal visits, ultrasounds, and NSTs. She is now 3 hours late for her induction. May I show up late to her delivery?” Another physician then commented on this post: “If it’s elective, it’d be canceled!” The OB-GYN at issue then responded: “Here is the explanation why I have put up with it/not cancelled induction: prior stillbirth.”

Although the OB-GYN did not reveal the patient’s name, controversy erupted after someone posted a screenshot of the post and response comments to the hospital’s Facebook page. The hospital issued a statement indicating that its privacy compliance staff did not find the posting to be a breach of privacy, but the hospital added it would use this opportunity to educate its staff about the appropriate use of social media. Many believe this physician got off too easy.

The penalties for patient privacy violations (or even alleged patient privacy violations) are multifaceted. Not only can the federal government impose civil and criminal sanctions under HIPAA on the physician and his/her affiliated parties (e.g. physician’s employer), but states can also impose penalties. State-imposed penalties for patient privacy violations vary from state to state. Additionally, the patient may sue the violating physician and his/her affiliated parties for privacy violations. Although HIPAA does not afford patients the right to bring a private cause of action against a physician, state law often does grant patients such a right. Also, state medical boards often have the right to impose penalties, monetary and non-monetary, on a physician for privacy violations. These can include suspension or termination of medical licensure.

Recent reports indicate that people who “like,” “share,” “re-tweet,” or comment on inappropriate social media posts are also getting reprimanded. Finally, the reputational harm associated with an inappropriate post on social media is immeasurable, especially in light of the availability of information on the Internet. Unfortunately, when the physicians described above enter their names in a search engine, they do not see their professional accomplishments and prestigious educations; instead, their top hits are news articles reporting on their inappropriate posts.

Post with caution.

Steven M. Harris, Esq., is a nationally recognized healthcare attorney and a member of the law firm McDonald Hopkins LLC in Chicago. Write to him at sharris@mcdonaldhopkins.com.

Facebook, Twitter, Instagram, Snapchat, YouTube, blogs, webpages, Google+, LinkedIn. What do all of these social media outlets have in common? Each can get physicians in trouble under the Health Insurance Portability and Accountability Act (HIPAA), state privacy laws, and state medical laws, to name a few. It seems that all too often, news outlets are reporting data breaches generated in the medical community, many of which arise out of physicians’ use of social media, and most of which could have been avoided.

Physicians should be aware of the intersection of social media—both for personal and professional use—and HIPAA and state laws. Even an inadvertent, seemingly innocuous disclosure of a patient’s protected health information (PHI) through social media can be problematic.

PHI is defined under HIPAA, in part, as health information that (i) is created or received by a physician, (ii) relates to the health or condition of an individual, (iii) identifies the individual (or with respect to which there is a reasonable basis to believe the information can be used to identify the individual), and (iv) is transmitted by or maintained in electronic media, or transmitted or maintained in another form or medium. Under HIPAA, a physician may use and disclose PHI for “treatment, payment, or healthcare operations.” Generally, using or disclosing PHI through social media does not qualify as treatment, payment, or healthcare operations. If a physician were to use or disclose a patient’s PHI without permission, this would be a violation of HIPAA—and likely state law as well.

In order to use or disclose a patient’s PHI without obtaining the patient’s consent, a physician must de-identify the information so that the information does not identify the patient and there is no reasonable basis to believe that the information can be used to identify the patient. One option under HIPAA is to retain an expert to determine “that the risk is very small that the information could be used, alone or in combination with other reasonably available information, by an anticipated recipient to identify an individual who is the subject of the information.” Alternatively, and more commonly, a physician seeking to use or disclose patient PHI can remove the following identifiers from the PHI:

1. Names;
2. Geographic information;
3. Dates (e.g. birth date, admission date, discharge date, date of death);
4. Telephone numbers;
5. Fax numbers;
6. E-mail addresses;
7. Social Security numbers;
8. Medical record numbers;
9. Health plan beneficiary numbers;
10. Account numbers;
11. Certificate/license numbers;
12. Vehicle identifiers and serial numbers, including license plate numbers;
13. Device identifiers and serial numbers;
14. URLs;
15. IP address numbers;
16. Biometric identifiers (e.g. finger and voice prints);
17. Full-face photographic images and any comparable images; and
18. Other unique identifying numbers, characteristics, or codes.

Identifier #18 is the most difficult to comply with in light of the significant amount of personal information available on the Internet, particularly through search engines like Google. Inputting even a small amount of information into a search engine will generate relevant “hits” that make it increasingly difficult to comply with the de-identification standards under HIPAA. Even if the first 17 identifiers are carefully removed, the broadness of #18 can turn a seemingly harmless post on social media into a patient privacy violation.

Do not let the following examples be you:

Example 1: An ED physician in Rhode Island was fired, lost her hospital medical staff privileges, and was reprimanded by the Rhode Island Board of Medical Licensure and Discipline for posting information about a trauma patient on her personal Facebook page. According to the Rhode Island Board of Medical Licensure and Discipline, “[She] did not use patient names and had no intention to reveal any confidential patient information. However, because of the nature of one person’s injury … the patient was identified by unauthorized third parties. As soon as it was brought to [her] attention that this had occurred, [she] deleted her Facebook account.” Despite the physician leaving out all information she thought might make the patient identifiable, she apparently did not omit enough.

Example 2: An OB-GYN in St. Louis took to Facebook to complain about her frustration with a patient: “So I have a patient who has chosen to either no-show or be late (sometimes hours) for all of her prenatal visits, ultrasounds, and NSTs. She is now 3 hours late for her induction. May I show up late to her delivery?” Another physician then commented on this post: “If it’s elective, it’d be canceled!” The OB-GYN at issue then responded: “Here is the explanation why I have put up with it/not cancelled induction: prior stillbirth.”

Although the OB-GYN did not reveal the patient’s name, controversy erupted after someone posted a screenshot of the post and response comments to the hospital’s Facebook page. The hospital issued a statement indicating that its privacy compliance staff did not find the posting to be a breach of privacy, but the hospital added it would use this opportunity to educate its staff about the appropriate use of social media. Many believe this physician got off too easy.

The penalties for patient privacy violations (or even alleged patient privacy violations) are multifaceted. Not only can the federal government impose civil and criminal sanctions under HIPAA on the physician and his/her affiliated parties (e.g. physician’s employer), but states can also impose penalties. State-imposed penalties for patient privacy violations vary from state to state. Additionally, the patient may sue the violating physician and his/her affiliated parties for privacy violations. Although HIPAA does not afford patients the right to bring a private cause of action against a physician, state law often does grant patients such a right. Also, state medical boards often have the right to impose penalties, monetary and non-monetary, on a physician for privacy violations. These can include suspension or termination of medical licensure.

Recent reports indicate that people who “like,” “share,” “re-tweet,” or comment on inappropriate social media posts are also getting reprimanded. Finally, the reputational harm associated with an inappropriate post on social media is immeasurable, especially in light of the availability of information on the Internet. Unfortunately, when the physicians described above enter their names in a search engine, they do not see their professional accomplishments and prestigious educations; instead, their top hits are news articles reporting on their inappropriate posts.

Post with caution.

Steven M. Harris, Esq., is a nationally recognized healthcare attorney and a member of the law firm McDonald Hopkins LLC in Chicago. Write to him at sharris@mcdonaldhopkins.com.

When diagnosing a patient, it can be tempting to run all types of tests to expedite the process—and protect yourself from litigation. Patients may push for more tests, too, thinking “the more the better.” But that may not be the best course of action. In fact, according to recommendations of the ABIM Foundations’ Choosing Wisely campaign, more tests can actually bring a host of negative consequences.

In an effort to help hospitalists decide which tests to perform and which to forgo, The Hospitalist asked medical societies that contributed to the Choosing Wisely campaign to tell us which one of their recommendations was the most applicable to hospitalists. Then, we asked some hospitalists to discuss how they might implement each recommendation.

1 American Gastroenterological Association (AGA)

Recommendation: For a patient with functional abdominal pain syndrome (as per Rome criteria), computed tomography (CT) scans should not be repeated unless there is a major change in clinical findings or symptoms.

When a patient first complains of abdominal pain, a CT scan usually is done prior to a gastroenterological consultation. Despite this initial scan, many patients with chronic abdominal pain receive unnecessary repeated CT scans to evaluate their pain even if they have previous negative studies.

“It is important for the hospitalist to know that functional abdominal pain can be managed without additional diagnostic studies,” says John M. Inadomi, MD, head of the division of gastroenterology at the University of Washington School of Medicine in Seattle. “Some doctors are uncomfortable with the uncertainty of a diagnosis of chronic abdominal pain without evidence of biochemical or structural disease [functional abdominal pain syndrome] and fear litigation.”

An abdominal CT scan is one of the higher radiation exposure tests, equivalent to three years of natural background radiation.¹

“Due to this risk and the high costs of this procedure, CT scans should be limited to situations in which they are likely to provide useful information that changes patient management,” Dr. Inadomi says.

According to Moises Auron, MD, FAAP, FACP, SFHM, assistant professor of medicine and pediatrics at Cleveland Clinic Lerner College of Medicine of Case Western University in Cleveland, Ohio, it should not be a difficult choice for hospitalists, “as the clinical context provides a safeguard to justify the rationale for a conservative approach. Hospitalists must be educated on the appropriate use of Rome criteria, as well as how to appropriately document it in the chart to justify a decision to avoid unnecessary testing.”

2 American College of Rheumatology (ACR)

Recommendation: Don’t test anti-nuclear antibody (ANA) sub-serologies without a positive ANA and clinical suspicion of immune-mediated disease.

“A fever of unknown origin is among the most common diagnoses the hospitalist encounters,” Dr. Auron says. “Nowadays, given the ease to order tests, as well as the increased awareness of patients with immune-mediated diseases, it may be tempting to order large panels of immunologic tests to minimize the risk of missing a diagnosis; however, because ANA has high sensitivity and poor specificity, it should only be ordered if the clinical context supports its use.”

Jinoos Yazdany, MD, MPH, assistant professor of medicine at the University of California at San Francisco and co-chair of the task force that developed the ACR’s Choosing Wisely list, points out that if you use ANAs as a broad screening test when the pretest probability of specific ANA-associated diseases is low, there is an increased chance of a false positive ANA result. This can lead to unnecessary further testing and additional costs. Furthermore, ANA sub-serologies are usually negative if the ANA (done by immunofluorescence) is negative.

“So it is recommended to order sub-serologies only once it is known that the ANA is positive,” she says. The exceptions to this are anti-SSA and anti-Jo-1 antibodies, which can sometimes be positive when the ANA is negative.

Mangla S. Gulati, MD, FACP, FHM, medical director for clinical effectiveness at the University of Maryland School of Medicine in Baltimore, says a positive ANA in conjunction with clinical information “will help to guide appropriate and cost-conscious testing. Hospitalists could implement this through a clinical decision support approach if using an electronic medical record.”

LISTEN NOW to Daniel Wolfson, MHSA, executive vice president and CEO of the ABIM Foundation, discuss how the Choosing Wisely campaign got started and its significance in U.S. healthcare.

3 American College of Physicians (ACP)

Recommendation: In patients with low pretest probability of venous thromboembolism (VTE), obtain a high-sensitive D-dimer measurement as the initial diagnostic test; don’t obtain imaging studies as the initial diagnostic test.

VTE, a common problem in hospitalized patients, has high mortality rates. “However, recent statistics suggest that we may be overdiagnosing non-clinically significant disease and exposing large numbers of patients to high doses of radiation unnecessarily in an attempt to rule out VTE disease,” says Cynthia D. Smith, MD, FACP, ACP senior medical associate for content development and adjunct associate professor of medicine at the Perelman School of Medicine in Philadelphia.

Instead, physicians should estimate pretest probability of disease using a validated risk assessment tool (i.e., Wells score). For patients with low clinical probability of VTE, hospitalists should use a negative high-sensitive D-dimer measurement as the initial diagnostic test.

Dr. Auron says the litigious environment of American medicine may trigger clinicians to order testing to minimize the risk of missing potential conditions; however, an adequate, evidence-based approach with appropriate documentation should be sufficient. In this case, that would entail using D-dimer testing to outline the low pretest probability of VTE and explaining to the patient the rationale for not pursuing further imaging.

Dr. Gulati adds that hospitalists should have little difficulty implementing this cost-effective approach.

“A reasonable way to justify the increased availability of the nuclear medicine department would be to document the number of CT chest scans done after hours in patients who would have instead had a V/Q scan.”

—Moises Auron, MD, FAAP, FACP, SFHM, assistant professor of medicine and pediatrics, Cleveland Clinic

4 American Geriatrics Society (AGS)

Recommendation: Don’t use antimicrobials to treat bacteriuria in older adults unless specific urinary tract symptoms are present.

Older adults with asymptomatic bacteriuria who received antimicrobial treatment show no benefit, according to multiple studies.² In fact, increased adverse antimicrobial effects occurred, such as greater resistance patterns and super-infections (e.g. Clostridium difficile).

The truth is that as many as 30% of frail elders (particularly women) have bacterial colonization of the urinary tract without infection, also known as asymptomatic bacteriuria, says Heidi Wald, MD, MSPH, associate professor of medicine and vice chair for quality in the department of medicine at the University of Colorado School of Medicine in Aurora. Therefore, before being prescribed antimicrobials, a patient should exhibit symptoms of urinary tract infection such as fever, frequent urination, urgency to urinate, painful urination, or suprapubic tenderness.

“Without localizing symptoms, you can’t assume bacteriuria equals infection,” Dr. Wald adds. “Too often, we make the urine a scapegoat for unrelated presentations, such as mild confusion.”

If the patient is stable and doesn’t have UTI symptoms, Dr. Wald says hospitalists should consider hydration and monitor the patient without antibiotics.

“This should not be difficult to implement,” Dr. Auron says, “as hospitalists are on the front lines of antibiotic stewardship in hospitals.”

LISTEN NOW to Linda Cox, MD, owner of Allergy and Asthma Center in Ft. Lauderdale, Fla., and president of American Academy of Allergy, Asthma & Immunology, discuss why it's important for hospitalists to not diagnose or manage asthma without spirometry.

5 American Society of Echocardiography (ASE)

Recommendation: Avoid echocardiograms for pre-operative/peri-operative assessment of patients with no history or symptoms of heart disease.

Echocardiography can diagnose all types of heart disease while being completely safe, inexpensive, and available at the bedside.

“These features may logically lead hospitalists to think, ‘Why not?’ Maybe there’s something going on and an echo can’t hurt,” says James D. Thomas, MD, FASE, FACC, FAHA, FESC, Moore Chair of Cardiovascular Imaging at Cleveland Clinic and ASE past president. “Unfortunately, tests can have false positive findings that lead to other, potentially more hazardous and invasive, tests downstream, as well as unnecessary delays.”

If a patient has no history of heart disease, no positive physical findings, or no symptoms, then an echo probably won’t be helpful. Hospitalists need to be aware of the lack of value of a presumed normal study, Dr. Auron says.

“Having appropriate standards of care allows clinicians in pre-operative areas to use risk stratification tools in an adequate fashion,” he notes.

6 American Society of Nephrology (ASN)

Recommendation: Do not place peripherally inserted central venous catheters (PICC) in stage three to five chronic kidney disease (CKD) patients without consulting nephrology.

Given the increase in patients with CKD in the later stages, as well as end-stage renal disease, clinicians need to protect patients’ upper extremity veins in order to be able to have an adequate vascular substrate for subsequent creation of an arteriovenous fistula (AVF), Dr. Auron maintains.

PICCs, along with other central venous catheters, damage veins and destroy sites for future hemodialysis vascular access, explains Amy W. Williams, MD, medical director of hospital operations and consultant in the division of nephrology and hypertension at Mayo Clinic in Rochester, Minn. If there are no options for AVF or grafts, patients starting or being maintained on hemodialysis will need a tunneled central venous catheter for dialysis access.

Studies have shown that AVFs have better patency rates and fewer complications compared to catheters, and there is a direct correlation of increased mortality and inadequate dialysis with tunneled central catheters.³ In addition, dialysis patients with a tunneled central venous catheter have a five-fold increase of infection compared to those with an AVF.⁴ The incidence of central venous stenosis associated with PICC lines has been shown to be 42% and the incidence of thrombosis 38%.^5,6 There is no significant difference in the rate of central venous complications based on the duration of catheter use or catheter size. In addition, prior PICC use has been shown to be an independent predictor of lack of a functioning AVF (odds ratio 2.8 [95 % CI, 1.5 to 5.5]).⁷

A better choice for extended venous access in patients with advanced CKD is a tunneled internal jugular vein catheter, which is associated with a lower risk of permanent vascular damage, says Dr. Williams, who is chair of the ASN’s Quality and Patient Safety Task Force.

Hospitalists who care for pediatric patients have the potential to significantly impact antibiotic overuse, as hospitalizations for respiratory illnesses due to viruses, such as bronchiolitis and croup, remain a leading cause of admission.

—James J. O’Callaghan, MD, FAAP, FHM, clinical assistant professor of pediatrics, Seattle Children’s Hospital at the University of Washington, Team Hospitalist member

7 The Society of Thoracic Surgeons (STS)

Recommendation: Patients who have no cardiac history and good functional status do not require pre-operative stress testing prior to non-cardiac thoracic surgery.

By eliminating routine stress testing prior to non-cardiac thoracic surgery for patients without a history of cardiac symptoms, hospitalists can reduce the burden of costs on patients and eliminate the possibility of adverse outcomes due to inappropriate testing.

“Functional status has been shown to be reliable to predict peri-operative and long-term cardiac events,” says Douglas E. Wood, MD, chief of the division of cardiothoracic surgery at the University of Washington in Seattle and president of the STS. “In highly functional asymptomatic patients, management is rarely changed by pre-operative stress testing. Furthermore, abnormalities identified in testing often require additional investigation, with negative consequences related to the risks of more procedures or tests, delays in therapies, and additional costs.”

Pre-operative stress testing should be reserved for patients with low functional capacity or clinical risk factors for cardiac complications. It is important to identify patients pre-operatively who are at risk for these complications by doing a thorough history, physical examination, and resting electrocardiogram.

8 Society of Nuclear Medicine and Molecular Imaging (SNMMI)

Recommendation: Avoid using a CT angiogram to diagnose pulmonary embolism (PE) in young women with a normal chest radiograph; consider a radionuclide lung (V/Q) study instead.

Hospitalists should be knowledgeable of the diagnostic options that will result in the lowest radiation exposure when evaluating young women for PE.

“When a chest radiograph is normal or nearly normal, a computed tomography angiogram or a V/Q lung scan can be used to evaluate these patients. While both exams have low radiation exposure, the V/Q lung scan results in less radiation to the breast tissue,” says society president Gary L. Dillehay, MD, FACNM, FACR, professor of radiology at Northwestern Memorial Hospital in Chicago. “Recent literature cites concerns over radiation exposure from mammography; therefore, reducing radiation exposure to breast tissue, when evaluating patients for suspected PE, is desirable.”

Hospitalists might have difficulty obtaining a V/Q lung scan when nuclear medicine departments are closed.

“The caveat is that CT scans are much more readily available,” Dr. Auron says. In addition, a CT scan provides additional information. But unless the differential diagnosis is much higher for PE than other possibilities, just having a V/Q scan should suffice.

Hospitalists could help implement protocols for chest pain evaluation in premenopausal women by having checklists for risk factors for coronary artery disease, connective tissue disease (essentially aortic dissection), and VTE (e.g. Wells and Geneva scores, use of oral contraceptives, smoking), Dr. Auron says. If the diagnostic branch supports the risk of PE, then nuclear imaging should be available.

“A reasonable way to justify the increased availability of the nuclear medicine department would be to document the number of CT chest scans done after hours in patients who would have instead had a V/Q scan,” he says.

LISTEN NOW to Rahul Shah, MD, FACS, FAAP, associate professor of otolaryngology and pediatrics at Children's National Medical Center in Washington, D.C, and co-chair of the American Academy of Otolaryngology-Head and Neck Surgery Foundation’s Patient Safety Quality Improvement Committee, explain why hospitalists should avoid routine radiographic imaging for patients who meet diagnostic criteria for uncomplicated acute rhinosinusitis.

9 American Academy of Pediatrics (AAP)

Recommendation: Antibiotics should not be used for apparent viral respiratory illnesses (sinusitis, pharyngitis, bronchitis).

Respiratory illnesses are the most common reason for hospitalization in pediatrics. Recent studies and surveys continue to demonstrate antibiotic overuse in the pediatric population, especially when prescribed for apparent viral respiratory illnesses.^8,9

“Hospitalists who care for pediatric patients have the potential to significantly impact antibiotic overuse, as hospitalizations for respiratory illnesses due to viruses such as bronchiolitis and croup remain a leading cause of admission,” says James J. O’Callaghan, MD, FAAP, FHM, clinical assistant professor of pediatrics at the University of Washington School of Medicine in Seattle.

Many respiratory problems, such as bronchiolitis, asthma, and even some pneumonias are caused or exacerbated by viruses, points out Ricardo Quiñonez, MD, FAAP, FHM, section head of pediatric hospital medicine at the Children’s Hospital of San Antonio and the Baylor College of Medicine, and chair of the AAP’s section on hospital medicine. In particular, there are national guidelines for bronchiolitis and asthma that recommend against the use of systemic antibiotics.

This recommendation may be difficult for hospitalists to implement, because antibiotics are frequently started by other providers (PCP or ED), Dr. O’Callaghan admits. It can be tricky to change or stop therapy without undermining patients’ or parents’ confidence in their medical decision-making. Hospitalists may need to collaborate with new partners, such as community-wide antibiotic reduction campaigns, in order to affect this culture change.

“Echocardiography can diagnose all types of heart disease while being completely safe, inexpensive, and available at the bedside. These features may logically lead hospitalists to think, ‘Why not?’ Maybe there’s something going on and an echo can’t hurt. Unfortunately, tests can have false positive findings that lead to other, potentially more hazardous and invasive, tests downstream, as well as unnecessary delays.”

—James D. Thomas, MD, FASE, FACC, FAHA, FESC, Moore Chair of Cardiovascular Imaging at the Cleveland Clinic in Ohio and past president of the American Society of Echocardiography.

10 American College of Obstetricians and Gynecologists (ACOB)

Recommendation: Don’t schedule elective inductions prior to 39 weeks, and don’t schedule elective inductions of labor after 39 weeks without a favorable cervix.

Studies show an increased risk to newborns that are electively inducted between 37 and 39 weeks. Complications include increased admission to the neonatal intensive care unit, increased risk of respiratory distress and need for respiratory support, and increased incidence of infection and sepsis.

This recommendation may be difficult for hospitalists to implement, because obstetrical providers typically schedule elective inductions. Implementation of this recommendation would involve collaboration with obstetrical providers, with possible support from maternal-fetal and neonatal providers.

“Recent quality measures and initiatives from such organizations such as CMS and the National Quality Forum … may help to galvanize institutional support for its successful implementation,” says Dr. O’Callaghan, a Team Hospitalist member.

Elective surgeries should only be done in cases where there is a medical necessity, such as when the mother is diabetic or has hypertension, adds Rob Olson, MD, FACOG, an OB/GYN hospitalist for PeaceHealth at St. Joseph Medical Center in Bellingham, Wash. “Hospitalists should not give in to pressures from patients who are either tired of the discomforts of pregnancy or have family pressure to end the pregnancy early.”

Karen Appold is a freelance writer in Pennsylvania.

References

1. U.S. Food and Drug Administration. Reducing radiation from medical X-rays. Available at: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm095505.htm. Accessed May 12, 2014.
2. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-654.
3. Hoggard J, Saad T, Schon D, et al. Guidelines for venous access in patients with chronic kidney disease. A position statement from the American Society of Diagnostic and Interventional Nephrology, Clinical Practice Committee and the Association for Vascular Access. Semin Dial. 2008;21(2):186-191.
4. Rayner HC, Besarab A, Brown WW, Disney A, Saito A, Pisoni RL. Vascular access results from the dialysis outcomes and practice patterns study (DOPPS): Performance against kidney disease outcomes quality initiative (K/DOQI)clinical practice guidelines. Am J Kidney Dis. 2004;44(5 Suppl 2):22-26.
5. Gonsalves CF, Eschelman DJ, Sullivan KL, DuBois N, Bonn J. Incidence of central vein stenosis and occlusion following upper extremity PICC and port placement. Cardiovasc Intervent Radiol. 2003;26(2):123-127.
6. Allen AW, Megargell JL, Brown DB, et al. Venous thrombosis associated with the placement of peripherally inserted central catheters. J Vasc Interv Radiol. 2000;11(10):1309-1314.
7. El Ters M, Schears GJ, Taler SJ, et al. Association between prior peripherally inserted central catheters and lack of functioning ateriovenous fistulas: A case control study in hemodialysis patients. Am J Kidney Dis. 2012;60(4):601-608.
8. Hersh AL, Shapiro DJ, Pavia AT, Shah SS. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics. 2011;128(6):1053-1061.
9. Knapp JF, Simon SD, Sharma V. Quality of care for common pediatric respiratory illnesses in United States emergency departments: Analysis of 2005 National Hospital Ambulatory Medical Care Survey data. Pediatrics. 2008;122(6):1165-1170.

When diagnosing a patient, it can be tempting to run all types of tests to expedite the process—and protect yourself from litigation. Patients may push for more tests, too, thinking “the more the better.” But that may not be the best course of action. In fact, according to recommendations of the ABIM Foundations’ Choosing Wisely campaign, more tests can actually bring a host of negative consequences.

In an effort to help hospitalists decide which tests to perform and which to forgo, The Hospitalist asked medical societies that contributed to the Choosing Wisely campaign to tell us which one of their recommendations was the most applicable to hospitalists. Then, we asked some hospitalists to discuss how they might implement each recommendation.

1 American Gastroenterological Association (AGA)

Recommendation: For a patient with functional abdominal pain syndrome (as per Rome criteria), computed tomography (CT) scans should not be repeated unless there is a major change in clinical findings or symptoms.

When a patient first complains of abdominal pain, a CT scan usually is done prior to a gastroenterological consultation. Despite this initial scan, many patients with chronic abdominal pain receive unnecessary repeated CT scans to evaluate their pain even if they have previous negative studies.

“It is important for the hospitalist to know that functional abdominal pain can be managed without additional diagnostic studies,” says John M. Inadomi, MD, head of the division of gastroenterology at the University of Washington School of Medicine in Seattle. “Some doctors are uncomfortable with the uncertainty of a diagnosis of chronic abdominal pain without evidence of biochemical or structural disease [functional abdominal pain syndrome] and fear litigation.”

An abdominal CT scan is one of the higher radiation exposure tests, equivalent to three years of natural background radiation.¹

“Due to this risk and the high costs of this procedure, CT scans should be limited to situations in which they are likely to provide useful information that changes patient management,” Dr. Inadomi says.

According to Moises Auron, MD, FAAP, FACP, SFHM, assistant professor of medicine and pediatrics at Cleveland Clinic Lerner College of Medicine of Case Western University in Cleveland, Ohio, it should not be a difficult choice for hospitalists, “as the clinical context provides a safeguard to justify the rationale for a conservative approach. Hospitalists must be educated on the appropriate use of Rome criteria, as well as how to appropriately document it in the chart to justify a decision to avoid unnecessary testing.”

2 American College of Rheumatology (ACR)

Recommendation: Don’t test anti-nuclear antibody (ANA) sub-serologies without a positive ANA and clinical suspicion of immune-mediated disease.

“A fever of unknown origin is among the most common diagnoses the hospitalist encounters,” Dr. Auron says. “Nowadays, given the ease to order tests, as well as the increased awareness of patients with immune-mediated diseases, it may be tempting to order large panels of immunologic tests to minimize the risk of missing a diagnosis; however, because ANA has high sensitivity and poor specificity, it should only be ordered if the clinical context supports its use.”

Jinoos Yazdany, MD, MPH, assistant professor of medicine at the University of California at San Francisco and co-chair of the task force that developed the ACR’s Choosing Wisely list, points out that if you use ANAs as a broad screening test when the pretest probability of specific ANA-associated diseases is low, there is an increased chance of a false positive ANA result. This can lead to unnecessary further testing and additional costs. Furthermore, ANA sub-serologies are usually negative if the ANA (done by immunofluorescence) is negative.

“So it is recommended to order sub-serologies only once it is known that the ANA is positive,” she says. The exceptions to this are anti-SSA and anti-Jo-1 antibodies, which can sometimes be positive when the ANA is negative.

Mangla S. Gulati, MD, FACP, FHM, medical director for clinical effectiveness at the University of Maryland School of Medicine in Baltimore, says a positive ANA in conjunction with clinical information “will help to guide appropriate and cost-conscious testing. Hospitalists could implement this through a clinical decision support approach if using an electronic medical record.”

LISTEN NOW to Daniel Wolfson, MHSA, executive vice president and CEO of the ABIM Foundation, discuss how the Choosing Wisely campaign got started and its significance in U.S. healthcare.

3 American College of Physicians (ACP)

Recommendation: In patients with low pretest probability of venous thromboembolism (VTE), obtain a high-sensitive D-dimer measurement as the initial diagnostic test; don’t obtain imaging studies as the initial diagnostic test.

VTE, a common problem in hospitalized patients, has high mortality rates. “However, recent statistics suggest that we may be overdiagnosing non-clinically significant disease and exposing large numbers of patients to high doses of radiation unnecessarily in an attempt to rule out VTE disease,” says Cynthia D. Smith, MD, FACP, ACP senior medical associate for content development and adjunct associate professor of medicine at the Perelman School of Medicine in Philadelphia.

Instead, physicians should estimate pretest probability of disease using a validated risk assessment tool (i.e., Wells score). For patients with low clinical probability of VTE, hospitalists should use a negative high-sensitive D-dimer measurement as the initial diagnostic test.

Dr. Auron says the litigious environment of American medicine may trigger clinicians to order testing to minimize the risk of missing potential conditions; however, an adequate, evidence-based approach with appropriate documentation should be sufficient. In this case, that would entail using D-dimer testing to outline the low pretest probability of VTE and explaining to the patient the rationale for not pursuing further imaging.

Dr. Gulati adds that hospitalists should have little difficulty implementing this cost-effective approach.

“A reasonable way to justify the increased availability of the nuclear medicine department would be to document the number of CT chest scans done after hours in patients who would have instead had a V/Q scan.”

—Moises Auron, MD, FAAP, FACP, SFHM, assistant professor of medicine and pediatrics, Cleveland Clinic

4 American Geriatrics Society (AGS)

Recommendation: Don’t use antimicrobials to treat bacteriuria in older adults unless specific urinary tract symptoms are present.

Older adults with asymptomatic bacteriuria who received antimicrobial treatment show no benefit, according to multiple studies.² In fact, increased adverse antimicrobial effects occurred, such as greater resistance patterns and super-infections (e.g. Clostridium difficile).

The truth is that as many as 30% of frail elders (particularly women) have bacterial colonization of the urinary tract without infection, also known as asymptomatic bacteriuria, says Heidi Wald, MD, MSPH, associate professor of medicine and vice chair for quality in the department of medicine at the University of Colorado School of Medicine in Aurora. Therefore, before being prescribed antimicrobials, a patient should exhibit symptoms of urinary tract infection such as fever, frequent urination, urgency to urinate, painful urination, or suprapubic tenderness.

“Without localizing symptoms, you can’t assume bacteriuria equals infection,” Dr. Wald adds. “Too often, we make the urine a scapegoat for unrelated presentations, such as mild confusion.”

If the patient is stable and doesn’t have UTI symptoms, Dr. Wald says hospitalists should consider hydration and monitor the patient without antibiotics.

“This should not be difficult to implement,” Dr. Auron says, “as hospitalists are on the front lines of antibiotic stewardship in hospitals.”

LISTEN NOW to Linda Cox, MD, owner of Allergy and Asthma Center in Ft. Lauderdale, Fla., and president of American Academy of Allergy, Asthma & Immunology, discuss why it's important for hospitalists to not diagnose or manage asthma without spirometry.

5 American Society of Echocardiography (ASE)

Recommendation: Avoid echocardiograms for pre-operative/peri-operative assessment of patients with no history or symptoms of heart disease.

Echocardiography can diagnose all types of heart disease while being completely safe, inexpensive, and available at the bedside.

“These features may logically lead hospitalists to think, ‘Why not?’ Maybe there’s something going on and an echo can’t hurt,” says James D. Thomas, MD, FASE, FACC, FAHA, FESC, Moore Chair of Cardiovascular Imaging at Cleveland Clinic and ASE past president. “Unfortunately, tests can have false positive findings that lead to other, potentially more hazardous and invasive, tests downstream, as well as unnecessary delays.”

If a patient has no history of heart disease, no positive physical findings, or no symptoms, then an echo probably won’t be helpful. Hospitalists need to be aware of the lack of value of a presumed normal study, Dr. Auron says.

“Having appropriate standards of care allows clinicians in pre-operative areas to use risk stratification tools in an adequate fashion,” he notes.

6 American Society of Nephrology (ASN)

Recommendation: Do not place peripherally inserted central venous catheters (PICC) in stage three to five chronic kidney disease (CKD) patients without consulting nephrology.

Given the increase in patients with CKD in the later stages, as well as end-stage renal disease, clinicians need to protect patients’ upper extremity veins in order to be able to have an adequate vascular substrate for subsequent creation of an arteriovenous fistula (AVF), Dr. Auron maintains.

PICCs, along with other central venous catheters, damage veins and destroy sites for future hemodialysis vascular access, explains Amy W. Williams, MD, medical director of hospital operations and consultant in the division of nephrology and hypertension at Mayo Clinic in Rochester, Minn. If there are no options for AVF or grafts, patients starting or being maintained on hemodialysis will need a tunneled central venous catheter for dialysis access.

Studies have shown that AVFs have better patency rates and fewer complications compared to catheters, and there is a direct correlation of increased mortality and inadequate dialysis with tunneled central catheters.³ In addition, dialysis patients with a tunneled central venous catheter have a five-fold increase of infection compared to those with an AVF.⁴ The incidence of central venous stenosis associated with PICC lines has been shown to be 42% and the incidence of thrombosis 38%.^5,6 There is no significant difference in the rate of central venous complications based on the duration of catheter use or catheter size. In addition, prior PICC use has been shown to be an independent predictor of lack of a functioning AVF (odds ratio 2.8 [95 % CI, 1.5 to 5.5]).⁷

A better choice for extended venous access in patients with advanced CKD is a tunneled internal jugular vein catheter, which is associated with a lower risk of permanent vascular damage, says Dr. Williams, who is chair of the ASN’s Quality and Patient Safety Task Force.

Hospitalists who care for pediatric patients have the potential to significantly impact antibiotic overuse, as hospitalizations for respiratory illnesses due to viruses, such as bronchiolitis and croup, remain a leading cause of admission.

—James J. O’Callaghan, MD, FAAP, FHM, clinical assistant professor of pediatrics, Seattle Children’s Hospital at the University of Washington, Team Hospitalist member

7 The Society of Thoracic Surgeons (STS)

Recommendation: Patients who have no cardiac history and good functional status do not require pre-operative stress testing prior to non-cardiac thoracic surgery.

By eliminating routine stress testing prior to non-cardiac thoracic surgery for patients without a history of cardiac symptoms, hospitalists can reduce the burden of costs on patients and eliminate the possibility of adverse outcomes due to inappropriate testing.

“Functional status has been shown to be reliable to predict peri-operative and long-term cardiac events,” says Douglas E. Wood, MD, chief of the division of cardiothoracic surgery at the University of Washington in Seattle and president of the STS. “In highly functional asymptomatic patients, management is rarely changed by pre-operative stress testing. Furthermore, abnormalities identified in testing often require additional investigation, with negative consequences related to the risks of more procedures or tests, delays in therapies, and additional costs.”

Pre-operative stress testing should be reserved for patients with low functional capacity or clinical risk factors for cardiac complications. It is important to identify patients pre-operatively who are at risk for these complications by doing a thorough history, physical examination, and resting electrocardiogram.

8 Society of Nuclear Medicine and Molecular Imaging (SNMMI)

Recommendation: Avoid using a CT angiogram to diagnose pulmonary embolism (PE) in young women with a normal chest radiograph; consider a radionuclide lung (V/Q) study instead.

Hospitalists should be knowledgeable of the diagnostic options that will result in the lowest radiation exposure when evaluating young women for PE.

“When a chest radiograph is normal or nearly normal, a computed tomography angiogram or a V/Q lung scan can be used to evaluate these patients. While both exams have low radiation exposure, the V/Q lung scan results in less radiation to the breast tissue,” says society president Gary L. Dillehay, MD, FACNM, FACR, professor of radiology at Northwestern Memorial Hospital in Chicago. “Recent literature cites concerns over radiation exposure from mammography; therefore, reducing radiation exposure to breast tissue, when evaluating patients for suspected PE, is desirable.”

Hospitalists might have difficulty obtaining a V/Q lung scan when nuclear medicine departments are closed.

“The caveat is that CT scans are much more readily available,” Dr. Auron says. In addition, a CT scan provides additional information. But unless the differential diagnosis is much higher for PE than other possibilities, just having a V/Q scan should suffice.

Hospitalists could help implement protocols for chest pain evaluation in premenopausal women by having checklists for risk factors for coronary artery disease, connective tissue disease (essentially aortic dissection), and VTE (e.g. Wells and Geneva scores, use of oral contraceptives, smoking), Dr. Auron says. If the diagnostic branch supports the risk of PE, then nuclear imaging should be available.

“A reasonable way to justify the increased availability of the nuclear medicine department would be to document the number of CT chest scans done after hours in patients who would have instead had a V/Q scan,” he says.

LISTEN NOW to Rahul Shah, MD, FACS, FAAP, associate professor of otolaryngology and pediatrics at Children's National Medical Center in Washington, D.C, and co-chair of the American Academy of Otolaryngology-Head and Neck Surgery Foundation’s Patient Safety Quality Improvement Committee, explain why hospitalists should avoid routine radiographic imaging for patients who meet diagnostic criteria for uncomplicated acute rhinosinusitis.

9 American Academy of Pediatrics (AAP)

Recommendation: Antibiotics should not be used for apparent viral respiratory illnesses (sinusitis, pharyngitis, bronchitis).

Respiratory illnesses are the most common reason for hospitalization in pediatrics. Recent studies and surveys continue to demonstrate antibiotic overuse in the pediatric population, especially when prescribed for apparent viral respiratory illnesses.^8,9

“Hospitalists who care for pediatric patients have the potential to significantly impact antibiotic overuse, as hospitalizations for respiratory illnesses due to viruses such as bronchiolitis and croup remain a leading cause of admission,” says James J. O’Callaghan, MD, FAAP, FHM, clinical assistant professor of pediatrics at the University of Washington School of Medicine in Seattle.

Many respiratory problems, such as bronchiolitis, asthma, and even some pneumonias are caused or exacerbated by viruses, points out Ricardo Quiñonez, MD, FAAP, FHM, section head of pediatric hospital medicine at the Children’s Hospital of San Antonio and the Baylor College of Medicine, and chair of the AAP’s section on hospital medicine. In particular, there are national guidelines for bronchiolitis and asthma that recommend against the use of systemic antibiotics.

This recommendation may be difficult for hospitalists to implement, because antibiotics are frequently started by other providers (PCP or ED), Dr. O’Callaghan admits. It can be tricky to change or stop therapy without undermining patients’ or parents’ confidence in their medical decision-making. Hospitalists may need to collaborate with new partners, such as community-wide antibiotic reduction campaigns, in order to affect this culture change.

“Echocardiography can diagnose all types of heart disease while being completely safe, inexpensive, and available at the bedside. These features may logically lead hospitalists to think, ‘Why not?’ Maybe there’s something going on and an echo can’t hurt. Unfortunately, tests can have false positive findings that lead to other, potentially more hazardous and invasive, tests downstream, as well as unnecessary delays.”

—James D. Thomas, MD, FASE, FACC, FAHA, FESC, Moore Chair of Cardiovascular Imaging at the Cleveland Clinic in Ohio and past president of the American Society of Echocardiography.

10 American College of Obstetricians and Gynecologists (ACOB)

Recommendation: Don’t schedule elective inductions prior to 39 weeks, and don’t schedule elective inductions of labor after 39 weeks without a favorable cervix.

Studies show an increased risk to newborns that are electively inducted between 37 and 39 weeks. Complications include increased admission to the neonatal intensive care unit, increased risk of respiratory distress and need for respiratory support, and increased incidence of infection and sepsis.

This recommendation may be difficult for hospitalists to implement, because obstetrical providers typically schedule elective inductions. Implementation of this recommendation would involve collaboration with obstetrical providers, with possible support from maternal-fetal and neonatal providers.

“Recent quality measures and initiatives from such organizations such as CMS and the National Quality Forum … may help to galvanize institutional support for its successful implementation,” says Dr. O’Callaghan, a Team Hospitalist member.

Elective surgeries should only be done in cases where there is a medical necessity, such as when the mother is diabetic or has hypertension, adds Rob Olson, MD, FACOG, an OB/GYN hospitalist for PeaceHealth at St. Joseph Medical Center in Bellingham, Wash. “Hospitalists should not give in to pressures from patients who are either tired of the discomforts of pregnancy or have family pressure to end the pregnancy early.”

Karen Appold is a freelance writer in Pennsylvania.

References

1. U.S. Food and Drug Administration. Reducing radiation from medical X-rays. Available at: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm095505.htm. Accessed May 12, 2014.
2. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-654.
3. Hoggard J, Saad T, Schon D, et al. Guidelines for venous access in patients with chronic kidney disease. A position statement from the American Society of Diagnostic and Interventional Nephrology, Clinical Practice Committee and the Association for Vascular Access. Semin Dial. 2008;21(2):186-191.
4. Rayner HC, Besarab A, Brown WW, Disney A, Saito A, Pisoni RL. Vascular access results from the dialysis outcomes and practice patterns study (DOPPS): Performance against kidney disease outcomes quality initiative (K/DOQI)clinical practice guidelines. Am J Kidney Dis. 2004;44(5 Suppl 2):22-26.
5. Gonsalves CF, Eschelman DJ, Sullivan KL, DuBois N, Bonn J. Incidence of central vein stenosis and occlusion following upper extremity PICC and port placement. Cardiovasc Intervent Radiol. 2003;26(2):123-127.
6. Allen AW, Megargell JL, Brown DB, et al. Venous thrombosis associated with the placement of peripherally inserted central catheters. J Vasc Interv Radiol. 2000;11(10):1309-1314.
7. El Ters M, Schears GJ, Taler SJ, et al. Association between prior peripherally inserted central catheters and lack of functioning ateriovenous fistulas: A case control study in hemodialysis patients. Am J Kidney Dis. 2012;60(4):601-608.
8. Hersh AL, Shapiro DJ, Pavia AT, Shah SS. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics. 2011;128(6):1053-1061.
9. Knapp JF, Simon SD, Sharma V. Quality of care for common pediatric respiratory illnesses in United States emergency departments: Analysis of 2005 National Hospital Ambulatory Medical Care Survey data. Pediatrics. 2008;122(6):1165-1170.

When diagnosing a patient, it can be tempting to run all types of tests to expedite the process—and protect yourself from litigation. Patients may push for more tests, too, thinking “the more the better.” But that may not be the best course of action. In fact, according to recommendations of the ABIM Foundations’ Choosing Wisely campaign, more tests can actually bring a host of negative consequences.

In an effort to help hospitalists decide which tests to perform and which to forgo, The Hospitalist asked medical societies that contributed to the Choosing Wisely campaign to tell us which one of their recommendations was the most applicable to hospitalists. Then, we asked some hospitalists to discuss how they might implement each recommendation.

1 American Gastroenterological Association (AGA)

Recommendation: For a patient with functional abdominal pain syndrome (as per Rome criteria), computed tomography (CT) scans should not be repeated unless there is a major change in clinical findings or symptoms.

When a patient first complains of abdominal pain, a CT scan usually is done prior to a gastroenterological consultation. Despite this initial scan, many patients with chronic abdominal pain receive unnecessary repeated CT scans to evaluate their pain even if they have previous negative studies.

“It is important for the hospitalist to know that functional abdominal pain can be managed without additional diagnostic studies,” says John M. Inadomi, MD, head of the division of gastroenterology at the University of Washington School of Medicine in Seattle. “Some doctors are uncomfortable with the uncertainty of a diagnosis of chronic abdominal pain without evidence of biochemical or structural disease [functional abdominal pain syndrome] and fear litigation.”

An abdominal CT scan is one of the higher radiation exposure tests, equivalent to three years of natural background radiation.¹

“Due to this risk and the high costs of this procedure, CT scans should be limited to situations in which they are likely to provide useful information that changes patient management,” Dr. Inadomi says.

According to Moises Auron, MD, FAAP, FACP, SFHM, assistant professor of medicine and pediatrics at Cleveland Clinic Lerner College of Medicine of Case Western University in Cleveland, Ohio, it should not be a difficult choice for hospitalists, “as the clinical context provides a safeguard to justify the rationale for a conservative approach. Hospitalists must be educated on the appropriate use of Rome criteria, as well as how to appropriately document it in the chart to justify a decision to avoid unnecessary testing.”

2 American College of Rheumatology (ACR)

Recommendation: Don’t test anti-nuclear antibody (ANA) sub-serologies without a positive ANA and clinical suspicion of immune-mediated disease.

“A fever of unknown origin is among the most common diagnoses the hospitalist encounters,” Dr. Auron says. “Nowadays, given the ease to order tests, as well as the increased awareness of patients with immune-mediated diseases, it may be tempting to order large panels of immunologic tests to minimize the risk of missing a diagnosis; however, because ANA has high sensitivity and poor specificity, it should only be ordered if the clinical context supports its use.”

Jinoos Yazdany, MD, MPH, assistant professor of medicine at the University of California at San Francisco and co-chair of the task force that developed the ACR’s Choosing Wisely list, points out that if you use ANAs as a broad screening test when the pretest probability of specific ANA-associated diseases is low, there is an increased chance of a false positive ANA result. This can lead to unnecessary further testing and additional costs. Furthermore, ANA sub-serologies are usually negative if the ANA (done by immunofluorescence) is negative.

“So it is recommended to order sub-serologies only once it is known that the ANA is positive,” she says. The exceptions to this are anti-SSA and anti-Jo-1 antibodies, which can sometimes be positive when the ANA is negative.

Mangla S. Gulati, MD, FACP, FHM, medical director for clinical effectiveness at the University of Maryland School of Medicine in Baltimore, says a positive ANA in conjunction with clinical information “will help to guide appropriate and cost-conscious testing. Hospitalists could implement this through a clinical decision support approach if using an electronic medical record.”

LISTEN NOW to Daniel Wolfson, MHSA, executive vice president and CEO of the ABIM Foundation, discuss how the Choosing Wisely campaign got started and its significance in U.S. healthcare.

3 American College of Physicians (ACP)

Recommendation: In patients with low pretest probability of venous thromboembolism (VTE), obtain a high-sensitive D-dimer measurement as the initial diagnostic test; don’t obtain imaging studies as the initial diagnostic test.

VTE, a common problem in hospitalized patients, has high mortality rates. “However, recent statistics suggest that we may be overdiagnosing non-clinically significant disease and exposing large numbers of patients to high doses of radiation unnecessarily in an attempt to rule out VTE disease,” says Cynthia D. Smith, MD, FACP, ACP senior medical associate for content development and adjunct associate professor of medicine at the Perelman School of Medicine in Philadelphia.

Instead, physicians should estimate pretest probability of disease using a validated risk assessment tool (i.e., Wells score). For patients with low clinical probability of VTE, hospitalists should use a negative high-sensitive D-dimer measurement as the initial diagnostic test.

Dr. Auron says the litigious environment of American medicine may trigger clinicians to order testing to minimize the risk of missing potential conditions; however, an adequate, evidence-based approach with appropriate documentation should be sufficient. In this case, that would entail using D-dimer testing to outline the low pretest probability of VTE and explaining to the patient the rationale for not pursuing further imaging.

Dr. Gulati adds that hospitalists should have little difficulty implementing this cost-effective approach.

“A reasonable way to justify the increased availability of the nuclear medicine department would be to document the number of CT chest scans done after hours in patients who would have instead had a V/Q scan.”

—Moises Auron, MD, FAAP, FACP, SFHM, assistant professor of medicine and pediatrics, Cleveland Clinic

4 American Geriatrics Society (AGS)

Recommendation: Don’t use antimicrobials to treat bacteriuria in older adults unless specific urinary tract symptoms are present.

Older adults with asymptomatic bacteriuria who received antimicrobial treatment show no benefit, according to multiple studies.² In fact, increased adverse antimicrobial effects occurred, such as greater resistance patterns and super-infections (e.g. Clostridium difficile).

The truth is that as many as 30% of frail elders (particularly women) have bacterial colonization of the urinary tract without infection, also known as asymptomatic bacteriuria, says Heidi Wald, MD, MSPH, associate professor of medicine and vice chair for quality in the department of medicine at the University of Colorado School of Medicine in Aurora. Therefore, before being prescribed antimicrobials, a patient should exhibit symptoms of urinary tract infection such as fever, frequent urination, urgency to urinate, painful urination, or suprapubic tenderness.

“Without localizing symptoms, you can’t assume bacteriuria equals infection,” Dr. Wald adds. “Too often, we make the urine a scapegoat for unrelated presentations, such as mild confusion.”

If the patient is stable and doesn’t have UTI symptoms, Dr. Wald says hospitalists should consider hydration and monitor the patient without antibiotics.

“This should not be difficult to implement,” Dr. Auron says, “as hospitalists are on the front lines of antibiotic stewardship in hospitals.”

LISTEN NOW to Linda Cox, MD, owner of Allergy and Asthma Center in Ft. Lauderdale, Fla., and president of American Academy of Allergy, Asthma & Immunology, discuss why it's important for hospitalists to not diagnose or manage asthma without spirometry.

5 American Society of Echocardiography (ASE)

Recommendation: Avoid echocardiograms for pre-operative/peri-operative assessment of patients with no history or symptoms of heart disease.

Echocardiography can diagnose all types of heart disease while being completely safe, inexpensive, and available at the bedside.

“These features may logically lead hospitalists to think, ‘Why not?’ Maybe there’s something going on and an echo can’t hurt,” says James D. Thomas, MD, FASE, FACC, FAHA, FESC, Moore Chair of Cardiovascular Imaging at Cleveland Clinic and ASE past president. “Unfortunately, tests can have false positive findings that lead to other, potentially more hazardous and invasive, tests downstream, as well as unnecessary delays.”

If a patient has no history of heart disease, no positive physical findings, or no symptoms, then an echo probably won’t be helpful. Hospitalists need to be aware of the lack of value of a presumed normal study, Dr. Auron says.

“Having appropriate standards of care allows clinicians in pre-operative areas to use risk stratification tools in an adequate fashion,” he notes.

6 American Society of Nephrology (ASN)

Recommendation: Do not place peripherally inserted central venous catheters (PICC) in stage three to five chronic kidney disease (CKD) patients without consulting nephrology.

Given the increase in patients with CKD in the later stages, as well as end-stage renal disease, clinicians need to protect patients’ upper extremity veins in order to be able to have an adequate vascular substrate for subsequent creation of an arteriovenous fistula (AVF), Dr. Auron maintains.

PICCs, along with other central venous catheters, damage veins and destroy sites for future hemodialysis vascular access, explains Amy W. Williams, MD, medical director of hospital operations and consultant in the division of nephrology and hypertension at Mayo Clinic in Rochester, Minn. If there are no options for AVF or grafts, patients starting or being maintained on hemodialysis will need a tunneled central venous catheter for dialysis access.

Studies have shown that AVFs have better patency rates and fewer complications compared to catheters, and there is a direct correlation of increased mortality and inadequate dialysis with tunneled central catheters.³ In addition, dialysis patients with a tunneled central venous catheter have a five-fold increase of infection compared to those with an AVF.⁴ The incidence of central venous stenosis associated with PICC lines has been shown to be 42% and the incidence of thrombosis 38%.^5,6 There is no significant difference in the rate of central venous complications based on the duration of catheter use or catheter size. In addition, prior PICC use has been shown to be an independent predictor of lack of a functioning AVF (odds ratio 2.8 [95 % CI, 1.5 to 5.5]).⁷

A better choice for extended venous access in patients with advanced CKD is a tunneled internal jugular vein catheter, which is associated with a lower risk of permanent vascular damage, says Dr. Williams, who is chair of the ASN’s Quality and Patient Safety Task Force.

Hospitalists who care for pediatric patients have the potential to significantly impact antibiotic overuse, as hospitalizations for respiratory illnesses due to viruses, such as bronchiolitis and croup, remain a leading cause of admission.

—James J. O’Callaghan, MD, FAAP, FHM, clinical assistant professor of pediatrics, Seattle Children’s Hospital at the University of Washington, Team Hospitalist member

7 The Society of Thoracic Surgeons (STS)

Recommendation: Patients who have no cardiac history and good functional status do not require pre-operative stress testing prior to non-cardiac thoracic surgery.

By eliminating routine stress testing prior to non-cardiac thoracic surgery for patients without a history of cardiac symptoms, hospitalists can reduce the burden of costs on patients and eliminate the possibility of adverse outcomes due to inappropriate testing.

“Functional status has been shown to be reliable to predict peri-operative and long-term cardiac events,” says Douglas E. Wood, MD, chief of the division of cardiothoracic surgery at the University of Washington in Seattle and president of the STS. “In highly functional asymptomatic patients, management is rarely changed by pre-operative stress testing. Furthermore, abnormalities identified in testing often require additional investigation, with negative consequences related to the risks of more procedures or tests, delays in therapies, and additional costs.”

Pre-operative stress testing should be reserved for patients with low functional capacity or clinical risk factors for cardiac complications. It is important to identify patients pre-operatively who are at risk for these complications by doing a thorough history, physical examination, and resting electrocardiogram.

8 Society of Nuclear Medicine and Molecular Imaging (SNMMI)

Recommendation: Avoid using a CT angiogram to diagnose pulmonary embolism (PE) in young women with a normal chest radiograph; consider a radionuclide lung (V/Q) study instead.

Hospitalists should be knowledgeable of the diagnostic options that will result in the lowest radiation exposure when evaluating young women for PE.

“When a chest radiograph is normal or nearly normal, a computed tomography angiogram or a V/Q lung scan can be used to evaluate these patients. While both exams have low radiation exposure, the V/Q lung scan results in less radiation to the breast tissue,” says society president Gary L. Dillehay, MD, FACNM, FACR, professor of radiology at Northwestern Memorial Hospital in Chicago. “Recent literature cites concerns over radiation exposure from mammography; therefore, reducing radiation exposure to breast tissue, when evaluating patients for suspected PE, is desirable.”

Hospitalists might have difficulty obtaining a V/Q lung scan when nuclear medicine departments are closed.

“The caveat is that CT scans are much more readily available,” Dr. Auron says. In addition, a CT scan provides additional information. But unless the differential diagnosis is much higher for PE than other possibilities, just having a V/Q scan should suffice.

Hospitalists could help implement protocols for chest pain evaluation in premenopausal women by having checklists for risk factors for coronary artery disease, connective tissue disease (essentially aortic dissection), and VTE (e.g. Wells and Geneva scores, use of oral contraceptives, smoking), Dr. Auron says. If the diagnostic branch supports the risk of PE, then nuclear imaging should be available.

“A reasonable way to justify the increased availability of the nuclear medicine department would be to document the number of CT chest scans done after hours in patients who would have instead had a V/Q scan,” he says.

LISTEN NOW to Rahul Shah, MD, FACS, FAAP, associate professor of otolaryngology and pediatrics at Children's National Medical Center in Washington, D.C, and co-chair of the American Academy of Otolaryngology-Head and Neck Surgery Foundation’s Patient Safety Quality Improvement Committee, explain why hospitalists should avoid routine radiographic imaging for patients who meet diagnostic criteria for uncomplicated acute rhinosinusitis.

9 American Academy of Pediatrics (AAP)

Recommendation: Antibiotics should not be used for apparent viral respiratory illnesses (sinusitis, pharyngitis, bronchitis).

Respiratory illnesses are the most common reason for hospitalization in pediatrics. Recent studies and surveys continue to demonstrate antibiotic overuse in the pediatric population, especially when prescribed for apparent viral respiratory illnesses.^8,9

“Hospitalists who care for pediatric patients have the potential to significantly impact antibiotic overuse, as hospitalizations for respiratory illnesses due to viruses such as bronchiolitis and croup remain a leading cause of admission,” says James J. O’Callaghan, MD, FAAP, FHM, clinical assistant professor of pediatrics at the University of Washington School of Medicine in Seattle.

Many respiratory problems, such as bronchiolitis, asthma, and even some pneumonias are caused or exacerbated by viruses, points out Ricardo Quiñonez, MD, FAAP, FHM, section head of pediatric hospital medicine at the Children’s Hospital of San Antonio and the Baylor College of Medicine, and chair of the AAP’s section on hospital medicine. In particular, there are national guidelines for bronchiolitis and asthma that recommend against the use of systemic antibiotics.

This recommendation may be difficult for hospitalists to implement, because antibiotics are frequently started by other providers (PCP or ED), Dr. O’Callaghan admits. It can be tricky to change or stop therapy without undermining patients’ or parents’ confidence in their medical decision-making. Hospitalists may need to collaborate with new partners, such as community-wide antibiotic reduction campaigns, in order to affect this culture change.

“Echocardiography can diagnose all types of heart disease while being completely safe, inexpensive, and available at the bedside. These features may logically lead hospitalists to think, ‘Why not?’ Maybe there’s something going on and an echo can’t hurt. Unfortunately, tests can have false positive findings that lead to other, potentially more hazardous and invasive, tests downstream, as well as unnecessary delays.”

—James D. Thomas, MD, FASE, FACC, FAHA, FESC, Moore Chair of Cardiovascular Imaging at the Cleveland Clinic in Ohio and past president of the American Society of Echocardiography.

10 American College of Obstetricians and Gynecologists (ACOB)

Recommendation: Don’t schedule elective inductions prior to 39 weeks, and don’t schedule elective inductions of labor after 39 weeks without a favorable cervix.

Studies show an increased risk to newborns that are electively inducted between 37 and 39 weeks. Complications include increased admission to the neonatal intensive care unit, increased risk of respiratory distress and need for respiratory support, and increased incidence of infection and sepsis.

This recommendation may be difficult for hospitalists to implement, because obstetrical providers typically schedule elective inductions. Implementation of this recommendation would involve collaboration with obstetrical providers, with possible support from maternal-fetal and neonatal providers.

“Recent quality measures and initiatives from such organizations such as CMS and the National Quality Forum … may help to galvanize institutional support for its successful implementation,” says Dr. O’Callaghan, a Team Hospitalist member.

Elective surgeries should only be done in cases where there is a medical necessity, such as when the mother is diabetic or has hypertension, adds Rob Olson, MD, FACOG, an OB/GYN hospitalist for PeaceHealth at St. Joseph Medical Center in Bellingham, Wash. “Hospitalists should not give in to pressures from patients who are either tired of the discomforts of pregnancy or have family pressure to end the pregnancy early.”

Karen Appold is a freelance writer in Pennsylvania.

References

1. U.S. Food and Drug Administration. Reducing radiation from medical X-rays. Available at: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm095505.htm. Accessed May 12, 2014.
2. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-654.
3. Hoggard J, Saad T, Schon D, et al. Guidelines for venous access in patients with chronic kidney disease. A position statement from the American Society of Diagnostic and Interventional Nephrology, Clinical Practice Committee and the Association for Vascular Access. Semin Dial. 2008;21(2):186-191.
4. Rayner HC, Besarab A, Brown WW, Disney A, Saito A, Pisoni RL. Vascular access results from the dialysis outcomes and practice patterns study (DOPPS): Performance against kidney disease outcomes quality initiative (K/DOQI)clinical practice guidelines. Am J Kidney Dis. 2004;44(5 Suppl 2):22-26.
5. Gonsalves CF, Eschelman DJ, Sullivan KL, DuBois N, Bonn J. Incidence of central vein stenosis and occlusion following upper extremity PICC and port placement. Cardiovasc Intervent Radiol. 2003;26(2):123-127.
6. Allen AW, Megargell JL, Brown DB, et al. Venous thrombosis associated with the placement of peripherally inserted central catheters. J Vasc Interv Radiol. 2000;11(10):1309-1314.
7. El Ters M, Schears GJ, Taler SJ, et al. Association between prior peripherally inserted central catheters and lack of functioning ateriovenous fistulas: A case control study in hemodialysis patients. Am J Kidney Dis. 2012;60(4):601-608.
8. Hersh AL, Shapiro DJ, Pavia AT, Shah SS. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics. 2011;128(6):1053-1061.
9. Knapp JF, Simon SD, Sharma V. Quality of care for common pediatric respiratory illnesses in United States emergency departments: Analysis of 2005 National Hospital Ambulatory Medical Care Survey data. Pediatrics. 2008;122(6):1165-1170.

CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.

In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.

"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.

"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.

Dr. Masters moderated the briefing but was not involved in the study.

Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (¹³¹I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.

There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.

Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.

In a phase II study, the drug showed clinical activity against ¹³¹I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.

They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.

The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.

As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.

The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.

The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.

As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.

The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).

Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.

Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.

Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.

"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.

Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.

The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.

CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.

In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.

"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.

"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.

Dr. Masters moderated the briefing but was not involved in the study.

Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (¹³¹I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.

There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.

Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.

In a phase II study, the drug showed clinical activity against ¹³¹I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.

They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.

The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.

As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.

The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.

The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.

As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.

The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).

Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.

Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.

Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.

"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.

Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.

The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.

CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.

In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.

"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.

"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.

Dr. Masters moderated the briefing but was not involved in the study.

Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (¹³¹I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.

There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.

Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.

In a phase II study, the drug showed clinical activity against ¹³¹I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.

They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.

The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.

As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.

The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.

The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.

As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.

The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).

Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.

Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.

Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.

"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.

Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.

The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.

This month in our issue, 10 medical specialty groups offer Choosing Wisely guidelines for hospitalists. Among them, Dr. Linda Cox notes why comprehensive pulmonary assessment, including spirometry, is important to diagnosing or ruling out asthma; and otolaryngologist Dr. Rahul Shah tells why hospitalists should stop routine radiographic imaging for patients who meet the diagnostic criteria for uncomplicated acute rhinosinusitis. Meanwhile, ABIM Foundation executive vice president and CEO Daniel Wolfson talks about why the Choosing Wisely campaign is not just another attempt at cost-containment.

Also in this issue, legal advice for hospitalists on the intersection of social media and HIPAA rules, clinical practice guidelines on red blood cell transfusions, and our Key Clinical Question explores which patients should be screened for hepatitis C infection.

Click here to listen to the June highlights Podcast.

This month in our issue, 10 medical specialty groups offer Choosing Wisely guidelines for hospitalists. Among them, Dr. Linda Cox notes why comprehensive pulmonary assessment, including spirometry, is important to diagnosing or ruling out asthma; and otolaryngologist Dr. Rahul Shah tells why hospitalists should stop routine radiographic imaging for patients who meet the diagnostic criteria for uncomplicated acute rhinosinusitis. Meanwhile, ABIM Foundation executive vice president and CEO Daniel Wolfson talks about why the Choosing Wisely campaign is not just another attempt at cost-containment.

Also in this issue, legal advice for hospitalists on the intersection of social media and HIPAA rules, clinical practice guidelines on red blood cell transfusions, and our Key Clinical Question explores which patients should be screened for hepatitis C infection.

Click here to listen to the June highlights Podcast.

This month in our issue, 10 medical specialty groups offer Choosing Wisely guidelines for hospitalists. Among them, Dr. Linda Cox notes why comprehensive pulmonary assessment, including spirometry, is important to diagnosing or ruling out asthma; and otolaryngologist Dr. Rahul Shah tells why hospitalists should stop routine radiographic imaging for patients who meet the diagnostic criteria for uncomplicated acute rhinosinusitis. Meanwhile, ABIM Foundation executive vice president and CEO Daniel Wolfson talks about why the Choosing Wisely campaign is not just another attempt at cost-containment.

Also in this issue, legal advice for hospitalists on the intersection of social media and HIPAA rules, clinical practice guidelines on red blood cell transfusions, and our Key Clinical Question explores which patients should be screened for hepatitis C infection.

Click here to listen to the June highlights Podcast.

THE CASE

A 46-year-old Caucasian female with a history of epilepsy came into our family medicine center complaining of weakness, fatigue, and arthralgia that made it difficult for her to walk. She’d had these symptoms for 6 months and reported having amenorrhea and hot flashes for the past 2 years.

The patient’s blood pressure was 133/72 mm Hg, heart rate was 82 beats per min, and respiratory rate was 20 breaths per min. Her skin was dry without hyperpigmentation, and her sclerae were anicteric. A musculoskeletal examination revealed tenderness of the metacarpophalangeal and metatarsophalangeal joints without edema, deformity, or evidence of synovitis.

She had no history of skin bronzing, jaundice, transfusions, hepatitis, abdominal pain, or diabetes and denied using tobacco, alcohol, or illicit drugs. Her medications included lamotrigine (250 mg BID) and over-the-counter iron supplementation. She had no family history of rheumatoid arthritis, lupus, cirrhosis, hemochromatosis, or other liver disease. Her mother died from colorectal cancer and her father’s cause of death was unknown; her sisters did not have any medical issues. The patient’s lab tests were normal, except for the following: aspartate aminotransferase, 89 U/L (normal, 13-45 U/L); alanine aminotransferase, 80 U/L (normal, 5-57 U/L); and alkaline phosphatase, 132 U/L (normal, 39-117 U/L). Her coagulation panel revealed a prothrombin time of 13.1 seconds, and an international normalized ratio of 1.3. Serology was negative for hepatitis A, B, and C. Additional testing revealed the following: ferritin, 4014.1 ng/dL (normal, 7-282 ng/dL); iron, 210 mg/dL (normal, 40-170 mg/dL); total iron binding capacity, 258 mg/dL (normal, 260-445 mg/dL); and transferrin saturation, 81% (normal, 20%-55%).

Abdominal ultrasonography revealed gallstones, an enlarged spleen, a dilated portal vein, and a fatty liver consistent with cirrhosis. X-rays showed soft-tissue swelling and demineralization in her hands consistent with osteopenia and degenerative arthritis in both feet.

THE DIAGNOSIS

Based on our patient’s complaints of fatigue, weakness, arthralgia, and amenorrhea, as well as her abnormal iron levels, we suspected hereditary hemochromatosis (HH). We ordered HFE genotyping, and the results indicated that the patient was homozygous for the C282Y mutation, confirming our diagnosis.

DISCUSSION

HH is an autosomal recessive disorder of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue deposition of iron. It is caused by mutations in the HFE gene (C282Y or H63D) located on chromosome 6 (locus 6p21) and commonly seen in Northern European Caucasians.¹ Approximately 85% of patients with HH are homozygous for C282Y; the H63D mutation can cause HH when in the presence of a single C282Y mutation.¹ Men manifest HH symptoms usually between the ages of 40 and 60 years,² although women may be affected at a later age than men because physiologic blood loss from menstruation and parturition limit the rate at which excess iron is accumulated.²

Signs and symptoms of HH include depression, fatigue, restless legs syndrome, weakness, and weight loss.³ In advanced HH, patients may develop progressive skin pigmentation or bronzing, and hypogonadism. Advanced HH can affect the patient’s organs, including the pancreas (diabetes), liver (hepatomegaly, abnormal liver function tests), pituitary gland (amenorrhea, decreased libido, erectile dysfunction), and heart (arrhythmias, congestive heart failure), as well as the musculoskeletal system (joint pain).^3,4 The spleen can also be affected after cirrhosis develops. Cirrhosis, hepatocellular carcinoma, and cardiomyopathy can reduce life expectancy.⁴

Testing for HH

Because symptoms of HH are common and nonspecific, a high degree of clinical suspicion is required for early diagnosis. The differential diagnosis includes conditions related to chronic liver disease or iron overload (TABLE).⁵ If the diagnosis goes undetected until complications arise, the risk of morbidity and mortality are greatly increased.⁵

The diagnosis of HH usually is confirmed by molecular testing for the C282Y and H63D mutations.If HH is suspected, serum ferritin concentration and fasting serum transferrin saturation (the ratio of serum iron level to total iron-binding capacity × 100) are recommended as initial tests.⁵ The normal range of transferrin saturation for males is 15% to 50% and the normal range for females is 12% to 45%. If the transferrin saturation exceeds 50% in women or 60% in men, further evaluation is warranted (FIGURE 1).^6,7 The sensitivity and specificity of elevated transferrin saturation for HH are 92% and 93%, respectively.⁵ These transferrin saturation cutoffs don’t apply to patients with a history of frequent blood transfusion (ie, patients with sickle cell disease or thalassemia).

Additional testing for patients in whom you suspect HH includes:
• a complete blood count, metabolic panel, and coagulation panel
• hepatitis serologies
• imaging (abdominal ultrasound, skeletal radiographs, echocardiogram, abdominal magnetic resonance imaging [MRI])
• a liver biopsy with iron staining and quantitative iron measurements.

The gold standard. Performing a liver biopsy to measure hepatic iron concentration by staining is considered the gold standard test for HH.⁸ But since genetic testing has become more readily available, liver biopsies aren’t widely used to confirm the diagnosis.⁸ The diagnosis of HH usually is confirmed by molecular testing for the C282Y and H63D mutations. Liver biopsy may be recommended to document the degree of fibrosis in all homozygotes over age 40 with elevated serum transaminase levels, clinical evidence of liver disease, or a serum ferritin level >1000 mcg/L.⁷

Phlebotomy helps lower iron levels

Treatment should not be delayed until symptoms develop.³ The mainstay of therapy is phlebotomy.⁹ If phlebotomy is started before the onset of organ damage, patients can anticipate a normal lifespan.⁹ Without treatment death may occur from cirrhosis, hepatocellular carcinoma, or cardiomyopathy.

Removal of 1 unit of red blood cells (450-500 mL) results in the loss of approximately 200 mg of iron. Serum ferritin level testing is the most reliable and least expensive method to monitor therapy.⁹ Iron depletion is complete when the serum ferritin level is 10 to 20 g/L, when the hemoglobin concentration is <11 g/dL, or the hematocrit is <33% for >3 weeks. HH patients need to undergo lifelong phlebotomy to maintain a serum ferritin level <50 g/L. Encourage patients to take in an adequate amount of dietary protein, vitamin B12, and folate to support the accelerated level of erythropoiesis that occurs during therapy.⁹

Chelation therapy is reserved for patients with advanced disease (eg, those with organ damage) or those who do not respond to phlebotomy.¹⁰ Deferoxamine given intravenously (IV) or subcutaneously has been the standard chelation agent. It’s usually administered by continuous subcutaneous infusion using a battery-operated pump at a dose of 40 mg/kg/d for 8 to 12 hours nightly for 5 to 7 nights weekly. A dose of approximately 2 g per 24 hours usually achieves maximal urinary iron excretion.

If phlebotomy is started before the onset of organ damage, patients with hereditary hemochromatosis can anticipate a normal lifespan.The use of deferoxamine therapy is limited by cost as well as the need for parenteral therapy, discomfort, inconvenience, and neurotoxicity.⁵ The US Food and Drug Administration recently approved an oral ironchelating agent, deferasirox, for the treatment of secondary iron overload due to ineffective erythropoiesis. Studies are ongoing to evaluate its potential use in HH.^5,9

Our patient’s outcome

Our patient declined liver biopsy and her sisters declined HFE genotyping. Our patient did, however, complete 7 phlebotomies over 4 months. Two months later, she reported shortness of breath during exertion, leg swelling, and palpitations. A chest x-ray revealed a right-sided pleural effusion and an electrocardiogram showed atrial fibrillation with rapid ventricular response. Our patient was admitted for telemetry monitoring and started on diltiazem IV. Echocardiogram showed a restrictive cardiomyopathy, with an ejection fraction of 15% (normal range >55%).

Six weeks later, her ejection fraction decreased to 10%. An MRI of her abdomen showed iron deposition in her liver, pancreas, and lymph nodes (FIGURE 2). She was started on deferoxamine IV and transferred to the coronary care unit for 3 weeks. She was discharged with a diagnosis of class IV heart failure and admitted 2 weeks later for exacerbation of heart failure symptoms. She did not want to pursue a heart transplant. Her condition deteriorated and she expired after a fatal cardiac arrhythmia.

THE TAKEAWAY

Patients with abnormal iron studies and those with evidence of liver disease should be evaluated for HH⁵ (strength of recommendation [SOR]: A). Fasting serum transferrin saturation and serum ferritin concentration are recommended as initial tests for HH¹¹ (SOR C). Liver biopsy is the gold standard for diagnosis of HH, but the diagnosis usually is confirmed by genetic testing8 (SOR C). Phlebotomy is the mainstay of therapy⁹ (SOR B). Chelation therapy is reserved for patients with advanced disease or for those who do not respond to phlebotomy¹⁰ (SOR C).

Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

THE CASE

A 46-year-old Caucasian female with a history of epilepsy came into our family medicine center complaining of weakness, fatigue, and arthralgia that made it difficult for her to walk. She’d had these symptoms for 6 months and reported having amenorrhea and hot flashes for the past 2 years.

The patient’s blood pressure was 133/72 mm Hg, heart rate was 82 beats per min, and respiratory rate was 20 breaths per min. Her skin was dry without hyperpigmentation, and her sclerae were anicteric. A musculoskeletal examination revealed tenderness of the metacarpophalangeal and metatarsophalangeal joints without edema, deformity, or evidence of synovitis.

She had no history of skin bronzing, jaundice, transfusions, hepatitis, abdominal pain, or diabetes and denied using tobacco, alcohol, or illicit drugs. Her medications included lamotrigine (250 mg BID) and over-the-counter iron supplementation. She had no family history of rheumatoid arthritis, lupus, cirrhosis, hemochromatosis, or other liver disease. Her mother died from colorectal cancer and her father’s cause of death was unknown; her sisters did not have any medical issues. The patient’s lab tests were normal, except for the following: aspartate aminotransferase, 89 U/L (normal, 13-45 U/L); alanine aminotransferase, 80 U/L (normal, 5-57 U/L); and alkaline phosphatase, 132 U/L (normal, 39-117 U/L). Her coagulation panel revealed a prothrombin time of 13.1 seconds, and an international normalized ratio of 1.3. Serology was negative for hepatitis A, B, and C. Additional testing revealed the following: ferritin, 4014.1 ng/dL (normal, 7-282 ng/dL); iron, 210 mg/dL (normal, 40-170 mg/dL); total iron binding capacity, 258 mg/dL (normal, 260-445 mg/dL); and transferrin saturation, 81% (normal, 20%-55%).

Abdominal ultrasonography revealed gallstones, an enlarged spleen, a dilated portal vein, and a fatty liver consistent with cirrhosis. X-rays showed soft-tissue swelling and demineralization in her hands consistent with osteopenia and degenerative arthritis in both feet.

THE DIAGNOSIS

Based on our patient’s complaints of fatigue, weakness, arthralgia, and amenorrhea, as well as her abnormal iron levels, we suspected hereditary hemochromatosis (HH). We ordered HFE genotyping, and the results indicated that the patient was homozygous for the C282Y mutation, confirming our diagnosis.

DISCUSSION

HH is an autosomal recessive disorder of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue deposition of iron. It is caused by mutations in the HFE gene (C282Y or H63D) located on chromosome 6 (locus 6p21) and commonly seen in Northern European Caucasians.¹ Approximately 85% of patients with HH are homozygous for C282Y; the H63D mutation can cause HH when in the presence of a single C282Y mutation.¹ Men manifest HH symptoms usually between the ages of 40 and 60 years,² although women may be affected at a later age than men because physiologic blood loss from menstruation and parturition limit the rate at which excess iron is accumulated.²

Signs and symptoms of HH include depression, fatigue, restless legs syndrome, weakness, and weight loss.³ In advanced HH, patients may develop progressive skin pigmentation or bronzing, and hypogonadism. Advanced HH can affect the patient’s organs, including the pancreas (diabetes), liver (hepatomegaly, abnormal liver function tests), pituitary gland (amenorrhea, decreased libido, erectile dysfunction), and heart (arrhythmias, congestive heart failure), as well as the musculoskeletal system (joint pain).^3,4 The spleen can also be affected after cirrhosis develops. Cirrhosis, hepatocellular carcinoma, and cardiomyopathy can reduce life expectancy.⁴

Testing for HH

Because symptoms of HH are common and nonspecific, a high degree of clinical suspicion is required for early diagnosis. The differential diagnosis includes conditions related to chronic liver disease or iron overload (TABLE).⁵ If the diagnosis goes undetected until complications arise, the risk of morbidity and mortality are greatly increased.⁵

The diagnosis of HH usually is confirmed by molecular testing for the C282Y and H63D mutations.If HH is suspected, serum ferritin concentration and fasting serum transferrin saturation (the ratio of serum iron level to total iron-binding capacity × 100) are recommended as initial tests.⁵ The normal range of transferrin saturation for males is 15% to 50% and the normal range for females is 12% to 45%. If the transferrin saturation exceeds 50% in women or 60% in men, further evaluation is warranted (FIGURE 1).^6,7 The sensitivity and specificity of elevated transferrin saturation for HH are 92% and 93%, respectively.⁵ These transferrin saturation cutoffs don’t apply to patients with a history of frequent blood transfusion (ie, patients with sickle cell disease or thalassemia).

Additional testing for patients in whom you suspect HH includes:
• a complete blood count, metabolic panel, and coagulation panel
• hepatitis serologies
• imaging (abdominal ultrasound, skeletal radiographs, echocardiogram, abdominal magnetic resonance imaging [MRI])
• a liver biopsy with iron staining and quantitative iron measurements.

The gold standard. Performing a liver biopsy to measure hepatic iron concentration by staining is considered the gold standard test for HH.⁸ But since genetic testing has become more readily available, liver biopsies aren’t widely used to confirm the diagnosis.⁸ The diagnosis of HH usually is confirmed by molecular testing for the C282Y and H63D mutations. Liver biopsy may be recommended to document the degree of fibrosis in all homozygotes over age 40 with elevated serum transaminase levels, clinical evidence of liver disease, or a serum ferritin level >1000 mcg/L.⁷

Phlebotomy helps lower iron levels

Treatment should not be delayed until symptoms develop.³ The mainstay of therapy is phlebotomy.⁹ If phlebotomy is started before the onset of organ damage, patients can anticipate a normal lifespan.⁹ Without treatment death may occur from cirrhosis, hepatocellular carcinoma, or cardiomyopathy.

Removal of 1 unit of red blood cells (450-500 mL) results in the loss of approximately 200 mg of iron. Serum ferritin level testing is the most reliable and least expensive method to monitor therapy.⁹ Iron depletion is complete when the serum ferritin level is 10 to 20 g/L, when the hemoglobin concentration is <11 g/dL, or the hematocrit is <33% for >3 weeks. HH patients need to undergo lifelong phlebotomy to maintain a serum ferritin level <50 g/L. Encourage patients to take in an adequate amount of dietary protein, vitamin B12, and folate to support the accelerated level of erythropoiesis that occurs during therapy.⁹

Chelation therapy is reserved for patients with advanced disease (eg, those with organ damage) or those who do not respond to phlebotomy.¹⁰ Deferoxamine given intravenously (IV) or subcutaneously has been the standard chelation agent. It’s usually administered by continuous subcutaneous infusion using a battery-operated pump at a dose of 40 mg/kg/d for 8 to 12 hours nightly for 5 to 7 nights weekly. A dose of approximately 2 g per 24 hours usually achieves maximal urinary iron excretion.

If phlebotomy is started before the onset of organ damage, patients with hereditary hemochromatosis can anticipate a normal lifespan.The use of deferoxamine therapy is limited by cost as well as the need for parenteral therapy, discomfort, inconvenience, and neurotoxicity.⁵ The US Food and Drug Administration recently approved an oral ironchelating agent, deferasirox, for the treatment of secondary iron overload due to ineffective erythropoiesis. Studies are ongoing to evaluate its potential use in HH.^5,9

Our patient’s outcome

Our patient declined liver biopsy and her sisters declined HFE genotyping. Our patient did, however, complete 7 phlebotomies over 4 months. Two months later, she reported shortness of breath during exertion, leg swelling, and palpitations. A chest x-ray revealed a right-sided pleural effusion and an electrocardiogram showed atrial fibrillation with rapid ventricular response. Our patient was admitted for telemetry monitoring and started on diltiazem IV. Echocardiogram showed a restrictive cardiomyopathy, with an ejection fraction of 15% (normal range >55%).

Six weeks later, her ejection fraction decreased to 10%. An MRI of her abdomen showed iron deposition in her liver, pancreas, and lymph nodes (FIGURE 2). She was started on deferoxamine IV and transferred to the coronary care unit for 3 weeks. She was discharged with a diagnosis of class IV heart failure and admitted 2 weeks later for exacerbation of heart failure symptoms. She did not want to pursue a heart transplant. Her condition deteriorated and she expired after a fatal cardiac arrhythmia.

THE TAKEAWAY

Patients with abnormal iron studies and those with evidence of liver disease should be evaluated for HH⁵ (strength of recommendation [SOR]: A). Fasting serum transferrin saturation and serum ferritin concentration are recommended as initial tests for HH¹¹ (SOR C). Liver biopsy is the gold standard for diagnosis of HH, but the diagnosis usually is confirmed by genetic testing8 (SOR C). Phlebotomy is the mainstay of therapy⁹ (SOR B). Chelation therapy is reserved for patients with advanced disease or for those who do not respond to phlebotomy¹⁰ (SOR C).

Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

THE CASE

A 46-year-old Caucasian female with a history of epilepsy came into our family medicine center complaining of weakness, fatigue, and arthralgia that made it difficult for her to walk. She’d had these symptoms for 6 months and reported having amenorrhea and hot flashes for the past 2 years.

The patient’s blood pressure was 133/72 mm Hg, heart rate was 82 beats per min, and respiratory rate was 20 breaths per min. Her skin was dry without hyperpigmentation, and her sclerae were anicteric. A musculoskeletal examination revealed tenderness of the metacarpophalangeal and metatarsophalangeal joints without edema, deformity, or evidence of synovitis.

She had no history of skin bronzing, jaundice, transfusions, hepatitis, abdominal pain, or diabetes and denied using tobacco, alcohol, or illicit drugs. Her medications included lamotrigine (250 mg BID) and over-the-counter iron supplementation. She had no family history of rheumatoid arthritis, lupus, cirrhosis, hemochromatosis, or other liver disease. Her mother died from colorectal cancer and her father’s cause of death was unknown; her sisters did not have any medical issues. The patient’s lab tests were normal, except for the following: aspartate aminotransferase, 89 U/L (normal, 13-45 U/L); alanine aminotransferase, 80 U/L (normal, 5-57 U/L); and alkaline phosphatase, 132 U/L (normal, 39-117 U/L). Her coagulation panel revealed a prothrombin time of 13.1 seconds, and an international normalized ratio of 1.3. Serology was negative for hepatitis A, B, and C. Additional testing revealed the following: ferritin, 4014.1 ng/dL (normal, 7-282 ng/dL); iron, 210 mg/dL (normal, 40-170 mg/dL); total iron binding capacity, 258 mg/dL (normal, 260-445 mg/dL); and transferrin saturation, 81% (normal, 20%-55%).

Abdominal ultrasonography revealed gallstones, an enlarged spleen, a dilated portal vein, and a fatty liver consistent with cirrhosis. X-rays showed soft-tissue swelling and demineralization in her hands consistent with osteopenia and degenerative arthritis in both feet.

THE DIAGNOSIS

Based on our patient’s complaints of fatigue, weakness, arthralgia, and amenorrhea, as well as her abnormal iron levels, we suspected hereditary hemochromatosis (HH). We ordered HFE genotyping, and the results indicated that the patient was homozygous for the C282Y mutation, confirming our diagnosis.

DISCUSSION

HH is an autosomal recessive disorder of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue deposition of iron. It is caused by mutations in the HFE gene (C282Y or H63D) located on chromosome 6 (locus 6p21) and commonly seen in Northern European Caucasians.¹ Approximately 85% of patients with HH are homozygous for C282Y; the H63D mutation can cause HH when in the presence of a single C282Y mutation.¹ Men manifest HH symptoms usually between the ages of 40 and 60 years,² although women may be affected at a later age than men because physiologic blood loss from menstruation and parturition limit the rate at which excess iron is accumulated.²

Signs and symptoms of HH include depression, fatigue, restless legs syndrome, weakness, and weight loss.³ In advanced HH, patients may develop progressive skin pigmentation or bronzing, and hypogonadism. Advanced HH can affect the patient’s organs, including the pancreas (diabetes), liver (hepatomegaly, abnormal liver function tests), pituitary gland (amenorrhea, decreased libido, erectile dysfunction), and heart (arrhythmias, congestive heart failure), as well as the musculoskeletal system (joint pain).^3,4 The spleen can also be affected after cirrhosis develops. Cirrhosis, hepatocellular carcinoma, and cardiomyopathy can reduce life expectancy.⁴

Testing for HH

Because symptoms of HH are common and nonspecific, a high degree of clinical suspicion is required for early diagnosis. The differential diagnosis includes conditions related to chronic liver disease or iron overload (TABLE).⁵ If the diagnosis goes undetected until complications arise, the risk of morbidity and mortality are greatly increased.⁵

The diagnosis of HH usually is confirmed by molecular testing for the C282Y and H63D mutations.If HH is suspected, serum ferritin concentration and fasting serum transferrin saturation (the ratio of serum iron level to total iron-binding capacity × 100) are recommended as initial tests.⁵ The normal range of transferrin saturation for males is 15% to 50% and the normal range for females is 12% to 45%. If the transferrin saturation exceeds 50% in women or 60% in men, further evaluation is warranted (FIGURE 1).^6,7 The sensitivity and specificity of elevated transferrin saturation for HH are 92% and 93%, respectively.⁵ These transferrin saturation cutoffs don’t apply to patients with a history of frequent blood transfusion (ie, patients with sickle cell disease or thalassemia).

Additional testing for patients in whom you suspect HH includes:
• a complete blood count, metabolic panel, and coagulation panel
• hepatitis serologies
• imaging (abdominal ultrasound, skeletal radiographs, echocardiogram, abdominal magnetic resonance imaging [MRI])
• a liver biopsy with iron staining and quantitative iron measurements.

The gold standard. Performing a liver biopsy to measure hepatic iron concentration by staining is considered the gold standard test for HH.⁸ But since genetic testing has become more readily available, liver biopsies aren’t widely used to confirm the diagnosis.⁸ The diagnosis of HH usually is confirmed by molecular testing for the C282Y and H63D mutations. Liver biopsy may be recommended to document the degree of fibrosis in all homozygotes over age 40 with elevated serum transaminase levels, clinical evidence of liver disease, or a serum ferritin level >1000 mcg/L.⁷

Phlebotomy helps lower iron levels

Treatment should not be delayed until symptoms develop.³ The mainstay of therapy is phlebotomy.⁹ If phlebotomy is started before the onset of organ damage, patients can anticipate a normal lifespan.⁹ Without treatment death may occur from cirrhosis, hepatocellular carcinoma, or cardiomyopathy.

Removal of 1 unit of red blood cells (450-500 mL) results in the loss of approximately 200 mg of iron. Serum ferritin level testing is the most reliable and least expensive method to monitor therapy.⁹ Iron depletion is complete when the serum ferritin level is 10 to 20 g/L, when the hemoglobin concentration is <11 g/dL, or the hematocrit is <33% for >3 weeks. HH patients need to undergo lifelong phlebotomy to maintain a serum ferritin level <50 g/L. Encourage patients to take in an adequate amount of dietary protein, vitamin B12, and folate to support the accelerated level of erythropoiesis that occurs during therapy.⁹

Chelation therapy is reserved for patients with advanced disease (eg, those with organ damage) or those who do not respond to phlebotomy.¹⁰ Deferoxamine given intravenously (IV) or subcutaneously has been the standard chelation agent. It’s usually administered by continuous subcutaneous infusion using a battery-operated pump at a dose of 40 mg/kg/d for 8 to 12 hours nightly for 5 to 7 nights weekly. A dose of approximately 2 g per 24 hours usually achieves maximal urinary iron excretion.

If phlebotomy is started before the onset of organ damage, patients with hereditary hemochromatosis can anticipate a normal lifespan.The use of deferoxamine therapy is limited by cost as well as the need for parenteral therapy, discomfort, inconvenience, and neurotoxicity.⁵ The US Food and Drug Administration recently approved an oral ironchelating agent, deferasirox, for the treatment of secondary iron overload due to ineffective erythropoiesis. Studies are ongoing to evaluate its potential use in HH.^5,9

Our patient’s outcome

Our patient declined liver biopsy and her sisters declined HFE genotyping. Our patient did, however, complete 7 phlebotomies over 4 months. Two months later, she reported shortness of breath during exertion, leg swelling, and palpitations. A chest x-ray revealed a right-sided pleural effusion and an electrocardiogram showed atrial fibrillation with rapid ventricular response. Our patient was admitted for telemetry monitoring and started on diltiazem IV. Echocardiogram showed a restrictive cardiomyopathy, with an ejection fraction of 15% (normal range >55%).

Six weeks later, her ejection fraction decreased to 10%. An MRI of her abdomen showed iron deposition in her liver, pancreas, and lymph nodes (FIGURE 2). She was started on deferoxamine IV and transferred to the coronary care unit for 3 weeks. She was discharged with a diagnosis of class IV heart failure and admitted 2 weeks later for exacerbation of heart failure symptoms. She did not want to pursue a heart transplant. Her condition deteriorated and she expired after a fatal cardiac arrhythmia.

THE TAKEAWAY

Patients with abnormal iron studies and those with evidence of liver disease should be evaluated for HH⁵ (strength of recommendation [SOR]: A). Fasting serum transferrin saturation and serum ferritin concentration are recommended as initial tests for HH¹¹ (SOR C). Liver biopsy is the gold standard for diagnosis of HH, but the diagnosis usually is confirmed by genetic testing8 (SOR C). Phlebotomy is the mainstay of therapy⁹ (SOR B). Chelation therapy is reserved for patients with advanced disease or for those who do not respond to phlebotomy¹⁰ (SOR C).

Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Listen to Daniel Wolfson explain how the Choosing Wisely campaign got started and its significance in U.S. healthcare

Listen to Daniel Wolfson explain how the Choosing Wisely campaign got started and its significance in U.S. healthcare

Listen to Daniel Wolfson explain how the Choosing Wisely campaign got started and its significance in U.S. healthcare

Listen to Dr. Cox, owner of Allergy and Asthma Center in Ft. Lauderdale, Fla., discuss why it's important for hospitalists to avoid diagnosing or managing asthma without spirometry.

Click here to listen to Dr. Shah, associate professor of otolaryngology and pediatrics at Children's National Medical Center in Washington, D.C, tell hospitalists why they should avoid routine radiographic imaging for patients who meet diagnostic criteria for uncomplicated acute rhinosinusitis.

Listen to Dr. Cox, owner of Allergy and Asthma Center in Ft. Lauderdale, Fla., discuss why it's important for hospitalists to avoid diagnosing or managing asthma without spirometry.

Click here to listen to Dr. Shah, associate professor of otolaryngology and pediatrics at Children's National Medical Center in Washington, D.C, tell hospitalists why they should avoid routine radiographic imaging for patients who meet diagnostic criteria for uncomplicated acute rhinosinusitis.

Listen to Dr. Cox, owner of Allergy and Asthma Center in Ft. Lauderdale, Fla., discuss why it's important for hospitalists to avoid diagnosing or managing asthma without spirometry.

Click here to listen to Dr. Shah, associate professor of otolaryngology and pediatrics at Children's National Medical Center in Washington, D.C, tell hospitalists why they should avoid routine radiographic imaging for patients who meet diagnostic criteria for uncomplicated acute rhinosinusitis.

EVIDENCE SUMMARY

Most data on the effectiveness of topical antibiotics focus on bacitracin, fusidic acid (not available in the United States), and mupirocin. Retapamulin 1% ointment, a topical antibiotic in the pleuromutilin class, is approved by the US Food and Drug Administration (FDA) for use in adults and children older than 9 months to treat impetigo caused by methicillin-susceptible Staphylococcus aureus and Streptococcus pyogenes.¹

Topical antibiotics outperform placebo

A 2003 meta-analysis of 16 studies (1944 patients) evaluated treatments for impetigo in both adults and children.² Investigators conducted most of the studies in outpatient settings in the United States, United Kingdom, Northern Europe, and Canada. They expressed outcomes in terms of cure or clinical improvement within 7 to 14 days of starting treatment.

Topical agents, including mupirocin, fusidic acid, and gentamicin, resulted in cure or improvement in more patients at 7 to 14 days than placebo (absolute benefit increase=20%; number needed to treat [NNT]=5; 95% confidence interval [CI], 1.49-4.86). Definitions of cure or improvement varied among the included studies, however.

A 2012 Cochrane review of various interventions included 68 RCTs with a total of 5708 participants, primarily from pediatric or dermatology hospital outpatient clinics in North America and Europe.³ Clinical cure (defined as clearance of crusts, blisters, and redness as determined by investigators) or improvement at one week were the primary outcomes (TABLE).^3,4 Mupirocin (relative risk [RR]=2.21; 95% CI, 1.16-3.13), fusidic acid (RR=4.42; 95% CI, 2.39-8.17), and retapamulin (RR=1.64; 95% CI, 1.30-2.07) all demonstrated higher rates of cure or improvement than placebo.

 

 

Retapamulin produces greater clinical response than placebo in an RCT

A 2008 randomized, double-blind, multicenter, industry-funded, placebo-controlled trial of 213 patients evaluated the effectiveness of retapamulin to treat uncomplicated impetigo with an outcome of clinical response at 7 days.⁴ Clinical response was defined as total absence of lesions, drying of treated lesions without crusts or erythema, decrease in the size of the affected area or decrease in the number of lesions. Retapamulin ointment produced a higher rate of clinical response than placebo (absolute risk reduction=33.5%; 95% CI, 20.5-46.5; NNT=3, P<.001).

TABLE
How well do impetigo treatments work?^3,4

^{ARR, absolute risk reduction; NNT, number needed to treat; NS, not significant.
*Cost data obtained from Medi-Span at www.uptodate.com. Accessed December 5, 2013.}

 

 

Topical antibiotics work slightly better than disinfectant solutions

In a pooled analysis from the 2012 Cochrane review, topical bacitracin and fusidic acid demonstrated slightly higher rates of cure or improvement than disinfectant solutions (RR=1.15; 95% CI, 1.01-1.32).³ Oral antibiotics may work as well as, or better than, topicals The 2012 Cochrane review found better rates of cure or improvement for topical mupirocin than oral erythromycin (RR=1.07; 95% CI, 1.01-1.13).³ Investigators noted no significant differences between topical mupirocin and bacitracin and oral antibiotics other than erythromycin, although in one small study (10 patients), oral cephalexin resulted in a higher rate of cure or improvement than topical bacitracin (absolute risk reduction [ARR]=56.7%; NNT=2).

Studies comparing oral antibiotics found that both erythromycin and cloxacillin (not available in the United States) produced higher rates of cure or improvement than penicillin (erythromycin, RR=1.29; 95% CI, 1.07-1.56; cloxacillin, RR=1.14; 95% CI, 0.80-1.62).

RECOMMENDATIONS

The Infectious Diseases Society of America recommends topical mupirocin as first-line therapy for impetigo, although resistance to the drug exists. Patients with numerous lesions or who fail to respond to topical treatment should be treated with oral antibiotics active against S pyogenes and S aureus. Recommended oral antibiotics include dicloxacillin, amoxicillin/clavulanate, cephalexin, erythromycin, and clindamycin.⁵

EVIDENCE SUMMARY

Most data on the effectiveness of topical antibiotics focus on bacitracin, fusidic acid (not available in the United States), and mupirocin. Retapamulin 1% ointment, a topical antibiotic in the pleuromutilin class, is approved by the US Food and Drug Administration (FDA) for use in adults and children older than 9 months to treat impetigo caused by methicillin-susceptible Staphylococcus aureus and Streptococcus pyogenes.¹

Topical antibiotics outperform placebo

A 2003 meta-analysis of 16 studies (1944 patients) evaluated treatments for impetigo in both adults and children.² Investigators conducted most of the studies in outpatient settings in the United States, United Kingdom, Northern Europe, and Canada. They expressed outcomes in terms of cure or clinical improvement within 7 to 14 days of starting treatment.

Topical agents, including mupirocin, fusidic acid, and gentamicin, resulted in cure or improvement in more patients at 7 to 14 days than placebo (absolute benefit increase=20%; number needed to treat [NNT]=5; 95% confidence interval [CI], 1.49-4.86). Definitions of cure or improvement varied among the included studies, however.

A 2012 Cochrane review of various interventions included 68 RCTs with a total of 5708 participants, primarily from pediatric or dermatology hospital outpatient clinics in North America and Europe.³ Clinical cure (defined as clearance of crusts, blisters, and redness as determined by investigators) or improvement at one week were the primary outcomes (TABLE).^3,4 Mupirocin (relative risk [RR]=2.21; 95% CI, 1.16-3.13), fusidic acid (RR=4.42; 95% CI, 2.39-8.17), and retapamulin (RR=1.64; 95% CI, 1.30-2.07) all demonstrated higher rates of cure or improvement than placebo.

 

 

Retapamulin produces greater clinical response than placebo in an RCT

A 2008 randomized, double-blind, multicenter, industry-funded, placebo-controlled trial of 213 patients evaluated the effectiveness of retapamulin to treat uncomplicated impetigo with an outcome of clinical response at 7 days.⁴ Clinical response was defined as total absence of lesions, drying of treated lesions without crusts or erythema, decrease in the size of the affected area or decrease in the number of lesions. Retapamulin ointment produced a higher rate of clinical response than placebo (absolute risk reduction=33.5%; 95% CI, 20.5-46.5; NNT=3, P<.001).

TABLE
How well do impetigo treatments work?^3,4

^{ARR, absolute risk reduction; NNT, number needed to treat; NS, not significant.
*Cost data obtained from Medi-Span at www.uptodate.com. Accessed December 5, 2013.}

 

 

Topical antibiotics work slightly better than disinfectant solutions

In a pooled analysis from the 2012 Cochrane review, topical bacitracin and fusidic acid demonstrated slightly higher rates of cure or improvement than disinfectant solutions (RR=1.15; 95% CI, 1.01-1.32).³ Oral antibiotics may work as well as, or better than, topicals The 2012 Cochrane review found better rates of cure or improvement for topical mupirocin than oral erythromycin (RR=1.07; 95% CI, 1.01-1.13).³ Investigators noted no significant differences between topical mupirocin and bacitracin and oral antibiotics other than erythromycin, although in one small study (10 patients), oral cephalexin resulted in a higher rate of cure or improvement than topical bacitracin (absolute risk reduction [ARR]=56.7%; NNT=2).

Studies comparing oral antibiotics found that both erythromycin and cloxacillin (not available in the United States) produced higher rates of cure or improvement than penicillin (erythromycin, RR=1.29; 95% CI, 1.07-1.56; cloxacillin, RR=1.14; 95% CI, 0.80-1.62).

RECOMMENDATIONS

The Infectious Diseases Society of America recommends topical mupirocin as first-line therapy for impetigo, although resistance to the drug exists. Patients with numerous lesions or who fail to respond to topical treatment should be treated with oral antibiotics active against S pyogenes and S aureus. Recommended oral antibiotics include dicloxacillin, amoxicillin/clavulanate, cephalexin, erythromycin, and clindamycin.⁵

EVIDENCE SUMMARY

Most data on the effectiveness of topical antibiotics focus on bacitracin, fusidic acid (not available in the United States), and mupirocin. Retapamulin 1% ointment, a topical antibiotic in the pleuromutilin class, is approved by the US Food and Drug Administration (FDA) for use in adults and children older than 9 months to treat impetigo caused by methicillin-susceptible Staphylococcus aureus and Streptococcus pyogenes.¹

Topical antibiotics outperform placebo

A 2003 meta-analysis of 16 studies (1944 patients) evaluated treatments for impetigo in both adults and children.² Investigators conducted most of the studies in outpatient settings in the United States, United Kingdom, Northern Europe, and Canada. They expressed outcomes in terms of cure or clinical improvement within 7 to 14 days of starting treatment.

Topical agents, including mupirocin, fusidic acid, and gentamicin, resulted in cure or improvement in more patients at 7 to 14 days than placebo (absolute benefit increase=20%; number needed to treat [NNT]=5; 95% confidence interval [CI], 1.49-4.86). Definitions of cure or improvement varied among the included studies, however.

A 2012 Cochrane review of various interventions included 68 RCTs with a total of 5708 participants, primarily from pediatric or dermatology hospital outpatient clinics in North America and Europe.³ Clinical cure (defined as clearance of crusts, blisters, and redness as determined by investigators) or improvement at one week were the primary outcomes (TABLE).^3,4 Mupirocin (relative risk [RR]=2.21; 95% CI, 1.16-3.13), fusidic acid (RR=4.42; 95% CI, 2.39-8.17), and retapamulin (RR=1.64; 95% CI, 1.30-2.07) all demonstrated higher rates of cure or improvement than placebo.

 

 

Retapamulin produces greater clinical response than placebo in an RCT

A 2008 randomized, double-blind, multicenter, industry-funded, placebo-controlled trial of 213 patients evaluated the effectiveness of retapamulin to treat uncomplicated impetigo with an outcome of clinical response at 7 days.⁴ Clinical response was defined as total absence of lesions, drying of treated lesions without crusts or erythema, decrease in the size of the affected area or decrease in the number of lesions. Retapamulin ointment produced a higher rate of clinical response than placebo (absolute risk reduction=33.5%; 95% CI, 20.5-46.5; NNT=3, P<.001).

TABLE
How well do impetigo treatments work?^3,4

^{ARR, absolute risk reduction; NNT, number needed to treat; NS, not significant.
*Cost data obtained from Medi-Span at www.uptodate.com. Accessed December 5, 2013.}

 

 

Topical antibiotics work slightly better than disinfectant solutions

In a pooled analysis from the 2012 Cochrane review, topical bacitracin and fusidic acid demonstrated slightly higher rates of cure or improvement than disinfectant solutions (RR=1.15; 95% CI, 1.01-1.32).³ Oral antibiotics may work as well as, or better than, topicals The 2012 Cochrane review found better rates of cure or improvement for topical mupirocin than oral erythromycin (RR=1.07; 95% CI, 1.01-1.13).³ Investigators noted no significant differences between topical mupirocin and bacitracin and oral antibiotics other than erythromycin, although in one small study (10 patients), oral cephalexin resulted in a higher rate of cure or improvement than topical bacitracin (absolute risk reduction [ARR]=56.7%; NNT=2).

Studies comparing oral antibiotics found that both erythromycin and cloxacillin (not available in the United States) produced higher rates of cure or improvement than penicillin (erythromycin, RR=1.29; 95% CI, 1.07-1.56; cloxacillin, RR=1.14; 95% CI, 0.80-1.62).

RECOMMENDATIONS

The Infectious Diseases Society of America recommends topical mupirocin as first-line therapy for impetigo, although resistance to the drug exists. Patients with numerous lesions or who fail to respond to topical treatment should be treated with oral antibiotics active against S pyogenes and S aureus. Recommended oral antibiotics include dicloxacillin, amoxicillin/clavulanate, cephalexin, erythromycin, and clindamycin.⁵

EVIDENCE SUMMARY

Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).^1-8

Meta-analyses evaluate effects of chromium and cinnamon

A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.¹ Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.

A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.² After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).

When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.

 

 

What about caiapo, fenugreek, milk thistle, and safflower oil?

Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.^3,4

TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes

^{CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.}

Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.^5-8

RECOMMENDATIONS

Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”^9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.⁹

EVIDENCE SUMMARY

Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).^1-8

Meta-analyses evaluate effects of chromium and cinnamon

A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.¹ Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.

A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.² After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).

When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.

 

 

What about caiapo, fenugreek, milk thistle, and safflower oil?

Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.^3,4

TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes

^{CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.}

Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.^5-8

RECOMMENDATIONS

Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”^9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.⁹

EVIDENCE SUMMARY

Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).^1-8

Meta-analyses evaluate effects of chromium and cinnamon

A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.¹ Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.

A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.² After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).

When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.

 

 

What about caiapo, fenugreek, milk thistle, and safflower oil?

Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.^3,4

TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes

^{CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.}

Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.^5-8

RECOMMENDATIONS

Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”^9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.⁹

ABSTRACT

Purpose Primary care physicians are at the center of a national prescription opioid epidemic, with little training or knowledge about the management of patients on opioids for chronic noncancer pain (CNCP). We developed an electronic medical record (EMR)-based protocol and educational intervention to standardize documentation and management of patients prescribed opioids by primary care providers. Our objective was to evaluate provider adherence to this protocol, attitudes toward the management of these patients, and knowledge of opioid prescribing.

Methods We trained providers and select staff from 3 primary care practices at the Division of General Internal Medicine at the University of Pennsylvania in the use of a protocol for managing patients taking opioids for CNCP. The following served as measures of protocol adherence: 1) the provider used a standard diagnosis (chronic pain, ICD-9 code 338.29A) in the problem list, 2) the provider ordered at least one urine drug screen (UDS) for the patient in the past year, and 3) the patient came in for at least one office visit every 6 months. We assessed physician and staff attitudes and knowledge with pre- and post-intervention surveys. Adherence to the protocol was linked to a monetary incentive.

Results Provider adherence to the protocol significantly improved measured outcomes. The number of UDSs ordered increased by 145%, and the diagnosis of chronic pain on the problem list increased by 424%. There was a statistically significant improvement in providers’ role adequacy, role support, and job satisfaction/role-related self-esteem when working with patients taking opioids. In addition, provider knowledge of proper management of these patients improved significantly. Eighty-nine percent of our physicians attained the monetary incentive.

Conclusions We developed a quality improvement intervention that addressed the need for better regulation of opioid prescribing, resulted in increased adherence to best-practice guidelines, and improved provider knowledge and attitudes.

In all 3 practices, the total number of patients prescribed >2 opioid medications declined during the year-long study period.Primary care physicians often express dissatisfaction with their competency in treating patients with opioids,¹ and at our institution, this includes residents and faculty, as well. Their concern, combined with apprehension about patient safety and the potential for addiction, can hinder appropriate opioid management.¹ We asked: Could a protocol that structures the intervention improve physician competence and performance in prescribing opioids and reduce patient risk?

Physician concerns are well-founded. Nonmedical use of prescription opioids is second only to smoking marijuana in the illicit use of drugs in the United States.² Since 2003, more overdose deaths have involved opioid analgesics than heroin and cocaine combined, leading the Centers for Disease Control and Prevention to declare in 2012 that the problem was a “national epidemic.”³ The Washington State Medical Quality Assurance Commission now mandates extensive patient evaluation and documentation, the use of a Controlled Medication Agreement (CMA), and specific education requirements for physicians prescribing long-acting or high-dose opioids.⁴

Necessary adjustments going forward. As the nation moves toward more regulated prescribing of opioids, physicians will need to develop a consistent approach to this complicated task. Primary care doctors must be at the center of this effort, as they generate most opioid prescriptions for the treatment of CNCP. Currently, providers vary widely in their management of this condition,^5-7 and recommended corrective steps include increased education8 and improved adherence to national guidelines. Our contention—and the basis of our study—was that a clinical protocol for opioid prescribing could improve the care that physicians and staff were providing to CNCP patients, as well as improve the satisfaction that clinicians felt in providing this care.

Our protocol intervention. Prior to our protocol intervention, no guidelines existed for managing patients on long-term opioid therapy in the clinical practices of the University of Pennsylvania Division of General Internal Medicine. Our providers, too, varied widely in their prescribing and management. Though regular urine drug screening is known to improve detection of opioid misuse and decrease the problem in patients treated for CNCP,^9,10 a study reviewing opioid prescribing practices in our clinics from 2004 to 2007 showed that physicians ordered UDSs for only 8% of patients.¹¹ Furthermore, only half of patients (49.8%) had regular office visits—even those at high risk for opioid misuse.¹¹

Based on expert opinion and national best-practice guidelines, we created a division-wide quality improvement intervention for opioid prescribing. The protocol required standardized evaluation and documentation of a patient’s pain history and treatment plan, and the use of a UDS and a CMA, which is known to decrease emergency room visits and improve physician satisfaction, respectively.^9,10 We trained attending physicians and staff on the protocol, and they in turn taught residents at their practice sites. The goal of this study was to determine whether this initiative would result in adherence to the protocol and improve provider and staff knowledge and satisfaction with management of patients prescribed opioids for CNCP.

METHODS

The intervention consisted of (1) the development of an EMR-based protocol to standardize documentation and management of patients with CNCP taking opioids; (2) instruction on using the protocol and on key components of opioid management; (3) collection of data; and (4) a monetary incentive for attending physicians to adhere to the protocol. We measured the impact of this intervention by assessing physician compliance with the protocol, provider satisfaction, and knowledge.

Protocol and process

We developed a division-wide protocol for managing primary-care patients with CNCP taking opioids, based on national guidelines, expert input, best practice data, and EMR capabilities (EpicCare Ambulatory Medical Record, version Summer 2009).

Health system experts from anesthesia, pain management, and psychiatry met regularly with our monthly workgroup to review the latest literature on UDSs and CMAs, and to assess best practices researched by the Center for Evidence Based Practice at our institution. We trained providers on the following steps:
• select patients who are taking opioids for CNCP (ie, receiving >2 opioid prescriptions in the 6 months prior to the intervention for a nonlimited pain condition)
• risk stratify these patients using the Opioid Risk Tool¹²
• follow high-risk patients monthly; low-to-moderate-risk patients every 3 to 6 months
• use a standard diagnosis (chronic pain, ICD-9 code 338.29A) in the EMR problem list
• complete a standardized EMR “smart set” documenting evaluation and management in the overview section of the EMR’s chronic pain diagnosis module (TABLE 1)
• complete a CMA
• order a UDS at regular intervals (at least one per year; every 1-3 months in high-risk patients)
• designate one provider (in the EMR) to be responsible for opioid prescribing. Medical residents were encouraged to specify a “Continuity Attending” to maintain continuity of care when they were not in clinic.

Educational intervention

The principal investigator conducted 4 training sessions that were available to all attending physicians and staff, to review the protocol as well as information on best practices in opioid prescribing. One session was a Quality Improvement Grand Rounds for the division, and 3 sessions were open presentations within each participating practice. During all sessions, we taught the protocol, provided instruction on riskstratifying patients, reviewed the definition and prevalence of chronic pain, described the national opioid problem, detailed the components of proper documentation, and explained how to interpret and manage UDS results.

We trained categorical internal medicine interns for 1 hour during their mandatory clinical lecture series. Primary care track residents received 4 hours of training as part of their regular educational program.

Through a straightforward protocol, we increased the number of UDSs ordered (145%) and documentation of chronic pain on the problem list (424%).Ongoing education for attending physicians occurred at 4 bimonthly opioid management case conferences, where difficult cases were presented to a rotating panel of experts from pain medicine, addiction psychiatry, and primary care. We held regular noon conferences on opioid management for residents.

Monetary incentive for physicians

Our division further aided our efforts by offering a monetary incentive ($1500) to attending physicians who achieved all 3 of the following measures of adherence with at least 80% of their chronic pain patients: at least one UDS in the past year, an office visit at least every 6 months, and a chronic pain diagnosis on the problem list in the EMR.

Data feedback

We gave providers a list of their patients receiving >2 opioid prescriptions over 6 months, and were able to exclude those patients treated for a limited pain condition. For the remainder of patients, physicians received quarterly individual reports on their adherence to the protocol.

Study population

Three internal medicine clinical practices of the University of Pennsylvania in Philadelphia took part in this initiative. We included all attending providers at these practices in the analysis assessing adherence to the protocol. Those who consented and completed a survey were included in the survey analysis. Providers were attending physicians and nurse practitioners. In Practice 1, primary care track residents are fully integrated into the practice and were included in the survey as their extended training was timed with our intervention. We did not survey residents at the other practices due to their variable schedules and inability to train as a group.

We believe this protocol will lead to improved management of patients with chronic noncancer pain by providing objective urine data to guide a treatment plan.Staff included registered nurses, licensed practical nurses, medical assistants, and patient service representatives. Because nurses and medical assistants are responsible for medication refills, they received education specifically about this intervention. The remaining staff also received instruction, as they have personal interactions with patients at the provider visit, and thus their attitudes were important to measure. Participants completed surveys at the time of the educational sessions and again 9 months following implementation of the intervention. This was a one-year intervention, with 3 initial months of teaching; the study period therefore lasted 9 months. Since surveys were anonymous, we could not link results to specific individuals. However, we provided post-intervention surveys only to those who reported completing the initial survey.

Survey design and administration

The provider survey contained an attitude component and a knowledge component (TABLE 2). The attitude component consisted of 6 items taken from the Drug Problems Perceptions Questionnaire,13 to address role adequacy, support, and self-esteem, as well as job satisfaction (the words “drug users” were replaced with “patients on [chronic] opioids”). We created an additional 3 items to further explore these domains (items 1-3). Three additional items addressed provider access to EMR specific tools (items 10-12).

The knowledge survey consisted of multiple choice questions created by the study team, and it reflected best practice guidelines for opioid management for CNCP and knowledge of protocol elements. Items included the definition of chronic pain, opioid medications not included on the UDS, interpretation of UDS results, addiction risk, intervals for office visits for patients on chronic opioid therapy, and pain medication dose escalation.

The staff survey included similar attitude components and a modified knowledge portion regarding which patients should have a CMA, where to document a CMA in the EMR, addiction risk, intervals for office visits, and how to handle early prescription refill requests.

Evaluation and statistical analysis

To assess the impact of the intervention, we chose 2 measures of physician adherence with the protocol (UDS and chronic pain diagnosis) because of our ability to access these measures within our approved protocol.

Individual attitude survey questions were compared using paired t-tests. We averaged knowledge test scores, and also used the paired t-test to compare pre- and posttest averages. We used Stata 11.2 (StataCorp LP, 2009) to analyze survey data.

This study was sponsored by the Matthew Slap Research Award and approved by the University of Pennsylvania Institutional Review Board.

RESULTS

Practice demographics

The 3 practices are located within the same zip code, a few city blocks from one another. Despite geographic proximity of the practices, their populations differ racially and ethnically as well as in neighborhood income distributions (TABLE 3). In all 3 practices, the total number of patients prescribed >2 opioid medications declined during the year-long study period. Practice 3 had the sharpest decline in the number of patients prescribed chronic opioids, likely due to provider turnover during the study period. Practices 1 and 2 had the highest adherence to guidelines. The marked variability in adoption of guidelines likely reflects a number of factors: the difference in baseline opioid prescribing (highest in Practice 3), the presence of physician champions in Practices 1 and 2, and more intensive training of the primary care residents in Practice 1.

Protocol adherence

We measured provider adherence to the protocol by comparing data from the year before the intervention to the year following the start of the intervention for the number of UDSs ordered, the number of chronic pain diagnoses on patients’ EMR problem lists, and the number of office visits with CNCP patients. UDSs ordered increased by 145% across all 3 practices, with the largest improvement seen in Practice 1 (430%; P<.05). Documentation of a chronic pain diagnosis in the EMR problem list increased by 424% across practices, with the largest improvement seen again in Practice 1 (918%, P<.05) (TABLE 4). Based on this performance, 24 of 27 (89%) full time physicians qualified for the financial incentive. We chose not to include the third measure (number of office visits) for analysis, as we discovered that >90% of patients were seen at least every 6 months before the intervention.

Survey results

Before the protocol training, we surveyed 26 providers and 33 staff members. Nine months after the initiation of the protocol, 25 providers and 26 staff were again surveyed. Surveys were anonymous so we were unable to link knowledge gains to individuals.

Our multicomponent intervention resulted in a marked improvement of provider and staff attitudes toward patients taking opioids for chronic noncancer pain.Providers exhibited statistically significant improvement of attitude for role adequacy (item 5), role support (item 6), job satisfaction/role-related self-esteem (item 9), and access to EMR-specific tools (items 10-12) (TABLE 2). In addition, the knowledge test score increased by 15% (P<.05) in the postintervention survey.

Staff surveys showed statistically significant improvement of attitude for job satisfaction/role-related self-esteem. There was no improvement in knowledge for staff, which is likely due to variability in training.

DISCUSSION

More than 40% of opioid prescriptions in the United States are written by primary care physicians.¹⁴ Therefore, interventions that enhance provider knowledge, institute best practices, and support role-related self-esteem in opioid management are vital to our profession.

Through a straightforward protocol, we greatly increased the number of UDSs ordered (145%) and documentation of chronic pain on the problem list (424%). By increasing adherence to best practice standards, we believe this protocol will lead to improved management of patients with CNCP by providing objective urine data to guide a treatment plan, patient education with the CMA, and a documented evaluation and care plan.

In addition to fostering adherence to the protocol, our multicomponent intervention resulted in marked improvement of provider and staff attitudes toward patients taking opioids for CNCP (TABLE 2). Participants’ satisfaction in working with these patients improved significantly (27%), as did their confidence in knowing whom to ask for help with management (43%). After this intervention, physicians reported a nonstatistically significant but large reductions in the perception that patients on opioids create stress for the office (-20%), and that patients on opioids make their job harder (-18%). Knowledge about chronic opioid prescribing also improved significantly for providers (15%).

At all practices, the number of patients receiving opioids decreased, likely due to the protocol intervention.

Previous studies have shown low adoption of best practices in opioid management without a structured intervention.¹⁰ Our findings suggest that a multicomponent quality improvement intervention that combines education, financial incentive, and a structured protocol can positively impact provider and staff attitudes and adherence to best practices in caring for patients with CNCP taking opioid medications. We believe that similar interventions could be adapted by other primary care clinics with a comparable favorable impact on physician behavior, attitudes, and knowledge.

Limitations

Our findings may not apply to nonacademic practices, as we required training and the use of an EMR. Additionally, our urban patient populations may not be generalizable to rural, suburban, or other populations in the management of patients taking prescription opioids. Further, the monetary incentive, which was included in a yearly incentive package at our institution, may not be feasible at other sites.

We did not design this study to allow for practice-level comparisons or to assess patient level variables. Analysis of patient data on safety, aberrant behavior, abnormal UDS results, and the impact of the intervention on these outcomes was outside of the scope of this study. We were unable to determine whether physician turnover, particularly high in one practice, could be linked to the results.

We believe that similar interventions could be adapted by other primary care clinics with a comparable favorable impact on physician behavior, attitudes, and knowledge.Providers often neglected to indicate their level of training on surveys, and we were therefore unable to compare adherence and knowledge between residents and attending physicians. Additionally, we lacked approval to search individual charts to completely investigate the components of our protocol (for example, completion of a CMA or UDS). Lastly, we did not design the study to control for confounders on a provider level (such as age, gender, and years of experience). A more comprehensive review of these important variables is warranted to assess the degree to which division- or practice-level quality improvement interventions can affect provider and patient behavior change and enhance patient safety.

CORRESPONDENCE
Robin E. Canada, MD, Medical Arts Building, Suite 102, 38th and Market Sts, Philadelphia, PA 19104; robin.canada@uphs.upenn.edu

Acknowledgement
The authors gratefully acknowledge Judy Shea, PhD and Joanna Starrels, MD, who provided valuable comments in the development of this manuscript.

ABSTRACT

Purpose Primary care physicians are at the center of a national prescription opioid epidemic, with little training or knowledge about the management of patients on opioids for chronic noncancer pain (CNCP). We developed an electronic medical record (EMR)-based protocol and educational intervention to standardize documentation and management of patients prescribed opioids by primary care providers. Our objective was to evaluate provider adherence to this protocol, attitudes toward the management of these patients, and knowledge of opioid prescribing.

Methods We trained providers and select staff from 3 primary care practices at the Division of General Internal Medicine at the University of Pennsylvania in the use of a protocol for managing patients taking opioids for CNCP. The following served as measures of protocol adherence: 1) the provider used a standard diagnosis (chronic pain, ICD-9 code 338.29A) in the problem list, 2) the provider ordered at least one urine drug screen (UDS) for the patient in the past year, and 3) the patient came in for at least one office visit every 6 months. We assessed physician and staff attitudes and knowledge with pre- and post-intervention surveys. Adherence to the protocol was linked to a monetary incentive.

Results Provider adherence to the protocol significantly improved measured outcomes. The number of UDSs ordered increased by 145%, and the diagnosis of chronic pain on the problem list increased by 424%. There was a statistically significant improvement in providers’ role adequacy, role support, and job satisfaction/role-related self-esteem when working with patients taking opioids. In addition, provider knowledge of proper management of these patients improved significantly. Eighty-nine percent of our physicians attained the monetary incentive.

Conclusions We developed a quality improvement intervention that addressed the need for better regulation of opioid prescribing, resulted in increased adherence to best-practice guidelines, and improved provider knowledge and attitudes.

In all 3 practices, the total number of patients prescribed >2 opioid medications declined during the year-long study period.Primary care physicians often express dissatisfaction with their competency in treating patients with opioids,¹ and at our institution, this includes residents and faculty, as well. Their concern, combined with apprehension about patient safety and the potential for addiction, can hinder appropriate opioid management.¹ We asked: Could a protocol that structures the intervention improve physician competence and performance in prescribing opioids and reduce patient risk?

Physician concerns are well-founded. Nonmedical use of prescription opioids is second only to smoking marijuana in the illicit use of drugs in the United States.² Since 2003, more overdose deaths have involved opioid analgesics than heroin and cocaine combined, leading the Centers for Disease Control and Prevention to declare in 2012 that the problem was a “national epidemic.”³ The Washington State Medical Quality Assurance Commission now mandates extensive patient evaluation and documentation, the use of a Controlled Medication Agreement (CMA), and specific education requirements for physicians prescribing long-acting or high-dose opioids.⁴

Necessary adjustments going forward. As the nation moves toward more regulated prescribing of opioids, physicians will need to develop a consistent approach to this complicated task. Primary care doctors must be at the center of this effort, as they generate most opioid prescriptions for the treatment of CNCP. Currently, providers vary widely in their management of this condition,^5-7 and recommended corrective steps include increased education8 and improved adherence to national guidelines. Our contention—and the basis of our study—was that a clinical protocol for opioid prescribing could improve the care that physicians and staff were providing to CNCP patients, as well as improve the satisfaction that clinicians felt in providing this care.

Our protocol intervention. Prior to our protocol intervention, no guidelines existed for managing patients on long-term opioid therapy in the clinical practices of the University of Pennsylvania Division of General Internal Medicine. Our providers, too, varied widely in their prescribing and management. Though regular urine drug screening is known to improve detection of opioid misuse and decrease the problem in patients treated for CNCP,^9,10 a study reviewing opioid prescribing practices in our clinics from 2004 to 2007 showed that physicians ordered UDSs for only 8% of patients.¹¹ Furthermore, only half of patients (49.8%) had regular office visits—even those at high risk for opioid misuse.¹¹

Based on expert opinion and national best-practice guidelines, we created a division-wide quality improvement intervention for opioid prescribing. The protocol required standardized evaluation and documentation of a patient’s pain history and treatment plan, and the use of a UDS and a CMA, which is known to decrease emergency room visits and improve physician satisfaction, respectively.^9,10 We trained attending physicians and staff on the protocol, and they in turn taught residents at their practice sites. The goal of this study was to determine whether this initiative would result in adherence to the protocol and improve provider and staff knowledge and satisfaction with management of patients prescribed opioids for CNCP.

METHODS

The intervention consisted of (1) the development of an EMR-based protocol to standardize documentation and management of patients with CNCP taking opioids; (2) instruction on using the protocol and on key components of opioid management; (3) collection of data; and (4) a monetary incentive for attending physicians to adhere to the protocol. We measured the impact of this intervention by assessing physician compliance with the protocol, provider satisfaction, and knowledge.

Protocol and process

We developed a division-wide protocol for managing primary-care patients with CNCP taking opioids, based on national guidelines, expert input, best practice data, and EMR capabilities (EpicCare Ambulatory Medical Record, version Summer 2009).

Health system experts from anesthesia, pain management, and psychiatry met regularly with our monthly workgroup to review the latest literature on UDSs and CMAs, and to assess best practices researched by the Center for Evidence Based Practice at our institution. We trained providers on the following steps:
• select patients who are taking opioids for CNCP (ie, receiving >2 opioid prescriptions in the 6 months prior to the intervention for a nonlimited pain condition)
• risk stratify these patients using the Opioid Risk Tool¹²
• follow high-risk patients monthly; low-to-moderate-risk patients every 3 to 6 months
• use a standard diagnosis (chronic pain, ICD-9 code 338.29A) in the EMR problem list
• complete a standardized EMR “smart set” documenting evaluation and management in the overview section of the EMR’s chronic pain diagnosis module (TABLE 1)
• complete a CMA
• order a UDS at regular intervals (at least one per year; every 1-3 months in high-risk patients)
• designate one provider (in the EMR) to be responsible for opioid prescribing. Medical residents were encouraged to specify a “Continuity Attending” to maintain continuity of care when they were not in clinic.

Educational intervention

The principal investigator conducted 4 training sessions that were available to all attending physicians and staff, to review the protocol as well as information on best practices in opioid prescribing. One session was a Quality Improvement Grand Rounds for the division, and 3 sessions were open presentations within each participating practice. During all sessions, we taught the protocol, provided instruction on riskstratifying patients, reviewed the definition and prevalence of chronic pain, described the national opioid problem, detailed the components of proper documentation, and explained how to interpret and manage UDS results.

We trained categorical internal medicine interns for 1 hour during their mandatory clinical lecture series. Primary care track residents received 4 hours of training as part of their regular educational program.

Through a straightforward protocol, we increased the number of UDSs ordered (145%) and documentation of chronic pain on the problem list (424%).Ongoing education for attending physicians occurred at 4 bimonthly opioid management case conferences, where difficult cases were presented to a rotating panel of experts from pain medicine, addiction psychiatry, and primary care. We held regular noon conferences on opioid management for residents.

Monetary incentive for physicians

Our division further aided our efforts by offering a monetary incentive ($1500) to attending physicians who achieved all 3 of the following measures of adherence with at least 80% of their chronic pain patients: at least one UDS in the past year, an office visit at least every 6 months, and a chronic pain diagnosis on the problem list in the EMR.

Data feedback

We gave providers a list of their patients receiving >2 opioid prescriptions over 6 months, and were able to exclude those patients treated for a limited pain condition. For the remainder of patients, physicians received quarterly individual reports on their adherence to the protocol.

Study population

Three internal medicine clinical practices of the University of Pennsylvania in Philadelphia took part in this initiative. We included all attending providers at these practices in the analysis assessing adherence to the protocol. Those who consented and completed a survey were included in the survey analysis. Providers were attending physicians and nurse practitioners. In Practice 1, primary care track residents are fully integrated into the practice and were included in the survey as their extended training was timed with our intervention. We did not survey residents at the other practices due to their variable schedules and inability to train as a group.

We believe this protocol will lead to improved management of patients with chronic noncancer pain by providing objective urine data to guide a treatment plan.Staff included registered nurses, licensed practical nurses, medical assistants, and patient service representatives. Because nurses and medical assistants are responsible for medication refills, they received education specifically about this intervention. The remaining staff also received instruction, as they have personal interactions with patients at the provider visit, and thus their attitudes were important to measure. Participants completed surveys at the time of the educational sessions and again 9 months following implementation of the intervention. This was a one-year intervention, with 3 initial months of teaching; the study period therefore lasted 9 months. Since surveys were anonymous, we could not link results to specific individuals. However, we provided post-intervention surveys only to those who reported completing the initial survey.

Survey design and administration

The provider survey contained an attitude component and a knowledge component (TABLE 2). The attitude component consisted of 6 items taken from the Drug Problems Perceptions Questionnaire,13 to address role adequacy, support, and self-esteem, as well as job satisfaction (the words “drug users” were replaced with “patients on [chronic] opioids”). We created an additional 3 items to further explore these domains (items 1-3). Three additional items addressed provider access to EMR specific tools (items 10-12).

The knowledge survey consisted of multiple choice questions created by the study team, and it reflected best practice guidelines for opioid management for CNCP and knowledge of protocol elements. Items included the definition of chronic pain, opioid medications not included on the UDS, interpretation of UDS results, addiction risk, intervals for office visits for patients on chronic opioid therapy, and pain medication dose escalation.

The staff survey included similar attitude components and a modified knowledge portion regarding which patients should have a CMA, where to document a CMA in the EMR, addiction risk, intervals for office visits, and how to handle early prescription refill requests.

Evaluation and statistical analysis

To assess the impact of the intervention, we chose 2 measures of physician adherence with the protocol (UDS and chronic pain diagnosis) because of our ability to access these measures within our approved protocol.

Individual attitude survey questions were compared using paired t-tests. We averaged knowledge test scores, and also used the paired t-test to compare pre- and posttest averages. We used Stata 11.2 (StataCorp LP, 2009) to analyze survey data.

This study was sponsored by the Matthew Slap Research Award and approved by the University of Pennsylvania Institutional Review Board.

RESULTS

Practice demographics

The 3 practices are located within the same zip code, a few city blocks from one another. Despite geographic proximity of the practices, their populations differ racially and ethnically as well as in neighborhood income distributions (TABLE 3). In all 3 practices, the total number of patients prescribed >2 opioid medications declined during the year-long study period. Practice 3 had the sharpest decline in the number of patients prescribed chronic opioids, likely due to provider turnover during the study period. Practices 1 and 2 had the highest adherence to guidelines. The marked variability in adoption of guidelines likely reflects a number of factors: the difference in baseline opioid prescribing (highest in Practice 3), the presence of physician champions in Practices 1 and 2, and more intensive training of the primary care residents in Practice 1.

Protocol adherence

We measured provider adherence to the protocol by comparing data from the year before the intervention to the year following the start of the intervention for the number of UDSs ordered, the number of chronic pain diagnoses on patients’ EMR problem lists, and the number of office visits with CNCP patients. UDSs ordered increased by 145% across all 3 practices, with the largest improvement seen in Practice 1 (430%; P<.05). Documentation of a chronic pain diagnosis in the EMR problem list increased by 424% across practices, with the largest improvement seen again in Practice 1 (918%, P<.05) (TABLE 4). Based on this performance, 24 of 27 (89%) full time physicians qualified for the financial incentive. We chose not to include the third measure (number of office visits) for analysis, as we discovered that >90% of patients were seen at least every 6 months before the intervention.

Survey results

Before the protocol training, we surveyed 26 providers and 33 staff members. Nine months after the initiation of the protocol, 25 providers and 26 staff were again surveyed. Surveys were anonymous so we were unable to link knowledge gains to individuals.

Our multicomponent intervention resulted in a marked improvement of provider and staff attitudes toward patients taking opioids for chronic noncancer pain.Providers exhibited statistically significant improvement of attitude for role adequacy (item 5), role support (item 6), job satisfaction/role-related self-esteem (item 9), and access to EMR-specific tools (items 10-12) (TABLE 2). In addition, the knowledge test score increased by 15% (P<.05) in the postintervention survey.

Staff surveys showed statistically significant improvement of attitude for job satisfaction/role-related self-esteem. There was no improvement in knowledge for staff, which is likely due to variability in training.

DISCUSSION

More than 40% of opioid prescriptions in the United States are written by primary care physicians.¹⁴ Therefore, interventions that enhance provider knowledge, institute best practices, and support role-related self-esteem in opioid management are vital to our profession.

Through a straightforward protocol, we greatly increased the number of UDSs ordered (145%) and documentation of chronic pain on the problem list (424%). By increasing adherence to best practice standards, we believe this protocol will lead to improved management of patients with CNCP by providing objective urine data to guide a treatment plan, patient education with the CMA, and a documented evaluation and care plan.

In addition to fostering adherence to the protocol, our multicomponent intervention resulted in marked improvement of provider and staff attitudes toward patients taking opioids for CNCP (TABLE 2). Participants’ satisfaction in working with these patients improved significantly (27%), as did their confidence in knowing whom to ask for help with management (43%). After this intervention, physicians reported a nonstatistically significant but large reductions in the perception that patients on opioids create stress for the office (-20%), and that patients on opioids make their job harder (-18%). Knowledge about chronic opioid prescribing also improved significantly for providers (15%).

At all practices, the number of patients receiving opioids decreased, likely due to the protocol intervention.

Previous studies have shown low adoption of best practices in opioid management without a structured intervention.¹⁰ Our findings suggest that a multicomponent quality improvement intervention that combines education, financial incentive, and a structured protocol can positively impact provider and staff attitudes and adherence to best practices in caring for patients with CNCP taking opioid medications. We believe that similar interventions could be adapted by other primary care clinics with a comparable favorable impact on physician behavior, attitudes, and knowledge.

Limitations

Our findings may not apply to nonacademic practices, as we required training and the use of an EMR. Additionally, our urban patient populations may not be generalizable to rural, suburban, or other populations in the management of patients taking prescription opioids. Further, the monetary incentive, which was included in a yearly incentive package at our institution, may not be feasible at other sites.

We did not design this study to allow for practice-level comparisons or to assess patient level variables. Analysis of patient data on safety, aberrant behavior, abnormal UDS results, and the impact of the intervention on these outcomes was outside of the scope of this study. We were unable to determine whether physician turnover, particularly high in one practice, could be linked to the results.

We believe that similar interventions could be adapted by other primary care clinics with a comparable favorable impact on physician behavior, attitudes, and knowledge.Providers often neglected to indicate their level of training on surveys, and we were therefore unable to compare adherence and knowledge between residents and attending physicians. Additionally, we lacked approval to search individual charts to completely investigate the components of our protocol (for example, completion of a CMA or UDS). Lastly, we did not design the study to control for confounders on a provider level (such as age, gender, and years of experience). A more comprehensive review of these important variables is warranted to assess the degree to which division- or practice-level quality improvement interventions can affect provider and patient behavior change and enhance patient safety.

CORRESPONDENCE
Robin E. Canada, MD, Medical Arts Building, Suite 102, 38th and Market Sts, Philadelphia, PA 19104; robin.canada@uphs.upenn.edu

Acknowledgement
The authors gratefully acknowledge Judy Shea, PhD and Joanna Starrels, MD, who provided valuable comments in the development of this manuscript.

ABSTRACT

Purpose Primary care physicians are at the center of a national prescription opioid epidemic, with little training or knowledge about the management of patients on opioids for chronic noncancer pain (CNCP). We developed an electronic medical record (EMR)-based protocol and educational intervention to standardize documentation and management of patients prescribed opioids by primary care providers. Our objective was to evaluate provider adherence to this protocol, attitudes toward the management of these patients, and knowledge of opioid prescribing.

Methods We trained providers and select staff from 3 primary care practices at the Division of General Internal Medicine at the University of Pennsylvania in the use of a protocol for managing patients taking opioids for CNCP. The following served as measures of protocol adherence: 1) the provider used a standard diagnosis (chronic pain, ICD-9 code 338.29A) in the problem list, 2) the provider ordered at least one urine drug screen (UDS) for the patient in the past year, and 3) the patient came in for at least one office visit every 6 months. We assessed physician and staff attitudes and knowledge with pre- and post-intervention surveys. Adherence to the protocol was linked to a monetary incentive.

Results Provider adherence to the protocol significantly improved measured outcomes. The number of UDSs ordered increased by 145%, and the diagnosis of chronic pain on the problem list increased by 424%. There was a statistically significant improvement in providers’ role adequacy, role support, and job satisfaction/role-related self-esteem when working with patients taking opioids. In addition, provider knowledge of proper management of these patients improved significantly. Eighty-nine percent of our physicians attained the monetary incentive.

Conclusions We developed a quality improvement intervention that addressed the need for better regulation of opioid prescribing, resulted in increased adherence to best-practice guidelines, and improved provider knowledge and attitudes.

In all 3 practices, the total number of patients prescribed >2 opioid medications declined during the year-long study period.Primary care physicians often express dissatisfaction with their competency in treating patients with opioids,¹ and at our institution, this includes residents and faculty, as well. Their concern, combined with apprehension about patient safety and the potential for addiction, can hinder appropriate opioid management.¹ We asked: Could a protocol that structures the intervention improve physician competence and performance in prescribing opioids and reduce patient risk?

Physician concerns are well-founded. Nonmedical use of prescription opioids is second only to smoking marijuana in the illicit use of drugs in the United States.² Since 2003, more overdose deaths have involved opioid analgesics than heroin and cocaine combined, leading the Centers for Disease Control and Prevention to declare in 2012 that the problem was a “national epidemic.”³ The Washington State Medical Quality Assurance Commission now mandates extensive patient evaluation and documentation, the use of a Controlled Medication Agreement (CMA), and specific education requirements for physicians prescribing long-acting or high-dose opioids.⁴

Necessary adjustments going forward. As the nation moves toward more regulated prescribing of opioids, physicians will need to develop a consistent approach to this complicated task. Primary care doctors must be at the center of this effort, as they generate most opioid prescriptions for the treatment of CNCP. Currently, providers vary widely in their management of this condition,^5-7 and recommended corrective steps include increased education8 and improved adherence to national guidelines. Our contention—and the basis of our study—was that a clinical protocol for opioid prescribing could improve the care that physicians and staff were providing to CNCP patients, as well as improve the satisfaction that clinicians felt in providing this care.

Our protocol intervention. Prior to our protocol intervention, no guidelines existed for managing patients on long-term opioid therapy in the clinical practices of the University of Pennsylvania Division of General Internal Medicine. Our providers, too, varied widely in their prescribing and management. Though regular urine drug screening is known to improve detection of opioid misuse and decrease the problem in patients treated for CNCP,^9,10 a study reviewing opioid prescribing practices in our clinics from 2004 to 2007 showed that physicians ordered UDSs for only 8% of patients.¹¹ Furthermore, only half of patients (49.8%) had regular office visits—even those at high risk for opioid misuse.¹¹

Based on expert opinion and national best-practice guidelines, we created a division-wide quality improvement intervention for opioid prescribing. The protocol required standardized evaluation and documentation of a patient’s pain history and treatment plan, and the use of a UDS and a CMA, which is known to decrease emergency room visits and improve physician satisfaction, respectively.^9,10 We trained attending physicians and staff on the protocol, and they in turn taught residents at their practice sites. The goal of this study was to determine whether this initiative would result in adherence to the protocol and improve provider and staff knowledge and satisfaction with management of patients prescribed opioids for CNCP.

METHODS

The intervention consisted of (1) the development of an EMR-based protocol to standardize documentation and management of patients with CNCP taking opioids; (2) instruction on using the protocol and on key components of opioid management; (3) collection of data; and (4) a monetary incentive for attending physicians to adhere to the protocol. We measured the impact of this intervention by assessing physician compliance with the protocol, provider satisfaction, and knowledge.

Protocol and process

We developed a division-wide protocol for managing primary-care patients with CNCP taking opioids, based on national guidelines, expert input, best practice data, and EMR capabilities (EpicCare Ambulatory Medical Record, version Summer 2009).

Health system experts from anesthesia, pain management, and psychiatry met regularly with our monthly workgroup to review the latest literature on UDSs and CMAs, and to assess best practices researched by the Center for Evidence Based Practice at our institution. We trained providers on the following steps:
• select patients who are taking opioids for CNCP (ie, receiving >2 opioid prescriptions in the 6 months prior to the intervention for a nonlimited pain condition)
• risk stratify these patients using the Opioid Risk Tool¹²
• follow high-risk patients monthly; low-to-moderate-risk patients every 3 to 6 months
• use a standard diagnosis (chronic pain, ICD-9 code 338.29A) in the EMR problem list
• complete a standardized EMR “smart set” documenting evaluation and management in the overview section of the EMR’s chronic pain diagnosis module (TABLE 1)
• complete a CMA
• order a UDS at regular intervals (at least one per year; every 1-3 months in high-risk patients)
• designate one provider (in the EMR) to be responsible for opioid prescribing. Medical residents were encouraged to specify a “Continuity Attending” to maintain continuity of care when they were not in clinic.

Educational intervention

The principal investigator conducted 4 training sessions that were available to all attending physicians and staff, to review the protocol as well as information on best practices in opioid prescribing. One session was a Quality Improvement Grand Rounds for the division, and 3 sessions were open presentations within each participating practice. During all sessions, we taught the protocol, provided instruction on riskstratifying patients, reviewed the definition and prevalence of chronic pain, described the national opioid problem, detailed the components of proper documentation, and explained how to interpret and manage UDS results.

We trained categorical internal medicine interns for 1 hour during their mandatory clinical lecture series. Primary care track residents received 4 hours of training as part of their regular educational program.

Through a straightforward protocol, we increased the number of UDSs ordered (145%) and documentation of chronic pain on the problem list (424%).Ongoing education for attending physicians occurred at 4 bimonthly opioid management case conferences, where difficult cases were presented to a rotating panel of experts from pain medicine, addiction psychiatry, and primary care. We held regular noon conferences on opioid management for residents.

Monetary incentive for physicians

Our division further aided our efforts by offering a monetary incentive ($1500) to attending physicians who achieved all 3 of the following measures of adherence with at least 80% of their chronic pain patients: at least one UDS in the past year, an office visit at least every 6 months, and a chronic pain diagnosis on the problem list in the EMR.

Data feedback

We gave providers a list of their patients receiving >2 opioid prescriptions over 6 months, and were able to exclude those patients treated for a limited pain condition. For the remainder of patients, physicians received quarterly individual reports on their adherence to the protocol.

Study population

Three internal medicine clinical practices of the University of Pennsylvania in Philadelphia took part in this initiative. We included all attending providers at these practices in the analysis assessing adherence to the protocol. Those who consented and completed a survey were included in the survey analysis. Providers were attending physicians and nurse practitioners. In Practice 1, primary care track residents are fully integrated into the practice and were included in the survey as their extended training was timed with our intervention. We did not survey residents at the other practices due to their variable schedules and inability to train as a group.

We believe this protocol will lead to improved management of patients with chronic noncancer pain by providing objective urine data to guide a treatment plan.Staff included registered nurses, licensed practical nurses, medical assistants, and patient service representatives. Because nurses and medical assistants are responsible for medication refills, they received education specifically about this intervention. The remaining staff also received instruction, as they have personal interactions with patients at the provider visit, and thus their attitudes were important to measure. Participants completed surveys at the time of the educational sessions and again 9 months following implementation of the intervention. This was a one-year intervention, with 3 initial months of teaching; the study period therefore lasted 9 months. Since surveys were anonymous, we could not link results to specific individuals. However, we provided post-intervention surveys only to those who reported completing the initial survey.

Survey design and administration

The provider survey contained an attitude component and a knowledge component (TABLE 2). The attitude component consisted of 6 items taken from the Drug Problems Perceptions Questionnaire,13 to address role adequacy, support, and self-esteem, as well as job satisfaction (the words “drug users” were replaced with “patients on [chronic] opioids”). We created an additional 3 items to further explore these domains (items 1-3). Three additional items addressed provider access to EMR specific tools (items 10-12).

The knowledge survey consisted of multiple choice questions created by the study team, and it reflected best practice guidelines for opioid management for CNCP and knowledge of protocol elements. Items included the definition of chronic pain, opioid medications not included on the UDS, interpretation of UDS results, addiction risk, intervals for office visits for patients on chronic opioid therapy, and pain medication dose escalation.

The staff survey included similar attitude components and a modified knowledge portion regarding which patients should have a CMA, where to document a CMA in the EMR, addiction risk, intervals for office visits, and how to handle early prescription refill requests.

Evaluation and statistical analysis

To assess the impact of the intervention, we chose 2 measures of physician adherence with the protocol (UDS and chronic pain diagnosis) because of our ability to access these measures within our approved protocol.

Individual attitude survey questions were compared using paired t-tests. We averaged knowledge test scores, and also used the paired t-test to compare pre- and posttest averages. We used Stata 11.2 (StataCorp LP, 2009) to analyze survey data.

This study was sponsored by the Matthew Slap Research Award and approved by the University of Pennsylvania Institutional Review Board.

RESULTS

Practice demographics

The 3 practices are located within the same zip code, a few city blocks from one another. Despite geographic proximity of the practices, their populations differ racially and ethnically as well as in neighborhood income distributions (TABLE 3). In all 3 practices, the total number of patients prescribed >2 opioid medications declined during the year-long study period. Practice 3 had the sharpest decline in the number of patients prescribed chronic opioids, likely due to provider turnover during the study period. Practices 1 and 2 had the highest adherence to guidelines. The marked variability in adoption of guidelines likely reflects a number of factors: the difference in baseline opioid prescribing (highest in Practice 3), the presence of physician champions in Practices 1 and 2, and more intensive training of the primary care residents in Practice 1.

Protocol adherence

We measured provider adherence to the protocol by comparing data from the year before the intervention to the year following the start of the intervention for the number of UDSs ordered, the number of chronic pain diagnoses on patients’ EMR problem lists, and the number of office visits with CNCP patients. UDSs ordered increased by 145% across all 3 practices, with the largest improvement seen in Practice 1 (430%; P<.05). Documentation of a chronic pain diagnosis in the EMR problem list increased by 424% across practices, with the largest improvement seen again in Practice 1 (918%, P<.05) (TABLE 4). Based on this performance, 24 of 27 (89%) full time physicians qualified for the financial incentive. We chose not to include the third measure (number of office visits) for analysis, as we discovered that >90% of patients were seen at least every 6 months before the intervention.

Survey results

Before the protocol training, we surveyed 26 providers and 33 staff members. Nine months after the initiation of the protocol, 25 providers and 26 staff were again surveyed. Surveys were anonymous so we were unable to link knowledge gains to individuals.

Our multicomponent intervention resulted in a marked improvement of provider and staff attitudes toward patients taking opioids for chronic noncancer pain.Providers exhibited statistically significant improvement of attitude for role adequacy (item 5), role support (item 6), job satisfaction/role-related self-esteem (item 9), and access to EMR-specific tools (items 10-12) (TABLE 2). In addition, the knowledge test score increased by 15% (P<.05) in the postintervention survey.

Staff surveys showed statistically significant improvement of attitude for job satisfaction/role-related self-esteem. There was no improvement in knowledge for staff, which is likely due to variability in training.

DISCUSSION

More than 40% of opioid prescriptions in the United States are written by primary care physicians.¹⁴ Therefore, interventions that enhance provider knowledge, institute best practices, and support role-related self-esteem in opioid management are vital to our profession.

Through a straightforward protocol, we greatly increased the number of UDSs ordered (145%) and documentation of chronic pain on the problem list (424%). By increasing adherence to best practice standards, we believe this protocol will lead to improved management of patients with CNCP by providing objective urine data to guide a treatment plan, patient education with the CMA, and a documented evaluation and care plan.

In addition to fostering adherence to the protocol, our multicomponent intervention resulted in marked improvement of provider and staff attitudes toward patients taking opioids for CNCP (TABLE 2). Participants’ satisfaction in working with these patients improved significantly (27%), as did their confidence in knowing whom to ask for help with management (43%). After this intervention, physicians reported a nonstatistically significant but large reductions in the perception that patients on opioids create stress for the office (-20%), and that patients on opioids make their job harder (-18%). Knowledge about chronic opioid prescribing also improved significantly for providers (15%).

At all practices, the number of patients receiving opioids decreased, likely due to the protocol intervention.

Previous studies have shown low adoption of best practices in opioid management without a structured intervention.¹⁰ Our findings suggest that a multicomponent quality improvement intervention that combines education, financial incentive, and a structured protocol can positively impact provider and staff attitudes and adherence to best practices in caring for patients with CNCP taking opioid medications. We believe that similar interventions could be adapted by other primary care clinics with a comparable favorable impact on physician behavior, attitudes, and knowledge.

Limitations

Our findings may not apply to nonacademic practices, as we required training and the use of an EMR. Additionally, our urban patient populations may not be generalizable to rural, suburban, or other populations in the management of patients taking prescription opioids. Further, the monetary incentive, which was included in a yearly incentive package at our institution, may not be feasible at other sites.

We did not design this study to allow for practice-level comparisons or to assess patient level variables. Analysis of patient data on safety, aberrant behavior, abnormal UDS results, and the impact of the intervention on these outcomes was outside of the scope of this study. We were unable to determine whether physician turnover, particularly high in one practice, could be linked to the results.

We believe that similar interventions could be adapted by other primary care clinics with a comparable favorable impact on physician behavior, attitudes, and knowledge.Providers often neglected to indicate their level of training on surveys, and we were therefore unable to compare adherence and knowledge between residents and attending physicians. Additionally, we lacked approval to search individual charts to completely investigate the components of our protocol (for example, completion of a CMA or UDS). Lastly, we did not design the study to control for confounders on a provider level (such as age, gender, and years of experience). A more comprehensive review of these important variables is warranted to assess the degree to which division- or practice-level quality improvement interventions can affect provider and patient behavior change and enhance patient safety.

CORRESPONDENCE
Robin E. Canada, MD, Medical Arts Building, Suite 102, 38th and Market Sts, Philadelphia, PA 19104; robin.canada@uphs.upenn.edu

Acknowledgement
The authors gratefully acknowledge Judy Shea, PhD and Joanna Starrels, MD, who provided valuable comments in the development of this manuscript.