© ASH/Scott Morgan 2018

SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.

Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.

And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.

Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.

Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.

The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.

The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).

The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).

The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).

The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).

“This was a very clean drug and a very safe drug,” Dr. List said.

The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.

The PACE study also included a small number of patients who had not previously received an ESA.

Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.

Dr. List reported research funding from Celgene. 

© ASH/Scott Morgan 2018

SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.

Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.

And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.

Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.

Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.

The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.

The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).

The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).

The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).

The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).

“This was a very clean drug and a very safe drug,” Dr. List said.

The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.

The PACE study also included a small number of patients who had not previously received an ESA.

Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.

Dr. List reported research funding from Celgene. 

© ASH/Scott Morgan 2018

SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.

Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.

And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.

Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.

Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.

The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.

The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).

The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).

The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).

The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).

“This was a very clean drug and a very safe drug,” Dr. List said.

The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.

The PACE study also included a small number of patients who had not previously received an ESA.

Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.

Dr. List reported research funding from Celgene. 

Image by Kevin MacKenzie

The American Society of Hematology (ASH) has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism (VTE).

The new guidelines contain more than 150 individual recommendations, including sections devoted to managing VTE during pregnancy and in pediatric patients.

Guideline highlights cited by some of the writing panel include a high reliance on low-molecular-weight heparin (LMWH) as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.

An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, of the University of Pennsylvania in Philadelphia and co-chair of the guideline-writing group, said during a webcast to unveil the new guidelines.

The guidelines, released on November 27, took more than 3 years to develop, an effort that began in 2015.

Prevention

For preventing VTE in hospitalized medical patients, the guidelines recommend initial assessment of the patient’s risk for both VTE and bleeding.

Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves.

But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, of the University of Vermont in Burlington and member of the guideline writing group.

For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, Dr. Cushman said.

The panel also endorsed LMWH over a direct-acting oral anticoagulant (DOAC), both during hospitalization and following discharge.

The guidelines for prevention in medical patients explicitly “recommended against” using a DOAC “over other treatments” both for hospitalized medical patients and after discharge. The guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.

Another important take-away from the prevention section is a statement that combining both mechanical and medical prophylaxis is not needed for medical inpatients.

And once patients are discharged, they have no need for compression stockings or aspirin on a long plane trip if their risk for thrombosis is not elevated.

People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.

Diagnosis

For diagnosis, Wendy Lim, MD, of McMaster University in Hamilton, Ontario, Canada, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and that helps avoid unnecessary testing.

For patients with low pretest probability, the guidelines recommend the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, Dr. Lim noted.

The guidelines also recommend using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.

Management

Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy.

But it’s a level of care that many U.S. patients don’t currently receive and, hence, is an area ripe for growth, said Daniel M. Witt, PharmD, of the University of Utah in Salt Lake City.

The guidelines recommend against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure.

The guidelines also call for “thoughtful” use of anticoagulant reversal agents, and they advise that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.

For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, according to Dr. Cuker, lead author of a paper on the subject published in Blood.

The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated each year with heparin, argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.

ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis for medical patients, diagnosis, anticoagulation therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children.

The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said these additional documents will post sometime in 2019.

At the time of the release, the guidelines panel published the following six articles in the journal Blood Advances that detail the guidelines and their documentation relating to VTE and:

• Prophylaxis
• Diagnosis
• Anticoagulation
• Heparin-induced thrombocytopenia
• Pregnancy
• Pediatrics

Drs. Cushman, Lim, and Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems. 

Image by Kevin MacKenzie

The American Society of Hematology (ASH) has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism (VTE).

The new guidelines contain more than 150 individual recommendations, including sections devoted to managing VTE during pregnancy and in pediatric patients.

Guideline highlights cited by some of the writing panel include a high reliance on low-molecular-weight heparin (LMWH) as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.

An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, of the University of Pennsylvania in Philadelphia and co-chair of the guideline-writing group, said during a webcast to unveil the new guidelines.

The guidelines, released on November 27, took more than 3 years to develop, an effort that began in 2015.

Prevention

For preventing VTE in hospitalized medical patients, the guidelines recommend initial assessment of the patient’s risk for both VTE and bleeding.

Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves.

But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, of the University of Vermont in Burlington and member of the guideline writing group.

For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, Dr. Cushman said.

The panel also endorsed LMWH over a direct-acting oral anticoagulant (DOAC), both during hospitalization and following discharge.

The guidelines for prevention in medical patients explicitly “recommended against” using a DOAC “over other treatments” both for hospitalized medical patients and after discharge. The guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.

Another important take-away from the prevention section is a statement that combining both mechanical and medical prophylaxis is not needed for medical inpatients.

And once patients are discharged, they have no need for compression stockings or aspirin on a long plane trip if their risk for thrombosis is not elevated.

People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.

Diagnosis

For diagnosis, Wendy Lim, MD, of McMaster University in Hamilton, Ontario, Canada, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and that helps avoid unnecessary testing.

For patients with low pretest probability, the guidelines recommend the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, Dr. Lim noted.

The guidelines also recommend using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.

Management

Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy.

But it’s a level of care that many U.S. patients don’t currently receive and, hence, is an area ripe for growth, said Daniel M. Witt, PharmD, of the University of Utah in Salt Lake City.

The guidelines recommend against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure.

The guidelines also call for “thoughtful” use of anticoagulant reversal agents, and they advise that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.

For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, according to Dr. Cuker, lead author of a paper on the subject published in Blood.

The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated each year with heparin, argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.

ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis for medical patients, diagnosis, anticoagulation therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children.

The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said these additional documents will post sometime in 2019.

At the time of the release, the guidelines panel published the following six articles in the journal Blood Advances that detail the guidelines and their documentation relating to VTE and:

• Prophylaxis
• Diagnosis
• Anticoagulation
• Heparin-induced thrombocytopenia
• Pregnancy
• Pediatrics

Drs. Cushman, Lim, and Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems. 

Image by Kevin MacKenzie

The American Society of Hematology (ASH) has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism (VTE).

The new guidelines contain more than 150 individual recommendations, including sections devoted to managing VTE during pregnancy and in pediatric patients.

Guideline highlights cited by some of the writing panel include a high reliance on low-molecular-weight heparin (LMWH) as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.

An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, of the University of Pennsylvania in Philadelphia and co-chair of the guideline-writing group, said during a webcast to unveil the new guidelines.

The guidelines, released on November 27, took more than 3 years to develop, an effort that began in 2015.

Prevention

For preventing VTE in hospitalized medical patients, the guidelines recommend initial assessment of the patient’s risk for both VTE and bleeding.

Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves.

But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, of the University of Vermont in Burlington and member of the guideline writing group.

For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, Dr. Cushman said.

The panel also endorsed LMWH over a direct-acting oral anticoagulant (DOAC), both during hospitalization and following discharge.

The guidelines for prevention in medical patients explicitly “recommended against” using a DOAC “over other treatments” both for hospitalized medical patients and after discharge. The guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.

Another important take-away from the prevention section is a statement that combining both mechanical and medical prophylaxis is not needed for medical inpatients.

And once patients are discharged, they have no need for compression stockings or aspirin on a long plane trip if their risk for thrombosis is not elevated.

People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.

Diagnosis

For diagnosis, Wendy Lim, MD, of McMaster University in Hamilton, Ontario, Canada, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and that helps avoid unnecessary testing.

For patients with low pretest probability, the guidelines recommend the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, Dr. Lim noted.

The guidelines also recommend using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.

Management

Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy.

But it’s a level of care that many U.S. patients don’t currently receive and, hence, is an area ripe for growth, said Daniel M. Witt, PharmD, of the University of Utah in Salt Lake City.

The guidelines recommend against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure.

The guidelines also call for “thoughtful” use of anticoagulant reversal agents, and they advise that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.

For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, according to Dr. Cuker, lead author of a paper on the subject published in Blood.

The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated each year with heparin, argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.

ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis for medical patients, diagnosis, anticoagulation therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children.

The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said these additional documents will post sometime in 2019.

At the time of the release, the guidelines panel published the following six articles in the journal Blood Advances that detail the guidelines and their documentation relating to VTE and:

• Prophylaxis
• Diagnosis
• Anticoagulation
• Heparin-induced thrombocytopenia
• Pregnancy
• Pediatrics

Drs. Cushman, Lim, and Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems. 

Recently, the Association of American Medical Colleges (AAMC) reiterated its projection of a physician shortage in the United States, predicting a shortfall of up to 121,300 physicians by 2030. The shortage would affect primary care as well as medical and surgical specialties. These projections are consistent with prior estimates and, AAMC says, take into account both utilization of NPs and PAs and future changes in how care is delivered.¹

However, other entities have suggested we are misinterpreting the situation. The Institute of Medicine (IOM) has argued that there is no physician shortage. According to their analysis, the health care system isn’t undermanned—rather, it’s inefficient and relies too heavily on physicians and not enough on advanced practice providers. Furthermore, the IOM posits that many of the studies upon which physician workforce projections have been based fail to account for advances in medicine and technology that impact care delivery: telehealth, new medications, and medical devices that give patients a more active role in their health maintenance.²

Who’s right? You might say, “Who cares?” but this isn’t simply a matter of institutional reputation; the data have informed action plans for offsetting the projected shortage. Since 2002, medical schools have increased class sizes by 30% and are working to ensure that the supply of physicians will be sufficient to meet future needs—even though funding for residency training has been frozen since 1997. At the same time, many thought leaders—including the IOM—have recognized NPs and PAs as significant contributors to the health care workforce. In 2007, for example, Cooper called on the NP and PA professions to expand their training capacity, predicting that neither would have a supply of practitioners to meet needs in the event of a physician shortage.³

Both professions took that message to heart. There are now more than 123,000 certified PAs (70% of whom work in specialty practice) and 248,000 licensed NPs (87% in primary care) in the United States.^4,5 There are 239 accredited PA programs (including those with provisional or probationary status), with the number of new graduates per year expected to reach 18,000 by 2026 (compared to 9,000 in 2018).^6,7 There are about 400 academic institutions in the US that have an NP program; in 2016-2017, more than 26,000 new graduates completed their training.^5,8 Overall, the Bureau of Labor Statistics projects that by 2024 the NP profession will have grown by 36%, the PA profession by 37%, and the physician population by 13% (excluding anesthesiologists and surgeons).⁹

There is no argument that NPs and PAs are making an enormous impact on the quality and accessibility of health care in this country. But I am starting to hear rumblings that we may be educating too many NPs and PAs—especially if the physician shortage is not as dire as predicted.

This entire conversation takes me back to the 1970s, when the Graduate Medical Education National Advisory Committee (GMENAC) projected a surplus of physicians, and a moratorium was placed on medical school enrollment. Those projections were validated and repeated through the 1990s; in fact, the aforementioned Cooper was among the first to flip the message around, using new calculations and considerations to project a physician shortage.¹⁰

GMENAC is a classic example of what happens when people and entities overreact to a projection of some kind. If there is a physician shortage today, GMENAC is probably partly responsible because their prediction of an oversupply triggered an arguably over-the-top response. Everyone worked so hard to avoid a surplus that they are creating a deficit!

Continue to: As I listen to...

As I listen to those rumblings of “too many NPs and PAs,” I wonder if this is a mirror to that GMENAC response. Have the NP and PA professions worked so hard to offset the physician shortage (real or imagined) that we may face a glut of NPs and PAs? If so, the concern is that within five to 10 years, we won’t have employment opportunities for all of them. That’s the fear driving these whispers, isn’t it?

As far back as 2000—when this conversation was in its infancy—Dehn and Cawley discussed the consequences of expanding the supply of NPs and PAs. They questioned how the number of, and demand for, NPs and PAs would be balanced in America’s future health care marketplace and wondered if a sharp growth in NP and PA graduates (in conjunction with similar increases in other health professions) could surpass demand and prompt an oversupply, resulting in underemployment and market saturation.¹¹

So, is it time to pause and take another look at the numbers and needs? Maybe. But I believe one of the aspects we must continue to focus on is the quality of our professions. In the wake of the projected physician shortage, the NP profession developed its Doctor of Nursing Practice and the PA profession added postgraduate training opportunities in specific specialties. These not only enhance NPs’ and PAs’ professional credentials—they equip us to provide better patient care. At the end of the day, our ability to care for patients will be the rubric upon which we are judged.

We’ve already been making the case for our professions and gaining recognition throughout this process. When Salsberg wrote about the physician shortage in Health Affairs (2015), he reminded us that a critical factor is the supply and availability of clinicians other than physicians (NPs, PAs, midwives) who can make a significant contribution to access and efficiency of health care. He called for NPs and PAs to be fully integrated into the delivery system and to be allowed scope of practice consistent with their education and training.⁷

Continue to: Both NPs and PAs have become...

Both NPs and PAs have become participants in dialogues on health policy and health care reform. Both professions are spending increasing dollars on national advertising to raise awareness of their critical role in expanding access to primary care for millions of Americans. In fact, Princeton University Professor of Economics Uwe E. Reinhardt told the New York Times, “The doctors are fighting a losing battle. The nurses are like insurgents. They are occasionally beaten back, but they’ll win in the long run. They have economics and common sense on their side.”¹² Some suggest that PAs need to fight a similar battle.

So, dear reader, what do you think? Should we be concerned that we are educating too many NPs and PAs? Does that argument become somewhat irrelevant if we can firmly establish a substantial role for ourselves in the future of health care? I would love to hear your thoughts; email me at [email protected].

Recently, the Association of American Medical Colleges (AAMC) reiterated its projection of a physician shortage in the United States, predicting a shortfall of up to 121,300 physicians by 2030. The shortage would affect primary care as well as medical and surgical specialties. These projections are consistent with prior estimates and, AAMC says, take into account both utilization of NPs and PAs and future changes in how care is delivered.¹

However, other entities have suggested we are misinterpreting the situation. The Institute of Medicine (IOM) has argued that there is no physician shortage. According to their analysis, the health care system isn’t undermanned—rather, it’s inefficient and relies too heavily on physicians and not enough on advanced practice providers. Furthermore, the IOM posits that many of the studies upon which physician workforce projections have been based fail to account for advances in medicine and technology that impact care delivery: telehealth, new medications, and medical devices that give patients a more active role in their health maintenance.²

Who’s right? You might say, “Who cares?” but this isn’t simply a matter of institutional reputation; the data have informed action plans for offsetting the projected shortage. Since 2002, medical schools have increased class sizes by 30% and are working to ensure that the supply of physicians will be sufficient to meet future needs—even though funding for residency training has been frozen since 1997. At the same time, many thought leaders—including the IOM—have recognized NPs and PAs as significant contributors to the health care workforce. In 2007, for example, Cooper called on the NP and PA professions to expand their training capacity, predicting that neither would have a supply of practitioners to meet needs in the event of a physician shortage.³

Both professions took that message to heart. There are now more than 123,000 certified PAs (70% of whom work in specialty practice) and 248,000 licensed NPs (87% in primary care) in the United States.^4,5 There are 239 accredited PA programs (including those with provisional or probationary status), with the number of new graduates per year expected to reach 18,000 by 2026 (compared to 9,000 in 2018).^6,7 There are about 400 academic institutions in the US that have an NP program; in 2016-2017, more than 26,000 new graduates completed their training.^5,8 Overall, the Bureau of Labor Statistics projects that by 2024 the NP profession will have grown by 36%, the PA profession by 37%, and the physician population by 13% (excluding anesthesiologists and surgeons).⁹

There is no argument that NPs and PAs are making an enormous impact on the quality and accessibility of health care in this country. But I am starting to hear rumblings that we may be educating too many NPs and PAs—especially if the physician shortage is not as dire as predicted.

This entire conversation takes me back to the 1970s, when the Graduate Medical Education National Advisory Committee (GMENAC) projected a surplus of physicians, and a moratorium was placed on medical school enrollment. Those projections were validated and repeated through the 1990s; in fact, the aforementioned Cooper was among the first to flip the message around, using new calculations and considerations to project a physician shortage.¹⁰

GMENAC is a classic example of what happens when people and entities overreact to a projection of some kind. If there is a physician shortage today, GMENAC is probably partly responsible because their prediction of an oversupply triggered an arguably over-the-top response. Everyone worked so hard to avoid a surplus that they are creating a deficit!

Continue to: As I listen to...

As I listen to those rumblings of “too many NPs and PAs,” I wonder if this is a mirror to that GMENAC response. Have the NP and PA professions worked so hard to offset the physician shortage (real or imagined) that we may face a glut of NPs and PAs? If so, the concern is that within five to 10 years, we won’t have employment opportunities for all of them. That’s the fear driving these whispers, isn’t it?

As far back as 2000—when this conversation was in its infancy—Dehn and Cawley discussed the consequences of expanding the supply of NPs and PAs. They questioned how the number of, and demand for, NPs and PAs would be balanced in America’s future health care marketplace and wondered if a sharp growth in NP and PA graduates (in conjunction with similar increases in other health professions) could surpass demand and prompt an oversupply, resulting in underemployment and market saturation.¹¹

So, is it time to pause and take another look at the numbers and needs? Maybe. But I believe one of the aspects we must continue to focus on is the quality of our professions. In the wake of the projected physician shortage, the NP profession developed its Doctor of Nursing Practice and the PA profession added postgraduate training opportunities in specific specialties. These not only enhance NPs’ and PAs’ professional credentials—they equip us to provide better patient care. At the end of the day, our ability to care for patients will be the rubric upon which we are judged.

We’ve already been making the case for our professions and gaining recognition throughout this process. When Salsberg wrote about the physician shortage in Health Affairs (2015), he reminded us that a critical factor is the supply and availability of clinicians other than physicians (NPs, PAs, midwives) who can make a significant contribution to access and efficiency of health care. He called for NPs and PAs to be fully integrated into the delivery system and to be allowed scope of practice consistent with their education and training.⁷

Continue to: Both NPs and PAs have become...

Both NPs and PAs have become participants in dialogues on health policy and health care reform. Both professions are spending increasing dollars on national advertising to raise awareness of their critical role in expanding access to primary care for millions of Americans. In fact, Princeton University Professor of Economics Uwe E. Reinhardt told the New York Times, “The doctors are fighting a losing battle. The nurses are like insurgents. They are occasionally beaten back, but they’ll win in the long run. They have economics and common sense on their side.”¹² Some suggest that PAs need to fight a similar battle.

So, dear reader, what do you think? Should we be concerned that we are educating too many NPs and PAs? Does that argument become somewhat irrelevant if we can firmly establish a substantial role for ourselves in the future of health care? I would love to hear your thoughts; email me at [email protected].

Recently, the Association of American Medical Colleges (AAMC) reiterated its projection of a physician shortage in the United States, predicting a shortfall of up to 121,300 physicians by 2030. The shortage would affect primary care as well as medical and surgical specialties. These projections are consistent with prior estimates and, AAMC says, take into account both utilization of NPs and PAs and future changes in how care is delivered.¹

However, other entities have suggested we are misinterpreting the situation. The Institute of Medicine (IOM) has argued that there is no physician shortage. According to their analysis, the health care system isn’t undermanned—rather, it’s inefficient and relies too heavily on physicians and not enough on advanced practice providers. Furthermore, the IOM posits that many of the studies upon which physician workforce projections have been based fail to account for advances in medicine and technology that impact care delivery: telehealth, new medications, and medical devices that give patients a more active role in their health maintenance.²

Who’s right? You might say, “Who cares?” but this isn’t simply a matter of institutional reputation; the data have informed action plans for offsetting the projected shortage. Since 2002, medical schools have increased class sizes by 30% and are working to ensure that the supply of physicians will be sufficient to meet future needs—even though funding for residency training has been frozen since 1997. At the same time, many thought leaders—including the IOM—have recognized NPs and PAs as significant contributors to the health care workforce. In 2007, for example, Cooper called on the NP and PA professions to expand their training capacity, predicting that neither would have a supply of practitioners to meet needs in the event of a physician shortage.³

Both professions took that message to heart. There are now more than 123,000 certified PAs (70% of whom work in specialty practice) and 248,000 licensed NPs (87% in primary care) in the United States.^4,5 There are 239 accredited PA programs (including those with provisional or probationary status), with the number of new graduates per year expected to reach 18,000 by 2026 (compared to 9,000 in 2018).^6,7 There are about 400 academic institutions in the US that have an NP program; in 2016-2017, more than 26,000 new graduates completed their training.^5,8 Overall, the Bureau of Labor Statistics projects that by 2024 the NP profession will have grown by 36%, the PA profession by 37%, and the physician population by 13% (excluding anesthesiologists and surgeons).⁹

There is no argument that NPs and PAs are making an enormous impact on the quality and accessibility of health care in this country. But I am starting to hear rumblings that we may be educating too many NPs and PAs—especially if the physician shortage is not as dire as predicted.

This entire conversation takes me back to the 1970s, when the Graduate Medical Education National Advisory Committee (GMENAC) projected a surplus of physicians, and a moratorium was placed on medical school enrollment. Those projections were validated and repeated through the 1990s; in fact, the aforementioned Cooper was among the first to flip the message around, using new calculations and considerations to project a physician shortage.¹⁰

GMENAC is a classic example of what happens when people and entities overreact to a projection of some kind. If there is a physician shortage today, GMENAC is probably partly responsible because their prediction of an oversupply triggered an arguably over-the-top response. Everyone worked so hard to avoid a surplus that they are creating a deficit!

Continue to: As I listen to...

As I listen to those rumblings of “too many NPs and PAs,” I wonder if this is a mirror to that GMENAC response. Have the NP and PA professions worked so hard to offset the physician shortage (real or imagined) that we may face a glut of NPs and PAs? If so, the concern is that within five to 10 years, we won’t have employment opportunities for all of them. That’s the fear driving these whispers, isn’t it?

As far back as 2000—when this conversation was in its infancy—Dehn and Cawley discussed the consequences of expanding the supply of NPs and PAs. They questioned how the number of, and demand for, NPs and PAs would be balanced in America’s future health care marketplace and wondered if a sharp growth in NP and PA graduates (in conjunction with similar increases in other health professions) could surpass demand and prompt an oversupply, resulting in underemployment and market saturation.¹¹

So, is it time to pause and take another look at the numbers and needs? Maybe. But I believe one of the aspects we must continue to focus on is the quality of our professions. In the wake of the projected physician shortage, the NP profession developed its Doctor of Nursing Practice and the PA profession added postgraduate training opportunities in specific specialties. These not only enhance NPs’ and PAs’ professional credentials—they equip us to provide better patient care. At the end of the day, our ability to care for patients will be the rubric upon which we are judged.

We’ve already been making the case for our professions and gaining recognition throughout this process. When Salsberg wrote about the physician shortage in Health Affairs (2015), he reminded us that a critical factor is the supply and availability of clinicians other than physicians (NPs, PAs, midwives) who can make a significant contribution to access and efficiency of health care. He called for NPs and PAs to be fully integrated into the delivery system and to be allowed scope of practice consistent with their education and training.⁷

Continue to: Both NPs and PAs have become...

Both NPs and PAs have become participants in dialogues on health policy and health care reform. Both professions are spending increasing dollars on national advertising to raise awareness of their critical role in expanding access to primary care for millions of Americans. In fact, Princeton University Professor of Economics Uwe E. Reinhardt told the New York Times, “The doctors are fighting a losing battle. The nurses are like insurgents. They are occasionally beaten back, but they’ll win in the long run. They have economics and common sense on their side.”¹² Some suggest that PAs need to fight a similar battle.

So, dear reader, what do you think? Should we be concerned that we are educating too many NPs and PAs? Does that argument become somewhat irrelevant if we can firmly establish a substantial role for ourselves in the future of health care? I would love to hear your thoughts; email me at [email protected].

The September 2018 Practice Alert, “CDC recommendations for the 2018-2019 influenza season” contained an error (J Fam Pract. 2018. 67:550-553). On page 552, under “Available vaccine products,” the article listed “one standard dose IIV4 intradermal option.” This was incorrect. Sanofi Pasteur, the manufacturer of standard dose Intradermal IIV4, discontinued the production and supply of Fluzone Intradermal Quadrivalent vaccine at the conclusion of the 2017-2018 influenza season.

The September 2018 Practice Alert, “CDC recommendations for the 2018-2019 influenza season” contained an error (J Fam Pract. 2018. 67:550-553). On page 552, under “Available vaccine products,” the article listed “one standard dose IIV4 intradermal option.” This was incorrect. Sanofi Pasteur, the manufacturer of standard dose Intradermal IIV4, discontinued the production and supply of Fluzone Intradermal Quadrivalent vaccine at the conclusion of the 2017-2018 influenza season.

The September 2018 Practice Alert, “CDC recommendations for the 2018-2019 influenza season” contained an error (J Fam Pract. 2018. 67:550-553). On page 552, under “Available vaccine products,” the article listed “one standard dose IIV4 intradermal option.” This was incorrect. Sanofi Pasteur, the manufacturer of standard dose Intradermal IIV4, discontinued the production and supply of Fluzone Intradermal Quadrivalent vaccine at the conclusion of the 2017-2018 influenza season.

In the Clinical Inquiry, “Does prophylactic azithromycin reduce the number of COPD exacerbations or hospitalizations?” (J Fam Pract. 2018;67:384-385), Lyon et al state that azithromycin “doesn’t benefit patients ≤65 years, patients with GOLD [Global Initiative for Obstructive Lung Disease] stage IV COPD [chronic obstructive pulmonary disease], current smokers, or patients not using oxygen (strength of recommendation [SOR]: B, randomized controlled trials [RCTs]).” These categorical statements are misleading, and clinicians should ignore most of them when considering azithromycin for their patients with severe COPD.

It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years.

The authors cited groups that were identified in a posthoc analysis¹ of the only large trial involving azithromycin for the treatment of COPD to date.²P values for the interaction of azithromycin with GOLD stage (P=.04), smoking (P=.03), and age (P=.02) were significant, but the mean effects (hazard ratios [HRs]) for GOLD stage IV, smoking, and age ≤65 were .84, .99, and .84, respectively. It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years. Only smokers appear to show no response, although the lower end of the 95% confidence interval was 0.71. The P value for the interaction of azithromycin with no long-term oxygen use (P=.23) was not significant, and it is incorrect to infer that oxygen use or nonuse predicts response.

The authors correctly state that the “significance of the results is limited because the study was not originally powered for this level of subgroup analysis,” but this statement is buried later in the article.

David L. Hahn, MD, MS
Madison, Wis

1. Han MK, Tayob N, Murray S, et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014;189:1503-1508.

2. Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Continue to: Author's response...

Author’s response:

Your statement that the evidence-based answer regarding the lack of benefit of azithromycin in patients ≤65 years of age, with stage IV COPD, current smokers, and patients not using oxygen is “misleading” is a bit of an overstatement.

It is fair to say, however, that our statement regarding lack of efficacy among these subgroups of patients should be softened a bit since the data are from subgroup analyses, which should never be the source of definitive conclusions. And you point out that the 95% confidence intervals [CIs] of the HRs for these subgroups of patients do not include a potentially significant effect (0.68, 0.71, 0.61, and 0.65, respectively), so it is possible there is a Type II error, which would lead one to conclude there is no effect for these subgroups when there is one.

Regarding oxygen therapy, in this Clinical Inquiry, we presented data from the direct subgroup analysis, which revealed no difference in COPD exacerbations between the azithromycin and placebo groups for patients not receiving long-term supplemental oxygen (HR=0.80; 95% CI, 0.62-1.03); however, you are correct to point out that the oxygen use subgroup interaction (patients on oxygen vs patients not on oxygen), which we did not include in this Clinical Inquiry, did not reach significance (P=.23), casting some doubt on the authors’ conclusion of no effect for patients not on oxygen.

On the whole, I feel this Clinical Inquiry accurately summarized the existing evidence and that additional research is needed to better define the utility of azithromycin in these subgroups of patients.

Corey Lyon, DO
Denver, Colo

In the Clinical Inquiry, “Does prophylactic azithromycin reduce the number of COPD exacerbations or hospitalizations?” (J Fam Pract. 2018;67:384-385), Lyon et al state that azithromycin “doesn’t benefit patients ≤65 years, patients with GOLD [Global Initiative for Obstructive Lung Disease] stage IV COPD [chronic obstructive pulmonary disease], current smokers, or patients not using oxygen (strength of recommendation [SOR]: B, randomized controlled trials [RCTs]).” These categorical statements are misleading, and clinicians should ignore most of them when considering azithromycin for their patients with severe COPD.

It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years.

The authors cited groups that were identified in a posthoc analysis¹ of the only large trial involving azithromycin for the treatment of COPD to date.²P values for the interaction of azithromycin with GOLD stage (P=.04), smoking (P=.03), and age (P=.02) were significant, but the mean effects (hazard ratios [HRs]) for GOLD stage IV, smoking, and age ≤65 were .84, .99, and .84, respectively. It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years. Only smokers appear to show no response, although the lower end of the 95% confidence interval was 0.71. The P value for the interaction of azithromycin with no long-term oxygen use (P=.23) was not significant, and it is incorrect to infer that oxygen use or nonuse predicts response.

The authors correctly state that the “significance of the results is limited because the study was not originally powered for this level of subgroup analysis,” but this statement is buried later in the article.

David L. Hahn, MD, MS
Madison, Wis

1. Han MK, Tayob N, Murray S, et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014;189:1503-1508.

2. Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Continue to: Author's response...

Author’s response:

Your statement that the evidence-based answer regarding the lack of benefit of azithromycin in patients ≤65 years of age, with stage IV COPD, current smokers, and patients not using oxygen is “misleading” is a bit of an overstatement.

It is fair to say, however, that our statement regarding lack of efficacy among these subgroups of patients should be softened a bit since the data are from subgroup analyses, which should never be the source of definitive conclusions. And you point out that the 95% confidence intervals [CIs] of the HRs for these subgroups of patients do not include a potentially significant effect (0.68, 0.71, 0.61, and 0.65, respectively), so it is possible there is a Type II error, which would lead one to conclude there is no effect for these subgroups when there is one.

Regarding oxygen therapy, in this Clinical Inquiry, we presented data from the direct subgroup analysis, which revealed no difference in COPD exacerbations between the azithromycin and placebo groups for patients not receiving long-term supplemental oxygen (HR=0.80; 95% CI, 0.62-1.03); however, you are correct to point out that the oxygen use subgroup interaction (patients on oxygen vs patients not on oxygen), which we did not include in this Clinical Inquiry, did not reach significance (P=.23), casting some doubt on the authors’ conclusion of no effect for patients not on oxygen.

On the whole, I feel this Clinical Inquiry accurately summarized the existing evidence and that additional research is needed to better define the utility of azithromycin in these subgroups of patients.

Corey Lyon, DO
Denver, Colo

In the Clinical Inquiry, “Does prophylactic azithromycin reduce the number of COPD exacerbations or hospitalizations?” (J Fam Pract. 2018;67:384-385), Lyon et al state that azithromycin “doesn’t benefit patients ≤65 years, patients with GOLD [Global Initiative for Obstructive Lung Disease] stage IV COPD [chronic obstructive pulmonary disease], current smokers, or patients not using oxygen (strength of recommendation [SOR]: B, randomized controlled trials [RCTs]).” These categorical statements are misleading, and clinicians should ignore most of them when considering azithromycin for their patients with severe COPD.

It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years.

The authors cited groups that were identified in a posthoc analysis¹ of the only large trial involving azithromycin for the treatment of COPD to date.²P values for the interaction of azithromycin with GOLD stage (P=.04), smoking (P=.03), and age (P=.02) were significant, but the mean effects (hazard ratios [HRs]) for GOLD stage IV, smoking, and age ≤65 were .84, .99, and .84, respectively. It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years. Only smokers appear to show no response, although the lower end of the 95% confidence interval was 0.71. The P value for the interaction of azithromycin with no long-term oxygen use (P=.23) was not significant, and it is incorrect to infer that oxygen use or nonuse predicts response.

The authors correctly state that the “significance of the results is limited because the study was not originally powered for this level of subgroup analysis,” but this statement is buried later in the article.

David L. Hahn, MD, MS
Madison, Wis

1. Han MK, Tayob N, Murray S, et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014;189:1503-1508.

2. Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Continue to: Author's response...

Author’s response:

Your statement that the evidence-based answer regarding the lack of benefit of azithromycin in patients ≤65 years of age, with stage IV COPD, current smokers, and patients not using oxygen is “misleading” is a bit of an overstatement.

It is fair to say, however, that our statement regarding lack of efficacy among these subgroups of patients should be softened a bit since the data are from subgroup analyses, which should never be the source of definitive conclusions. And you point out that the 95% confidence intervals [CIs] of the HRs for these subgroups of patients do not include a potentially significant effect (0.68, 0.71, 0.61, and 0.65, respectively), so it is possible there is a Type II error, which would lead one to conclude there is no effect for these subgroups when there is one.

Regarding oxygen therapy, in this Clinical Inquiry, we presented data from the direct subgroup analysis, which revealed no difference in COPD exacerbations between the azithromycin and placebo groups for patients not receiving long-term supplemental oxygen (HR=0.80; 95% CI, 0.62-1.03); however, you are correct to point out that the oxygen use subgroup interaction (patients on oxygen vs patients not on oxygen), which we did not include in this Clinical Inquiry, did not reach significance (P=.23), casting some doubt on the authors’ conclusion of no effect for patients not on oxygen.

On the whole, I feel this Clinical Inquiry accurately summarized the existing evidence and that additional research is needed to better define the utility of azithromycin in these subgroups of patients.

Corey Lyon, DO
Denver, Colo

EVIDENCE SUMMARY

A meta-analysis of 15 RCTs (5583 women) compared intentional artificial rupture of the amniotic membranes during labor (amniotomy) with intention to preserve the membranes (no amniotomy). The study found no differences in any of the measured primary outcomes: length of first stage of labor, cesarean section, maternal satisfaction with childbirth, or Apgar score <7 at 5 minutes.¹

Investigators included 9 trials with both nulliparous and multiparous women and 6 trials with only nulliparous women. Thirteen trials compared amniotomy with intention to preserve the membranes, and 2 trials performed amniotomy in the control group if the membranes were intact at full cervical dilation.

Amniotomy doesn’t affect first-stage labor or cesarean risk

Five trials (1127 women) reported no difference in length of the first stage of labor between the amniotomy and no amniotomy groups (mean difference [MD]= −20 minutes; 95% confidence interval [CI], −96 to 55). Subgroups of primiparous and multiparous women showed no difference (MD= −58 minutes; 95% CI, −153 to 37 and MD= +23 minutes; 95% CI, −51 to 97, respectively).

Nine trials (5021 women) reported no significant difference in cesarean section risk overall or when compared by parity, multiparous vs primiparous (risk ratio [RR]= 1.27; 95% CI, 0.99-1.63). One trial (84 women) found no difference in maternal satisfaction scores with childbirth experience. Six trials (3598 women) that reported risk of low Apgar score (<4 at 1 minute or <7 at 5 minutes) found no difference overall (RR=0.53; 95% CI, 0.28-1.00), or when compared by parity (multiparous vs primiparous).

Amniotomy doesn’t shorten spontaneous labor nor improve length of first-stage labor, cesarean section rate, or maternal satisfaction with childbirth.

Investigators reported that the included trials varied in quality and described the following limitations: inconsistent or unspecified timing of amniotomy during labor, proportion of women in the control group undergoing amniotomy, and ≥30% of women not getting the allocated treatment in all but one of the trials.

Secondary outcomes: Amniotomy reduces oxytocin use

Eight trials (4264 women) evaluated oxytocin augmentation and found that amniotomy decreased its use in multiparous (RR=0.43; 95% CI, 0.30-0.60), but not primiparous, women.

Eight trials (1927 women) reported length of second stage of labor as a secondary outcome, with no difference overall (MD= −1.33 minutes; 95% CI, −2.92 to 0.26). Amniotomy produced a statistical but not clinically significant shortening in subanalysis of primiparous women (MD= −5.43 minutes; 95% CI, −9.98 to −0.89) but not multiparous women.

Continue to: Three trials...

Three trials (1695 women) evaluated dysfunctional labor, defined as no progress in cervical dilation in 2 hours or ineffective uterine contractions. Amniotomy reduced dysfunctional labor in both primiparous (RR=0.49; 95% CI, 0.33-0.73) and multiparous women (RR=0.44; 95% CI, 0.31-0.62).

No differences found in other maternal and fetal outcomes

Investigators reported no differences in other secondary maternal outcomes: instrumental vaginal birth (10 trials, 5121 women); pain relief (8 trials, 3475 women); postpartum hemorrhage (2 trials, 1822 women); serious maternal morbidity or death (3 trials, 1740 women); umbilical cord prolapse (2 trials, 1615 women); and cesarean section for fetal distress, prolonged labor, or antepartum hemorrhage (1 RCT, 690 women).

Investigators also found no differences in secondary fetal outcomes: serious neonatal morbidity or perinatal death (8 trials, 3397 women); neonatal admission to neonatal intensive care (5 trials, 2686 women); abnormal fetal heart rate tracing in first stage of labor (4 trials, 1284 women); meconium aspiration (2 trials, 1615 women); and fetal acidosis (2 trials, 1014 women). Similarly, 1 RCT (39 women) that compared amniotomy with intent to preserve membranes in spontaneous labors that became prolonged found no difference in cesarean section, maternal satisfaction, or Apgar scores.

A few studies claim shorter labor with amniotomy

However, a later Iranian RCT (300 women) reported that early amniotomy shortened labor (labor duration: 7.5 ± 0.7 hours with amniotomy vs 9.9 ± 1.0 hours without amniotomy; P<.001) and reduced the risk of dystocia (RR=0.81; 95% CI, 0.59-0.90) and cesarean section (RR=0.82; 95% CI, 0.66-0.90).²

A similar Nigerian RCT (214 women) and an Indian RCT (144 women) both claimed that amniotomy also shortened labor (4.7 ± 0.9 hours vs 5.9 ± 1.3, and 3.9 ± 2 hours vs 6.1 ± 2.8 hours, respectively).^3,4 In neither trial, however, did investigators explain how the difference was significant when the duration of labor times overlapped within the margin of error.

EVIDENCE SUMMARY

A meta-analysis of 15 RCTs (5583 women) compared intentional artificial rupture of the amniotic membranes during labor (amniotomy) with intention to preserve the membranes (no amniotomy). The study found no differences in any of the measured primary outcomes: length of first stage of labor, cesarean section, maternal satisfaction with childbirth, or Apgar score <7 at 5 minutes.¹

Investigators included 9 trials with both nulliparous and multiparous women and 6 trials with only nulliparous women. Thirteen trials compared amniotomy with intention to preserve the membranes, and 2 trials performed amniotomy in the control group if the membranes were intact at full cervical dilation.

Amniotomy doesn’t affect first-stage labor or cesarean risk

Five trials (1127 women) reported no difference in length of the first stage of labor between the amniotomy and no amniotomy groups (mean difference [MD]= −20 minutes; 95% confidence interval [CI], −96 to 55). Subgroups of primiparous and multiparous women showed no difference (MD= −58 minutes; 95% CI, −153 to 37 and MD= +23 minutes; 95% CI, −51 to 97, respectively).

Nine trials (5021 women) reported no significant difference in cesarean section risk overall or when compared by parity, multiparous vs primiparous (risk ratio [RR]= 1.27; 95% CI, 0.99-1.63). One trial (84 women) found no difference in maternal satisfaction scores with childbirth experience. Six trials (3598 women) that reported risk of low Apgar score (<4 at 1 minute or <7 at 5 minutes) found no difference overall (RR=0.53; 95% CI, 0.28-1.00), or when compared by parity (multiparous vs primiparous).

Amniotomy doesn’t shorten spontaneous labor nor improve length of first-stage labor, cesarean section rate, or maternal satisfaction with childbirth.

Investigators reported that the included trials varied in quality and described the following limitations: inconsistent or unspecified timing of amniotomy during labor, proportion of women in the control group undergoing amniotomy, and ≥30% of women not getting the allocated treatment in all but one of the trials.

Secondary outcomes: Amniotomy reduces oxytocin use

Eight trials (4264 women) evaluated oxytocin augmentation and found that amniotomy decreased its use in multiparous (RR=0.43; 95% CI, 0.30-0.60), but not primiparous, women.

Eight trials (1927 women) reported length of second stage of labor as a secondary outcome, with no difference overall (MD= −1.33 minutes; 95% CI, −2.92 to 0.26). Amniotomy produced a statistical but not clinically significant shortening in subanalysis of primiparous women (MD= −5.43 minutes; 95% CI, −9.98 to −0.89) but not multiparous women.

Continue to: Three trials...

Three trials (1695 women) evaluated dysfunctional labor, defined as no progress in cervical dilation in 2 hours or ineffective uterine contractions. Amniotomy reduced dysfunctional labor in both primiparous (RR=0.49; 95% CI, 0.33-0.73) and multiparous women (RR=0.44; 95% CI, 0.31-0.62).

No differences found in other maternal and fetal outcomes

Investigators reported no differences in other secondary maternal outcomes: instrumental vaginal birth (10 trials, 5121 women); pain relief (8 trials, 3475 women); postpartum hemorrhage (2 trials, 1822 women); serious maternal morbidity or death (3 trials, 1740 women); umbilical cord prolapse (2 trials, 1615 women); and cesarean section for fetal distress, prolonged labor, or antepartum hemorrhage (1 RCT, 690 women).

Investigators also found no differences in secondary fetal outcomes: serious neonatal morbidity or perinatal death (8 trials, 3397 women); neonatal admission to neonatal intensive care (5 trials, 2686 women); abnormal fetal heart rate tracing in first stage of labor (4 trials, 1284 women); meconium aspiration (2 trials, 1615 women); and fetal acidosis (2 trials, 1014 women). Similarly, 1 RCT (39 women) that compared amniotomy with intent to preserve membranes in spontaneous labors that became prolonged found no difference in cesarean section, maternal satisfaction, or Apgar scores.

A few studies claim shorter labor with amniotomy

However, a later Iranian RCT (300 women) reported that early amniotomy shortened labor (labor duration: 7.5 ± 0.7 hours with amniotomy vs 9.9 ± 1.0 hours without amniotomy; P<.001) and reduced the risk of dystocia (RR=0.81; 95% CI, 0.59-0.90) and cesarean section (RR=0.82; 95% CI, 0.66-0.90).²

A similar Nigerian RCT (214 women) and an Indian RCT (144 women) both claimed that amniotomy also shortened labor (4.7 ± 0.9 hours vs 5.9 ± 1.3, and 3.9 ± 2 hours vs 6.1 ± 2.8 hours, respectively).^3,4 In neither trial, however, did investigators explain how the difference was significant when the duration of labor times overlapped within the margin of error.

EVIDENCE SUMMARY

A meta-analysis of 15 RCTs (5583 women) compared intentional artificial rupture of the amniotic membranes during labor (amniotomy) with intention to preserve the membranes (no amniotomy). The study found no differences in any of the measured primary outcomes: length of first stage of labor, cesarean section, maternal satisfaction with childbirth, or Apgar score <7 at 5 minutes.¹

Investigators included 9 trials with both nulliparous and multiparous women and 6 trials with only nulliparous women. Thirteen trials compared amniotomy with intention to preserve the membranes, and 2 trials performed amniotomy in the control group if the membranes were intact at full cervical dilation.

Amniotomy doesn’t affect first-stage labor or cesarean risk

Five trials (1127 women) reported no difference in length of the first stage of labor between the amniotomy and no amniotomy groups (mean difference [MD]= −20 minutes; 95% confidence interval [CI], −96 to 55). Subgroups of primiparous and multiparous women showed no difference (MD= −58 minutes; 95% CI, −153 to 37 and MD= +23 minutes; 95% CI, −51 to 97, respectively).

Nine trials (5021 women) reported no significant difference in cesarean section risk overall or when compared by parity, multiparous vs primiparous (risk ratio [RR]= 1.27; 95% CI, 0.99-1.63). One trial (84 women) found no difference in maternal satisfaction scores with childbirth experience. Six trials (3598 women) that reported risk of low Apgar score (<4 at 1 minute or <7 at 5 minutes) found no difference overall (RR=0.53; 95% CI, 0.28-1.00), or when compared by parity (multiparous vs primiparous).

Amniotomy doesn’t shorten spontaneous labor nor improve length of first-stage labor, cesarean section rate, or maternal satisfaction with childbirth.

Investigators reported that the included trials varied in quality and described the following limitations: inconsistent or unspecified timing of amniotomy during labor, proportion of women in the control group undergoing amniotomy, and ≥30% of women not getting the allocated treatment in all but one of the trials.

Secondary outcomes: Amniotomy reduces oxytocin use

Eight trials (4264 women) evaluated oxytocin augmentation and found that amniotomy decreased its use in multiparous (RR=0.43; 95% CI, 0.30-0.60), but not primiparous, women.

Eight trials (1927 women) reported length of second stage of labor as a secondary outcome, with no difference overall (MD= −1.33 minutes; 95% CI, −2.92 to 0.26). Amniotomy produced a statistical but not clinically significant shortening in subanalysis of primiparous women (MD= −5.43 minutes; 95% CI, −9.98 to −0.89) but not multiparous women.

Continue to: Three trials...

Three trials (1695 women) evaluated dysfunctional labor, defined as no progress in cervical dilation in 2 hours or ineffective uterine contractions. Amniotomy reduced dysfunctional labor in both primiparous (RR=0.49; 95% CI, 0.33-0.73) and multiparous women (RR=0.44; 95% CI, 0.31-0.62).

No differences found in other maternal and fetal outcomes

Investigators reported no differences in other secondary maternal outcomes: instrumental vaginal birth (10 trials, 5121 women); pain relief (8 trials, 3475 women); postpartum hemorrhage (2 trials, 1822 women); serious maternal morbidity or death (3 trials, 1740 women); umbilical cord prolapse (2 trials, 1615 women); and cesarean section for fetal distress, prolonged labor, or antepartum hemorrhage (1 RCT, 690 women).

Investigators also found no differences in secondary fetal outcomes: serious neonatal morbidity or perinatal death (8 trials, 3397 women); neonatal admission to neonatal intensive care (5 trials, 2686 women); abnormal fetal heart rate tracing in first stage of labor (4 trials, 1284 women); meconium aspiration (2 trials, 1615 women); and fetal acidosis (2 trials, 1014 women). Similarly, 1 RCT (39 women) that compared amniotomy with intent to preserve membranes in spontaneous labors that became prolonged found no difference in cesarean section, maternal satisfaction, or Apgar scores.

A few studies claim shorter labor with amniotomy

However, a later Iranian RCT (300 women) reported that early amniotomy shortened labor (labor duration: 7.5 ± 0.7 hours with amniotomy vs 9.9 ± 1.0 hours without amniotomy; P<.001) and reduced the risk of dystocia (RR=0.81; 95% CI, 0.59-0.90) and cesarean section (RR=0.82; 95% CI, 0.66-0.90).²

A similar Nigerian RCT (214 women) and an Indian RCT (144 women) both claimed that amniotomy also shortened labor (4.7 ± 0.9 hours vs 5.9 ± 1.3, and 3.9 ± 2 hours vs 6.1 ± 2.8 hours, respectively).^3,4 In neither trial, however, did investigators explain how the difference was significant when the duration of labor times overlapped within the margin of error.

In these first decades of the 21st century, the United States is the richest, strongest, most innovative nation on the planet. Americans like to chant “We’re Number 1”—and by many measures, they’re right. But in one crucial area of human endeavor—keeping people healthy—the mighty United States is a third-rate power.

All the other industrialized democracies have significantly better health outcomes than the United States—longer life expectancy, better recovery rates from illness or injury, less infant mortality.¹ Yet these nations spend, on average, half as much as the United States does for health care.¹ And these other rich democracies guarantee health care for everyone—while the United States leaves 29 million people ages <65 years with no health insurance, and another 50 million with deductibles so high that they are effectively uninsured.^2,3

This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.

Health care has become big business. As the physician-turned-reporter Dr. Elisabeth Rosenthal notes in An American Sickness: How Healthcare Became Big Business, profits have come to matter more than patients for much of the $3.3 trillion US health care industry.^4,5 And the financial winners in our system—notably the “Big Four” health insurance giants, the for-profit hospital chains, and “Big Pharma”—fight hard to protect their profits. When the Affordable Care Act (“ObamaCare”) was first proposed, one of its main goals was to cut the administrative costs of health insurance, to force the private insurers to run their business as efficiently as Medicare. The insurance industry didn’t like that; its lobbyists fought back, successfully. As passed, the law allows the insurers to add up to 20% in administrative fees to every doctor and hospital bill—which adds hundreds of billions of dollars to the nation’s total health care spending every year.

Primary care doctors earn significantly less than specialists. But it doesn’t have to be that way.

Then there’s the problem that health-care economists call “specialty distribution imbalance.” In plain English, this means that the United States has too many doctors working in narrow (but highly compensated) subspecialties and not enough in the primary care fields of family medicine, internal medicine, and pediatrics. This is one more area where our country is out of sync with other industrialized democracies.

When I traveled the world studying health care systems, economists and government health ministers regularly told me that an efficient system should have 2 primary care providers for every 1 specialist. That is, primary care should make up about 66% of the overall physician work force.

If a 2:1 ratio of primary care providers to specialists is right, then the United States is upside down.

Most rich countries come close to this desired ratio. In the United Kingdom, family doctors working out of their own offices (it’s called a “surgery”) and treating patients on the local High Street (that is, Main Street), control 70% of the National Health Service (NHS) budget.⁶ “That’s the framework of the NHS, and of course we want to keep it,” John Reid, the UK’s former Minister of Health, told me. “If you just pop into your doctor’s surgery on the high street, that’s often just as effective, but never as expensive, as waiting to see a specialist.”

Continue to: If that 2:1 ratio is the right proportion...

If that 2:1 ratio is the right proportion for an effective health care system, the United States is upside down. For decades now, some two-thirds of new medical graduates have gone into narrower specialties, leaving our country with a serious shortage of primary care physicians.⁷ This situation helps to explain the higher cost and poorer overall outcomes that characterize American health care.

“Health care is often delivered according to a model that concentrates on diseases, high technology, and specialist care,” a report from the World Health Organization noted.⁸ “The results are...higher overall costs, and exclusion of people who cannot pay.” The report concluded that an emphasis on primary care leads to better outcomes for the same level of investment. This simple truth has been called the “Iron Law” of health care systems.

How can the United States get more primary care physicians? One answer is compensation. American primary care doctors routinely earn significantly less than specialists. But it doesn’t have to be that way. When I asked my family doctor in London, Dr. Ahmed Badat, why it is that 62% of British physicians are in family care, he was blunt: “Under the NHS, I make twice as much as a cardiac surgeon.”

If the big payers—government programs and private insurers—beef up fees for primary care (and pay for it by reducing compensation for specialists), more young American med students are likely to choose that route. Repayment plans that forgive the student loans of those in primary care fields also would attract more newly-minted physicians; these programs already are in place in several states.⁹

Continue to: Medical schools also have a role...

Medical schools also have a role to play. It’s no secret that the schools have emphasized specialties, with faculty members often steering their best students into narrow fields. But schools could promote an atmosphere in which primary care is treated as the most desirable destination for new doctors. Actively seeking out, and accepting, applicants who say they want to practice primary care is another key tool the medical schools could employ to deal with this national problem.

More doctors in primary care would mean better health care at lower cost for American patients. It’s long past time to take the steps needed to reach that goal.

In these first decades of the 21st century, the United States is the richest, strongest, most innovative nation on the planet. Americans like to chant “We’re Number 1”—and by many measures, they’re right. But in one crucial area of human endeavor—keeping people healthy—the mighty United States is a third-rate power.

All the other industrialized democracies have significantly better health outcomes than the United States—longer life expectancy, better recovery rates from illness or injury, less infant mortality.¹ Yet these nations spend, on average, half as much as the United States does for health care.¹ And these other rich democracies guarantee health care for everyone—while the United States leaves 29 million people ages <65 years with no health insurance, and another 50 million with deductibles so high that they are effectively uninsured.^2,3

This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.

Health care has become big business. As the physician-turned-reporter Dr. Elisabeth Rosenthal notes in An American Sickness: How Healthcare Became Big Business, profits have come to matter more than patients for much of the $3.3 trillion US health care industry.^4,5 And the financial winners in our system—notably the “Big Four” health insurance giants, the for-profit hospital chains, and “Big Pharma”—fight hard to protect their profits. When the Affordable Care Act (“ObamaCare”) was first proposed, one of its main goals was to cut the administrative costs of health insurance, to force the private insurers to run their business as efficiently as Medicare. The insurance industry didn’t like that; its lobbyists fought back, successfully. As passed, the law allows the insurers to add up to 20% in administrative fees to every doctor and hospital bill—which adds hundreds of billions of dollars to the nation’s total health care spending every year.

Primary care doctors earn significantly less than specialists. But it doesn’t have to be that way.

Then there’s the problem that health-care economists call “specialty distribution imbalance.” In plain English, this means that the United States has too many doctors working in narrow (but highly compensated) subspecialties and not enough in the primary care fields of family medicine, internal medicine, and pediatrics. This is one more area where our country is out of sync with other industrialized democracies.

When I traveled the world studying health care systems, economists and government health ministers regularly told me that an efficient system should have 2 primary care providers for every 1 specialist. That is, primary care should make up about 66% of the overall physician work force.

If a 2:1 ratio of primary care providers to specialists is right, then the United States is upside down.

Most rich countries come close to this desired ratio. In the United Kingdom, family doctors working out of their own offices (it’s called a “surgery”) and treating patients on the local High Street (that is, Main Street), control 70% of the National Health Service (NHS) budget.⁶ “That’s the framework of the NHS, and of course we want to keep it,” John Reid, the UK’s former Minister of Health, told me. “If you just pop into your doctor’s surgery on the high street, that’s often just as effective, but never as expensive, as waiting to see a specialist.”

Continue to: If that 2:1 ratio is the right proportion...

If that 2:1 ratio is the right proportion for an effective health care system, the United States is upside down. For decades now, some two-thirds of new medical graduates have gone into narrower specialties, leaving our country with a serious shortage of primary care physicians.⁷ This situation helps to explain the higher cost and poorer overall outcomes that characterize American health care.

“Health care is often delivered according to a model that concentrates on diseases, high technology, and specialist care,” a report from the World Health Organization noted.⁸ “The results are...higher overall costs, and exclusion of people who cannot pay.” The report concluded that an emphasis on primary care leads to better outcomes for the same level of investment. This simple truth has been called the “Iron Law” of health care systems.

How can the United States get more primary care physicians? One answer is compensation. American primary care doctors routinely earn significantly less than specialists. But it doesn’t have to be that way. When I asked my family doctor in London, Dr. Ahmed Badat, why it is that 62% of British physicians are in family care, he was blunt: “Under the NHS, I make twice as much as a cardiac surgeon.”

If the big payers—government programs and private insurers—beef up fees for primary care (and pay for it by reducing compensation for specialists), more young American med students are likely to choose that route. Repayment plans that forgive the student loans of those in primary care fields also would attract more newly-minted physicians; these programs already are in place in several states.⁹

Continue to: Medical schools also have a role...

Medical schools also have a role to play. It’s no secret that the schools have emphasized specialties, with faculty members often steering their best students into narrow fields. But schools could promote an atmosphere in which primary care is treated as the most desirable destination for new doctors. Actively seeking out, and accepting, applicants who say they want to practice primary care is another key tool the medical schools could employ to deal with this national problem.

More doctors in primary care would mean better health care at lower cost for American patients. It’s long past time to take the steps needed to reach that goal.

In these first decades of the 21st century, the United States is the richest, strongest, most innovative nation on the planet. Americans like to chant “We’re Number 1”—and by many measures, they’re right. But in one crucial area of human endeavor—keeping people healthy—the mighty United States is a third-rate power.

All the other industrialized democracies have significantly better health outcomes than the United States—longer life expectancy, better recovery rates from illness or injury, less infant mortality.¹ Yet these nations spend, on average, half as much as the United States does for health care.¹ And these other rich democracies guarantee health care for everyone—while the United States leaves 29 million people ages <65 years with no health insurance, and another 50 million with deductibles so high that they are effectively uninsured.^2,3

This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.

Health care has become big business. As the physician-turned-reporter Dr. Elisabeth Rosenthal notes in An American Sickness: How Healthcare Became Big Business, profits have come to matter more than patients for much of the $3.3 trillion US health care industry.^4,5 And the financial winners in our system—notably the “Big Four” health insurance giants, the for-profit hospital chains, and “Big Pharma”—fight hard to protect their profits. When the Affordable Care Act (“ObamaCare”) was first proposed, one of its main goals was to cut the administrative costs of health insurance, to force the private insurers to run their business as efficiently as Medicare. The insurance industry didn’t like that; its lobbyists fought back, successfully. As passed, the law allows the insurers to add up to 20% in administrative fees to every doctor and hospital bill—which adds hundreds of billions of dollars to the nation’s total health care spending every year.

Primary care doctors earn significantly less than specialists. But it doesn’t have to be that way.

Then there’s the problem that health-care economists call “specialty distribution imbalance.” In plain English, this means that the United States has too many doctors working in narrow (but highly compensated) subspecialties and not enough in the primary care fields of family medicine, internal medicine, and pediatrics. This is one more area where our country is out of sync with other industrialized democracies.

When I traveled the world studying health care systems, economists and government health ministers regularly told me that an efficient system should have 2 primary care providers for every 1 specialist. That is, primary care should make up about 66% of the overall physician work force.

If a 2:1 ratio of primary care providers to specialists is right, then the United States is upside down.

Most rich countries come close to this desired ratio. In the United Kingdom, family doctors working out of their own offices (it’s called a “surgery”) and treating patients on the local High Street (that is, Main Street), control 70% of the National Health Service (NHS) budget.⁶ “That’s the framework of the NHS, and of course we want to keep it,” John Reid, the UK’s former Minister of Health, told me. “If you just pop into your doctor’s surgery on the high street, that’s often just as effective, but never as expensive, as waiting to see a specialist.”

Continue to: If that 2:1 ratio is the right proportion...

If that 2:1 ratio is the right proportion for an effective health care system, the United States is upside down. For decades now, some two-thirds of new medical graduates have gone into narrower specialties, leaving our country with a serious shortage of primary care physicians.⁷ This situation helps to explain the higher cost and poorer overall outcomes that characterize American health care.

“Health care is often delivered according to a model that concentrates on diseases, high technology, and specialist care,” a report from the World Health Organization noted.⁸ “The results are...higher overall costs, and exclusion of people who cannot pay.” The report concluded that an emphasis on primary care leads to better outcomes for the same level of investment. This simple truth has been called the “Iron Law” of health care systems.

How can the United States get more primary care physicians? One answer is compensation. American primary care doctors routinely earn significantly less than specialists. But it doesn’t have to be that way. When I asked my family doctor in London, Dr. Ahmed Badat, why it is that 62% of British physicians are in family care, he was blunt: “Under the NHS, I make twice as much as a cardiac surgeon.”

If the big payers—government programs and private insurers—beef up fees for primary care (and pay for it by reducing compensation for specialists), more young American med students are likely to choose that route. Repayment plans that forgive the student loans of those in primary care fields also would attract more newly-minted physicians; these programs already are in place in several states.⁹

Continue to: Medical schools also have a role...

Medical schools also have a role to play. It’s no secret that the schools have emphasized specialties, with faculty members often steering their best students into narrow fields. But schools could promote an atmosphere in which primary care is treated as the most desirable destination for new doctors. Actively seeking out, and accepting, applicants who say they want to practice primary care is another key tool the medical schools could employ to deal with this national problem.

More doctors in primary care would mean better health care at lower cost for American patients. It’s long past time to take the steps needed to reach that goal.

A 22-year-old Caucasian man with a history of atopic dermatitis (AD) was referred to our dermatology clinic for evaluation of a diffuse facial rash that had been present for the previous 7 days. The rash initially presented as erythema on the right malar cheek that rapidly spread to the entire face. Initially diagnosed as impetigo, empiric treatment with sulfamethoxazole/trimethoprim (800 mg/160 mg PO BID for 7 days), dicloxacillin (500 mg PO BID for 6 days), cephalexin (500 mg TID for 5 days), and mupirocin (2% topical cream applied TID for 6 days) failed to improve the patient’s symptoms. He reported mild pain associated with facial movements.

The patient had a history of similar (but more limited) rashes, which he described as “recurrent impetigo,” that began during his career as a high school and collegiate wrestler. These rashes were different from the rashes he described as his history of AD, which consisted of pruritic and erythematous skin in his antecubital and popliteal fossae. He denied any history of herpes simplex virus (HSV) infection.

A physical examination revealed numerous monomorphic, 1- to 3-mm, punched-out erosions and ulcers with overlying yellow-brown crust encompassing the patient’s entire face and portions of his anterior neck. Several clustered vesicles on erythematous bases also were noted (FIGUREs 1A and 1B). We used a Dermablade to unroof some of the vesicles and sent the scrapings to the lab for Tzanck, direct fluorescent antibody assay (DFA), and HSV polymerase chain reaction (PCR) testing.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Eczema herpeticum secondary to herpes gladiatorum

The patient’s laboratory results came back and the Tzanck preparation was positive for multinucleated giant cells, and both the DFA and HSV PCR were positive for HSV infection. This, paired with the widely disseminated rash observed on examination and the patient’s history of AD, was consistent with a diagnosis of eczema herpeticum (EH).

Rather than primary impetigo, the patient’s self-described history of recurrent rashes was felt to represent a history of HSV outbreaks. Given his denial of prior oral or genital HSV infection, as well as the coincident onset of these outbreaks during his career as a competitive wrestler, the most likely primary infection source was direct contact with another HSV-infected wrestler.

Herpes gladiatorum refers to a primary cutaneous HSV infection contracted by an athlete through direct skin-to-skin contact with another athlete.¹ It is common in contact sports, such as rugby and wrestling, and particularly common at organized wrestling camps, where mass outbreaks are a frequent occurrence.² Herpes gladiatorum is so common at these camps that many recommend prophylactic valacyclovir treatment for all participants to mitigate the risk of contracting HSV. In a 2016 review, Anderson et al concluded that prophylactic valacyclovir treatment at a 28-day high school wrestling camp effectively reduced outbreak incidence by 89.5%.²

Prophylactic valacyclovir treatment at a 28-day high school wrestling camp reduced outbreak incidence of herpes gladiatorum by 89.5%.

The lesions of herpes gladiatorum are classically limited in distribution and reflective of the areas of direct contact with infected skin, most commonly the face, neck, and arms. Our patient’s history of more limited outbreaks on his face was consistent with this typical presentation. His current outbreak, however, had become much more widely disseminated, which led to the diagnosis of EH secondary to herpes gladiatorum.

Eczema herpeticum: Pathogenesis and diagnosis

Also known as Kaposi’s varicelliform eruption, EH is a rapid, widespread cutaneous dissemination of HSV infection in areas of dermatitis or skin barrier disruption, most commonly caused by HSV-1 infection.³ It is classically associated with AD, but also can occur in patients with impaired epidermal barrier function due to other conditions, such as burns, pemphigus vulgaris, mycosis fungoides, and Darier disease.⁴ It occurs in <3% of patients with AD and is more commonly observed in infants and children with AD than adults.⁵

Continue to: Clinically, the most common manifestations are discrete..

Clinically, the most common manifestations are discrete, monomorphic, 2- to 3-mm, punched-out erosions with hemorrhagic crusts; intact vesicles are less commonly observed.⁴ Involved skin is typically painful and may be pruritic. Clinical diagnosis should be confirmed by laboratory evaluation, typically Tzanck preparation, DFA, and/or HSV PCR.

Complications and the importance of rapid treatment

The most common complication of EH is bacterial superinfection (impetigo), usually by Staphylococcus aureus or group A streptococci. Signs of bacterial superinfection include weeping lesions, pustules, honey-colored/golden crusting, worsening of existing dermatitis, and failure to respond to antiviral treatment. Topical mupirocin 2% cream is generally effective for controlling limited infection. However, systemic antibiotics (cephalosporins or penicillinase-resistant penicillins) may be necessary to control widespread disease.⁴ Clinical improvement should be observed within a single course of an appropriate antibiotic.

In contrast to impetigo, less common but more serious complications of EH can be life threatening. Systemic dissemination of disease is of particular importance in vulnerable populations such as pediatric and immunocompromised patients. Meningoencephalitis, secondary bacteremia, and herpes keratitis can all develop secondary to EH and incur significant morbidity and mortality.¹

Fever, malaise, lymphadenopathy, or eye pain should prompt immediate consideration of inpatient evaluation and treatment for these potentially deadly or debilitating complications. All patients with EH distributed near the eyes should be referred to ophthalmology to rule out ocular involvement.

A diagnosis of eczema herpeticum requires immediate treatment with oral or intravenous antiviral medication.

Immediately treat with antivirals

Due to the potential complications discussed above, a diagnosis of EH necessitates immediate treatment with oral or intravenous antiviral medication. Acyclovir, valacyclovir, or famciclovir may be used, with typical treatment courses ranging from 10 to 14 days or until all mucocutaneous lesions are healed.⁴ Although typically reserved for patients with recurrent genital herpes resulting in 6 or more outbreaks annually, chronic suppressive therapy also may be considered for patients with EH who suffer from frequent or severe recurrent outbreaks.

Continue to: Our patient

Our patient. Given his otherwise excellent health and the absence of symptoms of potentially serious complications, our patient was treated as an outpatient with a 10-day course of valacyclovir 1000 mg PO BID. He was additionally prescribed a 7-day course of cephalexin 500 mg PO TID for coverage of bacterial superinfection. He responded well to treatment.

Ten days after his initial presentation to our clinic, his erosions and vesicles had completely cleared, and the associated erythema had significantly improved (FIGURE 2). Given the severity of his presentation and his history of 2 to 3 outbreaks annually, he opted to continue prophylactic valacyclovir (500 mg/d) for long-term suppression.

CORRESPONDENCE
Jonathan Madden, MD, 221 3rd Street West, JBSA-Randolph, TX 78150, [email protected]

A 22-year-old Caucasian man with a history of atopic dermatitis (AD) was referred to our dermatology clinic for evaluation of a diffuse facial rash that had been present for the previous 7 days. The rash initially presented as erythema on the right malar cheek that rapidly spread to the entire face. Initially diagnosed as impetigo, empiric treatment with sulfamethoxazole/trimethoprim (800 mg/160 mg PO BID for 7 days), dicloxacillin (500 mg PO BID for 6 days), cephalexin (500 mg TID for 5 days), and mupirocin (2% topical cream applied TID for 6 days) failed to improve the patient’s symptoms. He reported mild pain associated with facial movements.

The patient had a history of similar (but more limited) rashes, which he described as “recurrent impetigo,” that began during his career as a high school and collegiate wrestler. These rashes were different from the rashes he described as his history of AD, which consisted of pruritic and erythematous skin in his antecubital and popliteal fossae. He denied any history of herpes simplex virus (HSV) infection.

A physical examination revealed numerous monomorphic, 1- to 3-mm, punched-out erosions and ulcers with overlying yellow-brown crust encompassing the patient’s entire face and portions of his anterior neck. Several clustered vesicles on erythematous bases also were noted (FIGUREs 1A and 1B). We used a Dermablade to unroof some of the vesicles and sent the scrapings to the lab for Tzanck, direct fluorescent antibody assay (DFA), and HSV polymerase chain reaction (PCR) testing.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Eczema herpeticum secondary to herpes gladiatorum

The patient’s laboratory results came back and the Tzanck preparation was positive for multinucleated giant cells, and both the DFA and HSV PCR were positive for HSV infection. This, paired with the widely disseminated rash observed on examination and the patient’s history of AD, was consistent with a diagnosis of eczema herpeticum (EH).

Rather than primary impetigo, the patient’s self-described history of recurrent rashes was felt to represent a history of HSV outbreaks. Given his denial of prior oral or genital HSV infection, as well as the coincident onset of these outbreaks during his career as a competitive wrestler, the most likely primary infection source was direct contact with another HSV-infected wrestler.

Herpes gladiatorum refers to a primary cutaneous HSV infection contracted by an athlete through direct skin-to-skin contact with another athlete.¹ It is common in contact sports, such as rugby and wrestling, and particularly common at organized wrestling camps, where mass outbreaks are a frequent occurrence.² Herpes gladiatorum is so common at these camps that many recommend prophylactic valacyclovir treatment for all participants to mitigate the risk of contracting HSV. In a 2016 review, Anderson et al concluded that prophylactic valacyclovir treatment at a 28-day high school wrestling camp effectively reduced outbreak incidence by 89.5%.²

Prophylactic valacyclovir treatment at a 28-day high school wrestling camp reduced outbreak incidence of herpes gladiatorum by 89.5%.

The lesions of herpes gladiatorum are classically limited in distribution and reflective of the areas of direct contact with infected skin, most commonly the face, neck, and arms. Our patient’s history of more limited outbreaks on his face was consistent with this typical presentation. His current outbreak, however, had become much more widely disseminated, which led to the diagnosis of EH secondary to herpes gladiatorum.

Eczema herpeticum: Pathogenesis and diagnosis

Also known as Kaposi’s varicelliform eruption, EH is a rapid, widespread cutaneous dissemination of HSV infection in areas of dermatitis or skin barrier disruption, most commonly caused by HSV-1 infection.³ It is classically associated with AD, but also can occur in patients with impaired epidermal barrier function due to other conditions, such as burns, pemphigus vulgaris, mycosis fungoides, and Darier disease.⁴ It occurs in <3% of patients with AD and is more commonly observed in infants and children with AD than adults.⁵

Continue to: Clinically, the most common manifestations are discrete..

Clinically, the most common manifestations are discrete, monomorphic, 2- to 3-mm, punched-out erosions with hemorrhagic crusts; intact vesicles are less commonly observed.⁴ Involved skin is typically painful and may be pruritic. Clinical diagnosis should be confirmed by laboratory evaluation, typically Tzanck preparation, DFA, and/or HSV PCR.

Complications and the importance of rapid treatment

The most common complication of EH is bacterial superinfection (impetigo), usually by Staphylococcus aureus or group A streptococci. Signs of bacterial superinfection include weeping lesions, pustules, honey-colored/golden crusting, worsening of existing dermatitis, and failure to respond to antiviral treatment. Topical mupirocin 2% cream is generally effective for controlling limited infection. However, systemic antibiotics (cephalosporins or penicillinase-resistant penicillins) may be necessary to control widespread disease.⁴ Clinical improvement should be observed within a single course of an appropriate antibiotic.

In contrast to impetigo, less common but more serious complications of EH can be life threatening. Systemic dissemination of disease is of particular importance in vulnerable populations such as pediatric and immunocompromised patients. Meningoencephalitis, secondary bacteremia, and herpes keratitis can all develop secondary to EH and incur significant morbidity and mortality.¹

Fever, malaise, lymphadenopathy, or eye pain should prompt immediate consideration of inpatient evaluation and treatment for these potentially deadly or debilitating complications. All patients with EH distributed near the eyes should be referred to ophthalmology to rule out ocular involvement.

A diagnosis of eczema herpeticum requires immediate treatment with oral or intravenous antiviral medication.

Immediately treat with antivirals

Due to the potential complications discussed above, a diagnosis of EH necessitates immediate treatment with oral or intravenous antiviral medication. Acyclovir, valacyclovir, or famciclovir may be used, with typical treatment courses ranging from 10 to 14 days or until all mucocutaneous lesions are healed.⁴ Although typically reserved for patients with recurrent genital herpes resulting in 6 or more outbreaks annually, chronic suppressive therapy also may be considered for patients with EH who suffer from frequent or severe recurrent outbreaks.

Continue to: Our patient

Our patient. Given his otherwise excellent health and the absence of symptoms of potentially serious complications, our patient was treated as an outpatient with a 10-day course of valacyclovir 1000 mg PO BID. He was additionally prescribed a 7-day course of cephalexin 500 mg PO TID for coverage of bacterial superinfection. He responded well to treatment.

Ten days after his initial presentation to our clinic, his erosions and vesicles had completely cleared, and the associated erythema had significantly improved (FIGURE 2). Given the severity of his presentation and his history of 2 to 3 outbreaks annually, he opted to continue prophylactic valacyclovir (500 mg/d) for long-term suppression.

CORRESPONDENCE
Jonathan Madden, MD, 221 3rd Street West, JBSA-Randolph, TX 78150, [email protected]

A 22-year-old Caucasian man with a history of atopic dermatitis (AD) was referred to our dermatology clinic for evaluation of a diffuse facial rash that had been present for the previous 7 days. The rash initially presented as erythema on the right malar cheek that rapidly spread to the entire face. Initially diagnosed as impetigo, empiric treatment with sulfamethoxazole/trimethoprim (800 mg/160 mg PO BID for 7 days), dicloxacillin (500 mg PO BID for 6 days), cephalexin (500 mg TID for 5 days), and mupirocin (2% topical cream applied TID for 6 days) failed to improve the patient’s symptoms. He reported mild pain associated with facial movements.

The patient had a history of similar (but more limited) rashes, which he described as “recurrent impetigo,” that began during his career as a high school and collegiate wrestler. These rashes were different from the rashes he described as his history of AD, which consisted of pruritic and erythematous skin in his antecubital and popliteal fossae. He denied any history of herpes simplex virus (HSV) infection.

A physical examination revealed numerous monomorphic, 1- to 3-mm, punched-out erosions and ulcers with overlying yellow-brown crust encompassing the patient’s entire face and portions of his anterior neck. Several clustered vesicles on erythematous bases also were noted (FIGUREs 1A and 1B). We used a Dermablade to unroof some of the vesicles and sent the scrapings to the lab for Tzanck, direct fluorescent antibody assay (DFA), and HSV polymerase chain reaction (PCR) testing.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Eczema herpeticum secondary to herpes gladiatorum

The patient’s laboratory results came back and the Tzanck preparation was positive for multinucleated giant cells, and both the DFA and HSV PCR were positive for HSV infection. This, paired with the widely disseminated rash observed on examination and the patient’s history of AD, was consistent with a diagnosis of eczema herpeticum (EH).

Rather than primary impetigo, the patient’s self-described history of recurrent rashes was felt to represent a history of HSV outbreaks. Given his denial of prior oral or genital HSV infection, as well as the coincident onset of these outbreaks during his career as a competitive wrestler, the most likely primary infection source was direct contact with another HSV-infected wrestler.

Herpes gladiatorum refers to a primary cutaneous HSV infection contracted by an athlete through direct skin-to-skin contact with another athlete.¹ It is common in contact sports, such as rugby and wrestling, and particularly common at organized wrestling camps, where mass outbreaks are a frequent occurrence.² Herpes gladiatorum is so common at these camps that many recommend prophylactic valacyclovir treatment for all participants to mitigate the risk of contracting HSV. In a 2016 review, Anderson et al concluded that prophylactic valacyclovir treatment at a 28-day high school wrestling camp effectively reduced outbreak incidence by 89.5%.²

Prophylactic valacyclovir treatment at a 28-day high school wrestling camp reduced outbreak incidence of herpes gladiatorum by 89.5%.

The lesions of herpes gladiatorum are classically limited in distribution and reflective of the areas of direct contact with infected skin, most commonly the face, neck, and arms. Our patient’s history of more limited outbreaks on his face was consistent with this typical presentation. His current outbreak, however, had become much more widely disseminated, which led to the diagnosis of EH secondary to herpes gladiatorum.

Eczema herpeticum: Pathogenesis and diagnosis

Also known as Kaposi’s varicelliform eruption, EH is a rapid, widespread cutaneous dissemination of HSV infection in areas of dermatitis or skin barrier disruption, most commonly caused by HSV-1 infection.³ It is classically associated with AD, but also can occur in patients with impaired epidermal barrier function due to other conditions, such as burns, pemphigus vulgaris, mycosis fungoides, and Darier disease.⁴ It occurs in <3% of patients with AD and is more commonly observed in infants and children with AD than adults.⁵

Continue to: Clinically, the most common manifestations are discrete..

Clinically, the most common manifestations are discrete, monomorphic, 2- to 3-mm, punched-out erosions with hemorrhagic crusts; intact vesicles are less commonly observed.⁴ Involved skin is typically painful and may be pruritic. Clinical diagnosis should be confirmed by laboratory evaluation, typically Tzanck preparation, DFA, and/or HSV PCR.

Complications and the importance of rapid treatment

The most common complication of EH is bacterial superinfection (impetigo), usually by Staphylococcus aureus or group A streptococci. Signs of bacterial superinfection include weeping lesions, pustules, honey-colored/golden crusting, worsening of existing dermatitis, and failure to respond to antiviral treatment. Topical mupirocin 2% cream is generally effective for controlling limited infection. However, systemic antibiotics (cephalosporins or penicillinase-resistant penicillins) may be necessary to control widespread disease.⁴ Clinical improvement should be observed within a single course of an appropriate antibiotic.

In contrast to impetigo, less common but more serious complications of EH can be life threatening. Systemic dissemination of disease is of particular importance in vulnerable populations such as pediatric and immunocompromised patients. Meningoencephalitis, secondary bacteremia, and herpes keratitis can all develop secondary to EH and incur significant morbidity and mortality.¹

Fever, malaise, lymphadenopathy, or eye pain should prompt immediate consideration of inpatient evaluation and treatment for these potentially deadly or debilitating complications. All patients with EH distributed near the eyes should be referred to ophthalmology to rule out ocular involvement.

A diagnosis of eczema herpeticum requires immediate treatment with oral or intravenous antiviral medication.

Immediately treat with antivirals

Due to the potential complications discussed above, a diagnosis of EH necessitates immediate treatment with oral or intravenous antiviral medication. Acyclovir, valacyclovir, or famciclovir may be used, with typical treatment courses ranging from 10 to 14 days or until all mucocutaneous lesions are healed.⁴ Although typically reserved for patients with recurrent genital herpes resulting in 6 or more outbreaks annually, chronic suppressive therapy also may be considered for patients with EH who suffer from frequent or severe recurrent outbreaks.

Continue to: Our patient

Our patient. Given his otherwise excellent health and the absence of symptoms of potentially serious complications, our patient was treated as an outpatient with a 10-day course of valacyclovir 1000 mg PO BID. He was additionally prescribed a 7-day course of cephalexin 500 mg PO TID for coverage of bacterial superinfection. He responded well to treatment.

Ten days after his initial presentation to our clinic, his erosions and vesicles had completely cleared, and the associated erythema had significantly improved (FIGURE 2). Given the severity of his presentation and his history of 2 to 3 outbreaks annually, he opted to continue prophylactic valacyclovir (500 mg/d) for long-term suppression.

CORRESPONDENCE
Jonathan Madden, MD, 221 3rd Street West, JBSA-Randolph, TX 78150, [email protected]

ILLUSTRATIVE CASE

A 63-year-old woman with a history of hypertension presents to the emergency department (ED) with acute onset shortness of breath and pleuritic chest pain after traveling across the country for a work conference. She has no history of cancer, liver disease, or renal disease. Her blood pressure is 140/80 mm Hg, and her heart rate is 90 bpm. You diagnose an acute PE in this patient and start anticoagulation. Should you admit her to the hospital to decrease morbidity and mortality?

According to the Centers for Disease Control and Prevention, venous thromboembolism (VTE) affects approximately 900,000 people each year, and approximately 60,000 to 100,000 of these patients die annually.² Pulmonary embolism is the third leading cause of death from cardiovascular disease, following heart attacks and strokes.³ Prompt diagnosis and treatment with systemic anticoagulation improves patient outcomes and decreases the risk of long-term complications.

The 2016 American College of Chest Physicians (CHEST) guideline on antithrombotic therapy for VTE disease recommends home treatment or early discharge over standard discharge (after the first 5 days of treatment) for patients who meet the following clinical criteria: “clinically stable with good cardiopulmonary reserve; no contraindications such as recent bleeding, severe renal or liver disease, or severe thrombocytopenia (ie, <70,000/mm³); expected to be compliant with treatment; and the patient feels well enough to be treated at home.”³

The guideline states that various clinical decision tools, such as the Pulmonary Embolism Severity Index (PESI), can aid in identifying low-risk patients to be considered for treatment at home. The PESI uses age, gender, vital signs, mental status, and a history of cancer, lung, and cardiac disease to stratify patients by risk.⁴

A systematic review of 1 randomized controlled trial (RCT) and 7 observational studies found that in low-risk patients, outpatient treatment was as safe as inpatient treatment.⁵ This more recent study determines the net clinical benefit of hospitalized vs outpatient management in a wider range of patients with acute PE, regardless of initial risk.¹

STUDY SUMMARY

Hospitalization confers no benefit to stable patients with acute PE

This retrospective, propensity-matched cohort study compared rates of adverse events in 1127 patients with acute PE managed in the hospital vs outpatient setting.¹ Patients were classified as outpatients if they were discharged from the ED or discharged from the hospital within 48 hours of admission. Patients were included if a symptomatic acute PE was diagnosed via computed tomography scan or high-probability ventilation-perfusion scan and excluded if they were <19 years of age, diagnosed with a PE during hospitalization, had chronic PE, or were hemodynamically unstable, among other factors. The investigators calculated PESI scores for all patients.

This trial supports guideline recommendations to manage hemodynamically stable patients with acute PE as outpatients.

Propensity scores matched patients on 28 patient characteristics and known risk factors for adverse events to ensure the groups were similar. The primary outcome was rate of adverse events, including recurrent VTE, major bleeding, or death at 14 days. The secondary outcome was rates of the above during the 3-month follow-up period.

Continue to: Of the 1127 eligible patients...

Of the 1127 eligible patients, 1081 were included in the matched cohort, with 576 (53%) treated as hospitalized patients and 505 (47%) treated as outpatients. The mean age of the matched cohorts was 63.2 years for the inpatient group and 63.6 years for the outpatient group. Overall, the cohorts were well matched.

The 14-day rate of adverse events was higher in hospitalized patients than in outpatients (13% vs 3.3%; odds ratio [OR] = 5.07; 95% confidence interval [CI], 1.68-15.28), with each of the adverse events that made up the primary outcome occurring more frequently in the hospitalized group (TABLE). The rate of adverse events at 3 months was also greater for hospitalized patients compared with outpatients (21.7% vs 6.9%; OR = 4.9; 95% CI, 2.62-9.17). The results remained similar for high-risk patients (Class III-V) based on their PESI score.

WHAT’S NEW

A higher rate of AEs in those treated as inpatients vs outpatients

This trial supports the CHEST guideline recommendations³ to manage hemodynamically stable patients with acute PE as outpatients. It adds to the conversation by demonstrating higher rates of adverse events with hospitalization, even in high-risk subgroups (PESI Class III-V).

CAVEATS

A good study, but it wasn’t an RCT

While this is a well-designed cohort study, it is not a randomized controlled trial (RCT). This study defined outpatient management as patients discharged from the ED or hospitalized for <48 hours. However, only 59 of the 544 patients in the outpatient group were early hospital discharges, while the rest were never admitted. Finally, a specialized thrombosis clinic followed up with the patients within 24 hours of discharge, and patients had telephone access to specialized health care professionals; such organization of care contributed to the safe outpatient management of these PE patients.

Continue to: CHALLENGES TO IMPLEMENTATION

Insurance coverage may present an issue

Medication coverage of direct oral anticoagulants and low molecular weight heparin may present a barrier to patients treated in the outpatient setting who have no insurance or are insured by certain insurance carriers.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 63-year-old woman with a history of hypertension presents to the emergency department (ED) with acute onset shortness of breath and pleuritic chest pain after traveling across the country for a work conference. She has no history of cancer, liver disease, or renal disease. Her blood pressure is 140/80 mm Hg, and her heart rate is 90 bpm. You diagnose an acute PE in this patient and start anticoagulation. Should you admit her to the hospital to decrease morbidity and mortality?

According to the Centers for Disease Control and Prevention, venous thromboembolism (VTE) affects approximately 900,000 people each year, and approximately 60,000 to 100,000 of these patients die annually.² Pulmonary embolism is the third leading cause of death from cardiovascular disease, following heart attacks and strokes.³ Prompt diagnosis and treatment with systemic anticoagulation improves patient outcomes and decreases the risk of long-term complications.

The 2016 American College of Chest Physicians (CHEST) guideline on antithrombotic therapy for VTE disease recommends home treatment or early discharge over standard discharge (after the first 5 days of treatment) for patients who meet the following clinical criteria: “clinically stable with good cardiopulmonary reserve; no contraindications such as recent bleeding, severe renal or liver disease, or severe thrombocytopenia (ie, <70,000/mm³); expected to be compliant with treatment; and the patient feels well enough to be treated at home.”³

The guideline states that various clinical decision tools, such as the Pulmonary Embolism Severity Index (PESI), can aid in identifying low-risk patients to be considered for treatment at home. The PESI uses age, gender, vital signs, mental status, and a history of cancer, lung, and cardiac disease to stratify patients by risk.⁴

A systematic review of 1 randomized controlled trial (RCT) and 7 observational studies found that in low-risk patients, outpatient treatment was as safe as inpatient treatment.⁵ This more recent study determines the net clinical benefit of hospitalized vs outpatient management in a wider range of patients with acute PE, regardless of initial risk.¹

STUDY SUMMARY

Hospitalization confers no benefit to stable patients with acute PE

This retrospective, propensity-matched cohort study compared rates of adverse events in 1127 patients with acute PE managed in the hospital vs outpatient setting.¹ Patients were classified as outpatients if they were discharged from the ED or discharged from the hospital within 48 hours of admission. Patients were included if a symptomatic acute PE was diagnosed via computed tomography scan or high-probability ventilation-perfusion scan and excluded if they were <19 years of age, diagnosed with a PE during hospitalization, had chronic PE, or were hemodynamically unstable, among other factors. The investigators calculated PESI scores for all patients.

This trial supports guideline recommendations to manage hemodynamically stable patients with acute PE as outpatients.

Propensity scores matched patients on 28 patient characteristics and known risk factors for adverse events to ensure the groups were similar. The primary outcome was rate of adverse events, including recurrent VTE, major bleeding, or death at 14 days. The secondary outcome was rates of the above during the 3-month follow-up period.

Continue to: Of the 1127 eligible patients...

Of the 1127 eligible patients, 1081 were included in the matched cohort, with 576 (53%) treated as hospitalized patients and 505 (47%) treated as outpatients. The mean age of the matched cohorts was 63.2 years for the inpatient group and 63.6 years for the outpatient group. Overall, the cohorts were well matched.

The 14-day rate of adverse events was higher in hospitalized patients than in outpatients (13% vs 3.3%; odds ratio [OR] = 5.07; 95% confidence interval [CI], 1.68-15.28), with each of the adverse events that made up the primary outcome occurring more frequently in the hospitalized group (TABLE). The rate of adverse events at 3 months was also greater for hospitalized patients compared with outpatients (21.7% vs 6.9%; OR = 4.9; 95% CI, 2.62-9.17). The results remained similar for high-risk patients (Class III-V) based on their PESI score.

WHAT’S NEW

A higher rate of AEs in those treated as inpatients vs outpatients

This trial supports the CHEST guideline recommendations³ to manage hemodynamically stable patients with acute PE as outpatients. It adds to the conversation by demonstrating higher rates of adverse events with hospitalization, even in high-risk subgroups (PESI Class III-V).

CAVEATS

A good study, but it wasn’t an RCT

While this is a well-designed cohort study, it is not a randomized controlled trial (RCT). This study defined outpatient management as patients discharged from the ED or hospitalized for <48 hours. However, only 59 of the 544 patients in the outpatient group were early hospital discharges, while the rest were never admitted. Finally, a specialized thrombosis clinic followed up with the patients within 24 hours of discharge, and patients had telephone access to specialized health care professionals; such organization of care contributed to the safe outpatient management of these PE patients.

Continue to: CHALLENGES TO IMPLEMENTATION

Insurance coverage may present an issue

Medication coverage of direct oral anticoagulants and low molecular weight heparin may present a barrier to patients treated in the outpatient setting who have no insurance or are insured by certain insurance carriers.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 63-year-old woman with a history of hypertension presents to the emergency department (ED) with acute onset shortness of breath and pleuritic chest pain after traveling across the country for a work conference. She has no history of cancer, liver disease, or renal disease. Her blood pressure is 140/80 mm Hg, and her heart rate is 90 bpm. You diagnose an acute PE in this patient and start anticoagulation. Should you admit her to the hospital to decrease morbidity and mortality?

According to the Centers for Disease Control and Prevention, venous thromboembolism (VTE) affects approximately 900,000 people each year, and approximately 60,000 to 100,000 of these patients die annually.² Pulmonary embolism is the third leading cause of death from cardiovascular disease, following heart attacks and strokes.³ Prompt diagnosis and treatment with systemic anticoagulation improves patient outcomes and decreases the risk of long-term complications.

The 2016 American College of Chest Physicians (CHEST) guideline on antithrombotic therapy for VTE disease recommends home treatment or early discharge over standard discharge (after the first 5 days of treatment) for patients who meet the following clinical criteria: “clinically stable with good cardiopulmonary reserve; no contraindications such as recent bleeding, severe renal or liver disease, or severe thrombocytopenia (ie, <70,000/mm³); expected to be compliant with treatment; and the patient feels well enough to be treated at home.”³

The guideline states that various clinical decision tools, such as the Pulmonary Embolism Severity Index (PESI), can aid in identifying low-risk patients to be considered for treatment at home. The PESI uses age, gender, vital signs, mental status, and a history of cancer, lung, and cardiac disease to stratify patients by risk.⁴

A systematic review of 1 randomized controlled trial (RCT) and 7 observational studies found that in low-risk patients, outpatient treatment was as safe as inpatient treatment.⁵ This more recent study determines the net clinical benefit of hospitalized vs outpatient management in a wider range of patients with acute PE, regardless of initial risk.¹

STUDY SUMMARY

Hospitalization confers no benefit to stable patients with acute PE

This retrospective, propensity-matched cohort study compared rates of adverse events in 1127 patients with acute PE managed in the hospital vs outpatient setting.¹ Patients were classified as outpatients if they were discharged from the ED or discharged from the hospital within 48 hours of admission. Patients were included if a symptomatic acute PE was diagnosed via computed tomography scan or high-probability ventilation-perfusion scan and excluded if they were <19 years of age, diagnosed with a PE during hospitalization, had chronic PE, or were hemodynamically unstable, among other factors. The investigators calculated PESI scores for all patients.

This trial supports guideline recommendations to manage hemodynamically stable patients with acute PE as outpatients.

Propensity scores matched patients on 28 patient characteristics and known risk factors for adverse events to ensure the groups were similar. The primary outcome was rate of adverse events, including recurrent VTE, major bleeding, or death at 14 days. The secondary outcome was rates of the above during the 3-month follow-up period.

Continue to: Of the 1127 eligible patients...

Of the 1127 eligible patients, 1081 were included in the matched cohort, with 576 (53%) treated as hospitalized patients and 505 (47%) treated as outpatients. The mean age of the matched cohorts was 63.2 years for the inpatient group and 63.6 years for the outpatient group. Overall, the cohorts were well matched.

The 14-day rate of adverse events was higher in hospitalized patients than in outpatients (13% vs 3.3%; odds ratio [OR] = 5.07; 95% confidence interval [CI], 1.68-15.28), with each of the adverse events that made up the primary outcome occurring more frequently in the hospitalized group (TABLE). The rate of adverse events at 3 months was also greater for hospitalized patients compared with outpatients (21.7% vs 6.9%; OR = 4.9; 95% CI, 2.62-9.17). The results remained similar for high-risk patients (Class III-V) based on their PESI score.

WHAT’S NEW

A higher rate of AEs in those treated as inpatients vs outpatients

This trial supports the CHEST guideline recommendations³ to manage hemodynamically stable patients with acute PE as outpatients. It adds to the conversation by demonstrating higher rates of adverse events with hospitalization, even in high-risk subgroups (PESI Class III-V).

CAVEATS

A good study, but it wasn’t an RCT

While this is a well-designed cohort study, it is not a randomized controlled trial (RCT). This study defined outpatient management as patients discharged from the ED or hospitalized for <48 hours. However, only 59 of the 544 patients in the outpatient group were early hospital discharges, while the rest were never admitted. Finally, a specialized thrombosis clinic followed up with the patients within 24 hours of discharge, and patients had telephone access to specialized health care professionals; such organization of care contributed to the safe outpatient management of these PE patients.

Continue to: CHALLENGES TO IMPLEMENTATION

Insurance coverage may present an issue

Medication coverage of direct oral anticoagulants and low molecular weight heparin may present a barrier to patients treated in the outpatient setting who have no insurance or are insured by certain insurance carriers.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ABSTRACT

Purpose Our study examined the efficacy of a primary-care intervention in reducing opioid use among patients who have chronic non-cancer pain (CNCP). We also recorded the intervention’s effect on patients’ decisions to leave (or stay) with the primary-care practice.

Methods A family physician (FP) identified 41 patients in his practice who had CNCP of at least 6 month’s duration and were using opioids. The intervention with each patient involved an initial discussion of ethical principles, evidence-based practice, and current published guidelines. Following the discussion, patients self-selected to participate with their FP in a continuing tapering program or to accept referral to a pain center for management of their opioid medications. Tapering ranged from a 10% reduction per week to a more rapid 25% to 50% reduction every few days. Twenty-seven patients continued tapering with their FP, and 6 months later were retrospectively placed in the Taper Group. Fourteen patients chose not to pursue the tapering option and were referred to a single-modality medical pain clinic (MPC). All patients had the option of staying with the FP for other medical care.

Results At baseline and again at 6 months post-initial intervention, the MPC Group was taking significantly higher daily doses of morphine equivalents than the Taper Group. The Taper Group at 6 months was taking significantly lower average daily narcotic doses in morphine equivalents than at baseline. No significant baseline-to-6 month differences were found in the MPC Group. Contrary to many physicians’ fear of losing patients following candid discussions about opioid use, 40 of the 41 patients continued with the FP for other health needs.

Conclusions FPs can frankly discuss opioid use with their patients based on ethical principles and evidence-based recommendations and employ a tapering protocol consistent with current opioid treatment guidelines without jeopardizing the patient-physician relationship.

[polldaddy:10180698]

Opioid prescriptions for chronic noncancer pain (CNCP) have increased significantly over the past 25 years in the United States.¹ Despite methodologic concerns surrounding research on opioid harms, prescription opioid misuse among CNCP patients is estimated to be 21% to 29% and prescription addiction 8% to 12%.² Tragically, with the overall increase in opioid use for CNCP, substance-related hospital admissions and deaths due to opioid overdose have also risen.³

Increased opioid use began in 1985 when the World Health Organization expanded its ethical mandate for pain relief in dying patients to include relief from all cancer pain.³ Opioid use then accelerated following Portenoy and Foley’s 1986 article⁴ and the 1997 consensus statement by the American Academy of Pain Medicine (AAPM) and the American Pain Society (APS),⁵ with both organizations arguing that opioids have a role in the treatment of CNCP. Increased use of opioids for CNCP continued throughout the 1990s and 2000s, as many states passed legislation removing sanctions on prescribing long-term and high-dose opioid therapy, and pharmaceutical companies aggressively marketed sustained-release opioids.³

A balanced approach to opioids. While acknowledging the serious public health problems of drug abuse, addiction, and diversion of opioids from licit to illicit uses, clinical research and regulation leaders have called for a balanced approach that recognizes the legitimate medical need for opioids for CNCP. In 2009 the APS, in partnership with the AAPM, published evidence-based guidelines on chronic opioid therapy (COT) for adults with CNCP.⁶ In developing these guidelines, a multidisciplinary panel of experts conducted systematic reviews of available evidence and made recommendations on formulating COT for individuals, initiating and titrating therapy, regularly monitoring patients, and managing opioid-related adverse effects. Additional recommendations addressed the use of therapies focusing on psychosocial factors. The APS-AAPM guidelines received the highest rating in a systematic review critically appraising 13 guidelines that address the use of opioids for CNCP.⁷

Continue to: When opioid use is prolonged...

When opioid use is prolonged. Most primary care physicians are aware of the risks of prolonged opioid use, and many have successfully tapered or discontinued opioid medications for patients in acute or pre-chronic stages of pain.⁸ However, many physicians face the challenge of patients who have used COT for a longer time. The APS-AAPM guidelines may help primary care physicians at any stage of treating CNCP patients.

METHODS

Purpose and design. This retrospective study, which reviewed pretest-posttest findings between and within study groups, received an exempt status from Creighton University’s institutional review board. We designed the study to determine the efficacy of an intervention protocol to reduce opioid use by patients with CNCP who had been in a family physician (FP)'s panel for quite some time. Furthermore, because a common fear among primary care providers is that raising concerns with patients about their opioid use may cause those patients to leave their panel,⁹ our study also recorded how many patients stayed with their FP after initiation of the opioid management protocol.

Subjects. This study tracked 41 patients with CNCP in 1 FP’s panel. Inclusion criteria for participation was: 1) presence of CNCP for at least 6 months, 2) current use of opioid medication for CNCP, 3) age of at least 16 years, and 4) ability to read and write English. Two exclusion criteria were the presence of a surgically correctable condition or an organic brain syndrome or psychosis.

Clinical intervention. The FP identified eligible patients in his practice that were taking opioids for CNCP and initiated a discussion with each of them emphasizing his desire to follow the ethical principles of beneficence, nonmaleficence, respect for autonomy, and justice.¹⁰ The FP also presented his reasons for wanting the patient to stop using opioid medication. They included his beliefs that:

1) COT was not safe for the patient based on a growing body of published evidence of harm and death from COT³;
2) long-term use of opioids could lead to misuse, abuse, or addiction²;
3) prolonged opioid use paradoxically increases pain sensitivity that does not resolve with discontinuation of opioid maintenance^11,12 (although pain tolerance does improve after opioid cessation); and
4) the patient’s current pain medications were not in line with published guidelines for use of opioids for CNCP.⁶

Initially, 45 patients were eligible for the study, but 4 declined participation before the intervention discussion and were immediately referred to a single-modality medical pain clinic (MPC). These patients were not included in subsequent analyses. Of the remaining 41 patients, all had a discussion with the MD about ethical principles, practice guidelines, and the importance of opioid tapering. After the discussion, patients decided whether to continue with the plan to taper their opioid therapy or to not taper their therapy and so receive a referral to an MPC.

Continue to: The 27 patients who chose to work with...

The 27 patients who chose to work with their FP started an individually tailored opioid-tapering program and were retrospectively placed in the Taper Group 6 months later. Tapering ranged from a slow 10% reduction in dosage per week to a more rapid 25% to 50% reduction every few days. Although evidence to guide specific recommendations on the rate of reduction is lacking, a slower rate may reduce unpleasant symptoms of opioid withdrawal.⁶ Following the patient-FP discussion, the 14 patients who chose not to pursue the tapering option were referred to an MPC for pain management, but could opt to remain with the FP for all other medical care. At 6 months post-discussion, we retrospectively assigned these 14 patients to the MPC Group.

Measures. We obtained demographic and medical information, including age, gender, race, marital status, and medication level in morphine equivalents, from the electronic health record. Medication level in morphine equivalents was recorded at the beginning of the intervention and again 6 months later. All analyses were conducted using SPSS Version 24 (IBM Corp, Armonk, NY) with P<.05 used to indicate statistical significance.

RESULTS

Between-group differences. The Taper and MPC groups did not differ significantly on demographic variables, with mean ages, respectively, at 57 and 51 years, sex 56% and 50% female, race 74% and 79% white, and marital status 48% and 50% married.

Patients who tapered opioid usage under FP guidance significantly reduced daily morphine equivalents over 6 months.

We found significant differences between the Taper and MPC groups on total daily dose in morphine equivalents at baseline and at 6 months following initial intervention. The Levene’s test for equality of variances was statistically significant, indicating unequal variances between the groups. In our SPSS analyses, we therefore used the option “equal variances not assumed.” TABLE 1 lists resultant means, standard deviations, individual sample t-test scores, and confidence intervals. The MPC Group was taking significantly higher daily doses of morphine equivalents than the Taper Group both at baseline and at 6 months following initial intervention.

Within-group differences. Paired sample t tests indicated significant differences between baseline and 6-month average daily narcotic doses in morphine equivalents for the Taper Group. No significant difference was found between baseline and 6-month daily morphine equivalents for the MPC group. These results indicated that patients who continued opioid tapering with the FP significantly reduced their daily morphine equivalents over the 6 months of the study. Patients in the MPC Group reduced morphine equivalents over the 6 months, but the reduction was not statistically significant. Paired sample t test results are presented in TABLE 2.

Continue to: Patient retention

Patient retention. All but one of the 41 patients in the Tapering and MPC groups continued with the FP for the remainder of their health care needs. Contrary to some physicians’ fears, the patients in this study maintained continuity with their FP.

DISCUSSION

Results of this study indicate that an intervention consisting of a physician-patient discussion of ethical principles and evidence-based practice, followed by individualized opioid tapering per published guidelines, led to a significant reduction in opioid use in patients with CNCP. The Taper Group, which completed the intervention, exhibited significant morphine reductions between baseline and 6-month follow-up. This did not hold true for the MPC Group.

The MPC Group, despite participating in the discussion with the FP, chose not to complete the tapering program and was referred to a single-modality MPC where opioids were managed rather than tapered. While the MPC group reduced daily opioid dose levels, the reduction was not statistically significant. A possible reason for no difference within the MPC Group may be that they had greater dependence on opioids, as their baseline average daily dose was much higher than that in the Taper Group (173 mg vs 31 mg, respectively). Although we did not assess anxiety directly, we speculate that the MPC Group was more anxious about opioid reduction than the Taper Group, and that this anxiety potentially led 4 patients to opt out of the initial FP discussion and 14 patients to self-select out of the tapering program following the discussion.

Of the 14 patients who opted not to participate with their FP in opioid tapering, 13 remained with him for all other care.

The FP intervention was successful for the Taper Group. For MPC patients, an enhanced intervention including behavior health strategies¹³ might have reduced anxiety and increased motivation¹⁴ to continue tapering. Based on moderate-quality evidence, APS-AAPM guidelines strongly recommend that CNCP be viewed as a complex biopsychosocial condition. Therefore, clinicians who prescribe opioids should routinely integrate psychotherapeutic interventions, functional restoration, interdisciplinary therapy, and other adjunctive nonopioid therapies.⁶

Opioid tapering within multidisciplinary rehabilitation programs is possible without significant worsening of pain, mood, and function.¹⁵ Recently, an outpatient opioid-tapering support intervention showed promise for efficacy in reducing prescription opioid doses without resultant increases in pain intensity or pain interference.¹⁶

Continue to: The tapering protocol in our study...

The tapering protocol in our study and the inclusion of behavioral health co-interventions are also recommended by the 2016 guidelines published by the Center for Disease Control and Prevention.¹⁷ More information on the similarities and differences among the various guidelines is available online.^18,19

Caveats with our study. Patients’ entry into the Taper or MPC groups occurred through self-selection rather than random assignment. Thus, caution is recommended in interpreting findings of the FP intervention. And, we did not measure patients’ levels of pain, so differences between groups may have been possible. In addition, the number of patients per group was relatively small, which may have accounted for the lack of significance in the MPC Group findings. Conversely, significant reductions in opioid use in the small tapering sample suggests a relatively robust intervention, despite a lack of random assignment to treatment conditions.

These findings suggest that FPs can have a frank conversation about opioid use with their patients based on ethical principles and evidence-based practice, and employ a tapering protocol consistent with current opioid treatment guidelines. Furthermore, this approach appears not to jeopardize the patient-physician relationship.

CORRESPONDENCE
Thomas P. Guck, PhD, Creighton University School of Medicine, 2412 Cuming Street, Omaha, NE 68131; [email protected].

ABSTRACT

Purpose Our study examined the efficacy of a primary-care intervention in reducing opioid use among patients who have chronic non-cancer pain (CNCP). We also recorded the intervention’s effect on patients’ decisions to leave (or stay) with the primary-care practice.

Methods A family physician (FP) identified 41 patients in his practice who had CNCP of at least 6 month’s duration and were using opioids. The intervention with each patient involved an initial discussion of ethical principles, evidence-based practice, and current published guidelines. Following the discussion, patients self-selected to participate with their FP in a continuing tapering program or to accept referral to a pain center for management of their opioid medications. Tapering ranged from a 10% reduction per week to a more rapid 25% to 50% reduction every few days. Twenty-seven patients continued tapering with their FP, and 6 months later were retrospectively placed in the Taper Group. Fourteen patients chose not to pursue the tapering option and were referred to a single-modality medical pain clinic (MPC). All patients had the option of staying with the FP for other medical care.

Results At baseline and again at 6 months post-initial intervention, the MPC Group was taking significantly higher daily doses of morphine equivalents than the Taper Group. The Taper Group at 6 months was taking significantly lower average daily narcotic doses in morphine equivalents than at baseline. No significant baseline-to-6 month differences were found in the MPC Group. Contrary to many physicians’ fear of losing patients following candid discussions about opioid use, 40 of the 41 patients continued with the FP for other health needs.

Conclusions FPs can frankly discuss opioid use with their patients based on ethical principles and evidence-based recommendations and employ a tapering protocol consistent with current opioid treatment guidelines without jeopardizing the patient-physician relationship.

[polldaddy:10180698]

Opioid prescriptions for chronic noncancer pain (CNCP) have increased significantly over the past 25 years in the United States.¹ Despite methodologic concerns surrounding research on opioid harms, prescription opioid misuse among CNCP patients is estimated to be 21% to 29% and prescription addiction 8% to 12%.² Tragically, with the overall increase in opioid use for CNCP, substance-related hospital admissions and deaths due to opioid overdose have also risen.³

Increased opioid use began in 1985 when the World Health Organization expanded its ethical mandate for pain relief in dying patients to include relief from all cancer pain.³ Opioid use then accelerated following Portenoy and Foley’s 1986 article⁴ and the 1997 consensus statement by the American Academy of Pain Medicine (AAPM) and the American Pain Society (APS),⁵ with both organizations arguing that opioids have a role in the treatment of CNCP. Increased use of opioids for CNCP continued throughout the 1990s and 2000s, as many states passed legislation removing sanctions on prescribing long-term and high-dose opioid therapy, and pharmaceutical companies aggressively marketed sustained-release opioids.³

A balanced approach to opioids. While acknowledging the serious public health problems of drug abuse, addiction, and diversion of opioids from licit to illicit uses, clinical research and regulation leaders have called for a balanced approach that recognizes the legitimate medical need for opioids for CNCP. In 2009 the APS, in partnership with the AAPM, published evidence-based guidelines on chronic opioid therapy (COT) for adults with CNCP.⁶ In developing these guidelines, a multidisciplinary panel of experts conducted systematic reviews of available evidence and made recommendations on formulating COT for individuals, initiating and titrating therapy, regularly monitoring patients, and managing opioid-related adverse effects. Additional recommendations addressed the use of therapies focusing on psychosocial factors. The APS-AAPM guidelines received the highest rating in a systematic review critically appraising 13 guidelines that address the use of opioids for CNCP.⁷

Continue to: When opioid use is prolonged...

When opioid use is prolonged. Most primary care physicians are aware of the risks of prolonged opioid use, and many have successfully tapered or discontinued opioid medications for patients in acute or pre-chronic stages of pain.⁸ However, many physicians face the challenge of patients who have used COT for a longer time. The APS-AAPM guidelines may help primary care physicians at any stage of treating CNCP patients.

METHODS

Purpose and design. This retrospective study, which reviewed pretest-posttest findings between and within study groups, received an exempt status from Creighton University’s institutional review board. We designed the study to determine the efficacy of an intervention protocol to reduce opioid use by patients with CNCP who had been in a family physician (FP)'s panel for quite some time. Furthermore, because a common fear among primary care providers is that raising concerns with patients about their opioid use may cause those patients to leave their panel,⁹ our study also recorded how many patients stayed with their FP after initiation of the opioid management protocol.

Subjects. This study tracked 41 patients with CNCP in 1 FP’s panel. Inclusion criteria for participation was: 1) presence of CNCP for at least 6 months, 2) current use of opioid medication for CNCP, 3) age of at least 16 years, and 4) ability to read and write English. Two exclusion criteria were the presence of a surgically correctable condition or an organic brain syndrome or psychosis.

Clinical intervention. The FP identified eligible patients in his practice that were taking opioids for CNCP and initiated a discussion with each of them emphasizing his desire to follow the ethical principles of beneficence, nonmaleficence, respect for autonomy, and justice.¹⁰ The FP also presented his reasons for wanting the patient to stop using opioid medication. They included his beliefs that:

1) COT was not safe for the patient based on a growing body of published evidence of harm and death from COT³;
2) long-term use of opioids could lead to misuse, abuse, or addiction²;
3) prolonged opioid use paradoxically increases pain sensitivity that does not resolve with discontinuation of opioid maintenance^11,12 (although pain tolerance does improve after opioid cessation); and
4) the patient’s current pain medications were not in line with published guidelines for use of opioids for CNCP.⁶

Initially, 45 patients were eligible for the study, but 4 declined participation before the intervention discussion and were immediately referred to a single-modality medical pain clinic (MPC). These patients were not included in subsequent analyses. Of the remaining 41 patients, all had a discussion with the MD about ethical principles, practice guidelines, and the importance of opioid tapering. After the discussion, patients decided whether to continue with the plan to taper their opioid therapy or to not taper their therapy and so receive a referral to an MPC.

Continue to: The 27 patients who chose to work with...

The 27 patients who chose to work with their FP started an individually tailored opioid-tapering program and were retrospectively placed in the Taper Group 6 months later. Tapering ranged from a slow 10% reduction in dosage per week to a more rapid 25% to 50% reduction every few days. Although evidence to guide specific recommendations on the rate of reduction is lacking, a slower rate may reduce unpleasant symptoms of opioid withdrawal.⁶ Following the patient-FP discussion, the 14 patients who chose not to pursue the tapering option were referred to an MPC for pain management, but could opt to remain with the FP for all other medical care. At 6 months post-discussion, we retrospectively assigned these 14 patients to the MPC Group.

Measures. We obtained demographic and medical information, including age, gender, race, marital status, and medication level in morphine equivalents, from the electronic health record. Medication level in morphine equivalents was recorded at the beginning of the intervention and again 6 months later. All analyses were conducted using SPSS Version 24 (IBM Corp, Armonk, NY) with P<.05 used to indicate statistical significance.

RESULTS

Between-group differences. The Taper and MPC groups did not differ significantly on demographic variables, with mean ages, respectively, at 57 and 51 years, sex 56% and 50% female, race 74% and 79% white, and marital status 48% and 50% married.

Patients who tapered opioid usage under FP guidance significantly reduced daily morphine equivalents over 6 months.

We found significant differences between the Taper and MPC groups on total daily dose in morphine equivalents at baseline and at 6 months following initial intervention. The Levene’s test for equality of variances was statistically significant, indicating unequal variances between the groups. In our SPSS analyses, we therefore used the option “equal variances not assumed.” TABLE 1 lists resultant means, standard deviations, individual sample t-test scores, and confidence intervals. The MPC Group was taking significantly higher daily doses of morphine equivalents than the Taper Group both at baseline and at 6 months following initial intervention.

Within-group differences. Paired sample t tests indicated significant differences between baseline and 6-month average daily narcotic doses in morphine equivalents for the Taper Group. No significant difference was found between baseline and 6-month daily morphine equivalents for the MPC group. These results indicated that patients who continued opioid tapering with the FP significantly reduced their daily morphine equivalents over the 6 months of the study. Patients in the MPC Group reduced morphine equivalents over the 6 months, but the reduction was not statistically significant. Paired sample t test results are presented in TABLE 2.

Continue to: Patient retention

Patient retention. All but one of the 41 patients in the Tapering and MPC groups continued with the FP for the remainder of their health care needs. Contrary to some physicians’ fears, the patients in this study maintained continuity with their FP.

DISCUSSION

Results of this study indicate that an intervention consisting of a physician-patient discussion of ethical principles and evidence-based practice, followed by individualized opioid tapering per published guidelines, led to a significant reduction in opioid use in patients with CNCP. The Taper Group, which completed the intervention, exhibited significant morphine reductions between baseline and 6-month follow-up. This did not hold true for the MPC Group.

The MPC Group, despite participating in the discussion with the FP, chose not to complete the tapering program and was referred to a single-modality MPC where opioids were managed rather than tapered. While the MPC group reduced daily opioid dose levels, the reduction was not statistically significant. A possible reason for no difference within the MPC Group may be that they had greater dependence on opioids, as their baseline average daily dose was much higher than that in the Taper Group (173 mg vs 31 mg, respectively). Although we did not assess anxiety directly, we speculate that the MPC Group was more anxious about opioid reduction than the Taper Group, and that this anxiety potentially led 4 patients to opt out of the initial FP discussion and 14 patients to self-select out of the tapering program following the discussion.

Of the 14 patients who opted not to participate with their FP in opioid tapering, 13 remained with him for all other care.

The FP intervention was successful for the Taper Group. For MPC patients, an enhanced intervention including behavior health strategies¹³ might have reduced anxiety and increased motivation¹⁴ to continue tapering. Based on moderate-quality evidence, APS-AAPM guidelines strongly recommend that CNCP be viewed as a complex biopsychosocial condition. Therefore, clinicians who prescribe opioids should routinely integrate psychotherapeutic interventions, functional restoration, interdisciplinary therapy, and other adjunctive nonopioid therapies.⁶

Opioid tapering within multidisciplinary rehabilitation programs is possible without significant worsening of pain, mood, and function.¹⁵ Recently, an outpatient opioid-tapering support intervention showed promise for efficacy in reducing prescription opioid doses without resultant increases in pain intensity or pain interference.¹⁶

Continue to: The tapering protocol in our study...

The tapering protocol in our study and the inclusion of behavioral health co-interventions are also recommended by the 2016 guidelines published by the Center for Disease Control and Prevention.¹⁷ More information on the similarities and differences among the various guidelines is available online.^18,19

Caveats with our study. Patients’ entry into the Taper or MPC groups occurred through self-selection rather than random assignment. Thus, caution is recommended in interpreting findings of the FP intervention. And, we did not measure patients’ levels of pain, so differences between groups may have been possible. In addition, the number of patients per group was relatively small, which may have accounted for the lack of significance in the MPC Group findings. Conversely, significant reductions in opioid use in the small tapering sample suggests a relatively robust intervention, despite a lack of random assignment to treatment conditions.

These findings suggest that FPs can have a frank conversation about opioid use with their patients based on ethical principles and evidence-based practice, and employ a tapering protocol consistent with current opioid treatment guidelines. Furthermore, this approach appears not to jeopardize the patient-physician relationship.

CORRESPONDENCE
Thomas P. Guck, PhD, Creighton University School of Medicine, 2412 Cuming Street, Omaha, NE 68131; [email protected].

ABSTRACT

Purpose Our study examined the efficacy of a primary-care intervention in reducing opioid use among patients who have chronic non-cancer pain (CNCP). We also recorded the intervention’s effect on patients’ decisions to leave (or stay) with the primary-care practice.

Methods A family physician (FP) identified 41 patients in his practice who had CNCP of at least 6 month’s duration and were using opioids. The intervention with each patient involved an initial discussion of ethical principles, evidence-based practice, and current published guidelines. Following the discussion, patients self-selected to participate with their FP in a continuing tapering program or to accept referral to a pain center for management of their opioid medications. Tapering ranged from a 10% reduction per week to a more rapid 25% to 50% reduction every few days. Twenty-seven patients continued tapering with their FP, and 6 months later were retrospectively placed in the Taper Group. Fourteen patients chose not to pursue the tapering option and were referred to a single-modality medical pain clinic (MPC). All patients had the option of staying with the FP for other medical care.

Results At baseline and again at 6 months post-initial intervention, the MPC Group was taking significantly higher daily doses of morphine equivalents than the Taper Group. The Taper Group at 6 months was taking significantly lower average daily narcotic doses in morphine equivalents than at baseline. No significant baseline-to-6 month differences were found in the MPC Group. Contrary to many physicians’ fear of losing patients following candid discussions about opioid use, 40 of the 41 patients continued with the FP for other health needs.

Conclusions FPs can frankly discuss opioid use with their patients based on ethical principles and evidence-based recommendations and employ a tapering protocol consistent with current opioid treatment guidelines without jeopardizing the patient-physician relationship.

[polldaddy:10180698]

Opioid prescriptions for chronic noncancer pain (CNCP) have increased significantly over the past 25 years in the United States.¹ Despite methodologic concerns surrounding research on opioid harms, prescription opioid misuse among CNCP patients is estimated to be 21% to 29% and prescription addiction 8% to 12%.² Tragically, with the overall increase in opioid use for CNCP, substance-related hospital admissions and deaths due to opioid overdose have also risen.³

Increased opioid use began in 1985 when the World Health Organization expanded its ethical mandate for pain relief in dying patients to include relief from all cancer pain.³ Opioid use then accelerated following Portenoy and Foley’s 1986 article⁴ and the 1997 consensus statement by the American Academy of Pain Medicine (AAPM) and the American Pain Society (APS),⁵ with both organizations arguing that opioids have a role in the treatment of CNCP. Increased use of opioids for CNCP continued throughout the 1990s and 2000s, as many states passed legislation removing sanctions on prescribing long-term and high-dose opioid therapy, and pharmaceutical companies aggressively marketed sustained-release opioids.³

A balanced approach to opioids. While acknowledging the serious public health problems of drug abuse, addiction, and diversion of opioids from licit to illicit uses, clinical research and regulation leaders have called for a balanced approach that recognizes the legitimate medical need for opioids for CNCP. In 2009 the APS, in partnership with the AAPM, published evidence-based guidelines on chronic opioid therapy (COT) for adults with CNCP.⁶ In developing these guidelines, a multidisciplinary panel of experts conducted systematic reviews of available evidence and made recommendations on formulating COT for individuals, initiating and titrating therapy, regularly monitoring patients, and managing opioid-related adverse effects. Additional recommendations addressed the use of therapies focusing on psychosocial factors. The APS-AAPM guidelines received the highest rating in a systematic review critically appraising 13 guidelines that address the use of opioids for CNCP.⁷

Continue to: When opioid use is prolonged...

When opioid use is prolonged. Most primary care physicians are aware of the risks of prolonged opioid use, and many have successfully tapered or discontinued opioid medications for patients in acute or pre-chronic stages of pain.⁸ However, many physicians face the challenge of patients who have used COT for a longer time. The APS-AAPM guidelines may help primary care physicians at any stage of treating CNCP patients.

METHODS

Purpose and design. This retrospective study, which reviewed pretest-posttest findings between and within study groups, received an exempt status from Creighton University’s institutional review board. We designed the study to determine the efficacy of an intervention protocol to reduce opioid use by patients with CNCP who had been in a family physician (FP)'s panel for quite some time. Furthermore, because a common fear among primary care providers is that raising concerns with patients about their opioid use may cause those patients to leave their panel,⁹ our study also recorded how many patients stayed with their FP after initiation of the opioid management protocol.

Subjects. This study tracked 41 patients with CNCP in 1 FP’s panel. Inclusion criteria for participation was: 1) presence of CNCP for at least 6 months, 2) current use of opioid medication for CNCP, 3) age of at least 16 years, and 4) ability to read and write English. Two exclusion criteria were the presence of a surgically correctable condition or an organic brain syndrome or psychosis.

Clinical intervention. The FP identified eligible patients in his practice that were taking opioids for CNCP and initiated a discussion with each of them emphasizing his desire to follow the ethical principles of beneficence, nonmaleficence, respect for autonomy, and justice.¹⁰ The FP also presented his reasons for wanting the patient to stop using opioid medication. They included his beliefs that:

1) COT was not safe for the patient based on a growing body of published evidence of harm and death from COT³;
2) long-term use of opioids could lead to misuse, abuse, or addiction²;
3) prolonged opioid use paradoxically increases pain sensitivity that does not resolve with discontinuation of opioid maintenance^11,12 (although pain tolerance does improve after opioid cessation); and
4) the patient’s current pain medications were not in line with published guidelines for use of opioids for CNCP.⁶

Initially, 45 patients were eligible for the study, but 4 declined participation before the intervention discussion and were immediately referred to a single-modality medical pain clinic (MPC). These patients were not included in subsequent analyses. Of the remaining 41 patients, all had a discussion with the MD about ethical principles, practice guidelines, and the importance of opioid tapering. After the discussion, patients decided whether to continue with the plan to taper their opioid therapy or to not taper their therapy and so receive a referral to an MPC.

Continue to: The 27 patients who chose to work with...

The 27 patients who chose to work with their FP started an individually tailored opioid-tapering program and were retrospectively placed in the Taper Group 6 months later. Tapering ranged from a slow 10% reduction in dosage per week to a more rapid 25% to 50% reduction every few days. Although evidence to guide specific recommendations on the rate of reduction is lacking, a slower rate may reduce unpleasant symptoms of opioid withdrawal.⁶ Following the patient-FP discussion, the 14 patients who chose not to pursue the tapering option were referred to an MPC for pain management, but could opt to remain with the FP for all other medical care. At 6 months post-discussion, we retrospectively assigned these 14 patients to the MPC Group.

Measures. We obtained demographic and medical information, including age, gender, race, marital status, and medication level in morphine equivalents, from the electronic health record. Medication level in morphine equivalents was recorded at the beginning of the intervention and again 6 months later. All analyses were conducted using SPSS Version 24 (IBM Corp, Armonk, NY) with P<.05 used to indicate statistical significance.

RESULTS

Between-group differences. The Taper and MPC groups did not differ significantly on demographic variables, with mean ages, respectively, at 57 and 51 years, sex 56% and 50% female, race 74% and 79% white, and marital status 48% and 50% married.

Patients who tapered opioid usage under FP guidance significantly reduced daily morphine equivalents over 6 months.

We found significant differences between the Taper and MPC groups on total daily dose in morphine equivalents at baseline and at 6 months following initial intervention. The Levene’s test for equality of variances was statistically significant, indicating unequal variances between the groups. In our SPSS analyses, we therefore used the option “equal variances not assumed.” TABLE 1 lists resultant means, standard deviations, individual sample t-test scores, and confidence intervals. The MPC Group was taking significantly higher daily doses of morphine equivalents than the Taper Group both at baseline and at 6 months following initial intervention.

Within-group differences. Paired sample t tests indicated significant differences between baseline and 6-month average daily narcotic doses in morphine equivalents for the Taper Group. No significant difference was found between baseline and 6-month daily morphine equivalents for the MPC group. These results indicated that patients who continued opioid tapering with the FP significantly reduced their daily morphine equivalents over the 6 months of the study. Patients in the MPC Group reduced morphine equivalents over the 6 months, but the reduction was not statistically significant. Paired sample t test results are presented in TABLE 2.

Continue to: Patient retention

Patient retention. All but one of the 41 patients in the Tapering and MPC groups continued with the FP for the remainder of their health care needs. Contrary to some physicians’ fears, the patients in this study maintained continuity with their FP.

DISCUSSION

Results of this study indicate that an intervention consisting of a physician-patient discussion of ethical principles and evidence-based practice, followed by individualized opioid tapering per published guidelines, led to a significant reduction in opioid use in patients with CNCP. The Taper Group, which completed the intervention, exhibited significant morphine reductions between baseline and 6-month follow-up. This did not hold true for the MPC Group.

The MPC Group, despite participating in the discussion with the FP, chose not to complete the tapering program and was referred to a single-modality MPC where opioids were managed rather than tapered. While the MPC group reduced daily opioid dose levels, the reduction was not statistically significant. A possible reason for no difference within the MPC Group may be that they had greater dependence on opioids, as their baseline average daily dose was much higher than that in the Taper Group (173 mg vs 31 mg, respectively). Although we did not assess anxiety directly, we speculate that the MPC Group was more anxious about opioid reduction than the Taper Group, and that this anxiety potentially led 4 patients to opt out of the initial FP discussion and 14 patients to self-select out of the tapering program following the discussion.

Of the 14 patients who opted not to participate with their FP in opioid tapering, 13 remained with him for all other care.

The FP intervention was successful for the Taper Group. For MPC patients, an enhanced intervention including behavior health strategies¹³ might have reduced anxiety and increased motivation¹⁴ to continue tapering. Based on moderate-quality evidence, APS-AAPM guidelines strongly recommend that CNCP be viewed as a complex biopsychosocial condition. Therefore, clinicians who prescribe opioids should routinely integrate psychotherapeutic interventions, functional restoration, interdisciplinary therapy, and other adjunctive nonopioid therapies.⁶

Opioid tapering within multidisciplinary rehabilitation programs is possible without significant worsening of pain, mood, and function.¹⁵ Recently, an outpatient opioid-tapering support intervention showed promise for efficacy in reducing prescription opioid doses without resultant increases in pain intensity or pain interference.¹⁶

Continue to: The tapering protocol in our study...

The tapering protocol in our study and the inclusion of behavioral health co-interventions are also recommended by the 2016 guidelines published by the Center for Disease Control and Prevention.¹⁷ More information on the similarities and differences among the various guidelines is available online.^18,19

Caveats with our study. Patients’ entry into the Taper or MPC groups occurred through self-selection rather than random assignment. Thus, caution is recommended in interpreting findings of the FP intervention. And, we did not measure patients’ levels of pain, so differences between groups may have been possible. In addition, the number of patients per group was relatively small, which may have accounted for the lack of significance in the MPC Group findings. Conversely, significant reductions in opioid use in the small tapering sample suggests a relatively robust intervention, despite a lack of random assignment to treatment conditions.

These findings suggest that FPs can have a frank conversation about opioid use with their patients based on ethical principles and evidence-based practice, and employ a tapering protocol consistent with current opioid treatment guidelines. Furthermore, this approach appears not to jeopardize the patient-physician relationship.

CORRESPONDENCE
Thomas P. Guck, PhD, Creighton University School of Medicine, 2412 Cuming Street, Omaha, NE 68131; [email protected].