ANSWER

The least likely diagnosis is staph infection (choice “b”). By their very nature, staph infections are suppurative, often involving redness, swelling, pain, and purulent drainage. They can be chronic (eg, MRSA) but are more typically of acute onset. And they usually resolve on their own or with treatment; recall that this patient was treated for staph infection many times without any change.

She was also treated repeatedly for scabies (choice “a”), a condition that could certainly last 15 years. However, the lack of improvement with treatment, combined with the absence of suggestive signs, make this diagnosis improbable.

Mycosis fungoides (MF; choice “c”) is a type of T-cell lymphoma that often develops with itching and plaque formation over the course of years. It was ultimately ruled out by the biopsy results (as were scabies and staph infection).

What the biopsy did show was epidermal thickening—a characteristic sign of prurigo nodularis (choice “d”).

DISCUSSION

Prurigo nodularis is a localized form of neurodermatitis caused by picking and scratching. As with the classic form, the more the patient scratches, the more the lesions itch and multiply. In this case, biopsy of the larger plaque showed hypertrophic scarring.

The patient’s skin-picking habit likely developed during (and perhaps because of) her methamphetamine use. Long-term exposure to the itch-scratch-itch cycle can make treatment problematic. In this case, a class 4 topical steroid cream was prescribed, along with injection of several larger lesions with 10 mg/mL triamcinolone suspension.

It’s worth mentioning that for patients with this type of history, general lab testing (ie, complete blood count and complete metabolic panel) should be performed to rule out organic disease and other serious conditions (eg, renal or hepatic failure, leukemia). Fortunately, this patient’s results were reassuring on that front.

ANSWER

The least likely diagnosis is staph infection (choice “b”). By their very nature, staph infections are suppurative, often involving redness, swelling, pain, and purulent drainage. They can be chronic (eg, MRSA) but are more typically of acute onset. And they usually resolve on their own or with treatment; recall that this patient was treated for staph infection many times without any change.

She was also treated repeatedly for scabies (choice “a”), a condition that could certainly last 15 years. However, the lack of improvement with treatment, combined with the absence of suggestive signs, make this diagnosis improbable.

Mycosis fungoides (MF; choice “c”) is a type of T-cell lymphoma that often develops with itching and plaque formation over the course of years. It was ultimately ruled out by the biopsy results (as were scabies and staph infection).

What the biopsy did show was epidermal thickening—a characteristic sign of prurigo nodularis (choice “d”).

DISCUSSION

Prurigo nodularis is a localized form of neurodermatitis caused by picking and scratching. As with the classic form, the more the patient scratches, the more the lesions itch and multiply. In this case, biopsy of the larger plaque showed hypertrophic scarring.

The patient’s skin-picking habit likely developed during (and perhaps because of) her methamphetamine use. Long-term exposure to the itch-scratch-itch cycle can make treatment problematic. In this case, a class 4 topical steroid cream was prescribed, along with injection of several larger lesions with 10 mg/mL triamcinolone suspension.

It’s worth mentioning that for patients with this type of history, general lab testing (ie, complete blood count and complete metabolic panel) should be performed to rule out organic disease and other serious conditions (eg, renal or hepatic failure, leukemia). Fortunately, this patient’s results were reassuring on that front.

ANSWER

The least likely diagnosis is staph infection (choice “b”). By their very nature, staph infections are suppurative, often involving redness, swelling, pain, and purulent drainage. They can be chronic (eg, MRSA) but are more typically of acute onset. And they usually resolve on their own or with treatment; recall that this patient was treated for staph infection many times without any change.

She was also treated repeatedly for scabies (choice “a”), a condition that could certainly last 15 years. However, the lack of improvement with treatment, combined with the absence of suggestive signs, make this diagnosis improbable.

Mycosis fungoides (MF; choice “c”) is a type of T-cell lymphoma that often develops with itching and plaque formation over the course of years. It was ultimately ruled out by the biopsy results (as were scabies and staph infection).

What the biopsy did show was epidermal thickening—a characteristic sign of prurigo nodularis (choice “d”).

DISCUSSION

Prurigo nodularis is a localized form of neurodermatitis caused by picking and scratching. As with the classic form, the more the patient scratches, the more the lesions itch and multiply. In this case, biopsy of the larger plaque showed hypertrophic scarring.

The patient’s skin-picking habit likely developed during (and perhaps because of) her methamphetamine use. Long-term exposure to the itch-scratch-itch cycle can make treatment problematic. In this case, a class 4 topical steroid cream was prescribed, along with injection of several larger lesions with 10 mg/mL triamcinolone suspension.

It’s worth mentioning that for patients with this type of history, general lab testing (ie, complete blood count and complete metabolic panel) should be performed to rule out organic disease and other serious conditions (eg, renal or hepatic failure, leukemia). Fortunately, this patient’s results were reassuring on that front.

GlaxoSmithKline asked the Food and Drug Administration to approve an interleuklin-5 antagonist as an add-on maintenance therapy for patients with eosinophilic chronic obstructive pulmonary disease (COPD).

The pharmaceutical and health care company is seeking approval of mepolizumab to be used specifically to treat COPD patients with an eosinophilic phenotype. The drug currently is indicated to treat patients aged 12 years or older with severe asthma and asthma with an eosinophilic phenotype and is sold under the name Nucala, according to a GlaxoSmithKline statement issued November 7.

[email protected]

GlaxoSmithKline asked the Food and Drug Administration to approve an interleuklin-5 antagonist as an add-on maintenance therapy for patients with eosinophilic chronic obstructive pulmonary disease (COPD).

The pharmaceutical and health care company is seeking approval of mepolizumab to be used specifically to treat COPD patients with an eosinophilic phenotype. The drug currently is indicated to treat patients aged 12 years or older with severe asthma and asthma with an eosinophilic phenotype and is sold under the name Nucala, according to a GlaxoSmithKline statement issued November 7.

[email protected]

GlaxoSmithKline asked the Food and Drug Administration to approve an interleuklin-5 antagonist as an add-on maintenance therapy for patients with eosinophilic chronic obstructive pulmonary disease (COPD).

The pharmaceutical and health care company is seeking approval of mepolizumab to be used specifically to treat COPD patients with an eosinophilic phenotype. The drug currently is indicated to treat patients aged 12 years or older with severe asthma and asthma with an eosinophilic phenotype and is sold under the name Nucala, according to a GlaxoSmithKline statement issued November 7.

[email protected]

Critically ill patients who received transfusions of the freshest-available red cells had a mortality rate similar to that of patients who received standard-issue, oldest-available red cells, according to results from a large randomized trial.

In some earlier studies, transfusion of older red cells was linked to increased mortality for critically ill, surgical, and trauma patients. But the new results provide “strong evidence” that transfusing very fresh red cells rather than older red cells “provides no clinically meaningful benefits” in the critically ill population, reported D. James Cooper, MD, of Monash University, Melbourne, and his colleagues.

“Our results support the current international usual practice of transfusing patients with the oldest red cells available,” the researchers wrote in the report on the trial, known as TRANSFUSE (Standard Issue Transfusion versus Fresher Red-Cell Use in Intensive Care).

Red cells are stored up to 42 days and can undergo biochemical, structural, or metabolic changes during that time that “may cause harm,” the researchers wrote. However, blood banks typically issue the oldest compatible red cell units available to them, and it’s uncertain whether doing so increases mortality.

To see if the age of red cells impacted mortality, Dr. Cooper and has colleagues at 59 centers in five countries randomized 4,994 critically ill adults to receive the freshest-available or standard oldest-available red cells (N Engl J Med. 2017;377:1858-67).

At 90 days after transfusion, mortality was 24.8% in the group of patients receiving the freshest-available red cells, and 24.1% for the oldest-available group, or an absolute risk difference of just 0.7 percentage points (95% confidence interval, –1.7 to 3.1; P = .57).

“Among the many secondary outcomes tested, we noted a nominal difference in febrile nonhemolytic transfusion reactions that was small, and we are not sure of its clinical significance,” the researchers wrote.

The average duration of red cell storage was 11.8 days versus 22.4 days for the freshest-available and oldest-available groups, respectively.

The TRANSFUSE trial is not the first to suggest that age of red blood cells does not make a difference in mortality after transfusion. There were two earlier trials, ABLE (Age of Blood Evaluation) and INFORM (Informing Fresh versus Old Red Cell Management) that came to similar conclusions. However, the ABLE trial had a small sample size, and INFORM had “limited outcome data” including a low mortality rate “suggesting low illness severity,” the researchers noted.

“The lower in-hospital mortality in the ICU subgroup in the INFORM trial (13.0%) than that observed in our trial at 90 days (24.5%) is consistent with lower illness severity in the INFORM patients,” they wrote.

The study was funded by organizations including the Australian National Health and Medical Research Council. Dr. Cooper reported receiving consulting fees from Eustralis Pharmaceuticals that were paid to Monash University. No other potential conflicts of interest were reported.
 

Critically ill patients who received transfusions of the freshest-available red cells had a mortality rate similar to that of patients who received standard-issue, oldest-available red cells, according to results from a large randomized trial.

In some earlier studies, transfusion of older red cells was linked to increased mortality for critically ill, surgical, and trauma patients. But the new results provide “strong evidence” that transfusing very fresh red cells rather than older red cells “provides no clinically meaningful benefits” in the critically ill population, reported D. James Cooper, MD, of Monash University, Melbourne, and his colleagues.

“Our results support the current international usual practice of transfusing patients with the oldest red cells available,” the researchers wrote in the report on the trial, known as TRANSFUSE (Standard Issue Transfusion versus Fresher Red-Cell Use in Intensive Care).

Red cells are stored up to 42 days and can undergo biochemical, structural, or metabolic changes during that time that “may cause harm,” the researchers wrote. However, blood banks typically issue the oldest compatible red cell units available to them, and it’s uncertain whether doing so increases mortality.

To see if the age of red cells impacted mortality, Dr. Cooper and has colleagues at 59 centers in five countries randomized 4,994 critically ill adults to receive the freshest-available or standard oldest-available red cells (N Engl J Med. 2017;377:1858-67).

At 90 days after transfusion, mortality was 24.8% in the group of patients receiving the freshest-available red cells, and 24.1% for the oldest-available group, or an absolute risk difference of just 0.7 percentage points (95% confidence interval, –1.7 to 3.1; P = .57).

“Among the many secondary outcomes tested, we noted a nominal difference in febrile nonhemolytic transfusion reactions that was small, and we are not sure of its clinical significance,” the researchers wrote.

The average duration of red cell storage was 11.8 days versus 22.4 days for the freshest-available and oldest-available groups, respectively.

The TRANSFUSE trial is not the first to suggest that age of red blood cells does not make a difference in mortality after transfusion. There were two earlier trials, ABLE (Age of Blood Evaluation) and INFORM (Informing Fresh versus Old Red Cell Management) that came to similar conclusions. However, the ABLE trial had a small sample size, and INFORM had “limited outcome data” including a low mortality rate “suggesting low illness severity,” the researchers noted.

“The lower in-hospital mortality in the ICU subgroup in the INFORM trial (13.0%) than that observed in our trial at 90 days (24.5%) is consistent with lower illness severity in the INFORM patients,” they wrote.

The study was funded by organizations including the Australian National Health and Medical Research Council. Dr. Cooper reported receiving consulting fees from Eustralis Pharmaceuticals that were paid to Monash University. No other potential conflicts of interest were reported.
 

Critically ill patients who received transfusions of the freshest-available red cells had a mortality rate similar to that of patients who received standard-issue, oldest-available red cells, according to results from a large randomized trial.

In some earlier studies, transfusion of older red cells was linked to increased mortality for critically ill, surgical, and trauma patients. But the new results provide “strong evidence” that transfusing very fresh red cells rather than older red cells “provides no clinically meaningful benefits” in the critically ill population, reported D. James Cooper, MD, of Monash University, Melbourne, and his colleagues.

“Our results support the current international usual practice of transfusing patients with the oldest red cells available,” the researchers wrote in the report on the trial, known as TRANSFUSE (Standard Issue Transfusion versus Fresher Red-Cell Use in Intensive Care).

Red cells are stored up to 42 days and can undergo biochemical, structural, or metabolic changes during that time that “may cause harm,” the researchers wrote. However, blood banks typically issue the oldest compatible red cell units available to them, and it’s uncertain whether doing so increases mortality.

To see if the age of red cells impacted mortality, Dr. Cooper and has colleagues at 59 centers in five countries randomized 4,994 critically ill adults to receive the freshest-available or standard oldest-available red cells (N Engl J Med. 2017;377:1858-67).

At 90 days after transfusion, mortality was 24.8% in the group of patients receiving the freshest-available red cells, and 24.1% for the oldest-available group, or an absolute risk difference of just 0.7 percentage points (95% confidence interval, –1.7 to 3.1; P = .57).

“Among the many secondary outcomes tested, we noted a nominal difference in febrile nonhemolytic transfusion reactions that was small, and we are not sure of its clinical significance,” the researchers wrote.

The average duration of red cell storage was 11.8 days versus 22.4 days for the freshest-available and oldest-available groups, respectively.

The TRANSFUSE trial is not the first to suggest that age of red blood cells does not make a difference in mortality after transfusion. There were two earlier trials, ABLE (Age of Blood Evaluation) and INFORM (Informing Fresh versus Old Red Cell Management) that came to similar conclusions. However, the ABLE trial had a small sample size, and INFORM had “limited outcome data” including a low mortality rate “suggesting low illness severity,” the researchers noted.

“The lower in-hospital mortality in the ICU subgroup in the INFORM trial (13.0%) than that observed in our trial at 90 days (24.5%) is consistent with lower illness severity in the INFORM patients,” they wrote.

The study was funded by organizations including the Australian National Health and Medical Research Council. Dr. Cooper reported receiving consulting fees from Eustralis Pharmaceuticals that were paid to Monash University. No other potential conflicts of interest were reported.
 

Women who stop adjuvant endocrine therapy after 5 years are still at substantial risk of distant recurrence over the next 15 years, even if their tumors were small, according to results of a recent meta-analysis of 88 clinical trials.

For women with T1N0 disease, the annual rate of distant recurrence was approximately 1% each year during 5-20 years, resulting in a cumulative risk of distant recurrence of 13%, authors of the meta-analysis reported (N Engl J Med. 2017 Nov. 8. doi: 10.1056/NEJMoa1701830).

Tumor diameter and nodal status was associated with the risk of distant recurrence during the later years and was approximately additive, with the risk increasing from 13% for T1N0 to 41% for T2N4–9 disease, wrote investigator Hongchao Pan, PhD, of the Nuffield Department of Population Health, University of Oxford, England, and his coauthors.

“Recognition of the magnitude of the long-term risks of ER-positive disease can help women and their health care professionals decide whether to extend therapy beyond 5 years and whether to persist if adverse events occur,” the authors wrote in the report.

The meta-analysis by Dr. Pan and his colleagues included 62,923 women with ER-positive breast cancer who were free of disease after 5 years of scheduled endocrine therapy.

They had hoped to identify a subgroup of women with a recurrence risks so small that the risk of additional side effects caused by extending endocrine therapy would outweigh any potential benefits of that additional treatment. However, the finding of measurable risk even in the women with T1N0 disease led them to recommend that extending endocrine therapy at least be considered for all patients.

“An absolute reduction of a few percentage points in the risk of distant metastases over the next 15 years might well be possible even for such low-risk women, with correspondingly greater absolute benefits for women with larger tumors or node-positive disease,” they wrote.

Whether reducing risk translates into improved survival remains to be seen.

As of now, “reliable trial evidence is not yet available” to confirm the clinical benefit of extending endocrine therapy beyond 5 years, the authors noted.

Cancer Research UK and others funded the study. Senior author Daniel F. Hayes, MD, reported grant support from Eli Lilly, Janssen Research & Development, Veridex, Puma, Pfizer, and AstraZeneca, among other disclosures. Full disclosures for all authors were provided on the NEJM website.

Women who stop adjuvant endocrine therapy after 5 years are still at substantial risk of distant recurrence over the next 15 years, even if their tumors were small, according to results of a recent meta-analysis of 88 clinical trials.

For women with T1N0 disease, the annual rate of distant recurrence was approximately 1% each year during 5-20 years, resulting in a cumulative risk of distant recurrence of 13%, authors of the meta-analysis reported (N Engl J Med. 2017 Nov. 8. doi: 10.1056/NEJMoa1701830).

Tumor diameter and nodal status was associated with the risk of distant recurrence during the later years and was approximately additive, with the risk increasing from 13% for T1N0 to 41% for T2N4–9 disease, wrote investigator Hongchao Pan, PhD, of the Nuffield Department of Population Health, University of Oxford, England, and his coauthors.

“Recognition of the magnitude of the long-term risks of ER-positive disease can help women and their health care professionals decide whether to extend therapy beyond 5 years and whether to persist if adverse events occur,” the authors wrote in the report.

The meta-analysis by Dr. Pan and his colleagues included 62,923 women with ER-positive breast cancer who were free of disease after 5 years of scheduled endocrine therapy.

They had hoped to identify a subgroup of women with a recurrence risks so small that the risk of additional side effects caused by extending endocrine therapy would outweigh any potential benefits of that additional treatment. However, the finding of measurable risk even in the women with T1N0 disease led them to recommend that extending endocrine therapy at least be considered for all patients.

“An absolute reduction of a few percentage points in the risk of distant metastases over the next 15 years might well be possible even for such low-risk women, with correspondingly greater absolute benefits for women with larger tumors or node-positive disease,” they wrote.

Whether reducing risk translates into improved survival remains to be seen.

As of now, “reliable trial evidence is not yet available” to confirm the clinical benefit of extending endocrine therapy beyond 5 years, the authors noted.

Cancer Research UK and others funded the study. Senior author Daniel F. Hayes, MD, reported grant support from Eli Lilly, Janssen Research & Development, Veridex, Puma, Pfizer, and AstraZeneca, among other disclosures. Full disclosures for all authors were provided on the NEJM website.

Women who stop adjuvant endocrine therapy after 5 years are still at substantial risk of distant recurrence over the next 15 years, even if their tumors were small, according to results of a recent meta-analysis of 88 clinical trials.

For women with T1N0 disease, the annual rate of distant recurrence was approximately 1% each year during 5-20 years, resulting in a cumulative risk of distant recurrence of 13%, authors of the meta-analysis reported (N Engl J Med. 2017 Nov. 8. doi: 10.1056/NEJMoa1701830).

Tumor diameter and nodal status was associated with the risk of distant recurrence during the later years and was approximately additive, with the risk increasing from 13% for T1N0 to 41% for T2N4–9 disease, wrote investigator Hongchao Pan, PhD, of the Nuffield Department of Population Health, University of Oxford, England, and his coauthors.

“Recognition of the magnitude of the long-term risks of ER-positive disease can help women and their health care professionals decide whether to extend therapy beyond 5 years and whether to persist if adverse events occur,” the authors wrote in the report.

The meta-analysis by Dr. Pan and his colleagues included 62,923 women with ER-positive breast cancer who were free of disease after 5 years of scheduled endocrine therapy.

They had hoped to identify a subgroup of women with a recurrence risks so small that the risk of additional side effects caused by extending endocrine therapy would outweigh any potential benefits of that additional treatment. However, the finding of measurable risk even in the women with T1N0 disease led them to recommend that extending endocrine therapy at least be considered for all patients.

“An absolute reduction of a few percentage points in the risk of distant metastases over the next 15 years might well be possible even for such low-risk women, with correspondingly greater absolute benefits for women with larger tumors or node-positive disease,” they wrote.

Whether reducing risk translates into improved survival remains to be seen.

As of now, “reliable trial evidence is not yet available” to confirm the clinical benefit of extending endocrine therapy beyond 5 years, the authors noted.

Cancer Research UK and others funded the study. Senior author Daniel F. Hayes, MD, reported grant support from Eli Lilly, Janssen Research & Development, Veridex, Puma, Pfizer, and AstraZeneca, among other disclosures. Full disclosures for all authors were provided on the NEJM website.

In antitumor immunity and immunotherapy, quality and fitness count.

Specifically, the quality and fitness of neoantigens – tumor-specific mutated peptides on the surface of cancer cells – can influence a patient’s response to immune checkpoint inhibitors, and mathematical models of neoantigen fitness can serve as biomarkers for response to immunotherapy, according to investigators of two separate but related studies published in Nature.

In one study, Marta Łuksza, PhD, from the Simons Center for Systems Biology at the Institute for Advanced Study in Princeton, N.J., and colleagues propose a neoantigen fitness model that can predict tumor response to checkpoint blockade immunotherapy.

“Our model predicts survival in anti-CTLA4–treated melanoma patients and anti-PD-1–treated lung cancer patients. Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies,” they wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24473).

In a related study, Vinod P. Balachandran, MD, from the David M. Rubinstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York and colleagues, including Dr. Łuksza and others, looked at T-cell antigens in long-term survivors of pancreatic cancer and identified specific neoantigens as T-cell targets.

“More broadly, we identify neoantigen quality as a biomarker for immunogenic tumors that may guide the application of immunotherapies,” Dr. Balachandran and colleagues wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24462).
 

Proof of concept

The studies provide a proof of concept that mathematical modeling of tumor evolution and the interactions of tumors with the immune system may soon provide clinicians with valuable and actionable information about responses to immunotherapy, Benjamin Greenbaum, PhD, senior author on the study by Łuksza et al., and a coauthor on the pancreatic cancer study said in an interview.

“We’re trying to come up with measures that take into account what we think the underlying processes are and what lies behind therapy response, and that should lead to better predictive models associated with response in the future,” said Dr. Greenbaum, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Medical Center, New York.

One of the key findings of the studies is that neoantigen quality – the ability of neoantigens to spark T-cell recognition – seems to be as or more important than neoantigen quantity for influencing immune responses during tumor evolution.

“The general logic behind the idea that mutational burden can be a good predictor of response is that the more mutations you have, the more likely that you have a neoantigen, a peptide generated by a tumor mutation, that elicits productive T-cell recognition. We tried to model that process that might lead to productive T-cell recognition, to assign a kind of number to every neoantigen to provide some estimate of how likely it was to undergo a productive process,” Dr. Greenbaum explained.
 

Melanoma and lung cancer survivors

In the study by Łuksza et al., the investigators created a mathematical fitness model that can predict how tumors respond to immunotherapy based on how neoantigens interact with the immune system and applied the model to data on three previously reported patient cohorts, including two groups of patients with malignant melanoma treated with a cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint such as ipilimumab (Yervoy), and one group of patients with non–small cell lung cancer treated with a programmed death-1 (PD-1) inhibitor (for example, nivolumab [Opdivo]).

They found that their proposed model is more accurate than genomic biomarkers for predicting how a specific tumor may respond to immunotherapy.

“Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies. By using an immune fitness model to study immunotherapy, we reveal broad similarities between the evolution of tumors and rapidly evolving pathogens,” they wrote.
 

Pancreatic cancer survivors

Fewer than 7% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) survive more than 5 years, despite the best surgical and medical therapy. But a few lucky patients are long-term survivors, and Dr. Balachandran and associates sought to examine what aspects of T-cell immunity contributed to their longevity.

Rather than relying on genomic analysis of tumor samples, however, they used a combination of genetic, immunohistochemical, and transcriptional immunoprofiling, as well as computational biophysics and function to identify T-cell antigens in the long-term survivors.

When they compared surgically resected patients matched by tumor stage, they found that tumors from those with a median overall survival (OS) of 6 years had a 3-fold greater density of CD8-positive T cells and a 12-fold greater density of cytolytic CD8-positive cells, as well as more mature dendritic cells, regulatory T cells, and macrophages, but decreased numbers of CD4-positive T cells, compared with patients with a more typical course of survival (median OS, 0.8 years). There were no differences between long- and short-term survivors in either B cells or major histocompatibility complex (MHC) class I–positive cells.

They then performed whole-exome sequencing on tumor samples to determine the frequency of neoantigens and found a median of 38 predicted neoantigens per tumor.

“Notably, patients with both the highest predicted neoantigen number and either the greatest CD3+, CD8+, or polyclonal T-cell repertoire, but neither alone, exhibited the longest survival,” they wrote.

When they looked for qualities of neoantigens responsible for promoting T-cell activation in the long-term survivors, they found that the tumors from the survivors, compared with others, were enriched in neoantigen qualities that could be described by a mathematical fitness model.

“Our results provide insight into the heterogeneous immunobiology of PDAC, a presumed poorly immunogenic and checkpoint blockade–refractory tumor, demonstrating that neoantigens may be T-cell targets in [long-term survivors]”, they wrote.

The investigators propose that immunity to neoantigens that are generated during the outgrowth of a primary tumor could at least partially explain the lower incidence of relapse and prolonged survival of a small minority of patients with pancreatic cancer.

“Our findings support the development of strategies to harness neoantigen-specific immunity to treat checkpoint blockade–refractory cancers, and the identification of immunogenic hot spots for directed neoantigen targeting,” they concluded.

The studies were supported by grants from Stand Up to Cancer, American Cancer Society, National Science Foundation, Lustgarten Foundation, Janssen Research & Development, the STARR Cancer Consortium, the Pershing Square Sohn Cancer Research Alliance, the National Institutes of Health, the V Foundation, Swim Across America, Ludwig Institute for Cancer Research, the Parker Institute for Cancer Immunotherapy, a National Cancer Institute Career Development Award, and a Memorial Sloan Kettering Cancer Center core grant. Dr. Łuksza and Dr. Greenbaum disclosed consulting for Merck. Dr. Balachandran disclosed research funding from Bristol-Myers Squibb.

In antitumor immunity and immunotherapy, quality and fitness count.

Specifically, the quality and fitness of neoantigens – tumor-specific mutated peptides on the surface of cancer cells – can influence a patient’s response to immune checkpoint inhibitors, and mathematical models of neoantigen fitness can serve as biomarkers for response to immunotherapy, according to investigators of two separate but related studies published in Nature.

In one study, Marta Łuksza, PhD, from the Simons Center for Systems Biology at the Institute for Advanced Study in Princeton, N.J., and colleagues propose a neoantigen fitness model that can predict tumor response to checkpoint blockade immunotherapy.

“Our model predicts survival in anti-CTLA4–treated melanoma patients and anti-PD-1–treated lung cancer patients. Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies,” they wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24473).

In a related study, Vinod P. Balachandran, MD, from the David M. Rubinstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York and colleagues, including Dr. Łuksza and others, looked at T-cell antigens in long-term survivors of pancreatic cancer and identified specific neoantigens as T-cell targets.

“More broadly, we identify neoantigen quality as a biomarker for immunogenic tumors that may guide the application of immunotherapies,” Dr. Balachandran and colleagues wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24462).
 

Proof of concept

The studies provide a proof of concept that mathematical modeling of tumor evolution and the interactions of tumors with the immune system may soon provide clinicians with valuable and actionable information about responses to immunotherapy, Benjamin Greenbaum, PhD, senior author on the study by Łuksza et al., and a coauthor on the pancreatic cancer study said in an interview.

“We’re trying to come up with measures that take into account what we think the underlying processes are and what lies behind therapy response, and that should lead to better predictive models associated with response in the future,” said Dr. Greenbaum, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Medical Center, New York.

One of the key findings of the studies is that neoantigen quality – the ability of neoantigens to spark T-cell recognition – seems to be as or more important than neoantigen quantity for influencing immune responses during tumor evolution.

“The general logic behind the idea that mutational burden can be a good predictor of response is that the more mutations you have, the more likely that you have a neoantigen, a peptide generated by a tumor mutation, that elicits productive T-cell recognition. We tried to model that process that might lead to productive T-cell recognition, to assign a kind of number to every neoantigen to provide some estimate of how likely it was to undergo a productive process,” Dr. Greenbaum explained.
 

Melanoma and lung cancer survivors

In the study by Łuksza et al., the investigators created a mathematical fitness model that can predict how tumors respond to immunotherapy based on how neoantigens interact with the immune system and applied the model to data on three previously reported patient cohorts, including two groups of patients with malignant melanoma treated with a cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint such as ipilimumab (Yervoy), and one group of patients with non–small cell lung cancer treated with a programmed death-1 (PD-1) inhibitor (for example, nivolumab [Opdivo]).

They found that their proposed model is more accurate than genomic biomarkers for predicting how a specific tumor may respond to immunotherapy.

“Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies. By using an immune fitness model to study immunotherapy, we reveal broad similarities between the evolution of tumors and rapidly evolving pathogens,” they wrote.
 

Pancreatic cancer survivors

Fewer than 7% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) survive more than 5 years, despite the best surgical and medical therapy. But a few lucky patients are long-term survivors, and Dr. Balachandran and associates sought to examine what aspects of T-cell immunity contributed to their longevity.

Rather than relying on genomic analysis of tumor samples, however, they used a combination of genetic, immunohistochemical, and transcriptional immunoprofiling, as well as computational biophysics and function to identify T-cell antigens in the long-term survivors.

When they compared surgically resected patients matched by tumor stage, they found that tumors from those with a median overall survival (OS) of 6 years had a 3-fold greater density of CD8-positive T cells and a 12-fold greater density of cytolytic CD8-positive cells, as well as more mature dendritic cells, regulatory T cells, and macrophages, but decreased numbers of CD4-positive T cells, compared with patients with a more typical course of survival (median OS, 0.8 years). There were no differences between long- and short-term survivors in either B cells or major histocompatibility complex (MHC) class I–positive cells.

They then performed whole-exome sequencing on tumor samples to determine the frequency of neoantigens and found a median of 38 predicted neoantigens per tumor.

“Notably, patients with both the highest predicted neoantigen number and either the greatest CD3+, CD8+, or polyclonal T-cell repertoire, but neither alone, exhibited the longest survival,” they wrote.

When they looked for qualities of neoantigens responsible for promoting T-cell activation in the long-term survivors, they found that the tumors from the survivors, compared with others, were enriched in neoantigen qualities that could be described by a mathematical fitness model.

“Our results provide insight into the heterogeneous immunobiology of PDAC, a presumed poorly immunogenic and checkpoint blockade–refractory tumor, demonstrating that neoantigens may be T-cell targets in [long-term survivors]”, they wrote.

The investigators propose that immunity to neoantigens that are generated during the outgrowth of a primary tumor could at least partially explain the lower incidence of relapse and prolonged survival of a small minority of patients with pancreatic cancer.

“Our findings support the development of strategies to harness neoantigen-specific immunity to treat checkpoint blockade–refractory cancers, and the identification of immunogenic hot spots for directed neoantigen targeting,” they concluded.

The studies were supported by grants from Stand Up to Cancer, American Cancer Society, National Science Foundation, Lustgarten Foundation, Janssen Research & Development, the STARR Cancer Consortium, the Pershing Square Sohn Cancer Research Alliance, the National Institutes of Health, the V Foundation, Swim Across America, Ludwig Institute for Cancer Research, the Parker Institute for Cancer Immunotherapy, a National Cancer Institute Career Development Award, and a Memorial Sloan Kettering Cancer Center core grant. Dr. Łuksza and Dr. Greenbaum disclosed consulting for Merck. Dr. Balachandran disclosed research funding from Bristol-Myers Squibb.

In antitumor immunity and immunotherapy, quality and fitness count.

Specifically, the quality and fitness of neoantigens – tumor-specific mutated peptides on the surface of cancer cells – can influence a patient’s response to immune checkpoint inhibitors, and mathematical models of neoantigen fitness can serve as biomarkers for response to immunotherapy, according to investigators of two separate but related studies published in Nature.

In one study, Marta Łuksza, PhD, from the Simons Center for Systems Biology at the Institute for Advanced Study in Princeton, N.J., and colleagues propose a neoantigen fitness model that can predict tumor response to checkpoint blockade immunotherapy.

“Our model predicts survival in anti-CTLA4–treated melanoma patients and anti-PD-1–treated lung cancer patients. Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies,” they wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24473).

In a related study, Vinod P. Balachandran, MD, from the David M. Rubinstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York and colleagues, including Dr. Łuksza and others, looked at T-cell antigens in long-term survivors of pancreatic cancer and identified specific neoantigens as T-cell targets.

“More broadly, we identify neoantigen quality as a biomarker for immunogenic tumors that may guide the application of immunotherapies,” Dr. Balachandran and colleagues wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24462).
 

Proof of concept

The studies provide a proof of concept that mathematical modeling of tumor evolution and the interactions of tumors with the immune system may soon provide clinicians with valuable and actionable information about responses to immunotherapy, Benjamin Greenbaum, PhD, senior author on the study by Łuksza et al., and a coauthor on the pancreatic cancer study said in an interview.

“We’re trying to come up with measures that take into account what we think the underlying processes are and what lies behind therapy response, and that should lead to better predictive models associated with response in the future,” said Dr. Greenbaum, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Medical Center, New York.

One of the key findings of the studies is that neoantigen quality – the ability of neoantigens to spark T-cell recognition – seems to be as or more important than neoantigen quantity for influencing immune responses during tumor evolution.

“The general logic behind the idea that mutational burden can be a good predictor of response is that the more mutations you have, the more likely that you have a neoantigen, a peptide generated by a tumor mutation, that elicits productive T-cell recognition. We tried to model that process that might lead to productive T-cell recognition, to assign a kind of number to every neoantigen to provide some estimate of how likely it was to undergo a productive process,” Dr. Greenbaum explained.
 

Melanoma and lung cancer survivors

In the study by Łuksza et al., the investigators created a mathematical fitness model that can predict how tumors respond to immunotherapy based on how neoantigens interact with the immune system and applied the model to data on three previously reported patient cohorts, including two groups of patients with malignant melanoma treated with a cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint such as ipilimumab (Yervoy), and one group of patients with non–small cell lung cancer treated with a programmed death-1 (PD-1) inhibitor (for example, nivolumab [Opdivo]).

They found that their proposed model is more accurate than genomic biomarkers for predicting how a specific tumor may respond to immunotherapy.

“Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies. By using an immune fitness model to study immunotherapy, we reveal broad similarities between the evolution of tumors and rapidly evolving pathogens,” they wrote.
 

Pancreatic cancer survivors

Fewer than 7% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) survive more than 5 years, despite the best surgical and medical therapy. But a few lucky patients are long-term survivors, and Dr. Balachandran and associates sought to examine what aspects of T-cell immunity contributed to their longevity.

Rather than relying on genomic analysis of tumor samples, however, they used a combination of genetic, immunohistochemical, and transcriptional immunoprofiling, as well as computational biophysics and function to identify T-cell antigens in the long-term survivors.

When they compared surgically resected patients matched by tumor stage, they found that tumors from those with a median overall survival (OS) of 6 years had a 3-fold greater density of CD8-positive T cells and a 12-fold greater density of cytolytic CD8-positive cells, as well as more mature dendritic cells, regulatory T cells, and macrophages, but decreased numbers of CD4-positive T cells, compared with patients with a more typical course of survival (median OS, 0.8 years). There were no differences between long- and short-term survivors in either B cells or major histocompatibility complex (MHC) class I–positive cells.

They then performed whole-exome sequencing on tumor samples to determine the frequency of neoantigens and found a median of 38 predicted neoantigens per tumor.

“Notably, patients with both the highest predicted neoantigen number and either the greatest CD3+, CD8+, or polyclonal T-cell repertoire, but neither alone, exhibited the longest survival,” they wrote.

When they looked for qualities of neoantigens responsible for promoting T-cell activation in the long-term survivors, they found that the tumors from the survivors, compared with others, were enriched in neoantigen qualities that could be described by a mathematical fitness model.

“Our results provide insight into the heterogeneous immunobiology of PDAC, a presumed poorly immunogenic and checkpoint blockade–refractory tumor, demonstrating that neoantigens may be T-cell targets in [long-term survivors]”, they wrote.

The investigators propose that immunity to neoantigens that are generated during the outgrowth of a primary tumor could at least partially explain the lower incidence of relapse and prolonged survival of a small minority of patients with pancreatic cancer.

“Our findings support the development of strategies to harness neoantigen-specific immunity to treat checkpoint blockade–refractory cancers, and the identification of immunogenic hot spots for directed neoantigen targeting,” they concluded.

The studies were supported by grants from Stand Up to Cancer, American Cancer Society, National Science Foundation, Lustgarten Foundation, Janssen Research & Development, the STARR Cancer Consortium, the Pershing Square Sohn Cancer Research Alliance, the National Institutes of Health, the V Foundation, Swim Across America, Ludwig Institute for Cancer Research, the Parker Institute for Cancer Immunotherapy, a National Cancer Institute Career Development Award, and a Memorial Sloan Kettering Cancer Center core grant. Dr. Łuksza and Dr. Greenbaum disclosed consulting for Merck. Dr. Balachandran disclosed research funding from Bristol-Myers Squibb.

The American Congress of Obstetricians and Gynecologists held its State Legislative Roundtable in late October in Arlington, Va., with ob.gyns. and their lobbyists from 46 states. This is the largest number of states ever represented at the roundtable event, and it reflects the increased participation and engagement in policy making by women’s health care providers.

Dr. Bohon is an ob.gyn. in private practice in Washington. She is an ACOG state legislative chair from the District of Columbia and a member of the Ob.Gyn. News Editorial Advisory Board. She reported having no relevant financial disclosures.

The American Congress of Obstetricians and Gynecologists held its State Legislative Roundtable in late October in Arlington, Va., with ob.gyns. and their lobbyists from 46 states. This is the largest number of states ever represented at the roundtable event, and it reflects the increased participation and engagement in policy making by women’s health care providers.

Dr. Bohon is an ob.gyn. in private practice in Washington. She is an ACOG state legislative chair from the District of Columbia and a member of the Ob.Gyn. News Editorial Advisory Board. She reported having no relevant financial disclosures.

The American Congress of Obstetricians and Gynecologists held its State Legislative Roundtable in late October in Arlington, Va., with ob.gyns. and their lobbyists from 46 states. This is the largest number of states ever represented at the roundtable event, and it reflects the increased participation and engagement in policy making by women’s health care providers.

Dr. Bohon is an ob.gyn. in private practice in Washington. She is an ACOG state legislative chair from the District of Columbia and a member of the Ob.Gyn. News Editorial Advisory Board. She reported having no relevant financial disclosures.

LAS VEGAS – When treating patients with psoriasis, “it is very important for us to treat the entire patient,” and consider the comorbidities, including depression, associated with psoriasis, Jeffrey M. Sobell, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Depression can be a particular concern for younger patients with more severe psoriasis, said Dr. Sobell of Tufts University, Boston.

When he sees patients aged 18-35 years with significant psoriasis in his practice, he has made it a habit to ask them about depression “and if they’ve ever had thoughts of hurting themselves,” and arranges for mental health follow-up visits for patients about whom he is concerned. “It’s something that’s hard to talk about, but so important,” he said.

Dr. Sobell disclosed relationships with multiple companies including AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, Sanofi, and Sun Pharma.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – When treating patients with psoriasis, “it is very important for us to treat the entire patient,” and consider the comorbidities, including depression, associated with psoriasis, Jeffrey M. Sobell, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Depression can be a particular concern for younger patients with more severe psoriasis, said Dr. Sobell of Tufts University, Boston.

When he sees patients aged 18-35 years with significant psoriasis in his practice, he has made it a habit to ask them about depression “and if they’ve ever had thoughts of hurting themselves,” and arranges for mental health follow-up visits for patients about whom he is concerned. “It’s something that’s hard to talk about, but so important,” he said.

Dr. Sobell disclosed relationships with multiple companies including AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, Sanofi, and Sun Pharma.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – When treating patients with psoriasis, “it is very important for us to treat the entire patient,” and consider the comorbidities, including depression, associated with psoriasis, Jeffrey M. Sobell, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Depression can be a particular concern for younger patients with more severe psoriasis, said Dr. Sobell of Tufts University, Boston.

When he sees patients aged 18-35 years with significant psoriasis in his practice, he has made it a habit to ask them about depression “and if they’ve ever had thoughts of hurting themselves,” and arranges for mental health follow-up visits for patients about whom he is concerned. “It’s something that’s hard to talk about, but so important,” he said.

Dr. Sobell disclosed relationships with multiple companies including AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, Regeneron, Sanofi, and Sun Pharma.

SDEF and this news organization are owned by the same parent company.

TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.

Debra L. Beck/Frontline Medical News

TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.

Debra L. Beck/Frontline Medical News

TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.

Debra L. Beck/Frontline Medical News

Patients who undergo interhospital transfer (IHT) are felt to benefit from receipt of unique specialty care at the receiving hospital.¹ Although only 1.5% of all hospitalized Medicare patients undergo hospital transfer,² the frequency of transfer is much greater within certain patient populations, as may be expected with diagnoses requiring specialty care.^3,4 Existent data demonstrate that 5% of Medicare patients admitted to the intensive care unit (ICU)⁵ and up to 50% of patients presenting with acute myocardial infarction (AMI) undergo IHT.⁶

More recent data suggest variability in hospital transfer practices not accounted for by differences in patient or hospital characteristics.² Although disease-specific guidelines for IHT exist for certain diagnoses,^3,4 the process remains largely nonstandardized for many patients,⁷ leading to ambiguity surrounding indications for transfer. Because limited data suggest worse outcomes for transferred versus nontransferred patients,⁸ a better understanding of the specialized care patients actually receive across the transfer continuum may help to elucidate potential indications for transfer and ultimately help delineate which patients are most (or least) likely to benefit from transfer and why.

In this national study, we examined a select cohort of transferred patients with diagnoses associated with specific specialty procedural services to determine if they received these procedures and where along the transfer continuum they were performed.

We performed a cross-sectional analysis using the Center for Medicare and Medicaid Services 2013 100% Master Beneficiary Summary and Inpatient claims files. Our study protocol was approved by the Partners Healthcare Human Subjects Review Committee.

Beneficiaries were eligible for inclusion if they were aged ≥65 years, continuously enrolled in Medicare A and B, and with an acute care hospitalization claim in 2013, excluding Medicare managed care and end stage renal disease beneficiaries due to incomplete claims data in these groups. We additionally excluded beneficiaries hospitalized at federal or nonacute care hospitals, or critical access hospitals given their mission to stabilize and then transfer patients to referral hospitals.⁹

Transferred patients were defined as beneficiaries with corresponding “transfer in” and “transfer out” claims, or those with either claim and a corresponding date of admission/discharge from another hospital within 1 day of the claim, as we used in our prior research.² Beneficiaries transferred to the same hospital, those with greater than 1 transfer within the same hospitalization, or those cared for at hospitals with “outlier” transfer-in rates equal to 100% or transfer-out rates greater than 35% were excluded from analysis given the suggestion of nonstandard claims practices.

We first identified the top 15 primary diagnoses at time of transfer using International Classification of Diseases, Ninth Revision (ICD-9) codes (supplementary Appendix), and then identified those 4 most likely to require specialty procedural services: AMI, gastrointestinal bleed (GI bleed), renal failure, and hip fracture/dislocation. We then chose associated ICD-9 procedure codes for each diagnosis, via expert opinion (authors SM and JS, hospitalist physicians with greater than 20 years of combined clinical experience), erring on overinclusion of procedure codes. We then quantified receipt of associated procedures at transferring and receiving hospitals, stratified by diagnosis.

We further explored the cohort of patients with hip fracture/dislocation who underwent an associated procedure at the transferring but not receiving hospital, examining the frequency with which these patients had other (nonrelated) procedures at the receiving hospital, and identifying which procedures they received.

Of the 101,507 patients transferred to another hospital, 19,613 (19.3%) had a primary diagnosis of AMI, GI bleed, renal failure, or hip fracture/dislocation. Table 1 lists the ICD-9 procedure codes associated with each diagnosis.

Distribution of receipt of specialty procedures at the transferring and receiving hospitals varied by disease (Figure). With the exception of GI bleed, patients more often received specialty procedural care at the receiving than the transferring hospital. Depending on primary diagnosis, between 32.4% and 89.1% of patients did not receive any associated specialty procedure at the receiving hospital.

Of the 370 (22.1%) hip fracture/dislocation patients that received a specialty procedure at the transferring but not receiving hospital, 132 (35.7%) did not receive any procedure at the receiving hospital, whereas the remaining 238 (64.3%) received an unrelated (not associated with the primary diagnosis) procedure. There was great variety in the types of procedures received, the most common being transfusion of blood products (ICD-9 Clinical Modification 9904).

Among transferred patients with primary diagnoses that have clearly associated specialized procedural services, we found that patients received these procedures at varying frequency and locations across the transfer continuum. Across 4 diagnoses, receipt of associated procedures was more common at the receiving than the transferring hospital, with the exception being patients with GI bleed. We additionally found that many transferred patients did not receive any associated specialty procedure at the receiving hospital. These findings suggest the strong likelihood of more diverse underlying reasons for transfer rather than solely receipt of specialized procedural care.

Despite the frequency with which AMI patients are transferred,⁶ and American Heart Association guidelines directing hospitals to transfer AMI patients to institutions able to provide necessary invasive treatments,⁴ prior studies suggest these patients inconsistently receive specialty intervention following transfer, including stress testing, cardiac catheterization, or coronary artery bypass graft surgery.^10,11 Our findings add to these data, demonstrating that only 47.3% of patients transferred with AMI received any cardiac-related procedure at the receiving hospital. Additionally, we found that 38.1% of AMI patients do not receive any specialty procedures at either the transferring or the receiving hospital. Taken together, these data suggest possible discrepancies in the perceived need for these procedures between transferring and receiving hospitals, reasons for transfer related to these conditions that don’t involve an associated procedure, or reasons for transfer unrelated to specialty care of the primary diagnosis (such as care of comorbidities, hospital location, prior relationships with that hospital, or desire for a second opinion). Although some of these alternate reasons for transfer likely still benefit the patient, some of these reasons may not justify the increased risks of discontinuity of care created by IHT.

Given limited data looking at IHT practices for patients with other diagnoses, the varying patterns of specialty procedural interventions we observed among transferred patients with GI bleed, renal failure, and hip fracture/dislocation are novel contributions to this topic. Notably, we found that among patients transferred with a primary diagnosis of renal failure, the vast majority (84.1%) did not receive any associated procedure at either the transferring or the receiving hospital. It is possible that although these patients carried the diagnosis of renal failure, their clinical phenotype is more heterogeneous, and they could still be managed conservatively without receipt of invasive procedures such as hemodialysis.

Conversely, patients transferred with primary diagnosis of hip fracture/dislocation were far more likely to receive associated specialty procedural intervention at the receiving hospital, presumably reflective of the evidence demonstrating improved outcomes with early surgical intervention.¹² However, these data do not explain the reasoning behind the substantial minority of patients who received specialty intervention at the transferring hospital prior to transfer or those that did not receive any specialty intervention at either the transferring or receiving hospital. Our secondary analysis demonstrating great variety in receipt and type of nonassociated procedures provided at the receiving hospital did not help to elucidate potential underlying reasons for transfer.

Notably, among patients transferred with primary diagnosis of GI bleed, receipt of specialty procedures was more common at the transferring (77.7%) than receiving (63.2%) hospital, with nearly half (49.3%) undergoing specialty procedures at both hospitals. It is possible that these findings are reflective of the broad array of specialty procedures examined within this diagnosis. For example, it is reasonable to consider that a patient may be stabilized with receipt of a blood transfusion at the transferring hospital, then transferred to undergo a diagnostic/therapeutic procedure (ie, endoscopy/colonoscopy) at the receiving hospital, as is suggested by our results.

Our study is subject to several limitations. First, given the criteria we used to define transfer, it is possible that we included nontransferred patients within our transferred cohort if they were discharged from one hospital and admitted to a different hospital within 1 day, although quality assurance analyses we conducted in prior studies on these data support the validity of the criteria used.² Second, we cannot exclude the possibility that patients received nonprocedural specialty care (ie, expert opinion, specialized imaging, medical management, management of secondary diagnoses, etc.) not available at the transferring hospital, although, arguably, in select patients, such input could be obtained without physical transfer of the patient (ie, tele-consult). And even in patients transferred with intent to receive procedural care who did not ultimately receive that care, there is likely an appropriate “nonprocedure” rate, where patients who might benefit from a procedure receive a timely evaluation to reduce the risk of missing the opportunity to receive it. This would be analogous to transferring a patient to an ICU even if they do not end up requiring intubation or pressor therapy. However, given the likelihood of higher risks of IHT compared with intrahospital transfers, one could argue that the threshold of perceived benefit might be different in patients being considered for IHT. Additionally, we limited our analyses to only 4 diagnoses; thus, our findings may not be generalizable to other diagnoses of transferred patients. However, because the diagnoses we examined were ones considered most effectively treated with specialty procedural interventions, it is reasonable to presume that the variability in receipt of specialty procedures observed within these diagnoses is also present, if not greater, across other diagnoses. Third, although we intentionally included a broad array of specialty procedures associated with each diagnosis, it is possible that we overlooked particular specialty interventions. For example, in assuming that patients are most likely to be transferred to receive procedural services associated with their primary diagnosis, we may have missed alternate indications for transfer, including need for procedural care related to secondary or subsequent diagnoses (ie, a patient may have presented with GI bleed in the context of profound anemia that requires a bone marrow biopsy for diagnosis, and thus was transferred for the biopsy). Our further examination of unrelated procedures received by hip fracture/dislocation patients at receiving hospitals argues against a select or subset of procedures driving transfers that are not associated with the primary diagnosis but does not fully rule out this possibility (ie, if there are a large variety of secondary diagnoses with distinct associated specialty procedures that are required for each). Lastly, although our examination provides novel information regarding variability in receipt of specialty procedures of transferred patients, we were not able to identify exact reasons for transfer. Instead, our results are hypothesis generating and require further investigation to better understand these reasons.

We found that Medicare patients who undergo IHT with primary diagnoses of AMI, GI bleed, renal failure, and hip fracture/dislocation receive associated specialty interventions at varying frequency and locations, and many patients do not receive any associated procedures at receiving hospitals. Our findings suggest that specialty procedural care of patients, even those with primary diagnoses that often warrant specialized intervention, may not be the primary driver of IHT as commonly suggested, although underlying reasons for transfer in these and other “nonprocedural” transferred patients remains obscure. Given known ambiguity in the transfer process,⁷ and unclear benefit of IHT,⁸ additional research is required to further identify and evaluate other potential underlying reasons for transfer and to examine these in the context of patient outcomes, in order to understand which patients may or may not benefit from transfer and why.

Disclosure

The authors have nothing to disclose.

Patients who undergo interhospital transfer (IHT) are felt to benefit from receipt of unique specialty care at the receiving hospital.¹ Although only 1.5% of all hospitalized Medicare patients undergo hospital transfer,² the frequency of transfer is much greater within certain patient populations, as may be expected with diagnoses requiring specialty care.^3,4 Existent data demonstrate that 5% of Medicare patients admitted to the intensive care unit (ICU)⁵ and up to 50% of patients presenting with acute myocardial infarction (AMI) undergo IHT.⁶

More recent data suggest variability in hospital transfer practices not accounted for by differences in patient or hospital characteristics.² Although disease-specific guidelines for IHT exist for certain diagnoses,^3,4 the process remains largely nonstandardized for many patients,⁷ leading to ambiguity surrounding indications for transfer. Because limited data suggest worse outcomes for transferred versus nontransferred patients,⁸ a better understanding of the specialized care patients actually receive across the transfer continuum may help to elucidate potential indications for transfer and ultimately help delineate which patients are most (or least) likely to benefit from transfer and why.

In this national study, we examined a select cohort of transferred patients with diagnoses associated with specific specialty procedural services to determine if they received these procedures and where along the transfer continuum they were performed.

We performed a cross-sectional analysis using the Center for Medicare and Medicaid Services 2013 100% Master Beneficiary Summary and Inpatient claims files. Our study protocol was approved by the Partners Healthcare Human Subjects Review Committee.

Beneficiaries were eligible for inclusion if they were aged ≥65 years, continuously enrolled in Medicare A and B, and with an acute care hospitalization claim in 2013, excluding Medicare managed care and end stage renal disease beneficiaries due to incomplete claims data in these groups. We additionally excluded beneficiaries hospitalized at federal or nonacute care hospitals, or critical access hospitals given their mission to stabilize and then transfer patients to referral hospitals.⁹

Transferred patients were defined as beneficiaries with corresponding “transfer in” and “transfer out” claims, or those with either claim and a corresponding date of admission/discharge from another hospital within 1 day of the claim, as we used in our prior research.² Beneficiaries transferred to the same hospital, those with greater than 1 transfer within the same hospitalization, or those cared for at hospitals with “outlier” transfer-in rates equal to 100% or transfer-out rates greater than 35% were excluded from analysis given the suggestion of nonstandard claims practices.

We first identified the top 15 primary diagnoses at time of transfer using International Classification of Diseases, Ninth Revision (ICD-9) codes (supplementary Appendix), and then identified those 4 most likely to require specialty procedural services: AMI, gastrointestinal bleed (GI bleed), renal failure, and hip fracture/dislocation. We then chose associated ICD-9 procedure codes for each diagnosis, via expert opinion (authors SM and JS, hospitalist physicians with greater than 20 years of combined clinical experience), erring on overinclusion of procedure codes. We then quantified receipt of associated procedures at transferring and receiving hospitals, stratified by diagnosis.

We further explored the cohort of patients with hip fracture/dislocation who underwent an associated procedure at the transferring but not receiving hospital, examining the frequency with which these patients had other (nonrelated) procedures at the receiving hospital, and identifying which procedures they received.

Of the 101,507 patients transferred to another hospital, 19,613 (19.3%) had a primary diagnosis of AMI, GI bleed, renal failure, or hip fracture/dislocation. Table 1 lists the ICD-9 procedure codes associated with each diagnosis.

Distribution of receipt of specialty procedures at the transferring and receiving hospitals varied by disease (Figure). With the exception of GI bleed, patients more often received specialty procedural care at the receiving than the transferring hospital. Depending on primary diagnosis, between 32.4% and 89.1% of patients did not receive any associated specialty procedure at the receiving hospital.

Of the 370 (22.1%) hip fracture/dislocation patients that received a specialty procedure at the transferring but not receiving hospital, 132 (35.7%) did not receive any procedure at the receiving hospital, whereas the remaining 238 (64.3%) received an unrelated (not associated with the primary diagnosis) procedure. There was great variety in the types of procedures received, the most common being transfusion of blood products (ICD-9 Clinical Modification 9904).

Among transferred patients with primary diagnoses that have clearly associated specialized procedural services, we found that patients received these procedures at varying frequency and locations across the transfer continuum. Across 4 diagnoses, receipt of associated procedures was more common at the receiving than the transferring hospital, with the exception being patients with GI bleed. We additionally found that many transferred patients did not receive any associated specialty procedure at the receiving hospital. These findings suggest the strong likelihood of more diverse underlying reasons for transfer rather than solely receipt of specialized procedural care.

Despite the frequency with which AMI patients are transferred,⁶ and American Heart Association guidelines directing hospitals to transfer AMI patients to institutions able to provide necessary invasive treatments,⁴ prior studies suggest these patients inconsistently receive specialty intervention following transfer, including stress testing, cardiac catheterization, or coronary artery bypass graft surgery.^10,11 Our findings add to these data, demonstrating that only 47.3% of patients transferred with AMI received any cardiac-related procedure at the receiving hospital. Additionally, we found that 38.1% of AMI patients do not receive any specialty procedures at either the transferring or the receiving hospital. Taken together, these data suggest possible discrepancies in the perceived need for these procedures between transferring and receiving hospitals, reasons for transfer related to these conditions that don’t involve an associated procedure, or reasons for transfer unrelated to specialty care of the primary diagnosis (such as care of comorbidities, hospital location, prior relationships with that hospital, or desire for a second opinion). Although some of these alternate reasons for transfer likely still benefit the patient, some of these reasons may not justify the increased risks of discontinuity of care created by IHT.

Given limited data looking at IHT practices for patients with other diagnoses, the varying patterns of specialty procedural interventions we observed among transferred patients with GI bleed, renal failure, and hip fracture/dislocation are novel contributions to this topic. Notably, we found that among patients transferred with a primary diagnosis of renal failure, the vast majority (84.1%) did not receive any associated procedure at either the transferring or the receiving hospital. It is possible that although these patients carried the diagnosis of renal failure, their clinical phenotype is more heterogeneous, and they could still be managed conservatively without receipt of invasive procedures such as hemodialysis.

Conversely, patients transferred with primary diagnosis of hip fracture/dislocation were far more likely to receive associated specialty procedural intervention at the receiving hospital, presumably reflective of the evidence demonstrating improved outcomes with early surgical intervention.¹² However, these data do not explain the reasoning behind the substantial minority of patients who received specialty intervention at the transferring hospital prior to transfer or those that did not receive any specialty intervention at either the transferring or receiving hospital. Our secondary analysis demonstrating great variety in receipt and type of nonassociated procedures provided at the receiving hospital did not help to elucidate potential underlying reasons for transfer.

Notably, among patients transferred with primary diagnosis of GI bleed, receipt of specialty procedures was more common at the transferring (77.7%) than receiving (63.2%) hospital, with nearly half (49.3%) undergoing specialty procedures at both hospitals. It is possible that these findings are reflective of the broad array of specialty procedures examined within this diagnosis. For example, it is reasonable to consider that a patient may be stabilized with receipt of a blood transfusion at the transferring hospital, then transferred to undergo a diagnostic/therapeutic procedure (ie, endoscopy/colonoscopy) at the receiving hospital, as is suggested by our results.

Our study is subject to several limitations. First, given the criteria we used to define transfer, it is possible that we included nontransferred patients within our transferred cohort if they were discharged from one hospital and admitted to a different hospital within 1 day, although quality assurance analyses we conducted in prior studies on these data support the validity of the criteria used.² Second, we cannot exclude the possibility that patients received nonprocedural specialty care (ie, expert opinion, specialized imaging, medical management, management of secondary diagnoses, etc.) not available at the transferring hospital, although, arguably, in select patients, such input could be obtained without physical transfer of the patient (ie, tele-consult). And even in patients transferred with intent to receive procedural care who did not ultimately receive that care, there is likely an appropriate “nonprocedure” rate, where patients who might benefit from a procedure receive a timely evaluation to reduce the risk of missing the opportunity to receive it. This would be analogous to transferring a patient to an ICU even if they do not end up requiring intubation or pressor therapy. However, given the likelihood of higher risks of IHT compared with intrahospital transfers, one could argue that the threshold of perceived benefit might be different in patients being considered for IHT. Additionally, we limited our analyses to only 4 diagnoses; thus, our findings may not be generalizable to other diagnoses of transferred patients. However, because the diagnoses we examined were ones considered most effectively treated with specialty procedural interventions, it is reasonable to presume that the variability in receipt of specialty procedures observed within these diagnoses is also present, if not greater, across other diagnoses. Third, although we intentionally included a broad array of specialty procedures associated with each diagnosis, it is possible that we overlooked particular specialty interventions. For example, in assuming that patients are most likely to be transferred to receive procedural services associated with their primary diagnosis, we may have missed alternate indications for transfer, including need for procedural care related to secondary or subsequent diagnoses (ie, a patient may have presented with GI bleed in the context of profound anemia that requires a bone marrow biopsy for diagnosis, and thus was transferred for the biopsy). Our further examination of unrelated procedures received by hip fracture/dislocation patients at receiving hospitals argues against a select or subset of procedures driving transfers that are not associated with the primary diagnosis but does not fully rule out this possibility (ie, if there are a large variety of secondary diagnoses with distinct associated specialty procedures that are required for each). Lastly, although our examination provides novel information regarding variability in receipt of specialty procedures of transferred patients, we were not able to identify exact reasons for transfer. Instead, our results are hypothesis generating and require further investigation to better understand these reasons.

We found that Medicare patients who undergo IHT with primary diagnoses of AMI, GI bleed, renal failure, and hip fracture/dislocation receive associated specialty interventions at varying frequency and locations, and many patients do not receive any associated procedures at receiving hospitals. Our findings suggest that specialty procedural care of patients, even those with primary diagnoses that often warrant specialized intervention, may not be the primary driver of IHT as commonly suggested, although underlying reasons for transfer in these and other “nonprocedural” transferred patients remains obscure. Given known ambiguity in the transfer process,⁷ and unclear benefit of IHT,⁸ additional research is required to further identify and evaluate other potential underlying reasons for transfer and to examine these in the context of patient outcomes, in order to understand which patients may or may not benefit from transfer and why.

Disclosure

The authors have nothing to disclose.

Patients who undergo interhospital transfer (IHT) are felt to benefit from receipt of unique specialty care at the receiving hospital.¹ Although only 1.5% of all hospitalized Medicare patients undergo hospital transfer,² the frequency of transfer is much greater within certain patient populations, as may be expected with diagnoses requiring specialty care.^3,4 Existent data demonstrate that 5% of Medicare patients admitted to the intensive care unit (ICU)⁵ and up to 50% of patients presenting with acute myocardial infarction (AMI) undergo IHT.⁶

More recent data suggest variability in hospital transfer practices not accounted for by differences in patient or hospital characteristics.² Although disease-specific guidelines for IHT exist for certain diagnoses,^3,4 the process remains largely nonstandardized for many patients,⁷ leading to ambiguity surrounding indications for transfer. Because limited data suggest worse outcomes for transferred versus nontransferred patients,⁸ a better understanding of the specialized care patients actually receive across the transfer continuum may help to elucidate potential indications for transfer and ultimately help delineate which patients are most (or least) likely to benefit from transfer and why.

In this national study, we examined a select cohort of transferred patients with diagnoses associated with specific specialty procedural services to determine if they received these procedures and where along the transfer continuum they were performed.

We performed a cross-sectional analysis using the Center for Medicare and Medicaid Services 2013 100% Master Beneficiary Summary and Inpatient claims files. Our study protocol was approved by the Partners Healthcare Human Subjects Review Committee.

Beneficiaries were eligible for inclusion if they were aged ≥65 years, continuously enrolled in Medicare A and B, and with an acute care hospitalization claim in 2013, excluding Medicare managed care and end stage renal disease beneficiaries due to incomplete claims data in these groups. We additionally excluded beneficiaries hospitalized at federal or nonacute care hospitals, or critical access hospitals given their mission to stabilize and then transfer patients to referral hospitals.⁹

Transferred patients were defined as beneficiaries with corresponding “transfer in” and “transfer out” claims, or those with either claim and a corresponding date of admission/discharge from another hospital within 1 day of the claim, as we used in our prior research.² Beneficiaries transferred to the same hospital, those with greater than 1 transfer within the same hospitalization, or those cared for at hospitals with “outlier” transfer-in rates equal to 100% or transfer-out rates greater than 35% were excluded from analysis given the suggestion of nonstandard claims practices.

We first identified the top 15 primary diagnoses at time of transfer using International Classification of Diseases, Ninth Revision (ICD-9) codes (supplementary Appendix), and then identified those 4 most likely to require specialty procedural services: AMI, gastrointestinal bleed (GI bleed), renal failure, and hip fracture/dislocation. We then chose associated ICD-9 procedure codes for each diagnosis, via expert opinion (authors SM and JS, hospitalist physicians with greater than 20 years of combined clinical experience), erring on overinclusion of procedure codes. We then quantified receipt of associated procedures at transferring and receiving hospitals, stratified by diagnosis.

We further explored the cohort of patients with hip fracture/dislocation who underwent an associated procedure at the transferring but not receiving hospital, examining the frequency with which these patients had other (nonrelated) procedures at the receiving hospital, and identifying which procedures they received.

Of the 101,507 patients transferred to another hospital, 19,613 (19.3%) had a primary diagnosis of AMI, GI bleed, renal failure, or hip fracture/dislocation. Table 1 lists the ICD-9 procedure codes associated with each diagnosis.

Distribution of receipt of specialty procedures at the transferring and receiving hospitals varied by disease (Figure). With the exception of GI bleed, patients more often received specialty procedural care at the receiving than the transferring hospital. Depending on primary diagnosis, between 32.4% and 89.1% of patients did not receive any associated specialty procedure at the receiving hospital.

Of the 370 (22.1%) hip fracture/dislocation patients that received a specialty procedure at the transferring but not receiving hospital, 132 (35.7%) did not receive any procedure at the receiving hospital, whereas the remaining 238 (64.3%) received an unrelated (not associated with the primary diagnosis) procedure. There was great variety in the types of procedures received, the most common being transfusion of blood products (ICD-9 Clinical Modification 9904).

Among transferred patients with primary diagnoses that have clearly associated specialized procedural services, we found that patients received these procedures at varying frequency and locations across the transfer continuum. Across 4 diagnoses, receipt of associated procedures was more common at the receiving than the transferring hospital, with the exception being patients with GI bleed. We additionally found that many transferred patients did not receive any associated specialty procedure at the receiving hospital. These findings suggest the strong likelihood of more diverse underlying reasons for transfer rather than solely receipt of specialized procedural care.

Despite the frequency with which AMI patients are transferred,⁶ and American Heart Association guidelines directing hospitals to transfer AMI patients to institutions able to provide necessary invasive treatments,⁴ prior studies suggest these patients inconsistently receive specialty intervention following transfer, including stress testing, cardiac catheterization, or coronary artery bypass graft surgery.^10,11 Our findings add to these data, demonstrating that only 47.3% of patients transferred with AMI received any cardiac-related procedure at the receiving hospital. Additionally, we found that 38.1% of AMI patients do not receive any specialty procedures at either the transferring or the receiving hospital. Taken together, these data suggest possible discrepancies in the perceived need for these procedures between transferring and receiving hospitals, reasons for transfer related to these conditions that don’t involve an associated procedure, or reasons for transfer unrelated to specialty care of the primary diagnosis (such as care of comorbidities, hospital location, prior relationships with that hospital, or desire for a second opinion). Although some of these alternate reasons for transfer likely still benefit the patient, some of these reasons may not justify the increased risks of discontinuity of care created by IHT.

Given limited data looking at IHT practices for patients with other diagnoses, the varying patterns of specialty procedural interventions we observed among transferred patients with GI bleed, renal failure, and hip fracture/dislocation are novel contributions to this topic. Notably, we found that among patients transferred with a primary diagnosis of renal failure, the vast majority (84.1%) did not receive any associated procedure at either the transferring or the receiving hospital. It is possible that although these patients carried the diagnosis of renal failure, their clinical phenotype is more heterogeneous, and they could still be managed conservatively without receipt of invasive procedures such as hemodialysis.

Conversely, patients transferred with primary diagnosis of hip fracture/dislocation were far more likely to receive associated specialty procedural intervention at the receiving hospital, presumably reflective of the evidence demonstrating improved outcomes with early surgical intervention.¹² However, these data do not explain the reasoning behind the substantial minority of patients who received specialty intervention at the transferring hospital prior to transfer or those that did not receive any specialty intervention at either the transferring or receiving hospital. Our secondary analysis demonstrating great variety in receipt and type of nonassociated procedures provided at the receiving hospital did not help to elucidate potential underlying reasons for transfer.

Notably, among patients transferred with primary diagnosis of GI bleed, receipt of specialty procedures was more common at the transferring (77.7%) than receiving (63.2%) hospital, with nearly half (49.3%) undergoing specialty procedures at both hospitals. It is possible that these findings are reflective of the broad array of specialty procedures examined within this diagnosis. For example, it is reasonable to consider that a patient may be stabilized with receipt of a blood transfusion at the transferring hospital, then transferred to undergo a diagnostic/therapeutic procedure (ie, endoscopy/colonoscopy) at the receiving hospital, as is suggested by our results.

Our study is subject to several limitations. First, given the criteria we used to define transfer, it is possible that we included nontransferred patients within our transferred cohort if they were discharged from one hospital and admitted to a different hospital within 1 day, although quality assurance analyses we conducted in prior studies on these data support the validity of the criteria used.² Second, we cannot exclude the possibility that patients received nonprocedural specialty care (ie, expert opinion, specialized imaging, medical management, management of secondary diagnoses, etc.) not available at the transferring hospital, although, arguably, in select patients, such input could be obtained without physical transfer of the patient (ie, tele-consult). And even in patients transferred with intent to receive procedural care who did not ultimately receive that care, there is likely an appropriate “nonprocedure” rate, where patients who might benefit from a procedure receive a timely evaluation to reduce the risk of missing the opportunity to receive it. This would be analogous to transferring a patient to an ICU even if they do not end up requiring intubation or pressor therapy. However, given the likelihood of higher risks of IHT compared with intrahospital transfers, one could argue that the threshold of perceived benefit might be different in patients being considered for IHT. Additionally, we limited our analyses to only 4 diagnoses; thus, our findings may not be generalizable to other diagnoses of transferred patients. However, because the diagnoses we examined were ones considered most effectively treated with specialty procedural interventions, it is reasonable to presume that the variability in receipt of specialty procedures observed within these diagnoses is also present, if not greater, across other diagnoses. Third, although we intentionally included a broad array of specialty procedures associated with each diagnosis, it is possible that we overlooked particular specialty interventions. For example, in assuming that patients are most likely to be transferred to receive procedural services associated with their primary diagnosis, we may have missed alternate indications for transfer, including need for procedural care related to secondary or subsequent diagnoses (ie, a patient may have presented with GI bleed in the context of profound anemia that requires a bone marrow biopsy for diagnosis, and thus was transferred for the biopsy). Our further examination of unrelated procedures received by hip fracture/dislocation patients at receiving hospitals argues against a select or subset of procedures driving transfers that are not associated with the primary diagnosis but does not fully rule out this possibility (ie, if there are a large variety of secondary diagnoses with distinct associated specialty procedures that are required for each). Lastly, although our examination provides novel information regarding variability in receipt of specialty procedures of transferred patients, we were not able to identify exact reasons for transfer. Instead, our results are hypothesis generating and require further investigation to better understand these reasons.

We found that Medicare patients who undergo IHT with primary diagnoses of AMI, GI bleed, renal failure, and hip fracture/dislocation receive associated specialty interventions at varying frequency and locations, and many patients do not receive any associated procedures at receiving hospitals. Our findings suggest that specialty procedural care of patients, even those with primary diagnoses that often warrant specialized intervention, may not be the primary driver of IHT as commonly suggested, although underlying reasons for transfer in these and other “nonprocedural” transferred patients remains obscure. Given known ambiguity in the transfer process,⁷ and unclear benefit of IHT,⁸ additional research is required to further identify and evaluate other potential underlying reasons for transfer and to examine these in the context of patient outcomes, in order to understand which patients may or may not benefit from transfer and why.

Disclosure

The authors have nothing to disclose.

As the hospitalist’s role in medicine grows, the transition of care from inpatient to primary care providers (PCPs, including primary care physicians, nurse practitioners, or physician assistants), becomes increasingly important. Inadequate communication at this transition is associated with preventable adverse events leading to rehospitalization, disability, and death.^1-3 While professional societies recommend PCPs be notified at every care transition, the specific timing and modality of this communication is not well defined.⁴

Providing PCPs access to the inpatient electronic health record (EHR) may reduce the need for active communication. However, a recent survey of PCPs in the general internal medicine division of an academic hospital found a strong preference for additional communication with inpatient providers, despite a shared EHR.⁵

We examined communication preferences of general internal medicine PCPs at a different academic institution and extended our study to include community-based PCPs who were both affiliated and unaffiliated with the institution.

METHODS

Between October 2015 and June 2016, we surveyed PCPs from 3 practice groups with institutional affiliation or proximity to The Johns Hopkins Hospital: all general internal medicine faculty with outpatient practices (“academic,” 2 practice sites, n = 35), all community-based PCPs affiliated with the health system (“community,” 36 practice sites, n = 220), and all PCPs from an unaffiliated managed care organization (“unaffiliated,” 5 practice sites ranging from 0.3 to 4 miles from The Johns Hopkins Hospital, n = 29).

All groups have work-sponsored e-mail services. At the time of the survey, both the academic and community groups used an EHR that allowed access to inpatient laboratory and radiology data and discharge summaries. The unaffiliated group used paper health records. The hospital faxes discharge summaries to all PCPs who are identified by patients.

The investigators and representatives from each practice group collaborated to develop 15 questions with mutually exclusive answers to evaluate PCP experiences with and preferences for communication with inpatient teams. The survey was constructed and administered through Qualtrics’ online platform (Qualtrics, Provo, UT) and distributed via e-mail. The study was reviewed and acknowledged by the Johns Hopkins institutional review board as quality improvement activity.

The survey contained branching logic. Only respondents who indicated preference for communication received questions regarding preferred mode of communication. We used the preferred mode of communication for initial contact from the inpatient team in our analysis. χ² and Fischer’s exact tests were performed with JMP 12 software (SAS Institute Inc, Cary, NC).

RESULTS

Fourteen (40%) academic, 43 (14%) community, and 16 (55%) unaffiliated PCPs completed the survey, for 73 total responses from 284 surveys distributed (26%).

Among the 73 responding PCPs, 31 (42%) reported receiving notification of admission during “every” or “almost every” hospitalization, with no significant variation across practice groups (P = 0.5).

Across all groups, 64 PCPs (88%) preferred communication at 1 or more points during hospitalizations (panel A of Figure). “Both upon admission and prior to discharge” was selected most frequently, and there were no differences between practice groups (P = 0.2).

DISCUSSION

Our findings add to previous evidence of low rates of communication between inpatient providers and PCPs⁶ and a preference from PCPs for communication during hospitalizations despite shared EHRs.⁵ We extend previous work by demonstrating that PCP preferences for mode of communication vary by practice setting. Our findings lead us to hypothesize that identifying and incorporating PCP preferences may improve communication, though at the potential expense of standardization and efficiency.

There may be several reasons for the differing communication preferences observed. Most academic PCPs are located near or have admitting privileges to the hospital and are not in clinic full time. Their preference for the telephone may thus result from interpersonal relationships born from proximity and greater availability for telephone calls, or reduced fluency with the EHR compared to full-time community clinicians.

The unaffiliated group’s preference for fax may reflect a desire for communication that integrates easily with paper charts and is least disruptive to workflow, or concerns about health information confidentiality in e-mails.

Our study’s generalizability is limited by a low response rate, though it is comparable to prior studies.⁷ The unaffiliated group was accessed by convenience (acquaintance with the medical director); however, we note it had the highest response rate (55%).

In summary, we found low rates of communication between inpatient providers and PCPs, despite a strong preference from most PCPs for such communication during hospitalizations. PCPs’ preferred mode of communication differed based on practice setting. Addressing PCP communication preferences may be important to future care transition interventions.

Disclosure

The authors report no conflicts of interest.

As the hospitalist’s role in medicine grows, the transition of care from inpatient to primary care providers (PCPs, including primary care physicians, nurse practitioners, or physician assistants), becomes increasingly important. Inadequate communication at this transition is associated with preventable adverse events leading to rehospitalization, disability, and death.^1-3 While professional societies recommend PCPs be notified at every care transition, the specific timing and modality of this communication is not well defined.⁴

Providing PCPs access to the inpatient electronic health record (EHR) may reduce the need for active communication. However, a recent survey of PCPs in the general internal medicine division of an academic hospital found a strong preference for additional communication with inpatient providers, despite a shared EHR.⁵

We examined communication preferences of general internal medicine PCPs at a different academic institution and extended our study to include community-based PCPs who were both affiliated and unaffiliated with the institution.

METHODS

Between October 2015 and June 2016, we surveyed PCPs from 3 practice groups with institutional affiliation or proximity to The Johns Hopkins Hospital: all general internal medicine faculty with outpatient practices (“academic,” 2 practice sites, n = 35), all community-based PCPs affiliated with the health system (“community,” 36 practice sites, n = 220), and all PCPs from an unaffiliated managed care organization (“unaffiliated,” 5 practice sites ranging from 0.3 to 4 miles from The Johns Hopkins Hospital, n = 29).

All groups have work-sponsored e-mail services. At the time of the survey, both the academic and community groups used an EHR that allowed access to inpatient laboratory and radiology data and discharge summaries. The unaffiliated group used paper health records. The hospital faxes discharge summaries to all PCPs who are identified by patients.

The investigators and representatives from each practice group collaborated to develop 15 questions with mutually exclusive answers to evaluate PCP experiences with and preferences for communication with inpatient teams. The survey was constructed and administered through Qualtrics’ online platform (Qualtrics, Provo, UT) and distributed via e-mail. The study was reviewed and acknowledged by the Johns Hopkins institutional review board as quality improvement activity.

The survey contained branching logic. Only respondents who indicated preference for communication received questions regarding preferred mode of communication. We used the preferred mode of communication for initial contact from the inpatient team in our analysis. χ² and Fischer’s exact tests were performed with JMP 12 software (SAS Institute Inc, Cary, NC).

RESULTS

Fourteen (40%) academic, 43 (14%) community, and 16 (55%) unaffiliated PCPs completed the survey, for 73 total responses from 284 surveys distributed (26%).

Among the 73 responding PCPs, 31 (42%) reported receiving notification of admission during “every” or “almost every” hospitalization, with no significant variation across practice groups (P = 0.5).

Across all groups, 64 PCPs (88%) preferred communication at 1 or more points during hospitalizations (panel A of Figure). “Both upon admission and prior to discharge” was selected most frequently, and there were no differences between practice groups (P = 0.2).

DISCUSSION

Our findings add to previous evidence of low rates of communication between inpatient providers and PCPs⁶ and a preference from PCPs for communication during hospitalizations despite shared EHRs.⁵ We extend previous work by demonstrating that PCP preferences for mode of communication vary by practice setting. Our findings lead us to hypothesize that identifying and incorporating PCP preferences may improve communication, though at the potential expense of standardization and efficiency.

There may be several reasons for the differing communication preferences observed. Most academic PCPs are located near or have admitting privileges to the hospital and are not in clinic full time. Their preference for the telephone may thus result from interpersonal relationships born from proximity and greater availability for telephone calls, or reduced fluency with the EHR compared to full-time community clinicians.

The unaffiliated group’s preference for fax may reflect a desire for communication that integrates easily with paper charts and is least disruptive to workflow, or concerns about health information confidentiality in e-mails.

Our study’s generalizability is limited by a low response rate, though it is comparable to prior studies.⁷ The unaffiliated group was accessed by convenience (acquaintance with the medical director); however, we note it had the highest response rate (55%).

In summary, we found low rates of communication between inpatient providers and PCPs, despite a strong preference from most PCPs for such communication during hospitalizations. PCPs’ preferred mode of communication differed based on practice setting. Addressing PCP communication preferences may be important to future care transition interventions.

Disclosure

The authors report no conflicts of interest.

As the hospitalist’s role in medicine grows, the transition of care from inpatient to primary care providers (PCPs, including primary care physicians, nurse practitioners, or physician assistants), becomes increasingly important. Inadequate communication at this transition is associated with preventable adverse events leading to rehospitalization, disability, and death.^1-3 While professional societies recommend PCPs be notified at every care transition, the specific timing and modality of this communication is not well defined.⁴

Providing PCPs access to the inpatient electronic health record (EHR) may reduce the need for active communication. However, a recent survey of PCPs in the general internal medicine division of an academic hospital found a strong preference for additional communication with inpatient providers, despite a shared EHR.⁵

We examined communication preferences of general internal medicine PCPs at a different academic institution and extended our study to include community-based PCPs who were both affiliated and unaffiliated with the institution.

METHODS

Between October 2015 and June 2016, we surveyed PCPs from 3 practice groups with institutional affiliation or proximity to The Johns Hopkins Hospital: all general internal medicine faculty with outpatient practices (“academic,” 2 practice sites, n = 35), all community-based PCPs affiliated with the health system (“community,” 36 practice sites, n = 220), and all PCPs from an unaffiliated managed care organization (“unaffiliated,” 5 practice sites ranging from 0.3 to 4 miles from The Johns Hopkins Hospital, n = 29).

All groups have work-sponsored e-mail services. At the time of the survey, both the academic and community groups used an EHR that allowed access to inpatient laboratory and radiology data and discharge summaries. The unaffiliated group used paper health records. The hospital faxes discharge summaries to all PCPs who are identified by patients.

The investigators and representatives from each practice group collaborated to develop 15 questions with mutually exclusive answers to evaluate PCP experiences with and preferences for communication with inpatient teams. The survey was constructed and administered through Qualtrics’ online platform (Qualtrics, Provo, UT) and distributed via e-mail. The study was reviewed and acknowledged by the Johns Hopkins institutional review board as quality improvement activity.

The survey contained branching logic. Only respondents who indicated preference for communication received questions regarding preferred mode of communication. We used the preferred mode of communication for initial contact from the inpatient team in our analysis. χ² and Fischer’s exact tests were performed with JMP 12 software (SAS Institute Inc, Cary, NC).

RESULTS

Fourteen (40%) academic, 43 (14%) community, and 16 (55%) unaffiliated PCPs completed the survey, for 73 total responses from 284 surveys distributed (26%).

Among the 73 responding PCPs, 31 (42%) reported receiving notification of admission during “every” or “almost every” hospitalization, with no significant variation across practice groups (P = 0.5).

Across all groups, 64 PCPs (88%) preferred communication at 1 or more points during hospitalizations (panel A of Figure). “Both upon admission and prior to discharge” was selected most frequently, and there were no differences between practice groups (P = 0.2).

DISCUSSION

Our findings add to previous evidence of low rates of communication between inpatient providers and PCPs⁶ and a preference from PCPs for communication during hospitalizations despite shared EHRs.⁵ We extend previous work by demonstrating that PCP preferences for mode of communication vary by practice setting. Our findings lead us to hypothesize that identifying and incorporating PCP preferences may improve communication, though at the potential expense of standardization and efficiency.

There may be several reasons for the differing communication preferences observed. Most academic PCPs are located near or have admitting privileges to the hospital and are not in clinic full time. Their preference for the telephone may thus result from interpersonal relationships born from proximity and greater availability for telephone calls, or reduced fluency with the EHR compared to full-time community clinicians.

The unaffiliated group’s preference for fax may reflect a desire for communication that integrates easily with paper charts and is least disruptive to workflow, or concerns about health information confidentiality in e-mails.

Our study’s generalizability is limited by a low response rate, though it is comparable to prior studies.⁷ The unaffiliated group was accessed by convenience (acquaintance with the medical director); however, we note it had the highest response rate (55%).

In summary, we found low rates of communication between inpatient providers and PCPs, despite a strong preference from most PCPs for such communication during hospitalizations. PCPs’ preferred mode of communication differed based on practice setting. Addressing PCP communication preferences may be important to future care transition interventions.

Disclosure

The authors report no conflicts of interest.