AUA: Testosterone may not deserve its reputation as a cardiovascular culprit

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AUA: Testosterone may not deserve its reputation as a cardiovascular culprit

NEW ORLEANS – Evidence seems to be mounting that the link between testosterone replacement therapy and increased hematocrit doesn’t lead to more cardiac or thrombotic events in men.

The association between testosterone and secondary erythrocytosis has been known for some time, Dr. Wayne J. G. Hellstrom said at the annual meeting of the American Urological Association. An increase in hematocrit almost invariably follows testosterone supplementation. “The question is, is there a causal relation between testosterone replacement therapy–induced erythrocytosis and venous thromboembolism or major cardiac events?” said Dr. Hellstrom of Tulane Medical Center, New Orleans. “The available evidence doesn’t support this claim.”

Erythrocytosis is defined as a packed red blood cell volume exceeding 125% of the age-predicted mass. This may be primary – an intrinsic alteration of the hematopoietic stem cells – or secondary. “And it may actually be a physiologically appropriate response to something, as in anemia,” Dr. Hellstrom said. “In fact, some anemias are primarily treated with testosterone.”

 

In the presence of exogenous testosterone, the condition may be due to a couple of things, he noted, such as:

• An overall increase in the erythropoietin set point.

• Increased availability of iron in the liver.

• The conversion of testosterone to estradiol, which tends to stimulate the bone marrow.

Erythrocytosis, obviously then, increases blood viscosity – and this is the primary concern for cardiovascular events.

Intramuscular testosterone is the only form that significantly increases hematocrit above normal levels. However, it does so strongly, with up to a 6% change from baseline. The runner-up is testosterone gel, with an average increase of 2.5% over baseline levels.

But despite concerns – which in March prompted the FDA to require on labeling a warning about the risk of cardiovascular events – the relationship has never been thoroughly investigated, Dr. Hellstrom said.

“We only have retrospective data, primarily extrapolating from the nephrology literature. When we look at the renal literature, we see that 10%-20% of kidney transplant patients develop polycythemia – an increase of both red and white cells, with hematocrit values of more than 51% or 52%.”

This has led to a recommendation by the American Society of Nephrology for frequent complete blood cell counts in the year after transplant and annual measurements thereafter.

The highest-quality mortality data for kidney transplant patients come from a 2013 study of 365 patients; the investigators found that those with polycythemia were 2.7 times more likely to die over 4 years. “But this is a true primary polycythemia,” which is often accompanied by procoagulative changes. It is not the secondary condition induced by testosterone, Dr. Hellstrom said.

Older studies suggested a significant link between increased hematocrit and cardiovascular or thrombotic events, especially after surgery. But prospective data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies have found no increased risk of cardiovascular death by increasing tertiles of either hematocrit or hemoglobin, with respective cut points of 43% and 14.5 g/dL.

In fact, a recent transgenic mouse model with hematopoietic overexpression, reaching an 85% hematocrit, found no evidence of either lung or cardiovascular thromboses. “This seems to be related to a reduction in clot strength and increased osmotic fragility in the presence of increasing hematocrit. It seems to mechanically deter the interaction of platelets and fibrin in the extravascular space and endothelium.”

He referred to an in-press mouse study showing that a short course of high-dose testosterone did raise whole blood viscosity and hematocrit. “But over time, this returned to normal, even with supraphysiolgic testosterone levels, so it seems likely that there is an adaptive mechanism that occurs in these animals.”

Additionally, he said, men who live at high altitudes develop naturally high hematocrits as a response to decreased oxygen in the atmosphere. “We routinely see men from these locations with hematocrits of 57% and 59% who have no problems at all.”

Extrapolating all these data to the testosterone/thrombosis link is confusing. The most recent study, however, provided some measure of reassurance. The large meta-analysis comprised 75 randomized, placebo-controlled trials involving about 5,500 men; they all examined cardiovascular risk and testosterone therapy.

“Our analyses, performed on the largest number of studies collected so far, indicate that testosterone supplementation is not related to any increase in cardiovascular risk, even when composite or single adverse events were considered,” wrote Dr. Giovanni Corona of the Maggiore-Bellaria Hospital, Bologna, Italy. “In randomized trials performed in subjects with metabolic derangements, a protective effect … was observed. … Our results are in agreement with a large body of literature from the last 20 years supporting testosterone supplementation of hypogonadal men as a valuable strategy in improving a patient’s metabolic profile, reducing body fat, and increasing lean muscle mass, which would ultimately reduce the risk of heart disease

 

 

“There is a definite need for large multicenter, randomized trials to determine the true risk,” Dr. Hellstrom said. However, in light of the current evidence, he recommends what he called a “conservative” approach to testosterone prescribing:

• Before prescribing, get a baseline complete blood count.

• If the baseline hematocrit is more than 47%, consider alternative treatments, but proceed if testosterone replacement therapy seems to be the best clinical option. Repeat testing at 3 and 12 months after therapy initiation and then annually.

• If hematocrit increases above 54%, discontinue treatment until there is a further clinical assessment, as detailed by the Endocrine Society.

• Closely monitor any new diagnoses of hypertension.

• If hematocrit does rise precipitously, phlebotomy rapidly resolved the problem.

Dr Hellstrom made the following financial disclosures: consultant, advisor, or leadership position for Abbvie, Allergan, American Medical Systems, Antares, Astellas, Auxilim, Allergan, Coloplast, Endo, Lilly, New England Research Institutes Inc. Pfizer, Promescent, Reros Therapeutics, and Theralogix.

 

[email protected]

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NEW ORLEANS – Evidence seems to be mounting that the link between testosterone replacement therapy and increased hematocrit doesn’t lead to more cardiac or thrombotic events in men.

The association between testosterone and secondary erythrocytosis has been known for some time, Dr. Wayne J. G. Hellstrom said at the annual meeting of the American Urological Association. An increase in hematocrit almost invariably follows testosterone supplementation. “The question is, is there a causal relation between testosterone replacement therapy–induced erythrocytosis and venous thromboembolism or major cardiac events?” said Dr. Hellstrom of Tulane Medical Center, New Orleans. “The available evidence doesn’t support this claim.”

Erythrocytosis is defined as a packed red blood cell volume exceeding 125% of the age-predicted mass. This may be primary – an intrinsic alteration of the hematopoietic stem cells – or secondary. “And it may actually be a physiologically appropriate response to something, as in anemia,” Dr. Hellstrom said. “In fact, some anemias are primarily treated with testosterone.”

 

In the presence of exogenous testosterone, the condition may be due to a couple of things, he noted, such as:

• An overall increase in the erythropoietin set point.

• Increased availability of iron in the liver.

• The conversion of testosterone to estradiol, which tends to stimulate the bone marrow.

Erythrocytosis, obviously then, increases blood viscosity – and this is the primary concern for cardiovascular events.

Intramuscular testosterone is the only form that significantly increases hematocrit above normal levels. However, it does so strongly, with up to a 6% change from baseline. The runner-up is testosterone gel, with an average increase of 2.5% over baseline levels.

But despite concerns – which in March prompted the FDA to require on labeling a warning about the risk of cardiovascular events – the relationship has never been thoroughly investigated, Dr. Hellstrom said.

“We only have retrospective data, primarily extrapolating from the nephrology literature. When we look at the renal literature, we see that 10%-20% of kidney transplant patients develop polycythemia – an increase of both red and white cells, with hematocrit values of more than 51% or 52%.”

This has led to a recommendation by the American Society of Nephrology for frequent complete blood cell counts in the year after transplant and annual measurements thereafter.

The highest-quality mortality data for kidney transplant patients come from a 2013 study of 365 patients; the investigators found that those with polycythemia were 2.7 times more likely to die over 4 years. “But this is a true primary polycythemia,” which is often accompanied by procoagulative changes. It is not the secondary condition induced by testosterone, Dr. Hellstrom said.

Older studies suggested a significant link between increased hematocrit and cardiovascular or thrombotic events, especially after surgery. But prospective data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies have found no increased risk of cardiovascular death by increasing tertiles of either hematocrit or hemoglobin, with respective cut points of 43% and 14.5 g/dL.

In fact, a recent transgenic mouse model with hematopoietic overexpression, reaching an 85% hematocrit, found no evidence of either lung or cardiovascular thromboses. “This seems to be related to a reduction in clot strength and increased osmotic fragility in the presence of increasing hematocrit. It seems to mechanically deter the interaction of platelets and fibrin in the extravascular space and endothelium.”

He referred to an in-press mouse study showing that a short course of high-dose testosterone did raise whole blood viscosity and hematocrit. “But over time, this returned to normal, even with supraphysiolgic testosterone levels, so it seems likely that there is an adaptive mechanism that occurs in these animals.”

Additionally, he said, men who live at high altitudes develop naturally high hematocrits as a response to decreased oxygen in the atmosphere. “We routinely see men from these locations with hematocrits of 57% and 59% who have no problems at all.”

Extrapolating all these data to the testosterone/thrombosis link is confusing. The most recent study, however, provided some measure of reassurance. The large meta-analysis comprised 75 randomized, placebo-controlled trials involving about 5,500 men; they all examined cardiovascular risk and testosterone therapy.

“Our analyses, performed on the largest number of studies collected so far, indicate that testosterone supplementation is not related to any increase in cardiovascular risk, even when composite or single adverse events were considered,” wrote Dr. Giovanni Corona of the Maggiore-Bellaria Hospital, Bologna, Italy. “In randomized trials performed in subjects with metabolic derangements, a protective effect … was observed. … Our results are in agreement with a large body of literature from the last 20 years supporting testosterone supplementation of hypogonadal men as a valuable strategy in improving a patient’s metabolic profile, reducing body fat, and increasing lean muscle mass, which would ultimately reduce the risk of heart disease

 

 

“There is a definite need for large multicenter, randomized trials to determine the true risk,” Dr. Hellstrom said. However, in light of the current evidence, he recommends what he called a “conservative” approach to testosterone prescribing:

• Before prescribing, get a baseline complete blood count.

• If the baseline hematocrit is more than 47%, consider alternative treatments, but proceed if testosterone replacement therapy seems to be the best clinical option. Repeat testing at 3 and 12 months after therapy initiation and then annually.

• If hematocrit increases above 54%, discontinue treatment until there is a further clinical assessment, as detailed by the Endocrine Society.

• Closely monitor any new diagnoses of hypertension.

• If hematocrit does rise precipitously, phlebotomy rapidly resolved the problem.

Dr Hellstrom made the following financial disclosures: consultant, advisor, or leadership position for Abbvie, Allergan, American Medical Systems, Antares, Astellas, Auxilim, Allergan, Coloplast, Endo, Lilly, New England Research Institutes Inc. Pfizer, Promescent, Reros Therapeutics, and Theralogix.

 

[email protected]

NEW ORLEANS – Evidence seems to be mounting that the link between testosterone replacement therapy and increased hematocrit doesn’t lead to more cardiac or thrombotic events in men.

The association between testosterone and secondary erythrocytosis has been known for some time, Dr. Wayne J. G. Hellstrom said at the annual meeting of the American Urological Association. An increase in hematocrit almost invariably follows testosterone supplementation. “The question is, is there a causal relation between testosterone replacement therapy–induced erythrocytosis and venous thromboembolism or major cardiac events?” said Dr. Hellstrom of Tulane Medical Center, New Orleans. “The available evidence doesn’t support this claim.”

Erythrocytosis is defined as a packed red blood cell volume exceeding 125% of the age-predicted mass. This may be primary – an intrinsic alteration of the hematopoietic stem cells – or secondary. “And it may actually be a physiologically appropriate response to something, as in anemia,” Dr. Hellstrom said. “In fact, some anemias are primarily treated with testosterone.”

 

In the presence of exogenous testosterone, the condition may be due to a couple of things, he noted, such as:

• An overall increase in the erythropoietin set point.

• Increased availability of iron in the liver.

• The conversion of testosterone to estradiol, which tends to stimulate the bone marrow.

Erythrocytosis, obviously then, increases blood viscosity – and this is the primary concern for cardiovascular events.

Intramuscular testosterone is the only form that significantly increases hematocrit above normal levels. However, it does so strongly, with up to a 6% change from baseline. The runner-up is testosterone gel, with an average increase of 2.5% over baseline levels.

But despite concerns – which in March prompted the FDA to require on labeling a warning about the risk of cardiovascular events – the relationship has never been thoroughly investigated, Dr. Hellstrom said.

“We only have retrospective data, primarily extrapolating from the nephrology literature. When we look at the renal literature, we see that 10%-20% of kidney transplant patients develop polycythemia – an increase of both red and white cells, with hematocrit values of more than 51% or 52%.”

This has led to a recommendation by the American Society of Nephrology for frequent complete blood cell counts in the year after transplant and annual measurements thereafter.

The highest-quality mortality data for kidney transplant patients come from a 2013 study of 365 patients; the investigators found that those with polycythemia were 2.7 times more likely to die over 4 years. “But this is a true primary polycythemia,” which is often accompanied by procoagulative changes. It is not the secondary condition induced by testosterone, Dr. Hellstrom said.

Older studies suggested a significant link between increased hematocrit and cardiovascular or thrombotic events, especially after surgery. But prospective data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies have found no increased risk of cardiovascular death by increasing tertiles of either hematocrit or hemoglobin, with respective cut points of 43% and 14.5 g/dL.

In fact, a recent transgenic mouse model with hematopoietic overexpression, reaching an 85% hematocrit, found no evidence of either lung or cardiovascular thromboses. “This seems to be related to a reduction in clot strength and increased osmotic fragility in the presence of increasing hematocrit. It seems to mechanically deter the interaction of platelets and fibrin in the extravascular space and endothelium.”

He referred to an in-press mouse study showing that a short course of high-dose testosterone did raise whole blood viscosity and hematocrit. “But over time, this returned to normal, even with supraphysiolgic testosterone levels, so it seems likely that there is an adaptive mechanism that occurs in these animals.”

Additionally, he said, men who live at high altitudes develop naturally high hematocrits as a response to decreased oxygen in the atmosphere. “We routinely see men from these locations with hematocrits of 57% and 59% who have no problems at all.”

Extrapolating all these data to the testosterone/thrombosis link is confusing. The most recent study, however, provided some measure of reassurance. The large meta-analysis comprised 75 randomized, placebo-controlled trials involving about 5,500 men; they all examined cardiovascular risk and testosterone therapy.

“Our analyses, performed on the largest number of studies collected so far, indicate that testosterone supplementation is not related to any increase in cardiovascular risk, even when composite or single adverse events were considered,” wrote Dr. Giovanni Corona of the Maggiore-Bellaria Hospital, Bologna, Italy. “In randomized trials performed in subjects with metabolic derangements, a protective effect … was observed. … Our results are in agreement with a large body of literature from the last 20 years supporting testosterone supplementation of hypogonadal men as a valuable strategy in improving a patient’s metabolic profile, reducing body fat, and increasing lean muscle mass, which would ultimately reduce the risk of heart disease

 

 

“There is a definite need for large multicenter, randomized trials to determine the true risk,” Dr. Hellstrom said. However, in light of the current evidence, he recommends what he called a “conservative” approach to testosterone prescribing:

• Before prescribing, get a baseline complete blood count.

• If the baseline hematocrit is more than 47%, consider alternative treatments, but proceed if testosterone replacement therapy seems to be the best clinical option. Repeat testing at 3 and 12 months after therapy initiation and then annually.

• If hematocrit increases above 54%, discontinue treatment until there is a further clinical assessment, as detailed by the Endocrine Society.

• Closely monitor any new diagnoses of hypertension.

• If hematocrit does rise precipitously, phlebotomy rapidly resolved the problem.

Dr Hellstrom made the following financial disclosures: consultant, advisor, or leadership position for Abbvie, Allergan, American Medical Systems, Antares, Astellas, Auxilim, Allergan, Coloplast, Endo, Lilly, New England Research Institutes Inc. Pfizer, Promescent, Reros Therapeutics, and Theralogix.

 

[email protected]

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EXPERT ANALYSIS FROM THE AUA ANNUAL MEETING

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Hodgkin lymphoma incidence on the decline worldwide

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Fri, 05/29/2015 - 06:00
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Hodgkin lymphoma incidence on the decline worldwide

Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

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Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

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DART molecule proves active against AML

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DART molecule proves active against AML

Cynomolgus monkey

Photo by Sakurai Midori

An artificial antibody that redirects T cells to target cancer cells shows promise for treating acute myeloid leukemia (AML), according to preclinical research.

The antibody, MGD006, induced tumor regression in mouse models of AML and was largely well-tolerated in cynomolgus monkeys.

Investigators say these results support clinical testing of MGD006 in AML, which is currently underway.

MGD006 is a humanized, dual-affinity re-targeting (DART) molecule that combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123.

MGD006 redirects T cells to kill cells expressing CD123, which is upregulated in AML and other hematologic diseases.

Gurunadh Chichili, PhD, of MacroGenics, Inc., in Rockville, Maryland, and his colleagues described their work with MGD006 in Science Translational Medicine. MacroGenics, the company developing MGD006, funded this research.

Because MGD006 is designed to be cleared rapidly, it requires continuous delivery. So in mice, the investigators administered the molecule continuously for up to a week via peritoneally implanted osmotic pumps.

The NSG/b2m−/− mice had been reconstituted with human peripheral blood mononuclear cells and grafted with KG-1a cells, an AML-M0 line. The mice received MGD006 after tumors were allowed to grow to an average size of about 100 mm3.

Treated mice experienced significant tumor regression at all doses of MGD006 (P<0.005), but there was no activity in mice treated with a control DART molecule. The investigators found that 500 ng/kg of MGD006 per day was sufficient to completely eliminate leukemic cells.

The team also tested MGD006 in macaques and found the molecule binds to human and cynomolgus monkey antigens with similar affinities and redirects T cells from either species to kill CD123-expressing target cells.

The monkeys received continuous infusions of MGD006, starting at 0.1 mg/kg per day and escalating weekly to up to 1 mg/kg per day for a 4-week period. The treatment depleted circulating CD123-positive cells beginning at 72 hours and continuing throughout the infusion period.

The monkeys experienced cytokine release, but it was transient and most significant after the first dose of MDG006. After the first dose, IL-6 concentration returned to baseline by 72 hours, and the magnitude of IL-6 response decreased with each successive MGD006 infusion, even when the dose was increased.

The animals experienced reversible reductions in hematocrit and red cell mass at the highest doses of MDG006 but no neutropenia or thrombocytopenia.

“This research paved the way for our initiation of a phase 1 clinical study of MGD006 in 2014,” said Scott Koenig, MD, PhD, President and CEO of MacroGenics.

“MGD006 has demonstrated great promise as a T-cell-redirected cancer immunotherapy in preclinical studies. We are hopeful that these studies will translate into clinical trial results indicative of clinical improvement for patients with AML, myelodysplastic syndrome, and several other forms of leukemia and lymphoma.”

Publications
Topics

Cynomolgus monkey

Photo by Sakurai Midori

An artificial antibody that redirects T cells to target cancer cells shows promise for treating acute myeloid leukemia (AML), according to preclinical research.

The antibody, MGD006, induced tumor regression in mouse models of AML and was largely well-tolerated in cynomolgus monkeys.

Investigators say these results support clinical testing of MGD006 in AML, which is currently underway.

MGD006 is a humanized, dual-affinity re-targeting (DART) molecule that combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123.

MGD006 redirects T cells to kill cells expressing CD123, which is upregulated in AML and other hematologic diseases.

Gurunadh Chichili, PhD, of MacroGenics, Inc., in Rockville, Maryland, and his colleagues described their work with MGD006 in Science Translational Medicine. MacroGenics, the company developing MGD006, funded this research.

Because MGD006 is designed to be cleared rapidly, it requires continuous delivery. So in mice, the investigators administered the molecule continuously for up to a week via peritoneally implanted osmotic pumps.

The NSG/b2m−/− mice had been reconstituted with human peripheral blood mononuclear cells and grafted with KG-1a cells, an AML-M0 line. The mice received MGD006 after tumors were allowed to grow to an average size of about 100 mm3.

Treated mice experienced significant tumor regression at all doses of MGD006 (P<0.005), but there was no activity in mice treated with a control DART molecule. The investigators found that 500 ng/kg of MGD006 per day was sufficient to completely eliminate leukemic cells.

The team also tested MGD006 in macaques and found the molecule binds to human and cynomolgus monkey antigens with similar affinities and redirects T cells from either species to kill CD123-expressing target cells.

The monkeys received continuous infusions of MGD006, starting at 0.1 mg/kg per day and escalating weekly to up to 1 mg/kg per day for a 4-week period. The treatment depleted circulating CD123-positive cells beginning at 72 hours and continuing throughout the infusion period.

The monkeys experienced cytokine release, but it was transient and most significant after the first dose of MDG006. After the first dose, IL-6 concentration returned to baseline by 72 hours, and the magnitude of IL-6 response decreased with each successive MGD006 infusion, even when the dose was increased.

The animals experienced reversible reductions in hematocrit and red cell mass at the highest doses of MDG006 but no neutropenia or thrombocytopenia.

“This research paved the way for our initiation of a phase 1 clinical study of MGD006 in 2014,” said Scott Koenig, MD, PhD, President and CEO of MacroGenics.

“MGD006 has demonstrated great promise as a T-cell-redirected cancer immunotherapy in preclinical studies. We are hopeful that these studies will translate into clinical trial results indicative of clinical improvement for patients with AML, myelodysplastic syndrome, and several other forms of leukemia and lymphoma.”

Cynomolgus monkey

Photo by Sakurai Midori

An artificial antibody that redirects T cells to target cancer cells shows promise for treating acute myeloid leukemia (AML), according to preclinical research.

The antibody, MGD006, induced tumor regression in mouse models of AML and was largely well-tolerated in cynomolgus monkeys.

Investigators say these results support clinical testing of MGD006 in AML, which is currently underway.

MGD006 is a humanized, dual-affinity re-targeting (DART) molecule that combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123.

MGD006 redirects T cells to kill cells expressing CD123, which is upregulated in AML and other hematologic diseases.

Gurunadh Chichili, PhD, of MacroGenics, Inc., in Rockville, Maryland, and his colleagues described their work with MGD006 in Science Translational Medicine. MacroGenics, the company developing MGD006, funded this research.

Because MGD006 is designed to be cleared rapidly, it requires continuous delivery. So in mice, the investigators administered the molecule continuously for up to a week via peritoneally implanted osmotic pumps.

The NSG/b2m−/− mice had been reconstituted with human peripheral blood mononuclear cells and grafted with KG-1a cells, an AML-M0 line. The mice received MGD006 after tumors were allowed to grow to an average size of about 100 mm3.

Treated mice experienced significant tumor regression at all doses of MGD006 (P<0.005), but there was no activity in mice treated with a control DART molecule. The investigators found that 500 ng/kg of MGD006 per day was sufficient to completely eliminate leukemic cells.

The team also tested MGD006 in macaques and found the molecule binds to human and cynomolgus monkey antigens with similar affinities and redirects T cells from either species to kill CD123-expressing target cells.

The monkeys received continuous infusions of MGD006, starting at 0.1 mg/kg per day and escalating weekly to up to 1 mg/kg per day for a 4-week period. The treatment depleted circulating CD123-positive cells beginning at 72 hours and continuing throughout the infusion period.

The monkeys experienced cytokine release, but it was transient and most significant after the first dose of MDG006. After the first dose, IL-6 concentration returned to baseline by 72 hours, and the magnitude of IL-6 response decreased with each successive MGD006 infusion, even when the dose was increased.

The animals experienced reversible reductions in hematocrit and red cell mass at the highest doses of MDG006 but no neutropenia or thrombocytopenia.

“This research paved the way for our initiation of a phase 1 clinical study of MGD006 in 2014,” said Scott Koenig, MD, PhD, President and CEO of MacroGenics.

“MGD006 has demonstrated great promise as a T-cell-redirected cancer immunotherapy in preclinical studies. We are hopeful that these studies will translate into clinical trial results indicative of clinical improvement for patients with AML, myelodysplastic syndrome, and several other forms of leukemia and lymphoma.”

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Urine test could reduce need for blood samples

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Urine test could reduce need for blood samples

Blood sample collection

Photo by Juan D. Alfonso

A new approach to urine testing could make the tests more versatile and therefore decrease the need for blood tests, according to researchers.

They believe the method could also reduce costs, produce results faster than current tests, and lower the volume of urine needed for a sample.

R. Kenneth Marcus, PhD, of Clemson University in South Carolina, and his colleagues described this method in Proteomics-Clinical Applications.

Dr Marcus noted that the trouble with testing urine is that it’s awash in salt, so it can be tricky to isolate the proteins that act as biomarkers.

To overcome this problem, he and his colleagues used a string made of capillary-channeled polymer fibers. The team packed the fibers into plastic tubes and then passed urine samples through the tubes by spinning them in a centrifuge for 30 seconds.

Then, the researchers ran de-ionized water through the tubes for a minute to wash off salt and other contaminants.

As proteins are hydrophobic, they remained stuck to the fibers. The team extracted the proteins by running a solvent through the tubes in the centrifuge for 30 seconds.

When this process was complete, the researchers were left with purified proteins that could be stored in a plastic vial and refrigerated until testing time.

The team was able to extract 12 samples in about 5 minutes, limited only by centrifuge capacity.

In addition to being faster and cheaper than current urine tests, the new testing method should also make it easier to test urine samples from infants, Dr Marcus said.

One of the challenges now is getting a large enough sample, but the new method requires only a few microliters of urine.

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Blood sample collection

Photo by Juan D. Alfonso

A new approach to urine testing could make the tests more versatile and therefore decrease the need for blood tests, according to researchers.

They believe the method could also reduce costs, produce results faster than current tests, and lower the volume of urine needed for a sample.

R. Kenneth Marcus, PhD, of Clemson University in South Carolina, and his colleagues described this method in Proteomics-Clinical Applications.

Dr Marcus noted that the trouble with testing urine is that it’s awash in salt, so it can be tricky to isolate the proteins that act as biomarkers.

To overcome this problem, he and his colleagues used a string made of capillary-channeled polymer fibers. The team packed the fibers into plastic tubes and then passed urine samples through the tubes by spinning them in a centrifuge for 30 seconds.

Then, the researchers ran de-ionized water through the tubes for a minute to wash off salt and other contaminants.

As proteins are hydrophobic, they remained stuck to the fibers. The team extracted the proteins by running a solvent through the tubes in the centrifuge for 30 seconds.

When this process was complete, the researchers were left with purified proteins that could be stored in a plastic vial and refrigerated until testing time.

The team was able to extract 12 samples in about 5 minutes, limited only by centrifuge capacity.

In addition to being faster and cheaper than current urine tests, the new testing method should also make it easier to test urine samples from infants, Dr Marcus said.

One of the challenges now is getting a large enough sample, but the new method requires only a few microliters of urine.

Blood sample collection

Photo by Juan D. Alfonso

A new approach to urine testing could make the tests more versatile and therefore decrease the need for blood tests, according to researchers.

They believe the method could also reduce costs, produce results faster than current tests, and lower the volume of urine needed for a sample.

R. Kenneth Marcus, PhD, of Clemson University in South Carolina, and his colleagues described this method in Proteomics-Clinical Applications.

Dr Marcus noted that the trouble with testing urine is that it’s awash in salt, so it can be tricky to isolate the proteins that act as biomarkers.

To overcome this problem, he and his colleagues used a string made of capillary-channeled polymer fibers. The team packed the fibers into plastic tubes and then passed urine samples through the tubes by spinning them in a centrifuge for 30 seconds.

Then, the researchers ran de-ionized water through the tubes for a minute to wash off salt and other contaminants.

As proteins are hydrophobic, they remained stuck to the fibers. The team extracted the proteins by running a solvent through the tubes in the centrifuge for 30 seconds.

When this process was complete, the researchers were left with purified proteins that could be stored in a plastic vial and refrigerated until testing time.

The team was able to extract 12 samples in about 5 minutes, limited only by centrifuge capacity.

In addition to being faster and cheaper than current urine tests, the new testing method should also make it easier to test urine samples from infants, Dr Marcus said.

One of the challenges now is getting a large enough sample, but the new method requires only a few microliters of urine.

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Understanding taste dysfunction in cancer

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Understanding taste dysfunction in cancer

Drawing of a taste bud

Image by Jonas Töle

Investigators have identified a molecular pathway that aids the renewal of taste buds, and they believe this discovery may have implications for cancer patients who suffer from an altered sense of taste during treatment.

“Taste dysfunction can . . . result from an alteration of the renewal capacities of taste buds and is often associated with psychological distress and malnutrition,” said Dany Gaillard, PhD, of the University of Colorado Anschutz Medical Campus in Aurora.

He and his colleagues decided to investigate this dysfunction using mouse models, and the group reported their findings in PLOS Genetics.

The investigators discovered that a protein in the Wnt pathway, ß-catenin, controls the renewal of taste cells by regulating separate stages of taste-cell turnover.

Previous research showed that Wnt/β-catenin signaling is crucial in developing taste buds in embryos and regulating the renewal of epithelial tissue in adults, including skin, hair follicles, the intestine, and the mouth.

“We show that activating this pathway directs the newly born cells to become, primarily, a specific taste- cell type whose role is to support the other taste cells and help them work efficiently,” said Linda Barlow, PhD, also of the University of Colorado Anschutz Medical Campus.

As chemotherapy destroys dividing precursor cells, including those that produce taste cells, the investigators believe that activating Wnt signaling may be a way to renew taste buds after chemotherapy.

New small-molecule drugs that specifically block the Wnt pathway are under development, and Drs Gaillard and Barlow predict these drugs could also cause taste dysfunction.

Dr Barlow said more research is needed to understand how taste is altered at the cellular level, but this research holds promise for developing new ways to improve cancer patients’ quality of life.

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Drawing of a taste bud

Image by Jonas Töle

Investigators have identified a molecular pathway that aids the renewal of taste buds, and they believe this discovery may have implications for cancer patients who suffer from an altered sense of taste during treatment.

“Taste dysfunction can . . . result from an alteration of the renewal capacities of taste buds and is often associated with psychological distress and malnutrition,” said Dany Gaillard, PhD, of the University of Colorado Anschutz Medical Campus in Aurora.

He and his colleagues decided to investigate this dysfunction using mouse models, and the group reported their findings in PLOS Genetics.

The investigators discovered that a protein in the Wnt pathway, ß-catenin, controls the renewal of taste cells by regulating separate stages of taste-cell turnover.

Previous research showed that Wnt/β-catenin signaling is crucial in developing taste buds in embryos and regulating the renewal of epithelial tissue in adults, including skin, hair follicles, the intestine, and the mouth.

“We show that activating this pathway directs the newly born cells to become, primarily, a specific taste- cell type whose role is to support the other taste cells and help them work efficiently,” said Linda Barlow, PhD, also of the University of Colorado Anschutz Medical Campus.

As chemotherapy destroys dividing precursor cells, including those that produce taste cells, the investigators believe that activating Wnt signaling may be a way to renew taste buds after chemotherapy.

New small-molecule drugs that specifically block the Wnt pathway are under development, and Drs Gaillard and Barlow predict these drugs could also cause taste dysfunction.

Dr Barlow said more research is needed to understand how taste is altered at the cellular level, but this research holds promise for developing new ways to improve cancer patients’ quality of life.

Drawing of a taste bud

Image by Jonas Töle

Investigators have identified a molecular pathway that aids the renewal of taste buds, and they believe this discovery may have implications for cancer patients who suffer from an altered sense of taste during treatment.

“Taste dysfunction can . . . result from an alteration of the renewal capacities of taste buds and is often associated with psychological distress and malnutrition,” said Dany Gaillard, PhD, of the University of Colorado Anschutz Medical Campus in Aurora.

He and his colleagues decided to investigate this dysfunction using mouse models, and the group reported their findings in PLOS Genetics.

The investigators discovered that a protein in the Wnt pathway, ß-catenin, controls the renewal of taste cells by regulating separate stages of taste-cell turnover.

Previous research showed that Wnt/β-catenin signaling is crucial in developing taste buds in embryos and regulating the renewal of epithelial tissue in adults, including skin, hair follicles, the intestine, and the mouth.

“We show that activating this pathway directs the newly born cells to become, primarily, a specific taste- cell type whose role is to support the other taste cells and help them work efficiently,” said Linda Barlow, PhD, also of the University of Colorado Anschutz Medical Campus.

As chemotherapy destroys dividing precursor cells, including those that produce taste cells, the investigators believe that activating Wnt signaling may be a way to renew taste buds after chemotherapy.

New small-molecule drugs that specifically block the Wnt pathway are under development, and Drs Gaillard and Barlow predict these drugs could also cause taste dysfunction.

Dr Barlow said more research is needed to understand how taste is altered at the cellular level, but this research holds promise for developing new ways to improve cancer patients’ quality of life.

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Verbal Communication at Discharge

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Improving the reliability of verbal communication between primary care physicians and pediatric hospitalists at hospital discharge

Timely and reliable communication of important data between hospital‐based physicians and primary care physicians is critical for prevention of medical adverse events.[1, 2] Extrapolation from high‐performance organizations outside of medicine suggests that verbal communication is an important component of patient handoffs.[3, 4] Though the Joint Commission does not mandate verbal communication during handoffs per se, stipulating instead that handoff participants have an opportunity to ask and respond to questions,[5] there is some evidence that primary care providers prefer verbal handoffs at least for certain patients such as those with medical complexity.[6] Verbal communication offers the receiver the opportunity to ask questions, but in practice, 2‐way verbal communication is often difficult to achieve at hospital discharge.

At our institution, hospital medicine (HM) physicians serve as the primary inpatient providers for nearly 90% of all general pediatric admissions. When the HM service was established, primary care physicians (PCPs) and HM physicians together agreed upon an expectation for verbal, physician‐to‐physician communication at the time of discharge. Discharge communication is provided by either residents or attendings depending on the facility. A telephone operator service called Physician Priority Link (PPL) was made available to facilitate this communication. The PPL service is staffed 24/7 by operators whose only responsibilities are to connect providers inside and outside the institution. By utilizing this service, PCPs could respond in a nonemergent fashion to discharge phone calls.

Over the last several years, PCPs have observed high variation in the reliability of discharge communication phone calls. A review of PPL phone records in 2009 showed that only 52% of HM discharges had a record of a call initiated to the PCP on the day of discharge. The overall goal of this improvement project was to improve the completion of verbal handoffs from HM physicians (residents or attendings) to PCPs. The specific aim of the project was to increase the proportion of completed verbal handoffs from on‐call residents or attendings to PCPs within 24 hours of discharge to more than 90% within 18 months.

METHODS

Human Subjects Protection

Our project was undertaken in accordance with institutional review board (IRB) policy on systems improvement work and did not require formal IRB review.

Setting

This study included all patients admitted to the HM service at an academic children's hospital and its satellite campus.

Planning the Intervention

The project was championed by physicians on the HM service and supported by a chief resident, PPL administrators, and 2 information technology analysts.

At the onset of the project, the team mapped the process for completing a discharge call to the PCPs, conducted a modified failure mode and effects analysis,[7, 8] and examined the key drivers used to prioritize interventions (Figure 1). Through the modified failure modes effect analysis, the team was able to identify system issues that led to unsuccessful communication: failure of call initiation, absence of an identified PCP, long wait times on hold, failure of PCP to call back, and failure of the call to be documented. These failure modes informed the key drivers to achieving the study aim. Figure 2 depicts the final key drivers, which were revised through testing and learning.

Figure 1
Preintervention processes and failure modes for discharge communication with PCPs.
Figure 2
Key driver diagram for verbal communication at hospital discharge.

Interventions Targeting Key Stakeholder Buy‐in

To improve resident buy‐in and participation, the purpose and goals of the projects were discussed at resident morning report and during monthly team meetings by the pediatric chief resident on our improvement team. Resident physicians were interested in participating to reduce interruptions during daily rounds and to improve interactions with PCPs. The PPL staff was interested in standardizing the discharge call process to reduce confusion in identifying the appropriate contact when PCPs called residents back to discuss discharges. PCPs were interested in ensuring good communication at discharge, and individual PCPs were engaged through person‐to‐person contact by 1 of the HM physician champions.

Interventions to Standardization the Communication Process

To facilitate initiation of calls to PCPs at hospital discharge, the improvement team created a standard process using the PPL service (Figure 3). All patients discharged from the HM service were included in the process. Discharging physicians (who were usually but not always residents, depending on the facility), were instructed to call the PPL operator at the time of discharge. The PPL operator would then page the patient's PCP. It was the responsibility of the discharging physician to identify a PCP prior to discharge. Instances where no PCP was identified were counted as process failures because no phone call could be made. The expectation for the PCPs was that they would return the page within 20 minutes. PPL operators would then page back to the discharging physician to connect the 2 parties with the expectation that the discharging physician respond within 2 to 4 minutes to the PPL operator's page. Standardization of all calls through PPL allowed efficient tracking of incomplete calls and operators to reattempt calls that were not completed. This process also shifted the burden of following up on incomplete calls to PPL. The use of PPL to make the connection also allowed the physician to complete other work while awaiting a call back from the PCP.

Figure 3
Final process map for verbal communication at discharge.

Leveraging the Electronic Health Record for Process Initiation

To ensure reliable initiation of the discharge communication pathway, the improvement team introduced changes to the electronic health record (HER) (EpicCare Inpatient; Epic Systems Corp., Verona, WI), which generated a message to PPL operators whenever a discharge order was entered for an HM patient. The message contained the patient's name, medical record number, discharge date, discharging physician, and PCP name and phone number. A checklist was implemented by PPL to ensure that duplicate phone calls were not made. To initiate communication, the operator contacted the resident via text page to ensure they were ready to initiate the call. If the resident was ready to place a call, the operator then generated a phone call to the PCP. When the PCP returned the call, the operator connected the HM resident with the PCP for the handoff.

As the project progressed, several adaptations were made to address newly identified failure modes. To address confusion among PPL operators about which resident physicians should take discharge phone calls after the discharging resident was no longer available (for example, after a shift change), primary responsibility for discharge phone calls was reassigned to the daily on‐call resident rather than the resident who wrote the discharge order. Because the on‐call residents carry a single pager, the pager number listed on the automated discharge notification to PPL would never change and would always reach the appropriate team member. Second, to address the anticipated increase in interruption of resident workflow by calls back from PCPs, particularly during rounds, operators accessed information on pending discharge phone calls in batches at times of increased resident availability to minimize hold times for PCPs and work interruptions for the discharging physicians. Batch times were 1 pm and 4 pm to allow for completion of morning rounds, resident conference at noon, and patient‐care activities during the afternoon. Calls initiated after 4 pm were dispatched at the time of the discharge, and calls initiated after 10 pm were deferred to the following day.

Transparency of Data

Throughout the study, weekly failure data were generated from the EHR and emailed to improvement team members, enabling them to focus on near real‐time feedback of data to create a visible and more reliable system. With the standardization of all discharge calls directed to the PPL operators, the team was able to create a call record linked to the patient's medical record number. Team‐specific and overall results for the 5 HM resident teams were displayed weekly on a run chart in the resident conference room. As improvements in call initiation were demonstrated, completion rate data were also shared every several months with the attending hospitalists during a regularly scheduled divisional conference. This transparency of data gave the improvement team the opportunity to provide individual feedback to residents and attendings about failures. The weekly review of failure data allowed team leaders to learn from failures, identify knowledge gaps, and ensure accountability with the HM physicians.

Planning the Study of the Intervention

Data were collected prospectively from July 2011 to March 2014. A weekly list of patients discharged from the HM service was extracted from the EHR and compared to electronic call logs collected by PPL on the day of discharge. A standard sample size of 30 calls was audited separately by PPL and 1 of the physician leads to verify that the patients were discharged from the HM service and validate the percentage of completed and initiated calls.

The percentage of calls initiated within 24 hours of discharge was tracked as a process measure and served as the initial focus of improvement efforts. Our primary outcome measure was the percentage of calls completed to the PCP by the HM physician within 24 hours of discharge.

Methods of Evaluation and Analysis

We used improvement science methods and run charts to determine the percentage of patients discharged from the HM service with a call initiated to the PCP and completed within 24 hours of discharge. Data on calls initiated within 24 hours of discharge were plotted on a run chart to examine the impact of interventions over time. Once interventions targeted at call initiation had been implemented, we began tracking our primary outcome measure. A new run chart was created documenting the percentage of calls completed. For both metrics, the centerline was adjusted using established rules for special cause variation in run charts.[9, 10, 11, 12, 13]

RESULTS

From July 2011 to March 2014, there were 6313 discharges from the HM service. The process measure (percentage of calls initiated) improved from 50% to 97% after 4 interventions (Figure 4). Data for the outcome measure (percentage of calls completed) were collected starting in August 2012, shortly after linking the EHR discharge order to the discharge call. Over the first 8 weeks, our median was 80%, which increased to a median of 93% (Figure 5). These results were sustained for 18 months.

Figure 4
Percent of calls made to primary care physicians within 24 hours of hospital discharge.
Figure 5
Percent of calls to primary care physicians completed within 24 hours of discharge.

Several key interventions were identified that were critical to achievement of our goal. Standardization of the communication process through PPL was temporally associated with a shift in the median rate of call initiation from 52% to 72%. Use of the discharge order to initiate discharge communication was associated with an increase from 72% to 97%. Finally, the percentage of completed verbal handoffs increased to more than 93% following batching of phone calls to PCPs at specific times during the day.

DISCUSSION

We used improvement and reliability science methods to implement a successful process for improving verbal handoffs from HM physicians to PCPs within 24 hours of discharge to 93%. This result has been sustained for 18 months.

Utilization of the PPL call center for flexible call facilitation along with support for data analysis and leveraging the EHR to automate the process increased reliability, leading to rapid improvement. Prior to mandating the use of PPL to connect discharging physicians with PCPs, the exact rate of successful handoffs in our institution was not known. We do know, however, that only 52% of calls were initiated, so clearly a large gap was present prior to our improvement work. Data collection from the PPL system was automated so that accurate, timely, and sustainable data could be provided, greatly aiding improvement efforts. Flexibility in call‐back timing was also crucial, because coordinating the availability of PCPs and discharging physicians is often challenging. The EHR‐initiated process for discharge communication was a key intervention, and improvement of our process measure to 97% performance was associated with this implementation. Two final interventions: (1) assignment of responsibility for communication to a team pager held by a designated resident and (2) batching of calls to specific times streamlined the EHR‐initiated process and were associated with achievement of our main outcome goal of >90% completed verbal communication.

There are several reports of successful interventions to improve receipt or content of discharge summaries by PCPs following hospital discharge available in the literature.[14, 15, 16, 17, 18, 19, 20] Recently, Shen et al. reported on the success of a multisite improvement collaborative involving pediatric hospitalist programs at community hospitals whose aim was to improve the timely documentation of communication directed at PCPs.[21] In their report, all 7 hospital sites that participated in the collaborative for more than 4 months were able to demonstrate substantial improvement in documentation of some form of communication directed at PCPs (whether by e‐mail, fax, or telephone call), from a baseline of approximately 50% to more than 90%. A limitation of their study was that they were unable to document whether PCPs had received any information or by what method. A recent survey of PCPs by Sheu et al. indicated that for many discharges, information in addition to that present in the EHR was desirable to ensure a safe transition of care.[6] Two‐way communication, such as with a phone call, allows for senders to verify information receipt and for receivers to ask questions to ensure complete information. To our knowledge, there have been no previous reports describing processes for improving verbal communication between hospitalist services and PCPs at discharge.

It may be that use of the call system allowed PCPs to return phone calls regarding discharges at convenient stopping points in their day while allowing discharging physicians to initiate a call without having to wait on hold. Interestingly, though we anticipated the need for additional PPL resources during the course of this improvement, the final process was efficient enough that PPL did not require additional staffing to accommodate the higher call volume.

A key insight during our implementation was that relying on the EHR to initiate every discharge communication created disruption of resident workflow due to disregard of patient, resident, and PCP factors. This was reflected by the improvement in call initiation (our process measure) following this intervention, whereas at the same time call completion (our outcome measure) remained below goal. To achieve our goal of completing verbal communication required a process that was highly reliable yet flexible enough to allow discharging physicians to complete the call in the unpredictable environment of inpatient care. Ultimately, this was achieved by allowing discharging physicians to initiate the process when convenient, and allowing for the EHR‐initiated process to function as a backup strategy to identify and mitigate failures of initiation.

An important limitation of our study was the lack of PCPs on the improvement team, likely making the success of the project more difficult than it might have been. For example, during the study we did not measure the time PCPs spent on hold or how many reattempts were needed to complete the communication loop. Immediately following the completion of our study, it became apparent that physicians returning calls for our own institution's primary care clinic were experiencing regular workflow interruptions and occasional hold times more than 20 minutes, necessitating ongoing further work to determine the root causes and solutions to these problems. Though this work is ongoing, average PCP hold times measured from a sample of call reviews in 2013 to 2014 was 3 minutes and 15 seconds.

This study has several other limitations. We were unable to account for phone calls to PCPs initiated outside of the new process. It may be that PCPs were called more than 52% of the time at baseline due to noncompliance with the new protocol. Also, we only have data for call completion starting after implementation of the link between the discharge order and the discharge phone call, making the baseline appear artificially high and precluding any analysis of how earlier interventions affected our outcome metric. Communication with PCPs should ideally occur prior to discharge. An important limitation of our process is that calls could occur several hours after discharge between an on‐call resident and an on‐call outpatient physician rather than between the PCP and the discharging resident, limiting appropriate information exchange. Though verbal discharge communication is a desirable goal for many reasons, the current project did not focus on the quality of the call or the information that was transmitted to the PCP. Additionally, direct attending‐to‐attending communication may be valuable with medically or socially complex discharges, but we did not have a process to facilitate this. We also did not measure what effect our new process had on outcomes such as quality of patient and family transition from hospital or physician satisfaction. The existence of programs similar to our PPL subspecialty referral line may be limited to large institutions. However, it should be noted that although some internal resource reallocation was necessary within PPL, no actual staffing increases were required despite a large increase in call volume. It may be that any hospital operator system could be adapted for this purpose with modest additional resources. Finally, although our EHR system is widely utilized, there are many competing systems in the market, and our intervention required utilization of EHR capabilities that may not be present in all systems. However, our EHR intervention utilized existing functionality and did not require modification of the system.

This project focused on discharge phone calls to primary care physicians for patients hospitalized on the hospital medicine service. Because communication with the PCP should ideally occur prior to discharge, future work will include identifying a more proximal trigger than the discharge order to which to link the EHR trigger for discharge communication. Other next steps to improve handoff effectiveness and optimize the efficiency of our process include identifying essential information that should be transmitted to the primary care physician at the time of the phone call, developing processes to ensure communication of this information, measuring PCP satisfaction with this communication, and measuring the impact on patient outcomes. Finally, though expert opinion indicates that verbal handoffs may have safety advantages over nonverbal handoffs, studies comparing the safety and efficacy of verbal versus nonverbal handoffs at patient discharge are lacking. Studies establishing the relative efficacy and safety of verbal versus nonverbal handoffs at hospital discharge are needed. Knowledge gained from these activities could inform future projects centered on the spread of the process to other hospital services and/or other hospitals.

CONCLUSION

We increased the percentage of calls initiated to PCPs at patient discharge from 52% to 97% and the percentage of calls completed between HM physicians and PCPs to 93% through the use of a standardized discharge communication process coupled with a basic EHR messaging functionality. The results of this study may be of interest for further testing and adaptation for any institution with an electronic healthcare system.

Disclosure: Nothing to report.

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References
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  19. Curran P, Gilmore DH, Beringer TR. Communication of discharge information for elderly patients in hospital. Ulster Med J. 1992;61(1):5658.
  20. Mant A, Kehoe L, Cockayne NL, Kaye KI, Rotem WC. A quality use of medicines program for continuity of care in therapeutics from hospital to community. Med J Aust. 2002;177(1):3234.
  21. Shen MW, Hershey D, Bergert L, Mallory L, Fisher ES, Cooperberg D. Pediatric hospitalists collaborate to improve timeliness of discharge communication. Hosp Pediatr. 2013;3(3):258265.
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Timely and reliable communication of important data between hospital‐based physicians and primary care physicians is critical for prevention of medical adverse events.[1, 2] Extrapolation from high‐performance organizations outside of medicine suggests that verbal communication is an important component of patient handoffs.[3, 4] Though the Joint Commission does not mandate verbal communication during handoffs per se, stipulating instead that handoff participants have an opportunity to ask and respond to questions,[5] there is some evidence that primary care providers prefer verbal handoffs at least for certain patients such as those with medical complexity.[6] Verbal communication offers the receiver the opportunity to ask questions, but in practice, 2‐way verbal communication is often difficult to achieve at hospital discharge.

At our institution, hospital medicine (HM) physicians serve as the primary inpatient providers for nearly 90% of all general pediatric admissions. When the HM service was established, primary care physicians (PCPs) and HM physicians together agreed upon an expectation for verbal, physician‐to‐physician communication at the time of discharge. Discharge communication is provided by either residents or attendings depending on the facility. A telephone operator service called Physician Priority Link (PPL) was made available to facilitate this communication. The PPL service is staffed 24/7 by operators whose only responsibilities are to connect providers inside and outside the institution. By utilizing this service, PCPs could respond in a nonemergent fashion to discharge phone calls.

Over the last several years, PCPs have observed high variation in the reliability of discharge communication phone calls. A review of PPL phone records in 2009 showed that only 52% of HM discharges had a record of a call initiated to the PCP on the day of discharge. The overall goal of this improvement project was to improve the completion of verbal handoffs from HM physicians (residents or attendings) to PCPs. The specific aim of the project was to increase the proportion of completed verbal handoffs from on‐call residents or attendings to PCPs within 24 hours of discharge to more than 90% within 18 months.

METHODS

Human Subjects Protection

Our project was undertaken in accordance with institutional review board (IRB) policy on systems improvement work and did not require formal IRB review.

Setting

This study included all patients admitted to the HM service at an academic children's hospital and its satellite campus.

Planning the Intervention

The project was championed by physicians on the HM service and supported by a chief resident, PPL administrators, and 2 information technology analysts.

At the onset of the project, the team mapped the process for completing a discharge call to the PCPs, conducted a modified failure mode and effects analysis,[7, 8] and examined the key drivers used to prioritize interventions (Figure 1). Through the modified failure modes effect analysis, the team was able to identify system issues that led to unsuccessful communication: failure of call initiation, absence of an identified PCP, long wait times on hold, failure of PCP to call back, and failure of the call to be documented. These failure modes informed the key drivers to achieving the study aim. Figure 2 depicts the final key drivers, which were revised through testing and learning.

Figure 1
Preintervention processes and failure modes for discharge communication with PCPs.
Figure 2
Key driver diagram for verbal communication at hospital discharge.

Interventions Targeting Key Stakeholder Buy‐in

To improve resident buy‐in and participation, the purpose and goals of the projects were discussed at resident morning report and during monthly team meetings by the pediatric chief resident on our improvement team. Resident physicians were interested in participating to reduce interruptions during daily rounds and to improve interactions with PCPs. The PPL staff was interested in standardizing the discharge call process to reduce confusion in identifying the appropriate contact when PCPs called residents back to discuss discharges. PCPs were interested in ensuring good communication at discharge, and individual PCPs were engaged through person‐to‐person contact by 1 of the HM physician champions.

Interventions to Standardization the Communication Process

To facilitate initiation of calls to PCPs at hospital discharge, the improvement team created a standard process using the PPL service (Figure 3). All patients discharged from the HM service were included in the process. Discharging physicians (who were usually but not always residents, depending on the facility), were instructed to call the PPL operator at the time of discharge. The PPL operator would then page the patient's PCP. It was the responsibility of the discharging physician to identify a PCP prior to discharge. Instances where no PCP was identified were counted as process failures because no phone call could be made. The expectation for the PCPs was that they would return the page within 20 minutes. PPL operators would then page back to the discharging physician to connect the 2 parties with the expectation that the discharging physician respond within 2 to 4 minutes to the PPL operator's page. Standardization of all calls through PPL allowed efficient tracking of incomplete calls and operators to reattempt calls that were not completed. This process also shifted the burden of following up on incomplete calls to PPL. The use of PPL to make the connection also allowed the physician to complete other work while awaiting a call back from the PCP.

Figure 3
Final process map for verbal communication at discharge.

Leveraging the Electronic Health Record for Process Initiation

To ensure reliable initiation of the discharge communication pathway, the improvement team introduced changes to the electronic health record (HER) (EpicCare Inpatient; Epic Systems Corp., Verona, WI), which generated a message to PPL operators whenever a discharge order was entered for an HM patient. The message contained the patient's name, medical record number, discharge date, discharging physician, and PCP name and phone number. A checklist was implemented by PPL to ensure that duplicate phone calls were not made. To initiate communication, the operator contacted the resident via text page to ensure they were ready to initiate the call. If the resident was ready to place a call, the operator then generated a phone call to the PCP. When the PCP returned the call, the operator connected the HM resident with the PCP for the handoff.

As the project progressed, several adaptations were made to address newly identified failure modes. To address confusion among PPL operators about which resident physicians should take discharge phone calls after the discharging resident was no longer available (for example, after a shift change), primary responsibility for discharge phone calls was reassigned to the daily on‐call resident rather than the resident who wrote the discharge order. Because the on‐call residents carry a single pager, the pager number listed on the automated discharge notification to PPL would never change and would always reach the appropriate team member. Second, to address the anticipated increase in interruption of resident workflow by calls back from PCPs, particularly during rounds, operators accessed information on pending discharge phone calls in batches at times of increased resident availability to minimize hold times for PCPs and work interruptions for the discharging physicians. Batch times were 1 pm and 4 pm to allow for completion of morning rounds, resident conference at noon, and patient‐care activities during the afternoon. Calls initiated after 4 pm were dispatched at the time of the discharge, and calls initiated after 10 pm were deferred to the following day.

Transparency of Data

Throughout the study, weekly failure data were generated from the EHR and emailed to improvement team members, enabling them to focus on near real‐time feedback of data to create a visible and more reliable system. With the standardization of all discharge calls directed to the PPL operators, the team was able to create a call record linked to the patient's medical record number. Team‐specific and overall results for the 5 HM resident teams were displayed weekly on a run chart in the resident conference room. As improvements in call initiation were demonstrated, completion rate data were also shared every several months with the attending hospitalists during a regularly scheduled divisional conference. This transparency of data gave the improvement team the opportunity to provide individual feedback to residents and attendings about failures. The weekly review of failure data allowed team leaders to learn from failures, identify knowledge gaps, and ensure accountability with the HM physicians.

Planning the Study of the Intervention

Data were collected prospectively from July 2011 to March 2014. A weekly list of patients discharged from the HM service was extracted from the EHR and compared to electronic call logs collected by PPL on the day of discharge. A standard sample size of 30 calls was audited separately by PPL and 1 of the physician leads to verify that the patients were discharged from the HM service and validate the percentage of completed and initiated calls.

The percentage of calls initiated within 24 hours of discharge was tracked as a process measure and served as the initial focus of improvement efforts. Our primary outcome measure was the percentage of calls completed to the PCP by the HM physician within 24 hours of discharge.

Methods of Evaluation and Analysis

We used improvement science methods and run charts to determine the percentage of patients discharged from the HM service with a call initiated to the PCP and completed within 24 hours of discharge. Data on calls initiated within 24 hours of discharge were plotted on a run chart to examine the impact of interventions over time. Once interventions targeted at call initiation had been implemented, we began tracking our primary outcome measure. A new run chart was created documenting the percentage of calls completed. For both metrics, the centerline was adjusted using established rules for special cause variation in run charts.[9, 10, 11, 12, 13]

RESULTS

From July 2011 to March 2014, there were 6313 discharges from the HM service. The process measure (percentage of calls initiated) improved from 50% to 97% after 4 interventions (Figure 4). Data for the outcome measure (percentage of calls completed) were collected starting in August 2012, shortly after linking the EHR discharge order to the discharge call. Over the first 8 weeks, our median was 80%, which increased to a median of 93% (Figure 5). These results were sustained for 18 months.

Figure 4
Percent of calls made to primary care physicians within 24 hours of hospital discharge.
Figure 5
Percent of calls to primary care physicians completed within 24 hours of discharge.

Several key interventions were identified that were critical to achievement of our goal. Standardization of the communication process through PPL was temporally associated with a shift in the median rate of call initiation from 52% to 72%. Use of the discharge order to initiate discharge communication was associated with an increase from 72% to 97%. Finally, the percentage of completed verbal handoffs increased to more than 93% following batching of phone calls to PCPs at specific times during the day.

DISCUSSION

We used improvement and reliability science methods to implement a successful process for improving verbal handoffs from HM physicians to PCPs within 24 hours of discharge to 93%. This result has been sustained for 18 months.

Utilization of the PPL call center for flexible call facilitation along with support for data analysis and leveraging the EHR to automate the process increased reliability, leading to rapid improvement. Prior to mandating the use of PPL to connect discharging physicians with PCPs, the exact rate of successful handoffs in our institution was not known. We do know, however, that only 52% of calls were initiated, so clearly a large gap was present prior to our improvement work. Data collection from the PPL system was automated so that accurate, timely, and sustainable data could be provided, greatly aiding improvement efforts. Flexibility in call‐back timing was also crucial, because coordinating the availability of PCPs and discharging physicians is often challenging. The EHR‐initiated process for discharge communication was a key intervention, and improvement of our process measure to 97% performance was associated with this implementation. Two final interventions: (1) assignment of responsibility for communication to a team pager held by a designated resident and (2) batching of calls to specific times streamlined the EHR‐initiated process and were associated with achievement of our main outcome goal of >90% completed verbal communication.

There are several reports of successful interventions to improve receipt or content of discharge summaries by PCPs following hospital discharge available in the literature.[14, 15, 16, 17, 18, 19, 20] Recently, Shen et al. reported on the success of a multisite improvement collaborative involving pediatric hospitalist programs at community hospitals whose aim was to improve the timely documentation of communication directed at PCPs.[21] In their report, all 7 hospital sites that participated in the collaborative for more than 4 months were able to demonstrate substantial improvement in documentation of some form of communication directed at PCPs (whether by e‐mail, fax, or telephone call), from a baseline of approximately 50% to more than 90%. A limitation of their study was that they were unable to document whether PCPs had received any information or by what method. A recent survey of PCPs by Sheu et al. indicated that for many discharges, information in addition to that present in the EHR was desirable to ensure a safe transition of care.[6] Two‐way communication, such as with a phone call, allows for senders to verify information receipt and for receivers to ask questions to ensure complete information. To our knowledge, there have been no previous reports describing processes for improving verbal communication between hospitalist services and PCPs at discharge.

It may be that use of the call system allowed PCPs to return phone calls regarding discharges at convenient stopping points in their day while allowing discharging physicians to initiate a call without having to wait on hold. Interestingly, though we anticipated the need for additional PPL resources during the course of this improvement, the final process was efficient enough that PPL did not require additional staffing to accommodate the higher call volume.

A key insight during our implementation was that relying on the EHR to initiate every discharge communication created disruption of resident workflow due to disregard of patient, resident, and PCP factors. This was reflected by the improvement in call initiation (our process measure) following this intervention, whereas at the same time call completion (our outcome measure) remained below goal. To achieve our goal of completing verbal communication required a process that was highly reliable yet flexible enough to allow discharging physicians to complete the call in the unpredictable environment of inpatient care. Ultimately, this was achieved by allowing discharging physicians to initiate the process when convenient, and allowing for the EHR‐initiated process to function as a backup strategy to identify and mitigate failures of initiation.

An important limitation of our study was the lack of PCPs on the improvement team, likely making the success of the project more difficult than it might have been. For example, during the study we did not measure the time PCPs spent on hold or how many reattempts were needed to complete the communication loop. Immediately following the completion of our study, it became apparent that physicians returning calls for our own institution's primary care clinic were experiencing regular workflow interruptions and occasional hold times more than 20 minutes, necessitating ongoing further work to determine the root causes and solutions to these problems. Though this work is ongoing, average PCP hold times measured from a sample of call reviews in 2013 to 2014 was 3 minutes and 15 seconds.

This study has several other limitations. We were unable to account for phone calls to PCPs initiated outside of the new process. It may be that PCPs were called more than 52% of the time at baseline due to noncompliance with the new protocol. Also, we only have data for call completion starting after implementation of the link between the discharge order and the discharge phone call, making the baseline appear artificially high and precluding any analysis of how earlier interventions affected our outcome metric. Communication with PCPs should ideally occur prior to discharge. An important limitation of our process is that calls could occur several hours after discharge between an on‐call resident and an on‐call outpatient physician rather than between the PCP and the discharging resident, limiting appropriate information exchange. Though verbal discharge communication is a desirable goal for many reasons, the current project did not focus on the quality of the call or the information that was transmitted to the PCP. Additionally, direct attending‐to‐attending communication may be valuable with medically or socially complex discharges, but we did not have a process to facilitate this. We also did not measure what effect our new process had on outcomes such as quality of patient and family transition from hospital or physician satisfaction. The existence of programs similar to our PPL subspecialty referral line may be limited to large institutions. However, it should be noted that although some internal resource reallocation was necessary within PPL, no actual staffing increases were required despite a large increase in call volume. It may be that any hospital operator system could be adapted for this purpose with modest additional resources. Finally, although our EHR system is widely utilized, there are many competing systems in the market, and our intervention required utilization of EHR capabilities that may not be present in all systems. However, our EHR intervention utilized existing functionality and did not require modification of the system.

This project focused on discharge phone calls to primary care physicians for patients hospitalized on the hospital medicine service. Because communication with the PCP should ideally occur prior to discharge, future work will include identifying a more proximal trigger than the discharge order to which to link the EHR trigger for discharge communication. Other next steps to improve handoff effectiveness and optimize the efficiency of our process include identifying essential information that should be transmitted to the primary care physician at the time of the phone call, developing processes to ensure communication of this information, measuring PCP satisfaction with this communication, and measuring the impact on patient outcomes. Finally, though expert opinion indicates that verbal handoffs may have safety advantages over nonverbal handoffs, studies comparing the safety and efficacy of verbal versus nonverbal handoffs at patient discharge are lacking. Studies establishing the relative efficacy and safety of verbal versus nonverbal handoffs at hospital discharge are needed. Knowledge gained from these activities could inform future projects centered on the spread of the process to other hospital services and/or other hospitals.

CONCLUSION

We increased the percentage of calls initiated to PCPs at patient discharge from 52% to 97% and the percentage of calls completed between HM physicians and PCPs to 93% through the use of a standardized discharge communication process coupled with a basic EHR messaging functionality. The results of this study may be of interest for further testing and adaptation for any institution with an electronic healthcare system.

Disclosure: Nothing to report.

Timely and reliable communication of important data between hospital‐based physicians and primary care physicians is critical for prevention of medical adverse events.[1, 2] Extrapolation from high‐performance organizations outside of medicine suggests that verbal communication is an important component of patient handoffs.[3, 4] Though the Joint Commission does not mandate verbal communication during handoffs per se, stipulating instead that handoff participants have an opportunity to ask and respond to questions,[5] there is some evidence that primary care providers prefer verbal handoffs at least for certain patients such as those with medical complexity.[6] Verbal communication offers the receiver the opportunity to ask questions, but in practice, 2‐way verbal communication is often difficult to achieve at hospital discharge.

At our institution, hospital medicine (HM) physicians serve as the primary inpatient providers for nearly 90% of all general pediatric admissions. When the HM service was established, primary care physicians (PCPs) and HM physicians together agreed upon an expectation for verbal, physician‐to‐physician communication at the time of discharge. Discharge communication is provided by either residents or attendings depending on the facility. A telephone operator service called Physician Priority Link (PPL) was made available to facilitate this communication. The PPL service is staffed 24/7 by operators whose only responsibilities are to connect providers inside and outside the institution. By utilizing this service, PCPs could respond in a nonemergent fashion to discharge phone calls.

Over the last several years, PCPs have observed high variation in the reliability of discharge communication phone calls. A review of PPL phone records in 2009 showed that only 52% of HM discharges had a record of a call initiated to the PCP on the day of discharge. The overall goal of this improvement project was to improve the completion of verbal handoffs from HM physicians (residents or attendings) to PCPs. The specific aim of the project was to increase the proportion of completed verbal handoffs from on‐call residents or attendings to PCPs within 24 hours of discharge to more than 90% within 18 months.

METHODS

Human Subjects Protection

Our project was undertaken in accordance with institutional review board (IRB) policy on systems improvement work and did not require formal IRB review.

Setting

This study included all patients admitted to the HM service at an academic children's hospital and its satellite campus.

Planning the Intervention

The project was championed by physicians on the HM service and supported by a chief resident, PPL administrators, and 2 information technology analysts.

At the onset of the project, the team mapped the process for completing a discharge call to the PCPs, conducted a modified failure mode and effects analysis,[7, 8] and examined the key drivers used to prioritize interventions (Figure 1). Through the modified failure modes effect analysis, the team was able to identify system issues that led to unsuccessful communication: failure of call initiation, absence of an identified PCP, long wait times on hold, failure of PCP to call back, and failure of the call to be documented. These failure modes informed the key drivers to achieving the study aim. Figure 2 depicts the final key drivers, which were revised through testing and learning.

Figure 1
Preintervention processes and failure modes for discharge communication with PCPs.
Figure 2
Key driver diagram for verbal communication at hospital discharge.

Interventions Targeting Key Stakeholder Buy‐in

To improve resident buy‐in and participation, the purpose and goals of the projects were discussed at resident morning report and during monthly team meetings by the pediatric chief resident on our improvement team. Resident physicians were interested in participating to reduce interruptions during daily rounds and to improve interactions with PCPs. The PPL staff was interested in standardizing the discharge call process to reduce confusion in identifying the appropriate contact when PCPs called residents back to discuss discharges. PCPs were interested in ensuring good communication at discharge, and individual PCPs were engaged through person‐to‐person contact by 1 of the HM physician champions.

Interventions to Standardization the Communication Process

To facilitate initiation of calls to PCPs at hospital discharge, the improvement team created a standard process using the PPL service (Figure 3). All patients discharged from the HM service were included in the process. Discharging physicians (who were usually but not always residents, depending on the facility), were instructed to call the PPL operator at the time of discharge. The PPL operator would then page the patient's PCP. It was the responsibility of the discharging physician to identify a PCP prior to discharge. Instances where no PCP was identified were counted as process failures because no phone call could be made. The expectation for the PCPs was that they would return the page within 20 minutes. PPL operators would then page back to the discharging physician to connect the 2 parties with the expectation that the discharging physician respond within 2 to 4 minutes to the PPL operator's page. Standardization of all calls through PPL allowed efficient tracking of incomplete calls and operators to reattempt calls that were not completed. This process also shifted the burden of following up on incomplete calls to PPL. The use of PPL to make the connection also allowed the physician to complete other work while awaiting a call back from the PCP.

Figure 3
Final process map for verbal communication at discharge.

Leveraging the Electronic Health Record for Process Initiation

To ensure reliable initiation of the discharge communication pathway, the improvement team introduced changes to the electronic health record (HER) (EpicCare Inpatient; Epic Systems Corp., Verona, WI), which generated a message to PPL operators whenever a discharge order was entered for an HM patient. The message contained the patient's name, medical record number, discharge date, discharging physician, and PCP name and phone number. A checklist was implemented by PPL to ensure that duplicate phone calls were not made. To initiate communication, the operator contacted the resident via text page to ensure they were ready to initiate the call. If the resident was ready to place a call, the operator then generated a phone call to the PCP. When the PCP returned the call, the operator connected the HM resident with the PCP for the handoff.

As the project progressed, several adaptations were made to address newly identified failure modes. To address confusion among PPL operators about which resident physicians should take discharge phone calls after the discharging resident was no longer available (for example, after a shift change), primary responsibility for discharge phone calls was reassigned to the daily on‐call resident rather than the resident who wrote the discharge order. Because the on‐call residents carry a single pager, the pager number listed on the automated discharge notification to PPL would never change and would always reach the appropriate team member. Second, to address the anticipated increase in interruption of resident workflow by calls back from PCPs, particularly during rounds, operators accessed information on pending discharge phone calls in batches at times of increased resident availability to minimize hold times for PCPs and work interruptions for the discharging physicians. Batch times were 1 pm and 4 pm to allow for completion of morning rounds, resident conference at noon, and patient‐care activities during the afternoon. Calls initiated after 4 pm were dispatched at the time of the discharge, and calls initiated after 10 pm were deferred to the following day.

Transparency of Data

Throughout the study, weekly failure data were generated from the EHR and emailed to improvement team members, enabling them to focus on near real‐time feedback of data to create a visible and more reliable system. With the standardization of all discharge calls directed to the PPL operators, the team was able to create a call record linked to the patient's medical record number. Team‐specific and overall results for the 5 HM resident teams were displayed weekly on a run chart in the resident conference room. As improvements in call initiation were demonstrated, completion rate data were also shared every several months with the attending hospitalists during a regularly scheduled divisional conference. This transparency of data gave the improvement team the opportunity to provide individual feedback to residents and attendings about failures. The weekly review of failure data allowed team leaders to learn from failures, identify knowledge gaps, and ensure accountability with the HM physicians.

Planning the Study of the Intervention

Data were collected prospectively from July 2011 to March 2014. A weekly list of patients discharged from the HM service was extracted from the EHR and compared to electronic call logs collected by PPL on the day of discharge. A standard sample size of 30 calls was audited separately by PPL and 1 of the physician leads to verify that the patients were discharged from the HM service and validate the percentage of completed and initiated calls.

The percentage of calls initiated within 24 hours of discharge was tracked as a process measure and served as the initial focus of improvement efforts. Our primary outcome measure was the percentage of calls completed to the PCP by the HM physician within 24 hours of discharge.

Methods of Evaluation and Analysis

We used improvement science methods and run charts to determine the percentage of patients discharged from the HM service with a call initiated to the PCP and completed within 24 hours of discharge. Data on calls initiated within 24 hours of discharge were plotted on a run chart to examine the impact of interventions over time. Once interventions targeted at call initiation had been implemented, we began tracking our primary outcome measure. A new run chart was created documenting the percentage of calls completed. For both metrics, the centerline was adjusted using established rules for special cause variation in run charts.[9, 10, 11, 12, 13]

RESULTS

From July 2011 to March 2014, there were 6313 discharges from the HM service. The process measure (percentage of calls initiated) improved from 50% to 97% after 4 interventions (Figure 4). Data for the outcome measure (percentage of calls completed) were collected starting in August 2012, shortly after linking the EHR discharge order to the discharge call. Over the first 8 weeks, our median was 80%, which increased to a median of 93% (Figure 5). These results were sustained for 18 months.

Figure 4
Percent of calls made to primary care physicians within 24 hours of hospital discharge.
Figure 5
Percent of calls to primary care physicians completed within 24 hours of discharge.

Several key interventions were identified that were critical to achievement of our goal. Standardization of the communication process through PPL was temporally associated with a shift in the median rate of call initiation from 52% to 72%. Use of the discharge order to initiate discharge communication was associated with an increase from 72% to 97%. Finally, the percentage of completed verbal handoffs increased to more than 93% following batching of phone calls to PCPs at specific times during the day.

DISCUSSION

We used improvement and reliability science methods to implement a successful process for improving verbal handoffs from HM physicians to PCPs within 24 hours of discharge to 93%. This result has been sustained for 18 months.

Utilization of the PPL call center for flexible call facilitation along with support for data analysis and leveraging the EHR to automate the process increased reliability, leading to rapid improvement. Prior to mandating the use of PPL to connect discharging physicians with PCPs, the exact rate of successful handoffs in our institution was not known. We do know, however, that only 52% of calls were initiated, so clearly a large gap was present prior to our improvement work. Data collection from the PPL system was automated so that accurate, timely, and sustainable data could be provided, greatly aiding improvement efforts. Flexibility in call‐back timing was also crucial, because coordinating the availability of PCPs and discharging physicians is often challenging. The EHR‐initiated process for discharge communication was a key intervention, and improvement of our process measure to 97% performance was associated with this implementation. Two final interventions: (1) assignment of responsibility for communication to a team pager held by a designated resident and (2) batching of calls to specific times streamlined the EHR‐initiated process and were associated with achievement of our main outcome goal of >90% completed verbal communication.

There are several reports of successful interventions to improve receipt or content of discharge summaries by PCPs following hospital discharge available in the literature.[14, 15, 16, 17, 18, 19, 20] Recently, Shen et al. reported on the success of a multisite improvement collaborative involving pediatric hospitalist programs at community hospitals whose aim was to improve the timely documentation of communication directed at PCPs.[21] In their report, all 7 hospital sites that participated in the collaborative for more than 4 months were able to demonstrate substantial improvement in documentation of some form of communication directed at PCPs (whether by e‐mail, fax, or telephone call), from a baseline of approximately 50% to more than 90%. A limitation of their study was that they were unable to document whether PCPs had received any information or by what method. A recent survey of PCPs by Sheu et al. indicated that for many discharges, information in addition to that present in the EHR was desirable to ensure a safe transition of care.[6] Two‐way communication, such as with a phone call, allows for senders to verify information receipt and for receivers to ask questions to ensure complete information. To our knowledge, there have been no previous reports describing processes for improving verbal communication between hospitalist services and PCPs at discharge.

It may be that use of the call system allowed PCPs to return phone calls regarding discharges at convenient stopping points in their day while allowing discharging physicians to initiate a call without having to wait on hold. Interestingly, though we anticipated the need for additional PPL resources during the course of this improvement, the final process was efficient enough that PPL did not require additional staffing to accommodate the higher call volume.

A key insight during our implementation was that relying on the EHR to initiate every discharge communication created disruption of resident workflow due to disregard of patient, resident, and PCP factors. This was reflected by the improvement in call initiation (our process measure) following this intervention, whereas at the same time call completion (our outcome measure) remained below goal. To achieve our goal of completing verbal communication required a process that was highly reliable yet flexible enough to allow discharging physicians to complete the call in the unpredictable environment of inpatient care. Ultimately, this was achieved by allowing discharging physicians to initiate the process when convenient, and allowing for the EHR‐initiated process to function as a backup strategy to identify and mitigate failures of initiation.

An important limitation of our study was the lack of PCPs on the improvement team, likely making the success of the project more difficult than it might have been. For example, during the study we did not measure the time PCPs spent on hold or how many reattempts were needed to complete the communication loop. Immediately following the completion of our study, it became apparent that physicians returning calls for our own institution's primary care clinic were experiencing regular workflow interruptions and occasional hold times more than 20 minutes, necessitating ongoing further work to determine the root causes and solutions to these problems. Though this work is ongoing, average PCP hold times measured from a sample of call reviews in 2013 to 2014 was 3 minutes and 15 seconds.

This study has several other limitations. We were unable to account for phone calls to PCPs initiated outside of the new process. It may be that PCPs were called more than 52% of the time at baseline due to noncompliance with the new protocol. Also, we only have data for call completion starting after implementation of the link between the discharge order and the discharge phone call, making the baseline appear artificially high and precluding any analysis of how earlier interventions affected our outcome metric. Communication with PCPs should ideally occur prior to discharge. An important limitation of our process is that calls could occur several hours after discharge between an on‐call resident and an on‐call outpatient physician rather than between the PCP and the discharging resident, limiting appropriate information exchange. Though verbal discharge communication is a desirable goal for many reasons, the current project did not focus on the quality of the call or the information that was transmitted to the PCP. Additionally, direct attending‐to‐attending communication may be valuable with medically or socially complex discharges, but we did not have a process to facilitate this. We also did not measure what effect our new process had on outcomes such as quality of patient and family transition from hospital or physician satisfaction. The existence of programs similar to our PPL subspecialty referral line may be limited to large institutions. However, it should be noted that although some internal resource reallocation was necessary within PPL, no actual staffing increases were required despite a large increase in call volume. It may be that any hospital operator system could be adapted for this purpose with modest additional resources. Finally, although our EHR system is widely utilized, there are many competing systems in the market, and our intervention required utilization of EHR capabilities that may not be present in all systems. However, our EHR intervention utilized existing functionality and did not require modification of the system.

This project focused on discharge phone calls to primary care physicians for patients hospitalized on the hospital medicine service. Because communication with the PCP should ideally occur prior to discharge, future work will include identifying a more proximal trigger than the discharge order to which to link the EHR trigger for discharge communication. Other next steps to improve handoff effectiveness and optimize the efficiency of our process include identifying essential information that should be transmitted to the primary care physician at the time of the phone call, developing processes to ensure communication of this information, measuring PCP satisfaction with this communication, and measuring the impact on patient outcomes. Finally, though expert opinion indicates that verbal handoffs may have safety advantages over nonverbal handoffs, studies comparing the safety and efficacy of verbal versus nonverbal handoffs at patient discharge are lacking. Studies establishing the relative efficacy and safety of verbal versus nonverbal handoffs at hospital discharge are needed. Knowledge gained from these activities could inform future projects centered on the spread of the process to other hospital services and/or other hospitals.

CONCLUSION

We increased the percentage of calls initiated to PCPs at patient discharge from 52% to 97% and the percentage of calls completed between HM physicians and PCPs to 93% through the use of a standardized discharge communication process coupled with a basic EHR messaging functionality. The results of this study may be of interest for further testing and adaptation for any institution with an electronic healthcare system.

Disclosure: Nothing to report.

References
  1. Goldman L, Pantilat SZ, Whitcomb WF. Passing the clinical baton: 6 principles to guide the hospitalist. Am J Med. 2001;111(9B):36S39S.
  2. Ruth JL, Geskey JM, Shaffer ML, Bramley HP, Paul IM. Evaluating communication between pediatric primary care physicians and hospitalists. Clin Pediatr. 2011;50(10):923928.
  3. Arora VM, Manjarrez E, Dressler DD, Basaviah P, Halasyamani L, Kripalani S. Hospitalist handoffs: a systematic review and task force recommendations. J Hosp Med. 2009;4(7):433440.
  4. Patterson ES, Roth EM, Woods DD, Chow R, Gomes JO. Handoff strategies in settings with high consequences for failure: lessons for health care operations. Int J Qual Health Care. 2004;16(2):125132.
  5. Agency for Healthcare Research and Quality. Patient safety primers: handoffs and signouts. Available at: http://www.psnet.ahrq.gov/primer.aspx?primerID=9. Accessed March 19, 2014.
  6. Sheu L, Fung K, Mourad M, Ranji S, Wu E. We need to talk: primary care provider communication at discharge in the era of a shared electronic medical record. J Hosp Med. 2015;10(5):307310.
  7. Cohen M, Senders J, Davis N. Failure mode and effects analysis: a novel approach to avoiding dangerous medication errors and accidents. Hosp Pharm. 1994;29:319330.
  8. DeRosier J, Stalhandske E, Bagian J, Nudell T. Using health care Failure Mode and Effect Analysis: the VA National Center for Patient Safety's prospective risk analysis system. Jt Comm J Qual Improv. 2002;28:248267, 209.
  9. Benneyan JC. Statistical quality control methods in infection control and hospital epidemiology, Part II: Chart use, statistical properties, and research issues. Infect Control Hosp Epidemiol. 1998;19(4):265283.
  10. Benneyan JC. Statistical quality control methods in infection control and hospital epidemiology, part I: Introduction and basic theory. Infect Control Hosp Epidemiol. 1998;19(3):194214.
  11. Benneyan JC, Lloyd RC, Plsek PE. Statistical process control as a tool for research and healthcare improvement. Qual Saf Health Care. 2003;12(6):458464.
  12. Langley GJ. The Improvement Guide: A Practical Approach to Enhancing Organizational +Performance. 2nd ed. San Francisco, CA: Jossey‐Bass; 2009.
  13. Provost LP, Murray SK. The Health Care Data Guide: Learning From Data for Improvement. 1st ed. San Francisco, CA: Jossey‐Bass; 2011.
  14. Dover SB, Low‐Beer TS. The initial hospital discharge note: send out with the patient or post? Health Trends. 1984;16(2):48.
  15. Kendrick AR, Hindmarsh DJ. Which type of hospital discharge report reaches general practitioners most quickly? BMJ. 1989;298(6670):362363.
  16. Smith RP, Holzman GB. The application of a computer data base system to the generation of hospital discharge summaries. Obstet Gynecol. 1989;73(5 pt 1):803807.
  17. Kenny C. Hospital discharge medication: is seven days supply sufficient? Public Health. 1991;105(3):243247.
  18. Branger PJ, Wouden JC, Schudel BR, et al. Electronic communication between providers of primary and secondary care. BMJ. 1992;305(6861):10681070.
  19. Curran P, Gilmore DH, Beringer TR. Communication of discharge information for elderly patients in hospital. Ulster Med J. 1992;61(1):5658.
  20. Mant A, Kehoe L, Cockayne NL, Kaye KI, Rotem WC. A quality use of medicines program for continuity of care in therapeutics from hospital to community. Med J Aust. 2002;177(1):3234.
  21. Shen MW, Hershey D, Bergert L, Mallory L, Fisher ES, Cooperberg D. Pediatric hospitalists collaborate to improve timeliness of discharge communication. Hosp Pediatr. 2013;3(3):258265.
References
  1. Goldman L, Pantilat SZ, Whitcomb WF. Passing the clinical baton: 6 principles to guide the hospitalist. Am J Med. 2001;111(9B):36S39S.
  2. Ruth JL, Geskey JM, Shaffer ML, Bramley HP, Paul IM. Evaluating communication between pediatric primary care physicians and hospitalists. Clin Pediatr. 2011;50(10):923928.
  3. Arora VM, Manjarrez E, Dressler DD, Basaviah P, Halasyamani L, Kripalani S. Hospitalist handoffs: a systematic review and task force recommendations. J Hosp Med. 2009;4(7):433440.
  4. Patterson ES, Roth EM, Woods DD, Chow R, Gomes JO. Handoff strategies in settings with high consequences for failure: lessons for health care operations. Int J Qual Health Care. 2004;16(2):125132.
  5. Agency for Healthcare Research and Quality. Patient safety primers: handoffs and signouts. Available at: http://www.psnet.ahrq.gov/primer.aspx?primerID=9. Accessed March 19, 2014.
  6. Sheu L, Fung K, Mourad M, Ranji S, Wu E. We need to talk: primary care provider communication at discharge in the era of a shared electronic medical record. J Hosp Med. 2015;10(5):307310.
  7. Cohen M, Senders J, Davis N. Failure mode and effects analysis: a novel approach to avoiding dangerous medication errors and accidents. Hosp Pharm. 1994;29:319330.
  8. DeRosier J, Stalhandske E, Bagian J, Nudell T. Using health care Failure Mode and Effect Analysis: the VA National Center for Patient Safety's prospective risk analysis system. Jt Comm J Qual Improv. 2002;28:248267, 209.
  9. Benneyan JC. Statistical quality control methods in infection control and hospital epidemiology, Part II: Chart use, statistical properties, and research issues. Infect Control Hosp Epidemiol. 1998;19(4):265283.
  10. Benneyan JC. Statistical quality control methods in infection control and hospital epidemiology, part I: Introduction and basic theory. Infect Control Hosp Epidemiol. 1998;19(3):194214.
  11. Benneyan JC, Lloyd RC, Plsek PE. Statistical process control as a tool for research and healthcare improvement. Qual Saf Health Care. 2003;12(6):458464.
  12. Langley GJ. The Improvement Guide: A Practical Approach to Enhancing Organizational +Performance. 2nd ed. San Francisco, CA: Jossey‐Bass; 2009.
  13. Provost LP, Murray SK. The Health Care Data Guide: Learning From Data for Improvement. 1st ed. San Francisco, CA: Jossey‐Bass; 2011.
  14. Dover SB, Low‐Beer TS. The initial hospital discharge note: send out with the patient or post? Health Trends. 1984;16(2):48.
  15. Kendrick AR, Hindmarsh DJ. Which type of hospital discharge report reaches general practitioners most quickly? BMJ. 1989;298(6670):362363.
  16. Smith RP, Holzman GB. The application of a computer data base system to the generation of hospital discharge summaries. Obstet Gynecol. 1989;73(5 pt 1):803807.
  17. Kenny C. Hospital discharge medication: is seven days supply sufficient? Public Health. 1991;105(3):243247.
  18. Branger PJ, Wouden JC, Schudel BR, et al. Electronic communication between providers of primary and secondary care. BMJ. 1992;305(6861):10681070.
  19. Curran P, Gilmore DH, Beringer TR. Communication of discharge information for elderly patients in hospital. Ulster Med J. 1992;61(1):5658.
  20. Mant A, Kehoe L, Cockayne NL, Kaye KI, Rotem WC. A quality use of medicines program for continuity of care in therapeutics from hospital to community. Med J Aust. 2002;177(1):3234.
  21. Shen MW, Hershey D, Bergert L, Mallory L, Fisher ES, Cooperberg D. Pediatric hospitalists collaborate to improve timeliness of discharge communication. Hosp Pediatr. 2013;3(3):258265.
Issue
Journal of Hospital Medicine - 10(9)
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Journal of Hospital Medicine - 10(9)
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574-580
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Improving the reliability of verbal communication between primary care physicians and pediatric hospitalists at hospital discharge
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Improving the reliability of verbal communication between primary care physicians and pediatric hospitalists at hospital discharge
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© 2015 Society of Hospital Medicine

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Address for correspondence and reprint requests: Grant Mussman, MD, MLC 3024, Division of Hospital Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; E‐mail: [email protected]
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Baby Boomer HCV Screening and Care

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Implementing hospital‐based baby boomer hepatitis c virus screening and linkage to care: Strategies, results, and costs

INTRODUCTION

The baby boomer generation, born from 1945 to 1965, accounts for 75% of the estimated 2.7 to 3.9 million persons with chronic hepatitis C virus (HCV) infection in the US.[1, 2, 3] Most HCV‐infected baby boomers do not know that they are infected.[4] With the advent of better‐tolerated, more‐effective therapies to treat chronic HCV infection,[5] and to reduce rates of complications such as cirrhosis, liver failure, and hepatocellular carcinoma,[6] universal 1‐time screening of baby boomers has been endorsed by the Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force.[1, 7] Hospitalized baby boomers may offer an important target for HCV screening. Our group conducted an anonymous HCV seroprevalence study of nearly 800 patients on general medicine and trauma services of 2 Philadelphia hospitals, and found that 8% had undiagnosed HCV infection, and 8% had diagnosed HCV. [8]

Little is known about barriers and facilitators to implementation of universal HCV screening of baby boomers. Lessons from implementing HIV screening offer a useful guide.[9] First, limited clinician knowledge and confusion about screening guidelines necessitated convenient, well‐designed educational programs.[10] Second, burdensome consent procedures were reduced by opt‐out consent for screening supplemented by patient education.[9] Third, electronic medical record (EMR) algorithms minimized burdens on staff by efficiently identifying and flagging eligible persons for screening.[11] Fourth, ancillary staff support for patient education and linkage to follow‐up care increased screening rates compared with usual care by physicians/staff.[11] Finally, routine human immunodeficiency virus (HIV) testing of inpatients increased rates of diagnosis, especially compared with physician referral systems.[12]

This article describes how HIV screening strategies informed the development in a baby boomer HCV screening and linkage to a care program in a safety‐net hospital serving a majority Hispanic population. We report results of the first 14 months of the screening program and linkage to care for chronically HCV‐infected persons after a minimum 10 months follow‐up. We also estimate costs for program implementation and maintenance to inform hospital administrators, healthcare policymakers, and clinicians about resources that may be required to effectively screen hospitalized baby boomers for HCV.

METHODS

Study Setting

The HCV baby boomer screening program was pilot tested in November 2012 and launched December 1, 2012 in a 498‐bed academic‐affiliated hospital of a healthcare system serving the indigent population of South Texas.

Project Development Phase

From October 1, 2012 to November 30, 2012, project infrastructure development and provider/staff education were conducted. A half‐hour PowerPoint lecture (in person or online) was developed about HCV epidemiology, birth‐cohort HCV screening guidelines, newer treatment modalities, and screening program components. Lectures were delivered to departmental chairs at the affiliated medical school, departmental grand rounds, and the hospital's nursing supervisors. One‐on‐one informational meetings were also held with hospital administrators and staff.

With the hospital's information technology team, screens were developed to identify eligible baby boomers from up to 7 years of previous inpatient and outpatient encounters in the EMR from: birth year (19451965) and no prior diagnosis of HCV infection (070.41, 070.44, 070.51, 070.54, 070.7x, V02.62) or any type of completed test for HCV. The algorithm also excluded patients admitted to psychiatry due to lack of decision‐making capacity or patients with a poor prognosis such as metastatic cancer. An audit of 100 consecutive excluded patients identified all as legitimate.

A new laboratory order for HCV screening was developed by laboratory administrators and pathology faculty for an anti‐HCV antibody test followed by reflex HCV RNA testing for positive results per CDC recommendations.[13] The anti‐HCV test was performed on serum or ethylenediaminetetraacetic acid plasma using the Advia Centaur HCV Assay (Bayer HealthCare LLC, Tarrytown, NY). This assay has excellent sensitivity (99.9%) and specificity (97.5%).[14, 15] The HCV RNA assay was performed using quantitative real‐time polymerase chain reaction (PCR) using the COBAS AmpliPrep/COBAS TaqMan HCV test (Roche Molecular Systems, Pleasanton, CA). Use of plasma preparation tubes (PPTs) (BD Vacutainer PPT tubes; Becton, Dickinson and Co., Franklin Lakes, NJ) permitted both anti‐HCV antibody and HCV PCR testing to be performed on the same specimen when anti‐HCV antibody was detected, eliminating a second blood draw for the PCR test. For patients eligible for screening, an EMR algorithm was created to add an HCV screening order to over 50 different admission order sets.

To educate patients newly diagnosed with HCV infection, we developed an interactive, low‐literacy, educational program in Spanish and English for an electronic tablet device that addressed: HCV epidemiology, transmission prevention, factors that can accelerate chronic HCV infection, and management/treatment strategies. At several points in the program, the patient needed to answer questions correctly to continue. The tablet retained responses linked to a study identification about alcohol consumption, history of past and current illicit drug use, sexual risk behavior, and offered risk reduction messages. The tablet content and presentation reflected suggestions by Hispanic patient‐reviewers about cultural appropriateness and comprehension.

Project Implementation and Maintenance Phase

We report implementation of the program from December 1, 2012 to January 31, 2014. An automated EMR report classified all baby boomers admitted in the previous 24 hours as: (1) eligible with pending screening test order, (2) eligible without an order, (3) ineligible due to prior HCV test or diagnosis, or (4) ineligible due to comorbidity (eg, metastatic cancer). For approximately one‐third of eligible patients, a study team member placed an order after review of the daily admission report because the order had not been automatically placed.

Admitting nurses initially asked for consent from eligible patients for HCV screening, but this was ultimately deemed too onerous a task along with all of their other duties. We then instituted opt‐out consent with patient education about testing and opportunities to refuse via posters placed throughout the hospital and flyers in admission packets. A bilingual HCV counselor provided HCV screening test results to all patients. She counseled patients who screened positive for HCV with the educational program on an electronic tablet and developed a follow‐up care plan.

A bilingual promotora (community health worker) contacted patients newly diagnosed with chronic HCV infection after hospital discharge to address the following: obtaining insurance, access to primary care and HCV specialty care, scheduling appointments, and treatment for alcohol problems or drug abuse. After obtaining signed consent, the promotora sent test results and recommendations for follow‐up care (eg, hepatitis A and B immunization) to a designated outpatient physician and reminded patients about appointments and pending tests. The promotora received training in motivational interviewing skills to engage patients with needed care including alcohol treatment.

Study Data

A summary report was developed from the EMR with demographic, insurance, clinical, and HCV screening data for all admitted baby boomers. For patients diagnosed with chronic HCV infection, the promotora obtained data about follow‐up HCV care through December 10, 2014 from the EMR, outside provider records, and patient reports.

Study Variables

The 2 outcome measures were a positive anti‐HCV antibody test and positive HCV RNA test. Insurance status was categorized as insured (private, public, Veterans Administration, Department of Defense) or uninsured (self‐pay or county‐based financial assistance program). Problem drinking was identified from International Classification of Diseases, Ninth Revision, Clinical Modification codes for the admission, notes by clinicians describing alcohol abuse/dependence, or quantity/frequency meeting National Institute on Alcohol Abuse and Alcoholism criteria for alcohol problems of >14 drinks/week or >4 drinks/day for men and >7 drinks per week or >3 drinks per day for women.[16]

Implementation costs included informatics support, mobile app development, other patient educational materials, costs of screening tests for uninsured, and 0.3 full‐time equivalent (FTE) of a clinician for half a year. Maintenance costs included salaries for the study team, HCV testing costs, and postage.

Analysis

Demographics by HCV antibody test results are compared using [2] tests or Student t tests as appropriate. Among persons with a positive HCV antibody test, HCV RNA results are similarly compared. This implementation project was approved by the University of Texas Health Science Center at San Antonio Institutional Review Board (HSC20130033N).

RESULTS

Within 14 months, 6410 unique baby boomers were admitted with a mean age 56.4 years (standard deviation [SD] 5.7), 55.9% men, 59.1% Hispanic, 8.2% nonwhite, and 46.7% uninsured (Table 1). Among admitted patients, 729 (11.4%) had a previous HCV diagnosis and 1904 (29.7%) had been tested for HCV (Figure 1). Anti‐HCV antibody testing was completed for 3168 (49.4% of all admitted patients and 83.9% of never‐tested patients). After exclusions such as significant comorbidity or psychiatric admission, 95% of eligible persons were tested. Of screened patients, 240 (7.6%) were positive; these patients were significantly younger (P<0.0001) and more likely to be men (P<0.0001) and uninsured (P=0.002) (Table 1). Notably, 10% of men were anti‐HCV positive versus 4% of women. In this predominantly Hispanic cohort, no significant difference appeared by race‐ethnicity, but African Americans had a higher prevalence (10.4%) than other groups.

Figure 1
Flowchart of all baby boomer patients born 1945 to 1965 hospitalized from December 1, 2012 through January 31, 2014, and HCV screening tests performed and test results. *Percent of unique admitted baby boomers. †Other exclusions: psychiatric hospitalization, metastatic carcinoma, poor prognosis based on clinician review, order not placed or canceled. ‡Ab = antibody. §Percent of patients tested for HCV Ab. ‖Percent of patients testing positive for HCV Ab; test not performed when HCV Ab obtained inappropriate tube for reflex HCV RNA. ¥Percent of those tested for HCV RNA. Abbreviations: Ab, antibody; HCV, hepatitis C virus.
Demographic Characteristics of Screened Patients and Anti‐HCV Antibody‐Positive Patients
CharacteristicAll Screened Patients, No.Anti‐HCV Antibody‐Positive Patients, No. (Row %)P Value*
  • NOTE: Abbreviations: HCV, hepatitis C virus; SD, standard deviation. *From 2‐sample t test or 2 test.

Overall3,168Total=240 (7.6) 
Age, mean (SD)57.0 (5.7)54.8 (5.0)<0.0001
Sex   
Men1,771185 (10.4)<0.0001
Women1,39755 (3.9) 
Race   
Non‐Hispanic white1,03686 (8.3)0.12
Hispanic1,872134 (7.2) 
African American16317 (10.4) 
Other973 (3.1) 
Insurance   
Insured1,740109 (6.3)0.002
Uninsured1,428131 (9.2) 

HCV RNA testing was completed for 214 (89.2%) anti‐HCVpositive patients, of whom 134 (62.6%) had detectable RNA, indicating chronic HCV infection (Figure 1). Overall, 4.2% of all eligible patients tested for HCV were chronically infected. No characteristics were significantly associated with chronic HCV, but persons with chronic infection tended to be younger, uninsured, and African American (Table 2).

Demographic Characteristics of HCV RNA‐Positive Patients
CharacteristicsAll HCV RNA‐Tested Patients, No.HCV RNA‐Positive Patients, No. (Row %)P Value*
  • NOTE: Abbreviations: HCV, hepatitis C virus; SD, standard deviation. *From 2‐sample t test or 2 test or Fisher exact test.

Overall214134 (62.6) 
Age, y, mean (SD)54.6 (5.0)54.2 (5.1)0.09
Sex   
Men165106 (64.2)0.37
Women4928 (57.1) 
Race   
Non‐Hispanic white7849 (62.8)0.65
Hispanic11873 (61.8) 
African American1511 (73.3) 
Other31 (33.3) 
Insurance   
Insured9252 (56.5)0.11
Uninsured12282 (67.2) 

Among patients with chronic HCV infection, 129 (96.3%) were counseled and follow‐up plans developed (Figure 2). By December 10, 2014, 108 (80.6%) patients had received follow‐up primary care, and 52 (38.8%) had care from a hepatologist. Five had initiated HCV‐specific treatment, but many others were awaiting approval for compassionate drug programs offering direct‐acting antivirals. Barriers to care included 82 (61.2%) uninsured, 45 (34%) problem drinkers, 22 (16%) homeless, and 25 (18.6%) incarcerated (not shown). The promotora addressed these issues by visiting homes or homeless shelters, assistance with obtaining county‐based or other types of insurance, offering alcohol risk‐reduction counseling, linking patients to alcohol‐treatment programs, and communicating with the county jail about follow‐up care.

Figure 2
Counseling and outpatient care by December 10, 2014 for patients with newly diagnosed chronic hepatitis C virus infection from the inpatient screening program from December 1, 2012 through January 31, 2014. Abbreviations: Ns, not significant.

Most of the developmental costs for the program were dedicated to developing EMR programs (Table 3). An optional cost was for the development of the tablet educational program about HCV. In regard to maintenance costs for the first 14 months, the majority was to support the program faculty, counseling/case management, and a nurse practitioner who helped with ordering tests. We also estimated costs for testing uninsured patients (45% of HCV antibody tested, 57% of HCV PCR tested, per Tables 1 and 2, respectively), as they must be borne by the hospital.

Estimated Costs for Development and Maintenance of HCV Screening Program
Program ComponentMonthly ($)Total ($)
  • NOTE: Abbreviations: Ab=antibody; FTE, full‐time equivalent; HCV, hepatitis C virus; PCR, polymerase chain reaction.

Development phase (2 months prior to start)  
Personnel  
Faculty physicians (0.3 FTE salary+benefits)6,64113,282
Role: Development educational materials, provider education, and pilot testing  
Technology  
Development of eligibility screen and order sets for electronic medical record 41,171
HCV counseling educational program for tabletdevelopment and pilot testing (optional) 15,000
Patient educational materials (posters, flyers) 400
Total for development phase 69,853
Maintenance phase (14 months)  
Personnel  
Faculty physicians (0.3 FTE, salary+benefits)6,64192,974
Role: Coordinate with hospital staff and faculty, liaison with laboratory, supervise study team, review all identified cases for eligibility and management plans  
Inpatient counselor and outpatient case management (2 FTE, salary+benefits)6,34388,802
Role: Inpatient and outpatient counseling of HCV Ab+patients and facilitation of follow‐up care for patients with chronic HCV infection  
Nurse practitioner ($35/hour @ 10 hours/month)3504,900
Role: Review daily list of admitted baby boomers and manually order HCV screening test for those missed by the automated order  
Postage10140
Laboratory costs for uninsured (based on % in cohort)  
HCV antibody in plasma preparation tubes ($13.41/test 1,423) 19,082
HCV RNA PCR ($87.96/test 122) 10,731
Total for maintenance phase 216,629
Total program costs 286,482

DISCUSSION

Implementation of universal HCV screening and linkage to care for hospitalized baby boomers utilizes a multicomponent infrastructure that reflects lessons learned from similar HIV programs. Use of an EMR algorithm to identify eligible patients and programs to automatically order HCV screening was a linchpin of our high testing rate and averted testing those who did not require screening. Of all 6410 baby boomers admitted to our safety‐net hospital, the EMR screen identified over 40% as ineligible due to prior diagnosis of HCV infection or prior HCV tests. Most of the additional 609 patients who were not tested were excluded due to comorbidities or admission to psychiatry. Overall, the EMR programs, tests ordered by the team, and opt‐out screening with education resulted in screening 95% of eligible patients. However, this program carries substantial costs, nearly $300,000 for the first 2 years, for unreimbursed services in this safety‐net hospital. The new guidelines for HCV screening[1, 2] are not accompanied by financial support either for program implementation or for screening and linkage to care for the uninsured, creating significant financial hurdles to achieve guideline compliance within already overtaxed public healthcare systems.

The infrastructure implemented in this hospital succeeded in achieving a higher rate of HCV screening of baby boomers than reported by other programs. In an emergency department in Birmingham, Alabama, a screening program for baby boomers tested 66% of 2325 persons who were HCV‐unaware.[17] In an outpatient clinic for men who have sex with men, only 54% of 1329 patients were screened for HCV.[18]

Among 3168 screened patients in our cohort, 7.6% were anti‐HCV antibody positive, which is over twice the prevalence of 3.5% (95% confidence interval: 2.2%‐4.8%) for anti‐HCVpositive tests in baby boomers based on National Health and Nutrition Examination Survey (NHANES) data from 2001 to 2010.[19] However, the Alabama emergency department study found that 11% of tested patients were anti‐HCV positive.[17] Although that study lacked race‐ethnicity data for half of the subjects, among those with this information, 13% of black and 7% of white subjects tested anti‐HCV positive. Compared with the Alabama study, the anti‐HCV prevalence in our cohort was somewhat lower for blacks (10.4%) but higher for non‐Hispanic whites (8.3%). Hispanics in our cohort had the lowest anti‐HCV prevalence (7.2%), whereas the Alabama study did not report this figure. National studies also find that the prevalence of anti‐HCVpositive results is twice as high for blacks compared with non‐Hispanic whites and Hispanics, and nearly twice as high for men compared with women.[19] In our cohort, the proportion of men with anti‐HCVpositive results was nearly 3 times that for women.

Diagnosis of chronic HCV infection requires 2 tests, similar to performing a Western blot test after a positive enzyme‐linked immunoassay for HIV. In a Veterans Affairs study, only 64% of patients with a positive anti‐HCV antibody test had a HCV RNA performed when reflex testing was not performed, and patients had to come in for a second test versus >90% of patients in sites that offer reflex testing.[20] At a somewhat increased price due to using more expensive PPTs ($96/100 PPT tubes vs $6.50/100 for serum red top tubes), both tests were performed on the same blood sample, resulting in 89% of anti‐HCV antibody‐positive patients being tested for HCV RNA.

Overall, 62% of patients in our cohort with a positive anti‐HCV antibody test had HCV RNA detected (viremic) compared with 71% of persons aged 20 years in an NHANES study from 2003 to 2010.[21] Several factors may contribute to this lower rate of chronic infection. In a study of HCV seropositive blood donors, Hispanics and non‐Hispanic whites were significantly more likely to have spontaneously cleared HCV infection than Asians and non‐Hispanic blacks.[22] Spontaneous clearance of HCV has also been associated with younger age at infection and HCV genotype 1.[23] Poorly understood genetic factors may also play a role.[24] The high rate of HCV clearance in our cohort reinforces the need to perform HCV RNA testing.

Overall, 4.2% of our cohort had chronic HCV infection. According to CDC estimates from 1999 to 2008 NHANES data, 2.74 million (3.25%) of 84.2 million US baby boomers have been infected with HCV, and 2.04 million (2.4%) have chronic infection.[1] Therefore, our safety‐net cohort of never‐tested baby boomers had over twice the prevalence of chronic HCV infection than the national estimate for this age group. This high proportion of chronic HCV may reflect our predominantly low‐income patient population. An analysis conducted by Milliman, Inc. using 2010 data estimated that half of all persons with undiagnosed HCV infection are uninsured.[25] This finding reinforces the need to conduct HCV screening in acute‐care settings such as hospitals, because the uninsured have poor access to ambulatory care.

Our chronic HCV‐infected cohort had many barriers to follow‐up care because most were uninsured and 15% were homeless. Our counselors addressed socioeconomic barriers to care[26] and concerns about the disease.[27] Many patients also had problem drinking based on either self‐report or documented in the medical record. Even moderate alcohol use may increase the risk of overall and liver‐related mortality from chronic HCV infection,[28] so our team offered brief alcohol counseling and partnered with healthcare providers and local Alcoholics Anonymous programs to offer support.

We linked 80% of newly diagnosed patients to primary care or hepatology providers, aided by a county‐level financial assistance program for healthcare services for uninsured residents, but it still required patients to pay out of pocket for care. Access to newer, highly effective, all‐oral therapy treatment[5] was slowed while awaiting US Food and Drug Administration approval in the first year of this project, then treatment provided only after lengthy applications to drug company assistance programs with priority given to persons with compensated cirrhosis.

Our project raises serious concerns for policymakers and payers. Should universal baby boomer HCV testing be undertaken without taking into account the financial and personnel resources required to implement this screening program or the substantial expenditures necessary to treat chronically infected persons? Although the Centers for Medicaid and Medicare Services pay for HCV screening costs,[29] our hospital had to cover costs for uninsured persons. Admittedly, Texas has the highest proportion of residents who are uninsured in the nation, but even in other states, Medicaid and other insurance programs are wrestling with how to deal with the high cost of HCV therapy.[30]

We acknowledge several limitations of this project. First, it was undertaken in only 1 hospital. Yet, our challenges and solutions are likely to be applicable to other hospitals nationally, especially those serving vulnerable populations. Second, patients in our cohort were usually admitted for comorbidities that needed to be managed before HCV infection could be addressed. However, persons with a poor prognosis, such as metastatic cancer, were excluded. We did not attempt to exclude other persons with serious comorbidities such as congestive heart failure, because the guidelines do not currently recommend this, and there may be benefits for patients, their families, and providers from knowing that an individual is chronically HCV infected even if they are not eligible to be treated. Third, the cost of the program was supported in part by a grant and would otherwise have to be borne by the hospital. Fourth, the EMR used by our hospital allows hundreds of admission order sets to be created and made automated order entry hard to implement. This is unlikely to be the situation in other hospitals using different types of EMRs.

It remains to be seen whether safety‐net hospitals with populations at greater risk of HCV infection can afford to support HCV testing and linkage to care. In view of several cost‐effectiveness studies that find screening and treating chronic HCV‐infected baby boomers cost‐effective within standard thresholds,[31, 32, 33] it may be important for policymakers and payers to consider lessons from HIV programs. Because HIV‐infected persons could not afford life‐saving medication, vigorous advocacy efforts led to legislation approving the Ryan White program in 1990 to fill gaps in HIV care that were not covered by other sources of support.[34] HCV infection is the most common blood‐borne infection in the nation, with potentially devastating consequences if ignored, but the underlying premise that universal HCV testing will save lives is in question if most of the individuals who are diagnosed with chronic HCV are low income, uninsured, or underinsured with limited access to curative medications. A rigorous public policy debate regarding both the merits of screening and the availability of treatment to those who are diagnosed is essential to the success of these programs.

Disclosure

Funding for this study was received from the Centers for Disease Control and Prevention CDC PS12‐1209PPHF12. The authors report no conflicts of interest.

Files
References
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  2. 2. Centers for Disease Control and Prevention. Vital signs: evaluation of hepatitis C virus infection testing and reporting–eight U.S. sites, 2005‐2011. MMWR Morb Mortal Wkly Rep. 2013;62:357361.
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  10. Berkenblit GV, Sosman JM, Bass M, et al. Factors affecting clinician educator encouragement of routine HIV testing among trainees. J Gen Intern Med. 2012;27:839844.
  11. Walensky RP, Reichmann WM, Arbelaez C, et al. Counselor‐versus provider‐based HIV screening in the emergency department: Results from the universal screening for HIV infection in the emergency room (USHER) randomized controlled trial. Ann Emerg Med. 2011;58:S126S132.e1–4.
  12. Greenwald JL, Hall J, Skolnik PR. Approaching the CDC's guidelines on the HIV testing of inpatients: physician‐referral versus nonreferral‐based testing. AIDS Patient Care STDS. 2006;20:311317.
  13. Centers for Disease Control and Prevention (CDC). Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62:362365.
  14. Advia Centaur Assay Manual. Malvern, PA: Siemens Medical Solutions Diagnostics; Pub# 07063235, Rev. C, 2005‐01.
  15. Taylor P, Pickard G, Gammie A, Atkins M. Comparison of the ADVIA Centaur and Abbott AxSYM immunoassay systems for a routine diagnostic virology laboratory. J Clin Virol. 2004;30:S11S15.
  16. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. Available at: http://www.niaaa.nih.gov/alcohol‐health/overview‐alcohol‐consumption/moderate‐binge‐drinking. Accessed June 12, 2014.
  17. Galbraith JW, Franco RA, Donnelly JP, et al. Unrecognized chronic hepatitis C virus infection among baby boomers in the emergency department. Hepatology. 2015;61:776782.
  18. Hoover KW, Butler M, Workowski KA, et al. Low rates of hepatitis screening and vaccination of HIV‐infected MSM in HIV clinics. Sex Transm Dis. 2012;39:349353.
  19. Ditah I, Ditah F, Devaki P, Ditah C, Kamath PS, Charlton M. The changing epidemiology of hepatitis C virus infection in the United States: National Health and Nutrition Examination Survey 2001 through 2010. J Hepatol. 2014;60:691698.
  20. Rongey CA, Kanwal , Hoang T, Gifford AL, Asch SM. Viral RNA testing in hepatitis C antibody‐positive veterans. Am J Prev Med. 2009;36:235238.
  21. Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States: National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160:293300.
  22. Busch MP, Glynn SA, Stramer SL, et al. NHLBI Retrovirus Epidemiology Donor Study (REDS) Group. Correlates of hepatitis C virus (HCV) RNA negativity among HCV‐seropositive blood donors. Transfusion. 2006;46:469475.
  23. Rolfe KJ, Curran MD, Alexander GJ, Wodall T, Andrews N, Harris HE. Spontaneous loss of hepatitis C virus RNA from serum is associated with genotype 1 and younger age at exposure. J Med Virol. 2011;83:13381344.
  24. Grebely J, Dore GJ, Kim AY, et al. Genetics of spontaneous clearance of hepatitis C virus infection: a complex topic with much to learn. Hepatology. 2014;60:21272128.
  25. Fitch K, Iwasaki K, Pyenson B, Engel T. Health care reform and hepatitis C: a convergence of risk and opportunity. Available at: http://us.milliman.com/uploadedFiles/insight/2013/convergence‐of‐risk‐and‐opportunity.pdf. Accessed February 5, 2015.
  26. Tohme RA, Xing J, Liao Y, Holmberg SD. Hepatitis C testing, infection, and linkage to care among racial and ethnic minorities in the United States, 2009‐2010. Am J Public Health. 2013;103:112119.
  27. McGowan CE, Fried MW. Barriers to hepatitis C treatment. Liver Int. 2012;32:151156.
  28. Younossi ZM, Zheng L, Stepanova M, Venkatesan C, Mir HM. Moderate, excessive or heavy alcohol consumption: Each is significantly associated with increased mortality in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2013;37:703709.
  29. Centers for Medicare and Medicaid Services. Proposed decision memo for screening for hepatitis c virus (HCV) in adults (CAG‐00436N). Available at: http://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=272. Accessed June 2, 2014.
  30. Hoofnagle JH, Sherker AH. Therapy for hepatitis C—the costs of success. N Engl J Med. 2014;370:15521553.
  31. McGarry LJ, Pawar VS, Panchmatia HR, et al. Economic model of a birth cohort screening program for hepatitis C. Hepatology. 2012;55:13441355.
  32. Liu S, Cipriano LE, Holodniy M, Goldhaber‐Fiebert JD. Cost‐effectiveness analysis of risk‐factor guided and birth‐cohort screening for chronic hepatitis C infection in the United States. PLoS One. 2013;8:e58975.
  33. Rein DB, Smith BD, Wittenborn JS, et al. The cost‐effectiveness of birth‐cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med. 2012;156:263270.
  34. U.S. Department of Health and Human Services. Health Resources and Services Administration: HIV/AIDS programs. Available at: http://hab.hrsa.gov/abouthab/legislation.html. Accessed April 8, 2015.
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INTRODUCTION

The baby boomer generation, born from 1945 to 1965, accounts for 75% of the estimated 2.7 to 3.9 million persons with chronic hepatitis C virus (HCV) infection in the US.[1, 2, 3] Most HCV‐infected baby boomers do not know that they are infected.[4] With the advent of better‐tolerated, more‐effective therapies to treat chronic HCV infection,[5] and to reduce rates of complications such as cirrhosis, liver failure, and hepatocellular carcinoma,[6] universal 1‐time screening of baby boomers has been endorsed by the Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force.[1, 7] Hospitalized baby boomers may offer an important target for HCV screening. Our group conducted an anonymous HCV seroprevalence study of nearly 800 patients on general medicine and trauma services of 2 Philadelphia hospitals, and found that 8% had undiagnosed HCV infection, and 8% had diagnosed HCV. [8]

Little is known about barriers and facilitators to implementation of universal HCV screening of baby boomers. Lessons from implementing HIV screening offer a useful guide.[9] First, limited clinician knowledge and confusion about screening guidelines necessitated convenient, well‐designed educational programs.[10] Second, burdensome consent procedures were reduced by opt‐out consent for screening supplemented by patient education.[9] Third, electronic medical record (EMR) algorithms minimized burdens on staff by efficiently identifying and flagging eligible persons for screening.[11] Fourth, ancillary staff support for patient education and linkage to follow‐up care increased screening rates compared with usual care by physicians/staff.[11] Finally, routine human immunodeficiency virus (HIV) testing of inpatients increased rates of diagnosis, especially compared with physician referral systems.[12]

This article describes how HIV screening strategies informed the development in a baby boomer HCV screening and linkage to a care program in a safety‐net hospital serving a majority Hispanic population. We report results of the first 14 months of the screening program and linkage to care for chronically HCV‐infected persons after a minimum 10 months follow‐up. We also estimate costs for program implementation and maintenance to inform hospital administrators, healthcare policymakers, and clinicians about resources that may be required to effectively screen hospitalized baby boomers for HCV.

METHODS

Study Setting

The HCV baby boomer screening program was pilot tested in November 2012 and launched December 1, 2012 in a 498‐bed academic‐affiliated hospital of a healthcare system serving the indigent population of South Texas.

Project Development Phase

From October 1, 2012 to November 30, 2012, project infrastructure development and provider/staff education were conducted. A half‐hour PowerPoint lecture (in person or online) was developed about HCV epidemiology, birth‐cohort HCV screening guidelines, newer treatment modalities, and screening program components. Lectures were delivered to departmental chairs at the affiliated medical school, departmental grand rounds, and the hospital's nursing supervisors. One‐on‐one informational meetings were also held with hospital administrators and staff.

With the hospital's information technology team, screens were developed to identify eligible baby boomers from up to 7 years of previous inpatient and outpatient encounters in the EMR from: birth year (19451965) and no prior diagnosis of HCV infection (070.41, 070.44, 070.51, 070.54, 070.7x, V02.62) or any type of completed test for HCV. The algorithm also excluded patients admitted to psychiatry due to lack of decision‐making capacity or patients with a poor prognosis such as metastatic cancer. An audit of 100 consecutive excluded patients identified all as legitimate.

A new laboratory order for HCV screening was developed by laboratory administrators and pathology faculty for an anti‐HCV antibody test followed by reflex HCV RNA testing for positive results per CDC recommendations.[13] The anti‐HCV test was performed on serum or ethylenediaminetetraacetic acid plasma using the Advia Centaur HCV Assay (Bayer HealthCare LLC, Tarrytown, NY). This assay has excellent sensitivity (99.9%) and specificity (97.5%).[14, 15] The HCV RNA assay was performed using quantitative real‐time polymerase chain reaction (PCR) using the COBAS AmpliPrep/COBAS TaqMan HCV test (Roche Molecular Systems, Pleasanton, CA). Use of plasma preparation tubes (PPTs) (BD Vacutainer PPT tubes; Becton, Dickinson and Co., Franklin Lakes, NJ) permitted both anti‐HCV antibody and HCV PCR testing to be performed on the same specimen when anti‐HCV antibody was detected, eliminating a second blood draw for the PCR test. For patients eligible for screening, an EMR algorithm was created to add an HCV screening order to over 50 different admission order sets.

To educate patients newly diagnosed with HCV infection, we developed an interactive, low‐literacy, educational program in Spanish and English for an electronic tablet device that addressed: HCV epidemiology, transmission prevention, factors that can accelerate chronic HCV infection, and management/treatment strategies. At several points in the program, the patient needed to answer questions correctly to continue. The tablet retained responses linked to a study identification about alcohol consumption, history of past and current illicit drug use, sexual risk behavior, and offered risk reduction messages. The tablet content and presentation reflected suggestions by Hispanic patient‐reviewers about cultural appropriateness and comprehension.

Project Implementation and Maintenance Phase

We report implementation of the program from December 1, 2012 to January 31, 2014. An automated EMR report classified all baby boomers admitted in the previous 24 hours as: (1) eligible with pending screening test order, (2) eligible without an order, (3) ineligible due to prior HCV test or diagnosis, or (4) ineligible due to comorbidity (eg, metastatic cancer). For approximately one‐third of eligible patients, a study team member placed an order after review of the daily admission report because the order had not been automatically placed.

Admitting nurses initially asked for consent from eligible patients for HCV screening, but this was ultimately deemed too onerous a task along with all of their other duties. We then instituted opt‐out consent with patient education about testing and opportunities to refuse via posters placed throughout the hospital and flyers in admission packets. A bilingual HCV counselor provided HCV screening test results to all patients. She counseled patients who screened positive for HCV with the educational program on an electronic tablet and developed a follow‐up care plan.

A bilingual promotora (community health worker) contacted patients newly diagnosed with chronic HCV infection after hospital discharge to address the following: obtaining insurance, access to primary care and HCV specialty care, scheduling appointments, and treatment for alcohol problems or drug abuse. After obtaining signed consent, the promotora sent test results and recommendations for follow‐up care (eg, hepatitis A and B immunization) to a designated outpatient physician and reminded patients about appointments and pending tests. The promotora received training in motivational interviewing skills to engage patients with needed care including alcohol treatment.

Study Data

A summary report was developed from the EMR with demographic, insurance, clinical, and HCV screening data for all admitted baby boomers. For patients diagnosed with chronic HCV infection, the promotora obtained data about follow‐up HCV care through December 10, 2014 from the EMR, outside provider records, and patient reports.

Study Variables

The 2 outcome measures were a positive anti‐HCV antibody test and positive HCV RNA test. Insurance status was categorized as insured (private, public, Veterans Administration, Department of Defense) or uninsured (self‐pay or county‐based financial assistance program). Problem drinking was identified from International Classification of Diseases, Ninth Revision, Clinical Modification codes for the admission, notes by clinicians describing alcohol abuse/dependence, or quantity/frequency meeting National Institute on Alcohol Abuse and Alcoholism criteria for alcohol problems of >14 drinks/week or >4 drinks/day for men and >7 drinks per week or >3 drinks per day for women.[16]

Implementation costs included informatics support, mobile app development, other patient educational materials, costs of screening tests for uninsured, and 0.3 full‐time equivalent (FTE) of a clinician for half a year. Maintenance costs included salaries for the study team, HCV testing costs, and postage.

Analysis

Demographics by HCV antibody test results are compared using [2] tests or Student t tests as appropriate. Among persons with a positive HCV antibody test, HCV RNA results are similarly compared. This implementation project was approved by the University of Texas Health Science Center at San Antonio Institutional Review Board (HSC20130033N).

RESULTS

Within 14 months, 6410 unique baby boomers were admitted with a mean age 56.4 years (standard deviation [SD] 5.7), 55.9% men, 59.1% Hispanic, 8.2% nonwhite, and 46.7% uninsured (Table 1). Among admitted patients, 729 (11.4%) had a previous HCV diagnosis and 1904 (29.7%) had been tested for HCV (Figure 1). Anti‐HCV antibody testing was completed for 3168 (49.4% of all admitted patients and 83.9% of never‐tested patients). After exclusions such as significant comorbidity or psychiatric admission, 95% of eligible persons were tested. Of screened patients, 240 (7.6%) were positive; these patients were significantly younger (P<0.0001) and more likely to be men (P<0.0001) and uninsured (P=0.002) (Table 1). Notably, 10% of men were anti‐HCV positive versus 4% of women. In this predominantly Hispanic cohort, no significant difference appeared by race‐ethnicity, but African Americans had a higher prevalence (10.4%) than other groups.

Figure 1
Flowchart of all baby boomer patients born 1945 to 1965 hospitalized from December 1, 2012 through January 31, 2014, and HCV screening tests performed and test results. *Percent of unique admitted baby boomers. †Other exclusions: psychiatric hospitalization, metastatic carcinoma, poor prognosis based on clinician review, order not placed or canceled. ‡Ab = antibody. §Percent of patients tested for HCV Ab. ‖Percent of patients testing positive for HCV Ab; test not performed when HCV Ab obtained inappropriate tube for reflex HCV RNA. ¥Percent of those tested for HCV RNA. Abbreviations: Ab, antibody; HCV, hepatitis C virus.
Demographic Characteristics of Screened Patients and Anti‐HCV Antibody‐Positive Patients
CharacteristicAll Screened Patients, No.Anti‐HCV Antibody‐Positive Patients, No. (Row %)P Value*
  • NOTE: Abbreviations: HCV, hepatitis C virus; SD, standard deviation. *From 2‐sample t test or 2 test.

Overall3,168Total=240 (7.6) 
Age, mean (SD)57.0 (5.7)54.8 (5.0)<0.0001
Sex   
Men1,771185 (10.4)<0.0001
Women1,39755 (3.9) 
Race   
Non‐Hispanic white1,03686 (8.3)0.12
Hispanic1,872134 (7.2) 
African American16317 (10.4) 
Other973 (3.1) 
Insurance   
Insured1,740109 (6.3)0.002
Uninsured1,428131 (9.2) 

HCV RNA testing was completed for 214 (89.2%) anti‐HCVpositive patients, of whom 134 (62.6%) had detectable RNA, indicating chronic HCV infection (Figure 1). Overall, 4.2% of all eligible patients tested for HCV were chronically infected. No characteristics were significantly associated with chronic HCV, but persons with chronic infection tended to be younger, uninsured, and African American (Table 2).

Demographic Characteristics of HCV RNA‐Positive Patients
CharacteristicsAll HCV RNA‐Tested Patients, No.HCV RNA‐Positive Patients, No. (Row %)P Value*
  • NOTE: Abbreviations: HCV, hepatitis C virus; SD, standard deviation. *From 2‐sample t test or 2 test or Fisher exact test.

Overall214134 (62.6) 
Age, y, mean (SD)54.6 (5.0)54.2 (5.1)0.09
Sex   
Men165106 (64.2)0.37
Women4928 (57.1) 
Race   
Non‐Hispanic white7849 (62.8)0.65
Hispanic11873 (61.8) 
African American1511 (73.3) 
Other31 (33.3) 
Insurance   
Insured9252 (56.5)0.11
Uninsured12282 (67.2) 

Among patients with chronic HCV infection, 129 (96.3%) were counseled and follow‐up plans developed (Figure 2). By December 10, 2014, 108 (80.6%) patients had received follow‐up primary care, and 52 (38.8%) had care from a hepatologist. Five had initiated HCV‐specific treatment, but many others were awaiting approval for compassionate drug programs offering direct‐acting antivirals. Barriers to care included 82 (61.2%) uninsured, 45 (34%) problem drinkers, 22 (16%) homeless, and 25 (18.6%) incarcerated (not shown). The promotora addressed these issues by visiting homes or homeless shelters, assistance with obtaining county‐based or other types of insurance, offering alcohol risk‐reduction counseling, linking patients to alcohol‐treatment programs, and communicating with the county jail about follow‐up care.

Figure 2
Counseling and outpatient care by December 10, 2014 for patients with newly diagnosed chronic hepatitis C virus infection from the inpatient screening program from December 1, 2012 through January 31, 2014. Abbreviations: Ns, not significant.

Most of the developmental costs for the program were dedicated to developing EMR programs (Table 3). An optional cost was for the development of the tablet educational program about HCV. In regard to maintenance costs for the first 14 months, the majority was to support the program faculty, counseling/case management, and a nurse practitioner who helped with ordering tests. We also estimated costs for testing uninsured patients (45% of HCV antibody tested, 57% of HCV PCR tested, per Tables 1 and 2, respectively), as they must be borne by the hospital.

Estimated Costs for Development and Maintenance of HCV Screening Program
Program ComponentMonthly ($)Total ($)
  • NOTE: Abbreviations: Ab=antibody; FTE, full‐time equivalent; HCV, hepatitis C virus; PCR, polymerase chain reaction.

Development phase (2 months prior to start)  
Personnel  
Faculty physicians (0.3 FTE salary+benefits)6,64113,282
Role: Development educational materials, provider education, and pilot testing  
Technology  
Development of eligibility screen and order sets for electronic medical record 41,171
HCV counseling educational program for tabletdevelopment and pilot testing (optional) 15,000
Patient educational materials (posters, flyers) 400
Total for development phase 69,853
Maintenance phase (14 months)  
Personnel  
Faculty physicians (0.3 FTE, salary+benefits)6,64192,974
Role: Coordinate with hospital staff and faculty, liaison with laboratory, supervise study team, review all identified cases for eligibility and management plans  
Inpatient counselor and outpatient case management (2 FTE, salary+benefits)6,34388,802
Role: Inpatient and outpatient counseling of HCV Ab+patients and facilitation of follow‐up care for patients with chronic HCV infection  
Nurse practitioner ($35/hour @ 10 hours/month)3504,900
Role: Review daily list of admitted baby boomers and manually order HCV screening test for those missed by the automated order  
Postage10140
Laboratory costs for uninsured (based on % in cohort)  
HCV antibody in plasma preparation tubes ($13.41/test 1,423) 19,082
HCV RNA PCR ($87.96/test 122) 10,731
Total for maintenance phase 216,629
Total program costs 286,482

DISCUSSION

Implementation of universal HCV screening and linkage to care for hospitalized baby boomers utilizes a multicomponent infrastructure that reflects lessons learned from similar HIV programs. Use of an EMR algorithm to identify eligible patients and programs to automatically order HCV screening was a linchpin of our high testing rate and averted testing those who did not require screening. Of all 6410 baby boomers admitted to our safety‐net hospital, the EMR screen identified over 40% as ineligible due to prior diagnosis of HCV infection or prior HCV tests. Most of the additional 609 patients who were not tested were excluded due to comorbidities or admission to psychiatry. Overall, the EMR programs, tests ordered by the team, and opt‐out screening with education resulted in screening 95% of eligible patients. However, this program carries substantial costs, nearly $300,000 for the first 2 years, for unreimbursed services in this safety‐net hospital. The new guidelines for HCV screening[1, 2] are not accompanied by financial support either for program implementation or for screening and linkage to care for the uninsured, creating significant financial hurdles to achieve guideline compliance within already overtaxed public healthcare systems.

The infrastructure implemented in this hospital succeeded in achieving a higher rate of HCV screening of baby boomers than reported by other programs. In an emergency department in Birmingham, Alabama, a screening program for baby boomers tested 66% of 2325 persons who were HCV‐unaware.[17] In an outpatient clinic for men who have sex with men, only 54% of 1329 patients were screened for HCV.[18]

Among 3168 screened patients in our cohort, 7.6% were anti‐HCV antibody positive, which is over twice the prevalence of 3.5% (95% confidence interval: 2.2%‐4.8%) for anti‐HCVpositive tests in baby boomers based on National Health and Nutrition Examination Survey (NHANES) data from 2001 to 2010.[19] However, the Alabama emergency department study found that 11% of tested patients were anti‐HCV positive.[17] Although that study lacked race‐ethnicity data for half of the subjects, among those with this information, 13% of black and 7% of white subjects tested anti‐HCV positive. Compared with the Alabama study, the anti‐HCV prevalence in our cohort was somewhat lower for blacks (10.4%) but higher for non‐Hispanic whites (8.3%). Hispanics in our cohort had the lowest anti‐HCV prevalence (7.2%), whereas the Alabama study did not report this figure. National studies also find that the prevalence of anti‐HCVpositive results is twice as high for blacks compared with non‐Hispanic whites and Hispanics, and nearly twice as high for men compared with women.[19] In our cohort, the proportion of men with anti‐HCVpositive results was nearly 3 times that for women.

Diagnosis of chronic HCV infection requires 2 tests, similar to performing a Western blot test after a positive enzyme‐linked immunoassay for HIV. In a Veterans Affairs study, only 64% of patients with a positive anti‐HCV antibody test had a HCV RNA performed when reflex testing was not performed, and patients had to come in for a second test versus >90% of patients in sites that offer reflex testing.[20] At a somewhat increased price due to using more expensive PPTs ($96/100 PPT tubes vs $6.50/100 for serum red top tubes), both tests were performed on the same blood sample, resulting in 89% of anti‐HCV antibody‐positive patients being tested for HCV RNA.

Overall, 62% of patients in our cohort with a positive anti‐HCV antibody test had HCV RNA detected (viremic) compared with 71% of persons aged 20 years in an NHANES study from 2003 to 2010.[21] Several factors may contribute to this lower rate of chronic infection. In a study of HCV seropositive blood donors, Hispanics and non‐Hispanic whites were significantly more likely to have spontaneously cleared HCV infection than Asians and non‐Hispanic blacks.[22] Spontaneous clearance of HCV has also been associated with younger age at infection and HCV genotype 1.[23] Poorly understood genetic factors may also play a role.[24] The high rate of HCV clearance in our cohort reinforces the need to perform HCV RNA testing.

Overall, 4.2% of our cohort had chronic HCV infection. According to CDC estimates from 1999 to 2008 NHANES data, 2.74 million (3.25%) of 84.2 million US baby boomers have been infected with HCV, and 2.04 million (2.4%) have chronic infection.[1] Therefore, our safety‐net cohort of never‐tested baby boomers had over twice the prevalence of chronic HCV infection than the national estimate for this age group. This high proportion of chronic HCV may reflect our predominantly low‐income patient population. An analysis conducted by Milliman, Inc. using 2010 data estimated that half of all persons with undiagnosed HCV infection are uninsured.[25] This finding reinforces the need to conduct HCV screening in acute‐care settings such as hospitals, because the uninsured have poor access to ambulatory care.

Our chronic HCV‐infected cohort had many barriers to follow‐up care because most were uninsured and 15% were homeless. Our counselors addressed socioeconomic barriers to care[26] and concerns about the disease.[27] Many patients also had problem drinking based on either self‐report or documented in the medical record. Even moderate alcohol use may increase the risk of overall and liver‐related mortality from chronic HCV infection,[28] so our team offered brief alcohol counseling and partnered with healthcare providers and local Alcoholics Anonymous programs to offer support.

We linked 80% of newly diagnosed patients to primary care or hepatology providers, aided by a county‐level financial assistance program for healthcare services for uninsured residents, but it still required patients to pay out of pocket for care. Access to newer, highly effective, all‐oral therapy treatment[5] was slowed while awaiting US Food and Drug Administration approval in the first year of this project, then treatment provided only after lengthy applications to drug company assistance programs with priority given to persons with compensated cirrhosis.

Our project raises serious concerns for policymakers and payers. Should universal baby boomer HCV testing be undertaken without taking into account the financial and personnel resources required to implement this screening program or the substantial expenditures necessary to treat chronically infected persons? Although the Centers for Medicaid and Medicare Services pay for HCV screening costs,[29] our hospital had to cover costs for uninsured persons. Admittedly, Texas has the highest proportion of residents who are uninsured in the nation, but even in other states, Medicaid and other insurance programs are wrestling with how to deal with the high cost of HCV therapy.[30]

We acknowledge several limitations of this project. First, it was undertaken in only 1 hospital. Yet, our challenges and solutions are likely to be applicable to other hospitals nationally, especially those serving vulnerable populations. Second, patients in our cohort were usually admitted for comorbidities that needed to be managed before HCV infection could be addressed. However, persons with a poor prognosis, such as metastatic cancer, were excluded. We did not attempt to exclude other persons with serious comorbidities such as congestive heart failure, because the guidelines do not currently recommend this, and there may be benefits for patients, their families, and providers from knowing that an individual is chronically HCV infected even if they are not eligible to be treated. Third, the cost of the program was supported in part by a grant and would otherwise have to be borne by the hospital. Fourth, the EMR used by our hospital allows hundreds of admission order sets to be created and made automated order entry hard to implement. This is unlikely to be the situation in other hospitals using different types of EMRs.

It remains to be seen whether safety‐net hospitals with populations at greater risk of HCV infection can afford to support HCV testing and linkage to care. In view of several cost‐effectiveness studies that find screening and treating chronic HCV‐infected baby boomers cost‐effective within standard thresholds,[31, 32, 33] it may be important for policymakers and payers to consider lessons from HIV programs. Because HIV‐infected persons could not afford life‐saving medication, vigorous advocacy efforts led to legislation approving the Ryan White program in 1990 to fill gaps in HIV care that were not covered by other sources of support.[34] HCV infection is the most common blood‐borne infection in the nation, with potentially devastating consequences if ignored, but the underlying premise that universal HCV testing will save lives is in question if most of the individuals who are diagnosed with chronic HCV are low income, uninsured, or underinsured with limited access to curative medications. A rigorous public policy debate regarding both the merits of screening and the availability of treatment to those who are diagnosed is essential to the success of these programs.

Disclosure

Funding for this study was received from the Centers for Disease Control and Prevention CDC PS12‐1209PPHF12. The authors report no conflicts of interest.

INTRODUCTION

The baby boomer generation, born from 1945 to 1965, accounts for 75% of the estimated 2.7 to 3.9 million persons with chronic hepatitis C virus (HCV) infection in the US.[1, 2, 3] Most HCV‐infected baby boomers do not know that they are infected.[4] With the advent of better‐tolerated, more‐effective therapies to treat chronic HCV infection,[5] and to reduce rates of complications such as cirrhosis, liver failure, and hepatocellular carcinoma,[6] universal 1‐time screening of baby boomers has been endorsed by the Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force.[1, 7] Hospitalized baby boomers may offer an important target for HCV screening. Our group conducted an anonymous HCV seroprevalence study of nearly 800 patients on general medicine and trauma services of 2 Philadelphia hospitals, and found that 8% had undiagnosed HCV infection, and 8% had diagnosed HCV. [8]

Little is known about barriers and facilitators to implementation of universal HCV screening of baby boomers. Lessons from implementing HIV screening offer a useful guide.[9] First, limited clinician knowledge and confusion about screening guidelines necessitated convenient, well‐designed educational programs.[10] Second, burdensome consent procedures were reduced by opt‐out consent for screening supplemented by patient education.[9] Third, electronic medical record (EMR) algorithms minimized burdens on staff by efficiently identifying and flagging eligible persons for screening.[11] Fourth, ancillary staff support for patient education and linkage to follow‐up care increased screening rates compared with usual care by physicians/staff.[11] Finally, routine human immunodeficiency virus (HIV) testing of inpatients increased rates of diagnosis, especially compared with physician referral systems.[12]

This article describes how HIV screening strategies informed the development in a baby boomer HCV screening and linkage to a care program in a safety‐net hospital serving a majority Hispanic population. We report results of the first 14 months of the screening program and linkage to care for chronically HCV‐infected persons after a minimum 10 months follow‐up. We also estimate costs for program implementation and maintenance to inform hospital administrators, healthcare policymakers, and clinicians about resources that may be required to effectively screen hospitalized baby boomers for HCV.

METHODS

Study Setting

The HCV baby boomer screening program was pilot tested in November 2012 and launched December 1, 2012 in a 498‐bed academic‐affiliated hospital of a healthcare system serving the indigent population of South Texas.

Project Development Phase

From October 1, 2012 to November 30, 2012, project infrastructure development and provider/staff education were conducted. A half‐hour PowerPoint lecture (in person or online) was developed about HCV epidemiology, birth‐cohort HCV screening guidelines, newer treatment modalities, and screening program components. Lectures were delivered to departmental chairs at the affiliated medical school, departmental grand rounds, and the hospital's nursing supervisors. One‐on‐one informational meetings were also held with hospital administrators and staff.

With the hospital's information technology team, screens were developed to identify eligible baby boomers from up to 7 years of previous inpatient and outpatient encounters in the EMR from: birth year (19451965) and no prior diagnosis of HCV infection (070.41, 070.44, 070.51, 070.54, 070.7x, V02.62) or any type of completed test for HCV. The algorithm also excluded patients admitted to psychiatry due to lack of decision‐making capacity or patients with a poor prognosis such as metastatic cancer. An audit of 100 consecutive excluded patients identified all as legitimate.

A new laboratory order for HCV screening was developed by laboratory administrators and pathology faculty for an anti‐HCV antibody test followed by reflex HCV RNA testing for positive results per CDC recommendations.[13] The anti‐HCV test was performed on serum or ethylenediaminetetraacetic acid plasma using the Advia Centaur HCV Assay (Bayer HealthCare LLC, Tarrytown, NY). This assay has excellent sensitivity (99.9%) and specificity (97.5%).[14, 15] The HCV RNA assay was performed using quantitative real‐time polymerase chain reaction (PCR) using the COBAS AmpliPrep/COBAS TaqMan HCV test (Roche Molecular Systems, Pleasanton, CA). Use of plasma preparation tubes (PPTs) (BD Vacutainer PPT tubes; Becton, Dickinson and Co., Franklin Lakes, NJ) permitted both anti‐HCV antibody and HCV PCR testing to be performed on the same specimen when anti‐HCV antibody was detected, eliminating a second blood draw for the PCR test. For patients eligible for screening, an EMR algorithm was created to add an HCV screening order to over 50 different admission order sets.

To educate patients newly diagnosed with HCV infection, we developed an interactive, low‐literacy, educational program in Spanish and English for an electronic tablet device that addressed: HCV epidemiology, transmission prevention, factors that can accelerate chronic HCV infection, and management/treatment strategies. At several points in the program, the patient needed to answer questions correctly to continue. The tablet retained responses linked to a study identification about alcohol consumption, history of past and current illicit drug use, sexual risk behavior, and offered risk reduction messages. The tablet content and presentation reflected suggestions by Hispanic patient‐reviewers about cultural appropriateness and comprehension.

Project Implementation and Maintenance Phase

We report implementation of the program from December 1, 2012 to January 31, 2014. An automated EMR report classified all baby boomers admitted in the previous 24 hours as: (1) eligible with pending screening test order, (2) eligible without an order, (3) ineligible due to prior HCV test or diagnosis, or (4) ineligible due to comorbidity (eg, metastatic cancer). For approximately one‐third of eligible patients, a study team member placed an order after review of the daily admission report because the order had not been automatically placed.

Admitting nurses initially asked for consent from eligible patients for HCV screening, but this was ultimately deemed too onerous a task along with all of their other duties. We then instituted opt‐out consent with patient education about testing and opportunities to refuse via posters placed throughout the hospital and flyers in admission packets. A bilingual HCV counselor provided HCV screening test results to all patients. She counseled patients who screened positive for HCV with the educational program on an electronic tablet and developed a follow‐up care plan.

A bilingual promotora (community health worker) contacted patients newly diagnosed with chronic HCV infection after hospital discharge to address the following: obtaining insurance, access to primary care and HCV specialty care, scheduling appointments, and treatment for alcohol problems or drug abuse. After obtaining signed consent, the promotora sent test results and recommendations for follow‐up care (eg, hepatitis A and B immunization) to a designated outpatient physician and reminded patients about appointments and pending tests. The promotora received training in motivational interviewing skills to engage patients with needed care including alcohol treatment.

Study Data

A summary report was developed from the EMR with demographic, insurance, clinical, and HCV screening data for all admitted baby boomers. For patients diagnosed with chronic HCV infection, the promotora obtained data about follow‐up HCV care through December 10, 2014 from the EMR, outside provider records, and patient reports.

Study Variables

The 2 outcome measures were a positive anti‐HCV antibody test and positive HCV RNA test. Insurance status was categorized as insured (private, public, Veterans Administration, Department of Defense) or uninsured (self‐pay or county‐based financial assistance program). Problem drinking was identified from International Classification of Diseases, Ninth Revision, Clinical Modification codes for the admission, notes by clinicians describing alcohol abuse/dependence, or quantity/frequency meeting National Institute on Alcohol Abuse and Alcoholism criteria for alcohol problems of >14 drinks/week or >4 drinks/day for men and >7 drinks per week or >3 drinks per day for women.[16]

Implementation costs included informatics support, mobile app development, other patient educational materials, costs of screening tests for uninsured, and 0.3 full‐time equivalent (FTE) of a clinician for half a year. Maintenance costs included salaries for the study team, HCV testing costs, and postage.

Analysis

Demographics by HCV antibody test results are compared using [2] tests or Student t tests as appropriate. Among persons with a positive HCV antibody test, HCV RNA results are similarly compared. This implementation project was approved by the University of Texas Health Science Center at San Antonio Institutional Review Board (HSC20130033N).

RESULTS

Within 14 months, 6410 unique baby boomers were admitted with a mean age 56.4 years (standard deviation [SD] 5.7), 55.9% men, 59.1% Hispanic, 8.2% nonwhite, and 46.7% uninsured (Table 1). Among admitted patients, 729 (11.4%) had a previous HCV diagnosis and 1904 (29.7%) had been tested for HCV (Figure 1). Anti‐HCV antibody testing was completed for 3168 (49.4% of all admitted patients and 83.9% of never‐tested patients). After exclusions such as significant comorbidity or psychiatric admission, 95% of eligible persons were tested. Of screened patients, 240 (7.6%) were positive; these patients were significantly younger (P<0.0001) and more likely to be men (P<0.0001) and uninsured (P=0.002) (Table 1). Notably, 10% of men were anti‐HCV positive versus 4% of women. In this predominantly Hispanic cohort, no significant difference appeared by race‐ethnicity, but African Americans had a higher prevalence (10.4%) than other groups.

Figure 1
Flowchart of all baby boomer patients born 1945 to 1965 hospitalized from December 1, 2012 through January 31, 2014, and HCV screening tests performed and test results. *Percent of unique admitted baby boomers. †Other exclusions: psychiatric hospitalization, metastatic carcinoma, poor prognosis based on clinician review, order not placed or canceled. ‡Ab = antibody. §Percent of patients tested for HCV Ab. ‖Percent of patients testing positive for HCV Ab; test not performed when HCV Ab obtained inappropriate tube for reflex HCV RNA. ¥Percent of those tested for HCV RNA. Abbreviations: Ab, antibody; HCV, hepatitis C virus.
Demographic Characteristics of Screened Patients and Anti‐HCV Antibody‐Positive Patients
CharacteristicAll Screened Patients, No.Anti‐HCV Antibody‐Positive Patients, No. (Row %)P Value*
  • NOTE: Abbreviations: HCV, hepatitis C virus; SD, standard deviation. *From 2‐sample t test or 2 test.

Overall3,168Total=240 (7.6) 
Age, mean (SD)57.0 (5.7)54.8 (5.0)<0.0001
Sex   
Men1,771185 (10.4)<0.0001
Women1,39755 (3.9) 
Race   
Non‐Hispanic white1,03686 (8.3)0.12
Hispanic1,872134 (7.2) 
African American16317 (10.4) 
Other973 (3.1) 
Insurance   
Insured1,740109 (6.3)0.002
Uninsured1,428131 (9.2) 

HCV RNA testing was completed for 214 (89.2%) anti‐HCVpositive patients, of whom 134 (62.6%) had detectable RNA, indicating chronic HCV infection (Figure 1). Overall, 4.2% of all eligible patients tested for HCV were chronically infected. No characteristics were significantly associated with chronic HCV, but persons with chronic infection tended to be younger, uninsured, and African American (Table 2).

Demographic Characteristics of HCV RNA‐Positive Patients
CharacteristicsAll HCV RNA‐Tested Patients, No.HCV RNA‐Positive Patients, No. (Row %)P Value*
  • NOTE: Abbreviations: HCV, hepatitis C virus; SD, standard deviation. *From 2‐sample t test or 2 test or Fisher exact test.

Overall214134 (62.6) 
Age, y, mean (SD)54.6 (5.0)54.2 (5.1)0.09
Sex   
Men165106 (64.2)0.37
Women4928 (57.1) 
Race   
Non‐Hispanic white7849 (62.8)0.65
Hispanic11873 (61.8) 
African American1511 (73.3) 
Other31 (33.3) 
Insurance   
Insured9252 (56.5)0.11
Uninsured12282 (67.2) 

Among patients with chronic HCV infection, 129 (96.3%) were counseled and follow‐up plans developed (Figure 2). By December 10, 2014, 108 (80.6%) patients had received follow‐up primary care, and 52 (38.8%) had care from a hepatologist. Five had initiated HCV‐specific treatment, but many others were awaiting approval for compassionate drug programs offering direct‐acting antivirals. Barriers to care included 82 (61.2%) uninsured, 45 (34%) problem drinkers, 22 (16%) homeless, and 25 (18.6%) incarcerated (not shown). The promotora addressed these issues by visiting homes or homeless shelters, assistance with obtaining county‐based or other types of insurance, offering alcohol risk‐reduction counseling, linking patients to alcohol‐treatment programs, and communicating with the county jail about follow‐up care.

Figure 2
Counseling and outpatient care by December 10, 2014 for patients with newly diagnosed chronic hepatitis C virus infection from the inpatient screening program from December 1, 2012 through January 31, 2014. Abbreviations: Ns, not significant.

Most of the developmental costs for the program were dedicated to developing EMR programs (Table 3). An optional cost was for the development of the tablet educational program about HCV. In regard to maintenance costs for the first 14 months, the majority was to support the program faculty, counseling/case management, and a nurse practitioner who helped with ordering tests. We also estimated costs for testing uninsured patients (45% of HCV antibody tested, 57% of HCV PCR tested, per Tables 1 and 2, respectively), as they must be borne by the hospital.

Estimated Costs for Development and Maintenance of HCV Screening Program
Program ComponentMonthly ($)Total ($)
  • NOTE: Abbreviations: Ab=antibody; FTE, full‐time equivalent; HCV, hepatitis C virus; PCR, polymerase chain reaction.

Development phase (2 months prior to start)  
Personnel  
Faculty physicians (0.3 FTE salary+benefits)6,64113,282
Role: Development educational materials, provider education, and pilot testing  
Technology  
Development of eligibility screen and order sets for electronic medical record 41,171
HCV counseling educational program for tabletdevelopment and pilot testing (optional) 15,000
Patient educational materials (posters, flyers) 400
Total for development phase 69,853
Maintenance phase (14 months)  
Personnel  
Faculty physicians (0.3 FTE, salary+benefits)6,64192,974
Role: Coordinate with hospital staff and faculty, liaison with laboratory, supervise study team, review all identified cases for eligibility and management plans  
Inpatient counselor and outpatient case management (2 FTE, salary+benefits)6,34388,802
Role: Inpatient and outpatient counseling of HCV Ab+patients and facilitation of follow‐up care for patients with chronic HCV infection  
Nurse practitioner ($35/hour @ 10 hours/month)3504,900
Role: Review daily list of admitted baby boomers and manually order HCV screening test for those missed by the automated order  
Postage10140
Laboratory costs for uninsured (based on % in cohort)  
HCV antibody in plasma preparation tubes ($13.41/test 1,423) 19,082
HCV RNA PCR ($87.96/test 122) 10,731
Total for maintenance phase 216,629
Total program costs 286,482

DISCUSSION

Implementation of universal HCV screening and linkage to care for hospitalized baby boomers utilizes a multicomponent infrastructure that reflects lessons learned from similar HIV programs. Use of an EMR algorithm to identify eligible patients and programs to automatically order HCV screening was a linchpin of our high testing rate and averted testing those who did not require screening. Of all 6410 baby boomers admitted to our safety‐net hospital, the EMR screen identified over 40% as ineligible due to prior diagnosis of HCV infection or prior HCV tests. Most of the additional 609 patients who were not tested were excluded due to comorbidities or admission to psychiatry. Overall, the EMR programs, tests ordered by the team, and opt‐out screening with education resulted in screening 95% of eligible patients. However, this program carries substantial costs, nearly $300,000 for the first 2 years, for unreimbursed services in this safety‐net hospital. The new guidelines for HCV screening[1, 2] are not accompanied by financial support either for program implementation or for screening and linkage to care for the uninsured, creating significant financial hurdles to achieve guideline compliance within already overtaxed public healthcare systems.

The infrastructure implemented in this hospital succeeded in achieving a higher rate of HCV screening of baby boomers than reported by other programs. In an emergency department in Birmingham, Alabama, a screening program for baby boomers tested 66% of 2325 persons who were HCV‐unaware.[17] In an outpatient clinic for men who have sex with men, only 54% of 1329 patients were screened for HCV.[18]

Among 3168 screened patients in our cohort, 7.6% were anti‐HCV antibody positive, which is over twice the prevalence of 3.5% (95% confidence interval: 2.2%‐4.8%) for anti‐HCVpositive tests in baby boomers based on National Health and Nutrition Examination Survey (NHANES) data from 2001 to 2010.[19] However, the Alabama emergency department study found that 11% of tested patients were anti‐HCV positive.[17] Although that study lacked race‐ethnicity data for half of the subjects, among those with this information, 13% of black and 7% of white subjects tested anti‐HCV positive. Compared with the Alabama study, the anti‐HCV prevalence in our cohort was somewhat lower for blacks (10.4%) but higher for non‐Hispanic whites (8.3%). Hispanics in our cohort had the lowest anti‐HCV prevalence (7.2%), whereas the Alabama study did not report this figure. National studies also find that the prevalence of anti‐HCVpositive results is twice as high for blacks compared with non‐Hispanic whites and Hispanics, and nearly twice as high for men compared with women.[19] In our cohort, the proportion of men with anti‐HCVpositive results was nearly 3 times that for women.

Diagnosis of chronic HCV infection requires 2 tests, similar to performing a Western blot test after a positive enzyme‐linked immunoassay for HIV. In a Veterans Affairs study, only 64% of patients with a positive anti‐HCV antibody test had a HCV RNA performed when reflex testing was not performed, and patients had to come in for a second test versus >90% of patients in sites that offer reflex testing.[20] At a somewhat increased price due to using more expensive PPTs ($96/100 PPT tubes vs $6.50/100 for serum red top tubes), both tests were performed on the same blood sample, resulting in 89% of anti‐HCV antibody‐positive patients being tested for HCV RNA.

Overall, 62% of patients in our cohort with a positive anti‐HCV antibody test had HCV RNA detected (viremic) compared with 71% of persons aged 20 years in an NHANES study from 2003 to 2010.[21] Several factors may contribute to this lower rate of chronic infection. In a study of HCV seropositive blood donors, Hispanics and non‐Hispanic whites were significantly more likely to have spontaneously cleared HCV infection than Asians and non‐Hispanic blacks.[22] Spontaneous clearance of HCV has also been associated with younger age at infection and HCV genotype 1.[23] Poorly understood genetic factors may also play a role.[24] The high rate of HCV clearance in our cohort reinforces the need to perform HCV RNA testing.

Overall, 4.2% of our cohort had chronic HCV infection. According to CDC estimates from 1999 to 2008 NHANES data, 2.74 million (3.25%) of 84.2 million US baby boomers have been infected with HCV, and 2.04 million (2.4%) have chronic infection.[1] Therefore, our safety‐net cohort of never‐tested baby boomers had over twice the prevalence of chronic HCV infection than the national estimate for this age group. This high proportion of chronic HCV may reflect our predominantly low‐income patient population. An analysis conducted by Milliman, Inc. using 2010 data estimated that half of all persons with undiagnosed HCV infection are uninsured.[25] This finding reinforces the need to conduct HCV screening in acute‐care settings such as hospitals, because the uninsured have poor access to ambulatory care.

Our chronic HCV‐infected cohort had many barriers to follow‐up care because most were uninsured and 15% were homeless. Our counselors addressed socioeconomic barriers to care[26] and concerns about the disease.[27] Many patients also had problem drinking based on either self‐report or documented in the medical record. Even moderate alcohol use may increase the risk of overall and liver‐related mortality from chronic HCV infection,[28] so our team offered brief alcohol counseling and partnered with healthcare providers and local Alcoholics Anonymous programs to offer support.

We linked 80% of newly diagnosed patients to primary care or hepatology providers, aided by a county‐level financial assistance program for healthcare services for uninsured residents, but it still required patients to pay out of pocket for care. Access to newer, highly effective, all‐oral therapy treatment[5] was slowed while awaiting US Food and Drug Administration approval in the first year of this project, then treatment provided only after lengthy applications to drug company assistance programs with priority given to persons with compensated cirrhosis.

Our project raises serious concerns for policymakers and payers. Should universal baby boomer HCV testing be undertaken without taking into account the financial and personnel resources required to implement this screening program or the substantial expenditures necessary to treat chronically infected persons? Although the Centers for Medicaid and Medicare Services pay for HCV screening costs,[29] our hospital had to cover costs for uninsured persons. Admittedly, Texas has the highest proportion of residents who are uninsured in the nation, but even in other states, Medicaid and other insurance programs are wrestling with how to deal with the high cost of HCV therapy.[30]

We acknowledge several limitations of this project. First, it was undertaken in only 1 hospital. Yet, our challenges and solutions are likely to be applicable to other hospitals nationally, especially those serving vulnerable populations. Second, patients in our cohort were usually admitted for comorbidities that needed to be managed before HCV infection could be addressed. However, persons with a poor prognosis, such as metastatic cancer, were excluded. We did not attempt to exclude other persons with serious comorbidities such as congestive heart failure, because the guidelines do not currently recommend this, and there may be benefits for patients, their families, and providers from knowing that an individual is chronically HCV infected even if they are not eligible to be treated. Third, the cost of the program was supported in part by a grant and would otherwise have to be borne by the hospital. Fourth, the EMR used by our hospital allows hundreds of admission order sets to be created and made automated order entry hard to implement. This is unlikely to be the situation in other hospitals using different types of EMRs.

It remains to be seen whether safety‐net hospitals with populations at greater risk of HCV infection can afford to support HCV testing and linkage to care. In view of several cost‐effectiveness studies that find screening and treating chronic HCV‐infected baby boomers cost‐effective within standard thresholds,[31, 32, 33] it may be important for policymakers and payers to consider lessons from HIV programs. Because HIV‐infected persons could not afford life‐saving medication, vigorous advocacy efforts led to legislation approving the Ryan White program in 1990 to fill gaps in HIV care that were not covered by other sources of support.[34] HCV infection is the most common blood‐borne infection in the nation, with potentially devastating consequences if ignored, but the underlying premise that universal HCV testing will save lives is in question if most of the individuals who are diagnosed with chronic HCV are low income, uninsured, or underinsured with limited access to curative medications. A rigorous public policy debate regarding both the merits of screening and the availability of treatment to those who are diagnosed is essential to the success of these programs.

Disclosure

Funding for this study was received from the Centers for Disease Control and Prevention CDC PS12‐1209PPHF12. The authors report no conflicts of interest.

References
  1. Smith BD, Morgan RL, Beckett GA, Falck‐Ytter Y, Holtzman D, Ward JW. Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rep. 2012;61:132.
  2. 2. Centers for Disease Control and Prevention. Vital signs: evaluation of hepatitis C virus infection testing and reporting–eight U.S. sites, 2005‐2011. MMWR Morb Mortal Wkly Rep. 2013;62:357361.
  3. Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C virus infection in USA: an estimate of true prevalence. Liver Int. 2011;31:10901101.
  4. Institute of Medicine. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Washington, DC: The National Academies Press; 2010.
  5. Liang TJ, Ghany MG. Current and future therapies for hepatitis C virus infection. N Engl J Med. 2013;368:19071917.
  6. Kanwal F, Hoang T, Kramer JR, et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology. 2011;140:11821188.
  7. U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159:349357.
  8. Brady KA, Weiner MJ, Turner BJ. Undiagnosed hepatitis C on the general medicine and trauma services of two urban hospitals. J Infect. 2009;59:6269.
  9. U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159:5160.
  10. Berkenblit GV, Sosman JM, Bass M, et al. Factors affecting clinician educator encouragement of routine HIV testing among trainees. J Gen Intern Med. 2012;27:839844.
  11. Walensky RP, Reichmann WM, Arbelaez C, et al. Counselor‐versus provider‐based HIV screening in the emergency department: Results from the universal screening for HIV infection in the emergency room (USHER) randomized controlled trial. Ann Emerg Med. 2011;58:S126S132.e1–4.
  12. Greenwald JL, Hall J, Skolnik PR. Approaching the CDC's guidelines on the HIV testing of inpatients: physician‐referral versus nonreferral‐based testing. AIDS Patient Care STDS. 2006;20:311317.
  13. Centers for Disease Control and Prevention (CDC). Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62:362365.
  14. Advia Centaur Assay Manual. Malvern, PA: Siemens Medical Solutions Diagnostics; Pub# 07063235, Rev. C, 2005‐01.
  15. Taylor P, Pickard G, Gammie A, Atkins M. Comparison of the ADVIA Centaur and Abbott AxSYM immunoassay systems for a routine diagnostic virology laboratory. J Clin Virol. 2004;30:S11S15.
  16. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. Available at: http://www.niaaa.nih.gov/alcohol‐health/overview‐alcohol‐consumption/moderate‐binge‐drinking. Accessed June 12, 2014.
  17. Galbraith JW, Franco RA, Donnelly JP, et al. Unrecognized chronic hepatitis C virus infection among baby boomers in the emergency department. Hepatology. 2015;61:776782.
  18. Hoover KW, Butler M, Workowski KA, et al. Low rates of hepatitis screening and vaccination of HIV‐infected MSM in HIV clinics. Sex Transm Dis. 2012;39:349353.
  19. Ditah I, Ditah F, Devaki P, Ditah C, Kamath PS, Charlton M. The changing epidemiology of hepatitis C virus infection in the United States: National Health and Nutrition Examination Survey 2001 through 2010. J Hepatol. 2014;60:691698.
  20. Rongey CA, Kanwal , Hoang T, Gifford AL, Asch SM. Viral RNA testing in hepatitis C antibody‐positive veterans. Am J Prev Med. 2009;36:235238.
  21. Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States: National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160:293300.
  22. Busch MP, Glynn SA, Stramer SL, et al. NHLBI Retrovirus Epidemiology Donor Study (REDS) Group. Correlates of hepatitis C virus (HCV) RNA negativity among HCV‐seropositive blood donors. Transfusion. 2006;46:469475.
  23. Rolfe KJ, Curran MD, Alexander GJ, Wodall T, Andrews N, Harris HE. Spontaneous loss of hepatitis C virus RNA from serum is associated with genotype 1 and younger age at exposure. J Med Virol. 2011;83:13381344.
  24. Grebely J, Dore GJ, Kim AY, et al. Genetics of spontaneous clearance of hepatitis C virus infection: a complex topic with much to learn. Hepatology. 2014;60:21272128.
  25. Fitch K, Iwasaki K, Pyenson B, Engel T. Health care reform and hepatitis C: a convergence of risk and opportunity. Available at: http://us.milliman.com/uploadedFiles/insight/2013/convergence‐of‐risk‐and‐opportunity.pdf. Accessed February 5, 2015.
  26. Tohme RA, Xing J, Liao Y, Holmberg SD. Hepatitis C testing, infection, and linkage to care among racial and ethnic minorities in the United States, 2009‐2010. Am J Public Health. 2013;103:112119.
  27. McGowan CE, Fried MW. Barriers to hepatitis C treatment. Liver Int. 2012;32:151156.
  28. Younossi ZM, Zheng L, Stepanova M, Venkatesan C, Mir HM. Moderate, excessive or heavy alcohol consumption: Each is significantly associated with increased mortality in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2013;37:703709.
  29. Centers for Medicare and Medicaid Services. Proposed decision memo for screening for hepatitis c virus (HCV) in adults (CAG‐00436N). Available at: http://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=272. Accessed June 2, 2014.
  30. Hoofnagle JH, Sherker AH. Therapy for hepatitis C—the costs of success. N Engl J Med. 2014;370:15521553.
  31. McGarry LJ, Pawar VS, Panchmatia HR, et al. Economic model of a birth cohort screening program for hepatitis C. Hepatology. 2012;55:13441355.
  32. Liu S, Cipriano LE, Holodniy M, Goldhaber‐Fiebert JD. Cost‐effectiveness analysis of risk‐factor guided and birth‐cohort screening for chronic hepatitis C infection in the United States. PLoS One. 2013;8:e58975.
  33. Rein DB, Smith BD, Wittenborn JS, et al. The cost‐effectiveness of birth‐cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med. 2012;156:263270.
  34. U.S. Department of Health and Human Services. Health Resources and Services Administration: HIV/AIDS programs. Available at: http://hab.hrsa.gov/abouthab/legislation.html. Accessed April 8, 2015.
References
  1. Smith BD, Morgan RL, Beckett GA, Falck‐Ytter Y, Holtzman D, Ward JW. Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rep. 2012;61:132.
  2. 2. Centers for Disease Control and Prevention. Vital signs: evaluation of hepatitis C virus infection testing and reporting–eight U.S. sites, 2005‐2011. MMWR Morb Mortal Wkly Rep. 2013;62:357361.
  3. Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C virus infection in USA: an estimate of true prevalence. Liver Int. 2011;31:10901101.
  4. Institute of Medicine. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Washington, DC: The National Academies Press; 2010.
  5. Liang TJ, Ghany MG. Current and future therapies for hepatitis C virus infection. N Engl J Med. 2013;368:19071917.
  6. Kanwal F, Hoang T, Kramer JR, et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology. 2011;140:11821188.
  7. U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159:349357.
  8. Brady KA, Weiner MJ, Turner BJ. Undiagnosed hepatitis C on the general medicine and trauma services of two urban hospitals. J Infect. 2009;59:6269.
  9. U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159:5160.
  10. Berkenblit GV, Sosman JM, Bass M, et al. Factors affecting clinician educator encouragement of routine HIV testing among trainees. J Gen Intern Med. 2012;27:839844.
  11. Walensky RP, Reichmann WM, Arbelaez C, et al. Counselor‐versus provider‐based HIV screening in the emergency department: Results from the universal screening for HIV infection in the emergency room (USHER) randomized controlled trial. Ann Emerg Med. 2011;58:S126S132.e1–4.
  12. Greenwald JL, Hall J, Skolnik PR. Approaching the CDC's guidelines on the HIV testing of inpatients: physician‐referral versus nonreferral‐based testing. AIDS Patient Care STDS. 2006;20:311317.
  13. Centers for Disease Control and Prevention (CDC). Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62:362365.
  14. Advia Centaur Assay Manual. Malvern, PA: Siemens Medical Solutions Diagnostics; Pub# 07063235, Rev. C, 2005‐01.
  15. Taylor P, Pickard G, Gammie A, Atkins M. Comparison of the ADVIA Centaur and Abbott AxSYM immunoassay systems for a routine diagnostic virology laboratory. J Clin Virol. 2004;30:S11S15.
  16. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. Available at: http://www.niaaa.nih.gov/alcohol‐health/overview‐alcohol‐consumption/moderate‐binge‐drinking. Accessed June 12, 2014.
  17. Galbraith JW, Franco RA, Donnelly JP, et al. Unrecognized chronic hepatitis C virus infection among baby boomers in the emergency department. Hepatology. 2015;61:776782.
  18. Hoover KW, Butler M, Workowski KA, et al. Low rates of hepatitis screening and vaccination of HIV‐infected MSM in HIV clinics. Sex Transm Dis. 2012;39:349353.
  19. Ditah I, Ditah F, Devaki P, Ditah C, Kamath PS, Charlton M. The changing epidemiology of hepatitis C virus infection in the United States: National Health and Nutrition Examination Survey 2001 through 2010. J Hepatol. 2014;60:691698.
  20. Rongey CA, Kanwal , Hoang T, Gifford AL, Asch SM. Viral RNA testing in hepatitis C antibody‐positive veterans. Am J Prev Med. 2009;36:235238.
  21. Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States: National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160:293300.
  22. Busch MP, Glynn SA, Stramer SL, et al. NHLBI Retrovirus Epidemiology Donor Study (REDS) Group. Correlates of hepatitis C virus (HCV) RNA negativity among HCV‐seropositive blood donors. Transfusion. 2006;46:469475.
  23. Rolfe KJ, Curran MD, Alexander GJ, Wodall T, Andrews N, Harris HE. Spontaneous loss of hepatitis C virus RNA from serum is associated with genotype 1 and younger age at exposure. J Med Virol. 2011;83:13381344.
  24. Grebely J, Dore GJ, Kim AY, et al. Genetics of spontaneous clearance of hepatitis C virus infection: a complex topic with much to learn. Hepatology. 2014;60:21272128.
  25. Fitch K, Iwasaki K, Pyenson B, Engel T. Health care reform and hepatitis C: a convergence of risk and opportunity. Available at: http://us.milliman.com/uploadedFiles/insight/2013/convergence‐of‐risk‐and‐opportunity.pdf. Accessed February 5, 2015.
  26. Tohme RA, Xing J, Liao Y, Holmberg SD. Hepatitis C testing, infection, and linkage to care among racial and ethnic minorities in the United States, 2009‐2010. Am J Public Health. 2013;103:112119.
  27. McGowan CE, Fried MW. Barriers to hepatitis C treatment. Liver Int. 2012;32:151156.
  28. Younossi ZM, Zheng L, Stepanova M, Venkatesan C, Mir HM. Moderate, excessive or heavy alcohol consumption: Each is significantly associated with increased mortality in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2013;37:703709.
  29. Centers for Medicare and Medicaid Services. Proposed decision memo for screening for hepatitis c virus (HCV) in adults (CAG‐00436N). Available at: http://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=272. Accessed June 2, 2014.
  30. Hoofnagle JH, Sherker AH. Therapy for hepatitis C—the costs of success. N Engl J Med. 2014;370:15521553.
  31. McGarry LJ, Pawar VS, Panchmatia HR, et al. Economic model of a birth cohort screening program for hepatitis C. Hepatology. 2012;55:13441355.
  32. Liu S, Cipriano LE, Holodniy M, Goldhaber‐Fiebert JD. Cost‐effectiveness analysis of risk‐factor guided and birth‐cohort screening for chronic hepatitis C infection in the United States. PLoS One. 2013;8:e58975.
  33. Rein DB, Smith BD, Wittenborn JS, et al. The cost‐effectiveness of birth‐cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med. 2012;156:263270.
  34. U.S. Department of Health and Human Services. Health Resources and Services Administration: HIV/AIDS programs. Available at: http://hab.hrsa.gov/abouthab/legislation.html. Accessed April 8, 2015.
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Journal of Hospital Medicine - 10(8)
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Journal of Hospital Medicine - 10(8)
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Implementing hospital‐based baby boomer hepatitis c virus screening and linkage to care: Strategies, results, and costs
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Implementing hospital‐based baby boomer hepatitis c virus screening and linkage to care: Strategies, results, and costs
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Insomnia in the ICU—and after

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Insomnia in the ICU—and after

Two recent studies—one conducted by researchers from Yale University in New Haven and one conducted by researchers from VA Puget Sound Health Care System in Seattle—suggest it is possible to help patients get better sleep, both in the intensive care unit (ICU) and after ICU discharge. However, protocol and policy changes—as well as education—are needed.

To read the full article, go to Federal Practitioner: http://www.fedprac.com/articles/the-latest/article/insomnia-in-the-icu-and-after/7823e1c993201366966884fa1863b588/ocregister.html.

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Two recent studies—one conducted by researchers from Yale University in New Haven and one conducted by researchers from VA Puget Sound Health Care System in Seattle—suggest it is possible to help patients get better sleep, both in the intensive care unit (ICU) and after ICU discharge. However, protocol and policy changes—as well as education—are needed.

To read the full article, go to Federal Practitioner: http://www.fedprac.com/articles/the-latest/article/insomnia-in-the-icu-and-after/7823e1c993201366966884fa1863b588/ocregister.html.

Two recent studies—one conducted by researchers from Yale University in New Haven and one conducted by researchers from VA Puget Sound Health Care System in Seattle—suggest it is possible to help patients get better sleep, both in the intensive care unit (ICU) and after ICU discharge. However, protocol and policy changes—as well as education—are needed.

To read the full article, go to Federal Practitioner: http://www.fedprac.com/articles/the-latest/article/insomnia-in-the-icu-and-after/7823e1c993201366966884fa1863b588/ocregister.html.

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Insomnia in the ICU—and after
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Helping patients afford the new hepatitis C medications

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Helping patients afford the new hepatitis C medications

New antiviral medications for hepatitis C are effective, but the cost of a full course of treatment can reach $100,000. In “How to pay for costly hepatitis C drugs,” which is available at http://www.everydayhealth.com/news/how-pay-costly-hepatitis-c-drugs/, Madeline Vann, MPH, details strategies that patients can use to obtain these medications, including negotiating directly with an insurance company, checking if the manufacturer offers a patient assistance program, and contacting the Patient Access Network Foundation.

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New antiviral medications for hepatitis C are effective, but the cost of a full course of treatment can reach $100,000. In “How to pay for costly hepatitis C drugs,” which is available at http://www.everydayhealth.com/news/how-pay-costly-hepatitis-c-drugs/, Madeline Vann, MPH, details strategies that patients can use to obtain these medications, including negotiating directly with an insurance company, checking if the manufacturer offers a patient assistance program, and contacting the Patient Access Network Foundation.

New antiviral medications for hepatitis C are effective, but the cost of a full course of treatment can reach $100,000. In “How to pay for costly hepatitis C drugs,” which is available at http://www.everydayhealth.com/news/how-pay-costly-hepatitis-c-drugs/, Madeline Vann, MPH, details strategies that patients can use to obtain these medications, including negotiating directly with an insurance company, checking if the manufacturer offers a patient assistance program, and contacting the Patient Access Network Foundation.

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AACE: Bisphosphonates do not prevent fractures in adults with osteogenesis imperfecta

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AACE: Bisphosphonates do not prevent fractures in adults with osteogenesis imperfecta

NASHVILLE, TENN. – Bisphosphonates help prevent fractures in some children with osteogenesis imperfecta, but they don't do the same for adults with the condition, according to a review from Johns Hopkins University and the Kennedy Krieger Institute.

Even so, bisphosphonates are used widely for adult osteogenesis imperfecta (OI) “because people have nothing else to hang their hat on, and the average physician doesn’t understand that osteogenesis imperfecta is not the same as age-related osteoporosis,” said senior investigator Dr. Jay R. Shapiro, director of Kennedy Krieger’s osteogenesis imperfecta program in Baltimore.

Dr. Jay R. Shapiro

“We see adults with OI all the time who have been on bisphosphonates for 10 years, 12 years. It’s not doing anything for them, and sooner or later they come to realize that.” Meanwhile, “I think people are getting a little bit of a queasy feeling about not fully understanding the effectiveness and side effects of long-term treatment with bisphosphonates,” said Dr. Shapiro, also professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore.

Adults with OI “also don’t respond to Forteo [teriparatide]. I do not recommend treatment with bisphosphonates or Forteo in” adults, he said at the annual meeting of the American Association of Clinical Endocrinologists.

Dr. Shapiro shared his thoughts during an interview regarding his latest study, an analysis of five children with OI under 18 years of age who responded to pamidronate (Aredia) and 11 who did not, meaning that they had two or more fractures per year while on the drug.

His team also compared fracture outcomes in 34 adults with OI treated with oral or intravenous bisphosphonates with 12 untreated adults. The adults were, on average, 52 years old.

The goal was to see if common bone markers predicted who would respond to bisphosphonates, but they did not. Vitamin D, phosphorus, alkaline phosphatase, C-telopeptide, and other measures were the same in children regardless of their response to pamidronate, and the same in adults with OI whether or not they were on bisphosphonates.

“We have not yet defined what the difference is between responders and nonresponders. If you take a crack at the simple things, they don’t help,” Dr. Shapiro said.

Children who responded had a mean of 4.8 fractures over an average of 42.6 months of treatment. Nonresponders had a mean of 15.6 fractures over an average of 72.7 months of treatment.

“For a period of time, you can expect about two-thirds of kids to respond. I would look to see a decrease in fracture rates within 2 years of treatment. If they haven’t decreased their fracture rate [by then], I would be very cautious about continuing,” he said, adding that the optimal duration of treatment in children is unknown.

In adults, the team found no difference in fracture rates at 5 and 10 years. Treated adults had an average of 1.71 fractures over 10 years, versus 1.23 in untreated adults (P = 0.109).

The numbers in the study were too small for meaningful subgroup analysis by OI type.

The findings parallel recent meta-analyses; some have found that bisphosphonates help OI children, but none has found benefits for adults (J. Bone. Miner. Res. 2015;30:929-33). “To date, there is no evidence indicating that bisphosphonates have a positive effect on fracture rates in adults,” Dr. Shapiro said.

Bone turnover declines after puberty, which may explain why the drugs lose their effectiveness after age 18 or so. “What happens in OI anyway is that, after puberty, the fracture rates normally go way down,” Dr. Shapiro said.

Dr. Shapiro said that he had no relevant disclosures, and that there was no outside funding for the work.

[email protected]

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NASHVILLE, TENN. – Bisphosphonates help prevent fractures in some children with osteogenesis imperfecta, but they don't do the same for adults with the condition, according to a review from Johns Hopkins University and the Kennedy Krieger Institute.

Even so, bisphosphonates are used widely for adult osteogenesis imperfecta (OI) “because people have nothing else to hang their hat on, and the average physician doesn’t understand that osteogenesis imperfecta is not the same as age-related osteoporosis,” said senior investigator Dr. Jay R. Shapiro, director of Kennedy Krieger’s osteogenesis imperfecta program in Baltimore.

Dr. Jay R. Shapiro

“We see adults with OI all the time who have been on bisphosphonates for 10 years, 12 years. It’s not doing anything for them, and sooner or later they come to realize that.” Meanwhile, “I think people are getting a little bit of a queasy feeling about not fully understanding the effectiveness and side effects of long-term treatment with bisphosphonates,” said Dr. Shapiro, also professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore.

Adults with OI “also don’t respond to Forteo [teriparatide]. I do not recommend treatment with bisphosphonates or Forteo in” adults, he said at the annual meeting of the American Association of Clinical Endocrinologists.

Dr. Shapiro shared his thoughts during an interview regarding his latest study, an analysis of five children with OI under 18 years of age who responded to pamidronate (Aredia) and 11 who did not, meaning that they had two or more fractures per year while on the drug.

His team also compared fracture outcomes in 34 adults with OI treated with oral or intravenous bisphosphonates with 12 untreated adults. The adults were, on average, 52 years old.

The goal was to see if common bone markers predicted who would respond to bisphosphonates, but they did not. Vitamin D, phosphorus, alkaline phosphatase, C-telopeptide, and other measures were the same in children regardless of their response to pamidronate, and the same in adults with OI whether or not they were on bisphosphonates.

“We have not yet defined what the difference is between responders and nonresponders. If you take a crack at the simple things, they don’t help,” Dr. Shapiro said.

Children who responded had a mean of 4.8 fractures over an average of 42.6 months of treatment. Nonresponders had a mean of 15.6 fractures over an average of 72.7 months of treatment.

“For a period of time, you can expect about two-thirds of kids to respond. I would look to see a decrease in fracture rates within 2 years of treatment. If they haven’t decreased their fracture rate [by then], I would be very cautious about continuing,” he said, adding that the optimal duration of treatment in children is unknown.

In adults, the team found no difference in fracture rates at 5 and 10 years. Treated adults had an average of 1.71 fractures over 10 years, versus 1.23 in untreated adults (P = 0.109).

The numbers in the study were too small for meaningful subgroup analysis by OI type.

The findings parallel recent meta-analyses; some have found that bisphosphonates help OI children, but none has found benefits for adults (J. Bone. Miner. Res. 2015;30:929-33). “To date, there is no evidence indicating that bisphosphonates have a positive effect on fracture rates in adults,” Dr. Shapiro said.

Bone turnover declines after puberty, which may explain why the drugs lose their effectiveness after age 18 or so. “What happens in OI anyway is that, after puberty, the fracture rates normally go way down,” Dr. Shapiro said.

Dr. Shapiro said that he had no relevant disclosures, and that there was no outside funding for the work.

[email protected]

NASHVILLE, TENN. – Bisphosphonates help prevent fractures in some children with osteogenesis imperfecta, but they don't do the same for adults with the condition, according to a review from Johns Hopkins University and the Kennedy Krieger Institute.

Even so, bisphosphonates are used widely for adult osteogenesis imperfecta (OI) “because people have nothing else to hang their hat on, and the average physician doesn’t understand that osteogenesis imperfecta is not the same as age-related osteoporosis,” said senior investigator Dr. Jay R. Shapiro, director of Kennedy Krieger’s osteogenesis imperfecta program in Baltimore.

Dr. Jay R. Shapiro

“We see adults with OI all the time who have been on bisphosphonates for 10 years, 12 years. It’s not doing anything for them, and sooner or later they come to realize that.” Meanwhile, “I think people are getting a little bit of a queasy feeling about not fully understanding the effectiveness and side effects of long-term treatment with bisphosphonates,” said Dr. Shapiro, also professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore.

Adults with OI “also don’t respond to Forteo [teriparatide]. I do not recommend treatment with bisphosphonates or Forteo in” adults, he said at the annual meeting of the American Association of Clinical Endocrinologists.

Dr. Shapiro shared his thoughts during an interview regarding his latest study, an analysis of five children with OI under 18 years of age who responded to pamidronate (Aredia) and 11 who did not, meaning that they had two or more fractures per year while on the drug.

His team also compared fracture outcomes in 34 adults with OI treated with oral or intravenous bisphosphonates with 12 untreated adults. The adults were, on average, 52 years old.

The goal was to see if common bone markers predicted who would respond to bisphosphonates, but they did not. Vitamin D, phosphorus, alkaline phosphatase, C-telopeptide, and other measures were the same in children regardless of their response to pamidronate, and the same in adults with OI whether or not they were on bisphosphonates.

“We have not yet defined what the difference is between responders and nonresponders. If you take a crack at the simple things, they don’t help,” Dr. Shapiro said.

Children who responded had a mean of 4.8 fractures over an average of 42.6 months of treatment. Nonresponders had a mean of 15.6 fractures over an average of 72.7 months of treatment.

“For a period of time, you can expect about two-thirds of kids to respond. I would look to see a decrease in fracture rates within 2 years of treatment. If they haven’t decreased their fracture rate [by then], I would be very cautious about continuing,” he said, adding that the optimal duration of treatment in children is unknown.

In adults, the team found no difference in fracture rates at 5 and 10 years. Treated adults had an average of 1.71 fractures over 10 years, versus 1.23 in untreated adults (P = 0.109).

The numbers in the study were too small for meaningful subgroup analysis by OI type.

The findings parallel recent meta-analyses; some have found that bisphosphonates help OI children, but none has found benefits for adults (J. Bone. Miner. Res. 2015;30:929-33). “To date, there is no evidence indicating that bisphosphonates have a positive effect on fracture rates in adults,” Dr. Shapiro said.

Bone turnover declines after puberty, which may explain why the drugs lose their effectiveness after age 18 or so. “What happens in OI anyway is that, after puberty, the fracture rates normally go way down,” Dr. Shapiro said.

Dr. Shapiro said that he had no relevant disclosures, and that there was no outside funding for the work.

[email protected]

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Key clinical point: Adult osteogenesis imperfecta patients don’t need bisphosphonates.

Major finding: Treated adults had an average of 1.71 fractures over 10 years; untreated adults had an average of 1.23 (P = 0.109).

Data source: Retrospective study of 16 pediatric and 46 adult OI patients.

Disclosures: There was no outside funding for the work, and the senior investigator had no relevant disclosures.