Only about one in three available hearts was accepted for transplant in the United States in 2010, down from 44% 2 decades ago, researchers reported online Feb. 9 in the American Journal of Transplantation.

The decline stems in part from transplant centers rejecting “marginal” donor hearts, belying a growing need for heart transplants, longer waiting times, and multiple campaigns to expand the use of organs donated for transplantation, said Dr. Kiran Khush of Stanford (Calif.) University and her associates.

The researchers analyzed data on 82,053 potential donor hearts from the Organ Procurement and Transplantation Network. In 1995, 44% of available hearts were accepted for transplant, compared with only 29% in 2006 and 32% in 2010, they found. Meanwhile, rejection rates for donor hearts rose from 37% in 1995 to 52% in 2010, they reported (Am. J. Transplant. 2015 Feb. 10 [doi:10.1111/ajt.13055]).

Several factors might explain the trends, the investigators said. Potential heart donors tended to be older and more often had hypertension and diabetes by the final years of the study period, and transplant centers were less likely to accept hearts from such individuals. Also, mechanical circulatory devices were more commonly used, and centers might hesitate to transplant “marginal” hearts into “stable” recipients of such devices, Dr. Khush and her associates said. Furthermore, government scrutiny of post-transplant outcomes might make centers more conservative when evaluating potential donors, they added.

The study also uncovered regional variations in acceptance rates for donor hearts, with the lowest – about 25%-28% – found primarily in the southeastern United States. “Unfortunately, there are no standard guidelines for donor heart evaluation and acceptance, resulting in considerable inconsistencies in the types of donor hearts that are accepted by different transplant centers, and likely resulting in nonrecovery of potentially useful organs,” the investigators said. The findings “lend support to research and policy efforts aimed at establishing evidence-based criteria for donor heart evaluation and acceptance,” they added.

The work was supported by the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the Health Resources and Services Administration. The authors reported having no conflicts of interest.

Only about one in three available hearts was accepted for transplant in the United States in 2010, down from 44% 2 decades ago, researchers reported online Feb. 9 in the American Journal of Transplantation.

The decline stems in part from transplant centers rejecting “marginal” donor hearts, belying a growing need for heart transplants, longer waiting times, and multiple campaigns to expand the use of organs donated for transplantation, said Dr. Kiran Khush of Stanford (Calif.) University and her associates.

The researchers analyzed data on 82,053 potential donor hearts from the Organ Procurement and Transplantation Network. In 1995, 44% of available hearts were accepted for transplant, compared with only 29% in 2006 and 32% in 2010, they found. Meanwhile, rejection rates for donor hearts rose from 37% in 1995 to 52% in 2010, they reported (Am. J. Transplant. 2015 Feb. 10 [doi:10.1111/ajt.13055]).

Several factors might explain the trends, the investigators said. Potential heart donors tended to be older and more often had hypertension and diabetes by the final years of the study period, and transplant centers were less likely to accept hearts from such individuals. Also, mechanical circulatory devices were more commonly used, and centers might hesitate to transplant “marginal” hearts into “stable” recipients of such devices, Dr. Khush and her associates said. Furthermore, government scrutiny of post-transplant outcomes might make centers more conservative when evaluating potential donors, they added.

The study also uncovered regional variations in acceptance rates for donor hearts, with the lowest – about 25%-28% – found primarily in the southeastern United States. “Unfortunately, there are no standard guidelines for donor heart evaluation and acceptance, resulting in considerable inconsistencies in the types of donor hearts that are accepted by different transplant centers, and likely resulting in nonrecovery of potentially useful organs,” the investigators said. The findings “lend support to research and policy efforts aimed at establishing evidence-based criteria for donor heart evaluation and acceptance,” they added.

The work was supported by the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the Health Resources and Services Administration. The authors reported having no conflicts of interest.

Only about one in three available hearts was accepted for transplant in the United States in 2010, down from 44% 2 decades ago, researchers reported online Feb. 9 in the American Journal of Transplantation.

The decline stems in part from transplant centers rejecting “marginal” donor hearts, belying a growing need for heart transplants, longer waiting times, and multiple campaigns to expand the use of organs donated for transplantation, said Dr. Kiran Khush of Stanford (Calif.) University and her associates.

The researchers analyzed data on 82,053 potential donor hearts from the Organ Procurement and Transplantation Network. In 1995, 44% of available hearts were accepted for transplant, compared with only 29% in 2006 and 32% in 2010, they found. Meanwhile, rejection rates for donor hearts rose from 37% in 1995 to 52% in 2010, they reported (Am. J. Transplant. 2015 Feb. 10 [doi:10.1111/ajt.13055]).

Several factors might explain the trends, the investigators said. Potential heart donors tended to be older and more often had hypertension and diabetes by the final years of the study period, and transplant centers were less likely to accept hearts from such individuals. Also, mechanical circulatory devices were more commonly used, and centers might hesitate to transplant “marginal” hearts into “stable” recipients of such devices, Dr. Khush and her associates said. Furthermore, government scrutiny of post-transplant outcomes might make centers more conservative when evaluating potential donors, they added.

The study also uncovered regional variations in acceptance rates for donor hearts, with the lowest – about 25%-28% – found primarily in the southeastern United States. “Unfortunately, there are no standard guidelines for donor heart evaluation and acceptance, resulting in considerable inconsistencies in the types of donor hearts that are accepted by different transplant centers, and likely resulting in nonrecovery of potentially useful organs,” the investigators said. The findings “lend support to research and policy efforts aimed at establishing evidence-based criteria for donor heart evaluation and acceptance,” they added.

The work was supported by the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the Health Resources and Services Administration. The authors reported having no conflicts of interest.

Among patients with advanced melanoma who were treated with ipilimumab, about 20%-26% survived to 3 years, and these patients are likely to have a good long-term outcome, according to a pooled analysis of survival data published online Feb. 9 in the Journal of Clinical Oncology.

Investigators pooled data from ten prospective (including two phase III trials) and two retrospective studies with a total of 1,257 previously treated and 604 treatment-naive patients. At least 3 years after receiving ipilimumab, 254 patients were still alive, with a median follow up for this subset of 69 months. Around year 3, the Kaplan-Meier overall survival (OS) curve began to plateau and extended to 9.9 years for the longest survival follow-up.

“These results suggest that the majority of patients who reached this milestone time point had a low risk of death thereafter,” wrote Dr. Dirk Schadendorf and his associates (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]).

Compared with patients who were previously treated, treatment-naive patients had a higher median overall survival (13.5 months [95% confidence interval, 11.9-15.4] vs. 10.7 months [9.6-11.4]) and higher 3-year-survival rates (26% [21%-30%] vs. 20% [18%-23%]). No definitive conclusion could be drawn from this observation, however, since nonrandomized subsets were used for this analysis. Subset analysis by dose showed similar median OS and 3-year survival rates for ipilimumab 3 mg/kg, 10 mg/kg, and other dosing regimens.

The researchers expanded the study to include overall survival (OS) data from 2,985 patients enrolled in a U.S. multicenter, open-label, expanded-access treatment protocol (EAP). This group included patients with poorer prognostic factors, some of whom were ineligible for clinical trials. The expanded group showed a lower median OS of 9.5 months and 3 year–survival rate of 21%, with the familiar OS curve plateau around 3 years that extended up to 10 years in some patients.

While this analysis only examined overall survival rates, individual ipilimumab studies that tracked patient responses to the drug have shown that some proportion of long-term survivors did not achieve a response. Identifying the specific disease characteristics of the long-term survivors will require further study.

“Considering the historic median OS of approximately 8-10 months and a 5-year survival rate of approximately 10% in advanced melanoma, the results presented herein are encouraging for patients diagnosed with this aggressive disease,” the authors wrote.

Among patients with advanced melanoma who were treated with ipilimumab, about 20%-26% survived to 3 years, and these patients are likely to have a good long-term outcome, according to a pooled analysis of survival data published online Feb. 9 in the Journal of Clinical Oncology.

Investigators pooled data from ten prospective (including two phase III trials) and two retrospective studies with a total of 1,257 previously treated and 604 treatment-naive patients. At least 3 years after receiving ipilimumab, 254 patients were still alive, with a median follow up for this subset of 69 months. Around year 3, the Kaplan-Meier overall survival (OS) curve began to plateau and extended to 9.9 years for the longest survival follow-up.

“These results suggest that the majority of patients who reached this milestone time point had a low risk of death thereafter,” wrote Dr. Dirk Schadendorf and his associates (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]).

Compared with patients who were previously treated, treatment-naive patients had a higher median overall survival (13.5 months [95% confidence interval, 11.9-15.4] vs. 10.7 months [9.6-11.4]) and higher 3-year-survival rates (26% [21%-30%] vs. 20% [18%-23%]). No definitive conclusion could be drawn from this observation, however, since nonrandomized subsets were used for this analysis. Subset analysis by dose showed similar median OS and 3-year survival rates for ipilimumab 3 mg/kg, 10 mg/kg, and other dosing regimens.

The researchers expanded the study to include overall survival (OS) data from 2,985 patients enrolled in a U.S. multicenter, open-label, expanded-access treatment protocol (EAP). This group included patients with poorer prognostic factors, some of whom were ineligible for clinical trials. The expanded group showed a lower median OS of 9.5 months and 3 year–survival rate of 21%, with the familiar OS curve plateau around 3 years that extended up to 10 years in some patients.

While this analysis only examined overall survival rates, individual ipilimumab studies that tracked patient responses to the drug have shown that some proportion of long-term survivors did not achieve a response. Identifying the specific disease characteristics of the long-term survivors will require further study.

“Considering the historic median OS of approximately 8-10 months and a 5-year survival rate of approximately 10% in advanced melanoma, the results presented herein are encouraging for patients diagnosed with this aggressive disease,” the authors wrote.

Among patients with advanced melanoma who were treated with ipilimumab, about 20%-26% survived to 3 years, and these patients are likely to have a good long-term outcome, according to a pooled analysis of survival data published online Feb. 9 in the Journal of Clinical Oncology.

Investigators pooled data from ten prospective (including two phase III trials) and two retrospective studies with a total of 1,257 previously treated and 604 treatment-naive patients. At least 3 years after receiving ipilimumab, 254 patients were still alive, with a median follow up for this subset of 69 months. Around year 3, the Kaplan-Meier overall survival (OS) curve began to plateau and extended to 9.9 years for the longest survival follow-up.

“These results suggest that the majority of patients who reached this milestone time point had a low risk of death thereafter,” wrote Dr. Dirk Schadendorf and his associates (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]).

Compared with patients who were previously treated, treatment-naive patients had a higher median overall survival (13.5 months [95% confidence interval, 11.9-15.4] vs. 10.7 months [9.6-11.4]) and higher 3-year-survival rates (26% [21%-30%] vs. 20% [18%-23%]). No definitive conclusion could be drawn from this observation, however, since nonrandomized subsets were used for this analysis. Subset analysis by dose showed similar median OS and 3-year survival rates for ipilimumab 3 mg/kg, 10 mg/kg, and other dosing regimens.

The researchers expanded the study to include overall survival (OS) data from 2,985 patients enrolled in a U.S. multicenter, open-label, expanded-access treatment protocol (EAP). This group included patients with poorer prognostic factors, some of whom were ineligible for clinical trials. The expanded group showed a lower median OS of 9.5 months and 3 year–survival rate of 21%, with the familiar OS curve plateau around 3 years that extended up to 10 years in some patients.

While this analysis only examined overall survival rates, individual ipilimumab studies that tracked patient responses to the drug have shown that some proportion of long-term survivors did not achieve a response. Identifying the specific disease characteristics of the long-term survivors will require further study.

“Considering the historic median OS of approximately 8-10 months and a 5-year survival rate of approximately 10% in advanced melanoma, the results presented herein are encouraging for patients diagnosed with this aggressive disease,” the authors wrote.

The American Society of Clinical Oncology has endorsed the American Cancer Society Prostate Cancer Survivorship Care Guidelines, a 39-point list with recommendations on continuing care for prostate care survivors, but with a number of qualifying statements and modifications.

The guidelines, developed by a workgroup of 16 multidisciplinary experts specializing in the care of prostate cancer patients and the long-term effects of their treatments, are intended as points of reference for primary care providers, medical oncologists, urologists, and other health care providers.

Areas covered in the guidelines include health promotion, surveillance for recurrence, screening and early detection of second primary cancers, assessment and management of physical and psychosocial long-term and late effects, and care coordination and practice implications.Read the full list of recommendations here: (doi: 10.1200/JCO.2014.60.2557).

The American Society of Clinical Oncology has endorsed the American Cancer Society Prostate Cancer Survivorship Care Guidelines, a 39-point list with recommendations on continuing care for prostate care survivors, but with a number of qualifying statements and modifications.

The guidelines, developed by a workgroup of 16 multidisciplinary experts specializing in the care of prostate cancer patients and the long-term effects of their treatments, are intended as points of reference for primary care providers, medical oncologists, urologists, and other health care providers.

Areas covered in the guidelines include health promotion, surveillance for recurrence, screening and early detection of second primary cancers, assessment and management of physical and psychosocial long-term and late effects, and care coordination and practice implications.Read the full list of recommendations here: (doi: 10.1200/JCO.2014.60.2557).

The American Society of Clinical Oncology has endorsed the American Cancer Society Prostate Cancer Survivorship Care Guidelines, a 39-point list with recommendations on continuing care for prostate care survivors, but with a number of qualifying statements and modifications.

The guidelines, developed by a workgroup of 16 multidisciplinary experts specializing in the care of prostate cancer patients and the long-term effects of their treatments, are intended as points of reference for primary care providers, medical oncologists, urologists, and other health care providers.

Areas covered in the guidelines include health promotion, surveillance for recurrence, screening and early detection of second primary cancers, assessment and management of physical and psychosocial long-term and late effects, and care coordination and practice implications.Read the full list of recommendations here: (doi: 10.1200/JCO.2014.60.2557).

NEW YORK – Incorporating psychiatric assessment and treatment into a busy primary care practice is not easy, but it is doable.

“Every time I start a patient on a [psychiatric] medication I have a moment of trepidation, even though I have now done this for about 4 years,” Dr. Diane E. Bloomfield said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry. “It still does not come easily to me,” said Dr. Bloomfield, a general-practice pediatrician at the family care center of Montefiore Medical Center in New York.

Inclusion of mental health as part of routine pediatric practice is a new concept. “Until recently, we pediatricians did not think of mental health as part of daily practice,” she said.

Dr. Bloomfield cited three factors that pose the greatest challenges to integrating psychiatry into her practice: time constraints, reimbursement, and knowledge gaps.

Reimbursement limitations contribute to the time issue. Most of Dr. Bloomfield’s patients are covered by Medicaid, which allows for a 15-minute session with each patient and family. That’s barely enough time to assess a child’s social and emotional development, in addition to all the other bases she must cover during an appointment, but she tries to carve out time for more challenging cases by scheduling them near the end of her day.

Dr. Bloomfield said that she routinely administers the Pediatric Symptom Checklist to all her patients who are 4-18 years old. She recommended that pediatricians take advantage of all the screening tools that the American Academy of Pediatrics (AAP) includes with its practice guidelines, along with the other mental health resources on the AAP website. Using improved coding on her billings also allowed her to arrange reimbursement for more of the time she spends on mental health conditions.

Reducing the knowledge gap can be more complicated. Many pediatricians, Dr. Bloomfield included, did not prescribe methylphenidate or selective serotonin reuptake inhibitors (SSRIs) during training. The boxed warning that the Food and Drug Administration put on antidepressants starting in 2004 has been another factor dampening drug psychotherapy by pediatricians, dissuading them from treating depression, she said.

Some of these dilemmas decreased when the AAP released in 2010 two algorithms that provided a framework for identifying and managing mental health and substance abuse concerns in primary care (Pediatrics 2010;125:S109-25). Neither algorithm, however, dealt with psychopharmacology.

Survey results have shown that many pediatricians become more willing to prescribe SSRIs if they can consult with a psychiatrist about the diagnosis and treatment. Pediatricians are generally more comfortable prescribing stimulants for attention-deficit/hyperactivity disorder (ADHD). “We see a lot of kids with ADHD, so we think we need to do something for them. In addition, medications for ADHD either work or don’t work, but they don’t cause suicidality,” Dr. Bloomfield said.

An AAP working group that included Dr. Bloomfield recently introduced a pilot program for a revised residency curriculum that includes a mental health module as well as a second module that focuses on anxiety diagnosis and management. In addition, certain states, including Massachusetts and New York, have introduced postresidency education programs that deal with child and adolescent psychiatry, including drug treatment.

Dr. Bloomfield said that she had taken training courses in the New York program. “It gave me the tools for evaluating patients and it taught me how to start medications in a safe way.” The midcareer training she received through New York’s Child and Adolescent Psychiatry for Primary Care program “made me much more confident that I could address my patients’ psychosocial needs.” Today, Dr. Bloomfield said she tries to manage children and adolescents with mild depression herself and not refer them to a specialist.

“Pediatricians are quite willing” to include psychiatric interventions in their practice, but we need support from psychiatrists to receive the necessary education and adequate reimbursement,” Dr. Bloomfield said.

[email protected]


On Twitter @mitchelzoler

NEW YORK – Incorporating psychiatric assessment and treatment into a busy primary care practice is not easy, but it is doable.

“Every time I start a patient on a [psychiatric] medication I have a moment of trepidation, even though I have now done this for about 4 years,” Dr. Diane E. Bloomfield said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry. “It still does not come easily to me,” said Dr. Bloomfield, a general-practice pediatrician at the family care center of Montefiore Medical Center in New York.

Inclusion of mental health as part of routine pediatric practice is a new concept. “Until recently, we pediatricians did not think of mental health as part of daily practice,” she said.

Dr. Bloomfield cited three factors that pose the greatest challenges to integrating psychiatry into her practice: time constraints, reimbursement, and knowledge gaps.

Reimbursement limitations contribute to the time issue. Most of Dr. Bloomfield’s patients are covered by Medicaid, which allows for a 15-minute session with each patient and family. That’s barely enough time to assess a child’s social and emotional development, in addition to all the other bases she must cover during an appointment, but she tries to carve out time for more challenging cases by scheduling them near the end of her day.

Dr. Bloomfield said that she routinely administers the Pediatric Symptom Checklist to all her patients who are 4-18 years old. She recommended that pediatricians take advantage of all the screening tools that the American Academy of Pediatrics (AAP) includes with its practice guidelines, along with the other mental health resources on the AAP website. Using improved coding on her billings also allowed her to arrange reimbursement for more of the time she spends on mental health conditions.

Reducing the knowledge gap can be more complicated. Many pediatricians, Dr. Bloomfield included, did not prescribe methylphenidate or selective serotonin reuptake inhibitors (SSRIs) during training. The boxed warning that the Food and Drug Administration put on antidepressants starting in 2004 has been another factor dampening drug psychotherapy by pediatricians, dissuading them from treating depression, she said.

Some of these dilemmas decreased when the AAP released in 2010 two algorithms that provided a framework for identifying and managing mental health and substance abuse concerns in primary care (Pediatrics 2010;125:S109-25). Neither algorithm, however, dealt with psychopharmacology.

Survey results have shown that many pediatricians become more willing to prescribe SSRIs if they can consult with a psychiatrist about the diagnosis and treatment. Pediatricians are generally more comfortable prescribing stimulants for attention-deficit/hyperactivity disorder (ADHD). “We see a lot of kids with ADHD, so we think we need to do something for them. In addition, medications for ADHD either work or don’t work, but they don’t cause suicidality,” Dr. Bloomfield said.

An AAP working group that included Dr. Bloomfield recently introduced a pilot program for a revised residency curriculum that includes a mental health module as well as a second module that focuses on anxiety diagnosis and management. In addition, certain states, including Massachusetts and New York, have introduced postresidency education programs that deal with child and adolescent psychiatry, including drug treatment.

Dr. Bloomfield said that she had taken training courses in the New York program. “It gave me the tools for evaluating patients and it taught me how to start medications in a safe way.” The midcareer training she received through New York’s Child and Adolescent Psychiatry for Primary Care program “made me much more confident that I could address my patients’ psychosocial needs.” Today, Dr. Bloomfield said she tries to manage children and adolescents with mild depression herself and not refer them to a specialist.

“Pediatricians are quite willing” to include psychiatric interventions in their practice, but we need support from psychiatrists to receive the necessary education and adequate reimbursement,” Dr. Bloomfield said.

[email protected]


On Twitter @mitchelzoler

NEW YORK – Incorporating psychiatric assessment and treatment into a busy primary care practice is not easy, but it is doable.

“Every time I start a patient on a [psychiatric] medication I have a moment of trepidation, even though I have now done this for about 4 years,” Dr. Diane E. Bloomfield said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry. “It still does not come easily to me,” said Dr. Bloomfield, a general-practice pediatrician at the family care center of Montefiore Medical Center in New York.

Inclusion of mental health as part of routine pediatric practice is a new concept. “Until recently, we pediatricians did not think of mental health as part of daily practice,” she said.

Dr. Bloomfield cited three factors that pose the greatest challenges to integrating psychiatry into her practice: time constraints, reimbursement, and knowledge gaps.

Reimbursement limitations contribute to the time issue. Most of Dr. Bloomfield’s patients are covered by Medicaid, which allows for a 15-minute session with each patient and family. That’s barely enough time to assess a child’s social and emotional development, in addition to all the other bases she must cover during an appointment, but she tries to carve out time for more challenging cases by scheduling them near the end of her day.

Dr. Bloomfield said that she routinely administers the Pediatric Symptom Checklist to all her patients who are 4-18 years old. She recommended that pediatricians take advantage of all the screening tools that the American Academy of Pediatrics (AAP) includes with its practice guidelines, along with the other mental health resources on the AAP website. Using improved coding on her billings also allowed her to arrange reimbursement for more of the time she spends on mental health conditions.

Reducing the knowledge gap can be more complicated. Many pediatricians, Dr. Bloomfield included, did not prescribe methylphenidate or selective serotonin reuptake inhibitors (SSRIs) during training. The boxed warning that the Food and Drug Administration put on antidepressants starting in 2004 has been another factor dampening drug psychotherapy by pediatricians, dissuading them from treating depression, she said.

Some of these dilemmas decreased when the AAP released in 2010 two algorithms that provided a framework for identifying and managing mental health and substance abuse concerns in primary care (Pediatrics 2010;125:S109-25). Neither algorithm, however, dealt with psychopharmacology.

Survey results have shown that many pediatricians become more willing to prescribe SSRIs if they can consult with a psychiatrist about the diagnosis and treatment. Pediatricians are generally more comfortable prescribing stimulants for attention-deficit/hyperactivity disorder (ADHD). “We see a lot of kids with ADHD, so we think we need to do something for them. In addition, medications for ADHD either work or don’t work, but they don’t cause suicidality,” Dr. Bloomfield said.

An AAP working group that included Dr. Bloomfield recently introduced a pilot program for a revised residency curriculum that includes a mental health module as well as a second module that focuses on anxiety diagnosis and management. In addition, certain states, including Massachusetts and New York, have introduced postresidency education programs that deal with child and adolescent psychiatry, including drug treatment.

Dr. Bloomfield said that she had taken training courses in the New York program. “It gave me the tools for evaluating patients and it taught me how to start medications in a safe way.” The midcareer training she received through New York’s Child and Adolescent Psychiatry for Primary Care program “made me much more confident that I could address my patients’ psychosocial needs.” Today, Dr. Bloomfield said she tries to manage children and adolescents with mild depression herself and not refer them to a specialist.

“Pediatricians are quite willing” to include psychiatric interventions in their practice, but we need support from psychiatrists to receive the necessary education and adequate reimbursement,” Dr. Bloomfield said.

[email protected]


On Twitter @mitchelzoler

Since 2004, there’s been almost a tripling of the number of nonalcoholic steatohepatitis patients waiting for liver transplants; the condition is now the second leading reason to be put on the waiting list in the United States, according to a study published in the March issue of Gastroenterology.*

Even so and for reasons that are not fully clear, adults with nonalcoholic steatohepatitis (NASH) are less likely to survive for 90 days on the wait list than are patients with alcoholic liver disease (ALD), and less likely to get a new liver within 90 days than are patients with ALD, hepatitis C virus (HCV), or a blend of both. For now, HCV remains the No. 1 reason for liver transplants in the United States (Gastroenterology 2014 Nov. 24 [doi: 10.1053/j.gastro.2014.11.039]).

“Our study provides valuable information about the changing epidemiology of chronic liver disease among wait-listed patients, and adds greatly to our understanding of the epidemiology of NASH in the United States,” the researchers wrote. The rapid rise in the prevalence of NASH is “a direct consequence of the worldwide obesity epidemic” as well as greater awareness of the condition. An expected decline in HCV-related cirrhosis due to effective antiviral therapy “will further contribute to the changing epidemiology of patients awaiting liver transplants in the United States,” said the authors, led by Dr. Robert Wong of the division of gastroenterology and hepatology at Highland Hospital, Oakland, Calif.

“Given the expected continued rise in the number of NASH patients awaiting liver transplant, additional research is needed to improve wait-list survival and ... outcomes among this cohort. In addition, the projection that overall donor availability will significantly diminish in the next 15-20 years emphasizes the need for additional research to improve liver transplant opportunities for NASH patients, including the option of living donor[s],” they said.

The researchers analyzed data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry.

From 2004 to 2013, new wait-list registrants with NASH increased by 170% from 804 to 2,174; those with ALD increased by 45% from 1,400 to 2,024; and those with HCV increased by 14% from 2,887 to 3,291. Registrants with both HCV and ALD decreased by 9% from 880 to 803. NASH became the second-leading disease among liver transplant wait-list registrants in 2013.

Patients with ALD had a significantly higher Model for End-Stage Liver Disease (MELD) score at the time of registration than did others. However, after adjustment for MELD and other variables, patients with ALD were less likely to die within 90 days than were NASH patients (OR 0.77; 95% CI 0.67–0.89; P < .001). No difference was seen in wait-list mortality between NASH and HCV and HCV/ALD patients.

Compared with NASH, patients with HCV (OR 1.45; 95% CI 1.35–1.55; P < .001), ALD (OR 1.15; 95% CI: 1.06–1.24; P < .001), and HCV/ALD (OR 1.29; 95% CI 1.18–1.42; P < .001) were all significantly more likely to receive a liver after 3 months on the wait list.

A “potential explanation for these observations might be etiology-specific differences in disease progression, such that more aggressive etiologies (e.g., HCV or HCV/ALD) can have a more rapid rise in MELD score, receive liver transplant, and have lower wait-list mortality, and etiologies with less rapid progression (e.g., NASH) can have slower rise in MELD score over time, lower rates of LT, but no significant increase in wait-list mortality,” the investigators said.

Overall 1-year wait-list survival among NASH patients decreased from 42.8% in 2004-2008 to 25.6% in 2009-2013, and overall 1-year probability of receiving liver transplant among NASH patients also decreased from 42.1% in 2004-2008 to 39.6% in 2009-2013. The trends were similar for other etiologies, perhaps in part because there are more people waiting for a liver.

The authors said they have no financial conflicts to disclose.

[email protected]

*A change was made to the text on 3/12/2015.

Since 2004, there’s been almost a tripling of the number of nonalcoholic steatohepatitis patients waiting for liver transplants; the condition is now the second leading reason to be put on the waiting list in the United States, according to a study published in the March issue of Gastroenterology.*

Even so and for reasons that are not fully clear, adults with nonalcoholic steatohepatitis (NASH) are less likely to survive for 90 days on the wait list than are patients with alcoholic liver disease (ALD), and less likely to get a new liver within 90 days than are patients with ALD, hepatitis C virus (HCV), or a blend of both. For now, HCV remains the No. 1 reason for liver transplants in the United States (Gastroenterology 2014 Nov. 24 [doi: 10.1053/j.gastro.2014.11.039]).

“Our study provides valuable information about the changing epidemiology of chronic liver disease among wait-listed patients, and adds greatly to our understanding of the epidemiology of NASH in the United States,” the researchers wrote. The rapid rise in the prevalence of NASH is “a direct consequence of the worldwide obesity epidemic” as well as greater awareness of the condition. An expected decline in HCV-related cirrhosis due to effective antiviral therapy “will further contribute to the changing epidemiology of patients awaiting liver transplants in the United States,” said the authors, led by Dr. Robert Wong of the division of gastroenterology and hepatology at Highland Hospital, Oakland, Calif.

“Given the expected continued rise in the number of NASH patients awaiting liver transplant, additional research is needed to improve wait-list survival and ... outcomes among this cohort. In addition, the projection that overall donor availability will significantly diminish in the next 15-20 years emphasizes the need for additional research to improve liver transplant opportunities for NASH patients, including the option of living donor[s],” they said.

The researchers analyzed data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry.

From 2004 to 2013, new wait-list registrants with NASH increased by 170% from 804 to 2,174; those with ALD increased by 45% from 1,400 to 2,024; and those with HCV increased by 14% from 2,887 to 3,291. Registrants with both HCV and ALD decreased by 9% from 880 to 803. NASH became the second-leading disease among liver transplant wait-list registrants in 2013.

Patients with ALD had a significantly higher Model for End-Stage Liver Disease (MELD) score at the time of registration than did others. However, after adjustment for MELD and other variables, patients with ALD were less likely to die within 90 days than were NASH patients (OR 0.77; 95% CI 0.67–0.89; P < .001). No difference was seen in wait-list mortality between NASH and HCV and HCV/ALD patients.

Compared with NASH, patients with HCV (OR 1.45; 95% CI 1.35–1.55; P < .001), ALD (OR 1.15; 95% CI: 1.06–1.24; P < .001), and HCV/ALD (OR 1.29; 95% CI 1.18–1.42; P < .001) were all significantly more likely to receive a liver after 3 months on the wait list.

A “potential explanation for these observations might be etiology-specific differences in disease progression, such that more aggressive etiologies (e.g., HCV or HCV/ALD) can have a more rapid rise in MELD score, receive liver transplant, and have lower wait-list mortality, and etiologies with less rapid progression (e.g., NASH) can have slower rise in MELD score over time, lower rates of LT, but no significant increase in wait-list mortality,” the investigators said.

Overall 1-year wait-list survival among NASH patients decreased from 42.8% in 2004-2008 to 25.6% in 2009-2013, and overall 1-year probability of receiving liver transplant among NASH patients also decreased from 42.1% in 2004-2008 to 39.6% in 2009-2013. The trends were similar for other etiologies, perhaps in part because there are more people waiting for a liver.

The authors said they have no financial conflicts to disclose.

[email protected]

*A change was made to the text on 3/12/2015.

Since 2004, there’s been almost a tripling of the number of nonalcoholic steatohepatitis patients waiting for liver transplants; the condition is now the second leading reason to be put on the waiting list in the United States, according to a study published in the March issue of Gastroenterology.*

Even so and for reasons that are not fully clear, adults with nonalcoholic steatohepatitis (NASH) are less likely to survive for 90 days on the wait list than are patients with alcoholic liver disease (ALD), and less likely to get a new liver within 90 days than are patients with ALD, hepatitis C virus (HCV), or a blend of both. For now, HCV remains the No. 1 reason for liver transplants in the United States (Gastroenterology 2014 Nov. 24 [doi: 10.1053/j.gastro.2014.11.039]).

“Our study provides valuable information about the changing epidemiology of chronic liver disease among wait-listed patients, and adds greatly to our understanding of the epidemiology of NASH in the United States,” the researchers wrote. The rapid rise in the prevalence of NASH is “a direct consequence of the worldwide obesity epidemic” as well as greater awareness of the condition. An expected decline in HCV-related cirrhosis due to effective antiviral therapy “will further contribute to the changing epidemiology of patients awaiting liver transplants in the United States,” said the authors, led by Dr. Robert Wong of the division of gastroenterology and hepatology at Highland Hospital, Oakland, Calif.

“Given the expected continued rise in the number of NASH patients awaiting liver transplant, additional research is needed to improve wait-list survival and ... outcomes among this cohort. In addition, the projection that overall donor availability will significantly diminish in the next 15-20 years emphasizes the need for additional research to improve liver transplant opportunities for NASH patients, including the option of living donor[s],” they said.

The researchers analyzed data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry.

From 2004 to 2013, new wait-list registrants with NASH increased by 170% from 804 to 2,174; those with ALD increased by 45% from 1,400 to 2,024; and those with HCV increased by 14% from 2,887 to 3,291. Registrants with both HCV and ALD decreased by 9% from 880 to 803. NASH became the second-leading disease among liver transplant wait-list registrants in 2013.

Patients with ALD had a significantly higher Model for End-Stage Liver Disease (MELD) score at the time of registration than did others. However, after adjustment for MELD and other variables, patients with ALD were less likely to die within 90 days than were NASH patients (OR 0.77; 95% CI 0.67–0.89; P < .001). No difference was seen in wait-list mortality between NASH and HCV and HCV/ALD patients.

Compared with NASH, patients with HCV (OR 1.45; 95% CI 1.35–1.55; P < .001), ALD (OR 1.15; 95% CI: 1.06–1.24; P < .001), and HCV/ALD (OR 1.29; 95% CI 1.18–1.42; P < .001) were all significantly more likely to receive a liver after 3 months on the wait list.

A “potential explanation for these observations might be etiology-specific differences in disease progression, such that more aggressive etiologies (e.g., HCV or HCV/ALD) can have a more rapid rise in MELD score, receive liver transplant, and have lower wait-list mortality, and etiologies with less rapid progression (e.g., NASH) can have slower rise in MELD score over time, lower rates of LT, but no significant increase in wait-list mortality,” the investigators said.

Overall 1-year wait-list survival among NASH patients decreased from 42.8% in 2004-2008 to 25.6% in 2009-2013, and overall 1-year probability of receiving liver transplant among NASH patients also decreased from 42.1% in 2004-2008 to 39.6% in 2009-2013. The trends were similar for other etiologies, perhaps in part because there are more people waiting for a liver.

The authors said they have no financial conflicts to disclose.

[email protected]

*A change was made to the text on 3/12/2015.

From the Rand Corporation and UCLA Fielding School of Public Health, Santa Monica, CA (Dr. Ahluwalia) and University of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA (Dr. Enguidanos).

Abstract

• Objective: To review the relevance of advance care planning to heart failure management, describe key advance care planning challenges, and provide clinicians with actionable guidance for engaging in advance care planning conversations.
• Methods: Review of the literature.
• Results: Although most patients with heart failure prefer to receive thorough and honest information about their health condition and prognosis, the unpredictability of the heart failure trajectory coupled with physician barriers including discomfort with emotionally-laden topics and difficulty identifying the “right” time to engage in advance care planning, and systems barriers such as inadequate clinic time and limited reimbursement, impede timely engagement in advance care planning discussions. Approaches to effective advance care planning communication include using open-ended questions to stimulate patient engagement, evaluating how much information the patient wants to ensure patient-centeredness, and using empathic language to demonstrate support and understanding. While successful models of advance care planning communication have been identified, replication is limited due to the resource intense nature of these approaches.
• Conclusion: Challenges to advance care planning discussions among patients with heart failure may be mitigated through the establishment of communication quality standards as well as guidelines promoting early and ongoing advance care planning discussions, as well as reimbursement for outpatient discussions.

Heart failure, a leading cause of death, disability, and health care costs in the United States, is an incurable and life-limiting illness that is becoming increasingly prevalent due to an aging population and improved life expectancy. Approximately 5.3 million Americans are currently living with heart failure [1], with more than 550,000 new cases diagnosed each year [2]. Heart failure disproportionately affects older adults; about 80% of all cases occur in persons aged 65 years or older [3], and heart failure is the leading cause of hospital admissions among older adults [4]. The burden and impact of heart failure peaks near the end of life; 80% of Medicare beneficiaries with heart failure are hospitalized in the last 6 months of life [5].

The Trajectory of Heart Failure

Patients with heart failure experience a highly variable, nonlinear clinical trajectory marked by progressive deterioration and frequent exacerbations requiring hospitalization [6]. Their prognosis, though uncertain, is poor, with reported 1-year mortality rates following a hospitalization between 30% and 50% and 5-year mortality as high as 75% [7–11], a survival rate worse than that of some cancers [12]. Patients with heart failure caused by ischemic heart disease are at high risk for sudden cardiac death, particularly at earlier stages of the disease, which can confound the ability to appropriately plan for the future [13]. Those who survive to more advanced stages of heart failure face worsening quality of life [14–16], driven by a high prevalence of fatigue, breathlessness, pain, and depression [17–24]. Indeed, patients with heart failure have a similar symptom burden to patients with advanced cancer [25]. Older adults with heart failure also have a high comorbidity burden that further complicates both symptomology and disease trajectory with implications for decision-making about life-prolonging heart failure therapies [26,27].

Advance Care Planning in Heart Failure

The unpredictable nature of heart failure makes it difficult for patients and families to plan and prepare for their future, yet it is this very uncertainty that makes advance care planning (ACP) so critical for heart failure patients. Clear and honest patient-clinician communication about ACP, including an exploration of patient values and goals for care in the context of prognostic information, is essential to patient-centered treatment decision-making [28]. This is particularly relevant in heart failure, where a range of high-intensity, invasive, and costly interventions are increasingly being applied (eg, ventricular assist devices) without equivalent attention to quality of life and patients’ long-term goals for care.

Patients with heart failure and their families face multiple complex treatment decisions along the trajectory of their illness, such as discontinuation of beta blockers among patients with refractory fluid overload or angiotensin-converting enzyme inhibitors in end-stage patients with symptomatic hypotension [29,30]. In end-stage heart failure patients, deactivation of an implantable cardiac defibrillator might be considered to avoid the pain and distress associated with repeated shocks. In contrast, other interventions such as cardiac resynchronization therapy and continuous inotropic infusion have quality of life benefits; continuation of these therapies may be appropriate even when discontinuing other interventions. Such decisions should be guided by a thorough understanding of the patient’s expressed preferences and values, ideally assessed early in the trajectory of the disease and continuously re-evaluated as the diseases progresses.

The American Heart Association supports early and regular patient-provider ACP discussions to guide heart failure patients’ future decision-making [31], and recommends that such discussions be initiated in the outpatient setting, prior to and in anticipation of clinical decline. ACP communication plays a critical role in enhancing patients’ understanding of their diagnosis, treatment, prognosis, and choices in end-of-life care [31]. ACP communication also helps the clinician to better understand the context within which patients and their caregivers might make health care decisions, including their values and preferences for care. Patient-provider discussions about ACP focused on understanding patient values and initiated early in the trajectory of serious illness can support future in-the-moment decision-making, and is likely more effective than asking patients to make specific treatment decisions in advance [32]. A growing body of rigorous research has shown that ACP communication is associated with greater preference-concordant care and congruence in patient-surrogate understanding of patient preferences, lower costs, and less aggressive care at the end of life [33–37].

Patient Preferences for ACP Communication

Most patients with heart failure and their caregivers want honest disclosure regarding prognosis and to receive information about the expected trajectory of their disease [38–41] as early as possible [38] to help them plan and prepare for their future. Patients and their caregivers prefer to have these conversations with their physician [38] or other provider most familiar with the patient and family [39]. Patients also express a preference for support with dealing with the uncertainty inherent to heart failure [39]. Although most patients and caregivers desire to receive clear and honest communication about their disease, it is important to note that patients may vary in the extent of information they prefer to receive about their heart failure, with some individuals preferring not to talk about the end of life and future care needs at all [39,42–44].

Challenges to ACP Communication in Heart Failure

Despite patient and caregiver preferences for ACP communication with their providers, evidence suggests such communication occurs infrequently [40,45] and that heart failure patients may lack important information about their prognosis and treatment options [40,44,46,47]. For example, patients may not recognize the terminal nature of heart failure, and may be unaware of the range of treatment options, including hospice, available to them. Evidence also demonstrates that ACP is infrequently discussed with their health care providers [40], resulting in these conversations being avoided or deferred until an emergent clinical situation [44,48] when hasty questions about treatment choices may yield uncertain and conflicting answers not representative of a patient’s underlying values.

The infrequent, late, and often lack of discussions about ACP are driven by several challenges. First, the uncertain trajectory of heart failure makes communication regarding “what to expect” difficult. Prognostication is an immense challenge in heart failure [40,49–52], making it harder to talk about end-of-life issues and hindering the ability of patients, caregivers and health care providers to plan and prepare for the future. It is often difficult for clinicians, who face the challenge of instilling hope in the face of truthful disclosure [53], to identify the “right time” to initiate such discussions.

Second, a lack of time, particularly during outpatient visits, impedes physician ability to have considered discussions about future care needs and preferences [32,54]. The U.S. health care system currently lacks financial reimbursement for these discussions, which poses a significant barrier to the integration of ACP conversations into routine clinical practice. Moreover, these conversations are lengthy and iterative [53]. ACP discussions that are focused on facilitating patient-centered decision-making ideally begin with a discussion of expected prognosis, followed by an exploration of patient preferences and values for health care, and then a review of treatment options to be considered in the context of those preferences. Often additional time is needed for completing advance directive documents or for charting key outcomes from these discussions. Clinicians today are frequently overloaded with addressing multiple medical issues during outpatient visits that leave little time for non-medical tasks such as ACP discussions. The lack of financial incentives to support in-depth discussions is a critical challenge in improving ACP.

Third, a lack of training in specialized communication skills, particularly focused on empathic and emotionally sensitive disclosure, may further hinder physicians from initiating frank discussions with their patients. ACP conversations are highly sensitive and fraught with emotional complexity, and clinicians understandably experience discomfort with breaking bad news [49,51,55] or with broader issues of decline and death [51,56,57]. Physicians tend to be most comfortable addressing cognitive aspects of communication; addressing the emotional needs of patients is harder. Medical school training teaches detachment in physician practice, perhaps as a way of coping with the sadness they regularly confront and in maintaining their ability to provide clinical care. In fact, physicians describe their most difficult encounters as those with the most negative expressed emotions and miss opportunities to respond with empathy [58–60], a critical skill in effective patient-physician communication that is associated with improved patient satisfaction [61,62]. While patients value good communication skills in their health care encounters, many providers feel they lack the necessary skills to lead effective ACP discussions [49,63].

Finally, information gaps with regards to heart failure contribute to delayed or absent conversations about planning for future care. Many heart failure patients have a limited understanding of their disease [32,40,44,55], particularly an inaccurate perception that heart failure is not a terminal and life-limiting illness [42,49,64]. Compounding this is the fact that even some health care providers are reluctant to acknowledge the terminal nature of heart failure [50,56]. Without frank acknowledgement of the terminal nature of heart failure, the initiation of discussions regarding end-of-life care will remain difficult if not impossible.

Approaches to ACP in Heart Failure

When Is the Right Time?

Given the complexity and unpredictable trajectory of heart failure, indicators of disease progression, including changes in health status and health service use, may serve as useful signals to help clinicians identify the appropriate time to initiate care planning discussions. Repeated hospital admissions for heart failure are strongly associated with increased mortality. In a sample of community heart failure patients [8], median survival after the first, second, and third hospitalization was 2.4, 1.4, and 1.0 years, respectively. In light of this, a patient with 1 or more hospitalizations in a 12-month period may be an appropriate candidate for an ACP conversation. Similarly, comorbidity in patients with heart failure may signal the relevance and need for discussions about future care. In a sample of Medicare beneficiaries with advanced heart failure, an increasing burden of comorbidity was associated with significantly higher mortality, as were certain conditions (COPD, CKD, dementia, depression) and combinations of conditions (eg, CKD and dementia) [26]. Davidson and colleagues [68] suggest a list of clinical indicators signaling the need for an ACP conversation, including any of the following:

1. > 1 episodes of exacerbation of heart failure leading to hospital admission
2. New York Heart Association Class IV heart failure
3. Decline in function and mobility
4. Unexplained weight loss
5. Resting pulse rate greater than 100  beats/minute
6. Raised serum creatinine (> 150 µmol/L)
7. Low serum sodium (< 135 mmol/L)
8. Low serum albumen (< 33 g/L)
9. High dose of loop diuretic (eg, furosemide ≥ 160 mg daily)

Given the considerable complexity and multisystem nature of heart failure, none of these indicators alone can signal certainty about disease progression and consequent outcomes; however, they can serve as a useful heuristic for helping clinicians identify appropriate times to raise the topic of ACP with their patients.

What Do I Say? Structuring the Conversation

Heart failure patients and their caregivers may vary in their preferences for hearing information about their disease; therefore, it is critical to open any conversation about planning for future in the context of their illness by asking what and how much information is desired. This includes evaluating how involved in decision-making the patient wants to be. Previously suggested language includes [69,70]:

• Would you like to consider all the options, or my opinion about the options that fit best with what I know about you?
• Some people like to know everything about their disease and be involved in all decision making. Others do not want all the news and would rather the doctor talk to __________.    Which kind of person are you? How involved do you want to be in these decisions?
• Would you like me to tell you the full details of your condition?
• If you prefer not to hear the details, is there someone in your family who you trust to receive this information?

After establishing the patient’s preferences for hearing different types of information and level of involvement in decision-making about their care, the ask-tell-ask model [69,71] provides a useful approach to communicating with patients and their families. The conversation generally begins by asking patients what he or she understands about their illness (eg, “What do you understand about your heart failure?”; “I want to make sure we’re on the same page; what have other doctors told you?”). Building on what the patient already knows, the clinician can then disclose new information, correct misunderstandings, or confirm impressions and expectations the patient might have. In this way, information is tailored to the patient’s understanding and aimed at addressing potential knowledge gaps, all within the context of their preferences. Finally, the clinician asks the patient to describe their new understanding and whether or not they have questions or concerns (eg, “To make sure I did a good job of explaining to you, can you tell me what you now know about your condition from our conversation?”; “I know I’ve covered a lot and I want to make sure I was clear. When you get home, how are you going to explain what I’ve told you to your spouse?”). This approach encourages communication and exchange between patient and physician. Additionally, expressions of concern promote relationship building and bonding between physician and patient.

Keeping the Conversation Going

ACP communication can cover a wide range of topics beyond disease and prognostic disclosure by the provider to the patient. A critical aspect of ACP conversations is an exploration of the patient’s values and preferences, which can be used to help contextualize treatment choices and subsequently guide in-the-moment decision-making [72]. Using open-ended questions throughout the conversation gives the patient an opportunity to reflect on and communicate their wishes and values and allows them to engage in the conversation on their own terms. Examples of discussion-stimulating questions include [69,73]:

• What concerns you most about your illness?
• How is treatment going for you (your family)?
• As you think about your illness, what is the best and worst that might happen?
• What are your greatest hopes about your health?
• What has been most difficult about this illness for you?
• Looking back at your life, what has been important to you?
• At this point, what is most important for you to do?

Language

Central to this process is the use of empathic language to demonstrate support and understanding. An expression of empathy is also an appropriate way to acknowledge and share difficult emotions when it becomes hard to know where to take the conversation next. Quill and colleagues [74] suggest the following empathic responses to patients’ emotional expressions:

• I wish for that too
• It's unfortunate that things aren't different
• I am so sorry that this happened to you
• I understand how much you want that
• It must be very hard to accept the seriousness of this illness

Relatedly, the use of medical jargon in ACP conversations can increase the distance between patients and their providers, and may hinder patient understanding. Physicians may use technical language out of habit, or as an unconscious way to emotionally separate themselves from the task of delivering bad news. However, clear communication using layperson terms is the most effective approach to providing information necessary to patient-centered decision making. Explaining medical procedures in simple terms can improve understanding and help to build trust with the physician (eg, “We will perform an angioplasty – a procedure where a special tube with a balloon on the end of it is inserted into your artery to stretch it open. This will improve blood flow and relieve some of the symptoms you are currently experiencing”.)

Cultural Issues in Communication

There are various cultural issues to consider and address when conducting ACP discussions with heart failure patients and their families. Heart failure disproportionately affects certain racial and ethnic groups (eg, African Americans) [77–79], and effective management of heart failure depends on the provision of culturally sensitive information and facilitation of culturally informed self-care behaviors. There is evidence of cultural variation in preferences for information and role in decision-making. For example, most white and African-American patients prefer to be fully informed of their condition [80], whereas other cultures may focus on protecting the patient from difficult information in order to maintain hope [80–86]. Moreover, even in cultures where nondisclosure is preferred, patients may want to be told the truth in an indirect, euphemistic, or even nonverbal manner [80,87–89]. These complexities underscore the importance of taking a patient-centered approach to ACP communication, respecting individuality and autonomy while ultimately facilitating decision-making [90,91].

Are There Effective Training Programs for ACP Communication?

Effective communication skills are a critical component of ACP conversations between clinicians and their patients; however, most clinicians do not receive formal training in ACP communication and believe it to be a difficult task [92]. Strong evidence of the effectiveness of communication skills training has yet to be established, largely due to variation in the approach to training and the specification of relevant outcomes. For example, a systematic review of communication skills training courses found that some courses are effective at improving different types of communication skills related to providing support and gathering information, but these courses lacked effectiveness in improving patient satisfaction or provider burnout and distress [93]. Similarly, a range of approaches to teaching clinicians effective ACP communication skills early in their medical training have been identified [94], but considerable variation in quality preclude any conclusions from being drawn about their effectiveness.

Despite these challenges, there are some studies of communication skills training courses that have demonstrated the ability to increase providers’ use of empathic and facilitative communication (eg, use of open-ended questions) [58,95], and to increase self-efficacy and confidence among providers [96]. One particular teaching model that is increasingly used in cancer care is Oncotalk (http://depts.washington.edu/oncotalk/). Oncotalk has been shown to significantly increase clinical skills in giving bad news and facilitating the transition to palliative care. Building on this success, the program has expanded to training courses focused on the intensive care setting (http://depts.washington.edu/icutalk/) and geriatrics care [97–99]. It is important to note, however, that the considerable time and resource-intensive nature of communication training programs limits widespread implementation of any one approach into routine medical education. More attention to the type and structure of communication skills training programs are needed as well as scalable approaches to assist clinicians in developing effective ACP communication skills.

Policy Implications of ACP and Future Directions

There is growing recognition of the need to improve ACP among patients with seriously illness, including heart failure. In a recent Institute of Medicine (IOM) report, Dying in America [100], the need for clinician-patient communication about ACP was identified as a primary area of improvement. Recommendations include the establishment of communication quality standards as well as guidelines promoting early and ongoing ACP discussions. This is supported by recommendations from medical professional societies for an iterative model of ACP that follows the course of a serious illness [2,101]. At early stages of the illness, ACP might be focused on helping patients clarify their broad health care values and raise awareness of their disease and expected prognosis. As the condition progresses, ACP discussion might focus on exploring disease-specific treatment options within the context of previously expressed preferences, as well as identifying changes in patients’ values over time, particularly as they gain experience with their illness and health status changes [102]. In late stages of the disease, ACP might focus on documenting specific treatment choices (eg, DNR orders) and on exploring options such as palliative care, while also ensuring that patients and caregivers are appropriately prepared for imminent decline and death.

The IOM report also calls for payment reforms to include reimbursement for outpatient ACP discussions [100]. There is burgeoning national support for developing reimbursement models for ACP discussions. The American Medical Association has recently released current procedural terminology (CPT) codes for ACP services, a first step toward urging Medicare to consider reimbursement for ACP discussions with physicians.

Finally, the IOM report calls for improved education and training in ACP communication across all disciplines and specialties providing care to patients with serious illness. These recommendations bring national attention to the current limitations surrounding ACP discussions for those with serious illness, including heart failure. Further research is needed to identify methods and care models to address the gap in communication skills, processes, and policies.

Corresponding author: Sangeeta C. Ahluwalia, Rand Corporation, 1776 Main St., Santa Monica, CA, 90401, [email protected].

Financial disclosures: None.

Author contributions: conception and design, SCA, SE; analysis and interpretation of data, SCA, SE; drafting of article, SCA, SE; critical revision of the article, SCA, SE.

From the Rand Corporation and UCLA Fielding School of Public Health, Santa Monica, CA (Dr. Ahluwalia) and University of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA (Dr. Enguidanos).

Abstract

• Objective: To review the relevance of advance care planning to heart failure management, describe key advance care planning challenges, and provide clinicians with actionable guidance for engaging in advance care planning conversations.
• Methods: Review of the literature.
• Results: Although most patients with heart failure prefer to receive thorough and honest information about their health condition and prognosis, the unpredictability of the heart failure trajectory coupled with physician barriers including discomfort with emotionally-laden topics and difficulty identifying the “right” time to engage in advance care planning, and systems barriers such as inadequate clinic time and limited reimbursement, impede timely engagement in advance care planning discussions. Approaches to effective advance care planning communication include using open-ended questions to stimulate patient engagement, evaluating how much information the patient wants to ensure patient-centeredness, and using empathic language to demonstrate support and understanding. While successful models of advance care planning communication have been identified, replication is limited due to the resource intense nature of these approaches.
• Conclusion: Challenges to advance care planning discussions among patients with heart failure may be mitigated through the establishment of communication quality standards as well as guidelines promoting early and ongoing advance care planning discussions, as well as reimbursement for outpatient discussions.

Heart failure, a leading cause of death, disability, and health care costs in the United States, is an incurable and life-limiting illness that is becoming increasingly prevalent due to an aging population and improved life expectancy. Approximately 5.3 million Americans are currently living with heart failure [1], with more than 550,000 new cases diagnosed each year [2]. Heart failure disproportionately affects older adults; about 80% of all cases occur in persons aged 65 years or older [3], and heart failure is the leading cause of hospital admissions among older adults [4]. The burden and impact of heart failure peaks near the end of life; 80% of Medicare beneficiaries with heart failure are hospitalized in the last 6 months of life [5].

The Trajectory of Heart Failure

Patients with heart failure experience a highly variable, nonlinear clinical trajectory marked by progressive deterioration and frequent exacerbations requiring hospitalization [6]. Their prognosis, though uncertain, is poor, with reported 1-year mortality rates following a hospitalization between 30% and 50% and 5-year mortality as high as 75% [7–11], a survival rate worse than that of some cancers [12]. Patients with heart failure caused by ischemic heart disease are at high risk for sudden cardiac death, particularly at earlier stages of the disease, which can confound the ability to appropriately plan for the future [13]. Those who survive to more advanced stages of heart failure face worsening quality of life [14–16], driven by a high prevalence of fatigue, breathlessness, pain, and depression [17–24]. Indeed, patients with heart failure have a similar symptom burden to patients with advanced cancer [25]. Older adults with heart failure also have a high comorbidity burden that further complicates both symptomology and disease trajectory with implications for decision-making about life-prolonging heart failure therapies [26,27].

Advance Care Planning in Heart Failure

The unpredictable nature of heart failure makes it difficult for patients and families to plan and prepare for their future, yet it is this very uncertainty that makes advance care planning (ACP) so critical for heart failure patients. Clear and honest patient-clinician communication about ACP, including an exploration of patient values and goals for care in the context of prognostic information, is essential to patient-centered treatment decision-making [28]. This is particularly relevant in heart failure, where a range of high-intensity, invasive, and costly interventions are increasingly being applied (eg, ventricular assist devices) without equivalent attention to quality of life and patients’ long-term goals for care.

Patients with heart failure and their families face multiple complex treatment decisions along the trajectory of their illness, such as discontinuation of beta blockers among patients with refractory fluid overload or angiotensin-converting enzyme inhibitors in end-stage patients with symptomatic hypotension [29,30]. In end-stage heart failure patients, deactivation of an implantable cardiac defibrillator might be considered to avoid the pain and distress associated with repeated shocks. In contrast, other interventions such as cardiac resynchronization therapy and continuous inotropic infusion have quality of life benefits; continuation of these therapies may be appropriate even when discontinuing other interventions. Such decisions should be guided by a thorough understanding of the patient’s expressed preferences and values, ideally assessed early in the trajectory of the disease and continuously re-evaluated as the diseases progresses.

The American Heart Association supports early and regular patient-provider ACP discussions to guide heart failure patients’ future decision-making [31], and recommends that such discussions be initiated in the outpatient setting, prior to and in anticipation of clinical decline. ACP communication plays a critical role in enhancing patients’ understanding of their diagnosis, treatment, prognosis, and choices in end-of-life care [31]. ACP communication also helps the clinician to better understand the context within which patients and their caregivers might make health care decisions, including their values and preferences for care. Patient-provider discussions about ACP focused on understanding patient values and initiated early in the trajectory of serious illness can support future in-the-moment decision-making, and is likely more effective than asking patients to make specific treatment decisions in advance [32]. A growing body of rigorous research has shown that ACP communication is associated with greater preference-concordant care and congruence in patient-surrogate understanding of patient preferences, lower costs, and less aggressive care at the end of life [33–37].

Patient Preferences for ACP Communication

Most patients with heart failure and their caregivers want honest disclosure regarding prognosis and to receive information about the expected trajectory of their disease [38–41] as early as possible [38] to help them plan and prepare for their future. Patients and their caregivers prefer to have these conversations with their physician [38] or other provider most familiar with the patient and family [39]. Patients also express a preference for support with dealing with the uncertainty inherent to heart failure [39]. Although most patients and caregivers desire to receive clear and honest communication about their disease, it is important to note that patients may vary in the extent of information they prefer to receive about their heart failure, with some individuals preferring not to talk about the end of life and future care needs at all [39,42–44].

Challenges to ACP Communication in Heart Failure

Despite patient and caregiver preferences for ACP communication with their providers, evidence suggests such communication occurs infrequently [40,45] and that heart failure patients may lack important information about their prognosis and treatment options [40,44,46,47]. For example, patients may not recognize the terminal nature of heart failure, and may be unaware of the range of treatment options, including hospice, available to them. Evidence also demonstrates that ACP is infrequently discussed with their health care providers [40], resulting in these conversations being avoided or deferred until an emergent clinical situation [44,48] when hasty questions about treatment choices may yield uncertain and conflicting answers not representative of a patient’s underlying values.

The infrequent, late, and often lack of discussions about ACP are driven by several challenges. First, the uncertain trajectory of heart failure makes communication regarding “what to expect” difficult. Prognostication is an immense challenge in heart failure [40,49–52], making it harder to talk about end-of-life issues and hindering the ability of patients, caregivers and health care providers to plan and prepare for the future. It is often difficult for clinicians, who face the challenge of instilling hope in the face of truthful disclosure [53], to identify the “right time” to initiate such discussions.

Second, a lack of time, particularly during outpatient visits, impedes physician ability to have considered discussions about future care needs and preferences [32,54]. The U.S. health care system currently lacks financial reimbursement for these discussions, which poses a significant barrier to the integration of ACP conversations into routine clinical practice. Moreover, these conversations are lengthy and iterative [53]. ACP discussions that are focused on facilitating patient-centered decision-making ideally begin with a discussion of expected prognosis, followed by an exploration of patient preferences and values for health care, and then a review of treatment options to be considered in the context of those preferences. Often additional time is needed for completing advance directive documents or for charting key outcomes from these discussions. Clinicians today are frequently overloaded with addressing multiple medical issues during outpatient visits that leave little time for non-medical tasks such as ACP discussions. The lack of financial incentives to support in-depth discussions is a critical challenge in improving ACP.

Third, a lack of training in specialized communication skills, particularly focused on empathic and emotionally sensitive disclosure, may further hinder physicians from initiating frank discussions with their patients. ACP conversations are highly sensitive and fraught with emotional complexity, and clinicians understandably experience discomfort with breaking bad news [49,51,55] or with broader issues of decline and death [51,56,57]. Physicians tend to be most comfortable addressing cognitive aspects of communication; addressing the emotional needs of patients is harder. Medical school training teaches detachment in physician practice, perhaps as a way of coping with the sadness they regularly confront and in maintaining their ability to provide clinical care. In fact, physicians describe their most difficult encounters as those with the most negative expressed emotions and miss opportunities to respond with empathy [58–60], a critical skill in effective patient-physician communication that is associated with improved patient satisfaction [61,62]. While patients value good communication skills in their health care encounters, many providers feel they lack the necessary skills to lead effective ACP discussions [49,63].

Finally, information gaps with regards to heart failure contribute to delayed or absent conversations about planning for future care. Many heart failure patients have a limited understanding of their disease [32,40,44,55], particularly an inaccurate perception that heart failure is not a terminal and life-limiting illness [42,49,64]. Compounding this is the fact that even some health care providers are reluctant to acknowledge the terminal nature of heart failure [50,56]. Without frank acknowledgement of the terminal nature of heart failure, the initiation of discussions regarding end-of-life care will remain difficult if not impossible.

Approaches to ACP in Heart Failure

When Is the Right Time?

Given the complexity and unpredictable trajectory of heart failure, indicators of disease progression, including changes in health status and health service use, may serve as useful signals to help clinicians identify the appropriate time to initiate care planning discussions. Repeated hospital admissions for heart failure are strongly associated with increased mortality. In a sample of community heart failure patients [8], median survival after the first, second, and third hospitalization was 2.4, 1.4, and 1.0 years, respectively. In light of this, a patient with 1 or more hospitalizations in a 12-month period may be an appropriate candidate for an ACP conversation. Similarly, comorbidity in patients with heart failure may signal the relevance and need for discussions about future care. In a sample of Medicare beneficiaries with advanced heart failure, an increasing burden of comorbidity was associated with significantly higher mortality, as were certain conditions (COPD, CKD, dementia, depression) and combinations of conditions (eg, CKD and dementia) [26]. Davidson and colleagues [68] suggest a list of clinical indicators signaling the need for an ACP conversation, including any of the following:

1. > 1 episodes of exacerbation of heart failure leading to hospital admission
2. New York Heart Association Class IV heart failure
3. Decline in function and mobility
4. Unexplained weight loss
5. Resting pulse rate greater than 100  beats/minute
6. Raised serum creatinine (> 150 µmol/L)
7. Low serum sodium (< 135 mmol/L)
8. Low serum albumen (< 33 g/L)
9. High dose of loop diuretic (eg, furosemide ≥ 160 mg daily)

Given the considerable complexity and multisystem nature of heart failure, none of these indicators alone can signal certainty about disease progression and consequent outcomes; however, they can serve as a useful heuristic for helping clinicians identify appropriate times to raise the topic of ACP with their patients.

What Do I Say? Structuring the Conversation

Heart failure patients and their caregivers may vary in their preferences for hearing information about their disease; therefore, it is critical to open any conversation about planning for future in the context of their illness by asking what and how much information is desired. This includes evaluating how involved in decision-making the patient wants to be. Previously suggested language includes [69,70]:

• Would you like to consider all the options, or my opinion about the options that fit best with what I know about you?
• Some people like to know everything about their disease and be involved in all decision making. Others do not want all the news and would rather the doctor talk to __________.    Which kind of person are you? How involved do you want to be in these decisions?
• Would you like me to tell you the full details of your condition?
• If you prefer not to hear the details, is there someone in your family who you trust to receive this information?

After establishing the patient’s preferences for hearing different types of information and level of involvement in decision-making about their care, the ask-tell-ask model [69,71] provides a useful approach to communicating with patients and their families. The conversation generally begins by asking patients what he or she understands about their illness (eg, “What do you understand about your heart failure?”; “I want to make sure we’re on the same page; what have other doctors told you?”). Building on what the patient already knows, the clinician can then disclose new information, correct misunderstandings, or confirm impressions and expectations the patient might have. In this way, information is tailored to the patient’s understanding and aimed at addressing potential knowledge gaps, all within the context of their preferences. Finally, the clinician asks the patient to describe their new understanding and whether or not they have questions or concerns (eg, “To make sure I did a good job of explaining to you, can you tell me what you now know about your condition from our conversation?”; “I know I’ve covered a lot and I want to make sure I was clear. When you get home, how are you going to explain what I’ve told you to your spouse?”). This approach encourages communication and exchange between patient and physician. Additionally, expressions of concern promote relationship building and bonding between physician and patient.

Keeping the Conversation Going

ACP communication can cover a wide range of topics beyond disease and prognostic disclosure by the provider to the patient. A critical aspect of ACP conversations is an exploration of the patient’s values and preferences, which can be used to help contextualize treatment choices and subsequently guide in-the-moment decision-making [72]. Using open-ended questions throughout the conversation gives the patient an opportunity to reflect on and communicate their wishes and values and allows them to engage in the conversation on their own terms. Examples of discussion-stimulating questions include [69,73]:

• What concerns you most about your illness?
• How is treatment going for you (your family)?
• As you think about your illness, what is the best and worst that might happen?
• What are your greatest hopes about your health?
• What has been most difficult about this illness for you?
• Looking back at your life, what has been important to you?
• At this point, what is most important for you to do?

Language

Central to this process is the use of empathic language to demonstrate support and understanding. An expression of empathy is also an appropriate way to acknowledge and share difficult emotions when it becomes hard to know where to take the conversation next. Quill and colleagues [74] suggest the following empathic responses to patients’ emotional expressions:

• I wish for that too
• It's unfortunate that things aren't different
• I am so sorry that this happened to you
• I understand how much you want that
• It must be very hard to accept the seriousness of this illness

Relatedly, the use of medical jargon in ACP conversations can increase the distance between patients and their providers, and may hinder patient understanding. Physicians may use technical language out of habit, or as an unconscious way to emotionally separate themselves from the task of delivering bad news. However, clear communication using layperson terms is the most effective approach to providing information necessary to patient-centered decision making. Explaining medical procedures in simple terms can improve understanding and help to build trust with the physician (eg, “We will perform an angioplasty – a procedure where a special tube with a balloon on the end of it is inserted into your artery to stretch it open. This will improve blood flow and relieve some of the symptoms you are currently experiencing”.)

Cultural Issues in Communication

There are various cultural issues to consider and address when conducting ACP discussions with heart failure patients and their families. Heart failure disproportionately affects certain racial and ethnic groups (eg, African Americans) [77–79], and effective management of heart failure depends on the provision of culturally sensitive information and facilitation of culturally informed self-care behaviors. There is evidence of cultural variation in preferences for information and role in decision-making. For example, most white and African-American patients prefer to be fully informed of their condition [80], whereas other cultures may focus on protecting the patient from difficult information in order to maintain hope [80–86]. Moreover, even in cultures where nondisclosure is preferred, patients may want to be told the truth in an indirect, euphemistic, or even nonverbal manner [80,87–89]. These complexities underscore the importance of taking a patient-centered approach to ACP communication, respecting individuality and autonomy while ultimately facilitating decision-making [90,91].

Are There Effective Training Programs for ACP Communication?

Effective communication skills are a critical component of ACP conversations between clinicians and their patients; however, most clinicians do not receive formal training in ACP communication and believe it to be a difficult task [92]. Strong evidence of the effectiveness of communication skills training has yet to be established, largely due to variation in the approach to training and the specification of relevant outcomes. For example, a systematic review of communication skills training courses found that some courses are effective at improving different types of communication skills related to providing support and gathering information, but these courses lacked effectiveness in improving patient satisfaction or provider burnout and distress [93]. Similarly, a range of approaches to teaching clinicians effective ACP communication skills early in their medical training have been identified [94], but considerable variation in quality preclude any conclusions from being drawn about their effectiveness.

Despite these challenges, there are some studies of communication skills training courses that have demonstrated the ability to increase providers’ use of empathic and facilitative communication (eg, use of open-ended questions) [58,95], and to increase self-efficacy and confidence among providers [96]. One particular teaching model that is increasingly used in cancer care is Oncotalk (http://depts.washington.edu/oncotalk/). Oncotalk has been shown to significantly increase clinical skills in giving bad news and facilitating the transition to palliative care. Building on this success, the program has expanded to training courses focused on the intensive care setting (http://depts.washington.edu/icutalk/) and geriatrics care [97–99]. It is important to note, however, that the considerable time and resource-intensive nature of communication training programs limits widespread implementation of any one approach into routine medical education. More attention to the type and structure of communication skills training programs are needed as well as scalable approaches to assist clinicians in developing effective ACP communication skills.

Policy Implications of ACP and Future Directions

There is growing recognition of the need to improve ACP among patients with seriously illness, including heart failure. In a recent Institute of Medicine (IOM) report, Dying in America [100], the need for clinician-patient communication about ACP was identified as a primary area of improvement. Recommendations include the establishment of communication quality standards as well as guidelines promoting early and ongoing ACP discussions. This is supported by recommendations from medical professional societies for an iterative model of ACP that follows the course of a serious illness [2,101]. At early stages of the illness, ACP might be focused on helping patients clarify their broad health care values and raise awareness of their disease and expected prognosis. As the condition progresses, ACP discussion might focus on exploring disease-specific treatment options within the context of previously expressed preferences, as well as identifying changes in patients’ values over time, particularly as they gain experience with their illness and health status changes [102]. In late stages of the disease, ACP might focus on documenting specific treatment choices (eg, DNR orders) and on exploring options such as palliative care, while also ensuring that patients and caregivers are appropriately prepared for imminent decline and death.

The IOM report also calls for payment reforms to include reimbursement for outpatient ACP discussions [100]. There is burgeoning national support for developing reimbursement models for ACP discussions. The American Medical Association has recently released current procedural terminology (CPT) codes for ACP services, a first step toward urging Medicare to consider reimbursement for ACP discussions with physicians.

Finally, the IOM report calls for improved education and training in ACP communication across all disciplines and specialties providing care to patients with serious illness. These recommendations bring national attention to the current limitations surrounding ACP discussions for those with serious illness, including heart failure. Further research is needed to identify methods and care models to address the gap in communication skills, processes, and policies.

Corresponding author: Sangeeta C. Ahluwalia, Rand Corporation, 1776 Main St., Santa Monica, CA, 90401, [email protected].

Financial disclosures: None.

Author contributions: conception and design, SCA, SE; analysis and interpretation of data, SCA, SE; drafting of article, SCA, SE; critical revision of the article, SCA, SE.

From the Rand Corporation and UCLA Fielding School of Public Health, Santa Monica, CA (Dr. Ahluwalia) and University of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA (Dr. Enguidanos).

Abstract

• Objective: To review the relevance of advance care planning to heart failure management, describe key advance care planning challenges, and provide clinicians with actionable guidance for engaging in advance care planning conversations.
• Methods: Review of the literature.
• Results: Although most patients with heart failure prefer to receive thorough and honest information about their health condition and prognosis, the unpredictability of the heart failure trajectory coupled with physician barriers including discomfort with emotionally-laden topics and difficulty identifying the “right” time to engage in advance care planning, and systems barriers such as inadequate clinic time and limited reimbursement, impede timely engagement in advance care planning discussions. Approaches to effective advance care planning communication include using open-ended questions to stimulate patient engagement, evaluating how much information the patient wants to ensure patient-centeredness, and using empathic language to demonstrate support and understanding. While successful models of advance care planning communication have been identified, replication is limited due to the resource intense nature of these approaches.
• Conclusion: Challenges to advance care planning discussions among patients with heart failure may be mitigated through the establishment of communication quality standards as well as guidelines promoting early and ongoing advance care planning discussions, as well as reimbursement for outpatient discussions.

Heart failure, a leading cause of death, disability, and health care costs in the United States, is an incurable and life-limiting illness that is becoming increasingly prevalent due to an aging population and improved life expectancy. Approximately 5.3 million Americans are currently living with heart failure [1], with more than 550,000 new cases diagnosed each year [2]. Heart failure disproportionately affects older adults; about 80% of all cases occur in persons aged 65 years or older [3], and heart failure is the leading cause of hospital admissions among older adults [4]. The burden and impact of heart failure peaks near the end of life; 80% of Medicare beneficiaries with heart failure are hospitalized in the last 6 months of life [5].

The Trajectory of Heart Failure

Patients with heart failure experience a highly variable, nonlinear clinical trajectory marked by progressive deterioration and frequent exacerbations requiring hospitalization [6]. Their prognosis, though uncertain, is poor, with reported 1-year mortality rates following a hospitalization between 30% and 50% and 5-year mortality as high as 75% [7–11], a survival rate worse than that of some cancers [12]. Patients with heart failure caused by ischemic heart disease are at high risk for sudden cardiac death, particularly at earlier stages of the disease, which can confound the ability to appropriately plan for the future [13]. Those who survive to more advanced stages of heart failure face worsening quality of life [14–16], driven by a high prevalence of fatigue, breathlessness, pain, and depression [17–24]. Indeed, patients with heart failure have a similar symptom burden to patients with advanced cancer [25]. Older adults with heart failure also have a high comorbidity burden that further complicates both symptomology and disease trajectory with implications for decision-making about life-prolonging heart failure therapies [26,27].

Advance Care Planning in Heart Failure

The unpredictable nature of heart failure makes it difficult for patients and families to plan and prepare for their future, yet it is this very uncertainty that makes advance care planning (ACP) so critical for heart failure patients. Clear and honest patient-clinician communication about ACP, including an exploration of patient values and goals for care in the context of prognostic information, is essential to patient-centered treatment decision-making [28]. This is particularly relevant in heart failure, where a range of high-intensity, invasive, and costly interventions are increasingly being applied (eg, ventricular assist devices) without equivalent attention to quality of life and patients’ long-term goals for care.

Patients with heart failure and their families face multiple complex treatment decisions along the trajectory of their illness, such as discontinuation of beta blockers among patients with refractory fluid overload or angiotensin-converting enzyme inhibitors in end-stage patients with symptomatic hypotension [29,30]. In end-stage heart failure patients, deactivation of an implantable cardiac defibrillator might be considered to avoid the pain and distress associated with repeated shocks. In contrast, other interventions such as cardiac resynchronization therapy and continuous inotropic infusion have quality of life benefits; continuation of these therapies may be appropriate even when discontinuing other interventions. Such decisions should be guided by a thorough understanding of the patient’s expressed preferences and values, ideally assessed early in the trajectory of the disease and continuously re-evaluated as the diseases progresses.

The American Heart Association supports early and regular patient-provider ACP discussions to guide heart failure patients’ future decision-making [31], and recommends that such discussions be initiated in the outpatient setting, prior to and in anticipation of clinical decline. ACP communication plays a critical role in enhancing patients’ understanding of their diagnosis, treatment, prognosis, and choices in end-of-life care [31]. ACP communication also helps the clinician to better understand the context within which patients and their caregivers might make health care decisions, including their values and preferences for care. Patient-provider discussions about ACP focused on understanding patient values and initiated early in the trajectory of serious illness can support future in-the-moment decision-making, and is likely more effective than asking patients to make specific treatment decisions in advance [32]. A growing body of rigorous research has shown that ACP communication is associated with greater preference-concordant care and congruence in patient-surrogate understanding of patient preferences, lower costs, and less aggressive care at the end of life [33–37].

Patient Preferences for ACP Communication

Most patients with heart failure and their caregivers want honest disclosure regarding prognosis and to receive information about the expected trajectory of their disease [38–41] as early as possible [38] to help them plan and prepare for their future. Patients and their caregivers prefer to have these conversations with their physician [38] or other provider most familiar with the patient and family [39]. Patients also express a preference for support with dealing with the uncertainty inherent to heart failure [39]. Although most patients and caregivers desire to receive clear and honest communication about their disease, it is important to note that patients may vary in the extent of information they prefer to receive about their heart failure, with some individuals preferring not to talk about the end of life and future care needs at all [39,42–44].

Challenges to ACP Communication in Heart Failure

Despite patient and caregiver preferences for ACP communication with their providers, evidence suggests such communication occurs infrequently [40,45] and that heart failure patients may lack important information about their prognosis and treatment options [40,44,46,47]. For example, patients may not recognize the terminal nature of heart failure, and may be unaware of the range of treatment options, including hospice, available to them. Evidence also demonstrates that ACP is infrequently discussed with their health care providers [40], resulting in these conversations being avoided or deferred until an emergent clinical situation [44,48] when hasty questions about treatment choices may yield uncertain and conflicting answers not representative of a patient’s underlying values.

The infrequent, late, and often lack of discussions about ACP are driven by several challenges. First, the uncertain trajectory of heart failure makes communication regarding “what to expect” difficult. Prognostication is an immense challenge in heart failure [40,49–52], making it harder to talk about end-of-life issues and hindering the ability of patients, caregivers and health care providers to plan and prepare for the future. It is often difficult for clinicians, who face the challenge of instilling hope in the face of truthful disclosure [53], to identify the “right time” to initiate such discussions.

Second, a lack of time, particularly during outpatient visits, impedes physician ability to have considered discussions about future care needs and preferences [32,54]. The U.S. health care system currently lacks financial reimbursement for these discussions, which poses a significant barrier to the integration of ACP conversations into routine clinical practice. Moreover, these conversations are lengthy and iterative [53]. ACP discussions that are focused on facilitating patient-centered decision-making ideally begin with a discussion of expected prognosis, followed by an exploration of patient preferences and values for health care, and then a review of treatment options to be considered in the context of those preferences. Often additional time is needed for completing advance directive documents or for charting key outcomes from these discussions. Clinicians today are frequently overloaded with addressing multiple medical issues during outpatient visits that leave little time for non-medical tasks such as ACP discussions. The lack of financial incentives to support in-depth discussions is a critical challenge in improving ACP.

Third, a lack of training in specialized communication skills, particularly focused on empathic and emotionally sensitive disclosure, may further hinder physicians from initiating frank discussions with their patients. ACP conversations are highly sensitive and fraught with emotional complexity, and clinicians understandably experience discomfort with breaking bad news [49,51,55] or with broader issues of decline and death [51,56,57]. Physicians tend to be most comfortable addressing cognitive aspects of communication; addressing the emotional needs of patients is harder. Medical school training teaches detachment in physician practice, perhaps as a way of coping with the sadness they regularly confront and in maintaining their ability to provide clinical care. In fact, physicians describe their most difficult encounters as those with the most negative expressed emotions and miss opportunities to respond with empathy [58–60], a critical skill in effective patient-physician communication that is associated with improved patient satisfaction [61,62]. While patients value good communication skills in their health care encounters, many providers feel they lack the necessary skills to lead effective ACP discussions [49,63].

Finally, information gaps with regards to heart failure contribute to delayed or absent conversations about planning for future care. Many heart failure patients have a limited understanding of their disease [32,40,44,55], particularly an inaccurate perception that heart failure is not a terminal and life-limiting illness [42,49,64]. Compounding this is the fact that even some health care providers are reluctant to acknowledge the terminal nature of heart failure [50,56]. Without frank acknowledgement of the terminal nature of heart failure, the initiation of discussions regarding end-of-life care will remain difficult if not impossible.

Approaches to ACP in Heart Failure

When Is the Right Time?

Given the complexity and unpredictable trajectory of heart failure, indicators of disease progression, including changes in health status and health service use, may serve as useful signals to help clinicians identify the appropriate time to initiate care planning discussions. Repeated hospital admissions for heart failure are strongly associated with increased mortality. In a sample of community heart failure patients [8], median survival after the first, second, and third hospitalization was 2.4, 1.4, and 1.0 years, respectively. In light of this, a patient with 1 or more hospitalizations in a 12-month period may be an appropriate candidate for an ACP conversation. Similarly, comorbidity in patients with heart failure may signal the relevance and need for discussions about future care. In a sample of Medicare beneficiaries with advanced heart failure, an increasing burden of comorbidity was associated with significantly higher mortality, as were certain conditions (COPD, CKD, dementia, depression) and combinations of conditions (eg, CKD and dementia) [26]. Davidson and colleagues [68] suggest a list of clinical indicators signaling the need for an ACP conversation, including any of the following:

1. > 1 episodes of exacerbation of heart failure leading to hospital admission
2. New York Heart Association Class IV heart failure
3. Decline in function and mobility
4. Unexplained weight loss
5. Resting pulse rate greater than 100  beats/minute
6. Raised serum creatinine (> 150 µmol/L)
7. Low serum sodium (< 135 mmol/L)
8. Low serum albumen (< 33 g/L)
9. High dose of loop diuretic (eg, furosemide ≥ 160 mg daily)

Given the considerable complexity and multisystem nature of heart failure, none of these indicators alone can signal certainty about disease progression and consequent outcomes; however, they can serve as a useful heuristic for helping clinicians identify appropriate times to raise the topic of ACP with their patients.

What Do I Say? Structuring the Conversation

Heart failure patients and their caregivers may vary in their preferences for hearing information about their disease; therefore, it is critical to open any conversation about planning for future in the context of their illness by asking what and how much information is desired. This includes evaluating how involved in decision-making the patient wants to be. Previously suggested language includes [69,70]:

• Would you like to consider all the options, or my opinion about the options that fit best with what I know about you?
• Some people like to know everything about their disease and be involved in all decision making. Others do not want all the news and would rather the doctor talk to __________.    Which kind of person are you? How involved do you want to be in these decisions?
• Would you like me to tell you the full details of your condition?
• If you prefer not to hear the details, is there someone in your family who you trust to receive this information?

After establishing the patient’s preferences for hearing different types of information and level of involvement in decision-making about their care, the ask-tell-ask model [69,71] provides a useful approach to communicating with patients and their families. The conversation generally begins by asking patients what he or she understands about their illness (eg, “What do you understand about your heart failure?”; “I want to make sure we’re on the same page; what have other doctors told you?”). Building on what the patient already knows, the clinician can then disclose new information, correct misunderstandings, or confirm impressions and expectations the patient might have. In this way, information is tailored to the patient’s understanding and aimed at addressing potential knowledge gaps, all within the context of their preferences. Finally, the clinician asks the patient to describe their new understanding and whether or not they have questions or concerns (eg, “To make sure I did a good job of explaining to you, can you tell me what you now know about your condition from our conversation?”; “I know I’ve covered a lot and I want to make sure I was clear. When you get home, how are you going to explain what I’ve told you to your spouse?”). This approach encourages communication and exchange between patient and physician. Additionally, expressions of concern promote relationship building and bonding between physician and patient.

Keeping the Conversation Going

ACP communication can cover a wide range of topics beyond disease and prognostic disclosure by the provider to the patient. A critical aspect of ACP conversations is an exploration of the patient’s values and preferences, which can be used to help contextualize treatment choices and subsequently guide in-the-moment decision-making [72]. Using open-ended questions throughout the conversation gives the patient an opportunity to reflect on and communicate their wishes and values and allows them to engage in the conversation on their own terms. Examples of discussion-stimulating questions include [69,73]:

• What concerns you most about your illness?
• How is treatment going for you (your family)?
• As you think about your illness, what is the best and worst that might happen?
• What are your greatest hopes about your health?
• What has been most difficult about this illness for you?
• Looking back at your life, what has been important to you?
• At this point, what is most important for you to do?

Language

Central to this process is the use of empathic language to demonstrate support and understanding. An expression of empathy is also an appropriate way to acknowledge and share difficult emotions when it becomes hard to know where to take the conversation next. Quill and colleagues [74] suggest the following empathic responses to patients’ emotional expressions:

• I wish for that too
• It's unfortunate that things aren't different
• I am so sorry that this happened to you
• I understand how much you want that
• It must be very hard to accept the seriousness of this illness

Relatedly, the use of medical jargon in ACP conversations can increase the distance between patients and their providers, and may hinder patient understanding. Physicians may use technical language out of habit, or as an unconscious way to emotionally separate themselves from the task of delivering bad news. However, clear communication using layperson terms is the most effective approach to providing information necessary to patient-centered decision making. Explaining medical procedures in simple terms can improve understanding and help to build trust with the physician (eg, “We will perform an angioplasty – a procedure where a special tube with a balloon on the end of it is inserted into your artery to stretch it open. This will improve blood flow and relieve some of the symptoms you are currently experiencing”.)

Cultural Issues in Communication

There are various cultural issues to consider and address when conducting ACP discussions with heart failure patients and their families. Heart failure disproportionately affects certain racial and ethnic groups (eg, African Americans) [77–79], and effective management of heart failure depends on the provision of culturally sensitive information and facilitation of culturally informed self-care behaviors. There is evidence of cultural variation in preferences for information and role in decision-making. For example, most white and African-American patients prefer to be fully informed of their condition [80], whereas other cultures may focus on protecting the patient from difficult information in order to maintain hope [80–86]. Moreover, even in cultures where nondisclosure is preferred, patients may want to be told the truth in an indirect, euphemistic, or even nonverbal manner [80,87–89]. These complexities underscore the importance of taking a patient-centered approach to ACP communication, respecting individuality and autonomy while ultimately facilitating decision-making [90,91].

Are There Effective Training Programs for ACP Communication?

Effective communication skills are a critical component of ACP conversations between clinicians and their patients; however, most clinicians do not receive formal training in ACP communication and believe it to be a difficult task [92]. Strong evidence of the effectiveness of communication skills training has yet to be established, largely due to variation in the approach to training and the specification of relevant outcomes. For example, a systematic review of communication skills training courses found that some courses are effective at improving different types of communication skills related to providing support and gathering information, but these courses lacked effectiveness in improving patient satisfaction or provider burnout and distress [93]. Similarly, a range of approaches to teaching clinicians effective ACP communication skills early in their medical training have been identified [94], but considerable variation in quality preclude any conclusions from being drawn about their effectiveness.

Despite these challenges, there are some studies of communication skills training courses that have demonstrated the ability to increase providers’ use of empathic and facilitative communication (eg, use of open-ended questions) [58,95], and to increase self-efficacy and confidence among providers [96]. One particular teaching model that is increasingly used in cancer care is Oncotalk (http://depts.washington.edu/oncotalk/). Oncotalk has been shown to significantly increase clinical skills in giving bad news and facilitating the transition to palliative care. Building on this success, the program has expanded to training courses focused on the intensive care setting (http://depts.washington.edu/icutalk/) and geriatrics care [97–99]. It is important to note, however, that the considerable time and resource-intensive nature of communication training programs limits widespread implementation of any one approach into routine medical education. More attention to the type and structure of communication skills training programs are needed as well as scalable approaches to assist clinicians in developing effective ACP communication skills.

Policy Implications of ACP and Future Directions

There is growing recognition of the need to improve ACP among patients with seriously illness, including heart failure. In a recent Institute of Medicine (IOM) report, Dying in America [100], the need for clinician-patient communication about ACP was identified as a primary area of improvement. Recommendations include the establishment of communication quality standards as well as guidelines promoting early and ongoing ACP discussions. This is supported by recommendations from medical professional societies for an iterative model of ACP that follows the course of a serious illness [2,101]. At early stages of the illness, ACP might be focused on helping patients clarify their broad health care values and raise awareness of their disease and expected prognosis. As the condition progresses, ACP discussion might focus on exploring disease-specific treatment options within the context of previously expressed preferences, as well as identifying changes in patients’ values over time, particularly as they gain experience with their illness and health status changes [102]. In late stages of the disease, ACP might focus on documenting specific treatment choices (eg, DNR orders) and on exploring options such as palliative care, while also ensuring that patients and caregivers are appropriately prepared for imminent decline and death.

The IOM report also calls for payment reforms to include reimbursement for outpatient ACP discussions [100]. There is burgeoning national support for developing reimbursement models for ACP discussions. The American Medical Association has recently released current procedural terminology (CPT) codes for ACP services, a first step toward urging Medicare to consider reimbursement for ACP discussions with physicians.

Finally, the IOM report calls for improved education and training in ACP communication across all disciplines and specialties providing care to patients with serious illness. These recommendations bring national attention to the current limitations surrounding ACP discussions for those with serious illness, including heart failure. Further research is needed to identify methods and care models to address the gap in communication skills, processes, and policies.

Corresponding author: Sangeeta C. Ahluwalia, Rand Corporation, 1776 Main St., Santa Monica, CA, 90401, [email protected].

Financial disclosures: None.

Author contributions: conception and design, SCA, SE; analysis and interpretation of data, SCA, SE; drafting of article, SCA, SE; critical revision of the article, SCA, SE.

From the University of Wisconsin School of Medicine and Public Health, Madison, WI.

Abstract

• Objective: To describe the contributing etiologies, common presentations, diagnosis, evaluation, and management of abnormal uterine bleeding (AUB).
• Methods: Review of the literature in the context of 3 cases.
• Results: AUB is one of the most common reasons that reproductive-aged women seek health care. The causes are varied, depending in large part on the age and life stage of the woman. Diagnosis requires a systematic approach that is driven by a thorough health history and review of presenting symptoms.  Determining whether the bleeding is ovulatory or anovulatory is a central part of the evaluation. A methodical history, physical examination, and laboratory evaluation may enable the physician to rule out causes such as pregnancy and pregnancy-related disorders, medications, iatrogenic causes, systemic conditions, and obvious genital tract pathology.
• Conclusion: Clinicians must be knowledgeable about AUB and partner with women to develop appropriate, individualized treatment plans.

Abnormal vaginal bleeding is a common complaint in primary care. The prevalence of some type of abnormal bleeding is up to 30% among women of reproductive age [1].Over 18% of all gynecology outpatient visits in the United States are for menorrhagia alone [2].A retrospective analysis of medical expenditures data compared 1.4 million women with abnormal uterine bleeding to over 50 million women without abnormal bleeding. This study found that women with abnormal bleeding were more likely to be younger, Caucasian, and obese and had poorer physical and mental health quality of life scores [3].

The estimated direct and indirect costs of abnormal bleeding are $1 billion and $12 billion annually, respectively [4]. Indirect costs of abnormal bleeding include time off from work and cost of products to protect clothing from bleeding (eg, tampons and pads). Abnormal bleeding is also a common reason for women to be referred to gynecologists and is an indication for up to 25% of all gynecologic surgeries [5].

History Taking

Taking a menstrual history is an important step in determining whether the current bleeding pattern is normal or abnormal. Regularity of menstrual bleeding is clarified by asking about the frequency of the menses and their duration. Other important questions include age at menarche, presence of premenstrual syndrome symptoms, breast tenderness, cervical mucus changes, and amount of bleeding. An ovulatory cycle will usually include premenstrual symptoms whereas an anovulatory cycle will be random in its symptomatology. Women’s estimates of the amount of menstrual bleeding are notoriously inaccurate. Traditionally, more than 80 cc of menstrual blood loss per cycle is considered menorrhagia. However, women and their health care providers do not measure menstrual blood volume outside of study settings, and one study found that only half of women who presented with menorrhagia actually had more than 80 cc of blood loss [6]. There is movement toward use of more patient-centered measures to diagnose men-orrhagia, such as bleeding interfering with a woman’s daily activities, needing to wake up at night to change tampons or pads, or inability to exercise during menses. Anemia in the setting of menorrhagia by history is a less subjective way to diagnose menorrhagia.

Nomenclature and Differential Diagnosis

Differential diagnosis will vary based on symptomatology as well as age. Pregnancy is a possible cause of any type of abnormal bleeding in any woman of reproductive age (ie, after menarche and before menopause). Many systemic illnesses and medications can affect menstrual bleeding and should be included in a broad differential diagnosis of a presenting woman.

Case 1—Heavy Menstrual Bleeding

Initial Presentation

A 42-year-old woman presents reporting increasingly heavy, somewhat painful periods over the last 6 to 8 months. She experienced menarche at age 12 and has had regular, moderately heavy periods throughout her adult life. She denies any inter-menstrual bleeding.

• What additional history should be obtained?

Heavy menstrual bleeding refers to abnormally heavy bleeding that occurs in an ovulatory, cyclical pattern. Women with anovulatory cycles can also have heavy bleeding as well, and distinguishing ovulatory vs anovulatory cycles is often the first step in the evaluation.

The initial evaluation of a woman presenting with heavy menstrual bleeding includes a detailed history and physical examination. The first goal of the history is to establish the severity of bleeding, including any symptoms of hemodynamically significant anemia such as dizziness or exertional dyspnea. Next, the clinician should determine whether the bleeding pattern is ovulatory or anovulatory. Ovulatory heavy menstrual bleeding is most often caused by structural lesions (leiomyomas, endometriosis, adenomyosis, cervical polyps, and endometrial polyps) or a coagulopathy (von Willebrand disease, anticoagulant use, etc). Less commonly, ovulatory heavy menstrual bleeding may be due to systemic illness (including thyroid disease, renal disease, and liver disease) or endometrial hyperplasia or carcinoma.

Once an ovulatory pattern is confirmed, a history of dysmenorrhea, pelvic pain, lower urinary tract symptoms, constipation, dyspareunia, or infertility should be elicited. 

Further history taking should seek to identify any symptoms suggestive of thyroid, kidney, or liver disease, 

• What are key elements of the physical examination?

The physical examination should include visual inspection and palpation of the thyroid gland as well as an abdominal exam to evaluate for hepatosplenomegaly or lower abdominal tenderness or masses. Signs of anemia such as pallor should also be noted. The gynecologic exam should include visual inspection of the external genitalia, a bimanual exam, and a speculum exam. Cervical and endometrial polyps may be visible as masses at the cervical os or extending into the vaginal canal. An enlarged mobile uterus with irregular contours is consistent with leiomyomas [8].Endometriosis may manifest as tenderness, thickening, or nodularity of the uterine corpus, the vaginal canal, the uterosacral ligaments, or the adnexa. Endometriosis may also cause an asymmetric, fixed position of the uterus, the cervix, or the adnexa [9].Adenomyosis may cause diffuse moderate uterine enlargement with or without tenderness [10].Endometrial carcinoma may also cause uterine enlargement and/or immobility.

• What laboratory testing should be performed?

• What additional testing would be useful in narrowing the differential diagnosis?

If the physical examination and initial laboratory testing is nondiagnostic, the decision to initiate a trial of symptom management or proceed with further testing (imaging and/or tissue sampling) is based on risk of endometrial cancer, severity of symptoms, and patient preference. In many women, body habitus makes a confirmatory pelvic examination difficult, which may lower the threshold for obtaining a pelvic ultrasound.

Women with risk factors for endometrial cancer should undergo office-based endometrial biopsy as the first step in evaluation of heavy menstrual bleeding [7].Risk factors include older age (45 years and older), obesity (BMI > 30), diabetes mellitus, nulliparity, and history of chronic anovulation (eg, polycystic ovary syndrome). Pelvic ultrasound is the first step in the evaluation of women with an abnormal physical exam suggesting a structural lesion [7].If the physical exam is abnormal and the pelvic ultrasound is nondiagnostic, a hysteroscopy or saline-infusion sonohysterogram should be performed, as these tests are more sensitive for the detection of intracavitary lesions and submucosal fibroids [13].Most endometrial polyps will appear as a thickened or irregular endometrium on pelvic ultrasound, but be clearly delineated on sonohysterogram. Women who have a negative initial evaluation but then go on to have persistent bleeding despite a trial of therapy also require further evaluation.

Case Continued

The patient reports that her periods are regular, with a cycle length of 30 to 31 days. She usually notes some bloating and breast tenderness in the days leading up to onset of menses. She experiences lower abdominal cramping during days 1–3 of her period. This has worsened somewhat over the last year, and sometimes radiates to her low back. Her reproductive history is significant for 3 uncomplicated vaginal deliveries and 1 first trimester spontaneous abortion. She did not experience postpartum hemorrhage, and has no history of significant oropharyngeal bleeding or unexplained bruising. Her BMI is 23.3. Her physical exam is unremarkable, including a normal thyroid, abdominal, bimanual and speculum exam. Laboratory evaluation demonstrates a low-normal hemoglobin, hematocrit, and MCV. The TSH is normal and a urine pregnancy test is negative. She had a normal pap smear and HPV assay 2 years ago.

• What is the most likely diagnosis?

• What treatment is recommended?

Oral tranexamic acid is an anti-fibrinolytic that was recently approved by the FDA for treatment of menorrhagia or heavy menstrual bleeding. It has been used for many years to prevent bleeding during surgery and to treat bleeding disorders. It has been used for over 30 years to treat menorrhagia in Europe. It has a different mechanism of action than NSAIDs and hormonal contraceptives, and is therefore an appropriate alternative for women who cannot tolerate other medication options [16,17].Tranexamic acid is contraindicated in women with an elevated risk of thromboembolic disease.

For women who have insufficient response to medical management or for women who present with more severe symptoms, anemia, or prominent bulk-related symptoms due to fibroids, gynecologic referral should be made for consideration of surgical intervention. The preferred interventional approach to the treatment of uterine fibroid tumors depends upon the type of fibroid (eg submucosal, intramural, subserosal), the number of fibroids, desire for future childbearing, risk for surgical complications, and patient preference. Effective options include myomectomy, uterine artery embolization, endometrial ablation, and hysterectomy [18].

By contrast, good evidence supports the use of medication as first-line therapy for heavy menstrual bleeding when it occurs in the setting of endometriosis. Estrogen-progestin oral contraceptive pills, oral progestins, and depot medroxyprogesterone have all been demonstrated to be effective in decreasing pain [19,20].The levonorgestrel-releasing intrauterine system is also effective in decreasing pain due to endometriosis [21].

Women who do not respond to first-line therapy should be referred to a gynecologist for consideration of other treatment options. Effective second-line treatment options include oral danazol, intramuscular GnRH agonists, and surgical approaches such as laparoscopic ablation and/or excision of endometriosis implants [22].

A similar range of treatment options appears to be effective in the management of heavy menstrual bleeding due to adenomyosis. First-line therapies include oral NSAIDs, oral tranexamic acid, estrogen-progestin oral contraceptive pills, and the levonorgestrel-releasing intrauterine system [23,24].Women with an inadequate response to first-line treatment should be referred to a gynecologist for consideration definitive treatment with hysterectomy versus uterine artery embolization or a trial of a GnRH agonist [24].

For some women with heavy menstrual bleeding, no specific underlying cause is identified. Current evidence suggests that such patients may have disorders of local endometrial hemostasis leading to increased blood loss during otherwise normal menstrual cycles [25].The levonorgestrel-releasing intrauterine system may be the most effective medical therapy for heavy menstrual bleeding in the absence of a specific target lesion [26].For women wishing to avoid hormonal treatment, scheduled oral NSAIDs or oral tranexamic acid are inexpensive and effective options for reducing blood loss [27–29].Other medical treatment options include estrogen-progestin contraceptive pills, cyclic oral progestin, and depot medroxy-progesterone.

For patients who experience treatment failure with pharmaceutical therapy or who desire definitive treatment, both endometrial ablation and hysterectomy have been shown to be effective and associated with high rates of patient satisfaction [30].

Follow-up

The patient reports that she would like to avoid invasive testing if possible. Given her relatively low risk for endometrial cancer, she elects a trial of scheduled NSAIDs. Unfortunately, after a couple of cycles she reports that her heavy bleeding has not been well-controlled. A pelvic ultrasound demonstrates an anterior submucosal fibroid measuring 2.4 cm and a posterior intramural fibroid measuring 1.5 cm. She agrees to insertion of a levonorgestrel IUD and calls 6 months later to report a significant decrease in her bleeding.

Case 2—Anovulation

Initial Presentation

A 27-year-old female presents for pregnancy testing. She is 2 weeks late for her period. She and her husband are attempting pregnancy and she seems disappointed that the pregnancy test is negative. She is having trouble tracking her periods. Her cycles range from 24 to 45 days apart and often she skips cycles altogether. Her flow is scant at times but some months are heavy with soaking tampons/pads.

• What are diagnostic considerations in evaluating this bleeding pattern?

Menstrual history can help differentiate between of ovulatory and anovulatory abnormal bleeding. Typically, anovulatory bleeding is marked by irregular or infrequent periods. Flow can be scant to excessive. Women experiencing anovulatory cycles may fail to notice common ovulation symptoms (thin watery cervical mucus) or pre-menstrual symptoms (breast tenderness) [31].

The International Federation of Gynecology and Obstetrics (FIGO) designates AUD-O as “abnormal uterine bleeding due to ovulatory dysfunction” or “anovulatory abnormal uterine bleeding” [7,31].In general, if women are having menses at regular cycles their bleeding is likely to be ovulatory.

Differential Diagnosis

Anovulatory bleeding may be physiologic. After menarche, the hypothalamic-pituitary-ovarian axis is immature. This may result in anovulatory cycles for 2 to 3 years. Women entering perimenopausal transition may also experience intermittent anovulation and subsequent abnormal uterine bleeding. Other physiologic examples include lactation and pregnancy [31].

Physical Examination

A thorough history will help to narrow the differential diagnosis. The physical exam can evaluate for other findings that indicate endocrine dysfunction such as low body weight, hirsutism, balding, acne, high blood pressure, obesity (especially centripetal fat distribution). Acanthosis nigricans is a sign of insulin resistance which is part of the pathophysiology of PCOS. The gynecologic exam is often unremarkable in AUB-O although a bimanual exam can reveal adnexal enlargement indicative of cystic ovaries. Of note, clitoromegally is not common in PCOS. This finding would increase the likelihood of other causes of hyperandrogenism [32].

• What is the pathophysiologic basis for this patient’s bleeding pattern?

Pathophysiology of Anovulatory Bleeding

Anovulatory bleeding presumes that there is a normal anatomic and genetic makeup. For example, a woman without ovaries will be, by definition, anovulatory. Using current terminology anovulatory bleeding implies a disruption in the hypothalamic-pituitary-ovarian axis and is therefore primarily an endocrine disorder [31,33].

At the level of the ovary and uterus, anovulation results in prolonged estrogen effect on the endometrium. After ovulation, the corpus luteum produces progesterone which stops endometrial thickening and stabilizes the endometrium. Without ovulation, estrogen continues endometrial stimulation and excess proliferation of endometrial lining. The endometrium becomes unstable, undifferentiated, and sheds unpredictably. The blood vessels become larger, more tortuous and have increased fragility. The result is light or heavy menstrual bleeding, decreased frequency of periods but overall unpredictable menstrual bleeding [33].

Effects of Chronic Anovulation

Irregular cycles can be more than a mere inconvenience. Women who have anovulatory cycles associated with heavy menstrual bleeding are at risk for anemia. Anovulation that is a result of hyperandrogen state or other endocrine disorder has other health ramifications. Infertility and its treatment are common sequelae. Finally, over time, unopposed estrogen in anovulation increases the risk of endometrial hyperplasia, or cancer [7,34].

Case Continued

The patient reports menarche at age 12. Her periods were irregular for the first 1–2 years but became more regular after that. She has been taking combination oral contraceptives since the age of 20 to prevent pregnancy. She stopped this 1 year ago and she and her husband began actively trying to conceive 6 months ago. Her family history is notable for diabetes and hypertension in her father. Her mother had heavy periods leading up to menopause and had a hysterectomy with no malignancy at the age of 47. She has a BMI of 33; blood pressure is mildly elevated at 134/84 mm Hg. She has oily skin and acne along her chin and neck. She has mild hirsutism of her face. Otherwise her skin is normal appearing. She has an elevated waist circumference of 35 inches. The remainder of her exam is normal.

• What is the likely diagnosis?

Women with PCOS are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, type 2 diabetes and cardiovascular disease, endometrial cancer, and infertility. Women with PCOS who become pregnant have increased risk of pregnancy complications such as hypertensive disorders and gestational diabetes.

• What tests are indicated in this patient?

Appropriate laboratory testing is often determined based on findings in the history and physical as well as the patient’s age. Anovulation in the first 18 months to 3 years after menarche is common and testing for pregnancy, infection, and anemia are often sufficient. Menorrhagia in adolescents warrants testing for bleeding disorders as well [7].Within 3 years of menarche, menstrual cycles should become more regular. Persistent anovulatory cycles increase the likelihood of pathologic causes and warrant additional evaluation. Pregnancy testing, thyroid stimulation hormone and prolactin levels are recommended first line evaluation [7,32,34].If PCOS is suspected an ultrasound can be performed but as noted above, polycystic ovaries are not required to make the diagnosis after adolescence.

Additional testing includes testosterone levels to look for androgen secreting tumors. Late onset congenital adrenal hyperplasia is an uncommon cause of hyperandrogenism but is more common in women of Ashkenazi Jewish descent and those with a family history [34].Morning hydroxyprogesterone can be performed to evaluate for this. If women exhibit abrupt change in menstrual pattern and other signs of cortisol excess (hypertension, abdominal striae) 24-hour urine cortisol can detect Cushing’s syndrome [34].

In patients with PCOS, additional testing to evaluate for medical comorbidities is recommended. This includes screening for diabetes, dyslipidemia, and liver dysfunction.

Case Continued

The patient’s prolactin and TSH are normal. Tests for diabetes are normal. Her LDL is elevated to 162, triglycerides are 200, and her HDL is 38. The physician informs her that she meets criteria for PCOS and also that she has obesity and metabolic syndrome.

• What factors should be considered when making treatment recommendations for this patient?

Treatment for anovulation is guided by the goals of therapy. Since anovulation is an endocrine abnormality, medical treatment is first line [31].If secondary causes are diagnosed, these should be treated first. Other goals of treatment can include reducing amount and irregularity of menstruation, provide contraception, increasing ovulation in women with desired fertility, and reducing androgenic sequelae such as acne and hirsutism.

When treating the irregular or heavy bleeding associated with anovulation, first-line treatment is exogenous hormone. This can be in the form of combined estrogen/progesterone formulations (pill, patch, and ring). Medroxyprogesterone (medroxyprogesterone acetate 5–10 mg daily) taken 10 to 14 days per month is another option. Standard consideration for medical eligibility in prescribing these agents should be considered (see U.S. medical eligibility criteria for contraceptive use available at www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm). Combined formulations offer contraception, while cyclic progesterone does not. Both offer cyclic withdrawal bleeding. A Cochrane review did not find any RCTs comparing one to the other and therefore either are reasonable options [36].The levonorgestrel IUD is effective at treating AUB as well [31].Women may still experience intermittent vaginal bleeding or amenorrhea so it is less likely to result in cyclic withdrawal bleeding.

All of the above treatments provide the additional benefit of thinning the endometrium and preventing unopposed estrogen effect. This provides further protection the endometrial hyperplasia with chronic anovulatory cycles and unopposed estrogen [31].

In women with PCOS and associated metabolic conditions, first-line treatment is weight loss and other lifestyle interventions to improve or prevent other sequelae of the condition. Weight loss has been shown to reduce circulating androgen levels and increase ovulation. It has been shown to reduce glucose and lipid levels and hirsutism. Pregnancy rates increase as well. Weight loss achieved through medications and gastric bypass has similar effects. There is no special diet that has been shown to be more effective than another [32]. As little as a 5% weight reduction from baseline can improve PCOS symptoms [34,35].

Metformin is also commonly added to lifestyle modifications in women with PCOS to reduce risks for developing diabetes. There is little high quality evidence of added benefit above lifestyle modifications [34].Statin therapy can be considered in women with hyperlipidemia and PCOS [32].

For women with PCOS who desire to conceive, treatment should target increased ovulation. Pre-conception counseling and lifestyle modifications are again first line [32].Ovulation induction interventions carry increased risk of multiple gestation. For ovulation induction, clomiphene citrate is first line therapy. Metformin is commonly used as noted above to improve comorbidities associated with PCOS and can increase ovulation compared to placebo [37].However, RCTs do not support its use as first-line treatment of infertility treatment in PCOS. Clomiphene is 3 times more effective than metformin alone [32].

Medications can improve but often do not resolve hirsutism in women with PCOS. Combined hormonal contraceptives are commonly used off-label and no one type of pill has been shown to be superior. Anti-androgens are also off-label but empirically used. They can also improve lipid and other metabolic variables. They are all teratogenic and therefore should not be used in women who desire conception, and be used with effective contraceptives. Spironolactone is an androgen receptor antagonist. It takes months for effect. Some women will have improved menstrual frequency with this medication as well. Often adjunctive therapy such as eflornithine facial cream or laser therapy or a combination is needed to further treat hirsutism [32,35,38].

Follow-up

After discussion, the patient decides to adopt therapeutic lifestyle changes. She desires to get pregnant and does not opt for hormonal contraceptives at this time. She sees a nutritionist and begins calorie restriction and exercise. Three months later she has lost 20 pounds and feels “healthier.” Her lipid panel shows LDL of 125 and HDL of 43. Her triglycerides are now 160. Her blood pressure in the office is 118/78 mm Hg. She has lost “inches” around her middle. She has had more regular periods as well. She is still not pregnant so the physician asks her to begin tracking ovulation with cervical mucus evaluation and basal body temperature prior to considering further infertility evaluations. Three months after that she misses a period but is pleased to report a positive home pregnancy test.

Case 3—Breakthough Bleeding On Combined Hormonal Contraceptives 

A 28-year-old G0P0 in a monogamous relationship presents to her physician. She has been on oral contraceptive pills for 8 years. For the last 3 years she has been taking the pills on an extended cycle schedule. She normally takes an active pill daily for 3 cycles of pills (9 weeks), and then takes a 7-day pill-free week when she gets a menstrual period. This had been working fine until the last 6 months. She has noticed breakthrough spotting up to 2 weeks at a time during the 2nd and 3rd pack of pills.

• What is the approach to evaluation and treatment in this patient?

Bleeding in Women on Combined Hormonal Contraception

Many women are now using combined hormonal contraceptives on different schedules. Extended-cycle contraception has been shown to be as effective as the traditional 21/7 schedule of active pills/pill-free week. The FDA has approved several packaged extended-cycle contraceptives. Extended-cycle contraception decreases overall number of bleeding days and improves many menstrual-related symptoms [39].Breakthrough bleeding is the most common side effect of extended cycle contraception. It is classified as AUB-I (abnormal uterine bleeding—iatrogenic). It is most common in the first few months of use, and decreases as use continues. Up to 86% of women will have unscheduled bleeding during the first 3 months of use of extended cycle contraception, but this bleedingdecreases as use continues [40].

There is no consensus as to the underlying mechanism causing this abnormal bleeding. Most clinicians believe that it is related to the balance of estrogen/progestin in each combined hormonal contraceptive. Each woman reacts differently to this combination, making it difficult to predict who will have abnormal bleeding. In women who are beginning an extended-cycle regimen, reassurance is sufficient. Most abnormal bleeding will normalize within the first 2 to 3 months. Missed pills and smoking are consistently related to breakthrough bleeding in women who take combined oral contraceptive pills [41].In women who have previously had stable bleeding patterns and who present with new breakthrough bleeding, evaluation for secondary causes of bleeding may be considered (ie, urine hCG, TSH, STI cultures, evaluation for cervical cancer screening). A pelvic examination may help determine a possible secondary cause of bleeding, but is not necessary.

Treatment of unscheduled bleeding in women on extended-cycle contraception includes shortening the hormone-free interval and adding medications for prevention/treatment of bleeding episodes. The 7-day hormone-free interval in the context of low-dose hormonal contraception may be too long. One study demonstrated that a 7-day hormone-free interval was associated with a lack of pituitary-ovarian suppression, follicular development, and possible ovulation [42].A systematic review found that shortened hormone-free intervals decreased the amount of unscheduled bleeding [39].A small RCT (65 women) of continuous contraceptive ring users found that the group that removed the ring for 4 days during an episode of unscheduled bleeding, and then reinserted it had overall reduction in unscheduled bleeding [43].Some clinicians will also recommend trying a different pill formlation or a different schedule. There is no evidence to support this recommendation, but it can be helpful in some women.

Low-dose doxycycline (40 mg daily) for prevention of unscheduled bleeding shows promise [44].This low- dose doxycycline is also helpful to prevent more unscheduled bleeding in extended-cycle oral contraceptive users [44].However, an RCT found that traditional-dose doxycline (100 mg BID) taken for 5 days at the onset of a bleeding episode, did not decrease the amount or length of unscheduled bleeding [40].Neither estrogen dose [45]nor progestin dose [45]affected bleeding patterns. There is some suggestion based on a small study that women on pills with norethindrone may have less unscheduled bleeding than those who are on pills with levonorgestrel, but more research needs to be done before clinicians change practice [46].A Cochrane review looked at one small study that suggested third-generation progestins had more favorable bleeding profiles than second-generation progestins [47].

Follow-up

The physician investigates for secondary causes of the bleeding. The patient’s urine hCG, TSH, and prolactin levels are all normal. No fibroids or polyps are seen on ultrasound. The physician and patient discuss treatment options, including a low-dose doxycycline pill to help minimize bleeding, trying a different pill formulation, or use of naproxen during the bleeding episodes, but the patient does not want to take 2 pills every day. After further discussion, the patient decides she would like to change to the contraceptive ring with the plan of removing the ring for 4 days at the onset of any unscheduled bleeding. In a phone call 6 months later, the patient states that her unscheduled bleeding has been controlled.

Corresponding author: Sarina Schrager, MD, MS, Dept. of Family Medicine, University of Wisconsin School of Medicine and Public Health, 1100 Delaplaine Ct., Madison, WI 53715, [email protected].

From the University of Wisconsin School of Medicine and Public Health, Madison, WI.

Abstract

• Objective: To describe the contributing etiologies, common presentations, diagnosis, evaluation, and management of abnormal uterine bleeding (AUB).
• Methods: Review of the literature in the context of 3 cases.
• Results: AUB is one of the most common reasons that reproductive-aged women seek health care. The causes are varied, depending in large part on the age and life stage of the woman. Diagnosis requires a systematic approach that is driven by a thorough health history and review of presenting symptoms.  Determining whether the bleeding is ovulatory or anovulatory is a central part of the evaluation. A methodical history, physical examination, and laboratory evaluation may enable the physician to rule out causes such as pregnancy and pregnancy-related disorders, medications, iatrogenic causes, systemic conditions, and obvious genital tract pathology.
• Conclusion: Clinicians must be knowledgeable about AUB and partner with women to develop appropriate, individualized treatment plans.

Abnormal vaginal bleeding is a common complaint in primary care. The prevalence of some type of abnormal bleeding is up to 30% among women of reproductive age [1].Over 18% of all gynecology outpatient visits in the United States are for menorrhagia alone [2].A retrospective analysis of medical expenditures data compared 1.4 million women with abnormal uterine bleeding to over 50 million women without abnormal bleeding. This study found that women with abnormal bleeding were more likely to be younger, Caucasian, and obese and had poorer physical and mental health quality of life scores [3].

The estimated direct and indirect costs of abnormal bleeding are $1 billion and $12 billion annually, respectively [4]. Indirect costs of abnormal bleeding include time off from work and cost of products to protect clothing from bleeding (eg, tampons and pads). Abnormal bleeding is also a common reason for women to be referred to gynecologists and is an indication for up to 25% of all gynecologic surgeries [5].

History Taking

Taking a menstrual history is an important step in determining whether the current bleeding pattern is normal or abnormal. Regularity of menstrual bleeding is clarified by asking about the frequency of the menses and their duration. Other important questions include age at menarche, presence of premenstrual syndrome symptoms, breast tenderness, cervical mucus changes, and amount of bleeding. An ovulatory cycle will usually include premenstrual symptoms whereas an anovulatory cycle will be random in its symptomatology. Women’s estimates of the amount of menstrual bleeding are notoriously inaccurate. Traditionally, more than 80 cc of menstrual blood loss per cycle is considered menorrhagia. However, women and their health care providers do not measure menstrual blood volume outside of study settings, and one study found that only half of women who presented with menorrhagia actually had more than 80 cc of blood loss [6]. There is movement toward use of more patient-centered measures to diagnose men-orrhagia, such as bleeding interfering with a woman’s daily activities, needing to wake up at night to change tampons or pads, or inability to exercise during menses. Anemia in the setting of menorrhagia by history is a less subjective way to diagnose menorrhagia.

Nomenclature and Differential Diagnosis

Differential diagnosis will vary based on symptomatology as well as age. Pregnancy is a possible cause of any type of abnormal bleeding in any woman of reproductive age (ie, after menarche and before menopause). Many systemic illnesses and medications can affect menstrual bleeding and should be included in a broad differential diagnosis of a presenting woman.

Case 1—Heavy Menstrual Bleeding

Initial Presentation

A 42-year-old woman presents reporting increasingly heavy, somewhat painful periods over the last 6 to 8 months. She experienced menarche at age 12 and has had regular, moderately heavy periods throughout her adult life. She denies any inter-menstrual bleeding.

• What additional history should be obtained?

Heavy menstrual bleeding refers to abnormally heavy bleeding that occurs in an ovulatory, cyclical pattern. Women with anovulatory cycles can also have heavy bleeding as well, and distinguishing ovulatory vs anovulatory cycles is often the first step in the evaluation.

The initial evaluation of a woman presenting with heavy menstrual bleeding includes a detailed history and physical examination. The first goal of the history is to establish the severity of bleeding, including any symptoms of hemodynamically significant anemia such as dizziness or exertional dyspnea. Next, the clinician should determine whether the bleeding pattern is ovulatory or anovulatory. Ovulatory heavy menstrual bleeding is most often caused by structural lesions (leiomyomas, endometriosis, adenomyosis, cervical polyps, and endometrial polyps) or a coagulopathy (von Willebrand disease, anticoagulant use, etc). Less commonly, ovulatory heavy menstrual bleeding may be due to systemic illness (including thyroid disease, renal disease, and liver disease) or endometrial hyperplasia or carcinoma.

Once an ovulatory pattern is confirmed, a history of dysmenorrhea, pelvic pain, lower urinary tract symptoms, constipation, dyspareunia, or infertility should be elicited. 

Further history taking should seek to identify any symptoms suggestive of thyroid, kidney, or liver disease, 

• What are key elements of the physical examination?

The physical examination should include visual inspection and palpation of the thyroid gland as well as an abdominal exam to evaluate for hepatosplenomegaly or lower abdominal tenderness or masses. Signs of anemia such as pallor should also be noted. The gynecologic exam should include visual inspection of the external genitalia, a bimanual exam, and a speculum exam. Cervical and endometrial polyps may be visible as masses at the cervical os or extending into the vaginal canal. An enlarged mobile uterus with irregular contours is consistent with leiomyomas [8].Endometriosis may manifest as tenderness, thickening, or nodularity of the uterine corpus, the vaginal canal, the uterosacral ligaments, or the adnexa. Endometriosis may also cause an asymmetric, fixed position of the uterus, the cervix, or the adnexa [9].Adenomyosis may cause diffuse moderate uterine enlargement with or without tenderness [10].Endometrial carcinoma may also cause uterine enlargement and/or immobility.

• What laboratory testing should be performed?

• What additional testing would be useful in narrowing the differential diagnosis?

If the physical examination and initial laboratory testing is nondiagnostic, the decision to initiate a trial of symptom management or proceed with further testing (imaging and/or tissue sampling) is based on risk of endometrial cancer, severity of symptoms, and patient preference. In many women, body habitus makes a confirmatory pelvic examination difficult, which may lower the threshold for obtaining a pelvic ultrasound.

Women with risk factors for endometrial cancer should undergo office-based endometrial biopsy as the first step in evaluation of heavy menstrual bleeding [7].Risk factors include older age (45 years and older), obesity (BMI > 30), diabetes mellitus, nulliparity, and history of chronic anovulation (eg, polycystic ovary syndrome). Pelvic ultrasound is the first step in the evaluation of women with an abnormal physical exam suggesting a structural lesion [7].If the physical exam is abnormal and the pelvic ultrasound is nondiagnostic, a hysteroscopy or saline-infusion sonohysterogram should be performed, as these tests are more sensitive for the detection of intracavitary lesions and submucosal fibroids [13].Most endometrial polyps will appear as a thickened or irregular endometrium on pelvic ultrasound, but be clearly delineated on sonohysterogram. Women who have a negative initial evaluation but then go on to have persistent bleeding despite a trial of therapy also require further evaluation.

Case Continued

The patient reports that her periods are regular, with a cycle length of 30 to 31 days. She usually notes some bloating and breast tenderness in the days leading up to onset of menses. She experiences lower abdominal cramping during days 1–3 of her period. This has worsened somewhat over the last year, and sometimes radiates to her low back. Her reproductive history is significant for 3 uncomplicated vaginal deliveries and 1 first trimester spontaneous abortion. She did not experience postpartum hemorrhage, and has no history of significant oropharyngeal bleeding or unexplained bruising. Her BMI is 23.3. Her physical exam is unremarkable, including a normal thyroid, abdominal, bimanual and speculum exam. Laboratory evaluation demonstrates a low-normal hemoglobin, hematocrit, and MCV. The TSH is normal and a urine pregnancy test is negative. She had a normal pap smear and HPV assay 2 years ago.

• What is the most likely diagnosis?

• What treatment is recommended?

Oral tranexamic acid is an anti-fibrinolytic that was recently approved by the FDA for treatment of menorrhagia or heavy menstrual bleeding. It has been used for many years to prevent bleeding during surgery and to treat bleeding disorders. It has been used for over 30 years to treat menorrhagia in Europe. It has a different mechanism of action than NSAIDs and hormonal contraceptives, and is therefore an appropriate alternative for women who cannot tolerate other medication options [16,17].Tranexamic acid is contraindicated in women with an elevated risk of thromboembolic disease.

For women who have insufficient response to medical management or for women who present with more severe symptoms, anemia, or prominent bulk-related symptoms due to fibroids, gynecologic referral should be made for consideration of surgical intervention. The preferred interventional approach to the treatment of uterine fibroid tumors depends upon the type of fibroid (eg submucosal, intramural, subserosal), the number of fibroids, desire for future childbearing, risk for surgical complications, and patient preference. Effective options include myomectomy, uterine artery embolization, endometrial ablation, and hysterectomy [18].

By contrast, good evidence supports the use of medication as first-line therapy for heavy menstrual bleeding when it occurs in the setting of endometriosis. Estrogen-progestin oral contraceptive pills, oral progestins, and depot medroxyprogesterone have all been demonstrated to be effective in decreasing pain [19,20].The levonorgestrel-releasing intrauterine system is also effective in decreasing pain due to endometriosis [21].

Women who do not respond to first-line therapy should be referred to a gynecologist for consideration of other treatment options. Effective second-line treatment options include oral danazol, intramuscular GnRH agonists, and surgical approaches such as laparoscopic ablation and/or excision of endometriosis implants [22].

A similar range of treatment options appears to be effective in the management of heavy menstrual bleeding due to adenomyosis. First-line therapies include oral NSAIDs, oral tranexamic acid, estrogen-progestin oral contraceptive pills, and the levonorgestrel-releasing intrauterine system [23,24].Women with an inadequate response to first-line treatment should be referred to a gynecologist for consideration definitive treatment with hysterectomy versus uterine artery embolization or a trial of a GnRH agonist [24].

For some women with heavy menstrual bleeding, no specific underlying cause is identified. Current evidence suggests that such patients may have disorders of local endometrial hemostasis leading to increased blood loss during otherwise normal menstrual cycles [25].The levonorgestrel-releasing intrauterine system may be the most effective medical therapy for heavy menstrual bleeding in the absence of a specific target lesion [26].For women wishing to avoid hormonal treatment, scheduled oral NSAIDs or oral tranexamic acid are inexpensive and effective options for reducing blood loss [27–29].Other medical treatment options include estrogen-progestin contraceptive pills, cyclic oral progestin, and depot medroxy-progesterone.

For patients who experience treatment failure with pharmaceutical therapy or who desire definitive treatment, both endometrial ablation and hysterectomy have been shown to be effective and associated with high rates of patient satisfaction [30].

Follow-up

The patient reports that she would like to avoid invasive testing if possible. Given her relatively low risk for endometrial cancer, she elects a trial of scheduled NSAIDs. Unfortunately, after a couple of cycles she reports that her heavy bleeding has not been well-controlled. A pelvic ultrasound demonstrates an anterior submucosal fibroid measuring 2.4 cm and a posterior intramural fibroid measuring 1.5 cm. She agrees to insertion of a levonorgestrel IUD and calls 6 months later to report a significant decrease in her bleeding.

Case 2—Anovulation

Initial Presentation

A 27-year-old female presents for pregnancy testing. She is 2 weeks late for her period. She and her husband are attempting pregnancy and she seems disappointed that the pregnancy test is negative. She is having trouble tracking her periods. Her cycles range from 24 to 45 days apart and often she skips cycles altogether. Her flow is scant at times but some months are heavy with soaking tampons/pads.

• What are diagnostic considerations in evaluating this bleeding pattern?

Menstrual history can help differentiate between of ovulatory and anovulatory abnormal bleeding. Typically, anovulatory bleeding is marked by irregular or infrequent periods. Flow can be scant to excessive. Women experiencing anovulatory cycles may fail to notice common ovulation symptoms (thin watery cervical mucus) or pre-menstrual symptoms (breast tenderness) [31].

The International Federation of Gynecology and Obstetrics (FIGO) designates AUD-O as “abnormal uterine bleeding due to ovulatory dysfunction” or “anovulatory abnormal uterine bleeding” [7,31].In general, if women are having menses at regular cycles their bleeding is likely to be ovulatory.

Differential Diagnosis

Anovulatory bleeding may be physiologic. After menarche, the hypothalamic-pituitary-ovarian axis is immature. This may result in anovulatory cycles for 2 to 3 years. Women entering perimenopausal transition may also experience intermittent anovulation and subsequent abnormal uterine bleeding. Other physiologic examples include lactation and pregnancy [31].

Physical Examination

A thorough history will help to narrow the differential diagnosis. The physical exam can evaluate for other findings that indicate endocrine dysfunction such as low body weight, hirsutism, balding, acne, high blood pressure, obesity (especially centripetal fat distribution). Acanthosis nigricans is a sign of insulin resistance which is part of the pathophysiology of PCOS. The gynecologic exam is often unremarkable in AUB-O although a bimanual exam can reveal adnexal enlargement indicative of cystic ovaries. Of note, clitoromegally is not common in PCOS. This finding would increase the likelihood of other causes of hyperandrogenism [32].

• What is the pathophysiologic basis for this patient’s bleeding pattern?

Pathophysiology of Anovulatory Bleeding

Anovulatory bleeding presumes that there is a normal anatomic and genetic makeup. For example, a woman without ovaries will be, by definition, anovulatory. Using current terminology anovulatory bleeding implies a disruption in the hypothalamic-pituitary-ovarian axis and is therefore primarily an endocrine disorder [31,33].

At the level of the ovary and uterus, anovulation results in prolonged estrogen effect on the endometrium. After ovulation, the corpus luteum produces progesterone which stops endometrial thickening and stabilizes the endometrium. Without ovulation, estrogen continues endometrial stimulation and excess proliferation of endometrial lining. The endometrium becomes unstable, undifferentiated, and sheds unpredictably. The blood vessels become larger, more tortuous and have increased fragility. The result is light or heavy menstrual bleeding, decreased frequency of periods but overall unpredictable menstrual bleeding [33].

Effects of Chronic Anovulation

Irregular cycles can be more than a mere inconvenience. Women who have anovulatory cycles associated with heavy menstrual bleeding are at risk for anemia. Anovulation that is a result of hyperandrogen state or other endocrine disorder has other health ramifications. Infertility and its treatment are common sequelae. Finally, over time, unopposed estrogen in anovulation increases the risk of endometrial hyperplasia, or cancer [7,34].

Case Continued

The patient reports menarche at age 12. Her periods were irregular for the first 1–2 years but became more regular after that. She has been taking combination oral contraceptives since the age of 20 to prevent pregnancy. She stopped this 1 year ago and she and her husband began actively trying to conceive 6 months ago. Her family history is notable for diabetes and hypertension in her father. Her mother had heavy periods leading up to menopause and had a hysterectomy with no malignancy at the age of 47. She has a BMI of 33; blood pressure is mildly elevated at 134/84 mm Hg. She has oily skin and acne along her chin and neck. She has mild hirsutism of her face. Otherwise her skin is normal appearing. She has an elevated waist circumference of 35 inches. The remainder of her exam is normal.

• What is the likely diagnosis?

Women with PCOS are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, type 2 diabetes and cardiovascular disease, endometrial cancer, and infertility. Women with PCOS who become pregnant have increased risk of pregnancy complications such as hypertensive disorders and gestational diabetes.

• What tests are indicated in this patient?

Appropriate laboratory testing is often determined based on findings in the history and physical as well as the patient’s age. Anovulation in the first 18 months to 3 years after menarche is common and testing for pregnancy, infection, and anemia are often sufficient. Menorrhagia in adolescents warrants testing for bleeding disorders as well [7].Within 3 years of menarche, menstrual cycles should become more regular. Persistent anovulatory cycles increase the likelihood of pathologic causes and warrant additional evaluation. Pregnancy testing, thyroid stimulation hormone and prolactin levels are recommended first line evaluation [7,32,34].If PCOS is suspected an ultrasound can be performed but as noted above, polycystic ovaries are not required to make the diagnosis after adolescence.

Additional testing includes testosterone levels to look for androgen secreting tumors. Late onset congenital adrenal hyperplasia is an uncommon cause of hyperandrogenism but is more common in women of Ashkenazi Jewish descent and those with a family history [34].Morning hydroxyprogesterone can be performed to evaluate for this. If women exhibit abrupt change in menstrual pattern and other signs of cortisol excess (hypertension, abdominal striae) 24-hour urine cortisol can detect Cushing’s syndrome [34].

In patients with PCOS, additional testing to evaluate for medical comorbidities is recommended. This includes screening for diabetes, dyslipidemia, and liver dysfunction.

Case Continued

The patient’s prolactin and TSH are normal. Tests for diabetes are normal. Her LDL is elevated to 162, triglycerides are 200, and her HDL is 38. The physician informs her that she meets criteria for PCOS and also that she has obesity and metabolic syndrome.

• What factors should be considered when making treatment recommendations for this patient?

Treatment for anovulation is guided by the goals of therapy. Since anovulation is an endocrine abnormality, medical treatment is first line [31].If secondary causes are diagnosed, these should be treated first. Other goals of treatment can include reducing amount and irregularity of menstruation, provide contraception, increasing ovulation in women with desired fertility, and reducing androgenic sequelae such as acne and hirsutism.

When treating the irregular or heavy bleeding associated with anovulation, first-line treatment is exogenous hormone. This can be in the form of combined estrogen/progesterone formulations (pill, patch, and ring). Medroxyprogesterone (medroxyprogesterone acetate 5–10 mg daily) taken 10 to 14 days per month is another option. Standard consideration for medical eligibility in prescribing these agents should be considered (see U.S. medical eligibility criteria for contraceptive use available at www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm). Combined formulations offer contraception, while cyclic progesterone does not. Both offer cyclic withdrawal bleeding. A Cochrane review did not find any RCTs comparing one to the other and therefore either are reasonable options [36].The levonorgestrel IUD is effective at treating AUB as well [31].Women may still experience intermittent vaginal bleeding or amenorrhea so it is less likely to result in cyclic withdrawal bleeding.

All of the above treatments provide the additional benefit of thinning the endometrium and preventing unopposed estrogen effect. This provides further protection the endometrial hyperplasia with chronic anovulatory cycles and unopposed estrogen [31].

In women with PCOS and associated metabolic conditions, first-line treatment is weight loss and other lifestyle interventions to improve or prevent other sequelae of the condition. Weight loss has been shown to reduce circulating androgen levels and increase ovulation. It has been shown to reduce glucose and lipid levels and hirsutism. Pregnancy rates increase as well. Weight loss achieved through medications and gastric bypass has similar effects. There is no special diet that has been shown to be more effective than another [32]. As little as a 5% weight reduction from baseline can improve PCOS symptoms [34,35].

Metformin is also commonly added to lifestyle modifications in women with PCOS to reduce risks for developing diabetes. There is little high quality evidence of added benefit above lifestyle modifications [34].Statin therapy can be considered in women with hyperlipidemia and PCOS [32].

For women with PCOS who desire to conceive, treatment should target increased ovulation. Pre-conception counseling and lifestyle modifications are again first line [32].Ovulation induction interventions carry increased risk of multiple gestation. For ovulation induction, clomiphene citrate is first line therapy. Metformin is commonly used as noted above to improve comorbidities associated with PCOS and can increase ovulation compared to placebo [37].However, RCTs do not support its use as first-line treatment of infertility treatment in PCOS. Clomiphene is 3 times more effective than metformin alone [32].

Medications can improve but often do not resolve hirsutism in women with PCOS. Combined hormonal contraceptives are commonly used off-label and no one type of pill has been shown to be superior. Anti-androgens are also off-label but empirically used. They can also improve lipid and other metabolic variables. They are all teratogenic and therefore should not be used in women who desire conception, and be used with effective contraceptives. Spironolactone is an androgen receptor antagonist. It takes months for effect. Some women will have improved menstrual frequency with this medication as well. Often adjunctive therapy such as eflornithine facial cream or laser therapy or a combination is needed to further treat hirsutism [32,35,38].

Follow-up

After discussion, the patient decides to adopt therapeutic lifestyle changes. She desires to get pregnant and does not opt for hormonal contraceptives at this time. She sees a nutritionist and begins calorie restriction and exercise. Three months later she has lost 20 pounds and feels “healthier.” Her lipid panel shows LDL of 125 and HDL of 43. Her triglycerides are now 160. Her blood pressure in the office is 118/78 mm Hg. She has lost “inches” around her middle. She has had more regular periods as well. She is still not pregnant so the physician asks her to begin tracking ovulation with cervical mucus evaluation and basal body temperature prior to considering further infertility evaluations. Three months after that she misses a period but is pleased to report a positive home pregnancy test.

Case 3—Breakthough Bleeding On Combined Hormonal Contraceptives 

A 28-year-old G0P0 in a monogamous relationship presents to her physician. She has been on oral contraceptive pills for 8 years. For the last 3 years she has been taking the pills on an extended cycle schedule. She normally takes an active pill daily for 3 cycles of pills (9 weeks), and then takes a 7-day pill-free week when she gets a menstrual period. This had been working fine until the last 6 months. She has noticed breakthrough spotting up to 2 weeks at a time during the 2nd and 3rd pack of pills.

• What is the approach to evaluation and treatment in this patient?

Bleeding in Women on Combined Hormonal Contraception

Many women are now using combined hormonal contraceptives on different schedules. Extended-cycle contraception has been shown to be as effective as the traditional 21/7 schedule of active pills/pill-free week. The FDA has approved several packaged extended-cycle contraceptives. Extended-cycle contraception decreases overall number of bleeding days and improves many menstrual-related symptoms [39].Breakthrough bleeding is the most common side effect of extended cycle contraception. It is classified as AUB-I (abnormal uterine bleeding—iatrogenic). It is most common in the first few months of use, and decreases as use continues. Up to 86% of women will have unscheduled bleeding during the first 3 months of use of extended cycle contraception, but this bleedingdecreases as use continues [40].

There is no consensus as to the underlying mechanism causing this abnormal bleeding. Most clinicians believe that it is related to the balance of estrogen/progestin in each combined hormonal contraceptive. Each woman reacts differently to this combination, making it difficult to predict who will have abnormal bleeding. In women who are beginning an extended-cycle regimen, reassurance is sufficient. Most abnormal bleeding will normalize within the first 2 to 3 months. Missed pills and smoking are consistently related to breakthrough bleeding in women who take combined oral contraceptive pills [41].In women who have previously had stable bleeding patterns and who present with new breakthrough bleeding, evaluation for secondary causes of bleeding may be considered (ie, urine hCG, TSH, STI cultures, evaluation for cervical cancer screening). A pelvic examination may help determine a possible secondary cause of bleeding, but is not necessary.

Treatment of unscheduled bleeding in women on extended-cycle contraception includes shortening the hormone-free interval and adding medications for prevention/treatment of bleeding episodes. The 7-day hormone-free interval in the context of low-dose hormonal contraception may be too long. One study demonstrated that a 7-day hormone-free interval was associated with a lack of pituitary-ovarian suppression, follicular development, and possible ovulation [42].A systematic review found that shortened hormone-free intervals decreased the amount of unscheduled bleeding [39].A small RCT (65 women) of continuous contraceptive ring users found that the group that removed the ring for 4 days during an episode of unscheduled bleeding, and then reinserted it had overall reduction in unscheduled bleeding [43].Some clinicians will also recommend trying a different pill formlation or a different schedule. There is no evidence to support this recommendation, but it can be helpful in some women.

Low-dose doxycycline (40 mg daily) for prevention of unscheduled bleeding shows promise [44].This low- dose doxycycline is also helpful to prevent more unscheduled bleeding in extended-cycle oral contraceptive users [44].However, an RCT found that traditional-dose doxycline (100 mg BID) taken for 5 days at the onset of a bleeding episode, did not decrease the amount or length of unscheduled bleeding [40].Neither estrogen dose [45]nor progestin dose [45]affected bleeding patterns. There is some suggestion based on a small study that women on pills with norethindrone may have less unscheduled bleeding than those who are on pills with levonorgestrel, but more research needs to be done before clinicians change practice [46].A Cochrane review looked at one small study that suggested third-generation progestins had more favorable bleeding profiles than second-generation progestins [47].

Follow-up

The physician investigates for secondary causes of the bleeding. The patient’s urine hCG, TSH, and prolactin levels are all normal. No fibroids or polyps are seen on ultrasound. The physician and patient discuss treatment options, including a low-dose doxycycline pill to help minimize bleeding, trying a different pill formulation, or use of naproxen during the bleeding episodes, but the patient does not want to take 2 pills every day. After further discussion, the patient decides she would like to change to the contraceptive ring with the plan of removing the ring for 4 days at the onset of any unscheduled bleeding. In a phone call 6 months later, the patient states that her unscheduled bleeding has been controlled.

Corresponding author: Sarina Schrager, MD, MS, Dept. of Family Medicine, University of Wisconsin School of Medicine and Public Health, 1100 Delaplaine Ct., Madison, WI 53715, [email protected].

From the University of Wisconsin School of Medicine and Public Health, Madison, WI.

Abstract

• Objective: To describe the contributing etiologies, common presentations, diagnosis, evaluation, and management of abnormal uterine bleeding (AUB).
• Methods: Review of the literature in the context of 3 cases.
• Results: AUB is one of the most common reasons that reproductive-aged women seek health care. The causes are varied, depending in large part on the age and life stage of the woman. Diagnosis requires a systematic approach that is driven by a thorough health history and review of presenting symptoms.  Determining whether the bleeding is ovulatory or anovulatory is a central part of the evaluation. A methodical history, physical examination, and laboratory evaluation may enable the physician to rule out causes such as pregnancy and pregnancy-related disorders, medications, iatrogenic causes, systemic conditions, and obvious genital tract pathology.
• Conclusion: Clinicians must be knowledgeable about AUB and partner with women to develop appropriate, individualized treatment plans.

Abnormal vaginal bleeding is a common complaint in primary care. The prevalence of some type of abnormal bleeding is up to 30% among women of reproductive age [1].Over 18% of all gynecology outpatient visits in the United States are for menorrhagia alone [2].A retrospective analysis of medical expenditures data compared 1.4 million women with abnormal uterine bleeding to over 50 million women without abnormal bleeding. This study found that women with abnormal bleeding were more likely to be younger, Caucasian, and obese and had poorer physical and mental health quality of life scores [3].

The estimated direct and indirect costs of abnormal bleeding are $1 billion and $12 billion annually, respectively [4]. Indirect costs of abnormal bleeding include time off from work and cost of products to protect clothing from bleeding (eg, tampons and pads). Abnormal bleeding is also a common reason for women to be referred to gynecologists and is an indication for up to 25% of all gynecologic surgeries [5].

History Taking

Taking a menstrual history is an important step in determining whether the current bleeding pattern is normal or abnormal. Regularity of menstrual bleeding is clarified by asking about the frequency of the menses and their duration. Other important questions include age at menarche, presence of premenstrual syndrome symptoms, breast tenderness, cervical mucus changes, and amount of bleeding. An ovulatory cycle will usually include premenstrual symptoms whereas an anovulatory cycle will be random in its symptomatology. Women’s estimates of the amount of menstrual bleeding are notoriously inaccurate. Traditionally, more than 80 cc of menstrual blood loss per cycle is considered menorrhagia. However, women and their health care providers do not measure menstrual blood volume outside of study settings, and one study found that only half of women who presented with menorrhagia actually had more than 80 cc of blood loss [6]. There is movement toward use of more patient-centered measures to diagnose men-orrhagia, such as bleeding interfering with a woman’s daily activities, needing to wake up at night to change tampons or pads, or inability to exercise during menses. Anemia in the setting of menorrhagia by history is a less subjective way to diagnose menorrhagia.

Nomenclature and Differential Diagnosis

Differential diagnosis will vary based on symptomatology as well as age. Pregnancy is a possible cause of any type of abnormal bleeding in any woman of reproductive age (ie, after menarche and before menopause). Many systemic illnesses and medications can affect menstrual bleeding and should be included in a broad differential diagnosis of a presenting woman.

Case 1—Heavy Menstrual Bleeding

Initial Presentation

A 42-year-old woman presents reporting increasingly heavy, somewhat painful periods over the last 6 to 8 months. She experienced menarche at age 12 and has had regular, moderately heavy periods throughout her adult life. She denies any inter-menstrual bleeding.

• What additional history should be obtained?

Heavy menstrual bleeding refers to abnormally heavy bleeding that occurs in an ovulatory, cyclical pattern. Women with anovulatory cycles can also have heavy bleeding as well, and distinguishing ovulatory vs anovulatory cycles is often the first step in the evaluation.

The initial evaluation of a woman presenting with heavy menstrual bleeding includes a detailed history and physical examination. The first goal of the history is to establish the severity of bleeding, including any symptoms of hemodynamically significant anemia such as dizziness or exertional dyspnea. Next, the clinician should determine whether the bleeding pattern is ovulatory or anovulatory. Ovulatory heavy menstrual bleeding is most often caused by structural lesions (leiomyomas, endometriosis, adenomyosis, cervical polyps, and endometrial polyps) or a coagulopathy (von Willebrand disease, anticoagulant use, etc). Less commonly, ovulatory heavy menstrual bleeding may be due to systemic illness (including thyroid disease, renal disease, and liver disease) or endometrial hyperplasia or carcinoma.

Once an ovulatory pattern is confirmed, a history of dysmenorrhea, pelvic pain, lower urinary tract symptoms, constipation, dyspareunia, or infertility should be elicited. 

Further history taking should seek to identify any symptoms suggestive of thyroid, kidney, or liver disease, 

• What are key elements of the physical examination?

The physical examination should include visual inspection and palpation of the thyroid gland as well as an abdominal exam to evaluate for hepatosplenomegaly or lower abdominal tenderness or masses. Signs of anemia such as pallor should also be noted. The gynecologic exam should include visual inspection of the external genitalia, a bimanual exam, and a speculum exam. Cervical and endometrial polyps may be visible as masses at the cervical os or extending into the vaginal canal. An enlarged mobile uterus with irregular contours is consistent with leiomyomas [8].Endometriosis may manifest as tenderness, thickening, or nodularity of the uterine corpus, the vaginal canal, the uterosacral ligaments, or the adnexa. Endometriosis may also cause an asymmetric, fixed position of the uterus, the cervix, or the adnexa [9].Adenomyosis may cause diffuse moderate uterine enlargement with or without tenderness [10].Endometrial carcinoma may also cause uterine enlargement and/or immobility.

• What laboratory testing should be performed?

• What additional testing would be useful in narrowing the differential diagnosis?

If the physical examination and initial laboratory testing is nondiagnostic, the decision to initiate a trial of symptom management or proceed with further testing (imaging and/or tissue sampling) is based on risk of endometrial cancer, severity of symptoms, and patient preference. In many women, body habitus makes a confirmatory pelvic examination difficult, which may lower the threshold for obtaining a pelvic ultrasound.

Women with risk factors for endometrial cancer should undergo office-based endometrial biopsy as the first step in evaluation of heavy menstrual bleeding [7].Risk factors include older age (45 years and older), obesity (BMI > 30), diabetes mellitus, nulliparity, and history of chronic anovulation (eg, polycystic ovary syndrome). Pelvic ultrasound is the first step in the evaluation of women with an abnormal physical exam suggesting a structural lesion [7].If the physical exam is abnormal and the pelvic ultrasound is nondiagnostic, a hysteroscopy or saline-infusion sonohysterogram should be performed, as these tests are more sensitive for the detection of intracavitary lesions and submucosal fibroids [13].Most endometrial polyps will appear as a thickened or irregular endometrium on pelvic ultrasound, but be clearly delineated on sonohysterogram. Women who have a negative initial evaluation but then go on to have persistent bleeding despite a trial of therapy also require further evaluation.

Case Continued

The patient reports that her periods are regular, with a cycle length of 30 to 31 days. She usually notes some bloating and breast tenderness in the days leading up to onset of menses. She experiences lower abdominal cramping during days 1–3 of her period. This has worsened somewhat over the last year, and sometimes radiates to her low back. Her reproductive history is significant for 3 uncomplicated vaginal deliveries and 1 first trimester spontaneous abortion. She did not experience postpartum hemorrhage, and has no history of significant oropharyngeal bleeding or unexplained bruising. Her BMI is 23.3. Her physical exam is unremarkable, including a normal thyroid, abdominal, bimanual and speculum exam. Laboratory evaluation demonstrates a low-normal hemoglobin, hematocrit, and MCV. The TSH is normal and a urine pregnancy test is negative. She had a normal pap smear and HPV assay 2 years ago.

• What is the most likely diagnosis?

• What treatment is recommended?

Oral tranexamic acid is an anti-fibrinolytic that was recently approved by the FDA for treatment of menorrhagia or heavy menstrual bleeding. It has been used for many years to prevent bleeding during surgery and to treat bleeding disorders. It has been used for over 30 years to treat menorrhagia in Europe. It has a different mechanism of action than NSAIDs and hormonal contraceptives, and is therefore an appropriate alternative for women who cannot tolerate other medication options [16,17].Tranexamic acid is contraindicated in women with an elevated risk of thromboembolic disease.

For women who have insufficient response to medical management or for women who present with more severe symptoms, anemia, or prominent bulk-related symptoms due to fibroids, gynecologic referral should be made for consideration of surgical intervention. The preferred interventional approach to the treatment of uterine fibroid tumors depends upon the type of fibroid (eg submucosal, intramural, subserosal), the number of fibroids, desire for future childbearing, risk for surgical complications, and patient preference. Effective options include myomectomy, uterine artery embolization, endometrial ablation, and hysterectomy [18].

By contrast, good evidence supports the use of medication as first-line therapy for heavy menstrual bleeding when it occurs in the setting of endometriosis. Estrogen-progestin oral contraceptive pills, oral progestins, and depot medroxyprogesterone have all been demonstrated to be effective in decreasing pain [19,20].The levonorgestrel-releasing intrauterine system is also effective in decreasing pain due to endometriosis [21].

Women who do not respond to first-line therapy should be referred to a gynecologist for consideration of other treatment options. Effective second-line treatment options include oral danazol, intramuscular GnRH agonists, and surgical approaches such as laparoscopic ablation and/or excision of endometriosis implants [22].

A similar range of treatment options appears to be effective in the management of heavy menstrual bleeding due to adenomyosis. First-line therapies include oral NSAIDs, oral tranexamic acid, estrogen-progestin oral contraceptive pills, and the levonorgestrel-releasing intrauterine system [23,24].Women with an inadequate response to first-line treatment should be referred to a gynecologist for consideration definitive treatment with hysterectomy versus uterine artery embolization or a trial of a GnRH agonist [24].

For some women with heavy menstrual bleeding, no specific underlying cause is identified. Current evidence suggests that such patients may have disorders of local endometrial hemostasis leading to increased blood loss during otherwise normal menstrual cycles [25].The levonorgestrel-releasing intrauterine system may be the most effective medical therapy for heavy menstrual bleeding in the absence of a specific target lesion [26].For women wishing to avoid hormonal treatment, scheduled oral NSAIDs or oral tranexamic acid are inexpensive and effective options for reducing blood loss [27–29].Other medical treatment options include estrogen-progestin contraceptive pills, cyclic oral progestin, and depot medroxy-progesterone.

For patients who experience treatment failure with pharmaceutical therapy or who desire definitive treatment, both endometrial ablation and hysterectomy have been shown to be effective and associated with high rates of patient satisfaction [30].

Follow-up

The patient reports that she would like to avoid invasive testing if possible. Given her relatively low risk for endometrial cancer, she elects a trial of scheduled NSAIDs. Unfortunately, after a couple of cycles she reports that her heavy bleeding has not been well-controlled. A pelvic ultrasound demonstrates an anterior submucosal fibroid measuring 2.4 cm and a posterior intramural fibroid measuring 1.5 cm. She agrees to insertion of a levonorgestrel IUD and calls 6 months later to report a significant decrease in her bleeding.

Case 2—Anovulation

Initial Presentation

A 27-year-old female presents for pregnancy testing. She is 2 weeks late for her period. She and her husband are attempting pregnancy and she seems disappointed that the pregnancy test is negative. She is having trouble tracking her periods. Her cycles range from 24 to 45 days apart and often she skips cycles altogether. Her flow is scant at times but some months are heavy with soaking tampons/pads.

• What are diagnostic considerations in evaluating this bleeding pattern?

Menstrual history can help differentiate between of ovulatory and anovulatory abnormal bleeding. Typically, anovulatory bleeding is marked by irregular or infrequent periods. Flow can be scant to excessive. Women experiencing anovulatory cycles may fail to notice common ovulation symptoms (thin watery cervical mucus) or pre-menstrual symptoms (breast tenderness) [31].

The International Federation of Gynecology and Obstetrics (FIGO) designates AUD-O as “abnormal uterine bleeding due to ovulatory dysfunction” or “anovulatory abnormal uterine bleeding” [7,31].In general, if women are having menses at regular cycles their bleeding is likely to be ovulatory.

Differential Diagnosis

Anovulatory bleeding may be physiologic. After menarche, the hypothalamic-pituitary-ovarian axis is immature. This may result in anovulatory cycles for 2 to 3 years. Women entering perimenopausal transition may also experience intermittent anovulation and subsequent abnormal uterine bleeding. Other physiologic examples include lactation and pregnancy [31].

Physical Examination

A thorough history will help to narrow the differential diagnosis. The physical exam can evaluate for other findings that indicate endocrine dysfunction such as low body weight, hirsutism, balding, acne, high blood pressure, obesity (especially centripetal fat distribution). Acanthosis nigricans is a sign of insulin resistance which is part of the pathophysiology of PCOS. The gynecologic exam is often unremarkable in AUB-O although a bimanual exam can reveal adnexal enlargement indicative of cystic ovaries. Of note, clitoromegally is not common in PCOS. This finding would increase the likelihood of other causes of hyperandrogenism [32].

• What is the pathophysiologic basis for this patient’s bleeding pattern?

Pathophysiology of Anovulatory Bleeding

Anovulatory bleeding presumes that there is a normal anatomic and genetic makeup. For example, a woman without ovaries will be, by definition, anovulatory. Using current terminology anovulatory bleeding implies a disruption in the hypothalamic-pituitary-ovarian axis and is therefore primarily an endocrine disorder [31,33].

At the level of the ovary and uterus, anovulation results in prolonged estrogen effect on the endometrium. After ovulation, the corpus luteum produces progesterone which stops endometrial thickening and stabilizes the endometrium. Without ovulation, estrogen continues endometrial stimulation and excess proliferation of endometrial lining. The endometrium becomes unstable, undifferentiated, and sheds unpredictably. The blood vessels become larger, more tortuous and have increased fragility. The result is light or heavy menstrual bleeding, decreased frequency of periods but overall unpredictable menstrual bleeding [33].

Effects of Chronic Anovulation

Irregular cycles can be more than a mere inconvenience. Women who have anovulatory cycles associated with heavy menstrual bleeding are at risk for anemia. Anovulation that is a result of hyperandrogen state or other endocrine disorder has other health ramifications. Infertility and its treatment are common sequelae. Finally, over time, unopposed estrogen in anovulation increases the risk of endometrial hyperplasia, or cancer [7,34].

Case Continued

The patient reports menarche at age 12. Her periods were irregular for the first 1–2 years but became more regular after that. She has been taking combination oral contraceptives since the age of 20 to prevent pregnancy. She stopped this 1 year ago and she and her husband began actively trying to conceive 6 months ago. Her family history is notable for diabetes and hypertension in her father. Her mother had heavy periods leading up to menopause and had a hysterectomy with no malignancy at the age of 47. She has a BMI of 33; blood pressure is mildly elevated at 134/84 mm Hg. She has oily skin and acne along her chin and neck. She has mild hirsutism of her face. Otherwise her skin is normal appearing. She has an elevated waist circumference of 35 inches. The remainder of her exam is normal.

• What is the likely diagnosis?

Women with PCOS are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, type 2 diabetes and cardiovascular disease, endometrial cancer, and infertility. Women with PCOS who become pregnant have increased risk of pregnancy complications such as hypertensive disorders and gestational diabetes.

• What tests are indicated in this patient?

Appropriate laboratory testing is often determined based on findings in the history and physical as well as the patient’s age. Anovulation in the first 18 months to 3 years after menarche is common and testing for pregnancy, infection, and anemia are often sufficient. Menorrhagia in adolescents warrants testing for bleeding disorders as well [7].Within 3 years of menarche, menstrual cycles should become more regular. Persistent anovulatory cycles increase the likelihood of pathologic causes and warrant additional evaluation. Pregnancy testing, thyroid stimulation hormone and prolactin levels are recommended first line evaluation [7,32,34].If PCOS is suspected an ultrasound can be performed but as noted above, polycystic ovaries are not required to make the diagnosis after adolescence.

Additional testing includes testosterone levels to look for androgen secreting tumors. Late onset congenital adrenal hyperplasia is an uncommon cause of hyperandrogenism but is more common in women of Ashkenazi Jewish descent and those with a family history [34].Morning hydroxyprogesterone can be performed to evaluate for this. If women exhibit abrupt change in menstrual pattern and other signs of cortisol excess (hypertension, abdominal striae) 24-hour urine cortisol can detect Cushing’s syndrome [34].

In patients with PCOS, additional testing to evaluate for medical comorbidities is recommended. This includes screening for diabetes, dyslipidemia, and liver dysfunction.

Case Continued

The patient’s prolactin and TSH are normal. Tests for diabetes are normal. Her LDL is elevated to 162, triglycerides are 200, and her HDL is 38. The physician informs her that she meets criteria for PCOS and also that she has obesity and metabolic syndrome.

• What factors should be considered when making treatment recommendations for this patient?

Treatment for anovulation is guided by the goals of therapy. Since anovulation is an endocrine abnormality, medical treatment is first line [31].If secondary causes are diagnosed, these should be treated first. Other goals of treatment can include reducing amount and irregularity of menstruation, provide contraception, increasing ovulation in women with desired fertility, and reducing androgenic sequelae such as acne and hirsutism.

When treating the irregular or heavy bleeding associated with anovulation, first-line treatment is exogenous hormone. This can be in the form of combined estrogen/progesterone formulations (pill, patch, and ring). Medroxyprogesterone (medroxyprogesterone acetate 5–10 mg daily) taken 10 to 14 days per month is another option. Standard consideration for medical eligibility in prescribing these agents should be considered (see U.S. medical eligibility criteria for contraceptive use available at www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm). Combined formulations offer contraception, while cyclic progesterone does not. Both offer cyclic withdrawal bleeding. A Cochrane review did not find any RCTs comparing one to the other and therefore either are reasonable options [36].The levonorgestrel IUD is effective at treating AUB as well [31].Women may still experience intermittent vaginal bleeding or amenorrhea so it is less likely to result in cyclic withdrawal bleeding.

All of the above treatments provide the additional benefit of thinning the endometrium and preventing unopposed estrogen effect. This provides further protection the endometrial hyperplasia with chronic anovulatory cycles and unopposed estrogen [31].

In women with PCOS and associated metabolic conditions, first-line treatment is weight loss and other lifestyle interventions to improve or prevent other sequelae of the condition. Weight loss has been shown to reduce circulating androgen levels and increase ovulation. It has been shown to reduce glucose and lipid levels and hirsutism. Pregnancy rates increase as well. Weight loss achieved through medications and gastric bypass has similar effects. There is no special diet that has been shown to be more effective than another [32]. As little as a 5% weight reduction from baseline can improve PCOS symptoms [34,35].

Metformin is also commonly added to lifestyle modifications in women with PCOS to reduce risks for developing diabetes. There is little high quality evidence of added benefit above lifestyle modifications [34].Statin therapy can be considered in women with hyperlipidemia and PCOS [32].

For women with PCOS who desire to conceive, treatment should target increased ovulation. Pre-conception counseling and lifestyle modifications are again first line [32].Ovulation induction interventions carry increased risk of multiple gestation. For ovulation induction, clomiphene citrate is first line therapy. Metformin is commonly used as noted above to improve comorbidities associated with PCOS and can increase ovulation compared to placebo [37].However, RCTs do not support its use as first-line treatment of infertility treatment in PCOS. Clomiphene is 3 times more effective than metformin alone [32].

Medications can improve but often do not resolve hirsutism in women with PCOS. Combined hormonal contraceptives are commonly used off-label and no one type of pill has been shown to be superior. Anti-androgens are also off-label but empirically used. They can also improve lipid and other metabolic variables. They are all teratogenic and therefore should not be used in women who desire conception, and be used with effective contraceptives. Spironolactone is an androgen receptor antagonist. It takes months for effect. Some women will have improved menstrual frequency with this medication as well. Often adjunctive therapy such as eflornithine facial cream or laser therapy or a combination is needed to further treat hirsutism [32,35,38].

Follow-up

After discussion, the patient decides to adopt therapeutic lifestyle changes. She desires to get pregnant and does not opt for hormonal contraceptives at this time. She sees a nutritionist and begins calorie restriction and exercise. Three months later she has lost 20 pounds and feels “healthier.” Her lipid panel shows LDL of 125 and HDL of 43. Her triglycerides are now 160. Her blood pressure in the office is 118/78 mm Hg. She has lost “inches” around her middle. She has had more regular periods as well. She is still not pregnant so the physician asks her to begin tracking ovulation with cervical mucus evaluation and basal body temperature prior to considering further infertility evaluations. Three months after that she misses a period but is pleased to report a positive home pregnancy test.

Case 3—Breakthough Bleeding On Combined Hormonal Contraceptives 

A 28-year-old G0P0 in a monogamous relationship presents to her physician. She has been on oral contraceptive pills for 8 years. For the last 3 years she has been taking the pills on an extended cycle schedule. She normally takes an active pill daily for 3 cycles of pills (9 weeks), and then takes a 7-day pill-free week when she gets a menstrual period. This had been working fine until the last 6 months. She has noticed breakthrough spotting up to 2 weeks at a time during the 2nd and 3rd pack of pills.

• What is the approach to evaluation and treatment in this patient?

Bleeding in Women on Combined Hormonal Contraception

Many women are now using combined hormonal contraceptives on different schedules. Extended-cycle contraception has been shown to be as effective as the traditional 21/7 schedule of active pills/pill-free week. The FDA has approved several packaged extended-cycle contraceptives. Extended-cycle contraception decreases overall number of bleeding days and improves many menstrual-related symptoms [39].Breakthrough bleeding is the most common side effect of extended cycle contraception. It is classified as AUB-I (abnormal uterine bleeding—iatrogenic). It is most common in the first few months of use, and decreases as use continues. Up to 86% of women will have unscheduled bleeding during the first 3 months of use of extended cycle contraception, but this bleedingdecreases as use continues [40].

There is no consensus as to the underlying mechanism causing this abnormal bleeding. Most clinicians believe that it is related to the balance of estrogen/progestin in each combined hormonal contraceptive. Each woman reacts differently to this combination, making it difficult to predict who will have abnormal bleeding. In women who are beginning an extended-cycle regimen, reassurance is sufficient. Most abnormal bleeding will normalize within the first 2 to 3 months. Missed pills and smoking are consistently related to breakthrough bleeding in women who take combined oral contraceptive pills [41].In women who have previously had stable bleeding patterns and who present with new breakthrough bleeding, evaluation for secondary causes of bleeding may be considered (ie, urine hCG, TSH, STI cultures, evaluation for cervical cancer screening). A pelvic examination may help determine a possible secondary cause of bleeding, but is not necessary.

Treatment of unscheduled bleeding in women on extended-cycle contraception includes shortening the hormone-free interval and adding medications for prevention/treatment of bleeding episodes. The 7-day hormone-free interval in the context of low-dose hormonal contraception may be too long. One study demonstrated that a 7-day hormone-free interval was associated with a lack of pituitary-ovarian suppression, follicular development, and possible ovulation [42].A systematic review found that shortened hormone-free intervals decreased the amount of unscheduled bleeding [39].A small RCT (65 women) of continuous contraceptive ring users found that the group that removed the ring for 4 days during an episode of unscheduled bleeding, and then reinserted it had overall reduction in unscheduled bleeding [43].Some clinicians will also recommend trying a different pill formlation or a different schedule. There is no evidence to support this recommendation, but it can be helpful in some women.

Low-dose doxycycline (40 mg daily) for prevention of unscheduled bleeding shows promise [44].This low- dose doxycycline is also helpful to prevent more unscheduled bleeding in extended-cycle oral contraceptive users [44].However, an RCT found that traditional-dose doxycline (100 mg BID) taken for 5 days at the onset of a bleeding episode, did not decrease the amount or length of unscheduled bleeding [40].Neither estrogen dose [45]nor progestin dose [45]affected bleeding patterns. There is some suggestion based on a small study that women on pills with norethindrone may have less unscheduled bleeding than those who are on pills with levonorgestrel, but more research needs to be done before clinicians change practice [46].A Cochrane review looked at one small study that suggested third-generation progestins had more favorable bleeding profiles than second-generation progestins [47].

Follow-up

The physician investigates for secondary causes of the bleeding. The patient’s urine hCG, TSH, and prolactin levels are all normal. No fibroids or polyps are seen on ultrasound. The physician and patient discuss treatment options, including a low-dose doxycycline pill to help minimize bleeding, trying a different pill formulation, or use of naproxen during the bleeding episodes, but the patient does not want to take 2 pills every day. After further discussion, the patient decides she would like to change to the contraceptive ring with the plan of removing the ring for 4 days at the onset of any unscheduled bleeding. In a phone call 6 months later, the patient states that her unscheduled bleeding has been controlled.

Corresponding author: Sarina Schrager, MD, MS, Dept. of Family Medicine, University of Wisconsin School of Medicine and Public Health, 1100 Delaplaine Ct., Madison, WI 53715, [email protected].

From Novant Health and Novant Health Medical Group, Winston-Salem, NC.

Abstract

• Objective: To evaluate the effect of an educational intervention with regular audit and feedback on reporting of patient safety events in a nonacademic, community practice setting with an established reporting system.
• Methods: A quasi-experimental with comparator design was used to compare a 6-practice collaborative group with a 27-practice comparator group with regard to safety event reporting rates. Baseline data were collected for a 12-month period followed by recruitment of 6 practices (3 family medicine, 2 pediatric, and 1 general surgery). An educational intervention was carried out with each, and this was followed by monthly audit and regular written and in-person feedback. Practice-level comparisons were made with specialty- and size-matched practices for the 6 practices in the collaborative group.
• Results: In the 12-month period following the intervention in March 2013, the 6 practices reported 175 patient safety events compared with only 19 events in the previous 12-month period. Each practice at least doubled reporting rates, and 5 of the 6 significantly increased rates. In contrast, rates for comparator practices were unchanged, with 84 events reported for the pre-intervention period and 81 for the post-intervention period. Event classification and types of events reported were different in the collaborative practices compared with the comparators for the post-intervention period. For the collaborative group, near miss events predominated as did diagnostic testing and communication event types.
• Conclusion: An initial educational session stressing anonymous, voluntary safety event reporting together with monthly audit and feedback and a focus on developing a nonpunitive environment can significantly enhance reporting of safety events.

Multiple challenges in the outpatient setting make establishing a culture of safety and improving care delivery more difficult than for inpatient settings. In the outpatient setting, care is often inaccessible, not well coordinated between providers and between facilities and providers, and delivered in many locations. It may also involve multiple sites and providers for a single patient, may require multiple visits in a single location, and can be provided by phone, email, mail, video, or in person [1]. Errors and adverse events may take long periods of time to become apparent and are more often errors of omission compared with those in the inpatient setting [2].

Incident reporting systems are considered important in improving patient safety [3], and their limitations and value have recently been reviewed [4]. However, limited research has been conducted on medical errors in ambulatory care, and even less is available on optimal monitoring and reporting strategies [5–12].Reporting in our system is time-consuming (about 15 minutes for entry of a single  report), is not tailored for outpatient practices, may be considered potentially punitive (staff may believe that reporting may place themselves at risk for performance downgrade or other actions), and marked under-reporting of safety events was suspected. Most but not all of the suggested characteristics considered important for hospital-based reporting systems are fulfilled in our ambulatory reporting system [13].

Several academic groups have reported much improved reporting and a much better understanding of the types of errors occurring in their respective outpatient settings [14–16]. The most compelling model includes a voluntary, nonpunitive, anonymous reporting approach and a multidisciplinary practice-specific team to analyze reported errors and to enact change through a continuous quality improvement process [14,15].

We implemented a project to significantly improve reporting of safety events in an outpatient, nonacademic 6-practice collaborative by using education, monthly audit, and regular feedback.

Methods

Setting

Novant Health Medical Group is a consortium of over 380 clinic sites, nearly 1300 physicians, and over 500 advanced practice clinicians. Clinic locations are found in Virginia, North Carolina, and South Carolina. Medical group members partner with physicians and staff in 15 hospitals in these geographic locations. Novant Health utilizes Epic (Epic Systems, Verona, WI) as an electronic health record. Safety event reporting is accomplished electronically in a single software program (VIncident, Verge Solutions, Mt. Pleasant, SC), used for all patients in our integrated care system (inpatient and outpatient facilities).

Intervention

Two of the authors (HWC and TC) met in March 2013 with the lead physician, practice manager, and patient safety coach at each clinic for approximately 1 hour. We discussed current reporting practice, delivered education for the safety event compendium, and detailed an anonymous, voluntary, and nonpunitive approach (stressing the use of the term “safety event” and not “error”) to reporting using a single page, 8-question paper report about the event. The report was not to be signed by the person completing the event data with placement in a drop box for later collection and electronic reporting as per usual practice in the clinic. We agreed that clinic leaders would stress to staff and providers that  the initiative was nonpunitive and anonymous and that the goal was to report all known safety events, as an improvement project.

Patient safety coaches were selected for each of the 6 practices by the manager. Patient safety coaches are volunteer clinical or nonclinical staff members whose role is to observe, model, and reinforce pre-established patient safety behaviors and use of error prevention tools among peers and providers. Training requirements include an initial 2-hour training session in which they learn fundamentals of patient safety science, high reliability principles, coaching techniques for team accountability, and concepts for continuous quality improvement. Additionally, they attend monthly meetings where patient safety concepts are discussed in greater detail and best practices are shared. Following this training, each clinic’s staff was educated on the project, a process improvement team (lead physician, manager, and patient safety coach) was constituted, and the project was begun in April 2013. In quarter 3 of 2013, each practice team selected a quality improvement project based upon reported safety events in their clinic. We asked our medical group risk managers to continue event discussion with practice managers as usual, as each event is discussed briefly after a report is made.

We audited reports monthly and provided feedback to the practice team with a written report at the end of each 3-month period starting in June 2013 and ending in June 2014 (5 reports). Individual on-site visits to meet and discuss progress were completed in September 2013 and March 2014, in addition to the initial visit in March 2013.

Evaluation

We compared reported monthly safety events for each of the 6 practices and for the 6-practice collaborative in the aggregate for the 12-month pre-intervention period (April 2012 through March 2013) and post-intervention period (April 2013 through March 2014). Each practice was compared with 3 specialty- and size (number of providers)-matched practices, none of whom received education or feedback on reporting or had patient safety coaches in the practice. In addition, for each of the 3 family medicine practices in the collaborative, we matched 1:3 other family medicine practices for specialty, size, and presence of a designated and trained patient safety coach. For the duration of the project, only 50 of 380 practices in the medical group had a trained patient safety coach.

The rate of safety events reported (ie, number of safety events reported/number of patient encounters) was compared for the 2 time periods using Poisson regression or zero-inflated Poisson regression. SASenterprise guide5.1 was used for all analyses. A P value of < 0.05 was considered statistically significant. The protocol was reviewed by the institutional review board of Novant Health Presbyterian Medical Center and a waiver for informed written consent was granted.

Results

To control for the presence of patient safety coaches in practices, the 3 family medicine clinics (clinics 4 through 6, Figure 2) were each matched 1:3 for size (number of providers) and specialty (other family medicine clinics), also with a patient safety coach. While the rates were significantly increased for the 3 collaborative family medicine clinics (P < 0.001), only 1 of the comparators clinic’s rate changed significantly (0.2 or 1/44,580 to 1.3 or 6/45,157), and this change was marginally significant (P = 0.048). This practice was the only one of the 27 comparator clinics to demonstrate any increased rate.

Discussion

In our nonacademic community practices, patient safety reporting rates improved following an initial educational session stressing anonymous, voluntary safety event reporting together with monthly audit and feedback. Our findings corroborate those of others in academic ambulatory settings, who found that an emphasis on patient safety reporting, particularly if an anonymous approach is taken in a nonpunitive atmosphere, can significantly increase the reporting of patient safety events [14–16]. We demonstrated marked under-reporting and stability of patient safety event reporting throughout our ambulatory practice group and a 10-fold increase in reporting among the 6-practice collaborative.

An unexpected finding was that with the exception of 1 practice, we found no increased reporting in comparator practices that had a patient safety coach. Additionally, we noted that general surgery practices report (or experience) very few ambulatory safety events, as a total of 4 events were reported for all 4 general surgery practices in 18 months.

We chose a quasi-experimental with a comparison group and pre-test/post-test design since randomization of practices was not feasible [17]. We used a 2-year period to control for any seasonal trends and to allow time after the intervention to see if meaningful improvement in reporting over time would continue. We attempted to address the potential for nonequivalence in the comparison group by matching for specialty and size of practice.

There are several  limitations to this study. Bias in the selection of collaborative practices may have occurred since each had a proven leader, and this may have led to more rapid adoption and utilization of this reporting approach. Also, our findings may not be generalizable to other integrated health systems given the unique approaches to patient safety culture development and the disparate nature of reporting systems. In addition, with our study design we could not be certain that anonymous reporting was a key factor in the increase in reporting rates, but de-briefing interviews indicated that both anonymous reporting and declaring a nonpunitive, supportive approach in each practice was important to enhanced reporting.

We expect increased reporting to decline over time without consistent feedback, as has been demonstrated in other studies [18], and we will continue to monitor rates over time.

As our current reporting system requires considerable reporter time for data input and discussion with risk managers, is not specifically configured for ambulatory reporting, is considered by staff and providers potentially punitive, and marked under-reporting is clear, we have proposed moving to a new system that is more user-friendly, ambulatory-focused, and has a provision for anonymous reporting.

Presented in part at the Institute for Healthcare Improvement 15th Annual International Summit on Improving Patient Care in the Office Practice and the Community, Washington DC, March 2014.

Acknowledgements: We gratefully acknowledge the work of collaborative practice team members, including Christopher Isenhour MD, Janet White, Shelby Carlyle, Mark Tillotson MD, Maria Migliaccio, Melanie Trapp, Jennifer Ochs, Gary DeRosa MD, Margarete Hinkle, Scott Wagner, Kelly Schetselaar, Timothy Eichenbrenner MD, Sandy Hite, Jamie Shelton, Raymond Swetenburg MD, James Lye MD, Kelly Morrison, Jan Rapisardo, Jane Moss, Rhett Brown MD, Dorothy Hedrick, Camille Farmer, and William Anderson, MS, for assistance with analysis.

Corresponding author: Herbert Clegg, MD, 108 Providence Road, Charlotte NC, 28207, [email protected].

Financial disclosures: None.

From Novant Health and Novant Health Medical Group, Winston-Salem, NC.

Abstract

• Objective: To evaluate the effect of an educational intervention with regular audit and feedback on reporting of patient safety events in a nonacademic, community practice setting with an established reporting system.
• Methods: A quasi-experimental with comparator design was used to compare a 6-practice collaborative group with a 27-practice comparator group with regard to safety event reporting rates. Baseline data were collected for a 12-month period followed by recruitment of 6 practices (3 family medicine, 2 pediatric, and 1 general surgery). An educational intervention was carried out with each, and this was followed by monthly audit and regular written and in-person feedback. Practice-level comparisons were made with specialty- and size-matched practices for the 6 practices in the collaborative group.
• Results: In the 12-month period following the intervention in March 2013, the 6 practices reported 175 patient safety events compared with only 19 events in the previous 12-month period. Each practice at least doubled reporting rates, and 5 of the 6 significantly increased rates. In contrast, rates for comparator practices were unchanged, with 84 events reported for the pre-intervention period and 81 for the post-intervention period. Event classification and types of events reported were different in the collaborative practices compared with the comparators for the post-intervention period. For the collaborative group, near miss events predominated as did diagnostic testing and communication event types.
• Conclusion: An initial educational session stressing anonymous, voluntary safety event reporting together with monthly audit and feedback and a focus on developing a nonpunitive environment can significantly enhance reporting of safety events.

Multiple challenges in the outpatient setting make establishing a culture of safety and improving care delivery more difficult than for inpatient settings. In the outpatient setting, care is often inaccessible, not well coordinated between providers and between facilities and providers, and delivered in many locations. It may also involve multiple sites and providers for a single patient, may require multiple visits in a single location, and can be provided by phone, email, mail, video, or in person [1]. Errors and adverse events may take long periods of time to become apparent and are more often errors of omission compared with those in the inpatient setting [2].

Incident reporting systems are considered important in improving patient safety [3], and their limitations and value have recently been reviewed [4]. However, limited research has been conducted on medical errors in ambulatory care, and even less is available on optimal monitoring and reporting strategies [5–12].Reporting in our system is time-consuming (about 15 minutes for entry of a single  report), is not tailored for outpatient practices, may be considered potentially punitive (staff may believe that reporting may place themselves at risk for performance downgrade or other actions), and marked under-reporting of safety events was suspected. Most but not all of the suggested characteristics considered important for hospital-based reporting systems are fulfilled in our ambulatory reporting system [13].

Several academic groups have reported much improved reporting and a much better understanding of the types of errors occurring in their respective outpatient settings [14–16]. The most compelling model includes a voluntary, nonpunitive, anonymous reporting approach and a multidisciplinary practice-specific team to analyze reported errors and to enact change through a continuous quality improvement process [14,15].

We implemented a project to significantly improve reporting of safety events in an outpatient, nonacademic 6-practice collaborative by using education, monthly audit, and regular feedback.

Methods

Setting

Novant Health Medical Group is a consortium of over 380 clinic sites, nearly 1300 physicians, and over 500 advanced practice clinicians. Clinic locations are found in Virginia, North Carolina, and South Carolina. Medical group members partner with physicians and staff in 15 hospitals in these geographic locations. Novant Health utilizes Epic (Epic Systems, Verona, WI) as an electronic health record. Safety event reporting is accomplished electronically in a single software program (VIncident, Verge Solutions, Mt. Pleasant, SC), used for all patients in our integrated care system (inpatient and outpatient facilities).

Intervention

Two of the authors (HWC and TC) met in March 2013 with the lead physician, practice manager, and patient safety coach at each clinic for approximately 1 hour. We discussed current reporting practice, delivered education for the safety event compendium, and detailed an anonymous, voluntary, and nonpunitive approach (stressing the use of the term “safety event” and not “error”) to reporting using a single page, 8-question paper report about the event. The report was not to be signed by the person completing the event data with placement in a drop box for later collection and electronic reporting as per usual practice in the clinic. We agreed that clinic leaders would stress to staff and providers that  the initiative was nonpunitive and anonymous and that the goal was to report all known safety events, as an improvement project.

Patient safety coaches were selected for each of the 6 practices by the manager. Patient safety coaches are volunteer clinical or nonclinical staff members whose role is to observe, model, and reinforce pre-established patient safety behaviors and use of error prevention tools among peers and providers. Training requirements include an initial 2-hour training session in which they learn fundamentals of patient safety science, high reliability principles, coaching techniques for team accountability, and concepts for continuous quality improvement. Additionally, they attend monthly meetings where patient safety concepts are discussed in greater detail and best practices are shared. Following this training, each clinic’s staff was educated on the project, a process improvement team (lead physician, manager, and patient safety coach) was constituted, and the project was begun in April 2013. In quarter 3 of 2013, each practice team selected a quality improvement project based upon reported safety events in their clinic. We asked our medical group risk managers to continue event discussion with practice managers as usual, as each event is discussed briefly after a report is made.

We audited reports monthly and provided feedback to the practice team with a written report at the end of each 3-month period starting in June 2013 and ending in June 2014 (5 reports). Individual on-site visits to meet and discuss progress were completed in September 2013 and March 2014, in addition to the initial visit in March 2013.

Evaluation

We compared reported monthly safety events for each of the 6 practices and for the 6-practice collaborative in the aggregate for the 12-month pre-intervention period (April 2012 through March 2013) and post-intervention period (April 2013 through March 2014). Each practice was compared with 3 specialty- and size (number of providers)-matched practices, none of whom received education or feedback on reporting or had patient safety coaches in the practice. In addition, for each of the 3 family medicine practices in the collaborative, we matched 1:3 other family medicine practices for specialty, size, and presence of a designated and trained patient safety coach. For the duration of the project, only 50 of 380 practices in the medical group had a trained patient safety coach.

The rate of safety events reported (ie, number of safety events reported/number of patient encounters) was compared for the 2 time periods using Poisson regression or zero-inflated Poisson regression. SASenterprise guide5.1 was used for all analyses. A P value of < 0.05 was considered statistically significant. The protocol was reviewed by the institutional review board of Novant Health Presbyterian Medical Center and a waiver for informed written consent was granted.

Results

To control for the presence of patient safety coaches in practices, the 3 family medicine clinics (clinics 4 through 6, Figure 2) were each matched 1:3 for size (number of providers) and specialty (other family medicine clinics), also with a patient safety coach. While the rates were significantly increased for the 3 collaborative family medicine clinics (P < 0.001), only 1 of the comparators clinic’s rate changed significantly (0.2 or 1/44,580 to 1.3 or 6/45,157), and this change was marginally significant (P = 0.048). This practice was the only one of the 27 comparator clinics to demonstrate any increased rate.

Discussion

In our nonacademic community practices, patient safety reporting rates improved following an initial educational session stressing anonymous, voluntary safety event reporting together with monthly audit and feedback. Our findings corroborate those of others in academic ambulatory settings, who found that an emphasis on patient safety reporting, particularly if an anonymous approach is taken in a nonpunitive atmosphere, can significantly increase the reporting of patient safety events [14–16]. We demonstrated marked under-reporting and stability of patient safety event reporting throughout our ambulatory practice group and a 10-fold increase in reporting among the 6-practice collaborative.

An unexpected finding was that with the exception of 1 practice, we found no increased reporting in comparator practices that had a patient safety coach. Additionally, we noted that general surgery practices report (or experience) very few ambulatory safety events, as a total of 4 events were reported for all 4 general surgery practices in 18 months.

We chose a quasi-experimental with a comparison group and pre-test/post-test design since randomization of practices was not feasible [17]. We used a 2-year period to control for any seasonal trends and to allow time after the intervention to see if meaningful improvement in reporting over time would continue. We attempted to address the potential for nonequivalence in the comparison group by matching for specialty and size of practice.

There are several  limitations to this study. Bias in the selection of collaborative practices may have occurred since each had a proven leader, and this may have led to more rapid adoption and utilization of this reporting approach. Also, our findings may not be generalizable to other integrated health systems given the unique approaches to patient safety culture development and the disparate nature of reporting systems. In addition, with our study design we could not be certain that anonymous reporting was a key factor in the increase in reporting rates, but de-briefing interviews indicated that both anonymous reporting and declaring a nonpunitive, supportive approach in each practice was important to enhanced reporting.

We expect increased reporting to decline over time without consistent feedback, as has been demonstrated in other studies [18], and we will continue to monitor rates over time.

As our current reporting system requires considerable reporter time for data input and discussion with risk managers, is not specifically configured for ambulatory reporting, is considered by staff and providers potentially punitive, and marked under-reporting is clear, we have proposed moving to a new system that is more user-friendly, ambulatory-focused, and has a provision for anonymous reporting.

Presented in part at the Institute for Healthcare Improvement 15th Annual International Summit on Improving Patient Care in the Office Practice and the Community, Washington DC, March 2014.

Acknowledgements: We gratefully acknowledge the work of collaborative practice team members, including Christopher Isenhour MD, Janet White, Shelby Carlyle, Mark Tillotson MD, Maria Migliaccio, Melanie Trapp, Jennifer Ochs, Gary DeRosa MD, Margarete Hinkle, Scott Wagner, Kelly Schetselaar, Timothy Eichenbrenner MD, Sandy Hite, Jamie Shelton, Raymond Swetenburg MD, James Lye MD, Kelly Morrison, Jan Rapisardo, Jane Moss, Rhett Brown MD, Dorothy Hedrick, Camille Farmer, and William Anderson, MS, for assistance with analysis.

Corresponding author: Herbert Clegg, MD, 108 Providence Road, Charlotte NC, 28207, [email protected].

Financial disclosures: None.

From Novant Health and Novant Health Medical Group, Winston-Salem, NC.

Abstract

• Objective: To evaluate the effect of an educational intervention with regular audit and feedback on reporting of patient safety events in a nonacademic, community practice setting with an established reporting system.
• Methods: A quasi-experimental with comparator design was used to compare a 6-practice collaborative group with a 27-practice comparator group with regard to safety event reporting rates. Baseline data were collected for a 12-month period followed by recruitment of 6 practices (3 family medicine, 2 pediatric, and 1 general surgery). An educational intervention was carried out with each, and this was followed by monthly audit and regular written and in-person feedback. Practice-level comparisons were made with specialty- and size-matched practices for the 6 practices in the collaborative group.
• Results: In the 12-month period following the intervention in March 2013, the 6 practices reported 175 patient safety events compared with only 19 events in the previous 12-month period. Each practice at least doubled reporting rates, and 5 of the 6 significantly increased rates. In contrast, rates for comparator practices were unchanged, with 84 events reported for the pre-intervention period and 81 for the post-intervention period. Event classification and types of events reported were different in the collaborative practices compared with the comparators for the post-intervention period. For the collaborative group, near miss events predominated as did diagnostic testing and communication event types.
• Conclusion: An initial educational session stressing anonymous, voluntary safety event reporting together with monthly audit and feedback and a focus on developing a nonpunitive environment can significantly enhance reporting of safety events.

Multiple challenges in the outpatient setting make establishing a culture of safety and improving care delivery more difficult than for inpatient settings. In the outpatient setting, care is often inaccessible, not well coordinated between providers and between facilities and providers, and delivered in many locations. It may also involve multiple sites and providers for a single patient, may require multiple visits in a single location, and can be provided by phone, email, mail, video, or in person [1]. Errors and adverse events may take long periods of time to become apparent and are more often errors of omission compared with those in the inpatient setting [2].

Incident reporting systems are considered important in improving patient safety [3], and their limitations and value have recently been reviewed [4]. However, limited research has been conducted on medical errors in ambulatory care, and even less is available on optimal monitoring and reporting strategies [5–12].Reporting in our system is time-consuming (about 15 minutes for entry of a single  report), is not tailored for outpatient practices, may be considered potentially punitive (staff may believe that reporting may place themselves at risk for performance downgrade or other actions), and marked under-reporting of safety events was suspected. Most but not all of the suggested characteristics considered important for hospital-based reporting systems are fulfilled in our ambulatory reporting system [13].

Several academic groups have reported much improved reporting and a much better understanding of the types of errors occurring in their respective outpatient settings [14–16]. The most compelling model includes a voluntary, nonpunitive, anonymous reporting approach and a multidisciplinary practice-specific team to analyze reported errors and to enact change through a continuous quality improvement process [14,15].

We implemented a project to significantly improve reporting of safety events in an outpatient, nonacademic 6-practice collaborative by using education, monthly audit, and regular feedback.

Methods

Setting

Novant Health Medical Group is a consortium of over 380 clinic sites, nearly 1300 physicians, and over 500 advanced practice clinicians. Clinic locations are found in Virginia, North Carolina, and South Carolina. Medical group members partner with physicians and staff in 15 hospitals in these geographic locations. Novant Health utilizes Epic (Epic Systems, Verona, WI) as an electronic health record. Safety event reporting is accomplished electronically in a single software program (VIncident, Verge Solutions, Mt. Pleasant, SC), used for all patients in our integrated care system (inpatient and outpatient facilities).

Intervention

Two of the authors (HWC and TC) met in March 2013 with the lead physician, practice manager, and patient safety coach at each clinic for approximately 1 hour. We discussed current reporting practice, delivered education for the safety event compendium, and detailed an anonymous, voluntary, and nonpunitive approach (stressing the use of the term “safety event” and not “error”) to reporting using a single page, 8-question paper report about the event. The report was not to be signed by the person completing the event data with placement in a drop box for later collection and electronic reporting as per usual practice in the clinic. We agreed that clinic leaders would stress to staff and providers that  the initiative was nonpunitive and anonymous and that the goal was to report all known safety events, as an improvement project.

Patient safety coaches were selected for each of the 6 practices by the manager. Patient safety coaches are volunteer clinical or nonclinical staff members whose role is to observe, model, and reinforce pre-established patient safety behaviors and use of error prevention tools among peers and providers. Training requirements include an initial 2-hour training session in which they learn fundamentals of patient safety science, high reliability principles, coaching techniques for team accountability, and concepts for continuous quality improvement. Additionally, they attend monthly meetings where patient safety concepts are discussed in greater detail and best practices are shared. Following this training, each clinic’s staff was educated on the project, a process improvement team (lead physician, manager, and patient safety coach) was constituted, and the project was begun in April 2013. In quarter 3 of 2013, each practice team selected a quality improvement project based upon reported safety events in their clinic. We asked our medical group risk managers to continue event discussion with practice managers as usual, as each event is discussed briefly after a report is made.

We audited reports monthly and provided feedback to the practice team with a written report at the end of each 3-month period starting in June 2013 and ending in June 2014 (5 reports). Individual on-site visits to meet and discuss progress were completed in September 2013 and March 2014, in addition to the initial visit in March 2013.

Evaluation

We compared reported monthly safety events for each of the 6 practices and for the 6-practice collaborative in the aggregate for the 12-month pre-intervention period (April 2012 through March 2013) and post-intervention period (April 2013 through March 2014). Each practice was compared with 3 specialty- and size (number of providers)-matched practices, none of whom received education or feedback on reporting or had patient safety coaches in the practice. In addition, for each of the 3 family medicine practices in the collaborative, we matched 1:3 other family medicine practices for specialty, size, and presence of a designated and trained patient safety coach. For the duration of the project, only 50 of 380 practices in the medical group had a trained patient safety coach.

The rate of safety events reported (ie, number of safety events reported/number of patient encounters) was compared for the 2 time periods using Poisson regression or zero-inflated Poisson regression. SASenterprise guide5.1 was used for all analyses. A P value of < 0.05 was considered statistically significant. The protocol was reviewed by the institutional review board of Novant Health Presbyterian Medical Center and a waiver for informed written consent was granted.

Results

To control for the presence of patient safety coaches in practices, the 3 family medicine clinics (clinics 4 through 6, Figure 2) were each matched 1:3 for size (number of providers) and specialty (other family medicine clinics), also with a patient safety coach. While the rates were significantly increased for the 3 collaborative family medicine clinics (P < 0.001), only 1 of the comparators clinic’s rate changed significantly (0.2 or 1/44,580 to 1.3 or 6/45,157), and this change was marginally significant (P = 0.048). This practice was the only one of the 27 comparator clinics to demonstrate any increased rate.

Discussion

In our nonacademic community practices, patient safety reporting rates improved following an initial educational session stressing anonymous, voluntary safety event reporting together with monthly audit and feedback. Our findings corroborate those of others in academic ambulatory settings, who found that an emphasis on patient safety reporting, particularly if an anonymous approach is taken in a nonpunitive atmosphere, can significantly increase the reporting of patient safety events [14–16]. We demonstrated marked under-reporting and stability of patient safety event reporting throughout our ambulatory practice group and a 10-fold increase in reporting among the 6-practice collaborative.

An unexpected finding was that with the exception of 1 practice, we found no increased reporting in comparator practices that had a patient safety coach. Additionally, we noted that general surgery practices report (or experience) very few ambulatory safety events, as a total of 4 events were reported for all 4 general surgery practices in 18 months.

We chose a quasi-experimental with a comparison group and pre-test/post-test design since randomization of practices was not feasible [17]. We used a 2-year period to control for any seasonal trends and to allow time after the intervention to see if meaningful improvement in reporting over time would continue. We attempted to address the potential for nonequivalence in the comparison group by matching for specialty and size of practice.

There are several  limitations to this study. Bias in the selection of collaborative practices may have occurred since each had a proven leader, and this may have led to more rapid adoption and utilization of this reporting approach. Also, our findings may not be generalizable to other integrated health systems given the unique approaches to patient safety culture development and the disparate nature of reporting systems. In addition, with our study design we could not be certain that anonymous reporting was a key factor in the increase in reporting rates, but de-briefing interviews indicated that both anonymous reporting and declaring a nonpunitive, supportive approach in each practice was important to enhanced reporting.

We expect increased reporting to decline over time without consistent feedback, as has been demonstrated in other studies [18], and we will continue to monitor rates over time.

As our current reporting system requires considerable reporter time for data input and discussion with risk managers, is not specifically configured for ambulatory reporting, is considered by staff and providers potentially punitive, and marked under-reporting is clear, we have proposed moving to a new system that is more user-friendly, ambulatory-focused, and has a provision for anonymous reporting.

Presented in part at the Institute for Healthcare Improvement 15th Annual International Summit on Improving Patient Care in the Office Practice and the Community, Washington DC, March 2014.

Acknowledgements: We gratefully acknowledge the work of collaborative practice team members, including Christopher Isenhour MD, Janet White, Shelby Carlyle, Mark Tillotson MD, Maria Migliaccio, Melanie Trapp, Jennifer Ochs, Gary DeRosa MD, Margarete Hinkle, Scott Wagner, Kelly Schetselaar, Timothy Eichenbrenner MD, Sandy Hite, Jamie Shelton, Raymond Swetenburg MD, James Lye MD, Kelly Morrison, Jan Rapisardo, Jane Moss, Rhett Brown MD, Dorothy Hedrick, Camille Farmer, and William Anderson, MS, for assistance with analysis.

Corresponding author: Herbert Clegg, MD, 108 Providence Road, Charlotte NC, 28207, [email protected].

Financial disclosures: None.

From Summa Health System, Akron, OH.

Abstract

• Background: Ischemic stroke is a major cause of morbidity and mortality for patients ≥ 80 years old. The use of intravenous recombinant tissue plasminogen activator (tPA) in patients ≥ 80 years for treatment of ischemic stroke remains controversial.
• Objective: To examine outcomes in patients ≥ 80 years old who received tPA in our institution.
• Methods: This was a retrospective cohort study at a community-based certified acute stroke center. Individuals age ≥ 80 years evaluated emergently for acute neurologic changes consistent with ischemic stroke were included (n = 184). The comparison groups within this sample were patients who received tPA versus with those who did not because they came to the ED outside of the treatment window. Outcome measures included length of stay, symptomatic intracerebral hemorrhage (ICH), discharge disposition, and in-hospital death
• Results: 38 patients (20.7%) received tPA. 50 patients (27.2%) presented outside of treatment windows and were included in comparative analysis. There was no difference between groups in age (P = 0.26) or initial National Institute of Health Stroke Scale (P = 0.598). One patient (2.6%) who received tPA developed symptomatic ICH. Those receiving tPA were more likely to be discharged to acute rehabilitation hospitals (P = 0.012) and less likely to experience in hospital death (P = 0.048).
• Conclusion: At this institution, the use of tPA in patients ≥ 80 years old is not associated with increased mortality or risk of symptomatic ICH. Those who received tPA were more likely to be discharged to acute rehabilitation hospitals, suggesting greater potential for functional recovery.

Acute ischemic stroke is a major cause of morbidity and mortality in patients 80 years or older. Though less than 5% of the United States population is over the age of 80 [1], studies have shown that up to one-third of patients presenting with ischemic stroke are ≥ 80 years old [2] and among first-time strokes, a third occur in those ≥ 80 [3]. Older adults present with worse symptoms associated with ischemic stroke as measured by the National Institutes of Health Stroke Scale (NIHSS) compared with younger (< 80 years) counterparts [4]. Older patients are more likely to be discharged to a location other than home [5]. Older age is associated with higher hospital, 30-day, and 1-year mortality [3,5,6]. Patients ≥ 80 are significantly more likely to die in the hospital compared to younger patients, 11.7% to 23.6% vs 5.1%, respectively [3,7].

The Food and Drug Administration (FDA) approved the use of intravenous recombinant tissue plasminogen activator (tPA) in 1996 for the treatment of ischemic stroke [8]. Studies evaluating the safety and efficacy of tPA in ischemic stroke excluded or underrepresented patients ≥ 80 [8,9]. The use of tPA in those ≥ 80 has not been shown consistently to improve outcomes [6,10,11]. Post-hoc analysis of the National Institute of Neurologic Disorders and Stroke (NINDS) study did not show worse outcomes or harms to older adults treated with tPA [12]. Likewise, data from the International Stroke Treatment (IST-3) collaborative group show that treatment with tPA up to 6 hours from the onset of symptoms improves outcomes in the elderly [13]. Use of tPA in the oldest adults remains controversial due to perceived higher risk of symptomatic intracerebral hemorrhage (ICH). Published data suggest overall ICH risk of 4.3% to 6.4% across all age-groups [9,14,15].Studies have failed to demonstrate an increased risk in the oldest adults [4,10,16,17], though they may have higher mortality rates associated with ICH [15]. Despite this, trends suggest increasing use of tPA in those ≥ 80 over the past decade [2]. Along with primary data from NINDS [12] and IST-3 [13], a meta-analysis conducted in 2014 suggests that regardless of age, patients have improved outcomes with tPA [18].With the increasing age of the population, effective treatment of strokes in patients ≥ 80 will continue to be an important clinical and research endeavor.

This study evaluates the outcomes of clinical use of tPA for treatment of patients ≥ 80 years old who present to a community-based certified stroke center with ischemic stroke.

Methods

The study setting was a 540-bed acute care hospital that is a community-based certified stroke center. This study was deemed nonhuman subjects research by the institutional review board as the goal was to evaluate processes and outcomes of this institution’s stroke team in treating a subgroup of patients according to clinically accepted practice (quality improvement initiative). All patients presenting to the emergency department (ED) between 1 January 2011 and 30 November 2013 with the onset of stroke-like neurological deficits underwent evaluation and treatment by a neurologist and/or specially trained stroke team. This team consists of the attending neurologist, ED physician, resident physicians, advanced practice nurses, and ED staff nurses and emergency medicine technicians. Team members involved in the evaluation and treatment of these patients undergo routine clinical education and testing to ensure standardization. Patients undergo emergent evaluation including the National Institutes of Health Stroke Scale (NIHSS) and obtain brain imaging with computed tomography (CT).

Patients ≥ 80 years were identified among all those who presented to the ED with ischemic stroke. Patients were included if they were subsequently diagnosed with ischemic stroke or transient ischemic attacks (TIA). They were excluded from analysis if neurological changes were due to primary hemorrhagic stroke, intracranial hemorrhage, subarachnoid hemorrhage, seizure, conversion disorder, or metabolic derangements. They were also excluded from analysis if the acute ischemic stroke treatment included intra-arterial administration of tPA or endovascular revascularization.

Patient data collected included age, NIHSS at presentation to ED, time to presentation at ED, treatment with tPA, contraindications to tPA, discharge disposition, length of stay and in-hospital mortality. Raw NIHSS values were collected at the time of presentation. NIHSS were categorized into mild symptoms (NIHSS < 6), moderate symptoms (NIHSS 6–19), or severe symptoms (NIHSS ≥ 20). Clinical indications for receiving tPA include NIHSS > 4, focal neurological deficit onset < 3 hours (for those ≥ 80 years old), and no evidence of acute hemorrhage or acute infarct on CT. Contraindications include rapidly improving symptoms (repeat NIHSS < 4), active or history of intracranial hemorrhage, history of stroke or head trauma in past 3 months, gastrointestinal or genitourinary hemorrhage within 21 days, major surgery within 14 days, arterial puncture at a noncompressible site in past 7 days, treatment with anticoagulation with therapeutic indices, systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg and not responding to treatment, or platelet count < 100,000/mm³. Patients who were not eligible for tPA based on contraindications with the exception of being outside the treatment window (3 hours) were excluded from comparative analysis. Patient length of stay was rounded to nearest full day. Discharge disposition was categorized as home, acute rehabilitation hospital, skilled nursing facility, home or facility with hospice services, other hospital setting, or death.

Statistics were calculated using SPSS statistical software. Variables were reported as means and percentages. Group means were compared using t tests and differences in proportions were compared using the chi square test. Correlations were performed using Pearson’s correlation. A 2-tailed P < 0.05 was considered statistically significant.

Results

Discussion

Ischemic stroke remains a major cause of morbidity and mortality for very old patients. Though less than 5% of the United States population is over the age of 80 [1], at this community-based hospital 18% of those presenting to the ED with ischemic stroke were in this age-group. With a population of increasing age, more people in this age-group will present with ischemic stroke and need effective treatment to limit the associated morbidity and mortality. Being able to quickly and safely treat acute ischemic stroke may help very old adults maintain independence or prevent institutionalization. While the original studies demonstrating the effectiveness of tPA for acute ischemic stroke excluded or underrepresented those ≥ 80 years, retrospective analysis has not been conclusive regarding its use in very old patients [4–6,10,12,13].However, post-hoc analysis of NINDS and IST-3 data demonstrate efficacy and safety of treatment [12,13].

This study explored the use of tPA at a community-based certified stroke center. Similar to previous studies, it demonstrates the large proportion of patients presenting with acute neurological findings consistent with ischemic stroke are ≥ 80 years old [3,6]. Our incidence of acute ischemic stroke in the oldest patients may be slightly lower than reported elsewhere, which may reflect community differences, with higher rates of younger patients with multiple comorbidities presenting with stroke-like symptoms. Amongst this very old cohort, age was positively correlated with stroke severity. Mortality in patients ≥ 80 years old who present with acute ischemic stroke approaches 25%.

The majority of patients who did not receive tPA had documented contraindications to receiving the medication. The most common reason was rapidly improving symptoms with repeat NIHSS often ≤ 4. The second most common reason was presentation outside the treatment window of 3 hours. We compared those who either arrived too late to receive treatment with tPA or already had ischemic changes on CT to those who received tPA as this suggests the natural history of stroke progression and outcome without effective, early treatment. The outcomes at this institution support this trend. Very old patients who received tPA did not experience harm as evidenced by similar lengths of stay and rates of discharge to home. Also, rates of symptomatic ICH were lower than those reported in the literature. In fact, patients who received tPA were less likely to experience in-hospital death and more likely to be discharged to acute rehabilitation hospitals, suggesting more functional ability to tolerate aggressive recovery efforts.

Very few people who presented with acute ischemic stroke and were eligible for treatment with tPA failed to receive it. This suggests that despite the perceived increased risk to treating these patients with tPA, the specialized stroke team aggressively treats patients age ≥ 80 years who present with acute ischemic stroke. However, those who did not receive tPA were more likely to have presented with mild or severe strokes. This may suggest that treatment time frames are more strongly held, or that treatment teams are more likely to use time frames as a reason to not treat with tPA for patients with mild or severe strokes. Also, very few patients and families who were eligible to receive tPA declined treatment despite the associated risks. This suggests that patients and families are eager for aggressive treatment in attempt to prevent death or disability associated with ischemic stroke.

There are several limitations associated with this evaluation. First, this is a retrospective analysis of a single institution’s acute stroke procedures. Data was collected in an effort to evaluate the processes and outcomes of the specialized stroke team in evaluating and treating this very old cohort who present to a community-based hospital. It involved individualized clinical evaluation and decision making by multiple care providers who may offer different perspectives on the risk of treating patients ≥ 80 years old with tPA, which may result in selection bias. While comparing those who arrived outside treatment windows offers a comparison group who represents the natural course of untreated strokes, patient characteristics that prevented timely evaluation may also impact their outcomes including baseline mobility, care giving availability and underlying medical comorbidities. The similarity in mean presenting NIHSS scores of the two groups, however, argues against this possibility. Lastly, exclusion criteria to receiving tPA may represent intrinsic characteristics that impart higher risk of negative outcomes.

Conculsion

Although there have been no randomized controlled trials that evaluate the safety and efficacy of tPA in the treatment of acute ischemic stroke in very old patients, use at the community-based stroke center was not associated with worse outcomes including symptomatic ICH, hospital length of stay, and in-hospital mortality. In fact, there were trends towards better outcomes in older patients who received tPA, including a significant reduction in in-hospital mortality. This evaluation supports the benefits of using tPA to treat acute ischemic stroke as seen in prior randomized controlled trials that included the treatment of very old patients. Though ongoing research is needed, a growing body of evidence supports the use of tPA to treat acute ischemic stroke in patients ≥ 80 years.

Corresponding author: Jennifer C. Drost, DO, MPH, Summa Health System, 75 Arch St., Ste. G1, Akron, OH 44304, [email protected].

Financial disclosures: None.

Author contributions: Conception and design, JCD, SMB; analysis and interpretation of data, JCD, SMB; drafting of article, JCD; critical revision of the article, JCD, SMB; provision of study materials or patients, SMB; collection and assembly of data, JCD.

From Summa Health System, Akron, OH.

Abstract

• Background: Ischemic stroke is a major cause of morbidity and mortality for patients ≥ 80 years old. The use of intravenous recombinant tissue plasminogen activator (tPA) in patients ≥ 80 years for treatment of ischemic stroke remains controversial.
• Objective: To examine outcomes in patients ≥ 80 years old who received tPA in our institution.
• Methods: This was a retrospective cohort study at a community-based certified acute stroke center. Individuals age ≥ 80 years evaluated emergently for acute neurologic changes consistent with ischemic stroke were included (n = 184). The comparison groups within this sample were patients who received tPA versus with those who did not because they came to the ED outside of the treatment window. Outcome measures included length of stay, symptomatic intracerebral hemorrhage (ICH), discharge disposition, and in-hospital death
• Results: 38 patients (20.7%) received tPA. 50 patients (27.2%) presented outside of treatment windows and were included in comparative analysis. There was no difference between groups in age (P = 0.26) or initial National Institute of Health Stroke Scale (P = 0.598). One patient (2.6%) who received tPA developed symptomatic ICH. Those receiving tPA were more likely to be discharged to acute rehabilitation hospitals (P = 0.012) and less likely to experience in hospital death (P = 0.048).
• Conclusion: At this institution, the use of tPA in patients ≥ 80 years old is not associated with increased mortality or risk of symptomatic ICH. Those who received tPA were more likely to be discharged to acute rehabilitation hospitals, suggesting greater potential for functional recovery.

Acute ischemic stroke is a major cause of morbidity and mortality in patients 80 years or older. Though less than 5% of the United States population is over the age of 80 [1], studies have shown that up to one-third of patients presenting with ischemic stroke are ≥ 80 years old [2] and among first-time strokes, a third occur in those ≥ 80 [3]. Older adults present with worse symptoms associated with ischemic stroke as measured by the National Institutes of Health Stroke Scale (NIHSS) compared with younger (< 80 years) counterparts [4]. Older patients are more likely to be discharged to a location other than home [5]. Older age is associated with higher hospital, 30-day, and 1-year mortality [3,5,6]. Patients ≥ 80 are significantly more likely to die in the hospital compared to younger patients, 11.7% to 23.6% vs 5.1%, respectively [3,7].

The Food and Drug Administration (FDA) approved the use of intravenous recombinant tissue plasminogen activator (tPA) in 1996 for the treatment of ischemic stroke [8]. Studies evaluating the safety and efficacy of tPA in ischemic stroke excluded or underrepresented patients ≥ 80 [8,9]. The use of tPA in those ≥ 80 has not been shown consistently to improve outcomes [6,10,11]. Post-hoc analysis of the National Institute of Neurologic Disorders and Stroke (NINDS) study did not show worse outcomes or harms to older adults treated with tPA [12]. Likewise, data from the International Stroke Treatment (IST-3) collaborative group show that treatment with tPA up to 6 hours from the onset of symptoms improves outcomes in the elderly [13]. Use of tPA in the oldest adults remains controversial due to perceived higher risk of symptomatic intracerebral hemorrhage (ICH). Published data suggest overall ICH risk of 4.3% to 6.4% across all age-groups [9,14,15].Studies have failed to demonstrate an increased risk in the oldest adults [4,10,16,17], though they may have higher mortality rates associated with ICH [15]. Despite this, trends suggest increasing use of tPA in those ≥ 80 over the past decade [2]. Along with primary data from NINDS [12] and IST-3 [13], a meta-analysis conducted in 2014 suggests that regardless of age, patients have improved outcomes with tPA [18].With the increasing age of the population, effective treatment of strokes in patients ≥ 80 will continue to be an important clinical and research endeavor.

This study evaluates the outcomes of clinical use of tPA for treatment of patients ≥ 80 years old who present to a community-based certified stroke center with ischemic stroke.

Methods

The study setting was a 540-bed acute care hospital that is a community-based certified stroke center. This study was deemed nonhuman subjects research by the institutional review board as the goal was to evaluate processes and outcomes of this institution’s stroke team in treating a subgroup of patients according to clinically accepted practice (quality improvement initiative). All patients presenting to the emergency department (ED) between 1 January 2011 and 30 November 2013 with the onset of stroke-like neurological deficits underwent evaluation and treatment by a neurologist and/or specially trained stroke team. This team consists of the attending neurologist, ED physician, resident physicians, advanced practice nurses, and ED staff nurses and emergency medicine technicians. Team members involved in the evaluation and treatment of these patients undergo routine clinical education and testing to ensure standardization. Patients undergo emergent evaluation including the National Institutes of Health Stroke Scale (NIHSS) and obtain brain imaging with computed tomography (CT).

Patients ≥ 80 years were identified among all those who presented to the ED with ischemic stroke. Patients were included if they were subsequently diagnosed with ischemic stroke or transient ischemic attacks (TIA). They were excluded from analysis if neurological changes were due to primary hemorrhagic stroke, intracranial hemorrhage, subarachnoid hemorrhage, seizure, conversion disorder, or metabolic derangements. They were also excluded from analysis if the acute ischemic stroke treatment included intra-arterial administration of tPA or endovascular revascularization.

Patient data collected included age, NIHSS at presentation to ED, time to presentation at ED, treatment with tPA, contraindications to tPA, discharge disposition, length of stay and in-hospital mortality. Raw NIHSS values were collected at the time of presentation. NIHSS were categorized into mild symptoms (NIHSS < 6), moderate symptoms (NIHSS 6–19), or severe symptoms (NIHSS ≥ 20). Clinical indications for receiving tPA include NIHSS > 4, focal neurological deficit onset < 3 hours (for those ≥ 80 years old), and no evidence of acute hemorrhage or acute infarct on CT. Contraindications include rapidly improving symptoms (repeat NIHSS < 4), active or history of intracranial hemorrhage, history of stroke or head trauma in past 3 months, gastrointestinal or genitourinary hemorrhage within 21 days, major surgery within 14 days, arterial puncture at a noncompressible site in past 7 days, treatment with anticoagulation with therapeutic indices, systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg and not responding to treatment, or platelet count < 100,000/mm³. Patients who were not eligible for tPA based on contraindications with the exception of being outside the treatment window (3 hours) were excluded from comparative analysis. Patient length of stay was rounded to nearest full day. Discharge disposition was categorized as home, acute rehabilitation hospital, skilled nursing facility, home or facility with hospice services, other hospital setting, or death.

Statistics were calculated using SPSS statistical software. Variables were reported as means and percentages. Group means were compared using t tests and differences in proportions were compared using the chi square test. Correlations were performed using Pearson’s correlation. A 2-tailed P < 0.05 was considered statistically significant.

Results

Discussion

Ischemic stroke remains a major cause of morbidity and mortality for very old patients. Though less than 5% of the United States population is over the age of 80 [1], at this community-based hospital 18% of those presenting to the ED with ischemic stroke were in this age-group. With a population of increasing age, more people in this age-group will present with ischemic stroke and need effective treatment to limit the associated morbidity and mortality. Being able to quickly and safely treat acute ischemic stroke may help very old adults maintain independence or prevent institutionalization. While the original studies demonstrating the effectiveness of tPA for acute ischemic stroke excluded or underrepresented those ≥ 80 years, retrospective analysis has not been conclusive regarding its use in very old patients [4–6,10,12,13].However, post-hoc analysis of NINDS and IST-3 data demonstrate efficacy and safety of treatment [12,13].

This study explored the use of tPA at a community-based certified stroke center. Similar to previous studies, it demonstrates the large proportion of patients presenting with acute neurological findings consistent with ischemic stroke are ≥ 80 years old [3,6]. Our incidence of acute ischemic stroke in the oldest patients may be slightly lower than reported elsewhere, which may reflect community differences, with higher rates of younger patients with multiple comorbidities presenting with stroke-like symptoms. Amongst this very old cohort, age was positively correlated with stroke severity. Mortality in patients ≥ 80 years old who present with acute ischemic stroke approaches 25%.

The majority of patients who did not receive tPA had documented contraindications to receiving the medication. The most common reason was rapidly improving symptoms with repeat NIHSS often ≤ 4. The second most common reason was presentation outside the treatment window of 3 hours. We compared those who either arrived too late to receive treatment with tPA or already had ischemic changes on CT to those who received tPA as this suggests the natural history of stroke progression and outcome without effective, early treatment. The outcomes at this institution support this trend. Very old patients who received tPA did not experience harm as evidenced by similar lengths of stay and rates of discharge to home. Also, rates of symptomatic ICH were lower than those reported in the literature. In fact, patients who received tPA were less likely to experience in-hospital death and more likely to be discharged to acute rehabilitation hospitals, suggesting more functional ability to tolerate aggressive recovery efforts.

Very few people who presented with acute ischemic stroke and were eligible for treatment with tPA failed to receive it. This suggests that despite the perceived increased risk to treating these patients with tPA, the specialized stroke team aggressively treats patients age ≥ 80 years who present with acute ischemic stroke. However, those who did not receive tPA were more likely to have presented with mild or severe strokes. This may suggest that treatment time frames are more strongly held, or that treatment teams are more likely to use time frames as a reason to not treat with tPA for patients with mild or severe strokes. Also, very few patients and families who were eligible to receive tPA declined treatment despite the associated risks. This suggests that patients and families are eager for aggressive treatment in attempt to prevent death or disability associated with ischemic stroke.

There are several limitations associated with this evaluation. First, this is a retrospective analysis of a single institution’s acute stroke procedures. Data was collected in an effort to evaluate the processes and outcomes of the specialized stroke team in evaluating and treating this very old cohort who present to a community-based hospital. It involved individualized clinical evaluation and decision making by multiple care providers who may offer different perspectives on the risk of treating patients ≥ 80 years old with tPA, which may result in selection bias. While comparing those who arrived outside treatment windows offers a comparison group who represents the natural course of untreated strokes, patient characteristics that prevented timely evaluation may also impact their outcomes including baseline mobility, care giving availability and underlying medical comorbidities. The similarity in mean presenting NIHSS scores of the two groups, however, argues against this possibility. Lastly, exclusion criteria to receiving tPA may represent intrinsic characteristics that impart higher risk of negative outcomes.

Conculsion

Although there have been no randomized controlled trials that evaluate the safety and efficacy of tPA in the treatment of acute ischemic stroke in very old patients, use at the community-based stroke center was not associated with worse outcomes including symptomatic ICH, hospital length of stay, and in-hospital mortality. In fact, there were trends towards better outcomes in older patients who received tPA, including a significant reduction in in-hospital mortality. This evaluation supports the benefits of using tPA to treat acute ischemic stroke as seen in prior randomized controlled trials that included the treatment of very old patients. Though ongoing research is needed, a growing body of evidence supports the use of tPA to treat acute ischemic stroke in patients ≥ 80 years.

Corresponding author: Jennifer C. Drost, DO, MPH, Summa Health System, 75 Arch St., Ste. G1, Akron, OH 44304, [email protected].

Financial disclosures: None.

Author contributions: Conception and design, JCD, SMB; analysis and interpretation of data, JCD, SMB; drafting of article, JCD; critical revision of the article, JCD, SMB; provision of study materials or patients, SMB; collection and assembly of data, JCD.

From Summa Health System, Akron, OH.

Abstract

• Background: Ischemic stroke is a major cause of morbidity and mortality for patients ≥ 80 years old. The use of intravenous recombinant tissue plasminogen activator (tPA) in patients ≥ 80 years for treatment of ischemic stroke remains controversial.
• Objective: To examine outcomes in patients ≥ 80 years old who received tPA in our institution.
• Methods: This was a retrospective cohort study at a community-based certified acute stroke center. Individuals age ≥ 80 years evaluated emergently for acute neurologic changes consistent with ischemic stroke were included (n = 184). The comparison groups within this sample were patients who received tPA versus with those who did not because they came to the ED outside of the treatment window. Outcome measures included length of stay, symptomatic intracerebral hemorrhage (ICH), discharge disposition, and in-hospital death
• Results: 38 patients (20.7%) received tPA. 50 patients (27.2%) presented outside of treatment windows and were included in comparative analysis. There was no difference between groups in age (P = 0.26) or initial National Institute of Health Stroke Scale (P = 0.598). One patient (2.6%) who received tPA developed symptomatic ICH. Those receiving tPA were more likely to be discharged to acute rehabilitation hospitals (P = 0.012) and less likely to experience in hospital death (P = 0.048).
• Conclusion: At this institution, the use of tPA in patients ≥ 80 years old is not associated with increased mortality or risk of symptomatic ICH. Those who received tPA were more likely to be discharged to acute rehabilitation hospitals, suggesting greater potential for functional recovery.

Acute ischemic stroke is a major cause of morbidity and mortality in patients 80 years or older. Though less than 5% of the United States population is over the age of 80 [1], studies have shown that up to one-third of patients presenting with ischemic stroke are ≥ 80 years old [2] and among first-time strokes, a third occur in those ≥ 80 [3]. Older adults present with worse symptoms associated with ischemic stroke as measured by the National Institutes of Health Stroke Scale (NIHSS) compared with younger (< 80 years) counterparts [4]. Older patients are more likely to be discharged to a location other than home [5]. Older age is associated with higher hospital, 30-day, and 1-year mortality [3,5,6]. Patients ≥ 80 are significantly more likely to die in the hospital compared to younger patients, 11.7% to 23.6% vs 5.1%, respectively [3,7].

The Food and Drug Administration (FDA) approved the use of intravenous recombinant tissue plasminogen activator (tPA) in 1996 for the treatment of ischemic stroke [8]. Studies evaluating the safety and efficacy of tPA in ischemic stroke excluded or underrepresented patients ≥ 80 [8,9]. The use of tPA in those ≥ 80 has not been shown consistently to improve outcomes [6,10,11]. Post-hoc analysis of the National Institute of Neurologic Disorders and Stroke (NINDS) study did not show worse outcomes or harms to older adults treated with tPA [12]. Likewise, data from the International Stroke Treatment (IST-3) collaborative group show that treatment with tPA up to 6 hours from the onset of symptoms improves outcomes in the elderly [13]. Use of tPA in the oldest adults remains controversial due to perceived higher risk of symptomatic intracerebral hemorrhage (ICH). Published data suggest overall ICH risk of 4.3% to 6.4% across all age-groups [9,14,15].Studies have failed to demonstrate an increased risk in the oldest adults [4,10,16,17], though they may have higher mortality rates associated with ICH [15]. Despite this, trends suggest increasing use of tPA in those ≥ 80 over the past decade [2]. Along with primary data from NINDS [12] and IST-3 [13], a meta-analysis conducted in 2014 suggests that regardless of age, patients have improved outcomes with tPA [18].With the increasing age of the population, effective treatment of strokes in patients ≥ 80 will continue to be an important clinical and research endeavor.

This study evaluates the outcomes of clinical use of tPA for treatment of patients ≥ 80 years old who present to a community-based certified stroke center with ischemic stroke.

Methods

The study setting was a 540-bed acute care hospital that is a community-based certified stroke center. This study was deemed nonhuman subjects research by the institutional review board as the goal was to evaluate processes and outcomes of this institution’s stroke team in treating a subgroup of patients according to clinically accepted practice (quality improvement initiative). All patients presenting to the emergency department (ED) between 1 January 2011 and 30 November 2013 with the onset of stroke-like neurological deficits underwent evaluation and treatment by a neurologist and/or specially trained stroke team. This team consists of the attending neurologist, ED physician, resident physicians, advanced practice nurses, and ED staff nurses and emergency medicine technicians. Team members involved in the evaluation and treatment of these patients undergo routine clinical education and testing to ensure standardization. Patients undergo emergent evaluation including the National Institutes of Health Stroke Scale (NIHSS) and obtain brain imaging with computed tomography (CT).

Patients ≥ 80 years were identified among all those who presented to the ED with ischemic stroke. Patients were included if they were subsequently diagnosed with ischemic stroke or transient ischemic attacks (TIA). They were excluded from analysis if neurological changes were due to primary hemorrhagic stroke, intracranial hemorrhage, subarachnoid hemorrhage, seizure, conversion disorder, or metabolic derangements. They were also excluded from analysis if the acute ischemic stroke treatment included intra-arterial administration of tPA or endovascular revascularization.

Patient data collected included age, NIHSS at presentation to ED, time to presentation at ED, treatment with tPA, contraindications to tPA, discharge disposition, length of stay and in-hospital mortality. Raw NIHSS values were collected at the time of presentation. NIHSS were categorized into mild symptoms (NIHSS < 6), moderate symptoms (NIHSS 6–19), or severe symptoms (NIHSS ≥ 20). Clinical indications for receiving tPA include NIHSS > 4, focal neurological deficit onset < 3 hours (for those ≥ 80 years old), and no evidence of acute hemorrhage or acute infarct on CT. Contraindications include rapidly improving symptoms (repeat NIHSS < 4), active or history of intracranial hemorrhage, history of stroke or head trauma in past 3 months, gastrointestinal or genitourinary hemorrhage within 21 days, major surgery within 14 days, arterial puncture at a noncompressible site in past 7 days, treatment with anticoagulation with therapeutic indices, systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg and not responding to treatment, or platelet count < 100,000/mm³. Patients who were not eligible for tPA based on contraindications with the exception of being outside the treatment window (3 hours) were excluded from comparative analysis. Patient length of stay was rounded to nearest full day. Discharge disposition was categorized as home, acute rehabilitation hospital, skilled nursing facility, home or facility with hospice services, other hospital setting, or death.

Statistics were calculated using SPSS statistical software. Variables were reported as means and percentages. Group means were compared using t tests and differences in proportions were compared using the chi square test. Correlations were performed using Pearson’s correlation. A 2-tailed P < 0.05 was considered statistically significant.

Results

Discussion

Ischemic stroke remains a major cause of morbidity and mortality for very old patients. Though less than 5% of the United States population is over the age of 80 [1], at this community-based hospital 18% of those presenting to the ED with ischemic stroke were in this age-group. With a population of increasing age, more people in this age-group will present with ischemic stroke and need effective treatment to limit the associated morbidity and mortality. Being able to quickly and safely treat acute ischemic stroke may help very old adults maintain independence or prevent institutionalization. While the original studies demonstrating the effectiveness of tPA for acute ischemic stroke excluded or underrepresented those ≥ 80 years, retrospective analysis has not been conclusive regarding its use in very old patients [4–6,10,12,13].However, post-hoc analysis of NINDS and IST-3 data demonstrate efficacy and safety of treatment [12,13].

This study explored the use of tPA at a community-based certified stroke center. Similar to previous studies, it demonstrates the large proportion of patients presenting with acute neurological findings consistent with ischemic stroke are ≥ 80 years old [3,6]. Our incidence of acute ischemic stroke in the oldest patients may be slightly lower than reported elsewhere, which may reflect community differences, with higher rates of younger patients with multiple comorbidities presenting with stroke-like symptoms. Amongst this very old cohort, age was positively correlated with stroke severity. Mortality in patients ≥ 80 years old who present with acute ischemic stroke approaches 25%.

The majority of patients who did not receive tPA had documented contraindications to receiving the medication. The most common reason was rapidly improving symptoms with repeat NIHSS often ≤ 4. The second most common reason was presentation outside the treatment window of 3 hours. We compared those who either arrived too late to receive treatment with tPA or already had ischemic changes on CT to those who received tPA as this suggests the natural history of stroke progression and outcome without effective, early treatment. The outcomes at this institution support this trend. Very old patients who received tPA did not experience harm as evidenced by similar lengths of stay and rates of discharge to home. Also, rates of symptomatic ICH were lower than those reported in the literature. In fact, patients who received tPA were less likely to experience in-hospital death and more likely to be discharged to acute rehabilitation hospitals, suggesting more functional ability to tolerate aggressive recovery efforts.

Very few people who presented with acute ischemic stroke and were eligible for treatment with tPA failed to receive it. This suggests that despite the perceived increased risk to treating these patients with tPA, the specialized stroke team aggressively treats patients age ≥ 80 years who present with acute ischemic stroke. However, those who did not receive tPA were more likely to have presented with mild or severe strokes. This may suggest that treatment time frames are more strongly held, or that treatment teams are more likely to use time frames as a reason to not treat with tPA for patients with mild or severe strokes. Also, very few patients and families who were eligible to receive tPA declined treatment despite the associated risks. This suggests that patients and families are eager for aggressive treatment in attempt to prevent death or disability associated with ischemic stroke.

There are several limitations associated with this evaluation. First, this is a retrospective analysis of a single institution’s acute stroke procedures. Data was collected in an effort to evaluate the processes and outcomes of the specialized stroke team in evaluating and treating this very old cohort who present to a community-based hospital. It involved individualized clinical evaluation and decision making by multiple care providers who may offer different perspectives on the risk of treating patients ≥ 80 years old with tPA, which may result in selection bias. While comparing those who arrived outside treatment windows offers a comparison group who represents the natural course of untreated strokes, patient characteristics that prevented timely evaluation may also impact their outcomes including baseline mobility, care giving availability and underlying medical comorbidities. The similarity in mean presenting NIHSS scores of the two groups, however, argues against this possibility. Lastly, exclusion criteria to receiving tPA may represent intrinsic characteristics that impart higher risk of negative outcomes.

Conculsion

Although there have been no randomized controlled trials that evaluate the safety and efficacy of tPA in the treatment of acute ischemic stroke in very old patients, use at the community-based stroke center was not associated with worse outcomes including symptomatic ICH, hospital length of stay, and in-hospital mortality. In fact, there were trends towards better outcomes in older patients who received tPA, including a significant reduction in in-hospital mortality. This evaluation supports the benefits of using tPA to treat acute ischemic stroke as seen in prior randomized controlled trials that included the treatment of very old patients. Though ongoing research is needed, a growing body of evidence supports the use of tPA to treat acute ischemic stroke in patients ≥ 80 years.

Corresponding author: Jennifer C. Drost, DO, MPH, Summa Health System, 75 Arch St., Ste. G1, Akron, OH 44304, [email protected].

Financial disclosures: None.

Author contributions: Conception and design, JCD, SMB; analysis and interpretation of data, JCD, SMB; drafting of article, JCD; critical revision of the article, JCD, SMB; provision of study materials or patients, SMB; collection and assembly of data, JCD.