Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy. Also today, disease-modifying therapies and stem cell transplants both reduce disease progression in MS, the American Academy of Pediatrics guidelines on hemangioma should empower primary care clinicians, and a treat-to-target approach for CVD risk factors decreased atherosclerosis in patients with rheumatoid arthritis.

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Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy. Also today, disease-modifying therapies and stem cell transplants both reduce disease progression in MS, the American Academy of Pediatrics guidelines on hemangioma should empower primary care clinicians, and a treat-to-target approach for CVD risk factors decreased atherosclerosis in patients with rheumatoid arthritis.

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Apple Podcasts

Google Podcasts

Spotify

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy. Also today, disease-modifying therapies and stem cell transplants both reduce disease progression in MS, the American Academy of Pediatrics guidelines on hemangioma should empower primary care clinicians, and a treat-to-target approach for CVD risk factors decreased atherosclerosis in patients with rheumatoid arthritis.

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Aplastic anemia is a clinical and pathological entity of bone marrow failure that causes progressive loss of hematopoietic progenitor stem cells (HPSC), resulting in pancytopenia.¹ Patients may present along a spectrum, ranging from being asymptomatic with incidental findings on peripheral blood testing to having life-threatening neutropenic infections or bleeding. Aplastic anemia results from either inherited or acquired causes, and the pathophysiology and treatment approach vary significantly between these 2 causes. Therefore, recognition of inherited marrow failure diseases, such as Fanconi anemia and telomere biology disorders, is critical to establishing the management plan. This article reviews the epidemiology, pathophysiology, clinical presentation, and diagnosis of aplastic anemia. Treatment of aplastic anemia is reviewed in a separate article.

Epidemiology

Aplastic anemia is a rare disorder, with an incidence of approximately 1.5 to 7 cases per million individuals per year.^2,3 A recent Scandinavian study reported that the incidence of aplastic anemia among the Swedish population is 2.3 cases per million individuals per year, with a median age at diagnosis of 60 years and a slight female predominance (52% versus 48%, respectively).² This data is congruent with prior observations made in Barcelona, where the incidence was 2.34 cases per million individuals per year, albeit with a slightly higher incidence in males compared to females (2.54 versus 2.16, respectively).⁴ The incidence of aplastic anemia varies globally, with a disproportionate increase in incidence seen among Asian populations, with rates as high as 8.8 per million individuals per year.^3-5 This variation in incidence in Asia versus other countries has not been well explained. There appears to be a bimodal distribution, with incidence peaks seen in young adults and in older adults.^2,3,6

Pathophysiology

Acquired Aplastic Anemia

The leading hypothesis as to the cause of most cases of acquired aplastic anemia is that a dysregulated immune system destroys hematopoietic progenitor cells. Inciting etiologies implicated in the development of acquired aplastic anemia include pregnancy, infection, medications, and exposure to certain chemicals, such as benzene.^1,7 The historical understanding of acquired aplastic anemia implicates cytotoxic T-lymphocyte–mediated destruction of CD34+ hematopoietic stem cells.^1,8,9 This hypothesis served as the basis for treatment of acquired aplastic anemia with immunosuppressive therapy, predominantly anti-thymocyte globulin (ATG) combined with cyclosporine A.^1,8 More recent work has focused on cytokine interactions, particularly the suppressive role of interferon (IFN)-γ on hematopoietic stem cells independent of T-lymphocyte–mediated hematopoietic destruction, which has been demonstrated in a murine model.⁸ The interaction of IFN-γ with the hematopoietic stem cells pool is dynamic. IFN-γ levels are elevated during an acute inflammatory response such as a viral infection, providing further basis for the immune-mediated nature of the acquired disease.¹⁰ Specifically, in vitro studies suggest the effects of IFN-γ on HPSC may be secondary to interruption of thrombopoietin and its respective signaling pathways, which play a key role in hematopoietic stem cell renewal.¹¹ Eltrombopag, a thrombopoietin receptor antagonist, has shown promise in the treatment of refractory aplastic anemia, with studies indicating that its effectiveness is independent of IFN-γ levels.^11,12

Inherited Aplastic Anemia

The inherited marrow failure syndromes (IMFSs) are a group of disorders characterized by cellular maintenance and repair defects, leading to cytopenias, increased cancer risk, structural defects, and risk of end organ damage, such as liver cirrhosis and pulmonary fibrosis.^13-15 The most common diseases include Fanconi anemia, dyskeratosis congenita/telomere biology disorders, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome, but with the advent of whole exome sequencing new syndromes continue to be discovered. While classically these disorders present in children, adult presentations of these syndromes are now commonplace. Broadly, the pathophysiology of inherited aplastic anemia relates to the defective hematopoietic progenitor cells and an accelerated decline of the hematopoietic stem cell compartment.

The most common IMFS, Fanconi anemia and telomere biology disorders, are associated with numerous mutations in DNA damage repair pathways and telomere maintenance pathways. TERT, DKC, and TERC mutations are most commonly associated with dyskeratosis congenita, but may also be found infrequently in patients with aplastic anemia presenting at an older age in the absence of the classic phenotypical features.^1,16,17 The recognition of an underlying genetic disorder or telomere biology disorder leading to constitutional aplastic anemia is significant, as these conditions are associated not only with marrow failure, but also endocrinopathies, organ fibrosis, and solid organ malignancies.^13-15 In particular, mutations in the TERT and TERC genes have been associated with dyskeratosis congenita as well as pulmonary fibrosis and cirrhosis.^18,19 The implications of early diagnosis of an IMFS lie in the approach to treatment and prognosis.

Clonal Disorders and Secondary Malignancies

Myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML) are 2 clonal disorders that may arise from a background of aplastic anemia.^9,20,21 Hypoplastic MDS can be difficult to differentiate from aplastic anemia at diagnosis based on morphology alone, although recent work has demonstrated that molecular testing for somatic mutations in ASXL1, DNMT3A, and BCOR can aid in differentiating a subset of aplastic anemia patients who are more likely to progress to MDS.²¹ Clonal populations of cells harboring 6p uniparental disomy are seen in more than 10% of patients with aplastic anemia on cytogenetic analysis, which can help differentiate the diseases.⁹ Yoshizato and colleagues found lower rates of ASXL1 and DNMT3A mutations in patients with aplastic anemia as compared with patients with MDS or AML. In this study, patients with aplastic anemia had higher rates of mutations in PIGA (reflecting the increased paroxysmal nocturnal hemoglobinuria [PNH] clonality seen in aplastic anemia) and BCOR.⁹ Mutations were also found in genes commonly mutated in MDS and AML, including TET2, RUNX1, TP53, and JAK2, albeit at lower frequencies.⁹ These mutations as a whole have not predicted response to therapy or prognosis. However, when performing survival analysis in patients with specific mutations, those commonly encountered in MDS/AML (ASXL1, DNMT3A, TP53, RUNX1, CSMD1) are associated with faster progression to overt MDS/AML and decreased overall survival (OS),^20,21 suggesting these mutations may represent early clonality that can lead to clonal evolution and the development of secondary malignancies. Conversely, mutations in BCOR and BCORL appear to identify patients who may have a favorable outcome in response to immunosuppressive therapy and, similar to patients with PIGA mutations, improved OS.⁹

Paroxysmal Nocturnal Hemoglobinuria

In addition to having an increased risk of myelodysplasia and malignancy due to the development of a dominant pre-malignant clone, patients with aplastic anemia often harbor progenitor cell clones associated with PNH.^1,17 PNH clones have been identified in more than 50% of patients with aplastic anemia.^22,23 PNH represents a clonal disorder of hematopoiesis in which cells harbor X-linked somatic mutations in the PIGA gene; this gene encodes a protein responsible for the synthesis of glycosylphosphatidylinositol (GPI) anchors on the cell surface.^22,24 The lack of these cell surface proteins, specifically CD55 (also known as decay accelerating factor) and CD59 (also known as membrane inhibitor of reactive lysis), predisposes red cells to increased complement-mediated lysis.²⁵ The exact mechanism for the development of these clones in patients with aplastic anemia is not fully understood. Current theories hypothesize that these clones are protected from the immune-mediated destruction of normal hematopoietic stem cells due to the absence of the cell surface proteins.^1,20 The role of these clones over time in patients with aplastic anemia is less clear, though recent work demonstrated that despite differences in clonality over the disease course, aplastic anemia patients with small PNH clones are less likely to develop overt hemolysis and larger PNH clones compared to patients harboring larger (≥ 50%) PNH clones at diagnosis.^23,26,27 Additionally, PNH clones in patients with aplastic anemia infrequently become clinically significant.²⁷ It should be noted that these conditions exist along a continuum; that is, patients with aplastic anemia may develop PNH clones, while conversely patients with PNH may develop aplastic anemia.²⁰ Patients with PNH clones should be followed via peripheral blood flow cytometry in addition to complete blood count to track clonal stability and identify clinically significant PNH among aplastic anemia patients.²⁸

Patients with aplastic anemia typically are diagnosed either due to asymptomatic cytopenias found on peripheral blood sampling, symptomatic anemia, bleeding secondary to thrombocytopenia, or wound healing and infectious complications related to neutropenia.²⁹ A thorough history to understand the timing of symptoms, recent infectious symptoms/exposure, habits, and chemical or toxin exposures (including medications, travel, and supplements) helps guide diagnostic testing. Family history is also critical, with attention given to premature graying, pulmonary, renal, and liver disease, and blood disorders.

Patients with an IMFS, (eg, Fanconi anemia or dyskeratosis congenita) may have associated phenotypical findings such as urogenital abnormalities or short stature; in addition, those with dyskeratosis congenita may present with the classic triad of oral leukoplakia, lacy skin pigmentation, and dystrophic nails.⁷ However, in patients with IMFS, classic phenotypical findings may be lacking in up to 30% to 40% of patients.⁷ As described previously, while congenital malformations are common in Fanconi anemia and dyskeratosis congenita, a third of patients may have no or only subtle phenotypical abnormalities, including alterations in skin or hair pigmentation, skeletal and growth abnormalities, and endocrine disorders.³⁰ The International Fanconi Anemia Registry identified central nervous system, genitourinary, skin and musculoskeletal, ophthalmic, and gastrointestinal system malformations among children with Fanconi anemia.^31,32 Patients with dyskeratosis congenita may present with pulmonary fibrosis, hepatic cirrhosis, or premature graying, as highlighted in a recent study by DiNardo and colleagues.³³ Therefore, physicians must have a heightened index of suspicion in patients with subtle phenotypical findings and associated cytopenias.

Diagnosis

Differential Diagnosis

The diagnosis of aplastic anemia should be suspected in any patient presenting with pancytopenia. Aplastic anemia is a diagnosis of exclusion.³⁴ Other conditions associated with peripheral blood pancytopenia should be considered including infections (HIV, hepatitis, parvovirus B19, cytomegalovirus, Epstein-Barr virus, varicella-zoster virus), nutritional deficiencies (vitamin B12, folate, copper, zinc), autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, hemophagocytic lymphohistiocytosis), hypersplenism, marrow-occupying diseases (eg, leukemia, lymphoma, MDS), solid malignancies, and fibrosis (Table).⁷

Diagnostic Evaluation

The workup for aplastic anemia should include a thorough history and physical exam to search simultaneously for alternative diagnoses and clues pointing to potential etiologic agents.⁷ Diagnostic tests to be performed include a complete blood count with differential, reticulocyte count, immature platelet fraction, flow cytometry (to rule out lymphoproliferative disorders and atypical myeloid cells and to evaluate for PNH), and bone marrow biopsy with subsequent cytogenetic, immunohistochemical, and molecular testing.³⁵ The typical findings in aplastic anemia include peripheral blood pancytopenia without dysplastic features and bone marrow biopsy demonstrating a hypocellular marrow.⁷ A relative lymphocytosis in the peripheral blood is common.⁷ In patients with a significant PNH clone, a macrocytosis along with elevated lactate dehydrogenase and elevated reticulocyte and granulocyte counts may be present.³⁶

The diagnosis (based on the Camitta criteria³⁷ and modified Camitta criteria³⁸ for severe aplastic anemia) requires 2 of the following findings on peripheral blood samples:

• Absolute neutrophil count (ANC) < 500 cells/µL
• Platelet count < 20,000 cells/µL
• Reticulocyte count < 1% corrected or < 20,000 cells/µL.³⁵

In addition to peripheral blood findings, bone marrow biopsy is essential for the diagnosis, and should demonstrate a markedly hypocellular marrow (cellularity < 25%), occasionally with an increase in T lymphocytes.^7,39 Because marrow cellularity varies with age and can be challenging to assess, additional biopsies may be needed to confirm the diagnosis.²⁹ A 1- to 2-cm core biopsy is necessary to confirm hypocellularity, as small areas of residual hematopoiesis may be present and obscure the diagnosis.³⁵

Excluding Hypocellular MDS and IMFS

A diagnostic challenge is the exclusion of hypocellular MDS, especially in the older adult presenting with aplastic anemia, as patients with aplastic anemia may have some degree of erythroid dysplasia on bone marrow morphology.³⁶ The presence of a PNH clone on flow cytometry can aid in diagnosing aplastic anemia and excluding MDS,³⁴ although PNH clones can be present in refractory anemia MDS. Patients with aplastic anemia have a lower ratio of CD34+ cells compared to those with hypoplastic MDS, with one study demonstrating a mean CD34+ percentage of < 0.5% in aplastic anemia versus 3.7% in hypoplastic MDS.⁴⁰ Cytogenetic and molecular testing can also aid in making this distinction by identifying mutations commonly implicated in MDS.⁷ The presence of monosomy 7 (-7) in aplastic anemia patients is associated with a poor overall prognosis.^34,41

Peripheral blood screening using chromosome breakage analysis (done using either mitomycin C or diepoxybutane as in vitro DNA-crosslinking agents) and telomere length testing (of peripheral blood leukocytes) is necessary to exclude the main IMFS, Fanconi anemia and telomere biology disorders, respectively. Ruling out these conditions is imperative, as the approach to treatment varies significantly between IMFS and aplastic anemia. Patients with shortened telomeres should undergo genetic screening for mutations in the telomere maintenance genes to evaluate the underlying defect leading to shortened telomeres. Patients with increased peripheral blood breakage should have genetic testing to detect mutations associated with Fanconi anemia.

Classification

Once the diagnosis of aplastic anemia has been made, the patient should be classified according to the severity of their disease. Disease severity is determined based on peripheral blood ANC:³⁴ non-severe aplastic anemia (NSAA), ANC > 500 polymorphonuclear neutrophils (PMNs)/µL; severe aplastic anemia (SAA), 200–500 PMNs/µL; and very severe (VSAA), 0–200 PMNs/µL.^4,34 Disease classification is important, as VSAA is associated with a decreased OS compared to SAA.² Disease classification may affect treatment decisions, as patients with NSAA may be observed for a short period of time, while conversely patients with SAA have a worse prognosis with delays in therapy.^42-44

Summary

Aplastic anemia is a rare but potentially life-threatening disorder characterized by pancytopenia and a marked reduction in the hematopoietic stem cell compartment. It can be acquired or associated with an IMFS, and the treatment and prognosis vary dramatically between these 2 etiologies. Work-up and diagnosis involves investigating IMFSs and ruling out malignant or infectious etiologies for pancytopenia. After aplastic anemia has been diagnosed, the patient should be classified according to the severity of their disease based on peripheral blood ANC.

Aplastic anemia is a clinical and pathological entity of bone marrow failure that causes progressive loss of hematopoietic progenitor stem cells (HPSC), resulting in pancytopenia.¹ Patients may present along a spectrum, ranging from being asymptomatic with incidental findings on peripheral blood testing to having life-threatening neutropenic infections or bleeding. Aplastic anemia results from either inherited or acquired causes, and the pathophysiology and treatment approach vary significantly between these 2 causes. Therefore, recognition of inherited marrow failure diseases, such as Fanconi anemia and telomere biology disorders, is critical to establishing the management plan. This article reviews the epidemiology, pathophysiology, clinical presentation, and diagnosis of aplastic anemia. Treatment of aplastic anemia is reviewed in a separate article.

Epidemiology

Aplastic anemia is a rare disorder, with an incidence of approximately 1.5 to 7 cases per million individuals per year.^2,3 A recent Scandinavian study reported that the incidence of aplastic anemia among the Swedish population is 2.3 cases per million individuals per year, with a median age at diagnosis of 60 years and a slight female predominance (52% versus 48%, respectively).² This data is congruent with prior observations made in Barcelona, where the incidence was 2.34 cases per million individuals per year, albeit with a slightly higher incidence in males compared to females (2.54 versus 2.16, respectively).⁴ The incidence of aplastic anemia varies globally, with a disproportionate increase in incidence seen among Asian populations, with rates as high as 8.8 per million individuals per year.^3-5 This variation in incidence in Asia versus other countries has not been well explained. There appears to be a bimodal distribution, with incidence peaks seen in young adults and in older adults.^2,3,6

Pathophysiology

Acquired Aplastic Anemia

The leading hypothesis as to the cause of most cases of acquired aplastic anemia is that a dysregulated immune system destroys hematopoietic progenitor cells. Inciting etiologies implicated in the development of acquired aplastic anemia include pregnancy, infection, medications, and exposure to certain chemicals, such as benzene.^1,7 The historical understanding of acquired aplastic anemia implicates cytotoxic T-lymphocyte–mediated destruction of CD34+ hematopoietic stem cells.^1,8,9 This hypothesis served as the basis for treatment of acquired aplastic anemia with immunosuppressive therapy, predominantly anti-thymocyte globulin (ATG) combined with cyclosporine A.^1,8 More recent work has focused on cytokine interactions, particularly the suppressive role of interferon (IFN)-γ on hematopoietic stem cells independent of T-lymphocyte–mediated hematopoietic destruction, which has been demonstrated in a murine model.⁸ The interaction of IFN-γ with the hematopoietic stem cells pool is dynamic. IFN-γ levels are elevated during an acute inflammatory response such as a viral infection, providing further basis for the immune-mediated nature of the acquired disease.¹⁰ Specifically, in vitro studies suggest the effects of IFN-γ on HPSC may be secondary to interruption of thrombopoietin and its respective signaling pathways, which play a key role in hematopoietic stem cell renewal.¹¹ Eltrombopag, a thrombopoietin receptor antagonist, has shown promise in the treatment of refractory aplastic anemia, with studies indicating that its effectiveness is independent of IFN-γ levels.^11,12

Inherited Aplastic Anemia

The inherited marrow failure syndromes (IMFSs) are a group of disorders characterized by cellular maintenance and repair defects, leading to cytopenias, increased cancer risk, structural defects, and risk of end organ damage, such as liver cirrhosis and pulmonary fibrosis.^13-15 The most common diseases include Fanconi anemia, dyskeratosis congenita/telomere biology disorders, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome, but with the advent of whole exome sequencing new syndromes continue to be discovered. While classically these disorders present in children, adult presentations of these syndromes are now commonplace. Broadly, the pathophysiology of inherited aplastic anemia relates to the defective hematopoietic progenitor cells and an accelerated decline of the hematopoietic stem cell compartment.

The most common IMFS, Fanconi anemia and telomere biology disorders, are associated with numerous mutations in DNA damage repair pathways and telomere maintenance pathways. TERT, DKC, and TERC mutations are most commonly associated with dyskeratosis congenita, but may also be found infrequently in patients with aplastic anemia presenting at an older age in the absence of the classic phenotypical features.^1,16,17 The recognition of an underlying genetic disorder or telomere biology disorder leading to constitutional aplastic anemia is significant, as these conditions are associated not only with marrow failure, but also endocrinopathies, organ fibrosis, and solid organ malignancies.^13-15 In particular, mutations in the TERT and TERC genes have been associated with dyskeratosis congenita as well as pulmonary fibrosis and cirrhosis.^18,19 The implications of early diagnosis of an IMFS lie in the approach to treatment and prognosis.

Clonal Disorders and Secondary Malignancies

Myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML) are 2 clonal disorders that may arise from a background of aplastic anemia.^9,20,21 Hypoplastic MDS can be difficult to differentiate from aplastic anemia at diagnosis based on morphology alone, although recent work has demonstrated that molecular testing for somatic mutations in ASXL1, DNMT3A, and BCOR can aid in differentiating a subset of aplastic anemia patients who are more likely to progress to MDS.²¹ Clonal populations of cells harboring 6p uniparental disomy are seen in more than 10% of patients with aplastic anemia on cytogenetic analysis, which can help differentiate the diseases.⁹ Yoshizato and colleagues found lower rates of ASXL1 and DNMT3A mutations in patients with aplastic anemia as compared with patients with MDS or AML. In this study, patients with aplastic anemia had higher rates of mutations in PIGA (reflecting the increased paroxysmal nocturnal hemoglobinuria [PNH] clonality seen in aplastic anemia) and BCOR.⁹ Mutations were also found in genes commonly mutated in MDS and AML, including TET2, RUNX1, TP53, and JAK2, albeit at lower frequencies.⁹ These mutations as a whole have not predicted response to therapy or prognosis. However, when performing survival analysis in patients with specific mutations, those commonly encountered in MDS/AML (ASXL1, DNMT3A, TP53, RUNX1, CSMD1) are associated with faster progression to overt MDS/AML and decreased overall survival (OS),^20,21 suggesting these mutations may represent early clonality that can lead to clonal evolution and the development of secondary malignancies. Conversely, mutations in BCOR and BCORL appear to identify patients who may have a favorable outcome in response to immunosuppressive therapy and, similar to patients with PIGA mutations, improved OS.⁹

Paroxysmal Nocturnal Hemoglobinuria

In addition to having an increased risk of myelodysplasia and malignancy due to the development of a dominant pre-malignant clone, patients with aplastic anemia often harbor progenitor cell clones associated with PNH.^1,17 PNH clones have been identified in more than 50% of patients with aplastic anemia.^22,23 PNH represents a clonal disorder of hematopoiesis in which cells harbor X-linked somatic mutations in the PIGA gene; this gene encodes a protein responsible for the synthesis of glycosylphosphatidylinositol (GPI) anchors on the cell surface.^22,24 The lack of these cell surface proteins, specifically CD55 (also known as decay accelerating factor) and CD59 (also known as membrane inhibitor of reactive lysis), predisposes red cells to increased complement-mediated lysis.²⁵ The exact mechanism for the development of these clones in patients with aplastic anemia is not fully understood. Current theories hypothesize that these clones are protected from the immune-mediated destruction of normal hematopoietic stem cells due to the absence of the cell surface proteins.^1,20 The role of these clones over time in patients with aplastic anemia is less clear, though recent work demonstrated that despite differences in clonality over the disease course, aplastic anemia patients with small PNH clones are less likely to develop overt hemolysis and larger PNH clones compared to patients harboring larger (≥ 50%) PNH clones at diagnosis.^23,26,27 Additionally, PNH clones in patients with aplastic anemia infrequently become clinically significant.²⁷ It should be noted that these conditions exist along a continuum; that is, patients with aplastic anemia may develop PNH clones, while conversely patients with PNH may develop aplastic anemia.²⁰ Patients with PNH clones should be followed via peripheral blood flow cytometry in addition to complete blood count to track clonal stability and identify clinically significant PNH among aplastic anemia patients.²⁸

Patients with aplastic anemia typically are diagnosed either due to asymptomatic cytopenias found on peripheral blood sampling, symptomatic anemia, bleeding secondary to thrombocytopenia, or wound healing and infectious complications related to neutropenia.²⁹ A thorough history to understand the timing of symptoms, recent infectious symptoms/exposure, habits, and chemical or toxin exposures (including medications, travel, and supplements) helps guide diagnostic testing. Family history is also critical, with attention given to premature graying, pulmonary, renal, and liver disease, and blood disorders.

Patients with an IMFS, (eg, Fanconi anemia or dyskeratosis congenita) may have associated phenotypical findings such as urogenital abnormalities or short stature; in addition, those with dyskeratosis congenita may present with the classic triad of oral leukoplakia, lacy skin pigmentation, and dystrophic nails.⁷ However, in patients with IMFS, classic phenotypical findings may be lacking in up to 30% to 40% of patients.⁷ As described previously, while congenital malformations are common in Fanconi anemia and dyskeratosis congenita, a third of patients may have no or only subtle phenotypical abnormalities, including alterations in skin or hair pigmentation, skeletal and growth abnormalities, and endocrine disorders.³⁰ The International Fanconi Anemia Registry identified central nervous system, genitourinary, skin and musculoskeletal, ophthalmic, and gastrointestinal system malformations among children with Fanconi anemia.^31,32 Patients with dyskeratosis congenita may present with pulmonary fibrosis, hepatic cirrhosis, or premature graying, as highlighted in a recent study by DiNardo and colleagues.³³ Therefore, physicians must have a heightened index of suspicion in patients with subtle phenotypical findings and associated cytopenias.

Diagnosis

Differential Diagnosis

The diagnosis of aplastic anemia should be suspected in any patient presenting with pancytopenia. Aplastic anemia is a diagnosis of exclusion.³⁴ Other conditions associated with peripheral blood pancytopenia should be considered including infections (HIV, hepatitis, parvovirus B19, cytomegalovirus, Epstein-Barr virus, varicella-zoster virus), nutritional deficiencies (vitamin B12, folate, copper, zinc), autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, hemophagocytic lymphohistiocytosis), hypersplenism, marrow-occupying diseases (eg, leukemia, lymphoma, MDS), solid malignancies, and fibrosis (Table).⁷

Diagnostic Evaluation

The workup for aplastic anemia should include a thorough history and physical exam to search simultaneously for alternative diagnoses and clues pointing to potential etiologic agents.⁷ Diagnostic tests to be performed include a complete blood count with differential, reticulocyte count, immature platelet fraction, flow cytometry (to rule out lymphoproliferative disorders and atypical myeloid cells and to evaluate for PNH), and bone marrow biopsy with subsequent cytogenetic, immunohistochemical, and molecular testing.³⁵ The typical findings in aplastic anemia include peripheral blood pancytopenia without dysplastic features and bone marrow biopsy demonstrating a hypocellular marrow.⁷ A relative lymphocytosis in the peripheral blood is common.⁷ In patients with a significant PNH clone, a macrocytosis along with elevated lactate dehydrogenase and elevated reticulocyte and granulocyte counts may be present.³⁶

The diagnosis (based on the Camitta criteria³⁷ and modified Camitta criteria³⁸ for severe aplastic anemia) requires 2 of the following findings on peripheral blood samples:

• Absolute neutrophil count (ANC) < 500 cells/µL
• Platelet count < 20,000 cells/µL
• Reticulocyte count < 1% corrected or < 20,000 cells/µL.³⁵

In addition to peripheral blood findings, bone marrow biopsy is essential for the diagnosis, and should demonstrate a markedly hypocellular marrow (cellularity < 25%), occasionally with an increase in T lymphocytes.^7,39 Because marrow cellularity varies with age and can be challenging to assess, additional biopsies may be needed to confirm the diagnosis.²⁹ A 1- to 2-cm core biopsy is necessary to confirm hypocellularity, as small areas of residual hematopoiesis may be present and obscure the diagnosis.³⁵

Excluding Hypocellular MDS and IMFS

A diagnostic challenge is the exclusion of hypocellular MDS, especially in the older adult presenting with aplastic anemia, as patients with aplastic anemia may have some degree of erythroid dysplasia on bone marrow morphology.³⁶ The presence of a PNH clone on flow cytometry can aid in diagnosing aplastic anemia and excluding MDS,³⁴ although PNH clones can be present in refractory anemia MDS. Patients with aplastic anemia have a lower ratio of CD34+ cells compared to those with hypoplastic MDS, with one study demonstrating a mean CD34+ percentage of < 0.5% in aplastic anemia versus 3.7% in hypoplastic MDS.⁴⁰ Cytogenetic and molecular testing can also aid in making this distinction by identifying mutations commonly implicated in MDS.⁷ The presence of monosomy 7 (-7) in aplastic anemia patients is associated with a poor overall prognosis.^34,41

Peripheral blood screening using chromosome breakage analysis (done using either mitomycin C or diepoxybutane as in vitro DNA-crosslinking agents) and telomere length testing (of peripheral blood leukocytes) is necessary to exclude the main IMFS, Fanconi anemia and telomere biology disorders, respectively. Ruling out these conditions is imperative, as the approach to treatment varies significantly between IMFS and aplastic anemia. Patients with shortened telomeres should undergo genetic screening for mutations in the telomere maintenance genes to evaluate the underlying defect leading to shortened telomeres. Patients with increased peripheral blood breakage should have genetic testing to detect mutations associated with Fanconi anemia.

Classification

Once the diagnosis of aplastic anemia has been made, the patient should be classified according to the severity of their disease. Disease severity is determined based on peripheral blood ANC:³⁴ non-severe aplastic anemia (NSAA), ANC > 500 polymorphonuclear neutrophils (PMNs)/µL; severe aplastic anemia (SAA), 200–500 PMNs/µL; and very severe (VSAA), 0–200 PMNs/µL.^4,34 Disease classification is important, as VSAA is associated with a decreased OS compared to SAA.² Disease classification may affect treatment decisions, as patients with NSAA may be observed for a short period of time, while conversely patients with SAA have a worse prognosis with delays in therapy.^42-44

Summary

Aplastic anemia is a rare but potentially life-threatening disorder characterized by pancytopenia and a marked reduction in the hematopoietic stem cell compartment. It can be acquired or associated with an IMFS, and the treatment and prognosis vary dramatically between these 2 etiologies. Work-up and diagnosis involves investigating IMFSs and ruling out malignant or infectious etiologies for pancytopenia. After aplastic anemia has been diagnosed, the patient should be classified according to the severity of their disease based on peripheral blood ANC.

Aplastic anemia is a clinical and pathological entity of bone marrow failure that causes progressive loss of hematopoietic progenitor stem cells (HPSC), resulting in pancytopenia.¹ Patients may present along a spectrum, ranging from being asymptomatic with incidental findings on peripheral blood testing to having life-threatening neutropenic infections or bleeding. Aplastic anemia results from either inherited or acquired causes, and the pathophysiology and treatment approach vary significantly between these 2 causes. Therefore, recognition of inherited marrow failure diseases, such as Fanconi anemia and telomere biology disorders, is critical to establishing the management plan. This article reviews the epidemiology, pathophysiology, clinical presentation, and diagnosis of aplastic anemia. Treatment of aplastic anemia is reviewed in a separate article.

Epidemiology

Aplastic anemia is a rare disorder, with an incidence of approximately 1.5 to 7 cases per million individuals per year.^2,3 A recent Scandinavian study reported that the incidence of aplastic anemia among the Swedish population is 2.3 cases per million individuals per year, with a median age at diagnosis of 60 years and a slight female predominance (52% versus 48%, respectively).² This data is congruent with prior observations made in Barcelona, where the incidence was 2.34 cases per million individuals per year, albeit with a slightly higher incidence in males compared to females (2.54 versus 2.16, respectively).⁴ The incidence of aplastic anemia varies globally, with a disproportionate increase in incidence seen among Asian populations, with rates as high as 8.8 per million individuals per year.^3-5 This variation in incidence in Asia versus other countries has not been well explained. There appears to be a bimodal distribution, with incidence peaks seen in young adults and in older adults.^2,3,6

Pathophysiology

Acquired Aplastic Anemia

The leading hypothesis as to the cause of most cases of acquired aplastic anemia is that a dysregulated immune system destroys hematopoietic progenitor cells. Inciting etiologies implicated in the development of acquired aplastic anemia include pregnancy, infection, medications, and exposure to certain chemicals, such as benzene.^1,7 The historical understanding of acquired aplastic anemia implicates cytotoxic T-lymphocyte–mediated destruction of CD34+ hematopoietic stem cells.^1,8,9 This hypothesis served as the basis for treatment of acquired aplastic anemia with immunosuppressive therapy, predominantly anti-thymocyte globulin (ATG) combined with cyclosporine A.^1,8 More recent work has focused on cytokine interactions, particularly the suppressive role of interferon (IFN)-γ on hematopoietic stem cells independent of T-lymphocyte–mediated hematopoietic destruction, which has been demonstrated in a murine model.⁸ The interaction of IFN-γ with the hematopoietic stem cells pool is dynamic. IFN-γ levels are elevated during an acute inflammatory response such as a viral infection, providing further basis for the immune-mediated nature of the acquired disease.¹⁰ Specifically, in vitro studies suggest the effects of IFN-γ on HPSC may be secondary to interruption of thrombopoietin and its respective signaling pathways, which play a key role in hematopoietic stem cell renewal.¹¹ Eltrombopag, a thrombopoietin receptor antagonist, has shown promise in the treatment of refractory aplastic anemia, with studies indicating that its effectiveness is independent of IFN-γ levels.^11,12

Inherited Aplastic Anemia

The inherited marrow failure syndromes (IMFSs) are a group of disorders characterized by cellular maintenance and repair defects, leading to cytopenias, increased cancer risk, structural defects, and risk of end organ damage, such as liver cirrhosis and pulmonary fibrosis.^13-15 The most common diseases include Fanconi anemia, dyskeratosis congenita/telomere biology disorders, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome, but with the advent of whole exome sequencing new syndromes continue to be discovered. While classically these disorders present in children, adult presentations of these syndromes are now commonplace. Broadly, the pathophysiology of inherited aplastic anemia relates to the defective hematopoietic progenitor cells and an accelerated decline of the hematopoietic stem cell compartment.

The most common IMFS, Fanconi anemia and telomere biology disorders, are associated with numerous mutations in DNA damage repair pathways and telomere maintenance pathways. TERT, DKC, and TERC mutations are most commonly associated with dyskeratosis congenita, but may also be found infrequently in patients with aplastic anemia presenting at an older age in the absence of the classic phenotypical features.^1,16,17 The recognition of an underlying genetic disorder or telomere biology disorder leading to constitutional aplastic anemia is significant, as these conditions are associated not only with marrow failure, but also endocrinopathies, organ fibrosis, and solid organ malignancies.^13-15 In particular, mutations in the TERT and TERC genes have been associated with dyskeratosis congenita as well as pulmonary fibrosis and cirrhosis.^18,19 The implications of early diagnosis of an IMFS lie in the approach to treatment and prognosis.

Clonal Disorders and Secondary Malignancies

Myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML) are 2 clonal disorders that may arise from a background of aplastic anemia.^9,20,21 Hypoplastic MDS can be difficult to differentiate from aplastic anemia at diagnosis based on morphology alone, although recent work has demonstrated that molecular testing for somatic mutations in ASXL1, DNMT3A, and BCOR can aid in differentiating a subset of aplastic anemia patients who are more likely to progress to MDS.²¹ Clonal populations of cells harboring 6p uniparental disomy are seen in more than 10% of patients with aplastic anemia on cytogenetic analysis, which can help differentiate the diseases.⁹ Yoshizato and colleagues found lower rates of ASXL1 and DNMT3A mutations in patients with aplastic anemia as compared with patients with MDS or AML. In this study, patients with aplastic anemia had higher rates of mutations in PIGA (reflecting the increased paroxysmal nocturnal hemoglobinuria [PNH] clonality seen in aplastic anemia) and BCOR.⁹ Mutations were also found in genes commonly mutated in MDS and AML, including TET2, RUNX1, TP53, and JAK2, albeit at lower frequencies.⁹ These mutations as a whole have not predicted response to therapy or prognosis. However, when performing survival analysis in patients with specific mutations, those commonly encountered in MDS/AML (ASXL1, DNMT3A, TP53, RUNX1, CSMD1) are associated with faster progression to overt MDS/AML and decreased overall survival (OS),^20,21 suggesting these mutations may represent early clonality that can lead to clonal evolution and the development of secondary malignancies. Conversely, mutations in BCOR and BCORL appear to identify patients who may have a favorable outcome in response to immunosuppressive therapy and, similar to patients with PIGA mutations, improved OS.⁹

Paroxysmal Nocturnal Hemoglobinuria

In addition to having an increased risk of myelodysplasia and malignancy due to the development of a dominant pre-malignant clone, patients with aplastic anemia often harbor progenitor cell clones associated with PNH.^1,17 PNH clones have been identified in more than 50% of patients with aplastic anemia.^22,23 PNH represents a clonal disorder of hematopoiesis in which cells harbor X-linked somatic mutations in the PIGA gene; this gene encodes a protein responsible for the synthesis of glycosylphosphatidylinositol (GPI) anchors on the cell surface.^22,24 The lack of these cell surface proteins, specifically CD55 (also known as decay accelerating factor) and CD59 (also known as membrane inhibitor of reactive lysis), predisposes red cells to increased complement-mediated lysis.²⁵ The exact mechanism for the development of these clones in patients with aplastic anemia is not fully understood. Current theories hypothesize that these clones are protected from the immune-mediated destruction of normal hematopoietic stem cells due to the absence of the cell surface proteins.^1,20 The role of these clones over time in patients with aplastic anemia is less clear, though recent work demonstrated that despite differences in clonality over the disease course, aplastic anemia patients with small PNH clones are less likely to develop overt hemolysis and larger PNH clones compared to patients harboring larger (≥ 50%) PNH clones at diagnosis.^23,26,27 Additionally, PNH clones in patients with aplastic anemia infrequently become clinically significant.²⁷ It should be noted that these conditions exist along a continuum; that is, patients with aplastic anemia may develop PNH clones, while conversely patients with PNH may develop aplastic anemia.²⁰ Patients with PNH clones should be followed via peripheral blood flow cytometry in addition to complete blood count to track clonal stability and identify clinically significant PNH among aplastic anemia patients.²⁸

Patients with aplastic anemia typically are diagnosed either due to asymptomatic cytopenias found on peripheral blood sampling, symptomatic anemia, bleeding secondary to thrombocytopenia, or wound healing and infectious complications related to neutropenia.²⁹ A thorough history to understand the timing of symptoms, recent infectious symptoms/exposure, habits, and chemical or toxin exposures (including medications, travel, and supplements) helps guide diagnostic testing. Family history is also critical, with attention given to premature graying, pulmonary, renal, and liver disease, and blood disorders.

Patients with an IMFS, (eg, Fanconi anemia or dyskeratosis congenita) may have associated phenotypical findings such as urogenital abnormalities or short stature; in addition, those with dyskeratosis congenita may present with the classic triad of oral leukoplakia, lacy skin pigmentation, and dystrophic nails.⁷ However, in patients with IMFS, classic phenotypical findings may be lacking in up to 30% to 40% of patients.⁷ As described previously, while congenital malformations are common in Fanconi anemia and dyskeratosis congenita, a third of patients may have no or only subtle phenotypical abnormalities, including alterations in skin or hair pigmentation, skeletal and growth abnormalities, and endocrine disorders.³⁰ The International Fanconi Anemia Registry identified central nervous system, genitourinary, skin and musculoskeletal, ophthalmic, and gastrointestinal system malformations among children with Fanconi anemia.^31,32 Patients with dyskeratosis congenita may present with pulmonary fibrosis, hepatic cirrhosis, or premature graying, as highlighted in a recent study by DiNardo and colleagues.³³ Therefore, physicians must have a heightened index of suspicion in patients with subtle phenotypical findings and associated cytopenias.

Diagnosis

Differential Diagnosis

The diagnosis of aplastic anemia should be suspected in any patient presenting with pancytopenia. Aplastic anemia is a diagnosis of exclusion.³⁴ Other conditions associated with peripheral blood pancytopenia should be considered including infections (HIV, hepatitis, parvovirus B19, cytomegalovirus, Epstein-Barr virus, varicella-zoster virus), nutritional deficiencies (vitamin B12, folate, copper, zinc), autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, hemophagocytic lymphohistiocytosis), hypersplenism, marrow-occupying diseases (eg, leukemia, lymphoma, MDS), solid malignancies, and fibrosis (Table).⁷

Diagnostic Evaluation

The workup for aplastic anemia should include a thorough history and physical exam to search simultaneously for alternative diagnoses and clues pointing to potential etiologic agents.⁷ Diagnostic tests to be performed include a complete blood count with differential, reticulocyte count, immature platelet fraction, flow cytometry (to rule out lymphoproliferative disorders and atypical myeloid cells and to evaluate for PNH), and bone marrow biopsy with subsequent cytogenetic, immunohistochemical, and molecular testing.³⁵ The typical findings in aplastic anemia include peripheral blood pancytopenia without dysplastic features and bone marrow biopsy demonstrating a hypocellular marrow.⁷ A relative lymphocytosis in the peripheral blood is common.⁷ In patients with a significant PNH clone, a macrocytosis along with elevated lactate dehydrogenase and elevated reticulocyte and granulocyte counts may be present.³⁶

The diagnosis (based on the Camitta criteria³⁷ and modified Camitta criteria³⁸ for severe aplastic anemia) requires 2 of the following findings on peripheral blood samples:

• Absolute neutrophil count (ANC) < 500 cells/µL
• Platelet count < 20,000 cells/µL
• Reticulocyte count < 1% corrected or < 20,000 cells/µL.³⁵

In addition to peripheral blood findings, bone marrow biopsy is essential for the diagnosis, and should demonstrate a markedly hypocellular marrow (cellularity < 25%), occasionally with an increase in T lymphocytes.^7,39 Because marrow cellularity varies with age and can be challenging to assess, additional biopsies may be needed to confirm the diagnosis.²⁹ A 1- to 2-cm core biopsy is necessary to confirm hypocellularity, as small areas of residual hematopoiesis may be present and obscure the diagnosis.³⁵

Excluding Hypocellular MDS and IMFS

A diagnostic challenge is the exclusion of hypocellular MDS, especially in the older adult presenting with aplastic anemia, as patients with aplastic anemia may have some degree of erythroid dysplasia on bone marrow morphology.³⁶ The presence of a PNH clone on flow cytometry can aid in diagnosing aplastic anemia and excluding MDS,³⁴ although PNH clones can be present in refractory anemia MDS. Patients with aplastic anemia have a lower ratio of CD34+ cells compared to those with hypoplastic MDS, with one study demonstrating a mean CD34+ percentage of < 0.5% in aplastic anemia versus 3.7% in hypoplastic MDS.⁴⁰ Cytogenetic and molecular testing can also aid in making this distinction by identifying mutations commonly implicated in MDS.⁷ The presence of monosomy 7 (-7) in aplastic anemia patients is associated with a poor overall prognosis.^34,41

Peripheral blood screening using chromosome breakage analysis (done using either mitomycin C or diepoxybutane as in vitro DNA-crosslinking agents) and telomere length testing (of peripheral blood leukocytes) is necessary to exclude the main IMFS, Fanconi anemia and telomere biology disorders, respectively. Ruling out these conditions is imperative, as the approach to treatment varies significantly between IMFS and aplastic anemia. Patients with shortened telomeres should undergo genetic screening for mutations in the telomere maintenance genes to evaluate the underlying defect leading to shortened telomeres. Patients with increased peripheral blood breakage should have genetic testing to detect mutations associated with Fanconi anemia.

Classification

Once the diagnosis of aplastic anemia has been made, the patient should be classified according to the severity of their disease. Disease severity is determined based on peripheral blood ANC:³⁴ non-severe aplastic anemia (NSAA), ANC > 500 polymorphonuclear neutrophils (PMNs)/µL; severe aplastic anemia (SAA), 200–500 PMNs/µL; and very severe (VSAA), 0–200 PMNs/µL.^4,34 Disease classification is important, as VSAA is associated with a decreased OS compared to SAA.² Disease classification may affect treatment decisions, as patients with NSAA may be observed for a short period of time, while conversely patients with SAA have a worse prognosis with delays in therapy.^42-44

Summary

Aplastic anemia is a rare but potentially life-threatening disorder characterized by pancytopenia and a marked reduction in the hematopoietic stem cell compartment. It can be acquired or associated with an IMFS, and the treatment and prognosis vary dramatically between these 2 etiologies. Work-up and diagnosis involves investigating IMFSs and ruling out malignant or infectious etiologies for pancytopenia. After aplastic anemia has been diagnosed, the patient should be classified according to the severity of their disease based on peripheral blood ANC.

Among people of the same age, the degree of frailty influences the association between Alzheimer’s disease pathology and Alzheimer’s dementia, according to research published online ahead of print Jan. 17 in Lancet Neurology. Data suggest that frailty reduces the threshold for Alzheimer’s disease pathology to cause cognitive decline. Frailty also may contribute to other mechanisms that cause dementia, such as inflammation and immunosenescence, said the investigators.

“While more research is needed, given that frailty is potentially reversible, it is possible that helping people to maintain function and independence in later life could reduce both dementia risk and the severity of debilitating symptoms common in this disease,” said Professor Kenneth Rockwood, MD, of the Nova Scotia Health Authority and Dalhousie University in Halifax, N.S., in a press release.
 

More susceptible to dementia?

The presence of amyloid plaques and neurofibrillary tangles is not a sufficient condition for the clinical expression of dementia. Some patients with a high degree of Alzheimer’s disease pathology have no apparent cognitive decline. Other factors therefore may modify the relationship between pathology and dementia.

Most people who develop Alzheimer’s disease dementia are older than 65 years, and many of these patients are frail. Frailty is understood as a decreased physiologic reserve and an increased risk for adverse health outcomes. Dr. Rockwood and his colleagues hypothesized that frailty moderates the clinical expression of dementia in relation to Alzheimer’s disease pathology.

To test their hypothesis, the investigators performed a cross-sectional analysis of data from the Rush Memory and Aging Project, which collects clinical and pathologic data from adults older than 59 years without dementia at baseline who live in Illinois. Since 1997, participants have undergone annual clinical and neuropsychological evaluations, and the cohort has been followed for 21 years. For their analysis, Dr. Rockwood and his colleagues included participants without dementia or with Alzheimer’s dementia at their last clinical assessment. Eligible participants had died, and complete autopsy data were available for them.

The researchers measured Alzheimer’s disease pathology using a summary measure of neurofibrillary tangles and neuritic and diffuse plaques. Clinical diagnoses of Alzheimer’s dementia were based on clinician consensus. Dr. Rockwood and his colleagues retrospectively created a 41-item frailty index from variables (e.g., symptoms, signs, comorbidities, and function) that were obtained at each clinical evaluation.

Logistic regression and moderation modeling allowed the investigators to evaluate relationships between Alzheimer’s disease pathology, frailty, and Alzheimer’s dementia. Dr. Rockwood and hus colleagues adjusted all analyses for age, sex, and education.

In all, 456 participants were included in the analysis. The sample’s mean age at death was 89.7 years, and 69% of participants were women. At participants’ last clinical assessment, 242 (53%) had possible or probable Alzheimer’s dementia.

The sample’s mean frailty index was 0.42. The median frailty index was 0.41, a value similar to the threshold commonly used to distinguish between moderate and severe frailty. People with high frailty index scores (i.e., 0.41 or greater) were older, had lower Mini-Mental State Examination scores, were more likely to have a diagnosis of dementia, and had a higher Braak stage than those with moderate or low frailty index scores.
 

Significant interaction between frailty and Alzheimer’s disease

After the investigators adjusted for age, sex, and education, frailty (odds ratio, 1.76) and Alzheimer’s disease pathology (OR, 4.81) were independently associated with Alzheimer’s dementia. When the investigators added frailty to the model for the relationship between Alzheimer’s disease pathology and Alzheimer’s dementia, the model fit improved. They found a significant interaction between frailty and Alzheimer’s disease pathology (OR, 0.73). People with a low amount of frailty were better able to tolerate Alzheimer’s disease pathology, and people with higher amounts of frailty were more likely to have more Alzheimer’s disease pathology and clinical dementia.

One of the study’s limitations is that it is a secondary analysis, according to Dr. Rockwood and his colleagues. In addition, frailty was measured close to participants’ time of death, and the measurements may thus reflect terminal decline. Participant deaths resulting from causes other than those related to dementia might have confounded the results. Finally, the sample came entirely from people living in retirement homes in Illinois, which might have introduced bias. Future research should use a population-based sample, said the authors.

Frailty could be a basis for risk stratification and could inform the management and treatment of older adults, said Dr. Rockwood and his colleagues. The study results have “the potential to improve our understanding of disease expression, explain failures in pharmacologic treatment, and aid in the development of more appropriate therapeutic targets, approaches, and measurements of success,” they concluded.

The study had no source of funding. The authors reported receiving fees and grants from DGI Clinical, GlaxoSmithKline, Pfizer, and Sanofi. Authors also received support from governmental bodies such as the National Institutes of Health and the Canadian Institutes of Health Research.

[email protected]

SOURCE: Wallace LMK et al. Lancet Neurol. 2019;18:177-84.

Among people of the same age, the degree of frailty influences the association between Alzheimer’s disease pathology and Alzheimer’s dementia, according to research published online ahead of print Jan. 17 in Lancet Neurology. Data suggest that frailty reduces the threshold for Alzheimer’s disease pathology to cause cognitive decline. Frailty also may contribute to other mechanisms that cause dementia, such as inflammation and immunosenescence, said the investigators.

“While more research is needed, given that frailty is potentially reversible, it is possible that helping people to maintain function and independence in later life could reduce both dementia risk and the severity of debilitating symptoms common in this disease,” said Professor Kenneth Rockwood, MD, of the Nova Scotia Health Authority and Dalhousie University in Halifax, N.S., in a press release.
 

More susceptible to dementia?

The presence of amyloid plaques and neurofibrillary tangles is not a sufficient condition for the clinical expression of dementia. Some patients with a high degree of Alzheimer’s disease pathology have no apparent cognitive decline. Other factors therefore may modify the relationship between pathology and dementia.

Most people who develop Alzheimer’s disease dementia are older than 65 years, and many of these patients are frail. Frailty is understood as a decreased physiologic reserve and an increased risk for adverse health outcomes. Dr. Rockwood and his colleagues hypothesized that frailty moderates the clinical expression of dementia in relation to Alzheimer’s disease pathology.

To test their hypothesis, the investigators performed a cross-sectional analysis of data from the Rush Memory and Aging Project, which collects clinical and pathologic data from adults older than 59 years without dementia at baseline who live in Illinois. Since 1997, participants have undergone annual clinical and neuropsychological evaluations, and the cohort has been followed for 21 years. For their analysis, Dr. Rockwood and his colleagues included participants without dementia or with Alzheimer’s dementia at their last clinical assessment. Eligible participants had died, and complete autopsy data were available for them.

The researchers measured Alzheimer’s disease pathology using a summary measure of neurofibrillary tangles and neuritic and diffuse plaques. Clinical diagnoses of Alzheimer’s dementia were based on clinician consensus. Dr. Rockwood and his colleagues retrospectively created a 41-item frailty index from variables (e.g., symptoms, signs, comorbidities, and function) that were obtained at each clinical evaluation.

Logistic regression and moderation modeling allowed the investigators to evaluate relationships between Alzheimer’s disease pathology, frailty, and Alzheimer’s dementia. Dr. Rockwood and hus colleagues adjusted all analyses for age, sex, and education.

In all, 456 participants were included in the analysis. The sample’s mean age at death was 89.7 years, and 69% of participants were women. At participants’ last clinical assessment, 242 (53%) had possible or probable Alzheimer’s dementia.

The sample’s mean frailty index was 0.42. The median frailty index was 0.41, a value similar to the threshold commonly used to distinguish between moderate and severe frailty. People with high frailty index scores (i.e., 0.41 or greater) were older, had lower Mini-Mental State Examination scores, were more likely to have a diagnosis of dementia, and had a higher Braak stage than those with moderate or low frailty index scores.
 

Significant interaction between frailty and Alzheimer’s disease

After the investigators adjusted for age, sex, and education, frailty (odds ratio, 1.76) and Alzheimer’s disease pathology (OR, 4.81) were independently associated with Alzheimer’s dementia. When the investigators added frailty to the model for the relationship between Alzheimer’s disease pathology and Alzheimer’s dementia, the model fit improved. They found a significant interaction between frailty and Alzheimer’s disease pathology (OR, 0.73). People with a low amount of frailty were better able to tolerate Alzheimer’s disease pathology, and people with higher amounts of frailty were more likely to have more Alzheimer’s disease pathology and clinical dementia.

One of the study’s limitations is that it is a secondary analysis, according to Dr. Rockwood and his colleagues. In addition, frailty was measured close to participants’ time of death, and the measurements may thus reflect terminal decline. Participant deaths resulting from causes other than those related to dementia might have confounded the results. Finally, the sample came entirely from people living in retirement homes in Illinois, which might have introduced bias. Future research should use a population-based sample, said the authors.

Frailty could be a basis for risk stratification and could inform the management and treatment of older adults, said Dr. Rockwood and his colleagues. The study results have “the potential to improve our understanding of disease expression, explain failures in pharmacologic treatment, and aid in the development of more appropriate therapeutic targets, approaches, and measurements of success,” they concluded.

The study had no source of funding. The authors reported receiving fees and grants from DGI Clinical, GlaxoSmithKline, Pfizer, and Sanofi. Authors also received support from governmental bodies such as the National Institutes of Health and the Canadian Institutes of Health Research.

[email protected]

SOURCE: Wallace LMK et al. Lancet Neurol. 2019;18:177-84.

Among people of the same age, the degree of frailty influences the association between Alzheimer’s disease pathology and Alzheimer’s dementia, according to research published online ahead of print Jan. 17 in Lancet Neurology. Data suggest that frailty reduces the threshold for Alzheimer’s disease pathology to cause cognitive decline. Frailty also may contribute to other mechanisms that cause dementia, such as inflammation and immunosenescence, said the investigators.

“While more research is needed, given that frailty is potentially reversible, it is possible that helping people to maintain function and independence in later life could reduce both dementia risk and the severity of debilitating symptoms common in this disease,” said Professor Kenneth Rockwood, MD, of the Nova Scotia Health Authority and Dalhousie University in Halifax, N.S., in a press release.
 

More susceptible to dementia?

The presence of amyloid plaques and neurofibrillary tangles is not a sufficient condition for the clinical expression of dementia. Some patients with a high degree of Alzheimer’s disease pathology have no apparent cognitive decline. Other factors therefore may modify the relationship between pathology and dementia.

Most people who develop Alzheimer’s disease dementia are older than 65 years, and many of these patients are frail. Frailty is understood as a decreased physiologic reserve and an increased risk for adverse health outcomes. Dr. Rockwood and his colleagues hypothesized that frailty moderates the clinical expression of dementia in relation to Alzheimer’s disease pathology.

To test their hypothesis, the investigators performed a cross-sectional analysis of data from the Rush Memory and Aging Project, which collects clinical and pathologic data from adults older than 59 years without dementia at baseline who live in Illinois. Since 1997, participants have undergone annual clinical and neuropsychological evaluations, and the cohort has been followed for 21 years. For their analysis, Dr. Rockwood and his colleagues included participants without dementia or with Alzheimer’s dementia at their last clinical assessment. Eligible participants had died, and complete autopsy data were available for them.

The researchers measured Alzheimer’s disease pathology using a summary measure of neurofibrillary tangles and neuritic and diffuse plaques. Clinical diagnoses of Alzheimer’s dementia were based on clinician consensus. Dr. Rockwood and his colleagues retrospectively created a 41-item frailty index from variables (e.g., symptoms, signs, comorbidities, and function) that were obtained at each clinical evaluation.

Logistic regression and moderation modeling allowed the investigators to evaluate relationships between Alzheimer’s disease pathology, frailty, and Alzheimer’s dementia. Dr. Rockwood and hus colleagues adjusted all analyses for age, sex, and education.

In all, 456 participants were included in the analysis. The sample’s mean age at death was 89.7 years, and 69% of participants were women. At participants’ last clinical assessment, 242 (53%) had possible or probable Alzheimer’s dementia.

The sample’s mean frailty index was 0.42. The median frailty index was 0.41, a value similar to the threshold commonly used to distinguish between moderate and severe frailty. People with high frailty index scores (i.e., 0.41 or greater) were older, had lower Mini-Mental State Examination scores, were more likely to have a diagnosis of dementia, and had a higher Braak stage than those with moderate or low frailty index scores.
 

Significant interaction between frailty and Alzheimer’s disease

After the investigators adjusted for age, sex, and education, frailty (odds ratio, 1.76) and Alzheimer’s disease pathology (OR, 4.81) were independently associated with Alzheimer’s dementia. When the investigators added frailty to the model for the relationship between Alzheimer’s disease pathology and Alzheimer’s dementia, the model fit improved. They found a significant interaction between frailty and Alzheimer’s disease pathology (OR, 0.73). People with a low amount of frailty were better able to tolerate Alzheimer’s disease pathology, and people with higher amounts of frailty were more likely to have more Alzheimer’s disease pathology and clinical dementia.

One of the study’s limitations is that it is a secondary analysis, according to Dr. Rockwood and his colleagues. In addition, frailty was measured close to participants’ time of death, and the measurements may thus reflect terminal decline. Participant deaths resulting from causes other than those related to dementia might have confounded the results. Finally, the sample came entirely from people living in retirement homes in Illinois, which might have introduced bias. Future research should use a population-based sample, said the authors.

Frailty could be a basis for risk stratification and could inform the management and treatment of older adults, said Dr. Rockwood and his colleagues. The study results have “the potential to improve our understanding of disease expression, explain failures in pharmacologic treatment, and aid in the development of more appropriate therapeutic targets, approaches, and measurements of success,” they concluded.

The study had no source of funding. The authors reported receiving fees and grants from DGI Clinical, GlaxoSmithKline, Pfizer, and Sanofi. Authors also received support from governmental bodies such as the National Institutes of Health and the Canadian Institutes of Health Research.

[email protected]

SOURCE: Wallace LMK et al. Lancet Neurol. 2019;18:177-84.

The Food and Drug Administration has modified the Risk Evaluation and Mitigation Strategy (REMS) Program for clozapine, a second-generation antipsychotic used for patients who do not respond adequately to standard antipsychotic treatment. Use of clozapine comes with the risk of neutropenia, which can make patients vulnerable to serious infections, so routine monitoring of absolute neutrophil counts is a must.

The new requirements, including one that requires both prescribers and pharmacies to be certified in the clozapine REMS program, take effect Feb. 28.

More information about clozapine and this change can be found on the FDA web page for the drug.

[email protected]

The Food and Drug Administration has modified the Risk Evaluation and Mitigation Strategy (REMS) Program for clozapine, a second-generation antipsychotic used for patients who do not respond adequately to standard antipsychotic treatment. Use of clozapine comes with the risk of neutropenia, which can make patients vulnerable to serious infections, so routine monitoring of absolute neutrophil counts is a must.

The new requirements, including one that requires both prescribers and pharmacies to be certified in the clozapine REMS program, take effect Feb. 28.

More information about clozapine and this change can be found on the FDA web page for the drug.

[email protected]

The Food and Drug Administration has modified the Risk Evaluation and Mitigation Strategy (REMS) Program for clozapine, a second-generation antipsychotic used for patients who do not respond adequately to standard antipsychotic treatment. Use of clozapine comes with the risk of neutropenia, which can make patients vulnerable to serious infections, so routine monitoring of absolute neutrophil counts is a must.

The new requirements, including one that requires both prescribers and pharmacies to be certified in the clozapine REMS program, take effect Feb. 28.

More information about clozapine and this change can be found on the FDA web page for the drug.

[email protected]

Young people enrolled in Medicaid who commit suicide are disproportionately female, younger, and more likely to die by hanging, compared with non-Medicaid youth, results of a large, observational, population-based study suggest.

Nearly 40% of young people in the study who died by suicide were covered by Medicaid, according to study lead author Cynthia A. Fontanella, PhD, of the department of psychiatry and behavioral health at the Ohio State University, Columbus. Those findings, in addition to those of other studies indicating that youth enrolled in Medicaid endure more maltreatment and poverty-related adversity, suggest a need for health care delivery systems to develop “trauma-informed approaches” and implement them, Dr. Fontanella and her coauthors reported in the American Journal of Preventive Medicine.

“Effective suicide screening of enrollees could substantially decrease suicide mortality in the United States,” they wrote.

Dr. Fontanella and her coauthors reviewed death certificate data from the 16 most populous states to identify all youth aged 10-18 who committed suicide during 2009-2013. They identified 4,045 deaths from suicide based on state death certificate data in California, Florida, Georgia, Illinois, Indiana, Massachusetts, Michigan, Minnesota, New York, North Carolina, Ohio, Oregon, Texas, Virginia, Washington, and Wisconsin. To identify the subset of youth who were enrolled in Medicaid, they used Social Security numbers to link the death certificate data to data from a Medicaid database.

Out of 4,045 youth suicide deaths that occurred during that time period, 39% were among youth enrolled in Medicaid, the investigators found.

Although the overall suicide rate did not differ significantly between the Medicaid and non-Medicaid groups, investigators said they did identify significant differences in age and sex subgroups. Specifically, those in the Medicaid group had a 28% increased risk of suicide among the 10- to 14-year age subgroup, and a 14% increased risk of suicide among females, the findings showed. Moreover, the risk of death by hanging was 26% greater among the Medicare youth.

Dr. Fontanella and her coauthors reported several limitations. One is that the findings might not be generalizable to all 50 states. Also, they said, because suicide is underreported as a cause of death, the prevalence of suicide found in the study might have been underreported.

Nevertheless, the findings confirm the importance of Medicaid as a “boundaried” setting for efforts targeting youth suicide prevention, Dr. Fontanella and her associates wrote. Boundaried populations are those defined by a service setting or organizational function. In other words, they wrote, findings based on an analysis of service use patterns captured in Medicaid claims “could prove helpful in identifying periods known to be associated with heightened suicide risk, such as that immediately following discharge from inpatient psychiatric care.”

The National Action Alliance for Suicide Prevention’s Research Prioritization Task Force has recommended that those populations be targeted for research on interventions designed to reduce suicide deaths, Dr. Fontanella and her coauthors wrote.

This is the first-ever study to evaluate suicide-related mortality among Medicaid-covered youth, the investigators said. Previous studies of suicide in Medicaid have focused on adults – specifically those in the Veterans Health Administration, specific state Medicaid programs, or health maintenance organization networks.

The American Foundation for Suicide Prevention and the National Institutes of Health funded the study. Dr. Fontanella and her coauthors reported no other financial conflicts of interest.

SOURCE: Fontanella CA et al. Am J Prev Med. 2019 Jan 17. doi: 10.1016/j.amepre.2018.10.008.

Young people enrolled in Medicaid who commit suicide are disproportionately female, younger, and more likely to die by hanging, compared with non-Medicaid youth, results of a large, observational, population-based study suggest.

Nearly 40% of young people in the study who died by suicide were covered by Medicaid, according to study lead author Cynthia A. Fontanella, PhD, of the department of psychiatry and behavioral health at the Ohio State University, Columbus. Those findings, in addition to those of other studies indicating that youth enrolled in Medicaid endure more maltreatment and poverty-related adversity, suggest a need for health care delivery systems to develop “trauma-informed approaches” and implement them, Dr. Fontanella and her coauthors reported in the American Journal of Preventive Medicine.

“Effective suicide screening of enrollees could substantially decrease suicide mortality in the United States,” they wrote.

Dr. Fontanella and her coauthors reviewed death certificate data from the 16 most populous states to identify all youth aged 10-18 who committed suicide during 2009-2013. They identified 4,045 deaths from suicide based on state death certificate data in California, Florida, Georgia, Illinois, Indiana, Massachusetts, Michigan, Minnesota, New York, North Carolina, Ohio, Oregon, Texas, Virginia, Washington, and Wisconsin. To identify the subset of youth who were enrolled in Medicaid, they used Social Security numbers to link the death certificate data to data from a Medicaid database.

Out of 4,045 youth suicide deaths that occurred during that time period, 39% were among youth enrolled in Medicaid, the investigators found.

Although the overall suicide rate did not differ significantly between the Medicaid and non-Medicaid groups, investigators said they did identify significant differences in age and sex subgroups. Specifically, those in the Medicaid group had a 28% increased risk of suicide among the 10- to 14-year age subgroup, and a 14% increased risk of suicide among females, the findings showed. Moreover, the risk of death by hanging was 26% greater among the Medicare youth.

Dr. Fontanella and her coauthors reported several limitations. One is that the findings might not be generalizable to all 50 states. Also, they said, because suicide is underreported as a cause of death, the prevalence of suicide found in the study might have been underreported.

Nevertheless, the findings confirm the importance of Medicaid as a “boundaried” setting for efforts targeting youth suicide prevention, Dr. Fontanella and her associates wrote. Boundaried populations are those defined by a service setting or organizational function. In other words, they wrote, findings based on an analysis of service use patterns captured in Medicaid claims “could prove helpful in identifying periods known to be associated with heightened suicide risk, such as that immediately following discharge from inpatient psychiatric care.”

The National Action Alliance for Suicide Prevention’s Research Prioritization Task Force has recommended that those populations be targeted for research on interventions designed to reduce suicide deaths, Dr. Fontanella and her coauthors wrote.

This is the first-ever study to evaluate suicide-related mortality among Medicaid-covered youth, the investigators said. Previous studies of suicide in Medicaid have focused on adults – specifically those in the Veterans Health Administration, specific state Medicaid programs, or health maintenance organization networks.

The American Foundation for Suicide Prevention and the National Institutes of Health funded the study. Dr. Fontanella and her coauthors reported no other financial conflicts of interest.

SOURCE: Fontanella CA et al. Am J Prev Med. 2019 Jan 17. doi: 10.1016/j.amepre.2018.10.008.

Young people enrolled in Medicaid who commit suicide are disproportionately female, younger, and more likely to die by hanging, compared with non-Medicaid youth, results of a large, observational, population-based study suggest.

Nearly 40% of young people in the study who died by suicide were covered by Medicaid, according to study lead author Cynthia A. Fontanella, PhD, of the department of psychiatry and behavioral health at the Ohio State University, Columbus. Those findings, in addition to those of other studies indicating that youth enrolled in Medicaid endure more maltreatment and poverty-related adversity, suggest a need for health care delivery systems to develop “trauma-informed approaches” and implement them, Dr. Fontanella and her coauthors reported in the American Journal of Preventive Medicine.

“Effective suicide screening of enrollees could substantially decrease suicide mortality in the United States,” they wrote.

Dr. Fontanella and her coauthors reviewed death certificate data from the 16 most populous states to identify all youth aged 10-18 who committed suicide during 2009-2013. They identified 4,045 deaths from suicide based on state death certificate data in California, Florida, Georgia, Illinois, Indiana, Massachusetts, Michigan, Minnesota, New York, North Carolina, Ohio, Oregon, Texas, Virginia, Washington, and Wisconsin. To identify the subset of youth who were enrolled in Medicaid, they used Social Security numbers to link the death certificate data to data from a Medicaid database.

Out of 4,045 youth suicide deaths that occurred during that time period, 39% were among youth enrolled in Medicaid, the investigators found.

Although the overall suicide rate did not differ significantly between the Medicaid and non-Medicaid groups, investigators said they did identify significant differences in age and sex subgroups. Specifically, those in the Medicaid group had a 28% increased risk of suicide among the 10- to 14-year age subgroup, and a 14% increased risk of suicide among females, the findings showed. Moreover, the risk of death by hanging was 26% greater among the Medicare youth.

Dr. Fontanella and her coauthors reported several limitations. One is that the findings might not be generalizable to all 50 states. Also, they said, because suicide is underreported as a cause of death, the prevalence of suicide found in the study might have been underreported.

Nevertheless, the findings confirm the importance of Medicaid as a “boundaried” setting for efforts targeting youth suicide prevention, Dr. Fontanella and her associates wrote. Boundaried populations are those defined by a service setting or organizational function. In other words, they wrote, findings based on an analysis of service use patterns captured in Medicaid claims “could prove helpful in identifying periods known to be associated with heightened suicide risk, such as that immediately following discharge from inpatient psychiatric care.”

The National Action Alliance for Suicide Prevention’s Research Prioritization Task Force has recommended that those populations be targeted for research on interventions designed to reduce suicide deaths, Dr. Fontanella and her coauthors wrote.

This is the first-ever study to evaluate suicide-related mortality among Medicaid-covered youth, the investigators said. Previous studies of suicide in Medicaid have focused on adults – specifically those in the Veterans Health Administration, specific state Medicaid programs, or health maintenance organization networks.

The American Foundation for Suicide Prevention and the National Institutes of Health funded the study. Dr. Fontanella and her coauthors reported no other financial conflicts of interest.

SOURCE: Fontanella CA et al. Am J Prev Med. 2019 Jan 17. doi: 10.1016/j.amepre.2018.10.008.

This week in MDedge Cardiocast: Too little sleep, too much sleep, and fragmented sleep are all linked to atherosclerosis; dabigatran matches aspirin for second stroke prevention; HDL particle subfractions may be prognostic in heart failure; and a novel drug safely reduced LDL cholesterol in statin-intolerant patients.

Subscribe to Cardiocast wherever you get your podcasts.
Amazon Alexa
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This week in MDedge Cardiocast: Too little sleep, too much sleep, and fragmented sleep are all linked to atherosclerosis; dabigatran matches aspirin for second stroke prevention; HDL particle subfractions may be prognostic in heart failure; and a novel drug safely reduced LDL cholesterol in statin-intolerant patients.

Subscribe to Cardiocast wherever you get your podcasts.
Amazon Alexa
Apple Podcasts






 

This week in MDedge Cardiocast: Too little sleep, too much sleep, and fragmented sleep are all linked to atherosclerosis; dabigatran matches aspirin for second stroke prevention; HDL particle subfractions may be prognostic in heart failure; and a novel drug safely reduced LDL cholesterol in statin-intolerant patients.

Subscribe to Cardiocast wherever you get your podcasts.
Amazon Alexa
Apple Podcasts






 

A majority of U.S. health care professionals report that their patients have been negatively affected by the federal government’s partial shutdown, according to a survey conducted Jan. 11 by health care market research company InCrowd.

The results showed that 58% of the 165 respondents (52 primary care physicians, 51 physician assistants, and 63 registered nurses) surveyed believe that their patents have been affected in some way by the shutdown: Three percent said that almost all of their patients have been affected, 32% said that some have been affected, and 23% said that only a few patients have been affected. The largest share of clinicians (42%), however, believes that none of their patients have experienced any effects from the shutdown, InCrowd reported Jan. 17.

That distribution changes considerably, however, when looking at the physicians only: 4% (almost all), 39% (some), 31% (a few), and 26% (none). Registered nurses (50%) and physician assistants (45%) were much more likely to say that none of their patients had been affected, InCrowd reported.

“Patient access to care and compliance issues due to financial concerns and loss of benefits are already being observed by respondents. Forty percent of respondents reported a high degree of both issues with patients affording medicine and incidences where patient avoided treatments and appointments all together,” the InCrowd investigators said.
 

[email protected]

This article was updated 1/18/19.

A majority of U.S. health care professionals report that their patients have been negatively affected by the federal government’s partial shutdown, according to a survey conducted Jan. 11 by health care market research company InCrowd.

The results showed that 58% of the 165 respondents (52 primary care physicians, 51 physician assistants, and 63 registered nurses) surveyed believe that their patents have been affected in some way by the shutdown: Three percent said that almost all of their patients have been affected, 32% said that some have been affected, and 23% said that only a few patients have been affected. The largest share of clinicians (42%), however, believes that none of their patients have experienced any effects from the shutdown, InCrowd reported Jan. 17.

That distribution changes considerably, however, when looking at the physicians only: 4% (almost all), 39% (some), 31% (a few), and 26% (none). Registered nurses (50%) and physician assistants (45%) were much more likely to say that none of their patients had been affected, InCrowd reported.

“Patient access to care and compliance issues due to financial concerns and loss of benefits are already being observed by respondents. Forty percent of respondents reported a high degree of both issues with patients affording medicine and incidences where patient avoided treatments and appointments all together,” the InCrowd investigators said.
 

[email protected]

This article was updated 1/18/19.

A majority of U.S. health care professionals report that their patients have been negatively affected by the federal government’s partial shutdown, according to a survey conducted Jan. 11 by health care market research company InCrowd.

The results showed that 58% of the 165 respondents (52 primary care physicians, 51 physician assistants, and 63 registered nurses) surveyed believe that their patents have been affected in some way by the shutdown: Three percent said that almost all of their patients have been affected, 32% said that some have been affected, and 23% said that only a few patients have been affected. The largest share of clinicians (42%), however, believes that none of their patients have experienced any effects from the shutdown, InCrowd reported Jan. 17.

That distribution changes considerably, however, when looking at the physicians only: 4% (almost all), 39% (some), 31% (a few), and 26% (none). Registered nurses (50%) and physician assistants (45%) were much more likely to say that none of their patients had been affected, InCrowd reported.

“Patient access to care and compliance issues due to financial concerns and loss of benefits are already being observed by respondents. Forty percent of respondents reported a high degree of both issues with patients affording medicine and incidences where patient avoided treatments and appointments all together,” the InCrowd investigators said.
 

[email protected]

This article was updated 1/18/19.

Investigators at the University of Michigan, Ann Arbor, found that a simple patient decision aid can be a useful tool in providing adequate postsurgical pain control to patients while reducing the number of opioid tablets in the community. The shared decision-making aid focuses on educating the patient about opioid use and engages her in an appropriate postoperative pain management plan. Results from this prospective quality improvement study were presented in a poster at the 47th AAGL Global Congress on Minimally Invasive Gynecology (Las Vegas, Nevada, November 11–15, 2018).¹

Annmarie Vilkins, DO, and colleagues’ aim was to evaluate the impact of shared decision-making through the use of a patient decision aid targeting posthysterectomy pain management and opioid use. Can such a targeted strategy help decrease posthysterectomy opioid distribution in the community without compromising patient pain control or satisfaction?

The authors noted that more than 46 people die each day from an overdose involving prescription opioids.² Studies have shown that patients actually use significantly fewer opioid tablets than the amount clinicians generally prescribe following ObGyn surgeries.^3,4 Unused prescription opioid availability has the potential for accidental use or intentional misuse of the unneeded drugs by others.

Study methods

The investigators included all English-speaking patients undergoing hysterectomy for benign disease at their institution from March 1 through July 31, 2018. Data were analyzed from women undergoing laparoscopic, vaginal, or abdominal hysterectomy before (n = 195) and after (n = 177) the decision aid was implemented.

Preoperative education. In the preoperative area, patients were uniformly educated regarding postoperative pain expectations (for example, it is normal to have some pain; the goal is to manage your pain so you can function; some women do not require opioid medications after surgery), risks of opioid medications (such as dependence or addiction; misuse of leftover pills by others), adverse effects (drowsiness; confusion), and the recommended postoperative pain management schedule.

Postoperatively, pain medications included ibuprofen around the clock, acetaminophen as needed (used with caution when hydrocodone with acetaminophen was also prescribed), and opioids only if needed.

Discharge medication planning. Using a visual scale, the investigators then educated patients regarding the maximum number of opioid tablets permitted to be prescribed according to department guidelines and the average number of opioid tablets that a typical patient uses. The number of opioid tablets prescribed varied based on route of hysterectomy (laparoscopic, abdominal, or vaginal). For example, for a laparoscopic hysterectomy, the maximum allowed prescription for oxycodone was 20 tablets, while patients used an average number of 10 tablets.

The patient was then asked to choose her desired number of tablets with which she would like to be discharged.

Structured telephone calls were made to patients 2 weeks postoperatively.

Impact of the decision aid on opioid prescribing

Before implementation of the decision aid, the average number of opioid pills prescribed at discharge was 25 (median, 20–35), while that number dropped to 10 (median, 10–15) after the aid’s implementation. Similarly, the average oral morphine equivalents (OMEs) at time of discharge was 150 (interquartile range [IQR], 120–200) before decision aid implementation and 75 (IQR, 25–150) after decision aid implementation. Similar reductions in average OMEs were observed before and after the aid’s implementation across the 3 hysterectomy routes.

Continue to: According to the type of opioid...

According to the type of opioid prescribed at discharge, hydrocodone 5 mg was prescribed in 99 cases (50.8%) before decision aid implementation and in 14 cases (7.9%) after implementation. By contrast, oxycodone 5 mg was prescribed in 85 cases (43.6%) before implementation and in 149 cases (84.2%) after implementation.

The number of refill requests was similar before (n = 11 [5.6%]) and after (n = 12 [6.8%]) the aid’s implementation.

Tool reduced opioid availability in the community

The use of a simple patient decision aid—which focuses on opioid education and engages patients in an appropriate postoperative pain management plan—can result in fewer opioid tablets in the community while still providing adequate pain control, the authors concluded.

Online resource. For more on targeted strategies to optimize opioid prescribing after surgery, visit the University of Michigan’s Opioid Prescribing Engagement Network (OPEN) at http://michigan-open.org.

Investigators at the University of Michigan, Ann Arbor, found that a simple patient decision aid can be a useful tool in providing adequate postsurgical pain control to patients while reducing the number of opioid tablets in the community. The shared decision-making aid focuses on educating the patient about opioid use and engages her in an appropriate postoperative pain management plan. Results from this prospective quality improvement study were presented in a poster at the 47th AAGL Global Congress on Minimally Invasive Gynecology (Las Vegas, Nevada, November 11–15, 2018).¹

Annmarie Vilkins, DO, and colleagues’ aim was to evaluate the impact of shared decision-making through the use of a patient decision aid targeting posthysterectomy pain management and opioid use. Can such a targeted strategy help decrease posthysterectomy opioid distribution in the community without compromising patient pain control or satisfaction?

The authors noted that more than 46 people die each day from an overdose involving prescription opioids.² Studies have shown that patients actually use significantly fewer opioid tablets than the amount clinicians generally prescribe following ObGyn surgeries.^3,4 Unused prescription opioid availability has the potential for accidental use or intentional misuse of the unneeded drugs by others.

Study methods

The investigators included all English-speaking patients undergoing hysterectomy for benign disease at their institution from March 1 through July 31, 2018. Data were analyzed from women undergoing laparoscopic, vaginal, or abdominal hysterectomy before (n = 195) and after (n = 177) the decision aid was implemented.

Preoperative education. In the preoperative area, patients were uniformly educated regarding postoperative pain expectations (for example, it is normal to have some pain; the goal is to manage your pain so you can function; some women do not require opioid medications after surgery), risks of opioid medications (such as dependence or addiction; misuse of leftover pills by others), adverse effects (drowsiness; confusion), and the recommended postoperative pain management schedule.

Postoperatively, pain medications included ibuprofen around the clock, acetaminophen as needed (used with caution when hydrocodone with acetaminophen was also prescribed), and opioids only if needed.

Discharge medication planning. Using a visual scale, the investigators then educated patients regarding the maximum number of opioid tablets permitted to be prescribed according to department guidelines and the average number of opioid tablets that a typical patient uses. The number of opioid tablets prescribed varied based on route of hysterectomy (laparoscopic, abdominal, or vaginal). For example, for a laparoscopic hysterectomy, the maximum allowed prescription for oxycodone was 20 tablets, while patients used an average number of 10 tablets.

The patient was then asked to choose her desired number of tablets with which she would like to be discharged.

Structured telephone calls were made to patients 2 weeks postoperatively.

Impact of the decision aid on opioid prescribing

Before implementation of the decision aid, the average number of opioid pills prescribed at discharge was 25 (median, 20–35), while that number dropped to 10 (median, 10–15) after the aid’s implementation. Similarly, the average oral morphine equivalents (OMEs) at time of discharge was 150 (interquartile range [IQR], 120–200) before decision aid implementation and 75 (IQR, 25–150) after decision aid implementation. Similar reductions in average OMEs were observed before and after the aid’s implementation across the 3 hysterectomy routes.

Continue to: According to the type of opioid...

According to the type of opioid prescribed at discharge, hydrocodone 5 mg was prescribed in 99 cases (50.8%) before decision aid implementation and in 14 cases (7.9%) after implementation. By contrast, oxycodone 5 mg was prescribed in 85 cases (43.6%) before implementation and in 149 cases (84.2%) after implementation.

The number of refill requests was similar before (n = 11 [5.6%]) and after (n = 12 [6.8%]) the aid’s implementation.

Tool reduced opioid availability in the community

The use of a simple patient decision aid—which focuses on opioid education and engages patients in an appropriate postoperative pain management plan—can result in fewer opioid tablets in the community while still providing adequate pain control, the authors concluded.

Online resource. For more on targeted strategies to optimize opioid prescribing after surgery, visit the University of Michigan’s Opioid Prescribing Engagement Network (OPEN) at http://michigan-open.org.

Investigators at the University of Michigan, Ann Arbor, found that a simple patient decision aid can be a useful tool in providing adequate postsurgical pain control to patients while reducing the number of opioid tablets in the community. The shared decision-making aid focuses on educating the patient about opioid use and engages her in an appropriate postoperative pain management plan. Results from this prospective quality improvement study were presented in a poster at the 47th AAGL Global Congress on Minimally Invasive Gynecology (Las Vegas, Nevada, November 11–15, 2018).¹

Annmarie Vilkins, DO, and colleagues’ aim was to evaluate the impact of shared decision-making through the use of a patient decision aid targeting posthysterectomy pain management and opioid use. Can such a targeted strategy help decrease posthysterectomy opioid distribution in the community without compromising patient pain control or satisfaction?

The authors noted that more than 46 people die each day from an overdose involving prescription opioids.² Studies have shown that patients actually use significantly fewer opioid tablets than the amount clinicians generally prescribe following ObGyn surgeries.^3,4 Unused prescription opioid availability has the potential for accidental use or intentional misuse of the unneeded drugs by others.

Study methods

The investigators included all English-speaking patients undergoing hysterectomy for benign disease at their institution from March 1 through July 31, 2018. Data were analyzed from women undergoing laparoscopic, vaginal, or abdominal hysterectomy before (n = 195) and after (n = 177) the decision aid was implemented.

Preoperative education. In the preoperative area, patients were uniformly educated regarding postoperative pain expectations (for example, it is normal to have some pain; the goal is to manage your pain so you can function; some women do not require opioid medications after surgery), risks of opioid medications (such as dependence or addiction; misuse of leftover pills by others), adverse effects (drowsiness; confusion), and the recommended postoperative pain management schedule.

Postoperatively, pain medications included ibuprofen around the clock, acetaminophen as needed (used with caution when hydrocodone with acetaminophen was also prescribed), and opioids only if needed.

Discharge medication planning. Using a visual scale, the investigators then educated patients regarding the maximum number of opioid tablets permitted to be prescribed according to department guidelines and the average number of opioid tablets that a typical patient uses. The number of opioid tablets prescribed varied based on route of hysterectomy (laparoscopic, abdominal, or vaginal). For example, for a laparoscopic hysterectomy, the maximum allowed prescription for oxycodone was 20 tablets, while patients used an average number of 10 tablets.

The patient was then asked to choose her desired number of tablets with which she would like to be discharged.

Structured telephone calls were made to patients 2 weeks postoperatively.

Impact of the decision aid on opioid prescribing

Before implementation of the decision aid, the average number of opioid pills prescribed at discharge was 25 (median, 20–35), while that number dropped to 10 (median, 10–15) after the aid’s implementation. Similarly, the average oral morphine equivalents (OMEs) at time of discharge was 150 (interquartile range [IQR], 120–200) before decision aid implementation and 75 (IQR, 25–150) after decision aid implementation. Similar reductions in average OMEs were observed before and after the aid’s implementation across the 3 hysterectomy routes.

Continue to: According to the type of opioid...

According to the type of opioid prescribed at discharge, hydrocodone 5 mg was prescribed in 99 cases (50.8%) before decision aid implementation and in 14 cases (7.9%) after implementation. By contrast, oxycodone 5 mg was prescribed in 85 cases (43.6%) before implementation and in 149 cases (84.2%) after implementation.

The number of refill requests was similar before (n = 11 [5.6%]) and after (n = 12 [6.8%]) the aid’s implementation.

Tool reduced opioid availability in the community

The use of a simple patient decision aid—which focuses on opioid education and engages patients in an appropriate postoperative pain management plan—can result in fewer opioid tablets in the community while still providing adequate pain control, the authors concluded.

Online resource. For more on targeted strategies to optimize opioid prescribing after surgery, visit the University of Michigan’s Opioid Prescribing Engagement Network (OPEN) at http://michigan-open.org.

Scrolling through the GoFundMe website reveals seemingly an endless number of people who need help or community support. A common theme: the cost of health care.

It didn’t start out this way. Back in 2010, when the crowdfunding website began, it suggested fundraisers for “ideas and dreams,” “wedding donations and honeymoon registry” or “special occasions.” A spokeswoman said the bulk of collection efforts from the first year were “related to charities and foundations.” A category for medical needs existed, but it was farther down the list.

In the 9 years since, campaigns to pay for health care have reaped the most cash. Of the $5 billion the company says it has raised, about a third has been for medical expenses from more than 250,000 medical campaigns conducted annually.

Take, for instance, the 25-year-old California woman who had a stroke and “needs financial support for rehabilitation, home nursing, medical equipment, and uncovered medical expenses.” Or the Tennessee couple who want to get pregnant, but whose insurance doesn’t cover the $20,000 worth of “medications, surgeries, scans, lab monitoring, and appointments [that] will need to be paid for upfront and out-of-pocket” for in vitro fertilization.

The prominence of the medical category is the symptom of a broken system, according to CEO Rob Solomon, 51, who has a long tech résumé as an executive at places like Groupon and Yahoo. He said he never realized how hard it was for some people to pay their bills: “I needed to understand the gigantic gaps in the system.”

This year, Time Magazine named Mr. Solomon one of the 50 most influential people in health care.

“We didn’t build the platform to focus on medical expenses,” Mr. Solomon said. But it turned out, he said, to be one of those “categories of need” with which many people struggle.

Mr. Solomon talked to Kaiser Health News’ Rachel Bluth about his company’s role in financing health care and what it says about the system when so many people rely on the kindness of strangers to get treatment. The conversation has been edited for length and clarity.
 

Q: KHN and other news outlets have reported that hospitals often advise patients to crowdfund their transplants. It’s become almost institutionalized to use GoFundMe. How do you feel about that?

It saddens me that this is a reality. Every single day on GoFundMe we see the huge challenges people face. Their stories are heartbreaking.

Some progress has been made here and there with the Affordable Care Act, and it’s under fire, but there’s ever-widening gaps in coverage for treatment, for prescriptions, for everything related to health care costs. Even patients who have insurance and supposedly decent insurance [come up short]. We’ve become an indispensable institution, indispensable technology, and indispensable platform for anyone who finds themselves needing help because there just isn’t adequate coverage or assistance.

I would love nothing more than for “medical” to not be a category on GoFundMe. The reality is, though, that access to health care is connected to the ability to pay for it. If you can’t do that, people die. People suffer. We feel good that our platform is there when people need it.
 

Q: Did anyone expect medical funding would become such a big part of GoFundMe?

I don’t think anyone anticipated it. What we realized early on is that medical need is a gigantic category.

A lot of insurance doesn’t cover clinical trials and research and things like that, where people need access to leading-edge potential treatments. We strive to fill these gaps until the institutions that are supposed to handle this handle it properly. There has to be a renaissance, a dramatic change in public policy, in how the government focuses on this and how the health care companies solve this.

This is very interesting. In the places like the United Kingdom, Canada, and other European countries that have some form of universal or government-sponsored health coverage, medical [costs] are still the largest category. So it’s not just medical bills for treatment. There’s travel and accommodations for families who have to support people when they fall ill.
 

Q: What have you learned that you didn’t know before?

I guess what I realized [when I came] to this job is that I had no notion of how severe the problem is. You read about the debate about single-payer health care and all the issues, the partisan politics. What I really learned is the health care system in the United States is really broken. Way too many people fall through the cracks.

The government is supposed to be there, and sometimes they are. The health care companies are supposed to be there, and sometimes they are. But for literally millions of people they’re not. The only thing you can really do is rely on the kindness of friends and family and community. That’s where GoFundMe comes in.

I was not ready for that at all when I started at the company. When you live and breathe it every day and you see the need that exists, when you realize there are many people with rare diseases but they aren’t diseases a drug company can make money from, they’re just left with nothing.
 

Q: But what does this say about the system?

The system is terrible. It needs to be rethought and retooled. Politicians are failing us. Health care companies are failing us. Those are realities. I don’t want to mince words here. We are facing a huge potential tragedy. We provide relief for a lot of people. But there are people who are not getting relief from us or from the institutions that are supposed to be there. We shouldn’t be the solution to a complex set of systemic problems. They should be solved by the government working properly, and by health care companies working with their constituents. We firmly believe that access to comprehensive health care is a right and things have to be fixed at the local, state, and federal levels of government to make this a reality.

Q: Do you ever worry that medical fundraising on your site is taking away from other causes or other things that need to be funded?

We have billions being raised on our platform on an annual basis. Everything from medical, memorial, and emergency to people funding Little League teams and community projects.

Another thing that’s happened in the last few years is we’ve really become the “take action button.” Whenever there’s a news cycle on something where people want to help, they create GoFundMe campaigns. This government shutdown, for example: We have over a thousand campaigns right now for people who have been affected by it – they’re raising money for people to pay rent, mortgages, car payments while the government isn’t.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Scrolling through the GoFundMe website reveals seemingly an endless number of people who need help or community support. A common theme: the cost of health care.

It didn’t start out this way. Back in 2010, when the crowdfunding website began, it suggested fundraisers for “ideas and dreams,” “wedding donations and honeymoon registry” or “special occasions.” A spokeswoman said the bulk of collection efforts from the first year were “related to charities and foundations.” A category for medical needs existed, but it was farther down the list.

In the 9 years since, campaigns to pay for health care have reaped the most cash. Of the $5 billion the company says it has raised, about a third has been for medical expenses from more than 250,000 medical campaigns conducted annually.

Take, for instance, the 25-year-old California woman who had a stroke and “needs financial support for rehabilitation, home nursing, medical equipment, and uncovered medical expenses.” Or the Tennessee couple who want to get pregnant, but whose insurance doesn’t cover the $20,000 worth of “medications, surgeries, scans, lab monitoring, and appointments [that] will need to be paid for upfront and out-of-pocket” for in vitro fertilization.

The prominence of the medical category is the symptom of a broken system, according to CEO Rob Solomon, 51, who has a long tech résumé as an executive at places like Groupon and Yahoo. He said he never realized how hard it was for some people to pay their bills: “I needed to understand the gigantic gaps in the system.”

This year, Time Magazine named Mr. Solomon one of the 50 most influential people in health care.

“We didn’t build the platform to focus on medical expenses,” Mr. Solomon said. But it turned out, he said, to be one of those “categories of need” with which many people struggle.

Mr. Solomon talked to Kaiser Health News’ Rachel Bluth about his company’s role in financing health care and what it says about the system when so many people rely on the kindness of strangers to get treatment. The conversation has been edited for length and clarity.
 

Q: KHN and other news outlets have reported that hospitals often advise patients to crowdfund their transplants. It’s become almost institutionalized to use GoFundMe. How do you feel about that?

It saddens me that this is a reality. Every single day on GoFundMe we see the huge challenges people face. Their stories are heartbreaking.

Some progress has been made here and there with the Affordable Care Act, and it’s under fire, but there’s ever-widening gaps in coverage for treatment, for prescriptions, for everything related to health care costs. Even patients who have insurance and supposedly decent insurance [come up short]. We’ve become an indispensable institution, indispensable technology, and indispensable platform for anyone who finds themselves needing help because there just isn’t adequate coverage or assistance.

I would love nothing more than for “medical” to not be a category on GoFundMe. The reality is, though, that access to health care is connected to the ability to pay for it. If you can’t do that, people die. People suffer. We feel good that our platform is there when people need it.
 

Q: Did anyone expect medical funding would become such a big part of GoFundMe?

I don’t think anyone anticipated it. What we realized early on is that medical need is a gigantic category.

A lot of insurance doesn’t cover clinical trials and research and things like that, where people need access to leading-edge potential treatments. We strive to fill these gaps until the institutions that are supposed to handle this handle it properly. There has to be a renaissance, a dramatic change in public policy, in how the government focuses on this and how the health care companies solve this.

This is very interesting. In the places like the United Kingdom, Canada, and other European countries that have some form of universal or government-sponsored health coverage, medical [costs] are still the largest category. So it’s not just medical bills for treatment. There’s travel and accommodations for families who have to support people when they fall ill.
 

Q: What have you learned that you didn’t know before?

I guess what I realized [when I came] to this job is that I had no notion of how severe the problem is. You read about the debate about single-payer health care and all the issues, the partisan politics. What I really learned is the health care system in the United States is really broken. Way too many people fall through the cracks.

The government is supposed to be there, and sometimes they are. The health care companies are supposed to be there, and sometimes they are. But for literally millions of people they’re not. The only thing you can really do is rely on the kindness of friends and family and community. That’s where GoFundMe comes in.

I was not ready for that at all when I started at the company. When you live and breathe it every day and you see the need that exists, when you realize there are many people with rare diseases but they aren’t diseases a drug company can make money from, they’re just left with nothing.
 

Q: But what does this say about the system?

The system is terrible. It needs to be rethought and retooled. Politicians are failing us. Health care companies are failing us. Those are realities. I don’t want to mince words here. We are facing a huge potential tragedy. We provide relief for a lot of people. But there are people who are not getting relief from us or from the institutions that are supposed to be there. We shouldn’t be the solution to a complex set of systemic problems. They should be solved by the government working properly, and by health care companies working with their constituents. We firmly believe that access to comprehensive health care is a right and things have to be fixed at the local, state, and federal levels of government to make this a reality.

Q: Do you ever worry that medical fundraising on your site is taking away from other causes or other things that need to be funded?

We have billions being raised on our platform on an annual basis. Everything from medical, memorial, and emergency to people funding Little League teams and community projects.

Another thing that’s happened in the last few years is we’ve really become the “take action button.” Whenever there’s a news cycle on something where people want to help, they create GoFundMe campaigns. This government shutdown, for example: We have over a thousand campaigns right now for people who have been affected by it – they’re raising money for people to pay rent, mortgages, car payments while the government isn’t.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Scrolling through the GoFundMe website reveals seemingly an endless number of people who need help or community support. A common theme: the cost of health care.

It didn’t start out this way. Back in 2010, when the crowdfunding website began, it suggested fundraisers for “ideas and dreams,” “wedding donations and honeymoon registry” or “special occasions.” A spokeswoman said the bulk of collection efforts from the first year were “related to charities and foundations.” A category for medical needs existed, but it was farther down the list.

In the 9 years since, campaigns to pay for health care have reaped the most cash. Of the $5 billion the company says it has raised, about a third has been for medical expenses from more than 250,000 medical campaigns conducted annually.

Take, for instance, the 25-year-old California woman who had a stroke and “needs financial support for rehabilitation, home nursing, medical equipment, and uncovered medical expenses.” Or the Tennessee couple who want to get pregnant, but whose insurance doesn’t cover the $20,000 worth of “medications, surgeries, scans, lab monitoring, and appointments [that] will need to be paid for upfront and out-of-pocket” for in vitro fertilization.

The prominence of the medical category is the symptom of a broken system, according to CEO Rob Solomon, 51, who has a long tech résumé as an executive at places like Groupon and Yahoo. He said he never realized how hard it was for some people to pay their bills: “I needed to understand the gigantic gaps in the system.”

This year, Time Magazine named Mr. Solomon one of the 50 most influential people in health care.

“We didn’t build the platform to focus on medical expenses,” Mr. Solomon said. But it turned out, he said, to be one of those “categories of need” with which many people struggle.

Mr. Solomon talked to Kaiser Health News’ Rachel Bluth about his company’s role in financing health care and what it says about the system when so many people rely on the kindness of strangers to get treatment. The conversation has been edited for length and clarity.
 

Q: KHN and other news outlets have reported that hospitals often advise patients to crowdfund their transplants. It’s become almost institutionalized to use GoFundMe. How do you feel about that?

It saddens me that this is a reality. Every single day on GoFundMe we see the huge challenges people face. Their stories are heartbreaking.

Some progress has been made here and there with the Affordable Care Act, and it’s under fire, but there’s ever-widening gaps in coverage for treatment, for prescriptions, for everything related to health care costs. Even patients who have insurance and supposedly decent insurance [come up short]. We’ve become an indispensable institution, indispensable technology, and indispensable platform for anyone who finds themselves needing help because there just isn’t adequate coverage or assistance.

I would love nothing more than for “medical” to not be a category on GoFundMe. The reality is, though, that access to health care is connected to the ability to pay for it. If you can’t do that, people die. People suffer. We feel good that our platform is there when people need it.
 

Q: Did anyone expect medical funding would become such a big part of GoFundMe?

I don’t think anyone anticipated it. What we realized early on is that medical need is a gigantic category.

A lot of insurance doesn’t cover clinical trials and research and things like that, where people need access to leading-edge potential treatments. We strive to fill these gaps until the institutions that are supposed to handle this handle it properly. There has to be a renaissance, a dramatic change in public policy, in how the government focuses on this and how the health care companies solve this.

This is very interesting. In the places like the United Kingdom, Canada, and other European countries that have some form of universal or government-sponsored health coverage, medical [costs] are still the largest category. So it’s not just medical bills for treatment. There’s travel and accommodations for families who have to support people when they fall ill.
 

Q: What have you learned that you didn’t know before?

I guess what I realized [when I came] to this job is that I had no notion of how severe the problem is. You read about the debate about single-payer health care and all the issues, the partisan politics. What I really learned is the health care system in the United States is really broken. Way too many people fall through the cracks.

The government is supposed to be there, and sometimes they are. The health care companies are supposed to be there, and sometimes they are. But for literally millions of people they’re not. The only thing you can really do is rely on the kindness of friends and family and community. That’s where GoFundMe comes in.

I was not ready for that at all when I started at the company. When you live and breathe it every day and you see the need that exists, when you realize there are many people with rare diseases but they aren’t diseases a drug company can make money from, they’re just left with nothing.
 

Q: But what does this say about the system?

The system is terrible. It needs to be rethought and retooled. Politicians are failing us. Health care companies are failing us. Those are realities. I don’t want to mince words here. We are facing a huge potential tragedy. We provide relief for a lot of people. But there are people who are not getting relief from us or from the institutions that are supposed to be there. We shouldn’t be the solution to a complex set of systemic problems. They should be solved by the government working properly, and by health care companies working with their constituents. We firmly believe that access to comprehensive health care is a right and things have to be fixed at the local, state, and federal levels of government to make this a reality.

Q: Do you ever worry that medical fundraising on your site is taking away from other causes or other things that need to be funded?

We have billions being raised on our platform on an annual basis. Everything from medical, memorial, and emergency to people funding Little League teams and community projects.

Another thing that’s happened in the last few years is we’ve really become the “take action button.” Whenever there’s a news cycle on something where people want to help, they create GoFundMe campaigns. This government shutdown, for example: We have over a thousand campaigns right now for people who have been affected by it – they’re raising money for people to pay rent, mortgages, car payments while the government isn’t.
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Question: You are moonlighting in the emergency department and have just finished treating a 5-year-old boy with an apparent Colles’ fracture, who was accompanied by his mother with bruises on her face. Her exam revealed additional bruises over her abdominal wall. The mother said they accidentally tripped and fell down the stairs, and spontaneously denied any acts of violence in the family.

Given this scenario, which of the following is best?

A. You suspect both child and spousal abuse, but lack sufficient evidence to report the incident.

B. Failure to report based on reasonable suspicion alone may amount to a criminal offense punishable by possible imprisonment.

C. You may face a potential malpractice lawsuit if subsequent injuries caused by abuse could have been prevented had you reported.

D. Mandatory reporting laws apply not only to abuse of children and spouses, but also of the elderly and other vulnerable adults.

E. All are correct except A.

Answer: E. All doctors, especially those working in emergency departments, treat injuries on a regular basis. Accidents probably account for the majority of these injuries, but the most pernicious are those caused by willful abuse or neglect. Such conduct, believed to be widespread and underrecognized, victimizes children, women, the elderly, and other vulnerable groups.

Mandatory reporting laws arose from the need to identify and prevent these activities that cause serious harm and loss of lives. Physicians and other health care workers are in a prime position to diagnose or raise the suspicion of abuse and neglect. This article focuses on laws that mandate physician reporting of such behavior. Not addressed are other reportable situations such as certain infectious diseases, gunshot wounds, threats to third parties, and so on.
 

Child abuse

The best-known example of a mandatory reporting law relates to child abuse, which is broadly defined as when a parent or caretaker emotionally, physically, or sexually abuses, neglects, or abandons a child. Child abuse laws are intended to protect children from serious harm without abridging parental discipline of their children.

Cases of child abuse are pervasive; four or five children are tragically killed by abuse or neglect every day, and each year, some 6 million children are reported as victims of child abuse. Henry Kempe’s studies on the “battered child syndrome” in 1962 served to underscore the physician’s role in exposing child maltreatment, and 1973 saw the enactment of the Child Abuse Prevention and Treatment Act, which set standards for mandatory reporting as a condition for federal funding.

All U.S. states have statutes identifying persons who are required to report suspected child maltreatment to an appropriate agency, such as child protective services. Reasonable suspicion, without need for proof, is sufficient to trigger the mandatory reporting duty. A summary of the general reporting requirements, as well as each state’s key statutory features, are available at Child Welfare Information Gateway.¹

Bruises, fractures, and burns are recurring examples of injuries resulting from child abuse, but there are many others, including severe emotional harm, which is an important consequence. Clues to abuse include a child’s fearful and anxious demeanor, wearing clothes to hide injuries, and inappropriate sexual conduct.² The perpetrators and/or complicit parties typically blame an innocent home accident for the victim’s injuries to mislead the health care provider.
 

Elder abuse

Elder abuse is broadly construed to include physical, sexual, and psychological abuse, as well as financial exploitation and caregiver neglect.³ It is a serious problem in the United States, estimated in 2008 to affect 1 in 10 elders. The figure is likely an underestimate, because many elderly victims are afraid or unwilling to lodge a complaint against the abuser whom they love and may depend upon.⁴

The law, which protects the “elderly” (e.g., those aged 62 years or older in Hawaii), may also be extended to other younger vulnerable adults, who because of an impairment, are unable to 1) communicate or make responsible decisions to manage one’s own care or resources, 2) carry out or arrange for essential activities of daily living, or 3) protect one’s self from abuse.⁵

The law mandates reporting where there is reason to believe abuse has occurred or the vulnerable adult is in danger of abuse if immediate action is not taken. Reporting statutes for elder abuse vary somewhat on the identity of mandated reporters (health care providers are always included), the victim’s mental capacity, dwelling place (home or in an assisted-living facility), and type of purported activity that warrants reporting.
 

Domestic violence

As defined by the National Coalition Against Domestic Violence, “Domestic violence is the willful intimidation, physical assault, battery, sexual assault, and/or other abusive behavior as part of a systematic pattern of power and control perpetrated by one intimate partner against another. ... The frequency and severity of domestic violence can vary dramatically; however, the one constant component of domestic violence is one partner’s consistent efforts to maintain power and control over the other.”⁶ Domestic violence is said to have reached epidemic proportions, with one in four women experiencing it at some point in her life.

Virtually all states mandate the reporting of domestic violence by health care providers if there is a reasonable suspicion that observed patient injuries are the result of physical abuse.⁷ California, for example, requires the provider to call local law enforcement as soon as possible or to send in a written report within 48 hours.

There may be exceptions to required reporting, as when an adult victim withholds consent but accepts victim referral services. State laws encourage but do not always require that the health care provider inform the patient about the report, but federal law dictates otherwise unless this puts the patient at risk. Hawaii’s domestic violence laws were originally enacted to deter spousal abuse, but they now also protect other household members.⁸

Any individual who assumes a duty or responsibility pursuant to all of these reporting laws is immunized from criminal or civil liability. On the other hand, a mandated reporter who knowingly fails to report an incident or who willfully prevents another person from reporting such an incident commits a criminal offence.

In the case of a physician, there is the added risk of a malpractice lawsuit based on “violation of statute” (breach of a legal duty), should another injury occur down the road that was arguably preventable by his or her failure to report.

Experts generally believe that mandatory reporting laws are important in identifying child maltreatment. However, it has been asserted that despite a 5-decade history of mandatory reporting, no clear endpoints attest to the efficacy of this approach, and it is argued that no data exist to demonstrate that incremental increases in reporting have contributed to child safety.

Particularly challenging are attempts at impact comparisons between states with different policies. A number of countries, including the United Kingdom, do not have mandatory reporting laws and regulate reporting by professional societies.⁹

In addition, some critics of mandatory reporting raise concerns surrounding law enforcement showing up at the victim’s house to question the family about abuse, or to make an arrest or issue warnings. They posit that when the behavior of an abuser is under scrutiny, this can paradoxically create a potentially more dangerous environment for the patient-victim, whom the perpetrator now considers to have betrayed his or her trust. Others bemoan that revealing patient confidences violates the physician’s ethical code.

However, the intolerable incidence of violence against the vulnerable has properly made mandatory reporting the law of the land. Although the criminal penalty is currently light for failure to report, there is a move toward increasing its severity. Hawaii, for example, recently introduced Senate Bill 2477 that makes nonreporting by those required to do so a Class C felony punishable by up to 5 years in prison. The offense currently is a petty misdemeanor punishable by up to 30 days in jail.
 

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. Child Welfare Information Gateway (2016). Mandatory reporters of child abuse and neglect. Washington, D.C.: U.S. Department of Health and Human Services, Children’s Bureau. Available at www.childwelfare.gov; email: [email protected]; phone: 800-394-3366.

2. Available at www.childwelfare.gov/topics/can.

3. Available at www.justice.gov/elderjustice/elder-justice-statutes-0.

4. Available at www.cdc.gov/violenceprevention/elderabuse/index.html.

5. Hawaii Revised Statutes, Sec. 346-222, 346-224, 346-250, 412:3-114.5.

6. Available at ncadv.org.

7. Ann Emerg Med. 2002 Jan;39(1):56-60.

8. Hawaii Revised Statutes, Sec. 709-906.

9. Pediatrics. 2017 Apr;139(4). pii: e20163511.

Question: You are moonlighting in the emergency department and have just finished treating a 5-year-old boy with an apparent Colles’ fracture, who was accompanied by his mother with bruises on her face. Her exam revealed additional bruises over her abdominal wall. The mother said they accidentally tripped and fell down the stairs, and spontaneously denied any acts of violence in the family.

Given this scenario, which of the following is best?

A. You suspect both child and spousal abuse, but lack sufficient evidence to report the incident.

B. Failure to report based on reasonable suspicion alone may amount to a criminal offense punishable by possible imprisonment.

C. You may face a potential malpractice lawsuit if subsequent injuries caused by abuse could have been prevented had you reported.

D. Mandatory reporting laws apply not only to abuse of children and spouses, but also of the elderly and other vulnerable adults.

E. All are correct except A.

Answer: E. All doctors, especially those working in emergency departments, treat injuries on a regular basis. Accidents probably account for the majority of these injuries, but the most pernicious are those caused by willful abuse or neglect. Such conduct, believed to be widespread and underrecognized, victimizes children, women, the elderly, and other vulnerable groups.

Mandatory reporting laws arose from the need to identify and prevent these activities that cause serious harm and loss of lives. Physicians and other health care workers are in a prime position to diagnose or raise the suspicion of abuse and neglect. This article focuses on laws that mandate physician reporting of such behavior. Not addressed are other reportable situations such as certain infectious diseases, gunshot wounds, threats to third parties, and so on.
 

Child abuse

The best-known example of a mandatory reporting law relates to child abuse, which is broadly defined as when a parent or caretaker emotionally, physically, or sexually abuses, neglects, or abandons a child. Child abuse laws are intended to protect children from serious harm without abridging parental discipline of their children.

Cases of child abuse are pervasive; four or five children are tragically killed by abuse or neglect every day, and each year, some 6 million children are reported as victims of child abuse. Henry Kempe’s studies on the “battered child syndrome” in 1962 served to underscore the physician’s role in exposing child maltreatment, and 1973 saw the enactment of the Child Abuse Prevention and Treatment Act, which set standards for mandatory reporting as a condition for federal funding.

All U.S. states have statutes identifying persons who are required to report suspected child maltreatment to an appropriate agency, such as child protective services. Reasonable suspicion, without need for proof, is sufficient to trigger the mandatory reporting duty. A summary of the general reporting requirements, as well as each state’s key statutory features, are available at Child Welfare Information Gateway.¹

Bruises, fractures, and burns are recurring examples of injuries resulting from child abuse, but there are many others, including severe emotional harm, which is an important consequence. Clues to abuse include a child’s fearful and anxious demeanor, wearing clothes to hide injuries, and inappropriate sexual conduct.² The perpetrators and/or complicit parties typically blame an innocent home accident for the victim’s injuries to mislead the health care provider.
 

Elder abuse

Elder abuse is broadly construed to include physical, sexual, and psychological abuse, as well as financial exploitation and caregiver neglect.³ It is a serious problem in the United States, estimated in 2008 to affect 1 in 10 elders. The figure is likely an underestimate, because many elderly victims are afraid or unwilling to lodge a complaint against the abuser whom they love and may depend upon.⁴

The law, which protects the “elderly” (e.g., those aged 62 years or older in Hawaii), may also be extended to other younger vulnerable adults, who because of an impairment, are unable to 1) communicate or make responsible decisions to manage one’s own care or resources, 2) carry out or arrange for essential activities of daily living, or 3) protect one’s self from abuse.⁵

The law mandates reporting where there is reason to believe abuse has occurred or the vulnerable adult is in danger of abuse if immediate action is not taken. Reporting statutes for elder abuse vary somewhat on the identity of mandated reporters (health care providers are always included), the victim’s mental capacity, dwelling place (home or in an assisted-living facility), and type of purported activity that warrants reporting.
 

Domestic violence

As defined by the National Coalition Against Domestic Violence, “Domestic violence is the willful intimidation, physical assault, battery, sexual assault, and/or other abusive behavior as part of a systematic pattern of power and control perpetrated by one intimate partner against another. ... The frequency and severity of domestic violence can vary dramatically; however, the one constant component of domestic violence is one partner’s consistent efforts to maintain power and control over the other.”⁶ Domestic violence is said to have reached epidemic proportions, with one in four women experiencing it at some point in her life.

Virtually all states mandate the reporting of domestic violence by health care providers if there is a reasonable suspicion that observed patient injuries are the result of physical abuse.⁷ California, for example, requires the provider to call local law enforcement as soon as possible or to send in a written report within 48 hours.

There may be exceptions to required reporting, as when an adult victim withholds consent but accepts victim referral services. State laws encourage but do not always require that the health care provider inform the patient about the report, but federal law dictates otherwise unless this puts the patient at risk. Hawaii’s domestic violence laws were originally enacted to deter spousal abuse, but they now also protect other household members.⁸

Any individual who assumes a duty or responsibility pursuant to all of these reporting laws is immunized from criminal or civil liability. On the other hand, a mandated reporter who knowingly fails to report an incident or who willfully prevents another person from reporting such an incident commits a criminal offence.

In the case of a physician, there is the added risk of a malpractice lawsuit based on “violation of statute” (breach of a legal duty), should another injury occur down the road that was arguably preventable by his or her failure to report.

Experts generally believe that mandatory reporting laws are important in identifying child maltreatment. However, it has been asserted that despite a 5-decade history of mandatory reporting, no clear endpoints attest to the efficacy of this approach, and it is argued that no data exist to demonstrate that incremental increases in reporting have contributed to child safety.

Particularly challenging are attempts at impact comparisons between states with different policies. A number of countries, including the United Kingdom, do not have mandatory reporting laws and regulate reporting by professional societies.⁹

In addition, some critics of mandatory reporting raise concerns surrounding law enforcement showing up at the victim’s house to question the family about abuse, or to make an arrest or issue warnings. They posit that when the behavior of an abuser is under scrutiny, this can paradoxically create a potentially more dangerous environment for the patient-victim, whom the perpetrator now considers to have betrayed his or her trust. Others bemoan that revealing patient confidences violates the physician’s ethical code.

However, the intolerable incidence of violence against the vulnerable has properly made mandatory reporting the law of the land. Although the criminal penalty is currently light for failure to report, there is a move toward increasing its severity. Hawaii, for example, recently introduced Senate Bill 2477 that makes nonreporting by those required to do so a Class C felony punishable by up to 5 years in prison. The offense currently is a petty misdemeanor punishable by up to 30 days in jail.
 

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. Child Welfare Information Gateway (2016). Mandatory reporters of child abuse and neglect. Washington, D.C.: U.S. Department of Health and Human Services, Children’s Bureau. Available at www.childwelfare.gov; email: [email protected]; phone: 800-394-3366.

2. Available at www.childwelfare.gov/topics/can.

3. Available at www.justice.gov/elderjustice/elder-justice-statutes-0.

4. Available at www.cdc.gov/violenceprevention/elderabuse/index.html.

5. Hawaii Revised Statutes, Sec. 346-222, 346-224, 346-250, 412:3-114.5.

6. Available at ncadv.org.

7. Ann Emerg Med. 2002 Jan;39(1):56-60.

8. Hawaii Revised Statutes, Sec. 709-906.

9. Pediatrics. 2017 Apr;139(4). pii: e20163511.

Question: You are moonlighting in the emergency department and have just finished treating a 5-year-old boy with an apparent Colles’ fracture, who was accompanied by his mother with bruises on her face. Her exam revealed additional bruises over her abdominal wall. The mother said they accidentally tripped and fell down the stairs, and spontaneously denied any acts of violence in the family.

Given this scenario, which of the following is best?

A. You suspect both child and spousal abuse, but lack sufficient evidence to report the incident.

B. Failure to report based on reasonable suspicion alone may amount to a criminal offense punishable by possible imprisonment.

C. You may face a potential malpractice lawsuit if subsequent injuries caused by abuse could have been prevented had you reported.

D. Mandatory reporting laws apply not only to abuse of children and spouses, but also of the elderly and other vulnerable adults.

E. All are correct except A.

Answer: E. All doctors, especially those working in emergency departments, treat injuries on a regular basis. Accidents probably account for the majority of these injuries, but the most pernicious are those caused by willful abuse or neglect. Such conduct, believed to be widespread and underrecognized, victimizes children, women, the elderly, and other vulnerable groups.

Mandatory reporting laws arose from the need to identify and prevent these activities that cause serious harm and loss of lives. Physicians and other health care workers are in a prime position to diagnose or raise the suspicion of abuse and neglect. This article focuses on laws that mandate physician reporting of such behavior. Not addressed are other reportable situations such as certain infectious diseases, gunshot wounds, threats to third parties, and so on.
 

Child abuse

The best-known example of a mandatory reporting law relates to child abuse, which is broadly defined as when a parent or caretaker emotionally, physically, or sexually abuses, neglects, or abandons a child. Child abuse laws are intended to protect children from serious harm without abridging parental discipline of their children.

Cases of child abuse are pervasive; four or five children are tragically killed by abuse or neglect every day, and each year, some 6 million children are reported as victims of child abuse. Henry Kempe’s studies on the “battered child syndrome” in 1962 served to underscore the physician’s role in exposing child maltreatment, and 1973 saw the enactment of the Child Abuse Prevention and Treatment Act, which set standards for mandatory reporting as a condition for federal funding.

All U.S. states have statutes identifying persons who are required to report suspected child maltreatment to an appropriate agency, such as child protective services. Reasonable suspicion, without need for proof, is sufficient to trigger the mandatory reporting duty. A summary of the general reporting requirements, as well as each state’s key statutory features, are available at Child Welfare Information Gateway.¹

Bruises, fractures, and burns are recurring examples of injuries resulting from child abuse, but there are many others, including severe emotional harm, which is an important consequence. Clues to abuse include a child’s fearful and anxious demeanor, wearing clothes to hide injuries, and inappropriate sexual conduct.² The perpetrators and/or complicit parties typically blame an innocent home accident for the victim’s injuries to mislead the health care provider.
 

Elder abuse

Elder abuse is broadly construed to include physical, sexual, and psychological abuse, as well as financial exploitation and caregiver neglect.³ It is a serious problem in the United States, estimated in 2008 to affect 1 in 10 elders. The figure is likely an underestimate, because many elderly victims are afraid or unwilling to lodge a complaint against the abuser whom they love and may depend upon.⁴

The law, which protects the “elderly” (e.g., those aged 62 years or older in Hawaii), may also be extended to other younger vulnerable adults, who because of an impairment, are unable to 1) communicate or make responsible decisions to manage one’s own care or resources, 2) carry out or arrange for essential activities of daily living, or 3) protect one’s self from abuse.⁵

The law mandates reporting where there is reason to believe abuse has occurred or the vulnerable adult is in danger of abuse if immediate action is not taken. Reporting statutes for elder abuse vary somewhat on the identity of mandated reporters (health care providers are always included), the victim’s mental capacity, dwelling place (home or in an assisted-living facility), and type of purported activity that warrants reporting.
 

Domestic violence

As defined by the National Coalition Against Domestic Violence, “Domestic violence is the willful intimidation, physical assault, battery, sexual assault, and/or other abusive behavior as part of a systematic pattern of power and control perpetrated by one intimate partner against another. ... The frequency and severity of domestic violence can vary dramatically; however, the one constant component of domestic violence is one partner’s consistent efforts to maintain power and control over the other.”⁶ Domestic violence is said to have reached epidemic proportions, with one in four women experiencing it at some point in her life.

Virtually all states mandate the reporting of domestic violence by health care providers if there is a reasonable suspicion that observed patient injuries are the result of physical abuse.⁷ California, for example, requires the provider to call local law enforcement as soon as possible or to send in a written report within 48 hours.

There may be exceptions to required reporting, as when an adult victim withholds consent but accepts victim referral services. State laws encourage but do not always require that the health care provider inform the patient about the report, but federal law dictates otherwise unless this puts the patient at risk. Hawaii’s domestic violence laws were originally enacted to deter spousal abuse, but they now also protect other household members.⁸

Any individual who assumes a duty or responsibility pursuant to all of these reporting laws is immunized from criminal or civil liability. On the other hand, a mandated reporter who knowingly fails to report an incident or who willfully prevents another person from reporting such an incident commits a criminal offence.

In the case of a physician, there is the added risk of a malpractice lawsuit based on “violation of statute” (breach of a legal duty), should another injury occur down the road that was arguably preventable by his or her failure to report.

Experts generally believe that mandatory reporting laws are important in identifying child maltreatment. However, it has been asserted that despite a 5-decade history of mandatory reporting, no clear endpoints attest to the efficacy of this approach, and it is argued that no data exist to demonstrate that incremental increases in reporting have contributed to child safety.

Particularly challenging are attempts at impact comparisons between states with different policies. A number of countries, including the United Kingdom, do not have mandatory reporting laws and regulate reporting by professional societies.⁹

In addition, some critics of mandatory reporting raise concerns surrounding law enforcement showing up at the victim’s house to question the family about abuse, or to make an arrest or issue warnings. They posit that when the behavior of an abuser is under scrutiny, this can paradoxically create a potentially more dangerous environment for the patient-victim, whom the perpetrator now considers to have betrayed his or her trust. Others bemoan that revealing patient confidences violates the physician’s ethical code.

However, the intolerable incidence of violence against the vulnerable has properly made mandatory reporting the law of the land. Although the criminal penalty is currently light for failure to report, there is a move toward increasing its severity. Hawaii, for example, recently introduced Senate Bill 2477 that makes nonreporting by those required to do so a Class C felony punishable by up to 5 years in prison. The offense currently is a petty misdemeanor punishable by up to 30 days in jail.
 

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. Child Welfare Information Gateway (2016). Mandatory reporters of child abuse and neglect. Washington, D.C.: U.S. Department of Health and Human Services, Children’s Bureau. Available at www.childwelfare.gov; email: [email protected]; phone: 800-394-3366.

2. Available at www.childwelfare.gov/topics/can.

3. Available at www.justice.gov/elderjustice/elder-justice-statutes-0.

4. Available at www.cdc.gov/violenceprevention/elderabuse/index.html.

5. Hawaii Revised Statutes, Sec. 346-222, 346-224, 346-250, 412:3-114.5.

6. Available at ncadv.org.

7. Ann Emerg Med. 2002 Jan;39(1):56-60.

8. Hawaii Revised Statutes, Sec. 709-906.

9. Pediatrics. 2017 Apr;139(4). pii: e20163511.