DUBROVNIK, CROATIA – Diagnosing chronic myelomonocytic leukemia (CMML) remains a challenge in 2018.

Even with updated World Health Organization (WHO) criteria, karyotyping, and genetic analyses, it can be difficult to distinguish CMML from other conditions, according to Nadira Durakovic, MD, PhD, of the University Hospital Centre Zagreb (Croatia).

However, there are characteristics that differentiate CMML from myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and atypical chronic myeloid leukemia (CML), Dr. Durakovic said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

Studies have suggested that monocyte subset distribution analysis can be useful for diagnosing CMML.

According to the 2016 WHO classification, patients have CMML if:

• They have persistent peripheral blood monocytosis (1×10⁹/L), with monocytes accounting for 10% of the white blood cell count.
• They do not meet WHO criteria for BCR-ABL1-positive CML, primary myelofibrosis, polycythemia vera, or essential thrombocythemia.
• There is no evidence of PCM1-JAK2 or PDGFRA, PDGFRB, or FGFR1 rearrangement.
• They have fewer than 20% blasts in the blood and bone marrow they have dysplasia in one or more myeloid lineages.

If myelodysplasia is absent or minimal, an acquired clonal cytogenetic or molecular genetic abnormality must be present. Alternatively, if patients have monocytosis that has persisted for at least 3 months, and all other causes of monocytosis have been excluded, “you can say that your patient has CMML,” Dr. Durakovic said.

Other causes of monocytosis include infections, malignancies, medications, inflammatory conditions, and other conditions, such as pregnancy.

However, Dr. Durakovic pointed out that the cause of monocytosis cannot always be determined, and, in some cases, CMML patients may not meet the WHO criteria.

“There are cases where there just aren’t enough monocytes to fulfill the WHO criteria,” Dr. Durakovic said. “You can have a patient with peripheral blood cytopenia and monocytosis who does not have 1,000 monocytes. Patients can have progressive dysplasia, can have splenomegaly, be really sick, but fail to meet WHO criteria.”
 

Differential diagnosis

“Differentiating CMML from myelodysplastic syndromes can be tough,” Dr. Durakovic said. “There are dysplastic features that are present in CMML ... but, in CMML, they are more subtle, and they are more difficult to appreciate than in myelodysplastic syndromes.”

The ratio of myeloid to erythroid cells is elevated in CMML, and patients may have atypical monocytes (paramyeloid cells) that are unique to CMML.

Dr. Durakovic noted that megakaryocyte dysplasia in CMML can be characterized by “myeloproliferative megakaryocytes,” which are large cells that cluster and have hyperlobulated nuclei, or “MDS megakaryocytes,” which are small, solitary cells with hypolobulated nuclei.

She noted that “MPN phenotype” CMML is characterized by leukocytosis, monocytosis, hepatomegaly, splenomegaly, and clinical features of myeloproliferation (fatigue, night sweats, bone pain, weight loss, etc.).

Thirty percent of cases are associated with splenomegaly, and 30% of patients can have an increase in bone marrow reticulin fibrosis.

Dr. Durakovic also noted that a prior MPN diagnosis excludes CMML. The presence of common MPN mutations, such as JAK2, CALR, or MPL, suggests a patient has an MPN with monocytosis rather than CMML.

Patients who have unclassified MPNs or MDS, rather than CMML, either do not have 1,000 monocytes or the monocytes do not represent more than 10% of the differential, Dr. Durakovic said.

It can also be difficult to differentiate CMML from atypical CML.

“Atypical CML is characterized by profound dysgranulopoiesis, absence of the BCR-ABL1 fusion gene, and neutrophilia,” Dr. Durakovic explained. “Those patients [commonly] have monocytosis, but, here, that 10% rule is valuable because their monocytes comprise less than 10% of the entire white blood cell count.”
 

Karyotyping, genotyping, and immunophenotyping

“There is no disease-defining karyotype abnormality [in CMML],” Dr. Durakovic said.

She said 30% of patients have abnormal karyotype, and the most common abnormality is trisomy 8. Unlike in patients with MDS, del(5q) and monosomal karyotypes are infrequent in patients with CMML.

Similarly, there are no “disease-defining” mutations or genetic changes in CMML, although CMML is genetically distinct from MDS, Dr. Durakovic said.

For instance, SRSF2 encodes a component of the spliceosome that is mutated in almost half of CMML patients and less than 10% of MDS patients. Likewise, ASLX1 and TET2 are “much more frequently involved” in CMML than in MDS, Dr. Durakovic said.

In a 2012 study of 275 CMML patients, researchers found that 93% of patients had at least one somatic mutation in nine recurrently mutated genes – SRFS2, ASXL1, CBL, EZH2, JAK2V617F, KRAS, NRAS, RUNX1, and TET2 (Blood. 2012;120:3080-8).

However, Dr. Durakovic noted that these mutations are found in other disorders as well, so this information may not be helpful in differentiating CMML from other disorders.

A 2015 study revealed a technique that does appear useful for identifying CMML – monocyte subset distribution analysis. For this analysis, monocytes are divided into the following categories:

• Classical/MO1 (CD14^bright/CD16⁻).
• Intermediate/MO2 (CD14^bright/CD16⁺).
• Nonclassical/MO3 (CD14^dim/CD16⁺).

The researchers found that CMML patients had an increase in the fraction of classical monocytes (with a cutoff value of 94%), as compared to healthy control subjects, patients with another hematologic disorder, and patients with reactive monocytosis (Blood. 2015 Jun 4;125[23]:3618-26).

A 2018 study confirmed that monocyte subset distribution analysis could differentiate CMML from other hematologic disorders, with the exception of atypical CML. This study also suggested that a decreased percentage of non-classical monocytes was more sensitive than an increased percentage of classical monocytes (Am J Clin Pathol. 2018 Aug 30;150[4]:293-302).

Despite the differences between these studies, “monocyte subset distribution analysis is showing promise as a method of identifying hard-to-identify CMML patients with ease and affordability,” Dr. Durakovic said.

She added that the technique can be implemented in clinical practice using the Hematoflow solution.

Dr. Durakovic did not report any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.
 

[email protected]
 

DUBROVNIK, CROATIA – Diagnosing chronic myelomonocytic leukemia (CMML) remains a challenge in 2018.

Even with updated World Health Organization (WHO) criteria, karyotyping, and genetic analyses, it can be difficult to distinguish CMML from other conditions, according to Nadira Durakovic, MD, PhD, of the University Hospital Centre Zagreb (Croatia).

However, there are characteristics that differentiate CMML from myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and atypical chronic myeloid leukemia (CML), Dr. Durakovic said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

Studies have suggested that monocyte subset distribution analysis can be useful for diagnosing CMML.

According to the 2016 WHO classification, patients have CMML if:

• They have persistent peripheral blood monocytosis (1×10⁹/L), with monocytes accounting for 10% of the white blood cell count.
• They do not meet WHO criteria for BCR-ABL1-positive CML, primary myelofibrosis, polycythemia vera, or essential thrombocythemia.
• There is no evidence of PCM1-JAK2 or PDGFRA, PDGFRB, or FGFR1 rearrangement.
• They have fewer than 20% blasts in the blood and bone marrow they have dysplasia in one or more myeloid lineages.

If myelodysplasia is absent or minimal, an acquired clonal cytogenetic or molecular genetic abnormality must be present. Alternatively, if patients have monocytosis that has persisted for at least 3 months, and all other causes of monocytosis have been excluded, “you can say that your patient has CMML,” Dr. Durakovic said.

Other causes of monocytosis include infections, malignancies, medications, inflammatory conditions, and other conditions, such as pregnancy.

However, Dr. Durakovic pointed out that the cause of monocytosis cannot always be determined, and, in some cases, CMML patients may not meet the WHO criteria.

“There are cases where there just aren’t enough monocytes to fulfill the WHO criteria,” Dr. Durakovic said. “You can have a patient with peripheral blood cytopenia and monocytosis who does not have 1,000 monocytes. Patients can have progressive dysplasia, can have splenomegaly, be really sick, but fail to meet WHO criteria.”
 

Differential diagnosis

“Differentiating CMML from myelodysplastic syndromes can be tough,” Dr. Durakovic said. “There are dysplastic features that are present in CMML ... but, in CMML, they are more subtle, and they are more difficult to appreciate than in myelodysplastic syndromes.”

The ratio of myeloid to erythroid cells is elevated in CMML, and patients may have atypical monocytes (paramyeloid cells) that are unique to CMML.

Dr. Durakovic noted that megakaryocyte dysplasia in CMML can be characterized by “myeloproliferative megakaryocytes,” which are large cells that cluster and have hyperlobulated nuclei, or “MDS megakaryocytes,” which are small, solitary cells with hypolobulated nuclei.

She noted that “MPN phenotype” CMML is characterized by leukocytosis, monocytosis, hepatomegaly, splenomegaly, and clinical features of myeloproliferation (fatigue, night sweats, bone pain, weight loss, etc.).

Thirty percent of cases are associated with splenomegaly, and 30% of patients can have an increase in bone marrow reticulin fibrosis.

Dr. Durakovic also noted that a prior MPN diagnosis excludes CMML. The presence of common MPN mutations, such as JAK2, CALR, or MPL, suggests a patient has an MPN with monocytosis rather than CMML.

Patients who have unclassified MPNs or MDS, rather than CMML, either do not have 1,000 monocytes or the monocytes do not represent more than 10% of the differential, Dr. Durakovic said.

It can also be difficult to differentiate CMML from atypical CML.

“Atypical CML is characterized by profound dysgranulopoiesis, absence of the BCR-ABL1 fusion gene, and neutrophilia,” Dr. Durakovic explained. “Those patients [commonly] have monocytosis, but, here, that 10% rule is valuable because their monocytes comprise less than 10% of the entire white blood cell count.”
 

Karyotyping, genotyping, and immunophenotyping

“There is no disease-defining karyotype abnormality [in CMML],” Dr. Durakovic said.

She said 30% of patients have abnormal karyotype, and the most common abnormality is trisomy 8. Unlike in patients with MDS, del(5q) and monosomal karyotypes are infrequent in patients with CMML.

Similarly, there are no “disease-defining” mutations or genetic changes in CMML, although CMML is genetically distinct from MDS, Dr. Durakovic said.

For instance, SRSF2 encodes a component of the spliceosome that is mutated in almost half of CMML patients and less than 10% of MDS patients. Likewise, ASLX1 and TET2 are “much more frequently involved” in CMML than in MDS, Dr. Durakovic said.

In a 2012 study of 275 CMML patients, researchers found that 93% of patients had at least one somatic mutation in nine recurrently mutated genes – SRFS2, ASXL1, CBL, EZH2, JAK2V617F, KRAS, NRAS, RUNX1, and TET2 (Blood. 2012;120:3080-8).

However, Dr. Durakovic noted that these mutations are found in other disorders as well, so this information may not be helpful in differentiating CMML from other disorders.

A 2015 study revealed a technique that does appear useful for identifying CMML – monocyte subset distribution analysis. For this analysis, monocytes are divided into the following categories:

• Classical/MO1 (CD14^bright/CD16⁻).
• Intermediate/MO2 (CD14^bright/CD16⁺).
• Nonclassical/MO3 (CD14^dim/CD16⁺).

The researchers found that CMML patients had an increase in the fraction of classical monocytes (with a cutoff value of 94%), as compared to healthy control subjects, patients with another hematologic disorder, and patients with reactive monocytosis (Blood. 2015 Jun 4;125[23]:3618-26).

A 2018 study confirmed that monocyte subset distribution analysis could differentiate CMML from other hematologic disorders, with the exception of atypical CML. This study also suggested that a decreased percentage of non-classical monocytes was more sensitive than an increased percentage of classical monocytes (Am J Clin Pathol. 2018 Aug 30;150[4]:293-302).

Despite the differences between these studies, “monocyte subset distribution analysis is showing promise as a method of identifying hard-to-identify CMML patients with ease and affordability,” Dr. Durakovic said.

She added that the technique can be implemented in clinical practice using the Hematoflow solution.

Dr. Durakovic did not report any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.
 

[email protected]
 

DUBROVNIK, CROATIA – Diagnosing chronic myelomonocytic leukemia (CMML) remains a challenge in 2018.

Even with updated World Health Organization (WHO) criteria, karyotyping, and genetic analyses, it can be difficult to distinguish CMML from other conditions, according to Nadira Durakovic, MD, PhD, of the University Hospital Centre Zagreb (Croatia).

However, there are characteristics that differentiate CMML from myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and atypical chronic myeloid leukemia (CML), Dr. Durakovic said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

Studies have suggested that monocyte subset distribution analysis can be useful for diagnosing CMML.

According to the 2016 WHO classification, patients have CMML if:

• They have persistent peripheral blood monocytosis (1×10⁹/L), with monocytes accounting for 10% of the white blood cell count.
• They do not meet WHO criteria for BCR-ABL1-positive CML, primary myelofibrosis, polycythemia vera, or essential thrombocythemia.
• There is no evidence of PCM1-JAK2 or PDGFRA, PDGFRB, or FGFR1 rearrangement.
• They have fewer than 20% blasts in the blood and bone marrow they have dysplasia in one or more myeloid lineages.

If myelodysplasia is absent or minimal, an acquired clonal cytogenetic or molecular genetic abnormality must be present. Alternatively, if patients have monocytosis that has persisted for at least 3 months, and all other causes of monocytosis have been excluded, “you can say that your patient has CMML,” Dr. Durakovic said.

Other causes of monocytosis include infections, malignancies, medications, inflammatory conditions, and other conditions, such as pregnancy.

However, Dr. Durakovic pointed out that the cause of monocytosis cannot always be determined, and, in some cases, CMML patients may not meet the WHO criteria.

“There are cases where there just aren’t enough monocytes to fulfill the WHO criteria,” Dr. Durakovic said. “You can have a patient with peripheral blood cytopenia and monocytosis who does not have 1,000 monocytes. Patients can have progressive dysplasia, can have splenomegaly, be really sick, but fail to meet WHO criteria.”
 

Differential diagnosis

“Differentiating CMML from myelodysplastic syndromes can be tough,” Dr. Durakovic said. “There are dysplastic features that are present in CMML ... but, in CMML, they are more subtle, and they are more difficult to appreciate than in myelodysplastic syndromes.”

The ratio of myeloid to erythroid cells is elevated in CMML, and patients may have atypical monocytes (paramyeloid cells) that are unique to CMML.

Dr. Durakovic noted that megakaryocyte dysplasia in CMML can be characterized by “myeloproliferative megakaryocytes,” which are large cells that cluster and have hyperlobulated nuclei, or “MDS megakaryocytes,” which are small, solitary cells with hypolobulated nuclei.

She noted that “MPN phenotype” CMML is characterized by leukocytosis, monocytosis, hepatomegaly, splenomegaly, and clinical features of myeloproliferation (fatigue, night sweats, bone pain, weight loss, etc.).

Thirty percent of cases are associated with splenomegaly, and 30% of patients can have an increase in bone marrow reticulin fibrosis.

Dr. Durakovic also noted that a prior MPN diagnosis excludes CMML. The presence of common MPN mutations, such as JAK2, CALR, or MPL, suggests a patient has an MPN with monocytosis rather than CMML.

Patients who have unclassified MPNs or MDS, rather than CMML, either do not have 1,000 monocytes or the monocytes do not represent more than 10% of the differential, Dr. Durakovic said.

It can also be difficult to differentiate CMML from atypical CML.

“Atypical CML is characterized by profound dysgranulopoiesis, absence of the BCR-ABL1 fusion gene, and neutrophilia,” Dr. Durakovic explained. “Those patients [commonly] have monocytosis, but, here, that 10% rule is valuable because their monocytes comprise less than 10% of the entire white blood cell count.”
 

Karyotyping, genotyping, and immunophenotyping

“There is no disease-defining karyotype abnormality [in CMML],” Dr. Durakovic said.

She said 30% of patients have abnormal karyotype, and the most common abnormality is trisomy 8. Unlike in patients with MDS, del(5q) and monosomal karyotypes are infrequent in patients with CMML.

Similarly, there are no “disease-defining” mutations or genetic changes in CMML, although CMML is genetically distinct from MDS, Dr. Durakovic said.

For instance, SRSF2 encodes a component of the spliceosome that is mutated in almost half of CMML patients and less than 10% of MDS patients. Likewise, ASLX1 and TET2 are “much more frequently involved” in CMML than in MDS, Dr. Durakovic said.

In a 2012 study of 275 CMML patients, researchers found that 93% of patients had at least one somatic mutation in nine recurrently mutated genes – SRFS2, ASXL1, CBL, EZH2, JAK2V617F, KRAS, NRAS, RUNX1, and TET2 (Blood. 2012;120:3080-8).

However, Dr. Durakovic noted that these mutations are found in other disorders as well, so this information may not be helpful in differentiating CMML from other disorders.

A 2015 study revealed a technique that does appear useful for identifying CMML – monocyte subset distribution analysis. For this analysis, monocytes are divided into the following categories:

• Classical/MO1 (CD14^bright/CD16⁻).
• Intermediate/MO2 (CD14^bright/CD16⁺).
• Nonclassical/MO3 (CD14^dim/CD16⁺).

The researchers found that CMML patients had an increase in the fraction of classical monocytes (with a cutoff value of 94%), as compared to healthy control subjects, patients with another hematologic disorder, and patients with reactive monocytosis (Blood. 2015 Jun 4;125[23]:3618-26).

A 2018 study confirmed that monocyte subset distribution analysis could differentiate CMML from other hematologic disorders, with the exception of atypical CML. This study also suggested that a decreased percentage of non-classical monocytes was more sensitive than an increased percentage of classical monocytes (Am J Clin Pathol. 2018 Aug 30;150[4]:293-302).

Despite the differences between these studies, “monocyte subset distribution analysis is showing promise as a method of identifying hard-to-identify CMML patients with ease and affordability,” Dr. Durakovic said.

She added that the technique can be implemented in clinical practice using the Hematoflow solution.

Dr. Durakovic did not report any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.
 

[email protected]
 

SAN DIEGO – About 25% of Fellows of the American College of Emergency Physicians acknowledged that health care disparities exist in their practices, according to a survey completed by 945 ACEP fellows in 36 states.

Doug Brunk/MDedge News

In conjunction with the American College of Emergency Physicians, Cheryl K. Zogg, MSPH, MHS, and her colleagues surveyed a nationally representative subset of ACEP fellows between September and December of 2017 to determine the extent to which emergency medicine physicians perceive that various forms of disparities exist and that there is “strong evidence” to support the existence of disparities.

The results were reported in an abstract presented during the annual meeting of the American College of Emergency Physicians.

“The existence of disparities in medicine has been widely acknowledged,” she said. “A lot of the modern conversation began in 2002, when the Institute of Medicine published its now-famous report, ‘Unequal Treatment.’ Since that time, a growing body of literature has discussed the existence of disparities in various medical fields and related to a number of factors including but not limited to race and ethnicity.”

The survey contained questions about perceptions of disparities related to insurance status, type of insurance, ability to speak English, educational attainment, race/ethnicity, sexual identity, and sexual orientation as well as the perceived strength of the evidence to support the existence of disparities in medicine in general and in emergency medicine specifically.

Ms. Zogg, an MD-PhD candidate at Yale University, New Haven, Conn., found that disparities of insurance status (85.6%) and type of insurance (81.3%) were the most widely acknowledged, followed by variations in care as a result of patients’ ability to speak English (73.7%) and level of educational attainment (61.5%).

Slightly more than half of respondents (51.9%) acknowledged the existence of disparities based on race/ethnicity in United States, but only 20.9% believe that such disparities exist in their hospitals and even fewer (3.9%) believe that they exist in their own personal practices. At the same time, more than one-third of respondents (40.6%) acknowledged the existence of disparities based on gender identity in the United States, but 22.4% believe that such disparities exist in their hospitals and even fewer (5.7%) believe that they exist in their own practices. Similar percentages were observed when respondents were asked about issues of sexual orientation (33.7%, 10.6%, and 2.3%, respectively).

Perceived strength of the evidence supporting the existence of disparities followed a similar trend. Between 74.7% and 82.2% of respondents believe there is strong evidence in medicine to support the existence of racial disparities in insurance status and insurance type, respectively. However, between 47% and 49.4% of respondents rated such evidence as strong in emergency medicine, and between 25.9% and 26.5% rated such evidence as strong in their own personal practices.

“While acknowledgment of disparities in the U.S. was strongly associated with perceived strength of the evidence in medicine in general (P less than .001), acknowledgment of disparities in one’s own practice was not associated with perceived strength of evidence in emergency medicine or with medicine in general,” Ms. Zogg said. “As evidence documenting disparities continues to increase, action is needed to address disparities in emergency care. This is important because as frontline providers of care, emergency physicians often act as the first point of contact for these patients within the U.S. health system. Ultimately, despite recognition of health care providers as a contributing factor to the existence of disparities and evidence to suggest the presence of disparities in emergency medicine, only one-fourth of FACEP openly acknowledge the potential for disparities in their personal practice.”

Ms. Zogg is supported by a National Institutes of Health Medical Scientist Training Program grant. The study was supported in part by a grant from the Emergency Medicine Foundation and the Society for Academic Emergency Medicine.

[email protected]

SOURCE: Zogg C et al. Ann Emerg Med. 2018 Oct;72(4):S118-9. doi: 10.1016/j.annemergmed.2018.08.306.

SAN DIEGO – About 25% of Fellows of the American College of Emergency Physicians acknowledged that health care disparities exist in their practices, according to a survey completed by 945 ACEP fellows in 36 states.

Doug Brunk/MDedge News

In conjunction with the American College of Emergency Physicians, Cheryl K. Zogg, MSPH, MHS, and her colleagues surveyed a nationally representative subset of ACEP fellows between September and December of 2017 to determine the extent to which emergency medicine physicians perceive that various forms of disparities exist and that there is “strong evidence” to support the existence of disparities.

The results were reported in an abstract presented during the annual meeting of the American College of Emergency Physicians.

“The existence of disparities in medicine has been widely acknowledged,” she said. “A lot of the modern conversation began in 2002, when the Institute of Medicine published its now-famous report, ‘Unequal Treatment.’ Since that time, a growing body of literature has discussed the existence of disparities in various medical fields and related to a number of factors including but not limited to race and ethnicity.”

The survey contained questions about perceptions of disparities related to insurance status, type of insurance, ability to speak English, educational attainment, race/ethnicity, sexual identity, and sexual orientation as well as the perceived strength of the evidence to support the existence of disparities in medicine in general and in emergency medicine specifically.

Ms. Zogg, an MD-PhD candidate at Yale University, New Haven, Conn., found that disparities of insurance status (85.6%) and type of insurance (81.3%) were the most widely acknowledged, followed by variations in care as a result of patients’ ability to speak English (73.7%) and level of educational attainment (61.5%).

Slightly more than half of respondents (51.9%) acknowledged the existence of disparities based on race/ethnicity in United States, but only 20.9% believe that such disparities exist in their hospitals and even fewer (3.9%) believe that they exist in their own personal practices. At the same time, more than one-third of respondents (40.6%) acknowledged the existence of disparities based on gender identity in the United States, but 22.4% believe that such disparities exist in their hospitals and even fewer (5.7%) believe that they exist in their own practices. Similar percentages were observed when respondents were asked about issues of sexual orientation (33.7%, 10.6%, and 2.3%, respectively).

Perceived strength of the evidence supporting the existence of disparities followed a similar trend. Between 74.7% and 82.2% of respondents believe there is strong evidence in medicine to support the existence of racial disparities in insurance status and insurance type, respectively. However, between 47% and 49.4% of respondents rated such evidence as strong in emergency medicine, and between 25.9% and 26.5% rated such evidence as strong in their own personal practices.

“While acknowledgment of disparities in the U.S. was strongly associated with perceived strength of the evidence in medicine in general (P less than .001), acknowledgment of disparities in one’s own practice was not associated with perceived strength of evidence in emergency medicine or with medicine in general,” Ms. Zogg said. “As evidence documenting disparities continues to increase, action is needed to address disparities in emergency care. This is important because as frontline providers of care, emergency physicians often act as the first point of contact for these patients within the U.S. health system. Ultimately, despite recognition of health care providers as a contributing factor to the existence of disparities and evidence to suggest the presence of disparities in emergency medicine, only one-fourth of FACEP openly acknowledge the potential for disparities in their personal practice.”

Ms. Zogg is supported by a National Institutes of Health Medical Scientist Training Program grant. The study was supported in part by a grant from the Emergency Medicine Foundation and the Society for Academic Emergency Medicine.

[email protected]

SOURCE: Zogg C et al. Ann Emerg Med. 2018 Oct;72(4):S118-9. doi: 10.1016/j.annemergmed.2018.08.306.

SAN DIEGO – About 25% of Fellows of the American College of Emergency Physicians acknowledged that health care disparities exist in their practices, according to a survey completed by 945 ACEP fellows in 36 states.

Doug Brunk/MDedge News

In conjunction with the American College of Emergency Physicians, Cheryl K. Zogg, MSPH, MHS, and her colleagues surveyed a nationally representative subset of ACEP fellows between September and December of 2017 to determine the extent to which emergency medicine physicians perceive that various forms of disparities exist and that there is “strong evidence” to support the existence of disparities.

The results were reported in an abstract presented during the annual meeting of the American College of Emergency Physicians.

“The existence of disparities in medicine has been widely acknowledged,” she said. “A lot of the modern conversation began in 2002, when the Institute of Medicine published its now-famous report, ‘Unequal Treatment.’ Since that time, a growing body of literature has discussed the existence of disparities in various medical fields and related to a number of factors including but not limited to race and ethnicity.”

The survey contained questions about perceptions of disparities related to insurance status, type of insurance, ability to speak English, educational attainment, race/ethnicity, sexual identity, and sexual orientation as well as the perceived strength of the evidence to support the existence of disparities in medicine in general and in emergency medicine specifically.

Ms. Zogg, an MD-PhD candidate at Yale University, New Haven, Conn., found that disparities of insurance status (85.6%) and type of insurance (81.3%) were the most widely acknowledged, followed by variations in care as a result of patients’ ability to speak English (73.7%) and level of educational attainment (61.5%).

Slightly more than half of respondents (51.9%) acknowledged the existence of disparities based on race/ethnicity in United States, but only 20.9% believe that such disparities exist in their hospitals and even fewer (3.9%) believe that they exist in their own personal practices. At the same time, more than one-third of respondents (40.6%) acknowledged the existence of disparities based on gender identity in the United States, but 22.4% believe that such disparities exist in their hospitals and even fewer (5.7%) believe that they exist in their own practices. Similar percentages were observed when respondents were asked about issues of sexual orientation (33.7%, 10.6%, and 2.3%, respectively).

Perceived strength of the evidence supporting the existence of disparities followed a similar trend. Between 74.7% and 82.2% of respondents believe there is strong evidence in medicine to support the existence of racial disparities in insurance status and insurance type, respectively. However, between 47% and 49.4% of respondents rated such evidence as strong in emergency medicine, and between 25.9% and 26.5% rated such evidence as strong in their own personal practices.

“While acknowledgment of disparities in the U.S. was strongly associated with perceived strength of the evidence in medicine in general (P less than .001), acknowledgment of disparities in one’s own practice was not associated with perceived strength of evidence in emergency medicine or with medicine in general,” Ms. Zogg said. “As evidence documenting disparities continues to increase, action is needed to address disparities in emergency care. This is important because as frontline providers of care, emergency physicians often act as the first point of contact for these patients within the U.S. health system. Ultimately, despite recognition of health care providers as a contributing factor to the existence of disparities and evidence to suggest the presence of disparities in emergency medicine, only one-fourth of FACEP openly acknowledge the potential for disparities in their personal practice.”

Ms. Zogg is supported by a National Institutes of Health Medical Scientist Training Program grant. The study was supported in part by a grant from the Emergency Medicine Foundation and the Society for Academic Emergency Medicine.

[email protected]

SOURCE: Zogg C et al. Ann Emerg Med. 2018 Oct;72(4):S118-9. doi: 10.1016/j.annemergmed.2018.08.306.

When I first began practice the COX-2 inhibitors had first come to market. My sample closet was awash with Celebrex and Vioxx.

Denise Fulton/MDedge News

I was young and naive. These drugs were allegedly safer than NSAIDs, so shouldn’t I be using them? They were new, and therefore had to be better, than plain old naproxen and ibuprofen. And hey, the samples were free.

As a result, I handed them out for pretty much all musculoskeletal stuff. “Here, try this ... ”

Of course, that came to a crashing halt when I encountered the realities of payers and drug coverage. No history of GI issues, no previous tries/fails ... Why on earth are you prescribing this? Obviously, the answer “because the samples were free” wasn’t going to pass muster.

Granted, history wasn’t particularly kind to the COX-2 drugs. Out of the three that made it to market, two were withdrawn and Celebrex’s star faded with them. But the lesson is still there.

Today, 20 years later, I use more generics. Maybe it’s because I’m familiar with them (many came to market during my career). Maybe it’s because years of calls from patients, pharmacies, and insurance companies have taught me to try them first. Probably a mixture of both.

This isn’t to say I don’t use branded drugs. I prescribe my share. There are plenty of times a generic isn’t appropriate, or a new approach is needed after a treatment failure.

But I’ve also learned that the sample closet is never a good basis for medical decisions.

We learn a lot about the many different medications available in medical school and residency. But learning facts about dosing, side effects, and mechanisms of action (while quite important) is quite different from the practical aspect of learning what is more likely to be covered and affordable. Only the experience of everyday practice will teach that.

It sure taught me.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

When I first began practice the COX-2 inhibitors had first come to market. My sample closet was awash with Celebrex and Vioxx.

Denise Fulton/MDedge News

I was young and naive. These drugs were allegedly safer than NSAIDs, so shouldn’t I be using them? They were new, and therefore had to be better, than plain old naproxen and ibuprofen. And hey, the samples were free.

As a result, I handed them out for pretty much all musculoskeletal stuff. “Here, try this ... ”

Of course, that came to a crashing halt when I encountered the realities of payers and drug coverage. No history of GI issues, no previous tries/fails ... Why on earth are you prescribing this? Obviously, the answer “because the samples were free” wasn’t going to pass muster.

Granted, history wasn’t particularly kind to the COX-2 drugs. Out of the three that made it to market, two were withdrawn and Celebrex’s star faded with them. But the lesson is still there.

Today, 20 years later, I use more generics. Maybe it’s because I’m familiar with them (many came to market during my career). Maybe it’s because years of calls from patients, pharmacies, and insurance companies have taught me to try them first. Probably a mixture of both.

This isn’t to say I don’t use branded drugs. I prescribe my share. There are plenty of times a generic isn’t appropriate, or a new approach is needed after a treatment failure.

But I’ve also learned that the sample closet is never a good basis for medical decisions.

We learn a lot about the many different medications available in medical school and residency. But learning facts about dosing, side effects, and mechanisms of action (while quite important) is quite different from the practical aspect of learning what is more likely to be covered and affordable. Only the experience of everyday practice will teach that.

It sure taught me.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

When I first began practice the COX-2 inhibitors had first come to market. My sample closet was awash with Celebrex and Vioxx.

Denise Fulton/MDedge News

I was young and naive. These drugs were allegedly safer than NSAIDs, so shouldn’t I be using them? They were new, and therefore had to be better, than plain old naproxen and ibuprofen. And hey, the samples were free.

As a result, I handed them out for pretty much all musculoskeletal stuff. “Here, try this ... ”

Of course, that came to a crashing halt when I encountered the realities of payers and drug coverage. No history of GI issues, no previous tries/fails ... Why on earth are you prescribing this? Obviously, the answer “because the samples were free” wasn’t going to pass muster.

Granted, history wasn’t particularly kind to the COX-2 drugs. Out of the three that made it to market, two were withdrawn and Celebrex’s star faded with them. But the lesson is still there.

Today, 20 years later, I use more generics. Maybe it’s because I’m familiar with them (many came to market during my career). Maybe it’s because years of calls from patients, pharmacies, and insurance companies have taught me to try them first. Probably a mixture of both.

This isn’t to say I don’t use branded drugs. I prescribe my share. There are plenty of times a generic isn’t appropriate, or a new approach is needed after a treatment failure.

But I’ve also learned that the sample closet is never a good basis for medical decisions.

We learn a lot about the many different medications available in medical school and residency. But learning facts about dosing, side effects, and mechanisms of action (while quite important) is quite different from the practical aspect of learning what is more likely to be covered and affordable. Only the experience of everyday practice will teach that.

It sure taught me.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Photo by Bill Branson

The European Medicine’s Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a change to the terms of the marketing authorization for the recombinant factor VIIa product eptacog alfa (NovoSeven).

The recommendation is to expand the approved use of eptacog alfa in patients with Glanzmann’s thrombasthenia.

Eptacog alfa is already approved by the European Commission (EC) for use in patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen who have past or present refractoriness to platelet transfusions.

Now, the CHMP has recommended expanding the use of eptacog alfa to include situations in which patients are not refractory to platelet transfusions but platelets are not readily available.

The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein. The EC usually makes a decision within 67 days of CHMP recommendations.

If the EC follows the CHMP’s recommendation for eptacog alfa, the product will be approved for the treatment of bleeding episodes and for the prevention of bleeding in those undergoing surgery or invasive procedures in the following patient groups:

• Patients with congenital hemophilia with inhibitors to coagulation factors VIII or IX > 5 Bethesda units
• Patients with congenital hemophilia who are expected to have a high anamnestic response to factor VIII or factor IX administration
• Patients with acquired hemophilia
• Patients with congenital FVII deficiency
• Patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen and past or present refractoriness to platelet transfusions, or where platelets are not readily available.

Photo by Bill Branson

The European Medicine’s Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a change to the terms of the marketing authorization for the recombinant factor VIIa product eptacog alfa (NovoSeven).

The recommendation is to expand the approved use of eptacog alfa in patients with Glanzmann’s thrombasthenia.

Eptacog alfa is already approved by the European Commission (EC) for use in patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen who have past or present refractoriness to platelet transfusions.

Now, the CHMP has recommended expanding the use of eptacog alfa to include situations in which patients are not refractory to platelet transfusions but platelets are not readily available.

The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein. The EC usually makes a decision within 67 days of CHMP recommendations.

If the EC follows the CHMP’s recommendation for eptacog alfa, the product will be approved for the treatment of bleeding episodes and for the prevention of bleeding in those undergoing surgery or invasive procedures in the following patient groups:

• Patients with congenital hemophilia with inhibitors to coagulation factors VIII or IX > 5 Bethesda units
• Patients with congenital hemophilia who are expected to have a high anamnestic response to factor VIII or factor IX administration
• Patients with acquired hemophilia
• Patients with congenital FVII deficiency
• Patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen and past or present refractoriness to platelet transfusions, or where platelets are not readily available.

Photo by Bill Branson

The European Medicine’s Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a change to the terms of the marketing authorization for the recombinant factor VIIa product eptacog alfa (NovoSeven).

The recommendation is to expand the approved use of eptacog alfa in patients with Glanzmann’s thrombasthenia.

Eptacog alfa is already approved by the European Commission (EC) for use in patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen who have past or present refractoriness to platelet transfusions.

Now, the CHMP has recommended expanding the use of eptacog alfa to include situations in which patients are not refractory to platelet transfusions but platelets are not readily available.

The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein. The EC usually makes a decision within 67 days of CHMP recommendations.

If the EC follows the CHMP’s recommendation for eptacog alfa, the product will be approved for the treatment of bleeding episodes and for the prevention of bleeding in those undergoing surgery or invasive procedures in the following patient groups:

• Patients with congenital hemophilia with inhibitors to coagulation factors VIII or IX > 5 Bethesda units
• Patients with congenital hemophilia who are expected to have a high anamnestic response to factor VIII or factor IX administration
• Patients with acquired hemophilia
• Patients with congenital FVII deficiency
• Patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen and past or present refractoriness to platelet transfusions, or where platelets are not readily available.

NEW YORK – A combination of nutrients offered protection against neurodegeneration in a rodent model of parkinsonism, according to a new study.

Kari Oakes/MDedge News

The findings pave the way for human studies to explore whether nutritional supplementation in early Parkinson’s disease (PD) can modify the disease course, said Azza Ali, PhD, speaking at the International Conference on Parkinson’s Disease and Movement Disorders.

The rodent study found improvement in a broad array of behavioral, biochemical, and histopathologic measures in rats who were dosed with a combination of whole foods known to have constituents beneficial in other disease states.

Dr. Ali, who is head of the department of pharmacology and toxicology at Al-Azzah University, Cairo, said that the element manganese ingested in excessive amounts is neurotoxic to both humans and rodents. Many elements of manganism, or manganese poisoning, she said, mimic PD in both species. She added that, in humans, “Chronic exposures to low levels of manganese may progressively extend the site of manganese deposition and toxicity to the entire area of the basal ganglia,” and that this chronic exposure can be a risk factor for PD.

Manganese-induced oxidative stress, with subsequent neuroinflammation, DNA damage, and cell apoptosis and necrosis, is a logical target for therapy by means of nutritional supplementation, said Dr. Ali.

Dr. Ali and her collaborators selected several supplements to test against both control rats fed a usual diet and those in whom manganism had been induced via a 17-day run-in period of manganese supplementation.

Wheatgrass has active constituents, including chlorophyll, vitamins, minerals, enzymes, and amino acids, and has been studied in a variety of inflammatory conditions, said Dr. Ali. Cocoa is a natural source of flavonoids and was another nutrient selected for study.

Coenzyme Q10 (CoQ10) “acts as an antioxidant that scavenges free radicals and ... protects the stability of cell membranes,” and is key to mitochondrial bioenergetics, Dr. Ali said. Finally, pomegranate contains vitamins and minerals, as well as phenolic compounds that have been studied in diabetes and Alzheimer’s disease, she said.

The study’s primary aim was to assess the neuroprotective effects of each of these four supplements singly and in combination against manganese-induced parkinsonism in rats, with a secondary aim of comparing the efficacy of each substance against the others and against the combination taken together.

The PD rats were divided into five groups, with four groups each receiving one of the supplements, and one group receiving all four in combination. The normal controls – who were dosed with saline rather than manganese – made up the sixth group of rodents studied.

After 28 days, all groups were put through a series of behavioral tests. The investigators also drew blood to assess levels of a variety of neurotransmitters, inflammatory markers, and hormones. Finally, the animals were sacrificed for histopathologic examination of the cerebral cortex, the hippocampus, and the striatum, all areas where PD-related neurodegeneration are seen.

Compared with the control rats, the manganese-dosed rats showed significantly abnormal behavior, with longer latency shown on the classic swimming test and worse working memory performance in a maze test. In most cases, though, giving a PD model rat each supplement individually resulted in significant improvements in the behavioral tests. The PD model rats given the full combination of supplements showed performance essentially equal to the control rats, Dr. Ali said. Turning to the many biochemical parameters measured in the rodent study, Dr. Ali said that the supplements all ameliorated, but did not normalize, the proinflammatory effects of manganese. Tumor necrosis factor–alpha and interleukin 1–beta levels fell by about one half with all kinds of supplementation – a significant effect – but levels still far exceeded those seen in the control rats, she said.

Dopamine and norepinephrine levels rose markedly with supplement administration as well, though serotonin levels did not. With combination therapy, both dopamine and norepinephrine values, as well as those of gamma-aminobutyric acid and glutamate, approached those of controls, said Dr. Ali.

Histology of the control rats’ brains, as expected, showed no abnormal changes in the areas examined. The manganese-dosed rats showed a variety of degenerative changes, including diffuse nuclear pyknosis, and eosinophilic plaque formation within the striatum. The brains of the rats fed the individual supplements showed essentially the same amount of degeneration. However, Dr. Ali noted, rats fed the combination therapy had brain tissue that essentially looked like that of the control rats, with “no histopathological alteration” in any area examined.

A more fine-grained examination of the data showed that overall, “Cocoa and pomegranate showed more pronounced protection against neuronal degeneration and behavioral impairments induced by manganese than wheatgrass or CoQ10,” Dr. Ali said.

Still, the combination of nutrients offered “maximum protection” against manganese-induced parkinsonism, she said. “This combination of nutrients could be a meaningful approach to reduce motor and nonmotor symptoms of Parkinson’s disease, and warrants further study in human subjects.”

Dr. Ali reported no relevant financial disclosures.

[email protected]
 

NEW YORK – A combination of nutrients offered protection against neurodegeneration in a rodent model of parkinsonism, according to a new study.

Kari Oakes/MDedge News

The findings pave the way for human studies to explore whether nutritional supplementation in early Parkinson’s disease (PD) can modify the disease course, said Azza Ali, PhD, speaking at the International Conference on Parkinson’s Disease and Movement Disorders.

The rodent study found improvement in a broad array of behavioral, biochemical, and histopathologic measures in rats who were dosed with a combination of whole foods known to have constituents beneficial in other disease states.

Dr. Ali, who is head of the department of pharmacology and toxicology at Al-Azzah University, Cairo, said that the element manganese ingested in excessive amounts is neurotoxic to both humans and rodents. Many elements of manganism, or manganese poisoning, she said, mimic PD in both species. She added that, in humans, “Chronic exposures to low levels of manganese may progressively extend the site of manganese deposition and toxicity to the entire area of the basal ganglia,” and that this chronic exposure can be a risk factor for PD.

Manganese-induced oxidative stress, with subsequent neuroinflammation, DNA damage, and cell apoptosis and necrosis, is a logical target for therapy by means of nutritional supplementation, said Dr. Ali.

Dr. Ali and her collaborators selected several supplements to test against both control rats fed a usual diet and those in whom manganism had been induced via a 17-day run-in period of manganese supplementation.

Wheatgrass has active constituents, including chlorophyll, vitamins, minerals, enzymes, and amino acids, and has been studied in a variety of inflammatory conditions, said Dr. Ali. Cocoa is a natural source of flavonoids and was another nutrient selected for study.

Coenzyme Q10 (CoQ10) “acts as an antioxidant that scavenges free radicals and ... protects the stability of cell membranes,” and is key to mitochondrial bioenergetics, Dr. Ali said. Finally, pomegranate contains vitamins and minerals, as well as phenolic compounds that have been studied in diabetes and Alzheimer’s disease, she said.

The study’s primary aim was to assess the neuroprotective effects of each of these four supplements singly and in combination against manganese-induced parkinsonism in rats, with a secondary aim of comparing the efficacy of each substance against the others and against the combination taken together.

The PD rats were divided into five groups, with four groups each receiving one of the supplements, and one group receiving all four in combination. The normal controls – who were dosed with saline rather than manganese – made up the sixth group of rodents studied.

After 28 days, all groups were put through a series of behavioral tests. The investigators also drew blood to assess levels of a variety of neurotransmitters, inflammatory markers, and hormones. Finally, the animals were sacrificed for histopathologic examination of the cerebral cortex, the hippocampus, and the striatum, all areas where PD-related neurodegeneration are seen.

Compared with the control rats, the manganese-dosed rats showed significantly abnormal behavior, with longer latency shown on the classic swimming test and worse working memory performance in a maze test. In most cases, though, giving a PD model rat each supplement individually resulted in significant improvements in the behavioral tests. The PD model rats given the full combination of supplements showed performance essentially equal to the control rats, Dr. Ali said. Turning to the many biochemical parameters measured in the rodent study, Dr. Ali said that the supplements all ameliorated, but did not normalize, the proinflammatory effects of manganese. Tumor necrosis factor–alpha and interleukin 1–beta levels fell by about one half with all kinds of supplementation – a significant effect – but levels still far exceeded those seen in the control rats, she said.

Dopamine and norepinephrine levels rose markedly with supplement administration as well, though serotonin levels did not. With combination therapy, both dopamine and norepinephrine values, as well as those of gamma-aminobutyric acid and glutamate, approached those of controls, said Dr. Ali.

Histology of the control rats’ brains, as expected, showed no abnormal changes in the areas examined. The manganese-dosed rats showed a variety of degenerative changes, including diffuse nuclear pyknosis, and eosinophilic plaque formation within the striatum. The brains of the rats fed the individual supplements showed essentially the same amount of degeneration. However, Dr. Ali noted, rats fed the combination therapy had brain tissue that essentially looked like that of the control rats, with “no histopathological alteration” in any area examined.

A more fine-grained examination of the data showed that overall, “Cocoa and pomegranate showed more pronounced protection against neuronal degeneration and behavioral impairments induced by manganese than wheatgrass or CoQ10,” Dr. Ali said.

Still, the combination of nutrients offered “maximum protection” against manganese-induced parkinsonism, she said. “This combination of nutrients could be a meaningful approach to reduce motor and nonmotor symptoms of Parkinson’s disease, and warrants further study in human subjects.”

Dr. Ali reported no relevant financial disclosures.

[email protected]
 

NEW YORK – A combination of nutrients offered protection against neurodegeneration in a rodent model of parkinsonism, according to a new study.

Kari Oakes/MDedge News

The findings pave the way for human studies to explore whether nutritional supplementation in early Parkinson’s disease (PD) can modify the disease course, said Azza Ali, PhD, speaking at the International Conference on Parkinson’s Disease and Movement Disorders.

The rodent study found improvement in a broad array of behavioral, biochemical, and histopathologic measures in rats who were dosed with a combination of whole foods known to have constituents beneficial in other disease states.

Dr. Ali, who is head of the department of pharmacology and toxicology at Al-Azzah University, Cairo, said that the element manganese ingested in excessive amounts is neurotoxic to both humans and rodents. Many elements of manganism, or manganese poisoning, she said, mimic PD in both species. She added that, in humans, “Chronic exposures to low levels of manganese may progressively extend the site of manganese deposition and toxicity to the entire area of the basal ganglia,” and that this chronic exposure can be a risk factor for PD.

Manganese-induced oxidative stress, with subsequent neuroinflammation, DNA damage, and cell apoptosis and necrosis, is a logical target for therapy by means of nutritional supplementation, said Dr. Ali.

Dr. Ali and her collaborators selected several supplements to test against both control rats fed a usual diet and those in whom manganism had been induced via a 17-day run-in period of manganese supplementation.

Wheatgrass has active constituents, including chlorophyll, vitamins, minerals, enzymes, and amino acids, and has been studied in a variety of inflammatory conditions, said Dr. Ali. Cocoa is a natural source of flavonoids and was another nutrient selected for study.

Coenzyme Q10 (CoQ10) “acts as an antioxidant that scavenges free radicals and ... protects the stability of cell membranes,” and is key to mitochondrial bioenergetics, Dr. Ali said. Finally, pomegranate contains vitamins and minerals, as well as phenolic compounds that have been studied in diabetes and Alzheimer’s disease, she said.

The study’s primary aim was to assess the neuroprotective effects of each of these four supplements singly and in combination against manganese-induced parkinsonism in rats, with a secondary aim of comparing the efficacy of each substance against the others and against the combination taken together.

The PD rats were divided into five groups, with four groups each receiving one of the supplements, and one group receiving all four in combination. The normal controls – who were dosed with saline rather than manganese – made up the sixth group of rodents studied.

After 28 days, all groups were put through a series of behavioral tests. The investigators also drew blood to assess levels of a variety of neurotransmitters, inflammatory markers, and hormones. Finally, the animals were sacrificed for histopathologic examination of the cerebral cortex, the hippocampus, and the striatum, all areas where PD-related neurodegeneration are seen.

Compared with the control rats, the manganese-dosed rats showed significantly abnormal behavior, with longer latency shown on the classic swimming test and worse working memory performance in a maze test. In most cases, though, giving a PD model rat each supplement individually resulted in significant improvements in the behavioral tests. The PD model rats given the full combination of supplements showed performance essentially equal to the control rats, Dr. Ali said. Turning to the many biochemical parameters measured in the rodent study, Dr. Ali said that the supplements all ameliorated, but did not normalize, the proinflammatory effects of manganese. Tumor necrosis factor–alpha and interleukin 1–beta levels fell by about one half with all kinds of supplementation – a significant effect – but levels still far exceeded those seen in the control rats, she said.

Dopamine and norepinephrine levels rose markedly with supplement administration as well, though serotonin levels did not. With combination therapy, both dopamine and norepinephrine values, as well as those of gamma-aminobutyric acid and glutamate, approached those of controls, said Dr. Ali.

Histology of the control rats’ brains, as expected, showed no abnormal changes in the areas examined. The manganese-dosed rats showed a variety of degenerative changes, including diffuse nuclear pyknosis, and eosinophilic plaque formation within the striatum. The brains of the rats fed the individual supplements showed essentially the same amount of degeneration. However, Dr. Ali noted, rats fed the combination therapy had brain tissue that essentially looked like that of the control rats, with “no histopathological alteration” in any area examined.

A more fine-grained examination of the data showed that overall, “Cocoa and pomegranate showed more pronounced protection against neuronal degeneration and behavioral impairments induced by manganese than wheatgrass or CoQ10,” Dr. Ali said.

Still, the combination of nutrients offered “maximum protection” against manganese-induced parkinsonism, she said. “This combination of nutrients could be a meaningful approach to reduce motor and nonmotor symptoms of Parkinson’s disease, and warrants further study in human subjects.”

Dr. Ali reported no relevant financial disclosures.

[email protected]
 

Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.

The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”

In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.

They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.  

Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.

At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).

In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.

The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.

“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.

The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.

“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.

“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.

They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.

SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.

Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.

The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”

In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.

They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.  

Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.

At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).

In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.

The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.

“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.

The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.

“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.

“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.

They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.

SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.

Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.

The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”

In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.

They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.  

Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.

At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).

In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.

The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.

“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.

The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.

“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.

“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.

They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.

SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.

NEW YORK – One reason to pursue a multimodality strategy to control the symptoms as well as the underlying pathophysiology of Parkinson’s disease (PD) is that a small but substantial proportion of patients with PD-like symptoms have a different diagnosis, according to an expert overview at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“Fifteen to 20% of patients treated for Parkinson’s disease, even in the most established centers of excellence, do not have Parkinson’s disease on necropsy,” said A.V. Srinivasan, MD, PhD, DSc, of The Tamil Nadu Dr. M.G.R. Medical University, Chennai, India.

This does not preclude benefit from antiparkinson drugs in those patients with PD-like symptoms but a different etiology. Many can benefit from increased dopamine availability, even in the absence of PD, but it emphasizes the complexity of clinical diseases associated with diminished dopamine function, according to Dr. Srinivasan. He characterized this complexity as a reason to avoid a regimented approach to PD management.

“You can just imagine how much this influences our data analysis,” said Dr. Srinivasan, referring to clinical trials designed to generate evidence-based treatment. “We should remember that we should not be too statistically oriented,” he added, citing the adage that “statistics can cause paralysis in your analysis.”

PD is associated with a vast array of neurologic and physical symptoms attributable to PD that overlap with other neurologic disorders, which is the reason that a definitive diagnosis is challenging, according to Dr. Srinivasan. Listing symptoms that should prompt consideration of an alternative diagnosis, Dr. Srinivasan said hallucinations suggest diffuse Lewy body disease, myoclonus suggests corticobasal degeneration, and amyotrophy suggests multiple system atrophy.

“These are only clues, however,” said Dr. Srinivasan, suggesting their presence should prompt consideration of alternative diagnoses, but their absence does not confirm PD.

In some cases, further work-up with one or more of the array of increasingly sophisticated imaging strategies, such as the combination of SPECT and PET, might help clinicians reach a more definitive diagnosis of the underlying pathology, a step that might guide use of dopaminergic therapies. However, effective treatment of PD symptoms does not depend on a definitive diagnosis.

Rather, Dr. Srinivasan advocated an open mind to the management of symptoms, which he indicated are best addressed empirically. As PD or other progressive movement disorders advance, the goal is to keep patients functional and comfortable.

This includes managing patients beyond prescription drugs to address such complications as dysphagia or impaired balance. He advocated practical solutions for causes of impaired quality of life such as soft foods to facilitate swallowing or walkers to keep patients ambulatory. No option that leads to symptom relief should be discounted, including alternative therapies.

“Some clinicians are strongly opposed to nontraditional therapies, such as naturopathy and homeopathy, but these have all been used in Parkinson’s,” Dr. Srinivasan said. Although he did not present data to show efficacy, he indicated that relief of symptoms and improvement of quality of life is the point of any treatment, which should be individualized by response in every patient.

And individualized therapy – in relationship to patient age – is particularly important, according to Dr. Srinivasan. While younger patients typically tolerate relatively aggressive therapies aimed at both PD and its specific symptoms, older patients may accept less ambitious functional improvements to achieve an adequate quality of life.

“After 70 years of age, every additional year is a bonus. After 80 years, every week is a bonus. After 90 years, every minute is a bonus,” said Dr. Srinivasan, in emphasizing an appropriate clinical perspective.

NEW YORK – One reason to pursue a multimodality strategy to control the symptoms as well as the underlying pathophysiology of Parkinson’s disease (PD) is that a small but substantial proportion of patients with PD-like symptoms have a different diagnosis, according to an expert overview at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“Fifteen to 20% of patients treated for Parkinson’s disease, even in the most established centers of excellence, do not have Parkinson’s disease on necropsy,” said A.V. Srinivasan, MD, PhD, DSc, of The Tamil Nadu Dr. M.G.R. Medical University, Chennai, India.

This does not preclude benefit from antiparkinson drugs in those patients with PD-like symptoms but a different etiology. Many can benefit from increased dopamine availability, even in the absence of PD, but it emphasizes the complexity of clinical diseases associated with diminished dopamine function, according to Dr. Srinivasan. He characterized this complexity as a reason to avoid a regimented approach to PD management.

“You can just imagine how much this influences our data analysis,” said Dr. Srinivasan, referring to clinical trials designed to generate evidence-based treatment. “We should remember that we should not be too statistically oriented,” he added, citing the adage that “statistics can cause paralysis in your analysis.”

PD is associated with a vast array of neurologic and physical symptoms attributable to PD that overlap with other neurologic disorders, which is the reason that a definitive diagnosis is challenging, according to Dr. Srinivasan. Listing symptoms that should prompt consideration of an alternative diagnosis, Dr. Srinivasan said hallucinations suggest diffuse Lewy body disease, myoclonus suggests corticobasal degeneration, and amyotrophy suggests multiple system atrophy.

“These are only clues, however,” said Dr. Srinivasan, suggesting their presence should prompt consideration of alternative diagnoses, but their absence does not confirm PD.

In some cases, further work-up with one or more of the array of increasingly sophisticated imaging strategies, such as the combination of SPECT and PET, might help clinicians reach a more definitive diagnosis of the underlying pathology, a step that might guide use of dopaminergic therapies. However, effective treatment of PD symptoms does not depend on a definitive diagnosis.

Rather, Dr. Srinivasan advocated an open mind to the management of symptoms, which he indicated are best addressed empirically. As PD or other progressive movement disorders advance, the goal is to keep patients functional and comfortable.

This includes managing patients beyond prescription drugs to address such complications as dysphagia or impaired balance. He advocated practical solutions for causes of impaired quality of life such as soft foods to facilitate swallowing or walkers to keep patients ambulatory. No option that leads to symptom relief should be discounted, including alternative therapies.

“Some clinicians are strongly opposed to nontraditional therapies, such as naturopathy and homeopathy, but these have all been used in Parkinson’s,” Dr. Srinivasan said. Although he did not present data to show efficacy, he indicated that relief of symptoms and improvement of quality of life is the point of any treatment, which should be individualized by response in every patient.

And individualized therapy – in relationship to patient age – is particularly important, according to Dr. Srinivasan. While younger patients typically tolerate relatively aggressive therapies aimed at both PD and its specific symptoms, older patients may accept less ambitious functional improvements to achieve an adequate quality of life.

“After 70 years of age, every additional year is a bonus. After 80 years, every week is a bonus. After 90 years, every minute is a bonus,” said Dr. Srinivasan, in emphasizing an appropriate clinical perspective.

NEW YORK – One reason to pursue a multimodality strategy to control the symptoms as well as the underlying pathophysiology of Parkinson’s disease (PD) is that a small but substantial proportion of patients with PD-like symptoms have a different diagnosis, according to an expert overview at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“Fifteen to 20% of patients treated for Parkinson’s disease, even in the most established centers of excellence, do not have Parkinson’s disease on necropsy,” said A.V. Srinivasan, MD, PhD, DSc, of The Tamil Nadu Dr. M.G.R. Medical University, Chennai, India.

This does not preclude benefit from antiparkinson drugs in those patients with PD-like symptoms but a different etiology. Many can benefit from increased dopamine availability, even in the absence of PD, but it emphasizes the complexity of clinical diseases associated with diminished dopamine function, according to Dr. Srinivasan. He characterized this complexity as a reason to avoid a regimented approach to PD management.

“You can just imagine how much this influences our data analysis,” said Dr. Srinivasan, referring to clinical trials designed to generate evidence-based treatment. “We should remember that we should not be too statistically oriented,” he added, citing the adage that “statistics can cause paralysis in your analysis.”

PD is associated with a vast array of neurologic and physical symptoms attributable to PD that overlap with other neurologic disorders, which is the reason that a definitive diagnosis is challenging, according to Dr. Srinivasan. Listing symptoms that should prompt consideration of an alternative diagnosis, Dr. Srinivasan said hallucinations suggest diffuse Lewy body disease, myoclonus suggests corticobasal degeneration, and amyotrophy suggests multiple system atrophy.

“These are only clues, however,” said Dr. Srinivasan, suggesting their presence should prompt consideration of alternative diagnoses, but their absence does not confirm PD.

In some cases, further work-up with one or more of the array of increasingly sophisticated imaging strategies, such as the combination of SPECT and PET, might help clinicians reach a more definitive diagnosis of the underlying pathology, a step that might guide use of dopaminergic therapies. However, effective treatment of PD symptoms does not depend on a definitive diagnosis.

Rather, Dr. Srinivasan advocated an open mind to the management of symptoms, which he indicated are best addressed empirically. As PD or other progressive movement disorders advance, the goal is to keep patients functional and comfortable.

This includes managing patients beyond prescription drugs to address such complications as dysphagia or impaired balance. He advocated practical solutions for causes of impaired quality of life such as soft foods to facilitate swallowing or walkers to keep patients ambulatory. No option that leads to symptom relief should be discounted, including alternative therapies.

“Some clinicians are strongly opposed to nontraditional therapies, such as naturopathy and homeopathy, but these have all been used in Parkinson’s,” Dr. Srinivasan said. Although he did not present data to show efficacy, he indicated that relief of symptoms and improvement of quality of life is the point of any treatment, which should be individualized by response in every patient.

And individualized therapy – in relationship to patient age – is particularly important, according to Dr. Srinivasan. While younger patients typically tolerate relatively aggressive therapies aimed at both PD and its specific symptoms, older patients may accept less ambitious functional improvements to achieve an adequate quality of life.

“After 70 years of age, every additional year is a bonus. After 80 years, every week is a bonus. After 90 years, every minute is a bonus,” said Dr. Srinivasan, in emphasizing an appropriate clinical perspective.

PHILADELPHIA – There was a significantly higher adenoma detection rate when the withdrawal rate in the right colon was more than 3 minutes in patients undergoing colonoscopy, according to a recent presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Although adenomas precede colon cancer in approximately 70% of cases, and detection of adenomas is associated with 5% risk of dying from colorectal cancer, miss rates of adenomas are high in both sides of the colon and ideal withdrawal times are not known, Fahad F. Mir, MD, MSc, from the University of Missouri-Kansas City, said.

“Miss rates are high, especially in the right side of the colon. A colonoscopy offers protection in up to 80% of the left side of the patients but only up to 40%-60% in the right side of patients,” Dr. Mir stated in his presentation. “The quality standard now [for withdrawal time] is 6 minutes, so we hypothesized that adenoma detection rate is not the same if the right colon withdrawal time is equal to or more than 3 minutes, compared to less than 3 minutes.”

The abstract received an ACG Governor’s Award for Excellence in Clinical Research.

Dr. Mir and his colleagues performed a prospective, randomized, case-controlled study of 226 patients undergoing colonoscopy at three endoscopy centers in St. Luke’s Health System, Kansas City, who were aged at least 50 years and had not undergone colonic resections, emergent procedures, or were unable to consent because of mental status or language barrier. Patients were randomized to a control group (113 patients) in whom right colon withdrawal time was under 3 minutes and an intervention group (113 patients) in whom withdrawal time was 3 minutes or more.

There was a 33% adenoma detection rate in the 3 minute or more group, compared with 14% in the less than 3 minutes group (odds ratio, 3.0; 95% confidence interval, 1.62-5.64; P less than .001). Polyp detection rates were 49% in the 3 minutes or more group and 14% in the less than 3 minutes group (OR 5.1; 95% CI, 2.84-9.32; P less than .001). The optimal cut-off point was 3 minutes and 1 second with optimal sensitivity and specificity with an area under the curve of 0.73 (95% CI, 0.65-0.81; P less than .001) for optimal cut-off time for withdrawal from the right colon.

“There was a difference in fellow involvement, where fellows were more likely to be involved when the withdrawal time was more than 3 minutes as opposed to less than 3 minutes; the ADR [adenoma detection rate] was not different based upon fellow involvement,” Dr. Mir said.

The researchers noted similar rates of retroflexion between both groups and said there were no adverse events related to the study in either group. Limitations of the study included its unblinded design, data collection from multiple centers, and a higher rate of previous polyps in patients in the withdrawal in more than 3 minutes group.

Dr. Mir report no relevant conflicts of interest.
 

SOURCE: Mir FF et al. ACG 2018, Presentation 5.

PHILADELPHIA – There was a significantly higher adenoma detection rate when the withdrawal rate in the right colon was more than 3 minutes in patients undergoing colonoscopy, according to a recent presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Although adenomas precede colon cancer in approximately 70% of cases, and detection of adenomas is associated with 5% risk of dying from colorectal cancer, miss rates of adenomas are high in both sides of the colon and ideal withdrawal times are not known, Fahad F. Mir, MD, MSc, from the University of Missouri-Kansas City, said.

“Miss rates are high, especially in the right side of the colon. A colonoscopy offers protection in up to 80% of the left side of the patients but only up to 40%-60% in the right side of patients,” Dr. Mir stated in his presentation. “The quality standard now [for withdrawal time] is 6 minutes, so we hypothesized that adenoma detection rate is not the same if the right colon withdrawal time is equal to or more than 3 minutes, compared to less than 3 minutes.”

The abstract received an ACG Governor’s Award for Excellence in Clinical Research.

Dr. Mir and his colleagues performed a prospective, randomized, case-controlled study of 226 patients undergoing colonoscopy at three endoscopy centers in St. Luke’s Health System, Kansas City, who were aged at least 50 years and had not undergone colonic resections, emergent procedures, or were unable to consent because of mental status or language barrier. Patients were randomized to a control group (113 patients) in whom right colon withdrawal time was under 3 minutes and an intervention group (113 patients) in whom withdrawal time was 3 minutes or more.

There was a 33% adenoma detection rate in the 3 minute or more group, compared with 14% in the less than 3 minutes group (odds ratio, 3.0; 95% confidence interval, 1.62-5.64; P less than .001). Polyp detection rates were 49% in the 3 minutes or more group and 14% in the less than 3 minutes group (OR 5.1; 95% CI, 2.84-9.32; P less than .001). The optimal cut-off point was 3 minutes and 1 second with optimal sensitivity and specificity with an area under the curve of 0.73 (95% CI, 0.65-0.81; P less than .001) for optimal cut-off time for withdrawal from the right colon.

“There was a difference in fellow involvement, where fellows were more likely to be involved when the withdrawal time was more than 3 minutes as opposed to less than 3 minutes; the ADR [adenoma detection rate] was not different based upon fellow involvement,” Dr. Mir said.

The researchers noted similar rates of retroflexion between both groups and said there were no adverse events related to the study in either group. Limitations of the study included its unblinded design, data collection from multiple centers, and a higher rate of previous polyps in patients in the withdrawal in more than 3 minutes group.

Dr. Mir report no relevant conflicts of interest.
 

SOURCE: Mir FF et al. ACG 2018, Presentation 5.

PHILADELPHIA – There was a significantly higher adenoma detection rate when the withdrawal rate in the right colon was more than 3 minutes in patients undergoing colonoscopy, according to a recent presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Although adenomas precede colon cancer in approximately 70% of cases, and detection of adenomas is associated with 5% risk of dying from colorectal cancer, miss rates of adenomas are high in both sides of the colon and ideal withdrawal times are not known, Fahad F. Mir, MD, MSc, from the University of Missouri-Kansas City, said.

“Miss rates are high, especially in the right side of the colon. A colonoscopy offers protection in up to 80% of the left side of the patients but only up to 40%-60% in the right side of patients,” Dr. Mir stated in his presentation. “The quality standard now [for withdrawal time] is 6 minutes, so we hypothesized that adenoma detection rate is not the same if the right colon withdrawal time is equal to or more than 3 minutes, compared to less than 3 minutes.”

The abstract received an ACG Governor’s Award for Excellence in Clinical Research.

Dr. Mir and his colleagues performed a prospective, randomized, case-controlled study of 226 patients undergoing colonoscopy at three endoscopy centers in St. Luke’s Health System, Kansas City, who were aged at least 50 years and had not undergone colonic resections, emergent procedures, or were unable to consent because of mental status or language barrier. Patients were randomized to a control group (113 patients) in whom right colon withdrawal time was under 3 minutes and an intervention group (113 patients) in whom withdrawal time was 3 minutes or more.

There was a 33% adenoma detection rate in the 3 minute or more group, compared with 14% in the less than 3 minutes group (odds ratio, 3.0; 95% confidence interval, 1.62-5.64; P less than .001). Polyp detection rates were 49% in the 3 minutes or more group and 14% in the less than 3 minutes group (OR 5.1; 95% CI, 2.84-9.32; P less than .001). The optimal cut-off point was 3 minutes and 1 second with optimal sensitivity and specificity with an area under the curve of 0.73 (95% CI, 0.65-0.81; P less than .001) for optimal cut-off time for withdrawal from the right colon.

“There was a difference in fellow involvement, where fellows were more likely to be involved when the withdrawal time was more than 3 minutes as opposed to less than 3 minutes; the ADR [adenoma detection rate] was not different based upon fellow involvement,” Dr. Mir said.

The researchers noted similar rates of retroflexion between both groups and said there were no adverse events related to the study in either group. Limitations of the study included its unblinded design, data collection from multiple centers, and a higher rate of previous polyps in patients in the withdrawal in more than 3 minutes group.

Dr. Mir report no relevant conflicts of interest.
 

SOURCE: Mir FF et al. ACG 2018, Presentation 5.

Cardiomyopathy induced by antimalarial treatment for systematic lupus erythematosus may not be as rare as previously thought, according to the authors of a case series published Oct. 15 in The Journal of Rheumatology.

The paper describes eight patients attending a lupus clinic, who were diagnosed with definite or possible antimalarial-induced cardiomyopathy over the course of 2 years.

Konstantinos Tselios, MD, PhD, a clinical research fellow at the University of Toronto Lupus Clinic, and his coauthors wrote that antimalarial-induced cardiomyopathy was thought to be relatively rare, with only 47 previous isolated reports, but they suggested the complication may be significantly underrecognized.

“Hypertrophic cardiomyopathy and heart failure, the most common clinical features of AM-induced cardiomyopathy (AMIC), may be falsely attributed to other causes, such as arterial hypertension or ischemic cardiomyopathy,” the authors wrote. “Consequently, nonspecific therapeutic approaches with diuretics and/or antihypertensives will exert minimum or even deleterious effects on such patients.”

All eight patients in this series were female, with a median age of 62.5 years, median disease duration of 35 years, and median antimalarial use of 22 years. They presented with conditions such as heart failure, exertional dyspnea, and pedal edema. Several patients were asymptomatic but had been found to have elevated heart biomarker levels that prompted further investigation.


All patients showed abnormal cardiac troponin I and brain natriuretic peptide levels, and seven of the eight also had chronically elevated creatine phosphokinase.

In three patients, endomyocardial biopsy showed cardiomyocyte vacuolation, intracytoplasmic myelinoid inclusions, and curvilinear bodies.

Four patients were diagnosed based on cardiac MRI, which showed features suggestive of antimalarial-induced cardiomyopathy, including ventricular hypertrophy with or without atrial enlargement and late gadolinium enhancement in a nonvascular pattern.

All patients had left ventricular hypertrophy, and four also had right ventricular hypertrophy. Only one patient showed impaired systolic function, compared with around half of patients in the literature with antimalarial-induced cardiomyopathy, but seven patients showed a restrictive filling pattern of the left ventricle.

“It seems possible that AMIC is a chronic process and systolic dysfunction will become apparent only in late stages,” the authors suggested.

One patient showed complete atrioventricular block, left ventricular and septal hypertrophy, and concomitant ocular toxicity.

After patients stopped antimalarials, the hypertrophy regressed and heart biomarkers decreased in seven patients, but one patient died from refractory heart failure.

Based on their findings, the authors proposed that heart-specific biomarkers be used as a regular screening tool for detecting myocardial injury, followed by more thorough investigations, such as cardiac MRI, in patients with positive biomarker findings.

“However, drug cessation should be prompt and probably upon suspicion of AMIC, because complete investigation may be delayed significantly.”

One author was supported by the Geoff Carr Fellowship from Lupus Ontario. The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. J Rheumatol, 2018 Oct 15. doi: 10.3899/jrheum.180124.

Cardiomyopathy induced by antimalarial treatment for systematic lupus erythematosus may not be as rare as previously thought, according to the authors of a case series published Oct. 15 in The Journal of Rheumatology.

The paper describes eight patients attending a lupus clinic, who were diagnosed with definite or possible antimalarial-induced cardiomyopathy over the course of 2 years.

Konstantinos Tselios, MD, PhD, a clinical research fellow at the University of Toronto Lupus Clinic, and his coauthors wrote that antimalarial-induced cardiomyopathy was thought to be relatively rare, with only 47 previous isolated reports, but they suggested the complication may be significantly underrecognized.

“Hypertrophic cardiomyopathy and heart failure, the most common clinical features of AM-induced cardiomyopathy (AMIC), may be falsely attributed to other causes, such as arterial hypertension or ischemic cardiomyopathy,” the authors wrote. “Consequently, nonspecific therapeutic approaches with diuretics and/or antihypertensives will exert minimum or even deleterious effects on such patients.”

All eight patients in this series were female, with a median age of 62.5 years, median disease duration of 35 years, and median antimalarial use of 22 years. They presented with conditions such as heart failure, exertional dyspnea, and pedal edema. Several patients were asymptomatic but had been found to have elevated heart biomarker levels that prompted further investigation.


All patients showed abnormal cardiac troponin I and brain natriuretic peptide levels, and seven of the eight also had chronically elevated creatine phosphokinase.

In three patients, endomyocardial biopsy showed cardiomyocyte vacuolation, intracytoplasmic myelinoid inclusions, and curvilinear bodies.

Four patients were diagnosed based on cardiac MRI, which showed features suggestive of antimalarial-induced cardiomyopathy, including ventricular hypertrophy with or without atrial enlargement and late gadolinium enhancement in a nonvascular pattern.

All patients had left ventricular hypertrophy, and four also had right ventricular hypertrophy. Only one patient showed impaired systolic function, compared with around half of patients in the literature with antimalarial-induced cardiomyopathy, but seven patients showed a restrictive filling pattern of the left ventricle.

“It seems possible that AMIC is a chronic process and systolic dysfunction will become apparent only in late stages,” the authors suggested.

One patient showed complete atrioventricular block, left ventricular and septal hypertrophy, and concomitant ocular toxicity.

After patients stopped antimalarials, the hypertrophy regressed and heart biomarkers decreased in seven patients, but one patient died from refractory heart failure.

Based on their findings, the authors proposed that heart-specific biomarkers be used as a regular screening tool for detecting myocardial injury, followed by more thorough investigations, such as cardiac MRI, in patients with positive biomarker findings.

“However, drug cessation should be prompt and probably upon suspicion of AMIC, because complete investigation may be delayed significantly.”

One author was supported by the Geoff Carr Fellowship from Lupus Ontario. The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. J Rheumatol, 2018 Oct 15. doi: 10.3899/jrheum.180124.

Cardiomyopathy induced by antimalarial treatment for systematic lupus erythematosus may not be as rare as previously thought, according to the authors of a case series published Oct. 15 in The Journal of Rheumatology.

The paper describes eight patients attending a lupus clinic, who were diagnosed with definite or possible antimalarial-induced cardiomyopathy over the course of 2 years.

Konstantinos Tselios, MD, PhD, a clinical research fellow at the University of Toronto Lupus Clinic, and his coauthors wrote that antimalarial-induced cardiomyopathy was thought to be relatively rare, with only 47 previous isolated reports, but they suggested the complication may be significantly underrecognized.

“Hypertrophic cardiomyopathy and heart failure, the most common clinical features of AM-induced cardiomyopathy (AMIC), may be falsely attributed to other causes, such as arterial hypertension or ischemic cardiomyopathy,” the authors wrote. “Consequently, nonspecific therapeutic approaches with diuretics and/or antihypertensives will exert minimum or even deleterious effects on such patients.”

All eight patients in this series were female, with a median age of 62.5 years, median disease duration of 35 years, and median antimalarial use of 22 years. They presented with conditions such as heart failure, exertional dyspnea, and pedal edema. Several patients were asymptomatic but had been found to have elevated heart biomarker levels that prompted further investigation.


All patients showed abnormal cardiac troponin I and brain natriuretic peptide levels, and seven of the eight also had chronically elevated creatine phosphokinase.

In three patients, endomyocardial biopsy showed cardiomyocyte vacuolation, intracytoplasmic myelinoid inclusions, and curvilinear bodies.

Four patients were diagnosed based on cardiac MRI, which showed features suggestive of antimalarial-induced cardiomyopathy, including ventricular hypertrophy with or without atrial enlargement and late gadolinium enhancement in a nonvascular pattern.

All patients had left ventricular hypertrophy, and four also had right ventricular hypertrophy. Only one patient showed impaired systolic function, compared with around half of patients in the literature with antimalarial-induced cardiomyopathy, but seven patients showed a restrictive filling pattern of the left ventricle.

“It seems possible that AMIC is a chronic process and systolic dysfunction will become apparent only in late stages,” the authors suggested.

One patient showed complete atrioventricular block, left ventricular and septal hypertrophy, and concomitant ocular toxicity.

After patients stopped antimalarials, the hypertrophy regressed and heart biomarkers decreased in seven patients, but one patient died from refractory heart failure.

Based on their findings, the authors proposed that heart-specific biomarkers be used as a regular screening tool for detecting myocardial injury, followed by more thorough investigations, such as cardiac MRI, in patients with positive biomarker findings.

“However, drug cessation should be prompt and probably upon suspicion of AMIC, because complete investigation may be delayed significantly.”

One author was supported by the Geoff Carr Fellowship from Lupus Ontario. The University of Toronto Lupus Research Program is supported by the University Health Network, Lou and Marissa Rocca, and the Lupus Foundation of Ontario.

SOURCE: Tselios K et al. J Rheumatol, 2018 Oct 15. doi: 10.3899/jrheum.180124.

An improvement of nearly 4 points on a 30-point, patient-scored disease severity index appears to be clinically meaningful for adults with active RA, according to a recent clinical trial analysis.

Richard Clark, NIAMS

A 3.8-point decrease represented the minimal clinically important improvement in the Routine Assessment of Patient Index Data 3 (RAPID-3) index, investigators reported in The Journal of Rheumatology.

“Clinicians may feel comfortable documenting and monitoring patient status, recognizing an improvement of 3.8 units in patients with active RA to be meaningful in routine patient care,” Michael M. Ward, MD, PhD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and his coinvestigators wrote.

The RAPID-3 index consists of three patient self-report measures out of the seven-item RA Core Data Set: physical function, pain, and patient’s global assessment. The index was initially designed to be feasible in routine care, such that a patient could fill it out in the waiting area, Dr. Ward and his colleagues noted in their report.

Previous investigations have shown that RAPID-3 is highly correlated with the 28-joint count Disease Activity Score (DAS28) and the Clinical Disease Activity Index, and in one study, it was more likely than erythrocyte sedimentation rate (ESR) to identify incomplete responses to methotrexate.

However, prior to the present study, there were no reported estimates of the minimal clinically important improvement for the RAPID-3 index.

Knowing whether or not a decrease in RAPID-3 is clinically meaningful to patients would help clinicians interpret those changes in response to treatment, Dr. Ward and his coauthors wrote.

In the current study, RAPID-3 was calculated before and after escalation of treatment in a prospective study involving 250 adults with active RA, including 195 women (78%). The mean age of the patients was 51 years, and the median duration of RA was more than 6 years.

At the patients’ baseline visit and evaluation, rheumatologists prescribed prednisone, a new disease-modifying treatment, a new biologic, or increased the dose of a current treatment. The follow-up visit occurred at 4 months for most patients, though follow-up was at 1 month for prednisone-treated patients because of an expected rapid response.

At baseline, the mean RAPID-3 score was 16.3, which improved to 11.1 at the follow-up visit, for a mean change of –5.2 points, according to the investigators. The standardized response mean was –0.79 (95% confidence interval, –0.71 to –0.88), which investigators said demonstrated good sensitivity to change.

They found that the minimal clinically important improvement was –3.8 in a statistical analysis that optimized sensitivity and specificity, and –3.5 and –4.1 by alternate statistical criteria.

However, Dr. Ward and his coauthors cautioned that these estimates should be applied only to patient groups that have high levels of RA activity, similar to this study, in which patients had a baseline mean DAS28-ESR of 6.16 and a mean Simplified Disease Activity Index of 38.6.

Patients with low RA activity are closer to an acceptable symptom state, making the minimal clinically important improvement less relevant. “The margin for symptom improvement becomes smaller and ultimately indiscernible as the level of activity decreases,” they explained in their report.

The study was supported in part through the NIAMS Intramural Research Program and a grant from the U.S. Public Health Service. No conflicts of interest were reported.

SOURCE: Ward MM et al. J Rheumatol. 2018 Oct 15. doi: 10.3899/jrheum.180153.

An improvement of nearly 4 points on a 30-point, patient-scored disease severity index appears to be clinically meaningful for adults with active RA, according to a recent clinical trial analysis.

Richard Clark, NIAMS

A 3.8-point decrease represented the minimal clinically important improvement in the Routine Assessment of Patient Index Data 3 (RAPID-3) index, investigators reported in The Journal of Rheumatology.

“Clinicians may feel comfortable documenting and monitoring patient status, recognizing an improvement of 3.8 units in patients with active RA to be meaningful in routine patient care,” Michael M. Ward, MD, PhD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and his coinvestigators wrote.

The RAPID-3 index consists of three patient self-report measures out of the seven-item RA Core Data Set: physical function, pain, and patient’s global assessment. The index was initially designed to be feasible in routine care, such that a patient could fill it out in the waiting area, Dr. Ward and his colleagues noted in their report.

Previous investigations have shown that RAPID-3 is highly correlated with the 28-joint count Disease Activity Score (DAS28) and the Clinical Disease Activity Index, and in one study, it was more likely than erythrocyte sedimentation rate (ESR) to identify incomplete responses to methotrexate.

However, prior to the present study, there were no reported estimates of the minimal clinically important improvement for the RAPID-3 index.

Knowing whether or not a decrease in RAPID-3 is clinically meaningful to patients would help clinicians interpret those changes in response to treatment, Dr. Ward and his coauthors wrote.

In the current study, RAPID-3 was calculated before and after escalation of treatment in a prospective study involving 250 adults with active RA, including 195 women (78%). The mean age of the patients was 51 years, and the median duration of RA was more than 6 years.

At the patients’ baseline visit and evaluation, rheumatologists prescribed prednisone, a new disease-modifying treatment, a new biologic, or increased the dose of a current treatment. The follow-up visit occurred at 4 months for most patients, though follow-up was at 1 month for prednisone-treated patients because of an expected rapid response.

At baseline, the mean RAPID-3 score was 16.3, which improved to 11.1 at the follow-up visit, for a mean change of –5.2 points, according to the investigators. The standardized response mean was –0.79 (95% confidence interval, –0.71 to –0.88), which investigators said demonstrated good sensitivity to change.

They found that the minimal clinically important improvement was –3.8 in a statistical analysis that optimized sensitivity and specificity, and –3.5 and –4.1 by alternate statistical criteria.

However, Dr. Ward and his coauthors cautioned that these estimates should be applied only to patient groups that have high levels of RA activity, similar to this study, in which patients had a baseline mean DAS28-ESR of 6.16 and a mean Simplified Disease Activity Index of 38.6.

Patients with low RA activity are closer to an acceptable symptom state, making the minimal clinically important improvement less relevant. “The margin for symptom improvement becomes smaller and ultimately indiscernible as the level of activity decreases,” they explained in their report.

The study was supported in part through the NIAMS Intramural Research Program and a grant from the U.S. Public Health Service. No conflicts of interest were reported.

SOURCE: Ward MM et al. J Rheumatol. 2018 Oct 15. doi: 10.3899/jrheum.180153.

An improvement of nearly 4 points on a 30-point, patient-scored disease severity index appears to be clinically meaningful for adults with active RA, according to a recent clinical trial analysis.

Richard Clark, NIAMS

A 3.8-point decrease represented the minimal clinically important improvement in the Routine Assessment of Patient Index Data 3 (RAPID-3) index, investigators reported in The Journal of Rheumatology.

“Clinicians may feel comfortable documenting and monitoring patient status, recognizing an improvement of 3.8 units in patients with active RA to be meaningful in routine patient care,” Michael M. Ward, MD, PhD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and his coinvestigators wrote.

The RAPID-3 index consists of three patient self-report measures out of the seven-item RA Core Data Set: physical function, pain, and patient’s global assessment. The index was initially designed to be feasible in routine care, such that a patient could fill it out in the waiting area, Dr. Ward and his colleagues noted in their report.

Previous investigations have shown that RAPID-3 is highly correlated with the 28-joint count Disease Activity Score (DAS28) and the Clinical Disease Activity Index, and in one study, it was more likely than erythrocyte sedimentation rate (ESR) to identify incomplete responses to methotrexate.

However, prior to the present study, there were no reported estimates of the minimal clinically important improvement for the RAPID-3 index.

Knowing whether or not a decrease in RAPID-3 is clinically meaningful to patients would help clinicians interpret those changes in response to treatment, Dr. Ward and his coauthors wrote.

In the current study, RAPID-3 was calculated before and after escalation of treatment in a prospective study involving 250 adults with active RA, including 195 women (78%). The mean age of the patients was 51 years, and the median duration of RA was more than 6 years.

At the patients’ baseline visit and evaluation, rheumatologists prescribed prednisone, a new disease-modifying treatment, a new biologic, or increased the dose of a current treatment. The follow-up visit occurred at 4 months for most patients, though follow-up was at 1 month for prednisone-treated patients because of an expected rapid response.

At baseline, the mean RAPID-3 score was 16.3, which improved to 11.1 at the follow-up visit, for a mean change of –5.2 points, according to the investigators. The standardized response mean was –0.79 (95% confidence interval, –0.71 to –0.88), which investigators said demonstrated good sensitivity to change.

They found that the minimal clinically important improvement was –3.8 in a statistical analysis that optimized sensitivity and specificity, and –3.5 and –4.1 by alternate statistical criteria.

However, Dr. Ward and his coauthors cautioned that these estimates should be applied only to patient groups that have high levels of RA activity, similar to this study, in which patients had a baseline mean DAS28-ESR of 6.16 and a mean Simplified Disease Activity Index of 38.6.

Patients with low RA activity are closer to an acceptable symptom state, making the minimal clinically important improvement less relevant. “The margin for symptom improvement becomes smaller and ultimately indiscernible as the level of activity decreases,” they explained in their report.

The study was supported in part through the NIAMS Intramural Research Program and a grant from the U.S. Public Health Service. No conflicts of interest were reported.

SOURCE: Ward MM et al. J Rheumatol. 2018 Oct 15. doi: 10.3899/jrheum.180153.