Background Complete remission (CR) in acute myeloid leukemia (AML) is defined as having ≤5% leukemic blast cells in the bone marrow and return of normal hematopoiesis after the first induction cycle. There is a subset of patients, however, who achieve reduction of leukemic blast cells with a subnormal platelet count, designated as CR with incomplete platelet recovery (platelet count, ≤100,000/mcL; normal, 150,000-450,000/mcL), which is associated with inferior outcomes when compared with CR. Furthermore, there is another subset of patients with CR but superior platelet counts (≥400,000/mcL) whose prognostic significance is unclear.

Objective To establish whether CR with superior platelet counts is associated with better outcomes and can be used as a separate entity for prognostication.

Methods A retrospective chart review of 104 cases of AML was conducted. The highest platelet count during days 25-35 from initiation of induction chemotherapy (designated as day 30 platelet count) was documented. A multivariate analysis for other factors such as age, sex, risk categories, day 14+ plasma cell count (average plasma cell percentage at days 14-21), infections, allogeneic bone marrow transplant, and remission status was done.

Results Day 30 platelet count was found to be an independent predictor of survival in AML. On the multivariate analysis, the subgroup with superior platelet counts (≥400,000/mcL) was found to be associated with better outcomes.

Limitations Results need to be validated in a larger cohort.

Conclusions CR with superior platelet recovery (≥400,000/mcL) is a unique subcategory in itself and has prognostic significance. This may help better assess response to chemotherapeutic agents and aid in further decision-making regarding treatment. 

Click on the PDF icon at the top of this introduction to read the full article.

Background Complete remission (CR) in acute myeloid leukemia (AML) is defined as having ≤5% leukemic blast cells in the bone marrow and return of normal hematopoiesis after the first induction cycle. There is a subset of patients, however, who achieve reduction of leukemic blast cells with a subnormal platelet count, designated as CR with incomplete platelet recovery (platelet count, ≤100,000/mcL; normal, 150,000-450,000/mcL), which is associated with inferior outcomes when compared with CR. Furthermore, there is another subset of patients with CR but superior platelet counts (≥400,000/mcL) whose prognostic significance is unclear.

Objective To establish whether CR with superior platelet counts is associated with better outcomes and can be used as a separate entity for prognostication.

Methods A retrospective chart review of 104 cases of AML was conducted. The highest platelet count during days 25-35 from initiation of induction chemotherapy (designated as day 30 platelet count) was documented. A multivariate analysis for other factors such as age, sex, risk categories, day 14+ plasma cell count (average plasma cell percentage at days 14-21), infections, allogeneic bone marrow transplant, and remission status was done.

Results Day 30 platelet count was found to be an independent predictor of survival in AML. On the multivariate analysis, the subgroup with superior platelet counts (≥400,000/mcL) was found to be associated with better outcomes.

Limitations Results need to be validated in a larger cohort.

Conclusions CR with superior platelet recovery (≥400,000/mcL) is a unique subcategory in itself and has prognostic significance. This may help better assess response to chemotherapeutic agents and aid in further decision-making regarding treatment. 

Click on the PDF icon at the top of this introduction to read the full article.

Background Complete remission (CR) in acute myeloid leukemia (AML) is defined as having ≤5% leukemic blast cells in the bone marrow and return of normal hematopoiesis after the first induction cycle. There is a subset of patients, however, who achieve reduction of leukemic blast cells with a subnormal platelet count, designated as CR with incomplete platelet recovery (platelet count, ≤100,000/mcL; normal, 150,000-450,000/mcL), which is associated with inferior outcomes when compared with CR. Furthermore, there is another subset of patients with CR but superior platelet counts (≥400,000/mcL) whose prognostic significance is unclear.

Objective To establish whether CR with superior platelet counts is associated with better outcomes and can be used as a separate entity for prognostication.

Methods A retrospective chart review of 104 cases of AML was conducted. The highest platelet count during days 25-35 from initiation of induction chemotherapy (designated as day 30 platelet count) was documented. A multivariate analysis for other factors such as age, sex, risk categories, day 14+ plasma cell count (average plasma cell percentage at days 14-21), infections, allogeneic bone marrow transplant, and remission status was done.

Results Day 30 platelet count was found to be an independent predictor of survival in AML. On the multivariate analysis, the subgroup with superior platelet counts (≥400,000/mcL) was found to be associated with better outcomes.

Limitations Results need to be validated in a larger cohort.

Conclusions CR with superior platelet recovery (≥400,000/mcL) is a unique subcategory in itself and has prognostic significance. This may help better assess response to chemotherapeutic agents and aid in further decision-making regarding treatment. 

Click on the PDF icon at the top of this introduction to read the full article.

Background The 3 fluoroquinolone (FQ) antibiotics – ciprofoxacin, levofoxacin, and moxifoxacin – are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia. New serious FQ-associated safety concerns have been identified through novel collaborations between FQ-treated persons who have developed long-term neuropsychiatric (NP) toxicity, pharmacovigilance experts, and basic scientists.

Objective To conduct basic science and clinical investigations of a newly identified adverse drug reaction, termed FQ-associated disability.

Methods 5 groups of C57BL/6 mice receiving the antibiotic ciprofoxacin in 10-mg increments (10 mg/kg-50 mg/kg) and 1 group of control mice were evaluated. The Southern Network on Adverse Reactions (SONAR) and a social network of FQ-treated persons with long-term NP toxicity (the Floxed Network) conducted a web-based survey. The clinical toxicity manifestations reported by 94 respondents to the web-based survey of persons who had received 1 or more doses of an FQ prescribed for any indication (generally at FDA-approved dosages) and who subsequently experienced possible adverse drug reactions were compared with adverse event information included on the product label for levofoxacin and with FQ-associated adverse events reported to the FDA’s MedWatch program.

Results Mice treated with ciprofoxacin had lower grip strengths, reduced balance, and depressive behavior compared with the controls. For the survey, 93 of 94 respondents reported FQ-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of FQ initiation or days to months of FQ discontinuation. The FDA Adverse Event Reporting System (FAERS) included 210,705 adverse events and 2,991 fatalities for FQs. Levofoxacin and ciprofoxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%), and psychiatric (10% and 2%). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria. In 2013 and 2014, SONAR fled citizen petitions requesting black box revisions identifying neuropsychiatric toxicities and mitochrondrial toxicity as serious levofoxacin-associated adverse drug reactions. In 2015, FDA advisors recommended that FQ product labels be revised to include information about this newly identified disability syndrome termed “FQ-associated disability” (FQAD).

Limitations Basic science studies evaluated NP toxicity for only 1 FQ, ciprofoxacin.

Conclusion Pharmacovigilance investigators, a social network, and basic scientists can collaborate on pharmacovigilance investigations. Revised product labels describing a new serious adverse drug reaction, levofoxacin-associated long-term disability, as recommended by an FDA advisory committee, are advised.

Funding This work was funded partly by the National Cancer Institute (1R01CA165609-01A1), the American Cancer Society (IRG-13-043-01), the South Carolina SmartState Program, and an unrestricted from Doris Levkoff Meddin to the South Carolina College of Pharmacy Center for Medication Safety and Efficacy.

Click on the PDF icon at the top of this introduction to read the full article.

Background The 3 fluoroquinolone (FQ) antibiotics – ciprofoxacin, levofoxacin, and moxifoxacin – are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia. New serious FQ-associated safety concerns have been identified through novel collaborations between FQ-treated persons who have developed long-term neuropsychiatric (NP) toxicity, pharmacovigilance experts, and basic scientists.

Objective To conduct basic science and clinical investigations of a newly identified adverse drug reaction, termed FQ-associated disability.

Methods 5 groups of C57BL/6 mice receiving the antibiotic ciprofoxacin in 10-mg increments (10 mg/kg-50 mg/kg) and 1 group of control mice were evaluated. The Southern Network on Adverse Reactions (SONAR) and a social network of FQ-treated persons with long-term NP toxicity (the Floxed Network) conducted a web-based survey. The clinical toxicity manifestations reported by 94 respondents to the web-based survey of persons who had received 1 or more doses of an FQ prescribed for any indication (generally at FDA-approved dosages) and who subsequently experienced possible adverse drug reactions were compared with adverse event information included on the product label for levofoxacin and with FQ-associated adverse events reported to the FDA’s MedWatch program.

Results Mice treated with ciprofoxacin had lower grip strengths, reduced balance, and depressive behavior compared with the controls. For the survey, 93 of 94 respondents reported FQ-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of FQ initiation or days to months of FQ discontinuation. The FDA Adverse Event Reporting System (FAERS) included 210,705 adverse events and 2,991 fatalities for FQs. Levofoxacin and ciprofoxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%), and psychiatric (10% and 2%). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria. In 2013 and 2014, SONAR fled citizen petitions requesting black box revisions identifying neuropsychiatric toxicities and mitochrondrial toxicity as serious levofoxacin-associated adverse drug reactions. In 2015, FDA advisors recommended that FQ product labels be revised to include information about this newly identified disability syndrome termed “FQ-associated disability” (FQAD).

Limitations Basic science studies evaluated NP toxicity for only 1 FQ, ciprofoxacin.

Conclusion Pharmacovigilance investigators, a social network, and basic scientists can collaborate on pharmacovigilance investigations. Revised product labels describing a new serious adverse drug reaction, levofoxacin-associated long-term disability, as recommended by an FDA advisory committee, are advised.

Funding This work was funded partly by the National Cancer Institute (1R01CA165609-01A1), the American Cancer Society (IRG-13-043-01), the South Carolina SmartState Program, and an unrestricted from Doris Levkoff Meddin to the South Carolina College of Pharmacy Center for Medication Safety and Efficacy.

Click on the PDF icon at the top of this introduction to read the full article.

Background The 3 fluoroquinolone (FQ) antibiotics – ciprofoxacin, levofoxacin, and moxifoxacin – are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia. New serious FQ-associated safety concerns have been identified through novel collaborations between FQ-treated persons who have developed long-term neuropsychiatric (NP) toxicity, pharmacovigilance experts, and basic scientists.

Objective To conduct basic science and clinical investigations of a newly identified adverse drug reaction, termed FQ-associated disability.

Methods 5 groups of C57BL/6 mice receiving the antibiotic ciprofoxacin in 10-mg increments (10 mg/kg-50 mg/kg) and 1 group of control mice were evaluated. The Southern Network on Adverse Reactions (SONAR) and a social network of FQ-treated persons with long-term NP toxicity (the Floxed Network) conducted a web-based survey. The clinical toxicity manifestations reported by 94 respondents to the web-based survey of persons who had received 1 or more doses of an FQ prescribed for any indication (generally at FDA-approved dosages) and who subsequently experienced possible adverse drug reactions were compared with adverse event information included on the product label for levofoxacin and with FQ-associated adverse events reported to the FDA’s MedWatch program.

Results Mice treated with ciprofoxacin had lower grip strengths, reduced balance, and depressive behavior compared with the controls. For the survey, 93 of 94 respondents reported FQ-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of FQ initiation or days to months of FQ discontinuation. The FDA Adverse Event Reporting System (FAERS) included 210,705 adverse events and 2,991 fatalities for FQs. Levofoxacin and ciprofoxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%), and psychiatric (10% and 2%). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria. In 2013 and 2014, SONAR fled citizen petitions requesting black box revisions identifying neuropsychiatric toxicities and mitochrondrial toxicity as serious levofoxacin-associated adverse drug reactions. In 2015, FDA advisors recommended that FQ product labels be revised to include information about this newly identified disability syndrome termed “FQ-associated disability” (FQAD).

Limitations Basic science studies evaluated NP toxicity for only 1 FQ, ciprofoxacin.

Conclusion Pharmacovigilance investigators, a social network, and basic scientists can collaborate on pharmacovigilance investigations. Revised product labels describing a new serious adverse drug reaction, levofoxacin-associated long-term disability, as recommended by an FDA advisory committee, are advised.

Funding This work was funded partly by the National Cancer Institute (1R01CA165609-01A1), the American Cancer Society (IRG-13-043-01), the South Carolina SmartState Program, and an unrestricted from Doris Levkoff Meddin to the South Carolina College of Pharmacy Center for Medication Safety and Efficacy.

Click on the PDF icon at the top of this introduction to read the full article.

NEW ORLEANS – A decline in levels of anti-müllerian hormone as women approach menopause – a phenomenon dubbed ovarian decline – appears associated with clinical disability and brain atrophy in women with multiple sclerosis, according to the findings of a study of more than 400 women with multiple sclerosis followed up for a decade.

This “accumulation of disability” may explain the often rapid transition from a benign disease course to secondary progressive multiple sclerosis (MS) in women as they approach menopause, Dr. Jennifer S. Graves reported at a meeting held by at the Americas Committee for Treatment and Research in Multiple Sclerosis.

Earlier in life, females often have a more benign initial course of MS than males. The mean age of onset of primary progressive MS and secondary progressive MS are both approximately 45 years. The mean age of menopause is 51 years. Ovarian aging involves up to a 10-year period of decline in ovarian function. After age 50, “women catch up in terms of disability with males” with MS, said Dr. Graves of the University of California, San Francisco. One explanation could be that ovarian aging contributes to the development of progressive disease.

The objective was to determine if ovarian decline as measured by the levels of anti-müllerian hormone (AMH) is associated with clinical disability or brain atrophy in women with MS. The cohort of 412 female patients with MS (mean age, 43 years) was from the UCSF EPIC (Expression, Proteomics, Imaging, Clinical) study, which has followed more than 500 people with MS since 2004 with the aim of identifying factors that drive the disease. Also included were 180 healthy controls with the exact same mean age. AMH levels were measured using an ultrasensitive enzyme-linked immunosorbent assay at baseline and at years 3, 5, 8, 9, and 10. Brain magnetic resonance imaging data also were acquired.

When the data were adjusted for chronologic age, women with MS and healthy controls displayed similar AMH levels (P = .97), implying a normal follicular reserve and rate of ovarian decline in those with MS. White matter volume was associated with AMH levels at baseline (P = .047). The association did not persist when adjusted for age as well as disease duration and body mass index (P = .24), while ovarian reserve was associated with normalized gray matter volume (P = .049) and MS functional composite z scores (P = .036) at baseline. Scrutiny of the follow-up period revealed that a twofold decrease in AMH was associated with a 1.85-mm³ decrease in gray matter volume (P = .060) in MS patients. Almost a third of the MS patients had undetectable levels of AMH, which was associated with a 0.60-point higher expanded disability status scale score (P =.039)

The results support the hypothesized association of ovarian decline with increased severity of MS. Furthermore, AMH may be a useful biomarker of MS progression, said Dr. Graves. “The advantage of this biomarker would be that it captures biological activity in women in their 40s, and so could let you know of imminent change.”

Validation of the findings needs to be done.

The study was funded by the National Institutes of Health, National MS Society, Race to Erase MS, Foundation for the Cedars-Sinai Medical Center, Biogen, and Genentech. Dr. Graves had no relevant financial disclosures.

NEW ORLEANS – A decline in levels of anti-müllerian hormone as women approach menopause – a phenomenon dubbed ovarian decline – appears associated with clinical disability and brain atrophy in women with multiple sclerosis, according to the findings of a study of more than 400 women with multiple sclerosis followed up for a decade.

This “accumulation of disability” may explain the often rapid transition from a benign disease course to secondary progressive multiple sclerosis (MS) in women as they approach menopause, Dr. Jennifer S. Graves reported at a meeting held by at the Americas Committee for Treatment and Research in Multiple Sclerosis.

Earlier in life, females often have a more benign initial course of MS than males. The mean age of onset of primary progressive MS and secondary progressive MS are both approximately 45 years. The mean age of menopause is 51 years. Ovarian aging involves up to a 10-year period of decline in ovarian function. After age 50, “women catch up in terms of disability with males” with MS, said Dr. Graves of the University of California, San Francisco. One explanation could be that ovarian aging contributes to the development of progressive disease.

The objective was to determine if ovarian decline as measured by the levels of anti-müllerian hormone (AMH) is associated with clinical disability or brain atrophy in women with MS. The cohort of 412 female patients with MS (mean age, 43 years) was from the UCSF EPIC (Expression, Proteomics, Imaging, Clinical) study, which has followed more than 500 people with MS since 2004 with the aim of identifying factors that drive the disease. Also included were 180 healthy controls with the exact same mean age. AMH levels were measured using an ultrasensitive enzyme-linked immunosorbent assay at baseline and at years 3, 5, 8, 9, and 10. Brain magnetic resonance imaging data also were acquired.

When the data were adjusted for chronologic age, women with MS and healthy controls displayed similar AMH levels (P = .97), implying a normal follicular reserve and rate of ovarian decline in those with MS. White matter volume was associated with AMH levels at baseline (P = .047). The association did not persist when adjusted for age as well as disease duration and body mass index (P = .24), while ovarian reserve was associated with normalized gray matter volume (P = .049) and MS functional composite z scores (P = .036) at baseline. Scrutiny of the follow-up period revealed that a twofold decrease in AMH was associated with a 1.85-mm³ decrease in gray matter volume (P = .060) in MS patients. Almost a third of the MS patients had undetectable levels of AMH, which was associated with a 0.60-point higher expanded disability status scale score (P =.039)

The results support the hypothesized association of ovarian decline with increased severity of MS. Furthermore, AMH may be a useful biomarker of MS progression, said Dr. Graves. “The advantage of this biomarker would be that it captures biological activity in women in their 40s, and so could let you know of imminent change.”

Validation of the findings needs to be done.

The study was funded by the National Institutes of Health, National MS Society, Race to Erase MS, Foundation for the Cedars-Sinai Medical Center, Biogen, and Genentech. Dr. Graves had no relevant financial disclosures.

NEW ORLEANS – A decline in levels of anti-müllerian hormone as women approach menopause – a phenomenon dubbed ovarian decline – appears associated with clinical disability and brain atrophy in women with multiple sclerosis, according to the findings of a study of more than 400 women with multiple sclerosis followed up for a decade.

This “accumulation of disability” may explain the often rapid transition from a benign disease course to secondary progressive multiple sclerosis (MS) in women as they approach menopause, Dr. Jennifer S. Graves reported at a meeting held by at the Americas Committee for Treatment and Research in Multiple Sclerosis.

Earlier in life, females often have a more benign initial course of MS than males. The mean age of onset of primary progressive MS and secondary progressive MS are both approximately 45 years. The mean age of menopause is 51 years. Ovarian aging involves up to a 10-year period of decline in ovarian function. After age 50, “women catch up in terms of disability with males” with MS, said Dr. Graves of the University of California, San Francisco. One explanation could be that ovarian aging contributes to the development of progressive disease.

The objective was to determine if ovarian decline as measured by the levels of anti-müllerian hormone (AMH) is associated with clinical disability or brain atrophy in women with MS. The cohort of 412 female patients with MS (mean age, 43 years) was from the UCSF EPIC (Expression, Proteomics, Imaging, Clinical) study, which has followed more than 500 people with MS since 2004 with the aim of identifying factors that drive the disease. Also included were 180 healthy controls with the exact same mean age. AMH levels were measured using an ultrasensitive enzyme-linked immunosorbent assay at baseline and at years 3, 5, 8, 9, and 10. Brain magnetic resonance imaging data also were acquired.

When the data were adjusted for chronologic age, women with MS and healthy controls displayed similar AMH levels (P = .97), implying a normal follicular reserve and rate of ovarian decline in those with MS. White matter volume was associated with AMH levels at baseline (P = .047). The association did not persist when adjusted for age as well as disease duration and body mass index (P = .24), while ovarian reserve was associated with normalized gray matter volume (P = .049) and MS functional composite z scores (P = .036) at baseline. Scrutiny of the follow-up period revealed that a twofold decrease in AMH was associated with a 1.85-mm³ decrease in gray matter volume (P = .060) in MS patients. Almost a third of the MS patients had undetectable levels of AMH, which was associated with a 0.60-point higher expanded disability status scale score (P =.039)

The results support the hypothesized association of ovarian decline with increased severity of MS. Furthermore, AMH may be a useful biomarker of MS progression, said Dr. Graves. “The advantage of this biomarker would be that it captures biological activity in women in their 40s, and so could let you know of imminent change.”

Validation of the findings needs to be done.

The study was funded by the National Institutes of Health, National MS Society, Race to Erase MS, Foundation for the Cedars-Sinai Medical Center, Biogen, and Genentech. Dr. Graves had no relevant financial disclosures.

NEW ORLEANS – Exercise can be beneficial in transiently improving cognitive impairment in people with multiple sclerosis.

Research presented at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis has extended the exercise benefit to cognitive impairment, as measured by reaction time in 24 subjects. The benefit, which was transient, also was evident in 14 subjects who were thermosensitive and displayed elevated core body temperature during exercise. Although preliminary, the data are sufficiently evocative to warrant randomized controlled trials (RCTs).

Brian Hoyle/Frontline Medical News

Cognitive impairment is prevalent in MS, being present in upward of 50% of affected individuals. Exercise may or may not be beneficial in cognitive improvement, given the inconsistent results from three RCTs that have been done. The different types of exercise used in the studies could be one reason for the uncertainty.

For people with MS who are fully ambulatory, treadmill walking could be the best form of exercise. But it’s not known how long and at what intensity someone should walk to realize any cognitive benefit. The investigators, led by Brian M. Sandroff, Ph.D., a postdoctoral fellow at the Kessler Foundation, West Orange, N.J., designed the study to assess these unknowns.

The study compared the influence of light, moderate, and vigorous treadmill walking on what is known as inhibitory control – a mental ability to react to stimuli. A period of quiet rest also was included prior to treadmill walking to assess the effects of no walking. The four conditions were tested in random order by the 24 participants with MS who had an Expanded Disability Status Scale (EDSS) score greater than or equal to 4, indicative of minimal or moderate disability. Prior to and soon after 20 minutes of treadmill walking, the reaction time of each participant was judged using a modified flanker task. The test requires a subject to respond to specific relevant information or ignore irrelevant information. The time for a correct response was the reaction time.

Light, moderate, and vigorous treadmill walking similarly and significantly improved reaction time, compared with quiet rest. To assess whether an increase in core body temperature might negate the exercise-related benefit, core body temperature was assessed in 14 thermosensitive MS patients (EDSS less than or equal to 4.0). Core body temperature was recorded every 10 seconds using an ingested sensor capsule and wireless data recorder during 20 minutes of vigorous treadmill exercise and 20 minutes of quiet rest. The core temperature of the subjects rose significantly by about 0.6° C during exercise. But this did not affect the exercise-related improved reaction time.

“There have been no published studies comparing the acute (transient) versus chronic effects of exercise on cognition in MS. We have hypothesized that the acute effects of single bouts of exercise on cognition will be both additive and cumulative over time, when delivered in a longitudinal intervention – much like the effects of a single bout of aerobic exercise on aerobic fitness. In this example, you get small, transient improvements in aerobic fitness after a single session of aerobic exercise; these small improvements add up with continued training, and eventually result in a meaningful improvement,” Dr. Sandroff said in an interview.

The researchers are planning an RCT on the longer-term effects of treadmill walking exercise training on cognition and brain structure/function.

The study was not funded by an external grant. Dr. Sandroff had no relevant financial disclosures.

NEW ORLEANS – Exercise can be beneficial in transiently improving cognitive impairment in people with multiple sclerosis.

Research presented at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis has extended the exercise benefit to cognitive impairment, as measured by reaction time in 24 subjects. The benefit, which was transient, also was evident in 14 subjects who were thermosensitive and displayed elevated core body temperature during exercise. Although preliminary, the data are sufficiently evocative to warrant randomized controlled trials (RCTs).

Brian Hoyle/Frontline Medical News

Cognitive impairment is prevalent in MS, being present in upward of 50% of affected individuals. Exercise may or may not be beneficial in cognitive improvement, given the inconsistent results from three RCTs that have been done. The different types of exercise used in the studies could be one reason for the uncertainty.

For people with MS who are fully ambulatory, treadmill walking could be the best form of exercise. But it’s not known how long and at what intensity someone should walk to realize any cognitive benefit. The investigators, led by Brian M. Sandroff, Ph.D., a postdoctoral fellow at the Kessler Foundation, West Orange, N.J., designed the study to assess these unknowns.

The study compared the influence of light, moderate, and vigorous treadmill walking on what is known as inhibitory control – a mental ability to react to stimuli. A period of quiet rest also was included prior to treadmill walking to assess the effects of no walking. The four conditions were tested in random order by the 24 participants with MS who had an Expanded Disability Status Scale (EDSS) score greater than or equal to 4, indicative of minimal or moderate disability. Prior to and soon after 20 minutes of treadmill walking, the reaction time of each participant was judged using a modified flanker task. The test requires a subject to respond to specific relevant information or ignore irrelevant information. The time for a correct response was the reaction time.

Light, moderate, and vigorous treadmill walking similarly and significantly improved reaction time, compared with quiet rest. To assess whether an increase in core body temperature might negate the exercise-related benefit, core body temperature was assessed in 14 thermosensitive MS patients (EDSS less than or equal to 4.0). Core body temperature was recorded every 10 seconds using an ingested sensor capsule and wireless data recorder during 20 minutes of vigorous treadmill exercise and 20 minutes of quiet rest. The core temperature of the subjects rose significantly by about 0.6° C during exercise. But this did not affect the exercise-related improved reaction time.

“There have been no published studies comparing the acute (transient) versus chronic effects of exercise on cognition in MS. We have hypothesized that the acute effects of single bouts of exercise on cognition will be both additive and cumulative over time, when delivered in a longitudinal intervention – much like the effects of a single bout of aerobic exercise on aerobic fitness. In this example, you get small, transient improvements in aerobic fitness after a single session of aerobic exercise; these small improvements add up with continued training, and eventually result in a meaningful improvement,” Dr. Sandroff said in an interview.

The researchers are planning an RCT on the longer-term effects of treadmill walking exercise training on cognition and brain structure/function.

The study was not funded by an external grant. Dr. Sandroff had no relevant financial disclosures.

NEW ORLEANS – Exercise can be beneficial in transiently improving cognitive impairment in people with multiple sclerosis.

Research presented at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis has extended the exercise benefit to cognitive impairment, as measured by reaction time in 24 subjects. The benefit, which was transient, also was evident in 14 subjects who were thermosensitive and displayed elevated core body temperature during exercise. Although preliminary, the data are sufficiently evocative to warrant randomized controlled trials (RCTs).

Brian Hoyle/Frontline Medical News

Cognitive impairment is prevalent in MS, being present in upward of 50% of affected individuals. Exercise may or may not be beneficial in cognitive improvement, given the inconsistent results from three RCTs that have been done. The different types of exercise used in the studies could be one reason for the uncertainty.

For people with MS who are fully ambulatory, treadmill walking could be the best form of exercise. But it’s not known how long and at what intensity someone should walk to realize any cognitive benefit. The investigators, led by Brian M. Sandroff, Ph.D., a postdoctoral fellow at the Kessler Foundation, West Orange, N.J., designed the study to assess these unknowns.

The study compared the influence of light, moderate, and vigorous treadmill walking on what is known as inhibitory control – a mental ability to react to stimuli. A period of quiet rest also was included prior to treadmill walking to assess the effects of no walking. The four conditions were tested in random order by the 24 participants with MS who had an Expanded Disability Status Scale (EDSS) score greater than or equal to 4, indicative of minimal or moderate disability. Prior to and soon after 20 minutes of treadmill walking, the reaction time of each participant was judged using a modified flanker task. The test requires a subject to respond to specific relevant information or ignore irrelevant information. The time for a correct response was the reaction time.

Light, moderate, and vigorous treadmill walking similarly and significantly improved reaction time, compared with quiet rest. To assess whether an increase in core body temperature might negate the exercise-related benefit, core body temperature was assessed in 14 thermosensitive MS patients (EDSS less than or equal to 4.0). Core body temperature was recorded every 10 seconds using an ingested sensor capsule and wireless data recorder during 20 minutes of vigorous treadmill exercise and 20 minutes of quiet rest. The core temperature of the subjects rose significantly by about 0.6° C during exercise. But this did not affect the exercise-related improved reaction time.

“There have been no published studies comparing the acute (transient) versus chronic effects of exercise on cognition in MS. We have hypothesized that the acute effects of single bouts of exercise on cognition will be both additive and cumulative over time, when delivered in a longitudinal intervention – much like the effects of a single bout of aerobic exercise on aerobic fitness. In this example, you get small, transient improvements in aerobic fitness after a single session of aerobic exercise; these small improvements add up with continued training, and eventually result in a meaningful improvement,” Dr. Sandroff said in an interview.

The researchers are planning an RCT on the longer-term effects of treadmill walking exercise training on cognition and brain structure/function.

The study was not funded by an external grant. Dr. Sandroff had no relevant financial disclosures.

Eight hospitalists have joined Team Hospitalist, the only reader involvement group of its kind in hospital medicine. Each of the new members has experience in the practice of HM; many offer specialized backgrounds in pediatrics, academics, quality and patient safety, and group administration. The new members will serve two-year terms and act as special editorial consultants to the magazine.

Geeta Arora, MD, is a locum tenens hospitalist.  She travels around the country practicing hospitalist medicine, telemedicine and travels the world practicing global medicine. Dr. Arora currently resides in New York City and holds board certifications in both internal medicine as well as integrative holistic medicine.

Michael J. Beck, MD, FAAP, is division chief of pediatric hospital medicine in the Department of Pediatrics, associate professor of pediatrics and internal medicine, and assistant program director, medicine/pediatrics residency program at Penn State Children's Hospital and Milton S. Hershey Medical Center in Pennsylvania.

Kevin M. Conrad, MD, MBA, is a hospitalist and medical director of community affairs and health policy at Ochsner Health Systems in New Orleans, La. He is an associate professor of medicine at Tulane University.

Stella Fitzgibbons, MD, FACP, FHM, is a hospitalist and emergency physician with Mint Physicians, primarily in Apollo Hospital System.

Benjamin Frizner, MD, FHM, is a hospitalist and director of the ventilator unit at Future Care, a Baltimore, Md.-based organization providing post-acute care across 12 facilities throughout southern Maryland.

Sarah A. Stella, MD, is an academic hospitalist in the division of hospital medicine and physician advisor for the department of care management at Denver Health in Colorado. She is an assistant professor of medicine at the University of Colorado School of Medicine in Aurora.

Miguel Angel Villagra Diaz, MD, is a hospitalist and medical director for the hospital medicine program at White River Medical Center in Batesville, Ark.

Jill Slater Waldman, MD, SFHM, is director of the adult hospital service at Phelps Memorial Hospital Center in Sleepy Hollow, N.Y. She is medical director and physician advisor for utilization management, assistant to the CMO, and course coordinator for the internal medicine rotation.

Eight hospitalists have joined Team Hospitalist, the only reader involvement group of its kind in hospital medicine. Each of the new members has experience in the practice of HM; many offer specialized backgrounds in pediatrics, academics, quality and patient safety, and group administration. The new members will serve two-year terms and act as special editorial consultants to the magazine.

Geeta Arora, MD, is a locum tenens hospitalist.  She travels around the country practicing hospitalist medicine, telemedicine and travels the world practicing global medicine. Dr. Arora currently resides in New York City and holds board certifications in both internal medicine as well as integrative holistic medicine.

Michael J. Beck, MD, FAAP, is division chief of pediatric hospital medicine in the Department of Pediatrics, associate professor of pediatrics and internal medicine, and assistant program director, medicine/pediatrics residency program at Penn State Children's Hospital and Milton S. Hershey Medical Center in Pennsylvania.

Kevin M. Conrad, MD, MBA, is a hospitalist and medical director of community affairs and health policy at Ochsner Health Systems in New Orleans, La. He is an associate professor of medicine at Tulane University.

Stella Fitzgibbons, MD, FACP, FHM, is a hospitalist and emergency physician with Mint Physicians, primarily in Apollo Hospital System.

Benjamin Frizner, MD, FHM, is a hospitalist and director of the ventilator unit at Future Care, a Baltimore, Md.-based organization providing post-acute care across 12 facilities throughout southern Maryland.

Sarah A. Stella, MD, is an academic hospitalist in the division of hospital medicine and physician advisor for the department of care management at Denver Health in Colorado. She is an assistant professor of medicine at the University of Colorado School of Medicine in Aurora.

Miguel Angel Villagra Diaz, MD, is a hospitalist and medical director for the hospital medicine program at White River Medical Center in Batesville, Ark.

Jill Slater Waldman, MD, SFHM, is director of the adult hospital service at Phelps Memorial Hospital Center in Sleepy Hollow, N.Y. She is medical director and physician advisor for utilization management, assistant to the CMO, and course coordinator for the internal medicine rotation.

Eight hospitalists have joined Team Hospitalist, the only reader involvement group of its kind in hospital medicine. Each of the new members has experience in the practice of HM; many offer specialized backgrounds in pediatrics, academics, quality and patient safety, and group administration. The new members will serve two-year terms and act as special editorial consultants to the magazine.

Geeta Arora, MD, is a locum tenens hospitalist.  She travels around the country practicing hospitalist medicine, telemedicine and travels the world practicing global medicine. Dr. Arora currently resides in New York City and holds board certifications in both internal medicine as well as integrative holistic medicine.

Michael J. Beck, MD, FAAP, is division chief of pediatric hospital medicine in the Department of Pediatrics, associate professor of pediatrics and internal medicine, and assistant program director, medicine/pediatrics residency program at Penn State Children's Hospital and Milton S. Hershey Medical Center in Pennsylvania.

Kevin M. Conrad, MD, MBA, is a hospitalist and medical director of community affairs and health policy at Ochsner Health Systems in New Orleans, La. He is an associate professor of medicine at Tulane University.

Stella Fitzgibbons, MD, FACP, FHM, is a hospitalist and emergency physician with Mint Physicians, primarily in Apollo Hospital System.

Benjamin Frizner, MD, FHM, is a hospitalist and director of the ventilator unit at Future Care, a Baltimore, Md.-based organization providing post-acute care across 12 facilities throughout southern Maryland.

Sarah A. Stella, MD, is an academic hospitalist in the division of hospital medicine and physician advisor for the department of care management at Denver Health in Colorado. She is an assistant professor of medicine at the University of Colorado School of Medicine in Aurora.

Miguel Angel Villagra Diaz, MD, is a hospitalist and medical director for the hospital medicine program at White River Medical Center in Batesville, Ark.

Jill Slater Waldman, MD, SFHM, is director of the adult hospital service at Phelps Memorial Hospital Center in Sleepy Hollow, N.Y. She is medical director and physician advisor for utilization management, assistant to the CMO, and course coordinator for the internal medicine rotation.

Zeshan Anwar, MD, is the new medical director of the hospitalist group at Evangelical Community Hospital in Lewisburg, Pa. Before arriving at Evangelical as a hospitalist in 2013, Dr. Anwar served as a hospitalist at Lock Haven Hospital in Linden, Pa., where he was also chair of the quality improvement committee and a physician advisor.

Deshini Moonesinghe, MD, is the new senior vice president and chief medical officer for the Howard Region of Community Howard Regional Health in Kokomo, Ind. Dr. Moonesinghe spearheaded the foundation of Community Howard’s hospitalist program in 2010, and she currently serves as lead hospitalist of the health system. Dr. Moonesinghe received Community Howard’s Physician of the Year Award in 2014.

Business Deals

Sound Physicians is celebrating with one of its partner hospitals, OSF St. Francis Hospital in Escanaba, Mich., which was recently named one of The Leapfrog Group’s Top Hospitals in the U.S. for the fourth consecutive year. Sound Physicians manages OSF St. Francis’s hospitalist physicians and oversees more than half of the hospital’s total inpatient admissions. The Leapfrog Group’s Top Hospitals list is compiled from survey results based on Leapfrog’s quality and safety standards.

Michael O’Neal is a freelance writer in New York City.

Zeshan Anwar, MD, is the new medical director of the hospitalist group at Evangelical Community Hospital in Lewisburg, Pa. Before arriving at Evangelical as a hospitalist in 2013, Dr. Anwar served as a hospitalist at Lock Haven Hospital in Linden, Pa., where he was also chair of the quality improvement committee and a physician advisor.

Deshini Moonesinghe, MD, is the new senior vice president and chief medical officer for the Howard Region of Community Howard Regional Health in Kokomo, Ind. Dr. Moonesinghe spearheaded the foundation of Community Howard’s hospitalist program in 2010, and she currently serves as lead hospitalist of the health system. Dr. Moonesinghe received Community Howard’s Physician of the Year Award in 2014.

Business Deals

Sound Physicians is celebrating with one of its partner hospitals, OSF St. Francis Hospital in Escanaba, Mich., which was recently named one of The Leapfrog Group’s Top Hospitals in the U.S. for the fourth consecutive year. Sound Physicians manages OSF St. Francis’s hospitalist physicians and oversees more than half of the hospital’s total inpatient admissions. The Leapfrog Group’s Top Hospitals list is compiled from survey results based on Leapfrog’s quality and safety standards.

Michael O’Neal is a freelance writer in New York City.

Zeshan Anwar, MD, is the new medical director of the hospitalist group at Evangelical Community Hospital in Lewisburg, Pa. Before arriving at Evangelical as a hospitalist in 2013, Dr. Anwar served as a hospitalist at Lock Haven Hospital in Linden, Pa., where he was also chair of the quality improvement committee and a physician advisor.

Deshini Moonesinghe, MD, is the new senior vice president and chief medical officer for the Howard Region of Community Howard Regional Health in Kokomo, Ind. Dr. Moonesinghe spearheaded the foundation of Community Howard’s hospitalist program in 2010, and she currently serves as lead hospitalist of the health system. Dr. Moonesinghe received Community Howard’s Physician of the Year Award in 2014.

Business Deals

Sound Physicians is celebrating with one of its partner hospitals, OSF St. Francis Hospital in Escanaba, Mich., which was recently named one of The Leapfrog Group’s Top Hospitals in the U.S. for the fourth consecutive year. Sound Physicians manages OSF St. Francis’s hospitalist physicians and oversees more than half of the hospital’s total inpatient admissions. The Leapfrog Group’s Top Hospitals list is compiled from survey results based on Leapfrog’s quality and safety standards.

Michael O’Neal is a freelance writer in New York City.

Blood smear showing
Plasmodium vivax
Image by Mae Melvin

Researchers say they have determined the structure of the protein PvRBP2a, which is used by the malaria parasite Plasmodium vivax to infect human red blood cells.

This revealed that PvRBP2a is structurally similar to PfRh5, the essential erythrocyte-binding protein in the parasite P falciparum.

The researchers believe these findings could help scientists generate new tools to prevent infection with malaria parasites.

Wai-Hong Tham, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and her colleagues conducted this research and reported the results in PNAS.

“We have produced the first 3-dimensional, atomic resolution structure of the protein [PvRBP2a] using the Australian Synchrotron in Melbourne,” Dr Tham said.

She and her colleagues found that PvRBP2a consists of 10 α-helices and 1 short β-hairpin. And although PvRBP2a is structurally similar to PfRh5, the 2 proteins have different surface properties.

“The 3-dimensional map showed us that the proteins are folded in the same way—like having similar origami instructions,” Dr Tham said. “The difference is actually in the electrical charge on the surface of the molecules.”

“Now that we have an atomic-resolution map, we hope to identify a common part of the protein that could be used to design a vaccine not only for Plasmodium vivax but potentially for both vivax and falciparum.”

“These two species of malaria are responsible for the majority of malaria infections worldwide, so a vaccine that targets both would be a critical addition to our arsenal.”

Dr Tham said there is growing evidence that developing better treatments or preventive strategies for P vivax malaria is imperative for malaria eradication.

“Not only is P vivax the most widespread species of malaria, it is also more difficult to treat because it can hide in the liver for long periods of time without symptoms,” she said. “In addition, studies show that effective treatment of falciparum malaria tends to be accompanied by a resurgence of P vivax, so it is critical to continue looking for better ways to manage this species.”

Blood smear showing
Plasmodium vivax
Image by Mae Melvin

Researchers say they have determined the structure of the protein PvRBP2a, which is used by the malaria parasite Plasmodium vivax to infect human red blood cells.

This revealed that PvRBP2a is structurally similar to PfRh5, the essential erythrocyte-binding protein in the parasite P falciparum.

The researchers believe these findings could help scientists generate new tools to prevent infection with malaria parasites.

Wai-Hong Tham, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and her colleagues conducted this research and reported the results in PNAS.

“We have produced the first 3-dimensional, atomic resolution structure of the protein [PvRBP2a] using the Australian Synchrotron in Melbourne,” Dr Tham said.

She and her colleagues found that PvRBP2a consists of 10 α-helices and 1 short β-hairpin. And although PvRBP2a is structurally similar to PfRh5, the 2 proteins have different surface properties.

“The 3-dimensional map showed us that the proteins are folded in the same way—like having similar origami instructions,” Dr Tham said. “The difference is actually in the electrical charge on the surface of the molecules.”

“Now that we have an atomic-resolution map, we hope to identify a common part of the protein that could be used to design a vaccine not only for Plasmodium vivax but potentially for both vivax and falciparum.”

“These two species of malaria are responsible for the majority of malaria infections worldwide, so a vaccine that targets both would be a critical addition to our arsenal.”

Dr Tham said there is growing evidence that developing better treatments or preventive strategies for P vivax malaria is imperative for malaria eradication.

“Not only is P vivax the most widespread species of malaria, it is also more difficult to treat because it can hide in the liver for long periods of time without symptoms,” she said. “In addition, studies show that effective treatment of falciparum malaria tends to be accompanied by a resurgence of P vivax, so it is critical to continue looking for better ways to manage this species.”

Blood smear showing
Plasmodium vivax
Image by Mae Melvin

Researchers say they have determined the structure of the protein PvRBP2a, which is used by the malaria parasite Plasmodium vivax to infect human red blood cells.

This revealed that PvRBP2a is structurally similar to PfRh5, the essential erythrocyte-binding protein in the parasite P falciparum.

The researchers believe these findings could help scientists generate new tools to prevent infection with malaria parasites.

Wai-Hong Tham, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and her colleagues conducted this research and reported the results in PNAS.

“We have produced the first 3-dimensional, atomic resolution structure of the protein [PvRBP2a] using the Australian Synchrotron in Melbourne,” Dr Tham said.

She and her colleagues found that PvRBP2a consists of 10 α-helices and 1 short β-hairpin. And although PvRBP2a is structurally similar to PfRh5, the 2 proteins have different surface properties.

“The 3-dimensional map showed us that the proteins are folded in the same way—like having similar origami instructions,” Dr Tham said. “The difference is actually in the electrical charge on the surface of the molecules.”

“Now that we have an atomic-resolution map, we hope to identify a common part of the protein that could be used to design a vaccine not only for Plasmodium vivax but potentially for both vivax and falciparum.”

“These two species of malaria are responsible for the majority of malaria infections worldwide, so a vaccine that targets both would be a critical addition to our arsenal.”

Dr Tham said there is growing evidence that developing better treatments or preventive strategies for P vivax malaria is imperative for malaria eradication.

“Not only is P vivax the most widespread species of malaria, it is also more difficult to treat because it can hide in the liver for long periods of time without symptoms,” she said. “In addition, studies show that effective treatment of falciparum malaria tends to be accompanied by a resurgence of P vivax, so it is critical to continue looking for better ways to manage this species.”

Activity of influenza-like illness (ILI) was at its highest level so far for week 18 of the 2015-2016 flu season, according to the Centers for Disease Control and Prevention.

That increased activity put Arizona and Puerto Rico at level 10 on the CDC’s 1-10 scale of ILI activity for the week ending Feb. 13. Joining them in the “high” range of activity was Oklahoma at level 8, the CDC reported Feb. 19.

The percentage of visits for ILI in week 18 was 3.1%, higher than the national baseline of 2.1% and the highest level of the flu season. For the week, 30 states were at level 2 or higher on the CDC’s 1-10 scale, which is the highest number for the season. States in the “moderate” range were Arkansas, Connecticut, Illinois, and New Mexico at level 7 and Florida, Hawaii, Maryland, Nevada, New Jersey, Texas, and Utah at level 6. California and South Carolina (level 5) and Georgia, Louisiana, Mississippi, and North Carolina (level 4) took their place in the “low” range, data from the CDC’s Outpatient Influenza-like Illness Surveillance Network show.

Two ILI-related pediatric deaths were reported for the week – one of which occurred during the week ending Jan. 16 – bringing the total to 13 for the season. Three of those deaths occurred in Florida and two in California, with Arizona, Illinois, Louisiana, Michigan, Nevada, Puerto Rico, Tennessee, and Washington each reporting one death, the CDC said.

Since Oct. 1, 2015, the overall ILI-related hospitalization rate is 4.1 per 100,000 population, with 1,147 laboratory-confirmed flu hospitalizations reported. Among all hospitalizations, 71.1% were associated with influenza A, 26.4% with influenza B, 1.7% with influenza A and B coinfection, and 0.8% had no virus type information. Hospitalization data come from the Influenza Hospitalization Surveillance Network, which covers more than 70 counties in 10 states as well as 3 additional states.

[email protected]

Activity of influenza-like illness (ILI) was at its highest level so far for week 18 of the 2015-2016 flu season, according to the Centers for Disease Control and Prevention.

That increased activity put Arizona and Puerto Rico at level 10 on the CDC’s 1-10 scale of ILI activity for the week ending Feb. 13. Joining them in the “high” range of activity was Oklahoma at level 8, the CDC reported Feb. 19.

The percentage of visits for ILI in week 18 was 3.1%, higher than the national baseline of 2.1% and the highest level of the flu season. For the week, 30 states were at level 2 or higher on the CDC’s 1-10 scale, which is the highest number for the season. States in the “moderate” range were Arkansas, Connecticut, Illinois, and New Mexico at level 7 and Florida, Hawaii, Maryland, Nevada, New Jersey, Texas, and Utah at level 6. California and South Carolina (level 5) and Georgia, Louisiana, Mississippi, and North Carolina (level 4) took their place in the “low” range, data from the CDC’s Outpatient Influenza-like Illness Surveillance Network show.

Two ILI-related pediatric deaths were reported for the week – one of which occurred during the week ending Jan. 16 – bringing the total to 13 for the season. Three of those deaths occurred in Florida and two in California, with Arizona, Illinois, Louisiana, Michigan, Nevada, Puerto Rico, Tennessee, and Washington each reporting one death, the CDC said.

Since Oct. 1, 2015, the overall ILI-related hospitalization rate is 4.1 per 100,000 population, with 1,147 laboratory-confirmed flu hospitalizations reported. Among all hospitalizations, 71.1% were associated with influenza A, 26.4% with influenza B, 1.7% with influenza A and B coinfection, and 0.8% had no virus type information. Hospitalization data come from the Influenza Hospitalization Surveillance Network, which covers more than 70 counties in 10 states as well as 3 additional states.

[email protected]

Activity of influenza-like illness (ILI) was at its highest level so far for week 18 of the 2015-2016 flu season, according to the Centers for Disease Control and Prevention.

That increased activity put Arizona and Puerto Rico at level 10 on the CDC’s 1-10 scale of ILI activity for the week ending Feb. 13. Joining them in the “high” range of activity was Oklahoma at level 8, the CDC reported Feb. 19.

The percentage of visits for ILI in week 18 was 3.1%, higher than the national baseline of 2.1% and the highest level of the flu season. For the week, 30 states were at level 2 or higher on the CDC’s 1-10 scale, which is the highest number for the season. States in the “moderate” range were Arkansas, Connecticut, Illinois, and New Mexico at level 7 and Florida, Hawaii, Maryland, Nevada, New Jersey, Texas, and Utah at level 6. California and South Carolina (level 5) and Georgia, Louisiana, Mississippi, and North Carolina (level 4) took their place in the “low” range, data from the CDC’s Outpatient Influenza-like Illness Surveillance Network show.

Two ILI-related pediatric deaths were reported for the week – one of which occurred during the week ending Jan. 16 – bringing the total to 13 for the season. Three of those deaths occurred in Florida and two in California, with Arizona, Illinois, Louisiana, Michigan, Nevada, Puerto Rico, Tennessee, and Washington each reporting one death, the CDC said.

Since Oct. 1, 2015, the overall ILI-related hospitalization rate is 4.1 per 100,000 population, with 1,147 laboratory-confirmed flu hospitalizations reported. Among all hospitalizations, 71.1% were associated with influenza A, 26.4% with influenza B, 1.7% with influenza A and B coinfection, and 0.8% had no virus type information. Hospitalization data come from the Influenza Hospitalization Surveillance Network, which covers more than 70 counties in 10 states as well as 3 additional states.

[email protected]

In heavily pretreated patients with chronic phase chronic myeloid leukemia (CP-CML), response to the tyrosine kinase inhibitor ponatinib did not depend on baseline mutation status, and no single or compound mutation was a major driver of primary or secondary resistance to ponatinib, according to researchers.

Irrespective of baseline mutation status, responses to ponatinib were durable. As determined by next-generation sequencing (NGS), patients with zero, one, or two or more BCR-ABL1 mutations had rates of 50%-61% for major cytogenetic response (MCyR) by 1 year and 29%-45% for major molecular response (MMR) at any time. The rates were similar to those observed with mutation status determined by Sanger sequencing. Rates of sustained response at 2 years for MCyR and MMR were 87% and 65%, respectively (Blood. 2016 Feb 11. doi: 10.1182/blood-2015-08-660977).

Difu Wu/CC BY-SA 3.0

Sanger sequencing typically is used to identify BCR-ABL1 mutations associated with tyrosine kinase inhibitor (TKI) resistance, but the method fails to detect low-level mutations that occur in less than 10%-20% of cells. Researchers used NGS to determine the impact of low-level mutations, as well as compound mutations, on the efficacy of the third generation TKI ponatinib.

Ponatinib is the most potent BCR-ABL1 TKI but is associated with considerable cardiovascular toxicity.

“The role of NGS in this setting may be to identify patients with (low level) T315I who are unlikely to derive lasting benefit from second-generation TKIs, but have a high likelihood of achieving durable cytogenetic and molecular responses to ponatinib, an important factor for balancing risks and benefits of salvage therapy selection,” wrote Dr. Michael W. Deininger, Chief of Hematology at the Huntsman Cancer Institute at the University of Utah, Salt Lake City, and his colleagues.

Patients with low-level mutations had similar response rates to those with no mutations: MCyR by one year and MMR at any time were 43% and 31%, respectively, compared with 50% and 29%. Response rates were higher in patients with compound mutations (64% and 52%) or one or more mutation (57% and 64%). The researchers speculated that the lower response rates in patients with low level or no mutations may reflect resistance mechanisms independent of BCR-ABL1.

Analysis of postbaseline samples from 127 patients (24 of whom had discontinued ponatinib for at least 1 month) determined the impact of acquired resistance. At a median follow-up of 30.1 months, emergence of previously undetected single and compound mutants during ponatinib therapy was observed in 8 patients.

The study analyzed patients from the PACE trial who had CP-CML with resistance or intolerance to dasatinib or nilotinib, or with a T315I mutation, and who were treated with ponatinib. All 267 patients had baseline mutation status determined by Sanger sequencing, with 161 mutations detected in 131 patients. NGS identified these and 105 additional mutations. Consistent with greater sensitivity of NGS, the proportion of patients with no baseline mutations by 39% by NGS vs. 51% by Sanger sequencing, and the proportion with multiple mutations was 23% vs. 10%.

The study was funded by ARIAD Pharmaceuticals. Dr. Deininger reported financial ties to ARIAD, Bristol Myers-Squibb, Novartis, Celgene, Genzyme, Gilead, Incyte, and Pfizer. Several of his coauthors reported ties to industry.

In heavily pretreated patients with chronic phase chronic myeloid leukemia (CP-CML), response to the tyrosine kinase inhibitor ponatinib did not depend on baseline mutation status, and no single or compound mutation was a major driver of primary or secondary resistance to ponatinib, according to researchers.

Irrespective of baseline mutation status, responses to ponatinib were durable. As determined by next-generation sequencing (NGS), patients with zero, one, or two or more BCR-ABL1 mutations had rates of 50%-61% for major cytogenetic response (MCyR) by 1 year and 29%-45% for major molecular response (MMR) at any time. The rates were similar to those observed with mutation status determined by Sanger sequencing. Rates of sustained response at 2 years for MCyR and MMR were 87% and 65%, respectively (Blood. 2016 Feb 11. doi: 10.1182/blood-2015-08-660977).

Difu Wu/CC BY-SA 3.0

Sanger sequencing typically is used to identify BCR-ABL1 mutations associated with tyrosine kinase inhibitor (TKI) resistance, but the method fails to detect low-level mutations that occur in less than 10%-20% of cells. Researchers used NGS to determine the impact of low-level mutations, as well as compound mutations, on the efficacy of the third generation TKI ponatinib.

Ponatinib is the most potent BCR-ABL1 TKI but is associated with considerable cardiovascular toxicity.

“The role of NGS in this setting may be to identify patients with (low level) T315I who are unlikely to derive lasting benefit from second-generation TKIs, but have a high likelihood of achieving durable cytogenetic and molecular responses to ponatinib, an important factor for balancing risks and benefits of salvage therapy selection,” wrote Dr. Michael W. Deininger, Chief of Hematology at the Huntsman Cancer Institute at the University of Utah, Salt Lake City, and his colleagues.

Patients with low-level mutations had similar response rates to those with no mutations: MCyR by one year and MMR at any time were 43% and 31%, respectively, compared with 50% and 29%. Response rates were higher in patients with compound mutations (64% and 52%) or one or more mutation (57% and 64%). The researchers speculated that the lower response rates in patients with low level or no mutations may reflect resistance mechanisms independent of BCR-ABL1.

Analysis of postbaseline samples from 127 patients (24 of whom had discontinued ponatinib for at least 1 month) determined the impact of acquired resistance. At a median follow-up of 30.1 months, emergence of previously undetected single and compound mutants during ponatinib therapy was observed in 8 patients.

The study analyzed patients from the PACE trial who had CP-CML with resistance or intolerance to dasatinib or nilotinib, or with a T315I mutation, and who were treated with ponatinib. All 267 patients had baseline mutation status determined by Sanger sequencing, with 161 mutations detected in 131 patients. NGS identified these and 105 additional mutations. Consistent with greater sensitivity of NGS, the proportion of patients with no baseline mutations by 39% by NGS vs. 51% by Sanger sequencing, and the proportion with multiple mutations was 23% vs. 10%.

The study was funded by ARIAD Pharmaceuticals. Dr. Deininger reported financial ties to ARIAD, Bristol Myers-Squibb, Novartis, Celgene, Genzyme, Gilead, Incyte, and Pfizer. Several of his coauthors reported ties to industry.

In heavily pretreated patients with chronic phase chronic myeloid leukemia (CP-CML), response to the tyrosine kinase inhibitor ponatinib did not depend on baseline mutation status, and no single or compound mutation was a major driver of primary or secondary resistance to ponatinib, according to researchers.

Irrespective of baseline mutation status, responses to ponatinib were durable. As determined by next-generation sequencing (NGS), patients with zero, one, or two or more BCR-ABL1 mutations had rates of 50%-61% for major cytogenetic response (MCyR) by 1 year and 29%-45% for major molecular response (MMR) at any time. The rates were similar to those observed with mutation status determined by Sanger sequencing. Rates of sustained response at 2 years for MCyR and MMR were 87% and 65%, respectively (Blood. 2016 Feb 11. doi: 10.1182/blood-2015-08-660977).

Difu Wu/CC BY-SA 3.0

Sanger sequencing typically is used to identify BCR-ABL1 mutations associated with tyrosine kinase inhibitor (TKI) resistance, but the method fails to detect low-level mutations that occur in less than 10%-20% of cells. Researchers used NGS to determine the impact of low-level mutations, as well as compound mutations, on the efficacy of the third generation TKI ponatinib.

Ponatinib is the most potent BCR-ABL1 TKI but is associated with considerable cardiovascular toxicity.

“The role of NGS in this setting may be to identify patients with (low level) T315I who are unlikely to derive lasting benefit from second-generation TKIs, but have a high likelihood of achieving durable cytogenetic and molecular responses to ponatinib, an important factor for balancing risks and benefits of salvage therapy selection,” wrote Dr. Michael W. Deininger, Chief of Hematology at the Huntsman Cancer Institute at the University of Utah, Salt Lake City, and his colleagues.

Patients with low-level mutations had similar response rates to those with no mutations: MCyR by one year and MMR at any time were 43% and 31%, respectively, compared with 50% and 29%. Response rates were higher in patients with compound mutations (64% and 52%) or one or more mutation (57% and 64%). The researchers speculated that the lower response rates in patients with low level or no mutations may reflect resistance mechanisms independent of BCR-ABL1.

Analysis of postbaseline samples from 127 patients (24 of whom had discontinued ponatinib for at least 1 month) determined the impact of acquired resistance. At a median follow-up of 30.1 months, emergence of previously undetected single and compound mutants during ponatinib therapy was observed in 8 patients.

The study analyzed patients from the PACE trial who had CP-CML with resistance or intolerance to dasatinib or nilotinib, or with a T315I mutation, and who were treated with ponatinib. All 267 patients had baseline mutation status determined by Sanger sequencing, with 161 mutations detected in 131 patients. NGS identified these and 105 additional mutations. Consistent with greater sensitivity of NGS, the proportion of patients with no baseline mutations by 39% by NGS vs. 51% by Sanger sequencing, and the proportion with multiple mutations was 23% vs. 10%.

The study was funded by ARIAD Pharmaceuticals. Dr. Deininger reported financial ties to ARIAD, Bristol Myers-Squibb, Novartis, Celgene, Genzyme, Gilead, Incyte, and Pfizer. Several of his coauthors reported ties to industry.