BERLIN—Gray matter–white matter (GM/WM) contrast ratio on T1 magnetization prepared rapid gradient echo (MPRAGE) is sensitive to multiple sclerosis (MS), but not to migraine pathology, according to research presented at ECTRIMS 2018. The diagnostic and prognostic value of this MRI marker could be subjects for future investigations, said the study authors.

Researchers have suggested that MRI brain T1 GM/WM contrast may be a marker of neurodegeneration in Alzheimer’s disease. Whether this contrast has diagnostic value in MS remains unknown, however. Tina Mitrovic, a research assistant at the University of Basel in Switzerland, and colleagues conducted a study to compare the T1 GM/WM contrast in patients with MS, migraineurs, and healthy controls. They also investigated whether the contrast was associated with disability outcomes in MS.

BERLIN—Gray matter–white matter (GM/WM) contrast ratio on T1 magnetization prepared rapid gradient echo (MPRAGE) is sensitive to multiple sclerosis (MS), but not to migraine pathology, according to research presented at ECTRIMS 2018. The diagnostic and prognostic value of this MRI marker could be subjects for future investigations, said the study authors.

Researchers have suggested that MRI brain T1 GM/WM contrast may be a marker of neurodegeneration in Alzheimer’s disease. Whether this contrast has diagnostic value in MS remains unknown, however. Tina Mitrovic, a research assistant at the University of Basel in Switzerland, and colleagues conducted a study to compare the T1 GM/WM contrast in patients with MS, migraineurs, and healthy controls. They also investigated whether the contrast was associated with disability outcomes in MS.

BERLIN—Gray matter–white matter (GM/WM) contrast ratio on T1 magnetization prepared rapid gradient echo (MPRAGE) is sensitive to multiple sclerosis (MS), but not to migraine pathology, according to research presented at ECTRIMS 2018. The diagnostic and prognostic value of this MRI marker could be subjects for future investigations, said the study authors.

Researchers have suggested that MRI brain T1 GM/WM contrast may be a marker of neurodegeneration in Alzheimer’s disease. Whether this contrast has diagnostic value in MS remains unknown, however. Tina Mitrovic, a research assistant at the University of Basel in Switzerland, and colleagues conducted a study to compare the T1 GM/WM contrast in patients with MS, migraineurs, and healthy controls. They also investigated whether the contrast was associated with disability outcomes in MS.

High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.

Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).

Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.

Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).

Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).

KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”

The authors reported that they had no conflict of interests.

SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.

High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.

Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).

Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.

Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).

Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).

KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”

The authors reported that they had no conflict of interests.

SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.

High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.

Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).

Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.

Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).

Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).

KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”

The authors reported that they had no conflict of interests.

SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.

ATLANTA—Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, according to results from a long-term analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” said lead study author Keenan Walker, PhD, a clinical neuropsychology postdoctoral fellow at the Johns Hopkins University School of Medicine in Baltimore. “For example, several studies have found higher levels of inflammatory markers in the blood and CSF of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four US communities and funded by the National Heart, Lung, and Blood Institute. Visit 1 occurred between 1987 and 1989, and Visit 2 took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (ie, fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at Visit 1 and measured C-reactive protein (CRP) at Visit 2. Next, they used measures of memory, executive function, and language to assess cognition over three visits spanning 20 years.

The average age of study participants at the first cognitive assessment was 57, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors, and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD. They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile. A similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” said Dr. Walker. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus that are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

—Doug Brunk

ATLANTA—Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, according to results from a long-term analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” said lead study author Keenan Walker, PhD, a clinical neuropsychology postdoctoral fellow at the Johns Hopkins University School of Medicine in Baltimore. “For example, several studies have found higher levels of inflammatory markers in the blood and CSF of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four US communities and funded by the National Heart, Lung, and Blood Institute. Visit 1 occurred between 1987 and 1989, and Visit 2 took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (ie, fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at Visit 1 and measured C-reactive protein (CRP) at Visit 2. Next, they used measures of memory, executive function, and language to assess cognition over three visits spanning 20 years.

The average age of study participants at the first cognitive assessment was 57, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors, and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD. They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile. A similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” said Dr. Walker. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus that are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

—Doug Brunk

ATLANTA—Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, according to results from a long-term analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” said lead study author Keenan Walker, PhD, a clinical neuropsychology postdoctoral fellow at the Johns Hopkins University School of Medicine in Baltimore. “For example, several studies have found higher levels of inflammatory markers in the blood and CSF of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four US communities and funded by the National Heart, Lung, and Blood Institute. Visit 1 occurred between 1987 and 1989, and Visit 2 took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (ie, fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at Visit 1 and measured C-reactive protein (CRP) at Visit 2. Next, they used measures of memory, executive function, and language to assess cognition over three visits spanning 20 years.

The average age of study participants at the first cognitive assessment was 57, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors, and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD. They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile. A similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” said Dr. Walker. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus that are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

—Doug Brunk

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

Immediate treatment of a first unprovoked seizure may be preferable to delayed treatment over a wide range of patients, including those who are at low risk of recurrent seizures, results of a decision analysis suggest.

Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, a model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.

The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patient with a single unprovoked seizure, according to the analysis, which was published in the October 9 issue of Neurology.

Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, Associate Professor of Neurology at Massachusetts General Hospital in Boston, and his coauthors.

“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said.

Weighing Risks and Benefits

To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.

The goal of the simulation was to determine which treatment strategy—immediate or delayed AED treatment—would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.

The first case was a 30-year-old man with no risk factors for recurrent seizure other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.

“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.

The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.

The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation favored deferred AED treatment by a small margin, the investigators said.

“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they said.

Findings May Shift Discussions About Therapy

The conclusion of this decision analysis by Dr. Westover and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to the authors of an accompanying editorial.

The decision analysis is based on a reasonable, though not comprehensive, set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, said editorialists Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, both with the Department of Neurology at Brigham and Women’s Hospital in Boston.

Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate that treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.

This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, QALYs can be difficult to integrate into clinical decision making.

Nonetheless, the findings are worth considering in clinical practice, the authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” said Drs. Jacob and Lee.

The study was supported by NINDS.

—Andrew D. Bowser

Suggested Reading

Bao EL, Chao LY, Ni P, et al. Antiepileptic drug treatment after an unprovoked first seizure: a decision analysis. Neurology. 2018;91(15):e1429-e1439.

Jacobs CS, Lee JW. Immediate vs delayed treatment of first unprovoked seizure: to treat, or not to treat? Neurology. 2018;91(15):684-685.

Immediate treatment of a first unprovoked seizure may be preferable to delayed treatment over a wide range of patients, including those who are at low risk of recurrent seizures, results of a decision analysis suggest.

Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, a model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.

The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patient with a single unprovoked seizure, according to the analysis, which was published in the October 9 issue of Neurology.

Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, Associate Professor of Neurology at Massachusetts General Hospital in Boston, and his coauthors.

“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said.

Weighing Risks and Benefits

To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.

The goal of the simulation was to determine which treatment strategy—immediate or delayed AED treatment—would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.

The first case was a 30-year-old man with no risk factors for recurrent seizure other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.

“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.

The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.

The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation favored deferred AED treatment by a small margin, the investigators said.

“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they said.

Findings May Shift Discussions About Therapy

The conclusion of this decision analysis by Dr. Westover and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to the authors of an accompanying editorial.

The decision analysis is based on a reasonable, though not comprehensive, set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, said editorialists Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, both with the Department of Neurology at Brigham and Women’s Hospital in Boston.

Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate that treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.

This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, QALYs can be difficult to integrate into clinical decision making.

Nonetheless, the findings are worth considering in clinical practice, the authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” said Drs. Jacob and Lee.

The study was supported by NINDS.

—Andrew D. Bowser

Suggested Reading

Bao EL, Chao LY, Ni P, et al. Antiepileptic drug treatment after an unprovoked first seizure: a decision analysis. Neurology. 2018;91(15):e1429-e1439.

Jacobs CS, Lee JW. Immediate vs delayed treatment of first unprovoked seizure: to treat, or not to treat? Neurology. 2018;91(15):684-685.

Immediate treatment of a first unprovoked seizure may be preferable to delayed treatment over a wide range of patients, including those who are at low risk of recurrent seizures, results of a decision analysis suggest.

Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, a model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.

The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patient with a single unprovoked seizure, according to the analysis, which was published in the October 9 issue of Neurology.

Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, Associate Professor of Neurology at Massachusetts General Hospital in Boston, and his coauthors.

“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said.

Weighing Risks and Benefits

To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.

The goal of the simulation was to determine which treatment strategy—immediate or delayed AED treatment—would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.

The first case was a 30-year-old man with no risk factors for recurrent seizure other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.

“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.

The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.

The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation favored deferred AED treatment by a small margin, the investigators said.

“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they said.

Findings May Shift Discussions About Therapy

The conclusion of this decision analysis by Dr. Westover and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to the authors of an accompanying editorial.

The decision analysis is based on a reasonable, though not comprehensive, set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, said editorialists Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, both with the Department of Neurology at Brigham and Women’s Hospital in Boston.

Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate that treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.

This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, QALYs can be difficult to integrate into clinical decision making.

Nonetheless, the findings are worth considering in clinical practice, the authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” said Drs. Jacob and Lee.

The study was supported by NINDS.

—Andrew D. Bowser

Suggested Reading

Bao EL, Chao LY, Ni P, et al. Antiepileptic drug treatment after an unprovoked first seizure: a decision analysis. Neurology. 2018;91(15):e1429-e1439.

Jacobs CS, Lee JW. Immediate vs delayed treatment of first unprovoked seizure: to treat, or not to treat? Neurology. 2018;91(15):684-685.

A lower threshold for platelet transfusions in preterm infants with severe thrombocytopenia is associated with significantly lower incidence of death and major bleeding, compared with a higher threshold, a new study suggests.

Fuse/Thinkstock

A new major bleeding episode or death occurred in 26% of infants in the high-threshold group, compared with 19% in the low-threshold group, representing a 57% higher risk of poor outcomes even after researchers adjusted for gestational age and intrauterine growth restriction (odds ratio, 1.57; P = .02).

Researchers reported the results of a trial in 660 infants with a mean gestational age of 26.6 weeks, who were randomized to a platelet infusion either at a high platelet–count threshold of 50,000/mm³ or a low threshold of 25,000/mm³.

“Although retrospective studies have suggested that platelet transfusions may cause harm in neonates independently of the disease process, data from randomized controlled trials to support this are lacking,” Anna Curley, MD, of the National Maternity Hospital in Dublin and her coauthors reported in the New England Journal of Medicine.

The rates of minor or worse bleeding were similar between the two groups, and the percentage of infants surviving with bronchopulmonary dysplasia at 36 weeks of corrected age was higher in the high-threshold group (63% vs. 54%; OR, 1.54).

The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups.

The outcomes of transfusions were not influenced by other factors such as intrauterine growth restriction, gestational age, or postnatal age at randomization.

“Our trial highlights the importance of trials of platelet transfusion involving patients with conditions other than haematological malignancies,” the authors wrote.

However they acknowledged that the reasons for the differences in mortality and outcomes between the two study groups were unknown.

“Platelets have recognized immunological and inflammatory effects, outside of effects on hemostasis,” they wrote. “The effect of transfusing adult platelets to a delicately balance neonatal hemostatic system with relatively hypofunctional platelets is also poorly understood.”

The study was supported by the National Health Service Blood and Transplant Research and Development Committee and other foundations. Authors reported financial disclosures related to Sanquin and Cerus.

SOURCE: Curley A et al. N Engl J Med. 2018 Nov 2. doi: 10.1056/NEJMoa1807320.

A lower threshold for platelet transfusions in preterm infants with severe thrombocytopenia is associated with significantly lower incidence of death and major bleeding, compared with a higher threshold, a new study suggests.

Fuse/Thinkstock

A new major bleeding episode or death occurred in 26% of infants in the high-threshold group, compared with 19% in the low-threshold group, representing a 57% higher risk of poor outcomes even after researchers adjusted for gestational age and intrauterine growth restriction (odds ratio, 1.57; P = .02).

Researchers reported the results of a trial in 660 infants with a mean gestational age of 26.6 weeks, who were randomized to a platelet infusion either at a high platelet–count threshold of 50,000/mm³ or a low threshold of 25,000/mm³.

“Although retrospective studies have suggested that platelet transfusions may cause harm in neonates independently of the disease process, data from randomized controlled trials to support this are lacking,” Anna Curley, MD, of the National Maternity Hospital in Dublin and her coauthors reported in the New England Journal of Medicine.

The rates of minor or worse bleeding were similar between the two groups, and the percentage of infants surviving with bronchopulmonary dysplasia at 36 weeks of corrected age was higher in the high-threshold group (63% vs. 54%; OR, 1.54).

The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups.

The outcomes of transfusions were not influenced by other factors such as intrauterine growth restriction, gestational age, or postnatal age at randomization.

“Our trial highlights the importance of trials of platelet transfusion involving patients with conditions other than haematological malignancies,” the authors wrote.

However they acknowledged that the reasons for the differences in mortality and outcomes between the two study groups were unknown.

“Platelets have recognized immunological and inflammatory effects, outside of effects on hemostasis,” they wrote. “The effect of transfusing adult platelets to a delicately balance neonatal hemostatic system with relatively hypofunctional platelets is also poorly understood.”

The study was supported by the National Health Service Blood and Transplant Research and Development Committee and other foundations. Authors reported financial disclosures related to Sanquin and Cerus.

SOURCE: Curley A et al. N Engl J Med. 2018 Nov 2. doi: 10.1056/NEJMoa1807320.

A lower threshold for platelet transfusions in preterm infants with severe thrombocytopenia is associated with significantly lower incidence of death and major bleeding, compared with a higher threshold, a new study suggests.

Fuse/Thinkstock

A new major bleeding episode or death occurred in 26% of infants in the high-threshold group, compared with 19% in the low-threshold group, representing a 57% higher risk of poor outcomes even after researchers adjusted for gestational age and intrauterine growth restriction (odds ratio, 1.57; P = .02).

Researchers reported the results of a trial in 660 infants with a mean gestational age of 26.6 weeks, who were randomized to a platelet infusion either at a high platelet–count threshold of 50,000/mm³ or a low threshold of 25,000/mm³.

“Although retrospective studies have suggested that platelet transfusions may cause harm in neonates independently of the disease process, data from randomized controlled trials to support this are lacking,” Anna Curley, MD, of the National Maternity Hospital in Dublin and her coauthors reported in the New England Journal of Medicine.

The rates of minor or worse bleeding were similar between the two groups, and the percentage of infants surviving with bronchopulmonary dysplasia at 36 weeks of corrected age was higher in the high-threshold group (63% vs. 54%; OR, 1.54).

The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups.

The outcomes of transfusions were not influenced by other factors such as intrauterine growth restriction, gestational age, or postnatal age at randomization.

“Our trial highlights the importance of trials of platelet transfusion involving patients with conditions other than haematological malignancies,” the authors wrote.

However they acknowledged that the reasons for the differences in mortality and outcomes between the two study groups were unknown.

“Platelets have recognized immunological and inflammatory effects, outside of effects on hemostasis,” they wrote. “The effect of transfusing adult platelets to a delicately balance neonatal hemostatic system with relatively hypofunctional platelets is also poorly understood.”

The study was supported by the National Health Service Blood and Transplant Research and Development Committee and other foundations. Authors reported financial disclosures related to Sanquin and Cerus.

SOURCE: Curley A et al. N Engl J Med. 2018 Nov 2. doi: 10.1056/NEJMoa1807320.

The long-term mesh removal rate in women with a midurethral mesh sling (MUS) insertion for treating stress urinary incontinence (SUI) was 3.3%, a British study found.

Ipek Gurol-Urganci, PhD, of the London School of Hygiene and Tropical Medicine, and her coauthors said their study comes as a result of safety concerns around the procedure, which resulted in a suspension of the operation in the United Kingdom.

“There is concern about problems that some women experience following MUS insertion, including pain, dyspareunia, persistent urinary incontinence, and exposure or erosion. However, there is little randomized, clinical trial evidence on these longer-term outcomes,” they wrote in JAMA, noting that an estimated 250,000 MUS operations were performed in 2010 in the United States.

The current study involved 95,057 women in England who underwent an MUS insertion procedure for SUI for the first time in a National Health Service hospital between 2006 and 2015. Overall, 60,194 of the women had a retropubic insertion and 34,863 had a transobturator insertion.

At 9 years after the initial insertion, the mesh was removed in 3.3% of women. The risk of removal was higher for women who had a retropubic insertion (3.6%), compared with those who had a transobturator insertion (2.7%).

“The risk of a removal was about 30% lower if the mesh sling had been inserted via the transobturator route, which may be explained by the removal of transobturator sling being a more complicated procedure,” Dr. Gurol-Urganci and her associates noted.

Mesh sling removal risk decreased with age, with the risk at 4.4% for women aged 18-39 years, compared with 2.1% in women aged 70 years and older at 9 years after insertion.

The authors wrote that the risks of removal and any reoperation (mesh removal and/or reoperation for SUI) were higher among women from a white racial/ethnic background. However, it was not possible to “disentangle explanations” for these possible differences in risk seen with patient characteristics, which ranged from higher morbidity to differences in the reasons for surgery.

Results also showed that the risk of reoperation was 4.5% at 9 years after the initial insertion, and was slightly higher for a transobturator insertion at 5.3%, compared with 4.1% for a retropubic insertion.

The risk of any reoperation, including mesh removal and/or reoperation for SUI, following the initial MUS insertion was 6.9% at 9 years (95% confidence interval, 6.7%-7.1%), but no statistically significant difference was observed between retropubic and transobturator insertion.

“The present results demonstrate that removal and reoperation risks were associated with the insertion route and patient factors,” Dr. Gurol-Urganci and her associates wrote.

“These findings may guide women and their surgeons when making decisions about surgical treatment of stress urinary incontinence,” they concluded.

The study was supported by a grant from the National Institute for Health Research Health Services and Delivery Research Programme and several of the authors reported receiving National Institute for Health Research research grants. One author reported providing consultancy services to Cambridge Medical Robotics, Femeda, and Astellas.

SOURCE: Gurol-Urganci I et al. JAMA. 2018 Oct 23. doi:10.1001/jama.2018.14997.

The long-term mesh removal rate in women with a midurethral mesh sling (MUS) insertion for treating stress urinary incontinence (SUI) was 3.3%, a British study found.

Ipek Gurol-Urganci, PhD, of the London School of Hygiene and Tropical Medicine, and her coauthors said their study comes as a result of safety concerns around the procedure, which resulted in a suspension of the operation in the United Kingdom.

“There is concern about problems that some women experience following MUS insertion, including pain, dyspareunia, persistent urinary incontinence, and exposure or erosion. However, there is little randomized, clinical trial evidence on these longer-term outcomes,” they wrote in JAMA, noting that an estimated 250,000 MUS operations were performed in 2010 in the United States.

The current study involved 95,057 women in England who underwent an MUS insertion procedure for SUI for the first time in a National Health Service hospital between 2006 and 2015. Overall, 60,194 of the women had a retropubic insertion and 34,863 had a transobturator insertion.

At 9 years after the initial insertion, the mesh was removed in 3.3% of women. The risk of removal was higher for women who had a retropubic insertion (3.6%), compared with those who had a transobturator insertion (2.7%).

“The risk of a removal was about 30% lower if the mesh sling had been inserted via the transobturator route, which may be explained by the removal of transobturator sling being a more complicated procedure,” Dr. Gurol-Urganci and her associates noted.

Mesh sling removal risk decreased with age, with the risk at 4.4% for women aged 18-39 years, compared with 2.1% in women aged 70 years and older at 9 years after insertion.

The authors wrote that the risks of removal and any reoperation (mesh removal and/or reoperation for SUI) were higher among women from a white racial/ethnic background. However, it was not possible to “disentangle explanations” for these possible differences in risk seen with patient characteristics, which ranged from higher morbidity to differences in the reasons for surgery.

Results also showed that the risk of reoperation was 4.5% at 9 years after the initial insertion, and was slightly higher for a transobturator insertion at 5.3%, compared with 4.1% for a retropubic insertion.

The risk of any reoperation, including mesh removal and/or reoperation for SUI, following the initial MUS insertion was 6.9% at 9 years (95% confidence interval, 6.7%-7.1%), but no statistically significant difference was observed between retropubic and transobturator insertion.

“The present results demonstrate that removal and reoperation risks were associated with the insertion route and patient factors,” Dr. Gurol-Urganci and her associates wrote.

“These findings may guide women and their surgeons when making decisions about surgical treatment of stress urinary incontinence,” they concluded.

The study was supported by a grant from the National Institute for Health Research Health Services and Delivery Research Programme and several of the authors reported receiving National Institute for Health Research research grants. One author reported providing consultancy services to Cambridge Medical Robotics, Femeda, and Astellas.

SOURCE: Gurol-Urganci I et al. JAMA. 2018 Oct 23. doi:10.1001/jama.2018.14997.

The long-term mesh removal rate in women with a midurethral mesh sling (MUS) insertion for treating stress urinary incontinence (SUI) was 3.3%, a British study found.

Ipek Gurol-Urganci, PhD, of the London School of Hygiene and Tropical Medicine, and her coauthors said their study comes as a result of safety concerns around the procedure, which resulted in a suspension of the operation in the United Kingdom.

“There is concern about problems that some women experience following MUS insertion, including pain, dyspareunia, persistent urinary incontinence, and exposure or erosion. However, there is little randomized, clinical trial evidence on these longer-term outcomes,” they wrote in JAMA, noting that an estimated 250,000 MUS operations were performed in 2010 in the United States.

The current study involved 95,057 women in England who underwent an MUS insertion procedure for SUI for the first time in a National Health Service hospital between 2006 and 2015. Overall, 60,194 of the women had a retropubic insertion and 34,863 had a transobturator insertion.

At 9 years after the initial insertion, the mesh was removed in 3.3% of women. The risk of removal was higher for women who had a retropubic insertion (3.6%), compared with those who had a transobturator insertion (2.7%).

“The risk of a removal was about 30% lower if the mesh sling had been inserted via the transobturator route, which may be explained by the removal of transobturator sling being a more complicated procedure,” Dr. Gurol-Urganci and her associates noted.

Mesh sling removal risk decreased with age, with the risk at 4.4% for women aged 18-39 years, compared with 2.1% in women aged 70 years and older at 9 years after insertion.

The authors wrote that the risks of removal and any reoperation (mesh removal and/or reoperation for SUI) were higher among women from a white racial/ethnic background. However, it was not possible to “disentangle explanations” for these possible differences in risk seen with patient characteristics, which ranged from higher morbidity to differences in the reasons for surgery.

Results also showed that the risk of reoperation was 4.5% at 9 years after the initial insertion, and was slightly higher for a transobturator insertion at 5.3%, compared with 4.1% for a retropubic insertion.

The risk of any reoperation, including mesh removal and/or reoperation for SUI, following the initial MUS insertion was 6.9% at 9 years (95% confidence interval, 6.7%-7.1%), but no statistically significant difference was observed between retropubic and transobturator insertion.

“The present results demonstrate that removal and reoperation risks were associated with the insertion route and patient factors,” Dr. Gurol-Urganci and her associates wrote.

“These findings may guide women and their surgeons when making decisions about surgical treatment of stress urinary incontinence,” they concluded.

The study was supported by a grant from the National Institute for Health Research Health Services and Delivery Research Programme and several of the authors reported receiving National Institute for Health Research research grants. One author reported providing consultancy services to Cambridge Medical Robotics, Femeda, and Astellas.

SOURCE: Gurol-Urganci I et al. JAMA. 2018 Oct 23. doi:10.1001/jama.2018.14997.

A retrospective study has revealed new potential risk factors for chemotherapy-induced febrile neutropenia in patients with solid tumors and non-Hodgkin lymphoma (NHL).

Researchers found the timing and duration of corticosteroid use were both associated with febrile neutropenia. The team also observed “marginal” associations between febrile neutropenia and certain dermatologic and mucosal conditions, as well as the use of intravenous antibiotics before chemotherapy.

However, there was no association found between oral antibiotic use and febrile neutropenia or between radiation therapy and febrile neutropenia.

Chun Rebecca Chao, PhD, of the Kaiser Permanente Southern California in Pasadena, and her colleagues reported these findings in the Journal of the National Comprehensive Cancer Network.

“Febrile neutropenia is life threatening and often requires hospitalization,” Dr. Chao said in a statement. “Furthermore, [febrile neutropenia] can lead to chemotherapy dose delay and dose reduction, which, in turn, negatively impacts antitumor efficacy. However, it can be prevented if high-risk individuals are identified and treated prophylactically.”

With this in mind, Dr. Chao and her colleagues set out to identify novel risk factors for febrile neutropenia by analyzing 15,971 patients who were treated with myelosuppressive chemotherapy at Kaiser Permanente Southern California between 2000 and 2009.

Patients had been diagnosed with NHL (n = 1,617) or breast (n = 6,323), lung (n = 3,584), colorectal (n = 3,062), ovarian (n = 924), or gastric (n = 461) cancers. In all, 4.3% of patients developed febrile neutropenia during their first cycle of chemotherapy.

The researchers found that corticosteroid use was associated with an increased risk of febrile neutropenia in a propensity score–adjusted (PSA) model. The hazard ratio was 1.53 (95% confidence interval, 1.17-1.98; P less than .01) for patients who received corticosteroids.

A longer duration of corticosteroid use was associated with a greater risk of febrile neutropenia. The adjusted HR, compared with no corticosteroid use, was 1.78 for corticosteroid treatment lasting less than 15 days and rose to 2.86 for treatment lasting 45-90 days.

“One way to reduce the incidence rate for [febrile neutropenia] could be to schedule prior corticosteroid use and subsequent chemotherapy with at least 2 weeks between them, given the magnitude of the risk increase and prevalence of this risk factor,” Dr. Chao said.

The researchers found a “marginally” increased risk of febrile neutropenia in patients with certain dermatologic conditions (dermatitis, psoriasis, pruritus) and mucosal conditions (gastritis, stomatitis, mucositis). In the PSA model, the HR was 1.40 (95% CI, 0.98-1.93; P = 0.05) for patients with these conditions.

Intravenous antibiotic use was also found to be marginally associated with an increased risk of febrile neutropenia in a restricted analysis covering patients treated in 2008 and 2009. In the PSA model, the HR was 1.35 (95% CI, 0.97-1.87; P = .08).

There was no association found between febrile neutropenia and oral antibiotic use in the restricted analysis. In the PSA model, the HR was 1.07 (95% CI, 0.77-1.48; P = .70) for patients who received oral antibiotics.

Dr. Chao and her colleagues wrote that these results suggest intravenous antibiotics may have a more profound impact than oral antibiotics on the balance of bacterial flora and other immune functions. Another possible explanation is that patients who received intravenous antibiotics were generally sicker and more prone to severe infection than patients who received oral antibiotics.

The researchers also found no association between febrile neutropenia and prior surgery, prior radiation therapy, and concurrent radiation therapy in the PSA model.

The study was funded by Amgen. Three of the authors reported being employees and stockholders of Amgen.

[email protected]

SOURCE: Chao CR et al. J Natl Compr Canc Netw. 2018;16(10):1201-8.

A retrospective study has revealed new potential risk factors for chemotherapy-induced febrile neutropenia in patients with solid tumors and non-Hodgkin lymphoma (NHL).

Researchers found the timing and duration of corticosteroid use were both associated with febrile neutropenia. The team also observed “marginal” associations between febrile neutropenia and certain dermatologic and mucosal conditions, as well as the use of intravenous antibiotics before chemotherapy.

However, there was no association found between oral antibiotic use and febrile neutropenia or between radiation therapy and febrile neutropenia.

Chun Rebecca Chao, PhD, of the Kaiser Permanente Southern California in Pasadena, and her colleagues reported these findings in the Journal of the National Comprehensive Cancer Network.

“Febrile neutropenia is life threatening and often requires hospitalization,” Dr. Chao said in a statement. “Furthermore, [febrile neutropenia] can lead to chemotherapy dose delay and dose reduction, which, in turn, negatively impacts antitumor efficacy. However, it can be prevented if high-risk individuals are identified and treated prophylactically.”

With this in mind, Dr. Chao and her colleagues set out to identify novel risk factors for febrile neutropenia by analyzing 15,971 patients who were treated with myelosuppressive chemotherapy at Kaiser Permanente Southern California between 2000 and 2009.

Patients had been diagnosed with NHL (n = 1,617) or breast (n = 6,323), lung (n = 3,584), colorectal (n = 3,062), ovarian (n = 924), or gastric (n = 461) cancers. In all, 4.3% of patients developed febrile neutropenia during their first cycle of chemotherapy.

The researchers found that corticosteroid use was associated with an increased risk of febrile neutropenia in a propensity score–adjusted (PSA) model. The hazard ratio was 1.53 (95% confidence interval, 1.17-1.98; P less than .01) for patients who received corticosteroids.

A longer duration of corticosteroid use was associated with a greater risk of febrile neutropenia. The adjusted HR, compared with no corticosteroid use, was 1.78 for corticosteroid treatment lasting less than 15 days and rose to 2.86 for treatment lasting 45-90 days.

“One way to reduce the incidence rate for [febrile neutropenia] could be to schedule prior corticosteroid use and subsequent chemotherapy with at least 2 weeks between them, given the magnitude of the risk increase and prevalence of this risk factor,” Dr. Chao said.

The researchers found a “marginally” increased risk of febrile neutropenia in patients with certain dermatologic conditions (dermatitis, psoriasis, pruritus) and mucosal conditions (gastritis, stomatitis, mucositis). In the PSA model, the HR was 1.40 (95% CI, 0.98-1.93; P = 0.05) for patients with these conditions.

Intravenous antibiotic use was also found to be marginally associated with an increased risk of febrile neutropenia in a restricted analysis covering patients treated in 2008 and 2009. In the PSA model, the HR was 1.35 (95% CI, 0.97-1.87; P = .08).

There was no association found between febrile neutropenia and oral antibiotic use in the restricted analysis. In the PSA model, the HR was 1.07 (95% CI, 0.77-1.48; P = .70) for patients who received oral antibiotics.

Dr. Chao and her colleagues wrote that these results suggest intravenous antibiotics may have a more profound impact than oral antibiotics on the balance of bacterial flora and other immune functions. Another possible explanation is that patients who received intravenous antibiotics were generally sicker and more prone to severe infection than patients who received oral antibiotics.

The researchers also found no association between febrile neutropenia and prior surgery, prior radiation therapy, and concurrent radiation therapy in the PSA model.

The study was funded by Amgen. Three of the authors reported being employees and stockholders of Amgen.

[email protected]

SOURCE: Chao CR et al. J Natl Compr Canc Netw. 2018;16(10):1201-8.

A retrospective study has revealed new potential risk factors for chemotherapy-induced febrile neutropenia in patients with solid tumors and non-Hodgkin lymphoma (NHL).

Researchers found the timing and duration of corticosteroid use were both associated with febrile neutropenia. The team also observed “marginal” associations between febrile neutropenia and certain dermatologic and mucosal conditions, as well as the use of intravenous antibiotics before chemotherapy.

However, there was no association found between oral antibiotic use and febrile neutropenia or between radiation therapy and febrile neutropenia.

Chun Rebecca Chao, PhD, of the Kaiser Permanente Southern California in Pasadena, and her colleagues reported these findings in the Journal of the National Comprehensive Cancer Network.

“Febrile neutropenia is life threatening and often requires hospitalization,” Dr. Chao said in a statement. “Furthermore, [febrile neutropenia] can lead to chemotherapy dose delay and dose reduction, which, in turn, negatively impacts antitumor efficacy. However, it can be prevented if high-risk individuals are identified and treated prophylactically.”

With this in mind, Dr. Chao and her colleagues set out to identify novel risk factors for febrile neutropenia by analyzing 15,971 patients who were treated with myelosuppressive chemotherapy at Kaiser Permanente Southern California between 2000 and 2009.

Patients had been diagnosed with NHL (n = 1,617) or breast (n = 6,323), lung (n = 3,584), colorectal (n = 3,062), ovarian (n = 924), or gastric (n = 461) cancers. In all, 4.3% of patients developed febrile neutropenia during their first cycle of chemotherapy.

The researchers found that corticosteroid use was associated with an increased risk of febrile neutropenia in a propensity score–adjusted (PSA) model. The hazard ratio was 1.53 (95% confidence interval, 1.17-1.98; P less than .01) for patients who received corticosteroids.

A longer duration of corticosteroid use was associated with a greater risk of febrile neutropenia. The adjusted HR, compared with no corticosteroid use, was 1.78 for corticosteroid treatment lasting less than 15 days and rose to 2.86 for treatment lasting 45-90 days.

“One way to reduce the incidence rate for [febrile neutropenia] could be to schedule prior corticosteroid use and subsequent chemotherapy with at least 2 weeks between them, given the magnitude of the risk increase and prevalence of this risk factor,” Dr. Chao said.

The researchers found a “marginally” increased risk of febrile neutropenia in patients with certain dermatologic conditions (dermatitis, psoriasis, pruritus) and mucosal conditions (gastritis, stomatitis, mucositis). In the PSA model, the HR was 1.40 (95% CI, 0.98-1.93; P = 0.05) for patients with these conditions.

Intravenous antibiotic use was also found to be marginally associated with an increased risk of febrile neutropenia in a restricted analysis covering patients treated in 2008 and 2009. In the PSA model, the HR was 1.35 (95% CI, 0.97-1.87; P = .08).

There was no association found between febrile neutropenia and oral antibiotic use in the restricted analysis. In the PSA model, the HR was 1.07 (95% CI, 0.77-1.48; P = .70) for patients who received oral antibiotics.

Dr. Chao and her colleagues wrote that these results suggest intravenous antibiotics may have a more profound impact than oral antibiotics on the balance of bacterial flora and other immune functions. Another possible explanation is that patients who received intravenous antibiotics were generally sicker and more prone to severe infection than patients who received oral antibiotics.

The researchers also found no association between febrile neutropenia and prior surgery, prior radiation therapy, and concurrent radiation therapy in the PSA model.

The study was funded by Amgen. Three of the authors reported being employees and stockholders of Amgen.

[email protected]

SOURCE: Chao CR et al. J Natl Compr Canc Netw. 2018;16(10):1201-8.

The things witnessed and actions taken during military service can lead to posttraumatic stress disorder and other debilitating illnesses.

val_shep/Thinkstock

Retired Command Sgt. Maj. Sam Rhodes, a nearly 30-year U.S. Army veteran, says he was scarred by nightmares of his combat experiences in Iraq upon returning home to Georgia. He also had depression, he says. Yet, Mr. Rhodes missed the camaraderie of his squad and felt lost when he returned home. For a time, he says, ending his life seemed the only way out.


Then he began to care for his stepdaughter’s horse. “Cleaning stalls, putting up fences; it made me feel like I had a purpose in life. It’s amazing how it really got me to calm down a little bit,” he relates in an interview with CNN.

Seeking to share the relief he felt, Mr. Rhodes built his own horse ranch and created Warrior Outreach, a nonprofit that, among other things, provides free access to horses for veterans, service members, and their families through its twice yearly Horsemanship Program. For Mr. Rhodes and the other veterans who frequent the ranch, there has been no miracle turnaround. Some of the veterans still experience darkness, but for some, interacting with the horses has proven therapeutic.

“Guys can come out here, especially if they are having a rough go at it, and just kind of forget about what’s going on in the real world,” veteran Michael Christensen says. “The fact that we can network and just say, ‘Anytime you need something, here’s my number, call me’ ... It builds a network of veterans that can help each other.”

Two perspectives on anorexia

Identical twins often share many of the same interests, but they also can experience differences in how they view themselves.

©b-d-s/Thinkstock

Take the case of Bridget Yard, an identical twin and journalist who, in a CBC radio report, describes her life with an eating disorder and a twin sister who proved to be her savior.

“I sometimes thought I wouldn’t survive my teenage years, or early adulthood, because of my illness. But once I let Brianna in on my secrets, we began to deal with them together. She continues to be my greatest support as I enter recovery and work hard to live a healthy, full life. But we both still struggle with something. Why did I develop an eating disorder, and not Brianna? We were raised in the same environment, by the same loving parents. Our DNA is identical. I want to know what tipped the balance. Why me?”

The clues were there early on. Bridget was insecure and shy as a teen, and she says she was struggling to accept issues that included her feelings of bisexuality. Brianna was confident and outgoing. Hunger became a way for Bridget to quiet the demons of insecurity and establish some control. “I pushed my sexuality further back into the closet than my eating disorder,” she says. “That closet was full up, and it was killing me to continue the charade.”

Howard Steiger, PhD, tells Bridget Yard that the twin with anorexia nervosa often is found to be more perfectionistic and prone to being concerned with making errors and with others judgments. “Now we don’t know, is that a sort of a life experience thing that causes that to become more expressed? Or is that a secondary thing because of starvation and the effects of malnutrition? Or is it maybe a prenatal effect, that meant that one of the twins was programmed to be a little more perfectionistic than the other?” says Dr. Steiger, director of the Douglas Mental Health University Institute’s Eating Disorders Program at McGill University in Montreal.

Genetic changes, even before birth, might have a role. Whatever the causes, personal acceptance and recognition of her strengths and frailties have helped Bridget find a new path.

“Brianna has a phrase that we use a lot: ‘Nothing to it but to get through it.’ I used to hate that. It’s so cold, and things aren’t always so simple,” Bridget says in the interview. “But now, I embrace it. I know I will never have to do this alone. There’s nothing to it but to get through it – honestly, and together.”
 

Is that phone call real or robo?

In the few minutes it takes to read this column, some 400,000 Americans will have picked up the phone to hear a robotic voice harping a product or cause. If robocalling were a disease, it would be an epidemic.

Some robocalls are positive, reminding us of appointments and coming events. But about 40% are scams.

“Every time my phone rings it interrupts the work I’m doing,” says Hannah Donahue, a media strategist in Los Angeles. “Even if I don’t answer the phone, it’s disruptive.” She receives about six robocalls a day, starting as early as 7 a.m. and continuing into the evening.

And it might not be as easy as simply not answering a call when your business life depends on your phone. Missing a call can mean lost work.

Robocalling has been around for decades. But the frequency of use has skyrocketed in recent years. In 2018, the estimated number of monthly robocalls in the United States has risen from about 2.5 billion to 4.5 billion, as reported by NBC News.

The increased efforts by robo-scammers might reflect changing consumer behaviors. “The [telecommunications carriers] started to identify the bad guys,” says Alex Quilici, CEO of YouMail, a company that provides voicemail and call-blocking services to iPhone and Android users. “Call-blocking apps started to scale up and get publicity. What we figure is that bad guys started having to call more to get through.”

Technology is another driver. Setting up a robocall enterprise is easy and cheap.

The best advice for now is not to answer calls from unfamiliar phone numbers. “We still get a ton of spam, but Google and everyone has gotten so good at filtering email that you don’t notice,” Mr. Quilici says. For now, robocalling remains a frustration of a plugged-in life.
 

Work, ethics, and the millennials

A few months ago, several Google employees reportedly quit over the company’s involvement in a military project. Their decision might have come with the knowledge that their skills were transferable and that another job would not prove hard to find.

Still, the decision to resign might be a sign of how different generations approach work, according to a BBC article. For millennials, sometimes called the job-hopping generation, switching jobs for ethical reasons might be more common than it is for Generation Xers or Baby Boomers.

Then again, the article says, these ideas about millennials might not hold true for most young workers.

Part of this may be tied to the economics of the present. Research supports the view that gaps in employment, whether deliberate or not, are neither good for the bank account nor the likelihood of future job satisfaction.

“For all the lip service we pay to ‘making a difference,’ evidence shows the primary driver for selecting a job is still the payslip. The most recent Deloitte survey on millennials underlines that 63% of millennials consider the financial reward a very important factor in weighing up a job offer – the highest ranking one,” writes BBC correspondent José Luis Peñarredonda.

As in generations past, the main reason for choosing a job in 2018 remains the wage. Real-life necessities to support a family can blunt youthful passion to change things in a low-paying way. Still, headway is being made, as some companies realize the value of aligning corporate priorities with employees’ desire to have their work better reflect their ethics.
 

Finding ways to overcome setbacks

The end of a relationship, or loss of a loved one – or a job – are inevitable life events – and there are steps people can take to be resilient and find happiness, writes Arthur B. Markman, PhD.

First, Dr. Markman says, it is important to focus on steps that can be taken to improve a situation.

“As you engage in those actions, you will find that you feel better about your work and will also become more productive,” writes Dr. Markman, professor of psychology and marketing at the University of Texas, Austin.

A second strategy, he writes, is “surrounding yourself with people if you don’t feel like it.” This helps, he says, because sharing challenges with others can help people focus on what they need to do do. Third, Dr. Markman advises, it’s best to focus on small victories rather than long-term projects.

And finally, he says, it helps to interpret the actions of others through a positive lens. Why? Because this approach is more likely to create “positive reactions with others,” he writes.

Find Dr. Markman’s article in Fast Company.

The things witnessed and actions taken during military service can lead to posttraumatic stress disorder and other debilitating illnesses.

val_shep/Thinkstock

Retired Command Sgt. Maj. Sam Rhodes, a nearly 30-year U.S. Army veteran, says he was scarred by nightmares of his combat experiences in Iraq upon returning home to Georgia. He also had depression, he says. Yet, Mr. Rhodes missed the camaraderie of his squad and felt lost when he returned home. For a time, he says, ending his life seemed the only way out.


Then he began to care for his stepdaughter’s horse. “Cleaning stalls, putting up fences; it made me feel like I had a purpose in life. It’s amazing how it really got me to calm down a little bit,” he relates in an interview with CNN.

Seeking to share the relief he felt, Mr. Rhodes built his own horse ranch and created Warrior Outreach, a nonprofit that, among other things, provides free access to horses for veterans, service members, and their families through its twice yearly Horsemanship Program. For Mr. Rhodes and the other veterans who frequent the ranch, there has been no miracle turnaround. Some of the veterans still experience darkness, but for some, interacting with the horses has proven therapeutic.

“Guys can come out here, especially if they are having a rough go at it, and just kind of forget about what’s going on in the real world,” veteran Michael Christensen says. “The fact that we can network and just say, ‘Anytime you need something, here’s my number, call me’ ... It builds a network of veterans that can help each other.”

Two perspectives on anorexia

Identical twins often share many of the same interests, but they also can experience differences in how they view themselves.

©b-d-s/Thinkstock

Take the case of Bridget Yard, an identical twin and journalist who, in a CBC radio report, describes her life with an eating disorder and a twin sister who proved to be her savior.

“I sometimes thought I wouldn’t survive my teenage years, or early adulthood, because of my illness. But once I let Brianna in on my secrets, we began to deal with them together. She continues to be my greatest support as I enter recovery and work hard to live a healthy, full life. But we both still struggle with something. Why did I develop an eating disorder, and not Brianna? We were raised in the same environment, by the same loving parents. Our DNA is identical. I want to know what tipped the balance. Why me?”

The clues were there early on. Bridget was insecure and shy as a teen, and she says she was struggling to accept issues that included her feelings of bisexuality. Brianna was confident and outgoing. Hunger became a way for Bridget to quiet the demons of insecurity and establish some control. “I pushed my sexuality further back into the closet than my eating disorder,” she says. “That closet was full up, and it was killing me to continue the charade.”

Howard Steiger, PhD, tells Bridget Yard that the twin with anorexia nervosa often is found to be more perfectionistic and prone to being concerned with making errors and with others judgments. “Now we don’t know, is that a sort of a life experience thing that causes that to become more expressed? Or is that a secondary thing because of starvation and the effects of malnutrition? Or is it maybe a prenatal effect, that meant that one of the twins was programmed to be a little more perfectionistic than the other?” says Dr. Steiger, director of the Douglas Mental Health University Institute’s Eating Disorders Program at McGill University in Montreal.

Genetic changes, even before birth, might have a role. Whatever the causes, personal acceptance and recognition of her strengths and frailties have helped Bridget find a new path.

“Brianna has a phrase that we use a lot: ‘Nothing to it but to get through it.’ I used to hate that. It’s so cold, and things aren’t always so simple,” Bridget says in the interview. “But now, I embrace it. I know I will never have to do this alone. There’s nothing to it but to get through it – honestly, and together.”
 

Is that phone call real or robo?

In the few minutes it takes to read this column, some 400,000 Americans will have picked up the phone to hear a robotic voice harping a product or cause. If robocalling were a disease, it would be an epidemic.

Some robocalls are positive, reminding us of appointments and coming events. But about 40% are scams.

“Every time my phone rings it interrupts the work I’m doing,” says Hannah Donahue, a media strategist in Los Angeles. “Even if I don’t answer the phone, it’s disruptive.” She receives about six robocalls a day, starting as early as 7 a.m. and continuing into the evening.

And it might not be as easy as simply not answering a call when your business life depends on your phone. Missing a call can mean lost work.

Robocalling has been around for decades. But the frequency of use has skyrocketed in recent years. In 2018, the estimated number of monthly robocalls in the United States has risen from about 2.5 billion to 4.5 billion, as reported by NBC News.

The increased efforts by robo-scammers might reflect changing consumer behaviors. “The [telecommunications carriers] started to identify the bad guys,” says Alex Quilici, CEO of YouMail, a company that provides voicemail and call-blocking services to iPhone and Android users. “Call-blocking apps started to scale up and get publicity. What we figure is that bad guys started having to call more to get through.”

Technology is another driver. Setting up a robocall enterprise is easy and cheap.

The best advice for now is not to answer calls from unfamiliar phone numbers. “We still get a ton of spam, but Google and everyone has gotten so good at filtering email that you don’t notice,” Mr. Quilici says. For now, robocalling remains a frustration of a plugged-in life.
 

Work, ethics, and the millennials

A few months ago, several Google employees reportedly quit over the company’s involvement in a military project. Their decision might have come with the knowledge that their skills were transferable and that another job would not prove hard to find.

Still, the decision to resign might be a sign of how different generations approach work, according to a BBC article. For millennials, sometimes called the job-hopping generation, switching jobs for ethical reasons might be more common than it is for Generation Xers or Baby Boomers.

Then again, the article says, these ideas about millennials might not hold true for most young workers.

Part of this may be tied to the economics of the present. Research supports the view that gaps in employment, whether deliberate or not, are neither good for the bank account nor the likelihood of future job satisfaction.

“For all the lip service we pay to ‘making a difference,’ evidence shows the primary driver for selecting a job is still the payslip. The most recent Deloitte survey on millennials underlines that 63% of millennials consider the financial reward a very important factor in weighing up a job offer – the highest ranking one,” writes BBC correspondent José Luis Peñarredonda.

As in generations past, the main reason for choosing a job in 2018 remains the wage. Real-life necessities to support a family can blunt youthful passion to change things in a low-paying way. Still, headway is being made, as some companies realize the value of aligning corporate priorities with employees’ desire to have their work better reflect their ethics.
 

Finding ways to overcome setbacks

The end of a relationship, or loss of a loved one – or a job – are inevitable life events – and there are steps people can take to be resilient and find happiness, writes Arthur B. Markman, PhD.

First, Dr. Markman says, it is important to focus on steps that can be taken to improve a situation.

“As you engage in those actions, you will find that you feel better about your work and will also become more productive,” writes Dr. Markman, professor of psychology and marketing at the University of Texas, Austin.

A second strategy, he writes, is “surrounding yourself with people if you don’t feel like it.” This helps, he says, because sharing challenges with others can help people focus on what they need to do do. Third, Dr. Markman advises, it’s best to focus on small victories rather than long-term projects.

And finally, he says, it helps to interpret the actions of others through a positive lens. Why? Because this approach is more likely to create “positive reactions with others,” he writes.

Find Dr. Markman’s article in Fast Company.

The things witnessed and actions taken during military service can lead to posttraumatic stress disorder and other debilitating illnesses.

val_shep/Thinkstock

Retired Command Sgt. Maj. Sam Rhodes, a nearly 30-year U.S. Army veteran, says he was scarred by nightmares of his combat experiences in Iraq upon returning home to Georgia. He also had depression, he says. Yet, Mr. Rhodes missed the camaraderie of his squad and felt lost when he returned home. For a time, he says, ending his life seemed the only way out.


Then he began to care for his stepdaughter’s horse. “Cleaning stalls, putting up fences; it made me feel like I had a purpose in life. It’s amazing how it really got me to calm down a little bit,” he relates in an interview with CNN.

Seeking to share the relief he felt, Mr. Rhodes built his own horse ranch and created Warrior Outreach, a nonprofit that, among other things, provides free access to horses for veterans, service members, and their families through its twice yearly Horsemanship Program. For Mr. Rhodes and the other veterans who frequent the ranch, there has been no miracle turnaround. Some of the veterans still experience darkness, but for some, interacting with the horses has proven therapeutic.

“Guys can come out here, especially if they are having a rough go at it, and just kind of forget about what’s going on in the real world,” veteran Michael Christensen says. “The fact that we can network and just say, ‘Anytime you need something, here’s my number, call me’ ... It builds a network of veterans that can help each other.”

Two perspectives on anorexia

Identical twins often share many of the same interests, but they also can experience differences in how they view themselves.

©b-d-s/Thinkstock

Take the case of Bridget Yard, an identical twin and journalist who, in a CBC radio report, describes her life with an eating disorder and a twin sister who proved to be her savior.

“I sometimes thought I wouldn’t survive my teenage years, or early adulthood, because of my illness. But once I let Brianna in on my secrets, we began to deal with them together. She continues to be my greatest support as I enter recovery and work hard to live a healthy, full life. But we both still struggle with something. Why did I develop an eating disorder, and not Brianna? We were raised in the same environment, by the same loving parents. Our DNA is identical. I want to know what tipped the balance. Why me?”

The clues were there early on. Bridget was insecure and shy as a teen, and she says she was struggling to accept issues that included her feelings of bisexuality. Brianna was confident and outgoing. Hunger became a way for Bridget to quiet the demons of insecurity and establish some control. “I pushed my sexuality further back into the closet than my eating disorder,” she says. “That closet was full up, and it was killing me to continue the charade.”

Howard Steiger, PhD, tells Bridget Yard that the twin with anorexia nervosa often is found to be more perfectionistic and prone to being concerned with making errors and with others judgments. “Now we don’t know, is that a sort of a life experience thing that causes that to become more expressed? Or is that a secondary thing because of starvation and the effects of malnutrition? Or is it maybe a prenatal effect, that meant that one of the twins was programmed to be a little more perfectionistic than the other?” says Dr. Steiger, director of the Douglas Mental Health University Institute’s Eating Disorders Program at McGill University in Montreal.

Genetic changes, even before birth, might have a role. Whatever the causes, personal acceptance and recognition of her strengths and frailties have helped Bridget find a new path.

“Brianna has a phrase that we use a lot: ‘Nothing to it but to get through it.’ I used to hate that. It’s so cold, and things aren’t always so simple,” Bridget says in the interview. “But now, I embrace it. I know I will never have to do this alone. There’s nothing to it but to get through it – honestly, and together.”
 

Is that phone call real or robo?

In the few minutes it takes to read this column, some 400,000 Americans will have picked up the phone to hear a robotic voice harping a product or cause. If robocalling were a disease, it would be an epidemic.

Some robocalls are positive, reminding us of appointments and coming events. But about 40% are scams.

“Every time my phone rings it interrupts the work I’m doing,” says Hannah Donahue, a media strategist in Los Angeles. “Even if I don’t answer the phone, it’s disruptive.” She receives about six robocalls a day, starting as early as 7 a.m. and continuing into the evening.

And it might not be as easy as simply not answering a call when your business life depends on your phone. Missing a call can mean lost work.

Robocalling has been around for decades. But the frequency of use has skyrocketed in recent years. In 2018, the estimated number of monthly robocalls in the United States has risen from about 2.5 billion to 4.5 billion, as reported by NBC News.

The increased efforts by robo-scammers might reflect changing consumer behaviors. “The [telecommunications carriers] started to identify the bad guys,” says Alex Quilici, CEO of YouMail, a company that provides voicemail and call-blocking services to iPhone and Android users. “Call-blocking apps started to scale up and get publicity. What we figure is that bad guys started having to call more to get through.”

Technology is another driver. Setting up a robocall enterprise is easy and cheap.

The best advice for now is not to answer calls from unfamiliar phone numbers. “We still get a ton of spam, but Google and everyone has gotten so good at filtering email that you don’t notice,” Mr. Quilici says. For now, robocalling remains a frustration of a plugged-in life.
 

Work, ethics, and the millennials

A few months ago, several Google employees reportedly quit over the company’s involvement in a military project. Their decision might have come with the knowledge that their skills were transferable and that another job would not prove hard to find.

Still, the decision to resign might be a sign of how different generations approach work, according to a BBC article. For millennials, sometimes called the job-hopping generation, switching jobs for ethical reasons might be more common than it is for Generation Xers or Baby Boomers.

Then again, the article says, these ideas about millennials might not hold true for most young workers.

Part of this may be tied to the economics of the present. Research supports the view that gaps in employment, whether deliberate or not, are neither good for the bank account nor the likelihood of future job satisfaction.

“For all the lip service we pay to ‘making a difference,’ evidence shows the primary driver for selecting a job is still the payslip. The most recent Deloitte survey on millennials underlines that 63% of millennials consider the financial reward a very important factor in weighing up a job offer – the highest ranking one,” writes BBC correspondent José Luis Peñarredonda.

As in generations past, the main reason for choosing a job in 2018 remains the wage. Real-life necessities to support a family can blunt youthful passion to change things in a low-paying way. Still, headway is being made, as some companies realize the value of aligning corporate priorities with employees’ desire to have their work better reflect their ethics.
 

Finding ways to overcome setbacks

The end of a relationship, or loss of a loved one – or a job – are inevitable life events – and there are steps people can take to be resilient and find happiness, writes Arthur B. Markman, PhD.

First, Dr. Markman says, it is important to focus on steps that can be taken to improve a situation.

“As you engage in those actions, you will find that you feel better about your work and will also become more productive,” writes Dr. Markman, professor of psychology and marketing at the University of Texas, Austin.

A second strategy, he writes, is “surrounding yourself with people if you don’t feel like it.” This helps, he says, because sharing challenges with others can help people focus on what they need to do do. Third, Dr. Markman advises, it’s best to focus on small victories rather than long-term projects.

And finally, he says, it helps to interpret the actions of others through a positive lens. Why? Because this approach is more likely to create “positive reactions with others,” he writes.

Find Dr. Markman’s article in Fast Company.

Photo by Chris Horry

A lower threshold for platelet transfusions may be safer for preterm infants with severe thrombocytopenia, a new study suggests.

Researchers randomized preterm infants with severe thrombocytopenia to receive transfusions at platelet count thresholds of 50,000/mm³ or 25,000/mm³.

The team found that patients in the high-threshold group had a significantly higher risk of major bleeding or death.

Anna Curley, MD, of the National Maternity Hospital in Dublin, Ireland, and her colleagues reported this finding in The New England Journal of Medicine.

The researchers studied 660 infants with a mean gestational age of 26.6 weeks. They were randomized to receive platelet transfusions at a high platelet-count threshold of 50,000/mm³ or a low threshold of 25,000/mm³.

Within 28 days of randomization, a new major bleeding episode or death occurred in 26% of the high-threshold group and 19% of the low-threshold group.

When the researchers adjusted for gestational age, intrauterine growth restriction, and trial site, the odds ratio (OR) for major bleeding or death was 1.57 (95% confidence interval [CI], 1.06-2.32; P=0.02).

The OR for death alone was 1.56 (95% CI, 0.95-2.55), and the hazard ratio for at least one major bleeding episode was 1.32 (95% CI, 1.00-1.74).

The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups—25% and 22%, respectively (OR=1.14; 95% CI, 0.78-1.67).

The researchers said the results of this trial suggest that reducing the transfusion threshold from 50,000/mm³ to 25,000/mm³ may prevent death or major bleeding in 7 of 100 preterm neonates with severe thrombocytopenia.

However, the team also acknowledged that it isn’t clear why reducing the threshold may reduce the risk of mortality or major bleeding in this patient group.

The researchers said a range of factors might play a role in adverse outcomes of platelet transfusion in preterm neonates, including inflammatory consequences, hemodynamic shifts, fragility of the germinal matrix, disturbances in organ and brain blood flow, preterm lungs with a large capillary bed and abundant immune cells, platelet-derived reactive oxygen species, proangiogenic factors, and vessel occlusion by platelet microthrombi.

This study was supported by the National Health Service Blood and Transplant Research and Development Committee, Sanquin Research, Addenbrooke’s Charitable Trust, the Neonatal Breath of Life Fund, and the National Institute for Health Research Clinical Research Network.

One study author reported consulting for Sanquin Research, and another declared travel funds from Cerus Corporation.

Photo by Chris Horry

A lower threshold for platelet transfusions may be safer for preterm infants with severe thrombocytopenia, a new study suggests.

Researchers randomized preterm infants with severe thrombocytopenia to receive transfusions at platelet count thresholds of 50,000/mm³ or 25,000/mm³.

The team found that patients in the high-threshold group had a significantly higher risk of major bleeding or death.

Anna Curley, MD, of the National Maternity Hospital in Dublin, Ireland, and her colleagues reported this finding in The New England Journal of Medicine.

The researchers studied 660 infants with a mean gestational age of 26.6 weeks. They were randomized to receive platelet transfusions at a high platelet-count threshold of 50,000/mm³ or a low threshold of 25,000/mm³.

Within 28 days of randomization, a new major bleeding episode or death occurred in 26% of the high-threshold group and 19% of the low-threshold group.

When the researchers adjusted for gestational age, intrauterine growth restriction, and trial site, the odds ratio (OR) for major bleeding or death was 1.57 (95% confidence interval [CI], 1.06-2.32; P=0.02).

The OR for death alone was 1.56 (95% CI, 0.95-2.55), and the hazard ratio for at least one major bleeding episode was 1.32 (95% CI, 1.00-1.74).

The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups—25% and 22%, respectively (OR=1.14; 95% CI, 0.78-1.67).

The researchers said the results of this trial suggest that reducing the transfusion threshold from 50,000/mm³ to 25,000/mm³ may prevent death or major bleeding in 7 of 100 preterm neonates with severe thrombocytopenia.

However, the team also acknowledged that it isn’t clear why reducing the threshold may reduce the risk of mortality or major bleeding in this patient group.

The researchers said a range of factors might play a role in adverse outcomes of platelet transfusion in preterm neonates, including inflammatory consequences, hemodynamic shifts, fragility of the germinal matrix, disturbances in organ and brain blood flow, preterm lungs with a large capillary bed and abundant immune cells, platelet-derived reactive oxygen species, proangiogenic factors, and vessel occlusion by platelet microthrombi.

This study was supported by the National Health Service Blood and Transplant Research and Development Committee, Sanquin Research, Addenbrooke’s Charitable Trust, the Neonatal Breath of Life Fund, and the National Institute for Health Research Clinical Research Network.

One study author reported consulting for Sanquin Research, and another declared travel funds from Cerus Corporation.

Photo by Chris Horry

A lower threshold for platelet transfusions may be safer for preterm infants with severe thrombocytopenia, a new study suggests.

Researchers randomized preterm infants with severe thrombocytopenia to receive transfusions at platelet count thresholds of 50,000/mm³ or 25,000/mm³.

The team found that patients in the high-threshold group had a significantly higher risk of major bleeding or death.

Anna Curley, MD, of the National Maternity Hospital in Dublin, Ireland, and her colleagues reported this finding in The New England Journal of Medicine.

The researchers studied 660 infants with a mean gestational age of 26.6 weeks. They were randomized to receive platelet transfusions at a high platelet-count threshold of 50,000/mm³ or a low threshold of 25,000/mm³.

Within 28 days of randomization, a new major bleeding episode or death occurred in 26% of the high-threshold group and 19% of the low-threshold group.

When the researchers adjusted for gestational age, intrauterine growth restriction, and trial site, the odds ratio (OR) for major bleeding or death was 1.57 (95% confidence interval [CI], 1.06-2.32; P=0.02).

The OR for death alone was 1.56 (95% CI, 0.95-2.55), and the hazard ratio for at least one major bleeding episode was 1.32 (95% CI, 1.00-1.74).

The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups—25% and 22%, respectively (OR=1.14; 95% CI, 0.78-1.67).

The researchers said the results of this trial suggest that reducing the transfusion threshold from 50,000/mm³ to 25,000/mm³ may prevent death or major bleeding in 7 of 100 preterm neonates with severe thrombocytopenia.

However, the team also acknowledged that it isn’t clear why reducing the threshold may reduce the risk of mortality or major bleeding in this patient group.

The researchers said a range of factors might play a role in adverse outcomes of platelet transfusion in preterm neonates, including inflammatory consequences, hemodynamic shifts, fragility of the germinal matrix, disturbances in organ and brain blood flow, preterm lungs with a large capillary bed and abundant immune cells, platelet-derived reactive oxygen species, proangiogenic factors, and vessel occlusion by platelet microthrombi.

This study was supported by the National Health Service Blood and Transplant Research and Development Committee, Sanquin Research, Addenbrooke’s Charitable Trust, the Neonatal Breath of Life Fund, and the National Institute for Health Research Clinical Research Network.

One study author reported consulting for Sanquin Research, and another declared travel funds from Cerus Corporation.