Bianca Nogrady

Uterine cancer incidence and mortality in the United States increased significantly from 1999 to 2015, with the greatest increases among nonwhite women, according to data published in the Morbidity and Mortality Weekly Report.

Uterine cancer is the fourth most common cancer diagnosed and the seventh most common cause of cancer death among women in the United States, wrote S. Jane Henley and her colleagues from the division of cancer prevention and control at the National Center for Chronic Disease Prevention and Health Promotion. Its incidence is thought to be on the rise because of the increasing prevalence of overweight and obesity.

In this report, researchers analyzed data from population-based cancer registries to find new cases of invasive uterine cancer from 1999 to 2015.

Over that period, incidence rates of uterine cancer increased around 0.7% per year on average, with an overall 12% increase. However, among American Indian and Alaskan Native women, the incidence rate during that time increased by 53%, among black women it increased by 46%, among Asian/Pacific Island women the incidence rate increased by 38%, and among Hispanic women it increased by 32%.

Uterine cancer death rates also increased by 21% from 1999 to 2015, representing approximately a 1.1% average increase per year. Again, the greatest increases were seen in American Indian and Alaskan Native women (52%), Hispanic women (33%), and black women (29%). Death rates increased by 18% among white women but were stable among Asian/Pacific Island women.

The most common type of uterine cancer was the endometrioid carcinomas, which accounted for 68% of uterine cancers overall. However black women had a higher percentage of other carcinomas, carcinosarcomas, and sarcomas, compared with women from other ethnic groups.

Two-thirds of cancer overall were diagnosed at a localized stage, but this was less common in black women than women of other ethnicities, while the proportion of cancers diagnosed at distant stage was higher among black women.

“This report found that black women were more likely to receive a diagnosis at distant stage and with more aggressive histologic types than were other women, which might in part account for the higher death rate among black women,” the authors wrote.

Despite the increasing incidence and mortality, the authors wrote that population-based screening tests are not recommended for uterine cancer, partly because around 90% of women with uterine cancer report abnormal vaginal bleeding.

“Uterine cancer outcomes could be improved by increasing awareness among women that abnormal vagi­nal bleeding should be evaluated promptly by a health care provider,” they wrote.

No conflicts of interest were reported.

SOURCE: Henley SJ et al. MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67:1333-8.
 

Uterine cancer incidence and mortality in the United States increased significantly from 1999 to 2015, with the greatest increases among nonwhite women, according to data published in the Morbidity and Mortality Weekly Report.

Uterine cancer is the fourth most common cancer diagnosed and the seventh most common cause of cancer death among women in the United States, wrote S. Jane Henley and her colleagues from the division of cancer prevention and control at the National Center for Chronic Disease Prevention and Health Promotion. Its incidence is thought to be on the rise because of the increasing prevalence of overweight and obesity.

In this report, researchers analyzed data from population-based cancer registries to find new cases of invasive uterine cancer from 1999 to 2015.

Over that period, incidence rates of uterine cancer increased around 0.7% per year on average, with an overall 12% increase. However, among American Indian and Alaskan Native women, the incidence rate during that time increased by 53%, among black women it increased by 46%, among Asian/Pacific Island women the incidence rate increased by 38%, and among Hispanic women it increased by 32%.

Uterine cancer death rates also increased by 21% from 1999 to 2015, representing approximately a 1.1% average increase per year. Again, the greatest increases were seen in American Indian and Alaskan Native women (52%), Hispanic women (33%), and black women (29%). Death rates increased by 18% among white women but were stable among Asian/Pacific Island women.

The most common type of uterine cancer was the endometrioid carcinomas, which accounted for 68% of uterine cancers overall. However black women had a higher percentage of other carcinomas, carcinosarcomas, and sarcomas, compared with women from other ethnic groups.

Two-thirds of cancer overall were diagnosed at a localized stage, but this was less common in black women than women of other ethnicities, while the proportion of cancers diagnosed at distant stage was higher among black women.

“This report found that black women were more likely to receive a diagnosis at distant stage and with more aggressive histologic types than were other women, which might in part account for the higher death rate among black women,” the authors wrote.

Despite the increasing incidence and mortality, the authors wrote that population-based screening tests are not recommended for uterine cancer, partly because around 90% of women with uterine cancer report abnormal vaginal bleeding.

“Uterine cancer outcomes could be improved by increasing awareness among women that abnormal vagi­nal bleeding should be evaluated promptly by a health care provider,” they wrote.

No conflicts of interest were reported.

SOURCE: Henley SJ et al. MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67:1333-8.
 

Uterine cancer incidence and mortality in the United States increased significantly from 1999 to 2015, with the greatest increases among nonwhite women, according to data published in the Morbidity and Mortality Weekly Report.

Uterine cancer is the fourth most common cancer diagnosed and the seventh most common cause of cancer death among women in the United States, wrote S. Jane Henley and her colleagues from the division of cancer prevention and control at the National Center for Chronic Disease Prevention and Health Promotion. Its incidence is thought to be on the rise because of the increasing prevalence of overweight and obesity.

In this report, researchers analyzed data from population-based cancer registries to find new cases of invasive uterine cancer from 1999 to 2015.

Over that period, incidence rates of uterine cancer increased around 0.7% per year on average, with an overall 12% increase. However, among American Indian and Alaskan Native women, the incidence rate during that time increased by 53%, among black women it increased by 46%, among Asian/Pacific Island women the incidence rate increased by 38%, and among Hispanic women it increased by 32%.

Uterine cancer death rates also increased by 21% from 1999 to 2015, representing approximately a 1.1% average increase per year. Again, the greatest increases were seen in American Indian and Alaskan Native women (52%), Hispanic women (33%), and black women (29%). Death rates increased by 18% among white women but were stable among Asian/Pacific Island women.

The most common type of uterine cancer was the endometrioid carcinomas, which accounted for 68% of uterine cancers overall. However black women had a higher percentage of other carcinomas, carcinosarcomas, and sarcomas, compared with women from other ethnic groups.

Two-thirds of cancer overall were diagnosed at a localized stage, but this was less common in black women than women of other ethnicities, while the proportion of cancers diagnosed at distant stage was higher among black women.

“This report found that black women were more likely to receive a diagnosis at distant stage and with more aggressive histologic types than were other women, which might in part account for the higher death rate among black women,” the authors wrote.

Despite the increasing incidence and mortality, the authors wrote that population-based screening tests are not recommended for uterine cancer, partly because around 90% of women with uterine cancer report abnormal vaginal bleeding.

“Uterine cancer outcomes could be improved by increasing awareness among women that abnormal vagi­nal bleeding should be evaluated promptly by a health care provider,” they wrote.

No conflicts of interest were reported.

SOURCE: Henley SJ et al. MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67:1333-8.
 

Premature babies may benefit more if caffeine therapy is given within 2 days of birth, based on a retrospective observational cohort study of more than 2,000 newborns.

When caffeine was given within the first 2 days of birth, neonates had an adjusted odds ratio of significant neurodevelopmental impairment of 0.68, compared with neonates who received caffeine after 2 or more days. Further, the early-caffeine group had a 0.67 adjusted odds ratio for having cognitive scores of less than 85 on the Bayley Scales of Infant and Toddler Development, Third Edition, compared with the late-caffeine group. After researchers corrected for small-for-gestational-age status and other risk factors, however, early-caffeine therapy was associated with lower odds of cerebral palsy and hearing impairment only, according to the study published online in Pediatrics.

Caffeine administration should be a priority once extremely preterm neonates are stabilized, Abhay Lodha, MD, of the University of Calgary (Alta.), and his coauthors wrote. “It is rather easy to organize the administration of caffeine as early as possible for Level 3 nurseries, and many units have already accomplished this. However, certain Level 2 nurseries may not have facilities available for such early administration. We do not have data that indicate the earliest that caffeine would have to be given to get maximum benefit, and thus, it should not be counted as an emergency medication yet,” they wrote.

The study examined data from 2,108 neonates born before 29 weeks of gestational age and given caffeine to treat or prevent apnea; 1,545 received the caffeine within 2 days of birth and the remaining 563 were treated with caffeine after 2 days. Data were adjusted for gestational age, sex, antenatal steroids, and SNAP-II (Score of Neonatal Acute Physiology-II) score.

The early-caffeine group had a significantly reduced odds of hearing impairment and cerebral palsy, bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury. When the data were further analyzed using propensity-matched groups – which also accounted for small-for-gestational-age status – the difference in outcomes was a nonsignificant trend in favor of early caffeine.

The authors noted that the late-caffeine group contained a higher proportion of infants born at or before 24 weeks’ gestational age, and a lower proportion of infants born at 25-28 weeks’ gestational age, compared with the early-caffeine group. The infants in the early-caffeine group also had higher Apgar scores, higher median birth weight, and lower SNAP-II scores, and received a longer median duration of caffeine treatment.

Dr. Lodha and his coauthors said the reason for the differences between the early- and late-caffeine groups was unclear. “However, it could be attributable to an increased growth of dendrites and spines in neurons that is initiated by the especially prolonged use of caffeine in the early-caffeine group,” they wrote. “The other speculation is that caffeine improves cardiac output and blood pressure in infants who are relatively stable.‍”

No funding or conflicts of interest were declared.
 

SOURCE: Lodha A et al. Pediatrics. 2018 Dec. 5. doi. org/10.1542/peds.2018-1348.

Premature babies may benefit more if caffeine therapy is given within 2 days of birth, based on a retrospective observational cohort study of more than 2,000 newborns.

When caffeine was given within the first 2 days of birth, neonates had an adjusted odds ratio of significant neurodevelopmental impairment of 0.68, compared with neonates who received caffeine after 2 or more days. Further, the early-caffeine group had a 0.67 adjusted odds ratio for having cognitive scores of less than 85 on the Bayley Scales of Infant and Toddler Development, Third Edition, compared with the late-caffeine group. After researchers corrected for small-for-gestational-age status and other risk factors, however, early-caffeine therapy was associated with lower odds of cerebral palsy and hearing impairment only, according to the study published online in Pediatrics.

Caffeine administration should be a priority once extremely preterm neonates are stabilized, Abhay Lodha, MD, of the University of Calgary (Alta.), and his coauthors wrote. “It is rather easy to organize the administration of caffeine as early as possible for Level 3 nurseries, and many units have already accomplished this. However, certain Level 2 nurseries may not have facilities available for such early administration. We do not have data that indicate the earliest that caffeine would have to be given to get maximum benefit, and thus, it should not be counted as an emergency medication yet,” they wrote.

The study examined data from 2,108 neonates born before 29 weeks of gestational age and given caffeine to treat or prevent apnea; 1,545 received the caffeine within 2 days of birth and the remaining 563 were treated with caffeine after 2 days. Data were adjusted for gestational age, sex, antenatal steroids, and SNAP-II (Score of Neonatal Acute Physiology-II) score.

The early-caffeine group had a significantly reduced odds of hearing impairment and cerebral palsy, bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury. When the data were further analyzed using propensity-matched groups – which also accounted for small-for-gestational-age status – the difference in outcomes was a nonsignificant trend in favor of early caffeine.

The authors noted that the late-caffeine group contained a higher proportion of infants born at or before 24 weeks’ gestational age, and a lower proportion of infants born at 25-28 weeks’ gestational age, compared with the early-caffeine group. The infants in the early-caffeine group also had higher Apgar scores, higher median birth weight, and lower SNAP-II scores, and received a longer median duration of caffeine treatment.

Dr. Lodha and his coauthors said the reason for the differences between the early- and late-caffeine groups was unclear. “However, it could be attributable to an increased growth of dendrites and spines in neurons that is initiated by the especially prolonged use of caffeine in the early-caffeine group,” they wrote. “The other speculation is that caffeine improves cardiac output and blood pressure in infants who are relatively stable.‍”

No funding or conflicts of interest were declared.
 

SOURCE: Lodha A et al. Pediatrics. 2018 Dec. 5. doi. org/10.1542/peds.2018-1348.

Premature babies may benefit more if caffeine therapy is given within 2 days of birth, based on a retrospective observational cohort study of more than 2,000 newborns.

When caffeine was given within the first 2 days of birth, neonates had an adjusted odds ratio of significant neurodevelopmental impairment of 0.68, compared with neonates who received caffeine after 2 or more days. Further, the early-caffeine group had a 0.67 adjusted odds ratio for having cognitive scores of less than 85 on the Bayley Scales of Infant and Toddler Development, Third Edition, compared with the late-caffeine group. After researchers corrected for small-for-gestational-age status and other risk factors, however, early-caffeine therapy was associated with lower odds of cerebral palsy and hearing impairment only, according to the study published online in Pediatrics.

Caffeine administration should be a priority once extremely preterm neonates are stabilized, Abhay Lodha, MD, of the University of Calgary (Alta.), and his coauthors wrote. “It is rather easy to organize the administration of caffeine as early as possible for Level 3 nurseries, and many units have already accomplished this. However, certain Level 2 nurseries may not have facilities available for such early administration. We do not have data that indicate the earliest that caffeine would have to be given to get maximum benefit, and thus, it should not be counted as an emergency medication yet,” they wrote.

The study examined data from 2,108 neonates born before 29 weeks of gestational age and given caffeine to treat or prevent apnea; 1,545 received the caffeine within 2 days of birth and the remaining 563 were treated with caffeine after 2 days. Data were adjusted for gestational age, sex, antenatal steroids, and SNAP-II (Score of Neonatal Acute Physiology-II) score.

The early-caffeine group had a significantly reduced odds of hearing impairment and cerebral palsy, bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury. When the data were further analyzed using propensity-matched groups – which also accounted for small-for-gestational-age status – the difference in outcomes was a nonsignificant trend in favor of early caffeine.

The authors noted that the late-caffeine group contained a higher proportion of infants born at or before 24 weeks’ gestational age, and a lower proportion of infants born at 25-28 weeks’ gestational age, compared with the early-caffeine group. The infants in the early-caffeine group also had higher Apgar scores, higher median birth weight, and lower SNAP-II scores, and received a longer median duration of caffeine treatment.

Dr. Lodha and his coauthors said the reason for the differences between the early- and late-caffeine groups was unclear. “However, it could be attributable to an increased growth of dendrites and spines in neurons that is initiated by the especially prolonged use of caffeine in the early-caffeine group,” they wrote. “The other speculation is that caffeine improves cardiac output and blood pressure in infants who are relatively stable.‍”

No funding or conflicts of interest were declared.
 

SOURCE: Lodha A et al. Pediatrics. 2018 Dec. 5. doi. org/10.1542/peds.2018-1348.

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

A gene therapy for Parkinson’s disease, focusing on the subthalamic nucleus, appears to lead to the formation of unique brain circuitry that correlates with clinical improvement.

copyright graphicsdunia4you/Thinkstock

In a paper published online Nov. 28 in Science Translational Medicine, researchers describe the findings of a metabolic imaging study to explore the mechanism underlying benefits seen in a phase 2, blinded, sham-controlled clinical trial of the gene therapy.

The therapy in question used an adeno-associated viral vector to deliver the gene for glutamic acid decarboxylase into the subthalamic nucleus – a region of the brain known to be overactivated in Parkinson’s disease – which was intended to have an inhibitory effect on the neurons in that region.

Martin Niethammer, MD, PhD, of the Center for Neurosciences at The Feinstein Institute for Medical Research in New York, and his coauthors used ¹⁸F-fluorodeoxyglucose positron emission tomography at baseline, 6, and 12 months in 15 gene-therapy patients and 21 sham-treated patients, which revealed the development of new brain circuits in patients treated with the gene therapy.

The circuits, which researchers called the glutamic acid decarboxylase-related pattern, or GADRP, presented with increased metabolism in the premotor region – which also extended into the adjacent motor cortex – and in the supramarginal gyrus. There was also decreased metabolic activity in the caudate, anterior putamen, and adjacent globus pallidus; the ventral anterior and medial dorsal thalamic nuclei; and in the inferior frontal gyrus.

All 15 patients who received the gene therapy showed significant trends in GADRP expression after the treatment, compared with patients who underwent the sham procedure. Furthermore, these correlated significantly with improved clinical outcomes.

The imaging also revealed increased connectivity between regions in the GADRP space among patients who received the gene therapy, with researchers noting five new intrahemispheric node-to-node connections in these patients that were not seen in the sham procedure group.

These included connection linking the left caudate nucleus to the left superior frontal node, the right superior frontal node to the right supramarginal gyrus, and linking the left anterior putamen and globus pallidus with the ipsilateral thalamic node.

The authors also found that overall connectivity in the network rose to “abnormal” levels in the 12 months after gene therapy, while no similar increases were seen in the sham group.

Given that deep brain stimulation for Parkinson’s disease also targets the subthalamic nucleus, researchers looked at changes to the GADRP network in these patients, compared with those who received sham therapy and those who received gene therapy.

They saw that changes in GADRP expression were significantly different between the gene therapy-treated patients and those treated with deep brain stimulation and sham surgery. However, the differences between deep brain stimulation and sham surgery were not significant.

“The current study indicates that customized networks can be characterized using functional imaging data acquired in randomized, controlled phase 2 clinical trials and, if validated, could be used as quantitative outcome measures in more definitive, later-stage clinical trials,” the authors wrote.

The study was supported by Neurologix. Two authors were consultants and stockholders of MeiraGTx.

SOURCE: Niethammer N et al. Sci Transl Med. 2018 Nov 28. doi: 10.1126/scitranslmed.aau0713.

A gene therapy for Parkinson’s disease, focusing on the subthalamic nucleus, appears to lead to the formation of unique brain circuitry that correlates with clinical improvement.

copyright graphicsdunia4you/Thinkstock

In a paper published online Nov. 28 in Science Translational Medicine, researchers describe the findings of a metabolic imaging study to explore the mechanism underlying benefits seen in a phase 2, blinded, sham-controlled clinical trial of the gene therapy.

The therapy in question used an adeno-associated viral vector to deliver the gene for glutamic acid decarboxylase into the subthalamic nucleus – a region of the brain known to be overactivated in Parkinson’s disease – which was intended to have an inhibitory effect on the neurons in that region.

Martin Niethammer, MD, PhD, of the Center for Neurosciences at The Feinstein Institute for Medical Research in New York, and his coauthors used ¹⁸F-fluorodeoxyglucose positron emission tomography at baseline, 6, and 12 months in 15 gene-therapy patients and 21 sham-treated patients, which revealed the development of new brain circuits in patients treated with the gene therapy.

The circuits, which researchers called the glutamic acid decarboxylase-related pattern, or GADRP, presented with increased metabolism in the premotor region – which also extended into the adjacent motor cortex – and in the supramarginal gyrus. There was also decreased metabolic activity in the caudate, anterior putamen, and adjacent globus pallidus; the ventral anterior and medial dorsal thalamic nuclei; and in the inferior frontal gyrus.

All 15 patients who received the gene therapy showed significant trends in GADRP expression after the treatment, compared with patients who underwent the sham procedure. Furthermore, these correlated significantly with improved clinical outcomes.

The imaging also revealed increased connectivity between regions in the GADRP space among patients who received the gene therapy, with researchers noting five new intrahemispheric node-to-node connections in these patients that were not seen in the sham procedure group.

These included connection linking the left caudate nucleus to the left superior frontal node, the right superior frontal node to the right supramarginal gyrus, and linking the left anterior putamen and globus pallidus with the ipsilateral thalamic node.

The authors also found that overall connectivity in the network rose to “abnormal” levels in the 12 months after gene therapy, while no similar increases were seen in the sham group.

Given that deep brain stimulation for Parkinson’s disease also targets the subthalamic nucleus, researchers looked at changes to the GADRP network in these patients, compared with those who received sham therapy and those who received gene therapy.

They saw that changes in GADRP expression were significantly different between the gene therapy-treated patients and those treated with deep brain stimulation and sham surgery. However, the differences between deep brain stimulation and sham surgery were not significant.

“The current study indicates that customized networks can be characterized using functional imaging data acquired in randomized, controlled phase 2 clinical trials and, if validated, could be used as quantitative outcome measures in more definitive, later-stage clinical trials,” the authors wrote.

The study was supported by Neurologix. Two authors were consultants and stockholders of MeiraGTx.

SOURCE: Niethammer N et al. Sci Transl Med. 2018 Nov 28. doi: 10.1126/scitranslmed.aau0713.

A gene therapy for Parkinson’s disease, focusing on the subthalamic nucleus, appears to lead to the formation of unique brain circuitry that correlates with clinical improvement.

copyright graphicsdunia4you/Thinkstock

In a paper published online Nov. 28 in Science Translational Medicine, researchers describe the findings of a metabolic imaging study to explore the mechanism underlying benefits seen in a phase 2, blinded, sham-controlled clinical trial of the gene therapy.

The therapy in question used an adeno-associated viral vector to deliver the gene for glutamic acid decarboxylase into the subthalamic nucleus – a region of the brain known to be overactivated in Parkinson’s disease – which was intended to have an inhibitory effect on the neurons in that region.

Martin Niethammer, MD, PhD, of the Center for Neurosciences at The Feinstein Institute for Medical Research in New York, and his coauthors used ¹⁸F-fluorodeoxyglucose positron emission tomography at baseline, 6, and 12 months in 15 gene-therapy patients and 21 sham-treated patients, which revealed the development of new brain circuits in patients treated with the gene therapy.

The circuits, which researchers called the glutamic acid decarboxylase-related pattern, or GADRP, presented with increased metabolism in the premotor region – which also extended into the adjacent motor cortex – and in the supramarginal gyrus. There was also decreased metabolic activity in the caudate, anterior putamen, and adjacent globus pallidus; the ventral anterior and medial dorsal thalamic nuclei; and in the inferior frontal gyrus.

All 15 patients who received the gene therapy showed significant trends in GADRP expression after the treatment, compared with patients who underwent the sham procedure. Furthermore, these correlated significantly with improved clinical outcomes.

The imaging also revealed increased connectivity between regions in the GADRP space among patients who received the gene therapy, with researchers noting five new intrahemispheric node-to-node connections in these patients that were not seen in the sham procedure group.

These included connection linking the left caudate nucleus to the left superior frontal node, the right superior frontal node to the right supramarginal gyrus, and linking the left anterior putamen and globus pallidus with the ipsilateral thalamic node.

The authors also found that overall connectivity in the network rose to “abnormal” levels in the 12 months after gene therapy, while no similar increases were seen in the sham group.

Given that deep brain stimulation for Parkinson’s disease also targets the subthalamic nucleus, researchers looked at changes to the GADRP network in these patients, compared with those who received sham therapy and those who received gene therapy.

They saw that changes in GADRP expression were significantly different between the gene therapy-treated patients and those treated with deep brain stimulation and sham surgery. However, the differences between deep brain stimulation and sham surgery were not significant.

“The current study indicates that customized networks can be characterized using functional imaging data acquired in randomized, controlled phase 2 clinical trials and, if validated, could be used as quantitative outcome measures in more definitive, later-stage clinical trials,” the authors wrote.

The study was supported by Neurologix. Two authors were consultants and stockholders of MeiraGTx.

SOURCE: Niethammer N et al. Sci Transl Med. 2018 Nov 28. doi: 10.1126/scitranslmed.aau0713.

Women who have a healthier lifestyle during the menopausal transition could significantly reduce their risk of cardiovascular disease, new research suggests.

kali9/E+

Because women experience a steeper increase in CVD risk during and after the menopausal transition, researchers analyzed data from the Study of Women’s Health Across the Nation (SWAN), a prospective longitudinal cohort study of 1,143 women aged 42-52 years. The report is in JAHA: Journal of the American Heart Association.

The analysis revealed that women with the highest average Healthy Lifestyle Score – a composite score of dietary quality, levels of physical activity, and smoking – over 10 years of follow-up had a 0.024-mm smaller common carotid artery intima-media thickness and 0.16-mm smaller adventitial diameter, compared to those with the lowest average score. This was after adjustment for confounders and physiological risk factors such as ethnicity, age, menopausal status, body mass index, and cholesterol levels.

“Smoking, unhealthy diet, and lack of physical activity are three well-known modifiable behavioral risk factors for CVD,” wrote Dongqing Wang of the University of Michigan, Ann Arbor, and his coauthors. “Even after adjusting for the lifestyle-related physiological risk factors, the adherence to a healthy lifestyle composed of abstinence from smoking, healthy diet, and regular engagement in physical activity is inversely associated with atherosclerosis in midlife women.”

Women with higher average health lifestyle score also had lower levels of carotid plaque after adjustment for confounding factors, but this was no longer significant after adjustment for physiological risk factors.

The authors analyzed the three components of the healthy lifestyle score separately, and found that not smoking was strongly and significantly associated with lower scores for all three measures of subclinical atherosclerosis. Women who never smoked across the duration of the study had a 49% lower odds of having a high carotid plaque index compared with women who smoked at some point during the follow-up period.

The analysis showed an inverse association between average Alternate Healthy Eating Index score – a measure of diet quality – and smaller common carotid artery adventitial diameter, although after adjustment for BMI this association was no longer statistically significant. Likewise, the association between dietary quality and intima-media thickness was only marginally significant and lost that significance after adjustment for BMI.

Long-term physical activity was only marginally significantly associated with common carotid artery intima-media thickness, but this was not significant after adjustment for physiological risk factors. No association was found between physical activity and common carotid artery adventitial diameter or carotid plaque.

The authors said that 1.7% of the study population managed to stay in the top category for all three components of healthy lifestyle at all three follow-up time points in the study.

“The low prevalence of a healthy lifestyle in midlife women highlights the potential for lifestyle interventions aimed at this vulnerable population,” they wrote.

In particular, they highlighted abstinence from smoking as having the strongest impact on all three measures of subclinical atherosclerosis, which is known to affect women more than men. However, the outcomes from diet and physical activity weren’t so strong: The authors suggested that BMI could partly mediate the effects of healthier diet and greater levels of physical activity.

One strength of the study was its ethnically diverse population, which included African American, Chinese, and Hispanic women in addition to non-Hispanic white women. However, the study was not powered to examine the impacts ethnicity may have had on outcomes, the researchers wrote.

The Study of Women’s Health Across the Nation is supported by the National Institutes of Health. No conflicts of interest were declared.

SOURCE: Wang D et al. JAHA 2018 Nov. 28.

Women who have a healthier lifestyle during the menopausal transition could significantly reduce their risk of cardiovascular disease, new research suggests.

kali9/E+

Because women experience a steeper increase in CVD risk during and after the menopausal transition, researchers analyzed data from the Study of Women’s Health Across the Nation (SWAN), a prospective longitudinal cohort study of 1,143 women aged 42-52 years. The report is in JAHA: Journal of the American Heart Association.

The analysis revealed that women with the highest average Healthy Lifestyle Score – a composite score of dietary quality, levels of physical activity, and smoking – over 10 years of follow-up had a 0.024-mm smaller common carotid artery intima-media thickness and 0.16-mm smaller adventitial diameter, compared to those with the lowest average score. This was after adjustment for confounders and physiological risk factors such as ethnicity, age, menopausal status, body mass index, and cholesterol levels.

“Smoking, unhealthy diet, and lack of physical activity are three well-known modifiable behavioral risk factors for CVD,” wrote Dongqing Wang of the University of Michigan, Ann Arbor, and his coauthors. “Even after adjusting for the lifestyle-related physiological risk factors, the adherence to a healthy lifestyle composed of abstinence from smoking, healthy diet, and regular engagement in physical activity is inversely associated with atherosclerosis in midlife women.”

Women with higher average health lifestyle score also had lower levels of carotid plaque after adjustment for confounding factors, but this was no longer significant after adjustment for physiological risk factors.

The authors analyzed the three components of the healthy lifestyle score separately, and found that not smoking was strongly and significantly associated with lower scores for all three measures of subclinical atherosclerosis. Women who never smoked across the duration of the study had a 49% lower odds of having a high carotid plaque index compared with women who smoked at some point during the follow-up period.

The analysis showed an inverse association between average Alternate Healthy Eating Index score – a measure of diet quality – and smaller common carotid artery adventitial diameter, although after adjustment for BMI this association was no longer statistically significant. Likewise, the association between dietary quality and intima-media thickness was only marginally significant and lost that significance after adjustment for BMI.

Long-term physical activity was only marginally significantly associated with common carotid artery intima-media thickness, but this was not significant after adjustment for physiological risk factors. No association was found between physical activity and common carotid artery adventitial diameter or carotid plaque.

The authors said that 1.7% of the study population managed to stay in the top category for all three components of healthy lifestyle at all three follow-up time points in the study.

“The low prevalence of a healthy lifestyle in midlife women highlights the potential for lifestyle interventions aimed at this vulnerable population,” they wrote.

In particular, they highlighted abstinence from smoking as having the strongest impact on all three measures of subclinical atherosclerosis, which is known to affect women more than men. However, the outcomes from diet and physical activity weren’t so strong: The authors suggested that BMI could partly mediate the effects of healthier diet and greater levels of physical activity.

One strength of the study was its ethnically diverse population, which included African American, Chinese, and Hispanic women in addition to non-Hispanic white women. However, the study was not powered to examine the impacts ethnicity may have had on outcomes, the researchers wrote.

The Study of Women’s Health Across the Nation is supported by the National Institutes of Health. No conflicts of interest were declared.

SOURCE: Wang D et al. JAHA 2018 Nov. 28.

Women who have a healthier lifestyle during the menopausal transition could significantly reduce their risk of cardiovascular disease, new research suggests.

kali9/E+

Because women experience a steeper increase in CVD risk during and after the menopausal transition, researchers analyzed data from the Study of Women’s Health Across the Nation (SWAN), a prospective longitudinal cohort study of 1,143 women aged 42-52 years. The report is in JAHA: Journal of the American Heart Association.

The analysis revealed that women with the highest average Healthy Lifestyle Score – a composite score of dietary quality, levels of physical activity, and smoking – over 10 years of follow-up had a 0.024-mm smaller common carotid artery intima-media thickness and 0.16-mm smaller adventitial diameter, compared to those with the lowest average score. This was after adjustment for confounders and physiological risk factors such as ethnicity, age, menopausal status, body mass index, and cholesterol levels.

“Smoking, unhealthy diet, and lack of physical activity are three well-known modifiable behavioral risk factors for CVD,” wrote Dongqing Wang of the University of Michigan, Ann Arbor, and his coauthors. “Even after adjusting for the lifestyle-related physiological risk factors, the adherence to a healthy lifestyle composed of abstinence from smoking, healthy diet, and regular engagement in physical activity is inversely associated with atherosclerosis in midlife women.”

Women with higher average health lifestyle score also had lower levels of carotid plaque after adjustment for confounding factors, but this was no longer significant after adjustment for physiological risk factors.

The authors analyzed the three components of the healthy lifestyle score separately, and found that not smoking was strongly and significantly associated with lower scores for all three measures of subclinical atherosclerosis. Women who never smoked across the duration of the study had a 49% lower odds of having a high carotid plaque index compared with women who smoked at some point during the follow-up period.

The analysis showed an inverse association between average Alternate Healthy Eating Index score – a measure of diet quality – and smaller common carotid artery adventitial diameter, although after adjustment for BMI this association was no longer statistically significant. Likewise, the association between dietary quality and intima-media thickness was only marginally significant and lost that significance after adjustment for BMI.

Long-term physical activity was only marginally significantly associated with common carotid artery intima-media thickness, but this was not significant after adjustment for physiological risk factors. No association was found between physical activity and common carotid artery adventitial diameter or carotid plaque.

The authors said that 1.7% of the study population managed to stay in the top category for all three components of healthy lifestyle at all three follow-up time points in the study.

“The low prevalence of a healthy lifestyle in midlife women highlights the potential for lifestyle interventions aimed at this vulnerable population,” they wrote.

In particular, they highlighted abstinence from smoking as having the strongest impact on all three measures of subclinical atherosclerosis, which is known to affect women more than men. However, the outcomes from diet and physical activity weren’t so strong: The authors suggested that BMI could partly mediate the effects of healthier diet and greater levels of physical activity.

One strength of the study was its ethnically diverse population, which included African American, Chinese, and Hispanic women in addition to non-Hispanic white women. However, the study was not powered to examine the impacts ethnicity may have had on outcomes, the researchers wrote.

The Study of Women’s Health Across the Nation is supported by the National Institutes of Health. No conflicts of interest were declared.

SOURCE: Wang D et al. JAHA 2018 Nov. 28.

A systematic literature review found an inverse association between serum vitamin D levels and severity of atopic dermatitis (AD) in children in the majority of studies, but evidence on whether supplementation can improve symptoms of the condition was inconsistent.

The data on the effect of vitamin D supplementation on AD severity “suggested potential benefit but were conflicting,” concluded Christina M. Huang, MD, of Queen’s University, Kingston, Ontario, and her coinvestigators from the department of dermatology, Hospital for Sick Children, Toronto. They reported the results of their systematic review of 21 studies published between 2008 and 2017, which included quantitative data on serum vitamin D levels or vitamin D supplementation and AD severity in patients aged 18 years or younger, in Pediatrics.

In the review, 16 studies explored the relationship between serum vitamin D status and disease severity (one was a randomized controlled trial; the rest were cohort, cross-sectional, or case control studies) in 1,847 children (average age, 5.6 years). Disease severity was measured with the SCORing Atopic Dermatitis (SCORAD) system. In 10 of the 16 studies, there was a significant inverse association between vitamin D levels and AD severity.

The studies that supported this association generally had larger sample sizes, which, the authors pointed out, suggested they were of higher quality and more reliable. However, the randomized controlled study of 89 children did not find a correlation, although in the study, vitamin D level and AD severity was a secondary outcome.

The randomized controlled trial of vitamin D supplementation used lower SCORAD cut-offs for the different severities of AD, which complicated interpretation the results, “as it may indicate that the severities reported in these articles were exaggerated as compared to other studies,” they wrote.

Six studies – four randomized controlled trials (including the study that was among the 16 studies on vitamin D and severity) and two cohort studies – with 354 participants (average age, 6.8 years) looked at the effects of oral vitamin D supplementation on the severity of AD, although dosage and duration of use varied across the studies. In four of the six studies, there were significant improvement in AD in patients given supplements, but the data were “conflicting,” partly because the largest study showing benefit used a different measure of disease severity, the Eczema Area and Severity Index (EASI), not SCORAD. “The inconsistency of tools used to measure outcomes makes it difficult to compare and understand results,” so the effects of vitamin D supplementation “are controversial and should be interpreted with caution, as certain patient populations may benefit more than others,” the authors wrote.

They also drew attention to previous research suggesting that vitamin D supplementation in the first year of life might actually increase the risk of AD in children. “Therefore, although there is a growing body of evidence supporting the beneficial effects of VD [vitamin D] supplementation, the age at which supplementation is given should be considered carefully.” The authors added that the inconclusive findings “may have been due to confounding factors that were not accounted for, such as age, season, latitude, dose, and duration. It is also possible that the lack of a true effect of VD may be contributing to the inconsistent results. Future large‐scale RCTs with consideration of these factors are needed.”

Funding and conflict of interest disclosures were not included in the study.

SOURCE: Huang C et al. Pediatr Dermatol. 2018;35: 754-60. doi: 10.1111/pde.13639.

A systematic literature review found an inverse association between serum vitamin D levels and severity of atopic dermatitis (AD) in children in the majority of studies, but evidence on whether supplementation can improve symptoms of the condition was inconsistent.

The data on the effect of vitamin D supplementation on AD severity “suggested potential benefit but were conflicting,” concluded Christina M. Huang, MD, of Queen’s University, Kingston, Ontario, and her coinvestigators from the department of dermatology, Hospital for Sick Children, Toronto. They reported the results of their systematic review of 21 studies published between 2008 and 2017, which included quantitative data on serum vitamin D levels or vitamin D supplementation and AD severity in patients aged 18 years or younger, in Pediatrics.

In the review, 16 studies explored the relationship between serum vitamin D status and disease severity (one was a randomized controlled trial; the rest were cohort, cross-sectional, or case control studies) in 1,847 children (average age, 5.6 years). Disease severity was measured with the SCORing Atopic Dermatitis (SCORAD) system. In 10 of the 16 studies, there was a significant inverse association between vitamin D levels and AD severity.

The studies that supported this association generally had larger sample sizes, which, the authors pointed out, suggested they were of higher quality and more reliable. However, the randomized controlled study of 89 children did not find a correlation, although in the study, vitamin D level and AD severity was a secondary outcome.

The randomized controlled trial of vitamin D supplementation used lower SCORAD cut-offs for the different severities of AD, which complicated interpretation the results, “as it may indicate that the severities reported in these articles were exaggerated as compared to other studies,” they wrote.

Six studies – four randomized controlled trials (including the study that was among the 16 studies on vitamin D and severity) and two cohort studies – with 354 participants (average age, 6.8 years) looked at the effects of oral vitamin D supplementation on the severity of AD, although dosage and duration of use varied across the studies. In four of the six studies, there were significant improvement in AD in patients given supplements, but the data were “conflicting,” partly because the largest study showing benefit used a different measure of disease severity, the Eczema Area and Severity Index (EASI), not SCORAD. “The inconsistency of tools used to measure outcomes makes it difficult to compare and understand results,” so the effects of vitamin D supplementation “are controversial and should be interpreted with caution, as certain patient populations may benefit more than others,” the authors wrote.

They also drew attention to previous research suggesting that vitamin D supplementation in the first year of life might actually increase the risk of AD in children. “Therefore, although there is a growing body of evidence supporting the beneficial effects of VD [vitamin D] supplementation, the age at which supplementation is given should be considered carefully.” The authors added that the inconclusive findings “may have been due to confounding factors that were not accounted for, such as age, season, latitude, dose, and duration. It is also possible that the lack of a true effect of VD may be contributing to the inconsistent results. Future large‐scale RCTs with consideration of these factors are needed.”

Funding and conflict of interest disclosures were not included in the study.

SOURCE: Huang C et al. Pediatr Dermatol. 2018;35: 754-60. doi: 10.1111/pde.13639.

A systematic literature review found an inverse association between serum vitamin D levels and severity of atopic dermatitis (AD) in children in the majority of studies, but evidence on whether supplementation can improve symptoms of the condition was inconsistent.

The data on the effect of vitamin D supplementation on AD severity “suggested potential benefit but were conflicting,” concluded Christina M. Huang, MD, of Queen’s University, Kingston, Ontario, and her coinvestigators from the department of dermatology, Hospital for Sick Children, Toronto. They reported the results of their systematic review of 21 studies published between 2008 and 2017, which included quantitative data on serum vitamin D levels or vitamin D supplementation and AD severity in patients aged 18 years or younger, in Pediatrics.

In the review, 16 studies explored the relationship between serum vitamin D status and disease severity (one was a randomized controlled trial; the rest were cohort, cross-sectional, or case control studies) in 1,847 children (average age, 5.6 years). Disease severity was measured with the SCORing Atopic Dermatitis (SCORAD) system. In 10 of the 16 studies, there was a significant inverse association between vitamin D levels and AD severity.

The studies that supported this association generally had larger sample sizes, which, the authors pointed out, suggested they were of higher quality and more reliable. However, the randomized controlled study of 89 children did not find a correlation, although in the study, vitamin D level and AD severity was a secondary outcome.

The randomized controlled trial of vitamin D supplementation used lower SCORAD cut-offs for the different severities of AD, which complicated interpretation the results, “as it may indicate that the severities reported in these articles were exaggerated as compared to other studies,” they wrote.

Six studies – four randomized controlled trials (including the study that was among the 16 studies on vitamin D and severity) and two cohort studies – with 354 participants (average age, 6.8 years) looked at the effects of oral vitamin D supplementation on the severity of AD, although dosage and duration of use varied across the studies. In four of the six studies, there were significant improvement in AD in patients given supplements, but the data were “conflicting,” partly because the largest study showing benefit used a different measure of disease severity, the Eczema Area and Severity Index (EASI), not SCORAD. “The inconsistency of tools used to measure outcomes makes it difficult to compare and understand results,” so the effects of vitamin D supplementation “are controversial and should be interpreted with caution, as certain patient populations may benefit more than others,” the authors wrote.

They also drew attention to previous research suggesting that vitamin D supplementation in the first year of life might actually increase the risk of AD in children. “Therefore, although there is a growing body of evidence supporting the beneficial effects of VD [vitamin D] supplementation, the age at which supplementation is given should be considered carefully.” The authors added that the inconclusive findings “may have been due to confounding factors that were not accounted for, such as age, season, latitude, dose, and duration. It is also possible that the lack of a true effect of VD may be contributing to the inconsistent results. Future large‐scale RCTs with consideration of these factors are needed.”

Funding and conflict of interest disclosures were not included in the study.

SOURCE: Huang C et al. Pediatr Dermatol. 2018;35: 754-60. doi: 10.1111/pde.13639.

Smaller inguinal hernias are associated with a greater risk of chronic postoperative inguinal pain than larger hernias, according to a study published in Annals of Surgery.

castillodominici/Thinkstock

Researchers used data from the European Herniamed registry to look at 1-year outcomes in 57,999 male patients who underwent primary unilateral inguinal hernia repair.

While patients with larger hernias showed significantly longer operation times and had a significantly larger body mass index, those with smaller hernias had significantly higher rates of pain at rest or on exertion, and chronic pain requiring treatment.

Individuals with smaller hernias (EHS I) had a 35% higher odds of pain at rest, compared with those with medium-sized hernias (EHS II), and 84% higher odds, compared with individuals with large hernias (EHS III). Smaller hernias were also associated with a 100% higher odds of pain on exertion and greater than 100% higher odds of chronic postoperative pain requiring treatment, compared with large hernias.

“CPIP [chronic postoperative inguinal pain] has become one of the most important surgical quality parameters after elective inguinal hernia repair with significant consequences affecting patient productivity, employment, and quality of life,” wrote Henry Hoffmann, MD, of the clinic for visceral surgery at the University Hospital Basel in Switzerland, and his coauthors. “With our findings we contribute to the important discussion of prevention, risk factors, and treatment of CPIP identifying smaller inguinal hernias [EHS I-II] as a new independent, patient-related risk factor for the development of CPIP.”

Noting that an association between smaller hernias and increased postoperative pain seems counterintuitive, the authors suggested that patients’ expectations of outcomes may be higher in those with smaller hernias than in patients with larger hernias. While larger hernias are likely more bothersome rather than painful or uncomfortable, smaller hernias may be associated more with pain and discomfort. As such, patients with smaller hernias may have higher hopes for relief from surgery, and therefore may be more likely to experience disappointment.

“Based on a cognitive information processing model it has been suggested that a greater discrepancy between expected and actual pain after surgery leads to significant postoperative distress,” the authors wrote.

The study also found patients aged younger than 55 years were also at greater risk of pain at rest, pain on exertion, and chronic pain requiring treatment.

Overall, around half the patients in the study underwent transabdominal preperitoneal repair, 35.6% underwent totally extraperitoneal repair, 10.1% had Lichtenstein repair, and 3.8% had Shouldice repair.

Lichtenstein was associated with more postoperative pain at rest and on exertion, compared with other surgical methods, and there was a trend toward an increased odds for developing pain requiring treatment in patients with smaller hernias.

The Herniamed Registry is supported by Johnson & Johnson, Karl Storz, pfm medical Cologne, Dahlhausen Cologne, B. Braun Tuttlingen, MenkeMed, and Bard. No conflicts of interest were reported.
 

SOURCE: Hoffmann H et al. Ann Surg. 2018 Oct 10. doi: 10.1097/SLA.0000000000003065.

Smaller inguinal hernias are associated with a greater risk of chronic postoperative inguinal pain than larger hernias, according to a study published in Annals of Surgery.

castillodominici/Thinkstock

Researchers used data from the European Herniamed registry to look at 1-year outcomes in 57,999 male patients who underwent primary unilateral inguinal hernia repair.

While patients with larger hernias showed significantly longer operation times and had a significantly larger body mass index, those with smaller hernias had significantly higher rates of pain at rest or on exertion, and chronic pain requiring treatment.

Individuals with smaller hernias (EHS I) had a 35% higher odds of pain at rest, compared with those with medium-sized hernias (EHS II), and 84% higher odds, compared with individuals with large hernias (EHS III). Smaller hernias were also associated with a 100% higher odds of pain on exertion and greater than 100% higher odds of chronic postoperative pain requiring treatment, compared with large hernias.

“CPIP [chronic postoperative inguinal pain] has become one of the most important surgical quality parameters after elective inguinal hernia repair with significant consequences affecting patient productivity, employment, and quality of life,” wrote Henry Hoffmann, MD, of the clinic for visceral surgery at the University Hospital Basel in Switzerland, and his coauthors. “With our findings we contribute to the important discussion of prevention, risk factors, and treatment of CPIP identifying smaller inguinal hernias [EHS I-II] as a new independent, patient-related risk factor for the development of CPIP.”

Noting that an association between smaller hernias and increased postoperative pain seems counterintuitive, the authors suggested that patients’ expectations of outcomes may be higher in those with smaller hernias than in patients with larger hernias. While larger hernias are likely more bothersome rather than painful or uncomfortable, smaller hernias may be associated more with pain and discomfort. As such, patients with smaller hernias may have higher hopes for relief from surgery, and therefore may be more likely to experience disappointment.

“Based on a cognitive information processing model it has been suggested that a greater discrepancy between expected and actual pain after surgery leads to significant postoperative distress,” the authors wrote.

The study also found patients aged younger than 55 years were also at greater risk of pain at rest, pain on exertion, and chronic pain requiring treatment.

Overall, around half the patients in the study underwent transabdominal preperitoneal repair, 35.6% underwent totally extraperitoneal repair, 10.1% had Lichtenstein repair, and 3.8% had Shouldice repair.

Lichtenstein was associated with more postoperative pain at rest and on exertion, compared with other surgical methods, and there was a trend toward an increased odds for developing pain requiring treatment in patients with smaller hernias.

The Herniamed Registry is supported by Johnson & Johnson, Karl Storz, pfm medical Cologne, Dahlhausen Cologne, B. Braun Tuttlingen, MenkeMed, and Bard. No conflicts of interest were reported.
 

SOURCE: Hoffmann H et al. Ann Surg. 2018 Oct 10. doi: 10.1097/SLA.0000000000003065.

Smaller inguinal hernias are associated with a greater risk of chronic postoperative inguinal pain than larger hernias, according to a study published in Annals of Surgery.

castillodominici/Thinkstock

Researchers used data from the European Herniamed registry to look at 1-year outcomes in 57,999 male patients who underwent primary unilateral inguinal hernia repair.

While patients with larger hernias showed significantly longer operation times and had a significantly larger body mass index, those with smaller hernias had significantly higher rates of pain at rest or on exertion, and chronic pain requiring treatment.

Individuals with smaller hernias (EHS I) had a 35% higher odds of pain at rest, compared with those with medium-sized hernias (EHS II), and 84% higher odds, compared with individuals with large hernias (EHS III). Smaller hernias were also associated with a 100% higher odds of pain on exertion and greater than 100% higher odds of chronic postoperative pain requiring treatment, compared with large hernias.

“CPIP [chronic postoperative inguinal pain] has become one of the most important surgical quality parameters after elective inguinal hernia repair with significant consequences affecting patient productivity, employment, and quality of life,” wrote Henry Hoffmann, MD, of the clinic for visceral surgery at the University Hospital Basel in Switzerland, and his coauthors. “With our findings we contribute to the important discussion of prevention, risk factors, and treatment of CPIP identifying smaller inguinal hernias [EHS I-II] as a new independent, patient-related risk factor for the development of CPIP.”

Noting that an association between smaller hernias and increased postoperative pain seems counterintuitive, the authors suggested that patients’ expectations of outcomes may be higher in those with smaller hernias than in patients with larger hernias. While larger hernias are likely more bothersome rather than painful or uncomfortable, smaller hernias may be associated more with pain and discomfort. As such, patients with smaller hernias may have higher hopes for relief from surgery, and therefore may be more likely to experience disappointment.

“Based on a cognitive information processing model it has been suggested that a greater discrepancy between expected and actual pain after surgery leads to significant postoperative distress,” the authors wrote.

The study also found patients aged younger than 55 years were also at greater risk of pain at rest, pain on exertion, and chronic pain requiring treatment.

Overall, around half the patients in the study underwent transabdominal preperitoneal repair, 35.6% underwent totally extraperitoneal repair, 10.1% had Lichtenstein repair, and 3.8% had Shouldice repair.

Lichtenstein was associated with more postoperative pain at rest and on exertion, compared with other surgical methods, and there was a trend toward an increased odds for developing pain requiring treatment in patients with smaller hernias.

The Herniamed Registry is supported by Johnson & Johnson, Karl Storz, pfm medical Cologne, Dahlhausen Cologne, B. Braun Tuttlingen, MenkeMed, and Bard. No conflicts of interest were reported.
 

SOURCE: Hoffmann H et al. Ann Surg. 2018 Oct 10. doi: 10.1097/SLA.0000000000003065.

Researchers have identified biomarkers that might eventually be used to flag cancer patients with severe cutaneous adverse reactions (SCARs) at an increased risk of mortality.

In a retrospective study, elevated elafin, interleukin (IL)-6, and tumor necrosis factor (TNF)–alpha levels were significantly associated with a greater risk of all-cause mortality among hospitalized cancer patients who developed SCARs, which includes Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome.

In the study, published in the Journal of the American Academy of Dermatology, Shoko Mori of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and coauthors looked at 49 cancer patients hospitalized (41) or treated at an urgent care center (8), between August 2016 and July 2017 who experienced a morbilliform rash. Overall, 27 patients had a simple morbilliform rash, without systemic involvement; 22 had a complex morbilliform rash with systemic involvement, including 9 with cutaneous manifestations of graft versus host disease (GVHD) and 13 with rashes secondary to drug exposure.

The majority of the patients had a hematologic malignancy (18 with a simple rash, and 16 with a complex rash); the rest had a solid organ malignancy (9 with a simple rash and 6 with a complex rash).

Nearly one-third (30.6%) of patients died within 6 months of having a dermatologic consultation. These patients showed significantly higher levels of serum elafin – a protein that is not detectable in normal skin but is overexpressed in wound healing and inflammatory disorders – as well as IL-6 and TNF-alpha, compared with patients who were alive at 6 months.

“While GVHD and drug-related SCARs are difficult to distinguish clinically, our results suggest that elafin may be a useful biomarker to identify patients with a suspected diagnosis of SCARs or GVHD who are at increased risk of death within 6 months,” the investigators wrote. “Given its broad anti-inflammatory activity, elafin’s potential as a therapeutic agent for SCARs should be further explored.”

They noted that elevated TNF-alpha levels pointed to another potential therapeutic target for SCARs among patients undergoing treatment for cancer. Patients who died were also less likely to have elevated bilirubin level relative to baseline than patients who survived past 6 months.

The patients with a complex morbilliform rash caused by drug exposure had significantly higher median levels of IL-10 and IL-6, compared with those with a complex rash related to GVHD or with a simple rash. “Thought to originate from activated keratinocytes in TEN [toxic epidermal necrolysis], elevated IL-10 may reflect a defense mechanism against drug-specific cytotoxic T cells that are activated during the disease process,” the authors wrote.

Patients with complex rash also had a significantly higher median white blood cell count and higher median values for all cytokines, compared with the simple rash group, although only differences in TNF-alpha levels were statistically significant.

“A larger, prospective study examining the association of cytokines with SCARs is needed, as well as longitudinal assessment of cytokine levels to assess their prognostic significance,” the authors wrote. “This exploratory analysis presents potential therapeutic targets in a high-risk patient population, for whom a ‘complex’ rash can disrupt and delay treatment of underlying disease.”

The study was partly funded by the National Cancer Institute/National Institutes of Health via a grant to the Memorial Sloan Kettering Cancer Center. One author declared support from a Dermatology Foundation Career Development Award.

SOURCE: Mori S et al. J Am Acad Dermatol, 2018 October 26. doi: 10.1016/j.jaad.2018.10.039.

Researchers have identified biomarkers that might eventually be used to flag cancer patients with severe cutaneous adverse reactions (SCARs) at an increased risk of mortality.

In a retrospective study, elevated elafin, interleukin (IL)-6, and tumor necrosis factor (TNF)–alpha levels were significantly associated with a greater risk of all-cause mortality among hospitalized cancer patients who developed SCARs, which includes Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome.

In the study, published in the Journal of the American Academy of Dermatology, Shoko Mori of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and coauthors looked at 49 cancer patients hospitalized (41) or treated at an urgent care center (8), between August 2016 and July 2017 who experienced a morbilliform rash. Overall, 27 patients had a simple morbilliform rash, without systemic involvement; 22 had a complex morbilliform rash with systemic involvement, including 9 with cutaneous manifestations of graft versus host disease (GVHD) and 13 with rashes secondary to drug exposure.

The majority of the patients had a hematologic malignancy (18 with a simple rash, and 16 with a complex rash); the rest had a solid organ malignancy (9 with a simple rash and 6 with a complex rash).

Nearly one-third (30.6%) of patients died within 6 months of having a dermatologic consultation. These patients showed significantly higher levels of serum elafin – a protein that is not detectable in normal skin but is overexpressed in wound healing and inflammatory disorders – as well as IL-6 and TNF-alpha, compared with patients who were alive at 6 months.

“While GVHD and drug-related SCARs are difficult to distinguish clinically, our results suggest that elafin may be a useful biomarker to identify patients with a suspected diagnosis of SCARs or GVHD who are at increased risk of death within 6 months,” the investigators wrote. “Given its broad anti-inflammatory activity, elafin’s potential as a therapeutic agent for SCARs should be further explored.”

They noted that elevated TNF-alpha levels pointed to another potential therapeutic target for SCARs among patients undergoing treatment for cancer. Patients who died were also less likely to have elevated bilirubin level relative to baseline than patients who survived past 6 months.

The patients with a complex morbilliform rash caused by drug exposure had significantly higher median levels of IL-10 and IL-6, compared with those with a complex rash related to GVHD or with a simple rash. “Thought to originate from activated keratinocytes in TEN [toxic epidermal necrolysis], elevated IL-10 may reflect a defense mechanism against drug-specific cytotoxic T cells that are activated during the disease process,” the authors wrote.

Patients with complex rash also had a significantly higher median white blood cell count and higher median values for all cytokines, compared with the simple rash group, although only differences in TNF-alpha levels were statistically significant.

“A larger, prospective study examining the association of cytokines with SCARs is needed, as well as longitudinal assessment of cytokine levels to assess their prognostic significance,” the authors wrote. “This exploratory analysis presents potential therapeutic targets in a high-risk patient population, for whom a ‘complex’ rash can disrupt and delay treatment of underlying disease.”

The study was partly funded by the National Cancer Institute/National Institutes of Health via a grant to the Memorial Sloan Kettering Cancer Center. One author declared support from a Dermatology Foundation Career Development Award.

SOURCE: Mori S et al. J Am Acad Dermatol, 2018 October 26. doi: 10.1016/j.jaad.2018.10.039.

Researchers have identified biomarkers that might eventually be used to flag cancer patients with severe cutaneous adverse reactions (SCARs) at an increased risk of mortality.

In a retrospective study, elevated elafin, interleukin (IL)-6, and tumor necrosis factor (TNF)–alpha levels were significantly associated with a greater risk of all-cause mortality among hospitalized cancer patients who developed SCARs, which includes Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome.

In the study, published in the Journal of the American Academy of Dermatology, Shoko Mori of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and coauthors looked at 49 cancer patients hospitalized (41) or treated at an urgent care center (8), between August 2016 and July 2017 who experienced a morbilliform rash. Overall, 27 patients had a simple morbilliform rash, without systemic involvement; 22 had a complex morbilliform rash with systemic involvement, including 9 with cutaneous manifestations of graft versus host disease (GVHD) and 13 with rashes secondary to drug exposure.

The majority of the patients had a hematologic malignancy (18 with a simple rash, and 16 with a complex rash); the rest had a solid organ malignancy (9 with a simple rash and 6 with a complex rash).

Nearly one-third (30.6%) of patients died within 6 months of having a dermatologic consultation. These patients showed significantly higher levels of serum elafin – a protein that is not detectable in normal skin but is overexpressed in wound healing and inflammatory disorders – as well as IL-6 and TNF-alpha, compared with patients who were alive at 6 months.

“While GVHD and drug-related SCARs are difficult to distinguish clinically, our results suggest that elafin may be a useful biomarker to identify patients with a suspected diagnosis of SCARs or GVHD who are at increased risk of death within 6 months,” the investigators wrote. “Given its broad anti-inflammatory activity, elafin’s potential as a therapeutic agent for SCARs should be further explored.”

They noted that elevated TNF-alpha levels pointed to another potential therapeutic target for SCARs among patients undergoing treatment for cancer. Patients who died were also less likely to have elevated bilirubin level relative to baseline than patients who survived past 6 months.

The patients with a complex morbilliform rash caused by drug exposure had significantly higher median levels of IL-10 and IL-6, compared with those with a complex rash related to GVHD or with a simple rash. “Thought to originate from activated keratinocytes in TEN [toxic epidermal necrolysis], elevated IL-10 may reflect a defense mechanism against drug-specific cytotoxic T cells that are activated during the disease process,” the authors wrote.

Patients with complex rash also had a significantly higher median white blood cell count and higher median values for all cytokines, compared with the simple rash group, although only differences in TNF-alpha levels were statistically significant.

“A larger, prospective study examining the association of cytokines with SCARs is needed, as well as longitudinal assessment of cytokine levels to assess their prognostic significance,” the authors wrote. “This exploratory analysis presents potential therapeutic targets in a high-risk patient population, for whom a ‘complex’ rash can disrupt and delay treatment of underlying disease.”

The study was partly funded by the National Cancer Institute/National Institutes of Health via a grant to the Memorial Sloan Kettering Cancer Center. One author declared support from a Dermatology Foundation Career Development Award.

SOURCE: Mori S et al. J Am Acad Dermatol, 2018 October 26. doi: 10.1016/j.jaad.2018.10.039.