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Recurrent acute pancreatitis significantly impairs both mental and physical quality of life
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
[email protected]
On Twitter @alz_gal
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
[email protected]
On Twitter @alz_gal
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT DDW
Key clinical point:
Major finding: On a physical QOL scale, patients scored a mean of 41 points – 10 points lower than controls. The mental QOL score was 7 points lower.
Data source: The database review comprised 2,619 subjects.
Disclosures: Dr. Cote had no financial disclosures.
FDA approves first specific treatment for giant cell arteritis
The Food and Drug Administration has approved subcutaneous tocilizumab (Actemra) for the treatment of giant cell arteritis, according to a May 22 announcement from the agency.
Giant cell arteritis is a type of vasculitis that inflames blood vessels in the head, causing arteries to narrow or become irregular. The temporal arteries are the most commonly affected blood vessels, but giant cell arteritis can also affect other large blood vessels such as the aorta. Tocilizumab is the first drug specifically intended to treat giant cell arteritis. The standard treatment has typically been high doses of corticosteroids, tapered over time.
The FDA’s approval of tocilizumab was based on results from a double-blind, placebo-controlled study of 251 patients with giant cell arteritis. After 1 year, patients who received tocilizumab and tapered prednisone achieved remission at a higher rate than did patients who received placebo and tapered prednisone. Safety was consistent with tocilizumab’s known safety profile.
Subcutaneous tocilizumab is also approved for moderate to severely active rheumatoid arthritis. The intravenous formulation is approved for the treatment of moderate to severely active rheumatoid arthritis, systemic juvenile idiopathic arthritis, and polyarticular juvenile idiopathic arthritis.
The FDA granted both Breakthrough Therapy and Priority Review designations to this supplemental new drug application of tocilizumab.
The Food and Drug Administration has approved subcutaneous tocilizumab (Actemra) for the treatment of giant cell arteritis, according to a May 22 announcement from the agency.
Giant cell arteritis is a type of vasculitis that inflames blood vessels in the head, causing arteries to narrow or become irregular. The temporal arteries are the most commonly affected blood vessels, but giant cell arteritis can also affect other large blood vessels such as the aorta. Tocilizumab is the first drug specifically intended to treat giant cell arteritis. The standard treatment has typically been high doses of corticosteroids, tapered over time.
The FDA’s approval of tocilizumab was based on results from a double-blind, placebo-controlled study of 251 patients with giant cell arteritis. After 1 year, patients who received tocilizumab and tapered prednisone achieved remission at a higher rate than did patients who received placebo and tapered prednisone. Safety was consistent with tocilizumab’s known safety profile.
Subcutaneous tocilizumab is also approved for moderate to severely active rheumatoid arthritis. The intravenous formulation is approved for the treatment of moderate to severely active rheumatoid arthritis, systemic juvenile idiopathic arthritis, and polyarticular juvenile idiopathic arthritis.
The FDA granted both Breakthrough Therapy and Priority Review designations to this supplemental new drug application of tocilizumab.
The Food and Drug Administration has approved subcutaneous tocilizumab (Actemra) for the treatment of giant cell arteritis, according to a May 22 announcement from the agency.
Giant cell arteritis is a type of vasculitis that inflames blood vessels in the head, causing arteries to narrow or become irregular. The temporal arteries are the most commonly affected blood vessels, but giant cell arteritis can also affect other large blood vessels such as the aorta. Tocilizumab is the first drug specifically intended to treat giant cell arteritis. The standard treatment has typically been high doses of corticosteroids, tapered over time.
The FDA’s approval of tocilizumab was based on results from a double-blind, placebo-controlled study of 251 patients with giant cell arteritis. After 1 year, patients who received tocilizumab and tapered prednisone achieved remission at a higher rate than did patients who received placebo and tapered prednisone. Safety was consistent with tocilizumab’s known safety profile.
Subcutaneous tocilizumab is also approved for moderate to severely active rheumatoid arthritis. The intravenous formulation is approved for the treatment of moderate to severely active rheumatoid arthritis, systemic juvenile idiopathic arthritis, and polyarticular juvenile idiopathic arthritis.
The FDA granted both Breakthrough Therapy and Priority Review designations to this supplemental new drug application of tocilizumab.
Skin cancer risk similar for liver and kidney transplant recipients
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
AT ACDASM 2017
Key clinical point: Liver transplant recipients should be screened and followed for the development of nonmelanoma skin cancers as closely as are kidney transplant recipients.
Major finding: Over 5 years, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, a difference that was not statistically significant after a multivariate analysis was done.
Data source: A longitudinal cohort study of 230 kidney or liver transplant recipients attending a dermatology clinic affiliated with an organ transplant unit.
Disclosures: No conflicts of interest were disclosed.
Pregnancy boosts risk of ventral hernia recurrence
Pregnancy is associated with a significant increase in the risk of ventral hernia recurrence after repair, according to a population-based cohort study published online in the American Journal of Surgery.
Analysis of registry data from 3,578 Danish women of reproductive age who had previously undergone ventral hernia repair showed that subsequent pregnancy was associated with a 56% higher risk of recurrence (95% confidence interval, 1.09-2.25; P = .016), compared with women who did not get pregnant (Am J Surg. 2017 April 5. doi: 10.1016/j.amjsurg.2017.03.044).
They noted that few studies have directly reported on the rate of ventral hernia recurrence after pregnancy, and the results that do exist are conflicting.
The overall rate of ventral hernia recurrence in the cohort was 12.5%, 67.9% of whom subsequently underwent reoperation to repair. The median time from hernia repair to pregnancy was 1.1 years, and median follow-up was 3.1 years.
Umbilical and incisional hernia repair were independently associated with a higher risk of recurrence (hazard ratio, 1.55 and 3.30, respectively) than epigastric repair, while larger hernia defects also increased the risk of recurrence.
“According to Laplace’s law, both the abdominal wall stretch and the raised intra-abdominal pressure theoretically strain the repaired ventral hernia site and are likely involved in the associated increased risk of recurrence,” the authors wrote. “Furthermore, prolonged duration of the second stage of labor and the use of manual fundal pressure might increase the risk of ventral hernia recurrence.”
The authors pointed out that inadequate fixation and lateral detachment of the mesh material were the most commonly reported mechanisms involved in ventral hernia recurrence after mesh repair. The fact that most mesh materials are far less elastic than the abdominal wall could account for the association between pregnancy and recurrence.
Based on the findings, they suggested that elective surgery for incisional or umbilical hernia repair be postponed until after the last planned pregnancy and that female patients of reproductive age be counseled on the increased risk of recurrence with pregnancy should they choose to undergo ventral hernia repair. They also noted that the natural course of an untreated ventral hernia, how it responds to pregnancy, and the risk of emergency repair during pregnancy need further investigation.
The study was supported by grants from Edgar Schnohr, MD, Dr MSc & Wife Gilberte Schnohr’s Foundation, and Bispebjerg Hospital. No conflicts of interest were declared.
Pregnancy is associated with a significant increase in the risk of ventral hernia recurrence after repair, according to a population-based cohort study published online in the American Journal of Surgery.
Analysis of registry data from 3,578 Danish women of reproductive age who had previously undergone ventral hernia repair showed that subsequent pregnancy was associated with a 56% higher risk of recurrence (95% confidence interval, 1.09-2.25; P = .016), compared with women who did not get pregnant (Am J Surg. 2017 April 5. doi: 10.1016/j.amjsurg.2017.03.044).
They noted that few studies have directly reported on the rate of ventral hernia recurrence after pregnancy, and the results that do exist are conflicting.
The overall rate of ventral hernia recurrence in the cohort was 12.5%, 67.9% of whom subsequently underwent reoperation to repair. The median time from hernia repair to pregnancy was 1.1 years, and median follow-up was 3.1 years.
Umbilical and incisional hernia repair were independently associated with a higher risk of recurrence (hazard ratio, 1.55 and 3.30, respectively) than epigastric repair, while larger hernia defects also increased the risk of recurrence.
“According to Laplace’s law, both the abdominal wall stretch and the raised intra-abdominal pressure theoretically strain the repaired ventral hernia site and are likely involved in the associated increased risk of recurrence,” the authors wrote. “Furthermore, prolonged duration of the second stage of labor and the use of manual fundal pressure might increase the risk of ventral hernia recurrence.”
The authors pointed out that inadequate fixation and lateral detachment of the mesh material were the most commonly reported mechanisms involved in ventral hernia recurrence after mesh repair. The fact that most mesh materials are far less elastic than the abdominal wall could account for the association between pregnancy and recurrence.
Based on the findings, they suggested that elective surgery for incisional or umbilical hernia repair be postponed until after the last planned pregnancy and that female patients of reproductive age be counseled on the increased risk of recurrence with pregnancy should they choose to undergo ventral hernia repair. They also noted that the natural course of an untreated ventral hernia, how it responds to pregnancy, and the risk of emergency repair during pregnancy need further investigation.
The study was supported by grants from Edgar Schnohr, MD, Dr MSc & Wife Gilberte Schnohr’s Foundation, and Bispebjerg Hospital. No conflicts of interest were declared.
Pregnancy is associated with a significant increase in the risk of ventral hernia recurrence after repair, according to a population-based cohort study published online in the American Journal of Surgery.
Analysis of registry data from 3,578 Danish women of reproductive age who had previously undergone ventral hernia repair showed that subsequent pregnancy was associated with a 56% higher risk of recurrence (95% confidence interval, 1.09-2.25; P = .016), compared with women who did not get pregnant (Am J Surg. 2017 April 5. doi: 10.1016/j.amjsurg.2017.03.044).
They noted that few studies have directly reported on the rate of ventral hernia recurrence after pregnancy, and the results that do exist are conflicting.
The overall rate of ventral hernia recurrence in the cohort was 12.5%, 67.9% of whom subsequently underwent reoperation to repair. The median time from hernia repair to pregnancy was 1.1 years, and median follow-up was 3.1 years.
Umbilical and incisional hernia repair were independently associated with a higher risk of recurrence (hazard ratio, 1.55 and 3.30, respectively) than epigastric repair, while larger hernia defects also increased the risk of recurrence.
“According to Laplace’s law, both the abdominal wall stretch and the raised intra-abdominal pressure theoretically strain the repaired ventral hernia site and are likely involved in the associated increased risk of recurrence,” the authors wrote. “Furthermore, prolonged duration of the second stage of labor and the use of manual fundal pressure might increase the risk of ventral hernia recurrence.”
The authors pointed out that inadequate fixation and lateral detachment of the mesh material were the most commonly reported mechanisms involved in ventral hernia recurrence after mesh repair. The fact that most mesh materials are far less elastic than the abdominal wall could account for the association between pregnancy and recurrence.
Based on the findings, they suggested that elective surgery for incisional or umbilical hernia repair be postponed until after the last planned pregnancy and that female patients of reproductive age be counseled on the increased risk of recurrence with pregnancy should they choose to undergo ventral hernia repair. They also noted that the natural course of an untreated ventral hernia, how it responds to pregnancy, and the risk of emergency repair during pregnancy need further investigation.
The study was supported by grants from Edgar Schnohr, MD, Dr MSc & Wife Gilberte Schnohr’s Foundation, and Bispebjerg Hospital. No conflicts of interest were declared.
FROM THE AMERICAN JOURNAL OF SURGERY
Key clinical point: Pregnancy after ventral hernia repair can significantly increase the risk of recurrence.
Major finding: Pregnancy is associated with a 56% increase in the risk of recurrence of ventral hernia after repair.
Data source: A population-based cohort study of 3,578 women of reproductive age who underwent ventral hernia repair.
Disclosures: The study was supported by grants from Edgar Schnohr MD, Dr MSc & Wife Gilberte Schnohr’s Foundation, and Bispebjerg Hospital. No conflicts of interest were declared.
Speedy sepsis care slows in-hospital mortality
WASHINGTON – Sepsis and septic shock patients treated within 3 hours had lower in-hospital mortality rates than those treated between hours 3 and 12, based on data from nearly 50,000 adult patients. The findings were presented at an international conference of the American Thoracic Society and published simultaneously in the New England Journal of Medicine.
“Considerable controversy exists about how rapidly sepsis must be treated,” wrote Christopher Seymour, MD, of the University of Pittsburgh, Pennsylvania, and his colleagues. The researchers reviewed data from New York State, where hospitals have mandated protocols for sepsis treatment, to assess the impact of treatment timing on risk-adjusted mortality (NEJM. 2017. doi: 10.1056/NEJMoa1703058).
The primary outcome was in-hospital mortality, and each hour taken to complete the 3-hour treatment bundle was associated with increased mortality (odds ratio, 1.04 per hour). Overall, patients whose 3-hour treatment bundle was completed between 3 and 12 hours after hospital admission were 14% more likely to die than those who received the treatment bundle within 3 hours.
“These associations appeared to be stronger among patients receiving vasopressors than among those who were not receiving vasopressors,” the researchers noted.
On average, patients received the complete 3-hour treatment bundle in 1.30 hours, antibiotics in 0.95 hours, and a fluid bolus in 2.56 hours.
Odds of risk-adjusted in-hospital mortality were significantly higher for those with a longer time to completion of the 3-hour bundle within 12 hours (OR, 1.04) and for those with a longer time to administration of antibiotics (OR, 1.04); however, the time to bolus of IV fluids did not significantly impact in-hospital mortality.
The study was limited as a review and not a randomized trial and by a lack of data on the appropriateness of broad-spectrum antibiotics, the researchers said. However, the data suggest that, if there is a causal relationship between treatment timing and mortality, “prompt recognition and faster treatment of sepsis and septic shock in the context of emergency care may reduce the incidence of avoidable deaths,” they said.
Lead author Dr. Seymour reported grants from the National Institutes of Health and financial relationships with Beckman Coulter and Edwards Lifesciences.
“To improve outcomes of sepsis, policymakers are increasingly using regulatory mechanisms intended to provide incentives to clinicians and hospitals to improve the quality of sepsis care,” wrote Tina B. Hershey, JD, MPH, and Jeremy M. Kahn, MD, in an accompanying editorial. The regulations implemented in New York State in 2013 “mandate that all hospitals in the state use evidence-based protocols for sepsis identification and management and that they report to the state government data on their sepsis-protocol adherence and treatment outcomes,” they said. Although the regulations in New York are fairly new, the data show an increased used of protocols and reduced mortality, they noted. “However, several crucial questions remain, concerning not only the regulations’ specific impact but also the broader question of the value of statewide mandates for protocolized sepsis care,” they said.
Ms. Hershey and Dr. Kahn are affiliated with the University of Pittsburgh, Pennsylvania, in the department of health policy and management and the department of critical care medicine, respectively. Both Ms. Hershey and Dr. Kahn disclosed that their institutions have applied for federal grants to study sepsis policymaking and its impact on health care costs and outcomes.
“To improve outcomes of sepsis, policymakers are increasingly using regulatory mechanisms intended to provide incentives to clinicians and hospitals to improve the quality of sepsis care,” wrote Tina B. Hershey, JD, MPH, and Jeremy M. Kahn, MD, in an accompanying editorial. The regulations implemented in New York State in 2013 “mandate that all hospitals in the state use evidence-based protocols for sepsis identification and management and that they report to the state government data on their sepsis-protocol adherence and treatment outcomes,” they said. Although the regulations in New York are fairly new, the data show an increased used of protocols and reduced mortality, they noted. “However, several crucial questions remain, concerning not only the regulations’ specific impact but also the broader question of the value of statewide mandates for protocolized sepsis care,” they said.
Ms. Hershey and Dr. Kahn are affiliated with the University of Pittsburgh, Pennsylvania, in the department of health policy and management and the department of critical care medicine, respectively. Both Ms. Hershey and Dr. Kahn disclosed that their institutions have applied for federal grants to study sepsis policymaking and its impact on health care costs and outcomes.
“To improve outcomes of sepsis, policymakers are increasingly using regulatory mechanisms intended to provide incentives to clinicians and hospitals to improve the quality of sepsis care,” wrote Tina B. Hershey, JD, MPH, and Jeremy M. Kahn, MD, in an accompanying editorial. The regulations implemented in New York State in 2013 “mandate that all hospitals in the state use evidence-based protocols for sepsis identification and management and that they report to the state government data on their sepsis-protocol adherence and treatment outcomes,” they said. Although the regulations in New York are fairly new, the data show an increased used of protocols and reduced mortality, they noted. “However, several crucial questions remain, concerning not only the regulations’ specific impact but also the broader question of the value of statewide mandates for protocolized sepsis care,” they said.
Ms. Hershey and Dr. Kahn are affiliated with the University of Pittsburgh, Pennsylvania, in the department of health policy and management and the department of critical care medicine, respectively. Both Ms. Hershey and Dr. Kahn disclosed that their institutions have applied for federal grants to study sepsis policymaking and its impact on health care costs and outcomes.
WASHINGTON – Sepsis and septic shock patients treated within 3 hours had lower in-hospital mortality rates than those treated between hours 3 and 12, based on data from nearly 50,000 adult patients. The findings were presented at an international conference of the American Thoracic Society and published simultaneously in the New England Journal of Medicine.
“Considerable controversy exists about how rapidly sepsis must be treated,” wrote Christopher Seymour, MD, of the University of Pittsburgh, Pennsylvania, and his colleagues. The researchers reviewed data from New York State, where hospitals have mandated protocols for sepsis treatment, to assess the impact of treatment timing on risk-adjusted mortality (NEJM. 2017. doi: 10.1056/NEJMoa1703058).
The primary outcome was in-hospital mortality, and each hour taken to complete the 3-hour treatment bundle was associated with increased mortality (odds ratio, 1.04 per hour). Overall, patients whose 3-hour treatment bundle was completed between 3 and 12 hours after hospital admission were 14% more likely to die than those who received the treatment bundle within 3 hours.
“These associations appeared to be stronger among patients receiving vasopressors than among those who were not receiving vasopressors,” the researchers noted.
On average, patients received the complete 3-hour treatment bundle in 1.30 hours, antibiotics in 0.95 hours, and a fluid bolus in 2.56 hours.
Odds of risk-adjusted in-hospital mortality were significantly higher for those with a longer time to completion of the 3-hour bundle within 12 hours (OR, 1.04) and for those with a longer time to administration of antibiotics (OR, 1.04); however, the time to bolus of IV fluids did not significantly impact in-hospital mortality.
The study was limited as a review and not a randomized trial and by a lack of data on the appropriateness of broad-spectrum antibiotics, the researchers said. However, the data suggest that, if there is a causal relationship between treatment timing and mortality, “prompt recognition and faster treatment of sepsis and septic shock in the context of emergency care may reduce the incidence of avoidable deaths,” they said.
Lead author Dr. Seymour reported grants from the National Institutes of Health and financial relationships with Beckman Coulter and Edwards Lifesciences.
WASHINGTON – Sepsis and septic shock patients treated within 3 hours had lower in-hospital mortality rates than those treated between hours 3 and 12, based on data from nearly 50,000 adult patients. The findings were presented at an international conference of the American Thoracic Society and published simultaneously in the New England Journal of Medicine.
“Considerable controversy exists about how rapidly sepsis must be treated,” wrote Christopher Seymour, MD, of the University of Pittsburgh, Pennsylvania, and his colleagues. The researchers reviewed data from New York State, where hospitals have mandated protocols for sepsis treatment, to assess the impact of treatment timing on risk-adjusted mortality (NEJM. 2017. doi: 10.1056/NEJMoa1703058).
The primary outcome was in-hospital mortality, and each hour taken to complete the 3-hour treatment bundle was associated with increased mortality (odds ratio, 1.04 per hour). Overall, patients whose 3-hour treatment bundle was completed between 3 and 12 hours after hospital admission were 14% more likely to die than those who received the treatment bundle within 3 hours.
“These associations appeared to be stronger among patients receiving vasopressors than among those who were not receiving vasopressors,” the researchers noted.
On average, patients received the complete 3-hour treatment bundle in 1.30 hours, antibiotics in 0.95 hours, and a fluid bolus in 2.56 hours.
Odds of risk-adjusted in-hospital mortality were significantly higher for those with a longer time to completion of the 3-hour bundle within 12 hours (OR, 1.04) and for those with a longer time to administration of antibiotics (OR, 1.04); however, the time to bolus of IV fluids did not significantly impact in-hospital mortality.
The study was limited as a review and not a randomized trial and by a lack of data on the appropriateness of broad-spectrum antibiotics, the researchers said. However, the data suggest that, if there is a causal relationship between treatment timing and mortality, “prompt recognition and faster treatment of sepsis and septic shock in the context of emergency care may reduce the incidence of avoidable deaths,” they said.
Lead author Dr. Seymour reported grants from the National Institutes of Health and financial relationships with Beckman Coulter and Edwards Lifesciences.
Key clinical point: In-hospital mortality rates were lower for sepsis patients who were treated more rapidly (within 3 hours) with a 3-hour bundle of sepsis care and antibiotics.
Major finding: Sepsis patients whose 3-hour treatment bundle was completed between hour 3 and 12 were 14% more likely to die than those who received the treatment within 3 hours.
Data source: A review of data from 49,331 sepsis and septic shock patients at 149 hospitals.
Disclosures: Lead author Dr. Seymour reported grants from the National Institutes of Health and financial relationships with Beckman Coulter and Edwards Lifesciences.
IL-2 and IL-8 elevated after gluten ingestion on gluten-free diet
CHICAGO – A gluten-free diet is often implemented by patients before they are evaluated for celiac disease, which, in turn, does not allow for accurate celiac disease testing.
A new study shows, however, that measuring serum cytokines following a gluten challenge may allow an accurate diagnosis of celiac disease to be made, even after patients have been on a gluten-free diet.
Levels of IL-2 and IL-8 were increased 2-4 hours after ingestion of gluten. Elevations in other cytokines occurred less frequently, and changes in cytokine levels were similar in both serum and plasma.
“IL-2 is a cytokine produced exclusively by T cells and goes up from 2 hours after gluten consumption in celiac patients and is highly specific,” said study author Robert P. Anderson, MD, of Immusant, Cambridge, Mass., who presented the findings of his study at Digestive Disease Week®. “Rises in IL 8 are less but significant as well.”
The authors note that individuals who are already on a gluten-free diet and who would like a definitive diagnosis of celiac disease all too often refuse or are unable to tolerate a gluten challenge for the time period that is needed – usually 4 or more weeks – for the serologic and histologic markers of celiac disease to become abnormal.
Dr. Anderson pointed out that elevated plasma levels of IL-2 and IL-8 accompanied by gastrointestinal symptoms have been observed 4 hours after receiving a single dose of Nexvax2, a therapeutic vaccine being developed by Immusant. The peptide-based vaccine is intended to protect against the effects of gluten exposure while maintaining a gluten-free diet in HLA-DQ2.5+ patients with celiac disease.
In this study, Dr. Anderson and his colleagues hypothesized that patients with celiac disease who were on a gluten-free diet would also exhibit elevated serum IL-2 and IL-8 after an oral gluten versus placebo challenge.
The cohort was comprised of 21 adults with HLA-DQ2.5+ celiac disease who were compliant with a gluten-free diet and who were randomized to consume either vital wheat gluten flour (5 g; ~ 3 g gluten) or a matched gluten-free flour drink (placebo) over 10 minutes.
Blood was collected prior to the challenge and then at 4, 6, and 24 hours afterwards. In addition, patient vital signs and reported outcomes were recorded hourly, and adverse events were tracked from day 1 to day 6.
At 4 hours after ingesting gluten, serum IL-2 and IL-8 were both significantly higher, compared with placebo.
“There was a 20-fold increase in IL-2 after gluten was consumed, between 3 and 5 hours afterwards,” said Dr. Anderson. “IL-8 went up but not as much.”
The median change from baseline for IL-2 after gluten intake was 19.5 ([7.0-47.1], vs. 0.7 [0.5-1.2] for placebo; P = .0001). For IL-8 it was 2.4 (1.2-4.9) vs. 1.1 (0.8-1.2) (P = .012).
Patient-reported outcomes were worse among those in the gluten group (7/12), compared with the placebo group (3/9), after 3 hours but did not reach statistical significance.
He added that his team is in the process of conducting a further study to assess the diagnostic utility of measuring cytokine activity.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – A gluten-free diet is often implemented by patients before they are evaluated for celiac disease, which, in turn, does not allow for accurate celiac disease testing.
A new study shows, however, that measuring serum cytokines following a gluten challenge may allow an accurate diagnosis of celiac disease to be made, even after patients have been on a gluten-free diet.
Levels of IL-2 and IL-8 were increased 2-4 hours after ingestion of gluten. Elevations in other cytokines occurred less frequently, and changes in cytokine levels were similar in both serum and plasma.
“IL-2 is a cytokine produced exclusively by T cells and goes up from 2 hours after gluten consumption in celiac patients and is highly specific,” said study author Robert P. Anderson, MD, of Immusant, Cambridge, Mass., who presented the findings of his study at Digestive Disease Week®. “Rises in IL 8 are less but significant as well.”
The authors note that individuals who are already on a gluten-free diet and who would like a definitive diagnosis of celiac disease all too often refuse or are unable to tolerate a gluten challenge for the time period that is needed – usually 4 or more weeks – for the serologic and histologic markers of celiac disease to become abnormal.
Dr. Anderson pointed out that elevated plasma levels of IL-2 and IL-8 accompanied by gastrointestinal symptoms have been observed 4 hours after receiving a single dose of Nexvax2, a therapeutic vaccine being developed by Immusant. The peptide-based vaccine is intended to protect against the effects of gluten exposure while maintaining a gluten-free diet in HLA-DQ2.5+ patients with celiac disease.
In this study, Dr. Anderson and his colleagues hypothesized that patients with celiac disease who were on a gluten-free diet would also exhibit elevated serum IL-2 and IL-8 after an oral gluten versus placebo challenge.
The cohort was comprised of 21 adults with HLA-DQ2.5+ celiac disease who were compliant with a gluten-free diet and who were randomized to consume either vital wheat gluten flour (5 g; ~ 3 g gluten) or a matched gluten-free flour drink (placebo) over 10 minutes.
Blood was collected prior to the challenge and then at 4, 6, and 24 hours afterwards. In addition, patient vital signs and reported outcomes were recorded hourly, and adverse events were tracked from day 1 to day 6.
At 4 hours after ingesting gluten, serum IL-2 and IL-8 were both significantly higher, compared with placebo.
“There was a 20-fold increase in IL-2 after gluten was consumed, between 3 and 5 hours afterwards,” said Dr. Anderson. “IL-8 went up but not as much.”
The median change from baseline for IL-2 after gluten intake was 19.5 ([7.0-47.1], vs. 0.7 [0.5-1.2] for placebo; P = .0001). For IL-8 it was 2.4 (1.2-4.9) vs. 1.1 (0.8-1.2) (P = .012).
Patient-reported outcomes were worse among those in the gluten group (7/12), compared with the placebo group (3/9), after 3 hours but did not reach statistical significance.
He added that his team is in the process of conducting a further study to assess the diagnostic utility of measuring cytokine activity.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – A gluten-free diet is often implemented by patients before they are evaluated for celiac disease, which, in turn, does not allow for accurate celiac disease testing.
A new study shows, however, that measuring serum cytokines following a gluten challenge may allow an accurate diagnosis of celiac disease to be made, even after patients have been on a gluten-free diet.
Levels of IL-2 and IL-8 were increased 2-4 hours after ingestion of gluten. Elevations in other cytokines occurred less frequently, and changes in cytokine levels were similar in both serum and plasma.
“IL-2 is a cytokine produced exclusively by T cells and goes up from 2 hours after gluten consumption in celiac patients and is highly specific,” said study author Robert P. Anderson, MD, of Immusant, Cambridge, Mass., who presented the findings of his study at Digestive Disease Week®. “Rises in IL 8 are less but significant as well.”
The authors note that individuals who are already on a gluten-free diet and who would like a definitive diagnosis of celiac disease all too often refuse or are unable to tolerate a gluten challenge for the time period that is needed – usually 4 or more weeks – for the serologic and histologic markers of celiac disease to become abnormal.
Dr. Anderson pointed out that elevated plasma levels of IL-2 and IL-8 accompanied by gastrointestinal symptoms have been observed 4 hours after receiving a single dose of Nexvax2, a therapeutic vaccine being developed by Immusant. The peptide-based vaccine is intended to protect against the effects of gluten exposure while maintaining a gluten-free diet in HLA-DQ2.5+ patients with celiac disease.
In this study, Dr. Anderson and his colleagues hypothesized that patients with celiac disease who were on a gluten-free diet would also exhibit elevated serum IL-2 and IL-8 after an oral gluten versus placebo challenge.
The cohort was comprised of 21 adults with HLA-DQ2.5+ celiac disease who were compliant with a gluten-free diet and who were randomized to consume either vital wheat gluten flour (5 g; ~ 3 g gluten) or a matched gluten-free flour drink (placebo) over 10 minutes.
Blood was collected prior to the challenge and then at 4, 6, and 24 hours afterwards. In addition, patient vital signs and reported outcomes were recorded hourly, and adverse events were tracked from day 1 to day 6.
At 4 hours after ingesting gluten, serum IL-2 and IL-8 were both significantly higher, compared with placebo.
“There was a 20-fold increase in IL-2 after gluten was consumed, between 3 and 5 hours afterwards,” said Dr. Anderson. “IL-8 went up but not as much.”
The median change from baseline for IL-2 after gluten intake was 19.5 ([7.0-47.1], vs. 0.7 [0.5-1.2] for placebo; P = .0001). For IL-8 it was 2.4 (1.2-4.9) vs. 1.1 (0.8-1.2) (P = .012).
Patient-reported outcomes were worse among those in the gluten group (7/12), compared with the placebo group (3/9), after 3 hours but did not reach statistical significance.
He added that his team is in the process of conducting a further study to assess the diagnostic utility of measuring cytokine activity.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
AT DDW
Key clinical point: Measuring serum cytokines can potentially be used to diagnose celiac disease after the patient has been on a gluten-free diet.
Major finding: There was a median 19.5-fold change from baseline for IL-2 after gluten intake (7.0-fold to 47.1-fold) and 24-fold for IL-8 (1.2-fold to 4.9-fold).
Data source: Randomized trial comprising 21 volunteers with celiac disease.
Disclosures: Dr. Anderson is employed by Immusant.
Healthy lifestyle, tree nuts may protect against colon cancer recurrence
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Compared with counterparts who have the least healthy lifestyle, patients with the healthiest lifestyle were 42%-51% less likely to die. Relative to peers who never ate nuts, patients who ate nuts at least twice a week had a 42% lower risk of disease-free survival events and a 57% lower risk of death.
Data source: A pair of prospective cohort studies among 992 patients and 826 patients with resected stage III colon cancer given adjuvant chemotherapy in a clinical trial (CALGB 89803).
Disclosures: Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
Adolescents and sleep, or the lack thereof
Every parent will attest that bright-eyed children grow into sleepy adolescents, and the science confirms their observations. There are multiple factors that prevent adolescents from getting the sleep they need, and inadequate sleep has serious consequences – from impaired learning to depressive symptoms, obesity to deadly accidents – all of which are potentially preventable with some practical strategies to promote adequate sleep.
Adolescence is a period of intense growth and development, so it is no surprise that adolescents require a lot of sleep, over 9 hours nightly. But surveys have shown that only 3% of American adolescents get 9 hours of sleep nightly, and the average amount of weeknight sleep is only 6 hours.1 Sleep deprivation is not a problem in childhood, so why can’t adolescents get enough sleep?
Over the last 15 years, a new factor – screen time – has worsened the adolescent sleep situation. Most teens have an electronic device in their bedroom and use it for homework, entertainment, and socializing well into the night. Multiple studies have confirmed that electronic exposure in the evening is associated with less sleep at night and more day time sleepiness,by competing with sleep and suppression of nocturnal melatonin release, which can delay the onset of sleep.2
It is ironic that many teens are staying up late for homework, when their lack of sleep can interfere with consolidation of learning. It also has powerful effects on working memory and reaction time, making both academic and athletic performance suffer. Chronically sleep-deprived teenagers often complain of difficulty with initiating and sustaining attention, which may lead to a mistaken diagnosis of ADHD, and stimulant treatment may further complicate sleep.
Good mental health is not the only casualty of inadequate sleep. A growing body of evidence links short sleep duration with an increased risk of obesity. This appears to be mediated by alterations in neurohormones associated with sleep, leading to higher carbohydrate and fat intake, more snacking and insulin resistance.
Anything that compromises attention and reaction time, including sleep deprivation, adds risk to driving, particularly for inexperienced and impulsive adolescent drivers. The National Highway Transportation Safety Administration estimates that drivers 25 and younger cause more than half of all “fall asleep” crashes.
Teenagers generally know that they are exhausted, but the strategies they might use to manage their fatigue can actually make things worse. Sleepy teenagers often consume large amounts of caffeine to get through their days and their homework at night. Caffeine, in turn, interferes with both the onset and quality of sleep, perpetuating the cycle. Even “catch-up” sleep on weekends is a strategy that can contribute to the problem, as it can lead to more disrupted sleep by pushing the onset of school night sleepiness even later.
While growing autonomy is part of why teenagers are sleep deprived, they will consider the caring and informed guidance of their pediatricians about their health. Ask your teenage patients how much sleep they usually get on a school night. It can be validating to show them how sleep deprived they are, and point out how strategies like caffeine and oversleeping might be making it worse. Explain that people (adults, too!) need to make time for sleep just as they might for exercise or friends. Tell them about “good sleep hygiene,” the practice of having consistent sleep times and routines that are conducive to restful sleep. This can include a hot shower before bed, reading for the last 30 minutes before lights out, and no screen time for at least 1 hour before bed. Indeed, it can be powerful to urge that everyone in the family takes screens out of their bedrooms.
Additionally, while they might sleep in on weekends, it shouldn’t be much more than an hour longer than on weekdays. And no naps after school! It is common for teens to feel overwhelmed by their commitments and that sleep must be the first thing to go. Use their growing sense of autonomy to remind them that they get to choose how to use their time, and balance will pay off much more than sacrificing sleep. A practical conversation about sleep can help them to make informed choices and thoughtfully take care of themselves before they head off to college.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Resources
1. “Adolescent Sleep Needs and Patterns: Research Report and Resource Guide.” (Arlington, Va.: National Sleep Foundation, 2000.)
2. Pediatrics. 2014 Sep;134(3):e921-32.
3. Sleep. 2004 Nov 1;27(7):1351-8.
Every parent will attest that bright-eyed children grow into sleepy adolescents, and the science confirms their observations. There are multiple factors that prevent adolescents from getting the sleep they need, and inadequate sleep has serious consequences – from impaired learning to depressive symptoms, obesity to deadly accidents – all of which are potentially preventable with some practical strategies to promote adequate sleep.
Adolescence is a period of intense growth and development, so it is no surprise that adolescents require a lot of sleep, over 9 hours nightly. But surveys have shown that only 3% of American adolescents get 9 hours of sleep nightly, and the average amount of weeknight sleep is only 6 hours.1 Sleep deprivation is not a problem in childhood, so why can’t adolescents get enough sleep?
Over the last 15 years, a new factor – screen time – has worsened the adolescent sleep situation. Most teens have an electronic device in their bedroom and use it for homework, entertainment, and socializing well into the night. Multiple studies have confirmed that electronic exposure in the evening is associated with less sleep at night and more day time sleepiness,by competing with sleep and suppression of nocturnal melatonin release, which can delay the onset of sleep.2
It is ironic that many teens are staying up late for homework, when their lack of sleep can interfere with consolidation of learning. It also has powerful effects on working memory and reaction time, making both academic and athletic performance suffer. Chronically sleep-deprived teenagers often complain of difficulty with initiating and sustaining attention, which may lead to a mistaken diagnosis of ADHD, and stimulant treatment may further complicate sleep.
Good mental health is not the only casualty of inadequate sleep. A growing body of evidence links short sleep duration with an increased risk of obesity. This appears to be mediated by alterations in neurohormones associated with sleep, leading to higher carbohydrate and fat intake, more snacking and insulin resistance.
Anything that compromises attention and reaction time, including sleep deprivation, adds risk to driving, particularly for inexperienced and impulsive adolescent drivers. The National Highway Transportation Safety Administration estimates that drivers 25 and younger cause more than half of all “fall asleep” crashes.
Teenagers generally know that they are exhausted, but the strategies they might use to manage their fatigue can actually make things worse. Sleepy teenagers often consume large amounts of caffeine to get through their days and their homework at night. Caffeine, in turn, interferes with both the onset and quality of sleep, perpetuating the cycle. Even “catch-up” sleep on weekends is a strategy that can contribute to the problem, as it can lead to more disrupted sleep by pushing the onset of school night sleepiness even later.
While growing autonomy is part of why teenagers are sleep deprived, they will consider the caring and informed guidance of their pediatricians about their health. Ask your teenage patients how much sleep they usually get on a school night. It can be validating to show them how sleep deprived they are, and point out how strategies like caffeine and oversleeping might be making it worse. Explain that people (adults, too!) need to make time for sleep just as they might for exercise or friends. Tell them about “good sleep hygiene,” the practice of having consistent sleep times and routines that are conducive to restful sleep. This can include a hot shower before bed, reading for the last 30 minutes before lights out, and no screen time for at least 1 hour before bed. Indeed, it can be powerful to urge that everyone in the family takes screens out of their bedrooms.
Additionally, while they might sleep in on weekends, it shouldn’t be much more than an hour longer than on weekdays. And no naps after school! It is common for teens to feel overwhelmed by their commitments and that sleep must be the first thing to go. Use their growing sense of autonomy to remind them that they get to choose how to use their time, and balance will pay off much more than sacrificing sleep. A practical conversation about sleep can help them to make informed choices and thoughtfully take care of themselves before they head off to college.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Resources
1. “Adolescent Sleep Needs and Patterns: Research Report and Resource Guide.” (Arlington, Va.: National Sleep Foundation, 2000.)
2. Pediatrics. 2014 Sep;134(3):e921-32.
3. Sleep. 2004 Nov 1;27(7):1351-8.
Every parent will attest that bright-eyed children grow into sleepy adolescents, and the science confirms their observations. There are multiple factors that prevent adolescents from getting the sleep they need, and inadequate sleep has serious consequences – from impaired learning to depressive symptoms, obesity to deadly accidents – all of which are potentially preventable with some practical strategies to promote adequate sleep.
Adolescence is a period of intense growth and development, so it is no surprise that adolescents require a lot of sleep, over 9 hours nightly. But surveys have shown that only 3% of American adolescents get 9 hours of sleep nightly, and the average amount of weeknight sleep is only 6 hours.1 Sleep deprivation is not a problem in childhood, so why can’t adolescents get enough sleep?
Over the last 15 years, a new factor – screen time – has worsened the adolescent sleep situation. Most teens have an electronic device in their bedroom and use it for homework, entertainment, and socializing well into the night. Multiple studies have confirmed that electronic exposure in the evening is associated with less sleep at night and more day time sleepiness,by competing with sleep and suppression of nocturnal melatonin release, which can delay the onset of sleep.2
It is ironic that many teens are staying up late for homework, when their lack of sleep can interfere with consolidation of learning. It also has powerful effects on working memory and reaction time, making both academic and athletic performance suffer. Chronically sleep-deprived teenagers often complain of difficulty with initiating and sustaining attention, which may lead to a mistaken diagnosis of ADHD, and stimulant treatment may further complicate sleep.
Good mental health is not the only casualty of inadequate sleep. A growing body of evidence links short sleep duration with an increased risk of obesity. This appears to be mediated by alterations in neurohormones associated with sleep, leading to higher carbohydrate and fat intake, more snacking and insulin resistance.
Anything that compromises attention and reaction time, including sleep deprivation, adds risk to driving, particularly for inexperienced and impulsive adolescent drivers. The National Highway Transportation Safety Administration estimates that drivers 25 and younger cause more than half of all “fall asleep” crashes.
Teenagers generally know that they are exhausted, but the strategies they might use to manage their fatigue can actually make things worse. Sleepy teenagers often consume large amounts of caffeine to get through their days and their homework at night. Caffeine, in turn, interferes with both the onset and quality of sleep, perpetuating the cycle. Even “catch-up” sleep on weekends is a strategy that can contribute to the problem, as it can lead to more disrupted sleep by pushing the onset of school night sleepiness even later.
While growing autonomy is part of why teenagers are sleep deprived, they will consider the caring and informed guidance of their pediatricians about their health. Ask your teenage patients how much sleep they usually get on a school night. It can be validating to show them how sleep deprived they are, and point out how strategies like caffeine and oversleeping might be making it worse. Explain that people (adults, too!) need to make time for sleep just as they might for exercise or friends. Tell them about “good sleep hygiene,” the practice of having consistent sleep times and routines that are conducive to restful sleep. This can include a hot shower before bed, reading for the last 30 minutes before lights out, and no screen time for at least 1 hour before bed. Indeed, it can be powerful to urge that everyone in the family takes screens out of their bedrooms.
Additionally, while they might sleep in on weekends, it shouldn’t be much more than an hour longer than on weekdays. And no naps after school! It is common for teens to feel overwhelmed by their commitments and that sleep must be the first thing to go. Use their growing sense of autonomy to remind them that they get to choose how to use their time, and balance will pay off much more than sacrificing sleep. A practical conversation about sleep can help them to make informed choices and thoughtfully take care of themselves before they head off to college.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Resources
1. “Adolescent Sleep Needs and Patterns: Research Report and Resource Guide.” (Arlington, Va.: National Sleep Foundation, 2000.)
2. Pediatrics. 2014 Sep;134(3):e921-32.
3. Sleep. 2004 Nov 1;27(7):1351-8.
Highlights From the 69th Annual Meeting of the American Academy of Neurology
Selected highlights from the 69th Annual Meeting of the American Academy of Neurology
Selected highlights from the 69th Annual Meeting of the American Academy of Neurology
Selected highlights from the 69th Annual Meeting of the American Academy of Neurology
Systems modeling advances precision medicine in alopecia
PORTLAND – Alopecia areata can resist treatment stubbornly, but dermatologists might soon have better tools to predict response to therapy.
Personalized gene sequencing is key to this type of precision medicine, but conventional sequencing can be “extremely cumbersome and clinically impractical,” James C. Chen, PhD, said at the annual meeting of the Society for Investigative Dermatology.
During alopecia trials at Columbia, researchers routinely perform RNA sequencing of scalp biopsies to analyze therapeutic response on a molecular level. Using these RNAseq data from patients with untreated alopecia areata and gene regulatory network analysis data from the Algorithm for the Reconstruction of Accurate Cellular Networks, Dr. Chen and his associates modeled the molecular mechanisms of action of the pan–Janus kinase inhibitor tofacitinib, the JAK1/JAK2 inhibitor ruxolitinib, the CTLA4 inhibitor abatacept, and intralesional triamcinolone acetonide (IL-TAC). Heat maps of molecular responses to treatment showed distinct mechanisms of action between IL-TAC and abatacept, Dr. Chen said.
Furthermore, these therapies showed distinct and much less robust molecular effects than either ruxolitinib or tofacitinib. A Venn diagram of the biosignatures and molecular mechanisms of action of all four therapies showed little overlap. In fact, the probability of so little overlap between tofacitinib and IL-TAC occurring by chance was 0.023. The lack of overlap between the two JAK inhibitors was even more pronounced (P = 2.21 x 10–11).
Only 5-10 transcription factors are needed to capture these molecular mechanisms of action, which could greatly streamline precision dermatology in the future, according to Dr. Chen. “Systems biology offers a foundation for developing precision medicine strategies and selecting treatments for patients based on their individual molecular pathology,” he concluded. “Even when patients with alopecia areata have the same clinical phenotype, the molecular pathways they take to get there are not necessarily the same. We need to define those paths to maximize our chances of matching drugs to patients.”
Dr. Chen acknowledged support from the National Institutes of Health, epiCURE, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. He had no relevant financial conflicts of interest.
PORTLAND – Alopecia areata can resist treatment stubbornly, but dermatologists might soon have better tools to predict response to therapy.
Personalized gene sequencing is key to this type of precision medicine, but conventional sequencing can be “extremely cumbersome and clinically impractical,” James C. Chen, PhD, said at the annual meeting of the Society for Investigative Dermatology.
During alopecia trials at Columbia, researchers routinely perform RNA sequencing of scalp biopsies to analyze therapeutic response on a molecular level. Using these RNAseq data from patients with untreated alopecia areata and gene regulatory network analysis data from the Algorithm for the Reconstruction of Accurate Cellular Networks, Dr. Chen and his associates modeled the molecular mechanisms of action of the pan–Janus kinase inhibitor tofacitinib, the JAK1/JAK2 inhibitor ruxolitinib, the CTLA4 inhibitor abatacept, and intralesional triamcinolone acetonide (IL-TAC). Heat maps of molecular responses to treatment showed distinct mechanisms of action between IL-TAC and abatacept, Dr. Chen said.
Furthermore, these therapies showed distinct and much less robust molecular effects than either ruxolitinib or tofacitinib. A Venn diagram of the biosignatures and molecular mechanisms of action of all four therapies showed little overlap. In fact, the probability of so little overlap between tofacitinib and IL-TAC occurring by chance was 0.023. The lack of overlap between the two JAK inhibitors was even more pronounced (P = 2.21 x 10–11).
Only 5-10 transcription factors are needed to capture these molecular mechanisms of action, which could greatly streamline precision dermatology in the future, according to Dr. Chen. “Systems biology offers a foundation for developing precision medicine strategies and selecting treatments for patients based on their individual molecular pathology,” he concluded. “Even when patients with alopecia areata have the same clinical phenotype, the molecular pathways they take to get there are not necessarily the same. We need to define those paths to maximize our chances of matching drugs to patients.”
Dr. Chen acknowledged support from the National Institutes of Health, epiCURE, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. He had no relevant financial conflicts of interest.
PORTLAND – Alopecia areata can resist treatment stubbornly, but dermatologists might soon have better tools to predict response to therapy.
Personalized gene sequencing is key to this type of precision medicine, but conventional sequencing can be “extremely cumbersome and clinically impractical,” James C. Chen, PhD, said at the annual meeting of the Society for Investigative Dermatology.
During alopecia trials at Columbia, researchers routinely perform RNA sequencing of scalp biopsies to analyze therapeutic response on a molecular level. Using these RNAseq data from patients with untreated alopecia areata and gene regulatory network analysis data from the Algorithm for the Reconstruction of Accurate Cellular Networks, Dr. Chen and his associates modeled the molecular mechanisms of action of the pan–Janus kinase inhibitor tofacitinib, the JAK1/JAK2 inhibitor ruxolitinib, the CTLA4 inhibitor abatacept, and intralesional triamcinolone acetonide (IL-TAC). Heat maps of molecular responses to treatment showed distinct mechanisms of action between IL-TAC and abatacept, Dr. Chen said.
Furthermore, these therapies showed distinct and much less robust molecular effects than either ruxolitinib or tofacitinib. A Venn diagram of the biosignatures and molecular mechanisms of action of all four therapies showed little overlap. In fact, the probability of so little overlap between tofacitinib and IL-TAC occurring by chance was 0.023. The lack of overlap between the two JAK inhibitors was even more pronounced (P = 2.21 x 10–11).
Only 5-10 transcription factors are needed to capture these molecular mechanisms of action, which could greatly streamline precision dermatology in the future, according to Dr. Chen. “Systems biology offers a foundation for developing precision medicine strategies and selecting treatments for patients based on their individual molecular pathology,” he concluded. “Even when patients with alopecia areata have the same clinical phenotype, the molecular pathways they take to get there are not necessarily the same. We need to define those paths to maximize our chances of matching drugs to patients.”
Dr. Chen acknowledged support from the National Institutes of Health, epiCURE, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. He had no relevant financial conflicts of interest.
EXPERT ANALYSIS FROM SID 2017