Later follow-up colonoscopy equals higher colorectal cancer risk

No rush, but sooner is better
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Patients who undergo follow-up colonoscopy 10 months or more after a positive fecal immunochemical test are at higher risk for colorectal cancer, and for having more advanced disease at diagnosis, than are those who undergo immediate (within 30 days) follow-up colonoscopy, according to a new report.

Clinical practice guidelines recommend follow-up colonoscopy after a positive fecal immunochemical test (FIT) result but differ about how quickly the procedure should be done, chiefly because there is little evidence on which to base any recommendation regarding timing, reported Douglas A. Corley, MD, PhD, of Kaiser Permanente Northern California, Oakland, and his associates. The study results were published in JAMA.

Dr. Douglas A. Corley


To examine whether the length of the interval between FIT testing and colonoscopy affected diagnosis, they analyzed clinical data for 70,124 adults aged 50-75 years who were members of two large health organizations and who completed FIT testing during a 3-year period. The investigators compared outcomes among the 27,176 patients who had follow-up colonoscopy within 30 days (the reference group) against those of patients who had follow-up colonoscopy after 2 months (24,644 patients), 3 months (8,666 patients), 4-6 months (5,251 patients), 7-9 months (1,335 patients), 10-12 months (748 patients), or more than 12 months (2,304 patients).

A total of 2,191 colorectal cancers were diagnosed at follow-up colonoscopy, including 601 cases of advanced disease, the investigators reported (JAMA. 2017;317[16]:1631-41).

There was no significant increase in risk for any colorectal cancer or for advanced colorectal cancer among patients who had follow-up colonoscopy within 9 months, compared with the reference group. However, the risks of any colorectal cancer and of advanced colorectal cancer increased significantly at 10 months, with odds ratios of 1.48 and 1.97, respectively.

These risks continued to rise as the interval between testing and colonoscopy lengthened, so that after 1 year, the odds ratios were 2.25 for any colorectal cancer and 3.22 for advanced-stage disease. After 1 year, the odds ratios were 1.32 for advanced adenomas, 2.94 for stage II, 3.07 for stage III, and 3.86 for stage IV colorectal cancer.

The National Cancer Institute supported the study. Dr. Corley reported receiving grant support from Wyeth/Pfizer.

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The study by Corley et al. provides important reassurance for patients and physicians. The findings indicate that there is no immediate need to rush to have a colonoscopy after a positive FIT result, reflecting the clinical understanding that colorectal cancer is a disease that generally develops slowly. Longer time to follow-up will reduce the benefit of FIT, with detection of more cancers and more late-stage disease.

The study had one important limitation: The authors were unable to adjust for an important confounder – the indication for colonoscopy. The problem with not being able to account for indication is that patients who wish to avoid colonoscopy may delay the procedure until the onset of symptoms. Patients who return later could disproportionately represent symptomatic patients if colonoscopy-avoidant patients without symptoms are less likely to return for follow-up colonoscopy as they get further from the time of their positive FIT result.
 

Carolyn M. Rutter, PhD, is at the RAND Corporation, Santa Monica, Calif. John M. Inadomi, MD, is at the University of Washington, Seattle. Dr. Inadomi reported receiving grants from NinePoint Medical. Dr. Rutter reported having no disclosures. These comments are adapted from an accompanying editorial (JAMA 2107;317[16]:1627-8).

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The study by Corley et al. provides important reassurance for patients and physicians. The findings indicate that there is no immediate need to rush to have a colonoscopy after a positive FIT result, reflecting the clinical understanding that colorectal cancer is a disease that generally develops slowly. Longer time to follow-up will reduce the benefit of FIT, with detection of more cancers and more late-stage disease.

The study had one important limitation: The authors were unable to adjust for an important confounder – the indication for colonoscopy. The problem with not being able to account for indication is that patients who wish to avoid colonoscopy may delay the procedure until the onset of symptoms. Patients who return later could disproportionately represent symptomatic patients if colonoscopy-avoidant patients without symptoms are less likely to return for follow-up colonoscopy as they get further from the time of their positive FIT result.
 

Carolyn M. Rutter, PhD, is at the RAND Corporation, Santa Monica, Calif. John M. Inadomi, MD, is at the University of Washington, Seattle. Dr. Inadomi reported receiving grants from NinePoint Medical. Dr. Rutter reported having no disclosures. These comments are adapted from an accompanying editorial (JAMA 2107;317[16]:1627-8).

Body

 

The study by Corley et al. provides important reassurance for patients and physicians. The findings indicate that there is no immediate need to rush to have a colonoscopy after a positive FIT result, reflecting the clinical understanding that colorectal cancer is a disease that generally develops slowly. Longer time to follow-up will reduce the benefit of FIT, with detection of more cancers and more late-stage disease.

The study had one important limitation: The authors were unable to adjust for an important confounder – the indication for colonoscopy. The problem with not being able to account for indication is that patients who wish to avoid colonoscopy may delay the procedure until the onset of symptoms. Patients who return later could disproportionately represent symptomatic patients if colonoscopy-avoidant patients without symptoms are less likely to return for follow-up colonoscopy as they get further from the time of their positive FIT result.
 

Carolyn M. Rutter, PhD, is at the RAND Corporation, Santa Monica, Calif. John M. Inadomi, MD, is at the University of Washington, Seattle. Dr. Inadomi reported receiving grants from NinePoint Medical. Dr. Rutter reported having no disclosures. These comments are adapted from an accompanying editorial (JAMA 2107;317[16]:1627-8).

Title
No rush, but sooner is better
No rush, but sooner is better

 

Patients who undergo follow-up colonoscopy 10 months or more after a positive fecal immunochemical test are at higher risk for colorectal cancer, and for having more advanced disease at diagnosis, than are those who undergo immediate (within 30 days) follow-up colonoscopy, according to a new report.

Clinical practice guidelines recommend follow-up colonoscopy after a positive fecal immunochemical test (FIT) result but differ about how quickly the procedure should be done, chiefly because there is little evidence on which to base any recommendation regarding timing, reported Douglas A. Corley, MD, PhD, of Kaiser Permanente Northern California, Oakland, and his associates. The study results were published in JAMA.

Dr. Douglas A. Corley


To examine whether the length of the interval between FIT testing and colonoscopy affected diagnosis, they analyzed clinical data for 70,124 adults aged 50-75 years who were members of two large health organizations and who completed FIT testing during a 3-year period. The investigators compared outcomes among the 27,176 patients who had follow-up colonoscopy within 30 days (the reference group) against those of patients who had follow-up colonoscopy after 2 months (24,644 patients), 3 months (8,666 patients), 4-6 months (5,251 patients), 7-9 months (1,335 patients), 10-12 months (748 patients), or more than 12 months (2,304 patients).

A total of 2,191 colorectal cancers were diagnosed at follow-up colonoscopy, including 601 cases of advanced disease, the investigators reported (JAMA. 2017;317[16]:1631-41).

There was no significant increase in risk for any colorectal cancer or for advanced colorectal cancer among patients who had follow-up colonoscopy within 9 months, compared with the reference group. However, the risks of any colorectal cancer and of advanced colorectal cancer increased significantly at 10 months, with odds ratios of 1.48 and 1.97, respectively.

These risks continued to rise as the interval between testing and colonoscopy lengthened, so that after 1 year, the odds ratios were 2.25 for any colorectal cancer and 3.22 for advanced-stage disease. After 1 year, the odds ratios were 1.32 for advanced adenomas, 2.94 for stage II, 3.07 for stage III, and 3.86 for stage IV colorectal cancer.

The National Cancer Institute supported the study. Dr. Corley reported receiving grant support from Wyeth/Pfizer.

 

Patients who undergo follow-up colonoscopy 10 months or more after a positive fecal immunochemical test are at higher risk for colorectal cancer, and for having more advanced disease at diagnosis, than are those who undergo immediate (within 30 days) follow-up colonoscopy, according to a new report.

Clinical practice guidelines recommend follow-up colonoscopy after a positive fecal immunochemical test (FIT) result but differ about how quickly the procedure should be done, chiefly because there is little evidence on which to base any recommendation regarding timing, reported Douglas A. Corley, MD, PhD, of Kaiser Permanente Northern California, Oakland, and his associates. The study results were published in JAMA.

Dr. Douglas A. Corley


To examine whether the length of the interval between FIT testing and colonoscopy affected diagnosis, they analyzed clinical data for 70,124 adults aged 50-75 years who were members of two large health organizations and who completed FIT testing during a 3-year period. The investigators compared outcomes among the 27,176 patients who had follow-up colonoscopy within 30 days (the reference group) against those of patients who had follow-up colonoscopy after 2 months (24,644 patients), 3 months (8,666 patients), 4-6 months (5,251 patients), 7-9 months (1,335 patients), 10-12 months (748 patients), or more than 12 months (2,304 patients).

A total of 2,191 colorectal cancers were diagnosed at follow-up colonoscopy, including 601 cases of advanced disease, the investigators reported (JAMA. 2017;317[16]:1631-41).

There was no significant increase in risk for any colorectal cancer or for advanced colorectal cancer among patients who had follow-up colonoscopy within 9 months, compared with the reference group. However, the risks of any colorectal cancer and of advanced colorectal cancer increased significantly at 10 months, with odds ratios of 1.48 and 1.97, respectively.

These risks continued to rise as the interval between testing and colonoscopy lengthened, so that after 1 year, the odds ratios were 2.25 for any colorectal cancer and 3.22 for advanced-stage disease. After 1 year, the odds ratios were 1.32 for advanced adenomas, 2.94 for stage II, 3.07 for stage III, and 3.86 for stage IV colorectal cancer.

The National Cancer Institute supported the study. Dr. Corley reported receiving grant support from Wyeth/Pfizer.

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Key clinical point: Patients with follow-up colonoscopy 10 or more months after a positive FIT are at higher risk for colorectal cancer.

Major finding: For patients who delayed follow-up colonoscopy for 10 months, the risks of any colorectal cancer (OR, 1.48) and of advanced colorectal cancer (OR, 1.97) increased significantly.

Data source: A retrospective cohort study involving 70,124 patients who had a positive FIT result and a follow-up colonoscopy during a 3-year period.

Disclosures: The National Cancer Institute supported the study. Dr. Corley reported receiving grant support from Wyeth/Pfizer.

Series supports viability of ambulatory laparoscopic sleeve gastrectomy

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– An ambulatory approach to laparoscopic sleeve gastrectomy is a safe and viable option to improve patient satisfaction and soften the economic blow of these procedures on patients, based on a large series at one surgery center in Cincinnati.

“With proper patient selection, utilization of enhanced recovery pathways with an overall low readmission rate and the complication profile point to the feasibility of laparoscopic sleeve gastrectomy [LSG] as a safe outpatient procedure,” said Sepehr Lalezari, MD, now a surgical fellow at Johns Hopkins University, Baltimore.

Dr. Sepehr Lalezari
Speaking at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons, Dr. Lalezari reported results from a retrospective review of 821 patients who had ambulatory LSG by a single surgeon from 2011 to 2015.

About 105,000 LSG operations were performed in the United States in 2015, representing 54% of all bariatric operations, according to the American Society for Metabolic and Bariatric Surgery.

Patient selection and strict adherence to protocols are keys to success for ambulatory LSG, Dr. Lalezari said. Suitable patients were found to be ambulatory, between ages 18 and 65 years; had a body mass index (BMI) less than 55 kg/m2 for males and less than 60 kg/m2 for females; weighed less than 500 lb; had an American Society of Anesthesiologists’ classification score less than 4; and had no significant cardiopulmonary impairment, had no history of renal failure or organ transplant, and were not on a transplant wait list.

In this series, 71% of patients (579) were female, and the average BMI was 43. The total complication rate was 2.3% (19); 17 of these patients required hospital admission.

Postoperative complications included gastric leaks (seven, 0.9%); intra-abdominal abscess requiring percutaneous drainage (four, 0.5%); dehydration, nausea, and/or vomiting (four, 0.5%); and one of each of the following: acute cholecystitis, postoperative bleeding, surgical site infection (SSI), and portal vein thrombosis/pulmonary embolism.

The two complications managed on an outpatient basis were the SSI and one intra-abdominal abscess, Dr. Lalezari said.

“The only readmissions in our series that could have been possibly prevented with an overnight stay in the hospital were the four cases of nausea, vomiting, and/or dehydration,” he said. “These only accounted for 0.5% of the total cases performed.”

The readmission rates for ambulatory LSG in this series compared favorably with large trials that did not distinguish between ambulatory and inpatient LSG procedures, Dr. Lalezari noted. A 2016 analysis of 35,655 patients in the American College of Surgeons National Surgical Quality Improvement Program database reported a readmission rate of 3.7% for LSG (Surg Endosc. 2016 Jun;30[6]:2342-50).

A larger study of 130,000 patients who had bariatric surgery reported an LSG readmission rate of 2.8% (Ann Surg. 2016 Nov 15. doi: 10.1097/SLA.0000000000002079). The most common cause for readmissions these trials reported were nausea, vomiting, and/or dehydration.

Bariatric surgeons have embraced enhanced recovery pathways and fast-track surgery, with good results, Dr. Lalezari said, citing work by Zhamak Khorgami, MD, and colleagues at the Cleveland Clinic (Surg Obes Relat Dis. 2017 Feb;13[2]:273-80).

“Looking at fast-track surgery, they found that patients discharged on postoperative day 1 vs. day 2 or 3 did not change outcomes”; those discharged later than postoperative day 1 trended toward a higher readmission rate of 2.8% vs. 3.6%, Dr. Lalezari said.

The enhanced recovery/fast track protocol Dr. Lalezari and his coauthors used involves placing intravenous lines and infusing 1 L crystalloid before starting the procedure, and administration of famotidine and metoclopramide prior to anesthesia. The protocol utilizes sequential compression devices and avoids Foley catheters and intra-abdominal drains. Patients receive dexamethasone and ondansetron during the operation. The protocol emphasizes early ambulation and resumption of oral intake.

The operation uses a 36-French bougie starting about 5 cm from the pylorus, and all staple lines are reinforced with buttress material. At the end of the surgery, all incisions are infiltrated with 30 cc of 0.5% bupivacaine with epinephrine.

Patients are ambulating about 90 minutes after surgery and are monitored for 3-4 hours. They receive a total volume of 3-4 L crystalloids. When they’re tolerating clear liquids, voiding spontaneously, and walking independently, and their pain is well controlled (pain score less than 5/10) and vital signs are within normal limits, they’re discharged.

Postoperative follow-up involves a call at 48 hours and in-clinic follow-up at weeks 1 and 4. Additional follow-up is scheduled at 3-month intervals for 1 year, then at 6 months for up to 2 years, and then yearly afterward.

“With proper patient selection and utilization of enhanced recovery pathways, the low overall readmission rate (2.1%) and complication profile (2.3%) in our series point to the feasibility of laparoscopic sleeve gastrectomy as a safe outpatient procedure,” Dr. Lalezari said.

He reported having no relevant financial disclosures.

 

 

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– An ambulatory approach to laparoscopic sleeve gastrectomy is a safe and viable option to improve patient satisfaction and soften the economic blow of these procedures on patients, based on a large series at one surgery center in Cincinnati.

“With proper patient selection, utilization of enhanced recovery pathways with an overall low readmission rate and the complication profile point to the feasibility of laparoscopic sleeve gastrectomy [LSG] as a safe outpatient procedure,” said Sepehr Lalezari, MD, now a surgical fellow at Johns Hopkins University, Baltimore.

Dr. Sepehr Lalezari
Speaking at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons, Dr. Lalezari reported results from a retrospective review of 821 patients who had ambulatory LSG by a single surgeon from 2011 to 2015.

About 105,000 LSG operations were performed in the United States in 2015, representing 54% of all bariatric operations, according to the American Society for Metabolic and Bariatric Surgery.

Patient selection and strict adherence to protocols are keys to success for ambulatory LSG, Dr. Lalezari said. Suitable patients were found to be ambulatory, between ages 18 and 65 years; had a body mass index (BMI) less than 55 kg/m2 for males and less than 60 kg/m2 for females; weighed less than 500 lb; had an American Society of Anesthesiologists’ classification score less than 4; and had no significant cardiopulmonary impairment, had no history of renal failure or organ transplant, and were not on a transplant wait list.

In this series, 71% of patients (579) were female, and the average BMI was 43. The total complication rate was 2.3% (19); 17 of these patients required hospital admission.

Postoperative complications included gastric leaks (seven, 0.9%); intra-abdominal abscess requiring percutaneous drainage (four, 0.5%); dehydration, nausea, and/or vomiting (four, 0.5%); and one of each of the following: acute cholecystitis, postoperative bleeding, surgical site infection (SSI), and portal vein thrombosis/pulmonary embolism.

The two complications managed on an outpatient basis were the SSI and one intra-abdominal abscess, Dr. Lalezari said.

“The only readmissions in our series that could have been possibly prevented with an overnight stay in the hospital were the four cases of nausea, vomiting, and/or dehydration,” he said. “These only accounted for 0.5% of the total cases performed.”

The readmission rates for ambulatory LSG in this series compared favorably with large trials that did not distinguish between ambulatory and inpatient LSG procedures, Dr. Lalezari noted. A 2016 analysis of 35,655 patients in the American College of Surgeons National Surgical Quality Improvement Program database reported a readmission rate of 3.7% for LSG (Surg Endosc. 2016 Jun;30[6]:2342-50).

A larger study of 130,000 patients who had bariatric surgery reported an LSG readmission rate of 2.8% (Ann Surg. 2016 Nov 15. doi: 10.1097/SLA.0000000000002079). The most common cause for readmissions these trials reported were nausea, vomiting, and/or dehydration.

Bariatric surgeons have embraced enhanced recovery pathways and fast-track surgery, with good results, Dr. Lalezari said, citing work by Zhamak Khorgami, MD, and colleagues at the Cleveland Clinic (Surg Obes Relat Dis. 2017 Feb;13[2]:273-80).

“Looking at fast-track surgery, they found that patients discharged on postoperative day 1 vs. day 2 or 3 did not change outcomes”; those discharged later than postoperative day 1 trended toward a higher readmission rate of 2.8% vs. 3.6%, Dr. Lalezari said.

The enhanced recovery/fast track protocol Dr. Lalezari and his coauthors used involves placing intravenous lines and infusing 1 L crystalloid before starting the procedure, and administration of famotidine and metoclopramide prior to anesthesia. The protocol utilizes sequential compression devices and avoids Foley catheters and intra-abdominal drains. Patients receive dexamethasone and ondansetron during the operation. The protocol emphasizes early ambulation and resumption of oral intake.

The operation uses a 36-French bougie starting about 5 cm from the pylorus, and all staple lines are reinforced with buttress material. At the end of the surgery, all incisions are infiltrated with 30 cc of 0.5% bupivacaine with epinephrine.

Patients are ambulating about 90 minutes after surgery and are monitored for 3-4 hours. They receive a total volume of 3-4 L crystalloids. When they’re tolerating clear liquids, voiding spontaneously, and walking independently, and their pain is well controlled (pain score less than 5/10) and vital signs are within normal limits, they’re discharged.

Postoperative follow-up involves a call at 48 hours and in-clinic follow-up at weeks 1 and 4. Additional follow-up is scheduled at 3-month intervals for 1 year, then at 6 months for up to 2 years, and then yearly afterward.

“With proper patient selection and utilization of enhanced recovery pathways, the low overall readmission rate (2.1%) and complication profile (2.3%) in our series point to the feasibility of laparoscopic sleeve gastrectomy as a safe outpatient procedure,” Dr. Lalezari said.

He reported having no relevant financial disclosures.

 

 

 

– An ambulatory approach to laparoscopic sleeve gastrectomy is a safe and viable option to improve patient satisfaction and soften the economic blow of these procedures on patients, based on a large series at one surgery center in Cincinnati.

“With proper patient selection, utilization of enhanced recovery pathways with an overall low readmission rate and the complication profile point to the feasibility of laparoscopic sleeve gastrectomy [LSG] as a safe outpatient procedure,” said Sepehr Lalezari, MD, now a surgical fellow at Johns Hopkins University, Baltimore.

Dr. Sepehr Lalezari
Speaking at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons, Dr. Lalezari reported results from a retrospective review of 821 patients who had ambulatory LSG by a single surgeon from 2011 to 2015.

About 105,000 LSG operations were performed in the United States in 2015, representing 54% of all bariatric operations, according to the American Society for Metabolic and Bariatric Surgery.

Patient selection and strict adherence to protocols are keys to success for ambulatory LSG, Dr. Lalezari said. Suitable patients were found to be ambulatory, between ages 18 and 65 years; had a body mass index (BMI) less than 55 kg/m2 for males and less than 60 kg/m2 for females; weighed less than 500 lb; had an American Society of Anesthesiologists’ classification score less than 4; and had no significant cardiopulmonary impairment, had no history of renal failure or organ transplant, and were not on a transplant wait list.

In this series, 71% of patients (579) were female, and the average BMI was 43. The total complication rate was 2.3% (19); 17 of these patients required hospital admission.

Postoperative complications included gastric leaks (seven, 0.9%); intra-abdominal abscess requiring percutaneous drainage (four, 0.5%); dehydration, nausea, and/or vomiting (four, 0.5%); and one of each of the following: acute cholecystitis, postoperative bleeding, surgical site infection (SSI), and portal vein thrombosis/pulmonary embolism.

The two complications managed on an outpatient basis were the SSI and one intra-abdominal abscess, Dr. Lalezari said.

“The only readmissions in our series that could have been possibly prevented with an overnight stay in the hospital were the four cases of nausea, vomiting, and/or dehydration,” he said. “These only accounted for 0.5% of the total cases performed.”

The readmission rates for ambulatory LSG in this series compared favorably with large trials that did not distinguish between ambulatory and inpatient LSG procedures, Dr. Lalezari noted. A 2016 analysis of 35,655 patients in the American College of Surgeons National Surgical Quality Improvement Program database reported a readmission rate of 3.7% for LSG (Surg Endosc. 2016 Jun;30[6]:2342-50).

A larger study of 130,000 patients who had bariatric surgery reported an LSG readmission rate of 2.8% (Ann Surg. 2016 Nov 15. doi: 10.1097/SLA.0000000000002079). The most common cause for readmissions these trials reported were nausea, vomiting, and/or dehydration.

Bariatric surgeons have embraced enhanced recovery pathways and fast-track surgery, with good results, Dr. Lalezari said, citing work by Zhamak Khorgami, MD, and colleagues at the Cleveland Clinic (Surg Obes Relat Dis. 2017 Feb;13[2]:273-80).

“Looking at fast-track surgery, they found that patients discharged on postoperative day 1 vs. day 2 or 3 did not change outcomes”; those discharged later than postoperative day 1 trended toward a higher readmission rate of 2.8% vs. 3.6%, Dr. Lalezari said.

The enhanced recovery/fast track protocol Dr. Lalezari and his coauthors used involves placing intravenous lines and infusing 1 L crystalloid before starting the procedure, and administration of famotidine and metoclopramide prior to anesthesia. The protocol utilizes sequential compression devices and avoids Foley catheters and intra-abdominal drains. Patients receive dexamethasone and ondansetron during the operation. The protocol emphasizes early ambulation and resumption of oral intake.

The operation uses a 36-French bougie starting about 5 cm from the pylorus, and all staple lines are reinforced with buttress material. At the end of the surgery, all incisions are infiltrated with 30 cc of 0.5% bupivacaine with epinephrine.

Patients are ambulating about 90 minutes after surgery and are monitored for 3-4 hours. They receive a total volume of 3-4 L crystalloids. When they’re tolerating clear liquids, voiding spontaneously, and walking independently, and their pain is well controlled (pain score less than 5/10) and vital signs are within normal limits, they’re discharged.

Postoperative follow-up involves a call at 48 hours and in-clinic follow-up at weeks 1 and 4. Additional follow-up is scheduled at 3-month intervals for 1 year, then at 6 months for up to 2 years, and then yearly afterward.

“With proper patient selection and utilization of enhanced recovery pathways, the low overall readmission rate (2.1%) and complication profile (2.3%) in our series point to the feasibility of laparoscopic sleeve gastrectomy as a safe outpatient procedure,” Dr. Lalezari said.

He reported having no relevant financial disclosures.

 

 

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Key clinical point: Laparoscopic sleeve gastrectomy is a safe outpatient procedure – with strict adherence to enhanced recovery pathways and fast-track protocols.

Major finding: This series reported an overall readmission rate of 2.1% and a complication rate of 2.3% in patients who had outpatient LSG.

Data source: A retrospective review of 821 patients who had ambulatory LSG by a single surgeon from 2011 to 2015.

Disclosures: Dr. Lalezari reported having no relevant financial disclosures.

VIDEO: Stroke risk in women deserves greater attention

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BOSTON – Texas neurologist Louise McCullough, MD, PhD, is determined to help women live longer by urging neurologists to focus on the unique risks and needs involved.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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BOSTON – Texas neurologist Louise McCullough, MD, PhD, is determined to help women live longer by urging neurologists to focus on the unique risks and needs involved.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

 

BOSTON – Texas neurologist Louise McCullough, MD, PhD, is determined to help women live longer by urging neurologists to focus on the unique risks and needs involved.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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The challenges of dating

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Dating during residency is a job unto itself – one that I didn’t expect to balance alongside my long and frequently odd hours of work. To make matters worse, I happen to be in a field where the examination is almost entirely through conversation, involving probing questions, where maintaining calm and strength is important in the face of patient stories that often tear at my heart. Then, on a date (first or otherwise) I spend more time listening to another person’s stories while trying hard not to interpret the information through the perspective of my profession. To orient my older readers, I primarily date using the Internet and dating applications. There, my profile names me as “Resident.” This title is unassuming and unintimidating. Resident of what, potential suitors wonder, while examining carefully curated pictures of travel to exotic places and of me smiling happily with friends. I swipe right and left, matching with people, chatting digitally at first, and, if there is mutual interest, arranging to meet in person.

I get a different reaction every time I tell a date I’m a psychiatrist. It seems each man has his own expectations of what it means to date a psychiatrist. This column is a shout-out to all the physicians, and especially psychiatrists, who have been single while practicing, required to pretend our work is just like everyone else’s. Because the truth is, our work is different. How can one really describe the goings-on at a psychiatric hospital to a potential partner? Or deal with fatigue that accompanies listening to emotional suffering while at work and then needing the energy to commiserate with the person across the table?

Dr. Jacqueline Posada
Dr. Jacqueline Posada
Two personal dating experiences highlight these challenges. Some time ago, I went out with a guy for just 2 weeks. It was nice, but not what I wanted, so I broke it off. His response to me: “I thought you really understood me. You seemed like you wanted to know me. Only a psychiatrist could be so cruel.” I didn’t think I was cruel, and I don’t know how well I understood him – or why he got that impression. Perhaps I do ask more intense questions earlier on in conversation than others might? Indeed, my profession requires accessing deep truths about people’s lives in a short period of time. After a day of hearing these real stories, I don’t want to exchange small talk. I want to know the person I’m sharing a meal with.

The second experience prompted this column – a recent breakup with a man I really felt and thought I could be with. I had begun perusing fellowships in the cities where he wanted to move. Perhaps predictably, my heart was broken. I am grateful to have a specialty that encourages a close connection to my patients. I am privileged to see and consider the motives, desires, fantasies, and fears of my patients. For dating, however, this skill is excessively fine tuned. I sense too subtly when something is going wrong. As a therapist in training, I am learning to hear the manifest content and listen for the latent content. I felt it with this man, despite knowing that he liked me and was serious about our relationship. I sensed the change in his approach to me – the transference, if you will. I suspected the reason was his stated desire to move to the West Coast “eventually.” When he actually revealed his plan to move and end the relationship, however, I cried as someone who has been hurt would cry. His response was: “ It will be okay. ... You’re supereligible. … Don’t cry. ... I’m surprised by all your emotion – especially the way you describe yourself at work.” He expected me to have control over my emotions because of my profession.

Psychiatrists are trained to examine emotions and behaviors, characterize them first as symptoms, then as diagnoses, and finally assess the best way to intervene. The emotions of my patients sometime get tangled with my own. I try to disentangle myself through my own therapy, and filling my life with productive activities and close friends. However, I think as a young, single psychiatrist, I have a space of loneliness that is too easily filled by the pain shared by my patients. I also expect better control over my emotions, but sometimes, my cup is already full, and all it can do is overflow with tears.
 

Dr. Posada is a second-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.

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Dating during residency is a job unto itself – one that I didn’t expect to balance alongside my long and frequently odd hours of work. To make matters worse, I happen to be in a field where the examination is almost entirely through conversation, involving probing questions, where maintaining calm and strength is important in the face of patient stories that often tear at my heart. Then, on a date (first or otherwise) I spend more time listening to another person’s stories while trying hard not to interpret the information through the perspective of my profession. To orient my older readers, I primarily date using the Internet and dating applications. There, my profile names me as “Resident.” This title is unassuming and unintimidating. Resident of what, potential suitors wonder, while examining carefully curated pictures of travel to exotic places and of me smiling happily with friends. I swipe right and left, matching with people, chatting digitally at first, and, if there is mutual interest, arranging to meet in person.

I get a different reaction every time I tell a date I’m a psychiatrist. It seems each man has his own expectations of what it means to date a psychiatrist. This column is a shout-out to all the physicians, and especially psychiatrists, who have been single while practicing, required to pretend our work is just like everyone else’s. Because the truth is, our work is different. How can one really describe the goings-on at a psychiatric hospital to a potential partner? Or deal with fatigue that accompanies listening to emotional suffering while at work and then needing the energy to commiserate with the person across the table?

Dr. Jacqueline Posada
Dr. Jacqueline Posada
Two personal dating experiences highlight these challenges. Some time ago, I went out with a guy for just 2 weeks. It was nice, but not what I wanted, so I broke it off. His response to me: “I thought you really understood me. You seemed like you wanted to know me. Only a psychiatrist could be so cruel.” I didn’t think I was cruel, and I don’t know how well I understood him – or why he got that impression. Perhaps I do ask more intense questions earlier on in conversation than others might? Indeed, my profession requires accessing deep truths about people’s lives in a short period of time. After a day of hearing these real stories, I don’t want to exchange small talk. I want to know the person I’m sharing a meal with.

The second experience prompted this column – a recent breakup with a man I really felt and thought I could be with. I had begun perusing fellowships in the cities where he wanted to move. Perhaps predictably, my heart was broken. I am grateful to have a specialty that encourages a close connection to my patients. I am privileged to see and consider the motives, desires, fantasies, and fears of my patients. For dating, however, this skill is excessively fine tuned. I sense too subtly when something is going wrong. As a therapist in training, I am learning to hear the manifest content and listen for the latent content. I felt it with this man, despite knowing that he liked me and was serious about our relationship. I sensed the change in his approach to me – the transference, if you will. I suspected the reason was his stated desire to move to the West Coast “eventually.” When he actually revealed his plan to move and end the relationship, however, I cried as someone who has been hurt would cry. His response was: “ It will be okay. ... You’re supereligible. … Don’t cry. ... I’m surprised by all your emotion – especially the way you describe yourself at work.” He expected me to have control over my emotions because of my profession.

Psychiatrists are trained to examine emotions and behaviors, characterize them first as symptoms, then as diagnoses, and finally assess the best way to intervene. The emotions of my patients sometime get tangled with my own. I try to disentangle myself through my own therapy, and filling my life with productive activities and close friends. However, I think as a young, single psychiatrist, I have a space of loneliness that is too easily filled by the pain shared by my patients. I also expect better control over my emotions, but sometimes, my cup is already full, and all it can do is overflow with tears.
 

Dr. Posada is a second-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.

 

Dating during residency is a job unto itself – one that I didn’t expect to balance alongside my long and frequently odd hours of work. To make matters worse, I happen to be in a field where the examination is almost entirely through conversation, involving probing questions, where maintaining calm and strength is important in the face of patient stories that often tear at my heart. Then, on a date (first or otherwise) I spend more time listening to another person’s stories while trying hard not to interpret the information through the perspective of my profession. To orient my older readers, I primarily date using the Internet and dating applications. There, my profile names me as “Resident.” This title is unassuming and unintimidating. Resident of what, potential suitors wonder, while examining carefully curated pictures of travel to exotic places and of me smiling happily with friends. I swipe right and left, matching with people, chatting digitally at first, and, if there is mutual interest, arranging to meet in person.

I get a different reaction every time I tell a date I’m a psychiatrist. It seems each man has his own expectations of what it means to date a psychiatrist. This column is a shout-out to all the physicians, and especially psychiatrists, who have been single while practicing, required to pretend our work is just like everyone else’s. Because the truth is, our work is different. How can one really describe the goings-on at a psychiatric hospital to a potential partner? Or deal with fatigue that accompanies listening to emotional suffering while at work and then needing the energy to commiserate with the person across the table?

Dr. Jacqueline Posada
Dr. Jacqueline Posada
Two personal dating experiences highlight these challenges. Some time ago, I went out with a guy for just 2 weeks. It was nice, but not what I wanted, so I broke it off. His response to me: “I thought you really understood me. You seemed like you wanted to know me. Only a psychiatrist could be so cruel.” I didn’t think I was cruel, and I don’t know how well I understood him – or why he got that impression. Perhaps I do ask more intense questions earlier on in conversation than others might? Indeed, my profession requires accessing deep truths about people’s lives in a short period of time. After a day of hearing these real stories, I don’t want to exchange small talk. I want to know the person I’m sharing a meal with.

The second experience prompted this column – a recent breakup with a man I really felt and thought I could be with. I had begun perusing fellowships in the cities where he wanted to move. Perhaps predictably, my heart was broken. I am grateful to have a specialty that encourages a close connection to my patients. I am privileged to see and consider the motives, desires, fantasies, and fears of my patients. For dating, however, this skill is excessively fine tuned. I sense too subtly when something is going wrong. As a therapist in training, I am learning to hear the manifest content and listen for the latent content. I felt it with this man, despite knowing that he liked me and was serious about our relationship. I sensed the change in his approach to me – the transference, if you will. I suspected the reason was his stated desire to move to the West Coast “eventually.” When he actually revealed his plan to move and end the relationship, however, I cried as someone who has been hurt would cry. His response was: “ It will be okay. ... You’re supereligible. … Don’t cry. ... I’m surprised by all your emotion – especially the way you describe yourself at work.” He expected me to have control over my emotions because of my profession.

Psychiatrists are trained to examine emotions and behaviors, characterize them first as symptoms, then as diagnoses, and finally assess the best way to intervene. The emotions of my patients sometime get tangled with my own. I try to disentangle myself through my own therapy, and filling my life with productive activities and close friends. However, I think as a young, single psychiatrist, I have a space of loneliness that is too easily filled by the pain shared by my patients. I also expect better control over my emotions, but sometimes, my cup is already full, and all it can do is overflow with tears.
 

Dr. Posada is a second-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.

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Can Posttraumatic Headache Characteristics Inform Prognosis and Treatment?

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Mon, 01/07/2019 - 10:29
Soldiers with continuous, holocephalic headaches after a traumatic brain injury may be less likely to return to duty.

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Alan G. Finkel, MD

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

 

 

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

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Soldiers with continuous, holocephalic headaches after a traumatic brain injury may be less likely to return to duty.
Soldiers with continuous, holocephalic headaches after a traumatic brain injury may be less likely to return to duty.

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Alan G. Finkel, MD

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

 

 

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Alan G. Finkel, MD

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

 

 

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

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What Is the Optimal Number of Antiplatelet Agents for Preventing Recurrent Stroke?

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Changed
Mon, 01/07/2019 - 10:29
Administering three antiplatelet drugs may provide no added benefit, compared with two antiplatelet agents.

HOUSTON—Although dual antiplatelet therapy provides a greater reduction in the risk of recurrent stroke than does antiplatelet monotherapy, adding a third agent may not increase the benefit, according to research presented at the International Stroke Conference 2017. Administering three antiplatelet agents does, however, increase the risk of bleeding, compared with dual antiplatelet therapy.

In 2012 and 2013, literature reviews suggested that the risk of recurrent stroke was reduced among patients who received two antiplatelet agents, compared with patients who received a single antiplatelet agent. These analyses prompted the question of whether triple antiplatelet therapy would provide a further risk reduction.

To examine this question, Philip Bath, MD, Chair of the Division of Clinical Neuroscience at the University of Nottingham, United Kingdom, and colleagues designed the Triple Antiplatelets for Reducing Dependency After Ischemic Stroke (TARDIS) trial. The researchers randomized patients with acute ischemic stroke or transient ischemic attack (TIA) to intensive therapy (ie, triple antiplatelet therapy) or standard of care (ie, dual antiplatelet therapy) for one month. After 30 days, all patients received standard of care. The study’s primary outcome was recurrent stroke or TIA at 90 days. Eligible patients entered the study within 48 hours of their index event, and patients with any level of stroke severity were accepted.

Philip Bath, MD

The investigators administered aspirin, clopidogrel, and dipyridamole to participants at standard doses. At the beginning of the trial, UK guidelines recommended the combination of aspirin and dipyridamole as first-line treatment for prevention of recurrent stroke. In 2010, the National Institute for Health and Care Excellence changed the guideline to recommend clopidogrel alone as first-line treatment. Dr. Bath and colleagues changed the treatment given to their standard-of-care group accordingly.

The researchers intended to enroll 4,100 participants, but ended the trial early on the recommendation of the data-monitoring committee. In all, 3,096 patients were enrolled. Their average age was 69. Approximately 63% of the population was male. The average time of stroke or TIA onset was 29 hours before enrollment. About one-third of patients had been taking antiplatelet therapy at baseline.

Dr. Bath and colleagues found no difference in the rate of recurrent stroke or TIA between treatment groups. Subgroup analysis found that people with an NIH Stroke Scale (NIHSS) score of 3 or lower at baseline tended to benefit from intensive therapy. Standard of care, however, tended to be superior for patients with an NIHSS score greater than 3. In addition, intensive therapy tended to be superior to the combination of aspirin and dipyridamole, but inferior to clopidogrel. Intensive therapy also was associated with significantly more bleeding and more severe bleeding.

Erik Greb

Suggested Reading

Geeganage CM, Diener HC, Algra A, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012;43(4):1058-1066.

TARDIS Trial Investigators, Krishnan K, Beridze M, et al. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388). Int J Stroke. 2015;10(7):1159-1165.

Wong KS, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation. 2013;128(15):1656-1666.

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Administering three antiplatelet drugs may provide no added benefit, compared with two antiplatelet agents.
Administering three antiplatelet drugs may provide no added benefit, compared with two antiplatelet agents.

HOUSTON—Although dual antiplatelet therapy provides a greater reduction in the risk of recurrent stroke than does antiplatelet monotherapy, adding a third agent may not increase the benefit, according to research presented at the International Stroke Conference 2017. Administering three antiplatelet agents does, however, increase the risk of bleeding, compared with dual antiplatelet therapy.

In 2012 and 2013, literature reviews suggested that the risk of recurrent stroke was reduced among patients who received two antiplatelet agents, compared with patients who received a single antiplatelet agent. These analyses prompted the question of whether triple antiplatelet therapy would provide a further risk reduction.

To examine this question, Philip Bath, MD, Chair of the Division of Clinical Neuroscience at the University of Nottingham, United Kingdom, and colleagues designed the Triple Antiplatelets for Reducing Dependency After Ischemic Stroke (TARDIS) trial. The researchers randomized patients with acute ischemic stroke or transient ischemic attack (TIA) to intensive therapy (ie, triple antiplatelet therapy) or standard of care (ie, dual antiplatelet therapy) for one month. After 30 days, all patients received standard of care. The study’s primary outcome was recurrent stroke or TIA at 90 days. Eligible patients entered the study within 48 hours of their index event, and patients with any level of stroke severity were accepted.

Philip Bath, MD

The investigators administered aspirin, clopidogrel, and dipyridamole to participants at standard doses. At the beginning of the trial, UK guidelines recommended the combination of aspirin and dipyridamole as first-line treatment for prevention of recurrent stroke. In 2010, the National Institute for Health and Care Excellence changed the guideline to recommend clopidogrel alone as first-line treatment. Dr. Bath and colleagues changed the treatment given to their standard-of-care group accordingly.

The researchers intended to enroll 4,100 participants, but ended the trial early on the recommendation of the data-monitoring committee. In all, 3,096 patients were enrolled. Their average age was 69. Approximately 63% of the population was male. The average time of stroke or TIA onset was 29 hours before enrollment. About one-third of patients had been taking antiplatelet therapy at baseline.

Dr. Bath and colleagues found no difference in the rate of recurrent stroke or TIA between treatment groups. Subgroup analysis found that people with an NIH Stroke Scale (NIHSS) score of 3 or lower at baseline tended to benefit from intensive therapy. Standard of care, however, tended to be superior for patients with an NIHSS score greater than 3. In addition, intensive therapy tended to be superior to the combination of aspirin and dipyridamole, but inferior to clopidogrel. Intensive therapy also was associated with significantly more bleeding and more severe bleeding.

Erik Greb

Suggested Reading

Geeganage CM, Diener HC, Algra A, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012;43(4):1058-1066.

TARDIS Trial Investigators, Krishnan K, Beridze M, et al. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388). Int J Stroke. 2015;10(7):1159-1165.

Wong KS, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation. 2013;128(15):1656-1666.

HOUSTON—Although dual antiplatelet therapy provides a greater reduction in the risk of recurrent stroke than does antiplatelet monotherapy, adding a third agent may not increase the benefit, according to research presented at the International Stroke Conference 2017. Administering three antiplatelet agents does, however, increase the risk of bleeding, compared with dual antiplatelet therapy.

In 2012 and 2013, literature reviews suggested that the risk of recurrent stroke was reduced among patients who received two antiplatelet agents, compared with patients who received a single antiplatelet agent. These analyses prompted the question of whether triple antiplatelet therapy would provide a further risk reduction.

To examine this question, Philip Bath, MD, Chair of the Division of Clinical Neuroscience at the University of Nottingham, United Kingdom, and colleagues designed the Triple Antiplatelets for Reducing Dependency After Ischemic Stroke (TARDIS) trial. The researchers randomized patients with acute ischemic stroke or transient ischemic attack (TIA) to intensive therapy (ie, triple antiplatelet therapy) or standard of care (ie, dual antiplatelet therapy) for one month. After 30 days, all patients received standard of care. The study’s primary outcome was recurrent stroke or TIA at 90 days. Eligible patients entered the study within 48 hours of their index event, and patients with any level of stroke severity were accepted.

Philip Bath, MD

The investigators administered aspirin, clopidogrel, and dipyridamole to participants at standard doses. At the beginning of the trial, UK guidelines recommended the combination of aspirin and dipyridamole as first-line treatment for prevention of recurrent stroke. In 2010, the National Institute for Health and Care Excellence changed the guideline to recommend clopidogrel alone as first-line treatment. Dr. Bath and colleagues changed the treatment given to their standard-of-care group accordingly.

The researchers intended to enroll 4,100 participants, but ended the trial early on the recommendation of the data-monitoring committee. In all, 3,096 patients were enrolled. Their average age was 69. Approximately 63% of the population was male. The average time of stroke or TIA onset was 29 hours before enrollment. About one-third of patients had been taking antiplatelet therapy at baseline.

Dr. Bath and colleagues found no difference in the rate of recurrent stroke or TIA between treatment groups. Subgroup analysis found that people with an NIH Stroke Scale (NIHSS) score of 3 or lower at baseline tended to benefit from intensive therapy. Standard of care, however, tended to be superior for patients with an NIHSS score greater than 3. In addition, intensive therapy tended to be superior to the combination of aspirin and dipyridamole, but inferior to clopidogrel. Intensive therapy also was associated with significantly more bleeding and more severe bleeding.

Erik Greb

Suggested Reading

Geeganage CM, Diener HC, Algra A, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012;43(4):1058-1066.

TARDIS Trial Investigators, Krishnan K, Beridze M, et al. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388). Int J Stroke. 2015;10(7):1159-1165.

Wong KS, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation. 2013;128(15):1656-1666.

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Vaccine for Respiratory Syncytial Virus Enters Phase 1 Testing

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The vaccine DS-CAv1 aims to fill a void in the prevention and treatment of respiratory syncytial virus.

A vaccine against respiratory syncytial virus (RSV) is entering a phase 1 safety and tolerability trial. The vaccine developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) is badly needed, according to Anthony Fauci, MD, director of NIAID. Although common and causing usually mild symptoms RSV infection also can lead to severe lower respiratory tract diseases, such as pneumonia and bronchiolitis in infants, children, the elderly, and immune-compromised patients. Globally, RSV infections cause upwards of 250,000 deaths each year. “RSV is underappreciated as a major cause of illness and death,” Fauci said.  

The vaccine (DS-Cav1) will fill a void. Currently no vaccine is available to prevent RSV infection, and no drug is available to treat it. The monoclonal antibody palivizumab is approved for preventing lower respiratory tract disease caused by RSV in high-risk children, but is not approved for use in the general population.

The study, VRC 317, will enroll healthy adults aged 18 to 50. Participants will be assigned randomly to receive 2 injections 12 weeks apart with the investigational vaccine or the investigational vaccine with alum, a compound commonly added to vaccines to enhance the immune response.

Participants also will be randomly assigned to receive 1 of 3 doses (50, 150, or 500 μg) at both time points. To start, 5 people will receive the 50-µg dose. If they experience no serious adverse reactions attributable to the vaccine the other participants will be vaccinated with the higher doses.

The participants will return for 12 clinic visits over 44 weeks  when researchers will conduct physical exams, collect blood samples, and test mucous samples to measure the immune response.

DS-Cav1 is the result of “years of research” at the Vaccine Research Center, the NIH says. Traditionally a vaccine is derived from a weakened or inactivated whole virus. By contrast, DS-Cav1 is a single, structurally engineered protein from the surface of RSV. Co-lead investigator Barney Graham, MD, PhD, deputy VRC director, says, “This work represents how new biological insights from basic research can lead to candidate vaccines for diseases of public health importance.”

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The vaccine DS-CAv1 aims to fill a void in the prevention and treatment of respiratory syncytial virus.
The vaccine DS-CAv1 aims to fill a void in the prevention and treatment of respiratory syncytial virus.

A vaccine against respiratory syncytial virus (RSV) is entering a phase 1 safety and tolerability trial. The vaccine developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) is badly needed, according to Anthony Fauci, MD, director of NIAID. Although common and causing usually mild symptoms RSV infection also can lead to severe lower respiratory tract diseases, such as pneumonia and bronchiolitis in infants, children, the elderly, and immune-compromised patients. Globally, RSV infections cause upwards of 250,000 deaths each year. “RSV is underappreciated as a major cause of illness and death,” Fauci said.  

The vaccine (DS-Cav1) will fill a void. Currently no vaccine is available to prevent RSV infection, and no drug is available to treat it. The monoclonal antibody palivizumab is approved for preventing lower respiratory tract disease caused by RSV in high-risk children, but is not approved for use in the general population.

The study, VRC 317, will enroll healthy adults aged 18 to 50. Participants will be assigned randomly to receive 2 injections 12 weeks apart with the investigational vaccine or the investigational vaccine with alum, a compound commonly added to vaccines to enhance the immune response.

Participants also will be randomly assigned to receive 1 of 3 doses (50, 150, or 500 μg) at both time points. To start, 5 people will receive the 50-µg dose. If they experience no serious adverse reactions attributable to the vaccine the other participants will be vaccinated with the higher doses.

The participants will return for 12 clinic visits over 44 weeks  when researchers will conduct physical exams, collect blood samples, and test mucous samples to measure the immune response.

DS-Cav1 is the result of “years of research” at the Vaccine Research Center, the NIH says. Traditionally a vaccine is derived from a weakened or inactivated whole virus. By contrast, DS-Cav1 is a single, structurally engineered protein from the surface of RSV. Co-lead investigator Barney Graham, MD, PhD, deputy VRC director, says, “This work represents how new biological insights from basic research can lead to candidate vaccines for diseases of public health importance.”

A vaccine against respiratory syncytial virus (RSV) is entering a phase 1 safety and tolerability trial. The vaccine developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) is badly needed, according to Anthony Fauci, MD, director of NIAID. Although common and causing usually mild symptoms RSV infection also can lead to severe lower respiratory tract diseases, such as pneumonia and bronchiolitis in infants, children, the elderly, and immune-compromised patients. Globally, RSV infections cause upwards of 250,000 deaths each year. “RSV is underappreciated as a major cause of illness and death,” Fauci said.  

The vaccine (DS-Cav1) will fill a void. Currently no vaccine is available to prevent RSV infection, and no drug is available to treat it. The monoclonal antibody palivizumab is approved for preventing lower respiratory tract disease caused by RSV in high-risk children, but is not approved for use in the general population.

The study, VRC 317, will enroll healthy adults aged 18 to 50. Participants will be assigned randomly to receive 2 injections 12 weeks apart with the investigational vaccine or the investigational vaccine with alum, a compound commonly added to vaccines to enhance the immune response.

Participants also will be randomly assigned to receive 1 of 3 doses (50, 150, or 500 μg) at both time points. To start, 5 people will receive the 50-µg dose. If they experience no serious adverse reactions attributable to the vaccine the other participants will be vaccinated with the higher doses.

The participants will return for 12 clinic visits over 44 weeks  when researchers will conduct physical exams, collect blood samples, and test mucous samples to measure the immune response.

DS-Cav1 is the result of “years of research” at the Vaccine Research Center, the NIH says. Traditionally a vaccine is derived from a weakened or inactivated whole virus. By contrast, DS-Cav1 is a single, structurally engineered protein from the surface of RSV. Co-lead investigator Barney Graham, MD, PhD, deputy VRC director, says, “This work represents how new biological insights from basic research can lead to candidate vaccines for diseases of public health importance.”

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WES misses genes associated with leukemia, other diseases

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WES misses genes associated with leukemia, other diseases

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Whole-exome sequencing (WES) may routinely miss genetic variations associated with leukemia and other diseases, according to research published in Scientific Reports.

The study revealed 832 genes that have low coverage across multiple WES platforms.

These genes are associated with leukemia, psoriasis, heart failure, and other diseases, and they may be missed by researchers using WES to study these diseases.

“Although it was known that coverage—the average number of times a given piece of DNA is read during sequencing—could be uneven in whole-exome sequencing, our new methods are the first to really quantify this,” said study author Santhosh Girirajan, MBBS, PhD, of The Pennsylvania State University, University Park.

“Adequate coverage—often as many as 70 or more reads for each piece of DNA—increases our confidence that the sequence is accurate, and, without it, it is nearly impossible to make confident predictions about the relationship between a mutation in a gene and a disease.”

“In our study, we found 832 genes that have systematically low coverage across 3 different sequencing platforms, meaning that these genes would be missed in disease studies.”

The researchers said low-coverage regions may result from limited precision in WES technologies due to certain genomic features.

Highly repetitive stretches of DNA can prevent the sequencer from reading the DNA properly. The study showed that at least 60% of low-coverage genes occur near DNA repeats.

“One solution to this problem is for researchers to use whole-genome sequencing, which examines all base pairs of DNA instead of just the regions that contain genes,” Dr Girirajan said. “Our study found that whole-genome data had significantly fewer low-coverage genes than whole-exome data, and its coverage is more uniformly distributed across all parts of the genome.”

“However, the costs of whole-exome sequencing are still significantly lower than whole-genome sequencing. Until the costs of whole-genome sequencing is no longer a barrier, human genetics researchers should be aware of these limitations in whole-exome sequencing technologies.”

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Image by Spencer Phillips
DNA helix

Whole-exome sequencing (WES) may routinely miss genetic variations associated with leukemia and other diseases, according to research published in Scientific Reports.

The study revealed 832 genes that have low coverage across multiple WES platforms.

These genes are associated with leukemia, psoriasis, heart failure, and other diseases, and they may be missed by researchers using WES to study these diseases.

“Although it was known that coverage—the average number of times a given piece of DNA is read during sequencing—could be uneven in whole-exome sequencing, our new methods are the first to really quantify this,” said study author Santhosh Girirajan, MBBS, PhD, of The Pennsylvania State University, University Park.

“Adequate coverage—often as many as 70 or more reads for each piece of DNA—increases our confidence that the sequence is accurate, and, without it, it is nearly impossible to make confident predictions about the relationship between a mutation in a gene and a disease.”

“In our study, we found 832 genes that have systematically low coverage across 3 different sequencing platforms, meaning that these genes would be missed in disease studies.”

The researchers said low-coverage regions may result from limited precision in WES technologies due to certain genomic features.

Highly repetitive stretches of DNA can prevent the sequencer from reading the DNA properly. The study showed that at least 60% of low-coverage genes occur near DNA repeats.

“One solution to this problem is for researchers to use whole-genome sequencing, which examines all base pairs of DNA instead of just the regions that contain genes,” Dr Girirajan said. “Our study found that whole-genome data had significantly fewer low-coverage genes than whole-exome data, and its coverage is more uniformly distributed across all parts of the genome.”

“However, the costs of whole-exome sequencing are still significantly lower than whole-genome sequencing. Until the costs of whole-genome sequencing is no longer a barrier, human genetics researchers should be aware of these limitations in whole-exome sequencing technologies.”

Image by Spencer Phillips
DNA helix

Whole-exome sequencing (WES) may routinely miss genetic variations associated with leukemia and other diseases, according to research published in Scientific Reports.

The study revealed 832 genes that have low coverage across multiple WES platforms.

These genes are associated with leukemia, psoriasis, heart failure, and other diseases, and they may be missed by researchers using WES to study these diseases.

“Although it was known that coverage—the average number of times a given piece of DNA is read during sequencing—could be uneven in whole-exome sequencing, our new methods are the first to really quantify this,” said study author Santhosh Girirajan, MBBS, PhD, of The Pennsylvania State University, University Park.

“Adequate coverage—often as many as 70 or more reads for each piece of DNA—increases our confidence that the sequence is accurate, and, without it, it is nearly impossible to make confident predictions about the relationship between a mutation in a gene and a disease.”

“In our study, we found 832 genes that have systematically low coverage across 3 different sequencing platforms, meaning that these genes would be missed in disease studies.”

The researchers said low-coverage regions may result from limited precision in WES technologies due to certain genomic features.

Highly repetitive stretches of DNA can prevent the sequencer from reading the DNA properly. The study showed that at least 60% of low-coverage genes occur near DNA repeats.

“One solution to this problem is for researchers to use whole-genome sequencing, which examines all base pairs of DNA instead of just the regions that contain genes,” Dr Girirajan said. “Our study found that whole-genome data had significantly fewer low-coverage genes than whole-exome data, and its coverage is more uniformly distributed across all parts of the genome.”

“However, the costs of whole-exome sequencing are still significantly lower than whole-genome sequencing. Until the costs of whole-genome sequencing is no longer a barrier, human genetics researchers should be aware of these limitations in whole-exome sequencing technologies.”

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Study reveals ‘substantial’ malaria burden in US

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Malaria imposes a substantial disease burden in the US, according to researchers.

Their study indicates that malaria hospitalizations and deaths in the US are more common than generally appreciated, as a steady stream of travelers return home with the disease.

In fact, malaria hospitalizations and deaths exceeded hospitalizations and deaths from other travel-related illnesses and generated about half a billion dollars in healthcare costs over a 15-year period.

These findings were published in the American Journal of Tropical Medicine and Hygiene.

“It appears more and more Americans are traveling to areas where malaria is common, and many of them are not taking preventive measures, such as using antimalarial preventive medications and mosquito repellents, even though they are very effective at preventing infections,” said study author Diana Khuu, PhD, of the University of California, Los Angeles.

For this study, Dr Khuu and her colleagues looked for malaria patients in a database maintained by the federal Agency for Healthcare Research and Quality that tracks hospital admissions nationwide.

The researchers found that, between 2000 and 2014, 22,029 people were admitted to US hospitals due to complications from malaria, 4823 patients were diagnosed with severe malaria, and 182 of these patients died.

Most of the deaths and severe disease were linked to infections with the Plasmodium falciparum parasite. However, in almost half of the malaria-related hospitalizations, there was no indication of parasite type.

The majority of malaria hospitalizations occurred in the eastern US in states along the Atlantic seaboard, and men accounted for 60% of the malaria-related hospital admissions.

Malaria hospitalizations were more common in the US than hospitalizations for many other travel-associated diseases. For example, between 2000 and 2014, dengue fever generated an average of 259 hospitalizations a year (compared with 1489 for malaria).

The average cost of treating a malaria patient was $25,789, and the total bill for treating malaria patients in the US from 2000 to 2014 was about $555 million.

The researchers estimated that, each year, there are about 2100 people in the US suffering from malaria, since about 69% require hospital treatment.

That case count would exceed the high end of the official estimate from the US Centers for Disease Control and Prevention (CDC) of 1500 to 2000 cases per year.

Dr Khuu attributed the difference to the fact that the CDC’s malaria count is based on reports submitted to the agency by hospitals or physicians, and hospital admission records that were used in the current study may capture additional cases that have not been reported to CDC.

While those admissions records did not include travel history, the researchers believe the malaria infections they documented most likely were acquired during travel to parts of Africa, Asia, and Latin America, where malaria is still common.

However, Dr Khuu noted that mosquitoes capable of carrying malaria are common in many parts of the US. So increases in the number of travelers coming home with the disease increases the risk of malaria re-establishing itself in the US.

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Photo courtesy of CDC
Doctor and hospitalized patient

Malaria imposes a substantial disease burden in the US, according to researchers.

Their study indicates that malaria hospitalizations and deaths in the US are more common than generally appreciated, as a steady stream of travelers return home with the disease.

In fact, malaria hospitalizations and deaths exceeded hospitalizations and deaths from other travel-related illnesses and generated about half a billion dollars in healthcare costs over a 15-year period.

These findings were published in the American Journal of Tropical Medicine and Hygiene.

“It appears more and more Americans are traveling to areas where malaria is common, and many of them are not taking preventive measures, such as using antimalarial preventive medications and mosquito repellents, even though they are very effective at preventing infections,” said study author Diana Khuu, PhD, of the University of California, Los Angeles.

For this study, Dr Khuu and her colleagues looked for malaria patients in a database maintained by the federal Agency for Healthcare Research and Quality that tracks hospital admissions nationwide.

The researchers found that, between 2000 and 2014, 22,029 people were admitted to US hospitals due to complications from malaria, 4823 patients were diagnosed with severe malaria, and 182 of these patients died.

Most of the deaths and severe disease were linked to infections with the Plasmodium falciparum parasite. However, in almost half of the malaria-related hospitalizations, there was no indication of parasite type.

The majority of malaria hospitalizations occurred in the eastern US in states along the Atlantic seaboard, and men accounted for 60% of the malaria-related hospital admissions.

Malaria hospitalizations were more common in the US than hospitalizations for many other travel-associated diseases. For example, between 2000 and 2014, dengue fever generated an average of 259 hospitalizations a year (compared with 1489 for malaria).

The average cost of treating a malaria patient was $25,789, and the total bill for treating malaria patients in the US from 2000 to 2014 was about $555 million.

The researchers estimated that, each year, there are about 2100 people in the US suffering from malaria, since about 69% require hospital treatment.

That case count would exceed the high end of the official estimate from the US Centers for Disease Control and Prevention (CDC) of 1500 to 2000 cases per year.

Dr Khuu attributed the difference to the fact that the CDC’s malaria count is based on reports submitted to the agency by hospitals or physicians, and hospital admission records that were used in the current study may capture additional cases that have not been reported to CDC.

While those admissions records did not include travel history, the researchers believe the malaria infections they documented most likely were acquired during travel to parts of Africa, Asia, and Latin America, where malaria is still common.

However, Dr Khuu noted that mosquitoes capable of carrying malaria are common in many parts of the US. So increases in the number of travelers coming home with the disease increases the risk of malaria re-establishing itself in the US.

Photo courtesy of CDC
Doctor and hospitalized patient

Malaria imposes a substantial disease burden in the US, according to researchers.

Their study indicates that malaria hospitalizations and deaths in the US are more common than generally appreciated, as a steady stream of travelers return home with the disease.

In fact, malaria hospitalizations and deaths exceeded hospitalizations and deaths from other travel-related illnesses and generated about half a billion dollars in healthcare costs over a 15-year period.

These findings were published in the American Journal of Tropical Medicine and Hygiene.

“It appears more and more Americans are traveling to areas where malaria is common, and many of them are not taking preventive measures, such as using antimalarial preventive medications and mosquito repellents, even though they are very effective at preventing infections,” said study author Diana Khuu, PhD, of the University of California, Los Angeles.

For this study, Dr Khuu and her colleagues looked for malaria patients in a database maintained by the federal Agency for Healthcare Research and Quality that tracks hospital admissions nationwide.

The researchers found that, between 2000 and 2014, 22,029 people were admitted to US hospitals due to complications from malaria, 4823 patients were diagnosed with severe malaria, and 182 of these patients died.

Most of the deaths and severe disease were linked to infections with the Plasmodium falciparum parasite. However, in almost half of the malaria-related hospitalizations, there was no indication of parasite type.

The majority of malaria hospitalizations occurred in the eastern US in states along the Atlantic seaboard, and men accounted for 60% of the malaria-related hospital admissions.

Malaria hospitalizations were more common in the US than hospitalizations for many other travel-associated diseases. For example, between 2000 and 2014, dengue fever generated an average of 259 hospitalizations a year (compared with 1489 for malaria).

The average cost of treating a malaria patient was $25,789, and the total bill for treating malaria patients in the US from 2000 to 2014 was about $555 million.

The researchers estimated that, each year, there are about 2100 people in the US suffering from malaria, since about 69% require hospital treatment.

That case count would exceed the high end of the official estimate from the US Centers for Disease Control and Prevention (CDC) of 1500 to 2000 cases per year.

Dr Khuu attributed the difference to the fact that the CDC’s malaria count is based on reports submitted to the agency by hospitals or physicians, and hospital admission records that were used in the current study may capture additional cases that have not been reported to CDC.

While those admissions records did not include travel history, the researchers believe the malaria infections they documented most likely were acquired during travel to parts of Africa, Asia, and Latin America, where malaria is still common.

However, Dr Khuu noted that mosquitoes capable of carrying malaria are common in many parts of the US. So increases in the number of travelers coming home with the disease increases the risk of malaria re-establishing itself in the US.

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A spouse’s cancer diagnosis can lower household income

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A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.

Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.

“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.

“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”

One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.

“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”

“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”

The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.

The women had lower average employment rates, so the decrease represented a larger relative decline for them.

When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.

When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.

Total family income decreased by up to 4.8% among men and 8.5% among women.

The investigators found the declines were due to lower earnings among both cancer patients and their spouses.

“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”

“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”

Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.

“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”

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University of Georgia
R. Vincent Pohl, PhD Photo courtesy of the

A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.

Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.

“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.

“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”

One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.

“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”

“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”

The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.

The women had lower average employment rates, so the decrease represented a larger relative decline for them.

When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.

When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.

Total family income decreased by up to 4.8% among men and 8.5% among women.

The investigators found the declines were due to lower earnings among both cancer patients and their spouses.

“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”

“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”

Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.

“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”

University of Georgia
R. Vincent Pohl, PhD Photo courtesy of the

A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.

Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.

“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.

“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”

One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.

“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”

“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”

The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.

The women had lower average employment rates, so the decrease represented a larger relative decline for them.

When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.

When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.

Total family income decreased by up to 4.8% among men and 8.5% among women.

The investigators found the declines were due to lower earnings among both cancer patients and their spouses.

“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”

“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”

Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.

“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”

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