Venous Thromboembolism and Travel

The association between venous thromboembolism (VTE) and travel was recognized as early as the 1950s, when John Homans, MD, best remembered in connection with Homans’ sign—pain in the calf on active or passive dorsiflexion of the foot that may signal deep venous thrombosis (DVT)—advised that “physicians should be alert to recognize the significance of lameness after airplane flights, automobile trips and other occasions of a prolonged seated position.”¹This article will review the risk of developing VTE associated with travel.

The notion that prolonged travel in a sedentary position increases the risk of VTE seems easy to accept, and clinicians are accustomed to asking about recent travel when they suspect VTE. However, symptomatic VTE after air travel is rare, as demonstrated in a cohort study of 8755 employees of large international companies and organizations.² A total of 22 symptomatic, objectively confirmed VTE events occurred within 8 weeks after 102,429 long-haul flights, defined as 4 hours or longer. This corresponded to an absolute risk of 1 VTE event per 4656 long-haul flights.

A systematic review by Philbrick and colleagues also found a low rate of symptomatic VTE after air travel, with an incidence of 0.5 pulmonary embolisms per 1 million travelers presenting on the day of arrival in the airport, and 27 VTEs (pulmonary embolism and DVT) per 1 million travelers presenting within 2 weeks of arrival.³ When ultrasounds are performed routinely in travelers, the rate of diagnosed DVT may be as high as 1.2%, but the majority of cases are asymptomatic. The risk of an asymptomatic DVT progressing to clinically significant disease is currently unknown.

While some large studies have documented a positive relationship between travel and VTE, others have not. Chandra and colleagues conducted a meta-analysis of observational studies to clarify the conflicting evidence.⁴ In the 14 included studies, the pooled relative risk for VTE associated with travel was 2.0 (95% CI, 1.5-2.7). However, there was significant heterogeneity, with 7 studies reporting an association between travel and VTE, and the other 7 reporting no association. The authors conducted a sub-analysis to exclude 8 case-control studies that had a certain bias in selecting the control participants. In the remaining 6 studies, the relative risk for VTE associated with travel was 2.8 (95% CI, 2.2-3.7). These results appear to resolve the conflicting data and point to an elevated risk of VTE with travel.

The Chandra meta-analysis also reported a significant travel dose-response relationship. The risk for VTE rose by 18% for each 2-hour increase in travel by any mode, and by 26% for each 2-hour increase in travel by air.⁴ The Philbrick systematic review also documented a dose-response relationship, with greatest risk for DVT occurring with flights longer than 8 hours.³

The data on VTE associated with car or train trips is less clear. In the Chandra meta-analysis, the risk of VTE with air travel was slightly higher than for ground travel, but the difference was not statistically significant.⁴ In the Philbrick systematic review, only air travel was associated with VTE, although not all studies assessed other modes of travel.³

Other than flight duration, baseline clinical factors may also influence the risk of VTE. A prospective cohort study monitored travelers with surveillance ultrasound within 24 hours after long flights (average duration, 12.4 hours).⁵ Eleven of the 389 high-risk travelers (previous history of DVT, known coagulation disorder, severe obesity, limited mobility, cancer, large varicose veins) were found to have DVT. In contrast, DVT was not found in any of the 355 low-risk travelers.

In conclusion, symptomatic VTE after travel is not a common event. But considering the popularity of air travel, it is important to recognize the elevated risk of VTE associated with long air flights, especially among patients with other risk factors for VTE. Patients at high risk for DVT induced by prolonged travel should be identified and counseled before they start their journeys.

Tomado de: medpagetoday.com

Epigenetics: A Key to Controlling Acute and Chronic Pain

 Epigenetics, the study of changes in gene expression through mechanisms outside of the DNA structure, has been found to control a key pain receptor related to surgical incision pain, according to a study in the November issue of Anesthesiology. This study reveals new information about pain regulation in the spinal cord.

"Postoperative pain is an incompletely understood and only partially controllable condition that can result in suffering, medical complications, unplanned hospital admissions and disappointing surgery outcomes," said David J. Clark, M.D., Ph.D., Professor of Anesthesia at Stanford University and Director of Pain Management at the VA Palo Alto Health Care System. "We know that histone acetylation and deacetylation modifies many cellular processes and produces distinct outcomes. In this study we found that histones can epigenetically activate or silence gene expression to either increase or decrease incision pain."

Human DNA is wrapped around proteins called histones, much like thread is wrapped around a spool. When a histone undergoes deacetylation, the DNA wraps more tightly around the spool, effectively silencing genes. Conversely, when it undergoes acetylation, the DNA is loosened, allowing for transcription or modifications of genes to occur.

In this study, groups of mice had small surgical incisions made in their hind paws after being anesthetized. These mice were then regularly injected with suberoylanilide hydroxamic acid (SAHA), which prevents deacetylation (thus promoting gene transcription), or anacardic acid, which prevents acetylation (thus reducing gene transcription). The authors tested the animals daily for the degree of pain sensitivity in their hind paws.

The study found that regulation of histone acetylation can control pain sensitization after an incision. Specifically, maintaining histone in a relatively deacetylated state reduced hypersensitivity after incision. This is due, in part, to the epigenetic regulation of a specific gene known as CXCR2 and one of its chemokine ligands (KC). The authors also found that these epigenetic changes far outlasted the recovery of animals from their incisions, a property that might help explain why some patients suffer from chronic postoperative pain. Study authors suggest that looking into the roles of these epigenetic mechanisms may help scientists find new ways to treat or prevent acute and chronic postoperative pain in the future.

"Epigenetics is a relatively underappreciated area of science, but the discoveries yet to be made in this field will be many," said Dr. Clark. "While fascinating information has been found by studying specific genes, we need to bridge the gap in science and focus on groups or systems of many genes simultaneously, which could be give us clues to greater breakthroughs in pain control and other areas of medicine."

Tomado de: American Society of Anesthesiologists (ASA). "Epigenetics: A key to controlling acute and chronic pain." ScienceDaily, 25 Oct. 2013. Web. 22 Nov. 2013.

Sigmoidoscopy may not be enough for older patients

Colon cancer screening with sigmoidoscopy alone could miss up to 50% of colon polyps in older patients.

As people age, polyps seem to develop more and more proximally, Dr. Victor Tsirline said at the annual clinical congress of the American College of Surgeons. His review of more than 120,000 colonoscopies found that a flexible sigmoidoscopy alone could miss 44% of polyps in patients aged 60-69 years and 50% in those aged 70-79 years.

"We found that proximal colon polyps are more frequent with advanced age than previously considered," said Dr. Tsirline of Carolinas Medical Center, Charlotte, N.C. "So if this is true, what happens if we use sigmoidoscopy instead of colonoscopy? If we had, we would have missed 22,800 polyps, and 16,800 of those would have been adenomatous. In [patients 59 and younger] 32%-36% would be missed and in the older patients, 45%-50%."

Dr. Tsirline obtained his data from the Provation MD endoscopy transcription system. He obtained information on 120,365 colonoscopies that were performed from 2003 to 2011.

He cross-referenced this with CoPathPlus, a pathology reporting system. This allowed him to cross-reference polyp pathology (adenoma vs. hyperplasia) by computer algorithm. There was complete information available on 43,833 polyps.

Because of the large sample size, he set his level of statistical significance at P = less than 0.01.

The patients in the study were aged 20-90 years. Of the entire group of procedures, 53,492 colonoscopies (44%) identified polyps. Most studies (64%) found a single polyp; 25% found two, and 11% found three or more. A subset of the colonoscopies was only for average risk screening (44,806). Of these, 46% identified polyps.

Overall, 48% of polyps were adenomatous; 37% were hyperplastic. Pathology was not available for the remainder.

The polyps were fairly evenly distributed throughout the colon: rectum, 18%; sigmoid, 26%; descending, 14%; transverse, 16%; ascending, 15%; cecum, 11%.

However, when broken down by patient age, the distribution changed significantly. With every advancing decade of life, patients were:

• 22% less likely to have polyps in the rectum or sigmoid.

• 7% more likely to have polyps in the descending colon.

• 19% more likely to have polyps in the transverse colon.

• 30% more likely to have polyps in the ascending colon.

• 22% more likely to have polyps in the cecum.

All of these risks were statistically significant, and they held for both adenomatous and hyperplastic polyps.

The findings led Dr. Tsirline to conclude that flexible sigmoidoscopy should not be relied upon as an effective colon cancer screening method in patients older than 60 years. The U.S. Preventive Services Task Force states that sigmoidoscopy every 5 years combined with high-sensitivity fecal occult blood testing every 3 years is an adequate screening alternative.

"From this study, it’s pretty apparent that sigmoidoscopy should not be used for colon cancer screening in older patients," he said.

During a discussion, Dr. Tsirline fielded a question about screening the very elderly – patients in their 80s and 90s. The study group did include a small number of these patients, he said.

"I think the argument for not screening older individuals is based on the question of whether finding a colon cancer would change anything. Most people think the risks of screening and treatment would outweigh the benefits. Yes, you may find anything, but what are you going to do about it?"

Tomado de internalmedicinenews.com

New Tool Predicts Survival in Advanced Prostate Cancer

But a good prognostic tool has been lacking in this setting, particularly since a new chemotherapy called cabazitaxel as been approved by the U.S. Food and Drug Administration as another line of treatment.

Now researchers at the Duke Cancer Institute have developed a tool for doctors to forecast the potential survival of individual patients, enabling faster, more accurate information on whether to try additional rounds of treatment or seek clinical trials.

The findings are published online in the Journal of the National Cancer Institute.

"Our findings provide a prognostic tool that relies on information that is routinely collected in clinical practice and should be readily available," said Susan Halabi, Ph.D., professor of biostatistics and bioinformatics at Duke and lead author of the study. "For patients with metastatic prostate cancer who are appropriate candidates for second-line chemotherapy, this model can be helpful for guiding care. It could also be used during clinical trials to assign patients in risk groups based on measurable criteria."

In their study, Halabi and colleagues developed and validated the new prognostic tool using two different clinical trials of prostate cancer patients whose cancer returned after they had undergone a regimen of docetaxel, the standard first-round chemotherapy that is used after hormone treatments have been ineffective.

The researcher's approach provides an understanding of the complex interactions between the host, the tumor factors and clinical outcomes.

By plugging in 17 variables -- including pain intensity, measurable disease, race, age, body mass index and others -- the researchers determined that certain key factors were relevant to overall survival.

Of the 17 variables, nine were determined to be predictive of survival: how a patient's physical performance is rated on a scale of 0-2; the length of time since the first chemotherapy ended; how extensive the disease is; whether the disease has spread to the liver, lungs or other organs; how much pain the patient is experiencing; the duration of hormone use; and levels of hemoglobin, prostate specific antigen and alkaline phosphatase.

Two of those factors had not previously been used in prognostic models -- the duration of hormone therapy and the amount of time since the first-round docetaxel treatment.

"Several new treatments have been developed in recent years that prolong life for men with metastatic prostate cancer," Halabi said. "As a result, it's increasingly important to provide a clear prognostic picture that can help guide both doctors and patients to the best options."

This tool is available online at  https://www.cancer.duke.edu/Nomogram/secondlinechemotheray.html

Duke Medicine. "New tool predicts survival in advanced prostate cancer." ScienceDaily, 18 Oct. 2013. Web. 15 Nov. 2013.