Primecuts – This Week In The Journals

March 9, 2015

By Anjali Mone, MD

Peer Reviewed

As the Northeast recovers from non-stop snowstorms and the frozen East River thaws, daylight savings time may finally mark the end of winter, except in Arizona and Hawaii who will not be “springing forward”. Arizona and Hawaii might be on the right track since “springing forward” and “falling back” have actually been associated with increased traffic accidents. While our nation debates whether losing an hour of sleep actually saves energy or increases productivity, one country in West Africa can finally say that it is Ebola free. However given that the disease remains prevalent there, much work is still needed, particularly in terms of developing a vaccine to combat this deadly epidemic.

Hepatitis C gets all the hype….

However another viral hepatitis has shown significant advancements in terms of vaccine development. Hepatitis E is thought to be a problem isolated only to pregnant women in resource-poor, underdeveloped countries, however it is also a significant cause of acute viral hepatitis in developed countries. In a rapidly globalizing world, with more and more travel and contact between distant nations and peoples, this disease is having an increasingly world-wide impact. Vaccines against Hepatitis E have been available for some time, however no studies had been conducted to demonstrate whether the vaccines are effective in the long-term. A recent study published in the NEJM confirms that the Hepatitis E vaccine has long-term efficacy and more importantly suggests that Hepatitis E is preventable with a vaccine. In a randomized, double-blinded, placebo-controlled trial conducted in China, Zhang et al. studied 112,604 healthy patients ages 16 to 65. Initially a phase 3 clinical trial was performed to demonstrate that the vaccine, commercially named Hecolin, was safe and 95% effective over a one year period after vaccination. [3] In the long-term follow-up study Zhang et al [4] demonstrate that the vaccine provides sustained protection against Hepatitis E for at least 54 months. Furthermore, no significant adverse events were noted. While it is true that this study is mainly relevant for the strain of Hepatitis E prevalent in China, it is promising research that suggests vaccines can now be developed to protect against all strains of Hepatitis E. This vaccine would effectively be able to eradicate a disease that was previously fatal among pregnant women, particularly those living in crowded, unsanitary conditions. Even though a Hepatitis E vaccine has been available for some time, limited data about disease burden in both developed and underdeveloped regions of the world have likely limited its availability. This is the first study in which Hepatitis E vaccines have progressed beyond a phase 2 clinical trial, and thus may have far-reaching impact in terms of preventing and controlling this disease.[5]

Ulcerative colitis and budesonide foam.

Patients with ulcerative proctitis and ulcerative proctosigmoiditis are traditionally limited to treatment with oral or rectal mesalamine along with suppositories and rectal enemas. However there are various limitations to this treatment modality including the fact that it is not only difficult to administer this therapy but also difficult for patients to retain. Although systemic steroids are effective against ulcerative colitis, targeted approaches are desired to avoid the side effects of systemic steroids including weight gain, decreased bone density, and adrenal abnormalities. A recent study with two randomized, double-blind, placebo-controlled phase 3 trials demonstrated that budesonide foam was a safe and effective method for delivery and retention of budesonide to induce remission in patients with ulcerative proctitis or ulcerative proctosigmoiditis. At 6 week follow-up, patients receiving budesonide foam achieved remission significantly more when compared with placebo (Study 1: 38.3% vs 25.8%; P =0.0324; Study 2: 44% vs 22.4%; P<0.0001). Furthermore, those using budesonide foam had significant improvement in rectal bleeding as well as endoscopic improvement. [6]

Could eating nuts be good for your heart?

The health benefits of a Mediterranean diet and more specifically consumption of peanuts and tree nuts has previously been demonstrated in various studies. Nut consumption has been linked to decreased risk of hypertension, diabetes mellitus, and coronary artery disease. [7] In fact, recent studies have shown that nut consumption was found to be inversely associated with total mortality and cause-specific mortality. However, studies looking at high intake of nuts and reduced mortality were primarily conducted in individuals of European descent and high socioeconomic status. A recent study published in JAMA addressed this disparity and demonstrated that eating nuts is associated with a lower risk of cardiovascular disease and death across many different ethnic and socioeconomic groups. This prospective study included 71,764 black and white Americans, primarily of lower socioeconomic status, as well as over 130,000 men and women living in Shanghai. Using well-validated food frequency questionnaires, researchers in this study gathered information about nut-consumption. After following participants for up to 12 years, and controlling for other confounding factors, they found that those with the highest nut consumption had a 21% lower risk of death in Americans of African and European descent and 17% lower risk among Asians. There was a similar association for lower risk of deaths from cardiovascular disease in all ethnicities, however decreased risk of ischemic and hemorrhagic stroke was only found to be significant in Asians. Overall this study suggests that nut consumption, which is fairly affordable for all socioeconomic classes, is a good intervention to prevent all cause mortality. [9]

Does intensity of exercise matter?

It is well established that regular exercise is essential for reducing obesity, diabetes, and heart disease. However until now it was unknown whether increased exercise intensity provided any additional health benefits. This single-center, parallel-group trial followed 300 patients with abdominal obesity over a 24 month period. The study had four trial arms: no exercise, low-amount, low-intensity exercise (LALI), high-amount, low-intensity exercise (HALI), or high-amount, high-intensity exercise (HAHI). In terms of their primary endpoints, waist circumference reduction was higher in the exercise groups than the control groups, but there were no significant differences among the exercise groups. The other primary endpoint, reduction in 2-hour glucose level, was greater in the HAHI group versus control, however did not differ between the LALI or HALI groups versus control group. As would be expected, overall weight loss was greater in all exercise groups compared with the control group. However weight loss did not differ among exercise groups, which suggests that higher exercise intensity provides no additional benefits in abdominal obesity reduction. Furthermore reductions in 2-hour glucose levels is best achieved by high amounts of high intensity exercise, however the benefit of reducing 2-hour glucose level in non-diabetic adults remains unclear. Either way these results do not provide any information that should affect current exercise guidelines. [10]

In other medical news…..

Twins and working out.

Researchers in Finland took advantage of the FinnTwin16 database and studied 10 pairs of adult identical twins in their early to mid twenties, particularly those whose exercise habits had become different since leaving their childhood homes. It was difficult to find these types of twins, because most had similar exercise habits. However in a few twin pairs, work or family pressures led one twin to work out less than the other. They measured body composition, insulin sensitivity, endurance capacity and also scanned each twin’s brain. The twin that worked out less had lower endurance, higher body fat percentage, and signs of insulin resistance, despite similar diets. Furthermore the active twin generally had more grey matter in the brain, particularly in motor control and coordination. This study only showed divergence over 3 years, which shows how quickly our bodies can change. [11]

Head transplant – Fantasy or reality?

In a provocative and controversial journal article, an Italian neuroscientist, Dr. Sergio Canavero outlines a possible technique to perform a human head transplant to help patients suffering from conditions such as muscular dystrophy or quadriplegia. Dr. Canavero suggests that the biggest obstacle to performing this procedure is reconnecting the donor and recipient spinal cords. However it remains unclear if this is just science fiction or a real possibility. [12]

Ebola vaccine on the horizon?

Now moving from fantasy to reality. In breaking news, the last Ebola patient in Liberia was recently discharged. However the disease remains a threat in neighboring countries including Sierra Leone and Guinea, and there is still a need for a vaccine. In a recent issue of JAMA, Lai et al report successful administration of postexposure experimental Ebola vaccination to a physician who had a needlestick while working in an Ebola treatment unit. While it is not possible to make any conclusions from one case report, it seems likely this intervention was helpful in controlling Ebola virus replication. There was a similar case in 2009 when a laboratory worker in Germany had a needlestick injury and also received the vaccine, with nearly identical results. These cases suggest that a much needed Ebola vaccine may become a reality in the near future. [13]

The first biosimilar drug – a step towards making medications more affordable.

On the subject of medications that need to be widely available, the US FDA took a major step towards making biotech drugs more affordable and approved Sandoz to make the first biosimilar cancer drug, Zarxio, which is almost identical to neupogen. Unlike generic drugs, biosimilar drugs are derived from living organisms.

Sleep and stroke.

Recently published in Neurology, researchers have found that people that sleep more may have higher risk for stroke. After controlling for multiple variables, the authors found that individuals that slept over 8 hours a day were at higher risk for stroke than those who slept 6-8 hours. Furthermore, the risk of stroke was higher among people who reported their sleep requirements increased over the study period. There is an important distinction to be made here and the authors caution the reader not to misinterpret the study as it is an association, not a causal relationship. Furthermore, their data was collected from surveys and self-reports which can be unreliable. However, this data suggests that there could be something happening in the brain preceding a stroke leading individuals to require more sleep, so maybe excessive sleep is an early sign of pending stroke. [14]

PPI use and CDI.

Although antibiotic use is the most well-established risk factor for infection with C. difficile (CDI) through its effect on the intestinal microbiota, there has been increasing literature suggesting a link between PPI use and CDI. Recently published in JAMA, a restrospective study shows that PPI use is associated with a higher risk of CDI recurrence. The authors suggest that unnecessary PPI use should be stopped at the time of CDI diagnosis. [15] This becomes more relevant in light of growing evidence of the increasing burden of CDI in the US- Lessa et al. recently published data in the NEJM that showed that CDI was responsible for almost ½ million infections. The need to reduce C. difficile risk factors is therefore more than evident. [16]

Dr. Anjali Mone is a 2nd year resident at NYU Langone Medical Center

Peer reviewed by Anish B. Parikh, MD, Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons


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2. Dalton HR, Bendall R, Ijaz S, Banks M. Hepatitis E: an emerging infection in developed countries. The Lancet. Infectious diseases. Nov 2008;8(11):698-709.

3. Zhu FC, Zhang J, Zhang XF, et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. Sep 11 2010;376(9744):895-902.

4. Zhang J, Zhang XF, Huang SJ, et al. Long-term efficacy of a hepatitis E vaccine. The New England journal of medicine. Mar 5 2015;372(10):914-922.

5. Teshale E, Ward JW. Making hepatitis E a vaccine-preventable disease. The New England journal of medicine. Mar 5 2015;372(10):899-901.

6. Sandborn WJ, Bosworth B, Zakko S, et al. Budesonide Foam Induces Remission in Patients With Mild to Moderate Ulcerative Proctitis and Ulcerative Proctosigmoiditis. Gastroenterology. Jan 30 2015.

7. Luo C, Zhang Y, Ding Y, et al. Nut consumption and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis. The American journal of clinical nutrition. Jul 2014;100(1):256-269.

8. Afshin A, Micha R, Khatibzadeh S, Mozaffarian D. Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: a systematic review and meta-analysis. The American journal of clinical nutrition. Jul 2014;100(1):278-288.

9. Luu HN, Blot WJ, Xiang YB, et al. Prospective Evaluation of the Association of Nut/Peanut Consumption With Total and Cause-Specific Mortality. JAMA internal medicine. Mar 2 2015.

10. Ross R, Hudson R, Stotz PJ, Lam M. Effects of exercise amount and intensity on abdominal obesity and glucose tolerance in obese adults: a randomized trial. Annals of internal medicine. Mar 3 2015;162(5):325-334.

11. Rottensteiner M, Leskinen T, Niskanen E, et al. Physical activity, fitness, glucose homeostasis, and brain morphology in twins. Medicine and science in sports and exercise. Mar 2015;47(3):509-518.

12. Canavero S. The “Gemini” spinal cord fusion protocol: Reloaded. Surgical neurology international. 2015;6:18.

13. Lai L, Davey R, Beck A, et al. Emergency Postexposure Vaccination With Vesicular Stomatitis Virus-Vectored Ebola Vaccine After Needlestick. JAMA : the journal of the American Medical Association. Mar 5 2015.

14. Leng Y, Cappuccio FP, Wainwright NW, et al. Sleep duration and risk of fatal and nonfatal stroke: A prospective study and meta-analysis. Neurology. Feb 25 2015.

15. McDonald EG, Milligan J, Frenette C, Lee TC. Continuous Proton Pump Inhibitor Therapy and the Associated Risk of Recurrent Clostridium difficile Infection. JAMA internal medicine. Mar 2 2015.

16. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. The New England journal of medicine. Feb 26 2015;372(9):825-834.