Primecuts – This Week In The Journals

August 10, 2015
Republican presidential candidates from left, Donald Trump, Jeb Bush, Mike Huckabee, Ted Cruz and Rand Paul take the stage for the first Republican presidential debate at the Quicken Loans Arena Thursday, Aug. 6, 2015, in Cleveland. (AP Photo/Andrew Harnik) ORG XMIT: OTK

Republican presidential candidates from left, Donald Trump, Jeb Bush, Mike Huckabee, Ted Cruz and Rand Paul take the stage for the first Republican presidential debate at the Quicken Loans Arena Thursday, Aug. 6, 2015, in Cleveland. (AP Photo/Andrew Harnik) ORG XMIT: OTK

By Samantha Kass Newman, MD

Peer Reviewed

This week we saw a dynamic cast of characters engage in a hearty debate with the hopes of earning the GOP’s nomination for the presidency in 2016. Although the candidates rarely agreed, they stood united in their intent to repeal the Affordable Care Act. The ideas for alternatives were as diverse as the candidates themselves. Trump describes a market-based approach, with the goal of increasing competition among insurance companies, while Huckabee wants individual states to control their own healthcare reforms. Carson, a physician himself, advocated for individualized Health Savings Accounts, effectively eliminating Medicare/Medicaid (1). Regardless of who rises to the top in the political realm, as practicing physicians we are undoubtedly headed toward dramatic changes in healthcare reform. As the flavor of these changes is largely unknown, we must continue to adapt as we strive to deliver high quality patient care.

This week, in medical news:

Does obesity cause pancreatic cancer?

As part of the ongoing quest to understand the complex biology behind pancreatic cancer, Rebours et al. (2) analyzed normal pancreatic tissue from 110 patients who had undergone pancreatic resection for neuroendocrine tumors. The surgical specimens were analyzed for the presence of fatty infiltration, fibrosis, and pancreatic intraepithelial neoplasia (PanIN), which is the precursor lesion to pancreatic ductal adenocarcinoma (3). The researchers correlated their findings with data points such as BMI, history of diabetes, and smoking history. They found a positive correlation between PanIN lesions and high BMI (p = 0.02), subcutaneous fat (p = 0.02), intravisceral fat (p = 0.02), and intralobular fibrosis (p = 0.003). This strongly suggests that obesity and pancreatic fatty infiltration are significant risk factors for the development of pancreatic cancer.

These results have profound clinical implications, as obesity and diabetes may be modifiable risk factors for pancreatic cancer. It is unclear how obesity drives pancreatic tumorigenesis; however, it has been suggested that a high fat diet increases adipocytokines, inflammatory factors, and growth factors in the pancreas that may promote the development of KRAS mutations (3). Since chemotherapy is minimally effective, a possible alternative treatment strategy for pancreatic cancer might include targeting the inflammatory cascade to mitigate the effects of fatty infiltration of the pancreas and PanIN. Further, these results emphasize the importance of lifestyle changes in preventing disease.

Can Tenofovir Gel Prevent Herpes Simplex Virus Type 2 Infection?

Herpes Simplex Virus Type 2 (HSV-2) is among the world’s most common sexually transmitted diseases, and is the leading cause of genital ulcers (5). Seeking effective prevention strategies, Abdool Karim et al. (5) conducted a randomized, double-blind, placebo-controlled trial to assess the effectiveness of pericoital application of tenofovir gel in preventing HSV-2 infection in Sub-Saharan Africa, where nearly 80% of sexually active women are affected. They enrolled 429 HSV-2-seronegative females who were concomitantly enrolled in the CAPRISA 004 trial, which evaluated whether tenofovir gel prevents HIV infection, and randomized them to receive either tenofovir (n = 205) or placebo gel (n = 224). The women were told to insert the gel within 12 hours before intercourse, and again within 12 hours after intercourse. Use of Tenofovir gel was associated with a 51% reduction in HSV-2 acquisition.

Currently, the only prevention strategies for HSV-2 infection are condoms and circumcision (5). As there is no vaccine or cure for HSV-2, the use of pericoital Tenofovir gel has the potential to assist in the prevention of infection. Interestingly, the article notes that the anti-herpes activity of Tenofovir is only effective topically, as high concentrations of the drug are not achievable through oral formulations. More questions remain as to whether or not oral medications to prevent HSV-2 are a viable alternative.

Is Mindfulness-Based Stress Reduction Effective for Refractory PTSD in Veterans?

PTSD affects nearly 30% of veterans who have returned from deployments in Afghanistan and Iraq, and many report that the standard treatments (prolonged exposure therapy and cognitive processing therapy) are ineffective (4). PTSD is associated with medical comorbidities, disabilities, and suicide; therefore, effectively treating this condition is of paramount importance.

In a randomized clinical trial published in JAMA, Polusny et al. (4) assigned participants to either standard treatment for PTSD in the form of present-centered group therapy (control arm) or mindfulness-based stress reduction therapy. In the experimental arm, veterans were taught to embrace each present moment in a non-judgmental manner in 8 weekly 2.5-hour sessions and a day-long retreat. The primary outcome was change in symptom severity, which was assessed using a standard PTSD checklist. The results indicated that participants in the experimental group had greater improvement in PTSD symptoms during treatment (p=0.002) and at 2-month follow up (p<0.001). Interestingly, despite this improvement, veterans in the experimental group were no more likely to lose their diagnosis of PTSD than veterans in the control group (p = 0.55). Veterans in both groups reported average improvement overall. Although mindfulness-based stress reduction therapy is promising as a teachable skill to promote internal management of PTSD symptoms (4), questions remain as to whether this is a viable alternative to the standard of care in PTSD.

A New Drug for the Reversal of Dabigatran

Dabigatran is an oral direct thrombin inhibitor that is approved for prevention of stroke in nonvalvular atrial fibrillation and for prevention and treatment of venous thromboembolism. While dabigatran is associated with an increased risk of life-threatening bleeding, there is currently no available reversal agent. Idarucizumab is a monoclonal antibody developed to bind dabigatran with 350-times higher affinity than thrombin itself. In an ongoing, multicenter, prospective cohort study, Pollack et al. (6) evaluated 90 adults taking dabigatran who had either a life threatening bleed necessitating reversal (group A) or who required immediate surgery/invasive procedures (group B), necessitating hemostasis. The patients received 5g of idarucizumab in 2 bolus doses, and the primary endpoint was the maximum percentage reversal of dabigatran’s anticoagulant effect. To measure this, multiple blood samples were evaluated for dilute thrombin time and ecarin clotting time. Unbound dabigatran and idarucizumab levels were also measured. These parameters were then used to calculate the percentage reversal of dabigatran’s effect.

The results demonstrated that idarucizumab completely reversed the effects of dabigatran in 88-98% of the patients who had elevated clotting at baseline. This effect occurred rapidly, within minutes after receiving the first dose. Importantly, there were no safety concerns in any of the patients who were administered idarucizumab, even in patients who were later found to have normal clotting function (6). While this trial is ongoing, it demonstrates an important leap forward in reversing oral anticoagulants in the setting of life threatening bleeding or emergent procedures.

Quick-Cuts

A commentary published in the current issue of JAMA stressed the need for physicians to develop cultural competence in firearm safety and take an active role in counseling patients who own weapons in order to prevent injuries and deaths (7).

A study in The Lancet reassessed the consequences of screening and treating for asymptomatic bacteriuria in pregnancy. Women with uncomplicated singleton pregnancies were found to be at low risk for preterm birth and pyelonephritis. These findings question the current method of screening and treating all pregnant women with asymptomatic bacteriuria with antibiotics (8).

Contact tracing methods and monitoring approaches for Ebola were implemented after the first patients with Ebola were hospitalized in the US in order to better understand risks of transmission to health care providers. Annals of Internal Medicine published a descriptive investigation study evaluating these methods (9).

Dr. Samantha Kass Newman is a first year internal medicine resident at NYU Langone Medical Center

Peer Reviewed by Jennifer Mulliken, MD, Contributing Editor, Clinical Correlations

References

  1. GOP Debate: Who Said What About Healthcare? Becker’s Hospital Review. 7 Aug 2015. http://www.beckershospitalreview.com/hospital-management-administration/the-gop-debate-who-said-what-about-healthcare.html
  2. Rebours, Gaujoux, et al. Obesity and fatty pancreatic infiltration are risk factors for pancreatic precancerous lesions (PanIN). Clin Cancer Res. 1 Aug 2015. 21(15):3522-8. http://clincancerres.aacrjournals.org/content/21/15/3522.abstract
  3. Wang H, Maitra A, and Wang H. Obesity, Intrapancreatic Fatty Infiltration, and Pancreatic Cancer. Clin Cancer Res. 1 Aug 2015. 21(15):3369-71. http://www.ncbi.nlm.nih.gov/pubmed/25995340
  4. Polusny MA, Erbes CR, Thuras PT et al. Mindfulness-based stress reduction for posttraumatic stress disorder among veterans: a randomized clinical trial. JAMA. 4 Aug 2015. 314(5): 456-465. http://jama.jamanetwork.com/article.aspx?articleid=2422542
  5. Abdool Karim SS, Abdul Karim Q, Kharsany ABM, et al. Tenofovir gel for the prevention of herpes simplex virus type 2 infection. N Engl J Med. 6 Aug 2015. 373(6):530-539. http://www.nejm.org/doi/full/10.1056/NEJMoa1410649
  6. Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 6 Aug 2015. 373(6):511-520. http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMoa1502000#t=articleDiscussion
  7. Betz ME, Wintemute GJ. Physician counseling on firearm safety: a new kind of cultural competence. JAMA. 4 Aug 2015. 314(5):449-450. http://jama.jamanetwork.com/article.aspx?articleID=2422552
  8. Kazemier BM, Koningstein FN, Schneeberger C, et al. Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: a prospective cohort study with an embedded randomized controlled trial. The Lancet. Published online 5 Aug  http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00070-5/fulltext?rss=yes2015.
  9. Chung WM, Smith JC, Weil LM. Active tracing and monitoring of contacts associated with the first cluster of Ebola in the United States. Ann Intern Med. 2015; 163(3):164-173. http://www.ncbi.nlm.nih.gov/pubmed/26005809

 

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