Annals of Internal Medicine tip sheet for Aug. 12, 2014

1. 19th Century medicine paves way for 'miraculous' Ebola serotherapy

Nineteenth Century discoveries in medical science inspired development of the 'miraculous' Ebola virus serotherapy credited with saving the lives of American missionaries, Kent Brantly and Nancy Writebol, according to a commentary being published early online in Annals of Internal Medicine (http://www.annals.org/article.aspx?doi=10.7326/M14-1810). Author, Scott Podolsky, MD is Associate Professor of Global Health and Social Medicine at Harvard Medical School and Director of the Center for the History of Medicine at the Countway Medical Library. In his commentary, Dr. Podolsky chronicles the history of medical advances from the 1880s and 1890s onward that led to the modern era of monoclonal antibodies. For example, in the 1890s, medical scientists fighting agents such as diphtheria and pneumonia discovered that exposing an animal to an identified microbial pathogen would cause that animal to develop antibodies that could be 'passively' transferred to an exposed animal or person. This method of treatment was refined in the 1910s through the 1940s when scientists performed controlled studies using an antiserum for pneumococcal pneumonia. They found that serotherapy was effective against certain serotypes, especially when administered early. Formerly terminally ill patients were found sitting in their beds reading the newspaper after treatment, reminiscent of Kent Brantly's recovery. Dr. Podolsky suggests that lessons learned from the Golden Age of Microbiology up to the fight against AIDS can help scientists today as they seek to cure emerging infections, such as the Ebola virus.

Note: The URL will go live at 5:00 p.m. on Monday, August 11 and can be included in news stories. For an embargoed PDF, please contact Megan Hanks. To interview the lead author, please contact David Cameron at david_cameron@hms.harvard.edu or 617-432-0441.

2. Reviews address challenges of interpreting troponin levels in patients with chronic kidney disease

Two reviews being published in Annals of Internal Medicine address the challenges associated with using troponin levels to diagnose cardiac disease in patients with chronic kidney disease (CKD). Cardiac troponins (troponin I and T) are muscle contraction regulatory proteins found almost exclusively in the heart and are the most useful biomarkers of cardiac injury. Patients with CKD have a high prevalence of elevated serum troponin levels, even without cardiac disease, making it difficult to interpret their diagnostic and prognostic significance. Researchers conducted two systematic reviews of published evidence to evaluate the utility of troponin in both CKD patients with or without acute coronary syndrome (ACS). In the first paper, researchers systematically reviewed 98 observational studies to determine the prognostic value of troponin in patients who had CKD but not ACS. They found elevated levels of troponin I or troponin T were associated with worse prognosis. Specifically, patients with elevated troponin levels had a 2-4-fold higher risk for all-cause mortality, cardiovascular-specific mortality, and major adverse cardiac events.

In the second paper, researchers systematically reviewed 23 studies to determine if troponin levels could inform diagnosis, management, and prognosis of CKD patients who also had ACS. They found that troponin levels could help to identify patients with poor prognosis, but their value must be considered in the context of other clinical factors. The evidence was unclear whether troponin levels could help to diagnose ACS in patients with CKD. The studies did not evaluate whether troponin measures could help reclassify patients into high- and low-risk groups that may require different treatment.

The authors of an accompanying editorial caution that measuring troponins in CKD patients with a low pretest probability of coronary disease is likely to result in many false positive results and the value of obtaining troponin levels to inform evaluation and management is still unclear. For patients with ACS, troponin levels may be fore useful for ruling out myocardial infarction than for diagnosing it. The editorialists recommend further research to identify optimal cut-points for troponin levels in various patient populations and suggest testing management strategies based on these levels.

Note: The URL will go live at 5:00 p.m. on Monday, August 11 and can be included in news stories. For an embargoed PDF, please contact Megan Hanks. To interview the lead authors of both troponin papers, please contact Ekaterina Pesheva at epeshev1@jhmi.edu. To speak with the editorialists, please contact Angela Collom.

3. Therapies containing rifamycin effective and well-tolerated for preventing active TB in patients with latent infection

Therapies containing rifamycin for three months or more were reasonably well-tolerated and efficacious for preventing active tuberculosis (TB) in patients with latent TB infection (LTBI), according to a study being published in Annals of Internal Medicine (http://www.annals.org/article.aspx?doi=10.7326/M14-1019). In countries with low incidence of TB, many new cases emerge as a result of reactivated LTBI. Current treatments are effective and safe for preventing reactivation, but they are lengthy, which may affect completion rates. The authors suggest that global elimination of TB depends on shorter, effective, and well-tolerated LTBI regimens. New regimens that may be more effective are being introduced, but few studies directly compare these newer options. Researchers conducted a network meta-analysis of 53 trials to address the benefits and harms of 15 regimens aimed at preventing active TB in patients with LTBI. They utilized a network meta-analysis approach because it enables the indirect comparison of regimens and thus produces inferences of relative efficacy that would not otherwise be possible. The evidence suggests that currently recommended regimens are efficacious, but regimens containing rifamycin, given for 3 months or more, may be just as, if not more, effective than prolonged isoniazid (INH) monotherapy for treating LTBI. An accompanying editorial suggests that this network meta-analysis is important because it provides clear evidence that it is time to move away from INH as a primary therapy for LTBI and towards rifamycin-containing regimens that provide better protection against TB, greater safety, and shorter duration of treatment.

Note: The URL will go live at 5:00 p.m. on Monday, August 11 and can be included in news stories. For an embargoed PDF, please contact Megan Hanks. To speak with an author, please contact Harry Dayantis at h.dayantis@ucl.ac.uk or +44(0)20 3108 3844 (Int: 53844). To speak with the editorialist, please contact Cynthia Lee at cynthia.lee@mcgill.ca or 514-398-6754.