As Melania and Barron Trump are (not) settling into the White House, our new president spent Friday afternoon issuing an executive order that bans individuals from seven Middle Eastern countries from entering the United States. Citizens of Muslim-dominant countries of Iraq, Syria, Iran, Libya, Somalia, Sudan, and Yemen are banned from entering the USA for approximately 90 days. This news comes in the wake of what will likely be a much more extensive ban, with the goal of protecting our nation from the “terror-prone” countries listed above.
Trump also suspended the entry of all refugees into the USA for approximately four months as his administration re-evaluates the already extensive admission process. Most concerning, Trump stated that permission of entry for refugees should be prioritized based on religion – in other words, he hopes to make it easier for Christian citizens in Muslim nations to enter than Muslim citizens of the same countries.
Now, on to happier news about C diff and Ebola. http://www.cnn.com/2017/01/27/politics/donald-trump-refugees-executive-order/index.html
Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection
Clostridium difficile infection remains a widespread problem in hospitals and also now communities nationwide, due to the extensive use of antibiotics and the highly infectious nature of the bacteria. Accordingly, Wilcox et al conducted two placebo-controlled, randomized, double blinded phase 3 studies evaluating monoclonal antibodies against C difficile toxins A and B (actoxumab and bezlotoxumab, respectively) and their effectiveness in decreasing episodes of recurrent infection.
2600 individuals currently on treatment for either primary or recurrent C diff were given a single dose of bezlotoxumab alone, bezlotoxumab plus actoxumab, or placebo. Participants were concomitantly being treated with oral vancomycin, fidoxomycin, or metronidazole as standard of care therapy. The treating physician chose the initial therapy, a factor that introduces bias into the study results. Patients were monitored for recurrence for 12 weeks after treatment. Interestingly, the rate of recurrent infection was lower in the bezlotoxumab alone group than either the placebo group or the group that received both drugs, and this finding was consistent amongst both studies. However – in individuals with the specific strains of C diff 027, 028, and 244, the rate of recurrence was similar between the groups receiving bezloxumab alone and the combined therapy. These results demonstrate promising new treatments for this persistent and difficult to treat problem. Further research must be done to assess which standard of care treatments are most effective in combination with bezlotoxumab.
A Recombinant Vesicular Stomatitis Virus Ebola Vaccine
The outbreak of Ebola virus from 2014-2016 was considered the worst in history, and since researchers have been hard at work to develop a safe vaccine. In two separate NIH-funded double-blinded, randomized control, phase 1 clinical trials, Regules et. Al. tested the efficacy of a recombinant vesiscular stomatitis virus (rVSV)-based vaccine that expressed a glycoprotein of a Zaire strain of Ebola virus that had shown promise in preclinical testing.
39 patients at Walter Reed Army Institute of Research and NIH received the study drug in 2 separate versions of this dose escalation trial. At Walter Reed each participant received a single shot of the vaccine while those at NIH received 2 shots of the vaccine, randomized to doses of 3, 20, or 100 million PFU. Volunteers were assessed by PCR for Ebola virus in plasma, saliva, and urine at frequent intervals.
A transient viremia was noted in all participants after the first dose of the vaccine. Though degree of viremia varied based on dose at various intervals, by day 28 all participants had developed titers of antibodies against the glycoprotein of the Ebola strain present in the vaccine. Those who received 20 or 100 million PFU doses developed higher antibody levels. Though the participants who received a second dose of the vaccine did generate a larger antibody response, the researchers found this effect was diminished by 6 months. Adverse effects were mild and limited to fatigue, headache, and myalgias. Both adverse effects and viremia were less prominent after the second dose in those who received it. This vaccine is a promising first step in protecting citizens and healthcare workers, and preventing another severe outbreak.
A View from the Front Line – Physicians’ Perspectives on ACA Repeal
As the new presidential administration takes office, many are left concerned by the constant threats from the Republican Party to repeal the Affordable Care Act (ACA). An estimated 30 million people will risk of losing their health insurance should the ACA be repealed in its entirety. Those within the medical community are divided regarding the ACA and how it will affect physicians and their patients. Given the controversial nature of this highly politicized issue, Pollack et al. sought to understand the perspective of the primary care physician on the potential ACA repeal. They conducted a survey over the past 8 weeks, since the 2016 election, by randomly sampling over 1000 primary care physicians (PCPs) via mailed survey and telephone call. Approximately 45% responded.
The results indicated less of a divisive split in ideology than previously thought. Only 15% of primary care physicians wanted to see the ACA repealed in its entirety, though 73% favored making legislative changes. None of these 15% reported being affiliated with the Democratic party. Amongst physicians who reported voting for Trump, only 38% wanted to see the ACA repealed. Regarding its specific aspects, some were viewed as more important than others – nearly all PCPs supported insurance regulation and permitting young adults to remain on their parents insurance until age 26; fewer supported tax penalties associated with failure to purchase insurance.
Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care
Many individuals approaching the end of life experience distress-related delirium that is troubling to both patients and their loved ones. Few studies exist that support the use of antipsychotic medications for symptom relief; despite this, these medications are widely used in the palliative setting. Accordingly, Agar et al conducted a double-blind randomized placebo-controlled clinical trial to assess the efficacy of risperidone and haloperidol in alleviating symptoms in this population.
Doses of the haloperidol versus risperidone versus placebo were administered to 247 patients, every 12 hours for 72 hours, with the goal of controlling symptoms of delirium. The medications were titrated according to effectiveness. The researchers used a delirium severity score to assess primary outcome. Throughout this time, physicians continued their efforts to treat alternative causes of delirium, and midazolam could be used if necessary.
Interestingly, the study found that patients in both the risperidone and haloperidol groups had greater delirium symptoms than those in the placebo group. Not surprisingly, these groups also reported more extrapyramidal side effects. Further, midazolam use was significantly increased in the experimental groups rather than the control groups. Finally, those in the haloperidol group demonstrated poorer survival than the other groups, for reasons that are unclear.
These results raise serious concerns about using antipsychotic medications to treat delirium in the palliative population, and calls into question this standard of care practice. More research is needed to both understand this concept and develop further therapies that mitigate distress-related symptoms of delirium in palliative patients.
Allocating organs to cognitively impaired patients
Some feel that cognitive impairment should not be a factor in determining eligibility for transplant of scarce organs, as it allows physicians to determine whether one life is higher than another in value. Others feel those with cognitive impairments will be less likely to adhere to strict post-operative therapeutic regimens and will be more likely to reject the transplanted organ. http://www.nejm.org/doi/full/10.1056/NEJMp1613858
Coverage and Access for Americans with Chronic Disease Under the Affordable Care Act
Individuals with chronic diseases in minority groups may not have benefitted as much from the Affordable Care Act as previously thought. Though overall coverage improved by 5%, coverage increased more in states that expanded Medicaid than those that did not. http://annals.org/aim/article/2599147/coverage-access-americans-chronic-disease-under-affordable-care-act-quasi
Screening for Obstructive Sleep Apnea
Per the USPSTF, there is unclear benefit and higher costs associated with screening asymptomatic patients for OSA. Despite this, 75% of individuals ultimately diagnosed with OSA did not initially report symptoms. http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2599421
Dr. Samantha K. Newman is 2nd year resident at NYU Langone Medical Center
Peer reviewed by Neil Shapiro, Editor-In-Chief, Clinical Correlations
Image courtesy of Wikimedia Commons
Wilcox MH, Gerding DN, Poxton IR et al. Bezlotoxumab for prevention of recurrent clostridium difficile infection. N Engl J Med. 2017 Jan 26:376(4):305-317.
Regules JA, Beigel JH, Paolino KM. A recombinant vesicular stomatitis virus Ebola vaccine. N Engl J Med. 2017 Jan 26;376(4):330-341.
Pollack CE, Armstrong K, Grande D. A view from the front line – physicians’ perspectives on ACA repeal. N Engl J Med. 2017 Jan 25.
Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: a randomized clinical trial. JAMA Intern Med. 2017 Jan 1:177(1)34-42.
Halpern SD, Goldberg D. Allocating organs to cognitively impaired patients. N Engl J Med. 2017 Jan 26;376(4):299-301.
Torres H, Poorman E, Tadepalli U, et al. Coverage and access for Americans with chronic disease under the affordable care act: a quasi-experimental study. Ann Intern Med. 2017 Jan 24.
Pendharkar SR, Clement FM. Screening for obstructive sleep apnea: important to find, but how hard should we look? JAMA Intern Med. 2017 Jan 24.