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Swine Flu Update: May 4
  • 226 confirmed cases in the US
  • WHO considering moving to "Stage 6"

 

Swine Flu Update: May 1
  • 109 cases in the US in 10 states
  • South Carolina newest state with confirmed cases
  • 11 countries now have cases, up from 9 yesterday
  • New cases in Switzerland, Netherlands

 
Swine Flu Update: April 30
  • WHO upgrades to stage 5
  • 9 countries with confirmed cases
  • New cases in Germany, England, and Austria
Q: If 36,000 Americans died during a recent year from seasonal flu, is that not about 100 per day? During the flu season, maybe twice that many, with half as many during the off season? How is swine flu special? I sort of understand that this could be different because it is a unique strain, but I think we need some perspective.
Keep up the good work.
Rich Wilson DO
 
A: It is too early to tell how this novel virus will spread throughout the world and what level of mortality to expect. While numerous deaths have been reported in Mexico, it is unclear what the total burden of cases (including mild cases) is in Mexico. It is true that seasonal flu kills 36,000 Americans yearly, but what increment the novel virus will produce remains to be seen. However, the fact that a novel influenza virus--to which people have no immunity and no vaccine is available--is efficiently spreading from person-to-person, is an extremely serious situation.
 

 
Swine Flu Update: April 29
  • There are 91 cases reported in the US
  • New cases have cropped up in Arizona, Indiana, Michigan, Massachusetts and Nevada
  • First US swine flu death confirmed in Texas
  • 5 hospitalizations (3 in CA, 2 in TX) have occurred.
  • Worldwide seven countries (USA, Canada, Mexico, Spain, New Zealand, and Israel) have confirmed cases according to the WHO.
  • The CDC's antiviral guidance was updated and now does not include recommendations for dual therapy  with an adamantane to cover seasonal influenza infection if oseltamivir is used.
  • An Emergency Use Authorization was also issued allowing for the use of oseltamivir in those aged under one year.


Swine Flu Update: April 28

 
What every emergency physician needs to know about swine flu today*
 
By Amesh Adalja, MD

*This article is adapted from the author's earlier report in the Clinician's Biosecurity Network, available at http://www.upmc-cbn.org/report_archive/2009/04_April_2009/04-09_Swine_Flu_2009/cbnreport_SF1_4-24-09_AM.html
 
On April 21, 2009, the Centers for Disease Control and Prevention (CDC) issued an MMWR Dispatch describing 2 cases of swine influenza A (H1N1) infection that occurred in Southern California in April. While both patients recovered uneventfully, the isolated viruses harbor novel genetic characteristics not seen in swine flu isolates in the U.S. prior to this event. The other striking feature of these cases is that there was no known contact with swine, raising the question of efficient human-to-human transmission of this virus [1] Subsequent investigation has uncovered 40 additional cases in the United States—all of whom have recovered uneventfully—and reports of severe morbidity and mortality in Mexico. Several other countries including Canada, Scotland, and Spain are reporting confirmed cases.

Why the Emergency Physician Should Know about Swine Flu
As with all emerging infectious diseases, emergency physicians are likely to find themselves on the front line contronting swine flu. It is vital that they be informed with the best information when confronting this potentially deadly virus.

Swine Flu 101


Influenza viruses circulate among waterfowl, swine, and humans, but other mammals may also be infected. Until 1997, avian viruses were thought to be unable to infect humans directly, as they were thought to require a “mixing-vessel” (e.g., swine) as an intermediary to allow the virus to adapt to humans. The experience with the H5N1 virus and other wholly avian viruses has proven that this step is unnecessary. However, swine do potentially play a major role in influenza epidemics given their ability to be infected efficiently with both avian and human strains, thus creating a potential platform for the recombination of viruses from different lineages. Swine are receptive to infection from avian and human viruses because they possess receptors for both. While avian influenza preferentially binds to receptors containing alpha-2,3 sialic acid-galactose linkages, human viruses bind to alpha-2,6 linkages. Humans contain only alpha 2,6 residues in the upper respiratory tract, while pigs have both types. Once an avian virus is in swine, it can develop tropism for human receptors.[2] A recent report from Indonesia indicates that H5N1 viruses have attenuated their virulence in swine, suggesting a degree of adaptation to mammalian hosts.[3] However, prior to the current situation there was no evidence to date that a pandemic strain has originated from swine, and this hypothesis was being questioned.[2]

Swine Flu in Humans


The first isolation of a swine flu virus from a human occurred in 1974, confirming a long held suspicion that swine flu viruses could infect humans.[4] A 2007 review article on this topic presented data from 50 cases reported in the medical literature and offered several salient points regarding human cases:
    •    Case fatality rates were 14% (likely reflecting case ascertainment bias).
    •    61% of civilian cases reported swine exposure.
    •    Person-to-person transmission did occur.[4]

CDC reports the receipt of approximately 1 human swine flu case report every 1 to 2 years (swine flu has been a nationally reportable condition since 2007). Since 2005, 12 cases have been reported in the U.S., most with exposure to pigs.1

Most swine influenza infections do not have a presentation distinct from human influenza infections. Seroprevalence studies have shown 23% positivity in those with occupational exposure to pigs.[2]

 
The Fort Dix Incident


The most widely known incident of swine flu in humans centers around an outbreak of a lethal influenza virus at Fort Dix in New Jersey in 1976. During that outbreak, 13 soldiers had severe respiratory illness, and 1 soldier died. A novel H1N1 swine influenza virus (Hsw1N1) was isolated, and approximately 230 other soldiers displayed evidence of infection.5 The virus did not spread outside Fort Dix, no swine exposure was ever elucidated, and swine were never definitively established as the source.[2,5] The incident prompted a massive vaccination campaign that was plagued with problems.[2,8]
 
The Current Outbreak
The Basics
    •Swine Flu is a reassortant type A influenza virus that originated from swine at some point in the past
    •Unlike past infections with swine flu, the current outbreak strain efficiently spreads from person to person—secondary attack rates are approximately 20%
    •The diagnosed cases in the US represent only the tip of the iceberg, it is likely to be circulating in your community

Symptoms
•All cases outside of Mexico reported to date have consisted of mild influenza-like illness with the exception of the prominence of nausea, vomiting, and diarrhea
•The US should be prepared to see severe cases with fulminant pneumonia given the experience in Mexico
•The incubation period is approximately one to seven days
•The infectiousness period begins 1 day prior to symptoms and continues for seven days after symptoms commence

Diagnosis
•Standard rapid tests may be falsely negative, but could be positive for influenza A    
•RT-PCR testing is required to confirm the diagnosis of swine flu    
•Viral culture can also be used to isolate the virus    
•The CDC has published case definitions for possible, probable and confirmed cases:
 
A confirmed case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests:
•real-time RT-PCR
•viral culture
 
A probable case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness who is:
•positive for influenza A, but negative for H1 and H3 by influenza RT-PCR, or
•positive for influenza A by an influenza rapid test or an influenza immunofluorescence assay (IFA) plus meets criteria for a suspected case

A suspected case of swine influenza A (H1N1) virus infection is defined as a person with acute febrile respiratory illness with onset
•within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection, or
•within 7 days of travel to community either within the United States or internationally where there are one or more confirmed swine influenza A(H1N1) cases, or
•resides in a community where there are one or more confirmed swine influenza cases.
 
Treatment
•The virus is susceptible to treatment with the neuraminidase inhibitors, oseltamivir and zanamivir; it is resistant to amantadine and rimantidine
•Standard treatment for seasonal flu should be employed (i.e. either zanamivir alone or oseltamivir in combination with an adamantane to cover the possibility of resistant seasonal flu)
•Antiviral guidelines are available at: http://www.cdc.gov/swineflu/recommendations.htm

Infection Control
•Full airborne protections are warranted (N-95 masks)
•Vaccination with seasonal influenza vaccine is not protective

Are we on the verge of a pandemic?
Prior to the current outbreak the World Health Organization (WHO) had designated the pandemic status of the world as stage 3, reflecting the limited cases of H5N1 Avian influenza infections in humans without evidence of human-to-human spread.On April 27, 2009 the WHO has raised the pandemic level to stage 4 indicating small clusters of localized human to human spread of the swine influenza.

The current reports of dozens of cases of swine flu worldwide, in individuals with no epidemiologic link to swine is clear evidence of intrusion of a novel influenza virus into the human species with potential for human-to-human spread. As the epidemic evolves it will be essential to understand patterns of illness and transmission characteristics. As this virus is making its debut at the tail end of the Northern Hemisphere’s influenza season, there is hope that the outbreak may abate. However Southern Hemisphere countries, whose flu season is about to begin, have reported suspect cases the virus may now begin to circulate in that hemisphere and reappear again in the Northern Hemisphere in the fall of 2009.


Emergency physicians will continue to be one of the first lines of defense against this virus and the care and advice they will provide will be an essential component of what may be a marathon battle against this virus.

 
Dr. Adalja is a fellow at the Center for Biosecurity of the University of Pittsburgh Medical Center, where he is also the chief fellow in the Division of Infectious Diseases. He is board-certified in both Emergency Medicine and Internal Medicine. He can be reached via email at: This email address is being protected from spambots. You need JavaScript enabled to view it.
 
 
Resources
Center for Biosecurity of UPMC: www.upmc-biosecurity.org
 
Centers for Disease Control and Prevention: http://www.cdc.gov/swineflu/
 
 
References 
1. CDC. Swine influenza A (H1N1) infection in two children---Southern California, March-April 2009. MMWR Dispatch 2009; 58:1-3. http://www.cdc.gov/mmwr/preview/mmwrhtml/
mm58d0421a1.htm. Accessed April 23, 2009.
 
2. VanReeth, K. Avian and swine influenza viruses: our current understanding of the zoonotic risk. Vet Res 2007; 38: 243-260. http://www.vetres.org/index.php?option=article&access=doi&doi=10.1051/vetres:2006062. Accessed April 23, 2009
 
3. Takano R, Nidom CA, Kiso M, et al. A comparison of the pathogenicity of avian and swine H5N1 influenza viruses in Indonesia. Arch Virol 2009; 154: 677-681. http://tiny.cc/FwqJd. Accessed April 23, 2009.
 
4. Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a review of the literature. Clin Infect Dis 2007;44:1084-1088. http://www.journals.uchicago.edu/doi/abs/10.1086/512813. Accessed April 23, 2009.
 
5. Gaydos JC, Top FH, Hodder RA, Russell PK. Swine influenza A outbreak, Fort Dix, New Jersey, 1976. Emerg Infect Dis 2006; 12: 23-28. http://www.cdc.gov/ncidod/EID/vol12no01/05-0965.htm. Accessed April 23, 2009.
 
6. Weingartl HM, Albrecht RA, Lager KM, et al. Experimental infection of pigs with the human 1918 pandemic influenza virus. J Virol 2009; 83: 4287-4296. http://jvi.asm.org/cgi/content/abstract/83/9/4287. Accessed April 23, 2009.
 
7. Robinson JL, Lee BE, Patel J, et al. Swine influenza (H3N2) infection in a child and possible community transmission, Canada. Emerg Infect Dis 2007; 13: 1865-1870. http://www.cdc.gov/eid/content/13/12/1865.htm. Accessed April 23, 2009.

8. Krause R. The swine flu episode and the fog of epidemics. Emerg Infect Dis 2006; 12:40-43. http://www.cdc.gov/ncidod/EID/vol12no01/05-1132.htm. Accessed April 23, 2009.
 
9. CDC. Human swine influenza investigation. http://www.cdc.gov/flu/swine/investigation.htm. Accessed April 23, 2009.

 

Comments   

# Mike Klevens 2009-04-28 12:42
So, who would you recommend getting an antiviral? From prior influenza--symp toms within 48 hours of ED arrival, children and elders?
Reply
# Amesh Adalja, MD 2009-04-28 15:05
The CDC's position is that "Empiric antiviral treatment should be considered for confirmed, probable or suspected cases of swine influenza A (H1N1) virus infection." Antivirals are most effective when given within 48 hrs. of symptom onset, but there is evidence of decreasing mortality and hospital stays with antiviral treatment started later than 48 hrs. I believe the highest priority should be treat those that hospitalized and at high-risk.
Reply
# Probenecid and oseltamivirJoe Howton MD 2009-04-28 15:18
If supplies of oseltamivir become tight, we should remember that giving probenecid will block excretion, thereby boosting levels of oseltamivir. We could thereby extend the supply of oseltamivir to treat more patients.
Reply
# Amesh Adalja, MD 2009-04-28 15:20
A good resource to print and hand to your patients is on the CDC website:

http://www.cdc.gov/swineflu/swineflu_you.htm
Reply
# mddon zweig 2009-04-28 15:37
What is the evidence that Oseltamifivr decreases mortality from influenza? I thought that this year a lot of influenza a was resistant and you needed to add amantadine. Is this still the case, even for swine flu?.
Reply
# Treatment for ed doctorsDr Radley 2009-04-28 15:43
For health care edit docs flu symptoms positive testing rapid influ a what exact recommendation would you start considering resistence pattern and side affects and avality to meds?

I am ed Md please state exact med dosage lenghth time understanding CDC will do some quess work for general pop. Also I don't hold you responsible for what you would take and understand you are not the CDC
Also why two agents? Tamiflu plus ?
Relafen alone. Probenecid plus?

I will need to continue working

Thanks
Reply
# Antiviral treatmentAmesh Adalja, MD 2009-04-28 15:56
Here's a link to a paper from CID regarding the decrease in mortality (OR 0.21) with use of oseltamivir: http://www.journals.uchicago.edu/doi/abs/10.1086/523584

The CDC is recommending use of either amantadine and rimantidine with oseltamivir because there are still seasonal influenza A strains (H1N1) circulating that are all resistant to oseltamivir. Rapid tests will not distinguish which virus is present. The current swine influenza isolate is resistant to amantadine and rimantidine, but unless you can rule out seasonal H1N1 influenza, 2 drugs are needed.

The dosage for adults with Tamiflu is 75mg orally twice daily for 5 days. For Relenza, dosing is two inhalations twice daily for 5 days.
Reply
# Consensus on Anti-viral TXE Heine 2009-04-28 17:04
My understanding of the CDC recommendations is for "consideration" of treatment with anti-virals for confirmed or suspected cases. I doubt a consensus exists at this point on whether we should treat all-comers or only those who need hospitalization or who have higher risks of complications. Of concern, of course, if we treat everyone with an URI with these drugs, the risk of resistance and drug availability for those who truly need it is very high. My preference would be not to treat the uncomplicated/l ow risk case. Is this justified?
Reply
# Antiviral treatmentAmesh Adalja, MD 2009-04-28 17:06
I think it would be justified to not treat uncomplicated cases. In fact, the vast majority of the early US cases did not receive antiviral treatment and recovered uneventfully.
Reply
# No more TamifluMatthew Perl, M.D. 2009-04-28 17:29
I called seven pharmacies in San Diego last night to find Tamiflu for a patient, including CVS, Sav-On, Rite-Aid and Costco; none had the medication, nor did they expect to be receiving any in the near future.
Reply
# RelenzaAmesh Adalja, MD 2009-04-28 18:20
If a patient is able to use the Relenza inhaler, that is an equally good option if Tamiflu is unavailable.
Reply
# New Antiviral GuidelinesAmesh Adalja, MD 2009-04-28 18:43
The CDC's most recent antiviral update has now dropped the recommendation for dual therapy with amantadine or rimantidine to cover seasonal influenza.

http://www.cdc.gov/swineflu/recommendations.htm
Reply
# MD, FACEPBryan Dunn 2009-04-28 19:02
What do you recommend for children under age 7? Tamiflu liquid is no longer available, and Relenza is not approved for this age. Thanks
Reply
# N-95Bryan Dunn 2009-04-28 19:05
Are N-95s recommended for patients, or are regular surgical masks adequate? I know N-95s are best for HC workers and contacts due to aerosolization, but since the patient is coughing/sneezi ng larger particles, is a surgical mask OK?
Reply
# Tamiflu and N-95sAmesh Adalja, MD 2009-04-28 19:38
I am not sure of the best course of action when Tamiflu pills can't be taken and Relenza is not a choice. I can't find any good information on whether Tamiflu can be crushed, etc.

Regarding infection control, the CDC recommends that patients should wear a surgical mask when outside their room.
Reply
# re: No more TamifluMatthew Perl, M.D. 2009-04-29 07:44
We've haven't had Relenza in San Diego at all this year. I called around for it in January, then again when trying to get Tamiflu yesterday.
Reply
# Decision Aids to Distinguish Swine Flu Victims from Others?Chris Carpenter 2009-04-29 15:17
The first US swine flu death was reported today (Texas toddler). Since the current flu epidemic is occurring concurrently with spring allergy season, can clinicians use any decision aids to differentiate swine flu from non-swine flu and/or allergic rhinitis? I know that fever is a distinguishing feature for flu vs. allergies, but I'm not sure of the sensitivity/spe cificity of fever nor am I confident when patients tell me they've not taken any anti-pyretics prior to my evaluation.

In 2004 shortly after the SARS epidemic, Wash U EM did a Journal Club on several SARS Clinical Decision Rules which are archived online
(https://emed.wustl.edu/emjclub_9_04.html). Is there any evidence to suggest these rules (or others) might be useful during the current swine flu epidemic? Were any descriptions of the diagnostic test performance of bedside signs/symptoms noted during the last swine flu epidemic in 1976?

Thanks for an informative synopsis and reliable updates on this flu outbreak, Amesh.
Reply
# Mike Klevens, MD 2009-04-29 15:54
I would like a comment from someone on the specificity and sensitivity of screening using nasal swabs. Our manufacturer claimed specificity is >95% and the manufacturer claimed sensitivity is 92%. I'll bet this is in line with other rapid influenza testing. In a setting of low prevalence (i.e. currently in Missouri) this is a pretty crappy screening tool. So, a CDR such as the rules for SARS noted by Dr. Carpenter, would be helpful prior to testing everyone with a URI or viral syndrome. Comments?
Reply
# Amesh Adalja, MD 2009-04-29 16:09
I don't think there is any reliable way to distinguish swine influenza from seasonal influenza clinically. Some cases have reported the presence of nausea, vomiting, and diarrhea--a clinical feature not characteristic of seasonal flu.
Reply
# Rapid Flu Tests and Clinical GestaltChris Carpenter 2009-04-29 16:13
Although I am not at all confident that this research can be extrapolated to swine flu, Wash U EM Journal Club had evaluated rapid point of care tests for Influenza in January 2007 (https:emed.wus tl.edu/emjclub_ 1_07.html) with the following bottom line:

QuickVue (one influenza POC test) is far superior (LR 28.2 for QuickVue vs. 3.8 for gestalt or 5.1 for Monto’s CDR). Clinical gestalt is improved when symptoms have been present for
Reply
# Rapid Flu Tests, continuedChris Carpenter 2009-04-29 16:17
Sorry -- above response got cut off for some reason.

Clinical gestalt is improved in adults when symptoms have been present for < 48 hours.

QuickVue Influenza test is a useful POC test in children under age 5 with LR 126 and LR- 0.18 with excellent reproducibility (Kappa = 0.98) when obtained by trained research nurses in those with non-specific upper respiratory symptoms. Despite these admirable test characteristics , a positive QuickVue test does not appear to impact overall or test-specific diagnostic testing, antibiotic prescribing or appropriate antiviral use. Appropriate use of POC tests like QuickVue have the potential to reduce ED LOS and inappropriate testing/prescri bing while relieving parental anxiety and maintaining up-to-date
regional surveillance data, but further studies will be needed to assess the utility and acceptability of these possibilities at various health care settings.
Reply
# Chief Mullah at my houseDavid Gray MD 2009-04-29 17:34
Amesh, where and how can this viral strain be identified? Can any lab do it, or does a specimen (what type?) have to be sent somewhere, ie; CDC?
Reply
# Amesh Adalja, MD 2009-04-29 17:51
Viral identification is done through your state health department laboratory. Some academic centers may be able to figure out that it is a probable case with PCR based diagnostics (i.e. finding out it is an untypable isolate).
Reply
# Please help interpret the dataBrian Melito 2009-05-01 03:59
In my reading of the studies to date, it seems that the current choices of antivirals are, at best, marginally effective. The 2007 Ontario study looked at a group with a median age of 77. There was reduction in mortality shown, but there were many reasons this data could not, and should not, be used in any way to make projections across the general population. My simple question is this: given the now extremely broad recommendations for use of these drugs during this period, how many people with "the flu" do I need to treat in order to save one individual? Thanks.
Reply
# Who to treat?Amesh Adalja, MD 2009-05-01 04:49
I agree that CDC guidance on antiviral treatment is overly broad. I think the people that must be treated are those that are hospitalized and those with high-risk features (HIV , immunosuppresse d, elderly, COPD, infants, etc). I am not sure there is enough enough evidence to say how many people need to be treated to save one life at this point. The vast majority of people will likely recover without antiviral treatment, so it should be prioritized to those at high risk of death and other serious complications.
Reply
# medical group supervisorJohn Murphy 2009-05-01 06:40
One of the major questions is the message to send the public regarding whether and how to access the health care system. We are trying an overriding message of "stay home but see us if you have risk factors." It's not a very catchy sound bite, and a little tough for the public to process. The upside with this approach is you might decrease clinic traffic, the risk is you might discourage a healthy 28 year-old from getting treatment who could develop a life-threatenin g complication...
Also, we're seeing a marked shortage of Tamiflu suspension, even in the stockpile meds. you might want to check with your pharmacies to see if they are willing to compound the capsules into the susp; instructions on Roche website.
Reply
# Vacation Plans Shot?VacationPlans 2009-05-01 13:57
I will be going on vacation with the family tomorrow to Orlando, FL. While I am less concerned, my wife is concerned. We have discussed cancelling the trip (tomorrow -w hich would cost a substantial amount of money ). We have two children a 1 year old and 2.5 year old, thus cancelling a trip is secondary concern, except that I really don't want to do so where there are unreasonable risks. Specifically, I don't want to cancel a vacation where the odds of any of us becoming fataly ill would be at the level of me dying of a heart attack prior to adding this comment.

My thoughts are that because the number of fatalities in Mexico, where the disease originated has been relatively low (and does not appear to be expanding), that the mortalitiy risk factors are also very low. That being said the one confirmed death in the US was a toddler, which off course is of concern even if the fatality was anecdotal.

Our pediatrition, went on to recommend to my wife that canceling the trip would be advisable because of the number of people one would come in contact with at a theme park. My response to that (from a non medical approach) is that wouldn't we have started to see some signs by now if this were blowing up?)

My feeling is that 300 confirmed cases worldwide, with the appearance of some stability at the source does not rise to the level of a serious concern.

Lastly, in the even my kids develop a cold or flud like symptoms, what specifically should we look for. My feeling is that if we are vigilent in the event one of us gets sick, we can mitigate against the risk of a mortal event.

I guess my questions is two fold:

1.) Does what you know rise to the level of cancelling a trip.

2.) If I take my chances, and react quickly with respect to symptoms, is it reasonable to assume that I will mitigate any serious risk of death.

Best Regards
Concerned Parent



Reply
# Dr. Besser of CDC says "flying is safe"Logan Plaster 2009-05-01 17:21
The following is an excerpt from today's Q&A teleconference with Dr. Besser of the CDC:

"Is it safe to fly? I ask that because today on the "Today" show, vice president Joe Biden said if it were his family members he would tell them not to fly at all, that it's not safe."

"There's a lot of things that we can do to try and reduce our risks. A lot of things people are doing on their own. For us in public health it's important to say what things are evidence-based, what things can you do to put yourself at risk and what things can you do to reduce your risk. In terms of flight, if you have a fever, flu-like symptoms, you should not be getting on an airplane. That is part of being a responsible part of our community. You don't want to put people at risk. I think flying is safe. Going on the subway is safe. People should go out and live their lives. There are some people who may not be comfortable doing that. As a public health community, we can put in context what the risk is. People are doing things to reduce their risk, hand washing, covering of the cough, avoiding ill people. And if we look to each other to be responsible and not get on airplanes and places when we're sick, that makes everyone else safer."
Reply
# The Virgin IslandsAndre 2009-05-11 03:39
What is the projection in terms of the time the H1N1 virus may reach the Virgin Islands or Puerto Rico?
Reply

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