hidden

Coronavirus Disease 2019 Vaccine

Coronavirus disease 2019 (Covid-19) has been declared a pandemic by the world health organization (WHO) on March 11, 2020. Since the outbreak, the WHO reported more than 70 million confirmed cases, and 1.5 million deaths globally. In the US, nearly 300,000 lost their lives and currently, we are facing another surge of cases with a record-breaking 3,124 new deaths in a single day last week. Over the past year, scientists, physicians, and pharmaceutical companies did phenomenal efforts to develop a safe and effective vaccine.

Finally, on December 11 2020, The Food and Drug Administration has issued an emergency use authorization (EUA) for Pfizer and BioNTech’s coronavirus vaccine (based on a 17 to 4 vote with one abstention). It is important to note that an EUA is not equivalent to FDA approval. As the latter requires safety data for at least six months. The FDA clearance occurred in a record-breaking time frame for a complicated process that usually takes years. This EUA makes the United States the sixth country to clear the vaccine after Bahrain, Canada, Saudi Arabia, Mexico, and the United Kingdom. In this blog, I will review the data behind the EUA.

The study behind the FDA’s EUA was a multinational, phase 2/3, Placebo-controlled, observer-blinded randomized trial. Between July 2020, and November 2020, 43,548 participants (16 years and older) who were healthy or had stable medical conditions underwent 1:1 randomization to receive vaccine or placebo (saline). Of which, 36,523 received two doses (21 days apart) and completed the 2 months follow up. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among the vaccine group and 162 cases among the placebo group. Hence the vaccine was 95% effective in preventing Covid-19. Moreover, among the 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in the placebo group and 1 in the vaccine group.

Figure 1: Efficacy of the vaccine against Covid-19 after the First Dose.

Each symbol represents Covid-19 cases starting on a given day; filled symbols represent severe Covid-19 cases. The inset shows the same data on an enlarged y-axis, through 21 days.

The noted side effects were short-term mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and similar in both groups (0.6% in the vaccine group and 0.5% in the placebo group).

Figure 2: Safety outcomes of the vaccine.

The Vaccine works simply as it contains a small piece of the virus’s mRNA that instructs cells in the body to produce the virus’s distinctive “spike” protein. After receiving the vaccine, the body will manufacture a piece of the COVID-19 virus named spike protein, which does not cause disease but triggers the immune system to learn to react defensively. Given the novel mechanism, theoretically, it carries no risk of infection, as it only codes for a piece of the virus. It is also important to note that currently, it is unclear how long the vaccine will provide protection, nor is there evidence that the vaccine prevents transmission of SARS-CoV-2 from person to person.

Given the promising results and the EUA, Pfizer is planning on shipping 2.9 million doses over this week and 100 million doses of the vaccine by next March. The pharmaceutical giant has a deal with the U.S. government, under that agreement, the vaccines will be free to the public. Understandably, the distribution will be in phases with the most critical workers and vulnerable people being on top of the list. At this point, strict monitoring of any side effects will be enforced at all sites. Apart from the approved vaccine, Moderna’s vaccine utilized a similar technology and is currently under review by the FDA and could obtain an EUA soon. Other pharmaceutical companies such as Johnson & Johnson, Oxford, and AstraZeneca, are in late-stage trials and their vaccines could be authorized in the near future. This Vaccine is the light at the end of the tunnel which gives humanity hope to reach an endpoint to this pandemic. In the meantime, we must practice social distancing, trust the data, and get vaccinated!

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

hidden

How to Publish a Case Report or an Image?

Five years ago, I was struggling to initiate my academic career and I started off with publishing an image. To this day, I remember my excitement and satisfaction when receiving the acceptance email. Writing a case report is the first step in establishing an academic medical profile. In this blog, I will guide you on how to publish a case report or image.

Recognize the opportunity and do your homework:

During rounds, you come across many interesting cases. If you recognize one of those cases, read a review article about the topic, which will give a very good idea of what you are dealing with. Search the web if there are any similar case reports and read one or two of them. At this point, most likely you would realize that the phenomenon that you thought was very rare is well documented and published in several other case reports. If you are lucky enough that there are no similar cases, then you have struck gold. If not, which happens in most of the cases, then find a different angle to your case. Try to think about your case from a different perspective. How can I make my case special? Find a unique angle and highlight it. After you have a solid grip of the topic, run it by your attending, fellow, or senior.

Gather the data:

Make sure you have gathered all the information you need from the patient and obtain written consent before the patient gets discharged. Support your case report with pictures if possible, hence take pictures if it’s applicable (skin changes, etc..). Visit the radiology department to get high-quality images/videos of the patient’s CT or MRI. Talk to the radiologist, he/she will guide you in selecting the best images. Also, make sure that you have a copy of the gross and microscopic pathology images.

Finding the right journal:

Case reports/images can be published in a very wide spectrum of journals. Evaluate your data in order to recognize a good fit for your manuscript. If you have exceptional images and by that, I mean excellent quality, unique finding, different imaging modalities you should aim high. Write it as an Image and try submitting your manuscript to NEJM, Lancet, JAMA, JACC, Circulation, and ESC families. Keeping in mind that the acceptance rate is around 10%. So even if you have an exquisite image, most likely it will get rejected. At a certain point, you might feel that this manuscript is worthless. The good news is, most journals will provide you with constructive feedback or point out the weakness in your image. Use this feedback to improve your manuscript and try again. If your manuscript was rejected in several high impact journals, then you should consider downgrading to journals with a lower impact factor. If it does not get accepted, then switch your image into a case report and explore different case report journals. The problem with case report journals is that they do not have an impact factor and most of them will charge you ranging from 300 to 1500 USD. So, make sure that you check the article processing charges (APC) beforehand.

Writing the case report:

If you are not familiar with any referencing software, learning how to use one is a crucial initial step for your academic career. Invest time to familiarize yourself with one (trust me on this one). There are many options, some of them are free, others offer discounts for students and doctors in training. Check with your institution, occasionally they offer it for free. The next step is writing, which is my favorite part. If it’s an image, then probably you will need to describe your case in around 250 words with a 2-liner conclusion and 0-4 references. If it’s a case report, then it’s highly variable between journals but it could reach 1000-2000 words. The discussion is the trickiest part. Hence, make sure you read several case reports and review articles on the topic before you start the discussion. Highlight what you like and what you think is relevant in different articles and then lay it out in your own words. After you are done, proofread it and use grammar check software. Use any help that you could have, talk to the resident who published several case reports before, look for a mentor with a prestigious academic profile, and definitely the team that was taking care of the patient. But keep in mind that some journals require only two authors on an image, so make sure you check before having a big author block.

Finalize the manuscript:

Once you have a version you are happy with, send it to your senior and accept the criticism with no hard feelings. We have all been there, after putting hours and days of effort into a manuscript, your mentor rips it apart and reconstructs the whole thing. This is how we all learn! After the modifications submit your manuscript and hope for the best and do not give up!!

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

 

 

 

 

hidden

The Impact of COVID on Medical Education

Since the beginning of the COVID-19 pandemic, our lives have been significantly affected on every level. Different countries reacted in various ways and almost everybody was under lockdown at a certain point. With time, everyone has adapted to the new “normal”. Masks are on all the time, no handshakes or hugs, and if anyone gets slightly closer physically, we tend to get extremely uncomfortable. On the professional side, all health care workers were impacted too. At the very beginning, all elective procedures were delayed, there were long working hours, more stress, and a lack of personal protective equipment. Patients who were legitimately sick did not seek medical advice and hospitals were at full capacity. Additionally, didactics were canceled, medical students were asked to stay at home, in-person national and international conferences were canceled, and many more. As a result, training and education were disrupted but the medical community stepped up to the challenge and explored different avenues to ensure steady and proper education for all healthcare workers.

In the past several months, all professional societies (AHA, ACC, ESC, TCT, ASE, and many more) did a phenomenal job in reducing the impact of the pandemic on medical education. All conferences were switched to a virtual platform, different ideas were applied to keep everyone engaged, registration fees were reduced significantly or completely waived. I must point out that now it is possible to attend all national and international conferences from the comfort of your living room, listen and interact with experts in the field, and attend the sessions that you have missed at your convenience. Additionally, for grand rounds and didactics, remote education facilitated learning from experts from all over the world. Although all these efforts helped mitigate the effect of the pandemic on education, however, everyone is still hoping for in-person conferences. Unfortunately, the ESC has decided to deliver its full portfolio of congresses and events virtually up to the ESC Congress in September 2021. Moreover, the ACC annual meeting was pushed back to May 2021 and it is expected to be in-person and virtual. Although recently, promising news about the vaccine has been published however it is unclear for how long will the pandemic last. In my opinion, the COVID pandemic expedited the development of remote education and eventually, it will become a cornerstone in medical education. In the time being, we have to work on overcoming this pandemic without impacting our education and most importantly staying safe.

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

hidden

The Story of SGLT-2 Inhibitors

There were a lot of interesting presentations at the American Heart Association 2020 Scientific Sessions today. However, I found the most interesting was “But Wait, There are More Targets: SGLT-2 inhibitor…” by Dr. Marc Pfeffer. In his presentation, he discussed how did we end up using an antihyperglycemic drug (SGLT-2 inhibitors) in treating and preventing heart failure.

In 2008, the Food and drug administration (FDA) mandated that in order to approve glucose-lowering medications, cardiovascular safety should be established. Which was defined at the time as cardiovascular death, myocardial infarction, and stroke (heart failure was not included). Subsequently, all antihyperglycemic drugs were passing the bar when it comes to cardiovascular events. Until 2015, unexpectedly the EMPA-REG OUTCOME study showed that in patients with type 2 diabetes, empagliflozin had a lower rate of cardiovascular deaths, heart failure hospitalizations, and death from any cause.(1) Following this study, the endocrinologic and metabolic drugs advisory committee vote was split in regards to the impact of SGLT-2 inhibitors on cardiovascular outcomes. The final vote was 12 “Yes” vs 11 “No”, and as a result, the FDA concluded that SGLT-2 inhibitors reduced cardiovascular death.

Afterward, EMPA-REG OUTCOME results were reproduced in several studies (CANVAS, DECLARE-TIMI). Most importantly, this effect was independent of HbA1c level. However, the population in the aforementioned studies were not predominantly heart failure patients. At this point, the cardiovascular community adopted the drug, and from 2017 to 2018 four large outcomes trials were launched (DAPA-HF, EMPEROR-Preserved, EMPEROR-Reduced and DELIVER) In 2019, DAPA showed that among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes.(2) In 2020, EMPEROR-Reduced showed that among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes.(3) The previous findings were confirmed in a metanalysis that included both studies.(4) Although it is not very clear how SGLT2 inhibitors decrease cardiovascular events and heart failure, currently we have robust evidence proving its efficacy.

While many discoveries in medicine are incidental. I find the story of SGLT2 inhibitors as fascinating as other landmark accidental discoveries in medicine such as penicillin and warfarin. The moral of the story is always be observant and trust the data.

References:

  1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28.
  2. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008.
  3. Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-24.
  4. Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. The Lancet. 2020;396(10254):819-29.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”