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Updates to the NIH Biosketch

For this week’s blog, I wanted to focus on a central component of any NIH grant — the biosketch. Did you know that the NIH is updating the biosketch format for all applications due on or after May 25th, 2021? Did you know that your application can get rejected if a biosketch in your grant application is formatted incorrectly? Regardless of where you are in your research career, if you are planning to apply for an NIH grant, it’s a great time to either get started on your biosketch or update what you have.

 What is an NIH biosketch?
An NIH biographical sketch (or biosketch) is a five-page resume of your scientific work. A biosketch is required for all NIH grant applications and renewals. Like a resume, the goal of the biosketch is to communicate to the reviewers that you are the ideal person to undertake the research proposed. In its current form, the biosketch consists of four sections: (A) Personal Statement, (B) Positions and Honors, (C) Contributions to Science, and (D) Additional Information: Research Support or Scholastic Performance.

How to get started writing your NIH biosketch?
There are two major types of biosketches: Fellowship (for F-awards) and Non-Fellowship (for most other awards, including K-awards and R-awards). The NIH biosketch needs to be written in a specific format. The format varies a tiny bit between Fellowship and Non-Fellowship types, so first determine which kind of biosketch you want to prepare. There are two options to get started:

  1. Download the appropriate biosketch sample from the NIH Grants and Funding website and modify it as needed.
  2. Use the NIH SciENcv website (linked to your My NCBI account) to create your biosketch. I love this website and highly recommend giving this approach a try. The NIH SciENcv website is a joy to work with and incredibly simple to use. All you need to do is create a personal NIH bibliography, input all your information, and then export your biosketch as either a Word Document or PDF. The NIH SciENcv website automatically formats your citations and correctly inserts your data into the biosketch layout.

What are the major changes to the new biosketch?

For a complete list of changes, read more about the upcoming changes to the biographical sketch and other support format page in the NIH notice here: NOT-OD-21-073. As you will read, the changes are few but significant. I’ve highlighted a few of the major changes here in bolded italics.

  1. Section B has been renamed. Instead of “Positions and Honors” it is now “Positions, Scientific Appointments, and Honors.” In this section you now need to include both domestic and foreign positions and scientific appointments. The NIH is asking that individuals now list any affiliations with foreign entities or governments. If this applies to you, definitely read through this section carefully as titles can include full-time, part-time, or even voluntary positions.
  2. In Section B, the “Positions, Scientific Appointments, and Honors” should now be listed in reverse chronological order. In the past, these materials were listed in chronological order.
  3. For non-Fellowship biosketches, Section D (Additional Information: Research Support) has been removed. In its place, details about ongoing and completed research projects from the past three years should be included in Section A (Personal Statement).

What are the major changes to the “Other Support” section?

While the changes to the NIH biosketch are minimal, in the same notice (NOT-OD-21-073) the NIH will now require more documentation for the “Other Support” section of your grant. These changes include:

  1. Inclusion of all resources, including in-kind contributions (i.e. office/laboratory space, equipment, supplies, or researchers supported by an outside source).
  2. Addition of a signature block (for the Principal Investigator and Other Senior/Key Personnel) to certify the accuracy of the information.

“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.”

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Get with the Guidelines (GWTG) – Stroke Patient Registry Use in Primary and Comprehensive Designated Stroke Centers during COVID-19 Pandemic

This year many of the professional conferences that traditionally took place live have had to change to virtual mode due to the global COVID-19 pandemic and its related social distancing rules.  The International Stroke Conference and Nursing Symposium was no exception. Yet it presented an excellent opportunity for many to attend, especially those who could not have joined the conference in-person had the opportunity to participate virtually.  Healthcare professionals, academicians, researchers, and supporters of stroke prevention were able to join from different places in the world, under different time zones. There were many options for participants to engage and interact in the many discussions and presentations through the online platform.

Earlier I had the opportunity to write about various topics presented during the #ISC21 (you can read them here: “Reducing Disparities through Diversity and Inclusion in Stroke Science, Clinical Trial Enrollment, and Community Engagement”; “Transformation of the GWTG – Stroke Patient Registry to into a National Representative Database of Acute Ischemic Strokes (AIS) in the U.S.”).

Today, I wanted to interview a couple of conference participants who could share with you about their experience attending this virtual conference. I also wanted them to share with you their experience with the GWTG Stroke Registry and the prevention of stroke in the midst of the COVID-19 pandemic. My guests for this post-conference interview are Ms. Jessilyn Pozo, Baptist Health South Florida System-Wide Stroke Program Manager, and Dawntray Radford, Stroke Coordinator for South Miami Hospital (You can follow them for more information here).  This transcript is a lightly edited version of the interview we conducted on webcam, shortly after the 2021 International Stroke Conference.

Catherina: How was your experience at the 2021 International Stroke Conference (ISC) delivered in virtual mode?

Dawntray: The International Stroke Conference was definitely different this year. However, I was appreciative that they (AHA) were able to extend the sessions’ timeframe so that we would be able to take a deeper dive, engage in deeper discussions opposed to the 10-15 minute sessions that we normally would have (in a live conference).  I think I got a lot more information (from the presentations and discussions), especially within the different scheduled presentations.  Therefore, I think there was an added bonus of extending the sessions’ timeframe.

 

Dawntray Radford, BSN, RN Stroke Coordinator South Miami Hospital

 

Jessilyn: This is my second time attending ISC. I went last year to Los Angeles for it. Although I do like the live version more, I liked that we were able to see lectures recorded and delivered on-demand. There were a lot of interesting topics this year, specifically hot topics with Tenecteplase1, which many hospitals are leaning towards converting its use. There were different topics like the nursing care guidelines, and reports from recent studies released.  We were able to take many good notes, and we were able to pause and write down things and keep going with the lectures.  I really enjoyed attending the conference, but I am excited for it to be live next year.

 

 

Jessilyn Pozo, BSN, RN, SCRN BHSF System-Wide Stroke Program Manager Baptist Hospital of Miami

 

Catherina: How would you describe your role in the stroke program at your organization?

Jessilyn: I oversee the stroke program for the Baptist Health system. Baptist Hospital of Miami is our comprehensive center. Dawntray Redford runs the South Miami Hospital stroke program, which is a primary stroke center, certified by the Joint Commission.2  She worked tirelessly to get it certified with no Requests for Improvements (RIFs).  So kudos to her! We are working with West Kendall Baptist Hospital to become a primary stroke center. We are working to have a few of our other entities to be acute stroke ready. We have oversight of the stroke program at each individual entity and as a system to provide standardized great stroke care for all patients.

Catherina: Please tell us Ms. Radford about your role in the stroke program at South Miami Hospital.

Dawntray: We went through our first initial certification as a primary stroke center.  There are a lot of moving parts in the program that we need to monitor.  In addition to providing care, since we are a primary stroke center, there is an urgency of transferring stroke patients to the comprehensive center.  This shows to our community and Emergency Medical Services (EMS) that we have the capabilities of readily identifying the acute stroke patients when they arrive and transferring them out at a target time of sixty minutes. Based on the feedback we received from the certification survey by the Joint Commission, it was very impressive! Because of the national times, the average goal is to push for at least 90 minutes.   The literature suggests and has proven (benefits) from taking about 2 hours to 3 hours to actually have a patient transferred out to an equipped hospital.  Emergency medical services (EMS) had tried to propose to bypass the primary stroke centers and go to the comprehensive one. They did not want these two-to-three-hour delays of the patient transferred because of so many logistics of trying to transfer a patient from one hospital to another system, as we had to go through that transfer process.  With the streamlined process at our Institute, the Miami Neuroscience Institute, we have our own streamlined process and our dedicated transfer center.  We can actually execute our transfers in sixty minutes.  We worked very hard with our internal system of identifying patients before they even arrived to our institution. We are having that proactive approach of readily identifying that patient that has that large vessel occlusion. We already have a transfer center in place before the patient even arrives. This would make our numbers soar to that target timeframe for patients to get excellent stroke care.  During our certification survey, we got compliments on our timeframe, less than the 90-minute-to-120-minutes timeframe, as we probably may be set back a new benchmark for the nation.

Catherina: What are the benefits of the GWTG Stroke Registry at your organizations?

Jessilyn: We are very lucky to have a data analyst team that is driven and just solely dedicated to the management of our stroke data. They are the ones who check on our stroke alert times; make these dashboards with turnaround times that they input in Get With The Guidelines. The Get With The Guidelines Stroke Registry helps us to stay on track.  It keeps us on our toes, making sure that we meet the (stroke) goals.  We aim to provide the care that we need to (deliver to stroke patients) based on the guidelines and the standards.  This (registry data) allows for feedback on how our programs are doing.

Dawntray: The use of The Get With The Guidelines at South Miami Hospital is imperative, especially with the fact that we have different stroke units. The staff at the stroke units would like to see how they are doing as an individual unit, so they know where they need to improve individually as opposed to the hospital as a whole.  Especially with the Emergency Department, their metrics would be different from the metrics of an inpatient unit.   At least with the registry, I could take the different core quality measures and give the appropriate information specific to their unit.  I use the registry 100% to monitor our quality measures and performance improvement measures.

Catherina: What has been your experience with stroke patients seeking stroke care in the midst of the COVID-19 pandemic?

Dawntray:  We definitely have seen a decrease in the volume of care, especially with EMS and the patients that walk in.  Eighty percent of our patients would arrive by their private vehicles. Many patients did not come through EMS during the pandemic.  We noticed at least 50% change in our volume for at least the first two months of the COVID pandemic.  We have also seen an increase in ischemic strokes with clots, with occlusive strokes in patients that were positive for COVID. They developed COVID first.  The developed stroke as a secondary diagnosis.

Jessilyn: From the comprehensive center standpoint, being like the hub of the system, we have seen internal patient transfers from our sister hospitals. These patients were initially admitted for COVID care. They developed an acute ischemic stroke and were transferred over for neuro intervention.  Unfortunately, these have been the trickiest patients. They were on the younger side, ended up being hypercoagulable. Our interventionalists are amazing! However, they do say it is more difficult, they find more clots. It is not just one. They seem to find several clots.  These patients also tend to reocclude, even though they have had a successful thrombectomy. Therefore, I think COVID has really posed quite a challenge in stroke care for all.

Catherina: What suggestions do you have for healthcare professionals in educating patients about the prevention of stroke, especially during this COVID-19 pandemic?

Jessilyn: I think one of the biggest issues in stroke is that as high as it is, 80% of the strokes are preventable. Stroke should probably be out of the top 10 issues that are the cause of mortality in our nation or in the world.  A lot of it has to do with the fact that people do not recognize the symptoms.  It also has to do with getting them in here (hospital) for early treatment.  We have those 24 hours for them to be a possible candidate for stroke care.  A lot of them do not just even recognize the symptoms or the risk factors of stroke.  They do not understand things that they just do in their daily life, that if they were to change one of these minute things, it can help them decrease their risk of stroke and relieve them from possible debilitating life symptoms.

Dawntray: (During the pandemic) we reached out to our marketing department.  We have a Facebook page where we have a post on Fridays.  (We posted) on recognition of the signs of early stroke: FAST: Face, Arm, Speech, Time of recognizing stroke, calling 911.   We also had information on what (symptoms) to look for.  We had a message built in to the post as well, stating that, “we know that you may be afraid to come in, that you want to stay at home, but you choose to be aware of, of not being afraid to seek services, to come in to the hospital where it is safe.”   “We take a lot of preventative measures to protect ourselves and to the community during the pandemic”.   We are just letting them know what the signs and symptoms were and not to be afraid to come in and to seek care (at the hospital).   We are just giving them that comfort that it is safe to come into the hospital.  Because that is what they feel… it was not safe, so they were afraid to come in (during the pandemic).

Catherina: Thank you for the opportunity to interview you and look forward to the next ICS conference.  Anything that you would like to share out there with stroke coordinators, any advice or word of guidance?

Jessilyn: Just hang in there.

Dawntray: You have to be inventive. Just know that a pandemic cannot hinder you from providing the care that you provide every day.   You just have to be creative, find a better way, a different way of still executing what you do on a daily basis.

I would like to thank Ms. Jessilyn Pozo and Ms. Dawntray Redford for sharing their experiences during this 2021 Virtual International Stroke conference as well as their experiences with the GWTG Stroke Registry, Primary and Comprehensive Stroke Program, and stroke prevention during the COVID-19 pandemic. For more information, you can reach them at JessilynP@baptisthealth.net and DawntrayTW@Baptisthealth.net

 

References:

  1. Warach SJ, Dula AN, Milling TJ Jr. Tenecteplase Thrombolysis for Acute Ischemic Stroke. Stroke. 2020;51(11):3440-3451. doi:10.1161/STROKEAHA.120.029749
  2. The Joint Commission. Primary Stroke Center Certification. (2021). Retrieved from https://www.jointcommission.org/accreditation-and-certification/certification/certifications-by-setting/hospital-certifications/stroke-certification/advanced-stroke/primary-stroke-center/
  3. American Heart Association. Get with the Guidelines Stroke Registry. (2021). Retrieved from https://www.heart.org/en/professional/quality-improvement/get-with-the-guidelines/get-with-the-guidelines-stroke

“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.”

 

 

 

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Listen to Your Heart: How to Prepare Yourself for A Career in Cardiology

The road to Cardiology fellowship can be a confusing one. Residency, with its breakneck pace and punishingly long hours, is already a Herculean challenge in and of itself. Simply completing residency is its own feat. Attempting to set yourself up for the next stage in your career in a hyper-competitive specialty adds an entirely new layer of complexity. Trainees on this path towards post-residency training in Cardiology often find themselves asking critical questions: How can I figure out if Cardiology is truly the right field for me? How can I prepare myself for fellowship? What can I do to make myself a competitive applicant?

As you can imagine, the real answer here is that there is no one right way to approach the journey of becoming a cardiologist. Everyone must forge their own path. Still, I would like to share some lessons I have learned from my experiences as a Cardiology-bound resident.

Trade into Cardiology rotations

The only way to find out if you like Cardiology is to ensure that you actually have exposure to it. Sometimes, this means trading into additional Cardiology rotations and increasing your exposure to both cardiologists and potential Cardiology mentors who can talk to you about this career. Only by rotating in Cardiology rotations can you decide if this is a field that you would like to pursue further!

Seek out outpatient Cardiology experiences

Much of the exposure that Internal Medicine residents have to Cardiology during residency comes in the form of inpatient Cardiology rotations (Cardiology wards, Cardiac ICUs). While these are wonderful entry points into the field, they represent only a fraction of the breadth and depth of Cardiology. They may even erroneously lead you to think that most Cardiology happens inside of the hospital (surprise: much of it happens in the outpatient setting). I did not realize this myself until I participated in an ambulatory Cardiology elective. I strongly encourage you to explore the world beyond the CCU or Cardiology wards, so that you can develop a more realistic view of how you will spend the majority of your clinical time later in your career.

But don’t do too much Cardiology!

A common misconception among residents, regardless of their intended career, is that they should only pursue experiences in their field of interest. While this is admirable and might make you feel more prepared for fellowship, you must remember that nothing can truly prepare you for a career in a subspecialty except for fellowship itself. You will have entire years of your academic life set aside to learn how to be a cardiologist. However, after residency, you will no longer have the opportunity to improve upon your weaknesses in other areas of Internal Medicine. One of my mentors once told me that I should use my spare elective time to learn about other subspecialties so that I can become a better and more well-rounded internist. You will have plenty of time to learn about Cardiology during the fellowship. Use this precious extra time to learn about other things that will make you a better doctor, and ultimately, a better cardiologist.

Seek mentors out early

One common mistake that I see people make is that they wait too long connect with potential mentors. Applying to Cardiology fellowship applications is an extremely competitive process.  Thus, it can only help to have mentors in your corner who help you think about your career goals, give you feedback about your fellowship application, help you plan research projects, connect you with other mentors, write letters of recommendation on your behalf, and go to bat for you when the time comes. However, mentor-mentee relationships are not born overnight. You need to dedicate time to building a relationship with mentors that understand you and advocate for you. Allow time to see if you and a mentor hit it off and give your mentor a chance to get to know the real you. The only way to accomplish this is to start early.

Find projects that excite you

It can be really tempting to fall into the trap of taking on as many research projects as possible with the sole purpose of “fluffing” your resume, without regard to a project’s value or quality. Remember that everything you put out into the world is a reflection on you; you should be willing to stand proudly by any work that you produce. Be judicious. Select only those projects in which you are genuinely invested. Don’t just pad your resume with countless meaningless abstracts or manuscripts. Quality will always triumph over quantity.

Set realistic research goals

At the end of the day, your primary job in residency is to be a resident. Sometimes you will be too busy to do research. Sometimes you will be too drained to do research. Sometimes you need to recharge instead of doing yet more work. That’s OK. You cannot do it all. During my first meeting with one of my mentors, we talked about pursuing smaller projects that I could realistically complete during residency rather than trying to take on huge untenable projects. In retrospect, it was incredibly thoughtful and kind of my mentor to be so deliberate. It helped me set more realistic goals about what I could accomplish during residency and it made my research experience more fulfilling. You are a very busy resident. You should accordingly select realistic, sustainable and completable projects.

Join the online Cardiology community!

There is a very active Cardiology community on social networks such as Twitter, talking about the latest high-profile articles, debating new guidelines, and sharing amazing tweetorials or interesting clinical experiences. Social media offers a great opportunity to get to know and make connections with people in the field. I “met” some people on Twitter before I formally met them on the interview trail. It was nice to already have that connection with others in Cardiology. It made me feel from the very beginning that I belonged to a larger Cardiology community. Moreover, it has enhanced both my learning and my excitement about becoming a cardiologist!

Integrity is everything

No matter what you do, put your best foot forward every time. Your reputation really does matter. Though it seems large, Cardiology is also a tightly knit community and people do talk. You will want to develop a reputation as a hardworking, honest, conscientious and reliable person. Actions always speak louder than words. Remember that everything you do will be a reflection on you and your character. When in doubt, ask yourself, can I proudly stand by this decision a month or a year from now? Do the right thing every time. Don’t cut corners. Work hard and be kind. Whether you do good or bad things, people will take notice, and they won’t forget.

 

“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.”

 

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Ramadan, COVID-19 and the cardiac patient

With the dawn of the Islamic lunar month of Ramadan, many Muslims around the world begin observing an absolute fast from dawn to dusk, abstaining from food, drink, and oral medications. The fast naturally also entails a change in lifestyle, sleeping patterns, and adjustments of salt and fluid intake, all of which have implications for the cardiac patient. Furthermore, as they are generally known to be on multiple medications, depending on the number of hours of fasting, there might be a need for adjusting drugs, doses, and timings.

Cardiac patients span across a wide range of diseases and differ in terms of symptoms, acuity, and hemodynamic stability. As such, while it might be entirely appropriate for stable patients to observe the fast, with adjustments to lifestyle, others who are less so may need to be advised against fasting, particularly as the sick are exempted. There is a paucity of data on best practices for fasting among cardiac patients. This blog provides a brief summary of the available data, some general suggestions, and links to useful resources pertinent to patients with common cardiac conditions on fasting during Ramadan.

Stable Coronary artery disease: Few observational studies suggest that with good monitoring, fasting may be safe in patients with stable treated coronary artery disease (CAD), particularly with normal left ventricular ejection fraction (EF), provided they adhere to medications.1-3

In fact, among stable patients with a previous history of cardiovascular disease (CVD), fasting during Ramadan has been shown to significantly improve 10-year Framingham cardiac risk score, as well as cardiovascular risk factors such as lipid profile, body mass index (BMI), and systolic blood pressure.4

Acute myocardial infarction (MI): Unlike stable CAD, however, in patients with a recent acute MI or immediate post-cardiac surgery, abstinence from fasting following the 6-week period of either of these events has been advised.5,6

Heart failure (HF): A prospective observational study examining the effect of Ramadan fasting on patients with chronic HF and reduced ejection fraction (< 40%), noted that as many as 92% of the patients that fasted had no changes or improved symptoms, while symptoms worsened in a minority of patients (8%).7 Furthermore, those with worsening symptoms were significantly less likely to have adhered to fluid and salt restrictions, and heart failure medications (p<0.0001). This clearly underscores the need for ensuring compliance with appropriately timed medications, particularly diuretics, in order to prevent acute decompensation of HF.

The British Islamic Medical Association has a structured guideline of recommendations based on risk for fasting among patients with heart failure:6

  • HF with preserved ejection fraction (HFpEF), and HF with reduced EF (up to an LV EF 35%) are at low/moderate risk for fasting (i.e. decision not to fast at the discretion of medical opinion and patient’s ability).6
  • Severe, but not advanced, heart failure is at high risk for fasting and should be advised not to fast. This would include patients on Cardiac Resynchronization Therapy (CRT) .6
  • Patients with advanced heart failure (including those on Left Ventricular Assist Devices), decompensated HF requiring large doses of diuretics 5, and those with severe pulmonary hypertension, are deemed very high risk, and MUST be advised against fasting.6

Hypertension: Fasting during Ramadan is generally well-tolerated in patients with well-controlled essential hypertension on the continuation of previous drug treatment 5,8, supported by ambulatory BP measurement (ABPM) data in observational studies.9-10. However, patients with resistant hypertension should be advised not to fast until their blood pressure is reasonably controlled.5 The key to blood pressure maintenance during Ramadan lies in compliance with medications, and non-pharmacological measures such as a low-salt diet.11. In those with fluctuating BP, home blood pressure monitoring with medication adjustment may be a feasible option.

Adjustment of medications: Cardiac medications are vital, and non-compliance has the potential to be life-threatening. Patients should be advised on adherence to medication, and efforts be made to ensure compliance, by adjusting dose and timings, or switching to a class of medication that might be a more compliant alternative.8 For drugs with two daily doses, it’s advisable to take them with as wide a gap as possible during non-fasting hours.8 In case a medication requires more than twice daily dosing, an adjustment that allows for better compliance may be preferred.

Antihypertensive drugs: For twice-daily medication, dose timings may need to be changed to coincide with the early morning meal (Suhoor) and the breaking-of-fast meal (Iftar).8 A switch to a once-daily medication with long-acting preparations may be preferred.8,11

Diuretics: Diuretics are particularly unpopular among patients who either stop or reduce its doses during Ramadan. Diuretics may also worsen fasting-associated dehydration (especially in hot weather), with non-compliance resulting in uncontrolled hypertension and decompensation of heart failure. If the indication is hypertension, switching to a suitable alternative is reasonable.6 However, strict compliance with diuretics must be advised among those with HF especially those with reduced EF. They may also be prescribed during the non-fasting period of the day (i.e. early evening), where there is minimal risk of associated dehydration.5 Alternatively, patients may consider taking it at dawn (suhoor) to prevent frequent micturition and disturbed night sleep.6

Anticoagulants: Compliance must be ensured for those requiring therapeutic anticoagulation, irrespective of indication, with patients being advised of the risks of stroke or systemic embolism in case of non-adherence.12,13 Some older small-scale observational studies have reported that Ramadan fasting does not appear to adversely influence the efficacy or safety of warfarin.14, 15 However, more recent data suggest that Ramadan fasting does in fact influence the therapeutic effect of warfarin in terms of lowered time spent in therapeutic range (TTR) with a reduced proportion of patients achieving therapeutic PT-INR and consequent increased risk of poor anticoagulation control.16, 17 As such, closer monitoring or dosage adjustments are necessary for patients maintained at the higher end of INR target ranges.16 This should extend to the post-Ramadan period, particularly in the elderly as they are more prone to over-anticoagulation and consequently the risk of bleeding.17, 18 ).

There is no randomized evidence on dosing adjustments for Novel oral anticoagulants (NOACs) with fasting during Ramadan.12 However, clinical practice suggests that drugs are taken once or twice daily, such as NOACs, do not require an adjustment.12 . Among patients on twice-daily NOACs such as apixaban, a switch to once-daily rivaroxaban might be feasible.6 Those taking rivaroxaban should be asked to take the NOAC with food even during the month of Ramadan.12

Antiplatelet medications: Patients must be strictly advised to continue dual antiplatelet therapy (DAPT), especially in case of a recent MI or percutaneous coronary stent implantation, with clear information on the adverse outcomes of non-compliance such as acute stent thrombosis, MI, and even death.6 In terms of P2Y12 inhibitors, given pharmacokinetics of ticagrelor, if twice-daily dosing proves challenging, a switch to single-dose P2Y12 inhibitors such as clopidogrel or prasugrel (if appropriate), may be considered.6

Ramadan, COVID-19, and vaccine uptake: With the rollout of vaccines currently underway globally, there are concerns about vaccine hesitancy, based on whether the intramuscular injection invalidates the fast, any possible side-effects, and if indeed the fast may have to be broken.19  Scholars have clarified that vaccination does NOT invalidate the fast and such clarifications must be widely disseminated among both cardiac patients and the general public in order to maximize vaccine uptake.20

The bottom line to good heart health during Ramadan remains in good communication and preemptive discussions. Although the current climate of the COVID-19 pandemic poses challenges to in-patient visits and physical examinations, virtual consultations must be leveraged to optimize cardiac care during the month of fasting. Some useful resources have been linked in the references. This blog is by no means exhaustive, and decisions regarding individual patients’ suitability for fasting and medication adjustments must be made following individualized discussions with their respective physicians, particularly as the duration of the fast varies in different geographical locations and as such, not all data derived from studies can be extrapolated generically.

References

  1. Salim I, Al Suwaidi J, Ghadban W, et al. Impact of religious Ramadan fasting on cardiovascular disease: a systematic review of the literature. Curr Med Res Opin. 2013;29(4):343-54.
  2. Al Suwaidi J, Zubaid M, Al-Mahmeed WA, et al. Impact of fasting in Ramadan in patients with cardiac disease. Saudi Med J. 2005;26(10):1579-83
  3. Mousavi M, Mirkarimi S, Rahmani, Get al. Ramadan fast in patients with coronary artery disease. Iran Red Crescent Med J. 2014;16:e7887.
  4. Nematy M, Alinezhad-Namaghi M, Rashed MM, et al. Effects of Ramadan fasting on cardiovascular risk factors: a prospective observational study. Nutr J. 2012;11:69.
  5. Chamsi-Pasha H, Ahmed WH, Al-Shaibi KF. The cardiac patient during Ramadan and Hajj. J Saudi Heart Assoc. 2014;26(4):212-5.
  6. Ramadan Rapid Review & Recommendations – British Islamic Medical Association. Available at: https://britishima.org/wp-content/uploads/2020/05/Ramadan-Rapid-Review-Recommendations-v1.2.pdf (Accessed on 10th April 2021)
  7. Abazid RM, Khalaf HH, Sakr HI, et al. Effects of Ramadan fasting on the symptoms of chronic heart failure. Saudi Med J. 2018;39(4):395-400.
  8. Aadil N, Houti IE, Moussamih S. Drug intake during Ramadan. BMJ. 2004;329(7469):778-82.
  9. Perk G, Ghanem J, Aamar S, Ben-Ishay D, Bursztyn M. The effect of the fast of Ramadan on ambulatory blood pressure in treated hypertensives. J Hum Hypertens. 2001;15(10):723-5.
  10. Habbal R, Azzouzi L, Adnan K, et al. Variations tensionnelles au cours du mois de Ramadan [Variations of blood pressure during the month of Ramadan]. Arch Mal Coeur Vaiss. 1998;91(8):995-8.
  11. Chamsi-Pasha M, Chamsi-Pasha H. The cardiac patient in Ramadan. Avicenna J Med. 2016 ;6(2):33-8.
  12. Hersi AS, Alhebaishi YS, Hamoui O, et al. Practical perspectives on the use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with nonvalvular atrial fibrillation: A view from the Middle East and North Africa. J Saudi Heart Assoc. 2018;30(2):122-139.
  13. Batarfi A, Alenezi H, Alshehri A, et al. Patient-guided modifications of oral anticoagulant drug intake during Ramadan fasting: a multicenter cross-sectional study. J Thromb Thrombolysis. 2021;51(2):485-493.
  14. Saour JN, Sieck J, Khan M, et al. Does Ramadan fasting complicate anticoagulation therapy?. Ann Saudi Med 1989; 9: 538– 40.
  15. Chamsi‐Pasha H, Ahmed WH. The effect of fasting in Ramadan on patients with heart disease. Saudi Med J 2004; 25: 47– 51.
  16. Lai Y, Cheen M, Lim S, et al. The effects of fasting in Muslim patients taking warfarin. J Thromb Haemost 2014; 12: 349– 54
  17. Sridharan K, Al Banna R, Qader AM, et al. Does fasting during Ramadan influence the therapeutic effect of warfarin? J Clin Pharm Ther. 2021 Feb;46(1):86-92.
  18. Awiwi MO, Yagli ZA, Elbir F, et al. The effects of Ramadan fasting on patients with prosthetic heart valve taking warfarin for anticoagulation. J Saudi Heart Assoc. 2017;29(1):1-6.
  19. Ali SN, Hanif W, Patel K, Khunti K; South Asian Health Foundation, UK. Ramadan and COVID-19 vaccine hesitancy-a call for action. Lancet. 2021:S0140-6736(21)00779-0.
  20. Sharifain H. COVID-19 vaccine does not invalid the fast during Ramadan: Abdul Rehman Al Sudais. Available at: https://www.haramainsharifain.com/2021/03/covid-19-vaccine-does-not-invalid-fast.html. (Accessed on: April 12 2021)
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Being an Immigrant Doctor in the USA in Midst of the Pandemic

Let’s go back to 2007. Very vividly I remember my first ever conversation at a coffee shop in Ahmedabad, India (my medical school town) which had sparked interest in this land of opportunity- The United States of America (USA) -thousands of miles away from home.  A few medical students were discussing their experience of clerkship in New York. “The air is so fresh and crisp,” they said. “By the way, if a patient with severe anemia gets admitted, they don’t discharge the patient just after giving blood transfusion- they actually find the etiology”! “Wow,” I said. “That’s how I want to practice. I want to find what’s wrong with my patients”. Having memorized all the possible causes of anemia, while witnessing lots of patients get discharged with outpatient follow up predominantly due to limited resources from the largest hospital in Asia- Civil Hospital, Ahmedabad, I was excited to learn physicians get to solve the jigsaw puzzle of diagnosis and then treat the patient in the USA. After quite a bit of back and forth with my family, I decided to come to the USA. I recall the day I left India. My entire extended family had gathered to say goodbye. After all, I was the first daughter amongst many, to leave the country alone, and pursue higher education in a distant land with no family whatsoever, at the tender age of 23. I remember, seeing tears and sadness amongst my family members but I was determined and happy. “I am going to the USA to be a cardiologist”, I had announced many times as the phone in our household kept ringing to wish me luck on my journey. I literally left on cloud seven, bursting with joy, on a one-way flight to Philadelphia, on February 18th, 2008.

Fast forward April 6th, 2021. India had recorded another surge in COVID numbers that day. Two in the morning, I kept tossing and turning in my bed. Three days later, I was supposed to fly on a bubble flight to India. India had done okay with COVID in early 2021 and my parents were vaccinated. I saw a chance to see them after 1.5 years but now this covid surge out of nowhere!? All these years, I always told my family, “I am only 17 hours away. I can fly if I need to. The world is smaller than ever”. COVID had changed a lot. The entire year I had literally imagined myself hanging over the Atlantic, with the body in the US and mind and heart in India, many times. To complicate the issue, I had to renew my visa to the USA this time, to return back to the USA. “what if India goes in lockdown”, “What if I catch the new highly infectious variant prevalent in India and give it to my mother, who has been diagnosed with pulmonary fibrosis” “What if they decide to quarantine me at the airport”, “what if I don’t get my visa renewed and cannot return to the USA”. 2:30 AM, I got up, canceled my flight tickets, my visa appointment, and other arrangements. Like a giant infant then, I cried for at least half an hour. It was not fair at so many levels. Yeah, I know, that I made that choice for myself. I know I had decided to leave my family and come to the USA. After all, Life is a matter of choices and every choice you make, makes you, as John Maxwell- an American author once said.  My stay in the USA had made me what I am today, but also made me feel how I felt during that night. I often think of the contrast in my experience when I came to this country compared to now.

This pandemic has been hard on immigrant physicians. During the early days of covid, I felt like stepping in a warzone as I entered the hospital. I would recite Hanuman Chalisa (Hindu hymn chanted for strength and courage) every single day multiple times as I saw COVID patients. I often discussed with fellow immigrant cardiologists- “we cannot get sick. God forbid if we get sick, who will take care of us? Who will update our families? what if we get so sick, we cannot do our jobs and get kicked out? What if we die? How will our family manage everything while thousands of miles away? For my married friends with children at home, it was challenging. Some were sleeping separately to keep the family safe. One of my friends who is an ICU physician told me he didn’t sleep well for months during the surge. The chances of getting COVID from super sick patients were high. If he became disabled or died, his family would lose their legal status, income and would be forced to leave the country. I have a close friend who lost his mother to COVID and couldn’t see her for the last time or do the death ritual as the eldest son. During hardship, it’s easy to think of extremes. Precovid, we were part of American society, flourishing professionally, doing well. COVID changed us. The sense of security and being home in the USA eluded. Where was home?

1/3 of the physicians in the USA are immigrants1. More than a third of those IMG (International Medical Graduates) have visa restrictions in spite of legally residing in the country and paying taxes as a US citizen. The top three countries that send IMGs to the USA are India, China, and the Philippines2. For those of you who think, immigrant physicians, take up opportunities from physicians that were born in the USA, the Association of American Medical Colleges projects a shortage of up to 139,000 physicians in the US by 20333. The jobs that offer visas often take advantage of the need for visas by foreign physicians by offering little compensation for a lot more work mostly in distant parts of the country. Professional and personal uncertainty posed by the pandemic has changed the future for many immigrants particularly the physicians having witnessed the surges of covid during the peak of the pandemic before vaccination started5.

I really hope in midst of an ongoing pandemic with no sight of the end, the immigration reform gives more flexibility to the physicians to travel to their home countries without the need for visa renewal. I also hope that this land of opportunity accelerates the permanent resident status for highly skilled physicians particularly those who are on the front lines during the pandemic and served their adopted country with vigor and in certain cases with their lives.

I don’t know how the COVID pandemic is going to change immigration patterns across the world. I often think about this, now being away from family for more than a year. This country has made me who I am today, and I am so incredibly grateful for my stay in the USA, for the education, incredible career opportunities, social status, and freedom I have acquired, particularly as a female cardiologist. However, I often wonder, if all the sacrifices that I have made are worth these successes. I guess the grass is always greener on the other side, but this pandemic has definitely made me pause and reflect on my choices and decisions.

 

References:

1  https://www.newamericaneconomy.org/issues/healthcare/

2  Harker YS. In rural towns, immigrant doctors fill a critical need. Health Affairs. 2018;37(1):161-164.  u

3  https://www.aamc.org/system/files/2020-06/stratcomm-aamc-physician-workforce-projections-june-2020.pdf

4  https://blogs.bmj.com/bmj/2021/02/04/my-blackness-enters-the-room-first-an-immigrant-physicians-perspective-on-systemic-racism-in-the-us/

5  Benji K Mathews, MD, SFHM, Manpreet Malik, MD, FHM, Immigrant Physicians Fill a Critical Need in COVID

 

“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.”

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5 Daily Struggles of an Early Career Physician

For this month’s blog entry, I’ve decided to share a more reflective piece. In now just over six months into my young career, my early morning routine is pretty set in stone. Wake up. Shower. Scrubs. Coffee. Mask. Keys. Go! But what happens from approximately 8 am – 5 pm is still evolving.

This blog will briefly go over my daily struggles, but I could just as easily share five daily rewards/positives/joys of an early career physician … and maybe next month I will.

  • I’m the attending (physician). Part of being fresh out of training is that nobody knows. Whether you stay at your home institution or move to a new setting, you’re likely the new kid on the block in the Doctors’ Lounge or the EMR’s attestation text box. Despite proudly wearing my “attending physician” ID badge, I find myself constantly having to reiterate that I’m the supervising doctor. I recently entered the room to begin time out for a transesophageal echo and was stopped by the anesthesiologist because we couldn’t begin the case without the cardiologist present. Another time, I was asked if I was the fellow doing the case with Dr. X, a well-known echocardiographer. Despite how this may sound, I quite like the shocked look on my patient’s faces when I walk in and introduce myself as the person who will be managing their complex cardiovascular disease – or my ability to walk through the medical center unbothered and largely unnoticed while taking in some much needed Miami sun.
  • One of my daily struggles is not knowing how to say “no.” As a medical trainee, you’re often the person called upon to do the tasks that no one else wants to take on. Whether it be consent for a procedure or calling the pharmacy to correct a prescription, you’re often faced with the rhetorical question of “can you please…?” or “ would you mind…?” Well, this doesn’t really stop when you’re a newly appointed faculty. I often reply to emails first or make phone calls because I’ve been there and I know that I CAN help in that way. Eventually, though, I will need to learn when this is impinging on time that could be well allocated to more important tasks.
  • To do or not to do. From the moment my first patient shares with me the reason for their visit, there is a tug-o-war in my head between doing something and doing nothing. A wise professor once told me that 70% of medical conditions resolve without the doctor doing anything. We’re tasked with identifying the 30% of the time when we can make an impactful difference in the disease course. I once read a Wall Street Journal article titled “When Doing Nothing is the Best Medicine.” This is much easier said than done, but I’ve found that many patients just want reassurance that what ails them will not lead to their untimely demise. Explaining my thought process, and clearly stating that we can always order more tests or perform more studies at a later date if things don’t get better, has served me well so far.
  • Leaving work at work. It’s not uncommon to find a trainee spending extra time in the hospital or in the clinic finishing tasks that their attending doesn’t want to find undone in the morning. When you’re the attending, the decision as to what can wait until later lies with you. When I first started my new job, I often stayed up late replying to emails or finishing notes, or making calls from home. What I’ve found is that not everything needs to be done now. I have frequently reminded myself of the following diagram, as it has helped me leave work at work and not take it home with me.

Source: https://luxafor.com/the-eisenhower-matrix/

  • Work/Life Balance. As physicians, we’re tuned to work work work until you can’t work anymore. It’s commonplace for physicians to work well past the retirement age, and sometimes until they are no longer with us. My mentors have shared with me that the decision to prioritize family, vacation, rest starts NOW. It is a lot harder to put into practice. There is always something that needs to be attended to, whether your “out of work” auto-reply is posted or not. I’ve made it a goal of mine to fully utilize the ample paid time off afforded to me by my employer, and to truly disconnect during these times. It’s still very hard, and I haven’t perfected it, but making it a priority is the first step.

Thank you for reading, and please share with me some struggles that you’re having as an early career physician. I can be reached on Twitter @DrDapo. Until next time!

 

“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.”

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The Rising Value of Plain Science Talk: Part 1

When it comes to placing value on something newly discovered or innovated in the scientific fields, a key yet somewhat lost-in-the-shuffle point is the ability to communicate to a wide audience why this discovery or innovation is rated as highly valuable. Most scientific discoveries, novel techniques, and significant leaps forward in knowledge and implementation are “communicated” via academic publications in journals that have significant value to academics and subspecialists but have limited general public exposure, and in specialty conferences and society meetings where only paying members and interested individuals are able to participate in.

Even when some of those journals are more widely distributed and recognized (Nature, Science, New England Journal of Medicine, The Lancet, etc.), the actual articles in those journals are written in extremely precise, yet somewhat too technical of a format, to capture the attention and translate the knowledge to the wide swath of the population that might encounter it. And Even when the conferences and meetings are more accessible and have reduced barriers to entry and participation, the actual presentations (the talks, the posters, the workshops) are all geared to communicate directly to peers in the field, not to an interested yet general-knowledge audience.

This is not to say the work itself and researchers doing it are not producing important knowledge. New discoveries and innovations are the keys to maintaining or improving the planet and all its inhabitants’ health.  Knowledge is the key to propelling societies forward. The issue is that for so long, the methods of communication of this type of information has been restricted, both by the avenues that contain this information (journals and conferences that are inaccessible to the public) and the written/spoken formats used to transmit this information (articles and talks delivered in overly technical ways).

The missing ingredient in a recipe that would serve a much greater audience with something more palatable and engaging is called Knowledge Transfer & Translation (KTT). There are many definitions and formats that shape what the KTT factor is, depending on the organization that places importance on it. In a generalized way, I’ll define KTT as: a plan to disseminate newly acquired information to the broadest set of interested parties, accompanied with a framework of how to advance this new knowledge into actions that benefit (sometimes “profit”, in business sectors) the knowledge seekers and broad general public.

Knowledge Transfer and Translation has not always been a focus in academic research circles. Most scientists think of KTT as someone else’s job. I did! In the years it took for me to gain enough education and real research experience (a journey that spans more than a decade, from BSc to MSc to PhD to research fellowship), the vast majority of my time learning has been with the singular aim of discovery & innovation. Once the discovery is made, the only requirement my academic world asks of me is to report this discovery, in the form of a research article that only my peers in knowledge can truly appreciate in full, and maybe talk about this discovery in a 10-min presentation at a conference where many of my peers and interested members of the field I occupy congregate on an annual basis.

However, this traditional and old-fashioned view of the role of an academic has begun to change in the past few years. Discovery and innovation are still the driving forces of academic research, but increasingly, the values placed on those discoveries and innovations are complemented by how much Knowledge Transfer and Translation is placed behind these discoveries and innovations to propel them beyond the circles of subspeciality academic fields. Novel avenues of sharing knowledge have entered the hallways and labs of academia: Online platforms. The digital world with its massive reach and accelerated speed of information sharing is an essential and increasingly irreplaceable tool to implement the KTT directives needed to advance our societies. Science communication (#SciComm) has taken on a new meaning and many new forms that were simply unavailable a few years ago. Social Media has complemented and amplified the use of Traditional Media in broadcasting research and academic data that normally had few ways to reach the proverbial “center stage”.

I’ll tackle this ever-growing list of new and exciting ways of science communication on Part 2 of this series of blogposts, coming May 2021. Until then, you can always reach me for feedback or just to say hi (Twitter: @MoAlKhalafPhD), I am an “Extremely Online Scientist”!

 

“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.”

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Bias

A middle-aged black woman presents to her local emergency department via emergency medical services (EMS) with chest and back pains, nausea, and vomiting. She has a history of IV drug abuse and is disheveled in appearance. Prior to her arrival, EMS notes that her chest pain appears non-cardiac and provides supportive care while en route to the hospital. She is triaged to the appropriate care and an emergency provider assesses the patient. 

The patient continues to have chest discomfort and nausea. The emergency team agrees with the EMS assessment and deems her symptoms as atypical for a cardiac etiology. An EKG is performed which demonstrates subtle ST-segment elevations in her inferior leads as well as faint reciprocal changes. However, the catheterization lab was not activated at this point. 

High sensitivity troponin ultimately revealed a modest enzyme leak and the cardiology team was consulted. The patient was urgently taken to the cath lab to reveal an acute lesion of her proximal right coronary artery. There were no complications during the procedure and she ultimately had an uneventful hospital course. 

Implicit bias refers to the attitudes or stereotypes that affect our understanding, actions and decisions in an unconscious manner. These biases are activated involuntarily, without an individual’s awareness or intentional control. Unfortunately, we are all susceptible to bias and there is extensive evidence showing how bias can lead to differential treatment of patients by race, gender, age, weight, language, socioeconomic status, and insurance status. As such, it begs the question, if our patient had no history of drug abuse or was white, would their acute myocardial infarction been treated faster? 

A seminal 2007 study of internal medicine and emergency medicine residents found that, while the participants reported no explicit racial bias, Implicit Association Tests (IATs) indicated an implicit preference towards White Americans. Further, the higher the preference, the more likely that physician was to treat Whites and not treat Blacks with early thrombolysis in the setting of acute myocardial infarction. 

While it is clear the effects of implicit bias in medicine, it is also clear that implicit bias is malleable. There are a number of leading strategies for combating implicit bias including stereotype replacement, counter-stereotypic imaging, individuation, perspective-taking, and increasing opportunities for contact with individuals from different groups. Further, new research must be conducted to find more innovative techniques for managing implicit bias. As clinicians, it is our responsibility to be constantly aware of our bias and to actively work to address that bias in every patient encounter. 

References 

  1. Green AR, Carney DR, Pallin DJ, et al. Implicit bias among physicians and its prediction of thrombolysis decisions for black and white patients. J Gen Intern Med. 2007;22(9):1231-1238. doi:10.1007/s11606-007-0258-5

“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.”

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On the Basis of Sex: Are males more vulnerable in severity and mortality from COVID-19?

Fig1: Data source: The sex, Gender and Covid-19 Project. (https://globalhealth5050.org/the-sex-gender-and-covid-19-project/about-us/)

As we just passed our first anniversary of fighting COVID-19, we are in a better position than we used to be a year ago. Nationwide vaccine efforts encourage us to see the light at the end of the tunnel. However, the virus is still lurking around and always finds its way back in many unpredictable forms as it evolves rapidly. We need to stay vigilant and use what we learned from the previous years’ knowledge to guide us defend any future attacks. One pertinent piece of information we discovered is that COVID-19 attacks us unequally. People are over 65 years old and people with any underlying complications are more at risk. Another important discovery is that there is a sex difference in infection, severity, and death among women and men.

In most countries, the incidence of infection (percent of cases) is similar in both sexes. However, men consistently develop more serious symptoms and have more mortalities across age groups on a global level (Fig1). More specifically, men account for about 59% to 75% of total mortality1. It’s indisputable that sex is an important factor when it comes to understand and combat COVID-19. Here are a couple of candidate mechanisms potentially contributing to sex-biased COVID-19 mortality.

Hormones

Many sex differences in the manifestation of disease development have long been attributed to sex hormones, particularly in the realm of immune responses. Both innate and adaptive immune responses are affected by sex-dependent factors2. Males are more susceptible to infections caused by parasites, fungi, bacteria, and viruses, one of the possible determining factors is sex hormone3. More specifically, the immune-suppressive androgens reside in males and immune protective estrogens reside in females. Females might produce more antibodies and launch a stronger immune defense to infection because of estrogens, while males lack the advantage to react the same way. Female hormones, estrogens, can ameliorate the severity of influenza infections by suppressing pro-inflammatory responses in mice4. The anti-inflammatory activity of estrogen is potentially through the regulation of the SOCS3 and STAT3 signaling pathways, specifically to promote the progression of the anti-inflammatory process towards the IL-10-dependent pathway in macrophages5. Sex hormones can regulate the immune response via regulating circadian rhythm, microbial composition, and transcriptional regulation such as estrogen receptors (ERs) and peroxisome proliferator-activated receptors (PPARs)6.

Fig2: Potential mechanisms of male bias of COVID-19 mortality7.

Sex chromosomes

One of the fundamental differences between men and women is the X and Y sex chromosomes. Females have two X chromosomes with a functional one and an inactive one to maintain the balance of chromosomal X gene dosage, while males only have one functional X chromosome and one Y chromosome to maintain the identity of sex-specific effects and testis development. This evolutional advantage in females provides a “back-up” plan in case of a “disease gene” on X chromosome inherited from either the maternal or paternal side. Some genes can escape from X chromosomal inactivation and consequently express higher levels. The gene encoding a receptor that is responsible for SAS-CoV-2 virus cellular entry is called ACE2. ACE2 locates at X chromosome and is potentially a target for ineffective chromosome inactivation, and which could cause a female-biased increased level of ACE2 expression7. A higher level of ACE2 in females promotes viral clearance. On the contrary, a lower level of ACE2 causes dysregulated inflammation, increased cardiovascular comorbidities, increased risk of respiratory failure in males7 (Fig2). Other inflammatory response-related genes on the X chromosome include pattern recognition receptors such as toll-like receptor 7 (TLR7), TLR8, interleukin-1 receptor-associated genes, and NFKB essential modulator genes8. Additionally, it has been shown that TLR3, TLR7, and TLR9 are female-biased while TLR2 and TLR4 are male-biased. These differences potentially reveal why males and females respond to infection differently7,8. The research on understanding sex dimorphisms in immunity is critical to help us fight COVID-19 more effectively.

In conclusion, strong evidence shows that COVID-19 affects men and women unequally. Aside from socio-economic, lifestyle and environmental differences, biology plays an important role in male-biased COVID-19 severity and mortality. To understand and combat infection more precisely, we need to consider sex as a biological variable and develop therapeutic strategies for men and women respectively.

References

  1. Griffith DM, Sharma G, Holliday CS, Enyia OK, Valliere M, Semlow AR, Stewart EC, Blumenthal RS. Men and COVID-19: A Biopsychosocial Approach to Understanding Sex Differences in Mortality and Recommendations for Practice and Policy Interventions. Preventing chronic disease. 2020;17:E63.
  2. Markle JG, Fish EN. SeXX matters in immunity. Trends in Immunology. 2014;35(3):97–104.
  3. Klein SL. The effects of hormones on sex differences in infection: from genes to behavior. Neuroscience & Biobehavioral Reviews. 2000;24(6):627–638.
  4. Robinson DP, Lorenzo ME, Jian W, Klein SL. Elevated 17β-Estradiol Protects Females from Influenza A Virus Pathogenesis by Suppressing Inflammatory Responses. PLOS Pathogens. 2011;7(7):e1002149.
  5. Villa A, Rizzi N, Vegeto E, Ciana P, Maggi A. Estrogen accelerates the resolution of inflammation in macrophagic cells. Scientific Reports. 2015;5(1):15224.
  6. Taneja V. Sex Hormones Determine Immune Response. Frontiers in immunology. 2018;9:1931.
  7. Bienvenu LA, Noonan J, Wang X, Peter K. Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities. Cardiovascular Research. 2020;116(14):2197–2206.
  8. Pradhan A, Olsson P-E. Sex differences in severity and mortality from COVID-19: are males more vulnerable? Biology of Sex Differences. 2020;11(1):53.

“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.”

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My Journey as a Physician-Scientist Trainee

In this blog, I discuss my journey as a physician-scientist trainee to provide some insights to aspiring physician-scientists and in the hopes of encouraging others to consider pursuing this very rewarding career.

During the early part of my undergraduate training, I was not sure whether I wanted to go to graduate or medical school. I worked in a basic science lab throughout my undergraduate education. I enjoyed my time in the lab and the scientific process. As I was researching graduate and medical schools, I discovered MD/PhD and Medical Scientist Training Programs (MSTP) and thought that this would be a great option to merge my passions for medicine and basic science research.

I was fortunate to have the opportunity to be a part of the MSTP at the Medical College of Wisconsin (MCW). Prior to starting medical school, I did not know what medical specialty I wanted to go into or what specific project I wanted to work on. My MSTP training lasted 8 years. I rotated through labs the summer before the first year of medical school and the summer between the first and second years of medical school. After the second year of medical school, I joined the lab of Howard Jacob, Ph.D. and studied the genetic basis of hypertension and renal disease for four years. I loved my time in graduate school and the research environment in the Department of Physiology. I was so fortunate to be in the Department of Physiology at MCW where many of the faculty were generous mentors to trainees. I am especially grateful for all the mentorship that I received from Dr. Jacob, Dr. Joseph Lazar, Dr. Allen Cowley, Dr. Andrew Greene, Dr. Joseph Barbieri and the entire MSTP. Serendipitously, Dr. Ivor Benjamin (AHA president from 2018-2019) moved to MCW when I was training there and was willing to be a member of my dissertation committee. He is a phenomenal role model for aspiring physician-scientists. I am very appreciative that he took the time to mentor me clinically and scientifically. With his encouragement and guidance, I subsequently decided to pursue additional training in Cardiology with the goal of becoming a cardiovascular translational researcher.

After completing my Ph.D., I returned to clinical training to complete the third and fourth years of medical school. I subsequently joined a dedicated Physician-Scientist Training Program (PSTP) at the University of Minnesota that allowed me to simultaneously match into Internal Medicine residency and Cardiology fellowship and secure protected research time for postdoctoral research training. After completing medical school, I finished two years of Internal Medicine training and the first year of clinical Cardiology fellowship. I then joined a basic science laboratory and am now conducting research investigating the mechanisms of right ventricular dysfunction in pulmonary hypertension. I am fortunate to have three years of protected research time (I am currently in year 2 of research). During my postdoctoral research fellowship, I also see pulmonary hypertension patients in the clinic one-half day a week. After I complete my research time, I will then return to a clinical Cardiology fellowship to complete the last year of clinical training.

My journey to becoming a physician-scientist is still ongoing but there is never a day that I regret choosing this career. While the training can be long and arduous, it is rewarding. The transitions between research and clinical training can be challenging and you may constantly feel that you are trying to catch up with your peers. However, the job is never boring and there is always so much to learn! In clinical training, you gain a wide breadth of knowledge and when doing research, you study a narrow topic in depth. As a physician-scientist, you provide unique insights into what are the clinically relevant questions that need to be addressed. Whenever I am frustrated with troubleshooting experiments in the lab, feel that I am losing focus, or am dejected after paper/grant/award rejections, I become re-inspired and motivated to advance my research after seeing patients and being reminded of the many gaps in our medical knowledge.

The delineated path above was my path towards becoming a physician-scientist. There are multiple paths to becoming a translational researcher. Many medical trainees join labs or research groups during or after clinical training.

Here are some pearls that I picked up as an aspiring translational researcher:

  • When you are at the beginning of your medical training as a medical or MSTP student, you do not need to know exactly what you will do in the future. Be open-minded.
  • Selecting a mentor and lab environment that are a good fit for you is more important than the specific project you work on as a Ph.D. student. It is not expected and highly unlikely that you will study the exact same topic that you did your PhD work on for the rest of your career.
  • Throughout your training, find supportive environments and mentors. I am very thankful for the support of Dr. Kurt Prins, Dr. Thenappan Thenappan, Dr. Joseph Metzger, Dr. Samuel Dudley, Dr. Peter Crawford, Dr. Jane Chen, Dr. Cliff Steer and the entire PSTP, the CTSI program, and the entire Cardiology fellowship program at the University of Minnesota.
  • Be persistent and resilient.
  • Mentor and encourage others to become physician-scientists, especially those who are underrepresented in the biomedical community.
  • Enjoy the journey.

For any early-career trainees who are interested in becoming physician-scientists, feel free to contact me if you have any questions! I really hope that some of you strongly consider joining this very gratifying and important

 

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