Why is Paxlovid (nirmatrelvir/ritonavir) a promising new drug in our fight against Covid-19?

Based on the manufacturer’s (Pfizer’s) report, there are several reasons why Paxlovid may be a promising drug:1

  • It’s the first oral drug approved by the FDA for Emergency Use Authorization (EUA)
  • It reduces risk of hospitalization or death by ~ 90% (when taken within 3-5 days of symptom onset) in patients at high risk of complications from Covid-19
  • It reduces viral load at day 5 of treatment by 10-fold compared to placebo, theoretically reducing infectivity at least in household settings 2
  • Serious adverse events were comparable to placebo; possible side effects include liver disease, diarrhea, altered sense of taste, hypertension and muscle aches
  • Nirmatrelvir component of Paxlovid has been found to be active against a variety of SARS-CoV-2 variants of concern such as alpha, beta, delta as well as the newer omicron variant. This finding is in contrast to significantly reduced or loss of neutralizing activity of many commercially-available monoclonal antibody products against the omicron variant (eg, Casirivimab/Imdevimab-REGEN-COV, Bamlanivimab/Etesevimab, but not Sotrovimab)  designed to reduce serious Covid-19 complications in mild to moderate disease. 3-4

Few caveats to keep in mind when prescribing Paxlovid at this time:

  • It’s only approved for adults and children 12 years of age or older weighing at least 88 lbs (40kg) who test positive for SARS-CoV-2
  • Patients should be at high risk for progression to severe Covid-19 such as hospitalization or death
  • Per manufacturer (Pfizer), Paxlovid should not be taken if a patient is on certain medications due to the possibility of adverse drug interactions. The list includes colchicine, lovastatin, simvastatin, sildenafil for pulmonary arterial hypertension, some anti-epileptics (eg, carbamazepine, phenytoin), rifampin and St. John’s Wort.
  • There is no experience with treating pregnant women or breastfeeding mothers.
  • Pfizer recommends effective barrier contraception or refraining from sexual activity while taking Paxlovid

Paxlovid comes in a box of blister packs containing 5 days’ worth of medications (two 150 mg tablets of nirmatrelvir plus one 100 mg tablet of ritonavir to be taken 2x/day).  

Bonus Pearl: Another preliminary study of Paxlovid, this time including unvaccinated adults at low risk of hospitalization or death, has found a 70% reduction in hospitalization and no death compared to placebo with marginal statistical significance (P=0.051) but still with a 10-fold drop in viral load. 1

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References

  1. Pfizer announces additional phase 2/3 study results confirming robust efficacy of novel COVID-19 oral antiviral treatment candidate in reducing risk of hospitalization or death. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-additional-phase-23-study-results . Accessed Dec 23, 2021.
  2. Marc A, kerioui M, Blanquart F, et. al. Quantifying the relationship between SARS-CoV-2 viral load and infectiousness. eLife 2021;10:e69302. https://elifesciences.org/articles/69302#:~:text=Based%20on%20the%20current%20knowledge,24%25%20to%2058%25%20in%20household  
  3. Aggarwal A, Stell AO, Walker G, et al. SARS-CoV-2 Omicron:evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. MedRxiv 2021. Doi:https://doi.org/10.1101/2021.12.14.21267772. https://www.medrxiv.org/content/10.1101/2021.12.14.21267772v1
  4. Planas D, Saunders N, Maes P, et al. Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization. MedRxiv 2021. https://www.biorxiv.org/content/10.1101/2021.12.14.472630v1

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Why is Paxlovid (nirmatrelvir/ritonavir) a promising new drug in our fight against Covid-19?

Can I have some tips on how to improve my PowerPoint presentation?

Effective or “high value” PowerPoint presentations take some planning and work. Here are some tips (by no means comprehensive) on how you can improve your PowerPoint presentation,1-4 divided into 4 stages:

Stage I: Planning for your talk

    • “Know your stuff”
    • Prioritize the main objectives of your talk given time  constraints ie, “What would you like your audience to really take away from your talk?”
    • Accept the fact that you will not be able to cover all that you know about the topic during the allotted time
    • Think about how you might keep your audience engaged throughout your talk as you introduce topics and concepts!

Stage II: Preparing your slides

  1. General rules
    • Keep them simple (“Less is more”)
      • Minimize number of slides eg, average no more than 1 slide/min
      • Minimize number of concepts/slide eg,1/slide
      • Minimize clutter 
    • Avoid “apologetic” slides ie, if not easily readable or visible or “too busy”, don’t use them!
    • Practice, practice, practice and edit as needed
  2.  Text
    • Minimize number of words/slide eg, 6×6 rule, maximum 6 words/line, 6 lines/slide
    • Use easily readable font types and sizes
      1. Minimum 24 for small rooms
      2. Minimum 36 for larger rooms
      3. If not readable 10 feet away from monitor, don’t include
    • Check spelling!
    • Choose high contrast colors between background and text eg, black text on white, yellow on dark blue background, not red on green
  3. Tables
    • Avoid reproduction of large tables with tons of data that cannot be read or can easily overwhelm the audience
    • If you use large tables, zero in on a particular section and display a magnified version of that section so that the audience can follow along with you

Stage III: Presenting your talk

  • Remember, you are the presenter, not PowerPoint
  • Engage the audience from the beginning to the end
    • Beginning: Use a “hook” ie, why should the audience be interested in your talk?
    • During
      • Maintain eye contact with the audience
      • Be dynamic/animate
      • Use speech intonations as if you are having a conversation with the audience
      • Do not read slides word-by-word
    • End: Highlight your take-home points eg, “if you don’t remember anything else…”

Stage IV: Post-Presentation

  • Ask for feedback from colleagues, audience, coordinators, etc… 
  • Self-reflect ie, what went well, what didn’t go so well?
  • Apply lessons learned to your next PowerPoint presentation!

Five take-home points for this pearl

  • Less is more, keep your presentation clear and simple
  • Time is limited; prioritize your message
  • Keep your audience engaged throughout the talk
  • Conclude with take-home points
  • Practice, practice, practice

Bonus Pearl: Did you know that people generally remember 20% of what they hear, 30% of what they see, and 50% of what they see and hear? 2

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References

  1. Collins J, et al. Evaluation of speakers at a national radiology continuing medical education course. Med Educ Online 2002;7:17 https://pubmed.ncbi.nlm.nih.gov/28253766/ 
  2. Collins J. Education techniques for lifelong learning. RadioGraphics 2004;24:1177-83. https://pubmed.ncbi.nlm.nih.gov/15256637/ 
  3. Harolds JA. Tips for giving a memorable presentation, Part IV. Using and composing PowerPoint slides. Current Nuclear Medicine 2012;37:977-80. https://pubmed.ncbi.nlm.nih.gov/22899205/ 
  4. Grech V. WASP (write a scientific paper):Optimization of PowerPoint presentations and skills. Early Human Development 2018;125:53-56.https://pubmed.ncbi.nlm.nih.gov/29929910/ 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Can I have some tips on how to improve my PowerPoint presentation?