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1 hour ago, Anastasis said:

Maybe we finally move on...

Early intervention, North America-based, HCQ RCT, writing on the wall for a while, finally hits the press. 

https://www.acpjournals.org/doi/10.7326/M20-4207

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Abstract

Background:

No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).

Objective:

To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.

Design:

Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668)

Setting:

Internet-based trial across the United States and Canada (40 states and 3 provinces).

Participants:

Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.

Intervention:

Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo.

Measures: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.

Results:

Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, −0.27 points [95% CI, −0.61 to 0.07 points]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non–COVID-19–related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).

Limitations:

Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.

Conclusion:

Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.

The doctors that swear by hydroxychloroquine say that it acts in concert with zinc.   So why no zinc in this study?

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5 minutes ago, JohnLocke said:

The doctors that swear by hydroxychloroquine say that it acts in concert with zinc.   So why no zinc in this study?

Additional post hoc analyses showed that self-reported use of zinc or vitamin C in addition to hydroxychloroquine did not improve symptoms over use of hydroxychloroquine alone (Supplement Table 2).

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10 hours ago, Anastasis said:

Additional post hoc analyses showed that self-reported use of zinc or vitamin C in addition to hydroxychloroquine did not improve symptoms over use of hydroxychloroquine alone (Supplement Table 2).

Only 63 people took zinc with hydroxychloroquine and 53 took it without.  What we don't know is what kind they took. 220 mg Zinc sulfate is what I have seen recommended; I doubt many took that.  If I read this right, those that did not take zinc reported increased severity of symptoms by 20%.  For a frame of reference that's about the difference between the 18-35 age group vs. the over 50 age group. Vitamin C had an even bigger effect. 

It's frustrating to me that all of these studies just seem designed to not really test what some doctors are touting.  Hydroxychoroquine, zinc,  & Vitamin C.  It just seems to me that you need to do something before you arrive at the hospital, because at that point, a good number of people are screwed.  At the least, I don't see any downside to that regimen. 

 

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Just now, JohnLocke said:

Only 63 people took zinc with hydroxychloroquine and 53 took it without.  What we don't know is what kind they took. 220 mg Zinc sulfate is what I have seen recommended; I doubt many took that.  If I read this right, those that did not take zinc reported increased severity of symptoms by 20%.  For a frame of reference that's about the difference between the 18-35 age group vs. the over 50 age group. Vitamin C had an even bigger effect. 

It's frustrating to me that all of these studies just seem designed to not really test what some doctors are touting.  Hydroxychoroquine, zinc,  & Vitamin C.  It just seems to me that you need to do something before you arrive at the hospital, because at that point, a good number of people are screwed.  At the least, I don't see any downside to that regimen. 

 

part of the problem is that it got out early the docs were taking HCQ as a prophylactic.  I think ChitownDoc even confirmed it.  that said, who really knows.  I think we are generally learning things.  co-worker got it(late 40's) and was out for 2-3 weeks.  went to hospital, said he had it, and they gave him IV and tylenol, sent him home and he had to track his O2 and that was it for the entire time.  he said the worst thing was beyond just being tired was dehydration and the revenge.  his family got it also.  2 young kids no symptoms, wife got it and had very mild for about a week.

It looks as though HCQ is a "don't care/not obivous" not sure on remdesivir but maybe that is a "looks promising"

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8 minutes ago, dcar00 said:

part of the problem is that it got out early the docs were taking HCQ as a prophylactic.  I think ChitownDoc even confirmed it.  that said, who really knows.  I think we are generally learning things.  co-worker got it(late 40's) and was out for 2-3 weeks.  went to hospital, said he had it, and they gave him IV and tylenol, sent him home and he had to track his O2 and that was it for the entire time.  he said the worst thing was beyond just being tired was dehydration and the revenge.  his family got it also.  2 young kids no symptoms, wife got it and had very mild for about a week.

It looks as though HCQ is a "don't care/not obivous" not sure on remdesivir but maybe that is a "looks promising"

Remdesivir clinical trials showed that it worked verses HCQ clinical trials which showed that it didn't work. Remdesivir is by no means a miracle cure but it does have a positive effect on outcomes.

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38 minutes ago, JohnLocke said:

Only 63 people took zinc with hydroxychloroquine and 53 took it without.  What we don't know is what kind they took. 220 mg Zinc sulfate is what I have seen recommended; I doubt many took that.  If I read this right, those that did not take zinc reported increased severity of symptoms by 20%.  For a frame of reference that's about the difference between the 18-35 age group vs. the over 50 age group. Vitamin C had an even bigger effect. 

It's frustrating to me that all of these studies just seem designed to not really test what some doctors are touting.  Hydroxychoroquine, zinc,  & Vitamin C.  It just seems to me that you need to do something before you arrive at the hospital, because at that point, a good number of people are screwed.  At the least, I don't see any downside to that regimen. 

 

Dude, that's true of literally every communicable disease.  Generally if you have to go to the hospital, you're in a bad fucking way.

While I get that you don't see a downside to the regimen, it doesn't change the fact that you're ignoring known adverse effects.  Dehydration, nausea, vomiting, diarrhea, irregular heart rate, all of those things would not be great to add to the body's stress load during an infection with covid.  

What doctors specifically are you referring to?

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16 minutes ago, JohnLocke said:

If I read this right, those that did not take zinc reported increased severity of symptoms by 20%.  For a frame of reference that's about the difference between the 18-35 age group vs. the over 50 age group. Vitamin C had an even bigger effect. 

If you are referring to the data in ST2, I don't think that you are reading it right.  The ~20% is the relative between-group difference (HCQ v PBO) among those not taking zinc.  The result favored HCQ over PBO among those not taking Zn (0.46 absolute difference on a 10 pt visual analog symptom severity scale).  The suggestion here is that NOT taking Zn was associated with greater level of reduction in symptom severity associated with HCQ, relative to PBO. Among those taking HCQ, there does not appear to be any effect associated with Zn (interaction term NS, but numerically favors no Zn). Same for Vit C (except the interaction term is statistically significant). You shouldn't read too much into these subgroup analyses though, as they break randomization and are unadjusted. 

 

As far as Zinc goes generally, I am a fan.  I take a supplement every day (chelated Zn picolinate) and have the whole family taking Zicam lozenges and spray. 

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On 7/16/2020 at 11:39 AM, GRHorn said:

No one has really answered so I’ll give you what I’ve observed. 
 

First of all, last week there was probably 4-5 patients sent home from the ER with a positive diagnosis for every one that was admitted. They are admitted for acute hypoxic respiratory failure. Low O2 sats, shortness of breath, usually tachypneic. Most do not progress to ICU. Just need O2 support for a day or two. They’re all getting oral steroids, anticoagulation prophylaxis with lovenox. Also getting the Vit C, zinc, axithromycin, rocephin combo. For any given day typically there’s twice as many floor patients vs icu. Evidently it’s pretty clear which patients are going to pitstop In the hospital for a day or two and go home, and which are gonna deteriorate.

I have one later today that follows a fairly typical pattern for the ones that do worse. Came to hospital after having cough for about 10 days at home. The last few days was short of breath with nausea and vomiting. Admitted to icu and started on above meds and high flow nasal bipap, similar to your cpap machine at home. Condition kind of waxed and waned a little. Consulted for remdesivir and convalescent plasma. He refused the plasma because he’s a Jehovah’s Witness. Committee approval required for remdesivir. On about hospital day 6 he gets a cold foot.  Taken for emergent thrombectomy (removal of clot from artery). Had to be intubated for surgery and stayed that way after. Put on heavier anticoagulation. Foot now dead a couple days later. Gonna have amputation. Kidneys failing. He’s fucked. 
71 year old. Diabetes, HTN. 

Thank you.  So it looks like prolonged shortness of breath with blue lips and/or high and prolonged fever might be the cues to go to the hospital?

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2 hours ago, TwiceHorn said:

Thank you.  So it looks like prolonged shortness of breath with blue lips and/or high and prolonged fever might be the cues to go to the hospital?

An easy to remember rule of thumb I’ve heard is, if you’re getting out of breath when you’re talking, you definitely need to go in. Sounds extreme but other milder signs of shortness of breath,like with exertion, don’t really signify disease severe enough to be admitted. So save yourself money and time of going to ER.  Or buy a pulse ox I suppose. 

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47 minutes ago, TwiceHorn said:

In the absence of a pulse ox, aren't the telltale signs of hypoxia blue lips and nail beds?

No. Those are signs of people with chronic bronchitis. “blue bloaters”. 
 

Just by looking at somebody you aren’t able to tell if they’re sats are 94% on room air (send them home) or 89% (admit and give oxygen). 
 

Also to your initial post, elevated CRP, ferritin, and D-Dimer on your labs at admission are a bad sign. 

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11 hours ago, Anastasis said:

If you are referring to the data in ST2, I don't think that you are reading it right.  The ~20% is the relative between-group difference (HCQ v PBO) among those not taking zinc.  The result favored HCQ over PBO among those not taking Zn (0.46 absolute difference on a 10 pt visual analog symptom severity scale).  The suggestion here is that NOT taking Zn was associated with greater level of reduction in symptom severity associated with HCQ, relative to PBO. Among those taking HCQ, there does not appear to be any effect associated with Zn (interaction term NS, but numerically favors no Zn). Same for Vit C (except the interaction term is statistically significant). You shouldn't read too much into these subgroup analyses though, as they break randomization and are unadjusted. 

 

As far as Zinc goes generally, I am a fan.  I take a supplement every day (chelated Zn picolinate) and have the whole family taking Zicam lozenges and spray. 

Thanks,  I get it now.  After a quick read through, here's the problems I see with the study. First, already mentioned,  no zinc with the hydroxychloriquine. Everyone claiming good results with hydroxychloriquine gives it with zinc, and a very specific form.  Second, they started the study with the intent of measuring hospitalizations and deaths.  The good news was that the hospitalization rate was much lower than expected, but it was so low that the sample size was too low to give statistically significant results. They calculated they needed a sample size of 6000 people to give valid results but they had fewer than 500.  So they switched midstream to the much more subjective measure of overall symptom severity.  In those taking hydroxychloriquine, they had 4 hospitalizations and 1 death. In those taking the placebo, they had 10 hospitalizations, (2 of which were not Covid) and 1 death.  So taking hydroxychloriquine cut the hospitalization rate in half, but the sample size was too small to have statistical significance.   A few tantalizing clues that hydroxychloriquine helped those that need it most-the biggest reduction in symptom severity occurred in those over 50, but that was only 23% of the participants-too few to draw conclusions.  I don't see this study disproves the effectiveness of taking hydroxychloriquine early; it just highlights the need for a bigger study with more participants who are at higher risk for hospitalization.  The headline could have been "Study shows 50% reduction in hospitalizations for those taking HQC"  or "No statistical significance in hospitalization and death rate for those taking HQC"  Both would have been technically correct.

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9 hours ago, JohnLocke said:

First, already mentioned,  no zinc with the hydroxychloriquine. Everyone claiming good results with hydroxychloriquine gives it with zinc, and a very specific form.

Maybe the effect is actually attributable to the Zn supplementation, and has nothing to do with HCQ.

9 hours ago, JohnLocke said:

Second, they started the study with the intent of measuring hospitalizations and deaths.

Changing endpoints mid stream would typically make me throw the study in the garbage, but in the case of a study rolled out during early phase of a global pandemic I'll let it slide. The sample size justification makes sense. 

9 hours ago, JohnLocke said:

I don't see this study disproves the effectiveness of taking hydroxychloriquine early

That's not how this works. 

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9 hours ago, JohnLocke said:

The headline could have been "Study shows 50% reduction in hospitalizations for those taking HQC"  or "No statistical significance in hospitalization and death rate for those taking HQC"  Both would have been technically correct.

Also not how this works. 

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16 minutes ago, Anastasis said:

Maybe the effect is actually attributable to the Zn supplementation, and has nothing to do with HCQ.

Changing endpoints mid stream would typically make me throw the study in the garbage, but in the case of a study rolled out during early phase of a global pandemic I'll let it slide. The sample size justification makes sense. 

That's not how this works. 

Granted, it failed to show the effectiveness of HCQ, but it did not prove that it doesn't work either. It isn't being reported that more studies are needed to draw conclusions. It is being reported that it HCQ isn't effective. It did NOT show that.  You can't design a study that will give you statistically insignificant results, and then claim you have proven something. The last criticism I have of this study is that it didn't go past 14 days.

As for Zinc, the claim is that HCQ opens up pathways to the cell, and makes it more effective. A totally different study would be needed to prove or disprove that.  That's really the starting point. Not a study that uses HCQ by itself.

 

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So it seems that zinc lozenges are effective against the type of coronaviruses that causes the common cold, but what about zinc taken orally that you swallow and gets absorbed in your digestive system? Is only the zinc dissolved in your mouth effective?

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1 minute ago, XYZ said:

So it seems that zinc lozenges are effective against the type of coronaviruses that causes the common cold, but what about zinc taken orally that you swallow and gets absorbed in your digestive system? Is only the zinc dissolved in your mouth effective?

I use both. 

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46 minutes ago, Anastasis said:

Empiricism is dead. 

On 7/16/2020 at 11:08 PM, Anastasis said:

Maybe we finally move on...

Early intervention, North America-based, HCQ RCT, writing on the wall for a while, finally hits the press. 

I admit to a bias here. I'd like to believe there is a low cost, safe, readily available drug that I can take to help keep me out of the hospital if I get covid.  However, I do live in reality, and if HCQ doesn't help, so be it.  But I'm tired of people dismissing it based on studies that appear to be designed to fail.

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23 hours ago, GRHorn said:

No. Those are signs of people with chronic bronchitis. “blue bloaters”. 
 

Just by looking at somebody you aren’t able to tell if they’re sats are 94% on room air (send them home) or 89% (admit and give oxygen). 
 

Also to your initial post, elevated CRP, ferritin, and D-Dimer on your labs at admission are a bad sign. 

I seem to run 95% at each office visit.

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Anyone know which brands are more reliable?

They’re all mostly cheap Chinese electronics. There was on study from U San Fran that indicated Contec is an accurate brand. I bought one and had some cheap knock off sent instead. The vendor eventually sent me a Contec, which was very similar. Both work about the same. They’re off by 1% from one another.
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9 hours ago, JohnLocke said:

I admit to a bias here. I'd like to believe there is a low cost, safe, readily available drug that I can take to help keep me out of the hospital if I get covid.

I'd like to believe the same. I'd also like a bj from emily ratajakowski while I got my salad tossed by jessica biel. Unfortunately the null hypothesis has been letting me down. 

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14 hours ago, Anastasis said:

I'd like to believe the same. I'd also like a bj from emily ratajakowski while I got my salad tossed by jessica biel. Unfortunately the null hypothesis has been letting me down. 

You know the whole "infinite monkeys on typewriters will eventually reproduce the works of Shakespeare" thing?  Well, you're more likely to get bj from monkeys while getting your salad tossed by Shakespeare.

Not judging if you're into that.

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I admit to a bias here. I'd like to believe there is a low cost, safe, readily available drug that I can take to help keep me out of the hospital if I get covid.  However, I do live in reality, and if HCQ doesn't help, so be it.  But I'm tired of people dismissing it based on studies that appear to be designed to fail.
They're designed to fail because they're studying a drug that doesn't do anything for COVID. It's been four months of various trails, publicity, etc. If it had any impact it'd be plainly obvious by now. Move on.
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How are these vaccines going to come into play for infants? Asking because my wife is due in January, which is around when the best-case scenarios have us with a vaccine. Would they be administered to young infants? Or is the hope that you'd vaccinate the rest of the family and hopefully the infant gets some protection via milk? Trying to figure out how this would work as we creep slowly closer to a vaccine (hopefully).

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https://jvi.asm.org/content/88/19/11034

This is an interesting article on immunity from 2014 that addresses some the issues and worries that people have with COVID vaccination or previous infection and subsequent immunity.  Some good takeaways are that CD8 immunity plays a key role in immunity and blunting severity of subsequent infections and this immunity last much longer than measured IgG response. The response also seems to be more robust with intranasal inoculation/immunization rather than systemic (intramuscular vaccine). This is from the original SARS virus but I would think most of the concepts could be brought forward to SARS CoV-2.

 

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1 hour ago, BradInATX said:

How are these vaccines going to come into play for infants? Asking because my wife is due in January, which is around when the best-case scenarios have us with a vaccine. Would they be administered to young infants? Or is the hope that you'd vaccinate the rest of the family and hopefully the infant gets some protection via milk? Trying to figure out how this would work as we creep slowly closer to a vaccine (hopefully).

Covid doesn't present much of a concern for infants and a vaccine for young children will be a long way off.

 

BTW, an infant’s immune system doesn’t mature until around 2 to 3 months. This means that a 2-week-old baby’s immune system can’t fight viruses or bacteria nearly as well as a 3-month-old infant’s can. OTOH, the mother’s immune system does continue to protect the infant with antibodies that were shared through the placenta immediately after birth. Those antibodies stay active for the first few weeks of a baby’s life and offer some protection from bacteria and viruses. Breastfeeding also boosts this early immunity.

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https://www.wired.com/story/covid-19-vaccines-with-minor-side-effects-could-still-be-pretty-bad/

Good point here - looks like the vaccines might cause a few pretty rough days in some people -that needs to get released and vetted now or the crazies and anti-vaxxers (subset of crazies) will jump all over how it was "hidden" and "they can't tell you this is safe," etc. 

I mean, how many people have told you they don't get a flu shot because "every time I get one I get sick from it"?

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On 7/18/2020 at 8:55 AM, JohnLocke said:

Granted, it failed to show the effectiveness of HCQ, but it did not prove that it doesn't work either. It isn't being reported that more studies are needed to draw conclusions. It is being reported that it HCQ isn't effective. It did NOT show that.  You can't design a study that will give you statistically insignificant results, and then claim you have proven something. The last criticism I have of this study is that it didn't go past 14 days.

As for Zinc, the claim is that HCQ opens up pathways to the cell, and makes it more effective. A totally different study would be needed to prove or disprove that.  That's really the starting point. Not a study that uses HCQ by itself.

 

 

Your first criticism of the study should be 

Quote

Limitations:

Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.

 

There's a LOT of positive studies out: https://c19study.com/   - site is updated with new studies regularly as they become available.  Negative studies are listed as well.

 

Really helpful conversation about safety, why a drug is OTC or not, off-label prescribing and what it means, and how the invisible hand of business and politics on health care decisions between physicians and patients in this pandemic are making matters much worse.  People are being denied a treatment that many studies show works, that over 2 dozen nations are widely employing with apparent major benefit, all when health side effects are negligible.  This ER doc gets it:

 

 

 

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From triples' link. This is such a lazy if not outright dishonest analysis. You can't compare CFRs across countries without adjusting for the age structure. Almost all of the green countries have single digit percentage of population 65+. Most of the red, and many of the green countries have double digit ~20% aged 65+.   Here is a link that discusses the topic of age-related confounding of CFR rates across countries and why comparison fo the crude rates can be misleading: https://www.medrxiv.org/content/10.1101/2020.05.09.20096503v3

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32 minutes ago, triplehorn said:

JFC, what.

She's a right wing nutbar.  And not a practicing physician. Anti-masker and much prouder of her law degree than her medical credentials.  Anti-lockdown.

Muh rights.

thegoldopinion.com

Quote

Not wearing a mask is not mere “personal choice” like deciding between a head covering or a t-shirt. It is a flashpoint for being a free human being who has consented to be governed but has not consented to be ruled. We do not consent to a masked America, because that is a fundamental change in American society, culture, norms, and rights.

 

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1 minute ago, TwiceHorn said:

She's a right wing nutbar.  And not a practicing physician. Anti-masker and much prouder of her law degree than her medical credentials.  Anti-lockdown.

Muh rights.

thegoldopinion.com

 

Where'd you see she's not practicing?  link would be great.  She's describing her own experience treating patients.  That website you linked indicates she's active and practicing on the ER frontlines today.   

Looking at this without political bias, I can't find anything I disagree with in that interview about basically all the areas she speaks about, especially re safety. On masks, I wouldn't characterize what she said in the interview as anti-mask because she doesn't discourage use, but she clearly doesn't see that as the answer alone.  

 

 

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