Well-capitalized Seattle startup seeks Unix developers (Amazon, 1994) - <AUTHOR> https://groups.google.com/forum/#!msg/mi.jobs/poXLCW8udK4/_GHzqB9sG9gJ <comment><USER2> The newer posts on there are the digital equivalent of graffiti. The original Linux post is clogged with a bunch of junk as well. It's always upsetting to see traffic driven to these posts leading to trash from visitors.

</comment><comment><USER3> Great expectations ought to demand great compensation. I think this is somewhat fair (even if perhaps slightly pompous):

> You must have experience designing and building large and complex (yet > maintainable) systems, and you should be able to do so in about one-third > the time that most competent people think possible.

> Your compensation will include meaningful equity ownership.

I think the problem with a lot of ridiculous-sounding job offers we see today is that that they include great expectations, and then "will work for pennies [of equity]" is kind of tacked on as an additional expectation.

</comment><comment><USER4> -1 for disabling zoom on mobile devices. I expect better from Google.

<comment><USER5> I downvoted you because you've repeatedly complained about the same thing on several stories for a while now. Pinch zoom gets disabled to remove the 300ms delay on mobile-friendly pages, and that's seems to be what most people want.

If you always want pinch zoom, I would suggest using Chrome -- there's an accessibility option that overrides the page's request to disable pinch zoom .

<comment><USER6> It's also possible to set a bookmark to something like

        javascript:document.querySelector('meta%5Bname=viewport%5D').setAttribute('content','width=device-width,initial-scale=1.0,maximum-scale=10.0,user-scalable=1');

To re-enable zoom. I get as annoyed as the the parent comment with sites that disable zooming not because of the act itself but the bad design and typography choices that seem to go along with it. Make text size and leading choices suitable for the device, set margins so that your text doesn't abut the absolute edge of the screen, and make sure links are large enough to tap reliably. If you feel you can't make those choices and want to include full site or text size links somewhere then they should be obvious and again big enough to tap.

</comment></comment></comment><comment><USER7> Here's a street-view of the mailing address listed in the post: [https://email@example.com,-122.198268,3a,75y,9h...](https://firstname.lastname@example.com,-122.198268,3a,75y,9h,90t/data=!3m4!1e1!3m2!1s70DAZTsUeh4HHVB6OfDpMw!2e0)

</comment><comment><USER8> sounds like a real ass.

</comment><comment><USER9> Repost: [https://news.ycombinator.com/item?id=3007622](https://news.ycombinator.com/item?id=3007622)

<comment><USER10> how was this a helpful, informative comment? yes this has been posted before, over 2 years ago with no comments, but you've added no information to this discussion at all.

<comment><USER11> Yes, that was a poor choice of indicating this is a repost.

If you search the archives for "Amazon 1994" you will find that this has been posted to Hackers News a lot (the one with the most comments seems to be [https://news.ycombinator.com/item?id=2044945](https://news.ycombinator.com/item?id=2044945)).</comment></comment></comment>


Why Zomato is better than Yelp in some markets - <AUTHOR> https://medium.com/@nikhilbd/why-zomato-is-better-than-yelp-in-some-markets-ce2ae6073136#.kwfbzu277 <comment><USER2> Great read. I am building an alternative take on food search. But my main challenge right now is figuring out how to populate it. I just want the very best signature dishes that places are known for as opposed to an entire menu.</comment>


ECS (entity-component-system) back and forth, part 2: insights – groups - <AUTHOR> https://skypjack.github.io/2019-03-21-ecs-baf-part-2-insights/ <comment><AUTHOR> With this post I wanted to go into details on the grouping functionalities that can be implemented with sparse sets. This is something I have been asked about since I published the last part of the series and I think it can help to better understand how EnTT works under the hood.

I hope the post can find the interest of many.</comment>


The downside of being a generalist - <AUTHOR> http://rix0r.nl/blog/2013/05/26/the-downside-of-being-a-generalist/

<comment><AUTHOR> This article really rings with me. It's odd, because usually employers say that they prefer generalists who are smart and quick learners, but in the very same job ads they want e.g. "at least 5 years of Rails experience" for any somewhat senior position.

<comment><USER2> The best generalist fit is leadership of diverse specialists(note leadership not management).having problem domain experience in divergent areas you can use people with deeper knowledge in specific niches and weave things together. However most companies regard that as an MBA problem domain.</comment></comment>


Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients - <AUTHOR> https://www.medrxiv.org/content/10.1101/2020.04.10.20060699v1 <comment><USER2> It's important to interpret these results carefully: "no evidence of efficacy" does _not_ imply evidence of no efficacy, and in fact the uncertainty in this study is quite large. The sample size is small enough that it would be very hard for this study to detect the effect of hydroxychloroquine unless that effect is very, very large.

From the abstract:

> In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no- > HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, > respectively, developed acute respiratory distress syndrome within 7 days > (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00).

The relative risks and confidence intervals are the important numbers here. For example, the relative risk for death is 0.61, meaning the observed risk of death was lower for patients treated with hydroxychloroquine -- but the confidence interval is 0.13 to 2.89, meaning the data is consistent with anything from the risk being much smaller to the risk being much _larger_. Since there were only 3 deaths in the treatment group and 4 deaths in the control group, it's very hard to draw precise conclusions about death rates.

I think we can interpret this result to mean that hydroxychloroquine doesn't have a miraculously large effect, but the evidence is weak. Other commenters are correct that large randomized trials will be more definitive.

(disclaimer: I am a statistician, not a doctor)

<comment><USER3> This is a great comment thanks.

Title of the paper could (with a tongue firmly in cheek) be called, _" Weak evidence for effectiveness of hydroxychloroquine but our sample was likely too small for it to pass a T-test"_

<comment><USER4> > _Title of the paper could (with a tongue firmly in cheek) be called, "Weak > evidence for effectiveness of hydroxychloroquine but our sample was likely > too small for it to pass a T-test"_

It would be irresponsible to choose an experimental design (like significance level) and then use wishy-washy language ("weak evidence") to work around it when the study criteria aren't met.

This would be more akin to the headline from the press release for the study from the university PR office.

<comment><USER5> In the US the phrase "tongue-in-cheek" means "kidding."

<comment><USER4> > _In the US the phrase "tongue-in-cheek" means "kidding."_

I took that to mean they obviously weren't suggesting something so conversational as the actual title, but the takeaway is the same and shouldn't be a conclusion taken from the OP comment.

</comment></comment></comment></comment></comment><comment><USER6> Personally I'm witholding judgment until the results of the PATCH trial ([https://clinicaltrials.gov/ct2/show/NCT04329923](https://clinicaltrials.gov/ct2/show/NCT04329923)) arrive, as it'll finally give us some decent statistical power, and be a full, double-blind RCT. It also has multiple study arms (health-care worker prophylaxis, home-quarantined early stage, hospitalized later-stage), so if it turns out that HCQ is effective but that by the time patients are hospitalized it's too late, as some are now suggesting, we should finally know with some degree of certainty.

<comment><USER7> Yeah, the devil is really in the details about exactly when and how you administer it.

Doctors are already saying that it's definitely no magic bullet, but they debate whether it is effective at a certain stage of illness.

What I don't understand is why we're focusing so much on this specific drug when there are some great antivirals out thee that have a more effective theoretical mechanism of action. (eg Remdesivir)

<comment><USER8> Because it's become an arbitrary political football to separate "left" vs "right"

<comment><USER9> As insane as that is.

And how funny is it (at least to me) that this is only because Trump came down on one side initially. If he had come out saying exactly the opposite, that HCQ was bad and we should be skeptical, everyone hoping it doesn't work now would be looking for the 10 person studies saying it totally works and defending its use.

It's almost beyond reason how hyper partisan this specific issue is.

<comment><USER10> This isn't left vs right; it's an unqualified politician vs pretty much all of the scientific community.

<comment><USER7> This is not accurate and kind of exposes your own bias.

If you listen to virologist podcast, TWIV, they talk about the effectiveness of HCQ. They aren't all "it's amazing!", but they do not make the claim that it doesn't work.

</comment></comment></comment></comment></comment></comment><comment><USER11> Given that I need hydroxychloroquine to treat my rheumatoid arthritis, I'd like this hypothesis to be either proven or disproven as rapidly and as unambiguously as possible.

<comment><USER12> Because HCQ's efficacy was briefly endorsed by a controversial political figure I fear that there's no evidence in either direction will convince the true believers. This is now a political issue, like global warming. Hopefully someone is ramping up production so availability improves for those that actually need it.

<comment><USER13> Imagine if Obama had "endorsed" Biden using the same language. Would you have considered it an endorsement? I find the interpretation of what he said to be very peculiar.

<comment><USER14> What is the comparison being made here? Endorsing the frontrunner for political candidacy isn't remotely the same as endorsing an unproven drug to treat an ongoing pandemic.

<comment><USER13> Noone endorsed an unproven drug.

<comment><USER15> [https://twitter.com/realDonaldTrump/status/12413672399007785...](https://twitter.com/realDonaldTrump/status/1241367239900778501)

HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine. The FDA has moved mountains - Thank You! Hopefully they will BOTH (H works better with A, International Journal of Antimicrobial Agents).........be put in use IMMEDIATELY. PEOPLE ARE DYING, MOVE FAST, and GOD BLESS EVERYONE! @US_FDA @SteveFDA @CDCgov @DHSgov

That's not an endorsement?

<comment> munk-a For a comparison (to the original point made above):

Joe Biden has a real chance to be one of the biggest game changers in the history of this country. The Democratic party has moved mountains in their support of them - Thank You! Hopefully he will take office IMMEDIATELY. PEOPLE ARE LOSING FAITH, MOVE FAST, and GOD BLESS EVERYONE! @US_DNC @JoeBidenPrez @POTUS @IowaElections

</comment></comment></comment></comment></comment></comment></comment><comment><USER16> This whole debate is insane to me -- some people that so-called "experts" don't like mentioned HCQ as a possible treatment for coronavirus, and we've ended up in some bizarro world where everyone is shouting and fingers are being pointed over something that really shouldn't be controversial or perceived as some sinister plot to destroy clever society.

1\. HCQ has been used for many decades

2\. The side effects are generally known

3\. It may have a positive impact on COVID-19, and it may not.

4\. Nobody is suggesting long term high doses for anyone, COVID patients or otherwise.

5\. If people are severe patients of COVID-19, this should certainly be tried as a treatment as long as the patient (or immediate family) is briefed on the potential side effects. The alternative, potential death, makes this a worthy discussion for a doctor/patient to have, with families being allowed to err on the side of right-to-try. HCQ is cheap, available, and has been used for decades.

The fact that "no evidence HCQ works!!" has 200 points of upvotes and counting _when the sample size for this study is 181 patients only_ just shows how high the temperature has become.

Everyone just calm down. As capnrefsmmat has eloquently pointed out, "absence of evidence" does not mean "evidence of absence".

If you enjoy the thrill of debates for debates sake, here are other potential topics for you: Whether masks are effective, condoms, seatbelts, helmets, or even parachutes[0] _:

[0][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/)

_Favourite part:

 _Results_ We were unable to identify any randomised controlled trials of parachute intervention.

 _Conclusions_ As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.

<comment><USER17> 1\. Not for coronaviruses.

2\. They are known but they are by no means mild. A trial in Brazil just got aborted due to severe heart problems.

3\. So does almost everything. If that's your threshold for taking a drug then I have a lot of homeopathic remedies to sell you!

4\. Actually the doses given for COVID are often higher. Not sure what long- term has to do with anything.

5\. That assumes that the risk of side effects is zero. It's not. Also, there is an opportunity cost to taking HCQ instead of something else.

I totally agree with you that we should do proper trials on this and see what happens. But right now there is zero evidence that it actually works, and some (admittedly low-quality) evidence that it might not.

<comment><USER18> > Actually the doses given for COVID are often higher.

Not just higher. The original article (the one out of China) that mentioned that there might be some positive effects reportedly suggested using doses that were a whopping 5 times higher than the usually prescribed amounts: 500mg/day vs the usual 100mg/day.

What more, the same article put forward that the drug was considered generally safe and without any potentially troublesome side effects. That raised more than a few eyebrows amongst the medical staff who knew the drug.

</comment></comment></comment><comment><USER19> This study is specifically about patients sick enough to be put on oxygen. The top ranked comments don't seem to address that detail.

Some thoughts:

My understanding is this is a powerful alkaloid. My experience has been that similar compounds can help combat inflammation. They also can work to help kill infection at times.

By the time people with Covid19 need oxygen, inflammation doesn't seem to be the primary problem. So I wouldn't think it would be particularly helpful at that point.

Ventilators get prescribed in part on the assumption that inflammation in the lungs is a major impediment to getting sufficient oxygen. Ventilators are failing at a shockingly high rate, with a death rate up around 80% or so. Some doctors are moving away from ventilators because the death rate is so high.

I spoke recently with a researcher who suggested impaired vasodilation was a possible explanation for the reports of low oxygen combined with a surprising lack of pneumonia and inflammation in some cases and that makes a lot of sense to me. The mechanism causing low oxygen does not appear to be the obvious answer of "lung inflammation and pneumonia."

That doesn't mean this drug can't play a meaningful role at some stage. It mostly means it's not the magic bullet solution for advanced cases that they were hoping for.

This in no way surprises me because the things it actually treats do not appear to be the cause of low oxygen in advanced covid19 cases.

<comment><USER20> You might find this thread interesting ("There's a growing body of data to strongly suggest #COVID19 predisposes to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization and diffuse intravascular coagulation.")

[https://twitter.com/scottgottliebmd/status/12500696095810314...](https://twitter.com/scottgottliebmd/status/1250069609581031428?s=21)

<comment><USER19> Thank you. It is interesting stuff and fits with some of my impression that they are overlooking important blood-related issues. Anemia (a blood disorder) is also a cause of low oxygen. That's not exclusive to lung function.

Glad to see some doctors are working on that angle. (crosses fingers, hopes for better treatments soon)

</comment></comment></comment><comment><USER21> Given the study's small sample size, it seems the only way it would have produced a conclusive result is if the effect size was huge (i.e. miracle cure). The study found some evidence of efficacy, but it was not significant given the sample size.

A better headline would say something like: "study finds that HCQ is not a miracle cure for already-hospitalized covid-19 patients".

<comment><USER22> How much are you willing to pay for "not a miracle cure" on the basis of "eh, it can't hurt"?

<comment><USER21> Your point doesn't really make sense, because the purpose of a study like this is not for making treatment decisions; it's for making research decisions.

I don't see anything in the study that discredits HCQ as a potential treatment, and therefore it makes sense to keep researching.

</comment></comment></comment><comment><USER23> This trial wasn't randomized, but a quasi randomized trial for HCQ whose preprint was leaked is here:[https://www.dropbox.com/s/8b2govfsa6n0xbq/NEJM_Clinical%20Ou...](https://www.dropbox.com/s/8b2govfsa6n0xbq/NEJM_Clinical%20Outcomes%20of%20Hydroxychlorquine%20in%20Patients%20with%20COVID19.pdf.pdf.pdf.pdf?dl=0) Study indicates that one adverse effect of HCQ (on top of not improving patient outcomes) is increased ventilator times.

<comment><USER24> From the paper:

A total of 63 patients were included with 32 in the hydroxychloroquine arm.

Hydroxychloroquine administration was associated with a need for escalation of respiratory support level compared to those that did not receive hydroxychloroquine at 5 days (p=0.013). The same findings were observed in a baseline-matched subgroup analysis. Absolute lymphocyte change in the hydroxychloroquine group was no different than supportive care alone (p=0.413).

Hydroxychloroquine use trended towards worsening neutrophil-to-lymphocyte ratio compared to supportive care alone (+9.59 vs +1.58, p=0.51) as well as a higher risk for intubation (p=0.051).

<comment><USER25>
        p=0.413
        p=0.51

So, basically coin toss?

<comment><USER24> You overlooked the major finding of the study:

> Hydroxychloroquine administration was associated with a need for escalation > of respiratory support level compared to those that did not receive > hydroxychloroquine at 5 days (p=0.013).

> p = 0.013

</comment></comment></comment></comment><comment><USER26> Lots of conflicting research happening[1], until we get multiple controlled trials we won't really know. Here's one that shows improvements.

[1] French ~50 patient study that tried Control, Hydroxychloroquine, and Hydroxychloroquine + Azithromycin combo: [https://www.mediterranee- infection.com/hydroxychloroquine-an...](https://www.mediterranee- infection.com/hydroxychloroquine-and-azithromycin-as-a-treatment-of-covid-19/)

<comment><USER27> > Lots of conflicting research happening

That's my main take-away at this point. I have seen enough reports saying it worked, and enough saying it didn't that I believe the answer is probably somewhere in the middle.

My understanding is the best guess for how it works is by keeping the viral infection from becoming serious enough to require hospitalization. Similar to how proper treatment of wounds early on keeps them from getting to the gangrene stage where you need amputation.

Unfortunately, politics. So the Left wants it to be completely no use at all, and the Right wants it to be a miracle drug. Most of the population really probably just wants effective treatments if they end up getting sick.

<comment><USER28> I'm out of the loop here: why would _any_ political faction not want an alleged cure to work? What's the goal here?

<comment><USER29> Trump pushed it as a miracle cure, at least at one point, and he evokes bitter opposition in many.

(I think this is quite irrational, but that's your answer.)

<comment><USER30> People are in opposition to the president promoting drugs with unproven effectiveness as a miracle cure for an ongoing pandemic.

I didn't think testing drugs before giving them to people was considered "irrational" as you state, but I guess that is where we are now.

<comment><USER29> It's "irrational" to oppose an idea just because it comes from someone you despise. It's not like this is coming from the _National Enquirer_ \--he has access to some of the brightest minds in the world.

The efficacy picture on these drugs is quite confusing, and it's not out of the question that they will turn out to be crucially useful. Giving up on them without further investigation doesn't seem wise at this point.

Beyond that, sometimes being a leader means giving people hope, even if that might involve shading things. Trump may not be an Adama, but I _do_ think he's pretty good at making people feel better, or at least distracting them from their troubles. And right now, that probably _is_ saving lives.

<comment><USER31> Let's say Trump instead proposed that people taking, I don't know, silver supplements was a proper treatment for covid-19.

Would you say it's irrational to oppose that idea? I mean it's not been proven to not work, so you gotta try anything you can, right? And he's giving people hope.

<comment><USER29> If a lot of scientists world-wide were looking at it, yes, I would think that irrational to not consider silver supplements. As far as I know, Trump has never advocated taking any drug without medical guidance.

We were (and largely still are) dealing with a _lot_ of unknowns. As far as I'm concerned, everything is on the table, as a possible improvement.

<comment><USER30> Isn't one of his quotes _" It's been out there for a long time. What do you have to lose?"_ though I guess he does followup by saying he will talk to his doctor before he takes it. But the overall sentiment makes me pretty uncomfortable.

</comment></comment></comment></comment></comment></comment></comment></comment></comment><comment><USER32> And to put this interpretation into perspective, people that need this drug for diseases that it has proven to have a large effect on are losing access to it because it may or may not help with COVID-19.

<comment><USER33> HCQ is an off-patent drug that is produced in every major country in the world. In fact, many countries have stockpiles of it because of its efficacy at preventing malaria.

If there's a risk of a supply run, it would definitely not last very long. For many people there's alternatives for treating arthritis and lupus.

If it's shown even to improve the patient's outcome by even just 10% or more (as this study suggests), every country should be ramping up production of it right now instead of letting it be politicized.

<comment><USER34> Face masks have been shown to be effective at controlling pandemics, and apparently no one (in many western countries) thought to stockpile those.

<comment><USER35> > Face masks have been shown to be effective at controlling pandemics, and > apparently no one (in many western countries) thought to stockpile those.

You're dropping the context of the hard decisions nations and governments actually deal in day to day, year to year when it comes to budgets. That's why not a single country had a proper stockpile of N95 masks for a pandemic like this. That isn't an exaggeration: literally not one nation had enough of a stockpile for this scenario, that includes South Korea, Japan, China.

To say that nobody thought to do it is outlandish. As one example Congress set aside funds in 2006 to stockpile 100 million N95 masks. That's not strange, as _many_ people were aware of the need to maintain such a stockpile. There is a big difference between being aware of the need, proposing plans and spending for it, and actually getting billions of dollars on a recurring basis to maintain the necessary proper stockpile perpetually with no event to push it with (yeah but we had a flu pandemic in 1957! try selling that premise). That's the actual reality of budgets and governments.

It's expensive to maintain a persistent _minimum_ stockpile of 1 billion non- expired N95 masks to cover the US population and the demand the US has seen. If it's a year-long pandemic, a billion masks isn't enough. You need several billion masks in that scenario. Coming out of the great recession, that is a very hard budget decision for all nations. And the fact is, most nations can't afford to do it at all. The easy retort of course is to say, well, look at the damage from this virus compared to that cost for masks. That's purely hindsight spouting that tries to pretend a comprehensive reality doesn't exist and that people who make budgets don't have to deal with difficult decisions every single year (while not factoring in every possible bad scenario every time they make a budget).

And let's not pretend it's enough to stockpile masks, regarding spending allocations. If we're doing hindsight fantasy, let's be correct about it. You need to constantly maintain a lot of other gear and training for a pandemic, costing large sums of money. In an ideal scenario a nation the size of the US should probably have over a million ventilators stockpiled, just in case. We should probably maintain 2x or 3x the ICU capacity we have, on a persistent basis and at a large cost.

This isn't an argument against being more prepared. Of course every nation should have a vast magical stockpile of N95 masks that never depletes, even the ~140 poor nations of the world that can't afford to do it. The point is, it's difficult to convince any nation to do it at the required persistent scale, and most can't afford to do it regardless.

<comment><USER36> I strongly agree with everything you wrote.

I think there is an alternative solution, though: Rather than maintaining a gigantic stockpile large enough to last a multi-year pandemic, it might be more efficient to maintain a modest stockpile sufficient for the breakout phase along with ready-to-deploy crash production capacity. This might be significantly cheaper.

This means that we need to ensure that we have the capacity to 100x, 1000x, 10,000x production--whatever is modeled to be enough to meet ongoing demand during a pandemic--within the time bought by drawing down the strategic reserve.

We don't need to maintain and refresh a complete stockpile of finished goods, or even a complete stockpile of production capacity (suitable factory floor space, meltblown nonwoven fabric equipment, etc.). We just need to know _where_ such things exist that can be quickly directed to the desired use either with cooperation from the owner or with the DPA, how much exists naturally, and only if there is a deficit, to maintain a stockpile sufficient in combination with those identified supplies: Government-owned sterile factory floor space, for example, or spare production lines for meltblown nonwoven fabric.

We can even enlist private companies to maintain the stockpile for us. It makes way more sense to just subsidize e.g. 3M to have lots of extra meltblown nonwoven fabric production capacity. They are in the business, they maintain and operate the machinery and have the know-how and commercial connections to produce and distribute the material. They will have the capability to quickly respond to demand spikes if the capital requirements for increased production capacity already exist thanks to Uncle Sam's foresight.

Finally, what is maybe even more important than stockpiles or production capacity subsidies is the organization this exercise entails (knowing who makes what critical parts in the supply chain, where they are, what their production capacity is and how quickly it can grow, etc.), which gives an ability to rapidly marshal resources and eliminate inefficiencies to surge production as quickly as possible.

</comment></comment></comment></comment></comment><comment><USER37> It was observed that between 7% and 28% of hospitalized have acute myocardial injury [1-4]. When one looks at Epocrates (database for drugs which is why I'm not linking anything here) the severe adverse reactions of hydroxycholoroquine include QT prolongation, cardiomyopathy, and torsade de pointes. Just to define some things here, QT prolongation is the time from your Q wave to your T wave, or the start of an electrical depolarization on your cardiac ventricles to repolarizations. QT elongation usually leads to cardiac arrest. Torsade de pointes is a syndrome where your cardiac ventricles beat so quickly that your heart paradoxically cannot fill up with blood potentially, and usually, leading to sudden cardiac death.

Giving someone who has had essentially a heart attack (by definition COVID patients have elevated troponin which is the marker we use to assess if one has had a heart attack) is probably a bad idea so my question is: why would we celebrate a drug that has massive cardiac adverse effects as a side effect? Don't get me wrong I understand that there are drugs that are even worse. Cyclosporine is the first line immunosuppresant for kidney transplant. Do you know what one of the most common adverse effects of cyclosporine is? Kidney failure. But we don't know what is causing the kidney failure in a kidney transplant (rejection vs adverse effect) so we have to biopsy. Kidney biopsy is a very invasive procedure, FYI. My point is, maybe waiting for double blind placebo research here is the best case. Also, I made this exact same point on here a month ago and people told that they would take my dose if it came to that and at this point I will say go ahead.

[1] [https://www.ncbi.nlm.nih.gov/pubmed/32169400](https://www.ncbi.nlm.nih.gov/pubmed/32169400)

[2] [https://www.nejm.org/doi/full/10.1056/NEJMoa2004500](https://www.nejm.org/doi/full/10.1056/NEJMoa2004500) [3] [https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.0...](https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.046941) [4] [https://jamanetwork.com/journals/jamacardiology/fullarticle/...](https://jamanetwork.com/journals/jamacardiology/fullarticle/2763524)

<comment><USER38> > between 7% and 28% of hospitalized have acute myocardial injury

So, for a younger (< 60) otherwise healthy person whose chance of death with covid is less than 1%, it would seem ill advised to take this medication at the onset of symptoms, unless the the disease itself causes similar or higher rates of heart damage.

<comment><USER14> It's only advised if it actually works. If it doesn't work, then there's still no point in taking it because the side effects are still bad. And there's no good evidence that it even works, and some mild evidence that it doesn't.

<comment><USER38> Yes, and _even if_ it did work to reduce severity of the illness (agreed that there is no evidence of this), it seems like for low-risk people, the risks of heart damage outweigh the benefits of taking it. After all, what's an extra week or two of illness vs a 7-28% chance of heart damage.

<comment><USER14> Yup. I'm in a relatively low risk factor group and got over COVID-19 at home, no hospitalization necessary and nothing stronger than acetaminophan needed. I don't think a decent change of permanent heart damage was what I needed through all this. Also, I would have had a higher chance of being hospitalized from the side effects of the HCQ than from the COVID-19, which is really not what the hospitals need right now.

The HCQ doesn't seem remotely merited based on its potential side effects unless you are in a higher risk factor for the disease, and of course even then, it's only merited it's actually efficacious (which it's seeming so far it isn't).

</comment></comment></comment></comment></comment><comment><USER39> Why is it taking so long to do a big study on this?

There are so many sick people and it's a cheap drug and only takes a week Or 2 to see if it works.

Can someone please just do a Really large trial, like, 2 weeks ago so we can put this to bed one way or the other.

</comment><comment><USER40> I think it's too bad that this drug has been so politicized. It's really unfortunate that its two original and most prominent champions are people that are so disliked. So many people spoke up (maybe prematurely) against it in a knee-jerk reaction to its advocates. Now many act as if they're more concerned about being right to ridicule the claims all along, than they are about whether the drug is actually helpful in fighting COVID-19. Which, for the rest of us without a stake in their stupid political feuds, is all that matters. And because of this idiotic battle of the egos we could be passing on something useful.

So here we all are, hanging by the edge of our seats, waiting for definitive proof that _HCQ does not help in fighting COVID-19_ and we keep getting these half-assed reports, seemingly more aimed at pushing a narrative than to present (or eliminate) an option in a fight.

One of the latest examples is the account of Rita Wilson (wife of Tom Hanks) who survived what seems like a difficult case of COVID-19 and shared her experience with the media: she felt very tired, extremely achy, uncomfortable, didn't want to be touched, on the ninth day her fever climbed up to 102 and she had chills like she'd "never had before" (her words), she lost her sense of taste and smell. Then she was given chloroquine, her fever broke (it's not clear how long after). She goes on to warn against the "extreme" (her word) side-effects she attributes to chloroquine: she was completely nauseous, she had vertigo, she could not walk and her muscles felt very weak. She then concludes that although her fever broke after been given chloroquine, she doesn't know if it helped or if it was just time, which is fair. What do you imagine the headline for that story should be? Well, to save you the trouble, most read like this _Rita Wilson warns against "extreme" side-effects of chloroquine_.

Are HCQ/CQ effective? We're still sitting here like idiots not knowing. If they are, should they be taken carelessly? Definitely not, we already got that, thanks, but _that is not the point_. We can't afford to have an "all or nothing" mindset with these drugs as we did with masks. Simply proclaiming that HCQ is useless because it is shown not to reduce viral load is just the best way to pass on some other ways it might be helping. If it is shown to have other palliative effects that actually help patients in their fight, such as reducing inflammation or helping cope with high fever long enough for your immune system to do the job, it's not _nothing_. It's information. It's an option.

</comment><comment><USER41> It's important to note that this study did not evaluate or note that Hydroxychloroquine had no effect on all people in all situations with COVID-19.

This was a targeted study looking at a specific circumstance. The situation was "all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min"

So, adults who were not on oxygen are not included in the study. How does it pertain to them? That's not covered by this.

It reads like it's saying people who are in bad shape and on ventilators did not have a positive impact by Hydroxychloroquine.

This still leaves open questions like, can the use of Hydroxychloroquine lower the rate of needing to get on a ventilator.

I look forward to someone reproducing this study and looking into the other areas.

</comment><comment><USER42> "collected data to _emulate_ a target trial" I take it this means it's not an actual clinical trial, just a virtual trial? What's the point? Of all the people that died, none were saved by the drug. Sounds like an insurance ad.

</comment><comment><USER43> The study is way underpowered (too small a sample). Based on the raw numbers, the HCQ group had less deaths and less ICU admissions, but the numbers we're talking about are 3 vs. 4 deaths and 16 vs. 21 ICU admissions (group sizes were different).

These numbers simply aren't enough to make a determination one way or the other. On mortality, the 95% confidence interval allows for a range of HCQ reducing death rates by 87% up to it increasing death rates by 2.9x.

</comment><comment><USER44> Point is that the study is done at the wrong stage, too late.

<comment><USER14> That may be, but it's gonna be harder logistically to do a study commencing from onset of symptoms vs at moment of hospitalization.

There's also the fact that study makes it less likely that pre-hospitalization HCQ will have any effect either. Applying a Bayesian analysis here, it's now likelier that the true ground truth is simply that HCQ doesn't do anything to COVID-19 at all, not necessarily that it works only in a narrow early window. HCQ has severe side effects too, that require close monitoring and can be fatal. If it's not clearly doing good then it definitely shouldn't be being given to COVID-19 patients.

Personally, my hopes are more on remdesivir and favipiravir, both of which are actual antivirals (HCQ is not) and thus were always more promising. HCQ was never the most promising drug candidate, and the only reason we're even talking about it as much as we are is that, for whatever random reason, that's the one Trump heard about first and then fixated on.

<comment><USER45> The study that made me think there might be something to it was looking at people taking it for unrelated illnesses and finding that they weren't tending to show up hospitalized with Covid-19.

I'd agree that we really don't have any evidence that giving it to hospitalized patients helps at all. Most antivirals have to be taken at the early stages of an infection.

The best looking treatment for people seriously ill with Covid-19 right now seems to be IL-6 inhibitors. That won't stop you from getting sick but might let you avoid intubation.

<comment><USER15> This could be correlation. People taking HCQ have autoimmune problems like lupus, and therefore would be more cautious and practicing social distancing earlier, therefore not getting infected in the first place. It also might be true that people who are agoraphobic shut ins are not contracting covid. But that doesn't tell us much about how covid interacts with agoraphobia.

</comment></comment></comment></comment><comment><USER46> A useful compilation of information on HCQ and COVID-19:

[https://docs.google.com/document/d/1O6Cls- Oz2ZAgJuyDbnICEGjM...](https://docs.google.com/document/d/1O6Cls- Oz2ZAgJuyDbnICEGjMvQPEyM-aaXARUomR9Ww/edit)

</comment><comment><USER47> This study is basically garbage. It applies to people who're so damaged from Covid they need at least 2 liters of oxygen per minute. It studies treatment with pure hydroxychloroquine--no zinc, no azithromycin/doxycycline/ivermectin. Hydroxychloroquine.

Patients who get their treatment from doctors less fraudulent than the authors of this study almost certainly see better outcomes.

</comment><comment><USER20> When the Covid crisis is over, one of the strangest sub- plots will have been the fracas around Hydroxychloroquine. Starting from medical practitioners worldwide adopting its usage in a 'cargo cult' way, mimicking what other doctors were doing, to Raoult's low- quality study. Then people in Silicon Valley (notably Elon Musk) picking up the idea. Followed by the explosion in the political sphere, from Trump pushing it at the White House podium, to Indian PM Modi reversing an HCQ export ban for Trump, to French PM Macron talking it up.

All the while HCQ remained unproven for Covid use, while people trying it got hurt by cardiac side- effects (and one couple in a prominent incident mistakenly took different chemicals with a similar name), and patients with other conditions ran out of HCQ due to shortages.

Maybe HCQ will be part of the standard of care for Covid- 19 in the future, but it's seeming less and less likely. Meanwhile it's definitely not a miracle cure, so the frenzied advocacy and adoption of this medicine will turn out to have been a bizarre story.

(I wrote this up here [https://twitter.com/firasd/status/1250125344469708801](https://twitter.com/firasd/status/1250125344469708801))

<comment><USER48> Politically, yes, there was/is a cargo cult. Both for those convinced it's a cure, and the anti-cargo-cult opposing party convinced it's somewhere between useless and actively harmful.

From a medical practice standpoint, you have a widely-available drug with well-known side effects that can be administered in a medical setting with low risk, and potential life-saving upside. When the research is early but potentially promising, it's not irrational to administer in cases where the side effects should be well-tolerated, even if later research shows no or low benefit.

The problem arises from self-administration without medical supervision, or with inadequate medical supervision.

<comment><USER20> The problem with 'low risk / high upside' is that it can apply to anything. We can try lemonade since it has low risk and high upside. But at some point we have to start wondering if we should all be obsessed with lemonade right?

Even when doctors were using HCQ before the politicians and random outsiders picked up on it, there were other drugs in the mix that they were also considering (Lopinavir, Remdesivir, etc). Incidentally Remdesivir trials have also come out lately seeming pretty weak. But there is still nowhere near the level of frenzy around Remdesivir as there has been around HCQ to the extent of advocacy at White House press briefings, international diplomatic incidents... it's beginning to seem like a very strange mass hallucination.

<comment><USER49> If there is a serious suggestion that lemonade works we should try it in medical settings. So far the only suggestions come from those who point to alternate theories without any science - even a case study. If you get a doctor to try it and it works ill be more interested. Until then it is quacks and I'm not.

</comment></comment></comment></comment><comment><USER50> I don't understand who gets to decide and how, which of these people receive / don't receive a specific treatment. I've always loved medical studies, but now the crisis got me to thinking about the moral decision (playing god?)

<comment><USER14> The answer is, by and large, doctors. Within the hospitals they really do have the power of life and death, deciding who gets treatment when supplies are thin. Generally the decisions are made using the heuristic of "With this limited stock of X, who should we give it to to save the maximum possible number and quality of lives?"

It's not playing god, it's just making rational decisions in times of scarcity. That's something humans do constantly, no god necessary.

</comment></comment><comment> pcj-github Aside from these results, what is the proposed mechanism of benefit here?

And why are we expecting a mechanism with hydroxychloroquine against this virus when essentially no small molecule therapies are effective against viruses in general?

<comment><USER22> Hydroxychloroquine is an immune suppressant and may help reduce the cytokine storm effect. How that interacts with the "you have to start it early" issue is unclear to me.

And it might keep you from getting malaria while you have COVID19.

<comment><USER51> The way HCQ is by accumulating in cells. It inhibits the replication of viruses by interfering with endosome/lysosome trafficking or viral protein maturation during virion maturation. (basically stops the virus from replicating)

<comment><USER52> and, correct me if i'm wrong, zinc helps

take it with a grain of salt but [https://www.snopes.com/fact- check/zelenko-669-coronavirus-pa...](https://www.snopes.com/fact- check/zelenko-669-coronavirus-patients/)

<comment><USER53> With the right grain of salt, you get zinc. Suggestions: zinc acetate, zinc chloride, zinc citrate

</comment></comment></comment></comment></comment><comment><USER54> There are dozens upon dozens of speculative treatments. Interactome research is churning out candidates.

I think the people have a right to know about cloroquine, since it became such a political point. But n=181 is not that small.

</comment><comment><USER55> That's because it's not hydroxychloroquine that helps them. It's Zinc. It just allows for much better absorption of the Zinc. Same can be achieved by combining Quercetin and Zinc.

</comment><comment><USER56> I know this study doesn't put anything to bed, but one has to understand that the basis for the HCQ and CQ (+/\- zinc) thing is the same as x kills cancer in vitro. Then, you get a motivated researcher who publishes a single arm study of essentially OK patients claiming zero deaths. Game changer? We'll see. But I imagine there are hospitals that are already using this as a first line treatment and there's no positive reviews from the front line.

Beyond that, we do have the ability to perform small sample studies (cf. Student) and decide whether we're headed in the right direction. Are we in a lull in statistics where we can't even use statistics to guide future research?

</comment><comment><USER57> See also [https://news.ycombinator.com/item?id=22851998](https://news.ycombinator.com/item?id=22851998)

</comment><comment><AUTHOR> TLDR: French publication, non randomized 181 patients (hospitalized with pneumonia and O2 requirement) with control group (84 with HCQ, 97 without HCQ), no efficacy but adverse effects for some.

<comment><USER58> If this is accurate, perhaps the title could be edited to reflect the fact that it's a single study?

<comment><USER59> It is, but these studies are done in a european setting, so more results may be coming.

</comment></comment></comment><comment><USER60> full title "No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen:..."

from the article:

 _" We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day...

This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group).

The median age of patients was 60 years ..."_

 _"...[Patients were from] four French tertiary care centres providing care to patients with COVID-19 pneumonia. Adult patients were eligible in this study if they were aged between 18 years and 80 years, had PCR-confirmed SARS-CoV-2 infection, and required oxygen by mask or nasal prongs (corresponding to a WHO progression score of 5)."_

 _" Among the 181 patients eligible for analysis, 84 received HCQ within 48 hours of admission and 97 did not (although 8 of them did receive HCQ later on)."_

So, first of all, these patients were infected with Covid-19 _days_ prior and now had progressed to pneumonia. The up to two-day delay in the administration of HCQ after admittance to the study is disheartening.

I am surprised that, despite the experimentors selecting an elderly, pneumonic, oxygen-dependent cohort in advanced stages of the disease, these patients did as well as they did. Its a credit to the human body.

But timing is everything...

Once a Covid-19 patient has developed pneumonia, it is too late for hydroxychloroquine to affect the Covid-19 virus' replication process significantly. The patient's body is saturated with the virus.

In a patient who has developed pneumonia the disease has progressed to a second phase wherein the virus _and other opportunistic pathogens (e.g., bacteria)_ attack the lungs and other tissue. Antibiotics may help at this point. But it is quite clear that the patients in this study arrived too late to gain any benefit from hydroxychloroquine which, when coupled with zinc sulfate, slows or halts viral replication _early_ in the disease, delays or halts the virus' progress and allows the body time to develop an immunological response to the virus.

The study's conclusion states explicitly that " These results ... do not support the use of HCQ in patients hospitalised for a documented SARS-CoV-2 pneumonia."

So, the trick is to treat _early_ with HCQ+zinc sulfate+azithromycin.

</comment><comment><USER61> 400+ points on Hackernews for... this?

There have been a variety of studies and reports, both for and against, the use of hydroxychloroquine. Is there any reason this particular study is so highly upvoted? Or is this just an attempt to dunk on Trump for suggesting the drug showed promise?

<comment><USER62> It's a study with a fairly high number of participants and it has not been conducted by the controversial author of the flawed first study.

</comment></comment><comment><USER63> Hm, the pseudo-study (it was a after the fact data review) found a near halving of mortality rates in the HCQ group. Yet that is described as no evidence of efficacy. Odd.

</comment><comment><USER64> Sample size is far too small.

If anything this study shows (albeit with small numbers) that HCQ doesn't make things worse.

But I have a feeling HCQ will be found to be effective. Big pharma have a lot of $$$ to make from their vaccine though.

</comment><comment><USER65> There is an obvious pushback on hydroxychloroquine. Not enough money to be made so other "solutions" are preferred. Something that was used for more than 50 years is being tested for safety? What a joke. I'm sure when vaccines arrive they'll be "safe and effective" and used all around the world from day one...

</comment><comment><USER65> There is an obvious pushback for hydroxychloroquine. Something that was used for more than 50 years should've been widely adopted by now but there is not enough money to be made (and let's not forget political issues). I'm sure when vaccine arrives it'll be "safe and effective" and widely used around the world from day one - no questions asked.

</comment><comment><USER66> The sample was 185 patients. There are anecdotal evidences that support the medicine which claim to have more, the letter came from a French doctor too. The study is discouraging for sure though.

</comment><comment><USER67> Instead high doses of vitamin C have proven to be very effective.

</comment><comment><USER68> It _really_ bothers me how hard both citizens and officials seem to be wanting Chloroquine to fail all because somebody they didn't like endorsed it publicly. Can't let him have that win, right? Like children.

The original studies that showed promise used combinations of Chloroquine, Azithromycin, and or zinc, and there is a speculated pathway by which these drugs interact to interfere with COVID replication. This study only looked at HCQ.

This kind of partisan, childlike pettiness is dangerous to all of us - what if Chloroquine works but we overlooked it because a couple shitty papers told us what we wanted to hear?

Was it appropriate to tweet about? Debatable. It is a presidents job to keep his people hopeful when possible, and this drug cocktail was in multiple (admittedly not perfect) papers at the time of the tweet. People need to be more objective when evaluating statements made by the president. That doesn't mean you have to like him.

<comment><USER69> I think there's a bunch of strawmen here. It's disingenuous to say that people who found [said person]'s comments to be a bad idea _want it to fail_.

Indeed, if that person had come up and said "there's a lot of promising treatments, such as ..." or "the experts are telling us that some studies involving [x, y, z] are showing some positive signs" or something of that ilk, nobody would have cared. Instead, the person multiple times touted something that is to date unproved. People find that irresponsible for a number of reasons, not least of which that there are legitimate users who need this and it's now in short supply.

So what people are protesting is someone not waiting for medical science and just causing noise.

Like many things, this person could have handled this all more responsibly.

<comment><USER68> >[https://youtu.be/oWQjWepaDv0](https://youtu.be/oWQjWepaDv0)

"Very promising early results".

>[https://www.google.com/search?q=trump+tweet+chloroquine&prmd...](https://www.google.com/search?q=trump+tweet+chloroquine&prmd=insv&source=lnms&tbm=isch&sa=X&ved=2ahUKEwjvzOjehOvoAhVICc0KHcxyD8gQ_AUoAXoECAwQAQ&biw=412&bih=556&dpr=2.63#imgrc=sU_DAlax8JfVaM)

"Have a real chance to be one of the biggest game changers"

Meanwhile the media response has been universally lamenting that a president would "tell people" [he didn't] to take this drug. How many outlets jumped on the single chloroquine phosphate overdose as proof of the president's responsibility? I encourage you to search "Trump" and "chloroquine" and find me _a single headline_ that doesn't tear into Trump.

Like most people, your views have been warped by headlines and op-eds being touted as "news."

The fact that the president acts like a child doesn't mean our news should too. The petty editorialization of the daily briefings are an excellent example - the media's job in such a case is to be an objective first source - not to force their point of view through adversarial headlines that change every 5 seconds and "fact checking" only his alleged untruths. But this is where the majority of Americans get their news. It's shameful.

Edit: hell, look at this absolutely _ridiculous_ headline at the top of the CNN "fact check" page: "Fact check: Trump denies saying another thing he said and makes more false claims at coronavirus briefing"

What kind of headline is that? Is anyone competent left at CNN? The media no longer deserves the soft power it wields. They lost that privilege when they strayed so far from any semblance of objectivity.

<comment><USER30> _" Have a real chance to be one of the biggest game changers"_

and

 _" Hopefully both will be used immediately. PEOPLE ARE DYING, MOVE FAST"_

Both seem pretty ridiculous when we don't even know if its effective at all, let alone "one of the biggest game changers".

<comment><USER68> There were multiple papers out of Europe and China by then. This was already floating around before Trump latched onto it because it was indeed promising, which is exactly what Trump said.

What else do you think the words "hopefully" and "real chance" are here to communicate?

What do you think "move fast" means? Administer the cure to everyone, or figure out if it works?

This was a clearly promising avenue and as the head of the executive this is one of the few things that the man has done right. This vitriol is pure, irrational bias.

<comment><USER69> It's neither vitriol nor irrational to expect a leader to yield to experts and to relay only reliable information.

What he did instead lacked context or information necessary to mass communicate. There's a way to communicate it and it wasn't this.

<comment><USER68> >it's neither vitriol nor irrational to expect a leader to yield to experts and to relay only reliable information.

And you want to tell me that from his tweet you already know he didn't get this information from so called experts? How exactly does this tweet indicate otherwise?

>What he did instead lacked context or information necessary to mass communicate. There's a way to communicate it and it wasn't this

Welcome to the new normal, where politicians communicate via tweet. I agree that it is inappropriate but this particular example is just being used to project the usual anger onto him with multiple plausible but ultimately inappropriate rationalizations. There was, again, nothing inappropriate about a passing mention of a safe, cheap, promising drug. He could have done the same in the middle of a speech for similar effect.

Besides, what did you expect him to do, cite the relevant studies on Twitter? Sure, ideally he would, but let's not pretend that more than, say, .01 percent of the population is even capable of reading studies...

This is a shitty hill to die on.

<comment><USER69> > And you want to tell me that from his tweet you already know he didn't get > this information from so called experts?

Given his experts wouldn't validate it after ... yeah, probably.

> I agree that it is inappropriate but

Then what's the argument here? We both agree it's inappropriate. Just as I do when any other politician misuses it.

> Besides, what did you expect him to do, cite the relevant studies on > Twitter?

No. I'd expect him to wait until there's something worth disseminating.

> This is a shitty hill to die on.

Who's dying on what hill here?

</comment></comment></comment></comment></comment></comment></comment></comment><comment><USER70> Wow, several HCQ stories on the front page. Means it's probably going to be proven effective soon.

</comment><comment><USER71> Totally out of my depth here. I've been following Dr. Chris Martenson's daily covid-19 updates since late January. He is adamant this treatment is only effective in combination with zinc supplements.

<comment><USER72> So why doesn't this guy setup clinical trials instead of providing non- confirmed medical advice on the daily?

Probably cause he is lazy and more interested in selling and promoting himself than he is actually solving problems.

This guy knows the scientific method, I assume. he knows that something needs to be observable and replicated. Instead, he is asking us to trust his brilliance on something where the side effect might be death and blindness??

</comment></comment><comment><USER22> While we're here,

"Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective" ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036/))

Hey, it can't hurt and it might help. China has had one of the best recoveries from the pandemic.

<comment><USER73> I cannot tell if you are purposefully trolling, or this is sincere.

Regardless, let's wade in…

1\. That's not's a study. That's not a metareview. That's a puff piece by people who have a strong, strong self-interest in promoting TCM, because they want to keep their department chairs.

2\. Oh heck, I'll just quote the entire last paragraph:

"The safety of TCM in the treatment of emerging coronavirus diseases was not included in the observation on SARS patients. It was reported that some herbs used in TCM contain nephrotoxins and mutagens, while the toxicological features of the most of Chinese herbal medicines remain to be fully understood. Furthermore, herbs used in TCM can mimic, or magnify, or oppose the effect of conventional medicines. Thus, the safety of TCM used in treatment of emerging coronavirus infections should be carefully evaluated. It is particularly important to avoid toxicity or interfere with the efficacy of conventional treatment caused by herb-drug interaction."

So, in conclusion, we don't know if this works, and this stuff may be toxic, and it may have drug interactions, and oh by the way there's no quality control on this so you have no idea what's in the medications.

Might as well recommend acupuncture and getting your chakras aligned, couldn't hurt! (Probably less of a chance it hurting than taking a wild dose of unregulated herbal supplements.)

<comment><USER22> " _Might as well recommend acupuncture and getting your chakras aligned, couldn 't hurt!_"

Indeed, it might help and it couldn't hurt.

" _(Probably less of a chance it hurting than taking a wild dose of unregulated herbal supplements.)_ "

Or possibly a known drug with no real evidence of efficacy and a long list of known side effects?

Oh, and by the way, " _That 's a puff piece by people who have a strong, strong self-interest in promoting TCM, because they want to keep their department chairs,_" is both an hominem and describes all academic publications.

</comment></comment></comment><comment><USER74> What a joke. An emulated trial only in patients already requiring oxygen. How about this [http://covexit.com/professor-didier-raoult-releases-the- resu...](http://covexit.com/professor-didier-raoult-releases-the-results-of-a- new-hydroxychloroquine-treatment-study-on-1061-patients/)

I'm taking the HQZ cocktail at first diagnosis even if I have to doctor shop.

</comment><comment><USER75> > documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a > target trial aimed at assessing the effectiveness of HCQ at 600 mg/day

Well hydroxychoroquine is only useful before ventilators are needed (it attacks the full lungs) and is actually detrimental - we know that - after by its nature.

What kind of bad science is this study where you actually push patients through a known dangerous path to try to prove the non efficiency of a potential treatment.

<comment><USER76> >Well hydroxychoroquine is only useful before ventilators are needed (it attacks the full lungs) and is actually detrimental - we know that - after by its nature.

I'm worried that this has totally left the realm of science and is just pure politics... there is no evidence for a 'magic window' for HCQ in COVID-19 treatment, or any solid evidence of a positive role.

Secondly, having supplemental oxygen is _not_ the same as being on a ventilator. I imagine most hospitalized COVID patients need oxygen (otherwise, they could be managed at home).

I hope we all avoid making comments (or even accepting comments) about medicine without either critical, independent study or background knowledge.</comment></comment>


Show HN: JinjaSQL – Generate SQL Queries using a Jinja Template - <AUTHOR> https://github.com/hashedin/jinjasql <comment><USER3> Looks interesting!

When we switched to Clojure (from nodejs), we decided against any kind of ORM and use HugSQL which allows us to write "plain SQL" in .sql files while still using parameters.

</comment><comment><USER4> Would be great if you can put in some examples where we can optimise parametric queries using this. One common instance is IN queries where if the number of params for IN clause is small, it might make sense to blow it up into multiple equals clauses, allowing better use of indexes. MySQL query optimiser is horrible with IN clauses and causes table-scans. I have seen table scans and skipping other indexes even when IN clause has zero cardinality (in which case its better to just remove it altogether).

Couldn't immediately think of other cases, but that one example sounds useful for this.

<comment><AUTHOR> In clauses are blown up. I have now added that to the documentation - <USER2> [https://github.com/hashedin/jinjasql#handling-in- clauses](https://github.com/hashedin/jinjasql#handling-in-clauses)

Skipping in clauses altogether - for now, you can handle that using an if condition.

</comment></comment><comment><USER5> Because we totally needed stored procedures to be re-implemented outside of the database in a templating language. /s

<comment><USER6> That's a rather short-sighted comment. We use similar functionality to build an end-user reporting system which queries multiple DBs, many of which are part of vendor applications. Trusted users write the SQL, parameterize it with django-templates. Users enter parameters in widgets. SQL is generated using the templates, executed on the target DB with RO credentials, and returned in a grid/csv/excel/json.

<comment><USER7> So we've reinvented Tableau and other data analytics packages instead.

<comment><USER6> Now you're just trolling.

<comment><USER7> Not at all! Just expressing that we keep showing off reinventions of the wheel.

</comment></comment></comment></comment></comment><comment><USER8> Groovy has had similar functionality in its standard library for years now, very handy!

<comment><USER9> Are you refering to this [http://groovy.329449.n5.nabble.com/Groovy-and-SQL- tt5710894....](http://groovy.329449.n5.nabble.com/Groovy-and-SQL- tt5710894.html#a5710895) August 2012 mailing list claim about Apache Groovy? There isn't any GROUP BY in that one.

<comment><USER8> No, I'm refering to the groovy.sql.Sql class: [http://docs.groovy- lang.org/latest/html/api/groovy/sql/Sql.h...](http://docs.groovy- lang.org/latest/html/api/groovy/sql/Sql.html)

It allows you to simply write SQL in a GString using placeholders that get replaced with parameters before being sent to the database, here's an example from the Javadoc:

sql.execute "insert into PROJECT (id, name, url) values ($map.id, $map.name, $map.url)"

Works great with Groovy's multiline strings.

</comment></comment></comment><comment><USER10> Can you interpolate table and column names? Those usually aren't amenable to change in prepared statements

<comment><AUTHOR> You can, the tool won't prevent you from doing so. It does however give you the |sqlsafe filter. Using that filter will append the value directly. You can use it to insert dynamic table or column names. Of course you've to be sure those table or column names are safe from sql injection.

</comment></comment><comment><USER11> What about using prepared statements?

<comment><USER12> > While JinjaSQL can handle insert/update statements, you are better off using > your ORM to handle such statements. JinjaSQL is mostly meant for dynamic > select statements that an ORM cannot handle as well.

[1] [https://github.com/hashedin/jinjasql#when-to-use- jinjasql](https://github.com/hashedin/jinjasql#when-to-use-jinjasql)

<comment><USER11> Sorry, but this doesn't answer my question. Prepared statements have nothing to do with ORMs.

<comment><USER13> This library doesn't run SQL, its only a template engine that gives you back a parameterized query and parameter array back. It's up to you to actually use them with an adapter, which means you can use prepared statements.

</comment></comment></comment></comment><comment><USER14> This is good. SQL templates are usually much faster for database queries than using ORMs.

<comment><USER15> I'll take the bait. It's easy to write a slow SQL query, and equally easy to write a fast ORM query. In the long run, for readability and maintainability, ORMs win most of the time. I've rarely found a slow ORM query that couldn't be fixed without resorting to SQL (half the time it's bad indexes, half the time it's doing something un-performant in the ORM).

The few times when I do need to force a certain SQL syntax that the ORM won't give me, I drop down to SQL. But doing that doesn't magically make all queries faster.

<comment><USER16> My favorite trick is binding a hook in unit test modules that basically runs an "explain q" for every query "q", and asserts that it found an appropriate index to use. Then as long as your unit tests exercise all queries your app needs, you know that your database indices are appropriate for your app's usages.

<comment><USER17> I wish laravel had this and an automated SQL debug comment feature.

</comment></comment></comment></comment><comment><USER18> Very nice. I made something similar a while back:

[https://www.youtube.com/watch?v=CzwikfCAdws](https://www.youtube.com/watch?v=CzwikfCAdws)

</comment><comment><USER19> Looks like a fantastic use of Jinja templates. This is cool.

</comment><comment><USER20> How does this protect against SQL injection attacks?

<comment><AUTHOR> It doesn't append the strings blindly.

Any variables are automatically replaced by placeholder strings. You also get an array of bind parameters. You then use your database library to bind the parameters into the placeholders.

</comment></comment><comment><USER21> How is this better than SQLAlchemy Core?

</comment><comment><USER22> Hmm, no convenience macros for common SQL situations (e.g. building WHERE-AND parts out of arrays)?

<comment><AUTHOR> I plan to add those macros in due course. Common where/and macros, utilities for date time manipulation are the ones that top the list.

</comment></comment><comment><USER23> Python 2.x only?

<comment><USER24> Doesn't seem to be – [https://github.com/hashedin/jinjasql/blob/master/setup.py#L5...](https://github.com/hashedin/jinjasql/blob/master/setup.py#L56) – so I don't know why the README implies that.

<comment><AUTHOR> It does support 3.x, there are test cases for it as well. I'll fix the readme, thanks for pointing that out!

</comment></comment></comment><comment><USER25> Reminds me of mybatis.</comment>


Do people care about the brand of their consumables? - <AUTHOR> Hi All, Do you people care about the brand of your consumables like paper towel, toilet paper, etc? Would you use a service which auto delivers such stuff when you are almost? All you have to choose is Good/Better/Best and Small/Medium/Large. Nothing else.
Or do people really want to use Downy, 409, pledge, etc? <comment><USER2> For me a brand is an identifier that groups price and different qualities. I chose my brands based on what gives me the most value for my money. So, yes, it's important. It's also personal.

Some carrots are thick, others are thin, and you can't say one is better than the other because some people will prefer the thick ones and others the thin ones. Thicker ones are easier to peel since you can hold them better and have a larger volume-to-skin ratio, and also result in larger slices. Thinner ones fit more easily in a juicer and are easier to bite down raw without cutting.

Same with paper towels. Some rolls come with few, super-resistant and reusable towels (Kleenex is amazing, it'd probably easily survive being put in a washing machine multiple times), others come with a bunch of super-weak, disposable towels. I pick both rolls and use them depending on the situation.

For my milk, one brand seems to spoil faster (always days before the expiration date), I'm not sure why, so I avoid it.

I also care for the brand of my bread. All bread brands are really different, so it matters. Some will have more slices, some will have wider slices, some will have thicker slices, some will be more dense, some will be more white, some will be more nutritious, etc.

Toilet paper from certain brands breaks too easily, others charge too much to make the paper super-soft, etc. Some will add a unique spin which you may or may not value, like how one brand flattened the rolls in its packaging to use less space and therefore be better for the environment. I suppose the argument comes from less plastic packaging and more rolls transported per trip when it's being distributed. I liked that one, mostly because the paper just happened to be wider than all other brands, but I can imagine some people would just find flat rolls to be too weird to buy even if they can easily unflatten them before use.

Brands of yogurt also differ a lot. Some are smoother, others are thicker.

<comment><AUTHOR> Interesting thought. Thanks for the feedback.</comment></comment>


The Case for Star Trek: Deep Space 9 (2016) - <AUTHOR> https://medium.com/maxistentialism-blog/star-trek-deep-space-nine-in-82-5-hours-10acde591fd2 <comment><USER3> The standard complaint about DS9 is its merely a ripoff of Babylon 5. I have not been able to stomach watching B5; if I ever have a couple hundred hours of spare time I'll attempt it, until then I'll have to trust other's opinion. Something not often mentioned is the sheer expense of these series; hundreds of hours of limited spare time have to be invested to experience it all. I watched all of DS9 when it was new and then decades later just a couple years ago; it was pleasant but compared to the alternatives I'm not sure it was a wise use of my time. I tried B5 but after a dozen or so hours invested I had barely scratched the surface yet was bored. These series are just painfully expensive. For a non-sci fi comparison try "The Sopranos" where if you're not addicted its very hard to get addicted and the time investment is insane like hundreds of hours required.

Garak is the most interesting character in all of Trek. The linked story was very human focused, but if you get past the species-ism then Garak is clearly the most interesting character in all of Trek. He certainly has the most unique and interesting lines of dialogue.

There are strange human sociology messages in DS9 that are kinda unrealistic. In DS9 land, individuals are extremely newness-seeking and would never interact with someone of their own kind if there's any possibility of interacting with a stranger, and the stranger the better; this political requirement has no relationship with reality of course, and as such the series suffers under a pallor of weirdness. Friendship and family and culture feel at best bolted on, or at worst are outright ridiculous.

There is some relationship between DS9 and Ian Banks Culture-verse, echos of one in the other. Both are kind of a window into a future that does not contain social media and the problems resulting from social media, which is kinda weird, like experiencing a science fiction novel from just before the broadcast era that naturally does not explore the numerous effects of broadcasting. Off the top of my head I can't think of any hard sci fi that is set substantially in the future yet contains aspects of social media from a decade ago, although someone here probably has some good suggestions.

<comment><USER4> Garak's rootbeer scene with Quark remains my personal favorite.

<comment><USER3> I would correct the linked article to add "our man bashir" S4E9 to be watched at the end of the series, its basically an hour of in-jokes about Garak's secret life.

Garak's blood type was "snarky" and that character might be a bit too much for some viewers. Its unusual on TV to have extreme levels of snark that doesn't divert into mere whinyness or fart jokes. I guess that was acceptable at the time of writing because Garak is a space alien.

"Tragedy is not the word I'd use. Farce would be more appropriate." in the context of the theatrical version of the assassination of Julius Caesar.

Or the time Garak made fun of aesops fables for being too violent (same episode as last)

"Treason, like beauty, is in the eye of the beholder."

WRT the linked article comment about Miles and his incredible tearing pants gag thru the series "Unlucky for you, my sewing kit went down with the ship." was seemingly inevitable...

</comment></comment></comment><comment><USER5> This is a great post. As a long time TNG fan (and fan of The Greatest Generation podcast), I never grokked DS9. I tried many times, but the first season episodes are just so bad that I can never make it though.

An episode guide like this is helpful as well as the behind-the-scenes on the show in general.

Thanks for sharing.

<comment><USER6> Never judge a show by the first season, or worse the first few episodes. Cast need time to get accustomed to the part, to create alchemy etc. Also, "unusual" shows like DS9 (IMO best Trek ever) or even Babylon5 (IMO best non- Trek ever) etc. need some adjustment from the viewer. I recall hating Farscape, but decided to keep watching it anyway and in the end I loved it so much that I cried after the last episode. Now I'm watching again Stargate Atlantis (IMO best SG ever) which started strong from the very first episode, but nonetheless grew anyway with time. I wished ST Voyager could get better as well... that show had so much potential:(

</comment></comment><comment><USER4> Great post. Fun learning some of the back story.

I love Deep Space Nine. All of it. As in: Best show ever made.

I agree that DS9, along with Babylon 5, pioneered the long form TV story arc. Every single character goes thru the heroes journey. Convincingly. I love it.

Benjamin Sisko is my favorite captain. I'd follow that guy into a black hole.

Quark makes the show. I don't know how Armin Shimerman pulled that off. Some of the best acting ever.

My favorite episodes remain the Ensign Kim stuff from Voyager. But overall, DS9 was just the best.

<comment><USER7> > favorite episodes remain the Ensign Kim stuff from Voyager

Wait wat? Which episodes?

<comment><USER4> Well. The two episodes I continue to think about feature Kim, but aren't necessarily about him. Maybe Kim is just my favorite character.

#1 Voyager gets stuck in a time thing, splits into two like Siamese Twins, Kim dies in one universe, surviving Kim gets sent across rift. That messes my head up.

#2 A mimic version of Voyager starts to disintegrate. They figure out they're not the real Voyager. Their last act is mimic Kim trying to send a message out, before they disappear, so the universe knows they existed. That one really messes my head up.

Please don't make me find the specific episodes. I am weak and am likely to binge watch. But I have chores to do. :)

<comment><USER7> I'm a huge Trekkie and I know exactly which episodes those are.

My brain kept getting stuck on the episode where he starts to transform into an alien of the male sex. Only to be at risk of sexual desiccation. I didn't put that episode on a GOAT list however :-)

<comment><USER4> Ya, Favorite Son, that one's brutal. Good one.

I'd love to hear your other faves.

My least/most favorite episode is Tuvix. Dilemma! I just can't take it. And the casting, portrayal of Tuvix is just so spot on.

Enterprise's Coginator is a close second.

Dammit, now I've started rereading episode guides.

Thanks for playing catch. This is fun.

<comment><USER7> The ethical issues with Tuvix were actually pretty interesting.

I tend to like story arcs more than specific episodes.

The idea of being far from home with high fallutin' ethical codes - how do those codes fair with out a support system nearby? (Janeway)

The idea of being transformed physically and mentally by a crime - is self identity fully recoverable? (Seven)

Are computer algorithms sentient - what lines must be crossed for an AI to become recognizably humanlike? (the Doctor)

</comment></comment></comment></comment></comment></comment><comment><USER8> Sadly I can't imagine a show like DS9 which made you think about moral ambiguity being made today, especially in the US. The "good guys" (i.e., the Bajorans) were terrorists (and religious ones at that). In some episodes, Kira openly discussed the fact that as part of the resistance, they had to accept killing civilians and other Bajoran as collateral damage.

<comment><USER9> I don't get it, isn't moral ambiguity very popular nowadays? Dexter, Breaking Bad, The Dark Knight...

<comment><USER10> For better or worse, it's really hard to find shows where one side is _clearly_ in the right and the other is _clearly_ wrong.

<comment><USER11> You could say this is shows finally reflecting real life more accurately.

</comment></comment></comment></comment><comment><USER12> > "O'Brien Must Suffer" episodes

Eh, these were among my less-liked episodes. None of them advanced the plot, they mostly made no sense relating to O'Brien's character (like, why did Starfleet choose him, a chief _engineer_ , to run an organized crime sting operation), and the sum of these was O'Brien gaining this weird parallel backstory of him as some woebegone magnet for unluck. They were all clearly contrived; at least from reading this article I now know _why_.

(To be fair, some were really good – like when Keiko (O'Brien's wife) was possessed by a Pa Wraith. Others were just like, what the heck, O'Brien's in jail _again_?)

> Season one's nadir, "Move Along Home."

Funny thing is, this is one of the more "traditionally" Trek episodes. Meet a weird species, have some misunderstanding during first contact, everyone almost dies, but j/k it's all OK in the end and we forget anything ever happened in the next episode.

> Season 2 establishes one of Star Trek's greatest characters, Elim Garak.

Glad he got a call out! Was disappointed he was missing from the cast drawing, given that he plays an increasingly prominent role in the later seasons.

> this would be a great time to abandon my guide and just watch the whole > thing.

Uhh… but make sure to skip _Profit and Lace_. It's objectively awful (and I love the Ferengi episodes), and I refuse to consider it canon. Unfortunately it advances the Ferengi subplot; just imagine a story that fits the plot points and you'll be better off than watching it.

> Optional episodes: Take Me Out To The Holosuite

I highly recommend watching this. It has nothing to do with the plot whatsoever, but it's fun to watch and does a lot of good (if silly) character building. You can tell the cast enjoyed it too.

<comment><USER13> The one where he has memories of being in prison implanted was fantastic, and I really enjoyed the one where he infiltrates the Orion Syndicate, though I don't know if they explained why an engineer was chosen for an intelligence mission...

<comment><USER12> You know, thinking some more, I _liked_ the episodes _individually_ (including the ones you mentioned). But they just always felt to me like they were made for another show or another character. So the article's explanation that O'Brien, as a "likable" character, was specifically chosen to suffer these misfortunes clears things up a bit.

Not to mention they usually didn't tie into the main plot at all. Like – O'Brien has 10 years of prison psychologically weighing on his mind now! For the rest of his life! That should be a character-defining change. But it's never brought up again _ever_.

Same thing with the "parallel universe" episodes. As set-piece action/adventure episodes, I _loved_ them; the Intendant and the Regent are among my favorite (if over-the-top) characters. But the set-ups never made sense and they never advanced the main plot, so I always started and finished each episode a little disappointed.

I think that's why the Keiko/Pa-Wraith episode stood out to me as much better than the others – it actually ties into and advances the main plot. Sure, O'Brien is again randomly the poor sap who takes the fall, but it's not forced and it actually advances the plot.

<comment><USER14> O'Brien is already massively psychologically traumatized (re: Next Gen) so the ten years of prison and other horrors weren't enough to really change his overall mental state?

</comment></comment></comment></comment><comment><USER15> I contend that DS9 remains some of the best television ever made (and yes, I've seen, and love, The Wire). It has plenty of dumb and boring moments, but when it hits the mark it hits it so squarely and soundly that it makes a mark on the viewer for life. It takes the ball that Star Trek serieses typically play with: issues of complexity and moral difficulty that our current society is struggling with, and does more than just play around with it, DS9 knocks it out of the park. DS9 knows what it's about and isn't afraid to put a very fine point on it.

Also, there's this: [https://www.youtube.com/watch?v=tmdrhfA0-Fw](https://www.youtube.com/watch?v=tmdrhfA0-Fw)

</comment><comment><USER16> For better or worse, Star Trek TNG and DS9 have played an important role in my development. I would like to think that is was a benefit.

The major message of Star Trek in general and DS9 in particular is that despite of - no! because of! - our petty differences, we can all live together harmoniously. That harmony may require to people to avoid contact, but that is a - relatively - rare exception.

A minor message, but an important one, I think, is that violence and force are rarely, if ever, the best way to solve a problem. With a little bit - or a lot - of cleverness you can find a solution that will be satisfactory to all the parties involved. Even if you have all the right cards, simply relying on strength is not a good foundation for a long-term arrangement. Diplomacy and Compromise is.

It is a lesson - Star Trek or not - that I think could help many young people these days, Star Trek or not.

</comment><comment><USER17> I respectfully disagree, that DS9 was a step up from TNG. It all got nailed in the Gene's quote about what you will and will not see in 24th century.

Star Trek for me is a sneak peak into a different future (maybe not 300 years, but 1000s). And DS9 is, basically, today, wrapped into a Sci-Fi suit.

Name one episode of DS9, where you'd see a problem and its solution, and be able to say "rare living human would do this". For TNG: the entire Borg thing, and that episode with Data trying to prove a tool became sentient - <USER2> something you can't find in Trump's twitter.

That is basically the same reason for the rants about Discovery: they can't make it past TNG's timeline.</comment>


Ask HN: Somebody pretends to be me when sending spam - <AUTHOR> Hey, I've just got email rejection from some internet forum, to which I had not subscribed, nor posted.
It was just regular spam with bitcoin blackmailing which you get a lot if you have public mail address.
What's not cool is that the mail was sent like it was from me (fake headers?), is there anything I can do about this? Even from the legal point of view - somebody could go after me because he wouldn't know I wasn't the real sender. <comment><USER2> It's fake headers and been done as long as email exists. If you have your own domain you can use anti spoofing measures like SPF, DMARC, DKIM [https://en.wikipedia.org/wiki/DomainKeys_Identified_Mail](https://en.wikipedia.org/wiki/DomainKeys_Identified_Mail) So you'd tell receivers only you (DNS entry of your mail server's IP) are allowed to send from this domain and if they ever see somebody else doing it they should mark it as spam.

</comment><comment><USER3> Are you domain forwarding, and if so, is your SPF record set up correctly?

<comment><AUTHOR> I just have MX set to google apps, I will have a look into SPF, thanks :)</comment></comment>