#epidemiologists get on that and credit me in your papers

[arctic-hands]

You: A patient sometimes if at all

Them: A chronic patient

Me: ✨ Forever Patient ✨

[kathleenseiber]

What we know about Ivermectin: correlation is not causation

Unlike the huge amount of high-quality data we have gathered on vaccines (5.6 billion doses and counting), the available data on Ivermectin is a dog’s breakfast – despite the fact that millions of people around the world have used it to treat COVID, especially in poor countries.

The hope that Ivermectin could vanquish COVID was seeded from Kylie Wagstaff’s lab at Melbourne’s Monash University. Knowing that the drug had anti-viral effects, they decided to test it against COVID using infected monkey cells growing in a dish. In April 2020 they published a paper describing how, 48 hours after dosing the monkey cells with Ivermectin at a concentration over 10 times that used to treat parasites, virtually no virus was detectable.

Credit: Cosmos Magazine

There was almost nothing around to treat COVID patients in April 2020. Given the horrific rising death toll in South America and India, and that Ivermectin was already widely used as a medication to treat diseases caused by parasitic worms like river blindness or scabies, the WHO kept an open mind, as they did for other cheap off-label drugs like dexamethasone and hydroxychloroquine.

But the WHO made it clear that Ivermectin should only be used in the context of a trial – drugs can make things better or worse. Indeed, thanks to trials, we now know that dexamethasone helps COVID patients; hydroxychloroquine makes them worse.

But in places reeling from the pandemic, particularly across South America, there was a massive uptake in the use of Ivermectin, sometimes officially sanctioned by local or national authorities as in Peru, Bolivia, Brazil, some states of India (Uttar Pradesh), Bangladesh and Zimbabwe.

June 2020 alone saw Brazilians purchase 12 million packets of Ivermectin – a year’s worth of the drug in a single month. It didn’t seem to affect the death rate. One Brazilian scientist observed, “the shape of COVID curves did not exhibit any modification when comparing groups of treated and untreated people from the same area”.

On the other hand, Zimbabwean doctor Jackie Stone trumpeted the success of Ivermectin, because after its use was authorised in Zimbabwe on 26 January 2021, death rates fell from 60–70 per day to zero by 2 February 2021.

That sort of correlation is intriguing. But it’s famously fallible – the “correlation is not causation” conundrum. You can show that drownings increase after ice cream consumption but it’s not because a belly full of ice cream cramps your muscles. It’s because both events are more common in summer. Statisticians refer to summer, the sneaky third wheel, as a confounding variable.

You can show that drownings increase after ice cream consumption but it’s not because a belly full of ice cream cramps your muscles. It’s because both events are more common in summer.

The fact is COVID death rates fluctuate and researchers have yet to figure out why.  Zimbabwe was back up to over 100 deaths per day in late July, and then down to 19 per day in September. As Gideon Meyerowitz-Katz, an epidemiologist from the University of Wollongong, put it: “Merely correlating news reports of Ivermectin use with later declines in mortality as if those two things are realistically connected; it’s not science in any meaningful sense.”

Meyerowitz-Katz’s blog on Ivermectin is a great source of information. So is this August article from Liam Mannix in the Sydney Morning Herald.

With so many people taking Ivermectin in some countries, it became hard to do placebo-controlled clinical trials.

Those that were done were often small – just dozens of people – and “observational”, meaning the doctor prescribed the drug to the patients and watched to see how they fared. If a drug has a large beneficial or adverse effect, observational studies should pick it up. But observational studies do poorly with small effects and can’t accurately measure their size. Without a concurrent matched control group who are not taking the drug, you can’t zero out the turning of that hidden third wheel.

Most of the observational studies aimed to see if Ivermectin could be used to treat patients at home and prevent them from progressing to severe disease. Some showed benefit in terms of lowering viral loads and quicker recovery times. Others did not. One of the few statistically significant placebo-controlled studies from Colombia showed no effect of Ivermectin.

A few of the studies weren’t just compromised by being flawed: they were possibly fraudulent. Taking advantage of the desperation for answers, some researchers sought to make a name for themselves in the dodgy world of online pre-prints. These are papers that have yet to clear the hurdle of peer review and their findings should be treated with caution. In the case of Ivermectin, two pre-prints that showed a significant protective effect of Ivermectin were later retracted; one from the Chicago-based data company Surgisphere and another from researchers at Benha University, in Egypt.

To try to read an overall signal from the many small studies, researchers have collected them in what is known as a ‘meta-analysis’. But it all depends on which studies they picked. Some meta-analyses showed a net positive effect (particularly if they used the retracted Egyptian data). Others found no conclusive effects.

The most reliable of these meta-analyses was a 28 July Cochrane review. This international organisation specialises in adjudicating medical controversies by deploying independent statisticians and medical experts to sift out and analyse credible published studies. Their review concluded: “We are uncertain whether Ivermectin reduces or increases mortality compared to no treatment.”

It’s easy to understand the desperation of people turning to Ivermectin in 2020. In 2021, it’s harder to fathom why people in the US and Australia – who have easy access to vaccines – would opt to bet their health and their life on it. Merck, the company that manufactures Ivermectin, is certainly not pushing its use for COVID.

A recent alert from the US CDC noted a 24-fold increase in Ivermectin prescriptions from pre-pandemic levels, as well as cases of people using veterinary products. It noted: “Overdoses of Ivermectin are linked with low blood pressure, confusion, hallucinations, seizures, coma and even death.”

“Overdoses of Ivermectin are linked with low blood pressure, confusion, hallucinations, seizures, coma and even death.”

The FDA took to Twitter to convey the dangers: “You are not a horse. You are not a cow. Seriously, y’all. Stop it.” It warned that “taking large doses of this drug is dangerous and can cause serious harm”.  Australia has followed suit, with prescriptions up 3-4 fold leading the TGA to take the extraordinary step of banning its off-label use for fear of depriving people who need to use Ivermectin to treat parasites.

One of my vaccine-hesitant friends who is keen on Ivermectin pointed me to the trials being done by Sydney doctor Thomas Borody. Borody has treated around 25 COVID-positive patients in home quarantine, some as young as 16. He says most recovered without being hospitalised, though one died. Yet we know 90% of people do recover without being hospitalised. These do not strike me as good statistics upon which to be making life-and-death decisions. Nor is Borody claiming that Ivermectin is an alternative to vaccines. It is, he says, “another string to the bow”.

To find out how well that string plays, we’ll need to wait for the results of large placebo-controlled clinical trials currently underway.

These include the Oxford trial known as PRINCIPLE, another at McMaster University in Canada called TOGETHER and one at the US National Institutes of Health known as Activ-6.

These trials focus on repurposed drugs like Ivermectin that are cheap and readily available. A key goal is to find the ones that will stop home-based patients from progressing to severe disease.  

So far there are two: the inhaled steroid budesonide and (surprisingly) the anti-depressant fluvoxamine.

PRINCIPLE has shown budesonide shortens recovery time by three days in some patients. And preliminary results from the TOGETHER trial showed that fluvoxamine was mildly effective, reducing the relative risk of getting worse by 30%. 

In August the TOGETHER trial showed Ivermectin had no statistically significant effect.

The other trials have yet to report – but don’t hold your breath.

“The evidence so far doesn’t point to a large effect, if any at all.  To detect a small effect you need a much larger sample size – hence it will take a long time.”

Oxford is loathe to predict when they will have their results, but after badgering head investigator Christopher Butler, he guessed it might be in the first quarter of next year. The NIH apparently won’t have anything to say till 2023.

That seems absurd, given the epidemic of people taking the drug in the hope it will work.

Carlos Chaccour, an infectious disease specialist at the Barcelona Institute for Global Health who works on Ivermectin for malaria control and has tested it in a small trial for COVID, helped clarify the situation for me. “The evidence so far doesn’t point to a large effect, if any at all.  To detect a small effect you need a much larger sample size – hence it will take a long time.”

YOUR COVID TOOLBOX: This article is one of a five-part series where Cosmos editor-at-large Elizabeth Finkel hunts down all the facts and figures you need to understand COVID-19 vaccines.

Elizabeth Finkel: A letter to my vaccine-hesitant friends

Are COVID-19 vaccines experimental?

The rollout: The danger of vaccines vs the danger of COVID

Adverse reactions: Guillain Barre, TTS and the fine mesh net

What we know about Ivermectin: correlation is not causation published first on https://triviaqaweb.weebly.com/

[dailykhaleej]

Tech-assisted COVID-19 tracking is having some issues

A smartphone app constructed for the state of Utah displaying coronavirus check websites. The app tracks signs and shares location knowledge for contact tracing, the method of figuring out who may need been uncovered to the virus. Picture Credit score: AP

Windfall, Rhode Island: Harnessing immediately’s know-how to the duty of combating the coronavirus pandemic is turning out to be extra sophisticated than it first appeared.

The primary US states that rolled out smartphone apps for tracing the contacts of COVID-19 sufferers are coping with technical glitches and a basic lack of curiosity by their residents. A second wave of tech-assisted pandemic surveillance instruments is on its means, this time with the imprimatur of tech giants Apple and Google. However these face their very own issues, amongst them potential accuracy issues and the truth that they will not share any info with governments that might assist monitor the unfold of the sickness.

Contact tracing is a pillar of an infection management. It is historically performed by educated public well being staff who interview those that might have been uncovered, then urge them to get examined and isolate themselves. Some estimates name for as many as 300,000 US staff to do the work successfully, however to this point these efforts have lagged.

All COVID-19 apps to this point are “fundamentally broken” as a result of they acquire an excessive amount of irrelevant info and do not work nicely with Android and iPhone working software program.

– Swiss epidemiologist Marcel Salathe

Different tech firms like Salesforce have provided database instruments to help guide tracing efforts, though these additionally elevate privateness considerations due to the necessity to acquire and retailer detailed details about individuals’s social connections, well being standing and whereabouts.

Privateness advocates warn that the hazard of making new authorities surveillance powers for the pandemic may result in a lot greater issues sooner or later. In a brand new coverage paper shared, the American Civil Liberties Union is warning state governments to tread extra fastidiously and set up stricter privateness procedures earlier than deploying know-how meant to detect and curb new coronavirus outbreaks.

Even probably the most privacy-minded instruments, corresponding to these to be launched quickly by Apple and Google, require constraints in order that they do not develop into devices of surveillance or oppression. “The risks of getting it wrong are enormous,” stated Neema Singh Guliani, a senior legislative counsel with the ACLU.

ACLU’s report says the worst location-tracking know-how ought to be rejected outright, corresponding to apps that monitor particular person actions by way of satellite-based GPS know-how and feed delicate private knowledge into centralized authorities databases. “Good designs don’t require you to gather people’s location information and store that,” Singh Guliani stated.

She urged governments to set guidelines addressing each privateness and efficacy in order that surveillance instruments do not intrude with extra standard public well being strategies.

Utah, North Dakota and South Dakota have been the primary US states to launch voluntary cellphone apps that allow public well being departments to trace the placement and connections of people that check optimistic for the coronavirus. However governors have not had a lot luck getting the widespread participation wanted for them to work successfully.

Almost a month after Utah launched its Wholesome Collectively app to enhance the state’s contact-tracing efforts by tracking cellphone places, state officers confirmed Monday that they have not accomplished any contact tracing out of the app but. As an alternative, individuals who obtain the app have been in a position to “assess their symptoms and get testing if appropriate,” Utah’s state epidemiologist, Angela Dunn, stated final week.

The state with the best identified price of participation to this point is South Dakota, the place final week about 2% of residents had the Care19 app on their telephones. Final week was additionally the primary time it recorded a single an infection. The identical app is getting even much less help in North Dakota.

“This is a red state,” stated Crystal Wolfrum, a paralegal in Minot, North Dakota, who says she’s one of many solely individuals amongst her neighbors and buddies to obtain the app. “They don’t want to wear masks. They don’t want to be told what to do. A lot of people I talk to are, like, `Nope, you’re not going to track me.”‘

Wolfrum stated she’s uncertain that the app might be helpful, each due to individuals’s wariness and its poor efficiency. She gave it a nasty assessment on Google’s app retailer after it failed to note prolonged buying journeys she made one weekend to Walmart and Goal shops.

North Dakota is now taking a look at beginning a second app based mostly on the Apple-Google know-how. The present app “was rushed to market, because of the urgent need, Vern Dosch, the state’s contact tracing facilitator, told KFYR-TV in Bismarck. “We knew that it would not be good.”

The ACLU is taking a extra measured method to the Apple and Google methodology, which is able to use Bluetooth wi-fi know-how to robotically notify individuals about potential COVID-19 publicity with out revealing anybody’s id to the federal government.

However even when the app is described as voluntary and private well being info by no means leaves the cellphone, the ACLU says it is essential for governments to set extra safeguards to make sure that companies and public companies do not make displaying the app a situation of entry to jobs, public transit, grocery shops and different providers.

Among the many governments experimenting with the Apple-Google method are the state of Washington and several other European international locations.

Swiss epidemiologist Marcel Salathe stated all COVID-19 apps to this point are “fundamentally broken” as a result of they acquire an excessive amount of irrelevant info and do not work nicely with Android and iPhone working software program. Salathe authored a paper favoring the privacy-protecting method that the tech giants have since adopted, and he considers it the very best hope for a instrument that might truly assist isolate contaminated individuals earlier than they present signs and unfold the illness.

“You will remember your work colleagues but you will not remember the random person next to you on a train or really close to you at the bar,” he stated.

Different US governors are taking a look at know-how designed to complement guide contact-tracing efforts. As early as this week, Rhode Island has stated it is set to launch a “one-stop” pandemic response cellphone app. It would pair with a brand new contact-tracing database system constructed by software program large Salesforce, which has stated it is additionally working with Massachusetts, California, Louisiana and New York Metropolis on the same method.

Salesforce says it may well use data-management software program to assist educated crews hint “relationships across people, places and events” and determine virus clusters all the way down to the extent of a neighborhood ironmongery shop. It depends on guide enter of knowledge gathered by means of conversations by cellphone, textual content or e mail.

“It’s only as good as a lot of us using it,” Democratic Gov. Gina Raimondo stated of the soon-to-be-launched cellular app at a information convention final week. “If 10% of Rhode Island’s population opts in, this won’t be effective.” The state hasn’t but outlined what individuals are anticipated to decide into.

The ACLU hasn’t weighed in on the Salesforce mannequin, however has urged contact-tracing public well being departments to guard individuals from pointless disclosure of private info and to not criminalize the requirement for self-isolation.

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[mastcomm]

Your Tuesday Briefing – The New York Times

Coronavirus slows China’s economy

As it works to contain the spread of a dangerous epidemic, one of the world’s largest economies has been largely idle, threatening a sharp reduction in the production of everything from cars to smartphones.

Chinese health officials said today that the death toll from the new coronavirus had passed 1,000. In Hong Kong, two people living on different floors of an apartment building were found to be infected, raising fears about how the virus can spread. Here are the latest updates and maps of where the virus has reached.

Quotable: “Let’s not shake hands in this special time,” said China’s leader, Xi Jinping, as he toured Beijing on Monday after facing criticism for his relatively low profile.

Another angle: During an Ebola outbreak in 2014, Donald Trump, then a private citizen, called for measures like canceling flights and forcing quarantines. Public health experts are now concerned that a president who has spoken openly about his phobia of germs might overreact to the coronavirus crisis.

Perspective: In an opinion piece for The Times, an epidemiologist discusses what is known, and not known, about the virus.

What’s at stake in New Hampshire

Three precincts voted just after midnight in the state’s primaries, kicking off a day that could help narrow down a Democratic presidential field that has remained unchanged since last week’s troubled Iowa caucuses. Here’s what to expect.

Only 24 delegates are up for grabs today, but New Hampshire offers the potential for momentum going into the Nevada caucuses next week and the South Carolina primary on Feb. 29.

The details: Most polls close at 7 p.m. Eastern. We’ll have live results for the Democratic race and the Republican primary, which President Trump is expected to win handily.

Closer look: Senator Elizabeth Warren has largely avoided engaging her opponents, even as the Democratic contest has gotten fiercer. Before a primary that she had hoped to win (and probably won’t, according to polls), we examined the state of her campaign.

“The Daily”: Today’s episode discusses how the uncertain results from Iowa have affected the campaign in New Hampshire.

If you have 6 minutes, this is worth it

Rescuing a California community’s voice

At the beginning of the year, California’s oldest weekly, The Mountain Messenger, looked like it would become the latest American newspaper to go out of business and turn its rural hometown, Downieville, into a “news desert.”

In stepped Carl Butz, above, a 71-year-old retiree, who bought the paper to save what he said was “something we need in order to know ourselves.”

Here’s what else is happening

Indictment in Equifax hack: The Justice Department charged four members of China’s military with the 2017 breach at the credit reporting agency, which exposed the personal data of about 145 million Americans.

More brain injuries: The Defense Department has again raised the number of U.S. service members it says suffered traumatic brain injuries from Iranian airstrikes last month. Of the 109 troops with diagnosed injuries, 76 have returned to duty, officials said.

T-Mobile-Sprint merger: The judge in a lawsuit that tried to stop the wireless carriers’ deal plans to rule in favor of the merger, three people briefed on the matter told The Times. The verdict is expected today.

Surprise in Germany: Annegret Kramp-Karrenbauer, the chosen successor of Chancellor Angela Merkel, said she would step aside after party representatives in one German state defied her by voting with the far right. Her decision leaves the race to replace Ms. Merkel wide open.

Snapshot: Above, Dane Jackson, a 26-year-old national kayaking champion from Tennessee, who recently traveled over Salto del Maule, a 134-foot waterfall in central Chile. “It’s just one of the most photogenic waterfalls I’ve ever seen,” he said. “And it’s also quite tall.” Watch video from his descent.

Late-night comedy: “That’s right, ‘Parasite’ is the first non-English speaking film to win best picture, though some Arnold Schwarzenegger movies come close,” Jimmy Fallon said.

What we’re reading: “The 10,000-Year Clock Is a Waste of Time,” in Wired. Adam Pasick of the Briefings team writes: “The piece takes a look at the complicated device being built in Texas — mind-boggling not just because of its ambition, but as an emblem of the hubris of tech megabillionaires.”

Now, a break from the news

Listen: Sharon Van Etten’s new single, “Beaten Down,” is all deliberation and determination, our critic writes, hovering between dirge and homily. Here are other recent releases we recommend.

Smarter Living: Better coffee at home is within reach. These five cheap(ish) things might help.

And now for the Back Story on …

The New Hampshire primary

Members of our politics team have been in New Hampshire for weeks. We talked to one, Matt Stevens, about the mood there ahead of today’s events.

We just came off a messy run in Iowa. Are there fears that New Hampshire’s vote could also go awry?

Short answer: Yes, absolutely. There are many, many things that could go wrong. But as some of our colleagues have pointed out, New Hampshire has a history of running elections smoothly, whereas the Iowa caucuses have encountered problems in three consecutive cycles.

How are New Hampshire voters feeling about their primary system?

Perhaps because of those divergent histories, the voters I have talked to here have both expressed confidence in their system and given the side-eye to Iowa. Caucuses and primaries are very different, and the folks here are pretty darn sure their system is best.

Last week, as the mess was unfolding in Iowa, a woman in Hampton, N.H., told me: “This is a national level campaign. You have all these years to get it straight and this is the embarrassment you’re causing the party?”

How is your team managing back-to-back votes?

Some of us went to Iowa; most of the rest of us came to New Hampshire. And a handful did both. (Bless them!) The consensus among the people who have been to both places seems to be that the workroom at our hotel here in Manchester has windows, and is therefore far superior to the one in Des Moines, but the food options around our New Hampshire hotel are way more limited. I, personally, have already been to the Olive Garden next door twice.

A correction: Monday’s briefing misstated the amount of President Trump’s budget proposal, which was released on Monday. It is $4.8 trillion, not $4.8 billion. Thanks to those readers who spotted the mistake.

That’s it for this briefing. See you next time.

— Chris

Thank you Mark Josephson and Kathleen Massara provided the break from the news. Remy Tumin, who writes our Evening Briefing, wrote today’s Back Story. You can reach the team at briefing@nytimes.com.

P.S. • We’re listening to “The Daily.” Today’s episode is on the New Hampshire primary. • Here’s today’s Mini Crossword, and a clue: Partner of peanut butter (five letters). You can find all our puzzles here. • If you’re looking for a last-minute Valentine’s Day gift, The Times’s online store has a collection of items related to our Modern Love column.

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