triplehorn

The VA study also involved initiating treatment after the onset of complicated illness requiring hospitalization - just like the bunk Lancet study and the UK study referenced in the Gottlieb tweet above. Initiating treatment after hospitalization is required is too late to do any good. I think the world all agrees with that. There are four phases to examine - pre-exposure prophylaxis, post-exposure prophylaxis, early post-infection treatment, and late-infection (rescue) treatment. Today there are glaring research gaps in 2 out of the 4 groups with major implications for HCQ use: 1) pre-exposure prophylaxis 2) as early as possible intervention with onset of detectable illness or positive test to possibly mitigate or prevent progression to hospitalization and/or death. The initial positive signal from the study by the Indian Council of Medical Research (ICMR) for pre-exposure prophylaxis, means this must get followed up. It's not like we're going to dose our entire population prophylactically, but this could be extremely beneficial to health care workers, those who live or work at long term care facilities, and anyone regularly exposed to a lot of people in a relatively enclosed space (ie food processing). The early intervention approach is also a no brainer given the highly favorable safety index for HCQ in uncomplicated cases, ie just like the circumstances in 1) and 2) above. But even if early intervention works, the pitfall for that strategy in the US is lack of coordinated mass screening and access to outpatient health care. And really, this entire situation that we Americans uniquely find ourselves in relative to the rest of the world is rooted in the abject failure of anticipation, coordination, and leadership at the federal level starting at the top with an ignorant, self dealing, destructive despot for a president. There are longer term issue we face as a nation re access to care, but it did not have to be this way. We did not have to lose 110,000 Americans in the first 3 months of this fight.

Basically the study using fraudulent data published by Lancet said that patients hospitalized with Cov19 (advanced illness) who received HCQ had a higher incidence of death. Apart from that, to my knowledge Anastasis hasn't shown any awareness of or made any distinctions between pre-exposure vs post-exposure prophylaxis, and hasn't pointed out that early intervention/progression of illness studies are lacking in the US, but has splashed around with the general HCQ scaremongering.

I read the ICMR abstract and linked this article on another thread that elaborates the design specifics and positive findings including describing the observed dose dependent pre-exposure prophylactic effect of HCQ with once weekly dosing, most notable after 4-6 weeks of dosing. The Boulware study in NEJM looks at post-exposure prophylactic effect with HCQ given for several consecutive days within 4 days of suspected exposure. That's a very significant difference in designs with respect to intervention against the virus. ----> You may have seen tv commercials for HIV prophylaxis medication. Does a person take that type of medication as pre-exposure maintenance or post-exposure prophylaxis. What happens if the initial dose is later than 48hrs after exposure? Does it still have a prophylactic effect to HIV, or only if you had been taking it prior to exposure. Different mechanism relative to COV19 and HCQ, but same critical considerations in timing. Also re the NEJM on the Boulware study, this is a weakness: "Adherence to the interventions [taking HCQ] could not be monitored, and participants reported less-than-perfect adherence, more notably in the group receiving hydroxychloroquine." Nothing in that that we haven't known already for over two months. That study involves initiating treatment with hospitalized patients (advanced complicated illness). We know HCQ is ineffective if started late. Apart from a replication/elaboration of the ICMR positive findings in the prophylaxis study, what we need is a study that tracks the course/progression of illness in patients who receive early intervention with HCQ. Are they less likely to end up in the ICU, or dead from Cov19? We don't have that done yet in a US study, and yet this is what the medical communities in multiple other nations have dialed in.

I haven't dug into this but one question is does this mean that all other Surgisphere data is bunk? Is this Lancet/NEJM debacle a Surgisphere one-off data event? If not, how many other published studies across various fields of medicine have used Surgisphere data? Is some Surgisphere data valid while other is bunk? Does Surgisphere know which of their data is valid and which is bunk? I don't believe the authors of the debunked study disclosed any present of past conflicts of interest with big pharma that have direct dogs in the hunt: Maybe @Anastasis can clarify if Mandeep Mehra and Frank Ruschitzka in fact don't have any present or past associations with Gilead to disclose, or Patel with Merck. If anyone ever wondered why such disclosures are made before presentations and publications, this would be an example of why. Maybe those author associations are twitter fabrications. I really don't know.

I'm not seeing why that should or would involve fraudulent data. Data is data, right? If data that says one thing over another brings in bigger license fees, then suddenly there's an incentive thrown into the mix. I can still see it both ways, but I am extremely leery of the reach of big pharma when it comes to turning a profit.

The relevant parties understand this stuff inside and out. They know what is legit and what isn't. What (or who) would motivate a company to produce fraudulent data? What does a company or person stand to get in return?

Turns all year 🤘 Opting for extreme social distancing, I summited Mt Hood yesterday. A climbing buddy and I skinned up from elevation 6k ft to 10k ft, then ditched skis and packs, put crampons on the ski boots and climbed another 1000ft to the top. ~7hrs round trip, only 45 min of which was skiing off the volcano. VVV Looking up with 1000 feet to go, you can see two climbers on the snow coming down from the summit center left up high VVV Reverse four point crawl down that ice chute off the summit. Would have felt a lot safer with ropes. The holds were solid but I won't be tempting the odds like that again any time soon, if ever if I can avoid it. There's no way around the final technical section below the summit. Most people don't rope up. The prevailing conditions determine the risk. We were fortunate to safely get up and down. re above, the view down from that point VVV Last ones off the mountain (climbing bud)

The first most obvious explanation is to follow the money. In this case via big pharma. If the authors of the fake study published by Lancet were acting to serve the interest of big pharma, the intent would be to bury generic HCQ as a safe low cost potentially effective treatment and put in its place a high cost alternative whether effective or not. In this case all eyes are on Gilead and Remdesivir. When you have less than a handful of pharmacologic options, none of which have been able to be subjected to thorough clinical trials for Cov19 amidst a deadly rapid onset pandemic, those few options will be applied in an all out effort to do something to prevent severe illness and death. So if a competitive option can get eliminated due to acute safety concerns when used with Cov19, even an unproven but "safe" alternative will become the default option. It looks like that is likely what is going on here. Even if Remdesivir doesn't really offer much clinical benefit to justify the cost, states and hospitals will go with that if there is nothing else, and Gilead wins out over an inexpensive generic alternative to reap large profits. Think of the implications if it turns out that aggressive early application of HCQ with or without combining it with other agents reduces the likelihood of illness severity progressing to ICU level of care or death. We still don't have US study results that examine that question. But that is exactly what other countries are reporting works well enough to justify continuing.

And Lancet's reputation just took one right on the nose. Would be interesting to see if any of the authors of the sham study have any associations with pharma company Gilead (and its attempt to repurpose Remdesivir). Any bets? It's stunning how lacking we are in initial studies to delineate potential applications of HCQ while many countries around the world have refined their approaches to such a degree that they immediately blew off the WHO's call for suspending use of HCQ based off the Lancet study. India's ICMR has a study suggesting prophylaxis may work best after several weeks of once weekly dosing. Meanwhile we have a UMinny prophylaxis study with a consecutive multi-day regimen more associated with mitigating symptoms or speeding recovery once infected. Unfortunately UMinny didn't do what we also need to assess - measure symptom progression or mitigation of early confirmed Cov19 positives with HCQ vs placebo. And even though the findings are potentially very informative, in the UMinny study, 83% of subjects didn't even get an actual test to confirm infection with Cov19. Meanwhile other nations using HCQ early with a consecutive multi-day regimen (in combination with other things) after exposure or initial infection appear to be demonstrating favorable recovery rates. As far as I know, we still don't have a basic US study on early use of HCQ in mitigating symptom severity or reducing rate of progression to complicated illness and/or death. How would you feel if it came to be known that big pharma had a direct hand in mucking up initial perception and understanding about application of a safe, cheap, generic competitor (maybe $20 per patient) in order to boost sales of their own failed ebola drug at $4400 per patient?

Stay on topic, please. Just some honest clear responses to carry on is all I’ve ever asked. Not holding my breath lol.

Another non-response response. The new study as reported by WaPo got posted. There are some relevant things to consider. Namely, evidently that 83% of "positive infection outcomes" were determined without lab confirmation. yeesh. Walk me back. The main thing that remains pretty clear is that, through various studies and in reports coming out of multiple countries, HCQ does not appear to represent a heightened imminent or direct safety threat in Cov19, and individual medical consideration basically eliminates it. You scaremongered about it way back. I think the safety notion has been shed. Taking this rapid post-exposure study at face value, the ICMR prophylaxis study, and studies of HCQ in hospitalized subjects with advanced illness, it looks like very early post-exposure and late post-exposure uses are not a hit. To repeat - are not a hit. It could be that true prophylaxis is where the lone benefit vs Cov19 rests. The ICMR study needs replication. The ICMR study design is substantively different in that the study followed subjects at least 3 times as long as this UMinn study, ICMR used actual testing for all subjects for confirmation before and after, and ICMR study used pre-medication for weeks after first confirming with a negative test. A greater separation in prophylactic benefit was observed beginning after 4 weeks of once weekly dosing of HCQ. The presence of a dose response curve spanning weeks warrants further understanding. Nothing crazy about wondering about that. And if the ICMR results hold that true prophylaxis can reduce infection formation by up to 80% in frontline health care workers under frequent exposure, that would be good to know. 400mg HCQ once per week has been dosed 10's of millions of times since around 1955. 'bout $0.60 per dose.

Your’re responding to me but not responding. From above: “The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.“ It appears only 17% percent of subject outcome measures were laboratory-confirmed. 83% of determinations of infection were made without testing confirmation. Is that what you’re seeing? Not what I’d expect, if accurate, examining a bug that has a high incidence of asymptomatic positivity. They indicate limited access to testing evidently.

Looks like only 17% of subjects had a lab confirmed result for being infected or not. Is that what you’re seeing? Not sure what to make of that if it’s the case.

Thanks. This new study had a different design than the ICMR study I posted on the DT medical discussion thread. I’d like to see more details but the WaPo says about this one: ”About two-thirds of the trial participants were health-care workers and the rest were a mix of other people exposed to someone with covid-19, he said. They were given hydroxychloroquine or a placebo for five days and then followed for two weeks to see who developed the disease.” The ICMR study gave a loading dose then HCQ 400mg once weekly for about 6 weeks. In particular, they observed a positive dose response curve preventing development of infection become notably more apparent after 4 weeks. @Captainant - I’d like to hear your thoughts on how differences in study design might hit on different cellular processes and timelines. Also this about the Minny study: “One weakness of the trial, he added, is that because testing was not widely available during the time of the trial, their analysis used a combination of lab-confirmed positive covid-19 tests and symptoms to count someone as infected.” I’d like to know more about the presumed exposure/dosing lag relationship in this new study. It’s a helpful study, but need more.

and stopped leaning against the wall during hospital rounds.

Bill Barr is the signal TrumpCo are going all the way in. They will go until they are forcefully stopped, and I'm not seeing who does that. We The People could do it in one extreme sense, and the Trump/Barr positioning is happening to control and neutralize it by force.

Bill fucking Barr prominently positioned in that disgraceful stage act.

Dangerous is him as the projectile in their military grade Water Winger.

ready made Schutzstaffel member right there.

"Yes, above ground. You're the bunker."

The power is in the non-violence

Here's an article about the ICMR's positive findings for HCQ prophylaxis: 80% reduction in odds of HCW's developing Covid infection. 4 or more hydroxychloroquine doses reduced risk of coronavirus in healthcare workers: ICMR study "The ICMR study indicates that "simply initiating HCQ prophylaxis did not reduce the odds of acquiring Covid-19 infection among HCWs. However, with the intake of four or more maintenance doses of HCQ, the protective effect started emerging. A significant reduction of about 80 per cent in the odds of Covid-19 infection in the HCWs was identified with the intake of six or more doses of HCQ prophylaxis. This dose-response relationship added strength to the study outcomes." "Biologically, it appears plausible that HCQ prophylaxis, before the onset of infection, may inhibit the virus from gaining a foothold," researchers said in the study. The National Task Force for coronavirus in India recommended once a week maintenance dose for seven weeks i.e., 400 mg once every week, following the loading dose of 400 mg. Adherence to this recommended regimen is underlined by the findings of the study, researchers said. [...]" Need more studies, but damn.

"Longing, rusted, furnace, daybreak, seventeen, benign, nine, homecoming, one, freight car."

Pre-print article on findings in India using HCQ only as prophylaxis to prevent Covid-19 infection (no Azithromycin): Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19 Date of Submission28-May-2020 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ijmr.IJMR_2234_20 Abstract Background & objectives: Healthcare workers (HCWs) are at an elevated risk of contracting COVID-19. While intense occupational exposure associated with aerosol-generating procedures underlines the necessity of using personal protective equipment (PPE) by HCWs, high-transmission efficiency of the causative agent [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] could also lead to infections beyond such settings. Hydroxychloroquine (HCQ), a repurposed antimalarial drug, was empirically recommended as prophylaxis by the National COVID-19 Task Force in India to cover such added risk. Against this background, the current investigation was carried out to identify the factors associated with SARS-CoV-2 infection among HCWs in the country. Methods: A case-control design was adopted and participants were randomly drawn from the countrywide COVID-19 testing data portal maintained by the ICMR. The test results and contact details of HCWs, diagnosed as positive (cases) or negative (controls) for SARS-CoV-2 using real-time reverse transcription-polymerase chain reaction (qRT-PCR), were available from this database. A 20-item brief-questionnaire elicited information on place of work, procedures conducted and use of PPE. Results: Compared to controls, cases were slightly older (34.7 vs. 33.5 yr) and had more males (58 vs. 50%). In multivariate analyses, HCWs performing endotracheal intubation had higher odds of being SARS-CoV-2 infected [adjusted odds ratio (AOR): 4.33, 95% confidence interval (CI): 1.16-16.07]. Consumption of four or more maintenance doses of HCQ was associated with a significant decline in the odds of getting infected (AOR: 0.44; 95% CI: 0.22-0.88); a dose-response relationship existed between frequency of exposure to HCQ and such reductions (χ2 for trend=48.88; P<0.001). In addition, the use of PPE was independently associated with the reduction in odds of getting infected with SARS-CoV-2. Interpretations & conclusions: Until results of clinical trials for HCQ prophylaxis become available, this study provides actionable information for policymakers to protect HCWs at the forefront of COVID-19 response. The public health message of sustained intake of HCQ prophylaxis as well as appropriate PPE use need to be considered in conjunction with risk homoeostasis operating at individual levels. ---> I didn't download the .pdf of the full text, but evidently there was a loading dose followed by HCQ 400mg once per week.