Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 , Skipper et al., Annals of Internal Medicine, July 16, is fraud.

This a second paper based on the same clinical trial NCT04308668, Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP). David Boulware, MD, was the Chief Investigator. The trial split into two parts: post-exposure prophylaxis (misreported in Boulware et al., NEJM, June 3), and early treatment (misreported in the currently discussed Skipper et al). Boulware and Skipper are among the authors in both papers, so they are referred here as BS-1 and BS-2, respectively. Dr. David Boulware is one of the leading authorities on hydroxychloroquine in COVID-19; the White House medical team asked his advice on COVID-19 prophylaxis. Caleb P Skipper (the guy with no photo) seems to be the designated scapegoat. His name did not appear on scientific papers before 2019.

Publication of BS-2 repeated the same pattern as BS-1 – puff media pieces, exaggerating the paper claims, are published before the actual study. The MSM bizarrely celebrates the news that a promising drug is useless for treatment or prophylaxis of the pandemic disease (as it erroneously believes it). The scientific community needs some time to evaluate the paper. When they do that, it is too late. When criticism comes ins, the media moves on to another hoax.

Timeline

The timeline shows the same thing that other source: hydroxychloroquine was not controversial before “touted” by Trump, but rather universally accepted as one of the most  useful tools in COVID-19 treatment and prophylaxis. The study was privately funded, apparently with a bona fide intent to investigate its use for early treatment / post exposure prophylaxis. The following is the table of changes in the records on ClinicalTrials.gov

Version	A	B	Submitted Date	Changes
1			March 11, 2020	None (earliest Version on record)
2			March 17, 2020	Recruitment Status, Study Status, Contacts/Locations, Oversight and Study Identification
3			March 19, 2020	Contacts/Locations, Arms and Interventions and Study Status
4			March 24, 2020	Study Status, Contacts/Locations, Study Identification, Outcome Measures, Study Design, Conditions, Study Description, Eligibility and Arms and Interventions
5			March 25, 2020	Outcome Measures and Study Status
6			April 1, 2020	Contacts/Locations, Study Description, Study Status, Eligibility, Study Design and Sponsor/Collaborators
7			April 6, 2020	Study Description, Study Status and Study Identification
8			April 28, 2020	IPDSharing, Outcome Measures, Study Status, Contacts/Locations, Eligibility and Study Description
9			June 24, 2020	Recruitment Status, Study Status, Contacts/Locations, IPDSharing, Study Design, Documents, References and Eligibility
10			July 15, 2020	Study Status and Study Identification

March 11, 2020. The study is registered.

March 17, 2020. Some initial information, including a 274-word Description, is posted.

March 19, 2020. The number of treatment days is changed from 1+6 to 1+4. This is the date when Trump “touted” chloroquines. Dr. Boulware still maintains a positive attitude toward HCQ.

March 24, 2020. The title is changed from “Post-exposure Prophylaxis” to “Post-exposure Prophylaxis / Preemptive Therapy”. Methodology is slightly tweaked. Let us not nitpick – the trial has just started. The anticipated study completion date changed from May 2021 to May 12, 2020 – possibly a mistake correction.

On the same day, Dr. David Boulware is hired by Revive Therapeutics Ltd. (PNK: RVVTF; Toronto, Canada) as Scientific Advisor for Infectious Diseases including COVID-19. RVVTF has just entered the business of psychedelic mushrooms. It also has rights for an “orphan drug” Bucillamine, which it positioned as a competitor to HCQ in an early COVID-19 treatment for COVID-19.

Despite that, Dr. Boulware answered NO to the question about relevant financial conflicts of interest.

April 1, 2020. The trial methodology is significantly changed. This is wrong. Pre-registration of clinical trials exists to assure that the methodology was decided before the trial and was not changed, compromising statistical integrity of the results.

April 6, 2020. The methodology is changed again, apparently to make results less favorable to HCQ. The endpoint in the sub-trial corresponding to BS-2 was changed from “decreas[ing] hospitalizations” to “decreasing hospitalizations and symptom severity”. The composite endpoints like the latter one are usually avoided. Of note, the hospitalization rate in the HCQ group was 50% of the hospitalization rate in the untreated group. This was disclosed in the paper: “We do note that 8 COVID-19–related hospitalizations (including 1 death) occurred with placebo versus 4 COVID-19 hospitalizations (and 1 additional death; 5 events in total) with hydroxychloroquine.”

Despite all these changes and additions, the study description remains too short, and provides a lot of wiggle room for study conduct and interpretation.

April 23, 2020. “Revive Therapeutics Announces U.S. FDA Recommendation to Proceed Directly Into A Phase 3 Confirmatory Clinical Trial” with Bucillamine, according to RVVTF press-release

April 24, 2020. U.S. FDA issues a strong worded Drug Safety Communication about the use of HCQ for COVID-19 treatment, with an odd caveat that it “Does not affect FDA-approved uses for malaria, lupus, and rheumatoid arthritis”.

April 28, 2020. The trials methodology is changed again. A proper document describing the study on 20+ pages, excluding introduction and references, was uploaded only on April 24, eight days before the enrollment ended.

May 6, 2020. Enrollment into the trial ends.

May 30-31, 2020. An Indian study of using HCQ for COVID-19 prophylaxis in healthcare workers is published in the Indian Journal of Medical Research. It reports success of hydroxychloroquine prophylaxis against COVID-19 in 80% of cases. Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19

June 3, 2020. BS-1 is published. Despite all the efforts of the researchers, it shows effectiveness of HCQ against COVID-19. But the interviews of Dr. Boulware and the big tech media claim otherwise.

July 16, 2020. BS-2 is published. It is not clear why it took so long to publish it.

In total, the trial methodology was substantially changed at least six times over the two months of the study.

Results

The paper reported two-fold decrease in hospitalizations in the HCQ group. HCQ was administered with neither azithromycin nor zinc, but at higher than usual dose. Considering the high noise / low resolution of the trial design, this confirms effectiveness of HCQ in prophylaxis and early treatment of COVID-19.

The study reported adverse effects in some of the HCQ recipients. HCQ might cause minor side effects. In this case, it was exacerbated by the fact that the participants the larger than usual doses 1,400 mg on the first day, 600 mg daily after that (instead of 400 mg/day, sometimes with an extra 400 mg on the first day).

Remarks

On a positive side, Dr. Boulware co-signed the open letter to The Lancet calling out Mehra et al. fraud.

Work in Progress

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July 18, 2020 at 08:00PM

The map shows that in Canada 8839 deaths have been attributed to Covid19, meaning people who died having tested positive for SARS CV2 virus.  This number accumulated over a period of 148 days starting January 31. The daily death rate reached a peak of 177 on May 6, 2020, and is down to 11 as of yesterday.  More details on this below, but first the summary picture. (Note: 2019 is the latest demographic report)

	Canada Pop	Ann Deaths	Daily Deaths	Risk per Person
2019	37589262	330786	906	0.8800%
Covid 2020	37589262	8591	60	0.0235%

Over the epidemic months, the average Covid daily death rate amounted to 7% of the All Causes death rate. During this time a Canadian had an average risk of 1 in 5000 of dying with SARS CV2 versus a 1 in 114 chance of dying regardless of that infection. As shown later below the risk varied greatly with age, much lower for younger, healthier people.

The Key Covid Metric

With easing of lockdowns and increased testing in many places, epidemiologists are focusing on a key metric to inform public policies: Positivity. The positivity metric is the rate (%) of people who test positive out all tests performed. The significance is that (by definition) a presumed case is a person who tests positive once. If a second test comes back positive it is a confirmed case. The metric is not perfect for two reasons.

The first problem is false positives from the testing procedure itself or from errors in the data processing and reporting. For this we have to hope that quality assurance protocols are being followed and mistakes corrected along the way.

The larger issue appeared in Florida recently when officials discovered that numerous batches of samples were reported 100% positive and other batches 100% negative. While the latter result is expected sometimes, all people testing positive seems unlikely. Behind this is the reality that in many situations (eg hospital ICU) a single patient will be tested many times with many positive results in the course of monitoring that individual’s clearing of the virus. Obviously a batch of samples from that ICU might legitimately be 100% positive.

But it is also true that 10 or 20 positive tests from one patient should not be reported as 10 or 20 new cases. In some jurisdictions, officials say they go to the effort to link test results to the individuals tested, and can distinguish between number of cases and number of positives. In other places, cases and positives may be the same number. Thus confirmed cases could be only 1/2 of the total positives, or less.

How is Canada Doing?

Recoveries are calculated as cases minus deaths with a lag of 24 days. Daily cases and deaths are averages of the seven days ending on the stated date. Recoveries are # of cases from 24 days earlier minus # of daily deaths on the stated date. Since both testing and reports of Covid deaths were sketchy in the beginning, this graph begins with daily deaths as of April 24, 2020 compared to cases reported on March 31, 2020.

The line shows the Positivity metric for Canada starting at nearly 8% for new cases April 24, 2020.  That is, for the 7 day period ending April 24, there were a daily average of 21,772 tests and 1715 new cases reported. Since then the rate of new cases has dropped down, now holding steady at ~1% for the last month. Yesterday, the daily average number of tests was 42,191 with 363 new cases. So despite double the testing, the positivity rate is not climbing.

Another view of the data is shown below.

The scale of testing has increased and is now exceeding 40,000 a day, while positive tests (cases) dwindled to 1%.  The shape of the recovery curve resembles the case curve lagged by 24 days, since death rates are a small portion of cases.  The recovery rate has grown from 83% to 97% steady over the last 3 weeks. This approximation surely understates the number of those infected with SAR CV2 who are healthy afterwards, since antibody studies show infection rates multiples higher than confirmed positive tests. In absolute terms, cases are now down to 320 a day and deaths 20 a day, while estimates of recoveries are 804 a day.

Note: We are expecting an initial report from the National Immunity Task Force any day now regarding a major program of testing random blood samples for SARS CV2 anti-bodies.

Background Updated from Previous Post

In reporting on Covid19 pandemic, governments have provided information intended to frighten the public into compliance with orders constraining freedom of movement and activity. For example, the above map of the Canadian experience is all cumulative, and the curve will continue upward as long as cases can be found and deaths attributed.  As shown below, we can work around this myopia by calculating the daily differentials, and then averaging newly reported cases and deaths by seven days to smooth out lumps in the data processing by institutions.

A second major deficiency is lack of reporting of recoveries, including people infected and not requiring hospitalization or, in many cases, without professional diagnosis or treatment. The only recoveries presently to be found are limited statistics on patients released from hospital. The only way to get at the scale of recoveries is to subtract deaths from cases, considering survivors to be in recovery or cured. Comparing such numbers involves the delay between infection, symptoms and death. Herein lies another issue of terminology: a positive test for the SARS CV2 virus is reported as a case of the disease COVID19. In fact, an unknown number of people have been infected without symptoms, and many with very mild discomfort.

 

This discussion takes the assumption that anyone reported as dying from COVD19 tested positive for the virus at some point prior. A recent article by Nic Lewis at Climate Etc. referred to evidence that the average time from infection to symptoms is 5.1 days, and from symptoms to death 18.8 days. A separate issue, of course, is that 95+% of those dying had one or more co-morbidities contributing to the patient’s demise. Setting aside the issue of dying with/from Covid19, it is reasonable to assume that 24 days after testing positive for the virus, survivors can be considered recoveries.

Previous Post May 20, 2020

It is really quite difficult to find cases and deaths broken down by age groups.  For Canadian national statistics, I resorted to a report from Ontario to get the age distributions, since that province provides 69% of the cases outside of Quebec and 87% of the deaths.  Applying those proportions across Canada results in this table. For Canada as a whole nation:

Age	Risk of Test +	Risk of Death	Population per 1 CV death
<20	0.05%	None	NA
20-39	0.20%	0.000%	431817
40-59	0.25%	0.002%	42273
60-79	0.20%	0.020%	4984
80+	0.76%	0.251%	398

In the worst case, if you are a Canadian aged more than 80 years, you have a 1 in 400 chance of dying from Covid19.  If you are 60 to 80 years old, your odds are 1 in 5000.  Younger than that, it’s only slightly higher than winning (or in this case, losing the lottery).

As noted above Quebec provides the bulk of cases and deaths in Canada, and also reports age distribution more precisely,  The numbers in the table below show risks for Quebecers.

Age	Risk of Test +	Risk of Death	Population per 1 CV death
0-9 yrs	0.13%	0	NA
10-19 yrs	0.21%	0	NA
20-29 yrs	0.50%	0.000%	289,647
30-39	0.51%	0.001%	152,009
40-49 years	0.63%	0.001%	73,342
50-59 years	0.53%	0.005%	21,087
60-69 years	0.37%	0.021%	4,778
70-79 years	0.52%	0.094%	1,069
80-89	1.78%	0.469%	213
90  +	5.19%	1.608%	62

While some of the risk factors are higher in the viral hotspot of Quebec, it is still the case that under 80 years of age, your chances of dying from Covid 19 are better than 1 in 1000, and much better the younger you are.

 

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July 18, 2020 at 03:28PM

By Paul Homewood

 

Slow Joe has now totally capitulated to the loony left agenda!

 

 

Joe Biden, the presumptive Democratic presidential candidate, laid out an ambitious climate plan for America Tuesday which includes overhauling the country’s energy industry to achieve 100 per cent emissions-free power by 2035.

The plan includes a pledge to invest $2 trillion in clean-energy infrastructure if Mr Biden wins the White House in November, along with a promise to build 1.5 million new energy-efficient homes and social housing units.

The expansive climate policy is a nod to the progressive wing of the Democratic Party, which has been largely unenthusiastic about Mr Biden’s campaign and demanded far more radical approaches to issues such as climate change, immigration and health care..

https://www.telegraph.co.uk/news/2020/07/14/joe-biden-unveils-ambitious-climate-policy-promising-100pc-clean/

 

As a rule of thumb, I reckon on the US economy being about ten times the size of Britain’s, so £2 trillion over four years equates to roughly £40bn a year here. (The NY Times explain that the $2 trillion is to be spent in the next four years).

At least Biden is being honest about the cost, which is more than can be said about our politicians. His full plan can be read here. It is heavily slanted towards the creation of green jobs, rather than saving the planet, which I suspect would not have gone down well with middle America. There are numerous references to “good, unionised jobs”, much as Corbyn’s climate plan had.

Biden even brags about the “five million green jobs”, which he and Obama promised in 2008. I wonder what happened to them!

 

The main pillars of his plan are:

1) Power Sector

Move ambitiously to generate clean, American-made electricity to achieve a carbon pollution-free power sector by 2035.

Good luck with that.

BP Energy Review

Last year renewables only supplied 11% of US electricity. With no plans to expand nuclear energy, Biden’s plan relies on building thousands of solar and wind farms, but is silent about how the grid can function with such an intermittent supply.

There’s the usual pipedreams about battery storage, carbon capture and green hydrogen at the same cost as conventional hydrogen within a decade.

2) Energy efficiency

Upgrade 4 million buildings and weatherize 2 million homes over 4 years, creating at least 1 million good-paying jobs with a choice to join a union; and also spur the building retrofit and efficient-appliance manufacturing supply chain by funding direct cash rebates and low-cost financing to upgrade and electrify home appliances and install more efficient windows, which will cut residential energy bills.

1 million jobs would cost in the region of £100bn a year, way above any energy savings, as we have seen in the UK. Which all brings us back to who will pay the bill.

 

3) Auto industry

Create 1 million new jobs in the American auto industry, domestic auto supply chains, and auto infrastructure, from parts to materials to electric vehicle charging stations,

There we are – another million jobs! Never knew it was that easy to create jobs.

There is no mention of the enormous costs the auto industry will face in developing new electric cars, only the promise of subsidies for buyers. As we know here, these have had very little effect.

He will also commit to purchase clean vehicles for federal, state, tribal, postal, and local fleets, regardless of the extra costs this may incur for taxpayers.

There will also need to be major public investments in 500,000 electric vehicle charging stations .

There is also the threat of ambitious fuel economy standards, which will accelerate the adoption of zero-emissions light- and medium duty vehicles. Forget about your SUVs then, America!

4) Public transport

Provide every American city with 100,000 or more residents with high-quality, zero-emissions public transportation options through flexible federal investments with strong labor protections that create good, union jobs and meet the needs of these cities – ranging from light rail networks to improving existing transit and bus lines to installing infrastructure for pedestrians and bicyclists.

And at what cost?

Most cities already have well established bus and rail systems. Will Biden waste billions converting these to low carbon?

 

5) Agriculture

Create jobs in climate-smart agriculture, resilience, and conservation, including 250,000 jobs plugging abandoned oil and natural gas wells and reclaiming abandoned coal, hardrock, and uranium mines

I have not a clue what climate smart farming is. Nor what capping abandoned wells has to do with anything.

But heh, it has magically created another 250,000 jobs! At this rate we will all have two jobs each.

 

As with the dotty net zero plans being proposed at home, Biden conveniently sidesteps the question of who will pay for all of this green drivel. Forget about all of the nonsense about green jobs. It has been proven beyond doubt that, for every green job created, something like three jobs elsewhere in the economy are destroyed.

What Biden forgets to tell the public is that his proposals will inevitably wipe out millions of jobs in productive areas of the economy, such as the oil and gas related sector, and more indirectly all of the sectors which will suffer from higher taxation and energy prices.

And most of the public will be far worse off as a result.

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July 18, 2020 at 02:54PM

The report states: ‘It is thought the tsunami, the largest to hit Northern Europe since the end of the last ice age, happened following a period of global climate change.’
We can only speculate as to the cause(s) of such climate happenings.
– – –
Scientists have found new evidence of a massive tsunami that devastated ancient Britain in the year 6200 BC on the east coast of England, reports the Daily Mail.

The giant tsunami event, known as the Storegga Slide, was caused when an area of seabed the size of Scotland – around 30,000 square miles – under the Norwegian Sea suddenly shifted.

New geological evidence reveals three successive waves tore across an ancient land bridge connecting Britain with the rest of Europe, known as Doggerland, now submerged beneath the North Sea.

The waves of biblical proportions would have caused devastating damage and had a catastrophic effect on human populations on the inhabited land.

Evidence of the event had already been found in Scandinavia, the Faroe Islands, northeast Britain, and Greenland, but no direct evidence for the event had been recovered from the southern end of the North Sea until now.

Underwater deposits including stones and broken shells taken from the North Sea, in an area south of a marine trough named the Outer Dowsing Deep just off the coast of Lincolnshire, show trademarks of the tsunami event.

Continued here.

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July 18, 2020 at 01:57PM