Friday, May 14, 2021

Mixing COVID-19 Vaccines (Heterologous Prime-Boost) - The Data So Far.

InterimReportsAre
JustThatVille


Given the ramped-up shipments of mRNA vaccines (i.e. Pfizer/BNT, Moderna) coming to British Columbia and the increased concern about significant, but still rare, clotting events after adenoviral vaccination (i.e. AstraZeneca, Johnson & Johnson), you may have pricked up your ears when you heard or read the following earlier this week:

British Columbians who received the AstraZeneca-Oxford COVID-19 vaccine as their first dose will likely be able to choose whether they want their second vial filled with the same vaccine, the province's top doctor has said.

Provincial Health Officer Dr. Bonnie Henry says as shipments of the Pfizer-BioNTech and Moderna vaccines increase, switching up the type of shot for the second dose is a possibility, as long as it is proven to be safe and effective.

"I expect people will have a choice," she told Stephen Quinn, host of CBC's The Early Edition, on Tuesday morning.

Henry said she is closely watching research being done now in the United Kingdom, where about 60 per cent of people were given AstraZeneca for their first shot. Researchers at Oxford University launched a study in early February to explore the possible benefits of alternating different COVID-19 vaccines...


It turns out that the group at Oxford (and Nottingham) that Dr. Henry referenced has now released preliminary data on the mixed vaccine regime, which they fancy up with the term 'Heterologous Prime-Boost'. This has led to a number of headlines like this...

Mixing COVID-19 vaccine doses leads to more reactions, study finds, which may be 'first sign of success'.


So.

With that in mind, what does this group have to say, based on a letter they published in the Lancet Wednesday?

First, all they have released so far are data which looks at how folks who received either the AZ  'ChAd' adenoviral or the Pfizer 'BNT' mRNA vaccines first (i.e. the 'prime') and then received either the AZ or the Pfizer later (i.e. the 'boost') self-reported their symptoms.

Second, they have only released data from folks who they received their 2nd 'boost' shot 28 days after their first dose. Here are the data of what those folks self-reported over the next 7 days: 



As you can see,  there are, indeed, increases in in reports for a number of indications (see 'Feverish' for example) after the mixing of the prime and boost (i.e. the second and fourth bar on each graph). However, most of this was self-reported as mild to moderate and there were no hospitalizations. The other thing, not noted in news reports, is that, generally, whenever anyone got the Pfizer/BNT vaccine, either once or twice (i.e. bars two through four on each graph), there were generally more events/symptoms reported.

Regardless, the kicker, according to the authors of the Lancet letter, is the following:

"(I)t is reassuring that all reactogenicity symptoms were short lived, and there were no concerns from the limited haematology and biochemistry data available..."


It is also important to note what was not (yet) reported in this letter - there was no report of these symptoms when the prime and boost were separated by 84 days (i.e. 12 weeks), as was done for most folks in the UK (and is closer to the Canadian/British Columbian paradigm, so far, of 16 weeks).

In addition, so far there have been no data reported on whether the vaccine mixture has positive effects on efficacy re: protection against infection and/or illness from the SARS-CoV-2 virus itself.

All of those data are supposed to be coming June which will be good timing around here as second dose times begin to roll in.


.

Monday, May 10, 2021

Pushing Olympic Tin...First Came The Flack, Then Came The Hackery.

PushMePollMe
RingADingALingMeVille


As noted previously, Vancouver 2010's man about town popped up out of nowhere the week before last and got the local media wurlitzer cranking with this:

...A 2030 Winter Olympic and Paralympic Games that encompasses more of B.C. than the Lower Mainland and a ski resort town will be part of John Furlong's pitch to the Vancouver Board of Trade on Friday...

{snip}

..."B.C. is not small. This is Germany, France and England combined. It's a very big area," Furlong said...


****

And then, on Friday last the wurlitzer shifted to overdrive when the following fuel was tossed into its boiler:

Vancouver, BC — Following a Vancouver Board of Trade event where John Furlong presented the merits of an Olympic bid for the 2030 games, a new Insights West poll shows that public support for this initiative sits at a healthy 55%...


You think that's something?

Well, just wait for the push:

...that level of support increases dramatically to 77% if the games could be held without requiring any public money...


Gosh.

Legacies Now!...Forever and ever, for free, indeed.

What's next, Senator Da Vinci scream-riding down a hastily constructed half-pipe as the set-up to a spectacular big-media splashdown in False Creek in front of the OVillage next weekend?



______
No word
 in either the Insights West press release thingy or the Vancouver Sun (non) story that 'reported' on the release who, if anyone, commissioned the poll...Interestingly, however, both mention the Vancouver Board of Trade prominently.



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Sunday, May 09, 2021

The Whackadoodle II.


AllHisDad'sMadchens
'RUsVille


We had to put the Whackadoodle down just as the pandemic began late last March.

Her real name was Rosie and she had a congenital heart defect that gradually got worse with time. In the end she couldn't make it up back stairs after she'd been out for one of her frequent pees underneath the hydrangea that grows up against the garage.

A spaniel-poodle cross, I was skeptical when Rosie first arrived at our house given that she was both little and excitable. However, she had such an agreeable disposition and was so up for anything that I really grew to love her over the years, never so much as when we took our weekly walks on the beach with the guitar. In fact, she didn't once complain about the 'music' - even when it involved warbled mash-ups of  of stuff like Martha Wainwright's BMFAHole and Van the Man's Astral Weeks.

For the past year or so the guitar and I have been taking those beach walks all on our own. Unlike when I was with the Whackadoodle, many passerby clearly find it a little strange to come upon a man in his early sixties, strings in hand. Still, I always slow down part way to pat the tangled skeleton of a washed up arbutus tree that somehow reminds me of Rosie. Then I head for the halfway point where we used to stop for treats, most often apple fritter bits from the Breka on Fraser near 49th avenue, followed by a little bit of leisurely newspaper reading and a whole lot of stick throwing/chasing at the water's edge before we packed up, headed back and started in on the mash-ups.

****

Now that the kids have moved out, pretty much for good I think, it wasn't immediately clear that we would get another dog.

Then, early in the New Year, C. started talking about it.

And in mid-March an eight week-old Whackadoodle II arrived.

Same breed, different colour, and now that her shots are all done she's ready for the beach, which is where we went early yesterday morning.

It took quite a while, but after a whole lot of stick soccer and rapid-fire sand digging we finally made it out to the treat spot - all healthy bits this time around though - promise.

I'm not really sure yet if Tilly/W-II likes the music. Hopefully, at the very least, she will learn to tolerate it.

Selah.


_______
Subheader courtesy David Sedaris who tells the story of his family's many pet lineages, including the great danes Madchen I and Madchen II,  in both audio and linear type form.
Our entire family went to see Springsteen when he brought Clarence and  the Circus to town in the spring of 2008...I'd like to think that that show had something to do with littler e.'s suggestion that we name the original Whackadoodle Rosalita when she arrived later that summer.


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Friday, May 07, 2021

The 'Foxitis' Defense.

AllTheirCodswallop'R
UsVille


You knew it had to be coming.

And now it has arrived...

The lawyer for one of the folks involved in the attack on the US Capitol on January 6th has said that a specific media organ made him due it.

Luke O'Neil of the Guardian has the story. Here is his lede:

The lawyer for a Delaware man charged over the Capitol attack in January is floating a unique defense: Fox News made him do it.

Anthony Antonio, who is facing five charges including violent entry, disorderly conduct and impeding law enforcement during civil disorder, fell prey to the persistent lies about the so-called “stolen election” being spread daily by Donald Trump and the rightwing network that served him, his attorney Joseph Hurley said during a video hearing on Thursday.

Antonio spent the six months before the riots mainlining Fox News while unemployed, Hurley said, likening the side effects of such a steady diet of misinformation to a mental health syndrome.

“Fox television played constantly,” he said. “He became hooked with what I call ‘Foxitis’ or ‘Foxmania’, and became interested in the political aspect and started believing what was being fed to him.”...


****

Now.

You know that the late night shows and the Bill Maher-types will have a field day with this.

However, I honestly think that there is merit to this position and the susceptibility to being swayed to extremism by demonstrably false codswallop that is both peddled and not immediately discredited as such.

And, further, as long as the fine folks doing the peddling do not pay a political and professional price for doing so we will never be rid of it.




______
And do not for one second think that we do not have our own Canuckistian variants of concern.

.

Wednesday, May 05, 2021

The Keef Report: Getting It Right For Once.

Keefin'It
1600Ville


Remember when the Keef said this:



****

Well, it looks like stopped watches and all that...

Banned by Facebook and Twitter, Donald Trump has gone back to the future with an online communication tool that might be described as a glorified blog.

His retro webpage, billed “From the Desk of Donald J Trump”, appears at DonaldJTrump.com/desk and features a small photo of the 45th president writing in a book on his desk...



Oh the humanity!

(not to mention, presumably, the fever swamps to come in the comment threads)


______
Previous Keef Report can be found...Here.


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Inconsistencies? We Don't Need No Stinking Inconsistencies!

SometimesAHockeyBag
IsJustAHockeyBagVille



A few days ago we pointed out just one that was then, this is nowish - type inconsistency in Rich Coleman's testimony before the Cullen Commission inquiry on money laundering. 

Well...

It turns out that the Commission itself has also noted inconsistencies.

As a result, they want Mr. Coleman to come back. Here is the lede of a report from the CBC's Rhianna Schmunk:

A formal inquiry into the issue of money laundering in B.C. is calling a former cabinet minister back to the stand to testify for a second time over inconsistencies in his first round of sworn testimony.

Rich Coleman, a six-term former Liberal member of the B.C. Legislature, will have to testify before the Cullen Commission again on May 14, sources confirmed Wednesday...


Gosh.

One can only only wonder if the good Mr. Coleman is still 'looking forward' to appearing before the Commission?


_______
Belle Puri's excellent CBC story last week appears to have been the lit match that got the Bonfire of the Inconsistencies blazing.
As she often does, Sandy Garossino gets to the heart of the matter on the Twittmachine.
And while we're on the subject of then vs. nowish - type inconconsistencies, perhaps the Commission could slip in a few questions about selective tree farm license release-type deals in there somewhere...Or some such thing.



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Friday, April 30, 2021

What Was Done 'Differently' After IGET Was Dismantled?

GordCoInc'sLimitedCasinoHangout
RevisitedVille


Former BC Liberal Government Minister of Gaming Rich Coleman testified at the Cullen inquiry on Wednesday.

From Sam Cooper's Global News report:

...The inquiry has previously heard testimony from a number of witnesses that said Coleman was alerted many times by his subordinates, police officers and even fellow B.C. Liberal MLAs, that money laundering was growing in B.C. Lottery Corporation casinos as organized crime took control of these venues.

But instead of seeking police investigations inside casinos, according to the testimony of former RCMP officer Fred Pinnock, Coleman disbanded the province’s anti-illegal gaming unit in 2009. The inquiry previously heard from Pinnock, the unit’s former commander, that former B.C. Liberal solicitor-general Kash Heed blamed Coleman for turning a blind eye and it was “all about the money.”...

{snip}

...On Wednesday, Cullen Commission lawyer Brock Martland asked Coleman to respond to the allegations...

Coleman said “it’s just ridiculous” that he turned a blind eye to money laundering to boost provincial revenue...


****

Ridiculous, indeed.

But what did the good Mr. Coleman specifically tell the Cullen Inquiry this week, in April of 2021, about why he dismantled the 'Illegal Gambling Enforcement Team' (IGET) back in 2009?

For that we return to Sam Cooper's report:

...Coleman acknowledged that he was responsible for disbanding the B.C. anti-illegal gaming unit, but he said he believed the unit was ineffective, and he expected other anti-gang police units in B.C. to target organized crime....

****

But what about back in the day? What did Mr. Coleman say his plan was then?

Well, to understand that, now is the time for us to once again re-visit an interview that Sean Holman held with the good Mr. Coleman in 2010:



The key, with respect to Mr. Coleman's stated plan to replace IGET is, in my opinion, the following from the 2010 interview, above:

"I had a team (IGET) that wasn't working (i.e. in 2009) and it was costing the taxpayers money. I decided to do it differently and get better results."

****

Well, I guess now we finally know precisely what Mr. Coleman meant about doing something 'differently' to fill the void after he dismantled the unit whose actual job it was to keep tabs on things like money laundering in casinos.

Because, according to his testimony this week, Mr. Coleman did not do things differently by forming a new unit to replace IGET.

And, according to his testimony this week, Mr. Coleman did not do things differently by actively working to put together members of existing teams to focus on money laundering problems in casinos.

Instead, according to his testimony this week, Mr. Coleman decided to do things differently by expecting that existing anti-gang units would fill the void.

And did they?

Well, it would appear that the proof is in the bundles of 12 year-old pudding.

None of which has been delivered to us in hockey bags.

If you get my drift.



_____
Note: I would have cited the transcript of Mr. Coleman's April 28th testimony in front of the inquiry directly...However, the transcript has not yet been uploaded to the Cullen Commission website.



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Friday, April 23, 2021

They're Baaaack!

They're(Still)Out
ThereVille


It would seem, based on events of the past week or so, that the Lords of GordCo, Inc. and the Keepers of Clarklandia may never leave us...

First, this, from Sam Cooper of Global News about our former premier's Sgt. Schultz defense b/w a light throwing of Darth Vader under the bus while responding to questions during the ongoing money laundering inquiry:

... (Cullen) Commission lawyer Patrick McGowan grilled (former B.C. Premier Christy) Clark on whether she was aware from 2011 of increasingly urgent reports coming from the enforcement branch and casino surveillance units, showing that bags of $20 bills were being commonly used by high rollers to buy casino chips and that the cash was dropped off inside or near casinos...

{snip}

...Clark said it wasn’t until 2015, after her then-finance minister Mike de Jong took casinos over from Coleman, that she was directly informed of an “all-time high” spike in suspicious cash transactions. Within two weeks of de Jong’s report, Clark said, the pair worked together to implement the Joint Illegal Gaming Investigation Team, a special casino-crime police task force...


****

And then Bob Mackin determined that former Clarklandian apparatchik Jean Paul Fraser has been 'assisting' Northern Vancouver Island mayors to help them put the fish farming industry's best foot forward:

Email obtained by theBreaker.news under the freedom of information law shows how closely mayors of four Northern Vancouver Island municipalities worked behind-the-scenes with salmon farming lobbyist John Paul Fraser...

{snip}

...Fraser was the BC Liberal government’s deputy minister of communications under ex-Premier Christy Clark. He is also the son of Paul Fraser, the late the conflict of interest commissioner who never found an MLA broke the law during his more than a decade in office...

****

And, apropos of absolutely nothing at all, the good Mr. Fraser once worked with Ms. Clark's former life partner, a fine fellow named Mark Marissen who himself both made and reported his own 'news' recently:


****

And then along came a very different finest of the fine fellow named John from days of yore pretending that the province of British Columbia is actually Europe.

Or some such thing:

...A 2030 Winter Olympic and Paralympic Games that encompasses more of B.C. than the Lower Mainland and a ski resort town will be part of John Furlong's pitch to the Vancouver Board of Trade on Friday...

{snip}

..."B.C. is not small. This is Germany, France and England combined. It's a very big area," Furlong said...


****

Finally, one of the Ghosts of GordCo, Inc. Land Deals Past is being forced to raise its still entirely opaque head above the public awareness parapet:

The B.C. Supreme Court has set aside two days to hear arguments on whether the public can see the contract that privatized the Little Mountain lands in Vancouver more than a decade ago.

The case could be heard as early as Thursday, although one of the lawyers involved says it's on an overflow list awaiting a judge.

The years-long effort to reveal the details of the purchase agreement between B.C. Housing and developer Holborn Properties has been the subject of a protracted freedom of information battle between the developer, the Crown corporation, the CBC and co-applicant David Chudnovsky...

{snip}

The Little Mountain lands lie between Queen Elizabeth Park and Main Street in East Vancouver, just south of Nat Bailey Stadium. The six-hectare site was home to 224 units of social housing that existed from the 1950s until the land was sold in 2008 by the B.C. Liberal government to developer the Holborn Group.

In 2009, all but four units of social housing were demolished.

While displaced residents were promised that they would be able to return to newly-built social housing, only 53 units were ever constructed...



Gosh.

Will we never be rid of them?



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Friday, April 16, 2021

Your Evening Audio...Peek-A-Boo

AllTheWorldsA
CoverVille


Just in case you all didn't know by now, I'm a sucker for covers.

Especially acoustical covers. 

So, because of this obsession the algorithm now follows me around with them and this week it through up a most excellent version of Daniel Johnston's 'Peek-A-Boo' by Phoebe Bridgers.

I think it's fair to surmise that both Ms. Bridgers and Mr. Johnston, who passed away recently, have been/were saddled with the descriptor 'genius kid' at various times in their lives.

Anyway, this song, I think, is about what happens when a genius kid decides that the only way forward for them is an an artist.

Here's my shot at it...



______
As anyone who has spent anytime around here at all knows, I'm no artist, but I'm surrounded by them...And it's a wonderful thing indeed.


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Tuesday, April 13, 2021

The Rare And Serious Adverse Blood Clotting Events Temporally Linked To The Johnson & Johnson COVID-19 Vaccine.



On the weekend (see post-script), we noted that blood clotting events have been noted in a small number of people after they received the Johnson & Johnson vaccine.

This has led to a call for a pause of the vaccine's use in the United States while the American Center for Disease Control's 'Advisory Committee on Immunization Practices' reviews the data (they are scheduled to meet tomorrow/Wednesday).

As Helen Branswell, who is an excellent science journalist, reports in STAT News, the events identified so far are very rare. However, they are also very serious and appear to be similar those that have occurred rarely after administration of the AstraZeneca vaccine:

Federal authorities on Tuesday recommended that states stop using Johnson & Johnson’s Covid-19 vaccine while an investigation is conducted into six serious cases of clotting problems — one of which was fatal — that were reported among women who received the vaccine.

The blood clots are similar to those reported by several European countries after use of AstraZeneca’s Covid-19 vaccine. And they are similar to an event that occurred during Johnson & Johnson’s U.S.-based clinical trial, an event that led to a temporary pause in that trial last fall. That case involved a man in his 20s, STAT reported at the time.

The clotting problem appears to be quite rare. As of Monday, more than 6.8 million doses of the Johnson & Johnson vaccine had been administered in this country...

{snip}

...The blood clots reported in the six cases are known as cerebral venous sinus thrombosis (CVST); in all cases, the clots were seen in combination with low levels of blood platelets, a condition known as thrombocytopenia. All occurred among women between the ages of 18 and 48, the statement from the CDC and FDA said, and symptoms occurred between six and 13 days after vaccination...



Clearly, this is an abundance of caution issueand the pause appears completely reasonable at this time. While the incidence rate is lower for the J&J vaccine than with the AZ vaccine at the moment, that could change with increase surveillance.

If the post-J&J vaccine events truly are the same as those post-AZ innoculation they will hopefully become increasingly diagnosable and treatable, as has been suggested by recently published findings in the New England Journal of Medicine (see Update IV at top of the post).


****

So, what might be causing the problem here?

Originally, some folks speculated that the AZ vaccine issue might be occurring because the spike protein produced by that vaccine was not in the 'locked' conformation which could lead to bits of the protein being released and an initiating a rare adverse immunological response. However, the J&J vaccine produces the 'locked' form of the spike protein, as do the mRNA vaccines for which these types of clotting events have not been reported. Thus, the unlocked spike protein hypothesis has fallen from favour.

Another hypothesis is that the problem might, at least in part, be caused by the adenoviral vehicle that is used to deliver both the J&J and AZ vaccines, but not the mRNA vaccines, to our cells. If that turns out to be the case this could also be problematic for the Russian Sputnik and the CanSino vaccines as well as they, too, are in the adenoviral vaccine 'class'. Helen Branswell reports on that as well:

...The concern over Johnson & Johnson’s vaccine is raising questions about whether there is what’s known as a “class effect” — a problem one would expect to see with all vaccines made in the way the J&J and AstraZeneca vaccines are made. The Sputnik V vaccine, made by Russia’s Gamaleya Research Institute and the vaccine made by CanSino, a Chinese manufacturer, are made in the same way as the Johnson & Johnson and AstraZeneca vaccines.

The four vaccines use modified adenoviruses — viruses that cause colds — to deliver instructions to human cells to make the SARS-CoV-2 spike protein, the exterior proteins that allow SARS-2 viruses to attach to and invade cells. Those vaccine-induced spike proteins teach the immune system to look out for and defend against SARS-2 viruses.

Theories about the cause of the rare clotting issues hinge on the possibility that, in small numbers of people, the adenoviruses trigger an aberrant immune response. That, in turn, results in a rare combination of widespread clotting and low platelet counts...

{snip}

...“It’s a reasonable but unproven assumption that the J&J and AstraZeneca vaccine safety concerns are linked by being related to an immune response against an adenovirus component,” he (John Moore, an immunologist at Weill Cornell University) said. “So, FDA and scientists need time to better understand what is going on, which means a pause is the right course of action.”...


Having noted that, it is important to realize that at this point this is only an hypothesis at this time. Thus, there are no hard data yet to either support or refute it.

****

Here in British Columbia there has been a delay in delivering Johnson & Johnson vaccine but we are  currently offering the AstraZeneca vaccine for folks between 55-65 where the risk/reward ratio tips more heavily towards the latter than it does in younger people. 

Again, the science on what causes these rare adverse clotting events is not clear, but protocols for diagnosing and treating them are being developed and apparently the first case identified in Canada has been successfully treated.

Finally, to reiterate, these events have not been found in people that have received the mRNA vaccines from Pfizer and Moderna.


______
Update, Wed April 14th: Drug development guy Derek Lowe has an excellent overview of all this, including from a regulatory point of view....Here.



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Saturday, April 10, 2021

You Have Not Heard This One Before...

TheEnemyOfYourViralEnemyIs
AlwaysYourFriendVille


And heckfire...

We even got the same lot on the same day!



(different pharmacies though - mine was at LD at 41st & Victoria)



________
Just a note that I've updated the eariler post about the rare and serious blood clotting events post-AZ vaccine inoculation to include the now published papers on one likely cause, and potential treatments, for the condition.
A group at Cambridge in the UK has put together a solid risk-reward analysis of getting the AZ vaccine... It tilts heavily towards the reward side with increasing age which, of course, is even more of a reason for semi-old folks like Mr. Wilkinson and myself to get this particular jab.
The European Medicines Agency is now investigating a still small number of reported blood clotting events that have been time-associated with Johnson & Johnson vaccine inoculation (scroll down)...Like the AstraZeneca vaccine this, too, is adenovirus-based (the mRNA vaccines from Pfizer and Moderna are not)...So...This is a subject you are likely to hear/read more about in the coming days, particularly given that the Sputnik and CanSino vaccines are also adenovirus-based...To be clear, however, at this point it is by no means certain that the adenoviral-delivery method is the, or even a, causal link to the rare, serious clotting events.



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Wednesday, April 07, 2021

Europe Updates Its Findings On Rare, Serious Blood Clotting Events Associated With AstraZeneca COVID-19 Vaccination.


_______

Update Saturday April 10th: The paper, mentioned as a pre-print in a previous post, from the German group that originally described the issue has now been peer-reviewed and published in the New England Journal of Medicine...Here....A companion paper that comes, essentially, to the same conclusions from a Norwegian group is...Here.

_______

Pre-post note: If you would like to cut right to the chase and go to an excellent description of this rare, but serious, side effect to the AZ vaccine, as well as specific diagnosis and treatment protocols, please go directly to the Ontario Science Table's  outstanding 'Science Brief'.

_______

As we noted previously, the European Medicines Agency's safety committee (PRAC) has been assessing reports of rare serious clotting issues in people who have received the adenovirus-based AstraZeneca/Oxford COVID-19 vaccine.

The report is now out. It is very worth reading in its entirety.

Here are some highlights:

EMA’s safety committee (PRAC) has concluded today that unusual blood clots with low blood platelets should be listed as very rare side effects of Vaxzevria (formerly COVID-19 Vaccine AstraZeneca)...

{snip}

...So far, most of the cases reported have occurred in women under 60 years of age within 2 weeks of vaccination. Based on the currently available evidence, specific risk factors have not been confirmed...

{snip}

...The Committee carried out an in-depth review of 62 cases of cerebral venous sinus thrombosis and 24 cases of splanchnic vein thrombosis reported in the EU drug safety database (EudraVigilance) as of 22 March 2021, 18 of which were fatal.1 The cases came mainly from spontaneous reporting systems of the EEA and the UK, where around 25 million people had received the vaccine...

{snip}

...One plausible explanation for the combination of blood clots and low blood platelets is an immune response, leading to a condition similar to one seen sometimes in patients treated with heparin (heparin induced thrombocytopenia, HIT). The PRAC has requested new studies and amendments to ongoing ones to provide more information and will take any further actions necessary.

The PRAC stresses the importance of prompt specialist medical treatment. By recognising the signs of bloods clots and low blood platelets and treating them early, healthcare professionals can help those affected in their recovery and avoid complications.

Patients should seek medical assistance immediately if they have the following symptoms

  • shortness of breath
  • chest pain
  • swelling in your leg
  • persistent abdominal (belly) pain
  • neurological symptoms, including severe and persistent headaches or blurred vision
  • tiny blood spots under the skin beyond the site of injection

****

So, the findings are similar to those we discussed last week, based on initial findings in Germany and other European jurisdictions. One important new thing  is that there are now data from the UK to support this finding.

To reiterate, this is a  rare condition. Specifically, there have been 86 events reported out of  ~25 million vaccinated so far. Importantly, the condition is more common in women under the age of 60. A British medical oversight group has attempted to estimate the incidence rate in that specific group. They still find that it is a very rare event but emphasize that more data are required to be certain of the rate of adverse events.

As the EMA notes, it appears that the post-AZ vaccine events may be similar to a rare immunological response to heparin that causes inappropriate clotting inside the blood vessels. 

Unfortunately, at this time it is not possible to tell who will respond to the AZ vaccine in this way  (i.e. 'specific risk factors have not been confirmed'), other than it occurs most often in women under 60. However, a number of post-vaccination physical symptoms of concern have been identified that indicate the need for immediate medical intervention. The latter are outlined in the box above.

As we noted last week, a group in Germany with expertise in the field, including a rare heparin-induced clotting syndrome, has proposed a way to diagnose and treat the AZ vaccine-associated condition. At this time the European Medicine Agency's safety committee (the 'PRAC' quoted above) has asked for more study on this matter. However, the British Hematological Society has posted a 'Guidance on Management' protocol as has a similar German Society For The Study Of Thrombosis and Hemostasis as well as the Ontario Science Table. 

In the case of the Ontario Science Table, they have outlined concrete diagnosis and treatment protocols.  As noted at the top of the post, they also explain things well - it is very worth reading.

Here's hoping that we receive an update on this matter from our National Advisory Committee On Immunization so that Canadians can be confident that we are moving forward with all the best and most appropriate information and procedures possible.



_________
The BCCDC statement on the AZ Vaccine,
which is now being offered to folks 55-65 years of age, is....here....A handout on AZ vaccine aftercare is....here.


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Monday, April 05, 2021

The SARS-CoV-2 Variants Of Concern.



The graphic above is from Eric Topol of the Scripps Research Institute in San Diego. He is a clinician researcher whose group published important work on asymptomatic spread of the SARS-CoV-2 virus and he has been following COVID-19 developments closely, including the latest on vaccines and variants of concern, including the three shown in the table. All of this is just by way of explaining Topol's bonafides to you. 

Below are some take aways/explanations, focusing on the receptor binding domain or 'RBD' of the 'spike' protein. Much of what I'm going to type can be gleaned from a very recently peer-reviewed and published paper from a group at Oxford in the top-ranked journal 'Cell' titled 'Antibody evasion by the P.1 strain of SARS-CoV-2':

How the variants arise: SARS-CoV-2, like all viruses that have RNA as their genetic material, has an error prone RNA polymerase. The latter is the enzyme that is required to make new genetic material/RNA. The errors lead to mutations in viral genes, including the gene for the spike (S) protein. This produces a viral variant and those mutations can change the 'code' for amino acids in numbered positions in the viral proteins. The mutation in the spike protein that is common to all three 'variants of concern' shown above, all of which are currently present in British Columbia, is the N501Y mutation. This means that 'asparagine' amino acid (code name 'N')  at position 501 in the spike protein has been changed to a 'tyrosine' (code name 'Y') which slightly changes the shape and electrostatic characteristics of the bit of the spike that binds to our cells (that 'receptor binding domain'/RBD again).

How the variants emerge/spread: The spike protein is critical for binding to our cells and getting the virus inside them via the RBD. Thus, when we make our own antibodies against the virus after we've been infected with it, or because we've seen the spike protein before due to vaccination, the ones we make against the RBD portion of the spike protein are the ones that can 'neutralize' the virus and prevent it from infecting our cells. Any mutation/amino acid change in the RBD that increases its ability bind our cells (i.e. could increase transmissibility) or decreases the ability of our antibodies to bind to the RBD (i.e. could cause immune evasion) will give the variant a selective advantage and so lead to its emergence and spread in a given locality/human population where community spread is occurring. When the variants 'take over' due to this advantage it can be a significant problem for public health-based control and vaccine efficacy as noted below.

The spike protein that all the (current) vaccines code for: They all code for the 'classic' spike protein coded for by the original Wuhan viral strain. Most of the vaccine-coded spike proteins have two changes (via 2 proline amino acid mutations/substitutions) that were engineered into them to 'lock' the protein into the configuration/shape that is normally found on the surface of the virus before it binds to cells. The two vaccines that do not have this 'lock' are the Oxford and Sputnik ones, and some researchers are now starting to think that this is why these vaccines aren't as good at producing neutralizing antibodies against some variant spike proteins.  Another thing worth knowing is that the mRNA vaccine makers are already at work making vaccine boosters based on the new varian forms of the spike proteins. Being able to do this quickly and efficiently is one of the advantages of the mRNA vaccine technology.

The B.117/UK variant: This one was first identified in the United Kingdom and, due to it's increased transmissibility, it very quickly spread and became the dominant form of the virus in the fall and early winter of 2020. It has a bunch of spike protein mutations but, as noted above, it also has that N501Y mutation that is common to the other two variants of concern and it is thought that this mutation increases transmissibility. This variant is also appears to be more lethal despite what it says in Topol's table above (about 1.6X). Luckily, it looks like all the current vaccines work reasonably well against this variant. This includes the AstraZeneca vaccine which has been the one that has been rolled out widely to good effect in the UK (for a comment on the rare, serious clotting disorder associated with taking this vaccine, see....here). According to the numbers we have so far, this is currently the most prevalent variant in British Columbia (scroll down). 

The P.1/Brazilian variant: In addition to the N501Y mutation seen in the UK variant, the P.1/Brazilian variant also has E484K (which is sometimes referred to as the 'eeek' mutant) and K417T mutations in the RBD that affect binding to cells and may also contribute to immune evasion. This is the variant that has been spreading rapidly in British Columbia recently, including at Whistler. P.1/Brazilian is also the variant where we have the least hard data. Topol's table states that the effect on transmissibility is not clear, but there is one non-peer reviewed report of an increase of greater than two fold which I assume is the one that local folks are basing their comments on in media reports. The lethality is also not clear, but there have been anecdotal reports that it is problematic in younger patients. 
    So, do the vaccines work against this variant? In a true clinical setting that is not clear as the data are not yet available, but in terms of making neutralizing antibodies it looks like there is reduced activity, but it is still there - the caveat here is that the mRNA vaccines look to be better than the AstraZeneca one (see Figure 7C/D). 

The B.1351/South African variant: It has very similar changes to the RBD as does the P.1 variant. The transmissibility and lethality changes are not clear. However, both the mRNA and Astra Zeneca vaccines least proficient at generating neutralizing antibodies against it (see the same Figure 7C/D). There are clinical data for this variant though. The mRNA vaccines work, but not as well against the 'classic' virus and a small scale, phase II clinical trial concluded that the AstraZeneca vaccine doesn't have much, if any, efficacy. This has caused a lot of concern but it is important to realize that they were only looking at mild-to-moderate disease as an endpoint (as opposed to severe disease, or worse) and the sample size was so small that the 95% confidence intervals were very wide (i.e. the statistical power was low). 
    Here in British Columbia, where we are now rolling out the AZ vaccine to folks 55-65 in a lot of locations (my appointment is on Thursday), one ray of hope on this front is that this variant is still at quite low numbers and it appears, assuming we are on top of things, to be increasing slowly compared to the other two variants.


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My usual disclaimer here is that, while I am a life scientist and a cell biologist, I am not a virus or vaccine expert...Thus, please understand, that I'm only trying to explain things that have been raised in media reports more fully based on what I can glean from the available scientific literature and the comments of true experts like Eric Topol mentioned above.
We here in B.C. have been lagging a bit with variant tracking but, as Andrea Woo reported in the Globe on the weekend, a group at St. Paul's led by Marc Romney has figured out how to speed that up - their actual paper is here....Here's hoping our PHO and the BCCDC adopt their methods so that we can get closer to real time variant tracking - it looks like it could really help keep us ahead of things, both from public health and vaccine implementation points of view.
Thanks again to all the readers who have sent helpful links to material to have a look at and consider.


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Saturday, April 03, 2021

Will Saturday Nights Be Alright Without Randy?


WhatEverHappenedTo
UkeCoverFightingVille


The grant applications went in on Thursday and, after a couple of sleeps, my brain is starting to recover.

Neither grant had anything whatsoever to do with viruses or vaccines which is not the least bit surprising given that, as noted previously, neither of those subjects is my specialty.

However, given recent developments, especially here in Lotusland (i.e. British Columbia's Lower Mainland), I am doing my best to get up to speed with the latest on the SARS-Cov-2 viral variants of concern and vaccine responses to them. Hopefully, if I can make reasonable sense of the rapidly evolving literature, I'll be able to write a coherent post soon.

In the meantime, now that we know for sure that Randy's Vinyl Tap has been officially cancelled, I thought now might be the time to point interested readers (here's looking at you E.G.) to a complete archive of a similarly themed but, dare I suggest superior, radio show called 'Theme Time Radio Hour' that the almost octagenerian Bob Dylan put together a few years ago.

Weirdly, it's hard to find Dylan's complete series on podcasting apps (at least the ones I use). Surprisingly, however, all 100+ episodes have been archived somehow by fans and enthusiasts (as opposed to a megamediacorporatocracitic entity)...Here.

Talk to you all soon




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Subheader?...It used to be a weekly thing 'round here.
Thanks to everyone who has sent me variant info...It's been helpful...I'm really doing my best to stay away from the finger pointing/hockey team stuff and stick to reading the most pertinent scientific publications, including an important recent one by a local group at St Paul's. 



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Monday, March 29, 2021

The AZ Vaccine And The Rare But Serious Clotting Disorder.

TheCautionFlagIs
OutVille

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Update IV, Sat April 10th: The paper, mentioned as a pre-print in the original post, from the German group that originally described the issue has now been peer-reviewed and published in the New England Journal of Medicine...Here....A companion paper that comes, essentially, to the same conclusions from a Norwegian group is...Here.

Update III, Wed April 7th...The European Medicines Agency has provided an update, supported by data from the UK and concludes that this is a rare adverse event...We discuss this update...Here.

Update II, Wed Mar 31st...BC is now offering AZ Vaccine to folks 55-65 in the Lower Mainland due to the high rates of viral infection in the region...Announcement is here....Pharmacies to contact are here...I'm in the age group and will be getting the vaccine...The syndrome described below is  very rare and there is now a protocol to treat it if it does occur.

Update I, Tues March 30th, at bottom of post
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On Saturday March 27th the top of the ladder journal Science published an information piece (i.e. not a primary data paper) on the rare but serious cases of blood clotting/thromboses with platelet problems in folks who have received the AstraZeneca COVID-19 vaccine. 

The piece was written by contributors Kai Kupferschmidt and Gretchen Vogel and it is good.

One of the issues is the differing incidence rates in various jurisdictions including...

The UK:

...The United Kingdom has officially reported only 5 cases—despite administering 11 million doses of the AstraZeneca vaccine...

Compared to, for example, Norway:

...Norway, which has administered the AstraZeneca vaccine to 130,000 people under 65, has reported five patients who had low platelets, hemorrhage, and widespread thromboses, three of whom died...


Why the difference?

Well, one possible explanation is the way the vaccine was initially used in continental Europe compared to the UK:

...So far, most cases have been observed in women under 65. But that could be because of the vaccinated population: Many countries initially used AstraZeneca only in people under 65 because early clinical trials included few older recipients. That meant the vaccine was used in priority groups such as health care workers and teachers, a majority of whom are women. In Norway, for example, 78% of the AstraZeneca doses went to women, says Sara Viksmoen Watle, chief physician at the Norway Institute of Public Health. The United Kingdom, however, used the vaccine first in older people, which may explain why fewer unusual clotting events have been spotted there...


So, can this problem be dealt with?

Well, there is a group in Germany led by a researcher named Andreas Greinacher that is calling the syndrome 'vaccine-induced prothrombotic immune thrombocytopenia' (VPIT). They think that VIPIT has similarities to another rare condition called 'heparin-induced thrmobmocytopenia' (HIT) that is caused when the body makes its own antibodies against a complex of the blood thinner heparin and a factor called PF4  that causes massive platelet activation and thus clotting. Greinacher says that VPIT can be diagnosed and treated in a manner similar to the way that HIT is dealt with:

...Greinacher agrees on the need for more data. But he says it's crucial to alert doctors to the potential complication. When recognized in time, HIT can be treated with immunoglobulins—nonspecific antibodies from blood donors—that help put the brakes on platelet activation. Non-heparin blood thinners can help dissolve the clots. VIPIT should be treated in a similar way, he says. In at least one case, Greinacher says, a doctor sought the group’s advice and the patient recovered...


The work of the German group has not yet been peer-reviewed, but they have placed the data on a public pre-print server so that it can be scrutinized by experts in the field. And, at the very least, the British Society for Hematology and the German Society for the Study of Thombosis and Hemostasis (of which Dr. Greinarcher is a member) are taking the matter very seriously and issuing guidelines for monitoring and potentially treating the issue. In addition, the European Medicines Agency is having a very close look at all the data and it is expected to report on the matter next week (Apr 6-9th). 

Given all this a number of jurisdictions have put age restrictions on the AZ vaccine:

...Many countries are, for now, accepting the risk that the AstraZeneca may carry, but several have restricted its use to people who are at the highest risk of dying from COVID-19: those aged 55 or older in France, 65 or older in Sweden and Finland, and 70 or older in Iceland...


It would appear that Canada's decision to do the same, despite the fact that no cases this disorder have yet been detected after the administration of 300,000 doses of the AZ vaccine nationally, is, at least for the moment, a prudent one, particularly given that we have other vaccines at hand.



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The National Advisory Committee on Immunization (NACI) recommendation and rationale is...Here.
The Ontario Science Table's COVID-19 Response website also has an excellent primer on VPIT....Here.
Apologies for being mostly offline as this and the variant growth has been unfolding locally but it's grant writing season for me which has curtailed my reading on all things COVID somewhat for the last couple of weeks or so.
Update, Tues Mar 30th: Kai Kupferschmidt, one of the co-authors of the piece quoted above, reports on Germany's updated numbers... 2.7 million AZ vaccine doses administered, 31 cases of cerebral venous thromboses (29 in women age 20-63), 19 with thrombocytopenia...This is likely a considerably higher rate than would be seen in the population.


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Wednesday, March 24, 2021

And So It Begins...

OhWoeAre
TheeVille



Following up on the good Mr. O'Toole's inability to yank the base toward a faux center last weekend, the self-proclaimed head trainer has grabbed hold of the leash and is attempting to lead the pack back to an old familiar kennel...



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Tip O' The Toque
to Alison of Creekside.

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Saturday, March 20, 2021

Erin O'Toole Learns That The Conservative Party Of Canada Is Full Of Conservatives.

RunRunRunRunRunRun
AwayVille


Mr. O'Toole, the man who would like Canadians to believe that he and his will meet them 'in the middle' during the next federal election campaign, made his case to the CPC faithful at their convention earlier today as reported by John Paul Tasker of the CBC:

...O'Toole told delegates the party "cannot ignore the reality of climate change" and that the debate "is over."

"We must also recognize that Canadians expect us to have a real plan for the environment. We need to boldly reclaim the environment as an area where Conservatives are leaders," he said.

O'Toole also said he doesn't want Conservative candidates to be branded as "climate change deniers" in the next election campaign...



A few hours later a majority of the faithful told O'Toole where to go:

...Conservative delegates at the party's policy convention have voted to reject adding green-friendly statements to the policy book — including a line that would have stated the party believes "climate change is real" and is "willing to act."...

{snip}

...Delegates issued a rebuke to climate-minded Conservatives and rejected the policy shift by a margin of 54 per cent to 46...



This could get interesting.



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SubHeader Earworm rising?....This.


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Thursday, March 18, 2021

Wednesday, March 17, 2021

A Great COVID Vaccination Story From The CBC's 'Roving Reporter' In Ontario...



You can listen to Haydn Watters' CBC radio report about 104 year old Patricia McSwain....Here (scroll down).

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Meanwhile, here in British Columbia we're moved things up a little bit for those 80, plus, to make appointments to get their first vaccine dose.

The details of where to call or make your appointment online if you are in Fraser Health are...Here.


Again, remember, elderly folks are only getting the Pfizer or Moderna mRNA vaccines as part of 'Phase 2'. Thus, do not be concerned about the safety issue that has recently been raised about the AstraZeneca vaccine (see footnotes, below). 

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As we've noted before, now is not the time to let down your guard regarding viral transmission. 

We also noted that double masking has been shown to increase the barrier to aerosols both for the transmitter and the receiver....The NY Times has a great video of how best to double mask...Here.



________
Regarding the AstraZeneca
, adenovirus-based vaccine that has been rolled out heavily in the UK, last week we noted that the flagging of a small number of time-associated blood clotting events in Europe was likely soon to become an issue in some jurisdictions. Clearly, that has come to pass with all kinds of points of view being expressed on numerous fronts. Derek Lowe, whose analysis is always critical but data-based and fair, weighs in on the details of this and some comparative efficacy concerns...Here. The safety issue that needs to be resolved is whether or not these events have occurred at a greater frequency than in the same cohort of the population that has not yet been vaccinated. While Britain has crunched its data and has come to the conclusion that the number of clotting events time-associated vaccine administration are not greater than those in the population, other jurisdictions in Europe have not done so, especially when it comes to a small number of serious cerebral sinus thrombosis events as has been documented in Germany...The follow-up issue that will need to be addressed, if there an increase in incidence, will be to determine the mechanistic cause of it.
As alluded to above, there is another potential concern with the AZ vaccine that involves efficacy rather than safety, specifically as it pertains to protection against the South African viral variant (B.1.351). We previously noted that concerns were raised that the COVID-19 vaccines might be less effective against the South African variant based on laboratory results that showed a somewhat decreased ability of recipients of the vaccines to generate antibodies that neutralize that form of the virus...Follow-up laboratory and clinical trial data have now been published in the New England Journal of Medicine that the AZ vaccine also shows a decreased ability to generate neutralizing antibodies against the variant as well as a decreased ability to protect against the onset of mild to moderate disease after infection with the South African variant...A caveat here is the relatively small sample size of the trial which resulted in very wide 95% confidence intervals...As for here in British Columbia, the documented number of South African variant infections is still low - all the more reason to double-mask up and keep on social distancing....
And don't forget that it is the more prevalent  B.117/UK variant that is most worrisome locally at the moment due to its increased transmissibility together with its ability to cause a small but significant increase in mortality Importantly, the UK variant is well whacked by all the approved vaccines...Sure hope I've dealt with reader Booey's concerns here.
Update, Thurs March 18th: The European Medicines Agency, has ruled the AZ vaccine beneficial with no increase in the overall risk of blood clots; however, they do state that administration of the vaccine may be associated with very rare cases of clotting associated with thrombocytopenia (low platelet levels) that can contribute to rare cases of clots in vessels draining the brain (i.e. the cerebral sinus thrombosis mentioned above).



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Tuesday, March 16, 2021

A Potential Case Of Future Post-Vaccine (Musical) Envy...

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AllThePostPandemicWorld'sA
StageVille


Yesterday, we brought up the reason why there is absolutely no reason to have vaccine envy given that the only way for things to work is for everyone to get jabbed. Thus, the most vulnerable among us should go first.

But...

I sure am envious of the folks who received an impromptu age appropriate post-jab concert in Berkshire, Mass the other day:

After Yo-Yo Ma received his second jab of a COVID-19 vaccine at Berkshire Community College Saturday, he transformed his 15-minute observation period into a concert for the newly inoculated.

The world-famous cellist and part-time Berkshires resident completed his vaccination course at the field house clinic, and he “wanted to give something back,” Richard Hall of the Berkshire COVID-19 Vaccine Collaborative told The Eagle.

Yo-Yo Ma took a seat along the wall of the observation area, masked and socially distanced away from the others.

He went on to pass 15 minutes in observation playing cello for an applauding audience, in what Hall called a “very special” concert that capped the day’s vaccination event...

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So, who in your age appropriate group  that just might be in youor town when the time comes would you like to see set up shop to serenade you after you get jabbed on down the line.

Me, for Lotuslandian fellow travellers of a certain age bracket, I'm thinking of maybe The Pointed Sticks.



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Monday, March 15, 2021

There Ain't No Vaccine Envy 'Round Here.

AllForOne
AndAllVille



Ian Brown had an opinion piece the Globe and Mail on the weekend about 'vaccine envy'.

It was one of those 'Why is she getting jabbed when I'm not?!' kind of deals that, while somewhat tongue-in-cheek, ultimately led to the following at the top of the third act:


The alternative – waiting your turn – can feel like impotence.


Personally, I honestly do not feel that way at all as this thing only works for everyone when everyone gets jabbed, which is precisely what the plan is.

Meanwhile, I'm perfectly willing to wait for those more at risk to go first, and that includes front line folks and people living in Prince Rupert when there is a risk-based rationale.

And, regardless, supply is ramping up rapidly

OK?




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Saturday, March 13, 2021

Our 'Other' Public Health Emergency.




The graph, above, is from a presentation made by our provincial health officer on Thursday, March 11th.

It shows the top 15 causes of death in British Columbia in 2020.

Clearly, while a terrible tragedy in terms of absolute numbers, in terms of the percentage/rate of deaths  we have done reasonably well in dealing with the COVID19 health emergency (green bars) compared to many other jurisdictions (scroll down to 'deaths per million residents').

However, take a look at those blue bars in the graph.

They represent the mortality statistics from our other public health emergency

And, unfortunately, it is a longterm, ongoing emergency that keeps getting worse. There is also no vaccine to make it magically end.

There is, however, a way to decrease the deaths substantially and that is something called 'safe supply' so that folks don't inadvertently take bad stuff, stuff like fentanyl mixed with benzodiazepines.

The current provincial government took the first few steps to make a safe supply a reality a few months ago, but things seem to have stalled.

As reported by the Tyee's Andrew MacLeod, Green Party MLA Adam Olsen raised the matter in the legislature this week:


...B.C. provincial health officer Dr. Bonnie Henry issued a public health order in September that allowed registered nurses and psychiatric nurses to prescribe pharmaceutical alternatives to street drugs.

But five months later, that health order has still not been put into action, and Olsen pointed out that over 700 people have died since the order was put in place.

While 30 nurses have been trained to prescribe Suboxone, an opioid replacement medication, critics say that falls short of true safer supply, which would provide pharmaceutical-grade versions of illicit substances instead of alternatives....




Clearly our PHO wants true safe supply to become a reality and, increasingly, so do law enforcement officials.

Which means we've got to get our elected officials at all levels to take things over the finish line.

OK?



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Thanks to reader e.a.f. for prodding me forward on this one.
Tip O' The Toque to independent ledge reporter Shannon Waters for flagging the graph on her Twittmachine feed and digging up the origin doc. 



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