Russia Sees Record Population Decline As Excess Deaths Hit 1M

 Russia recorded almost one million excess deaths between the start of the pandemic and the end of 2021, as the country also reported its sharpest annual fall in population since the fall of the Soviet Union.

Pushed down by record numbers of coronavirus fatalities and an already aging population, Russia's natural population declined by more than one million people during 2021 alone, the Rosstat statistics agency reported Friday.

It also said that more than 215,000 Russians died of all causes in December 2021 — 42% more than in the same month of 2019, before the outbreak of the coronavirus — and that some 662,000 people had succumbed to the disease since March 2020. That number is more than twice what has been reported by the government’s taskforce, which uses a different methodology and is reported daily by state media.

Independent demographers have repeatedly accused Russia of undercounting deaths associated with the coronavirus and downplaying the severity of the disease. The revelation that the country’s population shrank faster in 2021 than in any of the previous 30 years has only added fuel to those charges.

Experts say excess fatalities — which measure the increase in all deaths recorded throughout the pandemic compared with the pre-coronavirus period — is the most accurate measurement of the human cost of the virus. 

Russia has now recorded at least 995,000 excess deaths since March 2020, according to The Moscow Times’ calculations comparing fatalities in pandemic months with those recorded in 2019. Many demographers, including former Rosstat analyst Alexei Raksha and Tubingen University statistician Dmitry Kobak, say Russia’s true excess death toll could be higher, based on declining mortality trends in the years before the pandemic.

Critics have accused the Kremlin of prioritizing the country’s economy and refusing to introduce mobility restrictions even as cases surged and hospitals became overwhelmed on multiple occasions over the last 18 months. Russia had only one short lockdown during spring 2020.

More than half the Russian population remains unvaccinated against Covid-19 and the country is currently reporting record-high case numbers. The vaccination drive has practically ground to a halt in recent months, as nearly all Russians who say they are prepared to be vaccinated have already taken a jab.

Russia has seen more excess fatalities than any other country in the world except India.  

The Rosstat figures showed that mortality rates declined in December 2021 from levels seen in previous months, which had been the country’s most deadly period in decades. But a surge in Omicron infections since the start of the year has set back Russia’s latest efforts to stem the pandemic.

https://www.themoscowtimes.com/2022/01/28/russias-pandemic-excess-death-toll-almost-1m-a76194

Biden pick to lead FDA faces long odds

 Facing new hesitancy from Senators in both parties, President Joe Biden's pick to lead the FDA, Robert Califf, MD, does not yet have enough votes to give him the job, Politico reported Jan. 28. 

During a Senate committee meeting Jan. 13 to advance Dr. Califf's nomination, only four Republicans voted in his favor. Now, five Democratic senators have signaled their opposition.

"If the vote were held today, he would not have the votes," one source told Politico. 

Lawmakers cited concerns with Dr. Califf's commercial past at Google's parent company, Alphabet, where he most recently worked as head of health and policy strategy. Records show he was paid millions in stock and bonuses at the company. He also has holdings in Amgen, Gilead Sciences, Bristol Myers Squibb and Walgreens Boots Alliance that he would have to divest if voted into the position. Other senators are wary of his ties to the pharmaceutical industry and the FDA's record of regulating opioids during the time he previously served as commissioner. 

"If his meetings have gone as I’ve heard with other Democrats, he’s not making a great impression," one congressional aide told Politico. 

A white house spokesperson though refuted the claims saying, "We are confident Dr. Califf will be confirmed with bipartisan support, and it is critical to have confirmed leadership at the FDA in the midst of a pandemic."

As of now the dates for the senate confirmation have not been confirmed, but one source told Politico it is being considered for the first week of February. 

https://www.beckershospitalreview.com/hospital-management-administration/biden-pick-to-lead-fda-faces-long-odds.html

Tumors dramatically shrink with new approach to cell therapy

 Northwestern University scientists have developed a new tool to harness immune cells from tumors to fight cancer rapidly and effectively.

Their findings, to be published January 27 in the journal Nature Biomedical Engineering, showed a dramatic shrinkage in tumors in mice compared to traditional cell therapy methods. With a novel microfluidic device that could be 3D printed, the team multiplied, sorted through and harvested hundreds of millions of cells, recovering 400% more of the tumor-eating cells than current approaches.

Most treatments for cancer involve toxic chemicals and foreign substances, which cause harmful side effects and weaken the body's immune response. Using tissue from one's own body can eliminate side effects and risk of rejection, and many disease therapies in regenerative medicine and cancer treatment have gained traction in the clinic. But sometimes the wheels skid.

"People have been cured in the clinic of advanced melanoma through treatment with their own immune cells that were harvested out of tumor tissue," said Shana O. Kelley, a pioneer in translational biotechnology and corresponding author on the paper. "The problem is, because of the way the cells are harvested, it only works in a very small number of patients."

Kelley is the Neena B. Shwartz Professor of Chemistry and Biomedical Engineering at the Northwestern University Weinberg College of Arts and Sciences and McCormick School of Engineering, and a professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine.

The cells of interest, called tumor-infiltrating lymphocytes (TILs), are natural immune cells that invade tumor tissue by engaging cells in a form of hand-to-hand combat that looks like someone using insecticide on a weed. But, in this scenario, previous researchers have been attacking the weeds with a half-expired cannister of chemicals.

This is the case in cell therapies used in clinics today, where a mixture of "exhausted" and "naïve" cells is used to treat tumors. After they are extracted from tissue, cells are grown in labs far away from the patients they were harvested from. By the time they've multiplied and are ready to be placed back in the body, many of the cells are exhausted and unable to fight, having been in the tumor for too long.

Assembling the best fighters

Using a new technology called microfluidic affinity targeting of infiltrating cells (MATIC), researchers can pinpoint which cells are most active through cell sorting techniques enabled with nanotechnology. In the paper, scientists used MATIC to find what the authors called the "Goldilocks population" of cells, producing dramatic results for the mice population they were looking at. Tumors in mice shrank dramatically -- and in some mice disappeared completely -- producing a large improvement in survival rates compared to more traditional methods of TIL recovery.

"Instead of giving mice this mixture of cells with different phenotypes, we're giving them the one cell phenotype that can actually help them," Kelley said. "You see much more potency and a much higher response rate when you really home in on the sweet spot of T cell reactivity."

Reproducible, accessible technology

Because her team's technology is small and easily reproducible, Kelley said it would be feasible to bring the 3D-printed device into hospital settings, rather than confining it to a lab. Getting cell therapy closer to patients would dramatically reduce research and development costs and ultimately deliver the treatment to more people.

Kelley joined Northwestern in August from the University of Toronto and has continued to study how her platform might advance cancer treatments. Now, she's using the device to search for the same types of TILs in blood samples, which would eliminate the need for surgery to remove a small piece of tumor prior to this form of treatment.

Kelley has launched a small company to commercialize her devices and plans to work with industry partners and collaborators at Northwestern to continue expanding use cases for the tool.

The platform itself has been used across applications, mostly for the analysis and measurement of rare cells in the body.

"When we take on the development of a new technology, we typically end up with a hammer, and then need to go find a nail," Kelley said. "We got introduced to problems in cell therapy, and it was immediately apparent that this was a perfect fit."

The first author of the study, Ph.D. student Daniel Wang, is also joining Northwestern from the University of Toronto as a postdoctoral fellow and plans to continue developing new solutions for cell therapy in the Kelley group's labs on the Chicago campus.

Kelley also is a member of the International Institute for Nanotechnology (IIN), the Chemistry of Life Processes Institute, the Simpson Querrey Institute for BioNanotechnology and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

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Story Source:

Materials provided by Northwestern University. Original written by Lila Reynolds. Note: Content may be edited for style and length.

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Journal Reference:

1. Zongjie Wang, Sharif Ahmed, Mahmoud Labib, Hansen Wang, Xiyue Hu, Jiarun Wei, Yuxi Yao, Jason Moffat, Edward H. Sargent, Shana O. Kelley. Efficient recovery of potent tumour-infiltrating lymphocytes through quantitative immunomagnetic cell sorting. Nature Biomedical Engineering, 2022; DOI: 10.1038/s41551-021-00820-y

https://www.sciencedaily.com/releases/2022/01/220127114334.htm

Nearly 1 in 7 COVID patients in ICU had severe bleeding when given full-dose blood thinners

 Patients with COVID-19 in the intensive care unit (ICU) prescribed full-dose blood thinners are significantly more likely to experience heavy bleeding than patients prescribed a smaller yet equally effective dose, according to a recent University at Buffalo-led study.

The research, which compared the safety and effectiveness of blood clot treatment strategies for more than 150 critically ill COVID-19 patients at two hospitals, found that almost all patients who experienced significant bleeding were mechanically ventilated and receiving full-dose anticoagulants (blood thinners).

The results, published last month in Hospital Pharmacy, may inform treatment guidelines for blood clots in hospitalized COVID-19 patients, who are at an increased risk for both blood clots and severe bleeding. Previous reports have found that 17% of hospitalized COVID-19 patients experience blood clots, says first author Maya Chilbert, PharmD, clinical assistant professor in the UB School of Pharmacy and Pharmaceutical Sciences.

"A wide variety of practice exists when it comes to approaching blood clots in hospitalized patients with COVID-19, and there is little data to suggest improved outcomes using one strategy versus another," says Chilbert. "Caution should be used in mechanically ventilated patients with COVID-19 when selecting a regimen to treat blood clots, and the decision to use full-dose blood thinners should be based on a compelling indication rather than lab markers alone."

Additional investigators in the UB School of Pharmacy and Pharmaceutical Sciences include Collin Clark, PharmD, clinical assistant professor, and Ashley Woodruff, PharmD, clinical associate professor. The research was also conducted by investigators at the Buffalo General Medical Center, Millard Fillmore Suburban Hospital and Erie County Medical Center.

The study analyzed the outcome of blood clot treatments and the rate of bleeding events for more than 150 patients with COVID-19 who received either of two blood thinner regimens: a full-dose based on patient levels of D-dimer (a protein present in the blood after a blood clot dissolves), and the other a smaller but higher-than-standard dosage.

The average patient age was 58, and all experienced elevated levels of D-dimer, fibrinogen (a protein that helps the body form blood clots), and prothrombin time (a test that measures the time it takes for blood plasma to clot).

Nearly 14% of patients who received full-dose blood thinners experienced a significant bleeding event, compared to only 3% of patients who received a higher-than-standard dosage. All patients who experienced bleeding events were mechanically ventilated. No difference was reported in the regimens' effectiveness at treating blood clots.

Further investigation is needed to determine the optimal strategy for treating blood clots and bleeding in hospitalized COVID-19 patients, says Chilbert.

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Story Source:

Materials provided by University at Buffalo. Original written by Marcene Robinson. Note: Content may be edited for style and length.

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Journal Reference:

1. Maya R. Chilbert, Collin M. Clark, Ashley E. Woodruff, Kimberly Zammit, Cynthia Lackie, Kristen Kusmierski, Patrick McGrath, Gregory Fuhrer, Anna Augostini, Olivia Denny, Nicole Ross, Marissa Saber, Natalie DelGuidice. Comparison of Higher-Than-Standard to D-Dimer Driven Thromboprophylaxis in Hospitalized Patients With COVID-19. Hospital Pharmacy, 2021; 001857872110664 DOI: 10.1177/00185787211066456

https://www.sciencedaily.com/releases/2022/01/220128141330.htm

Mixing and Matching BP Meds? Consider Implications for Dementia

 The theory that certain antihypertensives can be tied to less dementia was supported by a secondary analysis of the hypertension trial SPRINT.

Between study participants with high blood pressure (BP) who only used medications that stimulate type 2 and 4 angiotensin II receptors and those who only used receptor-inhibiting drugs, the former tended to have a lower risk of cognitive impairment nearly 5 years later:

• Amnestic mild cognitive impairment or probable dementia: 45 vs 59 cases per 1,000 person-years (HR 0.76, 95% CI 0.66-0.87)

• Amnestic MCI alone: 40 vs 54 cases per 1,000 person-years (HR 0.74, 95% CI 0.64-0.87)

• Probable dementia alone: 8 vs 10 cases per 1,000 person-years (HR 0.80, 95% CI 0.57-1.14)

"On a population level, shifting antihypertensive prescribing from inhibiting to stimulating regimens, while adhering to current hypertension guideline recommendations, could be a promising strategy to reduce the burden of dementia," according to study authors led by Zachary Marcum, PharmD, PhD, of the University of Washington in Seattle, writing in JAMA Network Open.

"This strategy would mean shifting the treatment paradigm from ACE [angiotensin-converting enzyme] inhibitors to angiotensin II receptor type 1 blockers and reducing the amount of inappropriate β-blocker use in the absence of coronary heart disease or heart failure with reduced ejection fraction," the researchers continued.

Dementia is a growing public health problem with no good preventive measures to date.

"For now, we cannot recommend in the clinical setting that antihypertensives be prescribed for mild cognitive impairment or dementia. Yet, this study lays a solid foundation for future research on specific types of antihypertensives for the prevention of cognitive decline in aging," according to memory specialist Zoe Arvanitakis, MD, MS, of Rush University Medical Center in Chicago.

"While the results are based on secondary analyses from data collected for another research question, the findings that a certain group of BP medications are associated with a lower risk of developing cognitive impairment are very exciting," she commented.

SPRINT included over 9,000 people ages 50 and older at higher risk of cardiovascular disease. Participants were randomized to an intensive treatment strategy (targeting systolic BP <120 mm Hg) or a standard treatment strategy (targeting systolic BP <140 mm Hg).

It was on the basis of this trial that American guidelines started recommending 130/80 mm Hg as the new BP target for most people in 2017.

For the present analysis, Marcum's group analyzed the 8,685 people on BP-lowering medications at 6 months (mean age 67.7 years, 64.3% men). This cohort was split into three:

• 30.4% were users of only antihypertensives that stimulate type 2 and 4 angiotensin II receptors (e.g., angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics)

• 17.7% were users of only inhibitors of type 2 and 4 angiotensin II receptors (e.g., ACE inhibitors, β-blockers, and nondihydropyridine calcium channel blockers)

• 51.9% were users of both types of BP-lowering medication

Dementia screening was conducted at 24 and 48 months after randomization, as well as at the closeout visit and an extended follow-up visit.

The investigators said the cognitive findings were consistent when incorporating the competing risk of death and were independent of systolic BP, cardiovascular risk factors, sociodemographic characteristics, and baseline cognitive function.

Yet negative control analyses suggested the presence of unmeasured confounding.

It was already known that before weighted propensity score matching, people only on stimulating antihypertensives were more likely to be women, Black participants, and randomized to intensive treatment; and less likely to have a history of cardiovascular disease, coronary revascularization, atrial fibrillation, and statin use, compared with users of inhibiting regimens.

"Both underadjustment caused by unmeasured confounding and overadjustment caused by inclusion of covariates measured after treatment initiation, which may be intermediate on the causal pathway between treatment and outcome, are possible," Marcum's group acknowledged.

For now, more research is merited, even in persons with no high BP. The next step may include randomized trials specifically testing whether antihypertensives prevent mild cognitive impairment or dementia, according to Arvanitakis.

"A clinical trial to test the hypothesis assessed in our study for primary prevention would take years to complete. Alternatively, observational studies in larger samples, using a new-user design, with validated cognitive outcomes could provide a useful replication," the researchers suggested.

They also cautioned that SPRINT had excluded people with diabetes, advanced kidney disease, symptomatic heart failure, or a history of stroke -- limiting the study's generalizability.

Disclosures

The study was supported by grants from the National Institute on Aging.

Marcum reported no relevant conflicts of interest.

Primary Source

JAMA Network Open

Source Reference: Marcum ZA, et al "Association of antihypertensives that stimulate vs inhibit types 2 and 4 angiotensin II receptors with cognitive impairment" JAMA Netw Open 2022; DOI: 10.1001/jamanetworkopen.2021.45319.

https://www.medpagetoday.com/cardiology/prevention/96914

Beleaguered Trudeau rival embraces trucker protest despite concerns of violence

 Canada's beleaguered Conservative opposition leader is backing a trucker protest against the Liberal government's strict COVID-19 vaccine mandates, with critics warning the movement is led by far-right activists with a history of trying to incite violence.

The so-called "Freedom Convoy" - due to bring hundreds of trucks to Ottawa from east and west on Saturday - started out as a protest against a vaccine requirement for cross-border truckers https://www.reuters.com/world/americas/canadas-trudeau-slams-fear-mongering-over-covid-vaccine-mandate-truckers-2022-01-24, but has turned into a demonstration against government overreach during the pandemic with a strong anti-vaccine streak.

Some political analysts say embattled Conservative leader Erin O'Toole is now using the protest in a bid to gain more support. O'Toole has opposed vaccine mandates since Prime Minister Justin Trudeau announced them https://www.reuters.com/world/americas/canada-require-covid-19-vaccinations-federal-lawmakers-2021-10-20 in October on the eve of the election.

"The convoy itself is becoming a symbol of the fatigue and the division we're seeing in this country," O'Toole told reporters on Thursday.

Canada's Anti-Hate Network, an independent watchdog, said the convoy's leading promoters, a few of whom have described the protest as Canada's equivalent of the violent storming of U.S. Capitol Hill in Washington a year ago, are not truckers but members of the far-right https://www.antihate.ca/the_freedom_convoy_is_nothing_but_a_vehicle_for_the_far_right.

The Canadian Trucking Alliance, which represents some 4,500 carries, opposes the protest, saying this is "not how disagreement with government policies should be expressed." About 90% of Canada's cross-border truckers and 77% of the population has had two shots.

Action4Canada, one of the organizers, has vowed to stay in Ottawa until the mandates are reversed. "Put an end to the vaccine mandates and all things COVID! It is time for the tyranny and corruption to end," the group said on its website.

Organizers insist the demonstration will be peaceful, and that was the case for a few hundred people and vehicles that turned out on Friday, a day early. They paraded up and down the street in front of parliament, with some honking their horns while waving Canadian and "Fuck Trudeau" flags.

"We're staying here as long as it takes," said Jennifer from Prince Edward Island. She declined to provide her last name. She drove 18 hours to Ottawa in a convoy from the Atlantic coast.

Ottawa police were out in force on Friday, and said they would do the same on Saturday.

O'Toole, facing party calls for a leadership review due to September's election loss to Trudeau and flagging support in opinion polls, has said he would meet the truckers. He posted a video on social media blaming Trudeau for potential supply chain problems the trucker mandate may cause.

Among past Conservative voters, there was a 26 percentage point drop since last year's vote of those who have a favorable view of O'Toole, an Angus Reid Institute poll https://angusreid.org/federal-politics-january-2022 from this week showed.

'POLITICAL GIFT'

Around 20-25% of Conservative party voters oppose vaccine mandates, the highest rate among the parties in parliament, according to polls. Canada is now in the middle of a spike in Omicron variant cases that is straining hospitals https://www.reuters.com/world/americas/canadian-hospitals-strain-omicron-hits-health-workers-2022-01-24.

Some convoy participants have threatened and harassed journalists trying to interview them on their way to Ottawa. Ottawa police chief Peter Sloly said on Friday convoy supporters are "inciting hate, violence, and in some cases criminality" on social media.

In an editorial published Thursday in the Toronto Sun, O'Toole acknowledged he was concerned the protest could be hijacked by "individuals who plan to use (it) as a means for violence.... (which would) only serve to delegitimize valid and reasonable concerns."

Trudeau on Friday said he was concerned about the protest turning violent in an interview with the Canadian Press, and said this week the convoy represented https://www.reuters.com/world/americas/canadas-trudeau-slams-fear-mongering-over-covid-vaccine-mandate-truckers-2022-01-24 a "small fringe minority" who "do not represent the views of Canadians."

Just as a rock-throwing anti-vaccine https://www.reuters.com/world/americas/canadas-trudeau-trailing-polls-goes-attack-two-weeks-before-vote-2021-09-06 protester during last year's campaign brought Trudeau sympathy and support, disruptions resulting from the protest could bolster Trudeau at O'Toole's expense.

"This is a country that's all about peace, order and good government," said David Coletto, chief executive officer of Abacus Data polling company, so if there is violence or chaos, the Conservatives will be seen as "cheerleaders."

"This is a political gift to the Liberals," Coletto said. 

https://www.marketscreener.com/quote/currency/EURO-CANADIAN-DOLLAR-E-2358944/news/Beleaguered-Trudeau-rival-embraces-trucker-protest-despite-concerns-of-violence-37675920/

Cigna reportedly wants to buy Centene—but multi-billion dollar deal likely won’t happen

 Cigna has reportedly shown interest in buying fellow insurer Centene over the last few months, per Bloomberg. The deal discussions were reported preliminary and didn’t lead to serious negotiations, and it’s unclear whether or not the talks will be restarted anytime soon.

What a Centene merger could mean for Cigna: Combined, the duo would create a Medicaid and Medicare behemoth, rivaling insurance giants like United Healthcare (UHC).

Cigna would reach millions of Medicaid patients with Centene under its roof. Centene’s primary business is Medicaid: It covers over 26 million managed care members (1 in 15 individuals across the US), according to its website.

This would complement Cigna’s already massive existing member base: Cigna claims it serves over 180 million customer and patient relationships globally across its pharmacy (Express Scripts) and medical business, many of which are US-based Medicare members.

Plus, Cigna would become a much larger threat to market leader United Healthcare.

For context, UnitedHealth Group (UHG) holds the highest market share (15%) among all insurers, per a 2021 AMA report.

Cigna trails behind UHG in market share at 12%, but by adding Centene into the mix (2%), it would be inching closer to UHG’s top spot.

But… We don’t think it's likely Cigna will acquire Centene anytime soon considering the FTC’s crackdown of insurer M&A deals over the past few years.

Large mergers usually take significant time to close due to antitrust

UHG and health IT giant Change Healthcare announced their merger over a year ago, but the duo still has to earn approval from the federal government before the deal can be marked complete.

Plus, the federal government has shut down large insurer M&As in the past, which means a Cigna-Centene merger could see the same fate:

In 2017, a federal judge blocked insurer Anthem’s $52 billion acquisition of Cigna since the two giants combined would create the largest health insurance conglomerate in the US—and make it more difficult for employers to get fair rates for health plans.

And during the same year, Aetna and Humana called off their multi-billion dollar M&A merger after a federal judge blocked the deal since it would have substantially decreased competition in the health insurance industry.

https://www.emarketer.com/content/cigna-reportedly-wants-buy-centene-but-think-multi-billion-dollar-deal-won-t-happen