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Wednesday, April 5, 2023

Will Telehealth Save Patients Money or Drive Up Costs? Yes and Yes

 Barbara Rosebrock was heading to the doctor's office to learn how to use her 8-year-old daughter's new insulin pump when health care as she knew it forever changed. 

It was March 11, 2020. With a mysterious new virus entering the U.S., vulnerable patients like Aubrey ― recently diagnosed with type 1 diabetes ― were advised to stay home.

Her doctor canceled the appointment and suggested a remote video visit instead.

Rosebrock was skeptical.

"I didn't want to do something wrong and end up hurting my kid," she said.

But the virtual visit went well and set a pattern. Three years later, all of Aubrey's doctor's visits are done from home unless lab work or a physical exam is needed. Mom avoids an hour of driving and saves on gas and childcare for Aubrey's younger brother.

"It's pennies here and there, but it all adds up," said Rosebrock.

Telemedicine became routine for the Rosebrocks and tens of millions of others during the pandemic. Among Medicare patients, remote visits increased from 840,000 in 2019 to 52.7 million in 2020, a 63-fold jump. Doctors had shut their doors to only the sickest of patients, and insurers agreed to temporarilyreimburse audio and video visits at the same rate as in-person ones.

Usage has come down substantially since. But patients continue to demand remote options, with 70% of younger generations (Generation Zers, millennials, and Generation Xers) saying they prefer telehealth to in-person visits, and 44% saying they'll switch providers if it isn't offered, according to the American Hospital Association. 

But despite the demand, there remain long-run questions of cost, effectiveness, and choice of provider.

Some pandemic-era exceptions, including state-level rules allowing patients to see doctors across state lines, have already been scaled back. Other rules, like those allowing doctors to prescribe drugs for ADHD or opioid addiction via telehealth, are set to be rolled back May 11. And by December 2024, thanks to a 2-year extension,  lawmakers must decide whether to continue covering telehealth visits via Medicare. That decision will inevitably impact what private insurers do.

A key question: Does telehealth save money? 

"It depends," said James Marcin, MD, director of the University of California Davis Center for Health and Technology. The answer depends on how it is used, by whom, and whose money you're talking about.

"It is not a panacea," Marcin said. "But COVID has definitely enabled us to realize its potential."

Real Savings for Patients

When it comes to out-of-pocket savings, the benefits are clear, said Stephanie Crossen, MD, a Sacramento-based pediatric endocrinologist. Many of her patients, including quite a few from low-income, rural populations, travel several hours to see her. 

"My patients would pretty much always say that telemedicine saves them money," Crossen said. And regaining that kind of lost time in your day has value, too.

One recent study of 3 million outpatient telemedicine visits in California found that, on average, patients avoided a 17.6-mile, 35-minute commute, saving about $11 in transportation costs per visit. 

Throw in lost wages or child care costs and the savings are likely higher, especially where travel distances are farther, the authors said.

In-person visits often also come with extra facility fees not charged for telemedicine appointments, Marcin said. And doctors tend to order more scans and tests when a patient is on site (some necessary, some questionable), driving up costs. 

Telemedicine can also save tens of thousands in helicopter flights, such as when a stroke patient or child with a complicated medical history shows up at a rural emergency room lacking specialists

"We get a lot of patients transferred between hospitals that don't necessarily need to come to us," said Marcin, a pediatric critical care doctor who frequently patches in via video to evaluate and suggest treatments for young patients in distant hospitals.

In-person visits are usually ideal, but cars break down, buses don't come, and family members get sick. In such cases, telemedicine can avert a cancellation, saving money in the long run, said Crossen.

"We know that if our diabetes patients are seen more often, they are at lower risk for long-term kidney damage and all kinds of other issues," Crossen said.

In this respect, more visits can mean more cost to insurers in the short term, while in the long term it could avoid more expensive treatments.

That poses a dilemma for payers.

"The problem in our system is that the insurer who covers their costs now is not necessarily the same one who's going to cover their dialysis in 40 years. So it's hard to make the case that it's saving them money," she said.

More Access Means More Visits

In December, Congress extended Medicare coverage of telemedicine for 2 years, giving everyone time to decide how to handle the practice permanently. If telemedicine makes it so easy to see a doctor, will it be overused?

Ateev Mehrotra, MD, a professor of health care policy and medicine at Harvard Medical School, says he has seen no research to convince him that telemedicine saves the health care system money.

"From my perspective," he said, "the real question is: Does telemedicine increase health care spending, and if so by how much?"

In one 3-year study of people who went to the doctor for acute respiratory illnesses, he found that only 12% of telehealth visits replaced what would have otherwise been an in-person visit. The other 88% were "new utilization," meaning that had telehealth not been available, the patient probably would have just ridden out their cold and not gone to the doctor at all. In the end, telehealth increased net annual spending on colds by $45 per telehealth user. 

Another recent study by the Rand Corporation showed that in the arena of mental health, telemedicine visits more than made up for a drop in in-person visits during the pandemic, with treatment of some disorders up 20%. 

"If you make care more convenient, more people get care," Mehrotra said. 

Whether that is good or bad depends on lots of factors, including who is paying.

In the case of a cold, "if they are paying out of their own pocket to be reassured, more power to them," Mehrotra said.  "But if we as a society are paying for all those visits, we do worry because a lot of people get colds." 

Increased utilization could drive up premiums for everyone.

Doctors also may be more likely to prescribe antibiotics via telehealth, boosting costs and potentially promoting antibiotic resistance, suggests a 2022 review in  Clinical Infectious Diseases.

While research on return visits is mixed, another study, published in 2021 by University of Michigan researchers, found that patients who had their initial visit via telemedicine were significantly more likely to come back for a second visit within a week.

The authors said that "potential savings from shifting initial care to a direct-to-consumer telemedicine setting should be balanced against the potential for higher spending on downstream care."

Worth the Cost?

Mehrotra, a practicing doctor, contends that the question of whether telemedicine saves money is not a fair one.

"When a new drug or procedure or MRI machine comes out, we never say, 'Does it save money?'" he noted. "Instead, we ask whether the improvement in health we're observing is worth the cost."

Policymakers must assess how telemedicine affects patients and look specialty by specialty to see if it's cost-effective.

"For instance, from my research and what I see clinically, I think telemedicine for the treatment of opioid use disorder is a great idea. For telestroke, I'm sold," he said. "But if we're talking about telemedicine for colds, I'm not so sure."

He envisions a system in which visits deemed to be of "lower value" (like that reassuring video call for a cold) might come with a higher co-pay for the patient or a lower reimbursement for the doctor than an in-person version. 

Who is using telemedicine also matters.

Notably, during the pandemic, research found that white patients in urban areas were most likely to use telehealth for outpatient visits, while people in low-income and rural areas and racial minorities used it less, in part due to connectivity issues

Doctors say that addressing those access inequities could go a long way in getting telemedicine to the people who need it most and who will financially benefit from it most.

Priceless Care

For some patients, the benefits are hard to put a price on. Francis Richard, 72, who lived in Mendocino County, CA, took a 2-hour shuttle (one way) to visit a doctor for his late-stage type 2 diabetes and kidney disease. 

"My husband was not tired," said his wife, Marie. "He was tired of the transportation." She says wait times for an in-person visit were often weeks or months.

His nephrologist suggested Francis start seeing him via telemedicine.

He'd Zoom in for consults when Francis needed in-person care at a smaller hospital closer to home and was working to set up at-home dialysis.

Often their visits included Marie seated next to Francis in bed at home, holding the phone as the doctor looked him over, asking questions and exchanging the occasional joke.

She never met the man on the screen, Jose Morfin, MD, in person, and her husband met him only once. 

But she considers him family now.

"I wish my husband was still alive and he could tell you this himself," said Marie, who lost Francis in January.  "But this prolonged his life. They made us feel so supported."

That kind of care, she said, is priceless.

Sources

James Marcin, MD, pediatric critical care doctor; director, University of California Davis Center for Health and Technology.

Stephanie Crossen, MD, telemedicine researcher and pediatric endocrinologist, Sacramento, CA.

Ateev Mehrotra, MD, professor of health care policy and medicine, Harvard Medical School.

U.S. Department of Health and Human Services: "Medicare Beneficiaries' Use of Telehealth in 2020: Trends by Beneficiary Characteristics and Location." 

American Hospital Association: "There may be a generation gap in telehealth's future."

Telemedicine and ehealth "Environmental Impact of Ambulatory Telehealth Use by a Statewide University Health System During COVID-19."

JAMA Network Open: "Impact of Tele-Emergency Consultations on Pediatric Interfacility Transfers."

Health Affairs: "Direct-to-consumer telehealth may increase access to care but does not decrease spending."

 Rand Corporation: "Mental Health Telehealth Services Increased During Pandemic; Treatment Rates Increased for Some Disorders."

Clinical Infectious Diseases: "Antimicrobial Prescribing in the Telehealth Setting: Framework for Stewardship During a Period of Rapid Acceleration Within Primary Care."

Pediatrics: "Antibiotic Prescribing During Pediatric Direct-to-Consumer Telemedicine Visits."

Health Affairs: "Direct-To-Consumer Telemedicine Visits For Acute Respiratory Infections Linked To More Downstream Visits."

BJGP Open: "Telehealth-based diagnostic testing in general practice during the COVID-19 pandemic: an observational study."

https://www.medscape.com/viewarticle/990475

CRC Blood Tests: A Future Without Screening Colonoscopies?

 US regulators may soon clear blood-based biomarker tests for colorectal cancer (CRC), expanding potential options for patients seeking more convenient forms of screening.

Most recently, Guardant Health, Inc, announced the completion of its US premarket approval application for its Shield blood test to screen for CRC. Approval by the US Food and Drug Administration (FDA) would position Guardant to later secure Medicare coverage for its test.

Rival companies, including CellMax Life, Freenome, and Exact Sciences, which already offers the stool-based Cologuard product, are pursuing similar paths in their development of blood tests for CRC.

If these companies succeed, clinicians and patients could have a choice of several FDA-approved tests in a few years.

"They're coming, and they will be increasingly widely used," said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, who earlier in his career helped win broader insurance coverage of colonoscopy.

Blood tests for CRC have the potential to cause a shift in screening for colon cancer.

Screening colonoscopies ultimately could be largely phased out in the years ahead in favor of highly sensitive noninvasive tests, if the blood tests do as well as expected,

John M. Carethers, MD, president of the American Gastroenterological Association (AGA), told Medscape Medical News in an email.

"Holy Grail"?

"A blood test for cancer screening has been the 'holy grail' ever since the carcinoembryonic antigen blood test in the 1960s was claimed to have nearly 100% sensitivity and specificity — but turned out not to — for colorectal cancer," wrote David F. Ransohoff, MD, a gastroenterologist at the University of North Carolina (UNC), in a 2021 article. Ransohoff has studied noninvasive CRC screening for decades.

There is a great allure in the idea of such multicancer detection (MCD) tests.

This "technology offers the potential to detect asymptomatic cancer at several organ sites with a simple blood test, often called a 'liquid biopsy,'" the National Cancer Institute (NCI) said this month.

Several companies are selling MCD tests, some of which include CRC components.

Among the best-known MCD tests now sold is Grail's Galleri. At this time, however, the Galleri test, which tests for 50 types of cancer, should be used in addition to recommended colon cancer screening tests, such as colonoscopy, the company's website says.

Guardant has also noted that its CRC-specific blood test should only complement screening tools, including colonoscopy, not replace them.

The prospect of phasing out the standard CRC screening — colonoscopy — may be appealing, but it would require a big shift for a field in which procedures have dominated. According to a report from the Centers for Disease Control and Prevention, in 2018, 67% of US adults aged 50–75 years met the US Preventive Services Task Force (USPSTF) recommendations for CRC screening, and overall, 60.6% had a colonoscopy in the past 10 years.

Still, the NCI and the FDA have signaled the potential they see in MCD tests. The NCI highlighted its plans to aid MCD test development as part of its budget request for fiscal year 2024. The NCI is preparing to launch a 4-year pilot study for MCD tests to enroll 24,000 people aged 45–70 years. The study is intended as groundwork for a randomized controlled trial that will enroll 225,000 people.

The FDA has shown an interest in helping companies bring blood tests for cancer to market through its breakthrough device designation — a sign that the FDA places great priority on a product and seeks to streamline the application and review process.

CellMax Life appears to be the only CRC-specific screening blood test to have received a breakthrough device designation from the FDA, Atul Sharan, MS, MBA, co-founder and chief executive officer of CellMax Life, told Medscape Medical News in an email.

Lance Baldo, MD, Freenome's chief medical officer, told Medscape Medical News that the FDA may be reviewing parts of their application next year, allowing for a potential 2025 launch of a blood test for asymptomatic people at average risk for CRC.

A Spotty Track Record

Before anyone gets too excited about the prospect of phasing out screening colonoscopy, it's important to remember that CRC blood tests have proven disappointing in the past.

Germany's Epigenomics, for example, secured the first FDA approval for a CRC blood test, Epi ProColon, in 2016. But the company did not receive Medicare coverage for the test. In a 2021 memo explaining the decision, the Centers for Medicare & Medicaid Services (CMS) noted that, given more reliable alternatives, including stool-based tests, the Epi ProColon would result in harm to some patients.

CMS also does not cover Grail's blood test, which has a list price of $949, though the company has secured reimbursement arrangements with several self-insured employers and insurers, such as Point32Health.

But CMS officials have acknowledged the strong interest in CRC blood tests.

In that 2021 memo, the agency also outlined its requirements for Medicare coverage. CMS said it will cover blood-based screening tests for certain patients if these products meet the following standards:

  • Receive FDA market authorization with an indication for CRC screening

  • Have proven test performance characteristics for a blood-based screening test with sensitivity ≥74% and specificity ≥90% in the detection of CRC compared to the recognized standard (which at this time is colonoscopy) as minimal threshold levels, based on the pivotal studies included in the FDA labeling

In February 2023, CellLife Max presented data at ASCO Gastrointestinal Cancers Symposium that its blood test had sensitivity of 92.1% for detection of CRC and 54.5% for detection of advanced adenomas, at 91% specificity.

Prior to that, in December 2022, Guardant issued a press release with study results that met the CMS standard. The test had sensitivity of 83% in detecting individuals with CRC. Specificity was 90%, the company said. That translates to a false positive rate of just 10%.

While such results look promising, Asad Umar, DVM, PhD, the chief of gastrointestinal and other cancers at NCI's Division of Cancer Prevention, said physicians should be cautious when giving advice or answering questions about MCD tests, given limited data from prospective studies about their effect on health outcomes.

Even among physicians already using some MCD tests to screen patients, there is a lot of concern about false positive results that require diagnostic workup and false negative results that lead to a false sense of assurance, Umar said.

"Screening is a process and not just a test. The process involves follow-up testing for any positive test findings," Umar said. "At this point, doctors should inform patients that there is not sufficient data to know how best to use these tests."

Hurdles to Broad Acceptance

For companies seeking broad acceptance of a CRC blood test, two of the three major steps needed are securing FDA approval and Medicare coverage. The last step would be getting an A or B recommendation from the USPSTF, which would mandate coverage by health plans.

This is the "big trifecta," Baldo said.

In the USPSTF's current colon cancer screening recommendations, issued in 2021, it gave an A grade for CRC screening for adults aged 50–75 years and a B grade for those aged 45–49 years. The USPSTF's recommended forms of screening include colonoscopy, as well as stool, high-sensitivity guaiac fecal occult blood, and fecal immunochemical tests. But it said more research is needed to establish the accuracy and effectiveness of emerging screening technologies, such as blood or serum tests.

If CRC blood tests eventually win FDA approval, the USPSTF would likely provide guidance to clinicians on how patients can use them as a screening option.

Ransohoff noted that the mission of the USPSTF is different from that of the FDA and CMS. The FDA's approach on medical tests is to consider overall safety and efficacy, as does CMS, but neither agency makes recommendations, nor does it perform its own rigorous quantitative assessment of benefit vs harm. The USPSTF, however, does its own detailed evidence-based reviews of the benefit vs harm of products, Ransohoff said.

"To me, the Task Force is the gold standard," Ransohoff said. "You have to jump through the hoops with the FDA and CMS for making claims, to enable use, and to help get payment. But the Task Force looks at the choices and the consequences in a quantitative way and makes specific practice recommendations."

What the Future May Hold

Carethers sees a future in which highly sensitive blood tests are able to largely replace screening colonoscopies. He said that colonoscopies would be used for people who are most in need of diagnosis and treatment. Carethers addressed these points during an AGA podcast released in January 2023.

In 20–25 years, colonoscopies may be only a therapeutic procedure, much like endoscopic retrograde cholangiopancreatography is now, Carethers added.

Even if CRC-specific blood tests prove to be effective screening tools, Ransohoff of UNC stressed that colonoscopy will survive. Many people will eventually need to undergo colonoscopy as a diagnostic procedure following a positive blood-based test result, and some may also opt for screening colonoscopies in lieu of frequent blood tests.

And, overall, physicians and patients will need to weigh the tradeoffs of a noninvasive test that can only diagnose CRC vs a screening colonoscopy that offers preventative treatment as well.

"The best intent for screening is prevention of cancer, not detection of cancer," said Johnson of Eastern Virginia Medical School.

https://www.medscape.com/viewarticle/990465

Anti-Amyloids Linked to Accelerated Brain Atrophy

 Anti-amyloid-beta (anti-Aβ) drugs, which are used in the management of Alzheimer's disease (AD), have the potential to compromise long-term brain health by accelerating brain atrophy, a comprehensive meta-analysis of MRI data from clinical trials suggests.

Depending on the anti-Aβ drug class, these agents can accelerate loss of whole brain and hippocampal volume and increase ventricular volume. This has been shown for some of the beta-secretase inhibitors and with several of the anti-amyloid monoclonal antibodies, researchers note.

"These data warrant concern, but we can't make any firm conclusions yet. It is possible that the finding is not detrimental, but the usual interpretation of this finding is that volume changes are a surrogate for disease progression," study investigator Scott Ayton, PhD, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia, told Medscape Medical News.

"These data should be factored into the decisions by clinicians when they consider prescribing anti-amyloid therapies. Like any side effect, clinicians should inform patients regarding the risk of brain atrophy. Patients should be actively monitored for this side effect," Ayton said.

The study was published online March 27 in Neurology.

Earlier Progression From MCI to AD?

Ayton and colleagues evaluated brain volume changes in 31 clinical trials of anti-Aβ drugs that demonstrated a favorable change in at least one biomarker of pathological Aβ and included detailed MRI data sufficient to assess the volumetric changes in at least one brain region.

A meta-analysis on the highest dose in each trial on the hippocampus, ventricles, and whole brain showed drug-induced acceleration of volume changes that varied by anti-Aβ drug class.

Secretase inhibitors accelerated atrophy in the hippocampus (mean difference –37.1 μL; –19.6% relative to change in placebo) and whole brain (mean difference –3.3 mL; –21.8% relative to change in placebo), but not ventricles.

Conversely, monoclonal antibodies caused accelerated ventricular enlargement (mean difference +1.3 mL; +23.8% relative to change in placebo), which was driven by the subset of monoclonal antibodies that induce amyloid-related imaging abnormalities (ARIA) (+2.1 mL; +38.7% relative to change in placebo). There was a "striking correlation between ventricular volume and ARIA frequency," the investigators report.

The effect of ARIA-inducing monoclonal antibodies on whole brain volume varied, with accelerated whole brain volume loss caused by donanemab (mean difference –4.6 mL; +23% relative to change in placebo) and lecanemab (–5.2 mL; +36.4% relative to change in placebo). This was not observed with aducanumab and bapineuzumab.

Monoclonal antibodies did not cause accelerated volume loss to the hippocampus regardless of whether they caused ARIA.

The researchers also modeled the effect of anti-Aβ drugs on brain volume changes. In this analysis, participants with mild cognitive impairment (MCI) treated with anti-Aβ drugs were projected to have a "material regression" toward brain volumes typical of AD roughly 8 months earlier than untreated peers.

The data, they note, "permit robust conclusions regarding the effect of anti-Aβ drug classes on different brain structures, but the lack of individual patient data (which has yet to be released) limits the interpretations of our findings."

"Questions like which brain regions are impacted by anti-Aβ drugs and whether the volume changes are related to ARIA, plaque loss, cognitive/noncognitive outcomes, or clinical factors such as age, sex, and APOE Îµ4 genotype can and should be addressed with available data," said Ayton.

Ayton and colleagues call on data safety monitoring boards (DSMBs) for current clinical trials of anti-Aβ drugs to review volumetric data to determine if patient safety is at risk, particularly in patients who develop ARIA.

In addition, they note ethics boards that approve trials for anti-Aβ drugs "should request that volume changes be actively monitored. Long-term follow-up of brain volumes should be factored into the trial designs to determine if brain atrophy is progressive, particularly in patients who develop ARIA."

Finally, they add that drug companies that have conducted trials of anti-Aβ drugs should interrogate prior data on brain volume, report the findings, and release the data for researchers to investigate.

"I have been banging on about this for years," said Ayton. "Unfortunately, my raising of this issue has not led to any response. The data are not available, and the basic questions haven't been asked (publicly)."

Commendable Research

In an accompanying editorial, Frederik Barkhof, MD, PhD, with Amsterdam University Medical Centers, Netherlands, and David Knopman, MD, with Mayo Clinic Alzheimer's Disease Research Center, Rochester, Minnesota, write that the investigators should be "commended" for their analysis. 

"The reality in 2023 is that the relevance of brain volume reductions in this therapeutic context remains uncertain," they write.

"Longer periods of observation will be needed to know whether the brain volume losses continue at an accelerated rate or if they attenuate or disappear. Ultimately, it's the clinical outcomes that matter, regardless of the MRI changes," Barkhof and Knopman conclude.

The research was supported by funds from the Australian National Health & Medical Research Council. Ayton has reported being a consultant for Eisai in the past 3 years. Barkhof has reported serving on the DSMB for Prothena and the A45-AHEAD studies; being a steering committee member for Merck, Bayer, and Biogen; and being a consultant for IXICO, Roche, Celltrion, Rewind Therapeutics, and Combinostics. Knopman has reported serving on the DSMD for the Dominantly Inherited Alzheimer Network Treatment Unit study; serving on a DSMB for a tau therapeutic for Biogen (until 2021); being an investigator for clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. He has reported serving as a consultant for Roche, Samus Therapeutics, Magellan Health, BioVie, and Alzeca Biosciences; and attending an Eisai advisory board meeting for lecanemab in 2022.

Neurology. Published online March 27, 2023. Article, Editorial

https://www.medscape.com/viewarticle/990459

Mexico's President Slams 'Politically Motivated' Trump Arrest

 Former president Donald Trump has predictably gotten little support from European or other world leaders, but on Wednesday, a couple of notable heads of state expressed their support in the wake of his Tuesday booking on 34 felony counts and appearance before a New York City court.

Mexican President Andres Manuel López Obrador blasted the history-making charges. After previous statements decrying the case as "political", the Mexican leader said Wednesday, "Supposedly legal issues should not be used for electoral, political purposes." He then said: "That’s why I don’t agree with what they are doing to ex-President Trump."

"It should be the people who decide," López Obrador emphasized. The irony is of course that he's a leftist leader, though some have seen him as more of a centrist. But he and Trump have gotten along.

As The Telegraph reviews, "López Obrador had a strangely warm relationship with Trump in 2019 and 2020, despite the former U.S. president’s frequent criticisms of Mexico and migrants, and his plans to build a wall between the two countries."

"In fact, López Obrador had fewer public disagreements with Trump than with current President Joe Biden," the UK publication pointed out.

The other world leader to speak out is Hungarian Prime Minister Viktor Orban, who said of the charges, "Keep on fighting, Mr. President! We are with you," in a tweet.

The White House, for its part, has continued to maintain a stance of "no comment". The Kremlin too has refused to weigh in on the charges facing Trump when asked by reporters at a Wednesday briefing.

https://www.zerohedge.com/political/mexicos-president-slams-politically-motivated-trump-arrest

Ukraine 'Ready' To Give Up Crimea, Says Zelensky Advisor

 There has been much talk and reporting of the coming Spring counteroffensive by Ukraine forces, but with the fight for Bakhmut not going so well for Kiev, there's also been talk of the need for compromise, at a moment Ukrainian casualties in the east are believed to be high.

Last week we reported on President Volodymyr Zelensky's voicing rare doubts concerning Bakhmut - as if preparing his people for news of a devastating defeat. And now, on Wednesday, the Financial Times is reporting the single most important development to come out of the conflict in a long time: Zelensky's office says he's ready to compromise on the future of the Crimean peninsula

Naturally, the Ukrainians present themselves as speaking from a position of having the upper hand, which is the general tone of the remarks that Andriy Sybiha, who is deputy head of Zelensky’s office, gave to FT. Per the publication, "Kyiv is willing to discuss the future of Crimea with Moscow if its forces reach the border of the Russian-occupied peninsula" - which marks the "most explicit statement of Ukraine’s interest in negotiations since it cut off peace talks with the Kremlin last April."

"If we will succeed in achieving our strategic goals on the battlefield and when we will be on the administrative border with Crimea, we are ready to open [a] diplomatic page to discuss this issue," Sybiha said, previewing his high hopes for an imminent counteroffensive.

He explained however that "It doesn’t mean that we exclude the way of liberation [of Crimea] by our army." But given that Ukrainian forces are nearly completely surrounded in the strategic city of Bakhmut in Donetsk region, despite pouring in massive amounts of manpower and equipment, the whole notion of "liberation of Crimea" is a pipe dream.

Western officials themselves have in many cases long acknowledged the extreme unlikelihood of any Ukraine attempt to take Crimea at reaching success. The FT report hints at this in the following

Sybiha’s remarks may relieve western officials who are skeptical about Ukraine’s ability to reclaim the peninsula and worry that any attempt to do so militarily could lead President Vladimir Putin to escalate his war, possibly with nuclear weapons. To date Zelenskyy has ruled out peace talks until Russian forces leave all of Ukraine, including Crimea.

All of this represents a public reversal of sorts from Zelensky's prior hardened stance of seeking the return of every inch of Ukrainian territory. For example, last October while feeling emboldened after billions in defense aid was pledged from the US and Western allies, he declared in a nightly address, "We will definitely liberate Crimea."

More recently, Zelensky's outlook & messages on the future have been mixed to say the least:

"We will return this part of our country not only to the all-Ukrainian space, but also to the all-European space," Zelensky had said, not for the first time. He also repeated the same as recently as Sunday.

Interestingly, FT cites yet another high-ranking Western defense official who admits the near impossibility of Ukraine actually taking Crimea militarily

Rear Admiral Tim Woods, the British defense attaché in Washington, said on Wednesday that Crimea would need "a political solution because of just the concentration of force that is there and what it would mean for the Ukrainians to go in there". He added: "I don’t think there’s going to be a very quick military solution . . . hence we need to see what are favorable conditions for Ukraine to negotiate and I think Ukraine would be up for that."

Russia of course knows this. For Moscow the question will not be Crimea being at issue on the negotiating table, but the status of the eastern territories. Likely the Kremlin will base its willingness to strike a peace deal to end the war based on recognition of the eastern oblasts. On September 30, President Putin signed "accession treaties" declaring Luhansk, Donetsk, Zaporizhzhia and Kherson as part of the Russian Federation. 

At this point, Zelensky is unlikely to let the four territories go, but if Crimea is let go - that at least constitutes positive momentum toward the negotiating table. But still, all of these questions will likely be decided on the battlefield, until either side reaches the point of exhaustion. 

Meanwhile, while Washington has shown little interest in peaceful settlement based on ceding territory to Russia (in fact, many reports have alleged the opposite: that the US and UK have actively sabotaged the possibility of negotiations), Ukraine continues to be steadily pushed out of Bakhmut.

* * *

As for Zelensky himself, he's been sounding more and more pessimistic of late, as we described exactly a week ago...

Zelensky described that the capture of Bakhmut will mean that Putin will smell weakness. According to the Ukrainian leader's words:

Speaking with The Associated Press, Zelenskyy said that if Bakhmut were to fall, Putin could "sell this victory to the West, to his society, to China, to Iran," as leverage to push for a ceasefire deal that would see Ukraine agree to give up territory.

"If he will feel some blood — smell that we are weak — he will push, push, push," Zelensky continued.

"Our society will feel tired" if the Russians gain victory in Bakhmut, he said. "Our society will push me to have compromise with them." Implicit in these words are perhaps a first-time admission that significant sectors of the Ukrainian population are ready for compromise and peaceful negotiations to end the war.

And tellingly, CBS commentary on the AP interview included the following observation: "He appeared acutely aware of the risk that his country could see its vital support from the U.S. and Europe start to slip away as the 13-month war grinds on." Zelensky admitted: "The loss of Bakhmut would mean a political defeat, could lead to a general defeat in conflict."

https://www.zerohedge.com/geopolitical/ukraine-ready-give-crimea-says-zelensky-advisor

On Positive Data In Ulcerative Colitis Study, Immunic Prioritizes Vidofludimus Calcium

 

  • Immunic, Inc (NASDAQ: IMUXreported data from the maintenance phase of its phase 2b CALDOSE-1 trial of lead asset, vidofludimus calcium (IMU-838), in patients with moderate-to-severe ulcerative colitis (UC).

  • Data showed a dose-linear increase in clinical remission as compared to placebo at week 50.

  • An exploratory statistical analysis confirmed the 30 mg dose of vidofludimus calcium to be statistically superior (p=0.0358) in achieving clinical remission at week 50, with a 33.7% absolute improvement over the placebo.

  • A dose-linear increase in endoscopic healing was observed, with the 30 mg dose of vidofludimus calcium being associated with a 37.8% absolute improvement over the placebo.

  • Immunic says the maintenance phase data of CALDOSE-1 confirms vidofludimus calcium's activity in the absence of chronic corticosteroid co-administration.

  • Immunic has decided to focus its resources on vidofludimus calcium and IMU-856, deprioritizing the clinical portion of its izumerogant development program in psoriasis and castration-resistant prostate cancer.

  • For IMU-856, the part C portion of the ongoing phase 1 trial in celiac disease patients has been proceeding more quickly than anticipated, with initial data expected to become available in the current quarter.