Eli Lilly's diabetes drug back to shelf after two-month shortage

 Eli Lilly & Co said on Tuesday all doses of its new diabetes drug Mounjaro were now available with wholesalers having inventory on hand after a two-month-long shortage.

"Because Mounjaro is still a launch product with dynamic demand, some pharmacies may continue to experience intermittent delays from time to time," Eli Lilly told Reuters in an emailed statement.

In December, the U.S. health regulator had added Mounjaro to its list of drugs facing shortages, highlighting Lilly's struggles to meet booming demand for the newly approved diabetes injection.

Due to its potential to help patient lose weight, Mounjaro is being recommended by doctors for that purpose even though it has not been explicitly approved as an obesity treatment in a common practice known as off-label prescribing, according to a report by Bloomberg News.

Lilly said it did not promote or encourage the off-label use of any of its medicines.

Mounjaro was approved in the United States last May to help people with type 2 diabetes control their blood sugar levels. The company anticipates the drug, which has the common name tirzepatide, to get nod for obesity, an even bigger market, next year.

https://www.yahoo.com/lifestyle/eli-lillys-diabetes-drug-back-001343555.html

How North Korea could use a Pacific 'firing range' to perfect its missiles

 If North Korea follows through on its threat to turn the Pacific Ocean into a "firing range", it would allow the isolated and nuclear-armed state to make technical advances in addition to signalling its military resolve, analysts said.

North Korea launched two short-range ballistic missiles (SRBMs) on Monday, after firing a massive Hwasong-15 intercontinental ballistic missile (ICBM) on Saturday.

Like most North Korean tests, those missiles all fell in the Sea of Japan, which is known as the East Sea in both Koreas.

But Kim Yo Jong, the powerful sister of leader Kim Jong Un, threatened on Monday to go further, saying North Korea's use of the Pacific as a "firing range" would depend on the behaviour of U.S. forces.

"This type of testing would have technical value as well as communicate the credibility of their nuclear deterrent," said Ankit Panda of the U.S.-based Carnegie Endowment for International Peace.

So far North Korea has fired three variants of the Hwasong-12 intermediate range ballistic missiles (IRBMs) over Japan and into the Pacific Ocean. The last such launch, in October 2022, flew a record distance for any North Korean missile.

There have been no reports of damage or casualties from launches over Japan, but international organizations have criticized Pyongyang for conducting such tests with no warning to civil aircraft or ships.

North Korea has never launched an ICBM on anything but a lofted trajectory, which sends missiles high into space rather than on the lower and longer flight paths that they would follow in real use.

Pyongyang says it does this out of concern for the safety of its neighbours.

"This is a concerning threat and a credible one: North Korea likely seeks to technically validate its longer-range missiles through testing into the Northern Pacific, as it has done with the Hwasong-12 in the past," Panda said.

The Hwasong-15 and Hwasong-17 ICBMs are the main candidates for this type of testing, he added.

REENTRY VEHICLES

Officials in South Korea and the United States have said it is unclear if North Korea has perfected the reentry technology that would protect a nuclear warhead during the fiery decent through the atmosphere.

Kim Yo Jong referenced that debate in her Monday statement, disputing claims by some experts that footage shot from Japan showed a reentry vehicle failing in flight.

"We have possessed satisfactory technology and capability and now will focus on increasing the quantity," she wrote.

Full-range tests into the Pacific would allow North Korea to subject ICBM reentry vehicles to atmospheric stresses and aggregate heat loads that would be more realistic compared to highly lofted trajectories, Panda said.

North Korea's ICBM technology is coming of age, and perfecting reentry vehicles would increase the threat and pressure on the United States, Shin Seung-ki, a Research Fellow at Korea Institute for Defense Analyses (KIDA).

"If that technology is successfully implemented through the test, they will be able to attack the U.S. mainland, which is the purpose of their ICBMs," he said.

North Korea can likely receive telemetry from its short-range and lofted missile tests, but it is unclear if they could collect data from long-range weapons tests, said Markus Schiller, a Europe-based missile expert.

"They should be able to collect inflight data as long as the missile is in sight," he said. "As soon as it is out of range, or if it crosses below the horizon, North Korea will be blind."

Schiller said he is not aware of any tracking vessels that North Korea positions along the flight path, and for now it doesn't have data relay satellites.

NUCLEAR TEST?

South Korean officials are not wrong to note that the North's reentry vehicles are unproven, but those assertions also tempt Pyongyang to conduct the tests necessary to prove its capabilities, George William Herbert, an adjunct professor at the Center for Nonproliferation Studies and a missile consultant, said on Twitter.

To make its point North Korea could resort to conducting a full-range test and detonate a live nuclear warhead over the ocean, he said.

In 2017, North Korea's foreign minister suggested leader Kim Jong Un was considering testing “an unprecedented scale hydrogen bomb” over the Pacific in response to U.S. President Donald Trump’s threat to “totally destroy” the country.

"The so-called Juche Bird live weapon test is a fun joke until the day they actually fire it, then will be a major geopolitical incident and radioactive fallout disaster even if 'safely' detonated high over water," Herbert said. "We shouldn’t be encouraging it by disparaging their capability."

North Korea has completed preparations to possibly resume nuclear detonations in the underground tunnels of its nuclear test site for the first time since 2017, according to officials in Seoul and Washington.

With or without an atmospheric test, North Korea would likely conduct multiple full-range ICBM tests, as well use its underground testing to perfect smaller but more powerful nuclear warheads, said Yoji Koda, a former admiral with Japan's Maritime Self Defense Force.

If those two conditions are met, then North Korea will have fully demonstrated its deterrence capability against the United States, he said.

https://www.yahoo.com/now/analysis-north-korea-could-pacific-050357147.html

Fresenius with profit slump - 2023 earnings only stable at best

After a slump in profits last year, the Bad Homburg-based Fresenius Group is preparing for another difficult year in 2023. Operating income adjusted for currency effects and special items (adjusted EBIT) is expected to remain stable only in the best case, while a decline in the high single-digit percentage range is not ruled out in the worst case, the Group announced surprisingly on Tuesday evening.

Last year, the hospital and medical technology company struggled badly as inflation, rising costs, staff shortages and supply chain problems weighed heavily. Although sales rose nominally by nine percent year-on-year to around 40.8 billion euros, adjusted operating profit fell by six percent; including exchange rate effects, the decline was eleven percent. Adjusted for special items, net income decreased nominally by seven percent to 1.7 billion euros. Fresenius 2022 thus performed more or less as analysts had feared after the two profit warnings last year.

The dialysis subsidiary Fresenius Medical Care (FMC) was the biggest burden, with 2022 profits plummeting by ten percent. The slump at the service provider Vamed was even more serious, but the performance of the liquid medicine specialist Kabi was also mixed, while Fresenius was able to increase its hospital business (Helios) for the year as a whole

https://www.marketscreener.com/quote/stock/FRESENIUS-MEDICAL-CARE-AG-436087/news/Fresenius-with-profit-slump-2023-earnings-only-stable-at-best-43044877/

Enfamil maker recalls 145K cans of potentially contaminated baby formula

 The maker of Enfamil announced a recall of about 145,000 cans of infant formula due to the possibility of cross-contamination with a bacteria that can cause serious illness or death.

Reckitt, a UK-based consumer health and nutrition company, said over the weekend that it is voluntarily recalling two batches of Enfamil ProSobee Simply Plant-Based Infant Formula, but that no illnesses or “adverse events” have been reported. The company said it identified the cause of the potential cronobacter contamination and are no longer using the supplier.

According to the the Centers for Disease Control and prevention, cronobacter infections in infants can be deadly. The bacteria occurs naturally in soil, water and other parts of the environment and can live in dry foods, such as powdered milk, herbal teas, starches and baby formula.

According to the CDC, cronobacter infections in infants can be deadly. The bacteria occurs naturally in soil, water and other parts of the environment and can live in dry foods.

REUTERS
Almost all previous outbreaks in the US have been linked to powdered baby formulas, which don’t undergo the same high temperatures used to kill germs in many other foods. Cronobacter typically causes fever in infants and can sometimes lead to dangerous blood infections or swelling of the brain.

Last year, a nationwide baby formula shortage was triggered by an Abbott Nutrition plant that had to be closed for months because of contamination problems.

Abbott recalled various lots of three powdered infant formulas from the plant, after federal officials began investigating rare bacterial infections in four babies who were fed formula. Two of the infants died. But it’s not certain the bacteria came from the plant; strains found at the plant didn’t match the two available samples from the babies.

For the most recent recall, consumers should check the packaging of their formula to make sure they didn’t purchase the recalled product. The product is Enfamil ProSobee Powder, 12.9 ounce can with a UPC number of 300871214415; global batch number of ZL2HZF or ZL2HZZ; lot number of 0670975 or 0670979 and an expiration date of March 1, 2024.

Consumers can return the product to wherever they bought it for a full refund. They can also call Reckit at 1-800-479-0551 or email the company at consumer.relations (at) rb.com.

https://nypost.com/2023/02/21/enfamil-maker-recalls-potentially-contaminated-baby-formula/

Why America needs a COVID truth commission

 When America faced the national tragedy of the Space Shuttle Challenger exploding in 1986, Congress created a commission with independent outside experts, including the Nobel Prize-winning physicist Richard Feynman. His iconic demonstration of a faulty O-ring made brittle in the cold as the cause of the Challenger disaster led to fundamental reforms at NASA.

The American people deserve a similar bipartisan, scientifically minded COVID-19 commission so the public-health disaster of the past three years is not repeated.

Due to insufficient protection of older people — whose COVID-mortality risk is more than 1,000-fold higher than that of the young — official counts attribute more than 1 million deaths to COVID in the United States and almost 7 million worldwide. Though people vehemently disagreed about the wisdom of lockdowns, school closures, vaccine mandates and discrimination, masks and so much else, there is near-universal agreement that what we did failed.

By early 2022, about 95% of Americans had contracted COVID despite the harsh countermeasures. A John Hopkins University meta-analysis concluded that lockdowns failed to contain the spread of COVID. At best, they temporarily protected the laptop class, who could work from home while being served by the working class.

Workers manufacturing antigen testing kits for COVID-19.

REUTERS

The pandemic response itself has wrought tremendous collateral harm. There is now broad agreement that the school closures — in some states running a year or more — have set kids behind in ways that will lead them to worse outcomes as adults, including shorter, poorer lives.

One peer-reviewed paper estimated the spring 2020 closures alone may have cost American children millions of years in life expectancy. The damages are unequally distributed, with poor and minority children suffering the worst learning losses. Hundreds of thousands of kids never returned when schools finally opened.

So the American people deserve answers to fundamental questions about the pandemic. On what empirical basis were schools closed? Did public-health decision-makers consider the harms of their policies? Why do American public-health authorities insist on masking children as young as 2 years old when mask wearing “makes little or no difference” for COVID’s spread?

Perhaps the most perplexing sin of the public-health establishment is that it abandoned an essential commitment to science. For instance, why did public-health authorities ignore clear scientific data that COVID infection-acquired immunity is stronger than vaccine-acquired immunity? Vaccine mandates forced many frontline workers — heroes who contracted COVID early in the pandemic while doing essential work — to choose between their careers and a vaccine that provides less protection than the natural immunity they already had. University presidents forced young male students, including those with excellent immunity from a prior COVID infection, to accept an elevated risk of myocarditis as the price of a college education.

Many, faced with these anti-scientific choices, will never trust public-health authorities or university scientists again, even on vital topics such as the necessity of traditional childhood vaccines.

By early 2022, about 95% of Americans had contracted COVID despite the harsh countermeasures.

REUTERS/Eduardo Munoz

One reason for the public-health establishment’s systematic failure to arrive at correct answers to basic scientific questions is that the authorities sealed themselves off from outside criticism. Under the banner of combating “misinformation,” government health agencies used their power to collaborate with social-media companies to control the public conversation about COVID science and policy.

Though both of us have decades of experience on infectious-disease epidemiology and policy, the Twitter files revealed that we were both placed on “trends blacklists,” guaranteeing that few would hear our message when the government got the science wrong.

With such a litany of failures, the American people deserve an honest COVID commission to evaluate the response and document all the errors as well as the few successes. Working as part of a team of eight scientists with experience in infectious diseases, public health, epidemiology, immunology, clinical medicine and COVID treatment, we have produced a blueprint with 80 pages of questions that such a commission should ask. We call it the Norfolk Group document, and it is available at no charge at norfolkgroup.org.

We encourage lawmakers, public-health officials, scientists, journalists and the public to read, ask and answer these questions about the most ineffective and damaging public-health response in history.

Martin Kulldorff is a professor of medicine at Harvard University (on leave). Jay Bhattacharya is a professor of health policy at Stanford University School of Medicine. Both are founding fellows of the Academy for Science and Freedom, a Hillsdale College initiative to restore integrity and trust in science and public health.

https://nypost.com/2023/02/21/why-america-needs-a-covid-truth-commission/

Hong Kong pulls visa for ‘CRISPR babies’ scientist He Jiankui

 Hong Kong on Tuesday revoked a visa it granted to a Chinese scientist who set off an ethical debate five years ago with claims that he made the world’s first genetically edited babies, pulling it hours after he announced his research plans in the financial hub.

He Jiankui shocked the world in 2018 when he announced he had altered the embryos of twin girls, with many in the scientific community criticizing his work as unethical. He was convicted by a mainland Chinese court in 2019 of practicing medicine without a license and sentenced to three years in prison with a fine of 3 million yuan ($445,000).

Ten months after his release, He announced in Beijing on Tuesday that he had been granted a Hong Kong visa and was in contact with universities, research institutes, and companies in the financial hub.

He said he would consider working in Hong Kong if there were an appropriate opportunity, and that he plans to research gene therapy for rare hereditary diseases.

“My scientific research will comply with the ethics codes and international consensus on scientific research,” he said at a brief news conference.

But in a statement hours later in which it didn’t refer to He by name but said it was responding to reports about a visa applicant who was jailed because of illegal medical practices, the Hong Kong government said it had revoked the visa.

“After the immigration department reviewed the application, it suspected that someone had made false statements to get the visa approval,” the statement wrote. “The director of immigration has declared that the visa is invalid in accordance with the law.”

Law enforcement officers would conduct a criminal investigation to follow up the case, it added.

He didn’t immediately reply to an Associated Press request for comment.

His announcement in 2018 sparked a global debate over the ethics of gene editing. In interviews with The Associated Press, he said he had used a tool called CRISPR to try to disable a gene that allows HIV to enter cells in an attempt to give the babies the ability to resist AIDS.

The CRISPR tool has been tested elsewhere in adults to treat diseases, but many in the scientific community criticized He’s work as medically unnecessary and unethical partly because any genetic changes could be passed down to future generations.

In convicting him in 2019, the Chinese court in Shenzhen said he had not obtained qualifications as a doctor, had pursued fame and profit, deliberately violated Chinese regulations on scientific research, and crossed an ethical line in both scientific research and medicine. The court also confirmed a third birth, saying his project involved three gene-edited babies born to two women.

He was released last April and was invited to speak at the University of Oxford next month. But he wrote on Twitter this month that he was not ready to talk about his experiences over the last three years and decided to cancel the visit.

He invited about six media organizations to his news conference on Tuesday but left after reading a statement for about two minutes. He did not respond to questions as he left.

In a later written response, he said he plans to form an advisory committee on ethics to vet his future work and make sure the process is open and transparent.

He said he plans to research Duchenne muscular dystrophy, a genetic disorder that he said often causes people to die of heart and lung failure when they are about 20 years old. No medicine can cure the disease but gene therapy might help, he said.

He said his team hopes to use AI tools to improve gene therapy and lower the costs of the treatment to make it affordable to every family.

Earlier in Hong Kong, the granting of a visa to He under a new program to woo global talent raised concerns that recipients might have criminal records.

According to the Immigration Department, applicants should meet normal immigration requirements, including having a “clear criminal record” and raising “no security or criminal concerns” to Hong Kong.

Hong Kong Labour Minister Chris Sun refused to comment on individual cases but acknowledged that applicants have not needed to disclose any criminal record in the application process. He said applicants will have to do so starting Wednesday.

https://www.statnews.com/2023/02/21/hong-kong-pulls-visa-he-jiankui-crispr-babies/

Keeping Bones Healthy Through Exercise

 Studies looking into the impact of exercise continue to conclude that we all need to get moving, even little kids. So, how strange is it that, at the same time, the levels of inactivity are increasing worldwide?

On January 20, the 36th Scientific Day of the Osteoporosis Research and Information Group (GRIO) took place in Paris. This was an opportunity to remind people that physical activity has a significant influence on building and preserving bone mass.

We all know the public health messages about regular physical activity and its benefits. But what do we, in the year 2023, know about the role that regular physical activity plays in our bone health?

Laurence Vico, PhD, is the director of SAINBIOSE (Health, Engineering, Biology, Saint-Etienne), Unit U1059 of the French National Institute of Health and Medical Research (INSERM). This is the same laboratory that was featured in news stories reporting on the research that she conducted involving cosmonauts on the International Space Station. Vico attended the GRIO event, where she gave an overview on managing osteoporosis without medication.

Sports and Osteogenesis

Some sports are better for bones than others. Physical activities are associated with corresponding ground reaction forces. Examples include weightlifting (three to seven times one's body weight), jumping events (two to eight times one's body weight), running (1.5 to 3 times one's body weight), and walking (one time one's body weight). These mechanical loads stimulate osteoblasts, thus promoting bone remodeling.

By contrast, nonimpact sports — for example, cycling and swimming — are less osteogenic and, as such, significantly less beneficial to bone formation. Nothing new here, except that the latest scientific data are not as clear-cut. What they show is that an increase in bone mass could occur in swimmers, particularly in their upper limbs.

Researchers are particularly interested in sports like tennis and baseball, where one arm or leg is loaded more than the other. This is because the less active limb can act as an internal control for the more active limb. In addition, mean side differences in bone density have been observed in the humerus cortical area among tennis players.

Pediatric Osteoporosis

Being physically active in adolescence increases the chances of having healthier bones later in life. This makes perfect sense in light of biomechanical studies. "They all point in the same direction," said Vico. Intense physical exercise during the peripubertal period provides lasting benefits with respect to bone geometric parameters. According to a computer simulation of the bone remodeling process, the onset of osteoporosis is predicted to be delayed by 13 years if the young adult areal bone mineral density is 10% higher than the mean.

Prepuberty and early stages of puberty are the periods now viewed as the window of opportunity in which to increase peak bone mass. It is, however, known that what matters more than bone mineral density (BMD) is bone size.

Most available studies, though, are still about BMD. For example, there was a meta-analysis of 22 trials conducted in children and adolescents representing all Tanner stages (stage I through stage V). Exercise interventions included games, dance, resistance training, and jumping exercises. All trials in early pubertal children, six in prepubertal children, and two in pubertal children reported positive effects of exercise on bone. Mean increases in bone parameters over 6 months were 0.9%–4.9% in prepubertal children, 1.1%–5.5% in early pubertal children, and 0.3%–1.9% in pubertal children, compared with controls (P < .05).

An earlier study on female tennis and squash players showed that physical activity during the pubescent years is crucial for maximizing bone mass. Whereas there is the potential for exercise-induced bone gain in adults, the benefit is about two times greater if women start their playing careers at or before menarche (humeral side-to-side difference, 17%–24%) than after menarche (8%–14%).

Bones Over Time

More evidence of the benefits of exercise on bone health indicates that engaging in sports over a long period of time helps to keep a higher BMD in later years.

For example, one retrospective study sought to determine the long-term effect of exercise on BMD, bone mineral content (BMC), and body composition in 48 postmenopausal women (54-73 years of age). Half (24) of the women had been elite athletes during their youth; all had long-term (> 20 years) histories of significant training and performance. Half had been swimmers, and half runners. They were age matched with 24 sedentary controls. There were no significant differences in activity levels between athletes and controls at the time of this study.

BMD and BMC were not significantly different between athletes, but they were significantly higher in athletes than in controls. The researchers concluded that physical activity during youth seems to have a beneficial effect on bone mass and helps to prevent bone loss due to aging.

Bone Microarchitecture

It is now clear that trabecular and cortical bone microarchitectures are reinforced by the mechanical stresses induced by physical exercise, but in different ways. "The results of a study published in 2020 support previous findings, showing that these two types of bone — trabecular and cortical — do not behave in the same way," Vico explained.

"What these researchers found was that, no matter what the sport — in this case, cricket, running, swimming, hockey — the trabecular BMD is higher in all athletes, compared with controls. There are no credible differences between different sporting groups. The same cannot be said in terms of the cortical bones," Vico explained. "The study's results suggest that cortical midshaft hypertrophy is associated with impact loading, while trabecular BMD is positively associated with impact and nonimpact loading. This means that depending on the bone compartment, the adaptations are different...For cortical bone, there needs to be discontinuous rather than continuous impacts, having unusual directions and with sufficient force to create a stimulus. As for trabecular bone, we still don't know what type of signal can reach and stimulate bone cells, in particular osteoblasts."

Regarding bone adaptation in athletes who cease or who continue engaging in sports activities, a study of baseball pitchers found that at the level of the humerus, density-weighted polar moment of inertia (which indicates torsional bone strength) and cortical thickness were greater in continuing throwers than in former throwers.

On the other hand, for anything relating to trabecular bone and even BMC, there was no notable difference.

"Due to a different cortical thickness, those who continue the sport benefit in terms of biomechanical properties," said Vico. "It should also be noted that the more developed these properties are, the higher the bone's resistance to fracture. And so, it turns out that BMD, which has always been highlighted, is insufficient for assessing the adaptation of the bone to mechanical stimuli."

Vico, the director of SAINBIOSE, INSERM Unit U1059, reports that she has no relevant financial relationships in connection with this presentation.

https://www.medscape.com/viewarticle/988531