Survival rate improvement for extremely pre-term infants

 A new study co-authored by a University of Rochester Medical Center (URMC) researcher has found that the survival rates of extremely pre-term babies has increased significantly in the past decade.

The paper, "Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018," examined the survival outcomes of 10,877 infants born at 22-28 weeks' gestational age between January 1, 2013, and December 31, 2018, at 19 academic medical centers that form the NIH-funded Neonatal Research Network.

Survival among actively treated infants was 30.0% (60/200) at 22 weeks and 55.8% (535/958) at 23 weeks. This is a considerably higher rate of survival than when the study when previously conducted between 2008-2012, in which survival to discharge was 7% (22/334) for live-born infants at 22 weeks and 32% (252/779) for live-born infants at 23 weeks.

This improvement in outcomes for extremely pre-term infants can be attributed to multiple factors, including enhanced treatment protocols across participating medical centers, according to Carl D'Angio, M.D., co-author and Chief of the Division of Neonatology at URMC.

"Academic medical centers have been taking best-practices, applying them, and disseminating them to a wider and wider group nationally," said D'Angio.

Collective improvement in care in a variety of areas has contributed to the change in outcomes, according to D'Angio. "When we look at survival at almost any group of infants, it's a bundle of factors. There are similarities and differences in the way they're treated at various centers, but there are elements where we've collectively moved forward, such as ventilation, nutrition and hydration."

When infants are born at 22 or 23 weeks, nearly every organ is immature, with the lungs and the brain being among the systems most at risk, according to D'Angio.

In addition to studying survival outcomes, the paper assessed the health of severely pre-term infants after two years, including effects such as neurodevelopment, cerebral palsy, vision, hearing, rehospitalizations, and need for assistive devices. Slightly more than 8% had moderate to severe cerebral palsy, 1.5% had vision loss in both eyes, 2.5% needed hearing aids or cochlear implants, and 15% required mobility aids such as orthotics, braces, walkers, or wheelchairs.

Nearly 49% had no or only mild neurodevelopmental impairment, about 29% had moderate neurodevelopmental impairment and roughly 21% had severe neurodevelopmental impairment.

This study -- and overall improvement in outcomes -- can help clinicians provide clear information in discussions with families when babies are born extremely pre-term.

"We as clinicians support parents in a shared decision-making process when babies are born at the limits of viability," said D'Angio. "The imminent delivery of an extremely premature infant is a major stressor for families. An important part of helping parents cope is presenting the data we have and letting parents know what to expect in the long-haul. This latest study is positive news for shaping those discussions and providing a more optimistic probability for good outcomes."

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Story Source:

Materials provided by University of Rochester Medical Center. Original written by Scott Hesel. Note: Content may be edited for style and length.

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Journal Reference:

1. Edward F. Bell et al. Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA, 2022 DOI: 10.1001/jama.2021.23580

https://www.sciencedaily.com/releases/2022/04/220401160552.htm

Shanghai Lockdown Expanded To Cover Entire City

 Unfortunately for the CCP bureaucrats in charge of China's largest city, the punishing 9-day staggered lockdown imposed late last month on Shanghai has failed to suppress the omicron driven outbreak in the city. Instead,  cases have continued to rise, prompting authorities to expand the scope of what was supposed to be a short-lived staggered freeze to cover the city's entire population.

The eastern half of Shanghai remains under tight movement restrictions even after a four-day lockdown was supposed to have ended Friday morning. This means the entire city of roughly 26 million is currently under some form of restrictions as the lockdown in the western half of the city begins, Bloomberg reports.

While the lockdown of Shanghai’s east officially ended at 5 a.m. local time Friday, most residents were not able to leave their homes immediately under what the local government described as a tiered quarantine regime.

People with mild or no symptoms are required to be put under compulsory central quarantine for treatment or monitoring at mostly makeshift facilities built in massive gymnasiums or exhibition centers around the city. If parents with young kids are sent to central quarantine, authorities will try to help find volunteers or staff to look after the children left behind, Zeng Qun, deputy head of Shanghai Civil Affairs Bureau said at a briefing.

The rules also required anyone living in a building where a Covid case has been reported to stay confined in their home for two weeks. Residents of other buildings in the same compound as the block where a positive patient was reported will be subject to seven-day home quarantine.

Thanks to these "targeted" restrictions, nearly all of the nearly 9 million residents living in the eastern half of Shanghai were still subject to some form of COVID restrictions. Nearly 40% of Saturday’s newly reported infections in the city came from Pudong, the eastern part.

Now that the outbreak in Jilin Province has subsided (a punishing multi-week lockdown in that province has finally been lifted), Shanghai has emerged as the epicenter of China’s worst virus outbreak since the early days of the pandemic. The financial center's daily case count has surged from less than five at the beginning of March to a peak of more than 6,300 on Friday.

"At present, the epidemic situation is severe and complex, and the task of prevention and control is extremely arduous," Wu Qianyu, an official at the Shanghai municipal health commission, said at a media briefing.

To be sure, it's likely that the increase in new cases is a result of further screening. Authorities tested more than 14 million people in the western half of the city Friday as part of two-round tests.

Last month, President Xi Jinping instructed local authorities to take a more nuanced approach to combating COVID. While preserving human life must remainthe priority, the president urged policy makers to embrace more "targeted" measures - including an increase in testing and locally-focused lockdowns on residential complexes where cases had been confirmed.

But the continuing spread of the virus in Shanghai is the biggest test yet of Xi's plan to preserve economic growth without sacrificing lives. Amid reports of deaths of old folks homes and a surge in medical emergencies, local public health authorities have ordered hospitals and clinics across the city to reopen emergency wards amid reports that people were being denied access to treatment during the lockdown. There has even been a case of one individual dying after being turned away from a hospital due to COVID protocols, according to the SCMP.

Meanwhile, authorities have employed robot emissaries like this robot dog to bark instructions at local residents as the citywide testing campaign continues.

While millions of Chinese will likely suffer as the government scrambles to provide enough food, medicine and other emergency supplies to the increasingly desperate population, there's one individual who stands to benefit: President Joe Biden. Assuming news of the tighter lockdown sends crude oil prices lower, Biden might be able to take credit, given the timing of the SPR release announcement earlier this week (although few sell-side analysts expect the decision to have a meaningful impact on prices long term).

https://www.zerohedge.com/covid-19/shanghai-lockdown-expanded-cover-entire-city-covid-cases-continue-climb

Biden likely to sign bill that would crack down on China's chokehold on antibiotic supply

 The Senate on Monday passed (68-28) a wide-ranging, Biden-backed and already House-passed bill that would bolster American manufacturing, and try to crack down on China’s control of certain vital supplies like pharmaceuticals.

China quickly reached the forefront of API and generic drug manufacturing worldwide over the last decade, thanks in part to low labor costs, as the FDA’s data show the number of registered facilities making APIs in China more than doubled between 2010 and 2019.

Members of Congress on both sides of the aisle have warned of the national security implications of such an overreliance on China-made APIs and drugs, particularly as safety concerns have cropped over the years following inspections.

But the US is also equally reliant (if not more so) on India-made APIs and generic drugs. New USP data show that the number of manufacturing facilities with more than 10 active US-approved API products totaled 183 in India, 83 in Europe, and 35 in China. But for facilities making 30 or more active US-approved APIs, 114 are based in India, 45 in the EU, and 4 in China.

Still, the new COMPETES bill, which Biden previously supported, needs to have all its details ironed out between the House and Senate. But according to the Senate text, it would bring together the Department of Justice, the FTC and other federal agencies to investigate allegations of market manipulation and other potential violations of US laws by Chinese companies, such as controlling the supply of goods in critical industries of the US.

The first targeted industry listed by the bill is the pharmaceutical and medical devices industry.

The Senate bill’s text also calls on the US to work with its European counterparts to wean their overreliance on pharma products originating from China.

“The United States, European Union, and European countries should coordinate on joint strategies to diversify reliance on supply chains away from the People’s Republic of China, especially in the medical and pharmaceutical sectors,” the text says.

Both the Biden and former Trump administrations have sought to bring more pharma manufacturing back to the US, with hundreds of millions in funding for manufacturing companies like Phlow, but it remains to be seen how quickly this manufacturing can be brought onshore, or even the real extent of China’s control over these markets.

US-funded Phlow's first round of essential generics headed to children's hospitals, but they're made with foreign APIs

A 2019 op-ed in the Washington Post from California Democrat Reps. Anna Eshoo and Adam Schiff called China’s control of pharma manufacturing a national security issue, and discussed how China produces the ingredients found in almost every antibiotic and blood pressure medicine and hundreds of other drugs.

But the FDA previously explained that it still does not have the data to calculate the volume of APIs being used for US-marketed drugs from China, or India.

As former acting FDA commissioner (and current deputy commissioner) Janet Woodcock told a House subcommittee in 2019, “We do not know whether Chinese facilities are actually producing APIs, how much they are producing, or where the APIs they are producing are being distributed worldwide, including in the United States.”

https://endpts.com/biden-likely-to-sign-a-bill-that-would-crack-down-on-chinas-chokehold-on-the-antibiotic-supply/

Cancer drug developers will learn from speed of Covid vaccine race: FDA leaders

 The whole world watched in awe as the first two Covid-19 vaccines quickly made their way through clinical trials, offered stellar efficacy results and were quickly ushered across the FDA finish line in record time.

As a result, leaders of the FDA’s Oncology Center of Excellence wrote recently in the Cancer Journal that now is the time to leverage the lessons learned from that high-speed race and translate them into new opportunities for future oncology drug development.

Among the highlights worth repeating in cancer trials: frequent, open, clear communication and information sharing across FDA, academia, and community/industry partners, as well as the speed and agility of trial initiation, and the “collective sense of necessity,” all of which may benefit the development of new cancer therapies, Donna Rivera, associate director of pharmacoepidemiology in the FDA’s OCE, and colleagues wrote.

Offering the example of the UK’s RECOVERY trial, which swiftly brought conclusions on the merits of several Covid-19 treatments, the OCE authors called for more adaptive trial methods, common protocols and common control arms in oncology, as well as more on platform and basket trial designs, on which the agency recently offered guidance.

The FDA also explained how there’s now “ample evidence that protocols have become more complex over time and that a conscious effort to simplify will make participation more feasible for investigators, particularly when trials are conducted in the context of clinical care.”

And while cancer drug development has been slow to adopt decentralized trial methods and telehealth, due to concerns about data variability, OCE authors called to increase the flagging of remote assessments at the case-report form level to allow analyses to unlock further information on the potential effects of decentralized modifications on data variability.

The second iteration of the 21st Century Cures Act is also making its way through Congress and seeks to expand the use of real-world evidence in confirmatory trials for certain accelerated approvals.

Cures 2.0: Bipartisan House bill would allow RWE to satisfy confirmatory trial requirements for accelerated approvals

Rick Pazdur, head of the FDA’s OCE, told Endpoints News in a statement, “Use of RWE for aid in regulatory decision-making would depend on the strength of the available evidence and its applicability to the patient population.”

The OCE authors also noted that while the use of real-world data informed and guided the pandemic response, “there is a significant distinction” between the use of RWD for descriptive purposes and using RWD to generate evidence that determines whether a drug works.

“The pandemic provides the field with a clear lesson that the benefit of RWD availability and faster analytics must be balanced with the importance of careful design and methods to create the high-quality RWE necessary to support evidence-based intervention strategies,” they wrote. “The pandemic can become a watershed moment to forge unprecedented change in health care delivery and clinical trials through a dynamic modernization effort supported by adequate infrastructure funding and carefully coordinated global stakeholder collaboration.”

https://endpts.com/cancer-drug-developers-will-learn-from-the-blazing-speed-of-the-covid-19-vaccine-race-fda-leaders-say/

Celsius aims to cool down inflammation with new investors and more pharma deals

 Broad Institute spinout Celsius Therapeutics is turning up the heat on the financing front as it looks to ice the symptoms of inflammatory bowel disease.

The Cambridge, MA biotech has added $83 million in new financing — a mixture of a Series A extension and Series B funds — to chase its vision of precision therapies across autoimmune diseases and cancer. The Third Rock- and GV-backed startup, founded in 2018, brought in new investors like Amgen Ventures, Amplitude Ventures and Fast Track Initiative.

Keep an eye on Fast Track, the Tokyo VC firm that’s “very plugged into Japanese pharma companies and the Japanese business environment,” Celsius CEO Tariq Kassum told Endpoints News. Prior to his roles at Celsius and Obsidian Therapeutics, Kassum held multiple director and senior director positions at Takeda and its Millennium unit from 2009 to 2016.

“Certainly from my experience at Takeda, I have a lot of respect for” pharmas and academic institutions in Japan, Kassum said. Celsius is “talking to all kinds of pharma companies” about partnerships, including ones in Japan, the CEO added.

Celsius will deploy the new funds on bringing its first treatment into the clinic in early 2023. The first stop? IBD. Only 20% to 30% of patients experience sustained remission from approved drugs in the IBD space, Kassum said.

In steps Celsius’ anti-TREM-1 antibody, named CEL383. After an initial healthy volunteer study, Celsius wants to enable “patient selection and patient stratification,” as part of its precision therapeutics mission for the drug, Kassum said. He noted the precision medicine thesis of Casdin Capital, the Series B lead investor.

“The future of treatment of autoimmune disease is being able to identify subsets of patients who can respond to your therapy,” the CEO said.

Celsius chose TREM-1 based on the biotech’s single-cell analysis on hundreds of clinical samples, which is the result of collaborations with the University of Oxford, Cleveland Clinic, LMU University Hospital Munich and other academic institutions. The myeloid target plays a role in IBD by boosting inflammation “at the intersection of the microbiome and the immune system,” the company said.

TREM-1 is the basis of French startup Inotrem, which is studying nangibotide, an inhibitor of the pathway, in multiple mid-stage studies in patients with septic shock and Covid-19. Inotrem is expanding its anti-TREM-1 work with a monoclonal antibody, yet to be tested in humans. Also in the TREM-1 space is Pionyr, half-owned by Gilead, which is testing a mAb in patients with advanced solid tumors in a Phase Ia/Ib study.

Covid-19 roundup: Inotrem loads up on French funding to take septic shock candidate to the next stage; Belgian woman dies after being infected with 2 variants of concern

On the partnership side, Celsius said Thursday that it’s made progress on its $700 million colorectal cancer collaboration with Servier. The French pharma has selected the first target candidate in the three-program deal, a step that provides “great validation” for Celsius’ platform, Kassum said.

Celsius also has a partnership with J&J’s Janssen, but the biotech is more tight-lipped about this tie-up. Kassum said Celsius is performing analyses on certain Janssen clinical trials, declining to disclose which ones. The companies said in July 2019 that Celsius would use single-cell genomics and machine learning to “identify predictive biomarkers of response” in Janssen’s Phase IIa VEGA study.

That trial showed a combo therapy of Tremfya and Simponi ARIA led to better clinical response at week 12 versus either as a solo treatment in patients with ulcerative colitis, Janssen said last month.

https://endpts.com/celsius-aims-to-cool-down-inflammation-with-new-investors-and-more-pharma-collabs/

Dems fractured on response to end of Title 42

 The Biden administration’s decision to end to Title 42, a Trump-era policy restricting asylum claims, garnered a fractured response from Democratic lawmakers, advocates and the administration itself.  

Progressives and immigration advocates lauded the decision, arguing it was long overdue after President Biden pledged to end the rule during his 2020 campaign.  

However, moderate Senate Democrats issued a rebuke of the recission, claiming that the administration is not ready to manage a surge of migrants they say will come once the rule is nixed. 

The administration rescinded the rule on Friday, and administration officials distanced themselves politically from the decision, which they said was motivated by public health considerations. 

Under Title 42, which is slated to end May 23, migrants at the border were summarily expelled from the country, rather than being processed under regular immigration rules and allowed to exercise their right to claim asylum. 

The Biden administration used Title 42 around 1.7 million times, sometimes returning individuals back to Mexico on the same day, sometimes taking weeks to repatriate men, women and children to dangerous conditions in Haiti. 

While some Democrats openly celebrated the administration’s decision and called it a win, top Biden administration officials adopted a much more somber tone, warning the move could trigger an influx of migrants. 

“We have put in place a comprehensive, whole-of-government strategy to manage any potential increase in the number of migrants encountered at our border,” said Homeland Security Secretary Alejandro Mayorkas in a statement. 

Technically, Centers for Disease Control and Prevention (CDC) Rochelle Wollensky had sole authority to keep or remove Title 42, but few observers believe health care to be the true reasoning behind the policy. 

“It was increasingly hard to hear anybody with a straight face say this is completely about public health and not about immigration,” said Theresa Cardinal Brown, managing director of immigration and cross-border policy at the Bipartisan Policy Center. 

Brown added that migrants were expelled under Title 42 depending on various factors like their place of origin, “without regard to, honestly, the health risks from any particular group.” 

Still, top administration officials defended the sanitary reasoning both for keeping Title 42 for so long, and for announcing its upcoming end. 

“Title 42 is not an immigration authority, but rather a public health authority used by the Centers for Disease Control and Prevention to protect against the spread of communicable disease. Title 42 remains in place until May 23 and, until then, [the Department of Homeland Security] will continue to expel single adults and families encountered at the Southwest border,” said Mayorkas. 

Senate Majority Leader Chuck Schumer (D-N.Y.) was a leading critic of the Biden administration’s continued use of Title 42. 

Those critics were quiet shortly after the announcement, while other Democrats who were more reserved in picking a fight with the White House quickly came out to cheer the decision. 

“Today is a bright spot in our nation’s history with the end of the Trump-initiated Title 42 policy,” said Congressional Hispanic Caucus (CHC) Chair Rep. Raúl Ruiz (D-Calif.) in a statement. 

“The CHC repeatedly called for the end of this policy, which was fueled by Trump’s anti-immigrant hate and fear agenda that used the pandemic as an excuse to deny asylum seekers their legal right to due process,” he added. 

Progressives also celebrated the decision, crediting the Biden administration with doing the “right” and “moral” thing.  

“This is a momentous day for immigrant rights activists, and immigrants and refugees everywhere. Title 42 was a cruel and discriminatory policy that circumvented U.S. law, preventing people from accessing protections established by Congress,” said Congressional Progressive Caucus Chair Rep. Pramila Jayapal (D-Wash.) in a statement. 

“Today is the product of years of advocacy from both inside and outside Congress. I’m thrilled to see the Biden Administration do the right and moral thing by ending this extremely harmful, xenophobic, and shortsighted policy that disproportionately impacted Black and Brown migrants,” added Jayapal. 

Other progressives celebrated the announcement, withholding praise for administration officials. 

“After consistently calling on President Biden to end Title 42, I’m relieved to see the Administration has finally heeded our calls. Asylum seekers and their allies in the movement and in Congress have been organizing day in and day out to repeal this harmful policy,” said Rep. Ayanna Pressley (D-Mass.) 

“This long-overdue action will undoubtedly save lives and is a critical step towards building a fair and effective asylum system for all,” she added. 

Rep. Raúl Grijalva (D-Ariz.) took on a more diplomatic tone, neither celebrating nor criticizing the administration, but calling for a border management reset.

“The Biden administration must use this transition period to continue to address the longstanding backlog in the courts and the implementation of a comprehensive immigration plan that addresses not only enforcement, but rebuilds an asylum-seeking system that is just and humane,” said Grijalva in a statement. 

Some Democrats, however, came out hard against the rescission of Title 42, arguing that move would be disastrous for border management. 

Sen. Joe Manchin called its striking “a frightening decision” for an administration “nowhere near prepared” for an influx at the border. 

Both of Arizona’s Democratic senators sounded similar notes.  

“This is the wrong decision. It’s unacceptable to end Title 42 without a plan and coordination in place to ensure a secure, orderly, and humane process at the border,” Sen. Mark Kelly wrote. 

Sen. Kyrsten Sinema said the decision to end Title 42 “despite not yet having a comprehensive plan ready shows a lack of understanding about the crisis at our border.” 

Sen. Maggie Hassan (D-N.H.) who is up for reelection this year, also weighed in on Title 42 twice this week, saying Biden lifting the order “prematurely” would likely lead to a migrant surge “that the administration does not appear to be ready for.” 

Democratic Sens. Bob Menendez (N.J.) and Corey Booker (N.J. stated that while they supported the end of Title 42, but believed that it should be done in phases.

“While we support ending Title 42, extending this policy until the end of May will only incentivize more irregular migration to the border and create an unnecessary bottleneck effect when it finally sunsets,” they wrote.

“We hope the administration will expand exemptions to the original order and start lifting Title 42 in phases,” they added.

But amid the varied reactions, there is little data on whether the end of Title 42 will in fact cause a surge of migrants at the border, or how the Department of Homeland Security will deal with changing migration patterns.  

“As an immigration person, I’m thinking I still have no idea what’s going to happen to any individual person encountered,” said Brown, a former policy advisor at Customs and Border Protection (CBP). 

https://thehill.com/latino/3257470-democrats-fractured-on-response-to-end-of-title-42/

WHO suspends UN supply of Bharat Biotech's Covaxin vaccine for COVID-19

 

The World Health Organization said on Saturday it has suspended supply through United Nations agencies of COVID-19 vaccine Covaxin, produced by India's Bharat Biotech, to allow the manufacturer to upgrade facilities and address deficiencies found in an inspection.

The WHO asked countries that have received the vaccine to take appropriate actions, according to the statement, but did not specify what the appropriate actions would be.

The WHO said the vaccine is effective and no safety concerns exist, but the suspension of production for export will result in the interruption of Covaxin supply. It said the suspension is in response to the outcomes of WHO post emergency use listing (EUL) inspection conducted from March 14 to 22, and the vaccine maker has indicated its commitment to suspend production of Covaxin for export.

Bharat Biotech did not immediately respond to a request for comment sent outside business hours.

On Friday, the vaccine manufacturer said it was slowing production of Covaxin, as demand was dropping along with a fall in infections and wider immunisation coverage in the country.

The WHO said that the company has "committed to comply by addressing the GMP deficiencies and is developing a corrective and preventive action plan, for submission to the Drugs Controller General of India (DCGI)and WHO".

https://www.marketscreener.com/news/latest/WHO-suspends-UN-supply-of-Bharat-Biotech-s-Covaxin-vaccine-for-COVID-19--39951991/