Galapagos initiates Phase 3 in axial spondyloarthritis

 

• OLINGUITO Phase 3 program in adults with axial spondyloarthritis (AxSpA) to include two parallel studies to investigate the efficacy and safety of filgotinib in patients with active radiographic AxSpA (r-AxSpA) and non-radiographic AxSpA (nr-AxSpA)
• Results from Phase 2 TORTUGA study showed that filgotinib 200mg was efficacious and well-tolerated in patients with r-AxSpA
• Filgotinib, an oral, once-daily JAK1 preferential inhibitor, is currently approved in Europe and Japan for the treatment of rheumatoid arthritis (RA) and ulcerative colitis (UC)

https://www.biospace.com/article/releases/galapagos-initiates-phase-3-program-with-filgotinib-in-patients-with-active-axial-spondyloarthritis/

House advances debt bill, tossing ball to Biden

 

House Republicans approved a sweeping plan to raise the debt limit while pushing various proposals to curb government spending. The GOP hopes to use the bill to force President Biden to the negotiating table.

© Greg Nash, The Hill

House Republicans delivered a key victory for Speaker Kevin McCarthy (R-Calif.) on Wednesday by narrowly approving the party’s debt limit proposal.   The passage caps off grueling negotiations that put the deep divisions within the GOP conference on full display, foreshadowing the challenge that awaits both sides in striking a deal to prevent a default.   “It takes a lot of work when you have that slimmer majority,” Rep. Kevin Hern (R-Okla.), chair of the Republican Study Committee, told The Hill on Wednesday. “You have to manage the questions, you have to manage the expectations of members that may have a concern, how that’s gonna impact them back home or what they have an issue with personally.”   Republicans passed the Limit, Save, Grow Act in a 217-215 vote on Wednesday afternoon, with GOP Reps. Ken Buck (Colo.), Matt Gaetz (Fla.), Andy Biggs (Ariz.) and Tim Burchett (Tenn.) voting with every Democrat in opposition.   The bill would raise the debt ceiling by $1.5 trillion or through the end of next March, whichever happens first, in exchange for a wide range of Republican proposals to decrease government spending that, according to the Congressional Budget Office (CBO), would put $4.8 trillion toward deficit reduction over the next 10 years.   The bill would cap federal funding hashed out as part of the annual appropriations process at fiscal year 2022 levels, while also limiting spending growth to 1 percent every year over the next decade.    Republicans are hopeful the bill’s passage will put pressure on Democrats to come to the bargaining table to hammer out a bipartisan compromise to raise the debt ceiling with fiscal reforms.    “It’s long past time that President Biden gets off the sidelines and does his job, and gets to the negotiating table with Speaker McCarthy so we can solve this problem and put America on a stronger financial footing that will benefit all Americans,” House Majority Leader Steve Scalise (R-La.) said on the floor Wednesday. https://thehill.com/newsletters/business-economy/3974283-house-advances-debt-bill-tossing-ball-to-biden/

Biden admin files suit against Tennessee ban on 'lifesaving care' for transgender youth

 The Department of Justice filed a lawsuit Wednesday against Tennessee’s recently-signed law that bans gender-affirming care for minors, alleging the law violated the 14th Amendment’s equal protection clause.

Tennessee Gov. Bill Lee (R) signed the bill banning the care last month, making it just one of a number of Republican-led states that have taken similar action. The Biden administration is challenging the law in federal court. The DOJ called the Tennessee measure a “ law that denies necessary medical care to youth based solely on who they are.”

“The complaint alleges that SB 1’s ban on providing certain medically necessary care to transgender minors violates the Fourteenth Amendment’s Equal Protection Clause,” the DOJ said in a release on Wednesday.

The DOJ argued the law violates the equal protection clause because it prohibits transgender youth from accessing some “medically necessary” care while allowing others access to the same or similar care. 

“No person should be denied access to necessary medical care just because of their transgender status,” said Assistant Attorney General Kristen Clarke of the DOJ’s Civil Rights Division.

Major medical associations agree that the type of care being targeted by a number of Republican-led states is appropriate for adults — and kids — who have gender dysmorphia, which is defined by the American Psychiatric Association as “clinically significant distress or impairment related to gender incongruence”

At least 11 Republican-led states have total or partial bans on gender-affirming care for minors, according to an ABC News analysis.

The law in Tennessee states that minors cannot be held accountable for receiving the care but parents and legal guardians could face legal action if violating the state’s ban. It also allows the state’s attorney general to fine healthcare providers for providing care.

https://thehill.com/homenews/administration/3974334-biden-administration-files-suit-against-tennessee-ban-on-lifesaving-care-for-transgender-youth/

Testing antibiotic resistance with a fast, cheap, and easy method

 "We have developed a technique in our laboratories that allows us to obtain an antibiogram within 2-4 hours -- instead of the current 24 hours for the most common germs and one month for tuberculosis," says Dr Sandor Kasas at EPFL. Professor Ronnie Willaert at Vrije Universiteit Brussel adds: "Our technique is not only faster but also simpler and much cheaper than all those existing now."

Antibiotic resistance happens when bacteria develop the ability to defeat the drugs designed to kill them. It has now grown into a global public health issue. It was responsible for at least 1.27 million deaths worldwide in 2019 while being involved in nearly five million deaths. Every year, the US sees almost three million antimicrobial-resistant infections, with the cost of treating the six most common ones at over $4.6 billion. The EU sees almost 700,000 cases each year, which cost it an estimated €1.5 billion.

Antibiotic sensitivity testing (AST) uses culture methods that expose bacteria to antibiotics, or genetic methods to determine if bacteria possesses genes that confer resistance. Typical ASTs last up to 24 hours or even longer for slow-growing bacteria -- a timeframe that can mean life or death in a clinical setting. There have been some faster ASTs developed in recent years, but they tend to be complex, needing sophisticated and expensive equipment.

Now, researchers led by Kasas and Willaert have developed a fast, cheap, and widely accessible method based on optical microscopy that can perform an AST with single-cell sensitivity and without needing to attach or label bacteria. The technique uses a basic, conventional optical microscope, a camera or mobile phone, and dedicated software. The joint research project is published in PNAS.

The new technique is called optical nanomotion detection (ONMD), and involves the monitoring of nanoscale vibrations of single bacterial before and while being exposed to antibiotics. The monitoring is performed with a basic optical microscope, a video camera or a mobile phone.

The ONMD technique monitors the microscopic oscillations of bacterial cells (nanomotion) that characterize living organism and can be considered as a "signature of life." Indeed, nanomotion lasts as long the organism is alive but stops immediately when it is dead. In the ONMD technique, bacterial nanomotion is recorded in a movie in which all individual cell displacements are monitored with sub-pixel resolution.

The researchers used ONMD to successfully detect the sensitivity of numerous bacteria to antibiotics. Escherichia coli, Staphylococcus aureus, Lactobacillus rhamnosus, and Mycobacterium smegmatis (a non-pathogenic bacterial model for tuberculosis) sensitivities to the antibiotics ampicillin, streptomycin, doxycycline, and vancomycin was determined in less than two hours.

The ONMD not only monitors the bacteria life-death transitions upon exposure to different antibiotics but also highlights changes in the bacteria's metabolism caused by the availability of nutrients. The tests showed that ONMD can assess the sensitivity or resistance of bacterial cells to antibiotics in a simple and rapid way by monitoring cellular oscillations.

The authors state: "The simplicity and efficiency of the method make it a game-changer in the field of AST" as it can be applied to a wide range of bacteria, which has significant implications for clinical and research applications.

Journal Reference:

1. Maria I. Villalba, Eugenia Rossetti, Allan Bonvallat, Charlotte Yvanoff, Vjera Radonicic, Ronnie G. Willaert, Sandor Kasas. Simple optical nanomotion method for single-bacterium viability and antibiotic response testing. Proceedings of the National Academy of Sciences, 2023; 120 (18) DOI: 10.1073/pnas.2221284120

https://www.sciencedaily.com/releases/2023/04/230424162847.htm

Walking a leashed dog associated with risk of traumatic brain injury among adults

 Johns Hopkins University researchers have found that traumatic brain injuries (TBIs) were the second most common injury among adults treated in U.S. emergency rooms for injuries related to walking a leashed dog from 2001 to 2020. The researchers also found that women, and all adults age 65 and older, were more likely to sustain serious injuries, such as fractures and TBIs, than people in other demographic groups. The study was published in Medicine & Science in Sports & Exercise.

"According to a 2021-2022 national pet ownership survey, nearly 53%of U.S. households own at least one dog," says Ridge Maxson, the study's first author and a third-year medical student at The Johns Hopkins University. "Dog ownership also increased significantly in recent years during the COVID-19 pandemic. Although dog walking is a common daily activity for many adults, few studies have characterized its injury burden. We saw a need for more comprehensive information about these kinds of incidents."

The researchers were from the Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health. Using the National Electronic Injury Surveillance System database, which is operated by the U.S. Consumer Product Safety Commission, the researchers found that an estimated 422,659 adults sought treatment in U.S. emergency rooms for injuries resulting from leash-dependent dog walking from 2001 to 2020. Nearly half of all patients were adults age 40 to 64, and 75% of patients were women. Most injuries occurred due to falling after being pulled by, tangled in or tripped by the leash connected to a dog they were walking.

The three most common injuries among all adults were, in order, finger fracture, TBI, and shoulder sprain or strain. TBI and hip fracture were the two most common injuries among adults age 65 and older. TBIs identified in this study consisted of both concussions and nonconcussive internal head injuries, which can include brain contusion (a bruise of the brain tissue), epidural hematoma (bleeding in above the brain's outer membrane) or subdural hematoma (bleeding beneath the brain's outer membrane).

Notably, women with injuries related to dog walking were 50% more likely than men to sustain a fracture. Older dog walkers were more than three times as likely to experience a fall, more than twice as likely to have a fracture and 60% more likely to sustain a TBI than younger dog walkers.

Across the 20-year study period, the estimated annual incidence of injuries due to leash-dependent dog walking more than quadrupled. The researchers posit that this trend may be due to concurrent rising dog ownership rates and promotion of dog walking to improve fitness.

The team hopes its findings will promote awareness among dog owners and encourage clinicians to discuss the injury potential of leash-dependent dog walking with their patients.

"Clinicians should be aware of these risks and convey them to patients, especially women and older adults," says Edward McFarland, M.D., the study's senior author and director of the Division of Shoulder and Elbow Surgery at Johns Hopkins Medicine. "We encourage clinicians to screen for pet ownership, assess fracture and fall risk, and discuss safe dog walking practices at regular health maintenance visits for these vulnerable groups. Despite our findings, we also strongly encourage people to leash their dogs wherever it is legally required."

The team also analyzed cases of leash-dependent dog walking injuries among children under age 18. Those findings will be released in the near future.

Journal Reference:

1. Ridge Maxson, Christopher R. Leland, Edward G. McFarland, Jim Lu, Prashant Meshram, Vanya C. Jones. Epidemiology of Dog Walking-Related Injuries Among Adults Presenting to U.S. Emergency Departments, 2001-2020. Medicine & Science in Sports & Exercise, 2023; Publish Ahead of Print DOI: 10.1249/MSS.0000000000003184

https://www.sciencedaily.com/releases/2023/04/230425111154.htm

Invisalign maker Align Tech stock falls more than 5% after Q1 earnings

 Shares of Align Technology Inc. (ALGN) dropped more than 5% in the extended session Wednesday despite a beat for the maker of Invisalign orthodontic braces and other medical devices. Align earned $88 million, or $1.14 a share, in the first quarter, compared with $134.3 million, or $1.70 a share, in the year-ago quarter. Adjusted for one-time items, Align earned $1.82 a share. Revenue dropped 3.1% to $943.1 million, the company said. Analysts polled by FactSet expected adjusted EPS of $1.69 on sales of $903 million. The company guided for second-quarter revenue between $980 million and $1 billion, and flat to slightly higher gross margins. The FactSet analysts expect revenue of $951 million in the current quarter. Capital expenditures are likely to exceed $200 million, Align said, thanks to building construction and improvements as well as additional manufacturing capacity to support Align's ongoing international expansion. Shares of Align ended the regular trading day up 0.9%.

https://www.morningstar.com/news/marketwatch/20230426956/invisalign-maker-align-tech-stock-falls-more-than-5-after-q1-earnings

Fauci Admits Orwellian Mandates Fueled Anti-Vax Sentiment

 Anthony Fauci has admitted that government vaccine mandates he championed fueled vaccine hesitancy, and were 'counterproductive.'

In a wide-ranging interview with the NY Times, the now-retired Fauci admitted; "Man, I think, almost paradoxically, you had people who were on the fence about getting vaccinated thinking, why are they forcing me to do this?"

"And that sometimes-beautiful independent streak in our country becomes counterproductive," he added.

Fauci's comments come as fewer people are getting vaccinated for diseases that were once considered deadly in the United States, particularly among children's vaccinations for measles, pertussis and polio.

As the Daily Mail notes, the percentage of kindergarteners in America who have taken their required immunizations, including the measles, mumps, rubella (MMR) shot, fell to 93% for the 2021-2022 school year, dropping to 2% below the recommended levels for herd immunity, and well below vaccination rates in 2020-2021.

And though approximately 66 percent of US children aged five months were up to date for all childhood vaccines recommended by the Centers for Disease Control and Prevention in 2016 through 2019, that number declined to slightly over 49 percent by May 2020.

In all, US adults and adolescents have missed more than 37 million routine vaccinations during the Covid pandemic, according to an analysis of insurance claims from health consulting firm Avalere. 

Many experts believe the Covid shot requirements fueled vaccine hesitancy that had been brewing in the US for decades. -Daily Mail

Fauci, who gave conflicting information in both public and private regarding the effectiveness of masks, and quashed dissenting opinions over the origins of Covid-19 when a prominent scientist suggested that it looked potentially engineered (at a lab the NIH was funding), is believed to be one of the architects of the federal mandates - such as those issued by the Department of Labor's Occupational Safety and Health Administration (OSHA), the Centers for Medicare and Medicated Services (CMS), and the DoD.

In 2022, a review of vaccine mandates worldwide found that they could exacerbate cynicism and mistrust of the government.

"Compulsory COVID-19 vaccination would likely increase levels of anger, especially in those who are already mistrustful of authorities, and do little to persuade the already reluctant," reads the review, published in BMJ Global Health. "Two experiments in Germany and the USA found that a new COVID-19 vaccine mandate would likely energise anti-vaccination activism, reduce compliance with other public health measures, and decrease acceptance to future voluntary influenza or varicella (chickenpox) vaccines."

And in December, Cornell University found that mandates 'eroded public confidence' in vaccines even further.

"While significant percentages of vaccinated Americans and Democrats said that a vaccine mandate would make them more likely to re-engage in various aspects of pre-pandemic social and economic life, many fewer unvaccinated Americans and Republicans said the same," wrote the authors.

The federal mandates have since largely been struck down or rescinded amid multiple lawsuits - with President Biden's order that all federal workers be vaccinated having been blocked in court last month, while the Supreme Court issued a similar block on the private workforce in early 2022, the Mail reports.

In the fall of 2021, Fauci repeatedly defended state and private industry mandates for masks and vaccinations: "When you are in a public health crisis, sometimes unusual situations require unusual actions. In this case, it's things like mandating, be they masks or vaccinations."

The top-down push to get people vaccinated reaffirmed millions of Americans’ feelings that their personal autonomy was under threat and must be rejected wholeheartedly.

This bred widespread anti-vaccine sentiment, as many people believed cynically that the government was flexing its muscles to an authoritarian extent.

Nothing so effective could reasonably be made free for all; why would the government force the shots on the public if they failed to prevent infection; they were developed on such an accelerated timeline that there is no way they can be safe and effective; and any effort by the government to sidestep individual liberty must be sinister.

Vaccine mandates fed all of those arguments. -Daily Mail

And because of it, "you have that smoldering anti-science feeling, a divisiveness that’s palpable politically in this country," said Fauci.

https://www.zerohedge.com/political/fauci-admits-orwellian-mandates-fueled-anti-vax-sentiment