FDA to take steps to help gene therapies get accelerated approval

 The U.S. Food and Drug Administration is moving to optimize the development of gene therapies, including encouraging the use of biomarkers to help get accelerated approval of therapies for serious conditions, an agency official said.

Biomarkers, such as pulse and blood pressure, are characteristics of the body that you can measure. The FDA will support using biomarkers as substitutes for other biological indicators in gene-therapy clinical trials to help clinch "accelerated approval", the agency's Peter Marks said on Monday.

The U.S. health regulator grants the so-called accelerated approval mainly for drugs and therapies targeted at rare diseases or small patient populations that have had no effective treatments available to them. Companies are still required to conduct studies to confirm the anticipated clinical benefit.

"The FDA views gene therapy as an excellent opportunity to expedite the delivery of potentially life-saving therapies to patients with rare diseases," said Marks, who heads the FDA's Center for Biologics Evaluation and Research, in a statement.

For certain gene therapies, there may be a need to "accept some level of uncertainty" at the time of approval around questions like side-effects over long-term and safety during administration, the statement said, adding that post-marketing tools such as safety monitoring and the possible use of extra clinical trials are going to be key.

The comments from the FDA come days after Sarepta Therapeutics Inc said that the agency planned to hold a panel meeting to review its gene therapy for Duchenne muscular dystrophy, less than a month after saying it would not do so.

The company is seeking approval for its gene therapy under the FDA's accelerated pathway.

https://www.marketscreener.com/quote/stock/SAREPTA-THERAPEUTICS-INC-11204214/news/US-FDA-to-take-steps-to-help-gene-therapies-get-accelerated-approval-43295746/

Dollar General Corporation : Stronger than Walmart

 

Discount retailing is sometimes more profitable than you might think. Dollar General, which released its results last Friday, proves it with growth and margins higher than Walmart.

The latest figures invite a look at the ten-year financial performance, i.e., the 2013-2023 period, which is excellent by any measure for the Tennessee-based group and its 18,774 stores.

Sales increased from $16 billion to $38 billion over the period, while the operating margin remained remarkably stable at around 10%. Inflation has weighed a little on profitability over the past year, but it has been well absorbed by an increase in sales.

The latter, it should be noted, is itself a consequence of inflation, which is pushing consumers to redirect their purchases towards discount stores. The charm of this positioning is therefore to offer a good hedge against economic hazards.

Known for its excellent management, Dollar General clearly outperforms its less profitable rival Dollar Tree. Over the period 2013-2023, the former generates a total of $17.5 billion in profits, all of which is returned to shareholders via dividends and share buybacks.

The number of shares outstanding is thus decreasing by one third. This cocktail of growth, well-defended margins and cannibalized capital allocation has literally quadrupled earnings per share, from $2.8 in 2013 to $10.7 this year.

Over the decade, the market has pinged Dollar General's value, from a low of x15 earnings to a high of x30 earnings. These swings reflect the recognition of a remarkable performance, mixed however with the fear that the group has exhausted its growth potential.

In this regard, management announced eighteen months ago its intention to diversify into consumer pharmaceuticals in order to pursue a new growth driver. Whether this effort succeeds or not, the sustained share buybacks should in any case allow for the continued expansion of earnings per share.

A return of the valuation to the low end of x15 earnings would likely represent an attractive entry point.

https://www.marketscreener.com/quote/stock/DOLLAR-GENERAL-CORPORATIO-5699818/news/Dollar-General-Corporation-Stronger-than-Walmart-43293399/

Physician Assistant Fired For Reporting COVID-19 Vaccine Adverse Events To VAERS

 by Matt McGregor via The Epoch Times (emphasis ours),

For her efforts to report injuries to the Vaccine Adverse Events Reporting System (VAERS) and to educate others in her hospital system on doing the same, Physician Assistant Deborah Conrad said she was labeled an anti-vaxxer and fired from her job.

oday, the New York-based Conrad tells her story at medical freedom conferences throughout the country, the most recent being one in Mississippi where physicians, scientists, and the vaccine injured warned state lawmakers to pull the COVID-19 vaccines from the market.

Conrad told The Epoch Times she began to see early danger signals in 2021 upon the vaccine rollout, and with that, resistance among her colleagues to report on them.

“After the vaccines came out, there was this uptick in unusual symptoms, some of which I had never seen in my 20-year career,” Conrad said. “In every case, it was in somebody who had received the COVID-19 vaccine.”

Conrad said she had never admitted an adult patient with RSV (respiratory syncytial virus) until the COVID-19 vaccines.

“And every patient who came in with RSV was vaccinated for COVID,” Conrad said. “It wasn’t normal.”

Then, there were the adolescents with no previous medical conditions who had gotten the COVID-19 vaccine a week prior and, suddenly, they were struck with pneumonia and not able to function, she said.

“They weren’t able to walk or eat, and they were completely and totally fatigued,” Conrad said.

This was in 2021 before myocarditis was being discussed, so many of those early cases that were probably myocarditis were diagnosed as pneumonia, she said.

“A lot of these myocarditis cases came in with fevers because of this massive inflammatory response that was taking place in the body, so they would be labeled as septic, treated as if we were treating pneumonia or fevers of unknown origin,” Conrad said. “We’d treat them with antibiotics and all sorts of other things, not realizing that they were having heart failure.”

Conrad began reporting to VAERS, which she said was an overwhelming task not made easy by its multiple user-interface complications.

“My entire life had been taken over by doing these VAERS reports by myself,” she said.

In meetings with leadership, she would propose implementing a reporting system and hiring someone to manage the reports, she said.

‘A Hostile Environment’

“They kept telling me we’re looking into it and we’ll get back to you,” Conrad said. “Around April 2021, leadership came back and said no one else is reporting injuries—implying that I was crazy and there was nothing really going on with the vaccines.”

Leadership then audited her reports, she said and concluded that she was overreporting.

“I was then told that by doing VAERS reports and even discussing VAERS that it was an admission that the vaccines were unsafe, so it’s contributing to vaccine hesitancy,” Conrad said.

From there, it became a “very hostile environment” that compelled her to seek legal counsel, who wrote letters to the Department of Health, the CDC, and the FDA.

“No one cared,” Conrad said. “Finally, I had had it. It was so unethical; I couldn’t take it anymore. These VAERS reports are critical to assuring these vaccines are safe for us all. I could no longer be a part of a system that is lying to the American people.”

Conrad decided to become a whistleblower, telling her story on Del Bigtree’s The Highwire, knowing, she said, that it would cost her job.

“I couldn’t remain silent, even if it meant losing my career and everything I worked for,” she said. “I was fired a few weeks later and walked out like a criminal in front of all my peers.”

The initiative and education she had brought forth to report to VAERS were squashed that day, she said.

Whistleblower Deborah Conrad speaks about her termination for attempting to utilize the VAERS reporting in her hospital system, in Jackson, Miss., on Feb. 27, 2023. (Courtesy of Charlotte Stringer Photography)

National Vaccine Injury Act of 1986

According to Barbara Loe Fisher, co-founder and president of the National Vaccine Information Center (NVIC), under the National Vaccine Injury Act of 1986, it’s a federal requirement for health care workers to report vaccine-related adverse events to VAERS.

Fisher, whose son was harmed by the DTP vaccine in 1980, worked with other parents of vaccine-injured children in establishing the NVIC in 1982.

“The 1986 Act was driven by parents of DPT vaccine injured children asking the government to pass legislation to secure vaccine safety informing, recording, reporting, and research provisions in the vaccination system to make it safer, and to create a federal compensation system alternative to a lawsuit against manufacturers of vaccines that injure or kill children,” Fisher told The Epoch Times.

In addition to NVIC arguing that physicians and vaccine manufacturers should be giving informed consent and report injuries, the organization maintained they should also continue to be held accountable in a civil court to serve as an incentive for physicians to administer vaccines responsibly, for manufacturers to produce safer vaccines, and for adequate federal compensation to vaccine-injured children.

https://www.zerohedge.com/political/i-couldnt-remain-silent-physician-assistant-fired-reporting-covid-19-vaccine-adverse

COVID-19 is associated with an increased risk of developing gastrointestinal disorders

 COVID-19 is associated with an increased risk of developing long-term gastrointestinal disorders, including irritable bowel syndrome. This is what has been shown by a research published in the journal Gut, carried out by scholars of the University of Bologna and the IRCCS AOU S.Orsola Bologna.

"The data we collected show that those who have contracted COVID-19 experience gastrointestinal symptoms more frequently than those who have not been affected by it," explains Giovanni Barbara, full professor at the Department of Medical and Surgical Sciences at the University of Bologna and coordinator of the study. "Given the vast spread of COVID-19 globally, we should therefore expect an increase in diagnoses related to gut-brain interaction disorders."

It is well known that viral infections can affect the gastrointestinal system and specifically promote the development of irritable bowel syndrome. This condition tends to be chronic, characterized by a number of intestinal disorders affecting the colon, including altered bowel motility, bloating, and abdominal cramping. Until now, however, it was unclear whether coronavirus infection could also lead to these consequences.

The researchers then conducted a prospective survey with the aim of assessing the prevalence of gastrointestinal symptoms and gut-brain interaction disorders in patients hospitalized for SARS-CoV-2 infection. The study involved 2183 patients hospitalized in 36 facilities in 14 countries: Italy, Bangladesh, Cyprus, Egypt, Israel, India, Macedonia, Malaysia, Romania, Russian Federation, Serbia, Spain, Sweden, and Turkey.

Patients who had contracted COVID-19 were evaluated upon admission to the hospital and then followed up for the next 12 months, comparing their condition with that of patients not infected with the coronavirus.

The data collected and analysis carried out by the scholars thus showed that patients hospitalized for COVID-19 more frequently reported the presence of gastrointestinal symptoms (59.3%) than the control group (39.7%). And new diagnoses of irritable bowel syndrome also emerged more frequently, which were found to be associated with the coexistence of allergies, breathing difficulties during hospitalization for COVID-19, and chronic intake of proton pump inhibitors (gastroprotectant drugs that block acid production in the stomach).

In addition, at 6 months and 12 months after hospitalization, higher levels of anxiety and depression were reported among those who had COVID-19.

"We know that the SARS-CoV-2 virus can also infect the gastrointestinal tract, and this confirms the possibility that COVID-19 can lead to the development of irritable bowel syndrome," explains Giovanni Marasco, a researcher at the Department of Medical and Surgical Sciences at the University of Bologna and first author of the study.

"Traces of the coronavirus were indeed found in the small intestine even six months after infection: this leads us to believe that the prolonged state of inflammation and activation of the immune system may lead to the development of the gastrointestinal symptoms that were observed."

More information: Giovanni Marasco et al, Post COVID-19 irritable bowel syndrome, Gut (2022). DOI: 10.1136/gutjnl-2022-328483

https://medicalxpress.com/news/2023-03-covid-gastrointestinal-disorders.html

Co-infection with 'superbug' bacteria increases SARS-CoV-2 replication

 Global data shows nearly 10 percent of severe COVID-19 cases involve a secondary bacterial co-infection—with Staphylococcus aureus, also known as staph A, being the most common organism responsible for co-existing infections with SARS-CoV-2. Researchers at Western have found that the addition of a "superbug"—methicillin-resistant Staphylococcus aureus (MRSA)—into the mix could make the COVID-19 outcome even more deadly.

The mystery of how and why the combination of these two pathogens contributes to the severity of the disease remains unsolved. However, a team of Western researchers has made significant progress toward solving this "whodunit."

New research by Mariya Goncheva, Richard M. Gibson, Ainslie C. Shouldice, Jimmy D. Dikeakos and David E. Heinrichs has revealed that IsdA, a protein found in all strains of staph A, enhanced SARS-CoV-2 replication by 10- to 15-fold. The findings of this study are significant and could help inform the development of new therapeutic approaches for COVID-19 patients with bacterial co-infections.

Interestingly, the study, which was recently published in iScience, also showed that SARS-CoV-2 did not affect the bacteria's growth. This was contrary to what the researchers had initially expected.

"We started with an assumption that SARS-CoV-2 and hospitalization due to COVID-19 possibly caused patients to be more susceptible to bacterial infections which eventually resulted in worse outcomes," said Goncheva, who is a former postdoctoral associate, previously with the department of microbiology and immunology at Western University's Schulich School of Medicine & Dentistry.

Goncheva said bacterial infections are most commonly acquired in hospital settings and hospitalization increases the risk of co-infection. "Bacterial infections are one of the most significant complications of respiratory viral infections such as COVID-19 and Influenza A. Despite the use of antibiotics, 25 percent of patients co-infected with SARS-CoV-2 and bacteria, die as a result. This is especially true for patients who are hospitalized, and even more so for those in intensive care units. We were interested in finding why this happens," said Goncheva, lead investigator of the study.

Goncheva, currently Canada Research Chair in virology and professor of biochemistry and microbiology at the University of Victoria, studied the pathogenesis of multi-drug resistant bacteria (such as MRSA) supervised by Heinrichs, professor of microbiology and immunology at Schulich Medicine & Dentistry.

When the COVID-19 pandemic hit, she pivoted to study interactions between MRSA and SARS-CoV-2.

For this study conducted at Western's level 3 biocontainment lab, Imaging Pathogens for Knowledge Translation (ImPaKT), Goncheva's work created an out-of-organism laboratory model to study the interactions between SARS-CoV-2 and MRSA, a difficult-to-treat multi-drug resistant bacteria.

"At the beginning of the pandemic, the then-newly opened ImPaKT facility made it possible for us to study the interactions between live SARS-CoV-2 virus and MRSA. We were able to get these insights into molecular-level interactions due to the technology at ImPaKT," said Heinrichs, whose lab focuses on MRSA and finding drugs to treat MRSA infections. "The next step would be to replicate this study in relevant animal models."

More information: Mariya I. Goncheva et al, The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling, iScience (2023). DOI: 10.1016/j.isci.2023.105975

https://medicalxpress.com/news/2023-03-co-infection-superbug-bacteria-sars-cov-replication.html

Almost all countries around the world criminalize abortion in some circumstances

 Almost all countries around the globe criminalize abortion in some circumstances, despite the public health risks and impact on human rights, finds a review of the scope of penalties for the procedure in 182 nations, published in the open access journal BMJ Global Health.

Some 134 countries penalize those seeking an abortion, while 181 penalize providers, and 159 also punish those who assist in the procedure, the review shows.

The evidence indicates that criminalization doesn't deter women from deciding to have an abortion; rather, it limits or delays access to safe abortion and increases the need to turn to unsafe and unregulated services, point out the researchers.

Criminalization also helps erode the availability of trained abortion providers and relevant skills in the health workforce, they add.

To find out the extent of criminal penalties for seeking, providing, and assisting with abortions around the world, the researchers drew on data up to October 2022 from the Global Abortion Policies Database (GAPD), which covers UN member states.

Nine countries were excluded from the review because the regulation of abortion isn't uniform in different jurisdictions: Nigeria; Bosnia; the UK; Mexico; U.S.; Australia; China; Switzerland; and Canada.

Analysis of the data showed that in 163 countries, the definition of and penalties for abortion-related offenses are contained in the general penal code. In 12 countries, the offenses and penalties are found in abortion-specific laws; in 8 they are found in other types of legal sources, such as health codes, reproductive health laws, and laws about children.

In 11 countries, abortion is completely criminalized and prohibited in all circumstances, but the procedure is criminalized in some circumstances in most of the remainder.

In 134, the person seeking the abortion is penalized; in 181, it's the providers; and in 159, those who assist in access or provision are subject to criminal penalties.

The range of penalties that people convicted of abortion-related offenses can face is wide, although fines and imprisonment are the most common.

In 91 countries, the maximum penalty for those seeking a termination is up to 5 years of imprisonment for a consensual abortion, where no aggravating factors apply. In 25 countries, the maximum penalty is between 5 and 10 years, and between 10 years and life imprisonment in Equatorial Guinea and Zambia. In Kiribati, Solomon Islands, Tuvalu, Barbados, Belize and Jamaica, a person seeking an abortion can be imprisoned for life; 48 countries impose fines.

While in some countries, fines can be imposed as an alternative to prison, in most, fines can be imposed in addition to a prison sentence. Similar punishments apply to providers.

Where aggravating factors apply, such as a death, young age, withheld consent, the maximum prison sentence for providers can be 20 or more years in Algeria, Burundi, Malaysia, Mali, Morocco, Sri Lanka, Thailand, Ivory Coast and Turkey, and life imprisonment in Benin, Burkina Faso, Rwanda, Singapore, South Sudan and India.

Seventy-six countries fine abortion providers. Forty-eight apply professional sanctions, which include: seizure or forfeiture of equipment; demotion; closure of establishments; official warnings; termination of employment; suspension from practice; suspension of qualifications; and a total ban on working in the field again, or on holding certain posts.

For those assisting in access to or provision of an abortion, the maximum penalty is between 5 and 10 years' imprisonment in 16 countries, and between 10 years and life in Benin, Democratic Republic of Congo, Ireland, Equatorial Guinea, Saint Vincent and the Grenadines. In Barbados, the maximum penalty is life imprisonment.

Fifty-nine countries impose fines for people who assist in abortions; 33 apply professional sanctions for those acting in a medical capacity, such as pharmacists and nurse counselors.

Other penalties may apply in some countries. These include prohibitions on residence or on the exercise of civic and family rights, transportation for life, retributive justice, "blood money," community service, hard labor and forced labor.

Twenty-four countries prescribe some of these penalties for providers, 15 for those who assist in abortions and 13 for those seeking an abortion.

Thirty-four restrict the dissemination of information about abortion and abortion services, even when the procedure may be legal in some circumstances.

"The sheer range of penalties that persons involved in the abortion may face, depending on where they are, support the argument that provisions criminalizing abortions are arbitrary," say the researchers.

What's more, "Regulating abortions through the same legal instrument, and same institutional apparatus as murder, sexual assault and robbery may exacerbate the concerns associated with seeking and providing abortions when it is criminalized," they add.

"Studies in countries where abortion has been fully or partially decriminalized have also noted several benefits to abortion seekers as a result, including access to better quality care, lower rates of maternal mortality, and increased educational attainment, career outcomes and earnings," point out the researchers.

"International human rights law requires countries to undertake measures to reduce maternal mortality and morbidity," they note, adding that their findings "strengthen the case for decriminalization."

More information: A global review of penalties for abortion related offences in 182 countries, BMJ Global Health (2023). DOI: 10.1136/bmjgh-2022-010405

https://medicalxpress.com/news/2023-03-countries-world-criminalize-abortion-circumstances.html

16 Terrorists On FBI Watchlist Crossed Southern Border In February Alone: CBP Data

 by Steve Watson via Summit News,

Fresh data from Customs and Border Protection has revealed that sixteen people matched to the FBI’s terrorist watchlist were apprehended by Border Patrol agents in February alone.

As reported by Fox News, the total number of individuals on the watchlist found to be attempting to enter the country so far this fiscal year is now 69.

CBP expects the trend to continue, and to smash last fiscal year’s record 98 encounters.

Between FY17 and FY20 there were only 8 of these terror watchlist arrests, and in 2021 only 15.

Federal Data Quietly Reveals 100 Terror Suspects Caught At Southern Border

When border the Southern and Northern borders are taken into account, FY23 has seen 214 people in the Terrorist Screening Database stopped by CBP agents to date. Last year, the total was 380, yet the year before that there were only 157 encounters.

The Department of Homeland Security says the border is secure and claims that the biggest terror threat the U.S. faces is ‘domestic extremists’ radicalised by “false narratives propagated on online platforms.”

DHS Chief Says Biggest Terror Threat is Americans Radicalized by ‘Online Narratives’

The latest data shows that on the whole, CBP apprehended 128,877 people who crossed the border illegally in January and another 128,913 in February.

Those figures are down from December when a record amount of illegal crossings were recorded, as 251,487 illegal immigrants crossed, marking the highest monthly total in history. A total of 17 individuals on the terrorism watchlist were apprehended.

CBP Figures Show Highest Monthly Total Of Illegal Crossings EVER Recorded

Last week, during testimony before the House, Border Patrol chief Raúl Ortiz contradicted Biden administration officials by stating that there is a full on crisis on the southern border, urging that it is not secure, and calling for a wall to be built.

Video: Border Patrol Chief Testifies Border Is Not Secure, Wall Needed

Ortiz noted that there have already been approximately 385,000 known gotaways at the border since fiscal year 2023 began on Oct 1. That is in addition to 600,000 in FY’22, and 390,000 in FY’21. There have been approximately 1.4 million gotaways since start of FY’21.

Meanwhile:

https://www.zerohedge.com/political/16-terrorists-fbi-watchlist-crossed-southern-border-february-alone-cbp-data-shows