38% of surgeries involve adverse events, most preventable

 Among 1,009 patients who underwent surgery in a Massachusetts hospital in 2018, 38% experienced an adverse event — of which 26% were potentially preventable, according to a study published Nov. 13 in BMJ. 

To determine the frequency, severity and preventability of surgical complications, researchers from Harvard Medical School and Boston-based Brigham and Women's Hospital reviewed a sample from a dataset of 64,121 adults admitted for surgery across 11 Massachusetts hospitals. Nurses and physicians reviewed the 1,009 patient records.

The researchers found that, among 593 adverse events, 476 were either potentially or definitely preventable.

The most common adverse events were related to surgical procedures (49.3%), adverse drug events (26.6%), healthcare-associated infections (12.4%), patient care events (11.2%) and blood transfusion reactions (0.5%). 

Adverse events occurred most frequently in general care units, followed by operating rooms, intensive care units and recovery rooms. 

"While emphasizing safety as a collective responsibility for all health professionals is important, it is essential to recognize the expertise of those ultimately responsible for patient care, such as attending physicians," the researchers said in conclusion. "In modern healthcare systems where organizational and administrative factors often drive delivery of care, concern is growing that physicians have limited input into decision making processes.

"By valuing the perspectives of frontline staff and promoting collaborative approaches to care delivery, we can strive toward a system that prioritizes patient safety while also supporting the well-being of health professionals."

https://www.beckershospitalreview.com/patient-safety-outcomes/38-of-surgeries-involve-adverse-events-study-suggests.html

Rural health disparities widen for MA enrollees: 4 takeaways

 Health disparities among Medicare Advantage patients in rural areas widened in 2023, a new CMS report shows.

The report, published Nov. 12, examined 2023 data from Medicare Consumer Assessment of Healthcare Providers and Systems surveys and the Healthcare Effectiveness Data and Information Set. In total, seven CAHPS measures and 41 HEDIS measures were included in the analysis. The analysis was funded by CMS and performed by RAND Health Care.

Four takeaways: 

1. Thirty-four percent of HEDIS care measures for Medicare Advantage enrollees in rural areas were below the national average. This figure is up from 21% in 2022, suggesting a growing disparity in care quality for rural enrollees.

2. Care measures with the largest deficits among Medicare Advantage enrollees included:

• Kidney health evaluation for diabetes patients (15 percentage point difference compared to urban enrollees)
• Osteoporosis screening in older women (7 percentage point deficit)

3. The trend of urban residents having clinical scores similar to the national average and rural residents having scores below it was consistent across most racial and ethnic groups, except Hispanic Medicare Advantage enrollees. In rural areas, Hispanic enrollees had results below the national average on about 40% of measures (many involving behavioral healthcare) and above the national average for nearly 25% of measures.

4. In five of 10 HEDIS measures included in a 2017-2023 trends analysis, rural enrollees saw more improvement than their urban counterparts. However, rural residents still faced gaps compared to the national average, while urban residents maintained their advantage. 

View the full report here.

https://www.beckershospitalreview.com/health-equity/rural-health-disparities-widen-for-ma-enrollees-4-takeaways.html

NY nursing home operators to settle neglect, fraud case for $45M

 The operators of four New York nursing homes agreed Nov. 14 to pay $45 million to settle allegations of mistreatment, neglect and fraud. 

The settlement involves the Buffalo Center, the Martine Center in White Plains, and the Holliswood Center and the Beth Abraham Center in New York City. The nursing homes, along with their owners, operators, management company, landlords and other parties, agreed to increase staffing as part of the settlement. 

In a lawsuit filed in June 2023 by New York Attorney General Letitia James, the organizations were accused of multiple financial fraud schemes, misusing more than $83 million in taxpayer funds, and causing significant resident neglect, harm and humiliation. 

Insufficient care was tied to low staffing levels, with the lawsuit also citing noncompliance with COVID-19-era protections, such as staff failing to wear personal protective equipment. 

An independent financial monitor was installed in July 2023 and will oversee the centers through July 2026.

https://www.beckershospitalreview.com/legal-regulatory-issues/nursing-home-operators-to-settle-neglect-fraud-case-for-45m.html

Steward criminal investigation heats up

 As investigations deepen into financially troubled Dallas-based Steward Health Care, John Boehner, former U.S. House Speaker and Steward board member, testified Nov. 15 before a federal grand jury in Boston, The Boston Globe reported Nov. 14. 

Steward sought Chapter 11 bankruptcy protection on May 6 and has since offloaded the majority of its 31 hospitals. In July it was revealed that Steward is under criminal investigation by federal prosecutors at the U.S. Attorney's office in Boston. 

Mr. Boehner was questioned about corruption, bribery and potential fraud within the for-profit health system during his testimony. As a member of Steward's board, Mr. Boehner's position provided him with access to critical financial information as the health system struggled with operational and financial issues, including equipment and staffing shortages. 

Steward's domestic and international activities were also scrutinized by the grand jury, including potential Foreign Corrupt Practices Act violations, which is a law against overseas corruption and bribery. 

Prosecutors  also zeroed in on the financial transactions of former Steward Chairman and CEO Ralph de la Torre, MD, and other top Steward executives, which could have supported personal interests, The Globe reported.

Dr. de la Torre "amicably separated" from Steward Oct. 1 after a unanimous Senate vote on Sept. 25 to hold Dr. de la Torre in contempt for skipping a Health, Education, Labor and Pensions Committee hearing he was subpoenaed to attend.

On Sept. 30, Dr. de la Torre sued the HELP committee and its members in federal court, suggesting their actions were unconstitutional punishment for him invoking his Fifth Amendment right not to testify. 

Becker's has reached out to Steward and will update this story should more information become available. 

https://www.beckershospitalreview.com/legal-regulatory-issues/steward-criminal-investigation-heats-up.html

Effective use of gene therapy for muscular dystrophies and other large-gene diseases

 Gene therapy can effectively treat various diseases, but for some debilitating conditions like muscular dystrophies there is a big problem: size. The genes that are dysfunctional in muscular dystrophies are often extremely large, and current delivery methods can't courier such substantial genetic loads into the body.

A new technology, dubbed "StitchR," surmounts this obstacle by delivering two halves of a gene separately; once in a cell, both DNA segments generate messenger RNAs (mRNAs) that join seamlessly together to restore expression of a protein that is missing or inactive in disease.

Published in the journal Science, StitchR—short for "stitch RNA"—restored expression of large therapeutic muscle proteins to normal levels in two different animal models of muscular dystrophy. StitchR enabled expression of the protein Dysferlin, which is lacking in individuals with limb girdle muscular dystrophy type 2B/R2, as well as the protein Dystrophin, which is absent in patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy is the most common early onset form of muscular dystrophy; many boys become wheelchair bound in their teens and die in their twenties. People with limb girdle muscular dystrophy experience weakness and wasting in the shoulder, hip, and thigh muscles, and often have difficulty standing, moving, and doing everyday tasks.

"Gene therapy is a powerful tool for delivering a healthy gene copy back to a patient's cells to correct genetic diseases, but the vectors used to deliver this information are small, which has so far precluded their use for treating a whole host of diseases caused by mutations in large genes," said Douglas M. Anderson, Ph.D., lead study author and assistant professor of Medicine in the Aab Cardiovascular Research Institute at the University of Rochester School of Medicine and Dentistry (SMD).

"Instead of delivering the full gene in a single vector, which isn't possible, we've developed an efficient dual vector system where two halves of a gene are delivered separately but come together to reconstitute the large mRNA in the affected tissues."

The technology first arose from a serendipitous observation made in the lab several years ago, that when two separate mRNAs were cut by small RNA sequences called ribozymes, they became seamlessly ligated (joined) and translated into full-length protein. The team found that when ribozymes cleave or cut RNA, they leave ends that are recognized by a natural repair pathway.

"Similar to when CRISPR enzymes are used to cut DNA, the CRISPR enzymes are just the scissors, and it's a cell's natural repair enzymes that glue the DNA back together," noted Anderson, who is also a member of the University of Rochester Center for RNA Biology.

"We think something similar is happening here, but for RNA. The ribozymes are acting as the scissors and the cell's natural repair pathways are able to join the two RNAs back together. It's remarkable that two separate mRNAs are able to find themselves and that the process can be so efficient."

The lab optimized efficiency of the process (over 900-fold from their initial experiments) and adapted the technology into a powerful gene delivery mechanism.

When two halves of a large therapeutic gene are encoded into adeno-associated virus (AAV) vectors, which are the most commonly used vectors for gene therapy because they are safe and don't cause disease in humans, the ribozymes cut the ends of the mRNAs and they subsequently join, forming a single, seamless mRNA capable of producing protein in a desired tissue.

The research team, including co-first author Sean Lindley, who recently received his Ph.D. from the Anderson lab, found that the stitched mRNAs appear to behave essentially the same way as their natural full-length counterparts, effectively translating genetic information into functional proteins.

Self-cleaving ribozymes, which are essential for StitchR activity, are found naturally throughout the animal kingdom and are comprised of different families, which exhibit different cleavage activities. After testing numerous ribozyme families and sequences, they ultimately identified a formula that led to a high level of protein production and approached the levels achieved by genes expressed from just a single vector.

"Doug is extremely creative and detail oriented, and the fact that he's worked out how two different pieces of mRNA can find one another in a cell and be joined seamlessly to create a functional mRNA is really exciting," said Lynne E. Maquat, Ph.D., director of the UR Center for RNA Biology.

"The concept sounds simple, but this required considerable bench work to optimize the molecules involved, ensure they are stable in cells, and make the process as efficient as possible."

According to Anderson, StitchR can be coupled with many different types of vectors that are used to deliver or express a gene in cells and it appears to work efficiently with any mRNA sequence, opening the door for its use in a wide range of diseases and applications.

"StitchR is really plug and play at this point. The sequence requirements for StitchR are minimal, and we've now tested this with many different genes and sequences," he said.

Another feature of this technology is that only the full-length protein is produced.

"Other dual vector approaches have been in development for decades but have been plagued by lack of efficiency and the production of less than full-length products. Because StitchR occurs at the level of RNA, we can control and ensure that only the full-length protein product gets made. This differentiates StitchR from other dual vector technologies, for example inteins, a protein-ligation technology, which can be efficient but requires the expression of smaller protein fragments that may have unknown effects in a cell," added Anderson.

"It's been a long but fulfilling process to go from an initial research observation to a therapeutic application, but that's always been a major goal of our lab, and I think the promise of basic research. With StitchR and other tools we are working towards treatments for some of the most debilitating genetic diseases on the planet, many of which have no current treatments or cures," said Anderson.

The lab is now in the process of forming collaborations with other research labs and generating StitchR vectors to treat numerous diseases caused by large genes, of which there are thousands.

More information: Sean R. Lindley et al, Ribozyme-activated mRNA trans-ligation enables large gene delivery to treat muscular dystrophies, Science (2024). DOI: 10.1126/science.adp8179. www.science.org/doi/10.1126/science.adp8179

https://medicalxpress.com/news/2024-11-discovery-enables-effective-gene-therapy.html

'Company' Offers To Cryogenically Freeze Leftists For Four Years

 by Steve Watson via Modernity.news,

In an hilarious parody ad that is going viral, a fictional company called ‘Don’t Cry Cryo’ is offering to cryogenically freeze panicking leftists who can’t cope with president Trump’s election victory and wake them up after it’s all over.

The AI created ad, produced by Newzy, asks “are you distraught by the recent presidential election?” and offers to help, announcing “our expert team of cryogenic care providers can cryogenically freeze you until the Trump presidency is over.”

“No more crying, no more anxiety attacks, just blissful sleep until Trump is gone,” the ad further promises,” adding “it will be like his presidency never even happened.”

They even offer a JD Vance add on package!

There are more twists and turns in the ad, but we won’t give it all away.

Enjoy!

Lets send this supernova.

And give Newzy a follow, they deserve it for this!

*  *  *

https://www.zerohedge.com/political/company-offers-cryogenically-freeze-leftists-four-years

New drug targets for Alzheimer's identified from cerebrospinal fluid

 A multitude of genes have been linked to the development of Alzheimer's disease. Specifically how those genes might influence the progression of neurodegeneration remains something of a black box though, in part because of the challenges of examining in molecular detail the brain of a living patient.

Using cerebrospinal fluid (CSF) collected from living patients, a team of researchers at Washington University School of Medicine in St. Louis has for the first time linked disease-related proteins and genes to identify specific cellular pathways responsible for Alzheimer's genesis and progression. Because these proteins were gathered from CSF, they are a good proxy for activity in the brain, and several of them may be potential targets for therapies.

The findings are available in Nature Genetics.

The use of patients' CSF is a step forward for such studies and may be the best way to acquire relevant samples that help map out the constellation of protein activity, known as the proteome, said Carlos Cruchaga, Ph.D., the Barbara Burton and Reuben Morriss III professor of psychiatry and director of the NeuroGenomics and Informatics Center at WashU Medicine.

"Our goal is to identify risk-linked and protective genes, and also identify the causal role they play," Cruchaga said. "To do that, we need to study human-derived data. That is why we decided to do a large proteomic study of cerebrospinal fluid, because we know that CSF is a good representation of the pathology of the disease."

Cruchaga explained that similar investigations have relied on brain tissues collected postmortem, and therefore only provide information about the later stages of Alzheimer's. Other studies have looked at blood plasma, which is not specific to the tissues affected by the disease.

In the past decade and a half of researching Alzheimer's disease, scientists have increased the number of regions of our genome known to be associated with the condition from 10 to nearly 80. However, knowing the gene or region of DNA associated with the disease is only the first step.

Linking an individual's proteomic profile—that is, which proteins are active and to what degree—to their genetic code establishes a holistic view of the cellular activities in the brain. By comparing CSF samples from people with and without Alzheimer's disease, the researchers could then identify which cellular pathways are dysfunctional.

"Sometimes within a region of DNA known to be associated with Alzheimer's there are many genes, and we don't know which of those genes are driving the medical condition," Cruchaga said. "By adding the proteins to the analysis, we can determine the gene driving the association, determine the molecular pathway that they are part of, as well as to identify novel protein-to-protein interactions that otherwise will not be possible."

Cruchaga and his collaborators had access to a rich database of information through the Knight-ADRC and the Dominantly Inherited Alzheimer Network (DIAN), which are based at WashU Medicine, as well as other studies through their collaborators. These studies were also able to provide the genetic information and CSF samples of 3,506 individuals, both healthy donors and those with Alzheimer's disease.

The team cross-referenced proteomic data from the CSF samples with existing studies that had identified areas of the genome correlated with Alzheimer's. From this process, they narrowed in on 1,883 proteins of the 6,361 in the CSF proteomic atlas.

The investigators used three different established statistical analyses that can identify with high confidence genes and proteins that are part of the biological pathways leading to the disease. With this technique, they determined that 38 proteins are likely to have causal effects in Alzheimer's progression; 15 of these can be targeted by medicines.

"The novelty and the strength of this analysis is that we have defined proteins that modify risk," Cruchaga said. "So now that we have the causal steps, we can establish where the steps are leading to in the brain."

The immediate implications for understanding and developing treatments for Alzheimer's from this study are significant, but Cruchaga said he believes that CSF proteomics may yield a treasure trove of information for many neurological conditions, ranging from Parkinson's disease to schizophrenia.

"That's the power of this approach—once you have an atlas of genetic variants, and that of the protein levels, you can apply this to any disease," he said.

Proteins are not the only key to unlocking these conditions to be found in the CSF. Cruchaga is also investigating the potential of metabolites—substances released by cells when breaking down other compounds as part of their routine processes that are also found in CSF. In a separate paper, also published in Nature Genetics, he and his collaborators demonstrated the promise of this approach and reported associations between specific metabolites and conditions including Parkinson's disease, diabetes and dementia.

More information: Daniel Western et al, Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease, Nature Genetics (2024). DOI: 10.1038/s41588-024-01972-8

Ciyang Wang et al, Genetic architecture of cerebrospinal fluid and brain metabolite levels and the genetic colocalization of metabolites with human traits, Nature Genetics (2024). DOI: 10.1038/s41588-024-01973-7

https://medicalxpress.com/news/2024-11-drug-alzheimer-cerebrospinal-fluid.html