At least 1,000 US schools have closed due to Covid since late July

 At least 1,000 schools across 31 states have closed down due to COVID-19 since classes began to resume in late July, The Wall Street Journal reported Sunday, citing data service Burbio.

The news outlet noted that it is difficult to tell how badly schools have been affected by the pandemic due to variations in reporting.

Aaron Baker, a 12th-grade government teacher in Oklahoma, told the Journal that his school is struggling to find enough staff members, while many students are missing class due to infection or exposure. Baker, who is fully vaccinated against COVID-19, tested positive for for the virus after only one week of teaching fully in-person.

“That’s all it took—five days,” said Baker, who has since returned to teaching in-person.

A Texas school district temporarily closed down all of its campuses after two teachers died in the same week from COVID-19.

"Due to a continued increase in Covid-19 cases and an increase in absences (of staff and students), we have made the decision to close all Connally ISD campuses through Monday, September 6th," the Connally Independent School District said in a letter to parents last week.

The majority of parents in the U.S. no longer want their children to be attending school full-time, according to a survey released by the National Parent Teacher Association last week. The CDC-funded survey found that 43 percent of parents wanted their children in a classroom full-time.

According to Burbio's data, a review of the 200 largest school districts in the U.S. found that over 70 percent are requiring masks. The use of mask mandates in schools has become a heavily contested issue, with numerous Republican governors moving to ban mask mandates outright. 

Last month, President Biden criticized such governors, accusing them of "setting a dangerous tone." And his administration is investigating whether mask mandate bans violate the civil rights of students with disabilities. 

"This isn't about politics. It's about keeping our children safe. It's about taking on the virus together, united. I've made it clear that I'll stand with those who are trying to do the right thing," he said.

https://thehill.com/policy/healthcare/public-global-health/570946-at-least-1000-us-schools-have-closed-due-to-covid

Feeling Better in COPD: Simple Solution?

 Exercise capacity in patients with chronic obstructive pulmonary disease (COPD) increased substantially following a single IV iron infusion, a researcher reported.

With patients' tolerance for physical activity measured with two standard assessments -- the 6-minute walk test (6MWT) and a constant work-rate exercise test -- more than half the patients receiving the infusion achieved the primary endpoint of at least a 33% improvement, compared with 18% of those given a placebo infusion (P=0.009)in a small, single-blind trial, said Clara Martin Ontiyuelo, of Hospital del Mar-IMIM in Barcelona, in a presentation at the European Respiratory Society virtual meeting.

That worked out to a relative risk of 3.12 (95% CI 1.19-8.12) for reaching the primary endpoint, her group calculated.

One secondary endpoint also favored the iron therapy, at least numerically: COPD Assessment Test scores, a patient-reported measure of quality of life, decreased a mean of 3.0 points (95% CI 1.3-6.0) with active treatment compared with a decline of 1.0 points (95% CI -2.3 to 4.0) in the placebo group (P=0.236). There was no difference in daily physical activity or in adverse events, Martin Ontiyuelo said.

She explained that iron deficiency is a common feature in COPD and, of course, can negatively affect exercise ability. That suggests a potential role for supplementation in iron-deficient patients.

Her group is not the first to come to this conclusion. An even smaller trial in Germany was proposed in 2015, though whether it began or was completed couldn't be determined. Another small study conducted in Great Britain with IV iron was published last year; it found no improvement in blood oxygenation but, as in the Barcelona trial, 6MWT distance was lengthened with the active supplement.

All three used a ferric carboxymaltose product (Ferinject) for the infusion. Martin Ontiyuelo explained that, at least for her group, the choice was based on "logistical issues, as a single dose shows interesting and fast effects." Oral iron, she said, often has poor absorption and isn't always well tolerated.

Her group's trial, dubbed FACE, randomized 66 patients at a 2:1 ratio to the iron infusion or placebo. Patients had to show iron deficiency defined as either serum ferritin less than 100 ng/mL, or 100-299 ng/mL with coexisting transferrin saturation less than 20%. Patients did not need to show overt anemia, however.

The exercise tolerance tests were performed at baseline and again at 4 weeks following the infusion. Patients wore accelerometers during this follow-up period to measure physical activity. Dosage for the iron infusion was either 500 or 1,000 mg, according to patients' weight and baseline hemoglobin level.

In her presentation, Martin Ontiyuelo did not mention how much patients' iron levels improved with the infusions. When an online audience member asked about it afterward, she responded that there was "an important change in ferritin" that her group would report in detail as part of a forthcoming publication.

She also said there were no allergic reactions to the iron infusion.

Disclosures

Martin Ontiyuelo disclosed no relevant financial interests.

Primary Source

European Respiratory Society

Source Reference: Martin Ontiyuelo C, et al "Intravenous iron replacement improves exercise tolerance in COPD: A randomised trial" ERS 2021; Abstract OA1200.

https://www.medpagetoday.com/meetingcoverage/ers/94371

Patient Safety Is Heading in the Wrong Direction

 At the age of 15, my son, Lewis, died due to treatable surgical complications. Following a routine elective surgery, he developed signs of sepsis, a life-threatening response to infection. Like most patients in postsurgical distress, Lewis deteriorated slowly. As he became weaker and weaker over the course of many hours, his bedside caregivers downplayed the significance of his mounting pain and unstable vital signs. Finally, his blood pressure became undetectable and he went into cardiac arrest, from which he could not be saved. My son's death, like thousands of others, was preventable.

Lewis was a brilliant child, bursting with promise. And like most bereaved parents, his father and I were desperate to bring some good from his drastically shortened time on earth. We talked to other families and realized we were far from alone in losing someone we loved to what is known as "failure to rescue" from treatable postsurgical complications. We felt we could only find meaning in these deaths if healthcare providers learned from the mistakes that caused them. And we quickly understood that the first step toward learning was knowing the extent of the problem.

Over the years, we felt secure in the knowledge that CMS was publicly reporting critical patient safety information for hospitals, including the rates of deaths due to treatable surgical complications. CMS publishes this information on their consumer facing website, Care Compare. Businesses and rating organizations like The Leapfrog Group (and in its heyday, Consumer Reports) use CMS safety data to determine overall hospital safety for patients. Having this information publicly available allows families like ours to vote with their feet, and it gives employers and health plans a basis for decision-making for insurance coverage. It is an incentive to hospitals to maintain vigilance about safety.

Recently, however, we have seen an erosion of patient safety reporting at CMS. Each year, CMS proposes changes to quality reporting programs. Longstanding evidence-based patient safety measures, especially those used to detect harm to patients, are gradually being removed. These measures are largely extrapolated from hospital records and do not add to the workload of hospital staff. But they are embarrassing to hospitals, and hospital representatives lobby against them.

In the most recent round of updates, the measure that matters so much to families like ours, "Death Rate Among Surgical Inpatients with Serious Treatable Complications," was proposed for removal. After public protest from patient safety advocates, we were gratified that CMS reversed course and decided to keep the measure as part of their public reporting program. This was a win -- a rare one -- for patients and advocates. But in spite of this change, the trend of downgrading patient safety remains concerning.

As an example, CMS exempted hospitals from reporting hospital-acquired infections from early 2020 and may suppress hospital infection reporting from the second half of 2020, citing the stress hospitals have encountered during the pandemic. While this may seem like a reasonable compromise to free up the time of overtaxed hospital workers, the focus of the exemption is not on data collection; instead, the results are simply not made available to the public as they normally are.

We are all deeply grateful for hospital workers' sacrifices during the pandemic. But these sorts of concessions do not do anyone any favors. There are concerning indications that hospital safety performance has declined during the pandemic. In the most worrisome example, the CDC has noted a broad increase in healthcare-associated infections in hospitals, including invasive fungal infections like the deadly candida auris. During an epidemic of a highly infectious disease like COVID-19, more attention, not less, should be paid to tracking safety and infection. Operating in the dark creates fertile ground for safety lapses that risk the well-being of both healthcare workers and patients.

Even before the pandemic, patient safety lapses were a significant cause of death in hospitals. COVID-19 has only increased the risk. Had my scientifically minded son Lewis lived to adulthood, he could well have been one of the young doctors on the front lines fighting to save people from the ravages of this disease. I would like to think that we could be assured that he was doing so in an atmosphere of safety and transparency. This is the least we owe to our brave healthcare workers, to their vulnerable patients, and to the ghosts of those like Lewis who have already paid the price.

Helen Haskell, MA, is president of the nonprofit patient organization Mothers Against Medical Error.

https://www.medpagetoday.com/opinion/second-opinions/94358

Oregon Police, Firefighters Suing Governor In Resistance Of Vaccine Mandate

 Police and firefighters in Oregon are suing the governor and the state after it was mandated that state workers must get COVID vaccines.

KOIN-TV reports that the lawsuit was brought by the Oregon Fraternal Order of Police, as well as state troopers and firefighters at the Kingsley Field Air National Guard Base.

Gov. Kate Brown recently mandated vaccines for workers, as well as instituting a fresh mask mandate, which was roundly criticised for going against logic and science.

The police and firefighters want to see Brown’s executive order deemed “unenforceable” by a judge, noting that there are statutes in place to protect workers rights and that vaccine mandates will lead to wrongful dismissals.

Last week an Oregon trooper was placed on leave for posting a video to social media vowing to defy the mandate.

“I swore an oath to uphold the Constitution of the United States, to protect the freedom of the people who pay my salary,” said Zachary Kowing in the video, adding “I do not work for my governor but for them.”

Watch:

*  *  *

https://www.zerohedge.com/political/oregon-police-and-firefighters-suing-governor-resistance-vaccine-mandate

Portland to vote to ban Texas travel, trade following new abortion law

 The Portland, Ore., City Council is planning to vote on Wednesday on a proposal to ban doing business with the state of Texas following the controversial new abortion restrictions enacted in The Lone Star State. 

In a statement last week, Portland Mayor Ted Wheeler (D) said that the city council will vote whether to ban trading goods and services with Texas and bar state employee business travel as well, citing the abortion law that bans abortions after a fetal heartbeat is detected and allows private citizens to sue anyone they believe has helped a woman violate the limits.

“This law does not demonstrate concern for the health, safety, and well-being of those who may become pregnant. This law does not recognize or show respect for the human rights of those who may become pregnant,” Wheeler said in a statement. “This law rewards private individuals for exercising surveillance and control over others’ bodies. It violates the separation of church and state. And, it will force people to carry pregnancies against their will.”

“Portland City Council stands with the people who may one day face difficult decisions about pregnancy, and we respect their right to make the best decision for themselves.” 

The move from the Northwest city comes as Texas has faced considerable backlash surrounding the new law, which went into effect on Wednesday. 

The legislation, which was signed by Texas Gov. Gregg Abbott (R)  placed an effective ban on almost all abortions by about six weeks into a woman’s pregnancy when the heartbeat can usually be detected. 

The Supreme Court later in the week declined to block the law in a 5-4 vote.

https://thehill.com/homenews/state-watch/570956-portland-to-vote-to-ban-texas-travel-trade-following-new-abortion-law

How blockchain can revolutionise medical records and save lives

 Balancing medical privacy with ease of access for healthcare professionals is a challenge, but technology could provide the solution, says Aleph Zero Foundation’s Matthew Niemerg.

Most people don’t think of healthcare when they hear blockchain, and that’s understandable; the technology so far hasn’t gone much beyond financial instruments – at least, not in the eyes of the public. However, with the current state of affairs in healthcare, the time has come for change. And blockchain may well be at the heart of it.

One of the most challenging problems in the health-care industry is balancing people’s medical privacy with ease of access to medical history via electronic health records (EHRs). EHRs need to adhere to any mandated privacy laws which are distinct from jurisdiction to jurisdiction. Data standards across the myriad of solutions also poses a challenge as well.

If appropriately implemented, blockchain-based medical records systems of tomorrow could be far more accurate, secure and accessible than the one-size-fits-all approach applied to today’s electronic health records, all while putting additional power back in the hands of the patients. Here’s how.

The state of medical records today

The complexities and deficiencies of modern medical systems worldwide have strained healthcare professionals for decades. A transition to electronic health records, with opportunities for cost savings and reduced medical errors being the two primary benefits of an electronic-based system, made it hard to argue that a paper-based health record system longer held any merit.

Yet over time, EHRs have failed to live up to expectations, instead becoming the leading cause of physician burnout. This comes from a variety of issues linked to these systems, but there is a big one of note. Many practitioners have expressed the feeling that EHRs cause far too much of their time ultimately being spent on data entry. This takes away from other important aspects of tending to clients and can even eat into the physician’s personal time. Additionally, issues such as poor quality documentation due to template-based reporting, and incompatibilities between different systems have further caused headaches and increased inefficiencies.

“Despite its failings, the EHR remains the central tool for capturing the plethora of new streams of data bubbling through health care”

Furthermore, EHR vendors have been sued for selling non-functioning products to hospitals and accused of acts of fraud, and although EHRs improved safety in some areas, they also introduce new risks systemic in nature. Kaiser Health News and Fortune detail these and other shortcomings in Death by 1,000 clicks: where electronic health records went wrong.

In many ways though, despite its failings, the electronic health record (EHR) remains the central tool for capturing the plethora of new streams of data bubbling through health care, which is increasingly influencing clinical practice as well as pharma trials. Data such as phenotype measures, patient-reported outcomes, baseline genomic data, claims data and more needs to be captured, relying on the ability of all participants involved to properly use the electronic record-keeping systems, which is the biggest challenge on how well the system performs.

This is where the benefits of blockchain technology are frequently discussed and there is widespread agreement that its role could transform drug development and the supply chain, clinical trials management, the delivery of healthcare to patients and much more. Finally, there is now a compelling reason for blockchain’s implementation in life sciences, here’s why.

Blockchain: The ultimate electronic health record

Blockchain technology, popularised by cryptocurrencies such as Bitcoin, stands to hold the keys to a much more comprehensive and secure system of medical records. This is possible because of what a blockchain inherently is: a ledger cryptographically enforced to ensure the integrity of the data on it. When put to work on securing medical data, blockchain can store information in a way that is accessible to anyone on the network, completely immutable, and tamper-proof.

Blockchain-based electronic health records would give doctors and nurses control over the flow of information from a single, trusted platform. Everyone would be able to see the same data, and all updates would be visible to the whole network almost immediately. This means that medical teams can trust that what they learn about a patient is both accurate and up to date.

“One of the critical pieces of technology that can make this all possible is already in the pockets of much of the population – mobile devices”

There are various ways that a system like this could potentially be implemented in hospitals and doctors’ offices worldwide. But one of the critical pieces of technology that can make this all possible is already in the pockets of much of the population – mobile devices. Phones and similar devices now have the power and communication abilities to monitor an individual’s vitals and be an access point for both inputting and retrieving data.

Already many citizens use their phones or smartwatches to keep tabs on their movement, calorie intake, and even mental health, to name a few. Hence, blockchain enables an evolution of these types of services. Putting all forms of health monitoring into a single, standard platform accessible to health professionals streamlines the operation and allows for better oversight on the quality of care being provided. Backing up the information with blockchain means that once data is inputted, it cannot be tampered with or altered really in any way. Through blockchain-based electronic health records, it may even be feasible – in certain situations – to incentivise healthier life choices through a gamified and rewards system. Incorporating such a model would help elevate some of the pressure on publicly funded healthcare systems as patients start adopting healthier lifestyles.

Power to the patients 

At this point, some may have a growing concern over what this could mean for patient privacy. It admittedly sounds a little over-arching to have this level of access to highly personal information on a public network. Fortunately, here again, blockchain could actually put more control into the hands of patients and provide a greater level of privacy using tried-and-true cryptographic techniques. Users and their trusted care providers would be the only ones able to access the private medical data. This means there would be control over who has access and to what. This would be a particularly timely development, particularly in the wake of privacy scares over medical data sharing.

By putting ultimate decision-making power into the patient’s hands, they can decide who can see their medical history. They could also just grant access to specific data while keeping other parts secure, and limits could even be set on how long a given entity has access to that information. Compare this to the current system where records are fragmented, outdated, and unreliable, and the patient has almost no power over who can access it — if it is even accessible in the first place. By storing in a secure, immutable, easy to access, and real-time blockchain, this new approach stands to save many more lives and give agency back to the people.

Prognosis 

At a time when the medical system has never been more strained or more critical and its vulnerabilities exposed, it is solutions like blockchain that stand to help people on all sides. By giving control to patients, they stand to have more faith in their practitioners. Furthermore, giving medical professionals the tools to save lives stands to keep more people safe, which will also help their image in the public’s eyes. Ultimately, blockchain opens the door to an overall better healthcare system, and it’s just around the corner.

About the author
Matthew Niemerg, PhD, is the co-founder of Swiss non-profit the Aleph Zero Foundation.

https://pharmaphorum.com/digital/blockchain-healthcare-electronic-medical-records/

Another gene therapy safety scare hits

 Anyone hoping that last week’s benign FDA advisory committee meeting about gene therapies might restore confidence in this troubled space will have been disappointed this morning. Biomarin is the latest group to be hit by a safety scare, with its phenylketonuria project BMN 307 being put on clinical hold by the agency today.

There are reasons to believe that this could be a temporary blip: the hold came after tumours were seen in mouse studies, and a previous link between other AAV gene therapies and liver cancer in mice has not been replicated in humans. But, after a recent string of bad news, the latest development reinforces the concern that patients might choose to steer clear of gene therapies, especially if other options are available.

Unmet need

In PKU Biomarin already has two approved therapies, Kuvan and the newer Palynziq, which are forecast to sell $86m and $619m respectively by 2026, according to Evaluate Pharma sellside consensus. Both drugs are designed to reduce blood phenylalanine, which in PKU is not broken down owing to deficiencies in the phenylalanine hydroxylase (PAH) enzyme, caused by mutations in the PAH gene.

Still, these drugs leave a lot to be desired: Kuvan is only suitable for a fraction of patients and must be used alongside a restrictive diet, while Palynziq comes with a black box warning and is given by daily subcutaneous injection.

This unmet need explains why various companies are trying to get into the PKU market, although Rubius’s cell therapy RTX-134 failed to make a mark in the disease, while Sangamo has discontinued its gene therapy ST-101.

Whether Biomarin’s BMN 307 will join these projects on the scrapheap depends on the latest findings in mice being shown to be relevant to humans.

The preclinical trial found that six of seven animals receiving the highest dose of the project, 2x1014vg/kg, had tumours a year after dosing, with evidence of integration of the AAV vector into the genome.

This raises the spectre of insertional mutagenesis, wherein a vector-delivered gene tampers with a target cell’s chromosomal arrangement, triggering cancer. This has long been one of the big theoretical worries about gene therapy in humans, and was discussed at last week’s adcom.

Of mice and men

Other AAV gene therapies have led vector-induced liver cancers in neonatal mice, the panel heard.

Biomarin’s study used mice bearing two genetic mutations: one eliminating the PAH gene and another rendering the animals immunodeficient. The company noted that these mutations might predispose the mice to developing cancer.

Biomarin also stressed that cancers due to AAV integration have not been seen in larger animals or humans. But Leerink analysts covering the panel wrote that there is evidence that AAV vectors can integrate into the dog and non-human primate genomes, although there has been no link so far between integration and tumourigenesis.

Late last year, concerns about insertional mutagenesis came to a head when a case of liver cancer was seen in the pivotal study of Uniqure’s AAV5-based haemophilia B gene therapy, etranacogene dezaparvovec. This was later deemed unlikely to be due to the project, but the group’s stock has still not recovered.

BMN 307, meanwhile, is already in a phase 1/2 study, in which it is being dosed at 2x1013vg/kg or 6x1013vg/kg – notably lower than the dose in the mouse study. There is scope to add another dose group, but the company said during its second-quarter call that, based on the evidence so far, it could take forward 6x1013vg/kg.

Unless the hold is lifted, though, the question of the ideal dose is academic. In terms of the broader gene therapy space the FDA panel recommended against capping the dose of gene therapies, something that had been mooted ahead of the meeting. 

The PKU pipeline
Project	Company	Description	Trial details
Phase 2
PTC923	PTC Therapeutics	Synthetic prodrug of tetrahydrobiopterin	Ph3 Aphenity trial to begin Q3'21
SYNB1618	Synlogic	Engineered E coli strain (consumes Phe)	Ph2 Synpheny-1, data due H2'21
BMN 307	Biomarin Pharmaceutical	PAH gene therapy (AAV5 vector)	Ph1/2 Phearless on hold after preclinical findings
HMI-102	Homology Medicines	PAH gene therapy (AAVHSC vector)	Ph1/2 Phenix, first data due YE'21
Phase 1
SYNB1934	Synlogic	Engineered E coli strain (consumes Phe)	Healthy volunteer study vs SYNB1618
CDX-6114	Codexis/Nestlé	PAL-like enzyme	Ph1 completed, ph1b planned in 2022
Preclinical
HMI-103	Homology Medicines	In vivo PAH gene editing	Ph1/2 to start 2021
mRNA-3283	Moderna	PAH mRNA therapeutic	In IND-enabling GLP toxicology studies
Ery-PAL	Erydel	Recombinant PAL encapsulated in patients’ erythrocytes	NA
Unnamed	American Gene Technologies	PAH gene therapy (lentiviral vector)	NA
SOM1311	SOM Biotech	Pharmacological chaperone of PAH	NA
AAV=adeno-associated virus; PAL=phenylalanine ammonia lyase; Phe=phenylalanine. Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/trial-results/another-gene-therapy-safety-scare-hits