Month: March 2023

Categories : Medical Industry Respiratory DiseasesTags :

Analysis: Landmark SA Court Case Takes on US Maker of Cystic Fibrosis Drugs

On By ModernMedia
Photo by Mockup Graphics on Unsplash

By Catherine Tomlinson

Cystic fibrosis (CF), which is caused by a faulty gene inherited from one’s parents, is a debilitating disease requiring difficult and time-consuming treatment and resulting in premature death. CF causes mucus in the body to thicken, with often disastrous consequences in organs such as the lungs and pancreas, and triggers a range of symptoms in people living with the condition, including chronic coughing, wheezing, and malnutrition. Ongoing treatment of symptoms often requires children with CF to miss school and can make it difficult for adults with CF to hold steady employment.

Yet, a new class of medicines introduced over the past decade called CFTR modulator therapies offers new hope to people living with CF – dramatically reducing CF’s symptoms and allowing people with CF to live longer healthier, and more productive lives.

These new treatments, whose research and development benefited from significant public and philanthropic financing, have been hailed as a “miracle” for people with CF. As antiretrovirals did for HIV, the introduction of CFTR modulator therapies is transforming cystic fibrosis from a progressive, life-threatening illness into a chronic, manageable condition. CFTR modulator therapies are so effective because they address the underlying cause of cystic fibrosis symptoms – a malfunctioning protein made by the CFTR gene.

But, more than a decade after the introduction of the first CFTR modulator therapy to treat CF in the United States, no CFTR modulator therapies are yet registered in South Africa and only a fraction of patients who need this therapy have access to it, and that is only after jumping through some extraordinary hoops. As a result, the only way for the vast majority of people to manage CF in South Africa is to aggressively prevent and treat its symptoms using older therapies. This is no small task for patients and their families, as it can require time-consuming, daily physical therapy to loosen mucus in the lungs and weeks-long hospital stays to treat infections. In severe cases, treating cystic fibrosis can even require a lung transplant.

Without access to CFTR modulator therapies, people with CF in South Africa continue to die prematurely. The average age of death of people with CF in South Africa was 27.5 in 2020. People in the global North live almost twice as long. The life expectancy of people living with cystic fibrosis in the United States is now 50 and is expected to lengthen as a result of newly introduced treatments.

Why can’t people in South Africa access CFTR modulator therapies?

As a person living with cystic fibrosis, or the parent of a child with cystic fibrosis, it can be unbearable to know there is a medicine that could allow you to breathe easier, keep you or your child out of hospital, and even prevent the need for a lung-transplant or premature death, but that you can’t have it, largely due to decisions taken by one company.

As recently detailed in the New York Times, one company holds a monopoly on the manufacture and sale of CFTR modulator therapies and is choosing not to make new CF treatments available to people in the developing world through the normal channels. Vertex, the company that holds monopoly patents on all available CFTR modulator therapies, is – for the most part – not registering or marketing its CFTR modulator therapies in developing countries. Registration is typically required before a drug can be marketed in a country.

While Vertex does offer some compassionate use and donation access programmes in select developing countries, Vertex Save Us, a global coalitional of advocates seeking affordable and universal access to CFTR modulator therapies, says these efforts reach only a small minority of patients that could benefit from the treatments and are restricted to countries with which Vertex believes it can secure a reimbursement deal.

Some activists suggest that the neglect of patients in developing countries is part of a strategy to squeeze the highest possible prices for CFTR modulator therapies from health systems in wealthy countries, with which Vertex has been locked in extended negotiations. Offering lower prices to developing countries for its CF medicines could provide ammunition to wealthy countries in demanding lower prices.

“This is a really fundamental and really simple example of how unfettered profit-driven business practices basically sacrifice the lives of people, particularly those of people who happen to live in low- and middle-income countries,” says Diarmaid McDonald, medicine access advocate and Director of the UK-based advocacy group, Just Treatment.

Vertex charges over R5 million ($322 000) annually for its most effective CFTR therapy, Trikafta (which must be taken as a life-long treatment) in the United States. But researchers in the United Kingdom have shown that the medicine can be manufactured and profitably marketed at a fraction of that cost.

Does Vertex plan to register its products in South Africa?

In response to queries from Spotlight regarding whether Vertex plans to register its drugs in South Africa and what the timeline for doing this is, the company indicated that they did not plan to register their medicines but would supply them via Section 21 authorisations – a mechanism allowing for importation of unregistered medicines into the country.

“As seen in other rare disease areas, bringing medicines to patients in South Africa is challenging as the reimbursement system and willingness to invest do not support a viable path to sustainable access. Analyses show that most novel, high-value medicines targeting disease areas comparable to and including CF are not on the Prescribed Minimum Benefits (PBM) list. There is therefore no obligation for funders to reimburse the costs of these medicines even after a lengthy regulatory registration process,” said Vertex’s Director of International Communications Daria Munsel.

“Given this, we believe that sustainable access could be achieved through ‘Section 21’ (on a named patient basis), which provides the fastest and most efficient route to access for rare disease medicines in South Africa,” Munsel added. “As part of this effort, we are currently in discussions with relevant stakeholders in the private insurance system to ensure sustainable access is available to eligible CF patients in South Africa.”

However, Munsel declined to identify the local company with which Vertex has signed an agreement for distributing its medicines, saying, “We can confirm that we have recently signed a distribution contract with a local distribution partner for our CF medicine in South Africa. Given that reimbursement conversations are still ongoing, it is inappropriate for us to name other parties for the moment.”

For now, the lack of transparency about the local distributor effectively blocks the use of Section 21 authorisations for importing Vertex’s medicines into South Africa, as patients and clinicians must supply details of local distributors in their applications to the South African Health Products Regulatory Authority (SAHPRA) for authorisation to import unregistered drugs.

Vertex did not respond to a question from Spotlight regarding what price it would charge patients in South Africa able to secure Section 21 authorisations to import their medicines.

Landmark court case seeks to challenge Vertex’s monopoly in South Africa

Vertex has secured a global monopoly over CFTR modulator therapies by aggressively pursuing patents related to the class of drugs around the world. These patents prevent other companies from manufacturing and marketing CFTR modulator therapies and give Vertex wide latitude in setting prices.

Between 2007 and 2016, Vertex filed six patents in South Africa related to the CFTR modulator therapies, Kalydeco and Trikafta. While Vertex received marketing approval to sell Kalydeco and Trikafta to treat CF in the United States in 2012 and 2019, respectively – it has still not applied for registration of either product in South Africa.

What this means is that despite Vertex’s failure to take steps to register or market its medicines in South Africa years after doing so in the US, patents granted to Vertex in South Africa block any other companies from supplying the medicines to CF patients in the country.

“The bottom line is that people are dying, they need to be able to access affordable treatments,” says Kelly du Plessis, founder of Rare Diseases South Africa. “If Vertex isn’t going to be able to come to the party in South Africa, then fine. We respect their choice, but then move out the way and allow someone else to do it. You can’t maintain the market and hold it ransom, but also not do anything from your perspective to help.”

According to Fatima Hassan, director of the Health Justice Initiative, “You can’t have a system where you file your patents, [but then] you refuse to bring a product to market or you have it at such an excessive price in the country with the highest inequality in the world, but then you don’t allow any generic manufacturers to come in at a lower price.”

Cheri Nel, a woman living with cystic fibrosis in South Africa, and the Cystic Fibrosis Association have now gone to court to challenge Vertex’s monopoly. On 7 February 2023, Nel’s lawyers submitted a Notice of Motion to the Court of the Commissioner of Patents (within the High Court) requesting that the court grants a compulsory license to override Vertex’s patents on Kalydeco and Trikafta.

Nel and the Cystic Fibrosis Association are seeking a compulsory license on the grounds that the patents held by Vertex are being abused. Nel’s lawyers argue that by failing to register or supply their CF medicines in South Africa, make them available in South Africa at reasonable prices, or license other companies to supply the medicines, Vertex is abusing its patents. They further argue that Vertex’s actions are violating the Constitutional rights of people with cystic fibrosis in South Africa, including the right to health care.

If granted, a compulsory license in South Africa would effectively override Vertex’s monopoly and allow the importation of generic cystic fibrosis medicines into South Africa, as well as their manufacturing in the country.

The legal action taken in South Africa is being pursued simultaneously with broader global efforts, led by Vertex Save Us, to overcome Vertex’s monopoly on CFTR modulator therapies and ensure universal access for all people who can benefit from these treatments.

“South Africa is the only country where papers have been launched with courts to start a legal process to try and secure a compulsory license, although the process is playing out in other countries following the most logical, legal routes set out in their national law,” explains McDonald.

“Requests of the government to issue compulsory licenses [have been made] in both Ukraine and in Brazil. And in India, it’s a petition of the government requesting that they revoke the patent under the terms of the Indian patent law,” says McDonald.

Any precedent for granting compulsory license on a medicine in South Africa?

If Nel and the Cystic Fibrosis Association’s pursuit of a compulsory license on the cystic fibrosis medicines is ultimately successful, then the issuing of a compulsory license order will be the first time this type of license is granted in the country on a pharmaceutical product. While South Africa has not issued a compulsory license on a medicine, the Treatment Action Campaign (TAC) has previously used competition law to overcome patents impeding access to affordable antiretroviral medicines in South Africa.

TAC cases at the Competition Commission and the threat of ‘compulsory licensing’ resulting from these cases led several multinational companies to grant voluntary licenses that enabled manufacturing and marketing of generic ARVs in the country. Generic competition resulted in massive price decreases for ARVs and has been critical to South Africa’s success in building the world’s largest public sector HIV treatment programme.

While South Africa’s courts have not issued a compulsory license on a medicine, its own challenges in securing access to affordable HIV medicines contributed to the affirmation and strengthening of the rights of countries to issue compulsory licenses to address health challenges within international trade law in the early 2000s. Both developing and developed countries have subsequently used compulsory licensing to improve access to critical health tools under patent including for HIV, cancer, and more recently, COVID-19.

The Fix the Patent Laws coalition, a coalition of over forty patient groups in South Africa, has long called on government to amend South Africa’s patent laws to improve the usability of compulsory licensing provisions to address health challenges in the country. The landmark court case of Nel vs Vertex will provide important insight into the ongoing need for these reforms in the country.

Who can benefit from Kalydeco and Trikafta

While cystic fibrosis is caused by a defect of the CFTR gene, over a thousand different types of mutations can occur in the gene that causes CF. People with CF must inherit a mutated gene from each parent in order to develop CF illness. The type of gene mutations that each person with cystic fibrosis inherits from their parents determines their eligibility for different CFTR modulator therapies.

Vertex, which has a monopoly over the entire class of CFTR modulator therapies available for CF, currently markets six medicines made up of different combinations of active ingredients that seek to correct the faulty CFTR protein (produced by the CFTR gene).

Kalydeco, made with the active ingredient ivacaftor, was the first CFTR modulator therapy approved to treat CF, yet it is only effective in treating five percent of people living with CF. Trikafta, which was approved in the U.S. in 2019 and combines three active ingredients – elexacaftor, tezacaftor and ivacaftor – is effective in treating 90 percent of people living with cystic fibrosis.

How many people in South Africa could benefit from Trikafta?

The recently established South African Cystic Fibrosis Registry has compiled health and demographic data for 525 people diagnosed with cystic fibrosis in the country. According to 2020 registry data, 450 patients (85.7%) would benefit from currently available CFTR modulator treatments. Dr Marco Zampoli, paediatric pulmonologist at the University of Cape Town, estimates that around 35 patients are currently sourcing generic CFTR modulators in their personal capacity from overseas (see more below on how a small group of patients in the country are accessing treatment from Argentina).

While the registry counts 525 patients diagnosed with CF in South Africa, the true number of people born with CF in the country is likely far higher. Zampoli estimates (using population and genetic data) that between two and three thousand babies could have been born with cystic fibrosis in South Africa since 1999.

“We think a lot of them are probably dying from a very young age without being diagnosed with cystic fibrosis as it looks similar to other common things like malnutrition, TB, and HIV,” says Zampoli.

While improving CF detection and diagnosis can save lives and will also increase the number of known patients in the country that could benefit from currently available CFTR modulator therapies, many of the new patients identified from better detection efforts would be unable to benefit from existing treatments. This is because black Africans are less likely than people of Caucasian descent to have the mutations that are responsive to currently available treatment.

Zampoli, however, notes that research is underway that will likely deliver new treatments that benefit patients who are ineligible for currently available drugs and adds “we’re going to be facing the same issues [of unaffordability] down the line… when we do eventually license a drug that will target their specific genes.”

How do a few people in South Africa get access to CFTR modulators?

While the South African government is not currently in negotiations with Vertex, price negotiations with health systems in wealthy countries have often dragged on for years, as price remained a sticking point.

People living with severe cystic fibrosis, however, do not have years to wait as their disease advances, placing them at risk of severe complications and death. Some have joined together to start a CF Buyers Club. The Buyer’s Club supports CF patients from around the world in buying generic versions of CFTR modulators from Argentina.

Argentina has taken steps to set strict criteria for granting patents and limit the granting of patents on certain types of claims related to pharmaceutical products. As a result, Vertex has not been granted patents on its CFTR modulator treatments in Argentina, and two Argentinian pharmaceutical companies, Gador and Tuteur, are legally manufacturing generic versions of these medicines.

While the Argentinian companies producing these medicines are unwilling to export them to South Africa for fear of facing patent infringement challenges from Vertex, Argentinian pharmacies will supply medicines to CF patients from South Africa visiting Argentina.

“You need to have a doctor’s script and you need to have a Section 21 authorisation,” explains Belinda Nell, a South African advocate working to facilitate access to CF medicines in South Africa. “You’ve got to fly to Argentina in your personal capacity or have a family representative go there and collect [the medicines] and then fly back.”

South Africans holding Section 21 authorisations from SAHPRA can legally travel with up to six months’ medicine supply on them.

While the CF Buyers Club provides an important access pathway enabling some people in South Africa to access life-saving CFTR modulator therapies, this pathway is not a feasible mechanism to ensure access to the CF medicines for all patients that could benefit from them.

The cost of generic CF medicines from Argentina is a fraction of the prices charged by Vertex. They are, however, still prohibitively high for most people living in South Africa. The annual cost of generic Trikafta from Argentina is almost R1 million ($60 000) [other CFTR modulator therapies (tezacaftor/ivacaftor and lumacaftor/ivacaftor) can be bought from Argentina for around R245 000 ($15 000) annually]. The medicine costs, combined with the costs of biannual travel to Argentina, are simply unaffordable for most.

How can a CL further reduce prices?

As seen with other classes of drugs, such as antiretroviral medicines for HIV, and antiviral medicines for Hepatitis C, the introduction of generic competition is expected to substantially reduce the cost of CF medicines.

If compulsory licenses are granted in the countries that they are being sought by Vertex Save Us, or if Vertex buckles under the pressure for expanded and affordable access to CF medicines and grants voluntary licenses allowing other companies to produce generics, then prices are expected to fall.

An analysis of the costs of production of CF medicines produced by health economists shows that generic Trikafta can be manufactured and sold with a 10 percent profit margin for around R93 000 ($5700) per patient per year – 2% of what is charged for the medicine by Vertex in the United States. While supplying medicines at this price would remain a stretch for South Africa’s public health sector, the introduction of new CF medicines must be considered within the context of potential cost savings arising from reduced hospitalisation periods and fewer transplants.

“The ripple effects of an effective CL campaign and petition in South Africa would be felt globally,” says McDonald. “First of all, I think we would see increased interest from generic suppliers… that could help to… drive down prices… this would [also] show the rest of the world that… accepting the unquestioned, monopoly power of Vertex is not necessary – you can put the lives of your citizens over the profits of that drug company.”

Note: The Fix the Patent Laws coalition and the TAC are mentioned in this article. Tomlinson worked at the TAC until 2012 and was a member of the Fix the Patent Laws steering committee until 2019. SECTION27 has also applied to be admitted as amici curiae to the case. Spotlight is published by SECTION27 and the TAC, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.

Republished from Spotlight under a Creative Commons 4.0 Licence.

Source: Spotlight

Categories : Cardiovascular Disease Neurodegenerative DiseasesTags :

Atrial Fibrillation Linked to Dementia Risk

On By ModernMedia
Source: American Heart Association

A large representative study found that individuals with newly diagnosed atrial fibrillation had a modestly elevated risk of developing dementia. The Journal of the American Heart Association study found that this risk was higher in younger adults and those without chronic kidney disease, but did not substantially vary across sex, race, or ethnicity.

In this study of nearly 200 000 adults, incidence rates for dementia over a median follow-up of 3.3 years were 2.79 versus 2.04 per 100 person-years in individuals with versus without atrial fibrillation, respectively. (This means that over one year, there would be an average of 2.79 dementia diagnoses among 100 people with atrial fibrillation and 2.04 diagnoses among 100 people without atrial fibrillation. This translates to 279 per 10 000 and 204 per 10 000.)

After adjustments, atrial fibrillation was associated with a 13% higher risk of dementia. Adults aged <65 years had a 65% higher risk compared with older adults, those without chronic kidney disease had a 14% higher risk than those with chronic kidney disease.

“These data highlight a possible link between atrial fibrillation and risk of subsequent dementia in certain populations. Further studies are needed to understand the mechanisms to explain this association, which may inform the use of treatments for atrial fibrillation,” said corresponding author Nisha Bansal, MD, MAS, of the University of Washington School of Medicine.

Source: Wiley

Categories : Cancer Immune SystemTags :

Towards Treating Dangerous Immunotherapy Side Effects

On By ModernMedia
Photo by Tima Miroshnichenko on Pexels

While immunotherapy has been shown to greatly improve survival rates for certain types of cancer, in some cases, it can lead to a dangerous over-activation of the immune system. In a recent review published in Journal for ImmunoTherapy of Cancer, potential therapies have been identified, which might make it possible to continue with immunotherapy even when facing severe side effects.

The rare immunotherapy side effect of over-activation was only clinically recognised during regular clinical use rather than in clinical trials or animal experiments. To better understand this over-activation, Lisa Liu, Marco Gerling, and colleagues analysed data from all published international reports on this issue after cancer immunotherapy. Their findings indicate that potentially life-threatening inflammation may occur more frequently than previously thought, and might be treatable with existing drugs such as steroids or anti-inflammatory therapies commonly used for rheumatoid arthritis.

“It will be exciting to follow up on the main findings of our systematic review, says Marco Gerling at the Department of Biosciences and Nutrition, Karolinska Institutet and lead author.

“We believe that inhibition of a specific inflammatory molecule, interleukin-6, could allow patients to continue immunotherapy despite strong, systemic activation of the immune system”, he continues. “But we need more data to support the regular use of interleukin-6 inhibitors. We also want to thank Narcisa Hannerz and Sabine Gillsund from Karolinska University Library for their invaluable help with finding articles for this review.“

Source: Karolinska Institutet

Categories : UncategorizedTags :

New Review Finds Spinal Cord Stimulation Ineffective for Low Back Pain

On By ModernMedia
Photo by Sasun Bughdaryan on Unsplash

Spinal cord stimulation for the treatment of chronic pain does not provide long-term relief and may cause harm, according to a new Cochrane Review. Spinal cord stimulation involves an implanted device that sends electrical pulses to the spinal cord to interrupt nerve signals before they get to the brain.

The study reviewed published clinical data on spinal cord stimulation, including randomised controlled trials, the ‘gold standard’ for medical research. The researchers analysed the results of 13 clinical trials, looking at data from 699 participants, comparing spinal cord stimulation treatment with placebo or no treatment for low back pain.

Cochrane reviews are trusted by researchers, medical professionals and policymakers because they use robust methodologies to combine evidence from multiple sources, reducing the impact of bias and random error that can make individual studies less reliable.

The review concluded that spinal cord stimulation is no better than a placebo for treating low back pain, with probably little to no benefit for people with low back pain or improvement in their quality of life.

There was little to no clinical data regarding the long-term effectiveness of spinal cord stimulation.

The researchers also found that adverse side effects to the surgery were poorly documented overall, preventing them from concluding the level of risk involved. Harms from spinal cord stimulation could include nerve damage, infection, and the electrical leads moving, all of which may need repeated surgeries.

The review findings have been submitted to the Federal Department of Health and Aged Care prosthesis list review taskforce. The taskforce is reviewing the eligibility of current prostheses subsidised by Medicare.

In Australia, the devices’ long-term safety and performance are also being re-assessed by The Therapeutic Goods Administration (TGA), the country’s regulatory authority for therapeutic goods.

“Spinal cord stimulation is invasive and has a great financial cost to people who choose surgery as a last resort to alleviate their pain. Our review found that the long-term benefits and harms are essentially unknown,” said lead researcher Dr Adrian Traeger from Sydney Musculoskeletal Health, an initiative of the University of Sydney, Sydney Local Health District and Northern Sydney Local Health District.

“Our review of the clinical data suggests no sustained benefits to the surgery outweigh the costs and risks.

“Low back pain is one of the leading causes of disability worldwide. Our findings further emphasise the urgent need to review funding arrangements for chronic pain care to help patients in their search for relief. There are evidence-based physical and psychological therapies for back pain; ensuring access to these is essential.”

The review team found multiple gaps in clinical data.

There were no studies that investigated the long-term (more than 12 months) impact of spinal cord stimulation on low back pain. The longest was a single six-month trial.

The majority of clinical trials only looked at the immediate impact of the device, which is a time frame of less than a month.

The review team provided a list of recommendations, including that future spinal cord stimulation clinical trials be at least 12 months, clearly document the number of people who experience adverse events and make comparisons with other pain treatment options.

Professor Chris Maher,Co-Director of Sydney Musculoskeletal Health, said:

“Our review found that the clinical benefit of adding spinal cord stimulation to treat low back pain remains unknown. When coupled with the reality that these devices are very expensive and often break down there is clearly a problem here that should be of concern to regulators.”

A separate Cochrane review, in which the researchers were not involved, examined the effect of spinal cord stimulation versus placebo in people with chronic pain. Similar to this review, it concluded there was a lack of evidence to suggest long-term benefits in treating chronic pain.

Source: University of Sydney

Categories : Diseases, Syndromes and Conditions NeurologyTags :

A Molecular Mechanism for Hydrocephalus may Enable a Non-surgical Treatment

On By ModernMedia
MRI images of the brain
Photo by Anna Shvets on Pexels

Researchers at Massachusetts General Hospital have discovered a novel molecular mechanism behind the most common forms of acquired hydrocephalus – which could lead to the first non-surgical treatments for the life-threatening disease. Research in animal models uncovered a pathway through which infection or bleeding in the brain triggers inflammation, causing increased production of cerebrospinal fluid (CSF) by the choroid plexus and lead to swelling of the brain ventricles.

“Finding a nonsurgical treatment for hydrocephalus, given the fact neurosurgery is fraught with tremendous morbidity and complications, has been the holy grail for our field,” says Kristopher Kahle, MD, PhD, a paediatric neurosurgeon at MGH and senior author of the study in the journal Cell. “We’ve identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain bleed or brain infection in acquired hydrocephalus. We’re hopeful these findings will pave the way for approval of an anti-inflammatory drug to treat hydrocephalus, which could be a game-changer for populations in the US and around the world that don’t have access to surgery.”

Occurring in about 0.2% of births, acquired hydrocephalus is the most common cause of brain surgery in children, though it can affect people at any age. In underdeveloped regions where bacterial infection is the most prevalent form, hydrocephalus is often deadly for children due to the lack of surgical intervention. Brain surgery, where a shunt is implanted to drain fluid from the brain, is the only known treatment. But about half of all shunts in paediatric patients fail within two years of placement, according to the Hydrocephalus Association, requiring repeat neurosurgical operations and a lifetime of brain surgeries.

Pivotal to the process is the choroid plexus, the brain structure that routinely pumps cerebrospinal fluid into the four ventricles of the brain to keep the organ buoyant and injury-free within the skull. An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles with cerebral spinal fluid and immune cells from the periphery of the brain in a cytokine storm, swelling the brain ventricles.

“Scientists in the past thought that entirely different mechanisms were involved in hydrocephalus from infection and from haemorrhage in the brain,” explains co-author Bob Carter, MD, PhD, chair of the Department of Neurosurgery at MGH. “Dr Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the US Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection.”

MGH researchers are continuing to explore how rapamycin and other drugs which quell the inflammation seen in acquired hydrocephalus could be repurposed. “What has me most excited is that this noninvasive therapy could provide a way to help young patients who don’t have access to neurosurgeons or shunts,” says Kahle. “No longer would a diagnosis of hydrocephalus be fatal for these children.”

Source: Massachusetts General Hospital

Categories : COVID Diseases, Syndromes and ConditionsTags :

Macrophage Discovery Could Lead to Treatments for Diseases Such as Lupus and COVID

On By ModernMedia
A macrophage engulfing a yeast cell. Source: CC0

Scientistshave made an important breakthrough in understanding failures during the progression of inflammatory diseases and in doing so unearthed a potential new therapeutic target. The scientists report in Nature that an enzyme called Fumarate Hydratase is repressed in macrophages. These immune cells are already implicated in a range of diseases including Lupus, arthritis, sepsis and COVID.

Lead author Luke O’Neill, Professor of Biochemistry at Trinity said: “No-one has made a link from Fumarate Hydratase to inflammatory macrophages before and we feel that this process might be targetable to treat debilitating diseases like Lupus, which is a nasty autoimmune disease that damages several parts of the body including the skin, kidneys and joints.”

Joint first-author Christian Peace added: “We have made an important link between Fumarate Hydratase and immune proteins called cytokines that mediate inflammatory diseases. We found that when Fumarate Hydratase is repressed, RNA is released from mitochondria which can bind to key proteins ‘MDA5’ and ‘TLR7’ and trigger the release of cytokines, thereby worsening inflammation. This process could potentially be targeted therapeutically.”

Fumarate Hydratase was shown to be repressed in a model of sepsis, an often-fatal systemic inflammatory condition that can happen during bacterial and viral infections. Similarly, in blood samples from patients with Lupus, Fumarate Hydratase was dramatically decreased.

“Restoring Fumarate Hydratase in these diseases or targeting MDA5 or TLR7 therefore presents an exciting prospect for badly needed new anti-inflammatory therapies,” said Prof O’Neill.

Excitingly, this newly published work is accompanied by another publication by a group led by Professor Christian Frezza, now at the University of Cologne, and Dr Julien Prudent at the MRC Mitochondrial Biology Unit (MBU), who have made similar findings in the context of kidney cancer.

“Because the system can go wrong in certain types of cancer, the scope of any potential therapeutic target could be widened beyond inflammation,” added Prof O’Neill.

Source: Trinity College Dublin

Categories : Neurology PaediatricsTags :

Difficulty Picking up Audio-video Timing Mismatch a Predictor of Autism in Kids

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Photo by Helena Lopes on Pexels

Typically developing infants perceive audio-video synchrony better than high-risk for autism infants, according to new research published in the European Journal of Pediatrics. The research from Rutgers University might enable far earlier autism diagnoses.

If follow-up research demonstrates that most infants who miss unmatched audio and video develop autism spectrum disorder (ASD), physicians may be able to diagnose the condition years earlier – a potentially important step as early treatment strongly predicts better outcomes.

“We’re a long way from validating this as a diagnostic tool, but the results definitely suggest it could be a diagnostic tool,” said senior author Michael Lewis, professor at Rutgers Robert Wood Johnson Medical School.

Lewis and other researchers have long known children with ASD struggle to perceive audio-visual speech as a unified event, and they’ve hypothesised that this difficulty may contribute to social impairments and language deficits in such children.

To study whether these difficulties arise before it’s currently possible to diagnose ASD, generally around age 3, the researchers assembled two groups of infants ages 4 to 24 months, one comprising children whose developmental delays indicate an elevated risk of ASD and the other comprising typically developing children.

The researchers showed that participants from both groups two types of videos with progressively longer time separation between image and sound. The first videos featured a ball making noises as it bounced against a wall. The second showed a woman talking.

When watching videos of the ball, the two groups performed similarly. When watching videos of the woman, however, the differences were stark. Typically, developing children perceive audio-visual gaps that are, on average, a tenth of a second smaller than those perceived by the kids with developmental delays.

Although this result confirmed the researchers’ initial hypothesis, some findings were surprising. The ability to perceive audio-visual mismatch wasn’t associated with vocabulary size in children old enough to have a vocabulary.

If a high percentage of the children who were slowest to identify mismatched audio and video go on to be diagnosed with autism – and the findings are repeated with far more children than the 88 who participated in this study – audio-visual tests might prove a revolutionary diagnostic tool for a condition that’s becoming far more common, Lewis said.

However, scientific validation is just the first step to adoption, he said. Insurers would need to pay for tests, and paediatricians would need to embrace them before they could be used to begin providing support services to children in need.

“Earlier diagnosis won’t allow us to cure ASD anytime soon, but it will allow for the earlier provision of support services that can help such children in areas of weakness and direct them toward areas of strength,” Lewis said. “The goal is to create happy people whose schooling and, eventually, careers are well suited to them, and that’s certainly an achievable goal for most.”

Source: Rutgers University

Categories : Ageing Injury & TraumaTags :

Researchers Develop 5-factor Model for Nursing Home Fall Risks

On By ModernMedia
Carers help an old man to walk
Photo by Kampus Productions on Pexels

In research published in the Journal of the American Geriatrics Society, investigators developed and validated models that can predict the risk of fall-related injuries (FRI) in nursing home residents based on routinely collected clinical data.

The researchers conducted retrospective cohort study of long-stay US nursing home residents (mean age 85 years, 69.6% female) between January 1, 2016 and December 31, 2017 (n = 733 427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through statistical methods, from an original set of 70 predictors. To come up with a useful clinical tool, they calculated a score using the five strongest predictors in the model.

Within 2 years of follow-up, 6% of residents experienced one or more FRI. The prediction models achieved good discrimination and excellent calibration for accurately estimating individuals’ six-month and two-year risk of fall-related injuries. In the clinical tool to predict 2-year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14–2.41) and a history of non-hip fracture (HR 2.02; 95% CI 1.94–2.12). Performance results were similar in the validation sample.

“These models can be used by researchers and clinicians to accurately determine patient risk for fall-related injuries using routinely collected clinical assessment data,” the authors wrote. “In nursing homes, these models should be used to target preventive strategies.”

Source: Wiley

Categories : Healthcare Politics and Regulations HospitalsTags :

People’s Lives are ‘Not Our Responsibility’ Says NEHAWU Leader

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By Vincent Lali, Chris Gilili, Liezl Human, Tariro Washinyira, Nombulelo Damba-Hendrik, Thamsanqa Mbovane, and Mkhuseli Sizani

“You have shown the power of the people by closing all the hospitals,” National Education Health and Allied Workers’ Union (NEHAWU) Western Cape provincial secretary Baxolise Mali told striking union members on Wednesday. “The employer says people are dying. It is not our responsibility to keep people’s lives.”

Mali was speaking to strikers outside the Khayelitsha District Hospital in Cape Town, as NEHAWU members continued a wage strike which has disrupted hospitals and government offices across the country. The government considers the wage negotiations for 2022 to be settled but NEHAWU and several other unions are still demanding up to 12%.

Police presence outside the hospital had kept protesters away, said hospital CEO David Binza. He said the situation was “better than yesterday”, when “things were bad”.

Binza said services at the hospital had been severely affected by the strike on Monday.

Protesters had prevented people coming in and out of the hospital. Staff had ended up working 24 hours because there were not enough nurses to relieve them, and there was a shortage of nurses in childbirth wards. “Yesterday they prevented night staff from gaining access into the facility. It was mostly doctors that they allowed in. Doctors alone can’t work properly,” he said.

Today things had been better, he said, as the police had arrived early and kept protesters away from the hospital.

Western Cape health spokesperson Mark van der Heever said shift changes at the hospital were being closely monitored after patients in critical condition had to be transferred to other hospitals such as Helderberg, Tygerberg, Mitchells Plain and Karl Bremer.

Striking workers outside Khayelitsha District Hospital on Wednesday. Photo: Vincent Lali

“On Tuesday night, 7 March, protesters disrupted services and blocked staff from entering Khayelitsha District Hospital until 11pm. The ongoing disruption has directly resulted in staff shortages as they are prevented from entering, backlogs building up and other operational challenges.”

He said protests had been reported at Karl Bremer and Tygerberg hospitals, but services had not been disrupted.

Mali said NEHAWU’s intention was to “collapse the provision of government services” to force the government to the negotiating table. “Our tactics involve closing workplaces, to force workers to get out and switch off their computers.”

Home Affairs offices in Khayelitsha were closed. Disappointed, Luthando Tiso said he has been going to Khayelitsha Home Affairs to collect his ID since Monday. “I can’t get a job without an ID,” he said.

In the city centre, the Home Affairs office in Barrack Street and the offices of the Department of Labour were closed and there was a strong police presence.

One man said he had been to the Mitchells Plain Labour Department offices on Monday and Tuesday only to find them closed because of the strike, and had come to Cape Town hoping for help. “I desperately need to claim from the Unemployment Insurance Fund. I lost my job in January. My rent and children’s school fees are already behind,” he said.

Eastern Cape

In the Eastern Cape, Department of Health spokesperson Yonela Dekeda said hospitals were being run by skeleton staff.

“We had an incident early in the morning where striking workers blocked the Cecilia Makiwane Hospital’s entrance in East London. But police were called to remove them.”

Dekeda said unions which were not supporting the strike action had raised concerns that their members were being intimidated and denied access to workplaces.

“We do appreciate responsible shop stewards who have called their members to order, where necessary, and ensured that critical services continue and that our patients receive necessary care,” she said. “However, we take very seriously those employees who intimidate others, and cause services to be affected negatively.

“Appropriate action will be taken in all such instances, and law enforcement agencies are being deployed.”

At Laetitia Bam Day Hospital in KwaNobuhle, Kariega, Eastern Cape deputy secretary of NEHAWU, Busiswa Stokwe told about 100 striking workers: “We know we will be attacked even in the community, accused of not caring for patients. But the same community when you are doing the work of ten people, whilst you are four, would insult you, saying you are lazy. We must put ourselves first.”

A patient who did not want to give his name said he had arrived at 5am to have three teeth removed but had been ordered out by striking workers at 7am. “They came by car and on foot and sang in the corridors. We realized that we should go back home, with aching teeth.”

“We were about ten and have no money to remove teeth at a private doctor, who charges R350 per tooth,” he said.

Gauteng

In Tshwane, striking workers closed down the offices of the Department of Public Service and Administration, shouting and insulting some workers who were inside the offices.

There was a stand-off between the striking workers and police, as the workers closed off Hamilton and Edmond Streets with huge stones and turned cars away. Police moved the workers away.

Phumuzo Malahleni, a registry clerk at the Department of Agriculture, said his R12,000-a-month salary was too low to cope with the soaring cost of living. “As public servants we can’t afford anything. Violence and going to the streets is the only language our government understands.”

NEHAWU Gauteng provincial chairperson Mzikayise Tshontshi told GroundUp that the battle for a wage increase was far from over.

He said NEHAWU had been called to the Public Sector Bargaining Council on Thursday. “Our negotiators will be there, but the rest of us will continue shutting down public services.

“We believe our strike has been resoundingly successful. From Monday to today, the numbers have been growing. Tomorrow we want to intensify the strike,” said Tshontshi.

Addressing the crowd outside the department, Tshontshi called out those who were still at work.

“We are also aware of ‘amagundwane’ (rats). Some are sitting in cosy offices, and then when we win this battle they are going to be first in the queue because they think they deserve what we have fought for. There have always been traitors in every struggle; this is no different.”

At Tembisa hospital, striking workers blocked the entrance with burning tyres and debris while chanting slogans. Calm was later restored.

Free State

Free State health spokesperson Mondli Mvambi said the province had obtained an interdict on Wednesday morning to prevent strikers from disrupting services at hospitals and clinics. “The order does not stop the strike but stops acts of intimidation, violence, disruptions and instigating.”

Mvambi said hospitals hardest hit were National District Hospital, Universitas, Pelonomi and Medical Depot in Bloemfontein. “There were no nurses at work and patient care was seriously compromised.” Mvambi said calm had been restored but services remained strained as nurses were still not at work.

“At Manapo in QwaQwa they are not allowing nurses into the hospital. At Boitumelo in Kroonstad, picketers were singing at the gate but services are said to be continuing. At Pelonomi Hospital, nurses in ICU were forced out by the strikers.”

North West

In the North West, services at least six hospitals were disrupted by the strike: Klerksdorp-Tshepong, Potchefstroom, Taung District, Moses Kotane, Ganyesa District, and Gelukspan. There were pickets outside several other clinics and hospitals.

Mpumalanga

In Mpumalanga, spokesperson Christopher Nobela said that all health facilities had been affected and hospitals were working with skeleton staff in hospitals.

Limpopo

Limpopo health spokesperson Neil Shikwambana said, “We do not have reports of disruptions in any of our facilities so far.”

KwaZulu-Natal

Workers stopped work at Inkosi Albert Luthuli Central Hospital in Durban for several hours on Wednesday morning, singing outside the hospital. Patients were allowed to enter.

NEHAWU branch secretary Sikhumbuzo Gumbi said workers decided to go back to work at midday so they could assist patients. “As workers we decided to protest in the morning then attend to patients around lunchtime.”

Gumbi said the staff would continue protesting in the mornings until the strike ends.

Prince Mthalane, Durban NEHAWU regional secretary, said clinics had been closed in KwaMashu and at Polyclinic workers had burned tyres. Police had been called but workers had talked to them and no-one had been arrested.

“The aim is to have a peaceful strike,” he said.

GroundUp was unable to reach the health department spokespersons in KwaZulu-Natal or the Northern Cape.

Police

“Innocent patients have been caught in the crossfire and inconvenienced by something which has nothing to do with them,” said Department of Health national spokesperson Foster Mohale. He said the Minister of Health had asked the Minister of Police to strengthen the police presence in areas affected by the strike.

“Skeleton staff has also been available to give care to patients who could not be discharged,” said Mohale.

South African Police Union spokesperson Lesiba Thobakgale said the union had joined NEHAWU in the protest. “As SAPU, from today we have served a strike notice and we are joining the other unions,” said Thobakgale.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : CancerTags :

Digital Rectal Exam is not Useful in Detecting Prostate Cancers Early

On By ModernMedia
Healthcare worker pulling on gloves
Image by Gustavo Fring on Pexels

A common method of detecting prostate cancer may not be accurate enough as a reliable screening tool by itself, scientists in Germany have warned. The digital rectal exam (DRE) is widely used by medical professionals to check the prostate gland with a finger for unusual swelling or lumps in the rectum as an initial check for the signs of prostate cancer in men.

But new research by scientists of the PROBASE trial coordinated at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, suggests the technique may be missing many cancers in their early stages.

The findings, presented at the European Association of Urology Annual Congress in Milan, could have implications for the early detection of prostate cancer, say the researchers. They are calling for other testing methods to be used in routine screening instead.

“One of the main reasons for screening for prostate cancer is to detect it in patients as early as possible as this can lead to better outcomes from treatment,” said Dr Agne Krilaviciute, a researcher at DKFZ and lead author of the study. “But our study suggests that the DRE is simply not sensitive enough to detect those early stage cancers.”

The PROBASE trial is a multicentre German prostate cancer screening study involving 46 495 men aged 45 years who were enrolled between 2014 and 2019. The men have since been had follow ups to assess their health in the years after the screening. Half of the participants in the trial were offered prostate specific antigen (PSA) blood test immediately at age 45 while the other half were initially offered DRE with delayed PSA screening at age 50.

Ultimately, 6537 men in the delayed screening group underwent DRE and only 57 of these men were referred for a follow-up biopsy due to suspicious findings. Only three were found to have cancer.

When compared to the detection rate using other methods, such as a PSA test, the rate of detection using DRE was substantially lower, says Dr Krilaviciute.

“The DRE was giving a negative result in 99% of cases and even those that were deemed to be suspicious had a low detection rate,” says Dr Krilaviciute. “Results we’ve seen from the PROBASE trial show that PSA testing at the age of 45 detected four times more prostate cancers.”

The researchers believe one of the reasons why the DRE might be failing to detect cancers, particularly in younger men, is because the changes in the tissue in the prostate may be too slight to detect with a finger. In addition, some cancers occur in a part of the prostate that cannot be easily reached by a finger.

“Early stage cancer may not have the size and stiffness to be palpable,” said Professor Peter Albers, a urologist at Düsseldorf University who was the senior author of the study.

“Separate analysis that used MRI scans before biopsies to locate cancers in the prostate showed that about 80% of these are in an area that should be easy to reach with a finger and still cancers were not detectable by DRE.”

The researchers are now calling for widespread use of PSA testing and MRI scans as part of screening programmes instead of DRE.

“If the aim of a screening programme is to pick up cancers as early as possible and the current screening tool isn’t doing that job, then that is a fundamental failure of that approach,” said Professor Albers. “We speculate in our paper that not only is the DRE not useful for detecting cancer, but it may also be one reason why people don’t come to screening visits – the examination probably puts a lot of men off.

“In Germany, for example, the participation rate is less than 20% in the screening programme for men 45 to 50 years. If we were to offer PSA testing instead, more of them might be willing to come.”

Source: European Association of Urology