Month: April 2022

Can Public Clinics Be Fixed with The Right Technology?

Male doctor with smartphone
Photo by Ivan Samkov on Unsplash

Investigating the state of affairs in public clinics, Spotlight’s Daniel Steyn and Vusi Mokoena investigate whether the right technology could help them out of their predicament.

“I never look forward to clinic day,” says Nomtsato Tsietsi, 74, on a Monday morning while standing in the queue at Kayamandi Clinic in Stellenbosch, which she visits up to three times a month to collect pills, consult with a doctor, and have her blood tests taken.

Tsietsi has several diseases including diabetes and hypertension (high blood pressure). “We sit there for too long, sometimes all day,” she says.

Her experience is typical for people visiting state clinics. But for about 80% of South Africans, this is the only option: for most people private healthcare is unaffordable and public clinic services are free.

Some patients in the Kayamandi clinic queue said they sometimes pay people up to R80 to stand in the queue for them. One man, who had been paid by someone to stand in the queue, said that he had been there since 5am.

For employed people, a day at the clinic typically means taking a day off work, often without pay.

The pubIic health system is beset with problems: long waiting times, insufficient record keeping, poorly maintained infrastructure, and poor service delivery.

A 2018 study of nurses and doctors in Cape Town found that of 16 essential skills, ten were not performed in more than half of the consultations. In more than 60% of consultations, nurses and doctors in Cape Town did not greet patients, and in 90% of consultations, they did not attempt to understand the patient’s perspective. In nother study, 76% of Cape Town-based doctors in primary care reported that they are suffering from burnout.

During our visit to Kayamandi Clinic, we asked patients whether they would embrace technological solutions to make the experience more efficient. They all said they would. Almost all of them are smartphone users and some said they could not understand why appointments cannot be made and managed digitally, or why they cannot communicate with health workers online rather than in person.

Innovative technology solutions for primary care exist in South Africa. Phukulisa Health Solutions, for example, offers a platform that mimics a consultation with a healthcare practitioner. Equipped with Bluetooth sensors, the platform can screen patients for a range of health issues, focused specifically on HIV, TB, diabetes, and heart diseases.

Phukulisa’s CEO Raymond Campbell says that this testing and screening platform offers a more efficient screening service with a faster turnaround time. For example, the platform has been tested at an antenatal unit in Mamelodi, where the platform provided test results within 14 minutes, opposed to the usual 23 hours.

But Campbell says there is little interest from the public sector in his technology. Instead, he is finding more success licensing the platform to players in the private sector.

There have been some attempts to use innovative computer technology in public sector clinics. In Limpopo, the deputy director-general of the health department, Dr Muthei Dombo, has the vision to create a “clinic in the cloud”.

In 2018, Dombo partnered with the Mint Group to conduct a trial funded by Microsoft at Rethabile clinic. Dombo provided the team at Mint Group with several problems to solve.

The team, led by Peter Reid, developed a technology to alleviate the high rate of fraud at medicine dispensing points, the difficulty of transferring medical records between different clinics, and the long waiting times.

When a patient entered the clinic, they would register at reception. Their identity document would be scanned and a picture would be taken of the patient. At every station in the clinic visited by the patient, a camera would identify the patient and the patient’s records would pop up on the screen. When the patient left the station, the profile would automatically lock.

This ensured that only patients due for specific medication would receive that medication, thereby eliminating fraud. Because the records were all kept in the cloud, the records could easily be transferred to another clinic. Without this technology, patients need to return to the same clinic every time they need to restock their medication.

The trial also assisted with queue management. Upon entering the clinic, patients would choose a “journey” based on their reason for visiting the clinic. The system would then guide the patient from one station to the next on big screens on the wall. This made the journey more seamless while also providing visual feedback to officials at the clinic helping them to manage the queues more effectively.

The trial ended shortly before the start of the Covid pandemic. The project has not yet been restarted.

One project that has been implemented widely in the public sector is Vula Mobile. Founded by Dr William Mapham in 2014, Vula aims to bridge the gap between health workers and specialists.

There is a shortage of specialist doctors in the public sector and health workers at the primary care level often lack the information to refer patients to a relevant specialist.

With the Vula app, a nurse seeing a patient can be linked with the closest specialist. Through the built-in chat function, the nurse can provide the specialist with all the necessary info and refer the patient.

The app is available in six provinces with an emphasis on the Eastern Cape. More than 24,000 health workers are registered on the system.

But other innovators in the health space, frustrated by the public sector, are focusing on providing affordable private healthcare. This follows a growing trend in South Africa, as medical aid providers increasingly offer more affordable packages targeted to lower-income earners.

At the Kayamandi clinic during GroundUp’s visit, Mcoleseli Mlenze, a 34-year-old father who often visits the clinic for hypertension medication or when his son is sick, said that while he uses the clinic to collect medication, he has started seeing a private doctor when he is sick.

He says he cannot really afford the private doctor, which costs upwards of R350 per consultation. If there was some middle-ground where he could pay R150-R200 for a consultation at a clinic that is faster and more efficient, he would happily do so.

Others in the queue said they would pay up to R50 for a better healthcare experience.

Saul Kornik, the founder of Healthforce and the Kena App, aims to lower the cost of quality primary health care so that millions of people have access to it.

Available in almost 500 pharmacies throughout the country, Healthforce’s technology enables nurses to conduct all necessary screenings and diagnostic procedures. If and when a doctor becomes necessary, the nurse presses a button to start a video call with one of the doctors in the Healthforce network.

The nurse and patient can both see the doctor and the doctor, with the help of the nurse, can consult the patient. This reduces the amount of time that the doctor is needed, thereby reducing the cost.

The patient ends up paying on average R70 to R90 for the nurse and R115 to R250 for the doctor. If needed, the doctor can prescribe medication that the patient can purchase at the pharmacy or pick up from a government dispensary.

There are Healthforce doctors available to speak any of the 11 official languages and they are available seven days a week.

In March, Healthforce launched the Kena Health app, through which patients can have consultations with nurses, doctors and mental health practitioners via chat, voice or video. The first three consultations per year are free.

After the consultation, if necessary, the doctor can provide a script for medication and a sick note.

At Kayamandi clinic, Gcobisa Malithafa, a 30-year-old mother of a toddler told GroundUp that although she would pay a small amount for a better experience, it should not have to come to that.

Malithafa suggests that instead, the clinic’s management should consult the community on a regular basis and make immediate improvements to the running of the clinic. “This thing of having one doctor at the clinic is not right,” she says.

She is struggling to get her child immunised, having visited the clinic many times without success.

Whether they use technology or not, she says, something has to change.

By Daniel Steyn and Vusi Mokoena

Republished from the original at GroundUp under a Creative Commons Licence

New Drugs for Cryptococcal Meningitis Sorely Needed in SA

Brain scan image
Image source: Mart Production on Pexels

Despite the greater safety and efficacy of a new short course treatment for HIV-related cryptococcal meningitis (CM), access to the treatment in South Africa will be a challenge, according to a pair of articles by Spotlight.

Following positive results of a trial, the World Health Organization last week announced new recommendations for the treatment of CM, with a single high dose of L-AmB followed by two weeks of flucytosine and fluconazole.

Using L-AmB (AmBisome) and flucytosine for the treatment of CM will be a welcome change for South Africa, which has the world’s highest burden of the condition. This shorter course with fewer side effects than the current treatment involving amphotericin-B could save lives as well as clinical resources in the public sector, but at present the treatment is hamstrung by pricing and availability uncertainty, with a course of L-AmB currently only available at a steep cost.

Amphotericin B [deoxycholate] is a drug that doctors and nurses used to call ampho-terrible,” Amir Shroufi, Médecins Sans Frontières (MSF) Southern Africa board member told Spotlight.

He explained that “it’s a really nasty drug, doctors and nurses don’t like it because it can cause severe anaemia. It’s toxic to the kidneys, so it can cause kidney damage and even kidney failure… and the infusion line used for the drug can often become infected and it can cause inflammation of the veins where it’s going into the body.”

L-AmB is a “much better drug”, he said, with great benefits of administering it for one day as opposed to a week or two. The seriousness of CM meant hospitalisation will still be required, pointed out Dr Jacqui Miot, division director of the Wits Health Economics and Epidemiology Research office, but means that patients won’t be tethered to a drip and may be able to go home sooner.

Under the treatment regimen, a patient receives a single high dose of L-AmB on the first day of treatment, followed by a 14-day course of flucytosine and fluconazole pills.

For a 60kg patient at the recommended dosage, twelve 50mg vials of L-AmB are needed, which at Gilead’s promised access price would be R2 880. Key Oncologics’ currently charges R34 560 for 12 vials.

Even given the availability of L-AmB, Shrouifi warns that “whatever you’re doing, you have to have flucytosine. That’s your baseline, even if you’re giving liposomal amphotericin B, you have to have the flucytosine”.

Flucytosine is an old, off-patent medicine developed in the 1950s. Despite its age and its demonstrated efficacy in the landmark ACTA trial four years ago, flucytosine was only recently authorised for use in South Africa and is only slowly being rolled out.

Amir Shroufi warned that access to the life-saving medicine remains a major issue. “Doctors are not being given the tools they need to treat [CM],” he said. “The first tool they have to have is flucytosine and they still don’t have flucytosine. So, that’s the thing that needs to happen urgently, you know, tomorrow! Everyone with cryptococcal meningitis must get access to flucytosine.”

Like L-AmB, Mylan’s 250mg and 500mg flucytosine tablets were only registered recently, in December 2021. The Department of Health’s target price for a pack of 100 tablets is R1 500. Fortunately, it appears that the Clinton Health Access Initiative (CHAI) will be able to secure packs of 100 at R1 470 each for use in South Africa’s flucytosine access programme.

The next steps for rollout of flucytosine will be inclusion on the national essential medicines list and in CM treatment guidelines before tenders can be put out.

Source 1: Spotlight

Source 2: Spotlight

In Finger Osteoarthritis, Lipofilling Reduces Pain, Improves Function

Hand osteoarthritis
Source: Pixabay CC0

For patients with painful finger osteoarthritis, lipofilling  a nonsurgical procedure where a patient’s fat is transferred into the arthritic joints, may result in lasting improvements in hand function and especially pain, according to a study in Plastic and Reconstructive Surgery.

Researchers reported their experience with 18 patients undergoing fat transfer procedures for finger osteoarthritis.

“Even over a long-term follow-up, the transfer of fatty tissue to arthritic fingers joints appears to provide a safe and minimally invasive alternative to conventional surgery for patients with osteoarthritis,” commented the study’s lead author Max Meyer-Marcotty, MD, PhD.

In the lipofilling procedure, a sample of the patient’s own fatty tissue was obtained by liposuction from another part of the body: the upper thigh or hip area. Tiny volumes of lipid cells (< 1mL) were injected into the arthritic finger joints. For recovery, patients wore a splint around the treated finger and took pain relievers for a week. No infections or other complications were recorded.

The researchers analysed follow-up outcomes in a total of 25 finger joints treated by lipofilling. Hand function, pain scores, and patient satisfaction were evaluated an average of 44 months (maximum 50 months) after treatment.

Assessment showed a “highly significant clear improvement” in pain score: from a median of 6 points (on a 10-point scale) before treatment to 0.5 points at follow-up. “We believe that for our patients the reduction of pain represents the most striking and important result, which also has the most pronounced and highly significant effect,” Dr Meyer-Marcotty et al. wrote.

On functional evaluation, pinch grip strength of the treated fingers increased from a median of 2.0kg before lipofilling to 4.3kg at follow-up. Non-significant improvements were seen in fist closure force and score on a standard assessment of hand function during everyday tasks.

In severe cases of osteoarthritis, surgery is effective in relieving arthritis pain, but is associated with potential complications and lengthy recovery time.

Fat transfer procedures have been introduced in recent years for a growing range of purposes in plastic and reconstructive surgery. Animal studies have suggested that mesenchymal stromal cells found in fatty tissues can regenerate tissue in arthritic joints.

“The chance to preserve the joint with a minimally invasive procedure is of particular interest in the early, albeit painful, phases of finger osteoarthritis,” Dr. Meyer-Marcotty added. “Since the lipofilling procedure is nondestructive, conventional joint surgery can still be performed later, if needed.”

Larger long-term follow-up studies are needed to further corroborate these initial positive findings, the researchers said.

Source: EurekAlert!

Seven Hours’ Sleep is Optimal in Middle Age and Older

Sleeping woman
Photo by Cottonbro on Pexels

According to research published in Nature Aging, seven hours is the ideal amount of sleep for people in their middle age and upwards, with too little or too much little sleep associated with poorer cognitive performance and mental health.

Sleep plays an important role in enabling cognitive function and maintaining good psychological health, and also removes waste products from the brain. Alterations in sleep patterns appear during ageing, including difficulty falling asleep and staying asleep, and decreased quantity and quality of sleep. It is thought that these sleep disturbances may contribute to cognitive decline and psychiatric disorders in the ageing population.

Scientists from the UK and China examined data from nearly 500 000 adults aged 38–73 years from the UK Biobank. Participants were asked about their sleeping patterns, mental health and wellbeing, and took part in a series of cognitive tests. Brain imaging and genetic data were available for almost 40 000 of the study participants.

The researchers found in their analysis that both insufficient and excessive sleep duration were associated with impaired cognitive performance, such as processing speed, visual attention, memory and problem-solving skills. The optimal amount of sleep was found to be seven hours per night for cognitive performance and good mental health. More symptoms of anxiety and depression and worse overall wellbeing were associated with sleeping for longer or shorter durations.

The researchers say one possible reason for the association between insufficient sleep and cognitive decline may be due to the disruption of slow-wave — ‘deep’ — sleep. Disruption to this type of sleep has been shown to have a close link with memory consolidation as well as the build-up of amyloid — a key protein which, when it misfolds, can cause ‘tangles’ in the brain characteristic of some forms of dementia. Additionally, lack of sleep may hamper the brain’s ability to rid itself of toxins.

The amount of sleep was also linked differences in the structure of brain regions involved in cognitive processing and memory, again with greater changes associated with greater than or less than seven hours of sleep.

Consistently getting seven hours’ sleep each night was also important to cognitive performance and good mental health and wellbeing. Interrupted sleep patterns have previously been shown to be associated with increased inflammation, indicating a susceptibility to age-related diseases in older people.

Professor Jianfeng Feng from Fudan University in China said: “While we can’t say conclusively that too little or too much sleep causes cognitive problems, our analysis looking at individuals over a longer period of time appears to support this idea. But the reasons why older people have poorer sleep appear to be complex, influenced by a combination of our genetic makeup and the structure of our brains.”

The researchers say the findings suggest that insufficient or excessive sleep duration may be a risk factor for cognitive decline in ageing. This is supported by previous studies that have reported a link between sleep duration and the risk of developing Alzheimer’s disease and dementia, in which cognitive decline is a hallmark symptom.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge, one of the study’s authors, said: “Getting a good night’s sleep is important at all stages of life, but particularly as we age. Finding ways to improve sleep for older people could be crucial to helping them maintain good mental health and wellbeing and avoiding cognitive decline, particularly for patients with psychiatric disorders and dementias.”

Source: University of Cambridge

People with Blue Eyes Share a Single Ancestor

Source: Daniil Kuzelev on Unsplash

New research published in Human Genetics shows that people with blue eyes trace their ancestry back to a single individual. Researchers tracked down a genetic mutation which took place 6–10 000 years ago and is the cause of the eye colour of all blue-eyed humans without albinism alive on the planet today.

While blue eyes evolved only once, blonde hair has evolved at least twice: in Melanesian populations, blonde hair evolved independently to European populations, involving a mutation in a different gene.

“Originally, we all had brown eyes,” said Professor Hans Eiberg from the University of Copenhagen. “But a genetic mutation affecting the OCA2 gene in our chromosomes resulted in the creation of a ‘switch’, which literally ‘turned off’ the ability to produce brown eyes.” The OCA2 gene codes for the P protein, which is involved melanin production. This ‘switch’, located in the gene next to OCA2, does not completely shut off production but instead is limited to reducing the production of melanin in the iris, effectively ‘diluting’ brown eyes to blue. The switch’s effect on OCA2 is very specific therefore. If the OCA2 gene is completely destroyed or turned off, albinism would be the result.

Eye colours from brown to green depend on the amount of melanin in the iris, but blue-eyed individuals only have a small degree of variation in the amount of melanin in their eyes. “From this we can conclude that all blue-eyed individuals are linked to the same ancestor,” said Professor Eiberg. “They have all inherited the same switch at exactly the same spot in their DNA.” Brown-eyed individuals, by contrast, have considerable individual variation in the area of their DNA that controls melanin production.

Professor Eiberg and his team studied mitochondrial DNA and compared the eye colour of blue-eyed individuals in countries as diverse as Jordan, Denmark and Turkey. His research stretches back to 1996, when he first implicated the OCA2 gene as being responsible for eye colour.

The mutation of brown to blue eyes does not confer any evolutionary advantage, as with others such as hair colour.

As Professor Eiberg explained, “it simply shows that nature is constantly shuffling the human genome, creating a genetic cocktail of human chromosomes and trying out different changes as it does so.”

Source: University of Copenhagen

Obesity in Mice Causes AD Treatments to Backfire

Photo by Kanasi on Unsplash

In a new study published in Nature, researchers found that treatments that were effective for atopic dermatitis (AD) in lean mice actually worsened the condition in obese mice.

Tracking the development of AD in obese and lean mice, the researchers found that obese mice developed more inflammation and more severe AD. This increased inflammation was present even after obese mice lost weight. There were similar results in an experimental model of asthma, with obese mice developing more inflammation.

The researchers next looked in detail at immune cells called T cells in lean and obese mice with AD. Lean mice had more TH2 cells, a class of T cells known to play a role in the development of AD. Obese mice had more of a class of T cells called TH17. These cells trigger a different type of inflammation.

Similar trends were seen in blood samples taken from people. Markers of TH17 cell activity increased along with body mass index (BMI) in a database of serum collected from people with AD. Conversely, in samples from patients with severe asthma, TH2 cell activity decreased as BMI increased.

Drugs that block TH2 cell activity are used in the treatment of severe AD as well as asthma and other inflammatory conditions. The researchers tested antibodies to block TH2 cell activity in lean and obese mice with severe AD. While the antibodies reduced skin inflammation in lean mice as expected, they made the condition worse in obese mice. Analysis of immune cells suggested that blocking TH2 cell activity in the obese mice worsened other forms of inflammation.

Obese mice were also found to have less activity of peroxisome proliferator-activated receptor-γ (PPARɣ) in their TH2 cells. When lean mice were engineered to lack PPARɣ, their inflammatory response resembled that of obese mice.

Drugs that increase PPARɣ activity increase insulin sensitivity and are approved for the treatment of type 2 diabetes. The researchers found that giving one of these drugs to obese mice changed their inflammatory response to resemble that of lean mice. It also restored their sensitivity to the antibodies that block TH2 cell activity.

“Our findings demonstrate how differences in our individual metabolic states can have a major impact on inflammation, and how available drugs might be able to improve health outcomes,” said Dr Ronald Evans from the Salk Institute, who helped lead the work.

Source: National Institutes of Health

Gene Mutation in Young Girl May Finally Yield Lupus Treatment

Facial rash characteristic of lupus. Credit: Statpearls

A study published in Nature has identified mutations in an X chromosome gene that senses viral RNA, as a cause of the autoimmune disease lupus, a finding which may explain why the disease is far more common in females, and which might lead to new treatments.

In the study, whole genome sequencing was performed on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus at age 7. Such a severe case with early onset of symptoms is rare and suggests a single genetic cause.

In their genetic analysis, the researchers discovered a single point mutation in the TLR7 gene. Referrals from other institutions, they were able to identify other cases of severe lupus where this gene was also mutated.

To confirm that the mutation causes lupus, the team inserted the gene into mice, which went on to develop the disease and showed similar symptoms. The mouse model and the mutation were both named ‘kika’ by Gabriela, the young girl central to this discovery.

Carola Vinuesa, senior author and principal investigator said: “It has been a huge challenge to find effective treatments for lupus, and the immune-suppressors currently being used can have serious side effects and leave patients more susceptible to infection. There has only been a single new treatment approved by the FDA in about the last 60 years.

“This is the first time a TLR7 mutation has been shown to cause lupus, providing clear evidence of one way this disease can arise.”

Professor Nan Shen, co-director of CACPI adds: “While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”

The mutation identified by the researchers makes TLR7 protein bind more readily guanosine and become more active. This in turn increases the sensitivity of the immune cell, making it more likely to incorrectly target healthy tissue.

Interestingly, other studies have shown mutations that cause TLR7 to become less active are associated with some cases of severe COVID infection, highlighting the delicate balance of a healthy immune system.

The findings could also explain why lupus is 10 times more common in females than in males. Because TLR7 is located on the X chromosome, females have two copies of the gene while males have one. Usually, in females one of the X chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete. This means females with a mutation in this gene can have two functioning copies.

Study co-author Dr Carmen de Lucas Collantes, said: “Identification of TLR7 as the cause of lupus in this unusually severe case ended a diagnostic odyssey and brings hope for more targeted therapies for Gabriela and other lupus patients likely to benefit from this discovery.”

Gabriela, now a teenager, remains in touch with the research team. She said, “I hope this finding will give hope to people with lupus and make them feel they are not alone in fighting this battle. Hopefully the research can continue and end up in a specific treatment that can benefit so many lupus warriors who suffer from this disease.”

The researchers are now investigating the repurposing of existing treatments which target the TLR7 gene. By targeting this gene, they hope to be able to also help patients with related conditions.

Carola added: “There are other systemic autoimmune diseases, like rheumatoid arthritis and dermatomyositis, which fit within the same broad family as lupus. TLR7 may also play a role in these conditions.”

Source: Francis Crick Institute

GI Issues and Anxiety Linked in Children with Autism

Male doctor with young girl patient
Photo by National Cancer Institute on Unsplash

A new study has found a bi-directional relationship between gastrointestinal (GI) issues and internalised symptoms such as anxiety in children and adolescents with autism, which means the symptoms seem to be affecting each other. The findings could inform future precision medicine research aimed at developing personalised treatments for people with autism experiencing gastrointestinal issues. The study appears in the Journal of Autism and Developmental Disorders.

Autism is known to be often associated with GI issues, and is often overlooked in children despite being a source of pain and anxiety. Food preferences are often for carbohydrates and processed foods. The most common cause of GI issues in children with autism are abdominal pain, constipation, chronic diarrhea and gastroesophageal reflux disease (GERD).

“Research has shown gastrointestinal issues are associated with an increased stress response as well as aggression and irritability in some children with autism,” said Brad Ferguson, an assistant research professor. “This likely happens because some kids with autism are unable to verbally communicate their gastrointestinal discomfort as well as how they feel in general, which can be extremely frustrating. The goal of our research is to find out what factors are associated with gastrointestinal problems in individuals with autism so we can design treatments to help these individuals feel better.”

In the study, Ferguson and his team analysed health data from more than 620 under-18 patients with autism who experience gastrointestinal issues. Then, the researchers examined the relationship between the GI issues and internalised symptoms. Ferguson explained the findings provide more evidence on the importance of the ‘gut–brain axis’ in GI disorders in individuals with autism.

“Stress signals from the brain can alter the release of neurotransmitters like serotonin and norepinephrine in the gut which control gastrointestinal motility, or the movement of stool through the intestines. Stress also impacts the balance of bacteria living in the gut, called the microbiota, which can alter gastrointestinal functioning,” Ferguson said. “The gut then sends signals back to the brain, and that can, in turn, lead to feelings of anxiety, depression and social withdrawal. The cycle then repeats, so novel treatments addressing signals from both the brain and the gut may provide the most benefit for some kids with gastrointestinal disorders and autism.”

Ferguson is collaborating with David Beversdorf, a neurologist who also studies gastrointestinal problems in individuals with autism. Beversdorf had recently helped identify specific RNA biomarkers linked with gastrointestinal issues in children with autism.

“Interestingly, the study from Beversdorf and colleagues found relationships between microRNA that are related to anxiety behaviour following prolonged stress as well as depression and gastrointestinal disturbance, providing some converging evidence with our behavioural findings,” Ferguson said.

Ferguson and Beversdorf are now together investigating the effects of a stress-reducing medication on GI issues in a clinical trial. Ferguson cautioned that treatment could be effective for certain people with autism but not others.

“Our team uses a biomarker-based approach to find what markers in the body are common in those who respond favourably to certain treatments,” Ferguson said. “Our goal is to eventually develop a quick test that tells us which treatment is likely to work for which subgroups of patients based on their unique biomarker signature, including markers of stress, composition of gut bacteria, genetics, co-occurring psychological disorders, or a combination thereof. This way, we can provide the right treatments to the right patients at the right time.”

Source: University of Missouri-Columbia

Fenofibrate Confers Modest Risk Reduction for Diabetic Retinal Disease

Retina showing reticular pseudodrusen. Credit: National Eye Institute

Taking the cholesterol-lowering drug fenofibrate had a modest but statistically significant association with reduced risk of vision-threatening diabetic retinopathy (VTDR), according to results of a large study published in JAMA Ophthalmology. In the study, fenofibrate use was associated with an 8% lower risk of progression compared to non-use.

Fenofibrate use had a greater effect on the risk of proliferative diabetic retinopathy, with a 24% decrease in progression (PDR) but did not significantly affect the risk of developing diabetic macular oedema (DME).

The researchers noted that these findings are in line with evidence showing fenofibrate may protect against diabetes-associated breakdown of the blood-retinal barrier, although ophthalmologists rarely use the drug to treat diabetic eye disease.

“Our positive association for progression to PDR coincides with results of previous clinical trials and adds new information with regards to the impact on DME,” the researchers stated.

Protection against progression to PDR “was found without regards to underlying NPDR [nonproliferative diabetic retinopathy] severity level, which is not well coded within the claims database,” the researchers continued. “Understanding this limitation and how the inclusion of NPDR severity levels that may not benefit from fenofibrates would bias our findings to the null means that the positive association seen in our study is actually an underestimate of the true association.”

While fenofibrate’s mechanism of action in diabetic retinopathy is not well understood, “interest in the use of this oral agent has become substantial,” noted Robert N. Frank, MD. author of an accompanying editorial.

“From the point of view of a clinician with a long-time interest in diabetic retinopathy, its causal mechanisms, and its evolving treatments, the possibility that an oral medication originally used for a different disease may be beneficial for the management of diabetic eye disease is exciting,” Dr Frank wrote.

“The evidence that fenofibrate can slow the progression of diabetic retinopathy is growing, but it has not yet become a widely accepted treatment,” he added. “It will be interesting to see how this large population analysis and the results from the ongoing DRCR Retina Network  randomised clinical trial will affect clinical practice in the years to come.”

Two clinical trials that evaluated fenofibrate’s effect on diabetic eye disease, the FIELD study and the ACCORD-Eye trial yielded conflicted findings regarding DME, PDR and progression of diabetic retinopathy. Both trials suggested that only patients with mild nonproliferative eye disease were likely to benefit.

To help inform decision-making on fenofibrate in eye disease, researchers drew on a large health insurer database for 150 252 adults who had NPDR-associated lab values from January 2002 through June 2019. The primary outcomes were a new diagnosis of VTDR (composite of PDR or DME) or DME and PDR individually.

The analysis showed 5835 (3.9%) used fenofibrate. During follow-up, 27 325 patients progressed to VTDR, including 4 086 to PDR and 22 750 to DME. While men accounted for a larger proportion of fenofibrate users (61.1% vs 51.0% of nonusers), patients had similar baseline characteristics.

Study limitations included lack of clinical applicability, not accounting for duration of fenofibrate use, and data being drawn from a single database.

Source: MedPage Today

Shift in Recommendations for Aspirin in CVD Prevention

Anatomical model of a human heart
Photo by Robina Weermeijer on Unsplash

The US Preventive Services Task Force (USPSTF) has issued a recommendation statement on the use of aspirin in the prevention of cardiovascular disease (CVD). The recommendation shifts the use of aspirin to an earlier window, and making it an individualised decision for people in their 40s to 50s with a > 10% 10-year CVD risk.

The previous recommendation from 2016 had called for low-dose aspirin for people in their 50s with a > 10% 10-year CVD risk and individualised decisions for those in their 60s with similar risk. The update comes after new evidence emerged in a number of randomised controlled trials.

For the update, which appears in JAMA Network, a systematic review was conducted on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD. The effect of aspirin use on colorectal cancer incidence and mortality was also investigated in primary CVD prevention populations, as well as the harms (particularly bleeding) associated with aspirin use.

The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults aged 40–59 years with a 10% or greater 10-year CVD risk has a small net benefit, and starting low-dose aspirin use for CVD prevention should be an individual decision for them. Those not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit. The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older.

Aspirin’s mechanism of action in CVD protection is well known. Aspirin at low doses is an irreversible cyclooxygenase 1 (COX-1) enzyme inhibitor, and at higher doses, it also inhibits COX-2. By inhibiting platelet function through COX-1, aspirin reduces atherothrombosis risk, and has been used widely for the prevention of CVD events, particularly for secondary prevention. However the COX-1 is also involved with protection of the gastrointestinal mucosa, and inhibition of it can promote gastrointestinal bleeding. The mechanism for the possible antineoplastic effects of aspirin is not as well understood.

Older age is one of the strongest risk factors for CVD, and men have a higher overall CVD disease burden and tend to experience CVD events earlier in life. Race and ethnicity affects CVD burden, with Black persons having the highest prevalence of CVD.

Similar CVD benefits appear for a low aspirin dose (≤ 100mg/d) and for all doses that have been studied in CVD prevention trials (50 to 500mg/d). A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the US.

Because CVD risk estimation is imprecise and imperfect at the individual level, the USPSTF suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with > 15% or > 20% 10-year CVD risk).

In addition to age and estimated level of CVD risk, decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms, based on the relative values the patient places on these (reduced CVD risk vs increased bleeding and stroke risk).

Annual bleeding events in individuals without risk factors for increased bleeding (eg, history of gastrointestinal bleeding risk, history of peptic ulcer disease, or use of nonsteroidal anti-inflammatory drugs or corticosteroids) are rare, but risk for bleeding increases modestly with advancing age. For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. However, benefits shrink with advancing age because of increased bleeding risk, with modelling data suggesting stopping aspirin use around age 75.