A Holistic Approach will Build a Stronger Rural Healthcare System

Photo by Hush Naidoo on Unsplash

As part of a series of podcasts titled “Advancing Healthcare” that examine the critical issues that must be addressed to achieve universal healthcare, Russell Rensburg of the Rural Health Advocacy Project calls for a focus and prioritisation of rural health. 

Across rural South Africa, the health profile of South Africans is changing. Thanks to the rollout of antiretroviral drugs, South Africa’s life expectancy has increased, and with that, the population is getting older. While this is good news, an ageing population does bring new challenges to the healthcare system.

Rensburg noted that as part of the success of the HIV response in the last 10 years, there has been an increase in life expectancy. But the challenge is that as disease profiles change, health care needs change too. “We need to respond to the differing health needs of young people and older populations,” he adds.

According to Rensburg, available data shows we must start taking differentiated approaches to delivering healthcare for different population segments. However, more data is required because no one knows the prevalence of certain diseases, like cancer. Also, lacking management data means little information on how facilities are run. Without the right data, he says, “We haven’t figured out a way of doing health promotion and health literacy.” 

The Rural Health Advocacy Project is a division of Wits University’s health consortium, and it aims to promote better health care for rural communities. However, providing meaningful rural health care requires understanding that each province within South Africa has its own challenges.

In Kwazulu-Natal, for instance, a recent study involving basic screening found high levels of diseases like diabetes and tuberculosis in people who had never accessed the healthcare system.

The Eastern Cape, says Rensburg, has too many hospitals that are expensive to run. “Some of those hospitals they don’t need,” he said. “There are, like, 91 district hospitals in the Eastern Cape; many of them are like old mission hospitals that, in my view, are sometimes too expensive to run.”

Limpopo, says Rensburg, has a malnutrition problem. “They have severe acute malnutrition rates that are quite high, which is ironic because it’s kind of a breadbasket province,” he said.

Another overreaching problem that healthcare professionals have to deal with in the rural districts of South Africa is that patients often bypass the community clinics and go to the hospitals when they need medical attention.

These clinics are bypassed because of negative experiences where patients endure day-long queues and medicines that aren’t in stock. “They go to the hospital, which costs probably five or six times more for the state to deliver that care,” explained Rensburg.

Rensburg believes more community health workers should be hired, and their training should be standardised to improve rural health care. “We need to professionalise them because it’s an opportunity to create employment in parts of the country with low economic activity,” he said.

According to Rensburg, other interventions that could improve rural health care could include cutting queuing times, improving antenatal care, and making maternity care easier to access. Pregnant mothers can wait up to 14 hours to access a bed.

Access to better management data would help in the better running of facilities. “I think the first baseline into improving healthcare is getting more people to understand their health status. And I think how we do that is being much more focused on gathering information. And then using that information for decision-making,” Rensburg said.

However, improving the well-being of South Africans living in the rural parts of the country goes beyond what the health sector can offer. “So maybe something like a Basic Income Grant could have a massive impact on people’s health, particularly in the rural areas where unemployment is 90%.” The basic income grant could help reduce malnutrition, Rensburg adds.

What could influence rural health soon is NHI. “I think the NHI is an opportunity to change how we deliver healthcare,” said Rensburg. “But when you look at the NHI proposals, it was about restructuring public-funded health care services. The whole thing talks about how we better manage hospitals by giving them their budgets.” Rensburg adds that restructuring publicly funded services, prioritising district health services, and improving the efficiency and efficacy of central, tertiary and regional hospitals by giving them greater autonomy should also be considered key to improving rural health.

This podcast, which is part of a series that aims at creating critical discussion around achieving universal health care, can be accessed at https://hasa.co.za/hasa-podcasts/ 

Study Reveals Association Between Semaglutide Use and Optic Neuropathy

Photoreceptor cells in the retina. Credit: Scientific Animations

Researchers from Mass Eye and Ear have discovered an association between semaglutide use and an increased risk of nonarteritic anterior ischaemic optic neuropathy (NAION) in patients with type 2 diabetes, overweight or obesity. The findings, which appear in JAMA Ophthalmology, only show an association and cannot establish causation.

Though NAION is relatively rare, occurring in in about 10 in 100 000, it is the second most common cause of optic nerve blindness, behind glaucoma, and it is the most common cause of sudden optic nerve blindness. Caused by decreased blood flow to the optic disc, it usually affects only one eye but in 15% of cases both eyes are involved. There are no treatments for this disease and little prospect for improvement, although it is painless.

The study was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School.

In mid-2023 Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend – three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. They did notice however that all three were taking semaglutide.

“The use of these drugs has exploded throughout industrialised countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, corresponding author of the study. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

This prompted the Mass Eye and Ear research team to run a retrospective analysis of their patient population to see if they could identify a link between this disease and these drugs.

They performed matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–GLP-1 receptor agonist medications for diabetes or obesity.

The researchers found that patients with diabetes who were prescribed and took semaglutide were four times (hazard ratio [HR], 4.28) more likely to be receive a NAION diagnosis. The odds increased to more than seven times (HR, 7.64) when the prescription was for weight control in obesity.

The researchers analysed the records of more than 17 000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analysed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

Study limitations include the fact that Mass Eye and Ear sees an unusually high number of people with rare eye diseases, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. Medication adherence could also not be assessed.

Only correlation can be shown by the study, not causality. How or why this association exists remains unknown. Likewise, the reason for the reported difference between diabetic and overweight groups – but this does not appear to result from a difference in baseline characteristics. The optic nerve is known to host GLP-1 receptors, but the study did not adequately address all the confounding factors. They also caution against generalising the results (from a majority white population) since Black individuals have a lower risk of NAION.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is pre-existing significant visual loss from other causes.”

How Astrocytes Know to Give the Brain an Energy Boost

Image of an astrocyte, a subtype of glial cells. Glial cells are the most common cell in the brain. Credit: Pasca Lab, Stanford University

A key mechanism by which astrocytes detect when an energy boost is needed for the brain has been elucidated by University College of London researchers using mouse-based and in vitro studies.

The findings, published in Nature, could inform new therapies to maintain brain health and longevity, the researchers say, since other studies have found that brain energy metabolism can become impaired late in life and contribute to cognitive decline and the development of neurodegenerative disease.

Lead author Professor Alexander Gourine (UCL Neuroscience, Physiology & Pharmacology) said: “When our brain is more active, such as when we’re performing a mentally taxing task, our brain needs an immediate boost of energy, but the exact mechanisms that ensure on-demand local supply of metabolic energy to active brain regions are not fully understood.”

First and co-corresponding author Dr Shefeeq Theparambil, who began the study at UCL before moving to Lancaster University, said: “The normal activities of the brain require enormous amounts of energy, comparable to that of a human leg muscle running a marathon. This energy is primarily derived from blood glucose. Neurons in the brain consume more than 75% of this energy.”

Prior research has shown that numerous brain cells called astrocytes appear to play a role in providing the brain neurons with energy they need. Astrocytes, shaped like stars, are a type of glial cell, which are non-neuronal cells found in the central nervous system. When neighbouring neurons need an increase in energy supply, astrocytes jump into action by rapidly activating their own glucose stores and metabolism, leading to the increased production and release of lactate. Lactate supplements the pool of energy that is readily available for use by neurons in the brain.

Professor Gourine explained: “In our study, we have figured out how exactly astrocytes are able to monitor the energy use by their neighbouring nerve cells, and kick-start this process that delivers additional chemical energy to busy brain regions.”

In a series of experiments using mouse models and cell samples, the researchers identified a set of specific receptors in astrocytes that can detect and monitor neuronal activity, and trigger a signalling pathway involving an essential molecule called adenosine. The researchers found that the metabolic signalling pathway activated by adenosine in astrocytes is exactly the same as the pathway that recruits energy stores in the muscle and the liver, for example when we exercise.

Adenosine activates astrocyte glucose metabolism and supply of energy to neurons to ensure that synaptic function (neurotransmitters passing communication signals between cells) continues apace under conditions of high energy demand or reduced energy supply.

The researchers found that when they deactivated the key astrocyte receptors in mice, the animal’s brain activity was less effective, including significant impairments in global brain metabolism, memory and disruption of sleep, thus demonstrating that the signalling pathway they identified is vital for processes such as learning, memory and sleep.

Dr Theparambil said: “Identification of this mechanism may have broader implications as it could be a way of treating brain diseases where brain energetics are downregulated, such as neurodegeneration and dementia.”

Professor Gourine added: “We know that brain energy homeostasis is progressively impaired in ageing and this process is accelerated during the development of neurodegenerative diseases such as Alzheimer’s disease. Our study identifies an attractive readily druggable target and therapeutic opportunity for brain energy rescue for the purpose of protecting brain function, maintaining cognitive health, and promoting brain longevity.”

1 in 7 Patients Experience Symptoms After Discontinuing Antidepressants

Credit: Pixabay CC0

Approximately one in seven patients who discontinued their use of antidepressants experienced discontinuation symptoms, according to a wide-ranging analysis published in The Lancet Psychiatry. In arriving at this figure, the researchers accounted for a high frequency of anticipated discontinuation symptoms.

The emergence of adverse symptoms after antidepressant cessation has been described as far back as 1959, but was mostly neglected until the late 1990s. Today, the existence of antidepressant discontinuation symptoms is widely accepted, with transnational guidelines suggesting safe tapering. They can be highly variable and non-specific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. It has been reported that symptoms typically occur within a few days and are usually transient, but can last up to several weeks or months.

The incidence and severity of symptoms remained controversial however, with estimates ranging up to a majority (56%) of patients experiencing them, half of them severe. Previous reviews have been criticised for bias, and medical opinions are polarised on the subject.

The researchers reviewed 79 studies involving more than 21 000 participants, and found that about one-third of patients experienced symptoms such as headaches, nausea, insomnia, and irritability after accounting for patient expectations. Even in patients taking placebo, 17% experienced symptoms – suggesting that this is attributable to patient expectations about the adverse effects of stopping the drug.

After taking this into account, roughly one in seven individuals had antidepressant discontinuation symptoms. Neither tapering nor abrupt cessation of the drugs made no difference in the proportion of people who experienced discontinuation symptoms.

In addition, about 1 in 35 people experienced severe discontinuation symptoms. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with higher symptom severity. The authors cautioned that there was substantial heterogeneity of results.

Delaying Diabetes with Diet and Exercise for 4 Years Results in Better Long-term Health

Maintaining prediabetic status after diagnosis reduces risk of death decades later

Individuals diagnosed with prediabetes can reduce their long-term risk of death and diabetes-related health complications if they delay the onset of diabetes for just four years through diet and exercise. Guangwei Li of the China-Japan Friendship Hospital and colleagues report these findings in a new study published July 9thin the open-access journal PLOS Medicine.

Type 2 diabetes is associated with an increased risk of death and disability, and imposes a significant economic burden on individuals and societies worldwide. Lifestyle changes, such as eating a healthy diet and getting more exercise, can delay or reduce the risk of developing diabetes in people diagnosed with impaired glucose tolerance – commonly called prediabetes. However, it is unknown how long a person must delay diabetes to ensure better long-term health.

In the new study, researchers looked at health outcomes from 540 prediabetic individuals who participated in the original Da Qing Diabetes Prevention Study, a six-year trial conducted in Da Qing City in China, starting in 1986. Participants belonged to either a control group or one of three lifestyle intervention groups, which involved following a healthy diet, getting more exercise, or both. The trial followed up with participants for more than 30 years.

Li’s team determined the long-term risk of death, cardiovascular events – like heart attack, stroke or heart failure – and other diabetes-related complications for trial participants. They found that individuals who remained non-diabetic for at least four years after their initial diagnosis had a significantly lower risk of dying and a significantly lower risk of experiencing a cardiovascular event compared to those who developed diabetes sooner. This protective effect was not observed in individuals who remained non-diabetic for less than the “four-year threshold.”

Overall, the analysis suggests that the longer a prediabetic person can delay developing diabetes, the better their long-term health outcomes will be. However, even just a few years of maintaining prediabetic status can yield benefits for years to come.

The authors add, “This study suggests that a longer duration of non-diabetes status in those with IGT has beneficial health outcomes and reduces mortality. The implementation of effective interventions targeting those with IGT should be considered as part of preventative management for diabetes and diabetes related vascular complications.”

Provided by PLOS

Two New Species of Psilocybe Mushrooms Discovered in Southern Africa

Photo by Marek Piwnicki

Two new species of psychoactive mushrooms in the genus Psilocybe have been described from southern Africa, bringing the list to six known species indigenous to Africa.

This is even though Psilocybe species are amongst the most well-known and well-studied species of psychoactive mushrooms in the world, with around 140 described species.

In a paper published in the journal Mycologia this week, researchers from Stellenbosch University (SU) and citizen mycologists describe the two new species as Psilocybe ingeli and Psilocybe maluti.

Psilocybe ingeli was first found in 2023 growing in pastureland in KwaZulu-Natal by Talan Moult, a self-taught citizen mycologist.  Psilocybe maluti was first found on a Free State small holding in 2021 by Daniella Mulder, who sent photos of the mushrooms for identification to Andrew Killian, one of South Africa’s leading citizen mycologists based in Somerset West.

In both instances, the unusual looking specimens were sent to Breyten van der Merwe for DNA sequencing and analysis in the lab of Prof. Karin Jacobs in SU’s Department of Microbiology. Van der Merwe, now a postgraduate student in chemical engineering at SU, is a trained mycologist and first author of the paper.

The paper also contains information on the traditional use of P. maluti by Basotho traditional healers from the mountain kingdom of Lesotho. According to the researchers, this appears to be the only recorded first-hand report of hallucinogenic mushrooms being used traditionally in Africa.

Cullen Taylor Clark, a citizen mycologist and co-author, worked with Mamosebetsi Sethathi, a Mosotho traditional healer, to document the use of P. maluti (locally known as koae-ea-lekhoaba) in traditional healing practices. This forms part of a larger effort, led by Clark, to document the use of mushrooms by indigenous groups in southern Africa.

Van der Merwe says there are very likely more southern African species in this genus, and that more citizen scientists need to become involved: “These two species were sent to me by citizen scientists. It would be impossible for a single researcher to cover a fraction of an area these mushroom enthusiasts have access to. This is the only way we will be able to further studies in African mycology.”

Jacobs echoes this sentiment: “There are only a handful of mycologists in Africa documenting local biodiversity. Considering the vast mycological diversity on the continent, it is a daunting task. Collaborating with citizen mycologists is therefore hugely beneficial. In addition to more material, collaboration also opens avenues for conversation and exploration, which can lead to documenting mycophilia (the love of mushrooms) on the African continent.”

Source: Stellenbosch University

Codeine Addiction in SA: New Guideline Aims to Curb Abuse

Photo by cottonbro studio

By Jesse Copelyn

Rehab centres in South Africa have been admitting an increasing number of codeine users in recent years. Now, the country’s medicines regulator has published a draft guideline as part of a broader effort to track suspicious codeine sales.

South Africa’s medicines regulator – the South African Health Products Regulatory Authority (SAHPRA) – has released a new draft guideline which it says will help stem the misuse of codeine. The opioid, which is found in certain pain relief medicines and cough syrups, is used by some people in large doses to get high.

Under the new draft guideline, the regulator can request sales data (and other information) from manufacturers, suppliers or distributors of any scheduled medicines. This would allow them to track the flow of codeine all the way “from the manufacturer to the dispensary, be it a clinic, pharmacy, hospital, or doctor’s practice”, SAHPRA’s communications officer, Nthabi Moloi, told Spotlight.

Why is this important? Until now, health authorities have struggled to detect suspicious sales of codeine, which is found in both prescription and over-the-counter medicines. This problem manifests in two ways. For one, recreational users can often get a continuous supply of codeine directly from pharmacies. While people are only permitted to purchase a limited amount of the drug, many bypass this simply by buying from different pharmacies. It’s largely impossible to flag these individuals since there is no centralised data on what medicines people buy across vendors (though attempts have been made to address this).

The second issue relates to wholesale supply. Following a Carte Blanche investigation flighted last year, SAHPRA confirmed that a pharmacy group was making illicit bulk sales of codeine-based cough syrups. While patients are only allowed to get codeine from a licensed health worker or pharmacist, it’s thus no surprise that it can also be found on the black market.

The new draft guideline aims to tackle both of these problems by allowing SAHPRA to request information from companies and health workers about how much codeine they’re producing, selling or dispensing and who it is being provided to. This would “enable SAHPRA to detect anomalies in the distribution of medicines prone to abuse, such as abnormally large orders by dispensaries” Moloi explains.

It is the “first phase”, she says, of the codeine care initiative – which is an effort to centralise data on all codeine sales along the entire supply chain nationally. The plan is to ensure that the regulator can flag anything from an individual who is buying large amounts of codeine from multiple vendors to a wholesaler who is selling the drug to illicit dealers.

Codeine rehab admissions triple since 2019

The draft guideline, which is now available for public comment, comes at a time in which rates of codeine addiction are soaring throughout South Africa, according to admissions data from drug and alcohol treatment facilities. Most rehabilitation centres around the country are connected to a programme called the South African Community Epidemiology Network on Drug Use (SACENDU), which collects anonymised patient data from the different centres. Professor Nadine Harker, who oversees this project says “if you look at treatment admissions over time, there has been an increase [in codeine-related admissions] over the years – steadily but definitely”.

Indeed, SACENDU’s bi-annual reports show that in the first half of 2019, 277 people who went to SACENDU-linked rehab sites said they had been misusing codeine. This amounted to 3% of all admissions. But by the first half of 2023, this percentage had tripled to 9% – totalling 749 people. (In absolute terms the number slightly less than tripled).

Even before this uptick, health workers were concerned. In the mid-2010s, a survey of 238 (mostly private sector) doctors was conducted across South Africa. It found that 85% of these practitioners were worried about the easy availability of codeine in pharmacies.

Part of the concern is driven by the fact that people who use codeine-based medicines over a long time can develop a range of health complications, including stomach ulcers and liver damage (this is particularly when the medicines contain additional substances like paracetamol). And some people are more vulnerable than others, as genetic factors play a big role in how codeine affects a person.

Why is the problem getting worse?

Part of the spike in codeine use appears to be driven by a trend among young people, who sometimes mix codeine-based cough syrups with cooldrinks. The combination is often referred to as lean, and has become a popular party drug among high school students. Research shows that codeine’s low price and general accessibility is one reason for its popularity. Harker for instance notes that it’s often available at home, where kids “can pick it up out of their mom’s medicine cabinet”.

In other cases, people appear to be relying on the drug not for recreation but to cope with psychological distress. For instance, a 2022 study for which women were interviewed at rehab centres in the Western Cape and Eastern Cape found that many had turned to pharmaceutical products to deal with everything from trauma caused by physical abuse to grief over the loss of a child.

“I just wanted the pain to go away. I wanted my mind to switch off… [the tablets] actually made me dead inside if I can say that,” one woman explained.

A lack of awareness about the dangers of codeine also seems to play a role: 94% of doctors who were surveyed agreed that patients “do not fully understand the risk of dependence in taking over-the-counter medicines containing codeine”. The lack of regulatory control may contribute to this impression: one study at South African rehab centres found that “many participants were of the view that [over-the-counter] codeine-containing medicines were not drug[s] per se due to their free availability to purchase without any real regulations or protocols guiding their sale”.

Shouldn’t we just make codeine prescription-only?

Currently, the law states that codeine-based pills can be bought over the counter only under specific conditions. For one, they have to contain another active ingredient like paracetamol or ibuprofen, and each pill can contain a maximum of 10 milligrams of codeine. A person can only buy one pack and it must contain at most 5 days’ worth of medicine (with no more than 80 milligrams a day). Anything more and a script is needed.

Liquid codeine, like cough syrups, can be bought without a script if it contains no more than 10 milligrams of codeine per teaspoon (the maximum daily dose is 80 milligrams). The bottle itself may not contain more than 100 millilitres of syrup.

Products like Gen-payne, Myprodol, and Stopayne all contain small amounts of codeine – typically in combination with other painkillers such as paracetamol or ibuprofen. (Photo: Towfiqu Barbhuiya/Unsplash)

Some researchers that spoke to Spotlight argue these restrictions are too lenient, and that codeine should be ‘up-scheduled’, meaning that it would only be available if a patient has a script, regardless of the dose or combination. By doing this, children may find it harder to get a hold of cough syrups for lean, and people may generally become more aware of the addictiveness of the drug when used over the long-term.

Indeed, there are some studies which have found this approach to be effective in other countries. Research published in the journal Addiction found that when authorities in Australia made codeine prescription-only in 2018, a large poisoning information centre in the country began to receive significantly fewer calls about codeine-related incidents (both from health workers and members of the public).

But there are also potential downsides to this strategy. For one, as Spotlight has previously reported, increased regulation may make life harder for poorer patients seeking pain relief. This is given that they would have to spend more money for a consultation and prescription if they needed codeine-based painkillers.

Andy Gray, who chairs an advisory scheduling committee at SAHPRA, details a second issue: “I’m not convinced that up-scheduling would solve the issue if what we’re dealing with [in South Africa] is illegal behaviour… If [codeine] is being smuggled out of manufacturers or wholesalers, scheduling is not going to make a difference”.

Dr Andrew Scheibe, a harm reduction researcher at the University of Pretoria, notes a third related problem that may occur. “If people do have codeine-dependence and they’re unable to access the codeine, they might likely shift to accessing opioids… on the black market”.

Scheibe highlights the United States as an example, where prescription opioids like oxycodone and fentanyl have been at the centre of a major drug epidemic. “When they tried to increase restrictions on access to those opioids then people started using heroin,” he notes. A 2022 study found that this had taken place among opioid users interviewed in Connecticut, Kentucky and Wisconsin.

Whatever the answer, researchers agree that some basic steps need to be taken to educate the public. Harker says “a lot of awareness raising needs to happen at various levels, for instance at pharmacies”. She notes that “when someone purchases codeine over the counter, it’s important for a pharmacist to engage [with them and] make the consequences known to the individual if they use it outside of the dosages indicated… And we don’t do that enough from the medical or pharmacist’s side”.

Republished from Spotlight under a Creative Commons licence.

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Large Study Reveals Risk Factors for Long COVID

Photo by Usman Yousaf on Unsplash

Early in the pandemic, many people who had SARS-Cov-2 infection or COVID began to report that they couldn’t shake off their symptoms even after a month or more – unusually long for a viral infection of the upper respiratory tract – or developed new, persistent symptoms soon after the infection cleared.

Although it’s still not clear what causes post-COVID conditions or “long COVID” (symptoms and conditions that develop, linger, or reoccur weeks or months after SARS-CoV-2 infection), a new study by researchers at Columbia University Vagelos College of Physicians and Surgeons confirms the high burden of long COVID and sheds light on who’s at greatest risk.

The study, published in JAMA Network, found that people with a milder infection – including those who were vaccinated against SARS-CoV-2 and those who were infected with an Omicron variant – were more likely to recover quickly.

Recovery time was similar for subsequent infections.

“Our study underscores the important role that vaccination against COVID has played, not just in reducing the severity of an infection but also in reducing the risk of long COVID,” says Elizabeth C. Oelsner, the study’s lead author and the Herbert Irving Associate Professor of Medicine.

Study details

The study involved over 4700 participants from the Collaborative Cohort of Cohorts for COVID 19 Research (C4R), who were asked to report their time to recovery after infection with SARS-CoV-2.

The study found that, between 2020 and early 2023, the median recovery time after SARS-CoV2-infection was 20 days, and more than one in five adults did not recover within three months.

Women and adults with pre-pandemic cardiovascular disease were less likely to recover within three months. Other pre-pandemic health conditions, including chronic kidney disease, diabetes, asthma, chronic lung disease, depressive symptoms, and a history of smoking, were linked to longer recovery times, but these associations were no longer significant after accounting for sex, cardiovascular disease, vaccination, and variant exposure.

“Although studies have suggested that many patients with long COVID experience mental health challenges, we did not find that depressive symptoms prior to SARS-CoV-2 infection were a major risk factor for long COVID.” 

Other groups disproportionately affected by long COVID were American Indian and Alaska Native participants, in whom severe infections and longer recovery times were more common.

“Our study clearly establishes that long COVID poses a substantial personal and societal burden,” says Oelsner. “By identifying who was likely to have experienced a lengthy recovery, we have a better understanding of who should be involved in ongoing studies of how to lessen or prevent the long-term effects of SARS-CoV-2 infection.”

Source: Columbia University Irving Medical Center

Brain Fluid Dynamics is Key to the Mysteries of Migraine

Credit: University of Rochester Medical Center

New research describes how a spreading wave of disruption and the flow of fluid in the brain triggers headaches, detailing the connection between the neurological symptoms associated with aura and the migraine that follows. The study, which appears in Science, also identifies new proteins that could be responsible for headaches and may serve as foundation for new migraine drugs.

“In this study, we describe the interaction between the central and peripheral nervous system brought about by increased concentrations of proteins released in the brain during an episode of spreading depolarization, a phenomenon responsible for the aura associated with migraines,” said lead author Maiken Nedergaard, MD, DMSc, co-director of the University of Rochester Center for Translational Neuromedicine. “These findings provide us with a host of new targets to suppress sensory nerve activation to prevent and treat migraines and strengthen existing therapies.”

It is estimated that one out of 10 people experience migraines and in about a quarter of these cases the headache is preceded by an aura, a sensory disturbance that can includes light flashes, blind spots, double vision, and tingling sensations or limb numbness. These symptoms typically appear five to 60 minutes prior to the headache.

The cause of the aura is a phenomenon called cortical spreading depression, a temporary depolarization of neurons and other cells caused by diffusion of glutamate and potassium that radiates like a wave across the brain, reducing oxygen levels and impairing blood flow. Most frequently, the depolarization event is located in the visual processing centre of the brain cortex, hence the visual symptoms that first herald a coming headache.

While migraines auras arise in the brain, the organ itself cannot sense pain. These signals must instead be transmitted from the central nervous system to the peripheral nervous system. The process of communication between the brain and peripheral sensory nerves in migraines has largely remained a mystery.

Fluid dynamics models shed light on migraine pain origins

Nedergaard and her colleagues at the University of Rochester and the University of Copenhagen are pioneers in understanding the flow of fluids in the brain. In 2012, her lab was the first to describe the glymphatic system, which uses cerebrospinal fluid (CSF) to wash away toxic proteins in the brain. In partnership with experts in fluid dynamics, the team has built detailed models of how the CSF moves in the brain and its role in transporting proteins, neurotransmitters, and other chemicals.

The most widely accepted theory is that nerve endings resting on the outer surface of the membranes that enclose the brain are responsible for the headaches that follow an aura. The new study, which was conducted in mice, describes a different route and identifies proteins, many of which are potential new drug targets, that may be responsible for activating the nerves and causing pain.

As the depolarization wave spreads, neurons release a host of inflammatory and other proteins into CSF. In a series of experiments in mice, the researchers showed how CSF transports these proteins to the trigeminal ganglion, a large bundle of nerves that rests at the base of the skull and supplies sensory information to the head and face.

It was assumed that the trigeminal ganglion, like the rest of the peripheral nervous system, rested outside the blood-brain-barrier, which tightly controls what molecules enter and leave the brain. However, the researchers identified a previously unknown gap in the barrier that allowed CSF to flow directly into the trigeminal ganglion, exposing sensory nerves to the cocktail of proteins released by the brain.

Migraine-associated proteins double during brain wave activity

Analysing the molecules, the researchers identified twelve proteins called ligands that bind with receptors on sensory nerves found in the trigeminal ganglion, potentially causing these cells to activate. The concentrations of several of these proteins found in CSF more than doubled following a cortical spreading depression. One of the proteins, calcitonin gene-related peptide (CGRP), is already the target of a new class of drugs to treat and prevent migraines called CGRP inhibitors. Other identified proteins are known to play a role in other pain conditions, such as neuropathic pain, and are likely important in migraine headaches as well.

“We have identified a new signaling pathway and several molecules that activate sensory nerves in the peripheral nervous system. Among the identified molecules are those already associated with migraines, but we didn’t know exactly how and where the migraine inducing action occurred,” said Martin Kaag Rasmussen, PhD, a postdoctoral fellow at the University of Copenhagen and first author of the study. “Defining the role of these newly identified ligand-receptor pairs may enable the discovery of new pharmacological targets, which could benefit the large portion of patients not responding to available therapies.”

The researchers also observed that the transport of proteins released in one side of the brain reaches mostly the nerves in the trigeminal ganglion on the same side, potentially explaining why pain occurs on one side of the head during most migraines.

Source: University of Rochester Medical Center

Three Subtypes of IBS are Characterised by Different Extra-intestinal Symptoms

Irritable bowel syndrome. Credit: Scientific Animations CC4.0

While irritable bowel syndrome (IBS) is commonly associated with symptoms outside the intestine, it was not known whether these symptoms differed according to the subtypes of the condition. A new study published in Neurogastroenterology and Motility investigated the prevalence, and found that the IBS-M (mixed bowel habits) subtype had the highest prevalence of most extra-intestinal symptoms symptoms.

The researchers carried out a descriptive cross-sectional study patients with IBS according to Rome IV criteria. They were classified according to subtypes: IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant), and IBS-M (mixed bowel habits). Of the 4862 patients included; there were 608 IBS-D (12.5%), 1978 IBS-C (40.7%), and 2276 IBS-M (46.8%).

Participants completed a patient health questionnaire-9 (PHQ-9) score for depressive symptoms, with IBS-M the highest at 12.7 compared to 11.1 for IBS-D and 10.5 for IBS-C. They also completed an IBS-severity scoring system (IBS-SSS) questionnaire.

Overall, the study found the following results:

IBS-M:

  • Overweight
  • High IBS-SSS of 320
  • Depressive symptoms (80.0%)
  • Multiple extra-intestinal symptoms
  • Arthralgia (62.4%)
  • Chronic cervicalgia (81.0%)
  • Extremity numbness (64.5%)
  • Atopic dermatitis (28.2%)

IBS-C:

  • Lower body mass index
  • Low BS-SSS of 290

IBS-D:

  • Overweight (30.9%)
  • Higher food intolerance perception (9.5%)
  • History of cholecystectomy (17.8%)
  • Faecal incontinence (36.2%)

The authors concluded that, “The prevalence of most extra-intestinal symptoms is higher among patients with IBS-M. Further research is needed to better characterize IBS subtypes, which could potentially help refining tailored therapeutic strategies.”