New research in the Annals of Internal Medicine reports that the drug solriamfetol is the most effective treatment for excessive daytime sleepiness (EDS) for people with obstructive sleep apnoea (OSA).
The standard treatment for OSA is a positive airway pressure (PAP) mask that uses compressed air to support lung airways during sleep. However, some people with OSA still experience EDS and may benefit from anti-fatigue medication.
“The most important thing that people with OSA should do is use their PAP machine, but if they are still sleepy there are options in the form of medications that can reduce their tiredness,” said first author Tyler Pitre, a resident physician in internal medicine at McMaster University and incoming respirology fellow at the University of Toronto.
“Fifteen to 30 per cent of people in North America have a diagnosis of OSA and the prevalence could be much higher as many others are undiagnosed. Many people have symptoms as the condition is highly associated with obesity, which affects a large and increasing number of people in Canada, the United States and other high-income countries,” he said.
“Among those patients, many will have EDS, which affects their quality of life, making them less productive and also puts them at risk of other psychological issues. Improving this situation is of paramount importance to physicians.”
Pitre said that OSA affects nearly one billion people globally, leaving many of them at risk of EDS.
Zeraatkar and Pitre made their findings by conducting a systematic review of 14 clinical trials of anti-fatigue medications involving 3085 people, as well as analysing data from MEDLINE, CENTRAL, EMBASE and ClinicalTrials.gov in a specific network meta-analysis. They conducted their research from October 2022 to January 2023.
Senior author Zeraatkar said that while solriamfetol is likely the best medication for EDS, the drugs armodafinil-modafinil and pitolisant are also effective in combatting fatigue.
Solriamfetol can also raise blood pressure, especially risky for people with OSA, as many of them also have cardiovascular issues.
“It would be interesting to see how effective these anti-fatigue medications will be for treating related illnesses such as chronic fatigue syndrome and long COVID, now that we know they work for a similar condition,” said Zeraatkar, an assistant professor of the Department of Anesthesia.
Using new genetic tools to study statins in human cells and mice, researchers have uncovered how these drugs protect the cells that line blood vessels. Published in Nature Cardiovascular Research, the findings provide new insight into statins’ curiously wide-ranging benefits, for conditions ranging from arteriosclerosis to diabetes, that have long been observed in the clinic.
“The study gives us an understanding, at a very deep mechanistic level, of why statins have such a positive effect outside of reducing LDL [low-density lipoprotein],” said professor of medicine Joseph Wu, MD, PhD, the study’s senior author. “Given how many people take statins, I think the implications are pretty profound.”
Developed in the 1980s from compounds found in mould and fungi, statins target an enzyme that regulates cholesterol production in the liver. But clinical trials have shown that they also seem to safeguard against cardiovascular disease beyond their ability to lower cholesterol.
Heart failure patients who take statins, for example, are less likely to suffer a second heart attack. They have also been shown to prevent the clogging of arteries, reduce inflammation and even lower cancer risk. Yet these underlying mechanisms are poorly understood.
“Statins were invented to lower cholesterol by targeting the liver. But we didn’t know the targets or the pathways in the cardiovascular system,” said Chun Liu, PhD, an instructor at the Stanford Cardiovascular Institute and co-lead author.
Mesenchymal cells are poor substitutes
To take a closer look at statins’ effect on blood vessels, Liu and colleagues tested a common statin, simvastatin, on lab-grown human endothelial cells derived from induced pluripotent stem cells. Endothelial cells make up the lining of blood vessels, but in many diseases they transform into a different cell type, known as mesenchymal cells, which are poor substitutes.
“Mesenchymal cells are less functional and make tissues stiffer so they cannot relax or contract correctly,” Liu said.
The researchers suspected that statins could reduce this harmful transition. Indeed, endothelial cells treated with simvastatin in a dish formed more capillary-like tubes, a sign of their enhanced ability to grow into new blood vessels.
RNA sequencing of the treated cells offered few clues. The researchers saw some changes in gene expression, but they “didn’t find anything interesting,” Liu said.
It was not until they employed a newer technique called ATAC-seq that the role of statins became apparent. ATAC-seq reveals what happens at the epigenetic level, meaning the changes to gene expression that do not involve changes to the genetic sequence.
They found that the changes in gene expression stemmed from the way strings of DNA are packaged inside the cell nucleus. DNA exists in our cells not as loose strands but as a series of tight spools around proteins, together known as chromatin. Whether particular DNA sequences are exposed or hidden in these spools determines how much they are expressed.
“When we adopted the ATAC-seq technology, we were quite surprised to find a really robust epigenetic change of the chromatin,” Liu said.
ATAC-seq revealed that simvastatin-treated cells had closed chromatin structures that reduced the expression of genes that cause the endothelial-to-mesenchymal transition. Working backward, the researchers found that simvastatin prevents a protein known as YAP from entering the nucleus and opening chromatin.
The YAP protein is known to play important roles in development, such as regulating the size of our organs, but also has been implicated in the abnormal cell growth seen in cancer.
A look at diabetes
To see the drug in context, the researchers tested simvastatin on diabetic mice. Diabetes causes subtle changes to blood vessels that mimic the damage commonly seen in people who are prescribed statins — older patients who do not have a cardiovascular condition, Liu said.
They found that after eight weeks on simvastatin, the diabetic mice had significantly improved vascular function, with arteries that more easily relaxed and contracted.
“If we can understand the mechanism, we can fine-tune this drug to be more specific to rescuing vascular function,” Liu said.
The findings also provide a more detailed picture of the vascular disease process, which could help doctors identify and treat early signs of vascular damage.
A population-based study of 22 million people in the UK estimates that around one in ten individuals in the UK now live with an autoimmune disorder. The findings, published in The Lancet, also highlight important socioeconomic, seasonal and regional differences for several autoimmune disorders, providing new clues as to what factors may be involved in these conditions.
There are more than 80 known autoimmune diseases, including conditions like rheumatoid arthritis, type 1 diabetes and multiple sclerosis, some of which have been increasing in the last few decades.
This has raised the question whether overall incidence of autoimmune disorders is on the rise and what factors are involved, such as environmental factors or behavioural changes in society. The exact causes of autoimmune diseases remain largely unknown, including how much can be attributed to a genetic predisposition to disease and how much is down to exposure to environmental factors.
The study used anonymised electronic health data from 22 million individuals in the UK to investigate 19 of the most common autoimmune diseases. The authors examined whether incidence of autoimmune diseases is rising over time, who is most affected by these conditions and how different autoimmune diseases may co-exist with each other.
They found that the 19 autoimmune diseases studied affect around 10% of the population. This is higher than previous estimates, which ranged from 3–9% and often relied on smaller sample sizes and included fewer autoimmune conditions. The analysis also highlighted a higher incidence in women (13%) than men (7%).
The research discovered evidence of socioeconomic, seasonal and regional disparities for several autoimmune disorders, suggesting that these conditions are unlikely to be caused by genetic differences alone. This observation may point to the involvement of potentially modifiable risk factors such as smoking, obesity or stress. It was also found that in some cases a person with one autoimmune disease is more likely to develop a second, compared to someone without an autoimmune disease.
Dr Nathalie Conrad at the University of Oxford said: “We observed that some autoimmune diseases tended to co-occur with one another more commonly than would be expected by chance or increased surveillance alone. This could mean that some autoimmune diseases share common risk factors, such as genetic predispositions or environmental triggers. This was particularly visible among rheumatic diseases and among endocrine diseases. But this phenomenon was not generalised across all autoimmune diseases. Multiple sclerosis, for example, stood out as having low rates of co-occurrence with other autoimmune diseases, suggesting a distinct pathophysiology.”
These findings reveal novel patterns that will inform the design of further research into the possible common causes of different autoimmune diseases.
Professor Geraldine Cambridge at UCL Medicine said: “Our study highlights the considerable burden that autoimmune diseases place upon individuals and the wider population. Disentangling the commonalities and differences within this large and varied set of conditions is a complex task. There is a crucial need, therefore, to increase research efforts aimed at understanding the underlying causes of these conditions, which will support the development of targeted interventions to reduce the contribution of environmental and social risk factors.”
It has been believed speed of information transmitted among regions of the brain stabilised during early adolescence. A study in Nature Neuroscience has instead found that transmission speeds continue to increase into early adulthood, which may explain the emergence of mental health problems over this period. In fact, transmission speeds increase until around age 40, reaching a speed twice that of a 4-year old child.
As mental health problems such as anxiety, depression and bipolar disorders can emerge in late adolescence and early adulthood, a better understanding of brain development may lead to new treatments.
“A fundamental understanding of the developmental trajectory of brain circuitry may help identify sensitive periods of development when doctors could offer therapies to their patients,” says senior author Dora Hermes, PhD, a biomedical engineer at Mayo Clinic.
Called the human connectome, the structural system of neural pathways in the brain or nervous system develops as people age. But how structural changes affect the speed of neuronal signalling has not been well described.
“Just as transit time for a truck would depend on the structure of the road, so does the transmission speed of signals among brain areas depend on the structure of neural pathways,” Dr Hermes explains. “The human connectome matures during development and aging, and can be affected by disease. All these processes may affect the speed of information flow in the brain.” In the study, Dr Hermes and colleagues stimulated pairs of electrodes with a brief electrical pulse to measure the time it took signals to travel among brain regions in 74 research participants between the ages of 4 and 51. The intracranial measurements were done in a small population of patients who had electrodes implanted for epilepsy monitoring at University Medical Center Utrecht, Netherlands.
The response delays in connected brain regions showed that transmission speeds in the human brain increase throughout childhood and even into early adulthood. They plateau around 30 to 40 years of age.
The team’s data indicate that adult transmission speeds were about two times faster compared to those typically found in children. Transmission speeds also were typically faster in 30- or 40-year-old subjects compared to teenagers.
Brain transmission speed is measured in milliseconds, a unit of time equal to one-thousandth of a second. For example, the researchers measured the neuronal speed of a 4-year-old patient at 45 milliseconds for a signal to travel from the frontal to parietal regions of the brain. In a 38-year-old patient, the same pathway was measured at 20 milliseconds. For comparison, the blink of an eye takes about 100 to 400 milliseconds.
The researchers are working to characterise electrical stimulation-driven connectivity in the human brain. One of the next steps is to better understand how transmission speeds change with neurological diseases. They are collaborating with paediatric neurosurgeons and neurologists to understand how diseases change transmission speeds compared to what would be considered within the normal range for a certain age group.
Today we celebrate Nurses as we do every year on 12 May. The International Council of Nurses proclaimed this year’s slogan as ‘Our Nurses, Our Future’, but what is the future of nurses in South Africa?
During the height of the COVID pandemic, we saw a huge campaign launched by the World Health Organization, uplifting the stature of nurses and midwives and showcasing them as the backbone of health systems at a global level. In the South African context, the story goes that they will also be central to the health system once National Health Insurance is implemented yet there are many red flags raised as we continue the planning discussions in preparation for this change with little to no answers about that future.
“I will never be a nurse”
By the time my mother had to decide on a career, nursing was one of those professions that provided stability and security to black and coloured women during Apartheid. You had two choices – become a nurse or a teacher. That’s how my mother began her nursing journey, but she was so passionate about it so that it would probably have been her choice, regardless.
Her passion was not what spurred me on to become a nurse, though. I looked at her long hours and tireless devotion to her community and the mental health fraternity and literally uttered the words, “I will never be a nurse”. Then I met a young staff nurse during a youth weekend away. She was so proud of her profession. She just oozed pride, and at that moment, I went from a potential engineering student to a nursing student.
My father was livid. He could not comprehend why his only daughter would observe the work hours of her mother and still choose to become a nurse. But in many ways, I believe nursing chose me. Once I made the decision, I never looked back. I remember being mocked and berated for my choice in social circles, but feeling a deep connection to this calling.
I have not entered it blindly though. I was aware of my privilege and the weight of caring for people at their most vulnerable. The experiences I have made while holding the hand of someone taking their last breath, supporting a mother delivering a stillborn baby, to engaging with my first person living with HIV, or watching someone slip away after a huge battle with cancer have been deeply embedded in my consciousness. I do not believe these experiences to be without life-altering potential and believe it has shaped me into the healthcare worker I am today.
Threats to nurse autonomy
It is often believed that nurses are the handmaiden to the doctor and we should not think but do. Those sayings were so wrong, but even today, the inferiority of the quality of nurse training, lack of supervision, and only very limited mentoring all threaten the autonomy of the nurse.
Nurses, despite having a day and even a week dedicated to celebrating them, are still, for the most part, underpaid, overworked, and professionally stunted. By stunted I am referring to the lack of mandatory continuous professional development and upskilling. Somehow, as the backbone of primary healthcare, they are often unable to take time out for much-needed training.
One often hears of nurses being rude and impatient. Though some may very well display these horrible traits, for the most part, people have entered this profession to improve healthcare services to individuals, families, and communities at large. In my 21 years of experience, the issue is hugely exacerbated by the healthcare system, which does not support nurses. The hours are long and gruelling – exacerbated by staff shortages in facilities. The environment is hostile, the workload unequal, and the pay shoddy. Many nurses find themselves moonlighting to make ends meet.
Advocate for us
Though not an excuse for unprofessional behaviour, I do want activists and health advocates to fight for better working conditions, upskilling opportunities, and a larger health workforce in our public health sector.
The mental health of our clients and communities appears topical at the moment, but what about the nurse? The trauma of loss, observation of patient suffering, and abuse by many of the actors in the health space can take its toll on the mental health and well-being of our nurses, too. When we plan for the public, we must remember to include the healthcare workers and their health and well-being.
This is even more critical now as we embark on establishing the National Health Insurance (NHI) system.
As NHI looms, the threat that nurses will be ill-equipped to render quality healthcare services is a glaring reality. The South African Nursing Council (SANC) notes that 47% of the nurses on its database are older than 50 years of age. This narrative of aging nursing personnel started years ago and if we had a proactive plan to address this, South Africa may in fact have had some fighting chance to implement NHI smoothly.
In a damning article published in February, the Democratic Nursing Organisation of South Africa (DENOSA) highlighted that the South African public health sector has a deficit of 27 000 nurses and yet there are 5 000 nurses currently unemployed. How can this be acceptable? It further noted that the South African government has placed certain nursing specialities on a scarce skills list in the hope of recruiting from other countries instead of planning to upskill and uplift domestically.
Part of me wants to speak about accountability, collaboration, and change management, but the other part bleeds for nurses as the workload and responsibilities increase and the work environment becomes more hostile. All this makes it hard to see the silver lining.
I do, however, believe that if the South African Nursing Council and National Department of Health actually engage the people on the ground, those at the coal face, those with expertise, and review their current implementation plans, they will see the same glaring gaps that we see every day.
There must be a call to action for all nursing leadership, nursing activists, nurses, and nursing education establishments to collectively take a stand and demand that we revise our current approach to the nursing curriculum and work on making nursing more appealing to the youth. This could be one step in the right direction.
When I qualified as a nurse, it was a four-year course. The nursing degree I completed included Community Nursing, Psychiatric Nursing, General Nursing, and Midwifery, and although I might not practise it all, I am able to fall back on that knowledge during client or patient engagements. Now it is a five-year course with one qualification with the nurse trained as a generalist. The fear is how does that serve our communities? We need midwifery, for example, to do NIMART (initiate people on HIV treatment) and you need community nurses to be working in primary healthcare, If you come out with one general qualification – how exactly will this pan out?
We need a rethink of how we train nurses and how we can strengthen the curriculum so that we can get nurses who can address HIV and all issues in primary healthcare. In my programme – HIV testing, for example, nurses don’t get trained on HIV testing. It is just monkey see, monkey do and unfortunately, that doesn’t translate into quality service.
Very often nursing practice is see one, do one, and then you’re the expert. I’m arguing that these things must be part of the curriculum. For example, why must a nurse come out of nursing school and then only learn IMCI (Integrated Management of Childhood Illness) Why is IMCI not being done practically in the facility and the theory in class, as part of the curriculum?
Nurses, today, are expected to know everything, which is impossible but we are not upskilling them and making sure the curriculum is so robust that it addresses all disease profiles and our communities’ healthcare needs. We are talking about integrative and holistic healthcare so we cannot be only training nurses in one way. There is a malalignment of what our communities need and what nursing schools are churning out.
We must fix that.
We need an urgent change in the curriculum of nurses to ensure we can support the needs of the health system and communities, build great leadership for the future, and ensure quality health services for all.
* Sparks is a nurse, health equity advocate, and Tekano and Aspen New Voices Fellow with 21 years’ experience working across South Africa with a focus on ensuring equitable and just access to quality healthcare for all.She is also a Quote This Women + Voice of the Year Award Winner.
