A study published in Rheumatology & Autoimmunity challenges the assumption that achieving clinical remission in rheumatoid arthritis is sufficient, showing that patient-reported outcomes vary significantly by drug class even when disease activity is comparable.
Investigators found that patients taking TNF inhibitors reported better energy levels, mood, and emotional wellbeing than those taking older conventional drugs, while IL-6 and JAK inhibitors showed particular advantages for patients’ physical functioning. These differences persisted even after accounting for how well the underlying inflammation was controlled.
The study provides real-world evidence that different drug classes offer distinct advantages across quality-of-life domains, supporting a more nuanced, patient-centred approach to treatment selection rather than a one-size-fits-all strategy.
“Despite achieving clinical remission, patients with rheumatoid arthritis may still experience symptoms such as fatigue, sleep disturbances, and mental or communication issues compared with healthy individuals, highlighting the importance of evaluating patient-reported outcomes as a composite measure of treatment efficacy,” the authors wrote.
They noted that the study arrives at a moment when regulators are pushing for patient-reported outcomes to be formally incorporated into drug approvals and reimbursement decisions, and when artificial intelligence–based tools are beginning to use multiple data streams to match the right drug to the right patient.
Around 3.8 million people in South Africa developed depression in 2024, researchers estimate in a major modelling study. Photo from Pixabay CC0
By Gauta Mashego
Substance abuse is both a symptom and a consequence of untreated mental illness, and government needs to urgently step in to confront this dangerous overlap, argues Gauta Mashego of SECTION27.
Mental health globally has been in crisis for years. The strain on mental health was especially visible when the world stood still during the COVID-19 pandemic. The prevalence of anxiety and depression increased by 25% in the first year of the global outbreak of the SARS-CoV-2 virus, according to the World Health Organization. However, as the pandemic eased and life returned to the usual, open conversations around mental health also tapered off.
In South Africa, as in many low-and-middle income countries, people struggle with mental health disorders such as anxiety and depression. Around 3.8 million people in South Africa developed depression in 2024, estimate researchers in a major modelling study published as a preprint in March on medRxiv.
Mental health is shaped by many factors
Several studies worldwide report a high prevalence of substance use among people with mental illness compared to the general population.
Researchers have found that patients who suffer from psychotic disorders, such as schizophrenia and bipolar mood disorder, were more likely to abuse alcohol and illegal substances. Indeed, findings from a community survey highlighted a substantial burden of co-occurring mental disorders and alcohol use among men in three provinces in South Africa.
What also makes our society vulnerable to both mental health conditions and increased use of drugs and the development of substance use disorders, is our historical context of apartheid as well as socio-economic factors such as poverty, unemployment, and violence. Researchers have argued that mental health problems are related directly to poverty, while others also make the case that the poor are at greater risk than the rich to suffer from mental illness. At the same time, those living with mental illness are more likely to remain trapped in poverty due to high treatment costs, reduced productivity, and stigma around mental illness.
The kids are not alright
Underage drinking further complicates an already complex problem.
Up-to-date statistics of underage drinking in South Africa are limited, however the matter was thrust into the spotlight on Christmas day in 2025 when a disturbing video circulated on social media showing children between the ages of 6 and 12 consuming alcohol in the presence of adults.
Providing insights into the drinking behaviours of adolescents aged between 11 and 18, a 2019 Human Sciences Research Council study in townships across three provinces found that most had their first drink at the age of 13 or 14 years.
Highlighting the extent of underage drinking among Grade 8–11 learners from public schools in all nine provinces, the 2011 South African Youth Risk Behaviour Survey recorded that around 17% of 13-year-olds and 18% of 14-year-olds had engaged in drinking five or more drinks within a few hours on one or more days in the preceding month.
Mental disorders that commonly co-occur with alcohol use disorders in adolescents include antisocial disorders, mood disorders, and anxiety disorders.
Young people’s drinking habits are often linked to factors such as social norms, and the accessibility and affordability of alcohol. Added to this, since young people are often prolific consumers of media, they are frequently exposed to alcohol advertising and marketing, which encourages the consumption of alcohol.
But there is some hope.
The Liquor Amendment Bill aims to amend the Liquor Act of 2003 to prohibit the advertising, promotion or product placement of liquor in all forms of media. The Amendment Bill is at a very early stage in the legislative process, and it is likely to take time before we see any changes to the law (and longer before we see its implementation).
Other legislative changes debated include raising the legal drinking age from 18 to 21 and keeping schools alcohol-free, and more generally to place a moratorium on new liquor licences and stronger enforcement against Liquor Act violations.
South Africa also has a National Drug Master Plan 2019-2024. It was released by the Department of Social Development, and importantly, it recognises addiction as a chronic disease affecting the brain and behaviour.
However, experts say that while it is a great document, the Central Drug Authority which is tasked with implementing the plan, needs more power and resources to implement the plan’s recommendations.
South Africa also has a National Mental Health Policy Framework and Strategic Plan (2023-2030), that was introduced by the Department of Health. Similarly to its previous iteration, the latest plan envisions the integration of mental healthcare into primary healthcare. A key objective of the new plan is to ensure that mental healthcare users have access to care near their places of work. Another aim is to strengthen collaboration between government departments like education and social development to ensure that mental health is incorporated in planning and service development.
However, as it stands, many public healthcare facilities lack mental health professionals, with rural and underserved communities having little to no access to care. Only about 50% of public hospitals offering mental health services have a psychiatrist, while the country has less than one psychologist for every 100 000 people.
Shortages of mental health professionals mean patients often wait months for appointments. For an adolescent or a child who experiences anxiety, depression or suicidal thoughts, these delays can feel unbearable and it is quite possible that they may give up before receiving help. Currently, only one in ten children diagnosed with treatable mental conditions will have access to care.
While South Africa developed extensive legislative and policy frameworks to give effect to the constitutional right to healthcare, including mental healthcare, constitutional promises must make a difference in the lives of people. Unfortunately, millions of people in the country face barriers to mental healthcare, exposing the persistent gap between constitutional promises and lived reality.
When families lack access to counselling, community-based mental health services and early intervention programmes, harmful coping mechanisms continue to be passed down rather than prevented. To achieve the objectives of the Mental Health Policy Framework by 2030 and to catch up with the National Drug Master Plan that lapsed in 2024, stronger political will and meaningful action are urgently required. This is a crisis South Africa can’t evade.
*Mashego is a candidate attorney with SECTION27.
Note: Spotlight is published by SECTION27, but is editorially independent – an independence that the editors guard jealously. Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.
In many households in Mabopane and Soshanguve – townships on the northern outskirts of South Africa’s City of Tshwane that are marked by high poverty, unemployment and informal economic activity – evenings follow a familiar pattern.
When electricity cuts occur or power becomes unaffordable, families turn to gas stoves, paraffin heaters, or wood and coal fires to cook meals and keep warm. These energy sources contribute to air pollution, but the most harmful exposure often happens indoors, where children spend much of their time. These choices, though often unavoidable, put young children’s health at risk.
Children are particularly vulnerable to air pollution. Their lungs are still developing, their airways are narrower, and they breathe faster than adults.
In 2021, exposure to air pollution was linked to more than 700 000 deaths of children under five years old globally.
They are exposed by inhaling polluted air, swallowing contaminated dust or food, and through skin contact. Household fuel combustion releases tiny particles and harmful gases that irritate the lungs and airways. These pollutants can also damage the skin, triggering immune responses that worsen allergic conditions such as eczema and asthma.
As public health specialists, we examined the association between household air pollution and eczema and severe asthma symptoms among children aged seven years and younger in Mabopane and Soshanguve. We found that the use of polluting household fuels and gas was associated with an increased likelihood of eczema, followed by severe asthma symptoms.
Eczema and its impact
Eczema, or atopic dermatitis, is a chronic skin condition that causes itching, redness and inflammation.
It can significantly affect a child’s life by disrupting sleep and increasing the risk of skin infections. It also raises the likelihood of developing asthma, hay fever, or food allergies later. Visible rashes can equally affect confidence, social interactions and participation in school or play. Exposure to cigarette smoke inside the home further increases the risk of developing or worsening eczema, especially when mothers or female caregivers smoke.
Severe asthma and its impact
Asthma is a long-term condition affecting the lungs and airways, making breathing difficult. Symptoms include wheezing, coughing, chest tightness and shortness of breath. Global asthma prevalence ranges from 9.1% to 9.5% for children.
Severe asthma refers to frequent, hard-to-control, and sometimes life-threatening symptoms. Children with severe asthma may struggle to speak during attacks and are far more likely to need emergency care or hospitalisation. Young children are particularly vulnerable because their lungs, skin barrier and immune systems are still developing. Exposure to indoor air pollution during these early years increases the risk of long-term health problems.
Our study
To understand how household environments affect children’s health, we studied preschool-aged children in Mabopane and Soshanguve, in South Africa’s largely urban Gauteng province, between January 2022 and March 2023.
We randomly selected 42 preschools and collected health and household information from caregivers of 1840 children, including details on eczema, asthma symptoms, household fuel use, and exposure to cigarette smoke inside the home.
What we found
About one in eight children had experienced eczema at some point, and a similar proportion were currently experiencing symptoms. We also found that children from households using electricity for cooking and with no tobacco smoke exposure were less likely to have eczema than those who were exposed.
Children living in homes using open fires – such as paraffin, wood, or coal – for cooking or heating were more likely to have eczema. Exposure to cigarette smoke inside the home further increased this risk, particularly when mothers or female caregivers smoked.
Severe asthma symptoms were also common, affecting about one in six children. The use of gas for cooking or heating was strongly linked to severe asthma symptoms, even though gas is often viewed as a cleaner alternative during power cuts. Poor ventilation can increase indoor pollution, making these energy sources harmful to children.
The use of combined building materials in homes increased the likelihood of having eczema and corrugated iron significantly increased the likelihood of developing its symptoms. The frequency of trucks passing near the preschool children’s residences on weekdays was found to be associated with eczema and current symptoms. There was a significant association observed when trucks passed the children’s residences almost all day on weekdays. Children who walked to preschool had an increased risk of severe asthma symptoms compared with those using other modes of transport.
Why this matters
Although nearly 89% of residents in the study area have access to electricity, many households cannot rely on it consistently. Rising electricity costs and scheduled power cuts force families to use alternative fuels. These coping strategies, while understandable, increase children’s exposure to indoor air pollution during the most vulnerable stage of their development.
Our study confirmed that children in poorer communities face higher health risks due to their living environments, not just genetics. Susceptible groups, such as children, should be prioritised to reduce the adverse health effects of both outdoor and indoor air pollution.
What needs to change
Protecting children’s health requires more than asking parents to make better choices, as many families do not have safe, affordable alternatives.
Public health education on the dangers of cigarette smoke is crucial. Education campaigns, smoking cessation support and community-level interventions can help reduce children’s exposure to environmental tobacco smoke.
Stronger action on indoor and household air pollution is urgently needed. Evidence from this study can support the South African government in fast-tracking regulations and enforcing ambient air quality laws. It can also help in promoting safer household energy options.
Cleaner air inside homes is not a luxury. For South Africa’s children, it is a public health necessity.
Restricting calorie intake in species such as mice, rhesus monkeys, and fruit flies has been shown to extend their lifespans. In some cases, these animals not only live longer, but are also free of disease. But when pushed too far, calorie restriction can have negative impacts. Mice that undergo 40% reduction in calorie intake, for example, are more susceptible to infections, less likely to reproduce, and experience stunted growth.
Scientists have wondered whether there is a way to reap the longevity benefits of calorie restriction in humans without its negative repercussions. And in a new study, published April 13 in Nature Aging, they found a potential answer in an immune-related protein called complement component 3 (C3).
Yale researchers have previously shown that people who undergo moderate calorie restriction – a 14% reduction in calorie intake – for two years developed better immune defence without any growth or reproductive trade-offs.
“This concept demonstrates that ageing is actually malleable and a process that can be targeted,” says senior author Vishwa Deep Dixit, PhD, Waldemar Von Zedtwitz Professor of Pathology, professor of immunobiology and of comparative medicine, and director of the Yale Center for Research on Aging (Y-Age) at Yale School of Medicine.
Calorie restriction reduces inflammation-related protein
“It’s the only trial of its kind that has been done with such rigor and control and demonstrates relevance to human physiology,” Dixit says. During the trial, participants were able to reduce their calorie intake by 11 to 14% without feeling deprived.
In their analysis, the researchers detected more than 7000 proteins in the longitudinal plasma samples. Among them was an immune-related protein called complement component 3 (C3) that was significantly reduced following calorie restriction. C3 was of particular interest to the scientists as prior studies have suggested that activation of the complement system – a network of proteins involved in the defence against pathogens – could drive chronic inflammation, a major hallmark of ageing and age-associated diseases.
“But the causal effects of C3 in ageing and chronic inflammation have not been identified. So, we were very excited to find that in our study,” says Hee-Hoon Kim, PhD, a postdoctoral associate in the Dixit lab and a co-first author of the paper.
A target to slow ageing
When comparing the protein levels before and after two years of calorie restriction, the researchers identified white adipose tissue – the main type of fat tissue in mammals – as the primary site affected by calorie restriction.
The researchers confirmed their findings in animals. As with the human plasma, they found that C3 expression increased with age in mice. Further biochemical analyses showed that visceral white adipose tissue was responsible for an increase in C3 during ageing.
“We were not expecting that because these proteins are mainly synthesised in the liver,” says Manish Mishra, PhD, a postdoctoral associate in the Dixit lab and a co-first author of the study.
Single-cell RNA sequencing further revealed that the protein is produced by age-associated macrophages within the adipose tissues.
“This whole process was unknown in the beginning,” Mishra says. “Just to narrow it down to the subtypes of macrophages responsible for this complement protein production was very challenging.”
The body’s first line of immune defence, macrophages are mostly known for their role in engulfing pathogens. These immune cells also help maintain the balance of tissue functions, Dixit adds.
The question is whether the benefits gained from a reduction in C3 can be achieved without weight loss.
The researchers initially suspected that the shedding of adipose tissue or body fat due to weight loss may have stalled C3 production and slowed down the ageing process. After all, most of the study participants lost about 8.2kg after two years of moderate calorie restriction. However, when the researchers analysed the body mass index of the study participants, they did not observe any correlation between weight loss and a decrease in complement proteins.
“This suggests that calorie restriction has a beneficial effect that is unique to adipose tissues and is likely independent of weight loss,” Kim says.
Further, when the researchers inhibited C3 activation using a drug to mimic the effect of calorie restriction, the mice experienced less age-related inflammation.
The finding demonstrates that what is beneficial early on in life can be detrimental later on, Dixit says. This theory, known as antagonistic pleiotropy, was first proposed by biologist Peter Medawar in 1952 to describe the ageing process. A prime example of this theory is growth hormone production, which is essential in early development but could also drive cancer later in life.
Proteins like C3 are evolutionarily designed to protect us from infections, but as humans live much longer than their ancestors, these molecules can come back to harm us. Lowering the level of C3 proteins may be the key to enhancing health span, Dixit says.
The researchers are now investigating whether they could hold back C3 production to slow down ageing in humans using FDA-approved inhibitor drugs. “The idea is not to remove complement systems that are required for us to fight infections,” Dixit says. “Instead, the goal is to restore the balance.”
Blood protein levels change markedly already during childhood and adolescence, and differences between girls and boys become increasingly pronounced with age. This is shown by a new study in Nature Communications from Karolinska Institutet in collaboration with colleagues from SciLifeLab and KTH Royal Institute of Technology. The results suggest that blood protein levels change over the course of a lifetime, rendering adult reference values inadequate for children and adolescents.
In the study, the researchers analysed blood samples from 100 participants in the population-based BAMSE cohort at ages 4, 8, 16 and 24 years. Using advanced protein technology, over 5000 proteins were measured, of which just over 3500 could be tracked over time. More than half of these proteins changed with age even during childhood.
The greatest changes were observed between the ages of 8 and 16, a period that coincides with puberty. Many proteins increased sharply during this time, only to decrease again in early adulthood, whilst others showed more gradual increases or decreases from childhood to adulthood.
”Our study shows that reference values from adults cannot be used when interpreting protein levels in children and adolescents. Protein levels are strongly age-dependent even early in life, says one of the lead authors”, Sophia Björkander, assistant professor and docent at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.
The researchers also identified clear gender differences. In early childhood, the differences were few, but from adolescence onwards they increased markedly. By the age of 24, around 30 per cent of proteins differed between women and men, including those linked to growth, metabolism, the immune system and reproductive processes.
”Gender differences become very clear from adolescence and early adulthood. This shows that both age and gender are fundamental biological factors that must be taken into account when proteins are used as biomarkers”, says Sophia Björkander.
Blood proteins are used as biomarkers
Today, blood proteins are widely used as biomarkers to detect, for example, inflammation, hormonal imbalance, cardiovascular disease and metabolic disorders. An important finding from the study is that different levels of proteins in children may reflect normal development rather than disease.
”By mapping protein development, we are creating a reference that can be used to identify early deviations. This opens up possibilities for risk assessment of chronic diseases and more personalised medicine”, says senior/last author Erik Melén, project leader at BAMSE and professor at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.
The researchers point out that the number of participants is limited and that the results primarily apply to a relatively homogeneous population.
The study is part of the Human Disease Blood Atlas, which is a resource within the Human Protein Atlas and is based on the Swedish BAMSE cohort. The BAMSE project is jointly run by the Department of Clinical Science and Education, Södersjukhuset and the Institute of Environmental Medicine, both at Karolinska Institutet, as well as the Centre for Occupational and Environmental Medicine, Region Stockholm.
The research has been funded by, among others, the Swedish Research Council, Region Stockholm, the Swedish Heart-Lung Foundation and the Knut and Alice Wallenberg Foundation. The researchers state that there are no conflicts of interest.
