Real-world trial finds long-lasting benefit for TENS with physical therapy in reducing movement pain, fatigue
Credit: University of Iowa
Adding TENS (transcutaneous electrical nerve stimulation) to outpatient physical therapy reduced movement-based pain and fatigue in patients with fibromyalgia, and the effects lasted for at least six months, according to a new study led by researchers at University of Iowa Health Care.
“It is one of the few treatments that specifically targets movement-evoked pain and fatigue, which are major barriers to participation in daily activities,” says Sluka, UI professor of physical therapy and rehabilitation science.
TENS uses a small device with adhesive electrodes to send mild electrical pulses through the skin to block or reduce pain. The study found that the effect of TENS for reducing pain was similar, if not better, than current FDA-approved medications for fibromyalgia.
“We were excited to see that patients also had less fatigue,” Sluka added. “Right now, there are no good treatments for fatigue. So, the fact that we had anything that touched the fatigue was pretty powerful.”
Fibromyalgia: complicated, misunderstood, and hard to treat
Fibromyalgia affects about 4% to 7% of the population. It significantly impacts a person’s physical function, cognitive abilities, and sleep. In addition to chronic pain, a key feature of the condition is whole-body fatigue, which interferes with day-to-day life and contributes to patients’ inability to concentrate and perform functional activities.
Exercise is often the first line of treatment recommended to people with fibromyalgia, and research has shown that it can be beneficial. However, fibromyalgia causes fatigue and pain, which is a key reason why the research team focused on alleviating pain with movement.
“Pain with movement hinders a person’s ability to participate in an effective exercise program and do their day-to-day activities.” Sluka says.
Science translated to real-world benefit
Sluka and her colleagues have spent decades studying the biological mechanisms affected by TENS, developing the ideal parameters of TENS stimulation and testing the efficacy of TENS for treating chronic pain and fatigue in human trials.
They have previously shown that under the ideal conditions of a randomized, controlled clinical trial, TENS in conjunction with physical therapy can significantly decrease movement pain.
The new Fibromyalgia TENS in Physical Therapy (FM-TIPS) study was designed to test the effect of TENS under real-world conditions. The study was conducted in 28 outpatient physical therapy clinics across six health care systems in the Midwest, and included 384 people of different ages, education levels, and socioeconomic backgrounds. Almost 50% of the participants were from rural areas.
“It was a challenge to recruit participants for this study, but the clinics and the physical therapists we worked with were great. This would never have happened without them,” Sluka says.
The clinics were randomised to provide either physical therapy (PT) with TENS or physical therapy alone. In the PT-TENS group, participants were asked to use TENS for two hours a day for six months. That time could be split into short periods or done all at once. The TENS electrodes were placed on the upper and lower back and delivered a mixed frequency signal at an intensity as strong as the participant could tolerate.
After 60 days, movement-evoked pain during TENS treatment was significantly improved in the PT-TENS group. Adding TENS also significantly reduced resting pain and resting and movement-fatigue. In contrast, participants who received only physical therapy had no change in their movement-evoked pain.
When we gave the PT-only patients the TENS unit and they started using it, we also saw the same improvements as the PT with TENS patients, which is powerful. – Kathleen Sluka, PT, PhD
The response also was dose-dependent, with people who used TENS daily for 60 days having the best outcomes.
Unlike many pain-relieving drugs that can become less effective over time as the body develops a tolerance for the medication, the study shows that over time, TENS maintained its ability to improve pain and fatigue at a significant level.
After the primary endpoint at day 60, the PT-only group was also given TENS, and all the participants continued in the study for another four months.
“When we gave the PT-only patients the TENS unit and they started using it, we also saw the same improvements as the PT with TENS patients, which is powerful,” Sluka says.
Overall, the study showed that 80% of patients found TENS helpful. At six months, 80% were still using TENS once a week, and over 70% reported they felt better after using TENS.
TENS adds benefit
Dana Dailey, PT, PhD, UI assistant research scientist and the first author of the study, notes that it’s important for people to realize that the benefit of TENS comes from using it as a part of a total treatment plan that includes physical therapy.
“Using TENS on its own will not give the same benefits,” Dailey says. “However, the study shows that TENS provides an added benefit on top of any relief from other treatments. All the study participants were also using pain medications and receiving physical therapy, yet TENS still provided additional relief.”
Fibromyalgia often needs multiple interventions to help patients feel less pain and fatigue and improve their overall function. The new findings suggest that TENS could be particularly helpful as a part of a multipronged approach because it can be safely and easily used as a self-management tool that uniquely targets movement-associated pain and fatigue.
“Often, when you move a randomised, controlled clinical trial into a real-world setting, it doesn’t work because there are too many confounding factors. But this intervention still works,” Sluka says. “Not only did the treatment reduce movement pain and fatigue during the testing period, but patients continued to use it at six months.”
Autism has a significant and enduring sex bias, with roughly four boys diagnosed for every girl. For many years, experts have believed this disparity arises primarily from diagnostic inequities because much of autism research – and the screening tools that grew out of it – has historically focused on boys, effectively setting a male standard for what autism “looks like.” As a result, girls and women are more likely to be overlooked, misdiagnosed, or diagnosed much later in life.
This disparity has also shaped the science around autism. When fewer females with the condition are identified, fewer are included in research studies, creating a feedback loop where scientific understanding of autism in females remains limited. Because of this underrepresentation of females, it has been difficult for scientists to disentangle how much of the sex bias in autism reflects social inequities versus underlying biological differences between the sexes.
While the search for biological explanations has largely lagged behind, one leading theory, known as the “female protective effect,” proposes that females may be biologically buffered against developing autism in a way males aren’t.
The idea can be traced back to studies showing that females diagnosed with autism tend to carry a higher number of genetic mutations or “hits” than males with the condition, meaning that they require a higher load of the same genetic mutations for autism to manifest. But, until now, there’s been little clarity on the exact biological mechanism behind this apparent resilience.
Now, a perspective from the lab of Whitehead Institute Member David Page, published March 30 in Nature Genetics, proposes a genetic explanation for the female protective effect and suggests that biological differences between males and females contribute to autism’s strong sex bias.
The work is one of many projects from the Page lab uncovering the biological underpinnings of sex bias in everything from heart health and autoimmune disease to certain cancers.
“The fact that we see sex biases in disease all across the body gives credence to the notion that the sex bias in autism isn’t simply emerging from diagnostic inequities and gendered expectations of what the conditions looks like,” says Page, who is also a professor of biology at Massachusetts Institute of Technology and an investigator at the Howard Hughes Medical Institute (HHMI).
The researchers propose that this protective effect extends beyond autism, and could help explain why 17 other congenital and developmental disorders predominately affect males. By characterizing the biological factors that make one sex more or less likely to develop certain health conditions, scientists see an opportunity to improve how these conditions are diagnosed and how people receive care.
“The fact that we see sex biases in disease all across the body gives credence to the notion that the sex bias in autism isn’t simply emerging from diagnostic inequities and gendered expectations of what the conditions looks like,” says Page.
Page and Harvard-MIT MD-PhD student Maya Talukdar trace the female protective effect to the X chromosome. Talukdar is a graduate student in Page’s lab and the lead author of the perspective.
Most females have two X chromosomes (XX) while most males have one X and one Y chromosome (XY). Sex chromosomes can dial up and down the expression of thousands of genes on the other 22 pairs of chromosomes in a cell, impacting cell function across the entire body.
Historically, scientists believed that the second X chromosome in females is largely inactive. But, in recent years, research out of the Page lab has shown that the so-called “inactive X,” also called Xi, plays a crucial role in regulating gene expression on the active X chromosome, and the rest of the chromosomes.
In this perspective, the researchers point to a subset of genes that are expressed from both the active and inactive X chromosome — often known as genes that “escape” X chromosome inactivation. Many of these genes are dosage-sensitive regulators of key cellular processes. These processes influence thousands of other genes across the genome, including many linked to autism.
Because females have an extra copy of these regulatory genes expressed from Xi, Page and Talukdar propose that they may be better able to buffer the effects of autism-associated mutations than males.
The female protective effect beyond autism
This mechanism, the researchers say, extends beyond autism to a range of congenital and developmental diseases with a male bias.
“Many of the other congenital or developmental conditions we’re pointing to aren’t subject to diagnostic inequities in the way autism is,” says Talukdar. “This strengthens the idea that the female protective effect is emerging from genetic differences in males and females.”
One example is pyloric stenosis, which like autism, affects four boys for every girl. Infants with the condition experience severe vomiting due to thickening of the pyloric sphincter, the passage between the stomach and small intestine. As with autism, girls with pyloric stenosis appear to require more genetic “hits” in order to develop the condition.
The researchers’ new framework of looking at Xi to understand sex differences in disease could impact treatment and care not just for conditions that predominately affect males, but also for those that are more common in women, such as autoimmune diseases.
“Our biology isn’t one-size-fits-all,” Talukdar says “Sex differences clearly play a huge role in health, and it’s so important that we understand them.”
Many regions in the Northern Hemisphere experienced a slightly earlier start to their flu season, driven in some part by a novel variant of influenza A(H3N2). As our flu season also kicks off slightly earlier than usual, Spotlight reports on the detection of this variant in South Africa and what we might expect from this year’s flu season.
As the mercury slowly starts dropping across the country, so does the risk of picking up flu. For many, this might only mean a few days of illness and discomfort, but for some, especially the elderly, it can be life-threatening.
Despite temperatures throughout most of the country remaining moderate so far, this year’s flu season has started, somewhat ahead of schedule. This is according to the National Institute for Communicable Diseases (NICD) in a press release issued on Wednesday.
What we refer to as flu, is commonly caused by one of two types of influenza viruses, influenza A and influenza B. These two are further typed into different lineages, the most common for influenza A is A(H1N1) and A(H3N2) and for influenza B, the B-Victoria and B-Yamagata.
The Yamagata lineage has not been detected since 2020 and is thought to have gone extinct, said Dr Sibongile Walaza. She is a medical epidemiologist and head of epidemiology at the Centre for Respiratory Disease and Meningitis at the NICD.
A key reason why influenza viruses continue to circulate year after year is how fast they mutate and learn to dodge our immune defenses. These mutations eventually result in different subtypes of lineages that are called clades, within which there can be further sub-clades.
It was a sub-clade of the A(H3N2) virus, known as sub-clade K, that led to the flu season starting earlier than usual in some parts of the Northern Hemisphere. The World Health Organization (WHO) reported that the variant was identified in 2025 and spread fast.
“This [sub-clade] contributed to an earlier start to the influenza season in many countries, with several reporting higher‑than‑usual levels of activity. ‘Subclade K’ accounted for the majority of influenza viruses reported across regions,” the WHO stated in a press release.
Sub-clade K was also responsible for an unusual spike in flu cases in South Africa in October and November 2025. Walaza told Spotlight there weren’t enough flu cases detected to cross the seasonal threshold for an additional flu wave, but the increase so late in the year, outside of the typical flu season, was unusual.
Early start
Usually, South Africa’s flu season starts sometime in April or May and spans the winter months, said Walaza, but it is difficult to predict exactly what will happen in any particular year.
This year’s flu season officially started in the second week of March, according to the NICD’s latest report, albeit at a low transmission level for now. 134 samples were tested between 16 and 22 March. Of those, 12 (9%) tested positive for influenza, 12 (9%) were cases of RSV and 3 (2.2%) tested positive for SARS-CoV-2.
In a rather unusual occurrence, the NICD reported that the start of this year’s RSV season coincided with that of the flu season. RSV refers to respiratory illness caused by the Respiratory syncytial virus. The RSV season usually starts before the flu season, but infections can occur all year round.
“The fact that both the flu and RSV seasons are starting at the same time means clinicians could potentially see a high burden of patients with respiratory illness in medical facilities in the coming weeks,” the NICD said in the press release.
Two potential scenarios
Professor Tulio de Oliveira, the director of the Center for Epidemic Response Innovation at Stellenbosch University, said the reality is that we do not know what to expect for this year’s flu season.
“[At]t the moment, we are working with potentially two different scenarios,” he told Spotlight.
The one scenario is that we may be in for a more extreme flu season, he explained, since last year was an unusually mild season and population immunity against the viruses that cause flu may currently be lower. The other scenario, depending on which flu virus circulates, is that South Africa may have some herd immunity because of the unusual spike in flu cases near the end of last year.
In other words, it all comes down to which flu viruses, and their subtypes end up circulating.
“I think this year we’ll have the three influenza lineages [A(H3N2), A(H1N1)pdm09 and influenza B-Victoria] circulating, but in terms of which one is going to be dominant in the season, it’s difficult to tell in advance,” Walaza said.
What we know about sub-clade K
Based on what we’ve seen so far, it does seem that sub-clade K is more transmissible, but it doesn’t appear to cause more severe disease, according to Walaza. De Oliveira added that sub-clade K has between seven and 10 mutations on the surface protein that allow it to bind to a cell’s receptor and enter the body, making it more infectious.
Whether or not it will be the driver of our flu season this year remains to be seen, but Walaza said that within the sporadic cases of flu detected and sequenced so far this year, most of the cases have been sub-clade K. In an NICD report from March, of the 24 influenza samples that were sequenced between 29 December 2025 and 22 March 2026, 11 were confirmed as being sub-clade K.
Experts will be keeping a close eye on circulating flu viruses with real-time genomic surveillance.
“South Africa is considered to be one of the top virus genomic surveillance places in the world,” De Oliveira said. “[A]t the moment, we don’t see a big reason for concern [about the flu season],” he said. “We do genomic surveillance every week, both with public and private laboratories – and if we see anything unusual, that’s going to be highlighted very promptly.”
Trends seen in previous flu seasons
Overall, in the last ten years, influenza A seems to be the driver of the majority of flu cases in South Africa, said De Oliveira, usually causing a big wave of flu cases at the start of the season. This is usually followed by a smaller wave of influenza B cases. In this time period, the influenza A subtype that dominates during the flu season appears to alternate between A(H1N1) one year and A(H3N2) the following year, but it also doesn’t always follow this pattern.
Zooming in more closely, Walaza said that over the last six years, 2020 and 2021 were outliers, with reduced transmission during 2020 due to the measures taken to curb the spread of the SARS-CoV-2 virus and out of season influenza transmission in 2021. Since 2022, the number of people getting flu every year has returned to roughly similar levels as before 2020.
Last year’s flu season was slightly unusual since it had started in late March, according to Walaza, but wasn’t as intense as some of the previous years as transmission remained at a low threshold level. Flu cases peaked in mid-May and then rose again slightly in October and November.
Data on influenza comes from three sentinel monitoring programmes managed by the NICD, which cover both the public and private healthcare sectors, said Walaza. A sample of healthcare facilities in the public sector and doctors in the private sector are asked to supply swabs taken from people with influenza-like illnesses or respiratory illnesses. Some general practitioners in the private sector are also enrolled in a programme called Viral Watch.
She said that the swabs are sent to the NICD laboratory and tested for the presence of different viruses, including SARS-CoV-2, influenza, RSV, parainfluenza, human metapneumovirus and rhinoviruses. If the samples test positive for flu, the sample is further tested to identify the lineage. This data is included in the weekly reports published on their website.
Members of the public can contribute to flu surveillance through an online web platform called CoughWatch. People are invited to enroll and provide weekly information on whether they have symptoms of flu or other respiratory illnesses. This is aimed at picking up trends among people who aren’t necessarily getting sick enough to go to the doctor or clinic, said Walaza and can hopefully serve as an early warning system for increases in respiratory illnesses, including flu.
CoughWatch has already opened for enrollment this year. (More information can be found here).
Flu vaccination uptake in South Africa remains low
Each year, the WHO releases recommendations on what should be in upcoming flu vaccines for the Northern Hemisphere and then later the Southern Hemisphere, usually announced around six months before the start of the respective flu seasons.
This year’s flu shot’s formulation is a trivalent one, said Walaza meaning it contains inactivated strains of all three influenza strains, including coverage for the A(H3N2) sub-clade K. Because it contains an inactivated virus, the vaccine itself cannot give someone the flu.
The level of protection offered by flu shots vary, but generally it ranges in effectiveness against preventing infection from about 30% to 60%. This means the shot will offer most people protection from severe disease and death, but it won’t necessarily prevent them from getting sick with the flu altogether.
One of the things that makes it difficult to predict effectiveness ahead of time is the possibility that a strain might circulate that is not well covered by the flu shot. De Oliveira said this “mismatch” is what we saw play out in some of the regions in the Northern Hemisphere in their last flu season.
Despite the partial mismatch between the vaccine used in the northern hemisphere and sub-clade K, several surveillancereports from the Northern hemisphere show that the vaccine nevertheless provides some protection against severe flu caused by sub-clade K.
The WHO also recently touched on this, saying that: “While current influenza vaccines help reduce the burden of disease, their effectiveness can vary by season, product, and population group. Protection is limited to one season”. The majority of flu vaccines purchased each year are by upper-middle and high-income countries, the WHO noted.
Usually, South Africa’s National Department of Health procures about 1 million flu shots for the public health sector, said Walaza and sometimes not all these doses are used.
While flu shots are made available each year, the uptake of these shots in the private sector appears to be low. Based on data collected through the NICD’s Viral Watch initiative – last year the uptake of the influenza vaccine in the private sector, among those enrolled in the programme, was only around 3.4%. This is based on data collected from 768 people enrolled, of those, 26 had gotten a flu shot. As far as Spotlight could establish, there currently isn’t any routine publicly available data on uptake in the public sector. One study of around a thousand people aged 65 and older, found that just over 32% of them had gotten the flu jab in 2018.
Spotlight asked the National Department of Health how many flu vaccines were procured for this year’s flu season. A response had not been received by the time of publication.
Low flu vaccine uptake can in part be attributed to South Africa having much milder winters and less severe flu seasons than the Northern Hemisphere, said De Oliveira.
Lack of awareness of the flu vaccine can also play a role, according to Walaza. She encourages more education and efforts by healthcare workers to inform at risk groups of the flu shot and when it will be available.
The flu shot is recommended for people who are at risk of severe disease, including older persons, pregnant women, people who are immunocompromised or with chronic medical conditions, as well as healthcare workers. But anyone aged six months and older can get the shot.
“The influenza vaccine will be available in pharmacies from the first week of April. The early start to the season means that this year, the vaccine is only becoming available as the season is getting started, so members of the public who fall into groups at high risk for severe influenza are urged to get their vaccines as soon as possible,” the NICD press release stated.
The potential of next generation flu vaccines
Earlier this year, the WHO released results from an assessment report on the value of having improved flu vaccines. “If improved, next-generation, or universal influenza vaccines are available and widely used between 2025 and 2050, they could prevent up to [an estimated]18 billion cases of influenza and save up to 6.2 million lives globally,” the report stated.
“This assessment makes clear the potential benefits that improved influenza vaccines could offer across different settings,” said Dr Philipp Lambach, WHO technical lead of the project. “It provides all those working on future influenza vaccine investments, policy development and research priorities a common set of evidence to catalyse vaccine development.”
According to the WHO, as of February 2026, there are 46 next-generation influenza vaccines in clinical development.
Nicotine-based vapes (e-cigarettes) are likely to cause cancers of the lung and oral cavity, according to a new study led by UNSW Sydney and published in Carcinogenesis. The study is titled “The carcinogenicity of e-cigarettes: a qualitative risk assessment.”
The work analyses a wide body of global research and was led by UNSW cancer researcher Adjunct Professor Bernard Stewart AM, with investigators from The University of Queensland, Flinders University, The University of Sydney, as well as Royal North Shore, The Prince Charles and Sunshine Coast University hospitals.
The team brought together experts from multiple disciplines, including pharmacists, epidemiologists, thoracic surgeons, and public health researchers. Together, they examined the evidence from different scientific perspectives.
“To our knowledge, this review is the most definitive determination that those who vape are at increased risk of cancer compared to those who don’t,” Prof Stewart says.
This assessment of carcinogenicity review argues that while researchers have long focused on vaping as a gateway to smoking, less attention has been paid to whether the devices might cause cancer on their own.
It is one of the most detailed attempts yet to determine whether vaping itself may cause cancer, independent of tobacco smoking. The analysis draws together clinical studies, animal experiments, and laboratory research examining the chemicals produced by e-cigarettes.
“Considering all the findings—from clinical monitoring, animal studies and mechanistic data—e-cigarettes are likely to cause lung cancer and oral cancer,” Prof Stewart says.
He says that though the consistency of findings across those disciplines was striking, the exact number of attributable cancer cases remains unclear.
“Our assessment is qualitative and does not involve a numerical estimate of cancer risk or burden. We’ll only be able to determine the precise risk once longer-term studies are available.”
Growing public health concerns
E-cigarettes were first sold in the early 2000s. Early marketing framed them as a “safer” alternative to tobacco cigarettes, as well as a possible aid for quitting smoking.
But the colourful, flavoured devices of today have spread quickly and widely, particularly among young people.
“E-cigarettes are known to be a gateway to smoking and hence cancer,” says co-author UNSW Associate Professor Freddy Sitas. “But the extent to which they may cause cancer in their own right has not received as much attention in research. The evidence was remarkably consistent across fields. It dictated an unequivocal finding now, though human studies that estimate the risk will take decades to accumulate.”
A clear outcome
Smoking has been studied for more than a century. Though e-cigarettes are relatively new, inhaling nicotine-laced aerosols is already linked to addiction, poisoning, inhalation injuries, and burns.
While researchers wait for long-term population studies showing whether people who vape are more likely to develop cancer, they must rely on multiple other forms of evidence.
The team identified numerous carcinogenic compounds in e-cigarette aerosols, including volatile organic chemicals and metals released from heating coils.
They examined several types of evidence: biomarkers in people showing DNA damage, oxidative stress, and tissue inflammation; experiments in mice that caused lung tumours; and laboratory studies showing cellular damage and disrupted biological pathways linked to cancer.
Taking all the results together, the researchers say the evidence points strongly in one direction.
A compounding problem
There is also growing evidence that many smokers who switch to vaping don’t quit cigarettes.
“Most of those who use e-cigarettes to quit smoking end up in ‘dual-use limbo,’ unable to shake off either habit,” says A/Prof Sitas. “What we do know from recent epidemiological evidence from the U.S. is that those who both vape and smoke are at an additional four-fold increased risk of developing lung cancer.”
History repeating
A/Prof Sitas and Prof Stewart traced parallels between the early scientific evidence linking smoking to disease and emerging concerns about vaping.
It took nearly a century of scientific investigation—from the mid-1800s to the landmark US Surgeon General’s report in 1964—before smoking was officially recognised as a cause of lung cancer.
During that time, early warning signs were often dismissed or overlooked.
“Early reports linked smoking to infectious diseases such as tuberculosis, followed by cardiovascular disease, stroke and lung cancer,” A/Prof Sitas says.
He says the same pattern may now be unfolding with vaping, and that researchers should not repeat the delay that occurred with cigarettes.
“E-cigarettes were introduced about 20 years ago. We should not wait another 80 years to decide what to do.”
A combination of immunotherapy and targeted cancer treatment given before and after surgery may reduce the risk of recurrence and improve survival in patients with muscle‑invasive bladder cancer who cannot tolerate conventional chemotherapy. The findings come from a new study from Karolinska Institutet, published in The New England Journal of Medicine.
Muscle‑invasive bladder cancer is a serious disease with a high risk of recurrence. To lower the risk of recurrence, patients are often given cisplatin‑based chemotherapy before surgery, but around half of patients cannot receive this treatment, commonly due to impaired kidney function. In the phase 3 study, all participants underwent standard surgery, in which the bladder is removed. One of the groups also received a new combination treatment with the immunotherapy pembrolizumab and the targeted drug enfortumab vedotin before and after surgery.
Large differences between the groups
The results show that 75% of participants treated with the combination therapy were alive without recurrence two years after enrolment, compared with 39% in the control group. When the researchers looked at overall survival, a larger proportion of patients in the treatment group were also alive after two years. In addition, no tumour cells were found in the removed bladder tissue in 57% of patients in the treatment group, compared with 9% in the control group. In total, 344 participants from 27 countries took part in the study.
“These are very promising results for patients with few treatment options available before surgery. It is also reassuring that the treatment does not appear to affect the ability to proceed with surgery, which can otherwise be a concern when treatment is given beforehand,” says Anders Ullén, professor of oncology at the Department of Oncology‑Pathology at Karolinska Institutet and the study’s last author.
Side effects occurred in both groups
All patients who received the combination treatment experienced some form of side effect. Common side effects included itching and hair loss, and the most frequent serious side effect in both groups was urinary tract infection. Serious complications also occurred among those who underwent surgery alone, which the researchers note reflects the fact that many patients in this group are older and have other underlying health conditions.
“It is always important to balance the benefits of treatment against the risk of side effects. At the same time, the results indicate that the treatment may offer clinically meaningful improvements, reduce the risk of recurrence and improve survival for many patients. We hope that the findings can help inform future treatment practice,” says Anders Ullén.
