The study reveals that the combination of antibiotics reduces mortality in patients with high-risk Staphylococcus aureus bacteriaemia by half, if applied in a personalised way
A study led by researchers from the Infectious Diseases Service of the Bellvitge University Hospital (HUB), the Bellvitge Biomedical Research Institute (IDIBELL) and the University of Barcelona (UB) shows for the first time that the combination of antibiotics can significantly improve the prognosis of patients with high-risk Staphylococcus aureus bacteriaemia, if it is applied selectively and in a personalised way.
The article has been published in the prestigious scientific journal The Lancet Regional Health – Europe and is the result of the collaboration of a dozen Spanish hospitals.
A reanalysis that redefines the strategy against bacteriaemia
Bacteraemia for S. aureus is a frequent and serious infection, with mortality reaching 30%. Its management requires prolonged intravenous antibiotherapy, the removal of possible infected devices and a thorough evaluation to rule out complications such as endocarditis or metastatic focus. In recent years, several clinical trials evaluating the combination of antibiotics had failed to demonstrate clear benefits in the global set of patients, a fact that the authors of the present study attributed to the lack of stratification according to risk.
For this reason, the study has carried out a reanalysis of the individualised data of two previously performed randomised clinical trials, differentiating patients according to their risk profile. This stratification was done through the FEN-AUREUS classification – a recently developed clinical tool that allows estimating the risk of mortality with information available during the first 24 hours of evolution – and the complication criteria of the Infectious Diseases Society of America (IDSA).
A personalised medicine according to individual risk
The re-evaluated trials include, on the one hand, a study with 155 patients from 18 Spanish hospitals that compared the use of daptomycin with the combination of daptomycin and phosphomycin; and, on the other, a study with 215 patients from 19 hospitals that compared cloxacillin in monotherapy with the combination of cloxacillin and phosphomycin. In both cases, the initial conclusions had shown no significant benefits of combined therapy in the overall set of patients, beyond a reduction in the duration of bacteraemia in patients treated with phosphomycin.
After the new risk group analysis, the work shows that low-risk and uncomplicated patients do not obtain significant benefits from combined therapy. On the other hand, high-risk patients showed remarkable therapeutic success at eight weeks (69.2% vs. 25.8%) and lower mortality at 60 days (23.1% vs. 45.2%).
According to first author Dr Francesc Escrihuela-Vidal, “the integration of risk and complications criteria can help identify patients who can really benefit from combined therapy.”.
In the same vein, co-author Dr Jordi Carratalà points out that “the results represent a real paradigm shift in the approach to this infection: we move from a uniform strategy for all patients to a precision medicine based on individual risk”. In addition, it highlights that this approach allows to avoid unnecessary intensive treatments in low-risk patients and will contribute to improving the design of future clinical trials.
Researchers have found that sucrose can relieve newborn babies’ pain during common hospital procedures
Photo by Christian Bowen on Unsplash
A new Cochrane review has found that sucrose can help with pain relief in newborn babies during common hospital procedures, such as venepuncture. This involves drawing blood with a needle, typically for testing.
Newborns, especially preterm infants in neonatal intensive care units (NICUs), undergo numerous painful procedures. Because of their immature pain regulation, they can experience these procedures intensely. Preventing and treating procedural pain in hospitalized newborns is important, as repeated untreated pain has been associated with poorer physical growth and potential effects on brain development.
Accessible, low-cost solutions such as sucrose – a sweet sugar solution placed in a baby’s mouth shortly before needle procedures – have been used for decades. However, evidence specific to some procedures, such as venepuncture, has been limited.
Despite sucrose being recommended in multiple guidelines for procedural pain relief in infants, its use in clinical settings remains inconsistent.
Low-cost, safe intervention
The new review examined 29 clinical trials involving more than 2700 preterm and full-term babies undergoing venepuncture in hospital. It found that sucrose probably reduces pain during and immediately after the needle procedure when compared to no treatment, water or standard care. The findings also suggest that sucrose works especially well when combined with non-nutritive sucking, such as a pacifier or dummy.
“Newborn babies undergo frequent needle procedures in hospital without any pain relief or comforting measures, even though older children and adults rarely have these procedures done without pain care.
The evidence shows that a small amount of sucrose given just before the procedure is a simple, fast and effective way to reduce that pain. Our review helps clinicians use this evidence more confidently and consistently in practice.”
—Mariana Bueno, University of Toronto
None of the studies included in the review reported immediate side effects from sucrose when used in the small amounts required for pain relief. However, the studies focused on short-term effects, and more research is needed to understand any potential long-term effects of repeated use in babies who spend extended time in neonatal care.
“Parents may be surprised to learn that something as simple as a few drops of sugar solution can make a real difference to their baby’s comfort during blood tests.
This is a low-cost, safe intervention that works within minutes, and it can be especially helpful when other comforting methods like skin-to-skin contact or breastfeeding aren’t possible.”
—Ligyana Candido, University of Ottawa
Treated like other medications
Although sucrose is already widely used in neonatal units, the researchers found considerable variation in how it is given, including differences in dose and timing.
Bueno added:
“What stood out to me when doing this review was the wide variation in how sucrose was given to newborns.”
The authors suggest the findings can help inform clearer clinical protocols and more consistent practice.
They also highlight that sucrose should be used purposefully for painful procedures and documented appropriately, rather than being given routinely to settle a crying baby.
“To ensure safety and clinical consistency, sucrose must be administered under formal medication protocols that define specific timing and dosage for painful procedures.”
— Jiale Hu, Virginia Commonwealth University
The review authors say future research should focus on comparing effective comfort measures such as skin-to-skin contact, breastfeeding and sucrose with each other, rather than continuing to compare them to no treatment, and on understanding any potential long-term effects of repeated use in babies who spend extended time in neonatal care.
An international, randomised, double‑blind, placebo‑controlled phase 3 study, the largest of its kind for mpox, found that tecovirimat did not improve clinical outcomes for adults with clade II mpox compared with placebo, while demonstrating a similar safety profile. Results of the STOMP/A5418 trial, published in the New England Journal of Medicine underscore both the urgent need for alternative therapeutics and the critical importance of randomised trials during public health emergencies.
This Phase 3 study randomised 412 participants (344 with laboratory‑confirmed mpox), to receive either tecovirimat or a matching placebo for 14 days. Randomisation was stratified by early versus later symptom onset and by the presence of severe pain. Participants had active skin or mucosal lesions and self‑reported daily symptoms, pain scores, and lesion status through Day 29, with confirmatory clinical assessments at scheduled visits. Biospecimens, including lesion swabs, oral and rectal swabs, and blood samples, were collected at multiple time points to assess viral DNA clearance. The primary endpoint was time to clinical resolution of all lesions, and key secondary endpoints included pain reduction, complete lesion healing, and virologic response.
Conducted across seven countries at 49 sites, the phase 3 study showed that tecovirimat did not shorten the time to lesion resolution, reduce pain, or speed viral clearance compared with placebo. These results align with interim findings released in December 2024, which led the trial’s independent Data and Safety Monitoring Board to halt further enrolment due to statistical futility.
“In the midst of a global public health emergency, the ACTG team rapidly conducted this randomized controlled trial to deliver a clear answer for patients and clinicians,” said William A. Fischer II, MD, associate professor of pulmonary and critical care medicine at the UNC School of Medicine, and director of emerging pathogens research at the UNC Institute for Global Health and Infectious Diseases. “These findings advance our understanding of mpox and help the field refocus efforts on identifying safe, effective and accessible treatment strategies, particularly for people at highest risk of severe disease.”
Although the trial did not demonstrate efficacy, tecovirimat demonstrated a favourable safety profile, with no major safety concerns identified – an important confirmation as thousands of patients worldwide have already received the drug under expanded access protocols.
“The STOMP trial provides essential evidence at a critical time and demonstrates why randomized controlled trials are an indispensable part of outbreak response,” said Joe Eron, MD, chief of infectious diseases and chair of the ACTG network. “But now we must keep going to find safe and effective treatment for people as this virus continues to circulate globally.”
The study’s conclusions are expected to influence clinical practice and public health guidance worldwide. With mpox still causing outbreaks in multiple regions, researchers emphasise that developing and evaluating new antiviral candidates remains a top priority.
If someone living with HIV is not on antiretroviral therapy, the virus can cause inflammation in, among other places, the brain. Photo by Anna Shvets
By Biénne Huisman
Antiretroviral therapy has shifted HIV from a fatal to a chronic condition. But neuropsychiatrists say it is imperative for people living with the virus to start treatment immediately as the “duration of untreated exposure” may cause irreversible brain damage and impact long-term cognitive health.
It has been recognised for decades that cognitive impairment is a potential complication of HIV infection. Questions over how likely and how serious this potential complication is have become more urgent over time as the population of people living with HIV ages – ageing after all also increases the risk of cognitive decline.
There were around 1.75 million people over the age of 50 living with HIV in South Africa in 2024, according to Thembisa, the leading mathematical model of HIV in the country. This is just over 20% of the estimated eight million HIV positive people in the country. A study published in the Lancet medical journal also has the number at around 20% in sub-Saharan Africa.
This is a delicate field of enquiry as researchers walk a tightrope to avoid “the burden of double stigma”, while conceptualising the necessary tools to best diagnose brain problems and suitable interventions.
Within as little as two weeks
At Groote Schuur Hospital’s Neuroscience Institute, Professor John Joska, director of the University of Cape Town’s (UCT’s) HIV Mental Health Research Unit, explains that HIV can enter the brain within as little as two weeks after the initial infection – primarily through infected white blood cells, such as lymphocytes. If a person is not on antiretroviral therapy, the virus can cause inflammation in the brain and possibly also tissue damage.
“The brain is a protected compartment,” says Joska. “A theory as to how the virus, which is a protein particle, gets into the brain is through infected lymphocytes. This doesn’t directly infect nerve cells, what we call neurons. It infects other supporting tissues and cells in the brain, causing an inflammation which damages typically the white matter of the brain. Over time, that inflammation can cause loss of neurons, but indirectly.”
While antiretroviral therapy is crucial for clearing and suppressing HIV in all body compartments, including in the brain, he says that it does not reverse damage that occurred before the treatment was started.
“Today, people with HIV are living near normal lifespans,” he says. “The question is, will the fact that they’ve had HIV, with some duration of untreated exposure and potential loss of brain tissue, cause them to be at higher risk than the average person for developing dementias of old age – which really are mainly Alzheimer’s disease or vascular dementia.” It is these longer-term effects that are the main concern when it comes to the impact of HIV on the brain.
Part of the problem is that South Africa not only has an ageing population of people living with HIV, but many of these people would only have started treatment quite long after they contracted the virus. One key reason for this is the South African government’s reluctance to make antiretroviral treatment available in the early 2000s. It has been estimated that those delays resulted in over 300 000 avoidable deaths – they may also be contributing to brain health issues now and in the future.
From efavirenz to dolutegravir
Apart from HIV itself, some of the medicines used to treat the infection have also had an impact on the brain.
In 2019, the standard HIV treatment in South Africa changed from a three-drug combination containing an antiretroviral drug called efavirenz, to a combination containing the drug dolutegravir. This shift had mental health benefits, as evidenced in research lead by Joska’s fellow UCT Neuro-HIV researcher, Associate Professor Sam Nightingale.
Joska says: “The study looked at the period from 2017 to 2020 and the switch from efavirenz to dolutegravir based treatment. It was well known that efavirenz caused, certainly for the first two months, a bunch of psychotropic or psychological issues like nightmares or anxiety, even psychosis for some people. But our findings showed people who switched to dolutegravir actually do very well. They look more like people without HIV after eight months. So dolutegravir has been a huge advantage, not only because it’s robust, but because it’s neuro-protective.”
New models for HIV and cognitive impairment
A shift is underway in how experts are thinking about cognitive impairment in people with HIV. Some neuropsychiatrists, including Joska, are recommending a shift away from the 2007 HIV-Associated Neurocognitive Disorders model, arguing that its cognitive test scores do not adequately account for variables such as education and socioeconomic background, and that it can overdiagnose impairment. The argument is set out in an article, lead-authored by Nightingale, that was published in the journal Nature Reviews Neurology in 2023.
The authors argue that a label of cognitive impairment might cause a “double burden of stigma” for people living with HIV – affecting self-esteem, inciting fear and prompting further discrimination against persons already subject to stigma as it stands. To illustrate the point, they point out how, up until recently, people with HIV in the United Kingdom could not become airline pilots due to concerns over cognitive impairment. However, following a campaign by a pilot living with HIV, the United Kingdom’s Civil Aviation Authority removed the ban in 2022.
Nightingale and his colleagues argue that traditional test scores be used in conjunction with real-life symptoms and medical evidence of brain problems. It introduces the conceptual model of HIV-Associated Brain Injury, which refers specifically to damage caused by the virus. This distinguishes it from other causes of cognitive impairment such as depression, substance abuse, diabetes and cardiovascular disease. As Spotlight previously reported, HIV is also associated with an increased risk of depression, though this is at least partially driven by social factors.
Lower cognitive function associated with late diagnosis
At the 2026 Conference on Retroviruses and Opportunistic Infections hosted in Denver in the United States in late February, these issues were tabled at a discussion titled “When I’m 64: Neurodegeneration, Epigenetic Aging, and Cognition in Older People With HIV.”
Professor John Joska is the director of the University of Cape Town’s HIV Mental Health Research Unit. (Photo: Biénne Huisman/Spotlight)
In his presentation, Professor Alan Winston of Imperial College London, also a member of the International HIV-Cognition Working Group, and a frequent co-author alongside Joska and Nightingale, relayed existing research findings that on average, people living with HIV have lower cognitive function – including memory, attention span and executive function like planning – compared to people who don’t have HIV of the same age. He said that this manifests as an increased risk of lower grade early dementia.
Like Joska, Winston stressed that the most deteriorated cognitive function in people living with HIV is associated with untreated HIV and late HIV diagnosis. He reiterated that starting HIV treatment soon after diagnosis is protective, and that viral suppression is associated with better cognition. In groups of patients with HIV well controlled on dolutegravir-based HIV treatment, cognition appears similar to HIV negative groups, he said.
HIV clinicians need to pay better attention to the brain
In an impassioned presentation, Dr Shibani Mukerji, Associate Professor of Neurology at Harvard Medical School, argued that protecting the brain is an overlooked frontier in effective HIV treatment, and that clinicians need to pay more attention to it.
“By the time patients and clinicians notice cognitive decline – generally and in HIV – the damage to the brain is done and lives are affected negatively. People don’t raise cognitive concerns early enough due to stigma, fear, [and] lack of recognition of the issues. It is seen as ‘just getting old’,” she said.
Mukerji emphasised the need to prioritise brain health. “HIV doctors and treatment programmes are focused, almost exclusively, on viral load as the marker of successful treatment. They may be thinking laterally and consider TB and other infections, maybe cardiovascular disease – but they are definitely not paying enough attention to brain health. HIV doctors aren’t aware enough of brain health issues in people living with HIV, and even when they are, they often don’t feel comfortable diagnosing or managing it, so it is under recognised and under diagnosed.”
The perception that there is no way to manage or treat cognitive decline –generally and in people living with HIV – is wrong, she said, adding that optimising physical, mental and social health is critical for brain health.
“Almost half of dementia risk [in people in general] is linked to preventable causes,” she told conference delegates, along with a slide listing preventable causes including loss of hearing, social isolation, cardiovascular disease and depression.
She explained: “If someone has cognitive decline and for example you improve their hearing – if they have hearing issues – and you work on their social isolation, and treat their vascular disease, and treat their depression, you can see a marked improvement in their cognition.”
Ending her presentation with a twist of humour, Mukerji’s last slide referred to the session’s title, a reference to the Beatles song on aging “When I am 64”. She printed the song’s lyrics: “When I get older, losing my hair, many years from now…”, closing her talk by saying: “It’s okay to stand up and sing, in fact your doctor might prescribe it.”
Cyclone Gezani caused extensive damage across the region, displacing thousands and severely affecting homes, public infrastructure, and healthcare facilities
Following the devastating cyclone that struck Madagascar’s east coast, Mercy Ships (www.MercyShips.org) has joined with national disaster response efforts in Toamasina (Tamatave) through the provision of essential relief supplies, in coordination with the government’s disaster management authorities.
Cyclone Gezani caused extensive damage across the region, displacing thousands and severely affecting homes, public infrastructure, and healthcare facilities.“In moments like these, partnerships and solidarity matter most,” said Nicholas Ahadjie, Country Director of Mercy Ships in Madagascar. “We are committed to supporting the national response and ensuring that assistance reaches communities where the needs are greatest.”
As part of its own immediate response, Mercy Ships has delivered 537 bags of rice, 1000 roofing sheets, and 1000 ready-to-eat meals. These supplies arrived in Toamasina and were officially handed over to the government’s Designated Disaster Response Coordination Body for distribution to affected communities.
The roofing materials will enable families, schools, and community health facilities to begin urgent repairs. The rice will be distributed to households impacted by the storm that still have functional cooking facilities, while ready-to-eat meals will provide immediate support to individuals and displaced families.Although the Mercy Ships hospital vessel Africa Mercy®, is currently undergoing scheduled maintenance in South Africa, preparations are underway for her return to Madagascar. Sometime this May, she is expected to resume surgical services and medical training programs in collaboration with the Ministry of Health.
“Our presence in Madagascar is on-going,” added Nicholas Ahadjie. “While the ship is in maintenance, our engagement with partners continues. We stand with the Malagasy people today and remain dedicated to strengthening healthcare capacity for the future.
”For several years, Mercy Ships has partnered with Madagascar to provide free specialised surgeries, professional medical training, and infrastructure support. The recent disaster will not stop the organisation’s ongoing support for the Malagasy people as it continues to help reinforce their national health systems.Distributed by APO Group on behalf of Mercy Ships.
ABOUT MERCY SHIPS:
Mercy Ships operates hospital ships that deliver free surgeries and other healthcare services to those with little access to safe medical care. An international faith-based organisation, Mercy Ships has focused entirely on partnering with African nations for the past three decades. Working with in-country partners, Mercy Ships also provides training to local healthcare professionals and supports the construction of in-country medical infrastructure to leave a lasting impact. Each year, more than 2500 volunteer professionals from over 60 countries serve on board the world’s two largest non-governmental hospital ships, the Africa Mercy® and the Global Mercy™. Professionals such as surgeons, dentists, nurses, health trainers, cooks, and engineers dedicate their time and skills to accelerate access to safe surgical and anaesthetic care. Mercy Ships was founded in 1978 and has offices in 16 countries as well as an Africa Service Center in Dakar, Senegal. For more information, visit www.MercyShips.org and follow @MercyShips on social media.
Researchers at WashU Medicine have identified a potent pathway that begins in the brain and leads to loss of all body fat without reducing food intake. The study is reported in Nature Metabolism.
The team – led by senior author Erica L. Scheller, DDS, PhD, an associate professor in the Division of Bone and Mineral Diseases in the Department of Medicine; Xiao Zhang, PhD, a former graduate student in Scheller’s lab who is now a postdoctoral fellow at the University of Pennsylvania School of Medicine; and Sree Panicker, a graduate student in Scheller’s lab – was inspired by a unique population of fat cells located deep within the skeleton.
“About 70% of our bone marrow is filled with fat that doesn’t respond to diet or exercise,” said senior author Scheller. “We wanted to figure out why.”
The team found that these special cells, called constitutive bone marrow adipocytes, expressed high levels of proteins that inhibit fat breakdown. This causes resistance to fat loss in day-to-day settings. “We call these cells stable adipocytes,” said Zhang, the study’s first author. In mice, sustained injection of leptin, a hormone, into the brain was able to unlock the stable adipocytes by putting the body into a state of low glucose and insulin. This reduced the inhibitors of fat breakdown, causing complete loss of body fat within days, even though the mice were still eating normally.
This pathway is so powerful that the scientists caution against using it in humans until it is better understood. Stable adipocytes occur in places like the bone marrow, in the hands and feet, and around important glands. In severe wasting disorders, loss of fat within these cells is associated with bone fractures and reduced quality of life. Scheller’s team hopes to prevent this loss and preserve health in patients with severe wasting disorders by defining the mechanisms of stable fat loss. Conversely, methods to activate fat loss from stubborn adipocytes may support future treatments for obesity. This work was funded by the National Institutes of Health (NIH).
For patients with advanced melanoma without BRAF mutation who no longer respond to immune checkpoint inhibitors, treatment options remain frustratingly limited. A new study from Vanderbilt researchers led by Professor Emerita of Pharmacology Ann Richmond outlines a promising therapeutic strategy that may re-sensitise these resistant tumours to immunotherapy.
Figure 5b from the paper shows the difference between tumours treated with a just an antibody and vehicle (solution) or with trametinib and rigosertib and a CD40 agonist. Image cropped and shared from the paper by Yan et al. published in Nature Communications in 2026 in accordance with a CC BY-NC-ND 4.0 license.
The research introduces a three-drug combination that enhances immune activity and suppresses tumour-promoting immune cells by leveraging a low dose of the MEK inhibitor trametinib and multi-kinase inhibitor rigosertib alongside a CD40 agonist to shift the tumour microenvironment toward immune activation. Notably, all three agents have been either approved by the U.S. Food and Drug Administration or are currently in clinical trials, which may speed their path to patient testing.
“While agonist CD40 therapy can be helpful for treatment of melanoma, this therapy also induces the CD11b+ B regulatory cells that suppress the T cell response to tumours,” Richmond said. “We showed that combining CD40 therapy with trametinib and rigosertib prevents the induction of these B regulatory cells.”
Immune checkpoint inhibitors have become a mainstay of melanoma treatment, working by releasing the molecular “brakes” that prevent T cells from attacking cancer. But resistance to ICI is common in metastatic melanoma, especially in tumours that evolve immune-suppressive microenvironments. While CD40 agonists can activate immune cells, this therapy also unexpectedly expands CD11b+ regulatory B cells.
By combining CD40 activation with MEK and PI3K inhibition, the researchers blocked the expansion of suppressive B cells while retaining the benefits of CD40 stimulation. In preclinical mouse models of melanoma, the triple combination not only suppressed tumour growth but also restored responsiveness to checkpoint blockade.
Key findings
B cells as a resistance mechanism: CD40 therapy alone induced regulatory B cells that dampen T cell–mediated tumor immunity.
Triple combination prevents immune suppression: Co-treatment with trametinib and rigosertib blocked the agonist CD40 induction of regulatory B cells, allowing immune responses to proceed.
ICIs regain effectiveness: The drug cocktail slowed tumor progression and re-sensitized resistant melanomas to anti-PD-1 therapy.
Translational promise
Because trametinib, rigosertib, and CD40 agonists are already in human trials or approved for other indications, this therapeutic strategy may advance more quickly than approaches requiring new drug development. Richmond’s team sees potential for testing the triple therapy in clinical trials for melanoma patients who have progressed on ICI.
“This approach provides a new route to enhance antitumor immunity in patients with tumors that no longer respond to immunotherapy,” Richmond said.
Prenatal magnesium sulfate and steroids can reduce the risks of cerebral palsy and respiratory complications in preterm infants. A review in the International Journal of Gynecology & Obstetrics found that despite being recommended internationally for pregnant women at risk of preterm delivery, these medications are used variably between and within countries.
When they analysed 2012–2024 information on 45 619 babies born at 24–32 weeks’ gestation at 1111 hospitals in an international network, along with information from the UK National Neonatal Research Database and a literature review, investigators found that on average, less than half of infants had been exposed to preterm magnesium sulfate in middle-income countries, and approximately three-quarters in high-income countries. Even within high-income countries, there were large discrepancies in care. Preterm steroids were used more frequently with less variation, although treatment gaps were still apparent.
“Our study has highlighted the international disparities in how two key treatments to protect pre-term babies are implemented. These gaps aren’t because of a lack of evidence,” said corresponding author Hannah B. Edwards, MA, MSc, of the University of Bristol, in the UK. “Lessons can be learned from successful implementation programs like PReCePT, which has transformed use of magnesium sulphate in pre-term births in England. The bigger-picture goal should now be to ensure that no matter where a baby is born, their mother has access to the evidence-based treatments that offer the best start in life.”
We’ve known for a long time that women are more likely than men to have migraine attacks.
As children, girls and boys experience migraine equally. But after puberty, women are two to three times more likely to experience this potentially debilitating condition.
Recently, an Australian study showed it may be even more common than we previously thought – as many as one in three women live with migraine.
For comparison, migraine affects roughly one in 15 men in Australia.
So, what’s behind the difference? Here’s what we know.
More than a headache
Migraine is not just a bad headache – it is a complex disorder that causes the brain to process sensory information abnormally.
This means “migraine brains” can have difficulty processing information from any of the five senses:
sight (leading to problems with light sensitivity and glare)
sound (leading to noise sensitivity)
smell (certain smells can trigger headaches)
touch (leading to face or scalp tenderness)
taste (causing distorted taste, nausea and vomiting).
Migraine attacks typically last anywhere from four hours to three days – but can be longer.
In addition to the symptoms above, attacks can include throbbing head pain, dizziness, fatigue and difficulty concentrating. It is these extra symptoms that help diagnose migraine – not the location of head pain or pain severity.
Why are attacks more frequent in women?
Puberty is when the difference between men and women emerges. This is when our bodies massively increase the production of sex hormones.
People are often surprised to learn that both men and women produce oestrogen, progesterone and testosterone. Testosterone levels are higher in men, whereas women have higher levels of oestrogen and progesterone.
However, it is not just the type of hormone that makes a difference, but the way they fluctuate over time.
For many women, there are certain “milestone moments” when their migraine tends to worsen due to hormonal fluctuations – puberty, menstruation, pregnancy and perimenopause (the lead-up to your final period).
For example, some women notice migraine flare-ups every month, linked to phases in their monthly menstrual cycle when oestrogen levels drop.
They might even be able to predict when their period will start, as migraine attacks typically start a few days before the bleeding.
How hormones affect the brain
Women with migraine can be more sensitive to hormonal changes. This is particularly the case for sudden decreases in oestrogen. But even more subtle changes to hormone levels can cause migraine attacks.
These hormonal changes can activate brain processes that trigger migraine, such as cortical spreading depression. This is a very slow wave of electrical activity that spreads in the brain, causing some areas to function more slowly than others after it passes.
Decrease in oestrogen can also affect how we receive and process information through the trigeminal nerve. This plays a key role in the onset and maintenance of migraine pain.
Oestrogen can affect how we process information through the trigeminal nerve. ttsz/Getty
All kinds of fluctuations can be a trigger
Pregnancy can often destabilise migraine again and make attacks more likely, even when someone has previously enjoyed a period of good migraine control.
Migraine symptoms often become uncontrolled in the first trimester in particular, due to rapid hormonal changes needed to sustain a pregnancy. This usually settles in the second and third trimesters, when hormonal changes stabilise.
However, giving birth is yet another change.
Towards the end of pregnancy, oestrogen levels can be 30 times higher than pre-pregnancy levels, and progesterone can be 20 times higher. When these hormones plummet back to normal after giving birth, migraine attacks can often sharply worsen again.
Perimenopause can also involve random surges of oestrogen from the dwindling supplies of eggs within the ovaries – which previously produced these hormones cyclically and in abundance. This irregular hormone production can cause random spikes in migraine attacks. It can be extra challenging when combined with other symptoms of menopause such as hot flushes or mood changes.
Hormonal contraceptives and menopause hormone therapy can also affect migraine control. Sometimes, supplementing hormones at a regular, steady daily dose can help manage the hormone-sensitive headaches and other symptoms. However, for others, adding extra hormones can cause head pain to flare up.
Does migraine run in the family?
Genes also play a role. It’s not a coincidence that migraine is passed down in families through the maternal side.
This is because mothers pass on mitochondria to children (while fathers do not). Mitochondria are parts inside the cell that control energy.
People with migraine have fewer functional enzymes within their mitochondria, meaning their brains are in an energy-deficient state. This worsens with migraine attacks as there is even more stress to the system.
This is also why extra stress (such as sleep deprivation, missed meals, or emotional stress) can trigger a migraine and worsen pain.
There is also a strong link between migraine in women and anxiety and depression – conditions women are more likely to develop in response to stressful life events.
Knowing your own patterns
If you suspect hormones may be affecting your migraine attacks, it is helpful to keep a diary of symptoms, including headaches. Mark each day per month where you get migraine symptoms, as well as your period, to find patterns.
Identifying patterns in pain flares helps doctors guide you to a personalised medication plan, which may include hormone therapies or non-hormonal therapies.
Long-term data suggests an overall cure rate of 42%
Photo by National Cancer Institute on Unsplash
Unlike some other forms of lymphoma, advanced stage follicular lymphoma is considered incurable. But a new analysis of long-term data on patients treated for the disease years ago with standard regimens of immunotherapy and a chemotherapy combination known as CHOP suggests that many of those patients can now be considered cured.
The analysis is just published in the journal JAMA Oncology.
“A subset of advanced-stage follicular lymphoma patients can achieve cure with CHOP-based chemoimmunotherapy, as relapse rates decline over time,” said Wilmot Cancer Institute Director Jonathan W. Friedberg, MD, MMSc, at the University of Rochester Medical Center, who is senior and corresponding author on the paper.
“This finding represents a paradigm shift in our understanding and approach to follicular lymphoma, with broad implications for initial patient discussions and future research strategies.”
Historically, follicular lymphoma has been considered an incurable disease, with most patients experiencing relapses even years after initial treatment.
The JAMA Oncology paper reports on an analysis of follow-up data from patients with advanced follicular lymphoma who had been treated with a standard first-line chemoimmunotherapy regimen on a large clinical trial.
Roughly 70 percent of the patients remained alive 15 years after beginning treatment, and a statistical method known as cure modelling estimated that 42% of treated patients had been cured.
Cure modelling incorporates background mortality rates in an analysis of patient survival data to estimate what fraction of a group of patients can be considered cured of a disease. Such modelling accounts for the fact that over time some patient deaths will occur that are unrelated to the given disease.
The researchers applied a cure model to 15-year follow-up data from the S0016 clinical trial conducted by the SWOG Cancer Research Network, a clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), with the participation of other groups within the NCI-funded National Clinical Trials Network (NCTN).
This phase 3 trial, which opened in 2001, enrolled patients with untreated advanced-stage CD20-positive follicular lymphoma and randomised 531 of them to one of two treatments, both of which were built around a core chemotherapy regimen known as CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone). One arm treated patients with rituximab plus the CHOP combination (R-CHOP), while the other arm used CHOP followed by radioimmunotherapy (CHOP-RIT). Primary results of the S0016 trial were published in 2013 (Press, OW. J Clin Oncol. 2013).
The S0016 modeling, including cure analysis, was carried out by Michael LeBlanc, PhD, a biostatistician at Fred Hutch Cancer Center and director of SWOG’s Statistics and Data Management Center (SDMC), and Hongli Li, MS, also at Fred Hutch and the SWOG SDMC.
It showed that, with a median follow-up time of 15.5 years after a patient had begun treatment, the rate of disease relapse dropped substantially over time, falling from 6.8% of patients relapsing in the first 5 years to only 0.6% relapsing between years 15 and 20.
Fifteen years after starting treatment, about 70%of patients remained alive. The analysis also showed no statistically significant difference between the two treatment arms in the rates of 15-year overall survival.
Based on their work, the authors conclude that a substantial subset of patients with advanced-stage follicular lymphoma can, when treated with a standard regimen that includes immunotherapy and chemotherapy, achieve a functional cure – defined as having no chance of lymphoma recurring during the patient’s expected lifespan.
“These results reinforce that front-line chemoimmunotherapy remains an important option – particularly for appropriate patients – because it can deliver long-term disease control after a time-limited course of treatment, ” said first author Mazyar Shadman, MD, MPH, of Fred Hutch Cancer Center. Shadman is medical director of cellular immunotherapy at Fred Hutch, where he holds the Innovators Network Endowed Chair.
“As we bring novel agents into the first-line setting, the durability seen here sets a high benchmark; new strategies should aim not only to improve short-term response rates but to match or exceed long-term remission and cure potential.”
The idea that many of these patients can be cured could change how newly diagnosed patients are counseled and could eliminate the need for indefinite oncology and radiologic follow-up visits after treatment, with patients eventually transitioning from oncology care back to a primary care team.
