Categories : Exercise Mental HealthTags :

Pop Culture Highlights How Exercise Can Improve Mental Health

On By ModernMedia

The workplace should take note

Photo by Ketut Subiyanto on Pexels

A quarter of employees in South Africa have been diagnosed with depression, with the country’s economic contributors aged 25 to 44 being most affected and taking more than 18 days off work as a result, according to a recent study conducted by the South African Depression and Anxiety Group (SADAG). “While treatment or talking to someone is advised when dealing with mental health issues, the importance of exercise and healthy living is taking centre stage across pop culture channels,” says Sarah Rice, Chief People Officer at Skynamo.

This was illustrated in the recently released documentary produced by Jonah Hill on Netflix called ‘Stutz’. While highlighting the power of talk therapy, Hill’s therapist, Phil Stutz, outlines various tools that he has developed to help people manage depression, including his ‘life force’ model.

“This is a three levelled pyramid focussing on aspects that drive us forward,” shares Rice, who refers to the film where Stutz says that your life force is the only thing that’s capable of guiding you when you’re lost. “The bottom level of the pyramid is your relationship with your physical body, the second is your relationship with other people and the top level is your relationship with yourself.”

“While we are the only ones who are responsible for our relationship with ourselves, considering the fact that we spend a large amount of time in the office, companies should think about offering activities to improve employees’ wellbeing such as forming a running club or introducing yoga classes. These activities should be built into the company calendar so that it gives people permission to do them and not feel like they’re taking away from work time,” explains Rice.

Not only does this assist with the exercise aspect but also gives colleagues the opportunity to form a real connection and bond with each other, she says. “Additionally, it shows that the business is really keen on providing employees with a work-life balance – something which is trumping salary as a priority for most professionals.”

“This will improve the company’s wellbeing too as it will result in increased employee productivity, reduced absenteeism, higher quality work, and even an R83.40 return for every R20 the business invests in the physical and mental health of employees, not to mention a 14% increase in profitability,” points out Rice.

She notes that, luckily, international companies like Google, Accenture, Microsoft and Nike are recognising that physical health is part of mental health. “A number of South African companies such as Absa, Discovery, Alexander Forbes, Unilever and South African Breweries are tapping into this as well.”

Victoria Henry, Head of Group Marketing at Alphawave, a specialised technology investment group with 16 companies in its portfolio, of which Skynamo is a part, echoes this by saying, “Mental health has definitely moved up the agenda in the workplace. It’s good to see more and more companies taking this seriously. Happy and healthy employees are better employees. Supporting employee mental health can increase engagement and performance, so it’s important that companies are investing in this.”

To encourage corporates – as well as individuals – to get active and connected to each other, Skynamo, in partnership with Alphawave, will be sponsoring the third annual Skynamo CROSS CHALLENGE – South Africa’s biggest off-road triathlon. A crucial component of the event is the Skynamo Corporate Challenge where teams will get to cycle, run and swim for the chance to win prizes, bragging rights and a trophy to showcase in the office – not to mention a team building experience full of exhilarating adventure and healthy competition.

Jacques de Villiers, co-founder of event organising company Scuttle adds that being outdoors and exercising greatly enhances mental health, especially since this reduces employee screen time. “Funnily enough, 70% of employees say that they would exercise more if they spent less time at their computers.”

The Skynamo CROSS CHALLENGE will be taking place on Saturday, 25 February 2023 in Grabouw with races for all ages and fitness levels. The full race comprises a 1000m swim, 22km mountain bike ride and 7,2km trail run, while the sprint race is approximately half the distance. There are also race options available for kids.

In the lead up to the Skynamo CROSS CHALLENGE, teams can test their fitness levels and group dynamics at the Lomond and Franschhoek Cross Triathlons taking place in December 2022 and January 2023 respectively.

Rice concludes by saying, “To help employees’ mental health in 2023, businesses should be raising awareness around and encouraging healthy living. Employers need to see employees as whole people, not just as ‘work people’, and must support them in living their best lives.”

To register, or for more information, go to www.scuttle.co.za/scuttle-events/crosschallenge. Online entries close on 20 February 2023 and no entries will be taken at the event.

Categories : COVIDTags :

How to Prevent Dangerous Weight Loss in COVID Patients

On By ModernMedia
Photo by Stephen Andrews on Unsplash

COVID infection often causes adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality. Now, researchers at Karolinska Institutet have discovered that SARS-CoV-2 infection fuels blood vessel formation in fat tissues, thus revving up the body’s thermogenic metabolism. Blocking this process with an existing drug curbed weight loss in mice and hamsters that were infected with the virus, according to the study published in the journal Nature Metabolism.

“Our study proposes a completely new concept for treating COVID associated weight loss by targeting the blood vessels in the fat tissues,” says corresponding author Yihai Cao, professor at Karolinska Institutet.

The researchers examined how different types of fat, including brown fat and visceral and subcutaneous white fat, reacted when exposed to SARS-CoV-2 and how it impacted weight in mice and hamsters. They found that the animals lost significant amounts of weight in four days and that this weight loss was preceded by the activation of brown fat and the browning of both types of white fat. These fat tissues also contained more microvessels and high levels of a signaling protein called vascular endothelial growth factor (VEGF), which promotes the growth of new blood vessels.

Similar mechanisms in humans

The researchers observed the same mechanisms in human tissue samples from four patients who died of COVID, suggesting the findings could be clinically relevant for humans.

When the animals were treated with an anti-VEGF drug, the animals recovered most of their lost weight and their fat tissues exhibited fewer microvessels.

“Antiangiogenic drugs are currently used in the clinic to treat various types of cancers,” Yihai Cao says. “It’s possible these drugs could also be helpful in treating COVID-related problems such as excessive weight loss and metabolic changes, thus improving the quality of life and survival for these patients. Of course, we will need more research to validate if our preclinical findings also hold up in human trials.”

Source: Karolinska Institutet

Categories : CancerTags :

New Immunotherapy Sees 73% Success Rate in Multiple Myeloma Patients

On By ModernMedia
Woman using lab equipment
Source: NCI on Unsplash

A new immunotherapy to kill bone marrow cancer cells was successful in as many as 73% of patients in two clinical trials, according to Mount Sinai researchers. The new bispecific antibody therapy binds to both T cells and multiple myeloma cells and directs the T cells to kill multiple myeloma cells. The researchers described this strategy as “bringing your army right to the enemy.”

The success of the off-the-shelf immunotherapy, called talquetamab, was even seen in patients whose cancer resisted previous therapies. It uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells known as GPRC5D.

Talquetamab was tested in phase 1 and phase 2 trials. The phase 1 trial, reported in NEJM, established two recommended doses that were tested in the phase 2 trial. The results of the phase 2 trial were reported at the American Society of Hematology annual meeting. The study participants had all received at least three different therapies without achieving lasting remission, suggesting talquetamab could offer new hope for patients with hard-to-treat multiple myeloma.

“This means that almost three-quarters of these patients are looking at a new lease on life,” said lead author of the studies, Ajai Chari, MD, Director of Clinical Research in the Multiple Myeloma Program at The Tisch Cancer Institute. “Talquetamab induced a substantial response among patients with heavily pretreated, relapsed, or refractory multiple myeloma, the second-most-common blood cancer. It is the first bispecific agent targeting the protein GPRC5d in multiple myeloma patients.”

Nearly all patients with myeloma who receive standard therapies continually relapse. Patients who relapse or become resistant to all approved multiple myeloma therapies have a poor prognosis, so additional treatments are urgently needed. This study, while an early-phase trial designed to detect tolerability and find a safe dose, is an important step in meeting that need.

This international Phase 1 clinical trial enrolled 232 patients between January 2018 and November 2021. Patients received a variety of doses of the therapy either intravenously or subcutaneously; future studies will focus on doses only administered subcutaneously either weekly or every other week

The efficacy and safety findings in the phase 1 study were validated in the phase 2 trial presented at ASH. The phase 2 trial included 143 patients treated on a weekly dose and 145 patients treated at a higher biweekly dose.

The overall response rate in these two groups was about 73%, Dr Chari said. The response rate was maintained throughout various subgroups examined, with the exception of patients with a rare form of multiple myeloma that also extends to organs and soft tissues. More than 30% of patients in both groups had a complete response (no detection of myeloma-specific markers) or better, and nearly 60% had a “very good partial response” or better (indicating the cancer was substantially reduced but not necessarily down to zero).

The median time to a measurable response was approximately 1.2 months in both dosing groups and the median duration of response to date is 9.3 months with weekly dosing. Researchers are continuing to collect data on the duration of response in the group receiving 0.8 mg/kg every other week and for patients in both dosing groups who had a complete response or better.

Side effects were relatively frequent, but typically mild. About three-quarters of patients experienced a common side effect of immunotherapy – cytokine release syndrome, a constellation of symptoms including fever. About 60% experienced skin-related side effects such as rash, about half reported taste changes, and about half reported nail disorders. Only 5–6% of patients stopped treatment due to side effects.

The response rate observed in the study, which Dr Chari explained is higher than that for most currently accessible therapies, suggests talquetamab could offer a viable option for patients whose myeloma has stopped responding to most available therapies, offering a chance to extend life and benefit from other new and future therapies as they are developed.

Source: Mount Sinai Hospital

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Scientists Uncover Three Genes Linked to Multiple Sclerosis

On By ModernMedia
Genetics
Image source: Pixabay

New research published in the Annals of Clinical and Translational Neurology has identified three genes and their expressed proteins that may be involved in the pathogenesis of multiple sclerosis.

By comparing information on the genes and proteins expressed in the brains of thousands of individuals with and without multiple sclerosis, investigators discovered different expression levels of the SHMT1, FAM120B, and ICA1L genes (and their proteins) in brain tissues of patients versus controls.

Protein abundance alteration in human brain has linked to MS. For instance, protein abundance of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP)3 and thymosin β-46 was dysregulated in lesions from MS patients’ brain, and these proteins have been used for disease severity prediction and targeted therapy lately. In addition, compared to bodily fluid samples like cerebrospinal fluid and plasma, human brain tissue directly reflects the pathophysiology changes of MS and has become increasingly important in disease biomarker identification. However, few studies focused on specific subregions of the brain, ignoring the possible differences in protein types and abundance between subregions with distinct functions.

Studying the functions of these genes may uncover new information on the mechanisms involved in the development and progression of multiple sclerosis. “Our findings shed new light on the pathogenesis of MS and prioritised promising targets for future therapy research,” the authors wrote.

Source: Wiley

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

Promising New Treatment for Moderate to Severe Atopic Dermatitis

On By ModernMedia
Atopic dermatitis
Source: Wikimedia CC0

An international clinical trial of a new monoclonal antibody therapy showed promising results for patients moderate to severe atopic dermatitis both while taking the drug and up to 20 weeks after the therapy was stopped, according to Mount Sinai researchers in The Lancet.

The researchers said the results indicate that the new biologic, rocatinlimab, has the potential to change the genetic makeup of a person’s atopic dermatitis for the long term, and possibly help sustain lasting results without continued use. Rocatinlimab inhibits OX40. an immune molecule involved in activating inflammatory cells that play a key role in the development of atopic dermatitis and other inflammatory diseases.

“Atopic dermatitis, the most common type of eczema, is a debilitating chronic inflammatory skin disease that affects 1 in 10 Americans and millions of people worldwide,” said Emma Guttman, MD, PhD, Mount Sinai professor. “It often develops at a very young age, causing the skin to become inflamed, red, extremely itchy, painful, and very dry – all symptoms that greatly affect a patient’s quality of life. We are very optimistic about the results of this trial and the potential for disease modification and long-lasting effects to improve patients’ quality of life.”

In this phase 2b multicentre, double-blind, placebo-controlled study, 274 patients were recruited and (rocatinlimab: n = 217; placebo: n = 57) equally randomised to rocatinlimab every four weeks (150mg or 600mg) or every two weeks (300mg or 600mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up.

Percent change from baseline in the Eczema Area and Severity Index (EASI) score was assessed as the primary endpoint at week 16, and significance versus placebo was achieved with all active rocatinlimab doses (-48% to -61%) doses compared to placebo (-15%). All active dose cohorts also continued improving after week 16, and most patients maintained the response for at least 20 weeks off treatment.

The results support rocatinlimab as a safe and effective treatment for moderate to severe atopic dermatitis, with potentially long-lasting efficacy and disease modification. Adverse events reported were generally similar between rocatinlimab groups. Common adverse events during the double-blind period included fever, chills, headache, aphthous ulcers (canker sores), and nausea.

“At week 36, all participants had been on the treatment for at least 18 weeks,” added Dr Guttman, senior author of the study. “By this time, we saw that while the drug achieved the primary endpoints in all doses versus the placebo, it’s also a drug that improves over time, which is really unusual and unique among currently available treatment options.”

Researchers plan to continue this investigation in a phase 3 program in 2023. Future studies will also include a larger study population, longer follow-up, and explore combination therapy (eg with topical corticosteroids).

Source: Mount Sinai Hospital

Categories : CancerTags : 1 Comment

‘Landmark’ Drug Doubles Progression Time of Advanced Breast Cancer

On By ModernMedia
Source: National Cancer Institute

A new type of targeted medicine has shown ‘remarkable’ benefits for patients with advanced breast cancer in a major phase III clinical trial. Combined with hormone therapy, the drug capivasertib doubled the time it took for cancer to progress in people with advanced forms of the most common type of breast cancer.

Capivasertib is a potential first-in-class drug that blocks activity of the cancer-driving protein molecule AKT.

The findings, presented at the San Antonio Breast Cancer Symposium, show that capivasertib is a potential new treatment for people with oestrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer.

‘Effective across all patients treated in the trial’

The drug was found to be effective across all patients treated in the trial, including a group who had tumours with mutations in the AKT signalling pathway.

The phase III CAPItello-291 trial enrolled 708 women and men with an advanced form of ER-positive, HER-2 low or negative locally advanced or metastatic breast cancer.

Participants on the trial had seen their cancer recur or progress on standard hormone treatments, and the majority had also previously been treated with CDK4/6 inhibitors – drugs that block cancer cells from multiplying.

In current clinical practice, patients continue to receive fulvestrant hormone therapy, but this is often not effective, and many are left only with the option of chemotherapy, a treatment which can lead to debilitating side effects.

In the trial, adding capivasertib to fulvestrant hormone therapy doubled the median time to disease progression, from 3.6 months to 7.2 months. The treatment shrank tumours in 23% of patients, compared with 12% of patients who received fulvestrant hormone treatment plus a placebo.

Targeting the AKT pathway

The targeted drug was more effective for patients whose cancers had alterations to the AKT signalling pathway. Genetic alterations to the AKT pathway can drive both cancer’s development and treatment resistance.

Genetic alterations of the AKT pathway – revealed by tumour profiling – were present for 41% of patients on the trial. In this group treated with capivasertib and hormone therapy, it took an average of 7.3 months for the cancer to worsen compared with 3.1 months for those who received hormone therapy alone. Some 29% of patients with AKT pathway alterations who received capivasertib with hormone therapy saw their tumours shrink following treatment, compared with only 9.7% who received a placebo and hormone therapy.

Side effects from capivasertib with hormone therapy were manageable and consistent with previous studies.

More than two thirds of people with advanced breast cancer have ER-positive, HER-2 negative disease. ER-positive, HER-2 negative breast cancers have higher levels of the oestrogen receptor – allowing them to grow in the presence of oestrogen – but do not over-produce copies of the human epidermal growth factor.

Developing capivasertib

The development of capivasertib followed years of fundamental research at the Institute for Cancer Research (ICR), aimed at understanding how the AKT protein is regulated. In 2002, ICR scientists published the 3D structure of AKT and showed how the protein is activated.

Researchers then collaborated with Astex Pharmaceuticals to design small-inhibitors which would target AKT, based on its 3D structure.

In 2005, a series of prototype drug compounds discovered by the ICR and Astex was shown to have very promising activity against a range of human tumours grown in mice and was licensed to AstraZeneca. Then, in 2010, AstraZeneca announced its discovery of capivasertib, and began to develop the drug as a potential treatment for various forms of cancer.

The initial clinical development of capivasertib was centred on an early-stage trial which was led by the ICR and its partner hospital The Royal Marsden. Subsequently, phase II studies were completed in the UK in collaboration with the UK Cancer Research Network.

The trials used biomarkers that were developed at ICR to show proof of concept that the AKT protein was inhibited by capivasertib.

ICR researchers continue to study AKT biology to open up new ways of using treatments targeting the pathway.

Living well and longer with breast cancer

Trial leader Professor Nicholas Turner, Professor of Molecular Oncology at ICR London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“We are hopeful that capivasertib combined with hormone therapy will now become a new treatment option for patients whose cancer has progressed on hormone therapy plus a CDK4/6 inhibitor. We believe this new treatment could allow more women and men to live well and live longer with breast cancer.”

‘A landmark moment’

Professor Kristian Helin, Chief Executive at The Institute of Cancer Research, London, said:

“This is a landmark moment for the treatment of advanced forms of the most common type of breast cancer. It’s incredibly exciting to see a drug that was discovered following research conducted at the ICR now show remarkable benefits for patients in a phase III trial. Capivasertib could offer a completely new treatment option for these patients.

“I look forward to seeing further results from the CAPitello-291 trial, and I am hopeful that longer follow-up will show that capivasertib also extends the length of time that people survive with advanced breast cancer. But the existing findings are already strong enough for capivasertib to be submitted to regulators to be considered for approval as a new breast cancer treatment.”

Source: The Institute for Cancer Research

Categories : COVIDTags :

Review Finds Little, if Any, Difference in Safety among COVID Vaccines

On By ModernMedia
Covid vaccines
Photo by Mat Napo on Unsplash

A Cochrane review of all the evidence available from randomised controlled trials of COVID vaccines up to November 2021 has concluded that most protect against infection and severe or critical illness caused by the virus. In addition, the Johnson and Johnson vaccine and the Cuban Soberana 2 vaccine “probably” reduced all-cause mortality.

The independent, international expert reviewers also found that there was little or no difference between the number of people experiencing serious side effects after vaccination compared to those who were unvaccinated.

The researchers, led by Isabelle Boutron, Professor of Epidemiology at Université Paris Cité and Director of Cochrane France, analysed published data from 41 randomised controlled trials of 12 different COVID vaccines, involving 433 838 people in various countries around the world. They assessed the certainty of the evidence and the risk of bias in the different studies.

The trials compared COVID vaccines with placebo, no vaccine, or each other, and were published before 5 November 2021. Most trials were no longer than two months in length.

The review found that the following vaccines reduced or probably reduced the risk of COVID infection compared to placebo: Pfizer/BioNTech, Moderna, CureVac COVID-19, Oxford-AstraZeneca, J&J, Sputnik V (Gam-COVID-Vac), Sinopharm (WIBP CorV and BBIBP-CorV), Bharat (Covaxin), Novavax and Soberana 2 (Finlay-FR-2). The following reduced or probably reduced the risk of severe or critical disease: Pfizer/BioNTech, Moderna, Janssen, Sputnik V, Bharat and Novavax. In addition, the J&J and Soberana 2 vaccines probably decreased the all-cause mortality risk. There were very few deaths recorded in all the trials and so evidence on mortality for the other vaccines is uncertain.

For most of the vaccines, vaccinated individuals reported more localised or temporary side effects compared no-treatment or placebo groups. These included tiredness, headache, muscle pains, chills, fever and nausea. With respect to the very rare side effects associated with some vaccines such as thrombosis, the team found that the reporting of these events was inconsistent, and the number of events reported in the trials was very low.

Given the evidence of efficacy of these vaccines, the researchers question whether further placebo-controlled trials are ethical. They suggest that further research compares new vaccines with those already in use.

Source: Wiley

Categories : Obstetrics & GynaecologyTags :

A New Hormone-free Contraceptive Reinforces the Cervical Barrier

On By ModernMedia
Photo by Reproductive Health Supplies Coalition on Unsplash

A new non-hormonal contraceptive may be possible with a prophylactic gel made from naturally occurring ingredients, according to researchers writing in Science Translation Medicine. The gel reinforces the cervical mucus barrier, offering the first viable alternative to spermicides and contraception pills.

In tests on ovulating female sheep, the gel resulted in a 98% average decrease in uterine sperm numbers, compared to control animals. Birth control pills are recognised to be between 91 and 99% effective.

Only one of the eight sheep tested was found to have two sperm detected in its uterus after being treated with the topical gel. Thomas Crouzier, a biopolymers researcher at KTH, says the results demonstrate the potential of an unprecedented approach to preventing unwanted pregnancies by blocking sperm by engineering mucus rather than killing sperm cells as spermicides do.

Crouzier says that mechanism taps into cervical mucus’ natural capacity as a barrier that isolates the vagina, where bacteria proliferate, from the uterus and upper reproductive tract. Cervical mucus also regulates the movement of sperm. Leading up to ovulation the mucus barrier becomes a more selective gatekeeper, making exceptions for the passage of select sperm into the uterus.

The researchers change this dynamic by crosslinking molecules of mucin (the proteins that give mucus its lubricating property) with chitosan, a fibrous natural substance commonly used in medical materials such as hydrogels, meshes and sutures. This combination temporarily thickens cervical mucus so that sperm have more difficulty getting through.

The chitosan was shown to have a similar effect in lab tests using human cervical mucus and sperm. It reinforced the mucus barrier quickly, with a reduction in sperm penetration after one minute of exposure and full sperm blockage after five minutes.

Citing studies, Crouzier says that about 50% of women consider it important that their contraceptives do not contain hormones. “This new mechanism of action has the potential to be very effective, since it is reinforcing a barrier that already exists in the women’s reproductive tract,” he says.

“Vaginal gels like this can be applied in seconds,” Crouzier says. “We imagine that a product like this should be usable from seconds to a few hours before sexual intercourse. The effect could last for hours, but diminish over time as the mucus barrier is replaced naturally.”

Source: KTH Royal Institute of Technology

Categories : COVIDTags :

Patient Sex, Mental Health and Asthma may be Long COVID Risk Factors

On By ModernMedia
Man wearing mask with headache
Source: Usman Yousaf on Unsplash

Studies have described a variety of long-term effects of COVID, with symptoms including fatigue and malaise, breathing difficulties, and cognitive problems. A recent analysis in the Journal of Internal Medicine has identified several characteristics that may be risk factors for a long COVID diagnosis.

Researchers examined 204 805 individuals who tested positive for Sars-CoV-2 in Stockholm, Sweden from March 2020 through July 2021. They found that the proportion receiving a post COVID condition diagnosis was 1% among individuals not hospitalised for their COVID infection, 6% among hospitalised, and 32% among individuals treated in intensive care units (ICUs). The most common new-onset symptoms among individuals with a post COVID condition diagnosis were fatigue (29%) among non-hospitalised individuals, and breathing difficulties among both hospitalised (25%) and ICU-treated patients (41%). 

Female sex, previous mental health disorders, and asthma were associated with post-COVID condition among non-hospitalised and hospitalised individuals.

Among individuals with post-COVID condition, use of outpatient care was substantially increased up to one year after the acute infection.

“Our understanding of health effects beyond the acute SARS-CoV-2 infection is continuously improving. In this study, we observed a marked difference in the occurrence of post COVID condition diagnosis across different severities of the acute infection,” said corresponding author Pontus Hedberg, MD and postdoctoral researcher at Karolinska Institutet. “Furthermore, the elevated outpatient primary and specialist care use indicates poor recovery for individuals suffering from post-COVID condition, highlighting the urgent need to better understand this condition and its potential resolution over time.”    

Source: Wiley

Categories : Obstetrics & Gynaecology UrogenitalTags :

Oestrogen may Protect against Delirium in Older Women with UTIs

On By ModernMedia
Photo by Karolina Grabowska

Delirium is common among women with urinary tract infections (UTIs) – especially those who have experienced menopause. In mouse models, researchers have been able to prevent symptoms of the condition by administering oestrogen. Their study was published in the peer-reviewed journal Scientific Reports.

“There has been a resurgence of interest in hormone replacement therapy, and this study, which builds on our previous work, shows that it may be a tool to mitigate delirium,” said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and senior author of the study. “I think it is a major step toward a clinical trial of oestrogen in human patients with UTIs.”

Lahiri said that delirium is a common problem in older women with UTIs.

“Even as a medical student, you know that if an older woman comes to the hospital and she’s confused, one of the first things you check is whether the patient has a UTI,” Lahiri said.

In previous studies, Lahiri’s team found a connection between delirium and an immune-regulating protein called interleukin 6 (IL-6). Events such as lung injury or UTI cause IL-6 to travel through the blood to the brain, causing symptoms such as disorientation and confusion. Oestrogen is a known suppressor of IL-6, so the investigators designed experiments to test its effects on UTI-induced delirium.

The researchers compared pre- and postmenopausal mice with UTIs and observed their behaviour in several types of specialised environments. They found that the mice in which menopause had been induced exhibited symptoms of delirium, such as anxiousness and confusion, while the others did not.

When they treated the mice with oestrogen, levels of IL-6 in the blood and delirium-like behaviour were greatly reduced. The behavioural differences were not related to UTI severity, as bacterial levels in the urine weren’t markedly different between the two groups, Lahiri said.

The investigators also looked at the direct effects of oestrogen on neurons, using what Lahiri called a “UTI in a dish.”

“We exposed individual neurons to an IL-6 inflammation cocktail to create UTI-like injury,” Lahiri said. “But when we added oestrogen to the cocktail, it mitigated the injury. So, we showed that there are at least two ways that oestrogen helps reduce symptoms of delirium. It reduces IL-6 levels in the blood and protects the neurons directly.”

Just how oestrogen acts to protect neurons is still unexplained. And before conducting a clinical trial, researchers need to identify which patients with UTIs are most likely to experience delirium and at what point oestrogen treatment might be most effective.

“Currently, it is common practice to treat UTI-induced delirium using antibiotics, even though there are no clinical trials that indicate this practice is effective and it is not supported by clinical practice guidelines,” said Nancy Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “This work is an important step in determining whether modulating immune response via oestrogen replacement or other means is a more effective treatment.”

The team is also working to understand the different effects of delirium on females versus males, which was not a topic of this study. Effective treatment of delirium could be of long-term importance, Lahiri said, because it is a known risk factor for long-term cognitive impairments, such as Alzheimer’s disease and related dementia.

Source: Cedars-Sinai Medical Center