Year: 2023

Categories : Paediatrics Surgeries & ProceduresTags :

Early Cleft Palate Surgery Yields Better Speech Results

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According to a new international study published in the New England Journal of Medicine, cleft palate surgery at the age of six months provides better conditions for speech and language development compared to surgery at 12 months.

Isolated cleft palate is a congenital condition where the palate is not closed and there is an opening between the mouth and the nose. The condition occurs in 1 to 25 per 10 000 births worldwide.

“There has previously been limited evidence for the optimal age for cleft palate surgery in children to achieve the best results”, says Anette Lohmander, professor emeritus at at Karolinska Institutet and principal investigator for the Stockholm centre in the study.

The study, by researchers from Karolinska Institutet and Karolinska University Hospital, among others, involved 558 children from 23 different centres around Europe and South America. Of these, 235 children were randomly assigned to a group to undergo surgery at six months of age and 226 children were randomly assigned to undergo surgery at twelve months of age.

Speech-language therapists/pathologists performed standardised audio-video recordings at one, three and five years of age. The researchers then evaluated the children’s babbling, velopharyngeal function, and speech.

At age five, the researchers found insufficient velopharyngeal function in 21 children (8.9%) who had surgery at six months of age compared with 34 children (15%) who had surgery at age 12 months.

Complications resulting from surgery were rare in both groups. Four serious adverse events were reported but were resolved on follow-up.

The conclusion of the study was that velopharyngeal function for speech at five years was better in the children who had undergone surgery at six months of age than in those who had undergone surgery at 12 months of age. Risks associated with earlier repair may include maxillary arch constriction and the need for secondary surgery for velopharyngeal insufficiency.

“An additional advantage of the early surgery age was a higher incidence of canonical syllables. It is a milestone in children’s language development and is established in typically developed children by the age of ten months at the latest,” says Anette Lohmander, who continues. “The children included in the study had no developmental delay or other deviant conditions. The conclusion is that when it is possible to operate on the cleft palate early, it seems to provide the best conditions for speech and language development.”

Source: Karolinska Institutet

Categories : Cardiovascular Disease COVIDTags :

Study Explains a Link between COVID and Increased Cardiovascular Risk

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A study published in the journal Nature Cardiovascular Research shows that SARS-CoV-2 can directly infect the arteries of the heart and cause the fatty plaque inside arteries to become highly inflamed, increasing the risk of heart attack and stroke. The findings may help explain why certain people who get COVID have a greater chance of developing cardiovascular disease, or if they already have it, develop more heart-related complications.

In the National Institutes of Health (NIH)-funded study, researchers focused on older people with atherosclerotic plaque, who died from COVID. However, because the researchers found the virus infects and replicates in the arteries no matter the levels of plaque, the findings could have broader implications for anybody who gets COVID.

“Since the early days of the pandemic, we have known that people who had COVID have an increased risk for cardiovascular disease or stroke up to one year after infection,” said Michelle Olive, PhD, acting associate director of the Basic and Early Translational Research Program at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH. “We believe we have uncovered one of the reasons why.”

Though previous studies have shown that SARS-CoV-2 can directly infect tissues such as the brain and lungs, less was known about its effect on the coronary arteries. Researchers knew that after the virus reaches the cells, the body’s immune system sends in macrophages to help clear the virus. In the arteries, macrophages also help remove cholesterol, and when they become overloaded with cholesterol, they morph into a specialised type of cell called foam cells.

The researchers thought that if SARS-CoV-2 could directly infect arterial cells, the macrophages that normally are turned loose might increase inflammation in the existing plaque, explained Chiara Giannarelli, MD, PhD, associate professor in the departments of medicine and pathology at New York University’s Grossman School of Medicine and senior author on the study. To test their theory, Giannarelli and her team took tissue from the coronary arteries and plaque of people who had died from COVID and confirmed the virus was in those tissues. Then they took arterial and plaque cells – including macrophages and foam cells – from healthy patients and infected them with SARS-CoV-2 in a lab dish. They found that the virus had also infected those cells and tissues.

Additionally, the researchers found that when they compared the infection rates of SARS-CoV-2, they showed that the virus infects macrophages at a higher rate than other arterial cells. Cholesterol-laden foam cells were the most susceptible to infection and unable to readily clear the virus. This suggested that foam cells might act as a reservoir of SARS-CoV-2 in the atherosclerotic plaque. Having more build-up of plaque, and thus a greater number of foam cells, could increase the severity or persistence of COVID.

The researchers then looked at the predicted inflammation in the plaque after infecting it with the virus. They observed the release of inflammatory cytokines, also known to promote the formation of even more plaque. The cytokines were released by infected macrophages and foam cells. The researchers said this may help explain why people who have underlying plaque buildup and then get COVID may have cardiovascular complications long after getting the infection.  

“This study is incredibly important as it adds to the larger body of work to better understand COVID,” said Olive. “This is just one more study that demonstrates how the virus both infects and causes inflammation in many cells and tissues throughout the body. Ultimately, this is information that will inform future research on both acute and Long COVID.”

Though the findings conclusively show that SARS-CoV-2 can infect and replicate in the macrophages of plaques and arterial cells, they are only relevant to the original strains of SARS-CoV-2 that circulated in New York City between May 2020 and May 2021. The study was conducted in a small cohort of older individuals, all of whom had atherosclerosis and other medical conditions; therefore, the results cannot be generalised to younger, healthy individuals.

Source: National Institutes of Health

Categories : Mental Health PaediatricsTags :

Is There a Risk of Manic Episodes in Children Taking Antidepressants?

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Mania is a possible but rare side effect of treatment with antidepressant medication in adults, but there is little known about its occurrence in children and adolescents. A newly published paper in JAMA Psychiatry investigated this, finding no evidence of mania/hypomania induced by antidepressants by 12 weeks after treatment initiation. However, caution is necessary in treatment for children with more severe depression or where a parent has bipolar disorder.

“In children and adolescents with unipolar depression, we did not find evidence of antidepressant-induced mania/hypomania by 12 weeks after treatment initiation”, says first author Suvi Virtanen, postdoctoral researcher at Karolinska Insitutet. “This corresponds to the timeframe for antidepressants to exert their psychotropic effect and when treatment-induced mania is expected to emerge. Hospitalisations, parental bipolar disorder, and the use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania.”

Antidepressants are increasingly prescribed to paediatric patients with unipolar depression (as opposed to bipolar depression which is seldom diagnosed in childhood), but little is known about the risk of treatment-emergent mania (ie, the transition from depression into mania shortly after the initiation of antidepressant treatment). Previous research suggests paediatric patients may be particularly vulnerable to this adverse outcome. The results provide complementary information to randomised clinical trials (RCTs) from a large cohort of patients treated in a real-world setting.

The researchers conducted a register-based study on children and adolescents, aged 4–17, diagnosed with unipolar depression between 2006 and 2019. They applied the emulation of target trial framework to guide the study design and analysis, reducing the bias of observational studies and mimicking a RCT.

Antidepressant treatment was unrelated to the risk of mania/hypomania, suggesting other characteristics are more relevant when evaluating which patients may have an increased risk of switching from unipolar depression into mania. “Our model using administrative information from several national registers had a moderate predictive ability, suggesting it is possible to identify patients at high risk for mania/hypomania with a prognostic clinical prediction model. The model has potential to be improved in later work”, says senior author Zheng Chang, Principal Researcher at the Department of Medical Epidemiology and Biostatistics.

Source: Karolinska Institute

Categories : Cancer VaccinesTags :

First-in-human Treatment with Tumour Vaccine Shows Positive Results against Gliomas

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Tumour vaccines alert a cancer patient’s immune system to proteins that are carrying cancer-typical alterations, and may prove useful in gliomas, which are resistant to most forms of treatment including immune checkpoint inhibitors. Reporting in Nature Medicine, physicians and cancer researchers have now performed a first-in human treatment of eight adult patients with advanced midline gliomas with a peptide vaccine. The vaccine, which mimicked a histone protein mutation typical of this type of cancer, proved to be safe and induced the desired immune responses against the brain tumour, with one patient experiencing remission for more than 31 months.

Cancer vaccinations depend on distinct protein structures on cancer cells by which immune cells can differentiate them from healthy one. Mutations in the tumour genome often lead to protein structures that are altered in a way typical of cancer.

Diffuse midline gliomas are among the most aggressive brain tumours. They usually occur in children and young adults near the brain stem and are therefore difficult to access surgically. Chemotherapy or radiotherapy also have limited effectiveness. In this type of cancer, mutations characteristically occur in the gene encoding histone H3 (H3K27M), a packaging protein of DNA. The mutation gives rise to a novel protein structure (a neoepitope) that can be recognised as foreign by the patient’s immune system.

“Such mutations, which occur in identical form in many patients, are rare in cancer. They literally lend themselves to the development of tumor vaccines because they occur in all cancer cells, since the mutated histone is causative for the development of midline gliomas. This means that vaccination against the mutated protein gets to the root of the problem,” explains Michael Platten, Director of the Department of Neurology at the University Medical Center Mannheim and Head of Department at the German Cancer Research Center (DKFZ).

The researchers led by Katharina Sahm and Michael Platten synthetically reconstructed the section of the histone H3 protein with the characteristic mutation. Using this peptide, they were able to curb the growth of H3K27M-mutated tumours in a mouse model. Encouraged by the results, the team decided to test the mutation-specific vaccine produced at the University of Tübingen in patients in a phase I-trial*, which is still ongoing.

In parallel, the physicians, together with colleagues from Munich, Berlin, Bonn and Münster, treated eight adult patients with the peptide vaccine in time-limited individual curative trials. These patients, who could not be enrolled in the trial protocol, suffered from diffuse midline gliomas with H3K27M mutation that progressed after standard therapy. Some of the affected individuals received therapy with immune checkpoint inhibitors in addition to tumor vaccination.

No serious side effects were observed in any of the vaccinated patients. Five of the eight treated patients developed specific immune responses against the mutant protein, which were dominated by CD4 T-helper cells. In one of the patients who had shown a strong immune response, the tumour regressed completely and she remained tumour-free for 31 months.

The vaccine peptide, which is comparatively long at 27 amino acids, worked in patients with different HLA variants. HLA proteins are responsible for the presentation of the mutant peptide on the cell surface and differ from person to person depending on their genetic background. Supported by the HI-TRON Mainz — Helmholtz Institute of the DKFZ, the researchers also observed that immune responses decreased over time, so repeated administration of the vaccine could support a sustained effect.

“We cannot make any further statements about the efficacy of the vaccination based on these treatments. In any case, the current study has given us valuable information that will help us to further optimise the development of brain tumour vaccines in the future,” explains the study’s senior author Katharina Sahm, senior physician at the Neurological University Hospital Mannheim and DKFZ researcher. A phase I-trial is currently underway to test the vaccine against the H3K27M mutation in patients with newly diagnosed midline gliomas. Evaluation is expected to begin around 2025.

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Categories : Paediatrics Pain ManagementTags :

Children’s ‘Growing Pains’ may be Tied to Migraines

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New research published in the journal Headache reveals that, in children and adolescents, pain in the lower limbs – what are often called “growing pains” by clinicians and are commonly attributed to rapid growth – may indicate the presence or risk of migraines.

The study included 100 children and adolescents born to mothers with migraines seen at a headache clinic, with half of the youth experiencing growing pains.

“In families of children with growing pains, there is an increased prevalence of other pain syndromes, especially migraine among parents,” the authors wrote. “On the other hand, children with migraine have a higher prevalence of growing pains, suggesting a common pathogenesis; therefore, we hypothesised that growing pains in children are a precursor or comorbidity with migraine.”

After five years of follow-up, 78 patients completed the study, of which 42 were from the group that experienced growing pains and 36 were from the control group. Headaches occurred in 76% of participants who had growing pains and in 22% of controls. Growing pains persisted in 14% of participants who had growing pains at the start of the study and appeared in 39% of participants who were previously asymptomatic.

“Pain in the lower limbs of children and adolescents… may reflect a precursor or comorbidity with migraine,” the authors concluded.

Source: Wiley

Categories : Cardiovascular Disease ExerciseTags :

Yoga Therapy Improves Quality of Life and Cardiovascular Function

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Yoga therapy and lifestyle modifications have been shown to improve heart failure (HF) patients’ quality of life and enhance their cardiovascular function. A new study, presented at the American College of Cardiology Asia 2023 conference, examines the long-term outcomes of yoga therapy to determine the benefit of adding yoga therapy as a complementary treatment in the management of HF. After 12 months, participants with HF receiving yoga therapy continued to show improvement in left ventricular systolic function as well as quality of life.

The study included 75 heart failure patients (aged 30–70 years old) at a tertiary care centre in South India, who underwent coronary intervention, revascularisation or device therapy within in the previous six to 12 months. All of the patients included in the study were less than or equal to New York Heart Association (NYHA) Class III and had been on optimised medical therapy for at least 6 months to 12 months, and had a left ventricular ejection fraction (LVEF) of < 45%.

The interventional group included 35 participants (31 men and 4 women) and 40 (30 men and 10 women) were in the non-interventional (control) group. The interventional group received yoga therapy and guideline-directed medical therapy, while the control group only continued with standard guideline-directed medical therapy. Echocardiographic parameters were compared at various follow-ups to see the impact of yoga therapy on heart failure patients.

“Yoga is a combination of mind-body techniques, which is a set of physical exercises [asana] with breathing techniques [pranayama], relaxation and meditation that can be effectively used to stimulate physical and mental well-being,” said lead author Ajit Singh, PhD, research scientist for the Indian Council for Medical Research at Kasturba Medical College & Hospital, Manipal Academy of Heart Education in Manipal, India. “Our patients observed improvement in systolic blood pressure and heart rate compared to patients who were on medication without yoga.”

Participants in the yoga group were taken to the Department of Yoga at the hospital and an experienced yoga therapist taught selected yoga therapy like pranayama, meditation and relaxation techniques. Each session lasted around 60 minutes and participants were supervised for one week at the training centre before being asked to continue self-administered yoga at home. Those in the yoga group were advised to perform yoga at least five days a week for 12 months. At the training centre all the participants were taught together to perform the same steps, but individual support was available.

Researchers measured quality of life improvements using the World Health Organization Quality of Life questionnaire, which uses 26 questions to evaluate quality of life in four aspects: physical, psychological, social and environmental health. The participants completed the questionnaire at enrolment, as well as at 24 weeks and 48 weeks of follow-up. According to the researchers, the study showed participants in the yoga group had improvement in endurance, strength, balance, symptom stability and quality of life. They also observed that while patients improved physically and psychologically, there was no improvement in social and environmental health.

Echocardiographic parameters did not show any significant differences between the two groups at baseline. At both the six- and 12-month follow-up, improved biventricular systolic function was seen in the interventional (yoga) group compared to the control group. The interventional group also showed substantial improvement in functional outcomes as assessed by NHYA classification.

“This study proves that the addition of yoga therapy to standard medical management of heart failure leads to an improvement in left ventricular systolic function and quality of life in heart failure patients,” Singh said. “Hence, yoga therapy may improve physical well-being and left ventricular function among heart failure patients on guideline-directed optimal medical therapy.”

Source: American College of Cardiology

Categories : Environmental Effects HospitalsTags :

Netcare Group Signs Landmark Clean Energy Agreement

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Netcare well on track with environmental strategy targets

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In a tangible step towards further reducing its carbon footprint, the Netcare Group has successfully agreed commercial terms for a Renewable Energy (RE) Supply Agreement with independent clean energy solutions provider NOA Group Trading (NOA).

Netcare chief executive officer Dr Richard Friedland noted that the development is a significant milestone in realising the Group’s environmental sustainability strategy, which has made considerable strides since its implementation in 2013.

“Improvement of our energy efficiency initiatives remains a key focus area of this strategy. Netcare has also committed to procuring 100% of its purchased electrical energy from renewable energy sources by 2030, supporting the Race to Zero global campaign with targets that exceed the requirements of the Science Based Target initiative (SBTi) aimed at limiting global warming.

“This transaction represents Phase 1 of achieving this aim and includes six of our facilities where RE will be wheeled through the electricity grid from a combination of wind and solar farms, covering up to 100% of energy consumption at these facilities. This represents approximately 11% of the Group’s total energy consumption which is currently being supplied by Eskom’s predominantly coal fired power stations.

“In combination with other initiatives already implemented under Netcare’s sustainability programme, this transaction will increase the proportion of Netcare’s total energy consumption that is derived from RE sources to around 26%,” he says.

Dr Friedland noted that Netcare’s management teams are actively working towards finding viable solutions to supply RE to the remaining municipal-connected sites in the Group while continuing to build on existing renewable energy initiatives. The Group’s environmental sustainability programme also continues to demonstrate an impressive return on investment to date, illustrating the commercial opportunities in environmentally conscious engineering.

According to Karel Cornelissen, chief executive officer of NOA Group, renewable energy will be wheeled through the national grid to the six designated Netcare facilities via the existing Eskom distribution transmission network and delivery of renewable energy to these facilities is expected to commence by the first quarter of 2026. “The agreement represents a significant step towards a clean-energy future by one of South Africa’s healthcare industry leaders, and we are pleased to partner with Netcare on this crucial advancement,” he says. 

Netcare joined the Race to Zero global campaign in 2021 and was the first healthcare institution in Africa to do so. The campaign strives to rally leadership and support from businesses, cities, regions and investors for a healthy, resilient, zero carbon recovery that prevents future threats, creates jobs, and unlocks inclusive, sustainable growth.

“The devastation of climate change to the environment and among communities is already resulting in enormous hardship and tragedy not only in South Africa but around the world. We cannot sit idly by while this happens. Urgent action must be taken by implementing innovative solutions,” says Dr Friedland.  

“During the past decade, Netcare has actively been engaged in several planned energy, waste and water management initiatives. This meaningful transaction is yet another step towards implementing appropriate green solutions while contributing towards a healthier environment for the people of South Africa in the decades to come and beyond,” he concludes.   

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Study Links Hot Flashes to Cardiovascular Risk Factors

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It has long been known that hot flashes are linked to a number of adverse health effects. Emerging data suggests an association between them and cardiovascular disease. A new study is the first to link physiologically assessed hot flashes with heightened systemic inflammation – a risk factor for cardiac disease. Study results will be presented during the 2023 Annual Meeting of The Menopause Society in Philadelphia September 27-30.

Vasomotor symptoms, more often referred to as hot flashes, are one of the most common symptoms identified during the menopause transition, with roughly 70% of midlife women reporting them. Not only do they interfere with a woman’s quality of life, but they have also been related to physical health risks, such as cardiovascular disease.

Previous research linking hot flashes with heightened systemic inflammation has relied on self-reporting to document the frequency and severity of the hot flashes. These self-reports of hot flashes are limited as they ask women to recall hot flashes over weeks or longer and may be subject to memory or reporting biases. A new study that included 276 participants from the MsHeart study, however, utilised sternal skin conductance to physiologically assess hot flashes and tested whether more frequent physiologically assessed hot flashes are associated with heightened system inflammation.

While large increases in inflammatory markers indicate acute infection or clinical disease, small and sustained increases of markers of inflammation that are in the physiologically normal range are predictive of later disease risk. For example, small and/or sustained increases in inflammatory biomarkers (conceptualised as heightened levels of systemic inflammation) have been related to plaque development and atherosclerotic cardiovascular disease.

Based on the results, the researchers concluded that physiologically assessed hot flashes during wake were associated with higher levels of a high-sensitivity C-reactive protein, even after adjusting for potential explanatory factors such as age, education, race/ethnicity, body mass index, and oestradiol.

The results will be presented during the Annual Meeting of The Menopause Society as part of the presentation entitled “Physiologically measured vasomotor symptoms and systemic inflammation among midlife women.”

“This is the first study to examine physiologically measured hot flashes in relation to inflammation and adds evidence to a growing body of literature suggesting that hot flashes may signify underlying vascular risk and indicate women who warrant focused cardiovascular disease prevention efforts,” says Mary Carson, MS, lead author from the Department of Psychology at the University of Pittsburgh.

“Since heart disease is the leading cause of death for women in the US, studies like these are especially valuable,” adds Dr Stephanie Faubion, medical director of The Menopause Society. “Healthcare professionals need to ask their patients about their hot flash experiences as they not only interfere with their quality of life but may also indicate other risk factors.”

Source: EurekAlert!

Categories : Medical Research & TechnologyTags :

The Vagus Nerve also Plays a ‘Fight or Flight’ Role for the Heart

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Researchers have reported in Circulation that the vagus nerve, known for its parasympathetic role in ‘resting and digesting’, also has an important role in exercise, helping the heart pump blood.

Exercise science currently holds that the ‘fight or flight’ (sympathetic) nervous system is active during exercise, helping the heart beat harder, and the ‘rest and digest’ (parasympathetic) nervous system is lowered or inactive. However, University of Auckland physiology Associate Professor Rohit Ramchandra says that this current understanding is based on indirect estimates and a number of assumptions which this new study has proven to be wrong.

“Our study finds the activity in these ‘rest and digest’ vagal nerves actually increases during exercise,” Dr Ramchandra says. “Our group has used ‘tour de force’ electrical recording techniques to directly monitor vagal nerve activity in exercising sheep and has found the activity in these vagal nerves going to the heart increases during exercise.

”For the heart to sustain a high level of pumping, it needs a greater blood flow during exercise to fuel the increased work it is doing: our data indicate that the increase in vagal activity does just this.”

During exercise, there is a four to five-fold increase in the amount of blood pumped out by the heart per minute, requiring increased cardiac output. This is modulated by autonomic nerves that travel from the brain, including the sympathetic and parasympathetic vagal nerves.

The vagal nerve connects the brain to the heart, and other internal organs including the gut, regulating the ‘rest and digest’ parasympathetic nervous system responses. The new research finds the parasympathetic and sympathetic nervous systems work together in exercise to help increase cardiac output. The researchers also investigated the role of mediators released by the cardiac vagal nerve.

“The cardiac vagus nerve releases multiple mediators, and previous research has focused on a neurotransmitter, acetylcholine, which has no impact on our ability to exercise,” says Dr Ramchandra. “Our study focused on a different mediator, vasoactive intestinal peptide (VIP) and it shows that the vagus nerve releases this peptide during exercise, which helps the coronary vessels dilate allowing more blood to pump through the heart.”

The first and co-corresponding author Dr Julia Shanks says, “Vasoactive intestinal peptide was first found in the gut and it does help in digestion, but what we now know is that it is also important in exercise.”

The trial was conducted in sheep, because of their similarity to humans in many important respects including cardiac anatomy and physiology. They are also well-established as an animal model to assist with finding ways to combat heart disease that translate to humans.

These fundamental findings could have applications in diseases, including heart failure, where people cannot tolerate exercise.

“This inability to carry out simple tasks involving exertion means that quality of life is severely compromised in these patients,” Dr Ramchandra says. “One potential reason why exercise tolerance is reduced is that the diseased heart simply does not receive enough blood. Our follow-up study will try to see whether we can use this important role of cardiac vagal nerves to improve exercise tolerance in heart failure.”

There is a lot of interest in trying to ‘hack’ or improve vagal tone as a means to reduce anxiety. Investigating this was outside the scope of the current study.

Dr Ramchandra says we do know that the vagus mediates the slowing down of heart rate and if we have high vagal activity, then our hearts should beat slower.

“Whether this is the same as relaxation, I am not sure, but we can say that regular exercise can improve vagal activity and has beneficial effects.”

Source: University of Auckland

Categories : HIVTags :

An Injectable Hydrogel could Deliver Long-term ART for HIV Patients

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A new injectable solution that self-assembles into a gel under the right conditions could help manage HIV unlike any currently available methods, researchers report in the Journal of the American Chemical Society. Developed by John Hopkins University researchers, the new gel releases a steady dose of the antiretroviral lamivudine over six weeks, suggesting people living with HIV could have an alternative to the daily pill regimen.

“The primary challenge in HIV treatment is the need for lifelong management of the virus, and one way to address this is to reduce dosing frequencies to help patients stick to medical regimens,” said lead researcher Honggang Cui, a chemical and biomolecular engineer. “This new molecular design shows us a future in which drug hydrogelation can do that to improve HIV treatment.”

In plasma-like conditions, Cui’s team showed the gel quickly separates into molecules of lamivudine. By injecting the gel in the backs of mice, the researchers found one injection was sufficient to maintain effective and lasting drug concentrations for 42 days with nearly no side effects.

“Our goal is to help improve people’s quality of life,” Cui said. “The antiviral substance can be injected under the skin and remain in place over an extended period, releasing the therapeutic compound slowly and consistently – a critical need for individuals with HIV.”

For people living with HIV, the key is maintaining bloodstream drug levels at concentrations that suppress virus load in the body. But that can be difficult with traditional approaches because the body naturally rids itself of these chemicals, Cui said, which is why different treatments require different dosages and dosing frequencies to work.

Most antiretroviral therapies use a combination of drugs, so the researchers plan to include other drugs in tests. Because lamivudine is an FDA-approved drug to treat HIV and hepatitis B, the researchers said the hydrogel could also help manage hepatitis B.

“This is a novel way to deliver anti-HIV meds, and this platform has the advantage that a single polymer can be programmed to deliver several different drugs simultaneously,” said co-author Charles W. Flexner, a professor of medicine, pharmacology, and molecular sciences in the Johns Hopkins School of Medicine. “One of the drawbacks of the approved injectable HIV treatments is that none have activity against hepatitis B virus, which is a common co-infection with HIV, especially in Asia and Africa. This formulation delivers lamivudine, a drug active against both HIV and HBV, but can also be modified to deliver tenofovir, which is the current standard of care for HBV treatment.”

The team envisions their hydrogel working as a preventive measure, similar to how some people take anti-HIV drugs to avoid infection.

“Keeping the high drug levels in plasma for 42 days is very impressive,” Cui said. “But in the future, we hope it will be even longer.”

Hydrogels have unique water-absorbing properties that give them a jellylike consistency resembling biological tissue. The new gel undergoes self-formulation, stays close to the site of injection, and separates into molecules that can fend off the virus without the need for additional carriers or delivery materials.

“The most exciting aspect of these gel filaments is that they consist entirely of the therapeutic agent itself,” Cui said. “Everything originates from the same compound after injection, and this simplest drug formulation could streamline the regulatory approval process once clinical efficacy is demonstrated.”

The team tweaked the molecular properties of lamivudine to act as the building blocks of a supramolecular polymer, a large chain of repeating molecules that can either stick together tightly or come apart, depending on temperature, pH, and other external conditions.

Source: Johns Hopkins University