Tag: 28/9/23

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.