Year: 2023

Robust Analysis Challenges the Link Between Cancer and Anxiety and Depression

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Depression and anxiety are thought to increase a person’s risk of developing cancer, but research results have been inconclusive. In an analysis of multiple studies from the Netherlands, the UK, Norway, and Canada, investigators found that depression and anxiety are not linked to higher risks for most types of cancer among this population. The analysis is published in the journal CANCER.

Experts have suspected that depression and anxiety may increase cancer risk by affecting a person’s health-related behaviours or by having biological effects on the body that support cancer development. Some research has supported an association between depression, anxiety, and cancer incidence, while other investigations have found no or negligible associations.

To provide additional insights, Lonneke A. van Tuijl, PhD, of the University Medical Center Groningen, and her colleagues examined data from the international Psychosocial Factors and Cancer Incidence consortium, which includes information from 18 prospective study groups with more than 300 000 adults from the Netherlands, the United Kingdom, Norway, and Canada.

The team found no associations between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers during a follow-up of up to 26 years. The presence of depression or anxiety was linked with a 6% higher risk of developing lung cancer and smoking-related cancers, but this risk was substantially reduced after adjusting for other cancer-related risk factors including smoking, alcohol use, and body mass index. Therefore, this analysis supports the importance of addressing tobacco smoking and other unhealthy behaviours including those that may develop as a result of anxiety or depression.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” said Dr van Tuijl. “However, further research is needed to understand exactly how depression, anxiety, health behaviours, and lung cancer are related.”

Source: Wiley

Thymus has an Unexpected Role in Adults, Study Finds

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The thymus gland, which produces immune T cells before birth and during childhood, is often regarded as non-functional in adults, and is sometimes removed during cardiac surgery for easier access to the heart and major blood vessels. New research led by investigators at Massachusetts General Hospital (MGH) and published in the New England Journal of Medicine has uncovered evidence that the thymus is in fact critical for adult health generally and for preventing cancer and perhaps autoimmune disease.

To determine whether the thymus provides health benefits to adults, the team evaluated the risk of death, cancer, and autoimmune disease among 1146 adults who had thymectomy during surgery and among 1146 demographically matched patients who underwent similar cardiothoracic surgery without thymectomy. The scientists also measured T cell production and blood levels of immune-related molecules in a subgroup of patients.

Five years after surgery, 8.1% of patients who had a thymectomy died compared with 2.8% of those who did not have their thymus removed, equating to a 2.9-times higher risk of death. Also during that time, 7.4% of patients in the thymectomy group developed cancer compared with 3.7% of patients in the control group, for a 2.0-times higher risk.

“By studying people who had their thymus removed, we discovered that the thymus is absolutely required for health. If it isn’t there, people’s risk of dying and risk of cancer is at least double,” says senior author David T. Scadden, MD, director of the Center for Regenerative Medicine at MGH and co-director of the Harvard Stem Cell Institute. “This indicates that the consequences of thymus removal should be carefully considered when contemplating thymectomy.”

In an additional analysis involving all patients in the thymectomy group with more than five years of follow-up, the overall mortality rate was higher in the thymectomy group than in the general U.S. population (9.0% vs 5.2%), as was mortality due to cancer (2.3% vs 1.5%).

Although Scadden and his colleagues found that the risk of autoimmune disease did not differ substantially between the thymectomy and control groups as a whole in their study, they observed a difference when patients who had infection, cancer, or autoimmune disease before surgery were excluded from the analysis. After excluding these individuals, 12.3% of patients in the thymectomy group developed autoimmune disease compared with 7.9% in the control group, for a 1.5-times higher risk.

In the subgroup of patients in whom T cell production and immune-related molecules were measured (22 in the thymectomy group and 19 in the control group, with an average follow-up of 14.2 postoperative years), those who had undergone thymectomy had consistently lower production of new T cells than controls and higher levels of pro-inflammatory molecules in the blood.

Scadden and his team now plan to assess how different levels of thymus function in adults affect individuals’ health. “We can test the relative vigour of the thymus and define whether the level of thymus activity, rather than just whether it is present, is associated with better health,” he says.

Source: Massachusetts General Hospital

Modern Antidepressants may Reduce Risk of Bipolar Relapse

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Treatment with modern antidepressants may help prevent patients with bipolar disorder from relapsing into a depressive episode, according to an international clinical trial published in the New England Journal of Medicine. The findings challenge current clinical practice guidelines and could change how bipolar depression is managed around the world.

“Treating depression in bipolar disorder is challenging and the depressive episodes can be quite devastating for patients and their families,” said Dr Lakshmi Yatham, professor and head of the department of psychiatry at UBC, and the study’s lead author. “Reducing the risk of relapse is important because it can provide patients with a great deal of stability that ultimately lets them get back to the activities they enjoy and can greatly improve their quality of life.”

Patients with bipolar disorder experience extreme changes in their emotional state that cycle through periods of intense highs (mania or hypomania) and lows (depression). During depressive episodes, patients can experience feelings of sadness, hopelessness and loss of interest or pleasure in activities, in addition to trouble sleeping, changes in appetite and suicidal thoughts.

Antidepressant adjunctive therapy, in which antidepressants are prescribed alongside mood stabilisers and/or second-generation antipsychotic medications, is a commonly used strategy by clinicians to treat depressive episodes. However, the duration of this therapy is hotly debated due to a lack of evidence and concerns that antidepressants may induce mania, mixed states or rapid cycling between mania and depression.

Practice guidelines for the management of bipolar disorder published by the Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) currently recommend discontinuing antidepressant treatment eight weeks after remission of depression.

“It’s an area that hasn’t been widely studied and there is not a lot of consensus among experts,” said Dr Yatham. “Some studies have shown that up to 80 percent of patients continue receiving antidepressants for six months or longer.”

Now, results from the world’s first randomised clinical trial assessing the duration of adjunctive antidepressant therapy suggest that extending the treatment period beyond current guidelines may help prevent depressive relapses.

The clinical trial, conducted at sites in Canada, South Korea and India, involved 178 patients with bipolar I disorder who were in remission from a depressive episode following treatment with modern antidepressant drugs (escitalopram or bupropion XL). The patients were randomly assigned to either continue antidepressant treatment for 52 weeks, or begin tapering off antidepressants at six weeks and switch to a placebo at eight weeks.

Over the year-long study, 46% of patients in the placebo group experienced a relapse of a mood event, compared to only 31% in the group that continued antidepressant treatment. While this primary outcome was not found to be statistically significant, the comparison included relapses that occurred during the first six weeks of the study when both groups were receiving the same treatment.

However, in an analysis from week six onward, when treatment between the two groups differed, patients that continued antidepressant treatment were 40% less likely to experience a relapse of any mood event, and 59% less likely to experience a depressive episode relative to the placebo group. There was no significant difference in the rate of manic episodes or the rate of adverse events between groups.

“From the point where the two groups began receiving different treatments, we see a significant benefit for patients who continued treatment with antidepressants,” said Dr Yatham.

Patients with bipolar I disorder experience depressive symptoms three times more frequently than manic symptoms. Previous studies have shown that suicide attempts and suicide deaths are at least 18 times more common during depressive episodes compared to during manic episodes.

“Stabilizing patients and keeping them stable by preventing relapse is critical and can quite literally be lifesaving,” said Dr Yatham. “Future revisions of bipolar guidelines will incorporate the evidence from this study and contribute to changes in clinical practice on how antidepressants will be used to manage patients with bipolar disorder.”

Source: University of British Columbia

Newly Identified Lipid in Breast Milk Might Reduce Cerebral Palsy in Infants

Ten percent of babies born before 32 weeks will develop cerebral palsy resulting from infections that damage white matter, nerve fibres deep in the brain. While it’s known that the white matter loss will lead to neurological deficits, there is currently no treatment to avoid this.

Now, researchers at Duke Health have conducted experiments using neonatal mice and identified a fatty molecule in breast milk that triggers a process in which stem cells in the brain produce cells that create new white matter, reversing the injury.

The study appears in the journal Cell Stem Cell. Corresponding author Eric Benner, MD, PhD, said that further study in a clinical trial is needed, but the finding is promising.

“Developing therapies for children – especially such medically fragile children – is very difficult to do because there are justifiably strict safety concerns,” Benner said. “The fact that this molecule is already found in something that is safe for premature babies – breast milk – is extremely encouraging.

“It’s been known that fats in breast milk benefit a child’s brain development, but there are many types of fats in breast milk,” Benner said. “This work has identified a lipid molecule in breast milk that promotes white matter development. Now, we can begin to develop a therapy that isolates and delivers this lipid in a way that is safe for the unique challenges of these infants.”

Benner is a neonatologist at Duke University and one of the co-founders of Tellus Therapeutics, a Duke spinout company developed with the help of the Duke University Office for Translation & Commercialization to bring this therapy from the bench into the neonatal intensive care unit.

The fatty molecule identified in the study will be administered intravenously to patients in an upcoming clinical trial. This is significant because many of the infants who are part of this vulnerable population also have gastrointestinal issues and cannot safely be given milk or medication by mouth.

The lipid molecule enters the brain and binds with stem cells there, encouraging the stem cells to become or produce a type of cell called oligodendrocytes.

The oligodendrocytes are like a hub that allow for the production of white matter in the central nervous system. This newly produced white matter in pre-term infants prevents the neurological damage that would otherwise impact the child’s ability to move – the hallmarks of cerebral palsy.

“The timing of brain injury is extremely difficult to predict, thus a treatment that could be safely given to all preterm babies at risk would be revolutionary,” said Agnes Chao, MD, a former fellow in the Division of Neonatology and first author of the paper.

“As a neonatologist, I’m so excited that I may be able to offer a treatment to families with babies that are affected by preterm brain injury who would otherwise have no other options,” Chao said.

Source: Duke University Medical Center

Boehringer Ingelheim Appoints César Nieto as General Manager and Head of Human Pharma, Southern Africa

Boehringer Ingelheim, one of the world’s leading bio-pharmaceutical companies, appointed César Nieto as General Manager and Head of Human Pharma for the Southern Africa region. As part of his responsibilities, Cesar will manage the Southern Africa region which includes South Africa and Sub-Saharan Africa countries.

A qualified physician, César has previously held senior leadership positions with the company in North and Central America, Caribbean, United Arab Emirates, and the company’s headquarters in Germany.

Mohammed Tawil, Regional Managing Director and Head of Human Pharma for Boehringer Ingelheim’s India, Middle East, Turkey and Africa (IMETA) region, said, “César has a proven track record of success in driving growth for Boehringer Ingelheim. His diverse experience will be key to our ability to drive sustainable growth and we are confident that he will help us fulfil our purpose of transforming lives for generations by bringing innovative healthcare solutions to address areas of unmet medical needs in the region.”

Commenting on his appointment, Cesar Nieto said, “Through strong partnerships with our stakeholders and Boehringer Ingelheim team, I’m confident that we can positively impact the patients and communities and contribute to healthcare innovation.” 

César was previously the Regional Cardiovascular Therapeutic Area Lead at Boehringer Ingelheim IMETA, where he played a key role in the transformation of the company’s cardiovascular and stroke portfolio. His strategy in this role served as a blueprint for other regions such as Brazil, Mexico, UK and Ireland, and led to an increase in profitability in IMETA.

Boehringer Ingelheim has been in the South African market since 1962 and later grew the network into Namibia and Botswana. Recently, the regional headquarters has extended its representation to the Sub-Sharan African region.

Traditional Healers in Rural Mpumalanga Help Diagnose HIV

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An initiative of Wits University’s MRC/Wits Agincourt Research Unit, the Traditional Healers Project convened two ‘open houses’ at local primary healthcare facilities – Rolle Clinic and Thulamahashe Community Health Centre in rural Bushbuckridge, Mpumalanga – in March 2023.

An ‘open house’ is a community and stakeholder gathering hosted at a public health facility in partnership with the Department of Health.

The aim of these sessions is to build on the relationship that the MRC/Wits Agincourt Research Unit has established between local traditional healers, community members, and healthcare facility staff to support the end of HIV through regular HIV counselling and testing.

Traditional healers in public health

The sessions supplement research that began almost a decade ago, which focuses on the role of traditional healers in healthcare access and delivery.

Specifically, this research aims to determine:

  • whether traditional healers can conduct HIV counselling and testing (HCT)
  • whether the patients of traditional healers are willing to undergo HCT that is administered by a traditional healer
  • whether traditional healers and biomedical healthcare workers can work together to help link patients to HIV/AIDS diagnosis and care.

The open house sessions form part of this research and provide a platform where traditional healers and biomedical healthcare workers can come together and build mutual understanding and trust, with a view to linking those who test positive for HIV with healthcare providers who can then administer lifesaving antiretroviral treatment (ART) and care.

15 traditional healers certified HIV counsellors and testers

The open houses drew an audience of more than 150 participants, including 15 traditional healers, local indunas [tribal chiefs], community healthcare workers (CHWs), community members, and representatives from Right to Care (a local collaborating partner on HIV) and the Department of Health.

Mr Wonderful Mabuza, Project Manager at the MRC/Wits Agincourt Research Unit, oversees the open houses and says that the successes to date have far surpassed expectations:

“It is exciting to be part of the group that is doing this work, knowing that we have a lot of people who visit traditional healers in our communities. It’s groundbreaking to have traditional healers trained to provide HIV counselling and testing – and amazing to see community members respond, with some never having tested previously.”

Gogo Singabeni, one of the 15 traditional healers who has completed the programme, says: “I was very excited to be invited to the HIV training, and that we would be certified in HIV testing and counselling. It’s important to show people proof that I am certified to do HIV testing.”

She adds: “The first day of testing [a patient] was very difficult for me. I was even shaking as I was conducting the test. I started with the first client, although I was shaking, and I managed to complete the process according to how we were trained. After the client left, I drew strength in seeing that I am able to do it.”

Partnerships imperative

Dr Ryan Wagner, Senior Research Fellow at the MRC/Wits Agincourt Research Unit, leads the traditional healers programme known collectively as Ntirhisano (Shangaan for ‘working together’).

He emphasises the importance of the Ntirhisano team, traditional healers, community healthcare workers, and the Department of Health collaborating to strengthen the referral system. 

“In order to expand coverage and increase uptake of HIV testing – and thereby contribute to ending new HIV cases – we need to embrace innovative approaches, such as traditional healer-initiated HIV counselling and testing,” says Wagner.

“We have recruited and trained 15 traditional healers in the Thulamahashe/Rolle area who, for the past six months, have been successfully testing their patients for HIV/AIDS. Those who tested positive have been referred to a local clinic or community healthcare worker.”

The Department of Health’s Primary Healthcare Supervisor, Sister Mariah Mkhari, says: “The Department of Health alone cannot do it, but with such collaborations between MRC/Wits and other stakeholders we will be able to conquer HIV. We welcome the initiative, and we hope Wits can expand to other areas in Bushbuckridge and train all traditional healers to test for HIV.”

MRI Scan Combination Could Detect Hypertrophic Cardiomyopathy Early

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Combining two types of heart scan techniques could help detect hypertrophic cardiomyopathy (HCM) before symptoms and signs on conventional tests appear, according to a new study led by UCL researchers. To do this, they used two cutting-edge heart scanning techniques: cardiac diffusion tensor imaging (cDTI), which shows the heart’s microstructure and cardiac MRI perfusion (perfusion CMR), which reveals microvascular disease. Their findings, published in Circulation, will help doctors select appropriate treatments.

HCM is a disease which affects around 1 in 500 in the UK, causing thickening of heart muscle and can lead to heart failure and cardiac arrest.

Researchers studied the hearts of three groups: healthy people, people who already had HCM, and people with an HCM-causing genetic mutation but no overt signs of disease.

The scans showed that people with overt signs of HCM have very abnormal organisation of their heart muscle cells and a high rate and severity of microvascular disease compared to healthy volunteers, helping doctors more accurately spot the early signs of HCM.

Crucially, the scans were also able to identify abnormal microstructure and microvascular disease in the people who had a problematic gene but no symptoms or muscle thickening. They found that 28% had defects in their blood supply, compared to healthy volunteers. This meant that doctors were able to more accurately spot the early signs of HCM developing in patient’s hearts.

The first drug to slow HCM progression, mavacamten, has recently been approved for use in Europe and will allow doctors to reduce the severity of the disease once symptoms and muscle thickening have appeared. Genetic therapies are also in development which could prevent symptoms entirely by intercepting HCM development at an early stage.

Perfusion CMR is already being used in some clinics to help differentiate people with HCM from other causes of muscle thickening. The researchers think that these revolutionary new therapies, combined with cDTI and perfusion CMR scans, give doctors the best ever chance of treating people at risk of HCM early enough that the condition never develops.

Dr George Joy, who led the research with Professor James Moon and Dr Luis Lopes (all UCL Institute of Cardiovascular Science), said: “The ability to detect early signs of HCM could be crucial in trials testing treatments aimed at preventing early disease from progressing or correcting genetic mutations. The scans could also enable treatment to start earlier than we previously thought possible.

“We now want to see if we can use the scans to identify which patients without symptoms or heart muscle thickening are most at risk of developing severe HCM and its life-changing complications. The information provided from scans could therefore help doctors make better decisions on how best to care for each patient.”

Dr Luis Lopes (UCL Institute of Cardiovascular Science), senior author of the study, said: “By linking advanced imaging to our cohort of HCM patients (and relatives) with extensive genetic testing, this study detected microstructural abnormalities in vivo in mutation carriers for the first time and was the first to compare these parameters in HCM patients with and without a causal mutation.

“The findings allow us to understand more about the early subclinical manifestations of this serious condition but also provide additional clinical tools for screening, monitoring and hopefully in the near future for therapeutic decision-making.”

Source: University College London

Plasma Protein Biomarkers Could Detect Early Mental Health Problems in Adolescents

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Researchers at the University of Eastern Finland have identified plasma protein-based biomarkers capable of identifying adolescents at risk of developing mental health issues. Such biomarkers could revolutionise early detection and prevention of mental health problems in young people.The results were published in Nature Mental Health.

Some 10–20% of adolescents struggle with mental health conditions, with the majority going undiagnosed and untreated. This points to a need for new, early indicators of mental health problems to catch these cases and intervene with treatment before the conditions progress.

In the study carried out in the research group of Professor Katja Kanninen, the researchers used self-reported Strengths and Difficulties Questionnaire (SDQ) scores to evaluate mental health risk in participants aged between 11 and 16 years. Blood sample analyses showed that 58 proteins were significantly associated with the SDQ score. Bioinformatic analyses were used to identify the biological processes and pathways linked with the identified plasma protein biomarker candidates. Key enriched pathways related to these proteins included immune responses, blood coagulation, neurogenesis, and neuronal degeneration. The study employed a novel symbolic regression algorithm to create predictive models that best separate low and high SDQ score groups.

According to Professor Kanninen, plasma biomarker studies in mental disorders are an emerging field.

“Alterations in plasma proteins have been previously associated with various mental health disorders, such as depression, schizophrenia, psychotic disorders, and bipolar disorders. Our study supports these earlier findings and further revealed that specific plasma protein alterations could indicate a high risk for mental dysfunction in adolescents,” Professor Kanninen notes.

According to the researchers, this pilot study will be followed by more specific investigations of the potential biomarkers for identification of individuals at risk of mental health problems, opening a new avenue for advancements in adolescent mental health care.

Source: University of Eastern Finland

Review Identifies Most Effective Forms of Exercise to Reduce Blood Pressure

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A meta-analysis published in the British Journal of Sports Medicine has shown that isometric exercises, which involve contracting muscles to hold the body in position without moving such as in wall squats, are best for reducing resting blood pressure. The researchers reviewed 270 randomised clinical trials with a total of 15 827 participants.

All of the studies included measured blood pressure after two weeks or more of exercise intervention, and included non-intervention control groups. It was found that isometric exercises reduced systolic and diastolic blood pressure by 8.24 and 4.00mmHg respectively. The next most effective forms of training in reducing blood pressure were combined training, followed by dynamic resistance training, aerobic exercise, and high-intensity interval training (HIIT).

The researchers noted that current guidelines are based on older research and as such don’t include data from new forms of exercise such as HIIT. These guidelines tend to emphasise aerobic training such as running for controlling blood pressure. In addition to helping clinicians optimise individualised exercise recommendations, the new findings suggest that it might be time to update exercise guidelines for preventing and treating high blood pressure.

Source: JAMA Network

Study Finds No Evidence of Fungus Link to Pancreatic Cancer

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Four years ago, a report that a common species of fungus might fuel pancreatic cancer offered a promising new view of the deadly disease. But in working to validate the finding, Duke Health researchers have found no such association. In a study published in the journal Nature, the researchers conducted a multi-pronged analysis of data from the earlier study and found no link between the pancreatic microbiome and the development of pancreatic cancer.

“We were intrigued by the original finding, as were many research teams,” said senior author Peter Allen, MD, professor in the Department of Surgery and chief of the Division of Surgical Oncology at Duke University School of Medicine.

“There is a growing body of literature connecting the human microbiome to disease, and this was particularly compelling for pancreatic cancer,” Allen said. “But our findings did not support an association between fungi and the development of pancreatic cancer in humans.”

Allen and colleagues worked to recreate the 2019 findings published in Nature by a different research team. The original study raised hopes that there might be a possible method of preventing pancreatic cancer with the use of antifungals or some other approach to protect from infection.

Focusing on the research team’s original raw sequencing data, the Duke researchers were unable to reproduce the findings. Additional studies, using pancreatic cancer tissue in Duke repositories, also failed to produce the original results.

“We believe our findings highlight the challenges of using low biomass samples for microbiome sequencing studies,” Allen said. “The inclusion of appropriate negative controls and efforts to identify and remove sequencing contaminants is critical to the interpretation of microbiome data.”

Source: Duke University Medical Center