Day: January 19, 2024

Benefits of Adolescent Fitness to Future Cardiovascular Health Possibly Overestimated

Photo by Andrea Piacquadio on Pexels

There is a well-known relationship between good physical fitness at a young age and a lower risk of cardiovascular disease later in life. But when researchers adjusted for familial factors by means of sibling analysis, they found a weaker association, although the link between high body mass index (BMI) and cardiovascular disease remained strong. The study, which was conducted by researchers from Karolinska Institutet and other universities, is published in JAMA Network Open.

“This does not mean that fitness is irrelevant,” cautions the study’s last author Viktor Ahlqvist, doctoral student at the Department of Global Public Health, Karolinska Institutet. “We could still see an association, although it was weaker after taking into account factors shared by full siblings. We also think that adolescence is an important time in life for establishing good habits such as exercising and having a healthy diet.”

Many observational studies have previously demonstrated links between various risk factors at a young age and cardiovascular disease in adulthood. However, whether the associations are causal is challenging to prove because of the potential influence of unaccounted genetic and environmental factors. A collaborative team including researchers from Karolinska Institutet in Sweden has therefore tried to examine if a large proportion of cardiovascular diseases in adulthood could indeed be prevented with a lower BMI, lower blood pressure, improved physical fitness or improved muscle strength in adolescence.

Data from the Military Conscription Register

Sourcing data from the Swedish Military Conscription Register and other Swedish registries, the researchers identified over a million 18-year-old males and followed them for 60 years. Almost half of them were full brothers.

“The strength of our study, which makes it more reliable than many other conventional observational studies, is that we have used sibling analyses,” says the study’s first author Marcel Ballin, researcher at Uppsala University and analyst at Region Stockholm’s Centre for Epidemiology and Community Medicine. “By doing so we could examine how the relationship changes when controlling for all shared sibling factors. This includes environmental factors such as childhood environment and half of the genetics.”

The results show that a high BMI in late adolescence was strongly associated with future cardiovascular disease, even after the researchers had controlled for shared familial factors. However, the association between physical fitness and cardiovascular disease was considerably weaker in the sibling analysis, suggesting that many previous observational studies might have overestimated the relevance of adolescent fitness to cardiovascular health later in life.

High BMI the strongest risk factor

“Our conclusion is that of the risk factors studied, high BMI is the strongest individual risk factor for cardiovascular disease, and that efforts to tackle the obesity epidemic should continue to be given high priority,” says co-author Daniel Berglind, docent at the Department of Global Public Health, Karolinska Institutet. “A good level of fitness and muscle strength in adolescence doesn’t seem as crucial, but physical activity still remains important for public health, as it can bring other health benefits.”

The study examined the association between risk factors at a young age and future cardiovascular disease; other disease outcomes were not investigated. The researchers had no data on whether the participants’ risk factors varied later in life, and they only studied men, which makes it difficult to extend their findings to women. The Military Conscription Register also lacks details on certain risk factors for future cardiovascular disease, such as diet, alcohol consumption, smoking, blood lipids and blood glucose.

The researchers received no specific grant for this study. Co-author Martin Neovius is on the advisory panels for Ethicon, Johnson & Johnson and Itrim and has been a consultant for the Swedish armed forces outside the scope of this study. No other conflicts of interest have been reported.

Source: Karolinska Institutet

New Metastatic Breast Cancer Treatments have Aided Mortality Decline

Photo by National Cancer Institute on Unsplash

Deaths from breast cancer dropped 58% between 1975 and 2019 due to a combination of screening mammography and improvements in treatment, according to a new study led by Stanford Medicine clinicians and biomedical data scientists.

Nearly one-third of the decrease (29%) is due to advances in treating metastatic breast cancer, also known as stage 4 breast cancer or recurrent cancer. Although these advanced cancers are not considered curable, women with metastatic disease are living longer than ever.

The analysis helps cancer researchers assess where to focus future efforts and resources.

“We’ve known that deaths from breast cancer have been decreasing over the past several decades, but it’s been difficult or impossible to quantify which of our interventions have been most successful, and to what extent,” said Jennifer Caswell-Jin, MD, assistant professor of medicine. “This type of study allows us to see which of our efforts are having the most impact and where we still need to improve.”

Caswell-Jin and Liyang Sun are co-first authors of the study, which was published in the Journal of the American Medical Association. Sylvia Plevritis, PhD, professor and chair of biomedical data science, and Allison Kurian, MD, MSc, professor of medicine and of epidemiology and population health, are co-senior authors.

The study was a collaborative effort by a national consortium of researchers called CISNET, or the Cancer Intervention and Surveillance Modeling Network. CISNET was established in 2000 by the National Cancer Institute to understand the impact of cancer surveillance, screening and treatment on incidence and mortality. Doing so requires sophisticated computer algorithms capable of modelling the natural course of the disease and the typical treatment paths of individual patients, then translating that information to population-level data collected by the national Surveillance, Epidemiology, and End Results Program, or SEER registry, from 1975 to 2019.

The study is the third in a trio of papers from CISNET published since 2005 that assess the relative contributions of regular screening and treatment advances on breast cancer deaths. The previous two papers informed national guidelines and helped cancer researchers focus their efforts on the most intractable problems.

“Twenty years ago, there was a question whether routine screening mammography actually decreased the number of deaths from breast cancer,” Plevritis said. But in 2005, she and other CISNET researchers published a paper in the New England Journal of Medicine that conclusively demonstrated that screening was responsible for anywhere from 28% to 65% (different models came up with varying degrees of impact) of the reduction in mortality by 2000 between 1975 and 2000.

The second paper, published in 2018 in the Journal of the American Medical Association, highlighted the differences in treatment responsiveness and survival outcomes among women with differing breast cancer subtypes from 2000 to 2012, pinpointing subgroups with poorer survival.

“We found that, while screening still had an important impact, most of the decline in annual deaths was due to improvements in treating early-stage breast cancer based on each cancer’s molecular profile,” Plevritis said.

The current study is the first to explicitly include patients with metastatic breast cancer in its models. The finding that 29% of the decrease in mortality is due to advances in treating metastatic breast cancer both surprised and gratified the researchers.

“Initially, we assumed that treatment of advanced disease was unlikely to make a significant contribution to the declines in mortality we documented in the previous two papers,” Caswell-Jin said. “But our treatments have improved, and it’s clear that they are having a significant impact on annual mortality.”

The CISNET researchers used four computer models to assess the SEER data from 1975 to 2019 — one developed at Stanford Medicine in the Plevritis Lab, one by researchers at the Dana-Farber Cancer Institute, one at MD Anderson Cancer Center, and another jointly developed by researchers at the University of Wisconsin and Harvard Medical School. The four models came up with remarkably similar estimates for the impact of each intervention: screening mammography, treatment of early-stage (stages 1, 2 or 3) breast cancer and treatment of metastatic breast cancer.

The models reproduced the decline in mortality in breast cancer known from SEER data, from 48 per 100 000 women dying of breast cancer each year in 1975 to 27 per 100,000 in 2019, a decrease of about 44%. The models arrived at a larger estimated reduction in mortality of about 58% because the incidence of breast cancer has risen during the same period and more women would have died had screening and treatments not improved.

The models concluded that about 47% of this reduction in mortality is the result of improved treatments for early-stage breast cancer, and about 25% is attributed to screening mammography. The remainder, or about 29%, is due to improvements in treating metastatic disease.

“Designing the new model, which had to account for individuals with non-metastatic cancer who underwent treatment but later progressed to metastatic cancer, and who may have been treated with multiple drugs over the course of their disease, was extremely complex,” Plevritis said. “It took about four years. But it was really satisfying when we were able to validate the model’s behaviour and see that all four models from different institutions, which used the new model inputs in different ways, delivered consistent findings. The models not only make sense, but also produce meaningful insights.”

The impact of treating metastatic disease is exemplified by the increases in median survival time after metastasis: Patients diagnosed in 2000 with metastatic disease lived an average of 1.9 years versus an average of 3.2 years for those diagnosed in 2019. Survival time varies by subgroup status, however. Patients with what are known as oestrogen receptor-positive and HER2 positive cancers saw an average increase in survival time of 2.5 years. Those with oestrogen receptor-positive and HER2-negative cancers lived an average of 1.6 years longer, but those with cancers that are oestrogen receptor-negative and HER2-negative lived about 0.5 years longer in 2019 than in 2000.

“It was meaningful as a breast oncologist to spend time with this history and see real progress over the past decades,” Caswell-Jin said. “There is much more work to be done; metastatic breast cancer isn’t yet curable. But it is rewarding to see that advances have made a difference in these numbers,” she added. “Our scientific and clinical work is helping our patients live longer, and I believe deaths from breast cancer will continue to steadily decline as innovation continues to grow.”

Source: Stanford Medicine

Climate Change may Reduce Life Expectancy by Half a Year, Study Suggests

UPDATE: Concerns have been raised about the source of the data used in the study. Details below.

On its own, a 1°C temperature rise might shave off about five months, with women and people in developing nations disproportionately affected.

Photo by Markus Spiske

The cost of climate change may be six months off the average human lifespan, according to a study published January 18, 2024, in the open-access journal PLOS Climate by Amit Roy from Shahjalal University of Science and Technology and The New School for Social Research, US.

Temperature and rainfall – two telltale signals of climate change – cause myriad public health concerns, from the acute and direct (eg, natural disasters like flooding and heat waves) to the indirect yet equally devastating (eg, respiratory and mental illnesses). While impacts like these are observable and well documented, existing research has not established a direct link between climate change and life expectancy.

To clarify this relationship, the author evaluated average temperature, rainfall, and life expectancy data from 191 countries from 1940-2020, using GDP per capita to control for drastic differences between countries.

In addition to measuring the isolated impacts of temperature and rainfall, the author designed a first-of-its-kind composite climate change index, which combines the two variables to gauge the overarching severity of climate change.

Results indicate that in isolation, a global temperature increase of 1°C  is associated with an average human life expectancy decrease of approximately 0.44 years, or about five months and one week. A 10-point increase in the composite climate change index – which accounts for both temperature and rainfall – is expected to decrease the average life expectancy by six months. Women and individuals in developing nations are disproportionately affected.

Beyond the results of this study, Dr Roy is hopeful that the composite climate change index will standardise the global conversation about climate change; become a usable metric for the nonscientific public; and encourage collaboration and even friendly competition among countries to combat the impacts of climate change.

Mitigating greenhouse gas emissions and adapting to a changing environment are of particular importance, the author says.

To complement this large-scale approach, the author suggests localised future studies that consider specific severe weather events (eg, wildfires, tsunamis, and floods), the impacts of which cannot be fully captured through analysing temperature and rainfall alone.

Dr Roy adds: “The global threat posed by climate change to the well-being of billions underscores the urgent need to address it as a public health crisis, as revealed by this study, emphasising that mitigation efforts to reduce greenhouse gas emissions and proactive initiatives are essential to safeguard life expectancy and protect the health of populations worldwide.”

IMPORTANT UPDATE: Following publication of the paper referenced below, concerns have been raised about the reliability of global mean annual temperature data that are discussed in the article and used in the study’s analyses. The source of these data is reported as [1] in the article’s Materials and methods section, and as [2] in the Fig 4 legend.

1. World Bank. The Climate Change Knowledge Portal (CCKP) 2023. The World Bank; 2023. https://climateknowledgeportal.worldbank.org/

2. Akhtar R, Palagiano C. Climate change and air pollution: an introduction. Climate Change and Air Pollution: The Impact on Human Health in Developed and Developing Countries. 2018:3–8.

PLOS Climate is looking into the concerns that have been raised. Meanwhile, readers are advised to interpret this article’s results with caution. You may direct any specific questions to onepress@plos.org. We apologise sincerely for the inconvenience and thank you for your understanding. 

‘Exhalation’ System Improves Symptoms for Chronic Sinusitis

Photo by Brittany Colette on Unsplash

An exhalation delivery system that uses a patient’s own breath to carry the anti-inflammatory compound fluticasone (EDS-FLU) directly to the sinuses reduced chronic sinusitis symptoms as well as aggravations and infections associated with chronic sinus inflammation by more than 50%, researchers from the Perelman School of Medicine at the University of Pennsylvania reported.

The two randomised, international clinical trials (NCT03781804 and NCT03960580), published in The Journal of Allergy and Clinical Immunology: In Practice, compared EDS-FLU to a placebo in more than 500 adults with chronic rhinosinusitis with or without nasal polyps. Patients used either EDS-FLU or a placebo twice daily for 24 weeks.

EDS-FLU works through a patient exhaling into the device to send the medication deep into the far reaches of their sinus cavities, where the topical medication is most effective. Sinus symptom scores and CT scan results were significantly improved vs placebo.

Symptoms of nasal congestion, nasal discharge, facial pain/pressure, and loss of smell improved dramatically with EDS-FLU compared to placebo, as measured by the sinonasal outcome test-22, a standardized scoring measure for sinonasal symptoms.

“Chronic sinusitis affects as much of 10 percent of the United States population, and can make breathing uncomfortable and negatively impact a person’s daily life,” said lead author James N. Palmer, MD, professor of otorhinolaryngology and director of Rhinology at Penn Medicine.

“These findings provide strong evidence for an effective, non-invasive treatment option for people who continue to experience symptoms after over-the-counter medications have failed.”

Millions of Americans experience the symptoms of chronic sinus infections and inflammation, a largely inflammatory condition that causes nasal congestion, sinus pressure, and pain, when the sinus membranes are inflamed for long periods of time.

Although over-the-counter nasal sprays offer marginal relief, no FDA-approved medication exists for the most common form of the condition, chronic rhinosinusitis without nasal polyps, known as “chronic sinusitis.”

While some nasal sprays may offer some symptom relief, patients who were using a standard-delivery nasal spray before study enrollment still reported similar improvements in symptoms compared to others in the study.

These are the first placebo-controlled clinical trials to show that a medication reduces subjective symptoms and objective measures of sinus disease for patients with chronic sinusitis, both with and without polyps.

Currently, patients whose symptoms are not resolved by over-the-counter nasal sprays or other medications, have limited options for relief, including antibiotics, surgery, or in the case of nasal polyps, lifelong biologic therapies.

EDS-FLU was determined to be as safe as standard over the counter nasal sprays.

Source: University of Pennsylvania School of Medicine

Visions of Nonphysical World are Common Among Cognitively Healthy American Indians

Photo by Bruce Christianson on Unsplash

Visual hallucinations are common among people with Lewy body dementia and other types of dementia. Identifying visual hallucinations is an important component of a wide variety of medical and psychiatric diagnoses and treatments, but without cultural context, some patients’ symptoms can be misinterpreted or misdiagnosed.

There is little in medical literature about normal spiritual experiences in American Indian participants in the context of a neurocognitive evaluation. University of Minnesota Medical School researchers sought to understand how the culture and spirituality of the American Indian Ojibwe tribe affect a doctor’s assessment of normal aging.

Publishing in JAMA Network Open, the research team found that visions of the nonphysical world are common among cognitively healthy Ojibwe individuals and can represent normal spiritual experiences. 

“Consideration of a patient’s cultural background and belief system can help avert erroneous disqualification for disease-modifying therapy, exclusion from clinical trials and all the negative ramifications associated with a misdiagnosis of psychiatric disease,” said William Mantyh, MD, an assistant professor at the University of Minnesota Medical School and  behavioural neurologist with M Health Fairview.

In partnership with an Ojibwe Tribal Nation in Minnesota, the study recruited 33 cognitively healthy tribal elders aged 55 years or older. The research found 48% of participants reported frequent transient visions of the nonphysical world that generally were benevolent and involved spiritual beings and/or ancestors. 

According to the research team, clinicians would benefit from careful consideration of cultural or spiritual context to avoid misdiagnosis of neuropsychiatric disease. 

“Today’s environment of infrequent or insufficiently short cognitive evaluations – an average 16-minute face-to-face visit with a physician and increasing use of pre-visit symptom checklists increase the risk of falsely attributing a spiritual experience to a hallucination,” said Dr Mantyh. 

Dr Mantyh and his research team’s overarching goal is to ensure accurate diagnosis of neurodegenerative disease in American Indian communities. To reach this goal, the research team is including American Indian participants in the development of a new Alzheimer’s disease blood test. So far, more than 250 participants have been included. These new Alzheimer’s disease blood tests, up to 95% accurate, directly detect the proteins related to Alzheimer’s disease in the blood, but they also look at a patient’s APOE ε4 gene. APOE ε4 is the most significant genetic risk factor for Alzheimer’s disease, but its effect on Alzheimer’s disease depends on a patient’s ancestry. 

Source: University of Minnesota