Increase in Excessively Hot Nights Will Raise Mortality Rate

Sleeping woman
Photo by Cottonbro on Pexels

With the number of excessively hot nights expected to double due to climate change, it is predicted that their associated mortality rate will rise by up to 60% by the end of the century, according to the latest research published in published in The Lancet Planetary Health.

Ambient heat during the night may interrupt the normal physiology of sleep, leading to immune system damage and a higher risk of cardiovascular disease, chronic illnesses, inflammation and mental health conditions. The average intensity of hot night events will nearly double by 2090, from 20.4℃ to 39.7℃ across 28 cities from east Asia, increasing the burden of disease due to excessive heat that disrupts normal sleeping patterns.

This is the first study to estimate the impact of hotter nights on climate change-related mortality risk. The findings show that the burden of mortality could be significantly higher than estimated by average daily temperature increase, suggesting that warming from climate change could have a troubling impact, even under restrictions from the Paris Climate Agreement.

“The risks of increasing temperature at night were frequently neglected,” said study co-author Yuqiang Zhang, PhD, a climate scientist in the Department of Environmental Sciences and Engineering at the Gillings School. “However, in our study, we found that the occurrences of hot night excess are projected to occur more rapidly than the daily mean temperature changes. The frequency and mean intensity of hot nights would increase more than 30% and 60% by the 2100s, respectively, compared with less than 20% increase for the daily mean temperature.”

The team estimated the mortality due to excess heat in 28 cities in China, South Korea and Japan between 1980 and 2015 and applied it to two climate change modelling scenarios that aligned with carbon-reduction scenarios adapted by the respective national governments.

Through this model, the team was able to estimate that between 2016 and 2100, the risk of death from excessively hot nights would increase nearly six-fold. This prediction is much higher than the mortality risk from daily average warming suggested by climate change models.

“From our study, we highlight that, in assessing the disease burden due to non-optimum temperature, governments and local policymakers should consider the extra health impacts of the disproportional intra-day temperature variations. A more complete health risk assessment of future climate change can help policymakers for better resource allocation and priority setting,” said Haidong Kan, PhD, who is a professor at Fudan University in China and the study’s corresponding author.

In this study, the authors also found that regional differences in temperature accounted for many of the variances in nighttime temperature, and areas with the lowest average temperature were projected to have the largest warming potential.

“To combat the health risk raised by the temperature increases from climate change, we should design efficient ways to help people adapt,” said Dr Zhang. “Locally, heat during the night should be taken into account when designing the future heatwave warning system, especially for vulnerable populations and low-income communities who may not be able to afford the additional expense of air conditioning. Also, stronger mitigation strategies, including global collaborations, should be considered to reduce future impacts of warming.”

Since the study only included 28 cities from three countries, Dr Zhang said that “extrapolation of these results to the whole East Asia region or other regions should be cautious. Currently, based on these findings, authors are trying to extend the analysis to a global dataset. Then we could have a global picture of the deadly nighttime heat on health under climate change scenarios.”

Source: University of North Carolina at Chapel Hill

Infant BCG Vaccination Only Protects up to Five Years of Age

Syringe withdrawing from vaccine vial
Photo by Mufid Majnun

A study has found that the Bacillus Calmette-Guérin (BCG) vaccine, when administered in infancy, only protects against tuberculosis (TB) in children under five years of age. The findings, published in The Lancet Global Health, showed that the vaccine provided no protection among adolescents or adults in the study.

Despite the age and widespread use of the BCG vaccine, debate continues on how effective it is in preventing TB, and the duration of immunity after it is administered in infancy. And as experts study and propose new TB vaccines to supplement the BCG vaccine, an important consideration is the age at which these new vaccines should be administered to high-risk populations.

Gathered from 20 years of recent studies, this analysis provides new insight and clarity on these issues.

These results suggest that protectiveness from the BCG vaccine may begin to wane as children get older and, thus, children over 10 years old and adults should receive a booster BCG vaccine for immunity against TB beyond childhood. Unfortunately, a BCG booster has limited efficacy, so new vaccines are needed.

“Unlike many of the mRNA COVID vaccines, which we know are highly effective, there is widespread debate on the BCG vaccine’s effectiveness and duration of protection, as well as whether the vaccine only works in selective settings,” explained study lead author Leonardo Martinez, assistant professor of epidemiology at Boston University School of Public Health. “Our findings indicate that BCG vaccination is effective at preventing tuberculosis in young children. Since tuberculosis in children is a highly debilitating and severe disease, BCG vaccination should continue to be used.”

However, since the results show that the vaccine was ineffective in adolescents and adults, “boosting immunoprotection is needed for older populations,” Asst Prof Martinez said. “Novel vaccines are urgently needed to supplement BCG vaccination in high-burden settings.”

Most studies on this subject were done over 50 years ago, with varying results, and primarily in settings with a relatively low burden of the disease. This new analysis presents data over the past 10 years, from high-burden settings in 17 countries, including South Africa, China, Vietnam, Indonesia, Uganda, The Gambia, and Brazil.

For the study, Asst Prof Martinez and colleagues analysed individual-level data from 26 longitudinal studies that included nearly 70 000 participants exposed to TB from 1998 to 2018. The researchers examined the impact of BCG vaccination for all TB disease, as well as specifically for pulmonary and extrapulmonary TB. The analysis examined variability across the studies, including the use of skin and blood TB infection tests, and accounted for potentially confounding factors such as HIV, exposure status, and history of prior TB, amongst others.

Among all children under 5 years old, BCG vaccination was 37% effective. The researchers did not find conclusive evidence that the vaccine was protective among children over 10 or among adults. When focusing only on pulmonary TB, BCG vaccination was 19% effective, however this effect was also only among young children.

The researchers stress that substantial investment in TB vaccine development is critical to controlling global TB.

“We urgently need vaccines that are effective against tuberculosis in adults,” said study co-author C. Robert Horsburgh, professor of epidemiology. “There are a number of promising TB vaccine candidates under study and we hope that one or more of them will prove effective.”

Source: Boston University

Major Review Urges Tackling of Weight Stigma in Healthcare

Obesity
Image source: Pixabay CC0

Weight stigma is a negative bias known to limit both access to health services and treatments. A joint international consensus statement was recently published in Nature, aiming to end weight stigma in healthcare globally.

Researchers conducted a large review of over 3700 studies to evaluate weight stigma reduction strategies in healthcare practice and healthcare education, with a view to provide recommendations for interventions, learning, and research. The findings, published in Obesity Reviews, indicate that there is a need to move away from a weight-centric approach to healthcare.

Lead author, Dr Anastasia Kalea said: “Sadly healthcare, including general practice, is one of the most common settings for weight stigmatisation and we know this acts as a barrier to the services and treatments that can help people manage weight.

“A common misconception among medics and others, is that obesity is caused by factors within a person’s control, focusing on diet and exercise without recognition of, for instance, social and environmental determinants.

“In this review, it was clear more needs to be done to educate healthcare professionals and medical students on the complex range of factors regulating body weight, and to address weight stigma, explicitly emphasising its prevalence, origins, and impact.”

Researchers undertook a systematic review of 3773 international research articles. This included 25 weight stigma interventional initiatives, comprising a total of 3554 participants.

Weight-inclusive approaches to education in healthcare were identified as effective in challenging stereotypes and improving attitudes. They identified stigma reduction strategies in healthcare, which included ethics seminars discussing patient experiences, embedding virtual story-telling of patient case studies, or empathy evoking activities in the curriculum, such as following a calorie restricted diet or participation in clinical encounters with patients living with overweight and obesity. However, other methods such as video presentations and short lectures were not equally effective in improving attitudes in the long term.

Researchers are now calling on medical schools in both the UK and globally to ensure effective and sustained weight-inclusive teaching is embedded in medical doctor training and is added to the continuing professional development of clinicians.

Dr Kalea said: “Weight stigma needs to be addressed early on and continuously throughout healthcare education and practice, by teaching the genetic and socioenvironmental determinants of weight, by discussing the sources, impact and recognising the implications of stigma on treatment. We need to move away from a solely weight-centric approach to healthcare to a health-focussed weight-inclusive one. And it is equally important to assess the effects of weight stigma in epidemiological research.”

The urgency of tackling the obesity and overweight has been brought to the fore by evidence of the link to an increased risk from COVID.

Dr Kalea added: “Stigma reduction interventions are a current research priority. Improving the ways we educate healthcare professionals early on is a starting point, keeping the focus on our patients; we need to communicate better, listen carefully to our patients needs and let these inform our teaching and research agendas.”

Weight stigma is also known to cause ‘internalised weight bias’ (IWB), which is when a person applies negative societal or cultural beliefs about body weight to themselves. This can lead to psychological distress, depression, anxiety, low self-esteem and often leads to decreased health motivation and maladaptive coping such as avoidance of timely healthcare, social isolation, reduced physical activity and disordered eating behaviours.

Weight stigma has also been shown to increase risk of developing obesity, and healthcare is one of the most common contexts where weight stigmatisation occurs. Physicians have been reported as the second most common source of weight stigma and discrimination.

Source: University College London

Horses Work ‘Magic’ for Children with Disabilities

Children with disabilities enjoy free riding lessons at the South African Riding for the Disabled Association in Durban. Photo: Nokulunga Majola

GroundUp reports on the South African Riding for the Disabled Association, which provides 50 rides a week for children with disabilities near Durban.

“You make the world of difference one day of the week in the lives of the Browns Pre-Primary children, and for this I thank you,” Browns School teacher Fiona Muhl tells the volunteers at the South African Riding for the Disabled Association (SARDA) in Durban.

Based in Assagay on the outskirts of Durban, SARDA has been offering free therapeutic horse-riding lessons since 2007 for children with disabilities. They see about 50 children a week, aged five to 16.

From the minute the children arrive at the Ridgetop Equestrian Centre to the moment they leave, their day is filled with thrills. Children giggle on their horses in the riding arena as volunteers play with them and teach them riding.

Each child is allocated a suitable pony. Once they are all mounted, the lesson begins. There are obstacle courses and various activities, such as throwing a ball into a hoop, to encourage coordination, flexibility and cognitive development.

A SARDA volunteer said one child is still completely non-verbal at school, but laughed right through a riding session and at the end gave a cowboy style “Yeehaw”. What is happening at the riding school is magic, she said.

Susan Warrington, a volunteer at SARDA, said it is one of the most rewarding things she has ever done. “The joy on their faces, the often first words an autistic child speaks, and knowing that these little souls had a good day is the reason we do this,” said Warrington.

Libby Durk, chairperson of SARDA Durban, said children come from Browns School in Pinetown, Ethembeni School in Inchanga, West Park School in Malvern and the Open Air School in Glenwood.

The riding school depends on donor funding.

“We currently lease six ponies from Ridgetop Equestrian Centre and also pay a lease for the use of the property. Other costs include vet fees, farrier fees, dentist fees, insurance, cost of equipment, training days for volunteers, and training and therapy of our horses,” said Durk.

Three volunteers are also needed per child in addition to the instructor of the day – two side walkers and a leader for the horse.

“Our ponies are an integral part of our programme and require special training to become a therapeutic riding pony. The cost of keeping and caring for the horses is our main expense,” said Durk.

Written by Nokulunga Majola

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Falling Victim to Fraud Has a Lasting Impact on Men’s Blood Pressure

A new study published in the Journal of the American Geriatrics Society suggests that experiencing financial exploitation, fraudulent schemes, and scams may raise a person’s blood pressure, especially in later life. A key difference in the findings was that fraud victimisation was linked with elevated blood pressure in men, but not in women.

Instead of focusing on subjective measures of health after fraud vicitimisation, this study included objective measures of physical health, specifically, systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure. Chronic elevation of these measures are known to contribute to end organ damage including stroke, cardiovascular disease morbidity, and mortality. 

The study participants consisted of 1200 older adults from the Rush Memory and Aging Project. During up to 11 years of annual observations, participants were asked about fraud victimisation and underwent serial blood pressure measurements.

In men, blood pressure elevations were observed after they had been the victims of fraud. Those elevations, compounded over time, could indicate future poor health. The rise in blood pressure persisted for years after the fraud had taken place, especially in old age.

“These findings show that fraud victimisation has important public health consequences and underscore the need for efforts to prevent exploitation,” said lead author Melissa Lamar, PhD, of Rush University Medical Center.

Source: Wiley

Durvalumab Plus Radiotherapy Boosts NSCLC Survival Rate

Shown here is a pseudo-colored scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Photo by National Cancer Institute on Unsplash

Durvalumab with radiotherapy for unresectable locally advanced non-small cell lung cancer (NSCLC) without chemotherapy achieve had a much greater 12-month progression-free survival rate than expected, with tolerable adverse reactions.  This phase II clinical trial was reported at the IASLC 2022 World Conference on Lung Cancer in Vienna.

Immunotherapy plays an important role in NSCLC and combination of radiotherapy and immunotherapy have been reported to have a synergistic effect. Durvalumab after concurrent chemoradiotherapy has been standard of care with unresectable locally advanced NSCLC (stage III/postoperative recurrent NSCLC). But some patients are unable to complete concurrent curative radiation therapy and cannot receive durvalumab.

Dr M. Tachihara of Kobe University Graduate School of Medicine and colleagues developed the DOLPHIN study – the first Phase II study of immunotherapy combined with curative radiotherapy for unresectable locally advanced non-small cell lung cancer. 

The team enrolled 35 adult patients with unresectable locally advanced non-small cell lung cancer with an ECOG performance status (PS) 0-1, PD-L1≥1% (SP263 clone). Of the 35 patients (median age, 72 years), 88.6% were male, 54.3% had ECOG PS 0, 96.1% had a history of smoking, 57.1% had non-squamous histology, and 25.7% were postoperative recurrence.  

Patients received curative radiation therapy (60Gy) plus durvalumab 10 mg/kg every two weeks simultaneously, followed by maintenance with durvalumab for up to 12 months until disease progression (PD) or unacceptable toxicity.

Thirty-four patients were evaluated for safety, and 33 patients for efficacy. The 12-month progression-free survival rate by ICR was 72.1% (90% CI, 59.1-85.1) after a median follow-up of 18.7 months. Confirmed overall response rate was 90.9% (95% CI, 75.7-98.1, ICR-assessed) with complete and partial response rates of 36.4% and 54.5%, respectively. Median progression-free survival was not reached by ICR-assessed, and 24.1 months (95% CI, 16.0-NR) by investigator-assessed. Thirteen patients (39.4%) discontinued durvalumab; six patients due to progression disease and seven due to adverse events (AE). Grade 3/4 adverse events occurred in 47.1%; the most common adverse event of grade 3/4 was lung infection (11.8%) and pneumonitis (11.8%). Grade 5 adverse events of any cause occurred in 2 patients (5.9%), one with lung infection and one with broncho-oesophageal fistula because of tumour progression during follow-up.

“This DOLPHIN study is the first report of immunotherapy combined with curative radiotherapy for unresectable LA-NSCLC. The primary endpoint of 12-months PFS rate was met and much higher than expected value. It suggests that this treatment strategy is promising with tolerable adverse effects and appropriate as a study treatment for phase III trials,” said Dr. Tachihara.

Source: IASLC

Chronic Inflammation Link to Low Vitamin D Explains Some Controversies

Vitamin D pills
Photo by Michele Blackwell on Unsplash

New genetic research shows a direct link between low vitamin D levels and high levels of inflammation, providing an important biomarker to identify people at higher risk of or severity of chronic illnesses with an inflammatory component, such as type 2 diabetes. The findings, published in the International Journal of Epidemiology, also helps to settle some of the controversies surrounding the ‘sunshine vitamin’.

The study drew on genetic data for 294 970 participants in the UK Biobank, using Mendelian randomisation to show the association between vitamin D and C-reactive protein levels, an indicator of inflammation.

University of South Australia’s Dr Ang Zhou, the study’s lead researcher, said that the findings suggest that boosting vitamin D in people with a deficiency may reduce chronic inflammation.

“This study examined vitamin D and C-reactive proteins and found a one-way relationship between low levels of vitamin D and high levels of C-reactive protein, expressed as inflammation.

“Boosting vitamin D in people with deficiencies may reduce chronic inflammation, helping them avoid a number of related diseases.”

The study also raises the possibility that having adequate vitamin D concentrations may mitigate complications arising from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as CVDs, diabetes, and autoimmune diseases.

Senior investigator and Director of UniSA’s Australian Centre for Precision Health, Professor Elina Hyppönen, said that these results offer an explanation for some of the controversies in reported associations with vitamin D.

“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit.” Prof Hyppönen said.

“These findings highlight the importance of avoiding clinical vitamin D deficiency, and provide further evidence for the wide-ranging effects of hormonal vitamin D.”

Source: University of South Australia

Collagen’s Role in Breast Cancer Includes Triggering Metastasis

Breast cancer cells
Breast cancer cells. Image source: National Cancer Institute on Unsplash

Type XII collagen plays a key role in regulating the organisation of the tumour matrix, according to research published in the journal Nature Communications. The study investigators also discovered that high levels of collagen XII can trigger metastasis.

Cancer cells continually interact with the tumour microenvironment one component of which is the extracellular matrix. Collagen is an important part of this tumour microenvironment, but just how it influences tumours has not been understood.

“There’s still a lot we don’t know about the role of the extracellular matrix in cancer metastasis. Our study shows that collagen XII plays an important role in breast cancer progression and metastasis,” said Associate Professor Thomas Cox, senior author of the study.

“Imagine cancer cells as seeds, and the tumour microenvironment as the soil. By studying the soil – the extracellular matrix – we can begin to understand what makes some tumours more aggressive than others, and by extension, begin to develop new ways to treat cancer,” he explained.

The research also suggests that measuring the level of collagen XII in a patient’s tumour biopsy could potentially be used as an additional screening tool to identify aggressive breast cancers with higher rates of metastasis, such as in the triple-negative type of breast cancer. Furthermore, collagen XII might be a possible target for future treatments.

The extracellular matrix is a 3D meshwork of around 300–400 core molecules, including several collagen proteins. This matrix provides structural and functional support to cells and tissues in all parts of the body.

In this study, the researchers catalogued how the tumour matrix changes over time and have generated a comprehensive database of these changes, which has been made freely available to researchers.

The team focused on collagen XII, one of 28 types of collagen in the body. Collagen XII plays an important role in organising other collagens and can have profound effects on the 3D structure of the extracellular matrix.

The researchers studied tumours in mouse models from the earliest pre-clinical stages of cancer, right through to late-stage tumours. They found that as the tumours developed, many matrix molecules changed, and importantly the level of collagen XII was also increased.

“Collagen XII seems to be altering the properties of the tumour and makes it more aggressive,” said first author Michael Papanicolaou. “It changes how collagens are organised to support cancer cells escaping from the tumour and moving to other sites like the lungs.”

The team then genetically manipulated collagen XII production, looking at the effects of metastasis to other organs. They found that as levels of collagen XII increased, so did metastasis. These findings were then confirmed in human tumour biopsies, which showed that high levels of collagen XII are associated with higher metastasis and poorer overall survival rates.

Further research will focus on studying more human samples, and investigating possible therapeutic pathways.

Source: Garvan Institute of Medical Research

Aspirin and Antiplatelets after Coronary Artery Grafts are a Double-edged Sword

Source: Wikimedia Commons CC0

A new analysis published in JAMA shows that a combination of aspirin and another antiplatelet agent can prevent clotting after coronary artery bypass grafts but also increases the risk of potentially dangerous bleeding. This double-edged finding from investigators suggests physicians should carefully weigh the use of these medications after this procedure.

A Weill Cornell Medicine and NewYork-Presbyterian team led by Dr Mario Gaudino, a coronary artery bypass surgeon, examined data from 1668 grafts in which surgeons use a saphenous vein graft to circumvent blocked coronary arteries. It is common for blood clots to form within the grafted vein, for which patients are typically given aspirin. Some evidence suggests that aspirin along with a prescription strength antiplatelet agent such as ticagrelor can more effectively prevent this clotting.

“We found that, yes, this dual therapy significantly reduces the risk that the grafts will fail. However, for the first time, we have shown that this approach also carries a significant risk of clinically important bleeding,” said Dr Gaudino. “So, the benefit comes at a price.”

Taken together, these results indicate physicians should base their decisions on patients’ individual circumstances and avoid using this approach for those with conditions that put them at risk of bleeding, he said.

In more than 90% of coronary artery bypass grafts, surgeons take a graft from one of the patient’s saphenous veins, which return blood up the leg. However, within a year, up to a quarter of these grafts become obstructed.

While studies have examined the benefit of aspirin and ticagrelor, known as dual antiplatelet therapy (DAPT), these studies were small and had conflicting conclusions. The team contacted researchers on four such trials to obtain access to their raw data. They aggregated the data and effectively created a much larger study capable of generating more robust conclusions.

They found a failure rate of approximately 11% in patients who received a combination of aspirin and ticagrelor, while blockages occurred in 20% of grafts when patients received only aspirin. However, compared to aspirin alone, DAPT brought on more bleeding events that, while generally not life threatening, required medical attention.

In these previous trials, patients received DAPT for a full year. However, most graft failure occurs in the first few months after surgery. Dr Gaudino plans a further test of aspirin and ticagrelor over one to three months to see if a shortened course offers the same benefit with less risk of bleeding.

Source: Weill Cornell Medicine

Body Posture, Stomach Motility Affect Oral Pill Bioavailability

Photo by danilo.alvesd on Unsplash

While oral administration of a pill or capsule is a simple and cheap route, it is also the most complex way for the human body to absorb an active pharmaceutical ingredient, due to the stomach environment’s influence on bioavailability. Using highly detailed computer simulations, researchers have now found that stomach motility and posture (leaning right, left or backwards) significantly affect bioavailability.

The rate of dissolution and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum is modulated by gastric motility, physical properties of the pill, and the contents of the stomach. This results in varying rates of pill dissolution and nonuniform emptying of the drug into the duodenum and, occasionally, gastric dumping in the case of modified-release dosage. Current in vitro procedures for assessing dissolution of oral drugs do not simulate this process well.

In Physics of Fluids, researchers used a biomimetic computer simulation based on the realistic anatomy and morphology of the stomach (a ‘StomachSim’) to investigate and quantify the effect of body posture and stomach motility on drug bioavailability over the first few minutes of absoprtion.

 The simulations show that changes in posture can potentially have a significant (up to 83%) effect on the emptying rate of the API into the duodenum. A 45 degree lean to the left greatly reduced the amount of active ingredient per cycle released into the duodenum, while a lean to the right dramatically increased it over the upright case.

Similarly, the researchers found that a reduction in antral contractility associated with gastroparesis significantly reduced the dissolution of the pill as well as emptying of the API into the duodenum. The simulations show that for an equivalent motility index, the reduction in gastric emptying due to neuropathic gastroparesis is larger by a factor of about five compared to myopathic gastroparesis.

“Oral administration is surprisingly complex despite being the most common choice for drug administration,” said co-author Rajat Mittal. “When the pill reaches the stomach, the motion of the stomach walls and the flow of contents inside determine the rate at which it dissolves. The properties of the pill and the stomach contents also play a major role.

“However, current experimental or clinical procedures for assessing the dissolution of oral drugs are limited in their ability to study this, which makes it a challenge to understand how the dissolution is affected in different stomach disorders, such as gastroparesis, which slows down the emptying of the stomach.”

Together, these issues pose several challenges for the design of drug delivery.

“In this work, we demonstrate a novel computer simulation platform that offers the potential for overcoming these limitations,” said Mittal. “Our models can generate biorelevant data on drug dissolution that can provide useful and unique insights into the complex physiological processes behind the oral administration of pills.”

The researchers note that the simulation required a lot of computational time, only capturing the first few minutes of the process, and are working on faster methods to capture differences over the period of an hour.

Source: American Institute of Physics