Tag: 13/1/25

Categories : HIVTags : Leave a comment

Sub-Saharan Africa Leads Global HIV Decline

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Photo by Sergey Mikheev on Unsplash

The Institute for Health Metrics and Evaluation (IHME) has published a new study in The Lancet HIV journal that revealed significant progress in the global fight against HIV/AIDS, alongside a stark warning that current trends indicate the world is not on track to meet the ambitious UNAIDS 2030 targets.

The research, which analysed the global, regional, and national burden of HIV/AIDS among 204 countries and territories from 1990 to 2021 and forecasted trends to 2050, highlighted a mixed landscape of achievements and challenges in the battle against this global epidemic.

Between 2010 and 2021, new HIV infections decreased from 2.1 million to 1.7 million, and HIV-related deaths decreased from 1.2 million to 718 000. Despite this progress, researchers found regional variation in the HIV response and forecast the world is not on track to meet UNAIDS 2030 targets to cut new HIV infections and AIDS-related deaths by 90%.

Sub-Saharan Africa leads the world in cutting new HIV infections and deaths from the disease

The global decline in HIV incidence is largely driven by sub-Saharan Africa, where the likelihood of getting HIV over a lifetime has fallen by 60% since its peak in 1995. This region also achieved the largest decrease in population without a suppressed level of HIV (PUV), from 19.7 million people in 2003 to 11.3 million people in 2021.

In contrast, the lifetime probability of HIV acquisition increased from 0.4% to 2.8% between 1995 and 2021, while PUV rose from 310 000 people to 680 000 people between 2003 and 2021 in Central Europe, Eastern Europe, and Central Asia.

“The world has made remarkable global progress to significantly reduce the number of new HIV infections and lives lost to the disease, yet there are remaining challenges to overcome,” said Dr. Hmwe Kyu, IHME Associate Professor and study author. “More than a million people acquire a new HIV infection each year and, of the 40 million people living with HIV, a quarter are not receiving treatment,” she added.

Despite progress, UNAIDS’s HIV infection reduction and AIDS-related deaths 2030 targets won’t be met

Although substantial progress has been made against HIV incidence and AIDS-related mortality, the world is not on target to meet the UN’s 2030 targets to reduce new HIV infections and AIDS-related deaths by 90%.

The number of people living with HIV is expected to peak at 44.4 million by 2039, followed by a gradual decrease to 43.4 million people by 2050.

“The global community must make sustained and substantive efforts to sharpen the focus on prevention, optimize access to antiretroviral therapy, and make HIV testing widely available to achieve prompt diagnosis and linkage to care,” said Dr. Kyu.

New cases of HIV, and deaths associated with the disease, are expected to continue to decrease globally. However, long-term increases have been forecast in North Africa and the Middle East, where only 67% of people living with HIV are aware of their status, 50% access ART, and 45% are virally suppressed.

“Although new HIV infections and HIV-related mortality have fallen globally, they are increasing in several nations and regions. Our analysis is designed to inform countries’ sustained response to HIV that includes expanded access to lifesaving antiretroviral therapy (ART), effective prevention options, and innovative care models,” said Austin Carter, IHME Research Scientist.

The study authors set a series of recommendations to sustain and invigorate the global HIV response, including the strengthening of the US President’s Emergency Plan for AIDS Relief (PEPFAR) and other similar public health programs dedicated to HIV control, as well as the expansion of prevention services, with a multitude of existing and emerging technologies. Additionally, interventions and care delivery models that work must be studied and implemented effectively and equitably, with special emphasis on measuring progress and addressing remaining gaps in our collective goal of ending the HIV epidemic.

The findings and recommendations from the new study by the GBD 2021 HIV collaborators serve as a call to action for governments, health care providers, and the global community to renew their commitment to ending the HIV epidemic. Only through sustained, comprehensive, and equitable efforts will the world be able to achieve the UNAIDS 2030 targets and ultimately eradicate HIV/AIDS as a public health threat.

Source: Institute for Health Metrics and Evaluation

Categories : Antibiotics Lab Tests and ImagingTags : Leave a comment

PCT Test Fails to Shorten IV Antibiotics for Hospitalised Children

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Photo by Marcelo Leal on Unsplash

A groundbreaking UK study led by the University of Liverpool has examined whether an additional procalcitonin (PCT) blood test could safely shorten the time children spend on intravenous (IV) antibiotics in hospitals. Despite promising previous analysis, the findings showed that using the PCT biomarker to guide treatment decisions did not reduce antibiotic duration when compared to usual care.

The study, published in the Lancet Child & Adolescent Health, is part of the ‘Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection’ (BATCH) trial. BATCH is a UK national research trial to tackle antibiotic overuse in hospitalised children and reduce the spread of antimicrobial resistance (AMR).

Antibiotic overuse is a key driver of AMR, one of the world’s greatest public health challenges. Infections caused by resistant bacteria lead to longer hospital stays, higher healthcare costs, and increased mortality. Children are especially vulnerable, and smarter use of antibiotics is essential to protect their future health.

This study, conducted across 15 hospitals, enrolled nearly 2000 children aged between 72 hours and 18 years with suspected bacterial infections.

The researchers found that adding the PCT test to routine care did not reduce the duration of IV antibiotic use. The test was safe but costlier than standard methods, and healthcare teams faced challenges integrating it into their decision-making processes.

The study comes after a systematic review and cost-effectiveness analysis conducted by NICE in 2015 evaluated PCT testing to guide antibiotic therapy for the treatment of sepsis, and recommended further studies to adequately assess the effectiveness of adding PCT algorithms to guide antibiotic treatment in hospitalised adults and children with suspected or confirmed serious bacterial infection.

The results highlight that introducing new tools like PCT tests alone isn’t enough. Effective use requires:

  • Robust Antimicrobial Stewardship (AMS) programmes: Many hospitals already use AMS programmes to ensure antibiotics are prescribed responsibly, reducing unnecessary use.
  • Training and education for Clinicians: Familiarity with new tests and confidence in interpreting results are crucial for success.
  • Implementation research: Future studies should identify barriers and facilitators to implementation to optimise fidelity of the intervention.
  • Behaviour change: Better understanding of the complex interactions influencing whether/how/why clinicians act on information from diagnostic tests to make antibiotic prescribing decisions will improve trial intervention fidelity and facilitate implementation and adoption of tests shown to be effective.

The findings emphasise the importance of continuing to invest in AMS programmes and public health campaigns to reduce antibiotic misuse. The researchers note that although PCT-guided treatment didn’t provide clear benefits in this trial, it could still play a role in specific situations with further refinement.

Chief investigator Professor Enitan Carrol, from the University of Liverpool, said: “The BATCH study was a pragmatic trial evaluating if the intervention works under real-world conditions where clinicians do not have to adhere to diagnostic algorithms about antibiotic discontinuation. Adherence to the algorithm was low in our study, and there were challenges in integrating the test into routine clinical workflows. The study highlights the importance of including behaviour change and implementation frameworks into pragmatic trial designs.”

Source: University of Liverpool

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High-fat Diets are ‘Ticking Time Bombs’ for Liver Cancer

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These images show slices of mouse liver under the microscope, with tumours outlined in yellow and green indicating the expression of different proteins within cells. The left column is a control group. In the centre column, the protein detected (TBG-Cre) is expressed in all liver cells, so the entire image appears green. In the right column, the protein detected (p21-Cre) is only expressed in senescent liver cells. Because green is only visible within the tumour area, the results show that liver tumours originate from previously senescent liver cells. Photo credit: UC San Diego Health Sciences

A new study on the development of liver cancer reveals a complex interplay between cellular metabolism and DNA damage that drives the progression of fatty liver disease to cancer. The findings, published in Nature, suggest new paths forward for preventing and treating liver cancer and have significant implications on our understanding of cancer’s origin and the effects of diet on our DNA.

The incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC), has grown by 25-30% in the past two decades, with much of the growth attributed to the dramatic rise in fatty liver disease. About 20% of individuals with fatty liver disease have a severe form of the disease, called metabolic dysfunction-associated steatohepatitis (MASH), that greatly increases the risk of HCC. However, how MASH transitions to liver cancer is not well understood.

“Going from fatty liver disease to MASH to liver cancer is a very common scenario, and the consequences can be deadly,” said Michael Karin, PhD, Distinguished Professor in the Department of Pharmacology at UC San Diego School of Medicine. MASH ends up destroying the liver, or leading to often-fatal liver cancer, but little is know of the process at the subcellular level.

The researchers used a combination of mouse models and human tissue specimens and databases to demonstrate that MASH-inducing diets, which are rich in fat and sugar, cause DNA damage in liver cells that causes them to go into senescence, a state in which cells are still alive and metabolically active but can no longer divide. Senescence is a normal response to a variety of cellular stressors. In a perfect world, senescence gives the body time to repair damage or eliminate the damaged cells before they’re allowed to proliferate more widely and become cancerous.

“A poor, fast-food diet can be as dangerous as cigarette smoking in the long run. People need to understand that bad diets do far more than just alter a person’s cosmetic appearance. They can fundamentally change how our cells function, right down to their DNA.”

Michael Karin, PhD

However, as the researchers discovered, this isn’t what happens in liver cells, also known as hepatocytes. In hepatocytes, some damaged cells survive this process.

These cells are, according to Karin, “like ticking time bombs that could start proliferating again at any point and ultimately become cancerous.”

“Comprehensive genomic analyses of tumour DNA indicate that they originate from liver cells damaged by MASH, emphasising a direct link between diet-induced DNA damage and the development of cancer,” added study co-author Ludmil Alexandrov, PhD, associate professor of cellular and molecular medicine and bioengineering at UC San Diego and member of UC San Diego Moores Cancer Center.

The findings suggest that developing new drugs to prevent or reverse DNA damage could be a promising therapeutic approach for preventing liver cancer, particularly in people with MASH.

“There are a few possibilities for how this could be leveraged into a future treatment, but it will take more time and research to explore these ideas,” said Karin. “One hypothesis is that a high-fat diet could lead to an imbalance in the raw materials our cells use to build and repair DNA, and that we could use drugs or nutri-chemicals to correct these imbalances. Another idea is developing new antioxidants, much more efficient and specific than the ones we have now, and using those could help block or reverse the cellular stress that causes DNA damage in the first place.”

In addition to opening these new avenues of treatment for liver cancer, the study also offers new insight into the relationship between aging and cancer.

“We know that aging increases the risk of virtually all cancers and that aging is associated with cellular senescence, but this introduces a paradox since senescence is supposed to guard against cancer,” said Karin. “This study helps reveal the underlying molecular biology that allows cells to re-enter the cell cycle after undergoing senescence, and we believe that similar mechanisms could be acting in a wide range of cancers.”

The findings also help directly quantify the detrimental effects of poor diet on cellular metabolism which, according to Karin, could be used to help guide public health messaging related to fatty liver disease.

“A poor, fast-food diet can be as dangerous as cigarette smoking in the long run,” said Karin. “People need to understand that bad diets do far more than just alter a person’s cosmetic appearance. They can fundamentally change how our cells function, right down to their DNA.”

Source: University of California – San Diego

Categories : Gastrointestinal Obstetrics & GynaecologyTags : Leave a comment

The Massive Changes to Mothers’ Intestines in Pregnancy and Breastfeeding

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When women are pregnant and nurse their babies, their bodies change and various organs, such as the breasts or the immune system, are adapted to ensure the health of both mother and child. This happens throughout evolution in all mammals. An international research team led by Josef Penninger and Masahiro Onji, Medical University of Vienna, now reports the surprising finding that the intestine also changes completely in pregnant and nursing females, resulting in a doubling of the intestinal surface area and a striking structural reorganisation.

Reporting their findings in Nature, the researchers also provide the first genetic and mechanistic evidence of how this intestinal epithelial expansion occurs in mothers, with direct implications for the transgenerational health of the babies.

A multinational team led by Josef Penninger observed that the intestinal villi reorganise during pregnancy and breastfeeding and significantly enlarge, doubling their surface area. The studies were carried out in genetically modified mice and intestinal organoids from mice and humans – self-organised three-dimensional tissues derived from stem cells in the intestine. Mechanistically, the researchers identified the RANK receptor/RANK ligand (RANK/RANKL) system as the key to the villous enlargement of the small intestine during reproduction, which is regulated by sex and lactation hormones. When mice were engineered to lack the RANK/RANKL system in the intestine, the villous expansion during pregnancy and breastfeeding was significantly impaired.

For decades, researchers have studied the RANK/RANKL system as a key facilitator of essential, evolutionarily conserved processes. The Penninger group has already identified key functions of the RANK/RANKL system in bone turnover, in the biology of the mammary gland, in breast cancer, and in immune tolerance in pregnancy, contributing to the development of drugs against bone loss used by millions of people and clinical trials for breast cancer prevention and cancer immunotherapies are underway. The researchers now discovered that these intestinal changes, which appear to be completely reversible when nursing is stopped, are important for proper feeding and nourishment of the babies.

“Our study shows that the impairment of this intestinal expansion by the lack of the RANK/RANKL system during pregnancy changes the milk of the nursing mothers. This results in lower weights of the babies and transgenerational long-term metabolic consequences,” states lead author Masahiro Onji. “Mothers need to eat for themselves and their babies. These new studies provide for the first time a molecular and structural explanation of how and why the intestine changes to adapt to enhanced nutrient demand of mothers, which is probably the case in all pregnant and nursing mammals,” adds study leader Josef Penninger.

How mothers adapt to the demands of pregnancy and breastfeeding remains a central question of evolution and human health. During this phase, female hormones influence multiple organs to control and change their structure and functions, which is crucial for the health of the mother and the development of the offspring. It was known that pregnant women have enhanced nutrient demands. However, this fundamental aspect has not been well studied until now:

“By identifying the RANK/RANKL system as the driving force behind intestinal adaptation during pregnancy and lactation, our study contributes to a deeper understanding of biological processes that are of fundamental importance for evolution and human health”, says Josef Penninger, summarising the impact of the findings.

This massive expansion is controlled by sex and pregnancy hormones, which change the stem cells in the gut via the RANK/RANKL system and then give the intestinal cell a survival signal to grow much larger. This growth then leads to a near doubling of the intestinal surface area, which also increases the molecular machinery for the uptake of sugar, protein, and fat, and even leads to a profound architectural change in the intestinal villi, which probably slows down the flow of food, again maximising the uptake of nutrients.

Josef Penninger said: “Our team has discovered an amazing new way how mother’s bodies change to keep babies healthy. Hardly anybody knew about this, apart from a few old studies that have largely been forgotten. We have also found that this system, via stem cells, can directly affect tumours in the intestine; maybe we can learn from pregnant and nursing mothers to reversibly rewire this system to develop new treatments and a better understanding of intestinal cancer or gut regeneration.”

Source: Medical University of Vienna

Categories : Injury & Trauma NeurologyTags : Leave a comment

Men More Than Three Times as Likely to Die From a Brain Injury, New Study Shows

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Photo by Anna Shvets

A new analysis of mortality data reveals the disproportionate impact of traumatic brain injuries (TBI) on older adults, males and certain racial and ethnic groups. The study, published in the peer-reviewed journal Brain Injury, provides a comprehensive analysis of TBI-related deaths across different population groups across the US in 2021.

The findings indicate that suicides remain the most common cause of TBI-related deaths, followed by unintentional falls, and specific groups are disproportionately affected by these tragedies.

Men, in particular, were found to be most likely to die from a TBI – more than three times the rate of women (30.5 versus 9.4). The reasons observed were multifactorial and could reflect differences in injury severity following a fall or motor vehicle crash, to the interaction of sex and age – with TBI outcomes in men worsening with age, while postmenopausal women fare better than men of similar age.

“While anyone is at risk for getting a TBI, some groups have a higher chance than others of dying from one. We identified specific populations who are most affected. In addition to men, older adults are especially at risk, with unintentional falls being a major cause of TBI-related death. American Indian or Alaska Native people also have higher rates of these fatal injuries,” says lead author Alexis Peterson PhD, of the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention.

“These findings highlight the importance of tailored prevention strategies to reach groups who may be at higher risk and the role healthcare providers can play in reducing TBI-related deaths through early intervention and culturally sensitive care.”

TBI remains a leading cause of injury-related death in the US In 2020, TBIs were associated with around a quarter of all injury-related deaths.

Using data from the National Vital Statistics System, the new analysis identified 69 473 TBI-related deaths among US residents during 2021. The age-adjusted TBI-related mortality rate was 19.5 per 100 000, representing an 8.8% increase from 2020.

Through statistical modeling, the researchers examined the simultaneous effect of multiple factors such as geographic region, sex, race and ethnicity, and age, on TBI-related mortality.

Key findings include:

  • Older adults (75+) had the highest rates of TBI-related deaths, with unintentional falls being the most common cause in this age group.
  • Non-Hispanic American Indian/Alaska Native individuals experienced the highest TBI-related death rate (31.5) compared to other racial and ethnic groups.
  • There were 37,635 TBI-related deaths categorised as unintentional injuries (ie, motor vehicle crashes, unintentional falls, unintentionally struck by or against an object, other).
  • 30,801 were categorized as intentional injuries (ie, all mechanisms of suicide and homicide).
  • Children aged from birth to 17 years accounted for around 4% of TBI-related deaths (2,977).

The authors emphasise the critical role of healthcare providers in preventing TBI-related deaths, particularly with groups at higher risk. “By assessing patients who may be at higher risk for TBI, especially due to falls or mental health challenges, healthcare providers can make timely referrals and recommend culturally tailored interventions to prevent further injury or death,” says Dr Peterson.

Public health efforts should focus on addressing the underlying causes of TBI-related deaths, such as unintentional falls and mental health crises, to help prevent further loss of life. “TBIs remain a significant public health concern, especially among older adults, men, and certain racial and ethnic groups,” says Peterson.  “CDC has proven resources that healthcare providers can use to not only reduce health disparities that increase the risk for TBI but also improve care for anyone affected by a TBI.”

The authors note the COVID-19 pandemic could have influenced TBI-related death trends in 2021. They also acknowledge several limitations of this analysis, including potential misclassification or incomplete documentation of causes on death certificates, which may lead to inaccuracies in estimating TBI-related deaths.

Source: Taylor & Francis Group