Year: 2024

World’s First Gene-edited Pig Kidney Transplant into Living Recipient

Surgeons prepare the pig kidney for transplantation. Credit: Massachusetts General Hospital

Massachusetts General Hospital (MGH) has announced the world’s first successful transplant of a genetically-edited pig porcine) kidney into a 62-year-old man living with end-stage kidney disease (ESKD). Surgeons from the Mass General Transplant Center conducted the four-hour-long surgery on Saturday, March 16. The procedure marks a major milestone in the quest to provide more readily available organs to patients. Mass General Brigham is an internationally recognised leader in transplantation services, providing advanced care for a wide spectrum of organ and tissue transplants throughout its renowned academic medical system.

Under the leadership of Leonardo V. Riella, MD, PhD, Medical Director for Kidney Transplantation, Tatsuo Kawai, MD, PhD, Director of the Legorreta Center for Clinical Transplant Tolerance, along with Nahel Elias, MD, Interim Chief of Transplant Surgery and Surgical Director for Kidney Transplantation, a genetically-edited pig kidney with 69 genomic edits was successfully transplanted into a living patient.

Mass General Brigham has a rich history in organ transplant innovation, including the world’s first successful human organ transplant (kidney) performed at Brigham and Women’s Hospital in 1954 and the nation’s first penile transplant, performed at MGH in 2016. Mass General Brigham transplantation programs draw upon the deep, integrated expertise of some of the world’s leading transplant physicians and scientists who collaborate across experienced multidisciplinary teams to advance medicine and improve the lives of patients.

“Mass General Brigham researchers and clinicians are constantly pushing the boundaries of science to transform medicine and solve significant health issues facing our patients in their daily lives,” said Anne Klibanski, MD, President and CEO, Mass General Brigham. “Nearly seven decades after the first successful kidney transplant, our clinicians have once again demonstrated our commitment to provide innovative treatments and help ease the burden of disease for our patients and others around the world.”

“The tireless commitment of our clinicians, researchers and scientists to improving the lives of our transplant patients – both current and future – is at the very heart and soul of academic medicine and what it means to work and provide care at Mass General Brigham,” said David F. M. Brown, MD, President, Academic Medical Centers, Mass General Brigham. “We are so thankful to the incredible staff throughout our hospitals who helped make this surgery a success, and to the patient for his bravery and courage.”

“The success of this transplant is the culmination of efforts by thousands of scientists and physicians over several decades. We are privileged to have played a significant role in this milestone. Our hope is that this transplant approach will offer a lifeline to millions of patients worldwide who are suffering from kidney failure,” Kawai said.

The pig kidney was provided by eGenesis, from a pig donor that was genetically-edited using CRISPR-Cas9 technology to remove harmful pig genes and add certain human genes to improve its compatibility with humans. Additionally, scientists inactivated porcine endogenous retroviruses in the pig donor to eliminate any risk of infection in humans. Over the past five years, MGH and eGenesis have conducted extensive collaborative research, with the findings published in Nature in 2023.

This successful procedure in a living recipient is a historic milestone in the emerging field of xenotransplantation – the transplantation of organs or tissues from one species to another – as a potential solution to the worldwide organ shortage. According to the United Network for Organ Sharing (UNOS), more than 100 000 people in the U.S. await an organ for transplant and 17 people die each day waiting for an organ. A kidney is the most common organ needed for transplant, and end-stage kidney disease rates are estimated to increase 29-68% in the U.S. by 2030, according to literature published in the Journal of the American Society of Nephrology.

The patient, Mr. Richard ‘Rick’ Slayman of Weymouth, Mass., is recovering well at MGH and is expected to be discharged soon.

“The real hero today is the patient, Mr Slayman, as the success of this pioneering surgery, once deemed unimaginable, would not have been possible without his courage and willingness to embark on a journey into uncharted medical territory. As the global medical community celebrates this monumental achievement, Mr Slayman becomes a beacon of hope for countless individuals suffering from end-stage renal disease and opens a new frontier in organ transplantation,” said Joren C. Madsen, MD, DPhil, Director of the MGH Transplant Center.

Mr Slayman said in a statement, “I have been a Mass General Transplant Center patient for 11 years and have the highest level of trust in the doctors, nurses, and clinical staff who have cared for me. When my transplanted kidney began failing in 2023, I again trusted my care team at MGH to meet my goals of not just improving my quality of life but extending it. My nephrologist, Dr Winfred Williams, MD and the Transplant Center team suggested a pig kidney transplant, carefully explaining the pros and cons of this procedure. I saw it not only as a way to help me, but a way to provide hope for the thousands of people who need a transplant to survive. I want to thank everyone at MGH who has cared for me, especially Dr Williams, Dr Kawai, the surgeon who performed my first kidney transplant and now this one, and Dr Riella, who has orchestrated the logistics behind this new transplant. They have supported me during every step of the journey, and I have faith they will continue to do so.”

Mr Slayman, who has been living with Type 2 diabetes and hypertension for many years, previously received a kidney transplant from a human deceased donor in December 2018, performed at MGH by Kawai, after being on dialysis seven years prior. The transplanted kidney showed signs of failure approximately five years later and Mr Slayman resumed dialysis in May 2023. Since resuming dialysis, he encountered recurrent dialysis vascular access complications requiring visits to the hospital every two weeks for de-clotting and surgical revisions, significantly impacting his quality of life and a common problem among dialysis patients.

“The continued success of this groundbreaking kidney transplant represents a true milestone in the field of transplantation. It also represents a potential breakthrough in solving one of the more intractable problems in our field, that being unequal access for ethnic minority patients to the opportunity for kidney transplants due to the extreme donor organ shortage and other system-based barriers. This health disparity has been the target of many national policy initiatives for over 30 years, with only limited success. An abundant supply of organs resulting from this technological advance may go far to finally achieve health equity and offer the best solution to kidney failure – a well-functioning kidney – to all patients in need. I commend Mr Slayman, who has been my patient for many years, for his courageousness in becoming a trailblazer in the field of transplantation,” Williams said.

The procedure was performed under a single FDA Expanded Access Protocol (EAP) – known as compassionate use – granted to a single patient or group of patients with serious, life-threatening illnesses or conditions to gain access to experimental treatments or trials when no comparable treatment options or therapies exist. Mr. Slayman also received infusion of novel immunosuppressant drugs, tegoprubart, provided by Eledon Pharmaceuticals, Inc., and ravulizumab, provided by Alexion Pharmaceuticals, Inc.

Source: Massachusetts General Hospital

Harnessing Technology to Improve Tuberculosis Outcomes

Dr Phathokuhle Zondi, Clinical Lead: Unu Health

Few realise the extent of the global burden of tuberculosis (TB) or know how many people still succumb to this disease every year. The Centres for Disease Control in the United States estimates that two billion people – a quarter of the world’s population – may be infected with TB, with 10.6 million becoming ill each year. Although TB is preventable and treatable, around 3 500 people lose their lives to it every day, making up an annual mortality rate of 1.3 million people. This means that TB ranks third to only COVID-19 and HIV/Aids as the world’s most deadly infectious disease. 

These statistics are alarming and demand immediate attention from all sectors of society. It is crucial to recognise the potential of technology and digital platforms in revolutionising treatment outcomes. By harnessing the power of innovation, we can transform the way in which TB is diagnosed, treated and managed, ultimately saving lives and reducing the burden of this disease.

Equally as sobering is the fact that around 30 percent of people who become ill with TB are missed by healthcare screenings and do not get the care they need, leading to poor outcomes and an increased spread of the disease, especially in remote, rural and underserved communities. People infected with TB do not necessarily become ill but can pass on the bacteria that causes the infection to between ten and fifteen other people through coughing, sneezing or the transfer of saliva. Approximately 10% of those infected go on to develop an active form of disease at some time in their lives.

TB in South Africa

In South Africa, the first-ever National Tuberculosis Prevalence Survey, published in 2018, found that the country is one of 30 countries with the highest prevalence of TB in the world. When adjusted for population size, it is often ranked as the country with the highest prevalence in the word.

The power of digital healthcare has the potential to change this scenario radically. The greatest challenges we face are the low rate of diagnosis and poor access to – and compliance with – treatment. That’s where digital platforms have such a significant role to play.

How digital can make a difference

Digital health platforms have the potential to revolutionise the fight against TB by improving early detection, enhancing treatment adherence and strengthening healthcare delivery systems. Through the integration of mobile applications, telemedicine, artificial intelligence (AI) and big data analytics, we can address the key challenges of TB diagnosis, treatment access and patient support.

Firstly, digital tools enable early detection and diagnosis of TB cases. Advanced imaging techniques, supported by AI algorithms, can swiftly identify TB-related abnormalities in medical images, facilitating prompt intervention and preventing the progression of the disease. Predictive analytics can also forecast TB outbreaks and hotspot areas, enabling healthcare authorities to take proactive measures to contain the spread of the disease.

Secondly, digital health platforms facilitate remote consultations and monitoring, which is particularly beneficial for patients in remote or underserved areas. By providing timely medical intervention and personalised support, these platforms promote treatment adherence and improve patient outcomes.

Thirdly, mobile health applications empower patients to actively participate in their care management. Through features such as medication reminders, digital health checks and access to educational resources, individuals can adhere to treatment protocols better, ultimately contributing to improved health outcomes.

In addition, digital health platforms streamline healthcare delivery by facilitating data interoperability and real-time monitoring of TB trends. Innovative technologies such as TB Check, the free service application of the South African National Department of Health, are revolutionising TB testing as they are being used to determine the risk of contracting TB and to provide guidelines on how to access testing and treatment.

Further, applications such as One Impact, a comprehensive digital health platform, connects individuals with TB support groups, provides access to TB services and enables the reporting of difficulties in accessing care. By leveraging such platforms, national TB programmes can gain valuable insights into the needs and concerns of affected communities, leading to more responsive and effective service delivery.

TB is treatable and curable, especially when patients are diagnosed early, have access to the medication they need and can be carefully monitored throughout their treatment programme.

As we observe World TB Day on 24 March, it is encouraging to know that the integration of digital health platforms provides immense promise in transforming TB outcomes. To realise this potential, collaboration among governments, healthcare providers, technology companies and civil society organisations is essential. By prioritising investment in innovative solutions and leveraging digital technologies, we can accelerate progress towards the elimination of TB and save countless lives. It is time to harness the power of technology to combat TB and create a healthier, TB-free world for all.

New Research Affirms Five Factors to Ensure an Infant Thrives

Photo by Chayene Rafaela on Unsplash

The “Thrive 5” are five conditions to ensure an infant in the first year of life has what they need for healthy development. Those conditions include environmental stimulation, nutrition, neighbourhood safety, positive caregiving and regular circadian rhythms and sleep. Simple, and yet, it has not yet been prioritised for many reasons including the fact that researchers had not provided empirical data to support making the Thrive 5 a public health priority.

Researchers at Washington University in St. Louis think it’s time to change that. In new research published in JAMA Pediatrics, Deanna Barch and Joan Luby make the case that “Thrive Factor” is a key element of healthy human brain, behavioural and cognitive development.

“When they have access to these basic supports, even in the face of adverse environments, it enhances their brain development, cognition (measures of IQ) and social-emotional development,” said Luby, MD, the university’s Samuel and Mae S. Ludwig Professor of Child Psychiatry at the School of Medicine.

There have been plenty of studies touting the benefits of individual thrive factors, such as encouraging breast-feeding to facilitate growth in general, but this new study looks at several key factors known to influence brain development and shows their relationship to outcomes at age 3.

“The novelty here is putting them all together and thinking of them as a constellation of things that are necessary and important for a child to be able to thrive,” said Barch, PhD, vice dean of research, a professor of psychological & brain sciences in Arts & Sciences and the Gregory B. Couch Professor of Psychiatry at the School of Medicine.

The study is part of a change in thinking in the child development field as scientists have learned that much of our health is not just genetically predetermined but is powerfully influenced by the psychosocial environment. The human brain is still undergoing rapid development at birth, and researchers are trying to understand the environmental factors that shape this development.

The study of 232 infants and their mothers looked at positive factors in the environment in the foetal period and first year of life that enhance brain development, minimise negative behaviours and increase cognitive outcomes. Participants were evaluated on social disadvantage indexes beginning in utero and early life T-Factor scores were also calculated. As infants approached age 3, they were re-evaluated for social, emotional and cognitive development along with using MRIs to scan brain structure.

The results were clear that T-Factor is powerful: Even infants coming from adverse conditions and under-resourced backgrounds can have healthy development if they get their Thrive 5.

The researchers note that policymakers and paediatric primary care providers should be informed about the importance of focusing on elements of the T-Factor and how they can lead to many downstream advantages for both the child and society.

It may seem obvious to anyone that a baby needs care, sleep, food, stimulation and safety but “nobody has particularly focused on or prioritised the importance of this during foetal development and in the first year of life to enhance critical developmental outcomes,” Luby said.

“The Thrive Factor provides a solid foundation for healthy development. It has been underappreciated in primary care just how malleable the brain is to experience,” Luby added.

Barch said the next step will be setting up interventions to test in randomised controlled trials. Another advantage to T-Factor is it is highly feasible to share and promote in broad populations.

Interventions would likely take the form of multiple Zoom sessions with parents to educate and coach them on how to best provide each thrive factor. But that would just be the start, since parents need resources to help them provide thrive factors.

Though T-Factor can help kids overcome adverse conditions, Barch emphasised the need for understanding just how tough those adverse conditions can be on a new parent.

“If you’ve never suffered from financial adversity, you don’t understand how hard that makes life,” she said.

Parents can struggle to provide conditions to thrive because they may have to support many people in their household, may not have adequate number of rooms to ensure easier child sleep training, must work multiple jobs and can’t get away to breast feed, and live in unsafe neighbourhoods that keep them in a constant state of vigilance.

Though education can help caregivers, it will take public policy interventions to ensure parents can access all the Thrive Factors, especially when it comes to access to safe housing and adequate income to support even these basic needs of developing infants.

“We need to make it so families can have the resources necessary to provide these core things to kids because it’s going to have such a big impact on kids’ development across the course of their lifespan,” she said.

Source: Washington University in St. Louis

New Online Recovery School a First for South Africa

South Africa is a traumatised nation

Photo by Steinar Engeland on Unsplash

Dr Siya Mjwara, founder of the AskDrSiya Psychotherapy and Wellness Coaching Practice, has just launched the first online recovery school in South Africa. The Recovery School will support individuals in identifying and confronting their challenges and businesses in developing and implementing wellness solutions in order to reduce absenteeism and improve productivity, as well as overall workplace culture. Dr Mjwara will provide a supportive and transformative environment where healing and growth are possible for all.

She says, “We create a virtual sanctuary where individuals can find healing, empowerment and community support. We strive to cultivate a space where you can reclaim your life and thrive, no matter what you’ve been through.

“After 17 years of working with individuals, couples and families, I can say, without a doubt, that we South Africans are a traumatised nation. Unfortunately, many of us are completely unaware of how our traumas are negatively impacting our lives, as well as the decisions we take on a daily basis. Recently, I’ve been hearing people say, “avoid dating anyone who has never been to therapy”. This is an indication that more of us are recognising how unresolved trauma can negatively impact our relationships.

“Besides our personal experiences, such as childhood trauma, relationship, family and workplace traumas, many of us are still dealing with the effects of intergenerational trauma.

This is part of the background that informs the vision for The Recovery School. My wish is for individuals to not only cope with trauma, but also to be able to thrive and become the best version of themselves. It takes courage to face your fears and begin living authentically, and you don’t need to walk the journey alone.

The school’s programmes are primarily designed to enable individuals to

  1. Rediscover themselves
  2. Break free from limiting beliefs
  3. Cultivate resilience
  4. Forge meaningful connections
  5. Live fully in the present
  6. Achieve their goals

Dr Mjwara BSW Hons (UWC), MA FCS (UWC), Dphil (UNIZULU) can be contacted on Ask@DrSiya.co.za or 079 772 1950.

Metformin’s Weight Loss Tied to “Anti-hunger” Molecule

A new study finds that the modest weight loss from taking metformin is attributable to an appetite-suppressing molecule that is abundant after exercise

Photo by I Yunmai on Unsplash

An “anti-hunger” molecule produced after vigorous exercise is responsible for the moderate weight loss caused by the diabetes medication metformin, according to a new study in mice and humans. The anti-hunger molecule, lac-phe, was discovered by Stanford Medicine researchers in 2022.

The finding, made jointly by researchers at Stanford Medicine and at Harvard Medical School and published in Nature Metabolism, further cements the critical role the molecule, called lac-phe, plays in metabolism, exercise and appetite. It may pave the way to a new class of weight loss drugs.

“Until now, the way metformin, which is prescribed to control blood sugar levels, also brings about weight loss has been unclear,” said Jonathan Long, PhD, an assistant professor of pathology. “Now we know that it is acting through the same pathway as vigorous exercise to reduce hunger. Understanding how these pathways are controlled may lead to viable strategies to lower body mass and improve health in millions of people.”

Many people with diabetes who are prescribed metformin lose around 2% to 3% of their body weight within the first year of starting the drug. Although this amount of weight loss is modest when compared with the 15% or more often seen by people taking semaglutide, the discoveries that led to those drugs also grew from observations of relatively minor, but reproducible, weight loss in people taking first-generation versions of the medications.

Post-workout appetite loss

When Long and colleagues at Baylor University discovered lac-phe in 2022, they were on the hunt for small molecules responsible for curtailing hunger after vigorous exercise. What they found was a mishmash of lactate and an amino acid called phenylalanine. They dubbed the hybrid molecule lac-phe and went on to show that it’s not only more abundant after exercise but it also causes people (as well as mice and even racehorses) to feel less hungry immediately after a hard workout.

“There is an intimate connection between lac-phe production and lactate generation,” Long said. “Once we understood this relationship, we started to think about other aspects of lactate metabolism.”

Metformin was an obvious candidate because as it stimulates the breakdown of glucose (thus reducing blood sugar levels) it can trigger the generation of lactate.

The researchers found that obese laboratory mice given metformin had increased levels of lac-phe in their blood. They ate less than their peers and lost about 2 grams of body weight during the nine-day experiment.

Long and his colleagues also analysed stored blood plasma samples from people with Type 2 diabetes before and 12 weeks after they had begun taking metformin to control their blood sugar. They saw significant increases in the levels of lac-phe in people after metformin compared with their levels before treatment. Finally, 79 participants in a large, multi-ethnic study of atherosclerosis who were also taking metformin had significantly higher levels of lac-phe circulating in their blood than those who were not taking the drug.

“It was nice to confirm our hunch experimentally,” Long said. “The magnitude of effect of metformin on lac-phe production in mice was as great as or greater than what we previously observed with exercise. If you give a mouse metformin at levels comparable to what we prescribe for humans, their lac-phe levels go through the roof and stay high for many hours.”

Further research revealed that lac-phe is produced by intestinal epithelial cells in the animals; blocking the ability of mice to make lac-phe erased the appetite suppression and weight loss previously observed.

Finally, a statistical analysis of the people in the atherosclerosis study who lost weight during the several-year study and follow-up period found a meaningful association between metformin use, lac-phe production and weight loss.

“The fact that metformin and sprint exercise affect your body weight through the same pathway is both weird and interesting,” Long said. “And the involvement of the intestinal epithelial cells suggests a layer of gut-to-brain communication that deserves further exploration. Are there other signals involved?”

Long noted that, while semaglutide drugs are injected into the bloodstream, metformin is an oral drug that is already prescribed to millions of people. “These findings suggest there may be a way to optimize oral medications to affect these hunger and energy balance pathways to control body weight, cholesterol and blood pressure. I think what we’re seeing now is just the beginning of new types of weight loss drugs.”

Source: Stanford Medicine

In the Breast Cancer Fight, the Next Battleground is Malignancy Hibernation

Photo by Michelle Leman on Pexels

There is a surprising dearth of research about how breast cancer cells can go dormant, spread and then resurface years or even decades later, according to a new review of in vitro breast cancer studies conducted by researchers at the University of Massachusetts Amherst.

“[Our review found that] less than 1% of all these studies that combine cells with designer environments look at dormancy,” says Shelly Peyton, Provost Professor of Chemical Engineering. “It’s not enough. We just don’t understand what’s happening – and it’s killing patients.”

Breast cancer dormancy is a phenomenon in which breast cancer cells metastasise (typically to the liver, lungs, brain or bones) but don’t grow. “They’re not detectable or symptomatic tumours,” Peyton explains. “A patient will have their primary tumour removed and appear to be disease-free for months, years, even decades. And for reasons we don’t understand, something changes about the environment that causes those cells to start regrowing, and then you have a deadly metastasis.”

Patients with metastatic breast cancer have a 30% five-year survival rate, compared to a 99% survival rate for localised breast cancer. “Early detection is key, particularly in the Western world,” says Peyton. “You can have lumpectomies, radiation, small surgeries. And women can survive. It’s when that cancer has spread that it becomes much harder to treat.”

This relapse in distant organs impacts 40% of early-stage breast cancer patients, and breast cancer dormancy is a contributing factor. But while metastasis has known biomarkers, dormant cancer cells are very hard to identify. 

“When you have a single dormant breast cancer cell that’s hiding in a distant tissue, it’s really hard to detect that,” says Nate Richbourg, lead author on the paper and postdoctoral researcher in the Peyton Lab. “And you don’t want to do an invasive biopsy or prescribe toxic chemotherapy for something that might not be a problem.”

With these challenges in mind, the review, published in Science Advances, aimed to identify gaps in the research, particularly focusing on in vitro studies, or research using benchtop-model environments instead of animal models or humans. In vitro studies allow for the precise control of the environment, which Peyton’s research group says may play a deciding role in whether a cell remains dormant or reactivates into a deadly metastatic tumor. 

“What can we control in these artificial environments that will give us insight into how breast cancer dormancy happens, and what we can do to treat it as well?” Richbourg asks, describing the importance of in vitro modelling. “When we create this artificial dormancy, we can see how many of those cells could turn back into proliferating and potentially deadly cells.”

Their review highlights just how complex the role of the environment is. “If you have a [breast cancer] cell somewhere in the bone marrow, you’re going to have other cells there, the physical factors in your environment, and the biochemical factors,” Richbourg gives as an example. “We try to use reductive models to separate the thing that is influencing this behaviour. But what we’re seeing is that everything works together to create this breast cancer dormancy effect. The better we can create models that capture all that nuance, the better we’re going to be able to understand it.”

For Peyton, their work is also a call to action. “The paper is calling out to the field that we need to do more,” she says. This includes being more creative with the materials that already exist and developing new materials; identifying ways to model the decades-long progression of dormancy that is impossible to recreate in a single study; and expanding the diversity of cell lines used for research (Richbourg points out that many of the studies they reviewed used the same cell line, MDA-MB-231, derived from one 40-to-50-year-old white woman).

Finally, the researchers have an eye to the ultimate goal: better treatments to save patients. “We see that that there are some clinical trials that are happening that are derived from some of those in vitro models,” says Ninette Irakoze, graduate student in the Peyton Lab. “The paper gives hope that, with more development of these in vitro models, eventually we could find treatments to eradicate dormant cancer.”

Source: University of Massachusetts Amherst

Is AI a Help or Hindrance to Radiologists? It’s Down to the Doctor

New research shows AI isn’t always a help for radiologists

Photo by Anna Shvets

One of the most touted promises of medical artificial intelligence tools is their ability to augment human clinicians’ performance by helping them interpret images such as X-rays and CT scans with greater precision to make more accurate diagnoses.

But the benefits of using AI tools on image interpretation appear to vary from clinician to clinician, according to new research led by investigators at Harvard Medical School, working with colleagues at MIT and Stanford.

The study findings suggest that individual clinician differences shape the interaction between human and machine in critical ways that researchers do not yet fully understand. The analysis, published in Nature Medicine, is based on data from an earlier working paper by the same research group released by the National Bureau of Economic Research.

In some instances, the research showed, use of AI can interfere with a radiologist’s performance and interfere with the accuracy of their interpretation.

“We find that different radiologists, indeed, react differently to AI assistance – some are helped while others are hurt by it,” said co-senior author Pranav Rajpurkar, assistant professor of biomedical informatics in the Blavatnik Institute at HMS.

“What this means is that we should not look at radiologists as a uniform population and consider just the ‘average’ effect of AI on their performance,” he said. “To maximize benefits and minimize harm, we need to personalize assistive AI systems.”

The findings underscore the importance of carefully calibrated implementation of AI into clinical practice, but they should in no way discourage the adoption of AI in radiologists’ offices and clinics, the researchers said.

Instead, the results should signal the need to better understand how humans and AI interact and to design carefully calibrated approaches that boost human performance rather than hurt it.

“Clinicians have different levels of expertise, experience, and decision-making styles, so ensuring that AI reflects this diversity is critical for targeted implementation,” said Feiyang “Kathy” Yu, who conducted the work while at the Rajpurkar lab with co-first author on the paper with Alex Moehring at the MIT Sloan School of Management.

“Individual factors and variation would be key in ensuring that AI advances rather than interferes with performance and, ultimately, with diagnosis,” Yu said.

AI tools affected different radiologists differently

While previous research has shown that AI assistants can, indeed, boost radiologists’ diagnostic performance, these studies have looked at radiologists as a whole without accounting for variability from radiologist to radiologist.

In contrast, the new study looks at how individual clinician factors – area of specialty, years of practice, prior use of AI tools – come into play in human-AI collaboration.

The researchers examined how AI tools affected the performance of 140 radiologists on 15 X-ray diagnostic tasks – how reliably the radiologists were able to spot telltale features on an image and make an accurate diagnosis. The analysis involved 324 patient cases with 15 pathologies: abnormal conditions captured on X-rays of the chest.

To determine how AI affected doctors’ ability to spot and correctly identify problems, the researchers used advanced computational methods that captured the magnitude of change in performance when using AI and when not using it.

The effect of AI assistance was inconsistent and varied across radiologists, with the performance of some radiologists improving with AI and worsening in others.

AI tools influenced human performance unpredictably

AI’s effects on human radiologists’ performance varied in often surprising ways.

For instance, contrary to what the researchers expected, factors such how many years of experience a radiologist had, whether they specialised in thoracic, or chest, radiology, and whether they’d used AI readers before, did not reliably predict how an AI tool would affect a doctor’s performance.

Another finding that challenged the prevailing wisdom: Clinicians who had low performance at baseline did not benefit consistently from AI assistance. Some benefited more, some less, and some none at all. Overall, however, lower-performing radiologists at baseline had lower performance with or without AI. The same was true among radiologists who performed better at baseline. They performed consistently well, overall, with or without AI.

Then came a not-so-surprising finding: More accurate AI tools boosted radiologists’ performance, while poorly performing AI tools diminished the diagnostic accuracy of human clinicians.

While the analysis was not done in a way that allowed researchers to determine why this happened, the finding points to the importance of testing and validating AI tool performance before clinical deployment, the researchers said. Such pre-testing could ensure that inferior AI doesn’t interfere with human clinicians’ performance and, therefore, patient care.

What do these findings mean for the future of AI in the clinic?

The researchers cautioned that their findings do not provide an explanation for why and how AI tools seem to affect performance across human clinicians differently, but note that understanding why would be critical to ensuring that AI radiology tools augment human performance rather than hurt it.

To that end, the team noted, AI developers should work with physicians who use their tools to understand and define the precise factors that come into play in the human-AI interaction.

And, the researchers added, the radiologist-AI interaction should be tested in experimental settings that mimic real-world scenarios and reflect the actual patient population for which the tools are designed.

Apart from improving the accuracy of the AI tools, it’s also important to train radiologists to detect inaccurate AI predictions and to question an AI tool’s diagnostic call, the research team said. To achieve that, AI developers should ensure that they design AI models that can “explain” their decisions.

“Our research reveals the nuanced and complex nature of machine-human interaction,” said study co-senior author Nikhil Agarwal, professor of economics at MIT. “It highlights the need to understand the multitude of factors involved in this interplay and how they influence the ultimate diagnosis and care of patients.”

Source: Harvard Medical School

Low Social Status Increases Risk of Health Problems from Alcohol Problems

People with low income or education levels may benefit from screening for alcohol-related conditions

Photo from Pixabay CC0

Men and women with lower income or education levels are more likely to develop medical conditions related to alcohol abuse compared to similar individuals with a higher socioeconomic status. Alexis Edwards of Virginia Commonwealth University, US, and colleagues report these findings in a new study published March 19th in the open access journal PLOS Medicine.

The World Health Organization estimates that harmful alcohol use accounts for 5.1% of the global burden of disease and injury worldwide, and results in three million deaths each year. Excessive alcohol consumption can also take an economic toll. Previous studies have identified links between a person’s socioeconomic status and alcohol use, but currently it is unclear how an individual’s social class impacts their future risk of acquiring alcohol-related medical conditions, like alcoholic liver disease.

In the new study, researchers used a model that follows people over time to estimate their risk of developing medical conditions from alcohol abuse using two indicators for socioeconomic status: income and education level. The researchers analysed data from more than 2.3 million individuals in a Swedish database to show that both men and women with a lower income or education level were more likely to develop these conditions. The associations held true, even when researchers controlled for other relevant factors, such as marital status, history of psychiatric illness and having a genetic predisposition to abuse alcohol.

The new findings are important for understanding which populations are most likely to suffer from medical conditions resulting from alcohol abuse, and contribute to a growing body of literature on health disparities that stem from socioeconomic factors. The researchers recommend that individuals with lower income or education levels might warrant additional screening by clinicians to evaluate their alcohol consumption and identify related conditions.

The authors add, “Among individuals with an alcohol use disorder, those with lower levels of education or lower incomes are at higher risk for developing an alcohol-related medical condition, such as cirrhosis or alcoholic cardiomyopathy. Additional screening and prevention efforts may be warranted to reduce health disparities.”

Source: PLOS

Opinion Piece: Ripples of Change toward Building a World of Water Equity and Unity

By Robert Erasmus, Managing Director at Sanitech

Photo by Hush Naidoo Jade Photography on Unsplash

World Water Day 2024 resonates deeply in South Africa, where access to clean water remains a significant struggle for many. Recent protests sparked by water scarcity highlight the urgency of this issue, reminding us that water is not just a resource, but a fundamental human right.

This year’s theme, “Leveraging Water for Peace,” calls for unity and recognition of water’s universal significance. As we face the reality of inequality, it is important for us to renew our commitment to equitable water access for all, by fostering dialogue and taking action that is deeply rooted in empathy and ubuntu. Every drop should bring not only sustenance, but also the promise of peace and prosperity.

Connecting local struggles to global issues

South Africa’s water challenges mirror broader global concerns. Ranked a worrying fifth in global water risk, we share these strained resources with our neighbours. This interconnectedness cannot be ignored, and neglecting this truth is likely to fuel regional tensions. Instead, by highlighting our shared challenge, we can strengthen our position and emphasise the need for collaborative solutions. The depth of South Africa’s water scarcity isn’t just a domestic issue – it’s a regional one. Our ranking among the world’s worst puts us alongside stressed neighbours, suggesting the potential for cross-border conflict over shared resources.

Internally, competition between formal and informal users already creates friction, amplified by seasonal rainfall and inadequate infrastructure. To make matters worse, poor sanitation further contaminates water sources, escalating the crisis. The Institute for Security Studies’ Public Violence and Protest Monitor shows that in South Africa, community frustrations with water and sanitation delivery failures resulted in 585 cases of public protest between January 2013 and April 2021, of which incidents, 65% escalated into violent protests.

Aligning with the water rights framework

Although South Africa boasts a progressive water rights framework, our efforts must align with this framework, ensuring that the fight for water equity remains central to our pursuit of peace. Empowering communities with access to clean drinking water and sanitation and upholding water rights are essential steps toward conflict prevention.

Raising awareness is essential, but tangible action holds the key to progress. Businesses can play an important role in acknowledging South Africa’s water scarcity and investing in corporate social responsibility (CSR) projects that focus on addressing sanitation and water quality in the communities in which they operate. From an individual perspective, it is important that each citizen does their part to conserve water, while supporting organisations that work on improving water access, and raising awareness of related issues within their communities. At a government level, it is critical to prioritise infrastructure maintenance, address sewage contamination, and collaborate with regional partners and industries on sustainable water management strategies, to prevent civil unrest by addressing water equity issues.

Tapping into Ubuntu and empathy

Ubuntu, the South African philosophy of shared humanity, encourages us to understand and share the experiences of others. Cultivating empathy across communities, businesses, and government fosters inclusive dialogue and collaborative solutions. With the principles of ubuntu in mind, it is critical to address sewage contamination to preserve our scarce water resources. It is essential for municipalities and provincial governments to invest in infrastructure upgrades to reduce water loss and improve delivery.   Businesses operating within the sanitation and water treatment sectors have the potential to empower communities by providing filtration and treatment solutions for local water sources. Moreover, the broader private sector can contribute to corporate social responsibility (CSR) initiatives aimed at enhancing sanitation and water quality in vulnerable communities.

Amplifying voices through collaborative communication

Empowering community voices is vitally important. This can be achieved through increased awareness on water scarcity and its impact, as well as by supporting local initiatives that improve water access and quality. Based on the principles of ubuntu, we must advocate for the facilitation of open communication between communities, businesses, and government. Water advocacy groups such as South African Water Caucus (SAWC), and water project NGOs such as the Mvula Trust must continue to advocate for increased funding for water and sanitation projects, by holding the government accountable for meeting water rights and supporting regional cooperation on water management.

Uniting for peace and prosperity

In this way, individuals, organisations, and governments can turn the promise of World Water Day into tangible progress by working together. In prioritising equitable water access, addressing underlying challenges, and fostering collaboration, we can build a future where every drop flows towards peace, not conflict. Remember, water scarcity and strife does not have to be our inevitable future. Through collective action and commitment, we can ensure that this precious resource serves as a bridge to peace and prosperity for all.

ADHD Medication Associated with Reduced Mortality

Photo by Annie Spratt on Unsplash

A Swedish study of more than 140 000 individuals with attention-deficit/hyperactivity disorder (ADHD) found that initiation of ADHD medication was significantly associated with a 21% lower mortality two years after diagnosis, according to results published in JAMA. This reduction was especially pronounced for unnatural-cause mortality. Females and males also saw different reductions in types of mortality.

ADHD is the most prevalent neurodevelopmental condition, affecting 5.9% of youths and 2.5% of adults worldwide, according to the 2021 World Federation of ADHD International Consensus Statement. The disorder is associated with a broad range of psychiatric and physical comorbidities, as well as adverse functional outcomes. Furthermore, individuals with ADHD are at twice the risk of premature death, mainly due to unnatural causes.

Randomised controlled trials have demonstrated that ADHD medications, including stimulant and nonstimulant medications, are effective in reducing core ADHD symptoms for children and adults with ADHS. Pharmacoepidemiological studies have also shown reduced risks of negative outcomes, including injuries, traffic collisions, and criminality, which would be expected to decrease the mortality rate. However, there are concerns regarding the cardiovascular safety of ADHD medications, especially following long-term use, which could increase the mortality rate.

To date, three studies have examined the association between ADHD medication and mortality with mixed results. These studies had significant limitations, such as the absence of a control group. To date, there has been no study on the association in adults with ADHD. There are increasing diagnoses of ADHD among adults, who have a higher prevalence of somatic comorbidities, including cardiovascular diseases and other conditions, compared with children and adolescents.

Using the Swedish national registers, the researchers investigated whether initiation of ADHD medication was associated with mortality, using the target trial emulation approach to avoid key biases in pharmacoepidemiological studies.

They assessed for all 6 medications licensed for ADHD treatment in Sweden (methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, atomoxetine, and guanfacine) during the 2007-2020 period. Analysis of the data showed that, for a two-year follow-up, lower all-cause (hazard ratio [HR], 0.79) and unnatural-cause (HR, 0.75) mortality for the ADHD medication group, but there was no significant association with natural-cause mortality (HR, 0.86). Under unnatural causes, accidental poisoning mortality was halved (HR, 0.47).

Subgroup analysis revealed that for females, the only significant reduction in mortality was for natural causes. The authors noted that this may be due to higher rates of comorbid depression, sleep disorder, atrial fibrillation, and asthma.

When follow-up was extended to five years, associations attenuated save for unnatural-cause mortality (HR, 0.89).

The authors concluded, “ADHD medication may reduce the risk of unnatural-cause mortality by alleviating the core symptoms of ADHD and its psychiatric comorbidities, leading to improved impulse control and decision-making, ultimately reducing the occurrence of fatal events, in particular among those due to accidental poisoning.”

For limitations, the observational nature of the study cannot establish causation, and the authors noted confounding effects such as nonpharmaceutical treatment of ADHD. Potential type I error resulting from multiple comparisons regarding cause-specific mortality and subgroup analyses meant the results are only exploratory. Two more limitations were uncertain adherence to medication and potential misclassification of deaths such as potential cases of suicide being marked as accidental poisoning.