These results give hope to stroke patients worldwide who may not be able to access thrombolytic medications within the approved time window, which in China is within 4.5 hours, said the trial’s principal investigator Min Lou, MD, PhD, a professor at the Second Affiliated Hospital of Zhejiang University’s School of Medicine in China.
In the US, alteplase is approved to treat stroke within three hours of symptom onset and is recommended for use up to 4.5 hours for select patients. Other research has indicated it may also work well in some patients 4.5 to 9 hours after stroke onset.
Researchers enrolled 372 stroke patients whose symptoms began 4.5 hours to 24 hours earlier. They used widely available CT perfusion imaging (advanced brain scanning) to confirm that these patients still had brain tissue that could recover with treatment. Participants were randomised to receive alteplase, while the other received standard stroke care of antiplatelet therapy at the discretion of the investigator, based on the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2018. Functional recovery was assessed at 90 days.
“We believe these findings mean more people may return to normal or near-normal lives after a stroke, even if they receive treatment later than originally thought beneficial,” Lou said. “This method of treatment could become the new standard, especially in hospitals that use CT perfusion imaging. This technology helps health care professionals see how blood flows in different parts of the brain after an ischemic stroke. This could extend treatment eligibility to millions more patients across the globe.”
The study found:
40% of participants treated with alteplase had little to no disability after 90 days, compared to 26% of those who received standard care – a 54% higher chance of functional recovery.
Less than 3% of participants in either group received rescue mechanical clot removal as an additional treatment.
Rates of death were the same (10.8%) for both groups.
The risk of brain bleeding was higher among those who received alteplase than among participants who did not (3.8% vs. 0.5%), but researchers believe this is a manageable risk.
“We also need to look more closely at how safe and effective other clot-dissolving medications, like tenecteplase, are when given after a stroke, especially beyond the usual time frames. It’s also important to learn if our findings apply to other groups of people, especially in areas with different stroke risks and health care resources,” Lou explained.
Study limitations include the that both participants and researcher knew which treatment was being given, which could have introduced bias, and results may not be generalizable to patients outside of China.
Study design, background and details:
The study enrolled 372 stroke patients in a multicenter, prospective, randomized trial at 26 stroke centers in China.
The patient’s average age was 72 years, and 43% were women.
The trial used widely available CT perfusion imaging software to gauge salvageable brain tissue, making the findings more applicable to real-world clinical settings.
Enrolled patients were assigned to the alteplase group or a standard medical treatment group.
The primary outcome was a score of 0 or 1 on the modified Rankin scale, which scores disability from 0 (no symptoms) to 6 (death) at 90 days.
Study co-authors, funding and disclosures are available in the abstract.
Breast cancer is the world’s most prevalent cancer. Although earlier detection and targeted treatment have resulted in high survival rates, many breast cancer survivors experience fear of cancer recurrence. For some survivors this fear is occasional, for others it is persistent and often debilitating.
A new study of breast cancer survivors has found this psychosocial challenge impacts almost every important domain of their lives – the emotional, behavioural, cognitive, relational and professional. A larger number of domains was affected, and they were affected more frequently in those with greater fear of recurrence.
“Study participants were reportedly disease free and trying to rebuild their lives during their post-treatment survivorship,” said senior author Shelley Johns, PsyD, a researcher-clinician with the Regenstrief Institute, the Indiana University School of Medicine and the IU Melvin and Bren Simon Comprehensive Cancer Center. “Our findings provide clarity about how breast cancer survivors are impacted by fear of recurrence and insight into how they cope with this understandable fear.”
The impact of fear of recurrence ranged from mildly to severely disruptive. Women experiencing mild fear reported sporadic occurrences. Those with significant fear described it as persistent and/or easily triggered across multiple life domains.
Disturbed sleep prior to mammograms was reported by survivors with mild fear, while frequent need to absent themselves from social activities, get into bed and pull the blanket over their eyes to avoid thinking about cancer was an example of severe, also known as clinical, fear of recurrence. Approximately 74 percent of study participants were experiencing clinical fear of recurrence.
347 women completed the study’s open-ended survey:
Many reported feelings of stress, irritability and sadness.
Some said fear of recurrence frequently interrupted their train of thought, for example interfering with their job when their disease popped into their mind.
Survivors who thought that they were more worried than they should be compared to other breast cancer survivors reported feelings of embarrassment.
Some indicated it was too hard to be around their family because they were constantly wondering how many more Christmases and birthdays they were going to have with their children.
The paper’s title includes the phrase, “out of a dark place,” a direct quote from a breast cancer survivor who said that she joined the study to support “getting out of a dark place.”
Other survivors noted the specific impact of fear of cancer recurrence on daily life:
“It motivates me to maintain healthy habits. Such as eating five servings of fruits and vegetables, working out and drinking less alcohol. It also motivates me to maintain mental health and physical health.”
“Whenever I feel any kind of pain or discomfort in the area where I had cancer it concerns me and I feel anxious and irritable.”
“Cancer is all around us. Everything is a trigger. Anniversaries, other family/friends’ diagnosis, commercials about drugs, social media, etc. …it’s a daily thought or a daily emotion.”
“Sit for hours doing nothing, do not turn on TV, sleepless, find hours pass by and I am in the same place just thinking, do not participate in activities, get lost driving because I’m deep in thought, compulsive online shopping, collecting things.”
Survivors offered specifics on their coping mechanisms:
“Just trying to be positive, eat healthy, take my meds, get enough sleep, exercise three times a week, and hope for the best.”
“I try to avoid things that make me think about recurrence. For example, unfollowing social media accounts, fast forwarding or leaving the room when commercials about cancer medications are on.”
“I try not to focus on it. I also speak with family members who have lived with cancer longer than myself.”
“Prayer, meditation, staying in the moment, and focusing on making the best of each day.”
While many survivors cited avoidance of thoughts and feelings as their primary coping behaviour, Dr Johns, a health services researcher and clinical health psychologist, observes that research is needed to probe the function of various coping behaviours’ to determine if they are helpful.
In a question seldom posed to participants in a clinical trial, when asked what they hoped to gain by participating in the study, the majority indicated that they sought senses of purpose, belonging, control and connection with others.
The paper concludes, “Fear of cancer recurrence is one of the most common psychological challenges for cancer survivors. Understanding affected life domains, coping strategies employed prior to intervention, and reasons for seeking guidance can inform the development and implementation of evidence-based interventions to effectively address fear of cancer recurrence among persons living with breast cancer.”
A timely report on governance in South Africa’s healthcare sector released last year identified several serious shortcomings. As the political and administrative wheels again start turning in 2025, we unpack the report and ask if government is paying attention.
The signing of the National Health Insurance (NHI) Bill into law last year, sparked a renewed conversation on how the healthcare sector is governed, making the release of a consensus study on what was needed to achieve good governance and management in the South African healthcare system a few months later particularly timely. Commissioned by the Academy of Science of South Africa (ASSAF), the report was a three-year endeavour led by a panel of experts from multiple fields.
The spark for the project was concerns over the performance of the country’s healthcare system and the Life Esidimeni tragedy in particular, according to the chairperson of the ASSAF report panel Professor Lilian Dudley. The Life Esidimeni tragedy, in which 144 mental healthcare users in Gauteng died due to starvation and neglect, highlighted what the public health medicine specialist described as “not just poor performance but corruption and unethical practices in the health system”.
“There were concerns about the overall governance or oversight and leadership of the health system, and the panel was essentially asked to try and look at some of the challenges, as well as to go over the evidence and make recommendations which could be implemented to address it,” she told Spotlight.
After describing the “magnitude, the spread, and the effects of the governance challenges in the health system” as well as finding examples of where good governance was taking place, the report went on to make eight recommendations on practical strategies to improve the situation. This article focuses on three of these recommendations, so it is by no means exhaustive. The recommendations are interdependent, as is evident from the full report which can be found here.
Good governance is ‘patchy’
Sharon Fonn, Professor of Public Health at the University of the Witwatersrand who also worked on the report, told Spotlight it found that good governance in our healthcare system is “patchy”. She said there were two issues contributing to this: There are some people without the necessary competence and skills or sometimes motivation in key positions, and in some cases dysfunctional or inappropriate systems undermine the best efforts of those who are competent or have the right intentions.
There is no quick fix though. “You need to see this as a 10-year project,” Fonn said. “There’s some political leadership that’s needed, and then there’s some technical interventions that are needed. It’s about having a plan and getting people around the table,” she added.
Foundations for good governance are present but no longer ‘fit-for-purpose’
To contextualise governance within the healthcare system, the report needed to look at the past, according to Dudley. She explained that democratic South Africa “inherited a very flawed, fragmented health system, which was not being governed in order to address the needs of the majority of the population”. Thus, a lot of work had been done after 1994 to set up a unified healthcare system and establish systems and structures to lay foundations for good governance. “But we seem to have lost the plot along the way,” she said.
“One of our key findings was that there were some foundations that were put in place, but they would not be effective as governance structures and were no longer fit for purpose,” Dudley said. “Even though we have some structure, some systems, they are not really supporting and promoting the kind of governance that is needed.” In this regard, Dudley points to key legislation and policies such as the National Health Act (NHA) and the White Paper on Transformation for the Health system.
“The other context within which we are operating is the overall political environment, and health is political at the end of the day with levels of political interference,” Dudley added. “[H]aving the right people, the right competence and the right ethics in place has been a problem because a lot of senior managers in the health system are not necessarily accountable to the people they serve”.
The report stated that a conflict between two pieces of legislation – the Public Finance Management Act (PFMA) and the Public Services Act (PSA) – could be contributing to some of these problems with senior leadership and so-called “cadre deployment” in some provincial health systems. At issue are apparent contradictions and overlaps between the roles of purely political appointments, such as Members of the Executive Committees (MECs) for health, and those of senior officials like heads of health departments.
The PFMA is legislation aimed at regulating the financial management of government and providing for the responsibilities of the persons entrusted with that financial management. According to the report, the Act grants the power and responsibility for financial management, service delivery and human resource management to “accounting officers”, who are either the Head of Department or the Director-General – depending on the level of government being referred to.
By contrast, according to the ASSAF report, the PSA aims to regulate the organisation and administration of the public service, grants Ministers and MECs in the provinces the power of “executive authority” giving them the authority to, among other things, appoint people to government positions.
It is not unusual to have contradictions between pieces of legislation that were developed at different times and by different Ministers or Departments, Dr Andy Gray, a senior lecturer in the Division of Pharmacology at the University of KwaZulu-Natal’s School of Health Sciences, told Spotlight.
He said Section 38 of the PMFA describes the responsibilities of “accounting officers”, which is clearly describing a managerial function. However, every Head of Department is also subject to governance by a minister. The PSA repeats the same definition for an accounting officer as the PMFA but adds an additional definition for an executive authority.
Within the PSA, who the executive officer is depends on the level of government being referred to, for example in relation to “a provincial department or a provincial government component within an Executive Council portfolio”, the executive officer will be the member of the Executive Council responsible for that portfolio.
In the case of a provincial health department, this would mean the MEC for Health is an executive officer, who is granted by this Act all the powers and duties necessary for, among other things, “the recruitment, appointment, performance management, transfer, dismissal and other career incidents of employees of that department”.
“That does appear to contradict the separation between management and governance, so the ASSAF criticism appears to be valid,” Gray said.
Another function of governance that has not been working as it should, according to Dudley, has been the community participation aspect. She said that the NHA has delegated a lot of the power and responsibility for enabling community participation to the provincial governments. And in the cases where provincial governments have created appropriate regulations for the health committees that allow for community participation, it’s still inadequate.
As summarised by the report, the lack of clarity between these three Acts – NHA, PFMA, and PSA – “have contributed to conflicting mandates between politicians and senior managers in the public health sector, across levels of government, and between the health sector and structures for community representation”.
Legislation needs to be refined
To address some of these issues, the report recommended updating legislation and governance structures “to insulate them from vested interests and give them executive rather than merely advisory functions”.
To do so, it called for making accountability structures more effective by amending the conflicts within legislation that weaken or undermine the delegation of governance. This includes, among other steps, aligning the PFMA and the PSA, as well as clarifying and strengthening the way the NHA delegates authority between levels of government, particularly to health districts and health facilities.
The report also proposes taking steps to strengthen community governance structures like clinic committees, hospital boards and other entities. This included, among other things, reforming legislation to ensure “harmonised policies on roles and functions of such structures across all provinces” and extending community participation structures to the private sector. It also called for a common policy defining the “criteria and processes for appointments, role and functions, reimbursement of community committee members for costs, induction, and continuous capacity building”.
Systems are not working
Also hindering good governance, according to Fonn, is dysfunctional systems, such as overly complicated procurement processes and ineffective information systems. She said that whenever a problem arose with procurement, another layer of control was added, making the systems impossible to navigate.
“It must be possible to review it and to work out a more manageable process around procurement. And procurement is particularly important because it’s sort of what keeps things turning over. It’s also the space where vested interests can be exercised,” Fonn said.
Accurate information is another essential component of the health system that overall isn’t working very well, though there are exceptions. Fonn explained that the report found functional information systems in some provinces. Part of what can be done to improve governance, she said, is to take what worked in those instances and try to replicate or adapt it to work in other provinces.
Need functional fit-for-purpose systems
One of the recommendations in the report is to “surround managers and leaders with functional fit-for purpose systems (including human resources, procurement, health information systems) so that they can do their work”.
Part of this was a call to improve procurement processes by simplifying the existing overly complex and sometimes contradictory rules and delegating more of the actual procurement to facilities and district or sub-district managers.
“Overly complex procurement systems are inhibiting decentralisation, as the complexity of existing rules makes it difficult for decentralised managers,” the report stated. “This does not mean that every facility should be issuing its own medicine tenders, but there is no reason why strong sub-district offices or larger facilities should not be ordering supplies off transversal tenders without multiple layers of high-level signoff.”
Some of the suggested reforms include greater development and use of electronic systems like electronic catalogues, stock management systems, ordering systems and e-procurement systems. It also suggested including medical supplies and medical equipment in transversal tenders to achieve economies of scale.
The report also advocated for giving health institutions greater power, where appropriate, over hiring, firing and disciplinary procedures. “Within labour law and labour agreements, space must be made to allow managers to follow agreed procedures without sacrificing the public value mission of the service,” it stated.
Implementing the electronic National Health Information System of South Africa (NHISSA) was also identified by the report as an urgent priority so that patient-linked data can be collected.
Alleged lack of vision and stewardship by the National Department of Health
Another trend observed by the panelists, Fonn said, is an overall lack in a vision of the healthcare system that is being communicated by government – particularly the National Department of Health. She used the example of the NHI, where the government has been, as she described it, “unable to communicate that [NHI] in a way that captures the public imagination and in a way that makes sense to people on the ground who are actually [healthcare] providers”.
“The argument from government is that the NHI Act is simply setting in place the fund, that’s all it’s supposed to do. I understand that…and it’s a legitimate argument. The problem is then that doesn’t tell people what it means,” she added. “It’s that kind of lack of stewardship, lack of communicating a vision.”
Fonn also pointed out an apparent reluctance by the National Department of Health to engage with stakeholders and instead foster a “command-and-control environment”.
Another layer of this issue is that the healthcare system is set up in a way that makes the National Department of Health responsible for steering the system but, according to Fonn, they haven’t done this effectively and have focused on the wrong things.
“The way the South African health system is set up currently is that the National Department [of Health] is responsible for stewarding the system, for making sure that the right legislation exists, the right checks and balances exist, and the right controls exist,” said Fonn.
“I think that at least in part, they haven’t [fulfilled that responsibility]. It’s a complex thing to do so I’m not suggesting it’s easy. But I don’t think they’ve had their eye on the right place,” she said.
“What our report does acknowledge is that there are many good people in the health system who actually want to see improvements, who are committed to good leadership and management and governance,” Fonn said. “But I think we need leadership to kind of show the way and one of the first things that we felt was important was to revisit what our public values are, what are the social goals that we want to set for the health system, and can we all agree on that and move towards that? [We need] that kind of leadership and stewardship from the political and national government level.”
Mixed response from government
Spotlight asked the National Department of Health and Minister of Health Dr Aaron Motsoaledi for their responses to the report and its findings. The spokesperson for the health department indicated he had only been able to access an abstract of the report and would not be able to respond without seeing the full report. A copy of the report was then sent to the spokesperson, but no response or comment was received by the time of publication (more than a week later).
However, according to Dudley, the report was presented last year to the Minister of Health, senior managers in the provinces, and health MECs.
“There was actually quite a bit of interest from the new MECS [for health] … the MECs were quite keen to hear more about it, engage more about it and wanted to know what we need to do to actually respond and to start implementing some of these recommendations,” she said.
By comparison, Dudley said there was less interest from the National Department of Health.
She however pointed out that the burden of changing governance in the healthcare system doesn’t rest entirely on the health department’s shoulders.
“There are multiple stakeholders that need to take action, we do try to emphasise that in the report. Yes, government and politicians do have particular roles, but everybody has a role,” Dudley said.
These include academic institutions, she said, which need to ensure when training health professionals and leaders they are provided with the kind of competencies that will improve the management, leadership and governance of the health system.
Research institutions also have a role to play in addressing some of the unanswered questions around governance and how to implement interventions that can bring about change. Civil Society will also have a part to play through activism to hold those in positions of power to account.
Although obese individuals are at greater risk of diabetes, high blood pressure or high cholesterol, not all obese people develop metabolic diseases of this kind. With around a quarter of all obese individuals are healthy, scientists are trying to work out why some obese people become unhealthy while others do not.
Now, a comprehensive study by researchers from Zurich and Leipzig has provided a vital basis for this work. Specifically, the researchers have produced a detailed atlas with data from healthy and unhealthy overweight people, on their fat (adipose) tissue, and on the gene activity in this tissue’s cells. “Our results can be used to look for cellular markers that provide information on the risk of developing metabolic diseases,” explains Adhideb Ghosh, a researcher in ETH Professor Christian Wolfrum’s group and one of the two lead authors of the study. “The data is also of great interest for basic research. It could help us develop new therapies for metabolic diseases.”
For this study, Ghosh and his colleagues used the Leipzig Obesity Biobank, an extensive collection of biopsies taken from obese individuals. Compiled by scientists from the University of Leipzig, these samples originate from obese patients who underwent elective surgery and consented to the collection of adipose tissue samples for research purposes. The collection also includes extensive medical information on the patients’ health.
Since the tissue samples were all taken from obese individuals with or without metabolic diseases, they allow comparison between individuals with healthy and unhealthy obesity. In samples from 70 volunteers, the researchers at ETH Zurich examined which genes were active, and to what extent, on a cell-by-cell basis for two types of adipose tissue: subcutaneous and visceral.
Scientists and medical experts assume that visceral fat, which lies deep in the abdominal cavity and surrounds the internal organs, is primarily responsible for metabolic diseases. By contrast, experts generally believe that fat located directly beneath the skin is less problematic.
For the study, it was vital that the adipose tissue cells were not all simply lumped together, as this tissue comprises not only fat cells (adipocytes) but also cells of other types. “In fact, the adipocytes are in the minority,” explains lead author Isabel Reinisch, a postdoc in Wolfrum’s group. A large part of adipose tissue is made up of immune cells, cells that form blood vessels, and immature precursor cells of adipocytes. Another cell type, known as mesothelial cells, are found only in visceral adipose tissue and mark its outer boundary.
Abdominal fat remodelled – and gender differences
As the researchers were able to show, there are significant functional changes in cells in the visceral adipose tissue of people with metabolic diseases. This remodelling affects almost every cell type in this form of tissue. For example, the genetic analyses showed that the adipocytes of unhealthy individuals could no longer burn fats as effectively and instead produced greater quantities of immunologic messenger molecules. “These substances trigger an immune response in the visceral fat of obese people,” explains Reinisch. “It’s conceivable that this response promotes the development of metabolic diseases.”
The researchers also found very clear differences in the number and function of mesothelial cells: in healthy obese individuals, there is a far greater proportion of mesothelial cells in the visceral fat and these cells exhibit greater functional flexibility. Specifically, the cells can switch into a sort of stem cell mode and therefore convert into different cell types, such as adipocytes, in healthy individuals. “The ability of fully differentiated cells to convert into stem cells is otherwise primarily associated with cancer,” says Reinisch. She was surprised, therefore, to find this ability in adipose tissue as well. “We suspect that the flexible cells at the edge of the adipose tissue in healthy obese individuals facilitate smooth tissue expansion.”
Finally, the researchers also found differences between men and women: a certain type of progenitor cell is present only in the visceral fat of women. “This could explain differences in the development of metabolic diseases between men and women,” says Reinisch.
Finding new biomarkers
The new atlas of gene activity in overweight people describes the composition of cell types in adipose tissue and their function. “However, we cannot say whether the differences are the reason why someone is metabolically healthy or whether, conversely, metabolic diseases cause these differences,” says Ghosh. Instead, the scientists view their work as providing the basis for further research. They have published all the data in a publicly accessible web app so that it is available for other researchers to work with.
In particular, this atlas now makes it possible to find new markers that provide information on the risk of developing a metabolic disease. At present, the ETH researchers are also looking for these kinds of markers, which could help to improve the treatment of such diseases. For example, there is a new class of drugs that suppress the appetite and promote insulin release in the pancreas – but these medications are in short supply. “Biomarkers that can be derived from our data could help to identify those patients who are most in need of this treatment,” says Reinisch.
A new study on psoriasis has determined that a protein called NF-kB c-Rel can intensify the condition’s symptoms when activated by signals from the body’s immune system. Understanding how “c-Rel” affects skin inflammation could lead to new treatments, said the researchers at Case Western Reserve University School of Medicine.
The study, published recently in eBioMedicine, examined how c-Rel contributes to the function of dendritic cells (DCs), a type of immune cell. The study examined how c-Rel responds to specific immunological signals through Toll Like Receptor 7 (TLR7), which regulates innate immunity and inflammation, exacerbating psoriasis.
The researchers also found the absence of c-Rel alleviates inflammation that causes red, scaly patches on the skin. TLR7 meanwhile is known to be activated by diseases such as HIV and HPV, which are also linked to the development psoriasis.
“We believe that by focusing on c-Rel and TLR7, scientists might be able to create more targeted treatments that reduce inflammation and help psoriasis symptoms,” said Parameswaran Ramakrishnan, associate professor of pathology, member of the Case Comprehensive Cancer Center and researcher at Louis Stokes Cleveland VA Medical Center, the study’s principal investigator.
“This may help relieve the discomfort millions of people live with skin inflammation.”
The researchers examined skin samples from psoriasis patients and a mouse model with similar skin changes.
They analysed c-Rel levels and its behaviour in specially engineered cells lacking the protein; they also examined the mouse model lacking c-Rel.
Their goal: to better understand how c-Rel impacts the immune response in psoriasis.
“Our research shows that c-Rel plays a major role in psoriasis inflammation,” said Angela Liu, lead author and a recent graduate of the School of Medicine’s pathology department.
“We saw higher levels of c-Rel in psoriasis; mice lacking c-Rel were significantly protected from developing psoriasis and showed less inflammation.”
Ramakrishnan said their study revealed the potential role for TLR7 and c-Rel signalling in human psoriasis. A range of viruses that activates TLR7, including human immunodeficiency virus (HIV), human papilloma virus (HPV) and hepatitis C virus (HCV), are linked to the development of psoriasis.
“The research warrants future studies on TLR7-c-Rel-dependent molecular mechanism regulating DC function as a potential link for how viral TLR7 activation is involved in worsening psoriatic disease,” Ramakrishnan said. “From a broad perspective, it would be interesting to further explore the role of c-Rel and TLR7 in other biologically relevant diseases involving these proteins, such as systemic lupus erythematosus and wound-healing in diabetes.”
A new study finds that heavy drinkers with either diabetes, high blood pressure or a high waist circumference are as much as twice as likely to develop advanced liver disease.
The answer may lie in three common underlying medical conditions, according to a new study published in Clinical Gastroenterology and Hepatology from Keck Medicine of USC. The research found that heavy drinkers with either diabetes, high blood pressure or a high waist circumference are as much as 2.4 times more likely to develop advanced liver disease.
“The results identify a very high-risk segment of the population prone to liver disease and suggest that preexisting health issues may have a large impact on how alcohol affects the liver,” said Brian P. Lee, MD, MAS, a hepatologist and liver transplant specialist with Keck Medicine and principal investigator of the study.
Diabetes, high blood pressure and a high waist circumference (89cm for women; 101cm for men), which is associated with obesity, belong to a cluster of five health conditions that influence an individual’s risk for heart attack and stroke known as cardiometabolic risk factors.
Cardiometabolic risk factors have been linked to the buildup of fat in the liver (also known as metabolic dysfunction-associated steatotic liver disease), which can lead to fibrosis, or scarring of the liver. These risk factors affect more than one in three Americans, and cardiometabolic health has been worsening among the population, especially among those under 35, according to Lee.
Alcohol also causes fat buildup in the liver, and alcohol consumption has been on the rise since the COVID-19 pandemic, said Lee. Due to the prevalence of both cardiometabolic risk factors and drinking in the United States, Lee and his fellow researchers undertook the study to investigate which cardiometabolic risk factors predisposed the liver to damage from alcohol.
They analysed data from the National Health and Nutrition Examination Survey, a large national survey of more than 40 000 participants, looking at the intersection of heavy drinking, individual cardiometabolic risk factors and the incidences of significant liver fibrosis. Significant liver fibrosis refers to liver scarring that can lead to liver failure.
For the study, heavy drinking was characterised as 1.5 drinks a day for women (20 grams) and two drinks a day for men (30 grams).
Researchers discovered that heavy drinkers with either diabetes or a high waist circumference were 2.4 times more likely to develop advanced liver disease and those with high blood pressure 1.8 times more likely. They found that the other two cardiometabolic risk factors – high triglycerides and low HDL (high-density lipoprotein) had less significant correlations to liver disease.
While the study did not analyse why these three cardiometabolic risk factors are more dangerous for the liver, Lee speculates that these conditions share a common pathway to fat buildup in the liver that when combined with extra fat deposits in the liver from excessive alcohol, can cause significant damage.
Lee stresses that the study does not imply it is safe for those without these three cardiometabolic risks to consume large amounts of alcohol. “We know that alcohol is toxic to the liver and all heavy drinkers are at risk for advanced liver disease,” he said.
Lee hopes that the study results will encourage people to consider their individual health and risk profile when making decisions about alcohol consumption. He would also like to see practitioners offer more personalized health screenings and interventions for those who drink with cardiometabolic risk factors so that liver damage among this high-risk group can be caught early and treated.
In a paper recently published in The Lancet Digital Health, a scientific team led by Stanisa Raspopovic from MedUni Vienna looks at the progress and challenges in the research and development of brain implants. New achievements in the field of this technology are seen as a source of hope for many patients with neurological disorders and have been making headlines recently. As neural implants have an effect not only on a physical but also on a psychological level, researchers are calling for particular ethical and scientific care when conducting clinical trials.
The research and development of neuroprostheses has entered a phase in which experiments on animal models are being followed by tests on humans. Only recently, reports of a paraplegic patient in the USA who was implanted with a brain chip as part of a clinical trial caused a stir. With the help of the implant, the man can control his wheelchair, operate the keyboard on his computer and use the cursor in such a way that he can even play chess. About a month after the implantation, however, the patient realised that the precision of the cursor control was decreasing and the time between his thoughts and the computer actions was delayed.
“The problem could be partially, but not completely, resolved – and illustrates just one of the potential challenges for research into this technology,” explains study author Stanisa Raspopovic from MedUni Vienna’s Center for Medical Physics and Biomedical Engineering, who published the paper together with Marcello Ienca (Technical University of Munich) and Giacomo Valle (ETH Zurich). “The questions of who will take care of the technical maintenance after the end of the study and whether the device will still be available to the patient at all after the study has been cancelled or completed are among the many aspects that need to be clarified in advance in neuroprosthesis research and development, which is predominantly industry-led.”
Protection of highly sensitive data
Neuroprostheses establish a direct connection between the nervous system and external devices and are considered a promising approach in the treatment of neurological impairments such as paraplegia, chronic pain, Parkinson’s disease and epilepsy. The implants can restore mobility, alleviate pain or improve sensory functions. However, as they form an interface to the human nervous system, they also have an effect on a psychological level: “They can influence consciousness, cognition and affective states and even free will. This means that conventional approaches to safety and efficacy assessment, such as those used in clinical drug trials, are not suitable for researching these complex systems. New models are needed to comprehensively evaluate the subjective patient experience and protect the psychological privacy of the test subjects,” Raspopovic points out.
The special technological features of neuroimplants, in particular the ability to collect and process neuronal data, pose further challenges for clinical validation and ethical oversight. Neural data is considered particularly sensitive and requires an even higher level of protection than other health information. Unsecured data transmission, inadequate data protection guidelines and the risk of hacker attacks are just some of the potential vulnerabilities that require special precautions in this context. “The use of neural implants cannot be reduced to medical risks,” summarises Stanisa Raspopovic. “We are only in the initial phase of clinical studies on these technological innovations. But questions of ethical and scientific diligence in dealing with this highly sensitive topic should be clarified now and not only after problems have arisen in test subjects or patients.”
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health
Men undergoing radiation therapy for prostate cancer who experience side effects early in treatment may face a higher risk of developing more serious long-term urinary and bowel health issues, according to a new study led by investigators from the UCLA Health Jonsson Comprehensive Cancer Center.
The study found that patients who experienced moderate acute urinary side effects in the first three months after radiation were nearly twice as likely to develop late urinary complications years later compared to those without early symptoms. Similarly, patients with early bowel side effects had nearly double the risk of chronic bowel issues.
The findings, published in The Lancet Oncology, highlight the importance of developing strategies to better manage acute toxicities to help improve long-term outcomes and quality of life for patients.
“Men with prostate cancer are living longer than ever, and our goal is to reduce the risk of late toxicities, such as difficulty urinating or rectal bleeding, that can impact a patient’s quality of life for years,” said Dr Amar Kishan, executive vice chair of radiation oncology and senior author of the study. “This study highlights innovations we’re developing, such as using smaller treatment margins in prostate radiation to minimize early side effects, that can lead to lasting benefits by also reducing the risk of long-term complications for patients.”
Radiation therapy is often a key treatment for localised prostate cancer, often involving higher doses to better control the disease. While this approach effectively controls cancer, it can also harm nearby healthy tissues, causing acute and late-term side effects.
Acute toxicity refers to side effects that occur during treatment or within the first three months after it ends, and they are typically temporary. Common urinary side effects include increased frequency of urination, difficulty urinating and discomfort during urination. Bowel-related side effects may include softer stools or diarrhea, as well as rectal discomfort during bowel movements.
Late toxicity, on the other hand, can appear months or even years later and can last for years. Late urinary toxicities include narrowing of the urethra and having blood in the urine. Late bowel toxicities include having blood in the stool or having an ulcer in the wall of the rectum. These issues often can have a bigger impact on a person’s quality of life compared to acute side effects.
While both acute and late toxicities are caused by radiation’s effect on healthy tissues, the connection between the two hasn’t been well-studied, particularly using large-scale data.
To better understand this relationship, the researchers analysed data from over 6500 patients from six randomised phase 3 clinical trials that shared detailed, individual-level data on short-term and long-term side effects affecting the urinary and bowel systems.
The researchers found patients with moderate or worse early side effects were more likely to experience severe late effects, even years after treatment. Men with early urinary or bowel issues were also more likely to report significant drops in their ability to manage daily activities and overall quality of life.
For urinary toxicity, experiencing acute toxicity increased the rate of late toxicity from 7.5% to 12.5%, and for bowel toxicity, experiencing acute toxicity increased the rate of late toxicity from 12.7% to 22.5%.
The odds of having a clinically-significant decline in urinary quality of life were 1.4 times as high for men who had moderate acute urinary toxicity. The odds of having a clinically-significant decline in bowel quality of life were 1.5 times as high for men who had moderate acute bowel toxicity.
“These results show that acute toxicities following prostate radiotherapy are associated with late toxicities months and years later,” said first author Dr John Nikitas, oncology resident at UCLA Health. “This underscores the importance of measures that reduce the risk of acute toxicities because they may also potentially improve long-term outcomes and quality of life for patients.”
Kishan emphasised the potential impact of newer techniques to reduce both acute and late toxicities:
“Reducing early side effects through advanced techniques like MRI-guided radiation, which allows for more precise targeting of tumours, and urethral-sparing methods, which uses spacers between the prostate to protect surrounding tissues and rectum could potentially help lower the risk of lasting side effects.”
However, more studies are needed to determine if specific strategies to reduce early side effects will improve long-term outcomes and whether treating short-term side effects early can help prevent long-term complications.
New insights into what causes the painful and disruptive symptoms of urinary tract infections (UTIs) could offer hope for improved treatment. Nearly one in three women will experience UTIs before the age of 24, and many elderly people and those with bladder issues from spinal cord injuries can experience multiple UTI’s in a single year.
Findings from a new study led by Flinders University’s Dr Luke Grundy and SAHMRI’s Dr Steven Taylor show that UTIs cause the nerves in the bladder to become hypersensitive resulting in the extremely painful and frequent urge to urinate, pelvic pain, and burning pain while urinating.
“We found that UTIs, caused by bacterial infections such as E. coli, can significantly alter the function and sensitivity of the nerves that usually detect bladder fulness, a phenomenon known as ‘bladder afferent hypersensitivity’, says Dr Grundy, from the College of Medicine and Public Health.
“The study was the first of its kind to explore the impact of UTIs on the sensory signals that travel from the bladder to the brain, and the direct link this response has to causing bladder pain and dysfunction.”
A normal bladder will expand to store urine and can store up to two cups of urine for several hours. Once full, the bladders nervous system will signal that it is time to urinate, or empty the bladder.
Described in Brain, Behavior, & Immunity – Health, researchers analysed how UTIs cause sensory nerves that respond to bladder distension to become hypersensitive, so that they send signals of bladder fulness, even when the bladder is not yet full.
“Our findings show that UTIs cause the nerves in the bladder to become overly sensitive, which means that even when the bladder is only partly filled, it can trigger painful bladder sensations that would signal for the need to urinate,” he says.
“We think that these heightened sensory responses may serve as a protective mechanism, alerting the body to the infection and prompting more frequent urination to expel the bacteria.”
Building on previous research, the new study reveals a deeper understanding of how UTIs affect bladder function and the nervous system, and raises important questions about the role of bladder hypersensitivity in the development of UTI-related symptoms.
“Our findings go further in identifying the significant changes that occur during UTIs and provide a clearer picture of the mechanisms behind the painful and disruptive bladder sensations often associated with these infections,” says Dr Grundy.
The study also suggests that better understanding and targeting of bladder afferent hypersensitivity could improve treatment options for patients suffering from recurrent UTIs or other bladder conditions where sensory dysfunction plays a role.
“Theoretically we should be able to find a way to address hypersensitive nerves in the bladder and reduce or eliminate the painful and debilitating symptoms of a UTI,” he adds. This would improve quality of life whilst antibiotics are taking care of the infection.
Researchers are striving to address the limited treatments available for bladder pain by exploring how the findings may translate into clinical practice and improve the management of UTIs in patients.
Rotator-cuff disorders are the most common cause of shoulder symptoms. Tears of the rotator cuff can result from a substantial traumatic injury or can occur slowly over time. Most degenerative tears occur in the dominant arm of adults over the age of 40, and their prevalence increases with as you age. There are a variety of treatments.
In a recent publication in the New England Journal of Medicine, University of Michigan Health professor and chair of Physical Medicine and Rehabilitation, Nitin Jain, MD, MSPH, talks through the different treatments available for rotator-cuff tears to help bring together a better understanding of how to treat the issue for patients and providers.
Nonoperative treatment, such physical therapy, is the typical approach to treating rotator-cuff tears. However, surgery is considered in certain patients whose rotator-cuff tears don’t resolve with nonoperative treatments. Topical treatments also exist, such as glyceryl trinitrate (nitro-glycerine) gel which appears to have the greatest success.
Symptoms of rotator-cuff tears
“Patients with nontraumatic or degenerative rotator-cuff tears typically experience an onset of shoulder pain that seems to have no cause,” said Jain.
“However, it is not uncommon for tears to be asymptomatic and become slowly painful over time, or even cause no pain at all.”
Jain says there are some activities that make the injury more painful as the tear worsens. This can include sleeping on your shoulder, overhead activities and/or lifting items above your shoulder level.
“Rotator-cuff tears may also grow over time, but there’s a lack of correlation between patient symptoms and the size and thickness of the tear,” explained Jain.
Your active range of motion and arm strength are usually affected by the tear, which gets assessed by using certain protocols when providers are searching for a diagnosis.
Rehabilitation and physical therapy for rotator-cuff tears
This is the most common form of treatment for rotator-cuff tears, says Jain: “It is recommended that as the first line of specialist referral, patients seek care from a physical medicine and rehabilitation doctor (physiatrist) or sports medicine doctor.
“Rehabilitation and physical therapy routines address areas such as periscapular muscle weakness, correcting scapular posture and improve rotator cuff muscle strength and endurance.”
In observational studies, more than 80% of patients who received supervised physical therapy reported reduced pain and improved function between 6 months to a year. However, the trial populations consisted of patients with various types of rotator-cuff injuries and had no requirement for advanced imaging to confirm their diagnosis.
“One of the biggest factors in a successful rehabilitation was trust from patients that their physical therapy routine would improve their rotator-cuff condition,” said Jain. “The more patients leaned into the physical therapy routine, the better their outcomes were.”
Other nonpharmacologic therapies for rotator-cuff tears
Evidence suggests that psychosocial distress and depression are associated with shoulder pain and reduced function in patients with rotator-cuff tears.
“Despite this, though, there isn’t much data supporting psychosocial interventions in the treatment of rotator-cuff disorders, even though they show benefit in the treatment of other musculoskeletal disorders such as lower back pain,” said Jain.
In addition to the lack of data for psychological interventions for rotator-cuff repairs, there’s also a lack of high quality trials supporting the use of manual therapy, massage therapy, acupuncture, therapeutic ultrasonography, transcutaneous electrical nerve stimulation, shock-wave therapy or pulsed-electromagnetic-field therapy.
Topical and oral medications and injections for rotator-cuff tears
There isn’t a lot of evidence supporting the use of topical medications in treating rotator-cuff disorders. The topical treatment with the best outcomes so far has been glyceryl trinitrate.
In a small, randomised trial it showed short term benefits in the treatment of rotator-cuff disorders, but it also found there was a considerably high bias towards this treatment from participants in the study.
Topical nonsteroidal anti-inflammatory drugs such as diclofenac and ketoprofen have also been effective in providing pain relief in chronic musculoskeletal pain and tendinitis and have a better safety profile than oral, nonsteroidal anti-inflammatory drugs.
“But high quality evidence supporting their use in rotator-cuff disorders is still lacking,” explained Jain.
For oral medications, randomised research trials have shown that oral nonsteroidal anti-inflammatory drugs (NSAIDs) reduced pain, although modestly, in patients with rotator-cuff disorders.
“Opioid drugs are generally not recommended due to risks associated with their use and lack of evidence of superiority to nonopioid therapy in a variety of musculoskeletal conditions,” said Jain.
Jain says acetaminophen hasn’t been studied specifically in rotator-cuff disorders, but what has been studied has shown little or no benefit regarding pain or function.
“Rigorous evidence is lacking to inform the use of pain-modulating drugs such as gabapentin, duloxetine, and pregabalin, specifically regarding the nonoperative treatment of rotator-cuff disorders,” said Jain.
Injection of a glucocorticoid, together with a local anaesthetic, has been reported to provide symptomatic pain relief in patients with rotator-cuff disorders.
Small trials have shown short term benefit, about four weeks long, of pain relief through using this method. The injections are performed in the subacromial space of the rotator-cuff for those with subacromial impingement syndrome. Some centres use ultrasound guidance to administer this treatment, which can reduce the risk of an inadvertent injection into the tendon.
Surgical interventions for rotator-cuff injuries
“Surgical interventions are not the initial recommendation when it comes to rotator-cuff repairs. However, they may be considered in some patients whose condition does not improve with conservative treatment,” said Jain.
Observational data supports that surgery is associated with better function and reduced pain in patients who are under 65 years of age and have smaller tears.
Surgical repairs are mostly performed arthroscopically, involving the repair of the torn tendon and resecuring it to the humerus to allow for tendon-to-bone healing as well as a low incidence of complications, explains Jain.
The hypothesis that surgical intervention can reduce the progression of muscle degradation has led some experts to recommend early surgical intervention, but data is still lacking on outcomes of early surgery compared to surgery later.
