Day: June 18, 2024

Categories : AntibioticsTags :

Temperature may be a New Weapon in the Battle against Antibiotic Resistance

On By ModernMedia

Scientists from the University of Groningen in the Netherlands, together with colleagues from other European universities, have tested how a fever could affect the development of antimicrobial resistance. In laboratory experiments, they found that a small increase in temperature from 37 to 40 degrees Celsius drastically changed the mutation frequency in E. coli bacteria, which facilitates the development of resistance. If these results can be replicated in human patients, fever control could be a new way to mitigate the emergence of antibiotic resistance.

There are two ways to fight the threat of antimicrobial resistance: by developing new drugs, or by preventing the development of resistance. ‘We know that temperature affects the mutation rate in bacteria’, explains Timo van Eldijk, co-first author of the paper published in JAC-Antimicrobial Resistance. ‘What we wanted to find out was how the increase in temperature associated with fever influences the mutation rate towards antibiotic resistance.’

‘Most studies on resistance mutations were done by lowering the ambient temperature, and none, as far as we know, used a moderate increase above normal body temperature,’ Van Eldijk reports. Together with Master’s student Eleanor Sheridan, he cultured E. coli bacteria at 37 or 40 degrees Celsius, and subsequently exposed them to three different antibiotics to assess the effect. ‘Again, some previous human trials have looked at temperature and antibiotics, but in these studies, the type of drug was not controlled.’ In their laboratory study, the team used three different antibiotics with different modes of action: ciprofloxacin, rifampicin, and ampicillin.

The results showed that for two of the drugs, ciprofloxacin and rifampicin, increased temperature led to an increase in the mutation rate towards resistance. However, the third drug, ampicillin, caused a decrease in the mutation rate toward resistance at fever temperatures. ‘To be certain of this result, we replicated the study with ampicillin in two different labs, at the University of Groningen and the University of Montpellier, and got the same result,’ says Van Eldijk.

The researchers hypothesized that a temperature dependence of the efficacy of ampicillin could explain this result, and confirmed this in an experiment. This explains why ampicillin resistance is less likely to arise at 40 degrees Celsius. ‘Our study shows that a very mild change in temperature can drastically change the mutation rate towards resistance to antimicrobials,’ concludes Van Eldijk. ‘This is interesting, as other parameters such as the growth rate do not seem to change.’

If the results are replicated in humans, this could open the way to tackling antimicrobial resistance by lowering the temperature with fever-suppressing drugs, or by giving patients with a fever antimicrobial drugs with higher efficacy at higher temperatures. The team concludes in the paper: ‘An optimized combination of antibiotics and fever suppression strategies may be a new weapon in the battle against antibiotic resistance.’

Source: University of Groningen

Categories : HospitalsTags :

Global Trial Confirms Benefit of Antacids on Bleeding Prevention for Ventilated Patients

On By ModernMedia
Photo by Rodnae Productions on Pexels

A widely available drug helps prevent upper gastrointestinal bleeding in critically ill adults on a breathing machine, according to the results of a global study and meta-analysis led by researchers at McMaster University. 

The research, published on June 14, 2024 in The New England Journal of Medicine and NEJM Evidence, investigated the effect of the gastric acid suppressant pantoprazole, which is primarily used to treat heartburn caused by gastroesophageal reflux disease (GERD). 

Patients in the intensive care unit (ICU) who need a breathing machine (mechanical ventilator) also receive pantoprazole to prevent upper gastrointestinal bleeding, caused by stress-induced ulcers in the stomach. Concerns emerged about whether this complication of critical illness had disappeared over the years, and about side effects of pantoprazole, including increased risk of death in the sickest patients. The research provides critical care teams with certainty about whether the medications should be used in practice.   

“This is the largest randomized trial on this topic in the world, led by Canada. Physicians, nurses, and pharmacists working in the ICU setting will use this information in practice right away, and the trial results and the updated meta-analysis will be incorporated into international practice guidelines,” said lead author and principal investigator Deborah Cook, a professor in the Department of Medicine at McMaster. 

Global randomized control trial  

The Reevaluating the Inhibition of Stress Erosions (REVISE) Trial was a randomised control trial that compared the effect of pantoprazole to placebo in critically ill adults on a breathing machine. The trial was run in 68 centres in eight countries and over 4800 patients underwent randomization. Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo but not in a lower risk of death. 

Clinically important upper gastrointestinal bleeding occurred in 25 of 2417 patients (one per cent) receiving pantoprazole and in 84 of 2404 patients (nearly four per cent) receiving placebo. At 90 days, death was reported in 696 of 2390 patients (29 per cent) in the pantoprazole group and in 734 of 2379 patients (30 per cent) in the placebo group.   

Updated systematic review 

Researchers conducted a meta-analysis of 12 randomised trials of proton-pump inhibitors for GI bleeding prevention in 10 000 critically ill patients to summarise the current evidence on the outcomes of gastrointestinal bleeding, mortality, pneumonia and C. difficile infection. 

The medications were associated with a reduced incidence of clinically important upper gastrointestinal bleeding and may have little or no effect on mortality. The evidence also showed the medications may have no effect on pneumonia and little or no effect on C. difficile infection. 

The research was funded by the Canadian Institutes for Health Research, the Accelerating Clinical Trials Fund, Physicians Services Incorporated of Ontario, Hamilton Association of Health Sciences Organization, and the National Health Medical Research Council of Australia. 

The original text of this story is licensed under a Creative Commons Attribution-No Derivs 2.5 Canada (CC BY-ND 2.5 CA).

Source: McMaster University

Categories : Diet and Nutrition Mental HealthTags :

High-fat Diets can Interfere with Serotonin Pathways, Fuelling Anxiety

On By ModernMedia
Photo by Jonathan Borba

New research from CU Boulder shows that turning to junk food when we’re stressed out may backfire. The study found that in animals, a high-fat diet disrupts resident gut bacteria, alters behaviour and, through a complex pathway connecting the gut to the brain, influences brain chemicals in ways that fuel anxiety.

“Everyone knows that these are not healthy foods, but we tend to think about them strictly in terms of a little weight gain,” said lead author Christopher Lowry, a professor of integrative physiology at CU Boulder. “If you understand that they also impact your brain in a way that can promote anxiety, that makes the stakes even higher.”

For the study, published in the journal Biological Research in May, Lowry worked with first author Sylvana Rendeiro de Noronha, a doctoral student at the Federal University of Ouro Preto in Brazil.

In a previous study, the team found that rats fed a high-fat diet consisting primarily of saturated fat showed increases in neuroinflammation and anxiety-like behaviour.

While evidence is mixed, some human studies have also shown that replacing a high-fat, high-sugar, ultra-processed diet with a healthier one can reduce depression and anxiety.

The dark side of serotonin

To better understand what may be driving the fat-anxiety connection, Lowry’s team divided male adolescent rats into two groups: Half got a standard diet of about 11% fat for nine weeks; the others got a high-fat diet of 45% fat, consisting mostly of saturated fat from animal products.

The typical American diet is about 36% fat, according to the Centers for Disease Control and Prevention.

Throughout the study, the researchers collected faecal samples and assessed the animals’ gut microbiome. After nine weeks, the animals underwent behavioural tests.

When compared to the control group, the group eating a high-fat diet, not surprisingly, gained weight. But the animals also showed significantly less diversity of gut bacteria. Generally speaking, more bacterial diversity is associated with better health, Lowry explained. They also hosted far more of a category of bacteria called Firmicutes and less of a category called Bacteroidetes. A higher Firmicutes to Bacteroidetes ratio has been associated with the typical industrialised diet and with obesity.

The high-fat diet group also showed higher expression of three genes (tph2, htr1a, and slc6a4) involved in production and signalling of the neurotransmitter serotonin – particularly in a region of the brainstem known as the dorsal raphe nucleus cDRD, which is associated with stress and anxiety.

While serotonin is often billed as a “feel-good brain chemical,” Lowry notes that certain subsets of serotonin neurons can, when activated, prompt anxiety-like responses in animals. Notably, heightened expression of tph2, or tryptophan hydroxylase, in the cDRD has been associated with mood disorders and suicide risk in humans.

“To think that just a high-fat diet could alter expression of these genes in the brain is extraordinary,” said Lowry. “The high-fat group essentially had the molecular signature of a high anxiety state in their brain.”

A primal gut-brain connection

Just how a disrupted gut can change chemicals in the brain remains unclear. But Lowry suspects that an unhealthy microbiome compromises the gut lining, enabling bacteria to slip into the body’s circulation and communicate with the brain via the vagus nerve, a pathway from the gastrointestinal tract to the brain.

“If you think about human evolution, it makes sense,” Lowry said.  “We are hard-wired to really notice things that make us sick so we can avoid those things in the future.”

Lowry stresses that not all fats are bad, and that healthy fats like those found in fish, olive oil, nuts and seeds can be anti-inflammatory and good for the brain.

But his research in animals suggests that exposure to an ultra-high-fat diet consisting of predominantly saturated fats, particularly at a young age, could both boost anxiety in the short-term and prime the brain to be more prone to it in the future.

His advice: Eat as many different kinds of fruits and vegetables as possible, add fermented foods to your diet to support a healthy microbiome and lay off the pizza and fries. Also, if you do have a hamburger, add a slice of avocado. Research shows that good fat can counteract some of the bad.

Rodrigo Cunha de Menezes, professor of physiology at Federal University of Ouro Preto in Brazil, is co- senior author on this paper.

Source: University of Colorado Boulder

Categories : Cancer Healthcare Politics and RegulationsTags :

Increasing SA’s Blood Cancer Survival Rate Starts with the State Healthcare System

On By ModernMedia
Credit: National Cancer Institute

While cancer survivors are increasing in countries like the United States, South Africa faces a different reality, with 4000 people dying from blood cancer every year. Dr Sharlene Parasnath, Head of the Department of Clinical Haematology and Stem Cell Transplant Unit at Inkosi Albert Luthuli Central Hospital and DKMS Africa board member, believes that this discrepancy is largely due to the quality of care provided to patients who rely on the state healthcare system. 

Counting the costs

She explains that South Africa’s state sector relies predominantly on conventional chemotherapy to treat patients as opposed to newer targeted immunotherapies. “These may be accessible to some patients in the private sector and standard care in developed countries but are out of reach for public healthcare due to their unaffordability. Countries that use more targeted therapies not only improve overall survival but also decrease the undesirable adverse effects of cancer treatments. These therapies may be given with chemotherapy or on their own and work by attacking specific genetic mutations in cancer cells. Examples include monoclonal antibodies (MABs) and Bispecific T cell engagers (BiTES), which mimic the immune system to destroy cancer cells. There are also tyrosine kinase inhibitors (TKIs) which block the signals that promote cancer cell growth.”

“The prohibitive costs of these treatments are why stem cell transplants are being encouraged in South Africa since they offer those with blood cancers a chance of a cure,” points out Dr Parasnath. “However, this approach comes with challenges. For instance, the state will not pay for a transplant from an unrelated donor, despite two thirds of patients in need of a transplant being unable to find a suitable donor from within their family.”

Fewer nurses, fewer transplants

“Human resource constraints, particularly the shortage of specialist nurses, is another factor hindering more stem cell transplants from being carried out,” she notes. “Currently, there is no formalised training for nurses in haematology in South Africa. So, what tends to happen is that the majority of blood cancer patients end up being cared for either by oncology-trained nurses or registered general nurses with limited practical education and training in the kind of care they require. Important aspects of nursing which can improve patient outcomes include dietary restrictions, visitor guidelines, decreasing bleeding risk, infection control and early detection of potential complications such as graft rejection, graft vs. host disease and veno-occlusive disease that can develop following a stem cell transplant.”

Referring to an article in the South African Medical Journal titled Haematopoietic Stem Cell Transplantation in South Africa: Current limitations and future perspectives, Dr Parasnath adds that lack of staff ultimately leads to implicit rationing of healthcare, thereby limiting access to this life-changing medical procedure.

Mental health is health

She stresses that human resource constraints in terms of mental health support is also detrimental to patients with blood cancers. “Unfortunately, this tends to be the case both in the public and private sectors, as one out of three people diagnosed with cancer ends up struggling with a mental health disorder such as anxiety or depression as well, yet  less than 10% of patients are referred to seek help. The South African Society of Psychiatrists has even warned that if left untreated or undiagnosed, this could impact the patient’s ability to function on a daily basis, including undergoing treatment.”

Dr Parasnath emphasises another glaring gap in mental health support. “NGOs offer on-site social workers for hospitalised children with blood cancer, but adults, especially those who are not members of medical aid schemes, often have no options available to them. Not only do they grapple with the emotional toll of their diagnosis and treatment side effects, but this is further complicated by anxieties around their finances and the wellbeing of their children.”

The Cancer Association of South Africa’s (CANSA) Fact Sheet on Cancer and Mental Health highlights that there remains a huge unmet need for mental health in cancer care, calling for more effective clinical integration of relevant services, which must be informed by patient choice and clinical need, and accessible throughout the patient’s whole cancer journey. It also stresses the need for measurement of patient quality of life as a marker of treatment effectiveness.

“The Department of Health must recognise clinical haematology as a discipline in its own right with its own unique needs. For too long, it has had to feed off of the limited oncology budget. But if we are to up the blood cancer survival rate, funding must be provided for necessities such as more modern treatments, unrelated stem cell transplantation and formalised training of nurses,” says Dr Parasnath.

She also urges South Africans to increase the pool of available stem cell donors either by registering themselves or supporting organisations like DKMS Africa which connects patients with potential matches by providing access to a global registry of over 12 million donors. Financial donations directly address two critical needs: funding the registration of new donors and assisting patients facing financial challenges as a result of the transplant process.”

“With focused efforts, South Africa can join the global trend of increasing blood cancer survival rates, offering a brighter future for patients and their families,” concludes Dr Parasnath.

To register visit https://www.dkms-africa.org/register-now or for more information, contact DKMS Africa on 0800 12 10 82.