Tag: 28/7/22

Shortage of Blood Test Tubes Prompts Saving Efforts

Blood sample being drawn
Photo by Hush Naidoo Jade Photography on Unsplash

A pandemic-related shortage of a mundane item, ‘blue top’ blood test tubes used toollect blood samples from patients, has caused headaches for health systems worldwide.

But it may also have a silver lining: A lesson in how to reduce unneeded medical tests, whether or not there’s a shortage, according to a new study published in JAMA Internal Medicine.

The shortage gave researchers a chance to see if alerting doctors at the moment they’re placing an order could encourage them to seek a test only when results will immediately affect care.

In the new study, an alert led to a nearly immediate 29% drop in orders for one common test. The reduced level persisted for months.

“This shows that small interventions can make a big difference, and suggests the potential for other types of low-value care to benefit from a similar intervention,” says lead author Madison Breeden, MD, who conducted the study during her year as chief resident of Quality and Patient Safety. She’s already exploring if the approach might reduce unnecessary antibiotic prescriptionse

Breeden and her colleagues describe what happened in spring 2021 when University of Michigan Health supply chain and pathology experts began worrying about a potential shortage of ‘blue top’ tubes. The pandemic had created very high demand for the chemical the tubes contain: sodium citrate, which stabilises blood samples until a laboratory team can analyse three blood clotting-related properties, called PT, INR and PTT.

After emailing all providers, U-M Health added a ‘best practices alert’ to doctors’ test-ordering electronic system. They could still order PT/INR/PTT tests, but were asked for “thoughtful restraint in reflexive ordering.”

The alert began popping up a month before the FDA issued an official shortage notice and the issue got widespread attention. The shortage continues today and has grown to other types of tests.

The researchers looked at what happened for six months after the alert began appearing at U-M Health, and compared it with data from six months before.

“There are very important reasons to order this test in some patients, for instance before an operation or when managing certain conditions and treatments,” Breeden explains. “But it may also be part of a standard order set that’s put in during an emergency department visit and continues to be ordered repeatedly after the patient is admitted to the hospital, even though the results won’t change their care.” For such patients, a one-time test might be indicated, but not repeated testing.

Busy doctors entering orders for tests don’t tend to think about the supplies and people power needed to carry out those tests, Breeden notes. In the face of a shortage, or of strong evidence that a test is often over-ordered, an alert could help prioritize the tests for those who need them most.

Canadian experts have actually flagged PT/INR/PTT tests as a target for reducing unnecessary care, through the Choosing Wisely program. So has the American Society for Clinical Laboratory Science, a medical professional group.

Evolution of Lactose Tolerance Driven by Starvation and Disease

Source: Pixabay CC0

The ability to digest lactose is thought to have evolved in concert with milk entering the diet where dairy farming was commonplace, but a new study published in Nature paints a much grimmer picture: starvation and disease appeared to drive its spread through European populations.

Five thousand years ago virtually all humans were (like all other mammals) lactose intolerant, losing the ability to produce lactase to digest milk after weaning and suffering bloating, gas and diarrhoea as adults when they they drank milk.

Professor George Davey Smith, Director of the MRC Integrative Epidemiology Unit at the University of Bristol and a co-author of the study, said: “However, a genetic trait called lactase persistence has evolved multiple times over the last 10 000 years and spread in various milk-drinking populations in Europe, central and southern Asia, the Middle East and Africa. Today, around one third of adults in the world are lactase persistent.”

Using archaeological data, genetic samples and computer modelling, the team demonstrated that lactase persistence genetic trait was not common until around 1000 BCE, nearly 4000 years after it was first detected around 4700–4600 BCE.

“The lactase persistence genetic variant was pushed to high frequency by some sort of turbocharged natural selection. The problem is, such strong natural selection is hard to explain,” added Professor Mark Thomas, study co-author from University College London.

In order to establish how lactose persistence evolved, Professor Richard Evershed, the study’s leader, assembled a database of over 7000 animal fat residues from 13 181 pottery fragments. His findings showed that milk was used extensively in European prehistory, dating from the earliest farming nearly 9000 years ago, but its use waxed and waned in different areas and times.

To understand how this relates to the evolution of lactase persistence, the research team, led by Prof Thomas, tracked the presence of the lactase persistence gene using ancient DNA sequences from more than 1700 prehistoric European and Asian individuals. The first instance seen was after around 5000 years ago, and 2000 years later it was at appreciable frequencies and today is very common. Next, his team developed a new statistical approach to examine how well changes in milk use through time explain the natural selection for lactase persistence. Surprisingly, no association was found, challenging the long-held view the extent of milk use drove lactase persistence evolution.

Professor George Davey Smith’s team had been probing the UK Biobank data, comprising genetic and medical data for more than 300 000 living individuals, found only minimal differences in milk drinking behaviour between genetically lactase persistent and non-persistent people. Critically, the large majority of people who were genetically lactase non-persistent experienced no short or long-term negative health effects when they consume milk.

Professor Davey Smith added: “Our findings show milk use was widespread in Europe for at least 9000 years, and healthy humans, even those who are not lactase persistent, could happily consume milk without getting ill. However, drinking milk in lactase non-persistent individuals does lead to a high concentration of lactose in the intestine, which can draw fluid into the colon, and dehydration can result when this is combined with diarrhoeal disease.”

This can have implications for individuals who are unwell, according to Prof Smith. “If you are healthy and lactase non-persistent, and you drink lots of milk, you may experience some discomfort, but you not going to die of it. However, if you are severely malnourished and have diarrhoea, then you’ve got life-threatening problems. When their crops failed, prehistoric people would have been more likely to consume unfermented high-lactose milk – exactly when they shouldn’t.”

To test these ideas, Prof Thomas’s team applied indicators of past famine and pathogen exposure into their statistical models. Their results clearly supported both explanations – the lactase persistence gene variant was under stronger natural selection when there were indications of more famine and more pathogens.

The authors concluded: “Our study demonstrates how, in later prehistory, as populations and settlement sizes grew, human health would have been increasingly impacted by poor sanitation and increasing diarrheal diseases, especially those of animal origin. Under these conditions consuming milk would have resulted in increasing death rates, with individuals lacking lactase persistence being especially vulnerable. This situation would have been further exacerbated under famine conditions, when disease and malnutrition rates are increased. This would lead to individuals who did not carry a copy of the lactase persistence gene variant being more likely to die before or during their reproductive years, which would push the population prevalence of lactase persistence up.

“It seems the same factors that influence human mortality today drove the evolution of this amazing gene through prehistory.”

Source: University of Bristol

SARS-CoV-2 Variants are Evolving to Evade Human Interferons

SARS-CoV-2 infecting a human cell
Infected cell covered with SARS-CoV-2 viruses. Source: NIAID

Researchers have investigated how antiviral proteins called interferons interact with SARS-CoV-2. The study, published in PNAS, focuses on how the innate immune system defends against this coronavirus, which appears to be adapting to evade this interferon response.

The study was the result of a collaborative effort, including the laboratories of Mario Santiago, PhD, associate professor of medicine and Eric Poeschla, MD, professor of medicine, both at the University of Colorado School of Medicine.

While the adaptive arm of the immune system robustly deals with infection by generating antibodies and T cells, the innate arm forms an earlier, first line of defence by recognising conserved molecular patterns in pathogens.

“SARS-CoV-2 just recently crossed the species barrier into humans and continues to adapt to its new host,” said Prof Poeschla. “Much attention has deservedly focused on the virus’s serial evasions of neutralising antibodies. The virus seems to be adapting to evade innate responses as well.”

The type I Interferon system is a major player in antiviral defence against all kinds of viruses. Virus-infected cells release type I interferons (IFN-α/β), which warn the body of the intrusion. Secreted interferons cause susceptible cells to express powerful antiviral mechanisms to limit viral growth and spread. The interferon pathway could significantly reduce the levels of virus initially produced by an infected individual.

“They are clinically viable therapeutic agents that have been studied for viruses like HIV-1 for years,” explained Prof Santiago. “Here we looked at up to 17 different human interferons and found that some interferons, such as IFNalpha8, more strongly inhibited SARS-CoV-2. Importantly, later variants of the virus have developed significant resistance to their antiviral effects. For example, substantially more interferon would be needed to inhibit the omicron variant than the strains isolated during the earliest days of the pandemic.”

The data suggests that COVID clinical trials on interferons, dozens of which are listed in clinicaltrials.gov, may need to be interpreted based on which variants were circulating when the study was conducted. Researchers say that future work to decipher which of SARS-CoV-2’s multitude of proteins might be evolving to confer interferon resistance may contribute in that direction.

Source: University of Colorado Anschutz Medical Campus