Body

A study published in the journal Applied Ergonomics compared the standardised processes set out for community pharmacists to follow when dispending medication to what happens in reality. A gap was revealed and researchers also looked at the reasons for this.

The research, "Mind the gap: Examining work-as-imagined and work-as-done when dispensing medication in the community pharmacy setting"*, was conducted by the National Institute for Health Research Greater Manchester Patient Safety Translational Research Centre (NIHR GM PSTRC). The Centre is a partnership between The University of Manchester and Salford Royal NHS Foundation Trust.

The research involved observing pharmacists and pharmacy staff as they conducted the task of dispensing, and comparing this with what was documented to happen according to the procedures. The actions involved in dispensing were mapped out in detail, through the use of a human factors technique called task analysis. A focus group of community pharmacists helped the researchers understand why some of these differences between written standardised procedures and reality exist.

Ahmed Ashour, a researcher in the Medication Safety theme at the GM PSTRC and lead researcher for this study, said: "Once we had identified a gap between the theory and reality of medication dispensing in community pharmacy a further focus group helped us to recognise why the gap exists. Importantly, they were able to help put these reasons into four main themes, enabling us to understand the context around tasks that take place in a pharmacy."

These themes are:

The need to be more efficient due to factors such as time pressures

Lack of resources which are required (e.g., access to patient records)

Thoroughness (to ensure common mistakes were avoided)

Delegating safeguards which means staff members may skip a step or a check because they know a computer system or other safety measure will fill the gap.

Professor Darren Ashcroft, Theme Lead for Medication Safety at the GM PSTRC, said: "In recent years there has been a drive towards improving patient safety through greater standardisation of how tasks are completed in health care as a way of reducing the risk of errors. However, pharmacists work in incredibly busy and pressured pharmacies and it's crucial the protocols that are in place take that into account.

"That's why this research is vital as it looks at how these protocols perform in reality and identifies the gap which allows us to make recommendations to make medication dispensing safer."

The research suggests that more user testing of standardised operating procedures is required to better reflect the complexity of day-to-day working practices. In addition, in some instances greater flexibility may be needed in the procedures, to allow for safe variations in practice, when pharmacists deem it necessary to optimise patient safety.

Ahmed, concluded: "This research has shown that not all differences between procedures and practice are done to make tasks quicker. At times pharmacists feel it's necessary to be more thorough when dispensing or when they do not have access to the resources they need. Further research should look at each of these themes in-depth, and highlight how standardised procedures should be adapted in light of them."

BOSTON - Although abnormal blood clotting has been identified as one of the primary causes of death from COVID-19, early treatment in an intensive care unit (ICU) with therapeutic anticoagulation (anti-clotting) for adults who are critically ill with COVID-19 does not appear to improve chances of survival, and could do more harm than good by increasing the risk for major bleeding, a multicenter research group cautions.

"In patients critically ill with COVID-19, therapeutic dose anticoagulation started early in the ICU stay was not associated with improved survival,"says Hanny Al-Samkari, MD, an investigator in the Division of Hematology/Oncology at Massachusetts General Hospital (MGH) and lead author of a study reporting the findings in the journal Annals of Internal Medicine. (Whereas such patients almost always receive low, "prophylactic-dose" anticoagulation, therapeutic doses are much higher.)

Al-Samkari and colleagues at MGH, Brigham and Women's Hospital, and Harvard Medical School (HMS) analyzed health records from STOP-COVID (Study of the Treatment and Outcomes in Critically Ill Patients With COVID-19), a multicenter study that included adults 18 and older who had laboratory-confirmed COVID-19 and were admitted to participating ICUs at 67 geographically diverse hospitals in the United States.

The researchers evaluated the incidence of venous thromboembolism (VTE), a serious and potentially fatal blood clotting event, as well as the occurrence of major, life-threatening bleeding. They also examined the effects of early therapeutic anticoagulation on survival.

To do this, they used data from the study to simulate a randomized clinical trial in which patients are randomly assigned to receive or not receive therapeutic anticoagulation within two days of being admitted to an ICU. The model took into account detailed data on demographics, comorbidities, medications and severity of illness that might otherwise influence the results.

They found that 6.3% of the 3,239 patients had VTE confirmed on imaging studies and 2.8% had major bleeding events. The incidence of VTE was considerably less frequent than in previous, mostly smaller studies of patients with COVID-19, which reported VTE rates as high as 42%.

The only factors that accurately predicted higher risk for VTE were male sex and higher circulating levels of D-dimer, a protein fragment produced when a blood clot breaks up.

Importantly, the results showed that there was no survival benefit for patients who received therapeutic anticoagulation in the first two days of an ICU stay compared with patients who did not receive early therapeutic anticoagulation.

"We looked at multiple subgroups of patients, including by age, sex and severity of illness, and we did not find any subgroup that benefited from early therapeutic anticoagulation," says senior author and principal investigator of STOP-COVID, David E. Leaf, MD, MMSc, director of clinical and translational research in acute kidney injury in the Division of Renal Medicine at the Brigham.

The study results also reinforce that "bleeding matters. Bleeding is not trivial in these patients," Al-Samkari says. Of the 90 patients who had a major bleeding event in the study, 60 were receiving therapeutic anticoagulation at the time of the event, and 56 of the 90 patients (62%) with a major bleed died within 28 days. The most common sites of bleeding were in the gastrointestinal tract and within the skull.

In addition to the clinical findings, the study results support the use of target trial emulation, the type of simulation the researchers used, to quickly acquire information that can be used to improve clinical care in a rapidly changing environment, says co-first author Shruti Gupta, MD, MPH, from the Division of Renal Medicine at the Brigham.

"This is another example of how target trial emulation, which we've used in other important studies from our STOP-COVID consortium, can be applied to observational data and allow us to estimate the effects of different treatments on clinical outcomes. This is particularly important because randomized clinical trials often take time and require large numbers of patients to see meaningful differences in outcomes," she says.

Clinical staff at member institutions of the STOP-COVID consortium contributed data to the study. There was no outside funding source.

Studies examining the effectiveness of treatments for COVID-19 often do not include the very populations hardest hit by the disease, according to a new review by University of Chicago Medicine researchers.

The findings, based on an analysis of all US COVID-19 treatment trials registered on ClinicalTrials.gov, were published Jan. 27 in the Journal of General Internal Medicine.

"This study highlights the blind spot in how clinical trials are done in the United States," said senior author Neda Laiteerapong, MD, MS, a general internist and associate director of the Center for Chronic Disease Research and Policy at the University of Chicago. "Researchers, hospitals and pharmaceutical companies need to think hard about their commitment to improving the health of all people."

Since the pandemic began, certain communities have been disproportionately affected by COVID-19, with Black and Hispanic patients being 30% to 50% more likely than whites to test positive for COVID-19. Researchers attribute this to several factors, including systemic health disparities, working frontline jobs and living in multigenerational households.

The team examined 303 active U.S. COVID-19 treatment trials involving more than 92,000 patients and used Census data from the 2015 American Community Survey to estimate the proportion of Black and Hispanic individuals who could be potentially recruited from the geographic catchment area of each study's recruitment hospital. This study did not include data on COVID-19 prevention studies, such as those testing vaccine candidates.

The researchers found the studies were being undertaken at hospitals that less frequently cared for Black and Hispanic patients: Only about 17% of these hospitals' patients were Black and 14% were Hispanic. There are several reasons why this may be happening, the researchers theorize.

"Smaller community hospitals may have larger communities of color but may not be equipped to set up these sorts of trials for infectious diseases," said Sukarn Chokkara, a second-year medical student at the University of Chicago Pritzker School of Medicine and lead author of the paper.

These same institutions may lack the experienced research staff and pharmaceutical company relationships needed to conduct clinical trials. Meanwhile, it can be burdensome for larger institutions designing clinical trials to implement study sites at smaller hospitals. Recruiting minority populations also frequently requires cultural tailoring and awareness of the legacy of discrimination and unethical medical research.

After conducting their cross-sectional analysis of non-observational COVID-19 clinical trials, the team also found that:

51% of trials excluded patients with non-severe comorbid diseases, such as diabetes.

About 60% of trials excluded pregnant women and/or required using contraception.

47% of trials excluded lactating women.

95% of trials excluded children less than 18 years old.

Medically complex patients, pregnant women, lactating women and children are routinely excluded from clinical trials because these groups are viewed as potentially complicating the work of researchers in understanding and evaluating a new treatment, along with concerns about the unknown long-term consequences of a treatment. These exclusions, however, lead to unintended consequences, Laiteerapong said.

"Given how little is known about COVID-19, being overly cautious with these populations means we have little evidence as to how to actually take care of them when they do contract SARS-CoV-2," she said.

One group that was sought out in COVID-19 treatment trials was older Americans: 86% of the studies included people over 85 years old.

The researchers say more inclusive studies are possible if the clinical trials community is diligent about recruiting populations not usually represented.

"Greater effort is needed to develop and study treatments in vulnerable populations, and this is going to take a long-term commitment to prioritize health equity," said Chokkara.

"Examining the inclusivity of US trials of COVID-19 treatment" was written by Sukarn Chokkara, Anna Volerman, Siddhi Ramesh and Neda Laiteerapong of the University of Chicago.

PITTSBURGH, Feb. 3, 2020 - In a recurring pattern of evolution, SARS-CoV-2 evades immune responses by selectively deleting small bits of its genetic sequence, according to new research from the University of Pittsburgh School of Medicine.

Since these deletions happen in a part of the sequence that encodes for the shape of the spike protein, the formerly neutralizing antibody can't grab hold of the virus, the researchers report today in Science. And because the molecular "proofreader" that usually catches errors during SARS-CoV-2 replication is "blind" to fixing deletions, they become cemented into the variant's genetic material.

"You can't fix what's not there," said study senior author Paul Duprex, Ph.D., director of the Center for Vaccine Research at the University of Pittsburgh. "Once it's gone, it's gone, and if it's gone in an important part of the virus that the antibody 'sees,' then it's gone for good."

Ever since the paper was first submitted as a preprint in November, the researchers watched this pattern play out, as several variants of concern rapidly spread across the globe. The variants first identified in the United Kingdom and South Africa have these sequence deletions.

Duprex's group first came across these neutralization-resistant deletions in a sample from an immunocompromised patient, who was infected with SARS-CoV-2 for 74 days before ultimately dying from COVID-19. That's a long time for the virus and immune system to play "cat and mouse," and gives ample opportunity to initiate the coevolutionary dance that results in these worrisome mutations in the viral genome that are occurring all over the world.

Then, Duprex enlisted the help of lead author Kevin McCarthy, Ph.D., assistant professor of molecular biology and molecular genetics at Pitt and an expert on influenza virus--a master of immune evasion--to see whether the deletions present in the viral sequences of this one patient might be part of a larger trend.

McCarthy and colleagues pored through the database of SARS-CoV-2 sequences collected across the world since the virus first spilled over into humans.

When the project started, in the summer of 2020, SARS-CoV-2 was thought to be relatively stable, but the more McCarthy scrutinized the database, the more deletions he saw, and a pattern emerged. The deletions kept happening in the same spots in the sequence, spots where the virus can tolerate a change in shape without losing its ability to invade cells and make copies of itself.

"Evolution was repeating itself," said McCarthy, who recently started up a structural virology lab at Pitt's Center for Vaccine Research. "By looking at this pattern, we could forecast. If it happened a few times, it was likely to happen again."

Among the sequences McCarthy identified as having these deletions was the so-called "U.K. variant"--or to use its proper name, B.1.1.7. By this point, it was October 2020, and B.1.1.7 hadn't taken off yet. In fact, it didn't even have a name, but it was there in the datasets. The strain was still emerging, and no one knew then the significance that it would come to have. But McCarthy's analysis caught it in advance by looking for patterns in the genetic sequence.

Reassuringly, the strain identified in this Pittsburgh patient is still susceptible to neutralization by the swarm of antibodies present in convalescent plasma, demonstrating that mutational escape isn't all or nothing. And that's important to realize when it comes to designing tools to combat the virus.

"Going after the virus in multiple different ways is how we beat the shapeshifter," Duprex said. "Combinations of different antibodies, combinations of nanobodies with antibodies, different types of vaccines. If there's a crisis, we'll want to have those backups."

Although this paper shows how SARS-CoV-2 is likely to escape the existing vaccines and therapeutics, it's impossible to know at this point exactly when that might happen. Will the COVID-19 vaccines on the market today continue to offer a high level of protection for another six months? A year? Five years?

"How far these deletions erode protection is yet to be determined," McCarthy said. "At some point, we're going to have to start reformulating vaccines, or at least entertain that idea."

Like weeds sprouting from cracks in the pavement, cancer often forms in sites of tissue damage. That damage could be an infection, a physical wound, or some type of inflammation. Common examples include stomach cancer caused by H. pylori infection, Barrett's esophagus caused by acid reflux, and even smoking-induced lung cancer.

Exactly how tissue damage colludes with genetic changes to promote cancer isn't fully understood. Most of what scientists know about cancer concerns advanced stages of the disease. That's especially true for cancers such as pancreatic cancer that are usually diagnosed very late.

Researchers in Scott Lowe's lab at the Sloan Kettering Institute are now trying to zero in on the earliest stages of pancreatic cancer development.

"If we understood how these tumors form, maybe we could catch them before the cancer has progressed to an incurable stage," says Direna Alonso Curbelo, a postdoctoral fellow in the Lowe lab who is the first author of a new paper published February 3 in Nature.

Using advanced genomic techniques and innovative mouse models, the researchers were able to discern how tissue damage synergizes with specific genetic changes to promote the earliest stages of pancreatic cancer.

Wound Repair Gone Wrong

It starts with the activation of a normal repair process in response to damage -- damage, it turns out, that can be inflicted by the pancreas's own digestive enzymes.

"The pancreas is like a mini factory of enzymes made to break down food," Dr. Alonso Curbelo says. "If these enzymes are released out of place, they can degrade the tissue and cause pancreatitis [a form of inflammation]."

Fortunately, the pancreas is really good at repairing itself. During the repair response, the cells in the damaged area change their behavior. They temporarily shut down their production of digestive enzymes and take on a different form. They return to their normal functioning once the damage has been resolved. At least, that's what's supposed to happen.

But when these damaged cells also contain a genetic mutation in a gene called KRAS, the wound-healing response goes haywire and the cells never return to normal. Mutant KRAS is known to drive tumor growth in 95 percent of people with pancreatic cancer, but it has so far been unclear how mutant KRAS derails the wound-healing process to initiate the disease.

Dr. Alonso Curbelo and colleagues were able to identify what distinguishes the normal repair process from the cancer-initiating one at the molecular level. They found major changes in how chromatin is organized that were uniquely induced in damaged KRAS-mutant cells. (Chromatin is the combination of DNA and proteins that make up chromosomes.) As a result of these changes, different genes are turned on and off, and the cells take on early cancerous properties.

Opening the Wrong Instructions

Think of the process like opening and closing a zip file. Parts of a chromosome that should be open for normal pancreatic function are inadvertently zipped. Conversely, other parts that are usually zipped are opened. As a result, the wrong set of genetic instructions is available to the damaged cell, which gets confused about its identity.

The whole process happens very quickly. Researchers found that over half of the chromatin changes that typically characterize advanced pancreatic cancer were already present in these cells within 48 hours of tissue damage. Because these cancer-associated changes in gene expression are not caused by changes in DNA sequence, they are called epigenetic (epi meaning beyond, genetic meaning genes).

This discovery is important because it suggests that scientists could potentially block cancer development by interfering with the activation of genes that become inappropriately turned on. And indeed, the team showed that they could do just that: When they prevented their activation in the damaged cells in the mice, the initiation of pancreatic cancer was blunted.

It Takes Two

Interestingly, these early, cancer-associated epigenetic changes did not occur when either mutant KRAS or tissue damage were present separately. Only the combination triggered it.

"Our study provides some understanding of why cancers often arise at sites of tissue damage," Dr. Lowe says. "You need both a mutated gene and tissue damage to activate the epigenetic program that drives cancer initiation. Each alone does not do it."

The discovery of epigenetic changes at the heart of cancer initiation, and their high degree of specificity, opens up the possibility that scientists could try to target these newly turned-on genes as a way to selectively interrupt cancer development.

As well, scientists might one day be able to use these genes as markers to identify early signs of cancer and intervene before it's too late.

ATLANTA - FEBRUARY 3, 2021 - New study finds more than half (56.4%) of cancer survivors in the United States reported having additional underlying medical conditions associated with severe COVID-19 illness. The report appearing in JNCI: The Journal of the National Cancer Institute, suggests that prevalence of these conditions among cancer survivors is nearly 40% higher than that in the general population.

Cancer, and other underlying medical conditions, including chronic obstructive pulmonary disease, heart diseases, diabetes, chronic kidney disease, and obesity, are associated with increased risk of severe COVID-19 illness. For this study, investigators Changchuan (Charles) Jiang, MD, PhD, Roswell Park Comprehensive Cancer Center, Xuesong Han, PhD, American Cancer Society, and colleagues used data from the 2016-2018 National Health Interview Survey (NHIS), a national cross-sectional survey of the civilian, noninstitutionalized population, to examine the prevalence of underlying medical conditions associated with severe COVID-19 Illness in adult cancer survivors in the U.S.

“This study investigates the prevalence and factors associated with these underlying medical conditions among cancer survivors in the U.S. We felt it was important to compile and analyze the available data to inform the public and guide the policy makers on opportunities to prevent and control severe COVID-19–associated illness through strategies such as risk-stratified vaccine distribution,” said Dr. Jiang.

Most cancer survivors reported having more than one of the conditions associated with severe COVID-19 illness and nearly one-quarter reported more than two conditions. These conditions were more prevalent in survivors of kidney, liver and uterine cancers, as well as Black survivors, those with low socioeconomic status, and public insurance.

Older age was associated with higher prevalence of medical conditions among cancer survivors and adults without a cancer history. However, even in the youngest age group (18 to 44 years), nearly half of cancer survivors (47.6%) had at least one additional condition associated with severe COVID-19 illness. In addition to increasing prevalence with age, medical conditions were more prevalent among male survivors (59.9%), those with less than high school completion (68.0%), non-Hispanic Black (67.2%), low income (71.7%), and those living in the South (59.2%).

“The findings highlight the need to protect survivors against COVID-19 transmission and to prioritize cancer survivors in vaccine allocation,” said Dr. Han.

CLEVELAND, Ohio (Feb 3, 2021)--Postmenopausal women often complain of painful intercourse or a lack of desire caused by decreased estrogen levels, which affect vaginal elasticity and lubrication. Survivors of breast cancer typically experience worse symptoms as a result of cancer treatments, and concerns exist regarding hormone therapies. A new study suggests that fractional CO2 laser therapy may help. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

The menopause transition can subject women to genitourinary changes from a lack of estrogen and subsequent alterations in vaginal elasticity, moisture, tissue integrity, and pH levels. These changes can lead to troublesome vaginal and urinary symptoms that are collectively referred to as the genitourinary syndrome of menopause (GSM).

Although the condition is underdiagnosed, it can affect a woman's well-being and sexual function. Survivors of breast cancer are even more likely to experience GSM because of the effects of chemotherapy and/or endocrine therapy used to treat the cancer. An ongoing problem is that many healthcare providers do not address GSM as part of survivorship care for these women. Complicating matters is that treatment options are more limited for women with breast cancer because there are concerns about the use of even low-dose vaginal hormone therapies.

Fractional CO2 laser therapy is a nonhormone treatment approach for GSM that remodels vulvar and vaginal tissues. Early results indicate that the procedure is safe and effective. In this newest study, CO2 laser therapy appears to have reduced sexual function problems at the 4-week follow-up visit. Specifically, improvements were noted in sexual function in the areas of desire, arousal, lubrication, orgasm, satisfaction, and pain. At the 4-week follow-up visit, additional improvements occurred with regard to a woman's interest in sex and her level of sexual activity. Although sexual function scores were lower at 1 year than at 4 weeks and indicated that women continued to experience sexual problems, they remained significantly improved compared with baseline. Follow-up will be conducted again in 2 years to better identify the long-term effectiveness of laser therapy.

Although this new study was small, it provides valuable insights for healthcare providers treating postmenopausal women, especially postmenopausal women who are survivors of breast cancer. Additional, larger-scale studies will be needed to fully explore the long-term potential of fractional CO2 laser therapy for the treatment of GSM and associated sexual problems.

Study results appear in the article "Patient-reported sexual function of breast cancer survivors with genitourinary syndrome of menopause after fractional CO2 laser therapy."

"This study highlights the issue of sexual dysfunction affecting most survivors of breast cancer and the potential role for CO2 laser therapy in the treatment of GSM and related sexual problems. Additional study is needed to better understand the long-term safety and efficacy of this therapy," says Dr. Stephanie Faubion, NAMS medical director and one of the authors of the study.

Dogs have been faithful human companions ever since their domestication thousands of years ago. With various improvements in veterinary medicine in the past decades, their life expectancy has increased. However, an unfortunate side effect of this longevity, much like in humans, has been an increase in the occurrence of chronic and degenerative conditions.

In humans, modern efforts to fight such diseases have culminated in the development of regenerative therapies, largely based on stem cells. These "baby" cells have the potential to differentiate and mature into many specialized cell types-- called "pluripotency." By transplanting stem cells and guiding their differentiation into desired cell types, researchers are effectively able to regenerate damaged tissues, thereby reversing the course various complex diseases. Although this technology is widely studied in humans, the potential for stem cell therapy in dogs is lacking.

To this end, a research team from Japan, led by Associate Professor Shingo Hatoya from Osaka Prefecture University, has been working on isolating "induced pluripotent stem cells" (iPSCs) from canine blood samples. iPSCs are a type of stem cell that can be "programmed" from a developed (or "differentiated") cell by introducing a specific set of genes into them. These genes code for proteins called "transcription factors," which induce the change from a differentiated to a pluripotent stem cell, which then have the ability to mature into various cell types. iPSCs can proliferate very rapidly, providing a reliable supply of suitable stem cells for regenerative therapies. "We successfully established an efficient and easy generation method of canine iPSCs from peripheral blood mononuclear cells" explains Dr. Hatoya. He highlights the significance of these findings for veterinary science, stating he hopes that in the near future, "it may be possible to perform regenerative medicinal treatments in dogs." These findings were published in the journal Stem Cells and Development.

The previous attempts by these scientists to generate iPSCs from canine blood cells, using viral "vectors" to deliver the pluripotency-inducing transcription factors, were not as effective as hoped. Therefore, in this study, they tested a different combination of inducing factors, which they believe were key to harvesting the full potential of these cells. Most importantly, the researchers needed to control how the reprogrammed cells replicated in the host body. Viral vectors that encode pluripotency-inducing transcription factors can be used to infect cells obtained from the blood and convert them into iPSCs; however, the researchers needed to be cautious: because these vectors integrate into the host genome, re-expression of these pluripotency factors in the host cell can cause tumor formation when these cells are transplanted in patients. To avoid this, the team developed "footprint-free" stem cells by using a particular type of viral vector that can generate iPSCs without genomic insertion and can be automatically "silenced" via "microRNAs" expressed by the cells. Then, they grew these cells in a special type of medium that contained various factors enhancing their pluripotency (including a "small-molecule cocktail"). Indeed, these cells grew and successfully developed germ layers (which form the basis of all organs).

Fascinatingly, these findings have paved the way for an easy stem cell therapy technique for man's best friends. "We believe that our method can facilitate the research involving disease modeling and regenerative therapies in the veterinary field," says Dr. Hatoya. Furthermore, the authors also believe that additional research into regenerative therapies for canines might have some ripple effects for human medicine. "Dogs share the same environment as humans and spontaneously develop the same diseases, particularly genetic diseases."

Translating findings from one field to another might mean veterinarians are able to find treatments, maybe even cures, for some of the diseases that still plague humanity.

Eating too much fat and sugar as a child can alter your microbiome for life, even if you later learn to eat healthier, a new study in mice suggests.

The study by UC Riverside researchers is one of the first to show a significant decrease in the total number and diversity of gut bacteria in mature mice fed an unhealthy diet as juveniles.

"We studied mice, but the effect we observed is equivalent to kids having a Western diet, high in fat and sugar and their gut microbiome still being affected up to six years after puberty," explained UCR evolutionary physiologist Theodore Garland.

A paper describing the study has recently been published in the Journal of Experimental Biology.

The microbiome refers to all the bacteria as well as fungi, parasites, and viruses that live on and inside a human or animal. Most of these microorganisms are found in the intestines, and most of them are helpful, stimulating the immune system, breaking down food and helping synthesize key vitamins.

In a healthy body, there is a balance of pathogenic and beneficial organisms. However, if the balance is disturbed, either through the use of antibiotics, illness, or unhealthy diet, the body could become susceptible to disease.

In this study, Garland's team looked for impacts on the microbiome after dividing their mice into four groups: half fed the standard, 'healthy' diet, half fed the less healthy 'Western' diet, half with access to a running wheel for exercise, and half without.

After three weeks spent on these diets, all mice were returned to a standard diet and no exercise, which is normally how mice are kept in a laboratory. At the 14-week mark, the team examined the diversity and abundance of bacteria in the animals.

They found that the quantity of bacteria such as Muribaculum intestinale was significantly reduced in the Western diet group. This type of bacteria is involved in carbohydrate metabolism.

Analysis also showed that the gut bacteria are sensitive to the amount of exercise the mice got. Muribaculum bacteria increased in mice fed a standard diet who had access to a running wheel and decreased in mice on a high-fat diet whether they had exercise or not.

Researchers believe this species of bacteria, and the family of bacteria that it belongs to, might influence the amount of energy available to its host. Research continues into other functions that this type of bacteria may have.

One other effect of note was the increase in a highly similar bacteria species that were enriched after five weeks of treadmill training in a study by other researchers, suggesting that exercise alone may increase its presence.

Overall, the UCR researchers found that early-life Western diet had more long-lasting effects on the microbiome than did early-life exercise.

Garland's team would like to repeat this experiment and take samples at additional points in time, to better understand when the changes in mouse microbiomes first appear, and whether they extend into even later phases of life.

Regardless of when the effects first appear, however, the researchers say it's significant that they were observed so long after changing the diet, and then changing it back.

The takeaway, Garland said, is essentially, "You are not only what you eat, but what you ate as a child!"

A mitochondrial hormone expressed by cells deep in the brain appears to play a role in improving metabolism and fighting off obesity, according to a new study in mice.

A collaboration between the USC Leonard Davis School of Gerontology and researchers in South Korea has shown how moderate exercise prompts cells in the hypothalamus, the small region within the brain that controls metabolism, to release a hormone called MOTS-c. MOTS-c is a small protein that is encoded in cells' smaller mitochondrial genome, rather than the larger collection of genes in the nucleus, said Changhan David Lee, assistant professor of gerontology at the USC Leonard Davis School and co-senior author of the new study.

Mitochondria, while more commonly known as the energy-producing parts of cells, have in recent years been found to play much bigger roles in health and aging by providing instructions for cellular processes. Subsequent studies by Lee and his colleagues have shown how mitochondrial-encoded MOTS-c interacts with the nuclear genome and regulates cellular metabolism and stress responses.

Stress as a balancing act

The new study also illustrates how stress in the mitochondria can promote healthy metabolism - when kept in careful balance.

Existing research has shown how low-grade stress in mitochondria can promote health and longevity, a phenomenon termed mitohormesis, Lee said. Essentially, while high levels of a stressor such as a toxin can cause major harm, a small amount of a stressor may actually strengthen healthy mitochondrial function.

"As [philosopher Friedrich] Nietzsche once said, 'That which does not kill us makes us stronger,'" Lee remarked.

To examine the effects of mitochondrial stress on metabolism, Lee and colleagues examined mice that were bred to be either partially or completely deficient in a single gene within a specific type of brain cell, hypothalamic proopiomelanocortin (POMC) neurons. The missing gene, Crif1, controls how cells use proteins encoded by mitochondria.

The mice that were homodeficient in Crif1 - meaning that they had no copies of the Crif1 gene at all - experienced severe mitochondrial stress and showed indicators of metabolic problems when they reached adulthood, including weight gain and reduced energy expenditure. In addition, the mice missing Crif1 entirely also had insulin resistance and high blood sugar, much like type 2 diabetes in humans.

However, the mice that were heterodeficient in the Crif1 gene - they could partially express the gene, but not as much as normal mice - experienced mild mitochondrial stress and protection against obesity or insulin resistance. When fed a high-fat diet, the mice missing part of their Crif1 function gained less weight than normal mice on the same diet, even though the former ate more calories. Further study of the mice revealed that their affected neurons expressed both more MOTS-c as well as more beta-endorphin (β-END), a pain-suppressing molecule typically released during exercise.

The mice with mild mitochondrial stress in POMC neurons may have avoided obesity due to the fat tissues within their bodies changing. The researchers noticed that the Crif1 heterodeficient mice display more thermogenesis - the ability to generate heat - and further examination of the fat cells revealed increased amounts of brown fat cells.

Brown fat appears brown because of the presence of more mitochondria versus white fat. In babies, who don't yet have the ability to shiver to keep their bodies warm, their larger proportion of brown fat consumes sugar and white fat to generate energy and produce heat. Scientists are interested in the effects of "browning" fat, or turning white fat into brown fat, as a possible way to address obesity in adults, who typically retain only small pockets of brown fat.

MOTS-c treatment, exercise each give similar benefits

In later experiments, the researchers were able to mimic these changes, including increases in brown fat and thermogenesis, in normal mice by directly administering MOTS-c to the brain..

Tellingly, the same benefits also arose after mice engaged in moderate exercise. The study's findings indicate that the process of balancing mild mitochondrial stress may be a key part of why exercise improves metabolism. The process appears to be mediated by MOTS-c, adding to the body of research supporting the hormone's metabolic involvement.

"Our brain is a control center for a lot of physiological functions," Lee said. "This is a new mechanism of exercise physiology that may provide new venues for future therapeutic development of exercise-mimetics."

Lee and Pinchas Cohen, professor of gerontology, medicine and biological sciences and dean of the USC Leonard Davis School, first described MOTS-c in 2015, along with its role in restoring insulin sensitivity and counteracting diet-induced and age-dependent insulin resistance - effects commonly associated with exercising. In a separate paper published January 20 in Nature Communication, Lee, Cohen, and colleagues demonstrated that MOTS-c levels increase upon exercise in humans and, when given to mice, can double the running capacity of young and old animals. These studies raise the possibility of developing drugs to provide the health benefits of exercise to frail or disabled individuals who cannot safely exercise.

The current study indicates that the mitochondrial hormone is not just acting locally within muscle tissues but arising from the brain's headquarters for metabolism, Lee said.

"The question is, 'upon exercise, do mitochondria communicate to your command center, or do they bypass that and talk straight to the target (peripheral) organs?'" Lee said of the research surrounding MOTS-c's role in exercise and metabolism. "We're showing that it could be both."

Parasitic worms could hold the key to living longer and free of chronic disease, according to a review article published today in the open-access eLife journal.

The review looks at the growing evidence to suggest that losing our 'old friend' helminth parasites, which used to live relatively harmlessly in our bodies, can cause ageing-associated inflammation. It raises the possibility that carefully controlled, restorative helminth treatments could prevent ageing and protect against diseases such as heart disease and dementia.

"A decline in exposure to commensal microbes and gut helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders - the so-called 'old friends hypothesis'," explains author Bruce Zhang, Undergraduate Assistant at the UCL Institute of Healthy Ageing, London, UK. "A further possibility is that this loss of 'old friend' microbes and helminths increases the sterile, ageing-associated inflammation known as inflammageing."

Inflammageing is increasingly thought to be a contributory factor to the major diseases of later life, including heart disease, dementia, cancer, chronic obstructive pulmonary disease, osteoporosis, age-related eye disease and - more recently - symptom severity during SARS-CoV-2 (COVID-19) infections.

One theory is that changes in the gut microbiome might cause inflammageing, but until now little consideration has been given to the role of organisms comprising the macrobiome - the ecosystem of macro-organisms - including helminth parasites such as flukes, tapeworms and nematodes.

Helminths have infected humans throughout our evolutionary history, and as a result have become master manipulators of our immune response. Humans, in turn, have evolved levels of tolerance to their presence.

In their article, Zhang and co-author David Gems, Professor of Biogerontology and Research Director at the UCL Institute of Healthy Ageing, review the evidence for helminth therapy in two areas: treating known inflammatory disorders, such as coeliac disease, and stopping or reversing inflammageing as part of the ageing process.

They reveal how the loss of helminths has so far been linked to a range of inflammatory diseases, including asthma, atopic eczema, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and diabetes. Some studies have shown that natural infection with helminths can alleviate disease symptoms, for example in multiple sclerosis and eczema, while other studies in animal models suggest that intentional infection with helminths could have benefits against disease.

The safer, and perhaps more palatable, option is the concept of using helminth-derived proteins to achieve the same therapeutic benefits. This was tested recently in mice and shown to prevent the age-related decline in gut barrier integrity usually seen with a high-calorie diet. It also had beneficial effects on fat tissue, which is known to be a major source of inflammageing.

The authors speculate that if helminths have anti-inflammageing properties, you would expect to see lower rates of inflammageing-related disease in areas where helminth infection is more common. There is some evidence to support this. For example, in a region in Eastern India endemic for lymphatic filariasis caused by filarial worms, not a single person with rheumatoid arthritis (RA) tested positive for circulating filarial antigens, whereas a much higher proportion (40%) of people without RA tested positive for the nematode. Other epidemiological studies have shown protection from helminths against type 2 diabetes and blocked arteries.

"It goes without saying that improvements in hygiene and elimination of helminth parasites have been of incalculable benefit to humanity, but a cost coupled to this benefit is abnormalities of immune function," Gems concludes. "In the wake of successes during the last century in eliminating the evil of helminths, the time now seems right to further explore their possible benefits, particularly for our ageing population - strange as this may sound."

ADULT-PROVEN 'SMART' DIAGNOSTIC TOOL FOR DIABETIC RETINOPATHY ALSO WORKS FOR KIDS

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

Diabetic retinopathy -- a disorder characterized by damage to the small blood vessels lining the retina (light-focusing area) of the eye and a leading cause of vision loss worldwide -- has been on the rise in recent years as the number of children and adolescents diagnosed with either type 1 or type 2 diabetes increases. Although the American Diabetes Association (ADA) advises regular screening for pediatric diabetic retinopathy, it's estimated that fewer than half of all youth with diabetes follow the recommendation. Without early detection and treatment, these patients put themselves at risk for serious vision problems or blindness as they get older.

In a recent study reported online Jan. 21, 2021, in Diabetes Care, researchers in pediatric endocrinology and ophthalmology at Johns Hopkins Medicine and three other U.S. medical institutions demonstrated that autonomous artificial intelligence (AI) can be used to detect pediatric diabetic retinopathy with high sensitivity, specificity and diagnosability (accuracy of detection) -- and without the need for human interpretation. The technique had already been approved for adults with diabetes by the U.S. Food and Drug Administration and is part of the ADA's retinopathy screening guidelines for patients age 21 or older.

Because the AI screening does not require eye dilation, it takes less time to perform and is easier for pediatric patients to undergo. Therefore, the adherence of the patients in this study to getting regular retinopathy screenings, as defined by the ADA, more than doubled.

"Use of autonomous AI in adults has shown extremely high levels of sensitivity, specificity and accuracy in diagnosing referable [more than mild] diabetic retinopathy, when the disease is most treatable," says Risa Wolf, M.D., study lead author, Johns Hopkins Children's Center pediatric endocrinologist and assistant professor of pediatrics at the Johns Hopkins University School of Medicine. "So, with the rising incidence of pediatric diabetes -- especially type 2, which is associated with an earlier onset of retinopathy -- we felt it was important to see if AI could make an improvement in adherence to screening guidelines and early diagnosis for younger patients."

A total of 310 pediatric patients with diabetes were recruited over a 12-month period for the study. The participants had a mean age of 12, were 47% male and represented a broad range of ethnicities (57% white, 32% Black, 4% Hispanic, and 7% Asian or other). Patients predominantly had type 1 diabetes (82%) and a mean age of 9 at first diagnosis of diabetes, whether type 1 or type 2.

One hundred fifty-two participants (49%) reported having a diabetic eye exam with dilation before joining the study, but only 17 (11.3%) had a record of the screening test in their case files. However, using a special statistical calculation, the researchers were able to measure the improvement in screening adherence for these patients and then estimate it for the entire group.

In the study, digital fundus photography -- which does not require dilation, takes only a few minutes and produces high-quality images for detection of retinopathy by trained observers -- was used in conjunction with a fully autonomous AI system built into the camera. This eliminated the need for human evaluation to get a diagnosis.

For verification of the diagnoses made by the AI system, the same color photographs were reviewed independently by two retina specialists who were not told of the AI interpretations.

Of the 310 participants, AI gave an accurate interpretation for retinopathy or no retinopathy in 302 (97.5%) cases. The eight image sets not interpreted were due to the participant's inability to keep his or her eyes open during the photographic flash or to focus as needed.

Overall, sensitivity (85.7%), specificity (79.3%) and diagnosability (97%) of the AI interpretations in children were high, based on the reference standards for these characteristics defined by retina specialists. This high level was seen regardless of race, ethnicity, age and sex.

After implementing the AI screening system, the adherence rate improved from 49% to 95%, an increase of 111%.

"Our results show that autonomous AI -- proven as a safe and effective means of diagnosing diabetic retinopathy in adults -- also deserves a role in screening for this disease in younger patients," says retina specialist Roomasa Channa, M.D., senior study author and assistant professor of ophthalmology and visual sciences at the University of Wisconsin School of Medicine and Public Health.

Wolf is available for interviews.

CELLS THAT DETECT BRAIN ACTIVITY DRIVE THE NEED FOR SLEEP IN FRUIT FLIES

Media Contact: Vanessa McMains, vmcmain1@jhmi.edu

The longer someone stays awake, the more likely they'll start getting tired as their brain needs sleep. But how the brain senses that need for sleep hasn't always been clear. Now, Johns Hopkins Medicine researchers have shown in fruit flies that certain groups of brain cells called astrocytes sense electrical activity in different regions of the brain and use these signals to facilitate the process of falling asleep. The more activity that they detect, the stronger the need-for-sleep signals become, until they trigger a release mechanism that pushes sleep.

In their findings, published Jan. 11, 2021, in the journal Current Biology, the researchers say that understanding how we get sleepy may help us understand and eventually treat the kinds of sleep disorders in people who never feel rested no matter how much sleep they get.

"When you nod off in class during a boring lecture but still hear the professor calling your name, that is because only part of your brain is asleep," says Mark Wu, M.D., Ph.D., professor of neurology at the Johns Hopkins University School of Medicine. "We believe that different groups of these astrocyte cells monitor different parts of the brain to initiate sleep drive in those specific regions."

The researchers demonstrated in their study that prolonged wakefulness results in a buildup of calcium ions in the astrocytes, which eventually triggers a whole cascade of genes to be turned on. When this happens, the astrocytes release chemical molecules that induce sleep by acting on a central sleep drive circuit (an electrochemical network) in the brain.

Two recent publications by researchers at other institutions showed similar findings in mice to the results published in the Johns Hopkins Medicine paper. Together, these studies suggest that these processes are conserved across the animal kingdom and are likely applicable to humans as well.

Wu is available for interviews.

STUDY SAYS DOCTORS SHOULD DISCUSS HYPOGLYCEMIA MORE OFTEN WITH PATIENTS WHO HAVE DIABETES

Media Contact: Michel Morris, melben1@jhmi.edu

Johns Hopkins Medicine researchers recently found that although primary care physicians should discuss the problems of hypoglycemia, or low blood sugar, during each visit with patients who have diabetes and take high-risk medications such as insulin, the topic was only talked about in a quarter of those visits.

Hypoglycemia is the most common serious side effect caused by diabetes treatment. Severe hypoglycemic episodes can lead to negative consequences, including falls and emergency department visits, and may increase the risk for stroke and death. In a 2018 survey of 20,188 adults with diabetes, 12% reported experiencing severe hypoglycemia within the previous year.

"For patients to have safe diabetes treatment, there needs to be open communication between them and their healthcare provider about medication side effects, especially hypoglycemia," says Scott Pilla, M.D., M.H.S., assistant professor of medicine at the Johns Hopkins University School of Medicine. "For example, we found in our study that clinicians almost never counseled against driving a car if a patient thinks his or her blood sugar is low or may become low. This is an important discussion to have because low blood sugar could cause a person to think unclearly and have an accident."

Pilla and his research team's findings were published Jan. 21, 2021, in the Journal of General Internal Medicine.

Most outpatient diabetes treatment in the United States occurs in primary care offices, so doctor visits with patients who have diabetes offer a critical opportunity to promote hypoglycemia prevention. To find ways of improving hypoglycemia communication during doctor visits, Pilla and his team sought to define the frequency and content of assessments and counseling provided in the primary care setting related to hypoglycemia.

To do this, the researchers examined 83 primary care visits from one urban health practice, representing eight clinicians seeing 33 patients with diabetes who used insulin or sulfonylureas such as glipizide and glyburide. Audio during the visits was recorded as part of the Achieving Blood Pressure Control Together study, a randomized trial of behavioral interventions for high blood pressure.

Communication between the clinician and patient about hypoglycemia occurred in 24% of visits, while communication about hypoglycemia prevention took place in 21%. Despite patients voicing fear of hypoglycemia, clinicians rarely assessed hypoglycemia frequency, its severity or the impact it may have on the patient's quality of life.

While office visits are sometimes complicated and often focus on a variety of topics, Pilla says the study findings should encourage primary care clinicians to make hypoglycemia assessment counseling a priority for patients taking high-risk diabetes medications. He says that a system to routinely assess for hypoglycemia in primary care visits is currently lacking and he believes that his team's research shows the need for one.

Pilla also suggests that patients speak up about low blood sugar during medical visits. "Primary care clinicians should work together with patients to figure out how to best prevent low blood sugar episodes and choose the safest diabetes treatment," he says.

Pilla says he ultimately hopes to examine communications about hypoglycemia on a larger scale. With more data, he explains, researchers can better understand how to make such discussions more effective and productive, which could lead to improved safety for diabetes treatment in primary care.

Pilla is available for interviews.

There is an expression in English that says, "May you live in interesting times." To some, this is a blessing, while to others it is more of a curse. The Covid-19 pandemic has engendered a very interesting time--a time of extraordinary and unprecedented challenges that have thrown individuals and organizations headlong into battles for survival. Politicians, policy-makers, business leaders, and all professionals must dig deeper and come up with solutions to ensure that human civilization continues to survive and thrive in a post-pandemic world. Under these circumstances, the Frontiers of Business Research in China in China recently published six unique perspectives on the challenges that businesses--especially small- and medium-size enterprises (SMEs)--are facing, and the way forward.

The first article, by Prof. Hai Guo from Business School, Renmin University of China (Renmin Business School) and his research associates, argues that digitalization helps organizations to tap into their dynamic capabilities--their abilities to quickly build, integrate, and reorganize internal and external resources to adapt and promote organizational changes in the wake of crises. Prof. Guo opines, "(It) can help SMEs employ emergency responses as well as respond strategically to public crises in the long run, thus contributing to the improvement in SMEs' performance." Moreover, the researchers provide a definite framework that SMEs can use in their digitalization efforts during the pandemic.

In the second article, Prof. Jose C. Alves from the City University of Macao and his colleagues discuss a framework that combines insights on the sense-making processes of business leaders of six firms in Macao at the various crisis stages: how they dealt with internal and external stakeholders and responded to various challenges. The researchers found that most business leaders dealt with the pandemic situation as the "new normal". They adopted strategies that ensured flexibility in human resources management, cost reduction, enhanced customer relations, and capitalizing on government schemes. The researchers recommend that effective handling of the pandemic would require small firms to expand stakeholder engagement and develop new learning.

In the third article, Associate Prof. Ding Ding from the Singapore University of Social Sciences and her colleagues investigated the effects of the negative market sentiments stemming from the pandemic on the stock market. After comparing the closing stock prices of 1,567 firms from 37 sectors they found that some sectors--the ones with a greater degree of digital transformation--were more resilient to the negative market sentiment than others. Dr. Ding explains, "Even as (such) shutdowns have brought many corporeal economic activities to a near-complete standstill, consumer purchases and even trade continue to thrive online."

The fourth article, by Prof. Fengjun Liu of the Renmin Business School and his associates, investigates the impact of internal corporate social responsibility (ICSR) disclosures on consumer brand attitudes. They reveal that the perception of companies fulfilling their social responsibilities positively affects consumer attitudes. Prof. Liu says, "SMEs need to protect employee interests first and actively fulfill their ICSR to establish a good enterprise brand image. This in turn can help enterprises survive the epidemic and usher in greater development opportunities after the epidemic."

The fifth article, by Prof. Hua Song of the Renmin Business School, presents a closer look at the support that SMEs are receiving from financial service providers (FSPs). Their study compares and provides insights into the roles played by three types of FSPs: commercial banks, non-bank financial institutions, and credit-enhanced FSPs. They provide insights into how SMEs can raise capital in these trying times but call for greater collaboration between various stakeholders.

Lastly, in the sixth article, Prof. Fengbin Wang from the Renmin University of China and her colleague discuss the microstructures and dynamic processes within the five-phase system to offer a better understanding of Covid-19 as a complex system. Their study offers insight on possible dialogue between the Western process theory and the Chinese five-phase system that could help policymakers predict system evolution and guide policy decisions.

These perspectives throw light on the precarious situation that the world of business is in due to the pandemic. Nonetheless, they also provide hope and inspiration. We definitely live in interesting times, and the way our business leaders respond will ultimately decide the future of the world.

BLOOMINGTON, Ind. - In Lily Tomlin's classic SNL comedy sketch, her telephone operator "Ernestine" famously delivers the punchline, "We don't care. We don't have to. We're the Phone Company." But new research finds that satisfied customers mean increased profits even for public utilities that don't face competition.

Little is known about effect of customer satisfaction at utilities. As a result, utility managers are often unsure how much to invest in customer service - if anything at all. The issue also is of interest to regulators responsible for protecting consumers.

The study, in the Journal of Marketing Research, has important implications for both managers and regulators. Customer satisfaction predicts profits at utilities -- in spite of the fact that customers don't have an option to switch if they are unhappy. It shows how keeping customers happy lowers operating costs and ultimately saves utilities money.

"As with other companies, providing good customer service has efficiency-enhancing benefits for utility firms, such as lower direct and employee engagement costs of dealing with dissatisfied customers and it generates greater customer trust and cooperation from customers," said Neil Morgan, PETsMART, Inc. Distinguished Professor of Marketing at Kelley. "Our results indicate that -- at least as currently regulated -- greater satisfaction of utility customers not only ensures consumer welfare by improving utility provider efficiency but also increases the future profitability of the utility."

Using data from U.S. public utility firms from 2001 to 2017, researchers found utilities - as currently regulated - have a cost-based incentive to deliver and improve their customers' satisfaction.

Their findings run counter to prevailing assumptions that providing higher service quality raises utility system costs. They found "robust evidence" that customer satisfaction did not affect rates (prices per unit) or demand (unit sales volume). But they did find unambiguous evidence that it leads to profits only by reducing utility operating costs.

"Our study clearly indicates that if they aren't doing so already, utility managers need to track their customers' satisfaction," said Lopo Rego, associate professor of marketing and a Fettig/Whirlpool Fellow at Kelley. "They should set targets for customer satisfaction improvement and invest in strategies designed to accomplish this goal."

For the average utility in their sample, a one-unit (on the 1 to 100 point ACSI index) improvement in customer satisfaction decreases operating costs by $29 million overall, through lowering customer service, distribution, and selling and general administrative costs to lowered costs of $3, $8, and $13 million per year respectively.

Efficiency gains coming from improved customer satisfaction, trust and goodwill could lead to greater acceptance of costly, new technology initiatives that utilities want to introduce, researchers said.

"If greater customer satisfaction enhances both consumer willingness to allow utilities to introduce such technologies and subsequent consumer use of these innovations, then utility satisfaction improvement programs should be managed and aligned with their technology initiatives as well as their efficiency programs," they said.

"For policymakers, our findings that customer satisfaction does not lead to increased profits via higher rates or greater demand suggests current regulatory controls are effective." They added. "Our findings suggest regulators should view investments in customer satisfaction as recoverable costs."

Colorectal cancer is the second most common cause of cancer-related mortality among men and women in the United States, according to the American Cancer Society. At-home tests, which measure blood in stool as a potential marker for colon cancer, are often used for colorectal cancer screening.

Usage of these tests has increased during the COVID-19 pandemic as people try to avoid clinical visits. However, effectiveness of these screening tools, along with all colon cancer screenings, requires a follow-up colonoscopy if an abnormal test result occurs. The problem is that experts say current follow-up rates are low.

A new study, led by researchers at University of California San Diego School of Medicine, Veterans Affairs San Diego Healthcare System (VASDHS), Veterans Affairs Greater Los Angeles Healthcare System and University of California Los Angeles, found delayed time between abnormal stool-based screening and subsequent colonoscopy was associated with an increased risk of a cancer diagnosis and death from colorectal cancer.

The study, published in the February 2, 2021 online edition of Gastroenterology, found those who delayed a colonoscopy by more than twelve months after an abnormal screening test result were at an increased risk of being diagnosed with colorectal cancer. The odds of being diagnosed with late-stage colon cancer increased at 16 months by approximately 33 percent.

"Many colon cancers are asymptomatic and can be growing without the patient even knowing. That is why it is so important to screen. But as our study shows, it is also critical to follow up with a colonoscopy if the screening result is abnormal," said Samir Gupta, MD, corresponding author of the study and professor of medicine in the Division of Gastroenterology at UC San Diego School of Medicine and VASDHS.

"Early detection means less invasive treatments and excellent outcomes. When detected early, patients have a 90 percent survival rate with a low risk of recurrence. Late-stage colorectal cancer means more invasive and complex treatment with less than a 15 percent survival rate. As usage of more non-invasive tests for colorectal cancer screening continue to rise during the pandemic, and as more non-invasive screening tests come onto the market in the future, it is critical to ensure all patients with abnormal colorectal cancer screening tests get a timely colonoscopy."

The national study involved 204,733 veterans ages 50 to 75 with an abnormal screening test. A limitation of the study was a high proportion of men; 5,453 women were included.

"There are no national standards or mandates to guide patients, providers or health care systems on the clinically acceptable period of time between abnormal screening and colonoscopy," said Folasade May MD, PhD, senior author of the study and assistant professor of medicine at UCLA. "We hope our findings will inform national standards for appropriate time intervals and interventions to improve timely colonoscopies and colorectal cancer outcomes."

A family history, smoking and poor diet are significant risk factors of colon cancer. Symptoms include rectal bleeding, low-iron anemia, a change in bowel habits and unexplained weight loss.

In 2018, the American Cancer Society updated guidelines for colorectal cancer screening. It is now recommended that those age 45 with an average risk of colon cancer begin regular screenings. Previously, the guideline recommended screening begin at age 50 for people at average risk.

"In general, prevention and early detection efforts have substantially dropped death rates in the United States. However, the pandemic has resulted in many people missing cancer screenings or not doing follow-up colonoscopies after abnormal at-home screenings," said Gupta. "We strongly encourage patients to schedule an appointment if they receive an abnormal screening test. Our hospital and clinical settings are following all COVID-19 safety guidelines. Hesitancy to follow up on your health care could have fatal consequences."