Day: January 7, 2021

Mid-life Exercise Positively Shapes Late-life Brain Structure

That exercise in one’s middle years benefits health in later life is perhaps no surprise given our current understanding of its benefits, but and MRI study has shown to influence the brain’s structure in later years.

Using MRI scans, high levels (150 minutes per week or more) of self-reported moderate-to-high physical activity were associated with reduced risk of lacunar infarct in late life (OR 0.68, 95% CI 0.46-0.99) and more intact white matter integrity.

“Our study suggests that getting at least an hour and 15 minutes of moderate-to-vigorous intensity physical activity a week or more during midlife may be important throughout your lifetime for promoting brain health and preserving the actual structure of your brain,” said Priya Palta, PhD, of Columbia University Irving Medical Center. “In particular, engaging in more than 2 and a half hours of physical activity per week in middle age was associated with fewer signs of brain disease.”

There has been mixed evidence linking physical activity to brain measures or improvements in cognitive function. PhDs Nicole Spartano, of Boston University School of Medicine, and Leonardo Pantoni, MD, of University of Milan, noted in an accompanying editorial that the “most consistent evidence for the protective effect of physical activity against dementia risk has been reported to be leisure time physical activity, and it is unclear whether there is benefit to other types of physical activity that may be less ‘enriching.'”

“It is possible that future work will uncover the requirement that physical activity interventions to reduce dementia risk actually have an enriching element, such as in leisure-time activities, rather than be strictly rote, mechanical movement,” Spartano and Pantoni added.

Recruiting 1 604 individuals with a mean baseline age of 54, the participants had five examinations over 25 years and MRI at a mean age of 72. At baseline (1987-1989) and 25 years later, participants had their moderate-to-vigorous physical activity assessed in a questionnaire. 

At midlife, 11% had low levels of moderate-to-high intensity activity (1 to 74 minutes a week), 16% middle levels (75 to 149 minutes a week), and 39% high levels (150 minutes a week or more), with the remainder reporting none.

High moderate-to-vigorous midlife activity was associated with better white matter integrity in late life, compared with no moderate-to-vigorous midlife activity, but there was no association with grey matter volume.

While the risk of lacunar infarcts were lower with more intense midlife activity, risk of cortical infarcts or subcortical microhemorrhage were not. “The associations of greater levels of mid-life physical activity with fewer lacunar (but not cortical) infarcts and greater white matter microstructural integrity suggest cerebrovascular mechanisms are primarily at play,” Palta and colleagues wrote.

When adjusted for vascular risk factors, the association of midlife physical activity to lacunar infarcts was weakened, but the association with white matter microstructure. The editorialists said that it implies that “evidence from this study supports a hypothesis that the mechanisms linking physical activity and the brain are likely multi-dimensional, including mechanisms other than simply improving cerebrovascular health.” 

Late-life moderate-to-vigorous physical activity also was associated with most brain measures compared with no moderate-to-vigorous activity, but as this was a prospective study that spanned decades, the “association between midlife physical activity levels and later-life brain imaging features makes a much stronger case for causality than does the same relationship when measured only in late life,” the researchers noted.

The study had several limitations, which included using self-reported data, did not include non leisure-related activity, and participant attrition.

Source: MedPage Today

Journal information: Source Reference: Palta P, et al. A prospective analysis of leisure-time physical activity in midlife and beyond and brain damage on MRI in older adults, Neurology 2020; DOI: 10.1212/WNL.0000000000011375.

Opioid Use Linked to Pancreatic Cancer Risk

New research has shown that the use and misuse of the highly addictive opioid class of medications may pose an additional threat – pancreatic cancer

In the United States, opioid misuse has spiralled into one of the biggest healthcare epidemics facing the country. Of 70 000 deaths from substance abuse in the country in 2017, 68% involved opioids. Among patients prescribed opioids for chronic pain, 29% are misusing them and 12% have developed an opioid misuse disorder. Rates of pancreatic cancer are also on the increase in the US. In West Central Asia, opium use recently been linked to pancreatic cancer.Using Centres for Disease Control (CDC) data, the study’s researchers controlled for confounding variables, took opioid death rates as a surrogate for proscription and misuse, and compared it to incidences of pancreatic cancer. 

Analysing the dataset, they found that opioid use was associated with pancreatic cancer rates, with the opioid use rates predicting the pancreatic cancer trends years later.Faraz Bishehsari, MD, Ph.D., the corresponding author of the study, said: “Our mechanistic studies could provide further insights on the pathways that opioid could potentially impact progression of cancer.”

In order to confirm the findings, there is a need for sizeable population-based studies or longitudinal datasets that reliably track long-term outcomes in opioid users. Once these findings are confirmed by population-based studies, these will have an impact in considering alternative pain management methods in patients.Adding credence to this link is a recent post-hoc analysis of advanced cancer patients that showed patients receiving regular opioid antagonists had a significantly improved survival rate over placebo.

Source: Medical Xpress

Journal information: Usman Barlass et al. Opioid use as a potential risk factor for pancreatic cancer in the United States: An analysis of state and national level databases, PLOS ONE (2021). DOI: 10.1371/journal.pone.0244285

Ginger Promising in Countering Autoimmune Diseases

A pre-clinical study has shown that the common herbal remedy and condiment, ginger, may be effective in countering some autoimmune disease mechanisms.

It is already known that ginger has some anti-inflammatory and anti-oxidative properties, making it a popular herbal remedy for inflammatory conditions.Out of at least 14 bioactive compounds, 6-gingerol, which also gives it its distinctive aroma and taste, is reported by a news study to be therapeutic in countering certain autoimmune disease mechanisms in mice.
In mice with antiphospholipid syndrome or lupus, 6-gingerol inhibited the release of neutrophil extracellular traps, which is triggered in response to the autoantibodies produced by these diseases. 

“Neutrophil extracellular traps, or NETs, come from white blood cells called neutrophils,” said lead author Ramadan Ali, PhD. “These sticky spider-web like structures are formed when autoantibodies interact with receptors on the neutrophil’s surface.”

According to Ali, these webs play an important role in the pathogenesis of lupus and antiphospholipid syndrome where they trigger autoantibody formation and contribute to blood vessel clotting and damage.

The premise of the study was: “Will the anti-inflammatory properties of ginger extend to neutrophils, and specifically, can this natural medicine stop neutrophils from making NETs that contribute to disease progression?”
“This pre-clinical study in mice offers a surprising and exciting, ‘yes’,” Ali said.

The researchers discovered that after giving 6-gingerol, the mice had lower levels of NETs. Clot formation tendency was drastically reduced and 6-gingerol seemed to inhibit neutrophil enzymes called phosphodiesterases, in turn lowering neutrophil activation.

All of the mice had reduced autoantibodies, suggesting a disruption of the inflammatory cycle of autoantibodies stimulating NETs which stimulate more autoantibodies.

Study author and rheumatologist Jason Knight, MD, noted that patients often asked about herbal supplements, about which he had not been taught much. However, the pre-clinical trial results show that 6-gingerol has anti-neutrophil properties that may be protective against autoimmune disease progression.

“As for basically all treatments in our field, one size does not fit all. But, I wonder if there is a subgroup of autoimmune patients with hyperactive neutrophils who might benefit from increased intake of 6-gingerol,” said Knight. “It will be important to study neutrophils before and after treatment so we can determine the subgroup most likely to see benefit.”
For a patient with active antiphospholipid syndrome or lupus, the bioactive compound cannot be the primary therapy, but the natural supplement may help those at high risk for disease development.

“Those that have autoantibodies, but don’t have activated disease, may benefit from this treatment if 6-gingerol proves to be a protective agent in humans as it does in mice,” Ali said.

“Patients with active disease take blood thinners, but what if there was also a natural supplement that helped reduce the amount of clots they produce? And what if we could decrease their autoantibodies?”

Source: Medical Xpress

Journal Information: Ramadan A. Ali et al, Anti-neutrophil properties of natural gingerols in models of lupus, JCI Insight (2020). DOI: 10.1172/jci.insight.138385

COVID Cases Surge in Africa

Over the past month, Africa has recorded the highest growth in new infections, with a 13% growth over the last week. With only two million cases and 45 000 deaths, Sub-Saharan Africa still only has a small part of the caseload of other regions. 

Dr John Nkengasong, who heads the African Centres for Disease Control (CDC), said: “I think this is serious, the second wave is extremely aggressive.”  The latest surge is thought to be driven by the more transmissible South African variant, known as 501Y.V2. President Cyril Ramaphosa said this variant, found in 90% of new cases, was likely responsible for the country’s latest surge, which has caused morgues to fill up and hospitals to run short of staff and critical resources such as oxygen.  North of the border, Zimbabwe this week started a month-long lockdown to curb a rise in new cases and protect its own overburdened health care system. Nearly two million Zimbabweans live in SA and regularly travel and forth, potentially spreading the virus.

Rashida Ferrand, a London School of Hygiene and Tropical Medicine professor working at the Parirenyatwa Group of Hospitals in the Zimbabwean capital Harare told Reuters that there was “a pretty high likelihood” that the new SA strain of the virus identified could be circulating in Zimbabwe.

Lockdowns may now not be enough to control the spread of the new variant – certain studies of the similar, highly transmissible UK variant suggests that it may now spread too fast for its R (reproduction) value to be brought below 1, or otherwise cause a much slower decline in infections. Fortunately, it seems that lockdown measures in the UK are having some effect. 
Meanwhile, there are concerns that the SA variant may also be able to evade the protection of current vaccines, according to new research – but that has not been peer reviewed yet. Research in SA on the question is expected to provide answers. Meanwhile, 12 gene sequencing laboratories are being geared up around Africa to track the spread of the virus variants, and some genome sequencing work has been done since December, but not enough to paint a clear picture.

Source: The Telegraph

Medical Aid Schemes to Share Cost of Nationwide Vaccination

As arrangements are being made to pay for the COVID vaccination programme for South Africa, medical aid schemes are expected to contribute to the cost towards ensuring at least 67% of the population receives a vaccine, which is the minimum number to establish herd immunity.

Across South Africa, there are some 9 million medical aid beneficiaries, making up some 16% of the population and who collectively spent R186 billion last year on healthcare. The total cost of providing sufficient vaccines for the South African population is thought to range from R5 billion to R20 billion, depending on whether the vaccine is simply bought for the commercial price or whether the distribution and administration costs are factored in as well.

Discussions into paying for the mass vaccinations have suggested that mass-employers, such as mines, ought to contribute  This week, the Council for Medical Schemes (CMS) confirmed that vaccination would be a minimum prescribed benefit, so this will not be paid for out of medical savings.”The CMS acknowledges that there may be an additional cost burden to medical schemes for the provision of the vaccine, but this is not expected to be prohibitively high,” the body said. “In addition, industry associations have assured the CMS that vaccine costs can be absorbed by most medical schemes.”

South Africa’s vaccine source is not yet clear, although President Cyril Ramaphosa has hinted that Canada may share its excess vaccine stock. Canada currently has enough vaccine pre-purchase agreements to vaccinate its population five times over.

Source: Business Insider

Amazon to Enter the Health Industry

With the launch of Amazon Pharmacy in the US last November, online pharmacy companies are worried about the industry giant Amazon’s entry into the healthcare industry.

The head of Quick Meds, an online pharmacy firm that had only recently been established, believes it will have a huge impact on the industry.

“I’m worried,” he said. “They’ll have a massive marketing budget, and they’ll definitely take a sizeable chunk out of every other pharmacy on the market. There will be closures as a direct result of it.”

Pharmacies have complex, inefficient supply chains which the online retail giant could outcompete with its massive, streamlined operations. Amazon is already purchasing its first fleet of aircraft to compete directly with large courier companies like FedEx, taking advantage of plummeting aircraft prices in the wake of the pandemic.

Scott Galloway, professor of marketing at NYU Stern, entrepreneur and author of Post Corona: From Crisis to Opportunity, believes that consumers will benefit in the short and medium term.”For the most part of Amazon’s history, as a consumer you’re getting products for near cost or sometimes even below cost and that has just been an incredible boon for consumers and shareholders,” he said.

The company would use information from its other business areas to create a database of each customer’s health, enabling it to target goods and services.

“With their new wearable Amazon Halo, the company can build a 3D image of their consumers and they can then combine this with the foods you eat through Whole Foods, data from Amazon Prime and Alexa, and information such as your post code, relationship status, demographic data,” said Mr Galloway. Compared to the largely reactive medical industry, where consumers seek out medical services, this is a sea change.

“They can use this to offer proactive healthcare services,” he said.

Source: BBC News

Genetic Basis for Why Lithium is Effective for Only Some

Lithium was the first effective mood stabiliser for bipolar disorder (BD) and still the first-line treatment, but it is effective only in about 30% of patients, while the remainder are unresponsive. A new study implicates the decreased activation of a certain gene.

The study shows that decreased activation of a gene called LEF1 disrupts ordinary neuronal function and promotes hyperexcitability in brain cells—a hallmark of BD. The findings could lead to development of a new drug target for BD as well as a biomarker for lithium nonresponsiveness.

“Only one-third of patients respond to lithium with disappearance of the symptoms,” says Renata Santos, co-first author on the study. “We were interested in the molecular mechanisms behind lithium resistance, what was blocking lithium treatment in nonresponders. We found that LEF1 was deficient in neurons derived from nonresponders. We were excited to see that it was possible to increase LEF1 and its dependent genes, making it a new target for therapeutic intervention in BD.”

The study built on a previous one which discovered differences in the neurons of those with lithium unresponsiveness.

Using stem cell technology, the team grew neurons sampled from patients’ blood, who had BD and were responsive or unresponsive to lithium, and from normal patients. They compared the genetic characteristics and behaviour of those neurons.Lithium enables beta-catenin to pair with LEF1 to promote neural regulation in the normal controls and lithium responders.

Administration of valproic acid, a typical treatment for non-responders, increased LEF1 levels as well as activation of related genes. Silencing the LEF1 gene also deactivated related genes.”When we silenced the LEF1 gene, the neurons became hyperexcitable,” says Shani Stern, co-first author on the study. “And when we used valproic acid, expression of LEF1 increased, and we lowered the hyperexcitability. That shows there is a causative relationship, and that’s why we think LEF1 may be a possible target for drug therapy.”

The team wants to look at other types of cells, such as astrocytes, to better understand the role of LEF1 in the bipolar neural network.”LEF1 works in various ways in different parts of the body, so you can’t just turn it on everywhere,” said  co-corresponding author Carol Marchettor. “You want to be more specific, either activating LEF1 on a targeted basis or activating downstream genes that are relevant for lithium nonresponsiveness.”

Source: Medical Xpress

Vitamin D to Treat COVID: No Time for Perfect Evidence

An Op-Ed in MedPage Today highlights the evidence for the potential role of vitamin D in the fight against COVID. Low vitamin D levels are being linked to COVID fatality and ICU admission.

Some 40% of the US population is vitamin D deficient, while in Africa, some 20% are thought to be vitamin D deficient. With South Africa’s seasonal variations, vitamin D levels in adults and children may be adequate in summer and autumn but deficient in the winter, even given its ethnically diverse population.

The article reviews the evidence in favour of and against administering Vitamin D as an acute treatment. Causality can be inferred from correlational data by satisfying various criteria which includes consistency, specificity, temporality, and dose-responsiveness. This same approach was used to draw the link between lung cancer and smoking in 1964.
Studies have shown some striking associations between vitamin D sufficiency and COVID outcomes. In a study of 154 patients, patients with vitamin D deficiency (serum 25-OH-D <20 ng/mL) had a fatality rate of 21%, compared to a rate of 3% for those with higher levels. Firming up the case for causation, there is some randomised experimental data.

In a study of 76 COVID patients in Spain, 1 of 50 of patients who were given open-label calcifediol, a potent vitamin D analogue, were admitted to ICU whilst 13 of 26 who did not receive vitamin D were admitted to ICU.
Nursing homes in France often give vitamin D injections, and a quasi-experimental study showed that only 10% of nursing home residents receiving vitamin D progressed to severe COVID, compared to 31% who were not.

The authors conclude that doctors cannot always wait for perfect evidence as they have a duty of care, and given vitamin D’s safety profile, the evidence for its protective role should be acted upon.
Source: MedPage Today

Oncologist Forgives $650 000 in Patient Debts

An oncologist in the United States has forgiven $650 000 in patients’ debts. After 30 years of business, Dr Omar Atiq closed down his Arkansas cancer treatment centre last year. He had previously engaged a debt collector company to chase up clients’ outstanding bills.

“Over time I realised that there are people who just are unable to pay,” Dr Atiq said to ABC’s Good Morning America. “So my wife and I, as a family, we thought about it and looked at forgiving all the debt. We saw that we could do it and then just went ahead and did it.”

Dr Atiq is originally from Pakistan, and founded the Arkansas Cancer Clinic in 1991.”We thought there was not a better time to do this than during a pandemic that has decimated homes, people’s lives and businesses and all sorts of stuff,” Dr Atiq said, quoted by the Arkansas Democrat-Gazette.

When sending his Christmas greeting card to patients, he wrote, “The Arkansas Cancer Clinic was proud to serve you as a patient. Although various health insurances pay most of the bills for [the] majority of patients, even the deductibles and co-pays can be burdensome. Unfortunately, that is the way our health care system currently works. The clinic has decided to forego all balances owed to the clinic by its patients. Happy Holidays.”
In the view of the president of the debt collection company he engaged, Dr Atiq is “a very caring individual”.

Bea Cheesman, of RMC of America, said, “He’s always been extremely easy to work with as a client. It’s just a wonderful thing that he and his family did in forgiving this debt because the people with oncology bills do have more challenges than the bulk of the population.”Dr Atiq approached the Arkansas Medical Society to ensure there was nothing improper about the move.

Source:BBC News

Antibiotic Overuse by Children’s Hospitals Contributing to Antibiotic Resistance

Children’s hospitals may be contributing to antibiotic resistance by overprescription of antibiotics, according to a recent study.

The study, conducted by the University of Alabama at Birmingham (UAB),   found that in 51 children’s hospitals across the United States, rates of antibiotic administration ranged from 22% to 52%. Approximately a quarter of children receiving antibiotics were receiving them incorrectly. This adds to a growing body of evidence that points to antibiotics overuse and misuse by children’s hospitals – which ought to know better.Study co-author, Dr Jason Newland said, “There’s no doubt: We’ve seen some extra use of antibiotics, The impact of the pandemic on antibiotic use will be significant.

“The study’s numbers are likely an underestimate since the research involved 32 children’s hospitals already working together on proper antibiotic use. Newland said the US’ more than 250 children’s hospitals need to improve. Even though COVID fears have reduced the numbers of children’s hospital visits, antibiotics are still being prescribed via telemedicine.

“I hear a lot about antibiotic use for the ‘just in case’ scenarios,” said Dr Joshua Watson, at Nationwide Children’s Hospital in Ohio. “We underestimate the downsides.”

Dr Shannon Ross, an associate professor of paediatrics and microbiology at UAB, said that not all doctors have been taught the correct use of antibiotics. Regarding this overuse, she said, “Many of us don’t realize we’re doing it. It’s sort of not knowing what you’re doing until someone tells you.”
Unnecessary antibiotic use is a problem, and the pandemic “has thrown a little bit of gas on the fire,” said Dr Mark Schleiss, a paediatrics professor at the University of Minnesota Medical School.

“It’s irresponsible,” said Christina Fuhrman, who almost lost her infant daughter to a Clostridium difficile infection, and who now advocates for correct antibiotic use. Along with parents begging for antibiotics in paediatricians’ offices, the situation is “creating a monster.”
Many studies have attested to the rise of C. diff in children, which causes gastrointestinal problems. A 2017 study found that cases of a certain multidrug-resistant Enterobacteriaceae type rose 700% in American children in just eight years. And a steady stream of research points to the stubborn prevalence in kids of the better-known MRSA, or methicillin-resistant Staphylococcus aureus.

“It’s getting more and more worrisome,” said Ross. “We have had patients we have not been able to treat because we’ve had no antibiotics available.”

Source: News-Medical.Net

Journal information: Tribble A, Lee B, Flett K et al. Appropriateness of Antibiotic Prescribing in United States Children’s Hospitals: A National Point Prevalence Survey. Clinical Infectious Diseases. 2020;71(8):e226-e234. doi:10.1093/cid/ciaa036