Patients with new spinal cord injuries whose blood pressure is maintained within a newly defined range during surgery may stand a better chance of regaining some mobility and functionality – even in patients with the most devastating injuries – according to a new study by researchers at UC San Francisco.
The study, which draws from retrospective data from hospital operating rooms, published in the journal eLife, and follows preclinical research by Ferguson, using data from both published and unpublished studies. For one patient, in particular, a father of two injured in a surfing accident, the innovative insight and bench-to-bedside research that followed meant the difference between total paralysis and resuming his life.
Using a novel machine-learning technique called topological data analysis (TDA) – so-called because it borrows concepts from geometric topology – the researchers were able to identify patterns in large datasets to find connections never before understood that explain why some people recover some motor control after a significant injury, while others are left with total paralysis. The study also may have ramifications for patients undergoing spinal surgeries for more common conditions, the researchers said, although further investigation is needed.
“Without the use of TDA, data would be heterogenous, overwhelming and beyond human comprehension,” said co-corresponding author Adam Ferguson, PhD, director of data science at the UCSF Brain and Spinal Injury Center, who was the first scientist to harness machine learning as a tool to uncover the connection between spinal cord injury recovery and blood pressure, using data from both published and unpublished studies.
“Topological data analysis helped us to ‘see’ patterns that are difficult for humans to see,” said Ferguson, who is also affiliated with the UCSF Weill Institute for Neurosciences.
The study’s authors include those from four other institutions (see below) as well as TRACK-SCI investigators, a UCSF-led collaboration of researchers, clinical researchers and clinicians tasked with generating new treatments from the bench to the bedside.
Spinal cord injury affects approximately 18,000 people in the United States each year, with a total prevalence of around 300,000 cases, according to the National Spinal Cord Injury Statistical Center. Car accidents and falls are the most common causes with more than 50 per cent of injuries affecting the cervical spine, the neck region, which is associated with greater impairment and more serious complications.
In the current study, the researchers tracked data from 118 patients at two hospitals with Level 1 trauma centres: Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG) and Santa Clara Valley Medical Center.
They compared the estimated grade of injury on admission with the estimated grade of injury at discharge. Grades followed the American Spinal Injury Association Impairment Scale and ranged from A, denoting complete motor and sensory function loss below the level of injury, to E for normal sensation and full motor function.
The same machine-learning technique used by Ferguson with preclinical data in the earlier study was applied to the current study using clinical data collected at one-to-five-minute intervals while the patients were in the operating room. Of the 42 patients whose injuries had improved by at least one grade from admission to discharge, 18 had had a grade-A injury, eight grade B, 11 grade C and five grade D.
These TDA patterns were then verified by spinal cord injury experts and statisticians, who developed rigorous statistical models that “assessed their truth,” Ferguson said.
“This is an ideal use case for how machine learning could be implemented in biomedicine – it’s a partnership between machines and humans with clinical domain knowledge,” he said. “In essence, we are machine learning-assisted cyborgs.”
Patients with blood pressure that was too high or too low during surgery had poorer neuromotor recovery after surgery, the researchers concluded. Maximal recovery was associated with mean arterial blood pressure maintained between 76 mmHg and 104-117 mmHg, a range that is narrower than the current guidelines that have followed smaller clinical studies.
“It is particularly interesting that this work identified the upper limit of the blood pressure range, which hadn’t been considered harmful before in clinical practice,” said co-corresponding author Jonathan Pan, PhD, MD, from the UCSF Department of Anesthesia and Perioperative Care. “If the results can be validated in our prospective study, it has the potential to provide new guidance on our blood pressure management for patients with acute spinal cord injury.”
Paralysis following injury is due to swelling/bruising and a “storm of cellular stressors that may resolve after injury if the neurons survive the ultra-acute phase of spinal cord injury,” said co-lead author Abel Torres-Espin, PhD, of the UCSF Department of Neurological Surgery and of the UCSF Weill Institute for Neurosciences.
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Study finds cardiovascular disease, high cholesterol linked to plastics
A new study has found that phthalate—a chemical used to make plastics more durable—has led to increased plasma cholesterol levels.
The findings of the study were published in the journal ‘Environmental Health Perspectives’. “We found dicyclohexyl phthalate, or DCHP, strongly binds to a receptor called pregnane X receptor, or PXR,” said Changcheng Zhou, who is a professor in the UCR School of Medicine.
“DCHP ‘turns on’ PXR in the gut, inducing the expression of key proteins required for cholesterol absorption and transport. Our experiments show that DCHP elicits high cholesterol by targeting intestinal PXR signalling,” added Zhou.
DCHP, a widely used phthalate plasticiser, has recently been proposed by the Environmental Protection Agency as a high-priority substance for risk evaluation. Not much is known yet about DCHP’s adverse effects on humans.
“To our knowledge, our study is the first to show the effects of DCHP exposure on high cholesterol and cardiovascular disease risk in mouse models. Our results provide insights and new understandings of the impact of plastic-associated chemicals on high cholesterol—or dyslipidemia—and cardiovascular disease risk,” Zhou said.
Zhou’s team also found that mice exposed to DCHP had in their intestines higher circulating “ceramides”—a class of waxy lipid molecules associated with increased cardiovascular disease risk in humans—in a way that was PXR-dependent.
“This, too, points to the potentially important role of PXR in contributing to the harmful effects of plastic-associated chemicals on cardiovascular health in humans,” Zhou said.
Zhou was joined in the research by Zhaojie Meng, Jinwei Liu, Rebecca Hernandez, and Miko Gonzales of UCR; and Yipeng Sui, Taesik Gwag, and Andrew J. Morris of the University of Kentucky.
DEMENTIA CREATES LISTENING ISSUES IN QUIET, NOISY ENVIRONMENTS
Listening to the spoken word in noisy environments is challenging for everyone. Acoustic studies show people with mild dementia struggle to understand speech in both noisy and quiet environments, highlighting the need for everyone to communicate clearly.
During the 181st Meeting of the Acoustical Society of America, Kate McClannahan, from Washington University School of Medicine, discussed how background noise impacts have spoken word recognition in people with mild dementia. The talk, “The effect of mild dementia on speech perception in quiet and noise,” took place on Wednesday, December 1, at the Hyatt Regency Seattle.
Difficulty in understanding speech, especially in background noise, is a common concern for older adults. Using a word identification task in quiet and noisy conditions, researchers examined the impact of mild dementia on speech perception. They tested individuals with and without mild dementia.
The scientists found word identification scores of those without dementia were significantly better in all conditions, meaning people with mild dementia symptoms recalled fewer words in both quiet and noisy situations.
In the quiet condition, the group with mild dementia missed around 20 per cent of the words, while the control group missed approximately 5 per cent. The findings indicate individuals with mild dementia struggle with understanding speech, even without background noise.
“What is important to take away from this study is that people who are experiencing mild dementia symptoms may have difficulty understanding speech in both quiet and acoustically challenging situations,” said McClannahan.
McClannahan added, “Therefore, when conversing with someone who may be experiencing cognitive difficulties, considerations such as speaking more clearly and slowly, reducing background noise and distractions, making sure the listener can see the speaker’s face and providing ample contextual information, may help to improve the listener’s speech understanding.”
“If you or a loved one notice difficulty with your communication, seeking the advice and care of an audiologist is a great place to start!” McClannahan said taking these measures will aid effective communication for all listeners.
Study provides model for treating HIV/AIDS, depression
For people with HIV who are also struggling with depression, remaining healthy is often an insurmountable challenge, especially in South Africa, home to the highest number of cases in the world and a significant shortage of mental health professionals.
However, a new study has provided local and global implications for successfully treating both mental health and HIV/AIDS in settings like South Africa—or even Miami, the epicentre of new cases in the United States. The findings of the study were published in the ‘Journal of the International AIDS Society’.
In the study, an international team of researchers—led by the University of Miami’s Steven Safren and two colleagues—demonstrated the effectiveness of training nurses in public HIV clinics to deliver a specially adapted cognitive behaviour therapy (CBT) to help people with depression and uncontrolled HIV adhere to their prescribed medication regiment. CBT is a proven approach for changing faulty or unhelpful thinking or behavioural patterns.
“We know that treating HIV-positive people who are clinically depressed with antidepressants alone does not affect their viral loads. Their depression may improve, but their adherence does not,” said Safren, professor of psychology and director of the University’s Center for HIV/AIDS Research and Mental Health.
“So, given the global shortage of mental health professionals, we showed it is possible to train nurses to deliver cognitive-behavioural therapy for adherence and depression (CBT-AD), an intervention that successfully addresses both clinical depression and uncontrolled HIV,” added Safren.
Safren, who joined the University in 2015 from Harvard Medical School, conducted the study in a poor township just outside of Cape Town, South Africa, with fellow researchers John A Joska, director of the HIV Mental Health Research Unit and professor of psychiatry at the University of Cape Town, and Conall O’Cleirigh, associate professor of psychology at Harvard and director of Behavioral Medicine at Massachusetts General Hospital.
For their study, the researchers recruited 161 patients with uncontrolled HIV/AIDS and clinical depression from four public health clinics in the township of Khayelitsha. Although a medical officer could prescribe antidepressants to the patients, the clinics have limited psychological services—as does the country in general. According to the study, South Africa only has 0.28 psychiatrists and 0.32 psychologists per 100,000 people.
At the onset of the study, all participants received the usual enhanced care for clinically depressed HIV-AIDS patients who did not achieve viral suppression after receiving the first month of their antiretroviral medication. That customary treatment included another prescription and follow-up meetings with an adherence counsellor.
But half the patients were also randomly assigned to attend eight CBT-AD sessions, where specially trained nurses integrated strategies for treating depression with adherence counselling that included modules on life skills, depression, relaxation, mood monitoring, and problem-solving.
The idea, Safren said, was to help patients “turn down the volume” of their mental health symptoms, so they would be more open to counselling on the benefit of taking their medication. To track their adherence, the patients also received an electronic pillbox that, every time it was opened, transmitted a real-time signal to a web server.
And, researchers found, the task-shared approach delivered by nurses proved effective. Patients who completed the CBT-AD sessions were more than 2.5 times more likely to achieve undetectable viral loads than those who underwent the usual care.
Now, Safren noted, the next step will be for the research team to evaluate how to sustainably implement the CBT-AD approach in South Africa or even South Florida. He said the task-shared approach could be viable in Miami, where there are fewer services to help people achieve viral suppression than in other US cities with large populations of people living with the virus.
“South Africa has the most cases of HIV/AIDS in the world and Miami is the city with the highest incidence of new cases in the US—so there is a parallel,” Safren pointed out.
“And unlike places like New York or Massachusetts, where people are more likely to be virally suppressed, Florida doesn’t have the same public health resources. If, for example, you’re an HIV patient at Massachusetts General or Fenway Health, where I used to work, and you miss your visit, or your viral load becomes uncontrolled, social workers will swoop in and provide assistance. That doesn’t happen as often in Florida and other places in the US with less public health HIV/AIDS funding,” Safren added.
ALL YOU NEED TO KNOW ABOUT ZYCOV-D VACCINE
Zydus Cadila’s ZyCoV-D, the country’s second indigenous jab against coronavirus (Covid-19), is soon going to be supplied to seven states in India, indicating that our vaccination program will gain more strengthen. This needle-less jab, which received authorisation from the Drugs Controller General of India (DCGI) on 20 August, will be initially administered only to adults because of the company’s limited production capacity currently. However, once the production capacity is strengthened, the vaccine will be available to adolescents too.
HERE IS WHAT YOU SHOULD KNOW ABOUT THE VACCINE
ZyCoV-D is the first Covid-19 vaccine that can be administered using a needle-free applicator as opposed to traditional syringes. It is a three-dose vaccine, whose second and third doses are to be taken 28 and 56 days after the first. The approval has come after evaluating the interim phase III clinical trials in over 28,000 volunteers, in consultation with the Subject Expert Committee. It is also the first Covid-19 vaccine candidate developed on a plasmid DNA platform to be commercially introduced anywhere in the world. The single dose of the vaccine will be made available to the Centre at Rs 376 including the cost of the jet applicator and GST, taking the price of a three-dose jab to Rs 1,128.
WHAT IS A DNA-PLASMID VACCINE?
Most active vaccines are made from a killed or weakened form of the infectious agent. A DNA-plasmid vaccine is a new approach where a piece of DNA containing the genes for the antigens is injected. The body learns to develop an immune response against the antigen, and when the pathogen attacks, the body can then generate the specific antibodies against Covid-19.
HOW DOES THE ZYCOV-D WORK?
The vaccine is jointly developed in partnership with the Department of Biotechnology, had demonstrated a primary efficacy of 66.66% in phase 3 clinical trials. It was the first Covid-19 vaccine in India to be tested in the adolescent population—those in the 12-18-yr age group. It is based on DNA-plasmid technology; it can be administered using a needle-free injection system; and finally, it remains stable in room temperatures for three months. Unlike mRNA vaccines, DNA-based vaccines do not require ultra-cold storage systems and are said to be more cost-effective. The manufacturer also claims that its technology is ideal for tackling Covid-19 as it can be easily adapted to deal with mutations in the virus.
WHAT’S ITS EFFECTIVENESS?
According to the data collected during this trial, this vaccine had already exhibited robust immunogenicity, tolerability and safety profile in the adaptive Phase I/II clinical trials carried out earlier. It said this vaccine works against the Delta variant as the trials have been carried out in more than 50 clinical sites spread across the country, and during the peak of the second wave of Covid-19, have shown the vaccine’s efficacy against the new mutant strains, especially the Delta variant. Data also shows equivalent immunogenicity with that of the three-dose regimen. Therefore, a two-dose regimen approval is also expected. However, the expert panel will review more data on the same.
Going forward, with more vaccines available to the population we can help ebb the pandemic and bring back normalcy to life. Until then, maintaining Covid-19 appropriate behaviour would remain paramount.
The writer is Chief Intensivist, Fortis Hospital, Kalyan.
STUDY FINDS WHOLE FAT DAIRY AS GOOD AS LOW FAT FOR KIDS
A team of researchers from Edith Cowan University has found that when it comes to your kids, whole fat milk is as good as low-fat milk.
The study has been published in the ‘American Journal of Clinical Nutrition’. It suggested the current public health advice recommending children over the age of two consume low-fat dairy products may need to be revised.
ECU’s Associate Professor Therese O’Sullivan led the investigation into the consumption of full-fat dairy products in children as part of the Milky Way study.
Over a three-month period, 49 healthy children aged four to six were randomly allocated to receive either whole-fat or low-fat dairy products in place of their normal dairy intake.
Dairy products were home delivered every fortnight in plain packaging at no cost to the participants, to ensure purchase price wasn’t a factor.
Neither group knew whether they were consuming whole-fat or low-fat dairy, while any leftover products were weighed each fortnight to assess the children’s overall intake.
For the first time, researchers comprehensively measured the children’s obesity, body composition, blood pressure, and blood biomarkers to monitor the effects of their dairy consumption. Regardless of whether they were consuming whole-fat or low-fat dairy, both groups of children took in similar amounts of calories.
Although children consuming low-fat dairy took in fewer calories and fat from dairy, they naturally turned to other foods and drinks to make up for this difference.
Professor O’Sullivan said the findings showed no significant differences between the groups’ obesity or cardiovascular health.
“It had previously been thought young children would benefit from low-fat dairy products due to their lower levels of saturated fats and lower density of energy, in turn helping avoid obesity and risk of associated cardiometabolic diseases,” she said.
“Our results suggest healthy children can safely consume whole-fat dairy products without increased obesity or adverse cardiometabolic effects. With consideration of our results and previous research, future revisions of dietary guidelines should consider recommending children aged two and over can consume either whole fat or reduced-fat dairy,” she added.
Dietitian and PhD candidate on the study Analise Nicholl said that this would make life easier for parents.
“This evidence-based approach would help simplify parents’ dairy choices and allow children to consume dairy according to their individual preference,” Analise said.
Medical training takes less mental toll than a decade ago: Study
It took more than a decade for researchers to track the mental health of medical interns in their most stressful time of training. However, it has been found that things have gotten better now.
This research was published in the ‘Annals of Internal Medicine Journal’. But those first-year residents, or interns, still have a sizable risk of developing depression. And many who do still don’t seek help.
The jump in depression scored over the course of the first post-medical school year has gotten 25% smaller from 2007 to 2019, according to the study of nearly 17,000 new doctors led by a team from the University of Michigan Medical School.
To help understand potential drivers of the effect, the team explored individual and residency program factors previously shown to be linked to depression among training doctors. The study suggested, but can’t prove, that reduced work hours, slightly increased sleep, more feedback from supervisors and increased use of mental health care contributed to the change in depressive symptoms over time. Data from the participants showed significant changes in all of these measures.
The findings came from the Intern Health Study, which has used wearable activity trackers, mobile apps, surveys and genetic tests to study medical interns at hundreds of teaching hospitals.
In addition to tracking a group with a known high risk of depression, the study provided a way to study the effects of intense, prolonged stress more generally.
That’s why the new results could have impacted beyond medical training. Other stressful jobs and long-term stressful situations might also benefit from the increased attention to reducing depression-related stressors that the graduate medical education community has focused on in recent years.
“The Intern Health Study offers a unique dataset for us to study the trend of this population’s mental health over a long time span,” said Yu Fang, M.S.E., the study’s first author and a researcher at the Michigan Neuroscience Institute.
“The story we have learned from these data could help to make strategic plans in shaping a better medical internship experience in the future,” Fang added.
Srijan Sen, M.D., PhD, the leader of the Intern Health Study, said, “Given that depression rates are still very high, compared to the general population, we are hopeful that the drivers of improvement over the past 13 years can help guide areas to focus on to catalyse even more improvement going forward.”
Sen is director of the U-M Frances and Kenneth Eisenberg and Family Depression Center, and a professor in MNI and the Department of Psychiatry at Michigan Medicine.
The reduction in the size of the depression-score jump came despite the fact that interns in later years were more likely to have risk factors for depression, including a history of the condition.
The data showed that interns’ work hours dropped by 11 per cent over the 13-year period, sleep hours per day went up nearly 5 per cent, and the percentage of residents with current depression who were getting professional help went from 14 per cent to 38 per cent.
Over the course of the 13 years studied, female interns experienced a more pronounced reduction in the magnitude of depression symptom increases across the intern year, and they were much more likely to seek mental health care. The percentage of interns who were female also increased over the 13-year study period.
The same was true for interns in non-surgical fields compared with those pursuing training in surgery or another surgery-based speciality; the reduction in work hours was larger in non-surgical interns.
The study did not show any measurable difference between those whose intern year included the first months of the Covid-19 pandemic and those who trained before. Other research from the Intern Health Study is looking at the impacts of the pandemic, including one already-published study about interns taking part in the study in China.
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