Tag: 21/7/21

Categories : Ageing Skeletal SystemTags :

Bone Loss Linked to Cognitive Decline in Women

On By ModernMedia
Photo by Miikka Luotio on Unsplash
Photo by Miikka Luotio on Unsplash

Researchers  have discovered a link between cognitive decline and accelerated bone loss, and found that cognitive decline over five years increased future fracture risk in women. There was a less strong association in men.

The 16-year study enrolling individuals aged 65 and over was led by the Garvan Institute of Medical Research and , and has uncovered a potential new approach to help identify older people who may be at risk of fracture.
“Bone loss and cognitive decline are major public health issues, but both are ‘silent diseases’ that can go undetected and untreated for long periods, often until the conditions are severely progressed,” says Professor Jacqueline Center, Head of the Clinical Studies and Epidemiology lab at Garvan, endocrinologist at St Vincent’s Hospital and senior author of the findings published in the Journal of Bone and Mineral Research.

“Our study has revealed a link between the two in women, which suggests that cognition should be monitored together with bone health, as a decline in one could mean a decline in the other. These findings may help refine best practice guidelines of how cognition and bone health are monitored in older age, to ensure appropriate treatment can be more effectively administered.”

A growing problem with an ageing population

Osteoporosis affects some 200 million people worldwide, and more than 35 million for dementia — numbers set to double over the next 20 years due to rising life expectancy.

“Cognitive decline and bone loss both result in increased disability, loss of independence and an increased risk of mortality. There is some evidence that older individuals with dementia have a higher risk of hip fractures, but whether the decline of both bone and cognitive health are linked over time has not been studied,” said first author Dr Dana Bliuc from the Garvan Institute.

“We set out to understand the long-term association, with our study the first to investigate both cognitive and bone health data over more than 15 years.”

Data was drawn from the Canadian Multicentre Osteoporosis Study (CaMos), which has monitored skeletal health in community-dwelling people since 1995. The researchers examined cognitive and bone health measurements of 1741 women and 620 men aged 65 years and older, who were free of cognitive decline symptoms at the study outset.

Cognition link to bone health

“After adjusting for all other variables, we observed a significant link between a decline in cognitive health and bone loss in women. This association was weaker and not statistically significant in men,” said Dr Bliuc.

“Interestingly, we also saw that cognitive decline over the first five years was associated with a 1.7-fold increase in future fracture risk in women in the subsequent 10 years. This was independent of the level of bone loss,” Dr Bliuc added.

“While this study could not identify a causal link – whether a decline in cognitive function leads to a decline in bone loss, or vice versa – it suggests that cognitive decline should be monitored along with bone health, as a decline in one may signal the need for increased vigilance in the other,” said Professor Center.

The researchers add that the link could potentially be mediated by a third factor, such as oestrogen deficiency, linked to bone loss and cognitive decline. This research also opens the door for additional studies into what the link between these two common conditions may be.

“What our study highlights is that cognitive health is potentially an important factor for providing more information to individuals and their health professionals on fracture risk, and ultimately improve health outcomes for our older population,” said Professor Center.

Source: Garvan Institute of Medical Research

Journal information: Bliuc, D., et al. (2021) Cognitive decline is associated with an accelerated rate of bone loss and increased fracture risk in women: a prospective study from the Canadian Multicentre Osteoporosis Study. Journal of Bone & Mineral Research. doi.org/10.1002/jbmr.4402.

Categories : Injury & Trauma NeurologyTags :

Good Outcomes for Severe Brain Injury Still Possible

On By ModernMedia
Photo by Anna Shvets from Pexels

A new study adds to the growing body of evidence that decisions regarding moderate-to-severe traumatic brain injury (TBI) should not be made too soon after the injury, as a good prognosis can still emerge.

Researchers followed 484 patients with moderate-to-severe TBI and found that among the patients in a vegetative state, one quarter “regained orientation” — awareness of who, when and where they were —  within 12 months of their injury.

“Withdrawal of life-sustaining treatment based on early prediction of poor outcome accounts for most deaths in patients hospitalised with severe TBI,” said senior author Geoffrey Manley, MD, PhD,  noting that 64 of the 92 fatalities in the study occurred within two weeks of injury. Dr Manley is professor and vice chair of neurological surgery at UCSF and chief of neurosurgery at Zuckerberg San Francisco General Hospital.

“TBI is a life-changing event that can produce significant, lasting disability, and there are cases when it is very clear early on that a patient will not recover,” he said. “But results from this study show a significant proportion of our participants experienced major improvements in life functioning, with many regaining independence between two weeks and 12 months after injury.”

The patients in the study were enrolled by the brain injury research initiative TRACK-TBI, of which Dr Manley is the principal investigator. All patients were 17 and older and had presented to hospitals with level 1 trauma centers within 24 hours of injury. Their exams met criteria for either moderate TBI or severe TBI. The causes were falls, assault and primarily crashes involving a motor vehicle.

The patients, whose average ages were 35 in the severe TBI group (78 percent males) and 38 in the moderate TBI group (80 percent males), were assessed using the Glasgow Outcomes Scale Extended (GOSE), which ranges from 1 for death to 8 for “upper good recovery” and resumption of normal life. Impairment was also categorised with the Disability Rating Scale (DRS).

At two weeks post-injury, 93 percent of the severe TBI group and 79 percent of the moderate TBI group had moderate-to-severe disability, according to the DRS, and 80 percent had GOSE scores from 2 to 3, meaning they required assistance in basic everyday functioning.

But by 12 months, half of the severe TBI group and three-quarters of the moderate TBI group had GOSE scores of at least 4, indicating they could function independently at home for at least eight hours per day. Moreover, 19 percent of the severe TBI group had no disability, according to the DRS, and a further 14 percent had only mild injury, the researchers noted.

Most surprising were the findings for the 62 surviving patients who had been in a vegetative state. By the 12-month mark all patients had recovered consciousness and 1 in 4 had regained orientation. All but one survivor in this group recovered at least basic communication ability.

“These patients made the cut for favorable outcome,” said co-first author, Joseph Giacino, PhD, of Spaulding Rehabilitation Hospital, Massachusetts General Hospital and Harvard Medical School. “Their GOSE scores were 4 or higher, which meant they could be at home unsupervised for at least eight hours a day, since they were able to take care of basic needs, such as eating and toileting.”

In prior work, a significant percentage of patients with grave impairments had been shown to achieve favorable functionality after many months or years. This study coincided with the recommendation in 2018 from the American Academy of Neurology that in the first 28 days after injury, clinicians should refrain from telling families that a patient’s prognosis is beyond hope.

“While a substantial proportion of patients die or suffer lasting disability, our study adds to growing evidence that severe acute impairment does not portend uniformly poor long-term outcome,” said Manley, who is also affiliated with the UCSF Weill Institute for Neurosciences. “Even those patients in a vegetative state – an outcome viewed as dire – may improve, since this is a dynamic condition that evolves over the first year.”

Source: University of California, San Francisco

Journal information:JAMA Neurology (2021). DOI: 10.1001/jamaneurol.2021.2043

Categories : COVIDTags : 1 Comment

True COVID Toll in India Likely in the Millions

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Photo by camilo jimenez on Unsplash

Excess deaths in India during the pandemic could be as much as 10 times the official COVID toll, likely making it modern India’s worst human tragedy, according to a new report.

A report published by Arvind Subramanian, the Indian government’s former chief economic adviser, and two other researchers at the Center for Global Development and Harvard University, estimates that between 3.4 million and 4.7 million excess deaths have occurred in the country from January 2020 to June 2021.

The report said that the true toll was likely “an order of magnitude higher”, and the official count could have missed deaths with overwhelmed and disrupted healthcare systems, particularly during the devastating virus surge earlier this year. It also has recently come to light that the Indian government did not count any deaths due to a lack of oxygen.

The researchers from used three different data sources to estimate India’s excess all-cause mortality. They extrapolated death registrations from seven states, accounting for half of India’s population, but published data for annual mortality surveys are only available up to 2019. Second, the researchers applied international estimates of age-specific infection fatality rates to data from two countrywide antibody tests, also called sero surveys. Third, they looked at India’s thrice yearly consumer survey of 900 000 individuals, which also records deaths in households.

Taken together, the researchers arrived at an estimate of of 3.4 million to 4.7 million – about 10 times higher than India’s official COVID death toll of 414 000. This was also considerably higher than other estimates by epidemiologists, who estimated excess deaths were between five and seven times higher. Not all these deaths were caused by COVID and an estimation of the actual death toll by the disease would be difficult to give, said Subramanian. 

The data implied that four million people had died in the pandemic in India, according to Dr Subramanian.

“Two of our three estimates measure all-cause mortality and not COVID deaths. Our second measure is a bit closer to a number of [actual] COVID deaths, but it is only one of three estimates,” Dr Subramanian told the BBC.

The researchers also said that the first wave last year appeared to have been more lethal than what was popularly believed. Mortality only seemed to be moderate because it was “spread out in time and space”.

Dr Subramanian said one of the conclusions might be that “India has not been an outlier” and has had “mortality not dissimilar from countries of comparable size and infections”.

The researchers said the most “critical take-away, regardless of the sources and estimates”, was that actual deaths during the pandemic were “likely to be far greater than the official count”.

“The true deaths are likely to be in several millions, not hundreds of thousands, making this arguably India’s worst human tragedy since the partition and independence.” The 1947 Partition of the British-ruled Indian subcontinent into independent India and Pakistan resulted in up to 1 million people being killed in violence between Hindu and Muslim gangs.

Source: BBC News

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Heart Health Strongly Linked to Pregnancy Outcomes

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Photo by Anna Hecker on Unsplash
Photo by Anna Hecker on Unsplash

A strong and graded relationship between women’s heart health and pregnancy outcomes has been demonstrated by a study of more than 18 million pregnancies. 

Significant metabolic and haemodynamic changes occur to a woman’s body during pregnancy, some of which can later increase the risk of cardiovascular disease. Risk factors for cardiovascular disease also impact on pregnancy outcomes. The researchers examined the presence of four cardiovascular disease risk factors in women prior to pregnancy: unhealthy body weight, smoking, hypertension and diabetes. The risk of pregnancy complications – maternal intensive care unit (ICU) admission, preterm birth, low birthweight and foetal death – rose along with the number of pre-pregnancy cardiovascular risk factors.

“Individual cardiovascular risk factors, such as obesity and hypertension, present before pregnancy have been associated with poor outcomes for both mother and baby,” said study author Dr Sadiya Khan, Northwestern University Feinberg School of Medicine, Chicago, US. “Our study now shows a dose-dependent relationship between the number of risk factors and several complications. These data underscore that improving overall heart health before pregnancy needs to be a priority.”

The study, which was published in the European Journal of Preventive Cardiology, was a cross-sectional analysis of maternal and foetal data from the US National Center for Health Statistics (NCHS), which gathers information on all live births and foetal deaths after 20 weeks’ gestation. Individual-level data was pooled from births to women aged 15 to 44 years from 2014 to 2018. 

Information was collected on whether four cardiovascular risk factors were present before pregnancy: body mass index (BMI; under 18.5 kg/m2 or over 24.9 kg/m2), smoking, hypertension and diabetes. Women were categorised as having 0 to 4 risk factors. The researchers estimated the relative risks of maternal ICU admission, preterm birth (before 37 weeks), low birthweight (under 2500 g), and foetal death associated with risk factors compared with no risk factors (0). All analyses were adjusted for maternal age at delivery, race/ethnicity, education, receipt of prenatal care, parity, and birth plurality.

The analysis included a total of 18 646 512 pregnancies, with an average maternal age of 28.6 years. More than 60% of women had one or more pre-pregnancy cardiovascular risk factors, ranging from 52.5% with one risk factor and 0.02% with 4 risk factors.

Those with all four risk factors had an approximately 5.8-fold higher risk for ICU admission than those with none, 3.9-fold higher risk for preterm birth, 2.8-fold higher risk for low birthweight, and 8.7-fold higher risk for foetal death.

Graded associations were found between increasing numbers of pre-pregnancy risk factors and a higher odds of adverse outcomes. The risk ratio for maternal ICU admission compared to no risk factors was 1.12 for one risk factor, 1.86 for two risk factors, 4.24 for three risk factors, and 5.79 for four risk factors.

The analysis was repeated in women with their first pregnancy with consistent results. “We conducted this analysis since women with a complicated first pregnancy are more likely to have complications in subsequent pregnancies,” explained Dr Khan. “In addition, gestational weight gain can lead to a higher BMI going into the next pregnancy. We saw very similar results which strengthens the findings in the full cohort.”

She continued: “Levels of pre-pregnancy obesity and high blood pressure are rising and there are some indications that women are acquiring cardiovascular risk factors at earlier ages than before. In addition, pregnancies are occurring later in life, giving risk factors more time to accumulate. Taken together, this has created a perfect storm of more risk factors, earlier onset, and later pregnancies.”

Dr Khan concluded: “The findings argue for more comprehensive pre-pregnancy cardiovascular assessment rather than focussing on individual risk factors, such as BMI or blood pressure, in isolation. In reality not all pregnancies are planned, but ideally we would evaluate women well in advance of becoming pregnant so there is time to optimise their health. We also need to shift our focus towards prioritising and promoting women’s health as a society – so instead of just identifying hypertension, we prevent blood pressure from becoming elevated.”

Source: European Society of Cardiology (ESC)

Journal information: Wang, M.C., et al. (2021) Association of pre-pregnancy cardiovascular risk factor burden with adverse maternal and offspring outcomes. European Journal of Preventive Cardiology. doi.org/10.1093/eurjpc/zwab121.

Categories : Metabolic Disorders PaediatricsTags :

A Restful Sleep for Diabetic Children with New Glucagon Administration

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A new treatment has been developed that promises a way to prevent potentially lethal hypoglycaemic episodes in children.

For children with Type 1 diabetes, the risk of experiencing a severe hypoglycaemic episode can be quite high. Undetected drops in blood sugar overnight can result in coma and death — an event known as ‘dead in bed syndrome’. As well as being a threat to the child, parents also suffer psychological stress worrying about the situation and often losing sleep.

In severe situations, glucagon injections can stabilise blood glucose levels long enough for parents to get their child medical attention. But in a new study, published in the Journal of the American Chemical Society, Matthew Webber, associate professor of chemical and biomolecular engineering at the University of Notre Dame, is rethinking the traditional use of glucagon as an emergency response by administering it as a preventive measure.

The study describes how Prof Webber and his team successfully developed hydrogels that remain intact in the presence of glucose but slowly destabilise as levels drop, releasing glucagon into the system and raising glucose levels.

“In the field of glucose-responsive materials, the focus has typically been on managing insulin delivery to control spikes in blood sugar,” Prof Webber said. “There are two elements to blood glucose control. You don’t want your blood sugar to be too high and you don’t want it to be too low. We’ve essentially engineered a control cycle using a hydrogel that breaks down when glucose levels drop to release glucagon as needed.”

The water-based gels a three-dimensional structure. Prof Webber describes them as having a mesh-like architecture resembling a pile of spaghetti noodles with glucagon “sprinkled” throughout. In animal models the gels dissolved as glucose levels dropped, releasing their glucagon.

Ideally in future applications, the gels would be administered each night before bed, Webber explained. “If a hypoglycaemic episode arose later on, three or five hours later while the child is sleeping, then the technology would be there ready to deploy the therapeutic, correct the glucose imbalance and prevent a severe episode.”

Since research is in extremely early stages, parents and individuals living with Type 1 diabetes should not expect a therapy available anytime soon, Prof Webber cautioned.

“One of the big challenges was engineering the hydrogel to be stable enough in the presence of glucose and responsive enough in the absence of it,” he said. Another challenge was preventing the glucagon from leaking out of the hydrogel’s mesh-like structure. Though the team was successful in this regard, Prof Webber said he hopes to improve stability and responsiveness with further study.

Source: EurekAlert!

Categories : COVID Ethics and LawTags :

Large Ivermectin Study Retracted Due to Data Problems Ethical Concerns

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Photo by Markus Winkler on Unsplash

MedPage Today reports that a large ivermectin study has been retracted over concerns of plagiarism and serious problems with their raw data.

Michele Avissar-Whiting, PhD, editor-in-chief of the preprint server Research Square, wrote in a July 14 statement that the study was retracted “because we were presented with evidence of both plagiarism and anomalies in the dataset associated with the study, neither of which could reasonably be addressed by the author issuing a revised version of the paper.”

Dr Avissar-Whiting noted that the concerns were first raised by Jack Lawrence, a British medical student, according to The Guardian.

“Based on what Jack found, we have reason to believe the preprint’s conclusions are compromised, so the withdrawal was done to stop its propagation as sound science,” she said. “This is the strategy employed by a number of preprint servers, per best practice guidance.”

The 400-patient Egyptian trial, from Ahmed Elgazzar, MD, of Benha University, and colleagues, had been included in two recent meta-analyses (Bryant et al. and Hill et al.) which drew significant attention for their positive results — especially the much-anticipated Hill review. Two ivermectin proponent groups, the Front Line COVID-19 Critical Care Alliance (FLCCC) and the British Ivermectin Recommendation Development Group (BIRD), released a statement saying that removing the Algazzar data from the two studies did not change their overall positive result.

In an email to MedPage Today, lead author Andrew Hill, PhD, of the University of Liverpool in England, said  that his team will be “re-running our analysis with the Elgazzar trial removed.”

Dr Hill added that the analysis would also be updated with a recent 500-patient randomised controlled trial from Argentina, which found no effect for ivermectin in terms of preventing hospitalisation in patients with COVID. The study also fiend that patients receiving ivermectin required invasive ventilation sooner than those on placebo.

“In our published paper, we emphasised the preliminary nature of our results and the need to continue more definitive studies,” Hill wrote in his email.

The Elgazzar study’s main findings have already been cited by other publications: Hospitalised patients with COVID who were treated with ivermectin were 90% less likely to die than those who didn’t receive the drug. 

Lawrence had taken on an assignment for medical school which had prompted a deeper look at the paper, coming across plagiarism with entire paragraphs copied from other sources.

Additionally, the raw data, which can be purchased online, contradicted the study in several instances. Gideon Meyerowitz-Katz, an epidemiologist from the University of Wollongong in Australia, highlighted some of those discrepancies in a Medium post.

“For example, the study reports getting ethical approval and beginning on the 8th of June, 2020, but in the data file uploaded by the authors onto the website of the preprint fully 1/3 of the people who died from COVID were already dead when the researchers started to recruit their patients,” Meyerowitz-Katz wrote.

“Moreover, about 25% of the entire group of patients who were recruited for this supposedly prospective randomised trial appear to have been hospitalised before the study even started, which is either a mind-boggling breach of ethics or a very bad sign of potential fraud,” he continued.
Other phase III randomised clinical trials continue to investigate ivermectin for COVID such as the PRINCIPLE trial which seeks 1500 participants for its ivermectin arm.

Source: MedPage Today