Tag: 27/1/23

Categories : Mental Health PaediatricsTags :

UK Study Reveals Doubling in Antipsychotics Prescriptions for Under-18s

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A cohort study on the prescription of antipsychotics to children and adolescents in the UK has found that they have doubled over the past two decades. The findings, published in The Lancet Psychiatry, depict a concerning tendency for more, longer prescriptions of antipsychotics for a wider array of indications, many of them off-label, and which may be influenced by US and European approvals.

Studies around the world have reported an increase in the prescription of antipsychotics for children and adolescents. While this may reflect actual changing clinical needs, most antipsychotics are not approved for use in under-18s due to lacking safety data, especially in the long term. There is also little evidence on indications for, and doses of, antipsychotic prescribing in children and adolescents.

The study used a cohort of over 7 million children and adolescents (age 3–18 years) assembled from a large English primary care database, and found a doubling in the proportion of prescribed antipsychotics between 2000 and 2019.

This increase resulted from the accumulation of repeated prescriptions to the same individuals combined with an increase in new prescriptions. The researchers found that antipsychotic prescribing was more frequent for children in more deprived areas, which reflected a previous UK study on adults.

The study also revealed multiple clinical indications for antipsychotics beyond their initial approvals, most commonly for anxiety and depression. Risperidone was the most prescribed antipsychotic for all indications apart from depression, for which the most prescribed antipsychotic was quetiapine, and eating disorders, for which it was olanzapine.

Prescribing trends for certain disorders could be though to reflect prevalence. The authors noted however that “the most common indications for antipsychotics were ASD, ADHD, anxiety, and depression. It could be the increasing prevalence of these disorders that causes higher prescribing rates. However, increasing ASD prevalence results primarily from patients with less severe ASD, who are unlikely to receive antipsychotics.”

They also observed that increases in prescribing appeared to be linked to new US and European approvals.

Limitations included the database not identifying whether a prescription was for a first time, and not tying indications directly to prescriptions. Dosage regimen information was also only available for a third of prescriptions. The database was also not necessarily nationally representative, and only reflected prescriptions issued in secondary care – referral to primary care means that the rate of prescribing may be underestimated.

Categories : Injury & TraumaTags :

Head Injury Doubles Long-term Mortality Risk

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Adults who suffered any head injury during a 30-year study period had two times the rate of mortality than those who did not have any head injury, and mortality rates among those with moderate or severe head injuries were nearly three times higher, according to new research published in JAMA Neurology.

Head injury can be attributed to a number of causes, from motor vehicle crashes, unintentional falls, or sports injuries. Furthermore, head injury has been linked with a number of long-term health conditions, including disability, late-onset epilepsy, dementia, and stroke.

Previous studies have shown increased short-term mortality among hospitalised patients with head injuries. This longitudinal study evaluated 30 years of data from over 13 000 community-dwelling participants (ie not hospitalised or in nursing homes) to determine if head injury has an impact on mortality rates in adults over the long term. Of these, 18.4% reported one or more head injuries during the study period, and of those who suffered a head injury, 12.4% were recorded as moderate or severe. The median period of time between a head injury and death was 4.7 years.

Death from all causes was recorded in 64.6% of those individuals who suffered a head injury, and in 54.6% of those without any head injury. Accounting for participant characteristics, investigators found that the mortality rate from all-causes among participants with a head injury was 2.21 times the mortality rate among those with no head injury. Further, the mortality rate among those with more severe head injuries was 2.87 times the mortality rate among those with no head injury.

“Our data reveals that head injury is associated with increased mortality rates even long-term. This is particularly the case for individuals with multiple or severe head injuries,” explained the study’s lead author, Holly Elser, MD, PhD, MPH a Neurology resident at Penn. “This highlights the importance of safety measures, like wearing helmets and seatbelts, to prevent head injuries.”

Investigators also evaluated the data for specific causes of death among all participants. Overall, the most common causes of death were cancers, cardiovascular disease, and neurologic disorders (which include dementia, epilepsy, and stroke). Among individuals with head injuries, deaths caused by neurologic disorders and unintentional injury or trauma (like falls) occurred more frequently.

When investigators evaluated specific neurologic causes of death among participants with head injury, they found that nearly two-thirds of neurologic causes of death were attributed to neurodegenerative diseases, like Alzheimer’s and Parkinson’s disease. These diseases composed a greater proportion of overall deaths among individuals with head injury (14.2%) versus those without (6.6%). Further research into this association is recommended.

Source: University of Pennsylvania School of Medicine

Categories : Ageing ExerciseTags :

In Older Women, Physical Activity Reduces Risk of Dementia

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Senior women were less likely to develop mild cognitive impairment or dementia if they did more daily walking and moderate-to-vigorous physical activity, according to a new study published in of Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The University of California San Diego-led team reported that among women aged 65 or older, each extra 31 minutes per day of moderate-to-vigorous physical activity was linked to a 21% lower risk of developing mild cognitive impairment or dementia. Risk was also reduced by 33% with each extra 1865 daily steps.

“Given that the onset of dementia begins 20 years or more before symptoms show, the early intervention for delaying or preventing cognitive decline and dementia among older adults is essential,” said senior author Andrea LaCroix, PhD, MPH, UC San Diego professor.

Dementias are a debilitating neurological condition that can cause loss of memory, the ability to think, problem solve or reason. Mild cognitive impairment is an early stage of memory loss or thinking problems that is not as severe as dementias.

More women live with and are at higher risk of developing dementia than men.

“Physical activity has been identified as one of the three most promising ways to reduce risk of dementia and Alzheimer’s disease. Prevention is important because once dementia is diagnosed, it is very difficult to slow or reverse. There is no cure,” said LaCroix.

However, because few large studies have examined device measures of movement and sitting in relation to mild cognitive impairment and dementia, much of the published research on the associations of physical activity and sedentary behavior with cognitive decline and dementia is based on self-reported measures, said first author, Steven Nguyen, Ph.D., M.P.H., postdoctoral scholar at the Herbert Wertheim School of Public Health.

For this study, the researchers sampled data from 1,277 women as part of two Women’s Health Initiative (WHI) ancillary studies – the WHI Memory Study (WHIMS) and the Objective Physical Activity and Cardiovascular Health (OPACH) study. The women wore research-grade accelerometers and went about their daily activities for up to seven days to obtain accurate measures of physical activity and sitting.

The activity trackers showed the women averaged 3,216 steps, 276 minutes in light physical activities, 45.5 minutes of moderate-to-vigorous physical activity and 10.5 hours of sitting per day. Examples of light physical activity could include housework, gardening or walking. Moderate-to-vigorous physical activity could include brisk walking.

The study findings also showed that higher amounts of sitting and prolonged sitting were not associated with higher risk of mild cognitive impairment or dementia.

Together, this information has clinical and public health importance as there is little published information on the amount and intensity of physical activity needed for a lower dementia risk, said Nguyen.

“Older adults can be encouraged to increase movement of at least moderate intensity and take more steps each day for a lower risk of mild cognitive impairment and dementia,” said Nguyen.

“The findings for steps per day are particularly noteworthy because steps are recorded by a variety of wearable devices increasingly worn by individuals and could be readily adopted.”

The authors said further research is needed among large diverse populations that include men.

Source: University of California – San Diego

Categories : Mental Health NeurologyTags :

Schizophrenia Associated with 12-hour Gene Cycles in the Brain

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In the open-access journal PLOS Biology, researchers present the first evidence of 12-hour cycles of gene activity in the human brain. Led by Madeline R. Scott, the study also reveals that some of those 12-hour rhythms are missing or altered in the postmortem brains of patients with schizophrenia.

Schizophrenia patients are known to have disturbances in several types of 24-hour bodily rhythms, including sleep/wake cycles, hormone levels, and gene activity in the prefrontal cortex of the brain. However, virtually nothing is known about gene activity in the brain for cycles that are shorter than the usual 24-hour circadian rhythm. A few years ago, researchers discovered that certain genes in the body were associated with 12-hour bodily rhythms, which may have an origin in the 12-hour cycle of ocean tides.

As it is not possible to measure gene transcript levels in living brains, the new study instead used a time-of-death analysis to search for 12-hour rhythms in gene activity within postmortem brains. They focused on the dorsolateral prefrontal cortex as it is associated with cognitive symptoms and other abnormalities in gene expression rhythms that have been observed in schizophrenia.

Numerous genes in the normal dorsolateral prefrontal cortex were found to have 12-hour rhythms in activity. Among them, gene activity levels related to building connections between neurons peaked in the afternoon/night, while those related to mitochondrial function (and therefore cellular energy supply) peaked in the morning/evening.

In contrast, postmortem brains from patients with schizophrenia contained fewer genes with 12-hour activity cycles, and those related to neural connections were missing entirely. Additionally, although the mitochondria-related genes did maintain a 12-hour rhythm, their activity did not peak at the normal times. Whether these abnormal rhythms underlie the behavioural abnormalities in schizophrenia, or whether they result from medications, nicotine use, or sleep disturbances should be examined in future studies.

Co-author Colleen A. McClung adds: “We find that the human brain has not only circadian (24 hour) rhythms in gene expression but also 12-hour rhythms in a number of genes that are important for cellular function and neuronal maintenance. Many of these gene expression rhythms are lost in people with schizophrenia, and there is a dramatic shift in the timing of rhythms in mitochondrial-related transcripts which could lead to suboptimal mitochondrial function at the times of day when cellular energy is needed the most.”

Source: ScienceDaily

Categories : Diseases, Syndromes and Conditions Lab Tests and ImagingTags :

A Severe Form of Dementia may in Fact be Caused by a Cerebrospinal Fluid Leak

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MRI images of the brain
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A new study suggests that some patients diagnosed with behavioural-variant frontotemporal dementia (bvFTD) – a presently incurable, mentally debilitating condition – may instead have a cerebrospinal fluid leak, which is detectable on MRI scans and often treatable. The researchers say these findings, published in the peer-reviewed journal Alzheimer’s & Dementia: Translational Research and Clinical Interventions, could lead to a cure.

“Many of these patients experience cognitive, behavioural and personality changes so severe that they are arrested or placed in nursing homes,” said Wouter Schievink, MD, professor of Neurosurgery at Cedars-Sinai. “If they have behavioural-variant frontotemporal dementia with an unknown cause, then no treatment is available. But our study shows that patients with cerebrospinal fluid leaks can be cured if we can find the source of the leak.”

When cerebrospinal fluid (CSF) leaks into the body, the brain can sag, causing dementia symptoms. Schievink said many patients with brain sagging, detectable in MRI, go undiagnosed, and he advises clinicians to take a second look at patients with telltale symptoms.

“A knowledgeable radiologist, neurosurgeon or neurologist should check the patient’s MRI again to make sure there is no evidence for brain sagging,” Schievink said.

Clinicians can also ask about a history of severe headaches that improve when the patient lies down, significant sleepiness even after adequate night-time sleep, and whether the patient has ever been diagnosed with a Chiari brain malformation, a condition in which brain tissue extends into the spinal canal. Brain sagging, Schievink said, is often mistaken for a Chiari malformation.

Even when brain sagging is detected, the source of a CSF leak can be difficult to locate. When the fluid leaks through a tear or cyst in the surrounding membrane, it is visible on CT myelogram imaging with the aid of contrast medium.

Schievink and his team recently discovered an additional cause of CSF leak: the CSF-venous fistula. In these cases, the fluid leaks into a vein, making it difficult to see on a routine CT myelogram. To detect these leaks, technicians must use a specialized CT scan and observe the contrast medium in motion as it flows through the cerebrospinal fluid.

In this study, investigators used this imaging technique on 21 patients with brain sagging and symptoms of bvFTD, and they discovered CSF-venous fistulas in nine of those patients. All nine patients had their fistulas surgically closed, and their brain sagging and accompanying symptoms were completely reversed.

“This is a rapidly evolving field of study, and advances in imaging technology have greatly improved our ability to detect sources of CSF leak, especially CSF-venous fistula,” said Keith L. Black, MD, chair of the department of Neurosurgery at Cedars-Sinai. “This specialised imaging is not widely available, and this study suggests the need for further research to improve detection and cure rates for patients.”

The remaining 12 study participants, whose leaks could not be identified, were treated with nontargeted therapies designed to relieve brain sagging, such as implantable systems for infusing the patient with CSF. However, only three of these patients experienced relief from their symptoms.

“Great efforts need to be made to improve the detection rate of CSF leak in these patients,” Schievink said. “We have developed nontargeted treatments for patients where no leak can be detected, but as our study shows, these treatments are much less effective than targeted, surgical correction of the leak.”

Source: Cedars-Sinai Medical Center