Body

CLEVELAND--Using ultra-high field magnetic resonance imaging (MRI) to map the brains of people with Down syndrome (DS), researchers from Case Western Reserve University, Cleveland Clinic, University Hospitals and other institutions detected subtle differences in the structure and function of the hippocampus--a region of the brain tied to memory and learning.

Such detailed mapping, made possible by the high-powered MRI, is significant because it allowed the research team to better understand how each subregion of the hippocampus in people with DS is functionally connected to other parts of the brain.

"The ultimate goal of this approach is to have an objective technique to complement neuropsychological assessments to measure the functional skills of those with DS," said Alberto Costa, professor of pediatrics and psychiatry at the Case Western Reserve University School of Medicine and the study's senior author.

Their study was recently published in Brain Communications.

Down syndrome is a genetic condition typically caused by having an extra copy of chromosome 21. The extra chromosome changes how a baby's body and brain develop, which can cause mental and physical challenges throughout the person's life.

The intellectual and developmental disabilities of individuals with DS are typically generalized. In other words, although abilities can range widely among people with DS, different types of cognitive skills are usually affected in a similar way in the same person. However, for a given person with DS, cognitive abilities that are heavily dependent on the hippocampus are especially affected.

"That's why we focused on this structure deep inside the brain that is responsible for functions such as forming memories of episodes in one's life and spatial memory," Costa said.

MRI scanners at ultra-high magnetic field strengths are increasingly available for human research, allowing neuroscientists to map the brain at higher resolution without losing image clarity.

Taking advantage of the increased resolution afforded by high-powered MRI, the researchers performed the first in-vivo comparison of volumes of different anatomical segments of the hippocampus between people with DS and "control" individuals of the same age and sex without DS.

"The gains in sensitivity and image resolution achievable with ultra-high field MRI provide levels of detail and accuracy that have not previously been attainable in studies of live, non-sedated individuals with Down syndrome," said Katherine Koenig, an assistant professor of radiology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and the study's first author.

"We also found significant relationships between the size of subregions of the hippocampus and cognitive measures," Costa said. "Although more work will be necessary to validate some of our findings, these results support the investigation of specific MRI measures as potential markers to study drug efficacy for possibly enhancing cognitive function in persons with Down syndrome."

New Haven, Conn. -- The choice between two non-invasive diagnostic tests is a common dilemma in patients who present with chest pain. Yale cardiologist Rohan Khera, MD, MS, and colleagues have developed ASSIST©, a new digital decision-aiding tool.

By applying machine learning techniques to data from two large clinical trials, this new tool identifies which imaging test to pursue in patients who may have coronary artery disease or CAD, a condition caused by plaque buildup in the arterial wall.

The new tool, described in a study published April 21 in the European Heart Journal, focuses on the long-term outcome for a given patient.

"There are strengths and limitations for each of these diagnostic tests," said Khera, an assistant professor of cardiology at Yale School of Medicine. Patients may have calcium in their blood vessels or a more advanced stage of the disease than can be missed. "If you are able to establish the diagnosis correctly, you would be more likely to pursue optimal medical and procedural therapy, which may then influence the outcomes of patients."

Recent clinical trials have attempted to determine if one test is optimal. The PROMISE and SCOT-HEART clinical trials have suggested that anatomical imaging has similar outcomes to stress testing, but may improve long-term outcomes in certain patients.

"When patients present with chest pain you have two major testing strategies. Large clinical trials have been done without a conclusive answer, so we wanted to see if the trial data could be used to better understand whether a given patient would benefit from one testing strategy or the other," said Khera. Both strategies are currently used in clinical practice.

To create ASSIST, Khera and his team obtained data from 9,572 patients who were enrolled in the PROMISE trial through the National Heart, Lung and Blood Institute and created a novel strategy that embedded local data experiments within the larger clinical trial.

"A unique aspect of our approach is that we leverage both arms of a clinical trial, overcoming the limitation of real-world data, where decisions made by clinicians can introduce bias into algorithms," said Khera

The tool also proved effective in a distinct population of patients in the SCOT-HEART trial. Among 2,135 patients who underwent functional-first or anatomical-first testing, the authors observed a two-fold lower risk of adverse cardiac events when there was agreement between the test performed and the one recommended by ASSIST. Khera said he hopes this tool will provide further insight to clinicians while they make the choice between anatomical or functional testing in chest pain evaluation.

Functional testing, commonly known as a stress test, examines patients for CAD by detecting reduced blood flow to the heart. The second option, anatomical testing, or coronary computed tomography angiography (CCTA), identifies blockages in the blood vessels. Using machine learning algorithms ASSIST provides a recommendation for each patient.

"While we used advanced methods to derive ASSIST, its application is practical for the clinical setting. It relies on routinely captured patient characteristics and can be used by clinicians with a simple online calculator or can be incorporated in the electronic health record," said Evangelos Oikonomou, MD, DPhil, a resident physician in Internal Medicine at Yale and the study's first author.

Amsterdam, April 29, 2021 - The clinical presentation and underlying biology of Parkinson's disease (PD) varies significantly, but attempts to cluster cases into a limited number of subtypes have questionable applicability and relevance, reports the international Task Force for PD Subtypes in the Journal of Parkinson's Disease. Their systematic review of studies reporting a subtyping system for the first time concludes that new approaches are needed that acknowledge the individual nature of the disease and are more aligned with personalized medicine.

In 2018, the International Parkinson's Disease and Movement Disorders Society (MDS) convened the Task Force for PD Subtypes to critically appraise available PD subtyping studies and to provide guidance for the design and conduct of future studies.

"Subtyping of PD attempts to explain the disease mechanisms, its natural history and, more importantly, to inform therapeutic development, which has justified a large number of studies by different groups over the last 30 years. However, the impact of such efforts remains unclear. They have failed to substantially change the understanding of PD or clinical care thus far. Our current review critically appraises the state of the art in PD subtyping," explained lead authors Tiago A. Mestre, MD, PhD, Parkinson's Disease and Movement Disorders Center, Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, and Connie Marras, MD, PhD, Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network.

The Task Force conducted a systematic review of PD subtypes presented in 38 studies divided into two publication periods (1980-2014 and 2015-2019), which yielded a balanced distribution of included studies into a more recent group representing the current state of the field and older studies to test for temporal trends. They also compared two subtyping methodologic approaches (data-driven versus hypothesis-driven) and critically assessed the methodologic quality and clinical applicability of each study.

The clinical and biological signature of PD may be unique to the individual, rendering PD resistant to meaningful cluster solutions. This review revealed that subtyping studies undertaken to date have significant methodologic shortcomings, and most had questionable clinical applicability and unknown biological relevance. Twenty-six of the studies were cross-sectional and used a data-driven approach. Nonclinical biomarkers were rarely used. Motor characteristics were most commonly reported to differentiate PD subtypes. Most of the studies did not achieve high ratings across a Methodologic Quality Checklist. In a Clinical Applicability Checklist, the clinical importance of differences between subtypes, potential treatment implications, and applicability to the general population were rated poorly, and subtype stability over time and prognostic value were largely unknown.

Quality ratings revealed clear areas for improvement. More extensive use of longitudinal data was regarded as critical for gaining a better understanding of the stability of proposed subtypes and their prognostic value. Although historically, there is a paucity of longitudinal studies, the Task Force found that the use of longitudinal data to define or evaluate subtypes was more common in the last five years due to the public availability of large datasets. They noted that only one study had used longitudinal profiling as the basis for defining subtypes, incorporating data on the evolution of clinical or biological features across time into the definition of subtypes.

The Task Force proposed that serial cluster analyses could provide data about the stability of proposed subtypes and the influence of disease duration on their characteristics. Such approaches could provide additional prognostic value, using information about the early evolution of disease to inform later prognosis or underlying biology.

Contemporary medicine is increasingly focusing on personalized treatment, which extends to patients with PD, noted the Task Force. Subtyping places individuals in groups with similar but not identical features. While this may represent an important step toward identifying individuals who can respond preferentially to certain treatments, placing individuals within a group will inevitably fall short of the truly "personal" goal.

Many of the recommendations in this review could apply to future studies in which the unit of measure is the individual's disease fingerprint rather than the group phenotype, acknowledged the Task Force, while recognizing that such an individual approach poses financial and logistical challenges which will have to be overcome when it comes to clinical trials.

"Having reviewed the existing literature on subtyping and explored the methodologic pitfalls and challenges associated with performing the optimal subtyping studies described above, it is time to reevaluate our approach to understanding and describing PD heterogeneity," commented Dr. Mestre and Dr. Marras. "We have provided recommendations and formulated questions that, once addressed, will inform new approaches to better explain the variability in PD including emphasis on the variability at an individual level, more aligned with future application of personalized medicine principles."

PD is a slowly progressive disorder that affects movement, muscle control, and balance and is characterized by a broad range of motor and non-motor symptoms. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.

CLEVELAND - In a Correspondence article published in the April 29, 2021 issue of the New England Journal of Medicine, researchers from University Hospitals (UH) Cleveland Medical Center, and New York Presbyterian Hospital - Weill Cornell Medicine in New York, found a substantial reduction in the use of minimally invasive surgery for cervical cancer after publication of the results a major study called the Laparoscopic Approach to Cervical Cancer (LACC) in November 2018.

The earlier study, which compared minimally invasive surgery with open abdominal radical hysterectomy in patients with early-stage cervical cancer, found that minimally invasive surgery was associated with worse disease-free and overall survival than open surgery. As a result of that study and other related studies, many guidelines recommended that surgeons use open surgery rather than minimally invasive surgery.

In the new article, the researchers sought to answer the extent to how practice changed.

They assessed the use of minimally invasive surgery as compared with open radical hysterectomy for cervical cancer before and after publication of the LACC Trial.

They studied the records of 2,437 patients who received care at 283 medical centers between November 2015 and March 2020. About 61 percent of these patients were treated at academic centers and about 39 percent at nonacademic centers.

The percentage of hysterectomies performed with a minimally invasive approach was calculated each month, and the percentages before and after publication of the LACC Trial results were compared. A 3-month period to allow for the dissemination of the LACC Trial results was excluded from this comparison.

David Sheyn, MD, one of the authors and a gynecologist at UH Cleveland Medical Center and the UH Urology Institute, said the use of minimally invasive surgery decreased dramatically after publication of the LACC Trial.

"After adjustment, the odds of minimally invasive surgery were 59 percent lower following publication of the trial results; this demonstrates a remarkably fast response to solid clinical data," said Dr. Sheyn.

Before the trial results were published, the minimally invasive approach was used in 58 percent of hysterectomies, as compared with 42.9 percent after publication.

Jonathan Shoag, MD, the senior author of the study and a urologic oncologist from the UH Urology Institute, said that the odds were still higher for minimally invasive surgery at a non-academic medical center compared with an academic medical center; 0.81 versus 0.27. He said the results of the new study suggests an opportunity to improve outcomes at non-academic medical centers.

Spyridon Basourakos, MD, urology resident from New York Presbyterian Hospital - Weill Cornell Medicine in New York, stated that understanding the impact of clinical trials on real-world practice patterns may help to bridge the gap between new discoveries and population-level clinical outcomes.

Researchers at Karolinska Institutet and the Public Health Agency of Sweden have studied newborn babies whose mothers tested positive for SARS-CoV-2 during pregnancy or childbirth. The results show that although babies born of test-positive mothers are more likely to be born early, extremely few were infected with COVID-19. The study, which is published in the esteemed journal JAMA, supports the Swedish recommendation not to separate mother and baby after delivery.

The population-based study comprised 92 per cent of all neonates - almost 90,000 births - in Sweden during the first year of the pandemic (11 March 2020 to 31 January 2021), making it one of the largest datasets in the field to date.

The results show a slightly higher level of morbidity in neonates whose mothers tested positive for SARS-CoV-2, including an increased risk of respiratory disorders, which were largely due to the higher number of preterm births in this group. No direct correlation between maternal infection and neonatal respiratory infection or pneumonia could be observed.

A total of 2,323 babies were born to SARS-CoV-2-positive mothers, of whom about one third were tested close to or just after childbirth. Only 21 (0.9 per cent) of the babies of these women tested positive for the virus at some point during the newborn period (the first 28 days), the majority without displaying any symptoms; a few babies were treated for other reasons than COVID-19.

The study supports the Swedish recommendation that babies born of women who have tested positive for SARS-CoV-2 while pregnant or during delivery do not need to be routinely separated from their mothers at birth. In many countries such a precautionary measure is taken despite the lack of supporting evidence.

"Separating a newborn baby from its mother is a serious intervention with negative consequences for the health of both mother and baby that must be weighed against the possible benefits," says Mikael Norman, professor of paediatrics at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and one of the researchers leading the study. "Our study suggests that mother and baby can be cared for together and that nursing can be recommended without danger to the baby's health. This is good news for all pregnant women, their babies and postnatal and neonatal staff."

The study was made possible through daily reports to three Swedish registries: the National Quality Register for Pregnancy, the National Quality Register for Neonatal Care, and the Communicable Diseases Register (SmiNet). SmiNet is a system for reporting communicable diseases used jointly by the Public Health Agency of Sweden and the regional communicable diseases units to surveille the 60-plus notifiable diseases that must be reported in accordance with the Communicable Diseases Act.

"By cross-referencing the three registries we've been able to monitor and report outcomes for the neonates in real time during both the first and second waves of COVID-19," says Professor Norman.

Alzheimer's disease is characterized by the abnormal accumulation and spread of the tau protein in the brain. An international study can now show how tau spreads according to four distinct patterns that lead to different symptoms with different prognoses of the affected individuals. The study was published in Nature Medicine.

"In contrast to how we have so far interpreted the spread of tau in the brain, these findings indicate that tau pathology in the brain varies according to at least four distinct patterns. This would suggest that Alzheimer's is an even more heterogeneous disease than previously thought. We now have reason to reevaluate the concept of typical Alzheimer's, and in the long run also the methods we use to assess the progression of the disease", says Jacob Vo-gel from McGill University, and the lead author of the study.

The spread of tau in the cerebral cortex is a key marker for Alzheimer's. In recent years, it has become possible to monitor the accumulation of the toxic protein in the brain of Alz-heimer's patients with the help of PET technology, an advanced medical imaging technique.

For the past thirty years, many researchers have described the development of tau patholo-gy in Alzheimer's using a single model, despite recurring cases that do not fit that model. However, the current findings explain why different patients may develop different symp-toms.

"Because different regions of the brain are affected differently in the four subtypes of Alz-heimer's, patients develop different symptoms and also prognoses. This knowledge is im-portant for doctors who assess patients with Alzheimer's, and it also makes us wonder whether the four subtypes might respond differently to different treatments. Right now, research on various drugs that reduce the amount of tau in the brain is very active, and it will be exciting to see if they vary in efficacy depending on the subtype of Alzheimer", says Oskar Hansson, professor of neurology at Lund University, who supervised the study.

The current study is a collaboration between sites in Sweden, Canada, USA and Korea. To-gether, the researchers have examined the largest and most diverse population in the world to date with tau-PET, which spans the entire clinical picture of Alzheimer's disease. The study included participants who had not yet developed any symptoms, so-called pre-symptomatic Alzheimer's, participants with mild memory difficulties and those with fully developed Alzheimer's dementia.

In a first sample, long-term data was compiled from 1,612 individuals within five independ-ent multicenter studies. Among these, the researchers identified a total of 1,143 individuals who were either cognitively normal or individuals who had developed Alzheimer's in various stages.

An algorithm was applied to the data from the tau PET images from the 1,143 individuals, the so-called SuStaIn (Subtype and Staging Inference) algorithm. The material was pro-cessed with machine learning in an automated process, in order to be able to distinguish subtypes and patterns as impartially as possible.

As expected, many individuals did not show any abnormal tau PET signal, and these were therefore automatically assigned to a tau-negative group. By then cross-validating the tau PET images with a sixth independent cohort, and following up the individuals for about two years, the researchers were able to develop four patterns that best represented the data from the remaining individuals. Although the number of subgroups varied in relation to the individuals, all were represented in all cohorts.

"We identified four clear patterns of tau pathology that became distinct over time. The prevalence of the subgroups varied between 18 and 30 percent, which means that all these variants of Alzheimer's are actually quite common and no single one dominates as we pre-viously thought", says Oskar Hansson.

* Variant one: tau spreads mainly within the temporal lobe and primarily affects memory. Variant one occurred in 33 percent of all cases.

* Variant two: In contrast to variant one, this variant spreads in the rest of the cerebral cor-tex. The individual has less memory problems than in the first variant, but on the other hand has greater difficulties with executive functions, that is, the ability to plan and per-form an action. Variant two occurred in 18 percent of all cases.

* Variant three: The accumulation of tau takes place in the visual cortex, i.e. in the part of the cerebrum where information from the optic nerve is processed and classified. The visuospatial processing of sensory impressions in the brain is affected in individuals with this pattern. They have difficulty orienting themselves, distinguishing shapes and contours, distance, movement and the location of objects in relation to other objects. Variant three occurred in 30 percent of all cases.

* Variant four: Tau spreads asymmetrically in the left hemisphere and primarily affects the individual's language ability. Variant four occurred in 19 percent of all cases.

"The varied and large databases of tau-PET that exist today, along with newly developed methods for machine learning that can be applied to large amounts of data made it possi-ble for us to discover and characterize these four subtypes of Alzheimer's. However, we need a longer follow-up study over five to ten years to be able to confirm the four patterns with even greater accuracy", says Oskar Hansson.

The researchers believe that this new knowledge can give patients more individualized treatment methods in the future.

As part of a laboratory experiment, Rebecca Holmes examined water bottles that had been acquired from abroad expecting to find bisphenol A (BPA), a human-made component commonly found in polycarbonate plastics used to make consumer products.

What she found, however, was that those water bottles were just fine, yet some control bottles purchased in the United States and supposedly BPA-free actually contained traces of the chemical now thought to negatively impact heart health.

Holmes, a researcher formerly in the laboratory of Hong-Sheng Wang, PhD, professor in the University of Cincinnati Department of Pharmacology and Systems Physiology, was working on her master's degree in molecular, cellular and biochemical pharmacology in the College of Medicine at the time.

"We believed that it likely was BPA contaminant on the surface of the bottle," says Holmes, who is now clinical research coordinator at Ohio State University's Wexner Medical Center. "I thought there is something here. I was thinking people are buying those bottles off the shelves, and they are taking them home and probably not washing them. They are using them so they are consuming BPA."

Holmes, Wang and Jianyong Ma, PhD, a research scientist at UC, decided to test an array of drinking bottles made of Tritan to see if transient BPA was present. Tritan is a BPA-free plastic. They acquired 10 different Tritan bottles and detected BPA release from two kinds of Tritan bottles. The team then tested whether rinsing, handwashing or dishwashing removed the BPA from the Tritan bottles. The results of their study is available in the scholarly journal Chemosphere. It showed that multiple cycles through the dishwasher was the most effective at removing BPA.

"The release of BPA from these bottles could pose a health threat to the consumer," says Ma.

Wang says researchers decided to consider cleaning options for Tritan bottles after Holmes did an informal survey of 114 UC students about ways they commonly cleaned brand-name water bottles after purchase. Some used the bottle right away without washing, others rinsed them with water, while others either washed the bottle with water and soap or placed them in the dishwasher for cleaning.

"Water bottles are ubiquitous on college campuses," says Wang. "While most of the bottles we tested were indeed BPA-free our study showed that there is a possibility that some may have BPA contamination. If you are concerned about the possibility that the BPA-free bottles are contaminated, washing the bottles after purchase is a good idea. Dishwashing is an effective way of removing the contamination in the specific kind of bottle we tested."

Wang says it is also a good idea to follow a manufacturer's wash instructions on water bottles or other containers.

Researchers washed the Tritan bottles that showed release of BPA up to six times, and at that point there was no longer any detectable release of BPA. A past study by a different group of researchers shows rinsing was effective in removing BPA release from the Tritan bottles they tested, so effectiveness of washing methods likely depends on the specific bottle.
The bioactivity of the leached BPA from the bottles in the UC study was confirmed by examining the cardiovascular systems of transparent blackworms and the heart tissue of mice exposed to water in these containers over a seven-day period.

"BPA is an endocrine disruptor, and it acts like estrogen and it can affect the cardiovascular system along with other systems," says Holmes. "It can contribute to irregular heart rhythms."

Wang explains that as part of the team's project Holmes visited a plastics manufacturing factory to get a better understanding of how BPA might have gotten onto BPA-free containers.

"I wanted to go to a plant to see how plastic products are made," says Holmes. "I was able to tour the facility and none of the products in this facility were for consumer purposes. It was to see how the process works. What I found is that similar products with different types of plastic were being made closely together."

FINDINGS

A UCLA-led study shows that physicians frequently order preventive medical services for adult Medicare beneficiaries that are considered unnecessary and of "low value" by the U.S. Preventive Services Task Force -- at a cost of $478 million per year.

The researchers analyzed national survey data over a 10-year period, looking specifically at seven preventive services given a "D" rating by the task force, and discovered that these services were ordered more than 31 million times annually.

BACKGROUND

The U.S. Preventive Services Task Force, an independent panel appointed by the Department of Health and Human Services, makes recommendations on the value of clinical preventive services. Services rated D are considered to have no likely health benefit to specific patients and may even be harmful to them. Overall, the utilization of a variety of services considered unnecessary by the task force drives up health care spending by billions of dollars each year.

METHOD

The researchers examined data covering the years 2007 to 2016 from the annual National Ambulatory Medical Care Survey to determine how often, and at what cost, seven specific grade D services were utilized:

Asymptomatic bacteriuria screening in non-pregnant women

Cardiovascular disease screening in low-risk adults (rest or stress ECG)

Cervical cancer screening in women over age 65 (Papanicolaou or HPV test)

Colorectal cancer screening in those over age 85 (colonoscopy or sigmoidoscopy)

Chronic obstructive pulmonary disease screening in asymptomatic patients (peak flow or spirometry)

Prostate cancer screening in men 75 and older (prostate-specific antigen test)

Vitamin D supplementation for fracture preventing in postmenopausal women

The researchers note some limitations to the study. For instance, their method of estimating Medicare spending on these services may lack clinical details and therefore might misclassify some instances of appropriate care as low value.

IMPACT

Medicare could save nearly $500 million per year and protect patients against potential harm by no longer providing reimbursements for these services. Under the Affordable Care Act, the secretary of health and human services is authorized to prohibit payment for services rated D by the Preventive Services Task Force. In February 2021, the U.S. Office of Personnel Management's Federal Employees Health Benefits Program stopped covering (PDF) grade D services.

When they go to the dentist to get a tooth pulled or another procedure, patients might not think that the prescription they receive to ease their pain could put them or their family at risk of an opioid overdose.

But a new study from the University of Michigan shows that overdose rates were two and a half times higher among patients who filled a prescription for an opioid medication after a dental procedure, compared with those who didn't fill such a prescription.

Overdose rates were also higher among the family members of such patients - possibly from misuse of the leftover pills.

The study is published in the American Journal of Preventive Medicine by a team from the U-M Medical School and School of Dentistry. It used data from 8.5 million dental procedures in teen and adult patients between 2011 and 2018 whose care was covered by Medicaid or private dental insurance. Nearly 27% of these patients filled a prescription for an opioid such as hydrocodone or oxycodone.

The researchers identified 2,700 overdoses that occurred in the 90 days after a tooth extraction or 119 other dental procedures. That works out to about three overdoses for every 10,000 dental procedures. The rate was 5.8 per 10,000 among those who filled an opioid prescription within three days of their procedure, compared with 2.2 per 10,000 among those who didn't.

The researchers note that other data have shown that in 2016 alone, dentists wrote 11.4 million prescriptions for opioids. The new study's findings suggest that 1,700 overdoses a year could be happening because of dental opioid prescriptions.

Risks among family members

The study also used data from 3.5 million privately insured dental procedure patients to examine overdoses within 90 days in the patients' family members. The rate of overdose was 1.7 per 10,000 procedures in family members of privately insured patients who filled opioid prescriptions, compared with 1 per 10,000 procedures among those who didn't.

In the study, 400 family members of patients were treated for opioid overdoses in the 90-day period after the dental patient's procedure. In all, 42% of these overdoses were in the child of the patient who had a procedure, and another 25% were in a spouse; the rest were in parents and siblings.

Kao-Ping Chua, M.D., Ph.D., led the analysis. "Our paper shows that when patients fill dental opioid prescriptions, the risk of opioid overdose increases both for themselves and their family members," he says. "This underscores the importance of avoiding dental opioid prescribing when non-opioids like ibuprofen and acetaminophen are effective options for pain control, as is the case for the majority of dental procedures. Our finding of increased overdose risk in family members also shows the importance of emphasizing safe storage and disposal when prescribing opioids to dental patients."

Chua is a pediatrician at Michigan Medicine, a health care researcher at the Susan B. Meister Child Health Evaluation Research Center, and a member of the U-M Institute for Healthcare Policy and Innovation.

"To me, this is one of the most powerful truths we've unlocked in our 'big data' research on dental opioid prescribing," says senior author Romesh Nalliah, D.D.S., M.H.C.M. "That when a dentist, like me, prescribes an opioid to a patient I am putting their entire family at risk of overdose. Dentists should consider, if the family concerned was yours, would you take that risk?" Nalliah is associate dean for patient services at U-M School of Dentistry and a member of IHPI, and has led other research on dental opioid use.

The authors are part of the Michigan Opioid Prescribing Engagement Network (Michigan OPEN), which has developed guidelines for dentists and surgeons to reduce or eliminate the prescribing of opioids for many procedures and operations, while still providing effective pain relief. Michigan OPEN recommends that dentists avoid prescribing opioids for most dental procedures because non-opioids are just as effective for pain.

Groups at higher risk of overdose after receiving dental opioids

The study also identifies specific groups of dental patients who are at a higher risk of opioid overdose after receiving opioid prescriptions.

Those groups include patients with diagnosed mental health conditions and substance use disorders, and those with Medicaid health coverage.

This knowledge could help dentists and oral surgeons choose the pain treatment for their patients more carefully, and include a prescription for the overdose treatment naloxone if they prescribe opioids to someone with a higher risk of overdose.

Exposure before birth to persistent organic pollutants (POPs)-- organochlorine pesticides, industrial chemicals, etc.--may increase the risk in adolescence of metabolic disorders, such as obesity and high blood pressure. This was the main conclusion of a study by the Barcelona Institute for Global Health (ISGlobal), a research centre supported by the "la Caixa" Foundation. The study was based on data from nearly 400 children living in Menorca, who were followed from before birth until they reached 18 years of age.

POPs are toxic, degradation-resistant chemicals that persist in the environment. Examples of such compounds are pesticides and organochlorine insecticides (DDT, etc.). POPs have adverse effects on both human health and the environment and their use is regulated globally.

Prenatal exposure to these substances has been associated with cardiometabolic risk factors in childhood, but there were previously no studies assessing whether such associations continue into adolescence, a developmental stage characterised by significant changes in the endocrine system and rapid increases in body mass.

The aim of this investigation, carried out within the framework of the INMA Project-Environment and Childhood, was to study the associations between prenatal exposure to POPs and body mass index (BMI) as well as other markers of cardiovascular risk in adolescence. Data from 379 children in Menorca was analysed. POP levels were measured in umbilical cord blood samples and the children were then seen periodically between the ages of 4 and 18 years. At these visits, BMI, body fat percentage and blood pressure were recorded as they grew. When the child reached 14 years of age, the scientists measured blood biomarkers of cardiometabolic risk (cholesterol, triglycerides, glucose, etc.).

The results of this study, published in the journal Environment International, suggest an association between prenatal POP exposure and a higher BMI in adolescence, particularly in the case of the fungicide hexachlorobenzene (HCB) and the insecticide compound dichloro-diphenyl-trichloroethane (DDT).

Exposure to these two organochlorides--HCB and DDT¬--was also associated with higher blood pressure in childhood and adolescence and increased cardiometabolic risk at 14 years of age.

ISGlobal researcher Núria Güil-Oumrait, the first author of the study, explains that "this is the first longitudinal study to analyse the relationship between persistent organic pollutants and cardiometabolic risk throughout childhood and adolescence. Our findings show that the association between these substances and infant BMI does persist into adolescence and that prenatal exposures are associated with the main risk factors for metabolic syndrome in adults, a condition that today affects one in four people worldwide.

With respect to the mechanisms that might explain this association, Güil-Oumrait points out that "it is thought that POPs may interact with hormone receptors or with the generation of free radicals, and the chief problem is that these pollutants accumulate in the fatty tissues of living organisms, where they can persist for years, even decades".

Martine Vrijheid, study coordinator and head of the Childhood and Environment Programme at ISGlobal, highlights the fact that "some of these substances could be considered endocrine disruptors, that is, chemicals that interfere with hormonal regulation". In her view "more studies are needed in this field, especially focussing on childhood and adolescence, which are critical developmental stages characterised by particular vulnerability".

BUFFALO, N.Y. -- A national, University at Buffalo-led study on genes in pediatric cardiomyopathy demonstrates strong evidence for routine genetic screening in children with the disease. The study, published April 28 in the Journal of the American Heart Association, revealed wide variation in screening, with some centers conducting routine genetic testing and others conducting none.

Conducted at 14 centers, the National Institutes of Health-funded study of 152 children with cardiomyopathy found that only half had undergone genetic screening. Of those who hadn't undergone screening, 21% were found to have a genetic cause for the disease after undergoing genetic testing as part of the research study.

"Even in families without a family history of cardiomyopathy, we found that many children with cardiomyopathy have a genetic cause that we can establish," said Steven E. Lipshultz, MD, the study's senior author and principal investigator and A. Conger Goodyear Professor and Chair of the Department of Pediatrics in the Jacobs School of Medicine and Biomedical Sciences at UB.

First author on the paper is Stephanie M. Ware, MD, PhD, of the Indiana University School of Medicine.

The study's findings are of critical significance for treating and potentially curing this rare, sometimes fatal, pediatric disease. "We had assumed that many of the life-threatening cardiomyopathies in children resulted from genetic mutations," explained Lipshultz. "This research confirms that assumption. When we know the cause, we can more effectively treat, and in some cases even cure, these children with therapies targeted to the specific mutation causing their disease."

Screening can save lives

Genetic screening could provide critical, lifesaving information to families, Lipshultz said.

"Since some mutations are associated with rapidly progressive fatal outcomes, genetic screening could allow children with these mutations to be identified and prioritized for a lifesaving cardiac transplant," he said.

Information about which mutation may be involved in a patient's disease can also make a significant difference in the type of treatment prescribed, and the outcome. Lipshultz noted that he and his colleagues have published research demonstrating that children whose cardiomyopathy results from certain mutations that cause heart failure will deteriorate and even die if treated with therapies commonly prescribed for heart failure.

"This is because those therapies push the child's genetically impaired mitochondria to work harder," said Lipshultz. "This, tragically, can hasten the demise of these children. But by knowing that these types of mutations are present, alternative therapies that preserve and protect mitochondrial function can be employed. This is one of many examples where knowing the genetic cause of cardiomyopathy could make the difference between the life or death of a child."

The study also identified novel gene mutations associated with cardiomyopathy.

Genetic screening varies widely

Although the study was conducted at major children's hospitals with well-established cardiomyopathy programs, only some of them used genetic screening as a routine part of clinical care. Nationally, a minority of children and their families with cardiomyopathy have the opportunity to undergo genetic screening, a fact that Lipshultz and his co-authors hope this study will begin to change.

UB, for example, is one of only 40 cardiomyopathy centers in the world that have been critically and rigorously reviewed and certified as a recognized Cardiomyopathy Center of Care by the Children's Cardiomyopathy Foundation for providing high-quality cardiac care and specialized disease management to children with cardiomyopathy. (This study also received funding from the Children's Cardiomyopathy Foundation.) At UB and the John R. Oishei Children's Hospital, resources from federal and private sources are providing additional funding for more research and clinical care in pediatric cardiac clinical genetics, as well as genetic counseling.

Lipshultz added that, unfortunately, most children with the disease are not cared for in these specialized centers.

"One hurdle is having cardiologists and geneticists interested in ordering these genetic tests and then counseling the families about the results," he said. "The testing for the most common gene mutations associated with cardiomyopathy can be done pretty much anywhere, since laboratory companies provide the kits for collected patient samples."

The study supports existing clinical guidelines for pediatric cardiomyopathy, but, Lipshultz pointed out, these are not widely followed. "Our results show that with routine clinical judgment, a high percentage of children with genetic causes for their cardiomyopathy are missed," he said, adding, "If you don't look, you don't know."

The results also provide additional evidence for cardiac surveillance, where all immediate family members of a child with cardiomyopathy and an associated gene mutation are screened to find out if they, too, have the same mutation and cardiomyopathy.

At a time when gene-specific targeted therapies are increasingly possible, which can optimize care and planning, the failure to genetically screen these patients is no longer defensible, Lipshultz said.

Exome sequencing

In the study, the researchers performed whole exome sequencing on a large number of children with cardiomyopathy. Whole exome sequencing is a much more comprehensive way to identify gene mutations than simply searching for the six or eight most common mutations known to be associated with cardiomyopathy, Lipshultz explained.

"With whole exome sequencing, a much broader range of pathologic mutations are able to be identified, and novel new mutations that may be associated with cardiomyopathy can be identified," he said.

WASHINGTON - The Society for Cardiovascular Angiography and Interventions (SCAI) has released an expert consensus statement providing cardiologists, cath lab directors, and hospital leadership guidance for contemporary cath lab standards. The document, "SCAI Expert Consensus Update on Best Practices in the Cardiac Catheterization Laboratory" will be presented today at the SCAI 2021 Virtual Scientific Sessions with simultaneous publication in Catheterization & Cardiovascular Interventions. The statement has been endorsed by the American College of Cardiology Clinical Policy Approval Committee, American Heart Association, and the Heart Rhythm Society.

"First released in 2012, then updated in 2016 and now 2021, the document highlights a patient- centric approach to procedures in the cardiac catheterization laboratory, incorporating all the latest advances and standards," said Srihari S. Naidu, MD, FSCAI, chair of the writing committee. "Dividing the logistics into the pre-procedure, intra-procedure, and post-procedure periods, and including staffing, quality metrics, industry relations and governance, the document should hopefully further serve as a contemporary look at the optimal running of these busy areas. We have also included areas where operators overlap, such as interventional cardiologists and electrophysiologists, for a more collegial collaborative spirit towards these complex patients and provided guidance on procedures performed in various settings including outpatient labs," Dr. Naidu continued.

"This comprehensive statement, prepared by experts across a range of disciplines, builds on prior consensus statements and provides updates focused on current patient-centered and evidence-based approaches to care," stated Daniel Kolansky, MD, FSCAI, vice-chair of the writing committee and SCAI 2021 program chair. Dr. Kolansky continued "The document covers topics ranging from pre-procedure assessment to intraprocedural best practices and safe discharge and follow-up needs of the patient. The document highlights regulatory and accreditation requirements for cath labs, a heart team approach to complex care, and discussion of what constitutes an optimal cath lab team. It also addresses collaboration between disciplines such as interventional cardiology and cardiac electrophysiology. This document will serve as a guide for lab directors, hospitals, and health systems in establishing current best practices for catheterization labs."

The new 2021 recommendations include:

Emphasis on practical recommendations to optimize quality & outcomes through best practices, registries, risk calculators, and vascular access (radial first, vascular ultrasound)

Updated discussion of ambulatory surgery centers and settings without on-site surgery

Expanded section on CCL governance, including dyad leadership, respective roles, "culture-setting", industry relationships, and patient experience optimization

Emphasis on the heart team for various patient subsets, and new recommendations for coordination and collaboration with EP

Updated pre-procedure checklist and pre-PCI time out

Updated discussion of staff qualifications, certification, and optimal CCL team

Updated timing and discussion of H&P, informed consent, and required blood work

Updated infection control guidance, including use of PPE and hand anti-septic solutions

Emphasis on same-day discharge for select patients, with discussion of long-term GDMT and lifestyle modification, and bedside delivery of medications to improve adherence

WASHINGTON, D.C., (April 28, 2021) - Results from a retrospective observational study, presented today at Society for Cardiovascular Angiography and Interventions (SCAI) 2021 Virtual Scientific Sessions, reveal a 70% decline in the number of patients presenting with acute myocardial infarction (AMI) during April 2020 compared to April 2019. While the number of patients with AMI seeking care at hospitals dropped during the pandemic, those that did receive care experienced more severe symptoms because of delays in patients seeking emergency services.

AMI, commonly recognized as a heart attack, is responsible for more than one million deaths in the U.S. every year. For the best patient outcomes, seeking care within the first 90 minutes of heart attack symptoms is critical and delaying care can lead to complications or increased mortality. This study also comes at a time when heart disease remains the number one cause of death for Americans.

The single-center retrospective observational study was conducted at NYU Langone Health in New York City. Researchers compared patients with AMI who underwent invasive coronary angiography in April 2020 versus April 2019. The study was intended to compare characteristics and outcomes of patients with AMI during the peak of the pandemic.

Findings show there was a significant reduction in AMI cases referred for invasive angiography in April 2020 compared to April 2019. Of patients with AMI, a larger proportion (39%), had ST-Elevation Myocardial Infarction (STEMI) than in April 2019 (20%). There was a trend toward delayed times between symptom onset and hospitalization in 2020. Investigators noted no differences in demographics, comorbidities or baseline medications before or after the pandemic. Multi-vessel coronary disease was less common, but peak troponin concentrations were higher in 2020 than in the previous year.

"We were surprised to observe a significant reduction in the number of patients referred for coronary management of MI; this suggests that many patients may have stayed at home despite their symptoms of a heart attack," said Nina Talmor, MD, lead investigator and internal medicine resident, NYU Langone Health. "Our findings point to the need for improved public health messaging for future health crises, so that people do not remain at home out of fear, rather than seeking necessary and potentially lifesaving care. We hope our study will bring awareness to the need for timely cardiac care both in and out of a pandemic."

Study authors look to re-address public health messaging to direct patients to appropriately seek the best care for their condition for future health emergencies.

In almost ten per cent of myocardial infarctions, no obvious cause in the coronary artery can be found. Some of the patients are diagnosed with broken-heart syndrome, while others are left without a diagnosis. A new study from Karolinska Institutet in Sweden suggests that early magnetic resonance (MR) imaging of the heart can greatly increase the rate of diagnosis. The study has been published in the journal JACC Cardiovascular Imaging.

Myocardial infarction is one of the most common diseases in the West, and is usually caused by a blood clot that blocks the coronary artery on the heart's surface. However, in up to ten per cent of all myocardial infarctions, no obvious cause in the coronary artery is found. Such patients are given the working diagnosis MINOCA (myocardial infarction with non-obstructive coronary arteries), which can subsequently lead to one of several diagnoses.

The majority of the patients are women, many of whom are diagnosed with takotsubo cardiomyopathy (broken-heart syndrome). This is a condition characterised by reduced heart function that is probably related to stress and that presents the same symptoms as a regular heart attack.

"Around 80 to 90 per cent of broken-heart sufferers are women, and the disease is associated with mental stress," says principal investigator Per Tornvall, senior physician and professor at the Department of Clinical Science and Education, Södersjukhuset (Stockholm South General Hospital), Karolinska Institutet. "There also seems to be a link to hypersensitivity towards stress caused by low oestrogen levels. Unfortunately, research on the investigation and treatment of myocardial infarction is often done on men, while female heart disease is less studied."

Cardiovascular magnetic resonance (CMR) is often done when examining patients with MINOCA. CMR approximately ten days after onset can result in a diagnosis in under half the patients, normally takotsubo or myocarditis (inflammation of the heart muscle), according to an earlier study of 150 patients from Karolinska Institutet. The same researchers have now tested a new, more sensitive CMR technique two to four days after onset on a comparable group of 148 patients with a median age of 58. They found that a full 77 per cent of the patients could be given a diagnosis (35 per cent of takotsubo and 17 per cent of myocardial inflammation, compared with 19 and 7 per cent, respectively, in the first study).

"We don't know how much effect the improved CMR technique has, but the results suggest that with early examination more patients can get a correct diagnosis and therefore the right treatment," says Professor Tornvall. "The next step is for us to develop the CMR examination with pharmacological stress of the heart. This will enable us to study the smallest of the blood vessels and hopefully find a cause for the 23 per cent who received no diagnosis."

The study was conducted in close collaboration with the heart-MR department, clinical physiology, at Karolinska University Hospital and was financed by the Swedish Research Council, Region Stockholm and the Swedish Heart and Lung Foundation. Co-authors Peder Sörensson, Magnus Lundin and Martin Ugander are affiliated with Karolinska University Hospital, which has a research agreement with Siemens Healthineers regarding CMR. Jonas Spaak has received personal fees for the past three years from AstraZeneca, Vifor Pharma and Novo Nordisk, all unrelated to the present study.

ITHACA, N.Y. - Though more than 131 million Americans have received at least one dose of COVID-19 vaccine to date, public confusion and uncertainty about the importance of second doses and continued public health precautions threaten to delay a U.S. return to normalcy, according to Cornell-led research published April 28 in the New England Journal of Medicine.

In a nationally representative survey of more than 1,000 American adults conducted in February, less than half of respondents said they believed the Moderna and Pfizer-BioNTech vaccines provided strong protection against COVID-19 a week or two after a second dose, consistent with guidance from the U.S. Centers for Diseases Control and Prevention (CDC), the researchers found. One-fifth believed the vaccines provided strong protection after only one dose, and another 36% were unsure.

Among vaccinated survey respondents (19% of the sample), barely half reported being told about the timing of vaccine protection, and only slim majorities said they'd been advised to continue wearing masks, social distancing and avoiding crowds.

"Many Americans, including many of those who have already received a first vaccine dose, remain confused about the timing of protection and the necessity of a second dose," the researchers concluded. "Moreover, a large proportion of vaccinees report being uninformed about CDC guidance regarding the need to continue to take prophylactic measures."

The findings by an interdisciplinary, cross-college team were reported in "Beyond the First Shot - Covid-19 Vaccine Follow-through and Continued Protective Measures [LINK]." The co-authors are Jillian Goldfarb, assistant professor in the Department of Biological and Environmental Engineering in the College of Agriculture and Life Sciences; Sarah Kreps, the John L. Wetherill Professor in the Department of Government in the College of Arts and Sciences (A&S); Douglas Kriner, the Clinton Rossiter Professor in American Institutions in the Department of Government (A&S); and John Brownstein, professor at Harvard Medical School and chief innovation officer of Boston Children's Hospital.

Recent CDC data validates the authors' concerns about vaccine follow-through, showing that nearly 8% of Americans - more than 5 million people - who received a first Moderna or Pfizer-BioNTech shot last month had missed their scheduled second dose.

The research team warned that the problem could be more acute for minority racial and ethnic groups that historically have had higher attrition rates for multidose vaccines. The survey found Black and Latinx respondents were significantly less likely than whites to believe the vaccines provided strong protection after the second dose, and significantly more likely to be unsure.

"Failure to combat second-dose attrition among members of minority groups," the scholars wrote, "risks magnifying existing racial disparities in the virus's human toll."

Regarding the need to continue wearing masks after being vaccinated - just updated by the CDC - the researchers found broad support. More than 80% of respondents agreed or strongly agreed, with support highest among those age 60 or over, those already vaccinated, and Black people. Reflecting a national partisan divide, Republicans were significantly less supportive than Democrats of postvaccination mask wearing.

Less than a third of vaccinated respondents said they were told that their risk of transmitting the virus to others is unknown, one of the key reasons for continuing to wear masks in many settings.

"These findings suggest that there is a real need - and opportunity - for the medical community to provide fuller guidance and greater contextual explanations to vaccinees," the authors wrote, "about how life can change after vaccination as we gradually return to normalcy."

In particular, they said, enhanced education at the time of the first dose holds "considerable promise" for combatting second-dose attrition.

Goldfarb said she became concerned about a lack of information transfer when she received a first shot at a county-run site that was highly efficient, but provided no information about the importance of second shots or continued protective measures.

"It really sunk in that there could be a problem with vaccine attrition even more so than overcoming hesitancy," Goldfarb said. "We could end up prolonging the pandemic because people don't follow through."

Kriner said the survey results reflected the fragmented, public-private nature of the nation's vaccine administration involving states, counties and pharmacies, each providing different levels of information in different ways.

"This is an opportunity to take this fragmented system we have and think about how we can ensure people get the information they need to protect themselves and public health," Kriner said, "until viral circulation is much lower than it still is."

Kreps said the research illustrated the need to think about more than just vaccine safety and effectiveness, and to treat public behavior as a medical issue.

"You can't understand how this this virus will continue to progress," Kreps said, "unless you understand the behavior of the public that is receiving this vaccine."