Frankie Muniz Says He Walked Off Malcolm in the Middle for Two Episodes Over On-Set Tension IGN
Frankie Muniz Drops Bombshell Accusation Against ‘Malcom In The Middle’ Crew Yahoo Entertainment
Sitcom star ‘quit’ in the middle of filming news.com.au
Frankie Muniz Says ‘I Walked Off’ the ‘Malcolm in the Middle’ Set and Missed Two Episodes When ‘Everyone Was So Afraid to Stand Up’ Against Disrespect Variety
Why Frankie Muniz Walked Off the Set of ‘Malcolm in the Middle’ for 2 Episodes: ‘It Was Worth It’ PEOPLE
Cameron Diaz breaks silence on rumor that Jamie Foxx’s on-set meltdown caused her to quit acting Page Six
Cameron Diaz shuts down rumor Jamie Foxx made movie set ‘miserable’ before his hospitalization Fox News
Cameron Diaz ‘Angry’ Over Rumors That Jamie Foxx Was ‘Crazy’ on Netflix Film Set and ‘Made Everyone Miserable’: He’s a ‘Professional on Every Level’ Variety
Cameron Diaz Defends ‘Back in Action’ Co-Star Jamie Foxx From Set Rumors: “A Professional on Every Level” Hollywood Reporter
Cameron Diaz Says ‘Crazy’ Rumors About Jamie Foxx on ‘Back in Action’ Set ‘Really Made Me Angry’ PEOPLE
Summary: Researchers report six minutes of high-intensity exercise on a regular basis can slow brain aging and delay the onset of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. High-intensity exercise increases the production of BDNF, a protein implicated in memory, learning, and brain plasticity, which could protect the brain from age-related cognitive decline.
Source: The Physiological Society
Six minutes of high-intensity exercise could extend the lifespan of a healthy brain and delay the onset of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease.
New research published in The Journal of Physiology shows that a short but intense bout of cycling increases the production of a specialized protein that is essential for brain formation, learning and memory, and could protect the brain from age-related cognitive decline.
This insight on exercise is part of the drive to develop accessible, equitable and affordable non-pharmacological approaches that anyone can adopt to promote healthy aging.
The specialized protein named brain-derived neurotrophic factor (BDNF) promotes neuroplasticity (the ability of the brain to form new connections and pathways) and the survival of neurons.
Animal studies have shown that increasing the availability of BDNF encourages the formation and storage of memories, enhances learning and overall boosts cognitive performance. These key roles and its apparent neuroprotective qualities have led to the interest in BDNF for aging research.
Lead author Travis Gibbons from University of Otago, New Zealand stated, “BDNF has shown great promise in animal models, but pharmaceutical interventions have thus far failed to safely harness the protective power of BDNF in humans.
“We saw the need to explore non-pharmacological approaches that can preserve the brain’s capacity which humans can use to naturally increase BDNF to help with healthy aging.”
To tease apart the influence of fasting and exercise on BDNF production, the researchers, from the University of Otago, New Zealand, compared the following factors to study the isolated and interactive effects:
Fasting for 20 hours
Light exercise (90-minute low intensity cycling)
High-intensity exercise (six-minute bout of vigorous cycling)
Combined fasting and exercise
They found that brief but vigorous exercise was the most efficient way to increase BDNF compared to one day of fasting with or without a lengthy session of light exercise. BDNF increased by four to five-fold (396 pg L-1 to 1170 pg L-1) more compared to fasting (no change in BDNF concentration) or prolonged activity (slight increase in BDNF concentration, 336 pg L-1 to 390 pg L-1).
The cause for these differences is not yet known, and more research is needed to understand the mechanisms involved. One hypothesis is related to the cerebral substrate switch and glucose metabolism, the brain’s primary fuel source.
The cerebral substrate switch is when the brain switches its favored fuel source for another to ensure the body’s energy demands are met, for example metabolizing lactate rather than glucose during exercise. The brain’s transition from consuming glucose to lactate initiates pathways that result in elevated levels of BDNF in the blood.
They found that brief but vigorous exercise was the most efficient way to increase BDNF compared to one day of fasting with or without a lengthy session of light exercise. Image is in the public domain
The observed increase in BDNF during exercise could be due to the increased number of platelets (the smallest blood cell), which store large amounts of BDNF. The concentration of platelets circulating in the blood is more heavily influenced by exercise than fasting and increases by 20%.
Twelve physically active participants (six males, six females aged between 18 and 56 years) took part in the study. The balanced ratio of male and female participants was to provide a better representation of the population rather than indicate sex differences.
Further research is underway to delve deeper into the effects of calorie restriction and exercise to distinguish the influence on BDNF and the cognitive benefits.
Travis Gibbons noted, “We are now studying how fasting for longer durations, for example up to three days, influences BDNF. We are curious whether exercising hard at the start of a fast accelerates the beneficial effects of fasting.
“Fasting and exercise are rarely studied together. We think fasting and exercise can be used in conjunction to optimize BDNF production in the human brain.”
About this exercise and dementia research news
Author: Press Office Source: The Physiological Society Contact: Press Office – The Physiological Society Image: The image is in the public domain
See also
Original Research: Closed access. “Fasting for 20 h does not affect exercise-induced increases in circulating BDNF in humans” by Travis Gibbons et al. Journal of Physiology
Abstract
Fasting for 20 h does not affect exercise-induced increases in circulating BDNF in humans
Intermittent fasting and exercise provide neuroprotection from age-related cognitive decline. A link between these two seemingly distinct stressors is their capability to steer the brain away from exclusively glucose metabolism. This cerebral substrate switch has been implicated in upregulating brain-derived neurotrophic factor (BDNF), a protein involved in neuroplasticity, learning and memory, and may underlie some of these neuroprotective effects.
We examined the isolated and interactive effects of (1) 20-h fasting, (2) 90-min light exercise, and (3) high-intensity exercise on peripheral venous BDNF in 12 human volunteers.
A follow-up study isolated the influence of cerebrovascular shear stress on circulating BDNF. Fasting for 20 h decreased glucose and increased ketones (P ≤ 0.0157) but had no effect on BDNF (P ≥ 0.4637). Light cycling at 25% of peak oxygen uptake (${dot V_{{{rm{O}}_{rm{2}}}{rm{peak}}}}$) increased serum BDNF by 6 ± 8% (independent of being fed or fasted) and was mediated by a 7 ± 6% increase in platelets (P < 0.0001).
Plasma BDNF was increased from 336 pg l−1 [46,626] to 390 pg l−1 [127,653] by 90-min of light cycling (P = 0.0128). Six 40-s intervals at 100% of ${dot V_{{{rm{O}}_{rm{2}}}{rm{peak}}}}$ increased plasma and serum BDNF, as well as the BDNF-per-platelet ratio 4- to 5-fold more than light exercise did (P ≤ 0.0044). Plasma BDNF was correlated with circulating lactate during the high-intensity intervals (r = 0.47, P = 0.0057), but not during light exercise (P = 0.7407).
Changes in cerebral shear stress – whether occurring naturally during exercise or induced experimentally with inspired CO2 – did not correspond with changes in BDNF (P ≥ 0.2730).
BDNF responses to low-intensity exercise are mediated by increased circulating platelets, and increasing either exercise duration or particularly intensity is required to liberate free BDNF.
Francis Ford Coppola isn’t going to reinvent the wheel regarding his approach to directing even if it means replacing a couple of crew members. News of a rocky production might not be surprising; the documentary Hearts of Darkness highlighted the chaotic production of Apocalypse Now, during which Coppola worried the film would be a “failure” because of its numerous issues. Now, with his latest film, Megalopolis — starring Adam Driver, Forest Whitaker, Nathalie Emmanuel, Jon Voight, Laurence Fishburne, Aubrey Plaza, Jason Schwartzman, Shia LaBeouf, Chloe Fineman, and more — Coppola may be experiencing an Apocalypse Now–like déjà vu with his passion project. Coppola himself, however, denies the reports of issues on set. “I love my cast, I love what I’m getting each day, I am on schedule and on budget, and that’s what is important to me,” he told Deadline.The film is reportedly about a woman in New York who is divided by her loyalties to her traditional father and her progressive partner.
Coppola is funding the $120 million film himself from his successful wine and hotel business, something he’s been considering for quite some time, though this isn’t the first time he’s independently financed several of his own films, including Youth Without Youth, Tetro,and Twixt. But putting all your eggs in one basket may not be the best idea, especially with a hurricane brewing. Below is a developing story on the production of Coppola’s Megalopolis.
According to The Hollywood Reporter, several key members of the film’s creative-production team have been removed from the project. Production designer Beth Mickle and supervising art director David Scott reportedly left the production last week, leaving the film without an art department. A spokesperson for the Art Directors Guild told THR that it’s “currently looking into the situation” to “determine the next steps.” Coppola is reportedly trying to replace their positions.
As for the visual-effects team, Coppola allegedly fired most of its members in early December, including In The Heights’ Mark Russell. The production is reportedly shifting to more green-screen effects because of budget constraints.
Coppola himself is willing to acknowledge the turnover, as is Driver. “Yes, it is true that the art department resigned and VFX were let go,” Driver told Deadline. “Not all departments find cohesion on films and rather than suffer through and making decisions that leave a lasting impression on the film, people quit, get fired, or part ways. It’s unfortunate when it happens, but this production is not out of pocket in comparison to other productions; especially to the point that it merits an article about us descending into chaos. That characterization is inaccurate.”
But while those departments resigned, Coppola and his actors are doing extremely well. “I’ve never worked on a film where I was so happy with the cast,” the director said to Deadline. “I am so happy with the look and that we are so on schedule. These reports never say who these sources are. To them, I say, ha, ha, just wait and see. Because this is a beautiful film and primarily so because the cast is so great. I’ve never enjoyed working with a cast who are so hardworking and so willing to go search for the unconventional, to come upon hidden solutions. It is a thrill to work with these actors and the photography is everything I could hope for. The dailies are great. So if we’re on schedule, and I love the actors and the look is great, I don’t know what anyone’s talking about here.”
If you asking if this is a stressful film for all involved, then yeah, probably. But if you’re asking whether this will be a groundbreaking hit film, only time will tell. Hopefully someone has a camera rolling behind the scenes for a Hearts of Darkness moment.
UPDATE: Sharon Osbourne is out of the hospital, according to reports, and is home recovering after a medical emergency on Friday night.
The 70-year-old Osbourne’s son, Jack Osbourne, confirmed the news to TMZ. He said doctors gave her the “all-clear” on her condition, which was not specified. However, her son added she would talk about it when fully recovered.
Sharon Osbourne was filming scenes for an upcoming Night Of Terror when the incident occurred.
EARLIER: Sharon Osbourne fell ill on the set of a paranormal television shoot Friday night in Santa Paula, Calif., and was rushed to a nearby hospital.
The report by TMZ said the 70-year-old Osbourne was filming at the Glen Tavern Inn in Santa Paula, a location once featured on the Travel Channel’s Ghost Adventurers. There was no information on whether she was on-camera when the incident occurred.
The Ventura County Fire Dept. confirmed the incident to TMZ. The incident happened around 6:30 PM on Friday and transported Osbourne to the hospital. Her identity was confirmed by Santa Paula Police Chief Don Agular.
Deadline will update the story on Osbourne’s condition as more details become available.
A biologic therapy that delays the onset of type 1 diabetes received approval from the US Food and Drug Administration on Thursday.
It is the first therapy approved for prevention of type 1 diabetes.
The monoclonal antibody teplizumab, which will be marketed under the brand name Tzield, from ProventionBio and Sanofi is given through intravenous infusion.
It is thought to work by turning down the body’s misdirected attack on its own insulin-producing cells. The idea is that protecting these cells buys people more time before they become dependent on insulin to manage their condition.
In clinical trials, Tzield delayed progression to full-blown diabetes by a little over two years. But the benefits have lasted much longer in some of the study participants.
One of them, Mikayla Olsten, was screened for diabetes after her 9-year old sister, Mia, suddenly developed a life-threatening episode of diabetic ketoacidosis and was diagnosed with diabetes. There was no history of diabetes in the family, and Mikayla wasn’t sick, but she had four of the five types of autoantibodies that doctors look for to assess a person’s risk.
“They told us when somebody has that many markers, it’s not if they’re going to develop diabetes, it’s when,” said her mom, Tracy.
Mikayla was 15 when she joined the study and received teplizumab. She’s now 21 and a senior in college. She gets an annual battery of tests to check her pancreas and blood markers, and Tracy Olsten says her condition hasn’t progressed in six years.
According to a scientific statement from the Juvenile Diabetes Research Foundation, the Endocrine Society and the American Diabetes Association, when a person has markers for autoimmune disease and episodes of uncontrolled blood sugar, the five-year risk for progression to insulin-dependent symptomatic disease is 75%. The lifetime risk of developing insulin-dependent diabetes is nearly 100%.
So far, Mikayla seems to be beating those odds.
Tracy said that for Mia, who is dependent on insulin, managing her diabetes is a constant chore.
“She has a tremendous amount of juggling that her peers don’t have to do. She has to plan ahead when she has a basketball game or practice on making sure she carbs up and decreases her insulin levels,” Tracy said. “She cannot go a minute or a day without thinking about it nonstop, and to be able to give Mikayla the opportunity where she doesn’t have to think about it 24/7 is amazing.”
Aaron Kowalski, CEO of the Juvenile Diabetes Research Foundation, says the main challenge in prescribing Tzield will be finding people who need it. The drug is approved for people who don’t have any symptoms of the disease and may not know they’re on the road to getting it.
“Screening becomes a really big issue, because what we know is, about 85% of type 1 diagnoses today are in families that don’t have a known family history,” Kowalski said. “Our goal is to do general population screening” with blood tests to look for markers of the disease.
Tzield is approved for use in people 8 and older who are in stage 2 of their type 1 diabetes. In that stage, doctors can measure antibodies that attack insulin-producing beta cells in the person’s blood, and they have abnormal blood sugar levels, but their body can still make insulin.
“The way in which not just industry but our medical system go about managing autoimmune diseases, and especial type 1 diabetes, is really suboptimal in today’s day and age,” ProventionBio co-founder and CEO Ashleigh Palmer said. “What we do is, we wait until the symptoms of the disease present to doctors, and then doctors treat the patient’s symptoms chronically for a lifetime. The trouble is that in type 1 diabetes, when the symptoms first present, it’s too late.”
The treatment comes in a single 14-day course of infusions that each last 30 to 60 minutes.
The most common side effects reported in the trial participants were low white blood cells and lymph cells, rash and headache.
With type 1 diabetes, a person’s immune system attacks cells called beta cells in the pancreas that produce insulin, a hormone that helps blood sugar enter cells, where it’s used for energy. The attack can happen for years before any symptoms of diabetes appear. Without insulin, blood sugar can build up in the bloodstream and break down the body’s own fat and muscle.
Palmer says Tzield holds off the disease before symptoms appear by stopping the autoimmune disease process and the underlying destruction of beta cells. The treatment essentially reboots the immune system, preserving beta cell function.
“We really have no preventative measure for type 1 diabetes to date, and that is despite [the National Institutes of Health] funding hundreds of millions of dollars over the last 20-plus years of a program called TrialNet that has tested many, many different things, including this, and some of this came out of that work,” said Dr. Robert Gabbay, chief scientific and medical officer for the American Diabetes Association. “Finally, there is something that delays the onset of type 1 diabetes, and it’s so exciting.”
Unlike type 2 diabetes, which can be prevented with lifestyle changes like losing weight and exercising, type 1 is a genetic disease that has not had any prevention options until now.
“For some reason, we don’t screen for type 1 diabetes, even though there are biomarkers available to show that the autoimmune disease process is already underway,” Palmer said. He added that the hopes the drug will catalyze the medical system to start population-based screening during routine childhood well visits in order to intercept the disease and delay its onset.
With Tzield, doctors would screen individual family members of people with type 1 diabetes to see whether they have those specific antibodies. If antibody levels are high and it appears that the person is about to develop diabetes, the treatment will delay that process.
“If somebody has type 1, a common question that comes up is ‘well, what about my child? Are they going to develop type 1?’ It’s only about a 5% risk, so more often than not, they won’t, but if you could find the ones that would and treat them, that can make a big difference,” Gabbay said.
A delayed diagnosis of type 1 diabetes could have a significant impact.
“Obviously, the quality of life is substantially impacted, negatively impacted, if you are diagnosed with type 1 diabetes. It’s a disease that never goes away,” Palmer said.
People who are type 1 diabetics must monitor their blood glucose levels around the clock, affecting how they exercise and eat. High blood sugar can lead to diabetic ketoacidosis, in which the body starts to break down fat as its fuel, and can cause a buildup of acids called ketones in the bloodstream. That condition can lead to hospitalization, coma or death.
As of 2019, about 1.9 million people have type 1 diabetes in the United States, according to the American Diabetes Association, including 244,000 children and adolescents. Type 1 affects 8% of everyone with diabetes.
“The incidence of the type 1 is mainly in kids and teenagers, and when you are in the turmoil of adolescence, when you just want to forget that you have it,” said Olivier Bogillot, Sanofi’s head of US general medicines. “So when you have the ability with a treatment to just delay the onset of the disease, you can change the way the quality of life is impacted for families and for those kids.”
40 crew members who worked on Olivia Wilde’s new movie Don’t Worry Darlinghave issued a joint statement today, praising Wilde as “an incredible leader and director who was present with and involved in every aspect of production,” and denying that the reported on-set shouting match between Wilde and star Florence Pugh ever occurred.
“There was never a screaming match between our director and anyone, let alone a member of our cast,” according to the statement, which was signed by people at every level of the film’s production, including writer-producer Katie Silberman, director of photography Matthew Libatique, and executive producer Alex G. Scott, as well as electricians, lighting technicians, makeup artists, and many others who worked on the film’s set.
Here’s more from the statement, per People:
As a crew, we’ve avoided addressing the absurd gossip surrounding the movie we’re so proud of, but feel the need to correct the anonymous ‘sources’ quoted in a recent article. Any allegations about unprofessional behavior on the set of Don’t Worry Darling are completely false. We are happy to put our names on this, as real people who worked on the film, and who have witnessed and benefitted from the collaborative and safe space Olivia creates as a director and leader.
The statement comes just as Don’t Worry Darling arrives in theaters—where it’s projected to bring in ~$20 million this weekend—and as all involved seem to be making an effort to push back on the drama surrounding the film. Pugh herself—who supposedly refused to do any formal press for the movie—put out a statement on Instagram last night talking fondly about her experiences filming it, and included a picture of her and Wilde together in-character. (Wilde did something similar.)
You can see the full list of all 40 signatories on the statement below.
Data on medium-term outcomes in indivduals with myocarditis after mRNA COVID-19 vaccination are scarce. We aimed to assess clinical outcomes and quality of life at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults.
Methods
In this follow-up surveillance study, we conducted surveys in US individuals aged 12–29 years with myocarditis after mRNA COVID-19 vaccination, for whom a report had been filed to the Vaccine Adverse Event Reporting System between Jan 12 and Nov 5, 2021. A two-component survey was administered, one component to patients (or parents or guardians) and one component to health-care providers, to assess patient outcomes at least 90 days since myocarditis onset. Data collected were recovery status, cardiac testing, and functional status, and EuroQol health-related quality-of-life measures (dichotomised as no problems or any problems), and a weighted quality-of-life measure, ranging from 0 to 1 (full health). The EuroQol results were compared with published results in US populations (aged 18–24 years) from before and early on in the COVID-19 pandemic.
Findings
Between Aug 24, 2021, and Jan 12, 2022, we collected data for 519 (62%) of 836 eligible patients who were at least 90 days post-myocarditis onset: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both surveys. Median patient age was 17 years (IQR 15–22); 457 (88%) patients were male and 61 (12%) were female. 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis by their health-care provider, although at the last health-care provider follow-up, 104 (26%) of 393 patients were prescribed daily medication related to myocarditis. Of 249 individuals who completed the quality-of-life portion of the patient survey, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (20%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with depression. Mean weighted quality-of-life measure (0·91 [SD 0·13]) was similar to a pre-pandemic US population value (0·92 [0·13]) and significantly higher than an early pandemic US population value (0·75 [0·28]; p<0·0001). Most patients had improvements in cardiac diagnostic marker and testing data at follow-up, including normal or back-to-baseline troponin concentrations (181 [91%] of 200 patients with available data), echocardiograms (262 [94%] of 279 patients), electrocardiograms (240 [77%] of 311 patients), exercise stress testing (94 [90%] of 104 patients), and ambulatory rhythm monitoring (86 [90%] of 96 patients). An abnormality was noted among 81 (54%) of 151 patients with follow-up cardiac MRI; however, evidence of myocarditis suggested by the presence of both late gadolinium enhancement and oedema on cardiac MRI was uncommon (20 [13%] of 151 patients). At follow-up, most patients were cleared for all physical activity (268 [68%] of 393 patients).
Interpretation
After at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, most individuals in our cohort were considered recovered by health-care providers, and quality of life measures were comparable to those in pre-pandemic and early pandemic populations of a similar age. These findings might not be generalisable given the small sample size and further follow-up is needed for the subset of patients with atypical test results or not considered recovered.
Funding
US Centers for Disease Control and Prevention.
Introduction
Evidence from the USA and multiple international vaccine safety monitoring systems support a small but increased risk of myocarditis after mRNA COVID-19 vaccination.
1
WHO COVID-19 subcommittee of the World Health Organization Global Advisory Committee on Vaccine Safety: updated guidance regarding myocarditis and pericarditis reported with COVID-19 mRNA vaccines.
In 2021, data from the Vaccine Adverse Event Reporting System (VAERS) indicated that in US individuals aged 12 years or older, approximately 4·8 cases of myocarditis per million doses of mRNA COVID-19 vaccines administered were reported, with the highest reporting rates in those aged 12–29 years.
2
Gargano JW
Wallace M
Hadler SC
et al.
Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June, 2021.
Despite the higher than expected occurrence of myocarditis after COVID-19 vaccination, the benefits of mRNA COVID-19 vaccines have been shown to outweigh the risk of myocarditis.
2
Gargano JW
Wallace M
Hadler SC
et al.
Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June, 2021.
,
3
Block JP
Boehmer TK
Forrest CB
et al.
Cardiac complications after SARS-CoV-2 infection and mRNA COVID-19 vaccination—PCORnet, United States, January, 2021–January, 2022.
Research in context
Evidence before this study
In December, 2020, the US Food and Drug Administration (FDA) issued emergency use authorisations (EUAs) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine and the Moderna COVID-19 (mRNA-1273) vaccine. In May, 2021, FDA expanded the EUA for the BNT162b2 vaccine to include adolescents aged 12–15 years. By July, 2022, more than 200 million people in the USA had received two doses of a COVID-19 mRNA vaccine and more than 1500 cases of myocarditis with onset after mRNA COVID-19 vaccination were reported to the Vaccine Adverse Events Reporting System (VAERS). We searched PubMed for articles published up to April 30, 2022, using the keywords “mRNA vaccine” and “myocarditis”, without any language restrictions. Systematic reviews published in 2022 included more than 5299 individuals with myocarditis after mRNA vaccination and suggested the risk was highest in adolescents and young males after a second vaccine dose. Findings from these systematic reviews suggest that most cases of myocarditis after mRNA COVID-19 vaccination have resolution of symptoms at or soon after discharge from a short hospital stay. However, data on medium-term prognoses for adolescents and young adults diagnosed with myocarditis after mRNA COVID-19 vaccination are scarce.
Added value of this study
To our knowledge, this is the largest evaluation of outcomes among patients diagnosed with myocarditis after mRNA COVID-19 vaccination, with follow-up at least 90 days since onset. We collected data from both patients (or their parents or guardians) and health-care providers, and evaluated a comprehensive range of outcomes, including follow-up cardiac biomarkers, cardiac magnetic resonance imaging, echocardiograms, troponin levels, and electrocardiograms. We found that 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis, and quality of life measures were similar to pre-pandemic or early pandemic measurements. No single diagnostic test or clinical feature appeared to be associated with recovered status.
Implications of all the available evidence
Myocarditis after mRNA COVID-19 vaccination is rare, but potentially serious. To better understand possible longer term sequalae of myocarditis, continued follow-up is important, particularly for the patients not recovered by at least 90 days since symptom onset. Vaccination remains the most effective way of preventing morbidity and mortality from COVID-19.
Cardiac assessment of patients diagnosed with myocarditis after mRNA COVID-19 vaccination often shows increased cardiac biomarkers (eg, troponin concentrations) and atypical cardiac imaging (eg, echocardiograms), which are similar findings to those shown for viral or acute myocarditis.,
5
Oster ME
Shay DK
Su JR
et al.
Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December, 2020 to August, 2021.
Viral myocarditis unrelated to mRNA COVID-19 vaccination can lead to heart failure, cardiac transplantation, or death.
6
Ghelani SJ
Spaeder MC
Pastor W
Spurney CF
Klugman D
Demographics, trends, and outcomes in pediatric acute myocarditis in the United States, 2006 to 2011.
Conversely, case descriptions suggest that clinical outcomes following a diagnosis of myocarditis after mRNA COVID-19 vaccination are more favourable than those associated with viral myocarditis, with resolution of symptoms often described at or soon after discharge from a short hospital stay for myocarditis after mRNA COVID-19 vaccination.
5
Oster ME
Shay DK
Su JR
et al.
Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December, 2020 to August, 2021.
,
7
Sinagra G
Anzini M
Pereira NL
et al.
Myocarditis in clinical practice.
,
8
Witberg G
Barda N
Hoss S
et al.
Myocarditis after COVID-19 vaccination in a large health care organization.
,
9
Truong DT
Dionne A
Muniz JC
et al.
Clinically suspected myocarditis temporally related to COVID-19 vaccination in adolescents and young adults: suspected myocarditis after COVID-19 vaccination.
However, data on follow-up prognoses for adolescents and young adults diagnosed with myocarditis after mRNA COVID-19 vaccination are scarce.
10
Amir G
Rotstein A
Razon Y
et al.
CMR imaging 6 months after myocarditis associated with the BNT162b2 mRNA COVID-19 vaccine.
,
11
Fronza M
Thavendiranathan P
Karur GR
et al.
Cardiac MRI and clinical follow-up in COVID-19 vaccine-associated myocarditis.
,
12
Jain SS
Steele JM
Fonseca B
et al.
COVID-19 vaccination-associated myocarditis in adolescents.
To conduct surveillance, the US Centers for Disease Control and Prevention (CDC) developed a working myocarditis case definition with a team of subspecialists that has been used in several studies.
2
Gargano JW
Wallace M
Hadler SC
et al.
Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June, 2021.
,
5
Oster ME
Shay DK
Su JR
et al.
Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December, 2020 to August, 2021.
,
9
Truong DT
Dionne A
Muniz JC
et al.
Clinically suspected myocarditis temporally related to COVID-19 vaccination in adolescents and young adults: suspected myocarditis after COVID-19 vaccination.
,
13
Goddard K
Lewis N
Fireman B
et al.
Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination.
In August, 2021, the CDC began follow-up of myocarditis cases to describe medium-term outcomes in the age group with the highest risk of myocarditis after mRNA COVID-19 vaccination diagnosis (ie, individuals aged 12–29 years). We report findings of clinical outcomes and quality of life at least 90 days since the onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults aged 12–29 years.
Results
Between Jan 12 and Nov 5, 2021, 989 cases of myocarditis after mRNA COVID-19 vaccination in patients aged 12–29 years were reported to VAERS and met the CDC’s case definition for myocarditis. Of these, 836 (85%) patients were at least 90 days post-myocarditis onset (figure 1). Of the 836 patients, 204 (24%) patients had no telephone number available for contact and 257 (31%) patients were unreachable. Of the remaining 375 patients, 357 (95%) patients consented to the survey and 18 (5%) patients declined. Between Aug 24, 2021, and Jan 12, 2022, we contacted and collected data for 519 (62%) of the 836 eligible patients: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both the patient and health-care provider survey (figure 1). Median interval from myocarditis onset to survey completion was 143 days (IQR 131–162) for patients and 191 days (170–216) for health-care providers. We found no significant differences in VAERS reporter type (health-care provider or patient), geographical census region, age, sex, initial echocardiogram findings, or race or ethnicity in patients surveyed compared with patients who were not surveyed (appendix 1 p 8). In a subset of patients with abnormal echocardiograms, the abnormality identified was a left ventricular ejection fraction (LVEF) of less than 50%. Of the 100 survey respondents with LVEF values recorded at their initial diagnosis, 33 (33%) had LVEF values less than 50%, which was not statistically different from the results in non-respondents (27 [42%] of 65 non-respondents; χ2=1·24, p=0·265).
Figure 1Survey participation of patients with myocarditis after mRNA COVID-19 vaccination reported to VAERS at least 90 days since symptom onset
Show full caption
CDC=US Centers for Disease Control and Prevention. VAERS=Vaccine Adverse Event Reporting System.
For 393 (47%) of 836 patients, health-care providers were contacted; 241 (61%) of 393 were cardiologists. At the time of the survey, health-care providers considered 320 (81%) of 393 patients to be recovered: 261 (66%) patients were considered fully recovered and 59 (15%) patients were considered to be probably recovered but awaiting further information. An additional 61 (16%) patients had improved and four patients had the same cardiac status as at the initial myocarditis diagnosis; these 65 patients were categorised as not fully recovered (figure 1). The cumulative proportion of patients considered recovered in the time (weeks) since the last health-care provider encounter is shown in appendix 1 (p 15). The median time from myocarditis symptom onset to the last health-care provider encounter for patients who were considered probably fully recovered or fully recovered was 92 days (IQR 43–133), and for patients who were considered fully recovered the median time was 84 days (36–135).
Most patients were male (457 [88%] of 519 patients) and White non-Hispanic (274 [53%]), and the median age of all patients was 17 years (IQR 15–22; table 1). 98 (19%) of 519 patients were Hispanic of any race. There was no notable difference between recovered individuals compared with individuals who were not recovered across any ethnic or racial groups. Overall, patients considered to be recovered and not recovered from myocarditis were similar with respect to age (median age 17 years [IQR 15–21] for patients considered recovered vs 17 years [15–21] for those considered not recovered) and sex (290 [91%] male individuals who were considered recovered vs 56 [86%] of male individuals who were considered not to be recovered, and 30 [9%] female individuals who were considered recovered vs 9 [14%] of female individuals who were not considered recovered). The median time from illness onset to health-care provider interview for the 320 (81%) of 393 individuals who were considered recovered was 189 days (IQR 167–214), and for the 61 (16%) of 393 patients who were considered improved but not fully recovered the median time was 195 days (179–195).
Table 1Demographic characteristics and symptoms of patients by provider-reported recovery status from myocarditis after mRNA COVID-19 vaccination
Data are n (%) unless specified otherwise. Data are based on the completion of 357 patient surveys, 393 provider surveys, and 231 linked surveys, resulting in 519 patients for which data were collected. Health-care provider determination of patient myocarditis recovery was provided for 393 patients, of whom 320 were considered fully or probably fully recovered and 65 were not considered recovered (and eight patients had an undetermined recovery status; figure 1). Based on the last patient encounter, health-care providers reported that 62 (16%) of 393 patients had at least one symptom that might occur with myocarditis.
In the 2 weeks before the survey date, 178 (50%) of 357 patients reported having at least one symptom that might occur with myocarditis (chest pain or discomfort, fatigue, shortness of breath, or palpitations). Patients who were not considered recovered from myocarditis more frequently reported fatigue than did patients who were considered recovered (12 [43%] vs 40 [21%]; p=0·018; table 1). By contrast, based on the last patient encounter, health-care providers reported that 62 (16%) of 393 patients at least one symptom that might occur with myocarditis (table 1).
Of 357 patients surveyed, 267 (75%) were enrolled in school or in paid employment; 43 (16%) of whom reported missing school or workdays in the 2 weeks before the survey date. Of those 43 patients, 15 (35%) believed it was associated with myocarditis.
Of 357 patients surveyed, 249 (71%) consented to completing both the EQ-5D-5L and EQ-VAS components of the patient survey. Of 249 patients, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (21%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with anxiousness or depression (figure 2A). Overall, patients reported having good health, reflected by the high median weighted index score (0·94; IQR 0·88–1·00) and median overall health status (EQ-VAS) score (90; 80–95; figure 2B, C).
Figure 2Self-assessment of health-related quality of life among patients with myocarditis after mRNA COVID-19 vaccination
Show full caption
(A) Bar plot of health-related quality of life among patients. Patients were administered the EuroQol 5-dimension 5-severity level questionnaire; for analysis, the five health-related dimensions were dichotomised into the frequency of problems (severity levels 2–5) and no problems (level 1). (B) Violin plot of weighted quality of life measure (using value weights in appendix 1 p 7) converted from each patient health profile from (A) to an index score between 1 (perfect health) and 0 (equivalent to death). (C) Violin plot of patient self-assessed overall health on a scale from 0 to 100 (with 100 representing best possible health and 0 representing the worst possible health). The denominator for the EuroQol questionnaire was 249 respondents. In the violin plots (B, C), the limits of the boxes denote IQR and the horizontal line denotes median values. Whisker endpoints are equal to the maximum and minimum values below or above the median plus or minus 1·5 times the IQR. The width of the outer shape around the box plots indicates the probability density of values or responses with a given result.
The mean EQ-5D-5L weighted utility score in our group (0·91 [SD 0·13]) was significantly higher than that for US respondents aged 18–24 years who completed a EQ-5D-5L questionnaire during the pandemic, as reported by Hay and colleagues
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
(0·75 [0·28]; p<0·0001). Mean EQ-5D-5L weighted utility scores from the pre-pandemic timepoint among US respondents aged 18–24 years have also been reported by Jiang and colleagues, from face-to-face surveys and online surveys.
23
Jiang R
Janssen MFB
Pickard AS
US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.
The weighted score from our survey was not significantly different to that obtained in the face-to-face surveys (0·92 [0·13]), but our score was significantly higher than that from the online surveys (0·84 [0·18]; p<0·0001).
Most patients were admitted to hospital after an initial diagnosis of myocarditis (484 [93%] of 519 patients). Of these 484 patients, 393 (81%) patients had information on level of care, according to the health-care provider surveys; 99 (25%) of these 393 patients were treated in an intensive care unit and one (<1%) patient required extracorporeal membrane oxygenation (table 2). To our knowledge, no deaths occurred during follow-up among the patients eligible for the survey. Six (2%) of 357 patients who self-reported re-admission to hospital had a hospital admission because of an adverse event after myocarditis treatment (n=3; adverse reactions to intravenous immune globulin) or had any cardiac abnormality identified (n=3; appendix 1 p 6); all patients were discharged within 1 week.
Table 2Level of care, testing, and treatment by recovery status among patients with myocarditis after mRNA COVID-19 vaccination
Data are n (%) unless otherwise specified. Data are based on the completion of 393 health-care provider surveys. Health-care provider determination of patient myocarditis recovery was provided for 393 patients, of whom 320 were considered fully or probably fully recovered, 65 were not considered recovered, and the health-care provider was unsure of the recovery status in eight patients, as shown in figure 1. Follow-up cardiac testing was performed, although the result of the test was not available for troponin concentration in three patients, echocardiogram in five patients, cardiac MRI in seven patients, exercise stress testing in five patients, and ambulatory rhythm monitoring in nine patients.
At follow-up, fewer patients had restrictions on physical activity than at initial diagnosis, and 34 (52%) of 65 individuals with restrictions on physical activity at the time of follow-up who were not considered recovered were cleared for all physical activity; 31 (48%) individuals still had restrictions (table 2). Median interval from myocarditis onset to approval for all physical activity was 98 days (IQR 57–134; table 2).
104 (26%) of 393 patients were prescribed daily medications related to myocarditis at the last health-care provider encounter (table 2). Patients who were not considered recovered from myocarditis were more frequently prescribed daily medication than were patients who were considered to be recovered. The most prescribed medications, as of the last health-care provider follow-up, were colchicine, β-blockers, and non-steroidal anti-inflammatory drugs (table 2).
At follow-up, most patients had improvements in diagnostic marker and imaging data, including normal or back-to-baseline troponin concentrations, echocardiograms, exercise stress testing, ambulatory rhythm monitoring, and electrocardiograms (figure 3). In the ten patients with abnormal ambulatory rhythm monitoring results, we found eight (80%) had atrial, supraventricular, or ventricular arrhythmia, three (30%) had a conduction delay or block, and five (50%) had frequent atrial or ventricular ectopy. Of these 10 patients, three (30%) had evidence of late gadolinium enhancement on follow-up cardiac MRI; of the three with evidence of late gadolinium enhancement, two (67%) had evidence of an atrial, supraventricular, or ventricular arrhythmia. Among the 151 patients who had cardiac MRIs during outpatient follow-up, 81 (54%) patients had one or more abnormalities. Abnormal cardiac MRI findings included the presence of late gadolinium enhancement (71 [47%] patients), inflammation or oedema (22 [15%] patients), or wall motion abnormalities (six [4%] patients; figure 3, appendix 1 p 9). Evidence of ongoing myocarditis, defined by both late gadolinium enhancement and oedema using modified Lake Louise criteria,
25
Ferreira VM
Schulz-Menger J
Holmvang G
et al.
Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations.
was uncommon (20 [13%] of 151 patients; appendix 1 p 9). Median interval from symptom onset to evidence of ongoing myocarditis was 26 days (IQR, 9–94) and from symptom onset to evidence of late gadolinium enhancement was 109 days (58–163; appendix 1 p 10). Of the 67 patients with late gadolinium enhancement or evidence of ongoing myocarditis, additional follow-up testing indicated abnormal echocardiograms in five (7%) patients, abnormal troponin concentrations in five (7%) patients, and abnormal electrocardiograms in 14 (21%) patients (appendix 1 p 13).
Figure 3Follow-up functional status, biomarker testing, and cardiac imaging in patients at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination
Show full caption
Cardiac biomarker testing or imaging findings are from the health-care provider surveys completed for 393 patients. Not all patients received diagnostic testing or imaging and the denominator for each follow-up test is equal to the sum of the normal and abnormal findings; the type of abnormalities identified are not mutually exclusive.
In the subset of patients with abnormal findings at the time of myocarditis diagnosis, abnormal diagnostic markers or abnormal imaging were also observed at follow-up in seven (12%) of 60 with initial abnormal echocardiograms, 19 (5%) of 387 with initial elevated troponin levels, and 47 (32%) of 146 with initial abnormal cardiac MRIs (figure 4). There was substantial heterogeneity in cardiac biomarkers, imaging, and patient functional status between patients considered recovered or not recovered from myocarditis (appendix 1 p 16). All cardiac test results (ie, echocardiogram, electrocardiogram, cardiac MRI, and troponin) were available for follow-up review in only 199 (62%) of 320 patients considered recovered, 44 (68%) of 65 considered not recovered, and three (38%) of eight with an unknown recovery status.
Figure 4Changes in cardiac biomarker and imaging from the initial encounter and the health-care provider follow-up
Show full caption
Testing, including echocardiograms, cardiac MRIs, and troponin concentrations, performed at the time of initial myocarditis diagnosis and at follow-up are not necessarily matched because each patient had testing (or not) at the discretion of the treating health-care providers.
Discussion
We ascertained outcomes at least 90 days since onset of myocarditis among 519 patients aged 12–29 years who received an mRNA COVID-19 vaccination and met the CDC case definition for myocarditis. Most (81%) patients for whom a follow-up health-care provider survey was completed were considered recovered from myocarditis, and most self-reported overall good health on the EQ-5D-5L. Readmissions to hospital were uncommon, and no deaths were identified during the follow-up period. Myocarditis after mRNA COVID-19 vaccination is rare yet potentially serious, and although most patients were considered recovered by health-care providers at least 90 days since onset, nearly half of patients continued to self-report symptoms, including chest pain, and a quarter were prescribed daily cardiac medications. These findings suggest that continued follow-up and assessment of myocarditis after mRNA COVID-19 vaccination is needed to more fully understand recovery after vaccine-associated myocarditis.
From a clinical standpoint, our findings suggest that myocarditis after mRNA COVID-19 vaccination could have a more favourable prognosis than myocarditis after viral infection, based on data available from the pre-COVID-19 period. In a published study of outcomes in children within 90 days of viral or acute myocarditis onset in the USA, 119 (23%) of 514 individuals required extracorporeal membrane oxygenation or a ventricular-assisted device and 58 (11%) of 514 individuals required cardiac transplant or died.
6
Ghelani SJ
Spaeder MC
Pastor W
Spurney CF
Klugman D
Demographics, trends, and outcomes in pediatric acute myocarditis in the United States, 2006 to 2011.
In a recent nationwide study in Denmark of adults, 90-day all-cause mortality among those with acute myocarditis was 4·9%.
26
Kragholm KH
Lindgren FL
Zaremba T
et al.
Mortality and ventricular arrhythmia after acute myocarditis: a nationwide registry-based follow-up study.
A longer term follow-up study of acute myocarditis among older adults (median age 34 years [IQR 24–42]) in Italy observed cardiac mortality or heart transplant rates at 1 year and 5 years of 3·0% and 4·1%, respectively, although complicated cases had rates of adverse cardiac outcomes that were several times higher.
27
Ammirati E
Cipriani M
Moro C
et al.
Clinical presentation and outcome in a contemporary cohort of patients with acute myocarditis: multicenter Lombardy registry.
In contrast with these studies, we found that only four (1%) patients had the same cardiac status as at the initial myocarditis diagnosis (ie, did not improve but did not worsen), whereas more than 95% (381 of 393 patients) showed improvement or recovery. Consistent with our findings, a recent report comparing classic myocarditis to COVID-19 vaccine-related myocarditis in individuals aged younger than 21 years observed similar clinical presentations and found COVID-19 vaccine-related myocarditis had better outcomes and a more rapid cardiac recovery.
28
Patel T
Kelleman M
West Z
et al.
Comparison of multisystem inflammatory syndrome in children-related myocarditis, classic viral myocarditis, and COVID-19 vaccine-related myocarditis in children.
Published data for health-related quality of life in the USA among individuals aged 18–24 years, before the COVID-19 pandemic, showed that 45 (42%) of 107 individuals reported anxiety or depression and 35 (33%) of 107 individuals reported pain or discomfort.
23
Jiang R
Janssen MFB
Pickard AS
US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.
More recent quality of life measure data from Hay and colleagues
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
among US respondents during the early stages of the COVID-19 pandemic showed that 1653 (60·2%) of 2746 individuals reported anxiety or depression.
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
Consistent with these observations, we found that patients with myocarditis after mRNA COVID-19 vaccination reported similar or better quality of life measures than the general US population, with fewer patients with myocarditis reporting anxiety or depression than did individuals during the pandemic (46% [114/249] vs 60·2% [1653/2746]). However, absence of age-specific data in the previous analyses
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
,
23
Jiang R
Janssen MFB
Pickard AS
US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.
precluded any further statistical comparisons in this study.
Despite clinical improvements and normalisation of most diagnostic test results, as noted by health-care providers, half of patients (178/357) surveyed continued to report at least one symptom potentially associated with myocarditis after COVID-19 vaccination. One possible explanation for the persistence of symptoms is that approximately 50% of patients reported depression or anxiety, conditions that can manifest as symptoms associated with myocarditis, such as chest pain or palpitations.
29
Lipsitz JD
Masia-Warner C
Apfel H
et al.
Anxiety and depressive symptoms and anxiety sensitivity in youngsters with noncardiac chest pain and benign heart murmurs.
The meaning of the cardiac MRI findings among the subset of patients who received cardiac imaging is unclear. Evidence of ongoing myocarditis on follow-up cardiac MRIs based on modified Lake Louise criteria
25
Ferreira VM
Schulz-Menger J
Holmvang G
et al.
Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations.
was uncommon. However, consistent with the few published case series of myocarditis after mRNA COVID-19 vaccination, we observed that nearly half of patients (71/151) with follow-up cardiac MRIs had residual late gadolinium enhancement, suggestive of myocardial scarring.
10
Amir G
Rotstein A
Razon Y
et al.
CMR imaging 6 months after myocarditis associated with the BNT162b2 mRNA COVID-19 vaccine.
,
11
Fronza M
Thavendiranathan P
Karur GR
et al.
Cardiac MRI and clinical follow-up in COVID-19 vaccine-associated myocarditis.
,
12
Jain SS
Steele JM
Fonseca B
et al.
COVID-19 vaccination-associated myocarditis in adolescents.
,
25
Ferreira VM
Schulz-Menger J
Holmvang G
et al.
Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations.
We did not note the degree of late gadolinium enhancement identified during follow-up, but a recent study that assessed serial cardiac MRIs in patients younger than 19 years with myocarditis after COVID-19 vaccination and persistent late gadolinium enhancement showed improvement over time.
30
Hadley SM
Prakash A
Baker AL
et al.
Follow-up cardiac magnetic resonance in children with vaccine-associated myocarditis.
In a small subset of patients, initial cardiac imaging at diagnosis was normal but follow-up imaging was abnormal. It is possible that clinical findings in these patients continued to evolve after diagnosis. Another possibility is that the initial and follow-up imaging results were evaluated by different health-care providers, who had varying interpretations.
In previous studies during the pre-COVID era, cardiac scarring related to myocarditis on follow-up MRI was not uncommon, yet its clinical significance has remained controversial.
10
Amir G
Rotstein A
Razon Y
et al.
CMR imaging 6 months after myocarditis associated with the BNT162b2 mRNA COVID-19 vaccine.
,
31
Grün S
Schumm J
Greulich S
et al.
Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.
,
32
Law YM
Lal AK
Chen S
et al.
Diagnosis and management of myocarditis in children: a scientific statement from the American Heart Association.
,
33
Dubey S
Agarwal A
Nguyen S
Adebo D
Persistence of late gadolinium enhancement on follow-up CMR imaging in children with acute myocarditis.
Although late gadolinium enhancement during the acute episode of myocarditis has been shown in children and adults to be a possible indication of future adverse cardiac events, including arrythmias, extracorporeal membrane oxygenation, transplantation, and death,
31
Grün S
Schumm J
Greulich S
et al.
Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.
,
34
Aquaro GD
Perfetti M
Camastra G
et al.
Cardiac Magnetic Resonance Working Group of the Italian Society of Cardiology. Cardiac MR with late gadolinium enhancement in acute myocarditis with preserved systolic function: ITAMY study.
,
35
Lota AS
Tsao A
Owen R
et al.
Prognostic significance of nonischemic myocardial fibrosis in patients with normal LV volumes and ejection-fraction.
,
36
Gräni C
Eichhorn C
Bière L
et al.
Prognostic value of cardiac magnetic resonance tissue characterization in risk stratifying patients with suspected myocarditis.
the importance of late gadolinium enhancement noted on follow-up cardiac MRIs in patients with viral myocarditis is unclear.
31
Grün S
Schumm J
Greulich S
et al.
Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.
Indeed, guidelines regarding clearance of athletes for competitive sports after myocarditis acknowledge the unclear role of cardiac MRI in the follow-up of such patients.
37
Maron BJ
Udelson JE
Bonow RO
et al.
Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology.
Our follow-up evaluation is subject to several limitations. First, and most importantly, the absence of clear clinical practice guidelines for the outpatient follow-up of myocarditis meant that comparing clinical course among patients was challenging, as no standard level of care was provided. Therefore, some data pertinent to understanding potential residual symptoms and disease were unavailable. We found substantial heterogeneity in the initial evaluation and follow-up of patients, particularly in the cardiac diagnostic imaging received. Current guidelines recommend restricting patients with myocarditis (eg, athletes) from competitive sports for 3–6 months,
38
Bonow RO
Nishimura RA
Thompson PD
Udelson JE
Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 5: valvular heart disease: a scientific statement from the American Heart Association and American College of Cardiology.
although we noted some variability among health-care providers in clearing patients for a return to all physical activity. There are no standard criteria for myocarditis recovery, and we did not identify any clinical feature or diagnostic test results associated with recovery status in the patients we evaluated. Forthcoming expert guidelines regarding the follow-up management and testing of patients with myocarditis could help standardise care in the future.
A second limitation is the passive (or spontaneous) nature of VAERS reporting. Some US cases of myocarditis associated with mRNA COVID-19 vaccination will not have been reported; however, it is unclear how cases reported or not reported initially to VAERS could differ. Selection bias is a possible limitation in any survey activity. Third, although 519 (62%) of the 836 eligible patients with myocarditis who filed a report to VAERS were included in this follow-up evaluation, 275 (33%) declined to participate or were unreachable. Reassuringly, we found no significant differences in the age, sex, race, or census region of respondents compared with non-respondents, although our findings might not be generalisable to all US individuals aged 12–29 years who develop myocarditis after mRNA COVID-19 vaccination due to the small sample size. Fourth, we relied on health-care provider reports for all diagnostic data results. Unlike prospective studies, we did not have access to central interpretation of tests (eg, electrocardiograms, echocardiograms, and cardiac MRIs). Although this limitation probably introduces some variability into the findings, it also reflects real-world practice and data appeared not to be missing at random. A fifth limitation is the absence of a control group for the analysis of patient symptoms. Control groups are important for contextualising symptoms. For example, in a study of long COVID among children and adolescents (aged <21 years) in the USA, Rao and colleagues
39
Rao S
Lee GM
Razzaghi H
et al.
Clinical features and burden of postacute sequelae of SARS-CoV-2 infection in children and adolescents.
found that 41·9% of patients with a history of COVID-19 reported at least one symptom of post-acute sequelae of SARS-CoV-2 infection, as did 38·2% of a control group without a history of COVID-19. Although no pre-myocarditis measures were available for our group of patients with myocarditis, we found that quality of life measures among those with COVID-19 vaccine-associated myocarditis at follow-up were similar to or better than those of contemporary populations studied before or early in the pandemic.
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
,
23
Jiang R
Janssen MFB
Pickard AS
US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.
Finally, given limitations on the ability to determine causes of myocarditis other than mRNA vaccination, we included all cases in our analyses.
In summary, after at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, 81% of patients were considered recovered by their health-care provider. At the time of follow-up, these patients reported quality of life measures similar to pre-pandemic reports among individuals of similar ages in the USA. 50% of patients reported at least one symptom at follow-up. Among a subset of 151 patients who had follow-up cardiac MRI results, 54% had an abnormal finding. The CDC is conducting additional follow-up on patients who were not considered recovered at least 12 months since symptom onset, to better understand their longer term outcomes.
MEO, KRB, MJC, MMC, JS, JRS, SSM, JMD, CBC, EBW, DKS, and TTS were responsible for project conceptualisation. IK, JW, PM, and JS were responsible for data curation and data analysis. KRB, MMC, MG, KS, BR, ALV, SSM, AA, AR-C, SN, SSM, DKS, TTS, and SVB provided project administration, supervision, and resources. IK, SVB, MEO, DKS, and TTS wrote the original draft. All authors edited the final version. IK and JW had access to all the data and had final responsibility for the decision to submit for publication.
Exposure to blue light from phones and tablets in childhood can increase production of reproductive hormones and up the risk of early onset puberty and even disrupt future fertility, study finds
Blue light exposure can increase a child’s risk of going through puberty early and having fertility issues in the future
Researchers found that the blue light exposure increased levels of some reproductive hormones
As a result, young girls may go through puberty earlier, carrying an increased risk of cancer and mental health issues
Rates of precocious puberty have been increasing in the U.S. for decades to the worry of many experts
By Mansur Shaheen U.S. Deputy Health Editor For Dailymail.Com
Published: | Updated:
Exposure to the blue light emitted by cell phones and tablets in young age can increase a child’s risk of early onset puberty and can even damage their fertility in the future, a new study finds.
A Turkish research team found that blue light increased the levels of reproductive hormones in rats that were regularly exposed to it, causing them to go through puberty earlier and suffer changes to their ovaries that could potentially damage future fertility.
The dangers of blue light to sleep have long been explored and reported on, but experts fear that the rampant use of smartphones and tablets among the youth could be more harmful than anyone could have previously imagined.
It could also explain the jump in precocious puberty – when a child goes through puberty well before typical timing – suffered during the COVID-19 pandemic as millions of children spent hours more each day staring at screens.
Early puberty has been linked to higher rates of depression and anxiety throughout life, and even breast and uterine cancer.
A study finds that exposure to blue light during early childhood can increase a child’s risk of going through puberty early, and also cause them long-term fertility issues. Early puberty is linked to an increased risk of mental health problems and even certain cancers later in life (file photo)
‘We have found that blue light exposure, sufficient to alter melatonin levels, is also able to alter reproductive hormone levels and cause earlier puberty onset in our rat model. In addition, the longer the exposure, the earlier the onset,’ Dr Aylin Kilinç Uğurlu said in a statement.
Researchers, who will present their findings Friday at the 60th Annual European Society for Paediatric Endocrinology Meeting, gathered 18 female rats for the study.
Young girls are going through puberty earlier now than in the past – and experts say it could be setting them up for lifelong problems
Young girls in America are going through puberty at earlier ages than before, and while the causes are still in question, some experts fear this could have negative effects on young women’s health later in life – both mentally and physically.
The average age of puberty in the U.S. has dropped from the typical, biologically recognized, age of 12, to 10 for females. Black and Hispanic girls in particular are going through puberty around year earlier on average.
Experts tell DailyMail.com that America’s growing obesity crisis could be the root cause, blaming poor diets for pushing up puberty. Others think it could be caused by violent childhoods, and there is also the theory that it is linked to imbalance of certain hormones.
There are also the negative long-term downsides, like an association between early puberty and developing cancer – which remains unexplained for now – and the traumatic experiences caused by a young girl growing up just a little too quickly.
The phenomena was first detected by Dr Marcia Herman-Giddens, a public health expert at the University of North Carolina, when she began to gather data on more than 17,000 girls in the mid-1990s.
She found that the average age of puberty was dropping, falling to ten years old, with some girls developing as early as age six. Her findings spurred continued research into the topic, with experts across many fields investigating what caused this shift, and what its long-term effects may be.
Both the causes and effects of precocious puberty, when a child undergoes the process too early, are wide-reaching, and can not just be explained with a simple, one-size-fits-all solution.
Instead, the age of puberty shifting forward could be the result of a variety of factors. And the after-effects it can have on a girl’s life can be wide reaching.
The rodents were split into three groups. One was placed on a normal light cycle, while the other two were exposed to either six or 12 hours of blue light each day.
In both of the blue light groups, puberty occurred significantly earlier than what would be expected.
Rats in the 12 hour group had earlier puberty than the six hour group as well, showing a correlation between increased blue light exposure and time of puberty.
The rats in the two blue light groups displayed elevated levels of oestradiol and luteinising reproductive hormones as well, which is consistent with early onset puberty.
Physical changes within the rats’ ovarian tissue was noted by the research team as well.
Researchers are unsure how consistent these findings would be with humans, but still point out a potential risk these ever-present devices can carry.
‘As this a rat study, we can’t be sure that these findings would be replicated in children but these data suggest that blue light exposure could be considered as a risk factor for earlier puberty onset,’ Uğurlu said.
The rats in the study were also found to have lower levels of melatonin than their peers – consistent with the harm that blue light has on human sleep as well.
Researchers fear that a generation of young children raised in a world where the devices are near-all-consuming will cause rates of precocious puberty to spike – carrying many negative side-effects with it.
Rates of early puberty in young girls in particular are rising, and have been for decades.
The average age of puberty in the U.S. has dropped from the typical, biologically recognized, age of 12, to 10 for females. Black and Hispanic girls in particular are going through puberty around year earlier on average.
Experts told DailyMail.com in June that America’s growing obesity crisis could be the root cause, blaming poor diets for pushing up puberty.
Others think it could be caused by violent childhoods, and there is also the theory that it is linked to imbalance of certain hormones.
There are also the negative long-term downsides, like an association between early puberty and developing cancer – which remains unexplained for now – and the traumatic experiences caused by a young girl growing up just a little too quickly.
The Turkish research team notes that rates of precocious puberty are believed to have rocketed over the past two years, and fear that the increased screen time for many children during lockdowns may have played a role.
