Tag: paediatrics

Antibiotic Slashes Risk of Drug-resistant TB in Kids, Finds Major SA Study

Tuberculosis bacteria. Credit: CDC

By Elri Voigt for Spotlight

For decades, the standard way to prevent people who were exposed to tuberculosis (TB) from falling ill with the disease was to offer them a medicine called isoniazid, taken daily for six or more months. That changed in the last decade with the development of new preventive therapy regimens that are taken for four, three, or even just one month.

One complexity, however, is that both isoniazid and the new regimens are much better at preventing normal drug-sensitive TB than they are at preventing drug-resistant forms of TB. This is not surprising. As explained by Paediatric Infectious Disease doctor and Professor of Global Child Health at Imperial College London, Dr James Seddon, the two drugs that have mainly been used to prevent drug-susceptible TB are isoniazid and rifampicin (rifampicin’s sister drug rifapentine is also used). Now, by definition, he explains multidrug-resistant (MDR) TB is resistant to both these drugs so it’s unlikely to have any impact.

The situation is particularly tricky when it comes to children. In a 2020 statement the World Health Organization (WHO) says that it estimated that worldwide between 25 000 and 32 000 children develop MDR-TB each year, and mainly acquire it through transmission from close contact with an adult or adolescent who has MDR-TB. According to Seddon, while there is some emerging observational evidence on the use of drugs other than isoniazid and rifampicin to prevent MDR-TB, there has been no clinically tested regimen to give to children following MDR-TB exposure.

Now, much anticipated results from a phase three trial has shown that a single antibiotic pill, given daily for six months, is safe and effective to use in children who have been exposed to MDR-TB.

Results from TB CHAMP

The trial, called TB-CHAMP, looked at the efficacy and safety of using the antibiotic levofloxacin to prevent TB in children exposed to MDR-TB. Top-line findings from the study was presented last week at the Union World Lung Conference held in Paris, France.

“The paediatric population is probably the most neglected of all the populations affected by MDR-TB,” Dr Anneke Hesseling, Director of the Paediatric TB Research Programme at Stellenbosch University, told the conference. “Fewer than 20% who develop MDR-TB disease are actually diagnosed and treated, and so to find more cases and prevent more cases is really, really critical…So prevention is really key, and the TB-CHAMP trial is really a phase three efficacy trial looking at levofloxacin to prevent new cases of TB in children and also looking at the safety of levofloxacin.”

Hesseling, who is the Principal Investigator of the study, says that TB-CHAMP is the first trial to provide clinical data on what drug might be used to prevent TB in children who have been exposed to MDR-TB. It was conducted at five sites across South Africa, all with high MDR-TB burdens. The study was led by Stellenbosch University and the Desmund Tutu TB Centre. The findings have not yet been published in a peer-reviewed journal.

922 children were randomised to receive either levofloxacin or a placebo for six months. 453 children got levofloxacin and 469 got the placebo. The primary efficacy data featured data from 916 of those children, with 451 in the levofloxacin arm and 465 in the placebo arm.

Hesseling says that only children who were exposed to an adult in their household with confirmed MDR-TB were included in the study. At first children below the age of five were recruited, regardless of their TB infection status. Later children between the ages of five and 17 were included, but they had to either have a TB infection or be living with HIV. The majority of the children, 90%, were younger than five years. TB infection was confirmed with a blood test.

By 48 weeks, Hesseling says five children in the levofloxacin arm versus 12 in the placebo arm developed TB, which amounts to an incidence rate of 1.1% in the levofloxacin arm, and 2.6% in the placebo arm.

Implication of results

“While TB preventive therapy (TPT) has long been recommended and available for young child contacts of people with drug-susceptible TB, there has not been sufficient evidence to make strong recommendations for treatment that could prevent DR-TB. Therefore, the TB-CHAMP findings are critically important for a number of reasons,” says Professor Guy Marks, President and Interim Executive Director, International Union Against Tuberculosis and Lung Disease (The Union).

“The study provides the first high-quality evidence that DR-TB can be prevented in children by using six months of daily levofloxacin, and that this is a safe medication. Furthermore, this will encourage more community-based contact screening, which will also lead to early detection of children and contacts of all ages who already have disease, and initiate treatment,” he adds.

“The impact [of the TB-CHAMP results] is potentially tremendous as it would prevent DR TB among child contacts. DR TB is more complex to treat and cure and often children are marginalised, so this study puts the spotlight on an effective way to protect children. This is not just about the life and health of the child but the social, economic and mental health implications for the caregiver and the entire family,” says Dr Priashni Subrayen, Technical Director for TB at The Aurum Institute.

Seddon, who is also one of the Co-PIs for the study, tells Spotlight that it was important to establish the safety of levofloxacin since it belongs to a class of drugs called the fluoroquinolones, which were thought to have terrible side effects when used in children.

Results from TB-CHAMP show that this is not the case.

The side effects were mild, and the regimen was well tolerated, according to Hesseling, with only eight children having a grade one or higher adverse event in the levofloxacin arm compared to four in the placebo arm. Two deaths were reported, one in each study arm, but were unrelated to the study. Overall, six children in the levofloxacin arm discontinued treatment or left the study early.

Researchers from TB-CHAMP collaborated with researchers from the V-QUIN trial – a phase three study that looked at levofloxacin as TB prevention in adults in Vietnam – in order to combine their data which allowed them to show data for levofloxacin across different age groups. Seddon explains: “They’ve applied a novel analytic approach, which uses a Bayesian, or probabilistic, framework, where we take the results of TB-CHAMP and we say well, if we actually use some of the information from V-QUIN to inform the TB-CHAMP results, we can make that a slightly more confident estimate,” he says.

The combined results, according to Hesseling were able to also show that levofloxacin reduced the risk of TB by about 60% across the age spectrum but with a tighter confidence interval, indicating a more precise estimate of the effect.

Seddon tells Spotlight that the combined data showed that there were no serious adverse events, but the adult population experienced more grade one and grade two side effects than the children, but these went away either over time or when the drug was stopped. The side effects included inflammation in the joints and tendons, which is a known side effect of this class of drug.

Not a silver bullet

While the findings could be a game-changer and potentially inform MDR-TB prevention guidelines, particularly in children, the regimen is by no means a silver bullet. Seddon says that while the regimen was safe, when participants were asked whether they liked the medicine, more people said they didn’t like it in the levofloxacin group versus the placebo. Another downside is that the pill was an adult formulation and thus needed to be cut and/or crushed for the kids to swallow.

Seddon explains that the WHO, who have been provided with the data from both studies and expected to meet in early December, would need to consider a variety of factors before deciding what to recommend about the use of levofloxacin for prevention. That includes the fact that you need to treat a lot of children for six months who might not have TB despite being exposed in order to prevent a few cases.

“You have to weigh up the benefits versus the risks and the risks are low, but it is still giving a drug for six months to children and most of them don’t need it. But the consequences of getting MDR-TB are so bad that we really want to prevent that,” he says.

There is also the question around what effect using a broad antibiotic as preventive treatment will have on the microbiome of children and how this might drive resistance to the fluoroquinolones. Seddon says stool samples were collected from the study participants to determine how the drug affected a child’s microbiome and the potential for driving resistance. These data will also be provided to the WHO.

“I think that the evidence base is now very strong on the basis of these two trials. I think you can really say the issue of whether levofloxacin prevents MDR-TB, we’ve put that to bed,” he says. “Are there going to be other studies? Yes. I think that this is not over, levofloxacin is not the perfect drug for preventive therapy.”

Marks adds to this saying: “An important next step for TPT in DR-TB contacts will be studies that evaluate regimens that are shorter than six months – a long time to take medication every day, which can often be challenging. Effective and safe shorter regimens are now being used for child contacts of drug-susceptible TB and we hope the same progress can be made for contacts of DR-TB.”

As Marks has already stated, currently there are no strong recommendations for MDR-TB prevention by the WHO.  In the 2020 TB prevention guidelines, it recommends that the preventative treatment for MDR-TB should be either a fluroquinolone or other second-line agent. It does however caution that these recommendations are based on low-quality evidence. Because of this, it recommends that the preventative treatment for MDR-TB should be individualised, and it be based on the drug resistance profile of the presumed contact. The drugs levofloxacin and moxifloxacin- both fluoroquinolones – may be used unless resistance is suspected. For levofloxacin a dosing schedule for both adults and children are proposed in the document.

Subrayen says that in South Africa the 2019 guidelines for the management of Rifampicin Resistant-TB (RR-TB) does indicate the use of levofloxacin as prevention treatment. The guidelines state that for prevention treatment a fluoroquinolone-based, multidrug regimen is preferred (either levofloxacin and high-dose isoniazid or levofloxacin, high-dose isoniazid and ethambutol). And if exposed to fluoroquinolone-resistant RR-TB, then high-dose isoniazid could be given. Delamanid could be considered as a potential option in very select cases. A training manual published this year by the Department of Health suggests that levofloxacin can be given on its own – but also stresses that the evidence base is weak, something that TB-CHAMP has presumably now changed.

Future of TPT

Seddon says that in a perfect world the ideal TB preventive regimen would be a so-called Pan regimen that could be given for a short period of time, to someone who has been exposed to TB and it works regardless of whether they had been exposed to drug-susceptible or drug-resistant TB.

“There are studies planned to use other drugs for prevention. There’s a study planned to use bedaquiline for a month or two and potentially using injectables that you just have to give once every couple of weeks. So, I think although this [levofloxacin] is a good option now, and it’s probably the best option we have now, this is not perfect,” Seddon says.

The study Seddon is referring to is the BREACH-TB study, a phase three trial that will look at whether a one-month treatment regimen of oral bedaquiline could prevent all forms of tuberculosis. It would be given to people exposed to both drug-resistant and drug-susceptible TB, and in people with HIV infection, including pregnant women and children.

Responding to questions from Spotlight earlier this year when this study was announced in the press, Sonya Krishnan, Assistant Professor of Medicine at Johns Hopkins University and Eric Nuermberger, Professor of Medicine at Johns Hopkins University, said that they anticipate recruiting between 1600 and 2 00 people to take part in the study – they expect around 400 to 500 of these will be people living with HIV. They also said that the control arm will receive the current standard of care in the country rather than placebo.

When asked whether any South African study sites will be included in the clinical trial, they said, “We very much plan to partner with study sites in South Africa. South Africa has a long-standing history of research excellence in TB.”

“A shorter regimen that fights both drug-resistant and drug-susceptible TB would be a game-changer for those living with TB and get us closer to our shared goal of ending the epidemic by 2030,” said Dr. Atul Gawande, USAID assistant administrator for Global Health, in a statement on the study. “This clinical trial will lay the foundation for a remarkable innovation in our fight against TB: a single-dose, long-acting injectable medicine.”

Indeed, if the science and development pans out as Gawande suggests it might, the future of TB preventive therapy might well be an entire course of therapy delivered through a single injection rather than a month or more of pills. As indicated in an article in the journal Clinical Infectious Diseases, work is already underway on the development of bedaquline, isoniazid, and rifapentine long-acting injections – though the research is for now still only in mice.

‘Communities need to be involved’

Hesseling raises the point that when treating or preventing TB, more than just the latest research advancement is needed to improve TB outcomes.

“For me treatment follows diagnosis, actually strengthening healthcare services, making communities more aware and creating demand for kids accessing diagnosis, preventive treatment and appropriate treatment, is actually where it starts,” she says. “So tools are amazing, but we actually need to have strong, effective healthcare services and knowledgeable, empowered communities.”

Seddon adds to this saying that results like those from TB-CHAMP are “a bit irrelevant if it is all kind of top down, paternalistic coming from the researchers, coming from the health system”.

“We really need to generate a community demand for this, where individuals living in communities where this is a problem are calling for this and getting angry about this and demanding it in a way that I think we’ve achieved very well with the HIV community,” he says. “It’s all well and good doing the science and then even better to get it [levofloxacin] into a guideline, but until there’s real demand for from the end user, I think it’s only going to have a certain amount of reach.”

Note: The terms DR-TB and MDR-TB are used somewhat interchangeably – Spotlight uses DR-TB to refer to drug-resistant forms of TB in general and MDR-TB to refer specifically to TB that is resistant to isoniazid and rifampicin.

Republished from Spotlight under a Creative Commons Licence.

Source: Spotlight

No Cure for Myopia Progression in Sight as Eyedrops Trial Flops

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A US study shows that use of low-dose atropine eyedrops, commonly used in a higher dose to treat lazy eye, was no better than a placebo at slowing myopia progression and elongation of the eye among children treated for two years.

The first randomised controlled trial of its kind aimed at identifying an effective way to manage myopia was published last week in JAMA Ophthalmology. It was conducted by the Pediatric Eye Disease Investigator Group at at Vanderbilt University Medical Center (VUMC) and 11 other hospitals and practices across the United States and funded by the National Eye Institute (NEI).

“We found, interestingly, and honestly shockingly, that there was no difference in the use of 0.01% atropine and placebo in treating these children who ranged in age from 5 to 12,” said associate professor Lori Ann Kehler, OD, and the Vanderbilt site principal investigator for the study.

The onset of myopia usually occurs between the ages of 7 and 16 when developing eyes can start growing too long axially (from front to back). Instead of focusing images on the retina, images of distant objects are focused at a point in front of the retina which causes people to have poor distance vision while their near vision remains unchanged.

The condition results in the need for eyeglasses to improve distance vision, and it can also result in medical complications and serious uncorrectable vision loss later in life, like retinal detachments or myopic macular degeneration.

The study contradicts earlier studies from East Asia that showed the small dose of atropine is effective in slowing progression of myopia.

In 2017 the Academy of Ophthalmology endorsed the findings from East Asia saying that although the FDA had not approved atropine for this use, there was sufficient evidence for prescribing the low dose for myopia. Ophthalmologists across the country, including at VUMC, began to offer the prescription to young patients with myopia.

“That was a really exciting finding at the time because we had had no treatment options for many years,” Kehler said. The prescription of atropine for treating myopia is not covered by most insurance plans.

“The incidence of myopia is increasing worldwide,” Kehler said. “By 2030 it’s predicted that 39 million people in the US will have myopia. By 2050 that number is expected to increase to more than 44 million people in the US and to 50% of the global population. Once it’s detected in children, it tends to get worse every year,” she said. “Investigators all over the world have tried strategies to intervene, to either stop or slow the worsening of myopia.”

Kehler said it is not known why the incidence of myopia is increasing. “There are several theories. Some believe it’s the increase in the use of screens and screen time, but myopia was increasing even before screens were part of children’s lives. Others think it has to do with industrialisation. We were an agricultural society. We were outside more. We weren’t reading. We weren’t looking up close all day. Really, the prevailing thought is whether we’re at a screen or looking at a math book or reading most of the day, we think the lack of sunlight and sustained near effort is what’s causing the increase of myopia.”

Kehler said the percentage of children with myopia using the atropine drop at VUMC is low and estimates fewer than 5% of children with myopia are using the drops nationally.

Going forward, eye specialists should have a frank discussion with parents of children with myopia about the conflicting data between the Asian studies and the new U.S. study.

“The absence of a treatment benefit in our US-based study, compared to East Asian studies, may reflect racial differences in atropine response. The study enrolled fewer Asian children, whose myopia progresses more quickly, and included Black children, whose myopia progresses less quickly compared with other races,” noted the study’s lead co-author, Michael X. Repka, MD, professor of Ophthalmology at Johns Hopkins University, in a news release from the NEI.

“All the studies have shown the drops are safe, so we aren’t putting children at risk if we continue to prescribe the 0.01%,” Kehler said. “But we are telling them there is a difference in these studies and it might have to do with your genetics; it might be that it’s more effective in children from Asia than in the U.S. population,” she said.

Further study is needed, Kehler said. The next step is likely to study a higher dose of atropine to see if children in the U.S. experience a benefit.

The LAMP study out of Hong Kong found that 0.05% might be more effective.

Kehler said other groups are studying the use of red-light therapy to slow the progression of myopia, and there are also new eyeglass lenses that have been developed to slow the progression of myopia, but they are not yet available in the U.S.

“It’s much harder to get drops in very young children,” Kehler said. “But if we had a spectacle option, that would open the door to treating our younger patients.”

Myopia usually stabilises in about half of children around 16 years of age and among an increasingly larger percentage as they get older. By their early 20s, about 10% of individuals with myopia will continue to grow more nearsighted, and by age 24 that percentage is 4%.

Source: Vanderbilt University Medical Center

Childhood TV Watching Linked to Metabolic Syndrome in Adulthood

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A new study has added to the evidence that excessive TV watching as a child can lead to poor health in adulthood. The research, published this week in the journal Pediatrics, found that children who watched more television were more likely to develop metabolic syndrome as an adult.

Metabolic syndrome is a cluster of conditions including hypertension, hyperglycaemia, excess body fat, and abnormal cholesterol levels that lead to an increased risk of heart disease, diabetes and stroke.

Using data from 879 participants of the Dunedin study, researchers found those who watched more television between the ages of 5 and 15 were more likely to have these conditions at age 45.

Television viewing times were asked at ages 5, 7, 9, 11, 13 and 15. On average, they watched just over two hours per weekday.

“Those who watched the most had a higher risk of metabolic syndrome in adulthood,” says Professor Bob Hancox, who led the study.

“More childhood television viewing time was also associated with a higher risk of overweight and obesity and lower physical fitness.”

Boys watched slightly more television than girls and metabolic syndrome was more common in men, than women (34% and 20% respectively). The link between childhood television viewing time and adult metabolic syndrome was seen in both sexes however, and may even be stronger in women.

There was little evidence that watching less television as an adult reduced the association between childhood television viewing and adult health.

“While, like any observational study, researchers cannot prove that the association between television viewing at a young age directly causes adult metabolic syndrome, there are several plausible mechanisms by which longer television viewing times could lead to poorer long-term health.

“Television viewing has low energy expenditure and could displace physical activity and reduce sleep quality,” he says.

“Screentime may also promote higher energy intake, with children consuming more sugar-sweetened beverages and high-fat dietary products with fewer fruit and vegetables. These habits may persist into adulthood.”

The results are important because screen times have increased in recent years with new technologies.

“Children today have far more access to screen-based entertainment and spend much more time being sedentary. It is likely that this will have even more detrimental effects for adult health.

“These findings lend support to the World Health Organization recommendation that children and young teenagers should limit their recreational screen time.”

Source: University of Oregon

New Podcast Series Reflects on Childhood in South Africa Through and Beyond COVID-19

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The ‘Phezulu: Looking Up’ podcast series launched today by UNICEF South Africa (https://www.UNICEF.org/SouthAfrica/) tells the stories of the impact of the COVID-19 years on children and young people and how, with the right support and opportunities, children and young people are determined to build a safer, fairer and better post pandemic South Africa.  

The eight-part series delves into issues such as mental wellbeing, disrupted education and access to child healthcare; including routine childhood immunisations, through the voices of children and young people and experts working to mitigate the impact.

Children and adolescents were affected by every aspect of the COVID-19 pandemic and this podcast series tells their stories of resilience,” said Muriel Mafico, UNICEF South Africa Deputy Representative. “Importantly, the episodes also reflect on the response to share learnings, including how the roll-out of the COVID-19 vaccine saved countless lives and re-opened our world,”

The podcast series features expert analysis and voices, including contributions from academics, all of whom continue to play a critical role in the ongoing recovery for every child. The series not only highlights the indirect impact of COVID-19 on children and youth, but also how COVID-19 vaccinations changed the trajectory of the crisis by enabling children and adolescents to resume their childhoods.

The series will be available on a weekly basis, on all major podcast platforms from 23rd May 2023. Listeners can now subscribe and join the conversation. This production was made possible thanks to the generous support of the German Federal Foreign Office and other partners.

For more information, please see the following links:
https://www.UNICEF.org/southafrica/
https://apo-opa.info/42dIxHD

A Molecular Mechanism for Hydrocephalus may Enable a Non-surgical Treatment

MRI images of the brain
Photo by Anna Shvets on Pexels

Researchers at Massachusetts General Hospital have discovered a novel molecular mechanism behind the most common forms of acquired hydrocephalus – which could lead to the first non-surgical treatments for the life-threatening disease. Research in animal models uncovered a pathway through which infection or bleeding in the brain triggers inflammation, causing increased production of cerebrospinal fluid (CSF) by the choroid plexus and lead to swelling of the brain ventricles.

“Finding a nonsurgical treatment for hydrocephalus, given the fact neurosurgery is fraught with tremendous morbidity and complications, has been the holy grail for our field,” says Kristopher Kahle, MD, PhD, a paediatric neurosurgeon at MGH and senior author of the study in the journal Cell. “We’ve identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain bleed or brain infection in acquired hydrocephalus. We’re hopeful these findings will pave the way for approval of an anti-inflammatory drug to treat hydrocephalus, which could be a game-changer for populations in the US and around the world that don’t have access to surgery.”

Occurring in about 0.2% of births, acquired hydrocephalus is the most common cause of brain surgery in children, though it can affect people at any age. In underdeveloped regions where bacterial infection is the most prevalent form, hydrocephalus is often deadly for children due to the lack of surgical intervention. Brain surgery, where a shunt is implanted to drain fluid from the brain, is the only known treatment. But about half of all shunts in paediatric patients fail within two years of placement, according to the Hydrocephalus Association, requiring repeat neurosurgical operations and a lifetime of brain surgeries.

Pivotal to the process is the choroid plexus, the brain structure that routinely pumps cerebrospinal fluid into the four ventricles of the brain to keep the organ buoyant and injury-free within the skull. An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles with cerebral spinal fluid and immune cells from the periphery of the brain in a cytokine storm, swelling the brain ventricles.

“Scientists in the past thought that entirely different mechanisms were involved in hydrocephalus from infection and from haemorrhage in the brain,” explains co-author Bob Carter, MD, PhD, chair of the Department of Neurosurgery at MGH. “Dr Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the US Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection.”

MGH researchers are continuing to explore how rapamycin and other drugs which quell the inflammation seen in acquired hydrocephalus could be repurposed. “What has me most excited is that this noninvasive therapy could provide a way to help young patients who don’t have access to neurosurgeons or shunts,” says Kahle. “No longer would a diagnosis of hydrocephalus be fatal for these children.”

Source: Massachusetts General Hospital

Youth-onset Type 2 Diabetes Increased 77% During COVID Pandemic

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Published in The Journal of Pediatrics, a study reviewing medical records has found that new diagnoses of type 2 diabetes in children has surged 77% since the pandemic, accelerating a trend that is already a great concern for parents and healthcare professionals.

The new analysis documented the rise in cases with measures of increased body mass index (BMI) and higher blood glucose and haemoglobin A1c test results.

During the first year of the pandemic, medical records showed that more boys (55%) were diagnosed with type 2 diabetes than girls (45%), a reversal of the percentages during the pre-pandemic years.

In addition, during the pre-pandemic years, more patients were diagnosed while outpatients (57%) than during the pandemic year, when more were diagnosed and treated as inpatients (57%), suggesting greater severity.

Overall, the researchers found that 21% of the young people diagnosed presented with “metabolic decompensation,” of which the most serious symptoms include vomiting, lethargy, confusion and rapid breathing. Pre-pandemic, such symptoms occurred in only 9% of children with new-onset type 2 diabetes. Because the study involved a retrospective review of medical records, the investigators say there is a potential for inconsistencies in reporting or missing information.

“It used to be rare to hear about a child with type 2 diabetes, but its prevalence in adolescents has almost doubled in the past 20 years,” said Dr Kesley. “Type 2 diabetes is associated with rapidly progressive disease and early onset of complications and, unfortunately, was on the rise even prior to the COVID pandemic.”

Data suggests diagnoses of type 2 diabetes in children are increasing by 4 to 5% per year. The COVID pandemic introduced multiple challenges and increased attention to children with pre-existing disorders such as diabetes.

“In the spring of 2020 we were inundated with new youth-onset type 2 diabetes cases,” said Dr Kelsey. “We were used to seeing 50-60 new cases per year and that increased to more than 100 new cases in a year. Colleagues at other institutions were seeing the same thing, so we gathered a team of researchers to evaluate the frequency and severity of new cases during the first year of the pandemic compared to the mean of the prior two years. It was challenging because there is not a funded national registry for youth-onset type 2 diabetes, so this work was done with an enormous and voluntary effort of investigators across the country who are dedicated to treating diabetes in youth.

“To our knowledge, this is the first multicentre study to report the impact of the COVID pandemic on rates of newly diagnosed youth onset type 2 diabetes,” Dr Kesley said. “We found that the pandemic was associated with an increase in new type 2 diabetes cases compared to the two prior years, as well as an increase in proportion of youth presenting in metabolic decompensation.”

Contributing factors could be stem from the immense behavioural and environmental changes since the onset of the pandemic. Worldwide, children were enrolled in school virtually, extracurricular activities were limited and daily routines were adjusted to decrease the potential exposure to COVID. Consequences of this included increased screen time, unhealthy eating habits, decreased physical activity and poor sleep habits, which all have associations with increased BMI.

Whether COVID infection was the direct cause for the increase, or just associated with environmental changes and stressors during the pandemic is unclear. “Further studies are needed to determine whether this rise is limited to the United States and whether it will persist over time,” said Dr Kesley. “There is still a lot of work to be done.”

Source: EurekAlert!

UK Children’s Gender Identity Clinic to Close after Controversies

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Following a highly critical independent report and accusations of inadequate and unsafe care, the UK will shut down the Tavistock gender identity clinic for children – the only one in the country. It will be replaced by a number of smaller facilities with closer links with mental health care.

The Tavistock and Portman NHS Foundation Trust clinic, named the Gender Identity Development Service (GIDS), had faced complaints of both long waiting lists for a burgeoning number of referrals, as well as rushing to assign puberty-blocking drugs and cross-sex hormones to children experiencing gender dysphoria.

Concerns had been voiced as early as 2005, when a nurse working at the clinic said that patients were being assessed too quickly and giving in to pressure from interest groups. Nevertheless, demand for its services skyrocketed in later years, from less than 100 per year in 2010 to nearly 2500 by 2018. In 2018, concerns were raised anew, with staff going on to make serious public accusations.

In July 2019, Dr Kirsy Entwhisle, a psychologist at GIDS Leeds hub, said that staff misled patients and made decisions about young people’s “bodies and lives” without “robust evidence”. Some of the children had suffered “very traumatic early experiences” which had not been addressed by the staff. The trust’s safeguarding lead, Sonia Appleby, won a claim from an employment tribunal after trust managers tried to stop her from carrying out her role when staff raised concerns.

One of the loudest critics of Tavistock Centre is Keira Bell, who at 16 was assigned puberty blockers, then cross-sex hormones at 17, and had a double mastectomy at 20 before later de-transitioning.

The former patient, who said she was suffering from anxiety and depression at the time she received treatment, said medics should have considered her mental health issues, “not just reaffirm my naïve hope that everything could be solved with hormones and surgery”.

Along with the unnamed parent of an autistic girl at the clinic, she won a ruling against the NHS assigning cross-sex hormones to children under 16 – but was overturned on appeal.

Helen, a parent of a patient at the clinic, welcomed its closure, but expressed concern for the future of her son’s treatments, according to LGBT site Pink News. While she said her son was treated quickly and received puberty blocking drugs, “From that point on, it felt like it was a little bit like they were winging it,” she said.

During therapy sessions at Tavistock, she said her son was asked a lot of questions and treated “almost like a little bit of an academic curiosity”. She criticised the fact that the same staff evaluated children for medical interventions and also offered therapy session, creating “a fear that they would stop access to medical support”. In contrast to the legal claims of Keira Bell’s and the unnamed patient, she said that GIDS refused to even discuss cross-sex hormones.

Dr David Bell (no relation to Keira Bell) welcomed the closure of Tavistock, telling the BBC: “Some children have got the double problem of living with the wrong treatment, and the original problems weren’t addressed – with complex problems like trauma, depression, large instances of autism.”

Hospital Readmissions for Children with Asthma on The Increase

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Hospital readmissions for asthma are increasing among children, likely stemming from COVID lockdowns reducing immunity to common respiratory viruses. These are the findings of a new study published in the Journal of Asthma. The finding highlights the gaps in health care for this most common of chronic paediatric illnesses.

The Australian study, led by the Murdoch Children’s Research Institute, found about one in three children, mostly pre-schoolers, are readmitted to hospital for asthma compared to one in five a decade ago.

Most asthma hospital presentations were preventable, Murdoch Children’s Dr Katherine Chen said, which emphasises the need for a holistic evaluation of each child’s asthma management to prevent future readmissions.

The study involved 767 children, aged three to 18 years, who were admitted to three hospitals in Victoria state between 2017-2018 with a diagnosis of asthma. It found that 34.3% were readmitted to hospital for asthma, with those aged three to five years accounting for 69.2%. Of the 767 participants, 20.6% were readmitted once, and 13.7% had two or more readmissions in 12 months. 

“Our study highlighted gaps in the children’s asthma care,” Dr Chen said. Over a third of children hadn’t had a review of their inhaler technique, and only about a quarter were prescribed a preventer or asked to continue using it.

“Almost three quarters were discharged without a preventer medication, and over 80 per cent did not have a follow-up clinic booked at the hospital, often reserved for children with difficult-to-control asthma. Most families, therefore, need to navigate their child’s asthma follow-up with their GP.”

Recently, said Dr Chen, asthma admissions had spiked due to the rise in respiratory infections and children lacking immunity to common viruses as a result of COVID lockdowns.

Professor Harriet Hiscock at MCRI said that the findings confirmed the important role of GPs in paediatric asthma management and how targeted interventions at each hospital could reduce readmissions.

“Less than 10 per cent were readmitted within 30 days suggesting the importance of ongoing community care and longer-term asthma control,” she said. The need to regularly review overall asthma management, minimise risk factors, arrange follow-up, and support optimum care in the community are key.

“Interactive digital symptom monitoring with specialist nurse support, home-based education and a culturally tailored education program could also help.”

Prof Hiscock said linked datasets were important to objectively measure the burden of asthma cases on health services.

“Our current dataset cannot verify whether the follow-up appointment was attended, whether caregivers had arranged follow-up post-discharge and if the medications were used as prescribed,” she said. “Integrating datasets such as health services and medication use into clinical care will improve the clinician’s understanding of the child’s asthma control and medication adherence and would assist in providing targeted treatments.”

Asthma is the most common chronic paediatric illness in industrialised countries, affecting 8–10% of children.

Source: Murdoch Children’s Research Institute

ADHD Overdiagnosis Common and Racially Skewed, US Study Finds

Children in classroom
Photo by CDC

A study in the Journal of Learning Disabilities examining overdiagnosis of attention-deficit/hyperactivity disorder (ADHD) found that diagnoses are common in children who are functioning well, and that there is a racial bias.

ADHD overdiagnosis and subsequent overtreatment poses needless potential harm to children. It also contributes to scepticism toward those who do have moderate or severe symptoms and significant impairments, resulting in less supportive care.

Yet which sociodemographic groups of children are overdiagnosed and overtreated for ADHD is poorly understood. As a proxy for overdiagnosis, researchers selected elementary schoolchildren who had displayed above-average levels of independently assessed behavioural, academic, or executive functioning the year prior to their initial ADHD diagnoses and who did not have prior diagnostic histories. This suggested they were unlikely to have ADHD.

The researchers conducted descriptive and logistic regression analyses of a population-based subsample of 1070 elementary schoolchildren.

Among these children, (a) 27% of White children versus 19% of non-White children were later diagnosed with ADHD and (b) 20% of White children versus 14% of non-White children were later using medication. In adjusted analyses, White children are more likely to later be diagnosed (odds ratio [OR] range = 1.70–2.62) and using medication (OR range = 1.70–2.37) among those whose prior behavioural, academic, and executive functioning suggested that they were unlikely to have ADHD.

The findings also skewed toward older children, and differences in diagnoses according to race was not linked to socioeconomic status. The authors acknowledge limitations such as a small sample size as well as not being able to account for English-speaking versus non-English speaking families, but note that their results are significant for 9 out of the 10 tests used.

The researchers suggest that greater overdiagnosis in White children may be in part explained by greater access to better-resourced schools more likely to pick up (or attempt to pick up) ADHD in children. Non-White children may also need to display behaviours more consistent with ADHD to be referred for evaluation and treatment.

Cultural misconceptions about ADHD are less likely to be prevalent in non-White families, and there is evidence to suggest that ADHD overdiagnosis is being used to gain academic achievement.

They concluded: “Preventing or reducing ADHD overdiagnosis and overtreatment should contribute to more appropriate care, limit increasing ADHD prevalence, increase the academic and behavioural functioning of elementary schoolchildren being diagnosed with ADHD but who are displaying few or mild symptoms, reduce unnecessary exposure to adverse side effects of medication use, and better allocate limited mental health resources.”

Paediatric Kidney Transplants without Immunosuppressive Drugs

Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

Stanford Medicine physicians have developed a way to provide paediatric kidney transplants without immunosuppressive drugs. Their key innovation is a safe method to transplant the donor’s immune system to the patient before surgeons implant the kidney.

The medical team has dubbed the two-transplant combination a “dual immune/solid organ transplant,” or DISOT. The first three DISOT cases, all performed at Lucile Packard Children’s Hospital Stanford were described in the New England Journal of Medicine, accompanied by an an editorial about the research.

The Stanford innovation removes the possibility that the recipient will experience immune rejection of their transplanted organ, the most common reason for a second organ transplant The new procedure also rids recipients of the substantial side effects of a lifetime of immune-suppressing medications, including increased risks for cancer, diabetes, infections and hypertension.

“Safely freeing patients from lifelong immunosuppression after a kidney transplant is possible.”

Alice Bertaina, MD, PhD, report’s lead author, associate professor of paediatrics, Stanford University

The first three DISOT patients were children with a rare immune disease, but the team is expanding the types of patients who could benefit. The protocol received FDA approval on May 27, 2022, for treating patients with a variety of conditions that affect the kidneys. Dr Bertaina anticipates that the protocol will eventually be available to many people needing kidney transplants, starting with children and young adults, and later expanding to older adults. The researchers also plan to investigate DISOT’s utility for other types of solid-organ transplants.

The scientific innovation from Dr Bertaina’s team has another important benefit: It enables safe transplantation between a donor and recipient whose immune systems are genetically half-matched, meaning children can receive stem cell and kidney donations from a parent.

The advance is especially meaningful for Jessica and Kyle Davenport of Muscle Shoals, Alabama. Their two children, both born with a rare and potentially deadly immune disease, are among the first recipients of DISOT: 8-year-old Kruz received transplants from Jessica, while his 7-year-old sister, Paizlee, received transplants from Kyle.

“They’ve healed and recovered, and are doing things we never thought would be possible,” said Jessica Davenport. After years of helping Kruz and Paizlee cope with severe immune deficiency and its attendant infection riskk as well as kidney dialysis, she and her husband are thrilled that their children have more normal lives.

The idea of transplanting a patient with their organ donor’s immune system has been around for decades, but it has been difficult to implement. Transplants of stem cells from bone marrow provide the patient with a genetically new immune system, as some of the bone marrow stem cells mature into immune cells in the blood. First developed for people with blood cancers, stem cell transplants carry the risk of the new immune cells attacking the recipient’s body, a potentially lethal complication called graft-versus-host disease.

Source: Stanford Medicine