Sickle Cell Disease patients and the use of disease-modifying treatments

Published

12 months ago

November 23, 2023

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By Dr. Priyom Bose, Ph.D. Nov 23 2023 Reviewed by Lily Ramsey, LLM

For sickle cell disease (SCD), hydroxyurea is an established treatment. Despite this, hydroxyurea remains underutilized.

New disease-modifying treatments (DMTs), namely, crizanlizumab, L-glutamine, and voxelotor, have recently been approved. A new JAMA Network Open study delved deeper into understanding the uptake of these DMTs in the context of current treatment strategies.

Study: Use of Disease-Modifying Treatments in Patients With Sickle Cell Disease . Image Credit: angellodeco/Shutterstock.com Background

SCD is a red blood cell disorder that can cause extensive morbidity and mortality. Prior to 2017, the sole DMT to treat SCD was hydroxyurea, which was seen to diminish rates of vaso-occlusive crises (VOCs) by 44%.

New DMTs, i.e., crizanlizumab, L-glutamine, and voxelotor, have recently been approved. Limited existing evidence suggests that these new-world DMTs can also effectively reduce VOCs and improve the clinical course of SCD.

Despite the documented efficacy, DMTs are underused. One reason could be that the existing literature evaluating DMT uses some limitations. This research often predates the approval of new DMTs and often focuses on a single DMT outcome.

Another issue with existing research is that it often studies a single health-care site, thereby limiting the generalizability of the findings. About the study

As highlighted above, the existing literature on DMTs does not provide a clear idea about the current treatment landscape regarding population characteristics and treatment types.

Addressing this gap in research, the current study used a large claims database and explored the patterns of use of approved DMTs. Related StoriesAutologous stem cell transplant shows promise for young patients with severe juvenile systemic sclerosisHow to optimize nuclei extraction & counting for single cell sequencingBioengineered human heart muscle cells and micro-tissues take flight to space

The data to identify adults and children with SCD were obtained from the Clinformatics Data Mart Database between the 1st of January, 2014, and the 30th of September, 2021.

The yearly usage of crizanlizumab, voxelotor, hydroxyurea, and L-glutamine and characteristics of patients were noted. The main aim was to characterize patterns of annual DMT use and understand patient characteristics correlated with DMT use. Key findings

The sample comprised around five thousand patients with SCD. It was noted that older adults, females, and those who were relatively healthier did not use DMTs.

The health status was inferred by SCD complications, VOC events, and hospitalizations. Individuals with a history of opioid use, more use of health-care services, and more SCD complications were inconsistent DMT users. Avascular necrosis and thrombosis were SCD complications seen among consistent users.

Between 2014 and 2021, an increase in DMT use was observed. In 2014, 19.6% of patients had at least one prescription fill for a DMT.

This percentage increased to 28.3% in 2021, driven largely by the availability of voxelotor and crizanlizumab.

Despite the increase, fewer than 5% of the population was seen to use newer DMTs, and less than 25% used hydroxyurea. A surprising observation was that approximately 75% of patients were not treated with DMT.

Not many studies have explored the use of DMTs at a national level and are hence not indicative of the current treatment landscape. Prior research has also shown the underutilization of hydroxyurea.

These observations align with the findings documented here that the majority of patients did not get at least one prescription fill for hydroxyurea. This was also true when new DMT approvals were considered, i.e., about 72% did not have a prescription fill in 2021.

It was observed that individuals who had some form of DMT use reported more SCD-related complications relative to non-DMT users. This suggests that barriers to using DMT must be explored further.

Future research should uncover how different trajectories of DMT use can influence disease outcomes, and longitudinal studies should be conducted in this regard. Conclusions

This cross-sectional analysis showed that the uptake of DMTs was persistently low from 2014 to 2021, despite newer therapies being approved. More research should be conducted on the factors that make it easy to use DMTs, and new strategies should be devised to raise DMT uptake.

A key limitation of the present study is that it captures only prescription fill data. Data on actual medication use was unavailable, which could imply that the DMT use has been overestimated in this study.

It must be mentioned that despite the possible overestimation, the implication of the results should remain the same, i.e., sub-optimal use of DMTs.

Additionally, data on patient-level factors affecting eligibility for DMTs could not be accessed. This data could have helped shed light on the reasons for underutilizing DMTs.

The overarching recommendation stands, however, that most individuals with SCD should receive a DMT. Lastly, the Clinformatics data does not have details on patients receiving Medicaid, so the results documented here cannot be generalized to that sub-population. Journal reference:

Newman, V.T. et al. (2023) Use of Disease-Modifying Treatments in Patients With Sickle Cell Disease. JAMA Network Open. 6(11), e2344546. doi:10.1001/jamanetworkopen.2023.44546. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812261#:~:text=Current%20pharmacological%20management%20of%20SCD,available%20for%20use%20in%20SCD.

World

Under siege in Ukraine, schools go underground to keep life as normal as possible for children

Published

3 hours ago

November 17, 2024

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Under siege in Ukraine, schools go underground to keep life as normal as possible for children

If you know a teacher, or you are a teacher, you’ll understand that many in the profession consider their jobs one of the best in the world, while also acknowledging it can be one of the most stressful.

Teaching in a war zone takes it to another level on both fronts.

But imagine teaching in a war zone in say the London Underground or the Paris or New York metros?

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Well, that’s exactly what is happening in Kharkiv, Ukraine’s second largest city – a city attacked by Russia on a constant basis.

In 2023, the authorities banned children from being taught in regular school buildings here because of the threat they were under from missile strikes.

So Kharkiv city and its education department started working on a plan.

That plan has concluded with the construction of six schools in six metro stations, teaching 4,800 children daily whose families haven’t fled the war.

Intrigued by this new educational experiment, as it’s still considered, we were told to meet at the University metro station in the centre of the city and wait to be taken to the school.

Soviet-era metro stations, and particularly the platforms, are universally grand and ornate, although Ukraine’s are slightly more modest.

Pedestrian walkways though are always crammed with florists, newspaper stands, mobile phone shops and cafes, and Kharkiv’s are no different.

What is different though is that next to the main platform entrance, an adjacent passageway has been sealed off by a white wall with three doors built into it.

We were ushered inside, past a guard and into a concourse with two desks.

In front of us, we could see a wide staircase leading to a long corridor. Above us, large, shiny silver metal tubes stretched into the distance, pumping in air from above ground.

Lining the corridor, we could see a series of white interconnecting cabins, all brightly lit, and from them, we could hear the sounds of children laughing, music, and teachers conducting class in this strange subterranean school.

Perhaps the only school in the world with one corridor.

A door to one of the classes opened, and in pairs, a class of six and seven-year-olds emerged – their teacher at the front and an assistant at the rear.

They’re heading to the bathroom for a toilet break, the staff must keep an eye on them.

If any of the children were to make it out of the school, they could easily get lost in the underground system.

The pupils are spread across seven classrooms with a mix of yellow and green desks and chairs, and walls decorated with bright pictures like rainbows, sunshine and sunflowers, to try to create a cheery atmosphere.

“At first, the children were bewildered by studying here, it felt unfamiliar to them, but interacting with each other and with their teachers helped them to adapt,” Iryna Tarasenko from Kharkiv’s education department told me.

Iryna is showing me around the school. They feel it’s their way of contributing to the war effort.

She said: “In the summer of 2023, the Defence Council didn’t permit children to study in regular school buildings, so, we had to find a solution. This is our frontline – our educational frontline.”

There are of course health concerns for both the teachers and the pupils spending so much time underground, so medical examinations are done on a regular basis.

It is an opportunity for doctors and behavioural specialists to monitor the effects of this war on them.

Dmytro Mitelyov is the neurologist on duty monitoring the children’s behaviour, checking for any signs of stress – physical and mental.

He gently asks each child how they’re feeling, and asks if they have any aches and pains.

“These are children who haven’t left Kharkiv since the war began, they live in a constant state of stress, multifaceted stress caused by a range of factors. They are exposed to things they see and hear, like alarms, explosions, and they feel it all,” Dmytro told me.

“When these children grow older, all the trauma they’ve endured during their formative years can, unfortunately, leave a lasting and serious imprint on their mental health. They haven’t had a healthy, carefree childhood – the kind where they can learn, play, and feel safe as children normally would.”

As the first group’s school day ends, children from one of Kharkiv’s most bombed districts, wrap up warm before being led to the surface to catch a school bus to their old school – which was hit by a missile.

It’s still where they meet their parents for normal pick-up.

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We jump on the bus with them for the journey past destroyed government buildings, shopping centres and restaurants.

When the air raid suddenly sounds, I look around to see how the children and teachers on this bus will react.

They barely flinch it’s so common.

“People have, to some extent, adapted,” one of the headmistresses, Olena Nikolienko, said.

“If we see missiles coming, heaven forbid, we’ll stop near a designated shelter, following our evacuation plan, and that’s where the children will go for cover.”

Remember, these children are safe underground at school, up here they are not.

During the bus ride, 10-year-old Alisa began quietly sobbing. Her teacher told me her grandfather was killed four months ago on the frontline, and since then she has been prone to tears.

Alisa’s teacher comforted her and told her everything would be ok.

It feels like everyone here has to carry their own sadness.

Everyone.

Parents, standing in the first snowfall of the season, greet the children as they get off the bus.

The kids run off the bus, and start throwing snowballs at each other, enjoying this precious moment.

It will be the last time they’re outside today.

US

Xi Jinping says China is ‘ready to work’ with Donald Trump during last meeting with Joe Biden

Published

3 hours ago

November 17, 2024

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Xi Jinping says China is 'ready to work' with Donald Trump during last meeting with Joe Biden

Joe Biden has met with Xi Jinping for the last time as US president, where the Chinese leader said he is “ready to work” with Donald Trump.

Speaking at the Asia-Pacific Economic Cooperation forum in Lima, Peru, Mr Biden said the US and China’s relationship should be about “competition, not conflict”.

“We haven’t always agreed, but our conversations have always been candid and always been frank,” he said.

“We’ve never kidded one another. These conversations prevent miscalculations, and they ensure the competition between our two countries will not veer into conflict.

“We’ve been level with one another. I think that’s vital.”

Their last-ever meeting comes as president-elect Donald Trump vows to introduce blanket 60% tariffs on US imports of Chinese goods as part of a series of “America First” trade measures.

But despite Mr Trump’s proposed measures, Mr Xi said his country’s goal “of a stable, healthy and sustainable China-US relationship remains unchanged”.

“Our commitment to mutual respect, peaceful coexistence and… cooperation as principles for handling China-US relations remains unchanged,” he added.

The Chinese president then said the country is “ready to work with the new US administration to maintain communication, expand cooperation and manage differences, so as to strive for a steady transition”.

Neither Mr Xi nor Mr Biden responded to a question about whether there were concerns about Mr Trump’s proposed tariffs.

The president-elect has also named several China hawks to his transition team, such as Senator Marco Rubio as secretary of state and Representative Mike Waltz as national security adviser.

Under Mr Biden, Washington has introduced restrictions on US investment in Chinese artificial intelligence, quantum computing and semiconductors.

Former house speaker Nancy Pelosi also visited the island of Taiwan – which China views as a breakaway province – in April 2022.

In their meeting at this time last year – which followed a surge in tensions when an alleged Chinese spy balloon was shot down over the US – both leaders said direct communication between American and Chinese military forces would be restored.

US

Mike Tyson reveals he ‘almost died’ ahead of fight with YouTuber-turned-boxer Jake Paul

Published

3 hours ago

November 17, 2024

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Mike Tyson reveals he 'almost died' ahead of fight with YouTuber-turned-boxer Jake Paul

Former heavyweight champion Mike Tyson says the health scare in June, which forced the postponement of his boxing match with Jake Paul, almost cost him his life.

“I almost died in June,” Tyson wrote on X, adding that he “had 8 blood transfusions. Lost half my blood and 25lbs in hospital”.

The 58-year-old, who lost to the YouTuber-turned-boxer in a unanimous points decision in Texas, tweeted that the situation was far worse than people had realised.

Following Tyson’s recovery, after reportedly suffering an ulcer flareup, he reflected on the result of the fight.

“This is one of those situations when you lost but still won… no regrets to get in the ring one last time,” he said.

That contrasts with Tyson’s comments after the match in which he refused to confirm whether it would be his last fight.

“It depends on the situation,” Tyson said before suggesting a fight with Paul’s older brother, Logan Paul, who was standing near him in the ring.

Critics argued that the revised match – which involved fewer and shortened rounds, as well as heavier gloves – fell short of entertaining.

Some claimed it appeared more like a glorified sparring session.

It was Tyson’s first sanctioned pro bout since 2005, when he lost to Kevin McBride and then went into retirement – only briefly reappearing for an exhibition match in 2020 against Roy Jones Jr.

Paul has plenty to prove

Paul, 27, still has plenty to prove. The social media influencer wants to be a championship fighter and compete for a championship belt within two years. “I think it could happen in the next 24 months,” Paul said.

“I truly, truly believe in my skills and my ability and my power. And the cruiserweight division is seemingly open for the taking on that timeline,” he added.

The only professional match he has lost so far has been to Tommy Fury, the less-accomplished brother of former heavyweight champion Tyson Fury.

But there are questions about when Paul will fight a contender in his prime, as opposed to former champions or mixed martial artists.

Could Paul really take on Alvarez?

Intriguingly, in the days before his fight with Tyson, Paul mentioned super middleweight champion Canelo Alvarez, considered one of the best boxers in the world.

According to reports, the Texas bout earned Paul $40m (£31.7m) versus $20m (£15.8m) for Tyson.

Netflix said 60 million households worldwide viewed the contest on its streaming platform, and nearly 50 million tuned in to watch the undercard which saw Ireland’s Katie Taylor beat Puerto Rico’s Amanda Serrano.

Even so there were some technical glitches. More than 90,000 users reported problems on Netflix at its peak, according to the website Downdetector, which tracks outages.