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Tom Ulrich

ADHD long term drug safety rare adverse events FDA approval Kenneth Mandl Florence BourgeoisYou’d think drugs meant to be taken by children for years would be studied in children for a long time to measure their long-term safety.

You’d think drugs for a condition affecting millions of children would be tested in many, many children to catch any rare side effects.

You’d think all this would happen before the Food and Drug Administration, an agency known for its strict criteria, approved them for marketing.

But if a new PLoS ONE paper by Boston Children’s Hospital’s Florence Bourgeois, MD, MPH, and Kenneth Mandl, MD, MPH, is any indication, you’d be wrong.

In it, the pair reports that the FDA approved 20 attention deficit hyperactivity disorder (ADHD) drugs over the last 60 years without what would be considered sufficient long-term safety and rare adverse event data.

Their findings, they say, point to larger issues in how the FDA’s approval process addresses the long-term safety of drugs intended for chronic use in children. Full story »

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Wong-Baker pain faces subjective objective pain assessment systems neuroscience David Borsook

Subjective measures of pain, like the Wong-Baker face scale (above), are useful in assessing patients' pain, but objective measures would be far better.

“How much pain are you in?” It’s a harder question than you think. Tools for assessing patients’ pain—be they children or adults—rely on their perception: a subjective measure that eludes quantification and can change in response to any number of emotional, psychological or physiological factors.

Being able to objectively quantify pain could open the door to better pain management (especially for patients with chronic or neuropathic pain), better anesthetic dosing during surgical procedures, better understanding of addiction (and how to avoid it) and more.

To do so, we need measurable markers: physiologic parameters that reliably and quantitatively change during the experience of pain. But according to pain researcher David Borsook, MD, PhD—of Boston Children’s Hospital’s departments of Anesthesiology, Perioperative and Pain Medicine and Radiology—discovering such markers requires a better understanding of the larger context and of events that trigger pain, a perspective he refers to as “systems neuroscience.” Full story »

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Old car aging blood cell hematopoietic stem cell blood disorder Derrick Rossi

Like an old, unused car, our aging blood stem cells can accumulate damage over time that they can't fully repair.

My first car was my grandfather’s 1980 Chevrolet Malibu. For about two years before my family gave it to me, it sat unused in Grandpa’s garage—just enough time for all of the belts and hoses to rot and the battery to trickle down to nothing.

Why am I telling this story? Because it’s much like what happens to the DNA in our blood-forming stem cells as we age.

Hematopoietic stem cells (HSCs) spend very little of their lives in an active, cycling state. Much of the time they’re quiescent or dormant, keeping their molecular and metabolic processes dialed down. These quiet periods allow the cells to conserve resources, but also give time an opportunity to wear away at their genes.

“DNA damage doesn’t just arise from mistakes during replication,” explains Derrick Rossi, PhD, a stem cell biology researcher with Boston Children’s Hospital’s Program in Cellular and Molecular Medicine. “There are many ways for damage to occur during periods of inactivity, such as reactions with byproducts of our oxidative metabolism.”

The canonical view has been that HSCs always keep one eye open for DNA damage and repair it, even when dormant. But in a study recently published in Cell Stem Cell, Rossi and his team found evidence to the contrary­­—which might tell us something about age-related blood cancers and blood disorders. Full story »

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Surgical Sam beating heart pediatric trainer mannequin simulation Simulator Program The Chamberlain GroupWe often see medical magic in Hollywood, but it’s not often we see Hollywood magic brought into medicine. Now, Boston Children’s Hospital’s Simulator Program and special-effects collaborators at The Chamberlain Group (TCG) have done just that.

Simulation has become a key component in team training, crisis management, surgical practice and other medical training activities. With simulation, medical teams can add to and hone their skills in an environment where people can make mistakes without risking patient harm—”practicing before game time,” says Boston Children’s critical care specialist Peter Weinstock, MD, PhD, who runs the Simulator Program.

Mannequins are a key part of simulation, and Weinstock’s team, working together with companies, designers and engineers, has developed eerily lifelike ones that can bleed and “respond” to interventions based on computer commands from a technician.

But there are some things Weinstock’s mannequins haven’t been able to capture up to now, like the movements of a beating heart.

That’s where TCG and a new mannequin called Surgical Sam come in. Full story »

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John Kheir, MD, first envisioned an injectable form of oxygen eight years ago, the night one of his patients, a nine-month-old girl, died after catastrophic lung failure. Kheir, a cardiac intensive care specialist at Boston Children’s Hospital, spoke last night to WBZ-TV’s Mallika Marshall, MD, about his efforts to try to buy precious time for children whose lungs stop working:

Want to know more? Read Kheir’s own words about his hopes and challenges for intravenous oxygen in a post he penned for Vector.

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Emir Seyrek Wiskott-Aldrich syndrome WAS gene therapy Dana-Farber/Boston Children's Cancer and Blood Disorders Center

Emir Seyrek was the first patient with Wiskott-Aldrich syndrome to be treated in the U.S. in an international gene therapy trial.

Seeing that his mother, Kadriye, wasn’t looking, Emir Seyrek got an impish grin on his face, the kind only a two-year-old can have. He quietly dumped his bowl of dry cereal out on his bed and, with another quick look towards his mother, proceeded to pulverize the flakes to dust with his toy truck. The rest of the room burst out laughing while his mother scolded him. Despite the scolding, though, the impish grin remained.

It was hard to believe that he arrived from Turkey six months earlier fighting a host of bacterial and viral infections. Emir was born with Wiskott-Aldrich syndrome (WAS), a genetic immunodeficiency that left him with a defective immune system. He was here because he was the first patient—of two so far—to take part in an international trial of a new gene therapy treatment for WAS at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. And that day he was having his final checkup at Boston Children’s Hospital’s Clinical and Translational Study Unit before going home. Full story »

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Adult undergoes echocardiography guidelines for screening childhood cancer survivors for heart diseaseThe drugs and treatments developed over the last 50 years have transformed many childhood cancers from death sentences into largely curable diseases. However, those same drugs and treatments can have lasting or late effects on many different organ systems.

Such is the case with anthracyclines: Patients treated with these chemotherapy agents have a greatly elevated future risk of congestive heart failure (CHF).

For this reason, the Children’s Oncology Group (COG)—which brings together pediatric cancer experts from around the globe—currently recommends screening childhood cancer survivors with echocardiography every year or two, depending on their level of anthracycline exposure, for signs of asymptomatic left ventricular dysfunction (ALVD). If left untreated, this clinically silent condition can progress to congestive heart failure.

But are we screening the right survivors at the right times using the right methods? Answering that question for cancer and CHF would require prospectively studying thousands of survivors (itself a challenge, given childhood cancer’s relative rarity) for decades, which is neither financially nor logistically feasible. Full story »

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Cup of coffee caffeine helps premature babies breatheThe caffeine in coffee might help get you going in the morning, but for premature babies it can be lifesaving. For more than a decade neonatologists have routinely given premature newborns caffeine as a respiratory stimulant, helping their immature lungs and brains remember to breathe and reducing episodes of intermittent hypoxia (IH)—short, repetitive drops in blood oxygen levels.

Typically, babies are weaned off caffeine once they’re developmentally mature enough to breathe normally without help, usually around 34 weeks’ gestational age. “It’s at about that age that most babies stop having clinically obvious hypoxic spells,” explains Boston Children’s Hospital pulmonologist and neonatologist Lawrence Rhein, MD. “But the question has been, are there continued but less obvious episodes that we could and should be preventing? And can caffeine play a role in doing so?”

It’s an important question to ask. While no single IH episode has much effect, lack of oxygen over days or weeks can affect a baby’s lungs, brain and heart, and fuel inflammation within her tissues and organs—all of which can have long-term developmental impact.

Rhein and colleagues from 15 other hospitals across the U.S.—together comprising the Caffeine Pilot Study Group—came together to probe the question. Their answer: pour the baby another cup. Full story »

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Bone marrow on a chip organs on chips Wyss Institute Donald Ingber

Microscopic view of the engineered bone with an opening exposing the internal trabecular bony network, overlaid with colored images of blood cells and a supportive vascular network that fill the open spaces in the bone marrow-on-a-chip. (James Weaver, Harvard's Wyss Institute)

We’ve had a lung on a chip, and a gut on a chip. Now researchers at the Wyss Institute for Biologically Inspired Engineering have added another tissue to their list of “organs-on-chips”— devices that mimic in vitro tissues’ in vivo structure and function for pharmaceutical discovery and testing. In a paper published in Nature Methods, a team led by Donald Ingber, MD, PhD, (a member of Boston Children’s Hospital’s Vascular Biology Program and founding director of the Wyss), announced that they have developed “bone marrow-on-a-chip.”

The sheer complexity of the new device sets it apart from the Wyss’s previous organs, reflecting the greater natural complexity of bone marrow. Full story »

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Hematopoietic hierarchy blood development stem cells

The classic hematopoietic hierarchy. What if we could turn those arrows around?

Think, for a moment, of a cell as a computer, with its genome as its software, working to give cells particular functions. One set of genetic programs turns a cell into a heart cell, another set creates a neuron, still another a lymphocyte and so on.

The job of controlling which programs get booted up, and when, falls in part to transcription factors—genes that act like molecular switches to turn other genes on and off.

Derrick Rossi, PhD, spends a lot of his time thinking about transcription factors. A stem cell and blood development researcher in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine, Rossi believes that transcription factors hold the power to achieve one of the most sought-after goals in regenerative medicine: producing, from other cell types, transplantable hematopoietic stem cells (HSCs).

“There are about 50,000 HSC transplants every year,” Rossi explains, noting that the success of a transplant is highly dependent on the number of cells a patient receives from her donor. “But HSCs only comprise about one in every 20,000 cells in the bone marrow.

“If we could generate autologous HSCs from a patient’s other cells,” he continues, “it could be transformative for transplant medicine and for our ability to model diseases of blood development.”

As they reported April 24 in Cell, Rossi and his collaborators have taken a significant step toward that goal: Using a cocktail of eight transcription factors, they reprogrammed mature mouse blood cells into what they have dubbed induced HSCs (iHSCs). Full story »

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