FRANKFURT (Reuters) – Siemens will test the appetite of sovereign wealth funds ahead of the planned listing of its healthcare unit Healthineers next year, its chief executive told a German weekly, possibly to secure anchor investors for the flotation.
The listing of a minority of the unit, which makes X-ray and MRI machines, is set to take place in the first half of 2018 and is expected to value Healthineers as a whole at around 40 billion euros ($48 billion).
Siemens is expected to sell 15-25 percent of Healthineers, sources have said, implying stock worth 6-10 billion euros could be sold – Germany’s biggest share offering since Deutsche Telekom in 1996.
“Internal preparations are going well and we are still planning the listing in the first half of 2018, if markets play along,” Joe Kaeser told Frankfurt Allgemeine Sonntagszeitung in an interview published on Sunday.
“In any case, we are planning to test the interest of relevant anchor shareholders, including sovereign wealth funds.”
Asked whether this included Norway and China, home to the world’s largest and third-largest state funds, respectively, Kaeser said: “We will probably cover the range of the most important state funds, yes. The advantage would be that we would gain anchor investors. The disadvantage: the free float of shares is not as high.”
The move is designed to enable the unit to raise its own funds for takeovers and investments in the healthcare sector as well as crystallizing its standalone value, removing some of the “conglomerate discount” that weighs on Siemens’ valuation.
In 2016, utility RWE won BlackRock as an anchor investor in the initial public offering of its Innogy unit. RWE ended up selling a 23.2 percent stake in the networks, renewables and retail unit.
Reporting by Christoph Steitz; Editing by Alison Williams
Scientists at The Scripps Research Institute (TSRI) have peered deep into the heart of a key protein used in drug design and discovered dynamic structural features that may lead to new ways to target diseases. The protein, called the A2A adenosine receptor (A2aAR), is a member of the G-protein-coupled receptor (GPCR) family, which are the targets of roughly 40 percent of all approved pharmaceuticals.
The new, more detailed image of A2aAR’s signaling mechanism reveals key parts of its inner workings, including an amino acid that acts like a “toggle switch” to control signaling across the cell membrane.
“This basic knowledge is potentially helpful for improving drug design,” says Nobel laureate Kurt Wthrich, PhD, the Cecil H. and Ida M. Green Professor of Structural Biology at TSRI and senior author of the study.
The findings were published today in the journal Cell.
Imaging technique reveals how protein changes shape
All human cells contain A2aAR and other GPCRs embedded in their plasma membrane. More than 800 GPCRs have been discovered in the human body, and each has a role in regulating a bodily function. For example, A2aAR regulates blood flow and inflammation and mediates the effects of caffeine. A2aAR is also a validated target for treating Parkinson’s disease and a relatively new target for targeting cancers.
“GPCRs do just about everything you can imagine,” says Wthrich. “But for a long time, drug design was being done without knowing how GPCRs looked.”
For the new study, the researchers aimed to better understand the relationship between A2aAR function and dynamic changes in its structure to help inform drug design.
The research built on previous studies where scientists used an imaging technique called x-ray crystallography to determine A2aAR’s three-dimensional structure. The images showed that A2aAR looks like a chain that crisscrosses the cell membrane and has an opening on the side facing out of the cell. The region of the GPCR structure that sticks out of the membrane interacts with drugs and other molecules to signal to partner proteins inside the cell.
Although crystal structures provided a key outline of the receptor’s shape in inactive and active-like states, they could not show motion and changes in structure when A2aAR meets new binding partners, such as pharmaceutical candidates. In short, the researchers in the new study needed to investigate why A2aAR works the way it does.
To solve this problem, the researchers used a technique called nuclear magnetic resonance (NMR) spectroscopy, which creates strong magnetic fields to locate the positions of probes in a sample. Wthrich is a world-renowned leader in the NMR field and won the Nobel Prize in Chemistry in 2002 for pioneering work in NMR to study the structures of biological molecules. With NMR, scientists can determine the structures of proteins and study their dynamic properties in solution at physiological temperatures–the way they exist in the human body.
In work spearheaded by TSRI’s Matthew Eddy, PhD, first author of the new study, the researchers used NMR to observe A2aAR in many different conformations, shedding light on how it changes shape on the surface of human cells in response to drug treatments.
Importantly, NMR let the team visualize changes in the internal architecture of A2aAR. This took them beyond previous solution NMR studies, which focused on the technically less demanding observation of NMR-observable probes attached to flexible parts of GPCRs, mostly located at or near the surface of the receptor. The approach in the new study enabled researchers to follow the effects of drug binding at the extracellular surface on changes in protein structure and dynamics at the intracellular surface–the structural basis of signal transfer–across the heart of the GPCR.
It was like the researchers had seen a car, and with NMR, they could finally inspect its engine.
Rethinking how we design drugs
Two details in A2aAR’s structure gave researchers insight into how future drugs could manipulate the receptor. One key finding was that replacing one particular amino acid in the receptor’s center destroyed the receptor’s ability to send signals into the cell.
“With this finding, we can say ‘A-ha! It is this change in structure that kills the signaling activity.’ Maybe we can make a change in a drug to overcome this limit,” says Wthrich.
The researchers also revealed the activity of a “toggle switch” in A2aAR. Previous studies suggested that one of the tryptophan amino acids in A2aAR flips up and down in concert with A2aAR’s activity. With NMR, the scientists directly observed this unique tryptophan as it changed orientations in response to different drugs. Chemists could potentially modify drugs to manipulate this switch and control A2aAR signaling.
The researchers emphasize that this new study is potentially relevant for much of the large family of GPCRs. In fact, structural details from this study could apply to more than 600 “class A” GPCRs in our bodies.
ADEN (Reuters) – Nahla Arishi, chief pediatrician at the al-Sadaqa hospital in this Yemeni port city, had not seen diphtheria in her 20-year career. Then, late last month, a three-year-old girl with high fever was rushed to Arishi’s ward. Her neck was swollen, and she gasped for air through a lump of tissue in her throat. Eight days later, she died.
Soon after, a 10-month-old boy with similar symptoms died less than 24 hours after arriving at the hospital.
Two five-year-old cousins were admitted; only one survived.
A 45-day-old boy, his neck swollen and bruised, lasted a few hours. His last breath was through an oxygen mask.
One morning in early December, 16-month-old Sameh arrived at the hospital carried by his aunt and delirious with fever. Arishi immediately recognized a new case of diphtheria. “Put on your mask,” she ordered the aunt.
Sameh’s father, a fighter in Yemen’s three-year war, rushed in, grabbed his son, yanked off the baby’s shoes and threw them on the floor. “Sameh is the light of the house,” he wailed, feeling the boy’s feverish brow and body.
This is the emergency ward to a nation. After three years of warfare, cholera and hunger, Yemen faces a new battle: In the past four months, doctors across the country have recorded at least 380 cases of diphtheria, a bacterial disease that last appeared here in 1992.
Arishi, like her country around her, is struggling to cope. Every month, she and her team drip-feed dozens of Yemen’s half a million severely malnourished children. Her ward has also treated hundreds of the one million people infected by cholera.
This spring, Arishi and her colleagues reopened an abandoned wing of al-Sadaqa hospital, fenced it with chicken wire and created a makeshift cholera treatment center. Now, they are converting part of that center into a diphtheria ward, cordoning off isolation units by barring hallway doors.
But with rusty oxygen tanks and only two functional ventilators in a different part of the hospital – and with the expectation that the cholera epidemic will worsen in coming months — her triage upon triage is no longer working.
“We’re getting more patients but we can’t deal with them. We don’t have supplies. We don’t have money,” said Arishi, “This war has got to end.”
For the past three years, Yemen has been the combat zone of a struggle for regional supremacy between Saudi Arabia and Iran. Riyadh and some of its Arab allies jumped into Yemen’s civil war in 2015 to help quell an uprising by the Houthis, an Islamic political-religious movement backed by Iran. In addition to airstrikes, Riyadh – with U.S. and U.N. backing – has positioned ships in Yemeni waters as a way to stop arms reaching Houthi militia.
But the blockade has ended up isolating a country that was already the poorest in the Middle East. Vital provisions – food, medicine, fuel, medical equipment, batteries, solar panels and more – are not getting through. Humanitarian shipments of food and medicine have mostly been allowed into the country. Yet Saudi-led forces have severely delayed aid shipments or closed ports outright, especially in northern Yemen where fighting and the humanitarian crisis are most acute.
The war and blockade have also thwarted Yemen’s vaccination programs.
Seven years ago, 80 percent of children were fully immunized with three doses of diphtheria, whooping cough and tetanus vaccine, or DTP as the combined shot is called, according to Zaher Sahloul, a critical-care specialist who cofounded a nonprofit called MedGlobal. Now, he says, that has dropped to 60 percent.
Poor record keeping means there are discrepancies in data related to vaccine coverage. Yemen’s Ministry of Health says 85 percent of Yemeni children have been immunized against diphtheria, whooping cough, tetanus, Hepatitis B and bacterial influenza since the beginning of the conflict, a mere two percentage point drop from pre-war years.
In late November, the U.N.’s World Health Organization (WHO) sent a shipment of diphtheria antitoxins – designed to treat those already infected – and vaccines to the capital Sanaa. The vaccines were delayed by the Saudi blockade for a week, the WHO said.
In July, the Geneva-based International Coordinating Group on Vaccine Provision earmarked a million cholera vaccines for Yemen. An initial shipment of 500,000 doses was sent to the African Horn country of Djibouti, and was ready to send on to Sanaa. But the WHO and local authorities in Sanaa decided together to scrap the vaccination plan, citing logistical and technical issues.
“Yemen needs a Marshall Plan,” said Sahloul, who was visiting al-Sadaqa’s treatment center in December. “It is difficult to foresee an optimistic scenario if the current conditions persist,” he said.
DISEASE AFTER DISEASE
Arishi began her medical career in the mid-1990s after Yemen unified following years of conflict between communist and pro-western forces. She joined the al-Sadaqa hospital, which was built in the 1980s with funds from the Soviet Union.
In her two decades at the hospital’s pediatric ward, Arishi has seen Yemen slowly come apart again. Even in the mid 2000s, the country faced widespread hunger because of rising food prices. The feeding center of al-Sadaqa’s hospital, she said, was crowded even before the new civil war began.
In the spring of 2015, Houthi forces, aided by the now-deceased former president Ali Abdullah Saleh, advanced south from their stronghold in the Yemeni capital Sanaa and took over Aden’s airport. It was then that the coalition of Arab states led by Saudi Arabia joined the war and began launching airstrikes against Houthi-held enclaves. Fighting raged until troops backing the officially-recognized government wrenched Aden from Houthi control in July of that year.
During the first months of fighting, al-Sadaqa filled with hundreds of wounded children and adults.
By the middle of 2016, another group of patients began pouring into the hospital. A cholera outbreak that started in Sanaa had spread to Aden. Dehydrated children, their condition made worse by malnutrition, flooded into her pediatric ward. Many did not survive, Arishi said.
Cholera can kill because patients quickly lose their fluids through vomiting and watery diarrhea. When caught early, it can be treated by replacing fluids.
When a second wave of cholera infections swept Yemen in April this year, Arishi and her colleagues decided to set up the new treatment center. They picked a building away from the main wings of the hospital to avoid contamination and repaired it with funds from the WHO and medical aid group Médecins Sans Frontières (MSF). Converting the building, which had been abandoned for two years after the war, required “heavy cleaning work, electricity, water system repairs as well as installing air conditioners,” according to MSF.
Yet, like the country itself, al-Sadaqa was overwhelmed by the cholera epidemic. Nationwide, a million people have been infected, according to the International Committee of the Red Cross. The WHO says cholera has killed more than 2,200 people.
Nahla Arishi, a pediatrician, checks a boy infected with diphtheria at the al-Sadaqa teaching hospital in the southern port city of Aden, Yemen December 18, 2017. REUTERS/Fawaz Salman
Most of the infected were in the populous north of the country. But al-Sadaqa, which took in patients from across south Yemen, was also unprepared. Arishi and her colleagues had expected 10 patients at a time. Instead, by the summer, they were treating more than a hundred, mostly adults, a day.
Since September, the spread of cholera across the country has abated. However, doctors agree that a new wave of infections is likely in March, when the country’s rainy season returns. Cholera spreads more easily in wet weather, because the bacteria live in rivers and coastal waters which swell with the rain. Rain brings sewage into sources of drinking water.
In August, a new disease began to emerge. In Ibb governorate, 170 km south of Sanaa, a 17-year-old boy was diagnosed with diphtheria, according to the WHO.
Diphtheria is caused by bacteria that mainly infect the throat, nose and airways and send toxins into the bloodstream. It has largely receded as a global health threat, because much of the world’s population is protected through routine immunization.
But the disease is highly contagious once it takes root, doctors say, since it spreads in the droplets from coughing and sneezing. Small children are particularly vulnerable because toxins from the bacteria build up a coating of dead tissue that blocks their small airways.
Since the mid-August case, more than 380 patients have been admitted to hospitals across Yemen with diphtheria-like symptoms, according to the WHO. Doctors diagnosed the cases based solely on patients’ symptoms. Close to 40 of the patients have died, by WHO estimates.
The first case of suspected diphtheria reached al-Sadaqa in November. Of the seven children who arrived within a fortnight, nearly all were initially misdiagnosed with mumps or flu. Four died.
Arishi faced the problem of isolating children with symptoms of diphtheria. She asked hospital administrators to block a hallway door with a cupboard. Behind it, she tried to isolate those who might infect others.
But she lacked basic resources to treat the new disease. Al-Sadaqa hospital, like most others in Yemen, does not have the reagents needed to test for diphtheria. In fact, none of Arishi’s diagnoses has been confirmed by laboratory tests.
Marc Poncin, an MSF emergency coordinator in Ibb governorate, said the lack of recent experience means it could be harder to treat diphtheria.
Slideshow (8 Images)
“There has been a loss of knowledge regarding its treatment, because it’s become something of a neglected and forgotten disease,” he said.
After a diagnosis, treatment is far from easy. Doctors can prescribe antitoxins and antibiotics. But until a few weeks ago, Yemen had no such antitoxin stocks.
The United Nations Children’s Fund and the WHO have imported more than 5 million doses of vaccines to immunize children in the worst affected areas. The WHO has already distributed antibiotics to patients and, as prophylactics, to their families.
Some diphtheria patients need emergency surgery to remove blockages from their airways or need machines to breathe. But most of Yemen’s hospitals don’t have such equipment. As of early December, only two of al-Sadaqa’s three mechanical ventilators were working, and the hospital didn’t have an isolated operating room for diphtheria patients.
The lack of resources has caused strains with the hospital’s supporters. When Arishi cordoned off a part of the cholera ward for the incoming diphtheria patients a couple of weeks ago, the WHO was not happy with the decision, according to Hussein Hassan, head of the WHO’s Aden office.
“We cannot confidently say that cholera is over. It is a seasonal problem and it may come back. What happens if another wave starts and the ward is filled with diphtheria patients?” said Hassan.
“I DIDN‘T WANT TO LOSE MY KID”
Arishi says there is another sign that Yemen is breaking down: parents’ waning faith.
She sees more examples of families that have not vaccinated their children because they distrust both their government and international organizations.
Earlier this month she confronted Saleh Khaled, the father of a five-year-old boy called Yasir, who arrived with severe diphtheria symptoms.
“Why did you not vaccinate your son?” Arishi asked.
Yasir’s first cousin, who was also five years old and unvaccinated, had died a few days earlier. When the first symptoms had appeared on Yasir’s neck and chin, the boy’s parents had given him honey.
Khaled said he had heard rumors, years earlier, about children who had died after healthcare workers had allegedly switched vaccine vials with insulin during a door-to-door vaccination campaign.
“I didn’t want to lose my kid because of something like this,” he said. “We don’t trust the people who work in the health department.”
Others in the al-Sadaqa ward that day echoed similar fears.
“We live only because of God’s mercy,” said Khaled Nasser, the father of 16-month-old Sameh. Nasser, a member of a local armed group that fights alongside Saudi-allied forces, said fellow fighters had helped him buy medicine when Sameh got sick.
Arishi herself barely ekes out a living. She makes $210 a month at al-Sadaqa and works at a private clinic three days a week to supplement her income. The mother of three treats neighbors and relatives without getting paid. Her husband, also a pediatrician, works at another clinic in Aden.
For Arishi, war is both burden and inspiration. She says it has made her commitment to medicine stronger.
“If I leave and my husband leaves and everyone leaves, who will stay to treat our patients?” she said. “Aden is my city. It is my responsibility.”
Additional reporting by Kate Kelland in London and Stephanie Nebehay in Geneva. Edited by Alessandra Galloni and Simon Robinson
PARIS (Reuters) – Russia has reported an outbreak of highly pathogenic H5N2 bird flu on a farm in the central region of Kostromskaya Oblast that led to the death of more than 660,000 birds, the Paris-based World Organisation for Animal Health (OIE) said on Friday.
The virus killed more than 44,000 birds in an outbreak first detected on Dec. 17, the OIE said, citing a report from the Russian Ministry of Agriculture.
The rest of the 663,500 birds on the farm were slaughtered, it said in the report. It did not specify the type of birds that were infected.
It is the first outbreak of the H5N2 strain in Russia this year but the country has been facing regular outbreaks of H5N8 since early December last year, with the last one reported to the OIE detected late November.
Bird flu has led to the death or culling of more than 2.6 million poultry between December last year and November this year, a report posted on the OIE website showed.
Neither the H5N2 or H5N8 strains has been found in humans.
The virulence of highly pathogenic bird flu viruses has prompted countries to bar poultry imports from infected countries in earlier outbreaks.
Reporting by Sybille de La Hamaide; Writing by Sybille de La Hamaide and Mathieu Rosemain; Editing by Alison Williams
(Reuters) – About 8.7 million people enrolled in healthcare plans for 2018 using the federal Obamacare marketplace, according to updated government figures released on Thursday.
The number represented a slight decline from the 2017 enrollment figure when about 9.2 million people signed up for health insurance policies from private insurers on the HealthCare.gov platform. It was slightly lower than the 8.8 million figure given last week by the Centers for Medicare and Medicaid Services (CMS).
The revised figure was due to some late cancellations, CMS said.
Proponents of Obamacare, as former President Barack Obama’s healthcare law is known, said the 2018 figure was relatively strong given President Donald Trump slashed the program’s advertising and outreach budget and cut the enrollment period in half.
Critics say the program is a failure as it is expensive and offers few plan choices.
The figures represent individual plan selections for the 39 Exchanges that used HealthCare.gov during the enrollment period which began on Nov. 1 and expired on Dec. 15.
The deadline was extended to Dec. 31 in seven states affected by storms, including Florida and Texas. The figures did not include selections from state-based exchanges which do not use the HealthCare.gov platform.
CMS said it would put out a final report in March including figures from those states.
Reporting by Toni Clarke in Washington; Editing by Andrew Hay
(Reuters Health) – Lead exposure during childhood has been tied to a variety of developmental problems, but a new study suggests it may not be associated with higher odds of criminal behavior later in life.
The study set out to address a flaw in much of the previous research linking lead and crime: mainly that it’s hard to determine how much of this connection might be explained by poverty and other socioeconomic circumstances that can influence both criminal activity and lead exposure.
Researchers followed 553 people born in Dunedin, New Zealand, in 1972 and 1973, when lead exposure was common among children of all economic backgrounds because of widespread use of leaded gasoline. All of the kids were tested for lead exposure when they were 11 years old, and the study team followed them until age 38 to see how many of them were convicted of crimes.
By the end of the study, 154 participants, or 28 percent, had at least one criminal conviction, the researchers report in JAMA Pediatrics. But the odds of this happening were barely influenced by the amount of lead exposure people had during childhood. Just being male had a stronger effect than lead levels, the researchers note.
“Many studies have shown that higher exposure to lead could predict more criminal behavior, but our study actually found that there isn’t a clear connection between the two,” said lead author Amber Beckley, a researcher at Duke University in Durham, North Carolina.
The reason for the different results this time is that the current study found children from all walks of life had high lead levels, Beckley said by email.
“In our study, socioeconomic status was not associated with childhood lead exposure,” she added.
There’s no safe level of lead exposure. This toxin can damage the developing nervous system in young children, and blood lead levels as low as 5 micrograms per deciliter may lower intelligence quotient (IQ), according to the World Health Organization.
Participants in the current study had average blood lead levels more than twice that high when they were 11 years old in the early 1980s: 11.01 micrograms/dL.
Blood lead levels ranged from 4 to 31 micrograms/dL and didn’t vary according to socioeconomic status.
To see how many of these kids were later convicted of crimes, researchers searched police records and also interviewed participants six times to inquire about any criminal activity.
A total of 68 participants, or 12 percent, had a single criminal conviction and another 86 people had more than one conviction, the study found.
Only 53 people were violent offenders, while 101 participants were convicted of non-violent crimes.
Childhood lead exposure didn’t appear to influence at all whether people would commit violent crimes or become repeat offenders.
But it did appear to influence the odds that teens would participate in criminal activity, though this connection was weak and didn’t persist over time, the authors conclude.
One limitation of the study is that children only got one blood test for lead exposure, and multiple assessments can give a more accurate picture of total exposure, the researchers note. It’s also possible that results would be different today, when children typically have less exposure to lead than they did in the 1970s and 1980s.
It’s also possible that the connection between childhood lead exposure and criminal behavior might be stronger than the authors concluded, David Farrington of Cambridge University writes in an accompanying editorial. It may not be appropriate to describe the strength of the connection as “weak,” Farrington writes.
“More research is needed, of course, to investigate the independent, interactive and sequential effects of blood lead levels in relation to other risk factors for offending,” Farrington writes. He didn’t respond to emails seeking comment.
SOURCES: bit.ly/2lo9xSh and bit.ly/2lniM51 JAMA, online December 26, 2017.
CHICAGO — The day before his 30th birthday, Marqus Valentine was in a panic. “I was so scared for midnight to come rolling around because subconsciously I was like, ‘This is it. Tomorrow’s my last day on Earth,’” he said.
Valentine has sickle cell disease, an inherited blood disorder, and his doctors had warned him throughout his life that he was not likely to make it to 30.
That birthday passed without event, and so have four more. Still, Valentine’s disease has left him severely disabled and ill. “Instead of 34, I feel like I’m 68, just with all the stuff I’ve been through,” he said.
He uses a portable oxygen tank, needs a hip replacement and sleeps in a hospital bed on the first floor of his parents’ house — he is in too much pain to make it up the stairs to his bedroom. And an early death still looms: “I could wake up in the morning, brush my teeth, eat breakfast and by the time afternoon comes rolling around, I could possibly be dead.”
Like many people with sickle cell, Valentine has watched as one successful advocacy campaign after another brought attention and resources to other disorders, including breast cancer, HIV, cystic fibrosis and Lou Gehrig’s disease (amyotrophic lateral sclerosis or ALS). But little is heard about sickle cell. With drug development and other treatments, outcomes for the vast majority of diseases have improved over the past few decades, while life expectancy for sickle cell patients has declined.
To sickle cell patients and their families — most of whom are African-American — efforts to fight the disease appear slow, underfunded, ineffective or too limited in scope, perpetuating disparities that have existed for more than a century.
“You feel like the baldheaded stepchild that no one cares about,” Valentine said from his bed at Edward Hospital in Naperville, Ill., where he was recovering from one of his bimonthly blood transfusions. A catheter dangled from his neck. “What about us? We’re here too.”
Sickle cell disease affects an estimated 100,000 people in the United States, causing chronic pain, multi-organ failure and stroke. With annual costs to treat the disease soaring past $1 billion, new efforts are afoot to improve the lot of patients. But each of these developments faces limitations and obstacles:
In July, the FDA approved the first new drug to treat sickle cell in two decades. Yet specialists say the drug, Endari, will likely have limited benefit, and insurers are already balking at covering it. Physicians associations are working to disseminate guidelines to improve care and reduce discrimination against sickle cell patients, who often are assumed to be drug addicts when they come to emergency rooms in severe pain. Still, there has been so little research on sickle cell that it is difficult even to write evidence-based protocols.
Legislation in Congress to fund research and treatment, stalled since 2009, is finally moving out of committee. But the bill would provide only $4 million — less than half its original funding level.
Meanwhile, most sickle cell patients struggle to access even the most basic care.
“It’s appalling. This country ought to be ashamed of itself,” said Valentine’s mother, Francesca Valentine, who has been a registered nurse for over 35 years and, with Marqus and the rest of the family, has become an activist for sickle cell patients. “I am baffled that in 2017, we’re still not treating the disease based on science, and we still deal with racism and stigma and inaccurate information.”
Francesca Valentine, a sickle cell mother and advocate, sits in her home in Lisle, Ill. (Jenny Gold/Kaiser Health News)
The Fight For Medicine
Francesca Valentine is gearing up for a fight with her insurance company over Endari, the new FDA-approved drug, which will likely be on the market in January. Endari is a highly refined version of a nutritional supplement called L-Glutamine, which has been shown to relax the stiff, sickle-shaped red blood cells of people with the disease. It’s the first of a number of new drugs in the pipeline and will cost about $3,300 per month for the average adult.
But many insurers plan to restrict how the drug covered.
Several, including the Valentines’ Blue Cross Blue Shield’s Federal Employee Program, will cover Endari only if patients have “failed first” at other treatments, including blood transfusions and hydroxyurea (the only other drug available to treat sickle cell) — even though in studies Endari appeared to be of benefit when given in conjunction with other treatments.
At least one insurer, Cigna, which covers 15 million people, says it will not cover Endari at all because it is a nutritional supplement.
If insurance doesn’t cover the drug for her son, Francesca Valentine said she and her husband would both need second jobs. Because Marqus is disabled, he is on his mother’s insurance plan, which she gets through her job at the Department of Veterans Affairs. If necessary, she plans to challenge her insurer by writing letters explaining the science. “It’s like this disease has to fight for everything. We should not have to fight for everything,” she said.
A nurse removes the catheter from sickle cell patient Marqus Valentine’s neck, following a blood transfusion at Edward Hospital in Naperville, Ill. (Jenny Gold/Kaiser Health News)
Marqus Valentine prepares to take his evening medications, including hydroxyurea, until recently the only FDA-approved drug for sickle cell disease. (Jenny Gold/Kaiser Health News)
While the Valentines and many other sickle cell families have high hopes for Endari, doctors already question whether it will mark a significant improvement in care.
“We have one treatment option, so it’s lovely to have a second treatment option, but I don’t think this will change the world of sickle cell,” said Sophie Lanzkron, who directs the adult sickle cell clinic at Johns Hopkins Medicine. “It’s not a game changer.”
And because Endari is a powder that must be taken twice a day, Lanzkron worries it will be an inconvenience for patients, leading to poor compliance.
As it stands, few patients even receive the current standard of care: hydroxyurea. The chemotherapy drug, approved for sickle cell treatment in 1998, is considered safe and costs less than $100 per month.
About 3 in 4 sickle cell patients who could benefit from hydroxyurea are not being treated with it, according to a study published in 2015 in the Journal of the American Medical Association.
“We should be prescribing it to everybody who’s eligible, and everyone who’s eligible should be taking it,” Lanzkron said.
Some patients do not want to take it because of side effects such as hair loss, skin changes and nausea, but many others lack access to doctors who understand how to prescribe the drug.
“What amazed me are the number of people in their 30s who have never seen a hematologist,” said Julie Kanter, who runs the sickle cell program at the Medical University of South Carolina in Charleston. Many hematologists do not treat sickle cell patients, and a 2014 survey found that just 20 percent of family physicians are comfortable caring for them, mainly due to a lack of training on the complex disease.
“In general, 80 percent of the patients are not well cared for, are not on the right medications and have not been screened for the right issues,” said Kanter.
Francesca Valentine has been advocating for her son Marqus, who has sickle cell disease, since he was born. (Jenny Gold/Kaiser Health News)
The Fight For Informed Care
Instead, these patients often go to emergency rooms in severe pain, as the misshapen red blood cells clog the vessels and cut off oxygen to joints and organs.
“It feels like you want to die almost. You just want the pain to stop — nothing but pure, unfiltered pain,” Marqus Valentine described. “Your mind starts to race, your brain cannot process it. And it just doesn’t stop. It does not stop until someone intervenes and you get medication.”
But emergency room doctors rarely understand how to treat these crises, and many patients are misdiagnosed and inappropriately sent home, said Patricia Kavanagh, a pediatrician and emergency department physician at Boston Medical Center. “What we learn about sickle cell disease in med school is usually covered in 20 minutes.”
Nearly 40 percent of sickle cell patients have to be readmitted to the hospital within 30 days — more than for any other diagnosis, according to the federal government’s Agency for Healthcare Research and Quality.
Kavanagh brought protocols established by national experts for sickle cell treatment to her own emergency room, but says ER doctors are “coming late to the table.”
In 2014, the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, put out guidelines for physicians, and 11 national organizations endorsed the protocols — not the American College of Emergency Physicians (ACEP), however.
Recently, Kavanagh has been working with ACEP to get more emergency departments to adopt the guidelines and to triage sickle cell patients faster, so they don’t have to wait for care in a crisis or get misdiagnosed.
But protocols are only as good as the science behind them, and “the evidence for most of the guidelines is not strong,” because there have not been enough studies on the disease, said Rosalyn Stewart, a Johns Hopkins physician who is an investigator on a federal grant to improve care for people with sickle cell.
“In the totality of health care, the research that has been devoted to sickle cell has been very small compared to other diseases with the same frequency,” she said.
The Fight For Funding
Sickle cell funding pales in comparison to other diseases. Cystic fibrosis, which affects 30,000 people in the U.S., for example, gets seven to 11 times more funding per patient than sickle cell disease, according to a 2013 study in the journal Blood. The ALS challenge in 2014 raised $115 million for approximately 20,000 patients in the U.S.
There are some new studies in the works, including eight funded by the Patient-Centered Outcomes Research Institute, but many questions remain unanswered.
One major problem is that no national data registry exists for sickle cell disease, unlike most other diseases, said Mary Hulihan, director of the sickle cell program at the Centers for Disease Control and Prevention.
Marqus Valentine sits on the edge of his hospital bed, following a blood transfusion at Edward Hospital in Naperville, Ill. (Jenny Gold/Kaiser Health News)
“It means we don’t know what is happening to the patients. We don’t have even basic information like how many people in the U.S. have sickle cell disease or where they are getting their health care or what their health care utilization looks like,” said Hulihan. “The most basic questions you would like to have answered cannot be answered at a national level for this condition. It makes things very difficult.”
Congress has not passed funding or a directive for such a registry, said Hulihan, so instead the CDC Foundation has obtained limited funding from pharmaceutical companies to collect data — and only in California and Georgia. There is no funding to expand the program to other states.
So far, Congress has taken little action. In 2004, it provided $10 million per year in funding for sickle cell research, surveillance and treatment as part of the American Jobs Creation Act, but those funds expired in 2009.
Since then, Rep. Danny Davis (D-Ill.) has been trying to get a reauthorization passed, with little success. “Sickle cell does not have the priority in this country that it had in the 1960s, when I started working on it,” said Davis. “Congress has been cutting everything that wasn’t nailed down.”
Family photos hang on the wall of the Valentines’ home in Lisle, Ill. (Jenny Gold/Kaiser Health News)
Even with all the delays and setbacks, experts and patients alike remain hopeful that the treatment of sickle cell disease can gain momentum and attention.
“Things are happening that have never happened before. I’ve been around sickle cell for a while, and never before have you seen this kind of buzz,” said Derek Robertson, president of the Maryland Sickle Cell Disease Association. Robertson, whose brother died in 1977 from the disease, said he would like to see sickle cell take its turn on the national stage.
“I would like to see the NBA have a day where they talk about sickle cell or wear a color. I don’t realistically expect sickle cell to be like breast cancer, but we could have more. I don’t know if LeBron James knows about sickle cell disease.”
(Reuters Health) – An experimental blood test accurately identifies people who do, or don’t, have celiac disease, even if they are following gluten-free diets, researchers say.
Celiac disease is an autoimmune disorder that affects roughly one percent of people in the U.S. Those with the disease must avoid foods that contain the gluten protein from wheat, barley or rye. But far more than one percent of the population is following a gluten-free diet, which makes it harder to diagnose real cases of celiac disease.
The two main blood tests used to screen for celiac disease rely on detecting an immune response to gluten, but that immune response gradually disappears in people who avoid gluten.
“Unfortunately, many persons with gluten sensitivity go gluten-free without consulting their clinician for exclusion of celiac disease,“ said lead study author Dr. Vikas K. Sarna’s from Oslo University Hospital in Norway. ”In such cases, guidelines recommend . . . performing a gluten challenge involving daily consumption of gluten for up to 8 weeks, followed by an endoscopic procedure for a biopsy taken from the small intestine (duodenum). Our blood test may replace such a gluten challenge and duodenal biopsy.”
The new test is designed to detect immune cells in a blood sample that are specifically targeted at gluten proteins, even when the individual hasn’t been recently exposed to gluten.
Sarna’s team tried their test on 62 patients with celiac disease and 19 individuals without celiac disease who were on a gluten-free diet, 10 patients with celiac disease who were eating foods containing gluten and 52 healthy individuals following normal diets. They also used the currently available celiac tests on these participants for comparison.
The old tests detected celiac disease in 9 out of 10 patients who weren’t on a gluten-free diet. But the old tests identified celiac disease in only 4 of the 62 patients who’d been following a gluten-free diet.
The new test, by comparison, was 96 percent accurate in distinguishing celiac disease patients from people who didn’t have celiac disease but were still following gluten-free diets.
It was 95 percent accurate for distinguishing celiac disease patients who were eating gluten-containing foods from healthy individuals following normal diets, the researchers report in Gastroenterology.
“We calculated that our test is stronger to exclude rather than confirm the diagnosis of celiac disease in gluten sensitive persons,” Sarna said. “Although we need more research in this field, we propose that the test be used to exclude celiac disease in persons on a gluten-free diet,” he told Reuters Health by email.
“It is important to point out that this test is still not available for commercial use, although there is a huge demand of a test for celiac disease that can be applied for persons that are already on a gluten-free diet,” Sarna said. “I do hope that the promising results from our study can initiate commercial initiatives along with more research, to allow this test to be used in the general public in the near future.”
Several members of the research team have applied for a patent on this testing technology, and some disclose that they are consultants for companies. The clinical trial in the current study was paid for by the Research Council of Norway, the authors note.
”Researchers are actively working to identify tests that may allow for screening for celiac disease in patients on a gluten-free diet,” said Dr. Maureen Leonard from Harvard Medical School’s Center for Celiac Research and Treatment in Boston, who was not involved in the study. “These are not clinically available tests and require further work before they are accurate and available for clinical use,” she said in an email.
“Additionally, these tests may benefit only people with a certain genetic background,” Leonard said. “Therefore, the general public should be aware that before self-imposing a gluten-free diet they must be tested for celiac disease.”
Celiac disease must be confirmed with a duodenal biopsy, Leonard added. “If a patient begins a gluten-free diet prior to being screened for celiac disease, all available blood tests to screen for celiac disease and duodenal biopsies will no longer be accurate.”
SOURCE: bit.ly/2B7EeBP Gastroenterology, online November 13, 2017.