Can Stem Cells be Used to Treat Epilepsy?

Epilepsy is a neurological condition characterised by recurrent episodes of seizures. Most cases of epilepsy do not have a clear known cause, apart from susceptible genetic factors.
The primary pathogenesis of genetic forms of epilepsy is an abnormal expression of certain receptors in the brain that lead to an enhanced excitation and reduced inhibition. Some cases occur following oxygenation deprivation during birth.
Other later-life forms of epilepsy may be attributed to damage to the brain e.g. stroke, brain tumours, traumatic brain injury, drug misuse or a brain infection.
To date, there are several key treatment strategies to help people have fewer seizures. Predominantly, anti-epileptic drugs are used to treat the frequency and severity of epilepsy. However, these have to be taken routinely, and are not a long-term solution. They also have many undesired side-effects. However, anti-epileptic drugs may not work for everyone, therefore other treatments are used, including surgery and dietary modifications (e.g. keto-diet). Therefore, the need to find effective long-term solutions is needed to treat epilepsy.

 

What are Stem Cells?

Stem cells are cells that have the ability to develop into different specialised cell types of the body. Most cells in the body are post-mitotic, meaning they are unable to divide and grow into new types of tissues. However, stem cells are able to divide after periods of no apparent activity and are able to transform into different body cell types, including muscle cells, nerve cells and blood cells.

 

Stem cells therefore have the potential to be used in the treatment of many disorders where the normal body cells are dysfunctional or abnormal. This includes conditions where the body’s own cells begin to degenerate e.g. stroke, heart attacks, spinal cord injury and macular degeneration.
Traditionally, stem cells were only able to be isolated from embryos (animal and human) and some adult somatic stem cells, such as those found in e.g. bone marrow. However, due to advances in science and technology, adult cells taken from tissues such as e.g. skin, are now able to be reprogrammed into stem-cell like cells called induced pluripotent stem cells (iPSCs). These iPSCs may be able to function in very similar ways to those previously only obtainable through embryo donation.
iPSCs can be genetically manipulated to form a variety of different body cells e.g. neurons and muscle cells. However, much more work is needed before iPSCs can be used to replace dysfunctional cells within the body, though many advances have been made, especially in animal studies, including successful replacement of damaged heart cells with lab grown heart cells from the animals.

Can Stem Cells be Used to Treat Epilepsy?

As most cases of epilepsy can be attributed to receptor expression differences within the brain (due to mutations), correcting these may in theory reduce the likelihood of electrical seizures developing in the brain.
In addition, during status epilepticus, the excitation overload sometimes kills neurons, especially within the hippocampus. This can actually worsen the condition over time and lead to the development of temporal lobe epilepsy (TLE). Whilst anti-epileptic medication may treat the seizures, the damage caused to the temporal lobe is often irreversible and permanent, and current therapies do not address this.
As previously discussed, the reduction in inhibition in the brain, primarily due to loss of GABA-ergic interneurons, coupled with increased excitation of neurons, is key in the development of epilepsy including TLE.
Scientists therefore have speculated that enhancing inhibition by GABA-neurons may alleviate status epilepticus due to renewed inhibitory balance.
A study by Upadhya and colleagues (published in 2019 in PNAS); aimed to investigate whether iPSCs grafted into the brain of rats could reduce seizures and reverse damage in the hippocampus. They found that medial ganglionic eminence (MGE) cells derived from human-derived iPSCs, grafted into the hippocampus successfully reduced the frequency of seizures and reduced GABA-ergic neuronal loss.
Furthermore, there was an improvement to cognition and mood. Although this study was performed in rats, the implications of this research has far reaching potential to be used clinically.
Another study, a Phase I clinical trial in 22 patients, using autologous mesenchymal stem cells in epilepsy patients was shown to reduce overall seizure frequency (published in Advances in Medical Sciences by Hlebokazov and colleagues in 2017). Stem cells were obtained from patients’ own bone marrow, and administered intravenously and through a single injection into the spinal cord. After 1 year, 3 out of 10 patients achieved complete remission (no seizures) and another 5 patients that previously did not respond to drugs began to respond favourably. No side effects were observed in any of the patients.
This study is promising and showed a good safety profile for the patients. It appears that stem cells were associated with  alleviation of pathological hallmarks as well as the symptoms of epilepsy. Though this was only a Phase I trial with a very small cohort, additional controlled trials with placebos are needed in a larger cohort to make any definitive conclusions on the efficacy and safety.
In summary, stem cell based therapies, show promising results in the treatment of diseases including epilepsy. Animal and clinical studies have shown the remarkable efficacy of stem cells’ regenerative properties. However, larger clinical trials are needed before stem cell therapy can become routine. It is also expensive with therapies starting at around $5,000-$8,000 per treatment, though they can be as expensive as $25,000. In the UK, the NHS does not offer stem cell therapy routinely, only for a very small number of people in designated centres for diseases such as MS.
In the United States, the only type of stem cell therapy that has been extensively studied and approved for human treatment involves use of hematopoietic stem cells for patients with certain types of cancer.

Sources:

1. NHS.uk, 2019. Epilepsy. https://www.nhs.uk/conditions/epilepsy/
2. NIH.gov, 2019. Stem Cell Information. https://stemcells.nih.gov/info/basics/1.htm
3. Upadhya et al, 2019. Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration. PNAS. 116(1):287-96. https://www.pnas.org/content/116/1/287.short?rss=1
4. Hlebokazov et al, 2017. Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. Adv Med Sci. 62(2):273-279. https://www.ncbi.nlm.nih.gov/pubmed/28500900

https://www.news-medical.net/health/Can-Stem-Cells-be-Used-to-Treat-Epilepsy.aspx

Cutting opioid prescriptions by stopping pain before it starts

Doctors today are reducing their patients’ need for strong opioid medications after surgery by pre-treating patients with other pain relievers before they even enter the operating room.

While opioids relieve patients‘ pain and suffering, between 8% and 12% of those who take these drugs develop an opioid use disorder. At Keck Medicine of USC, health professionalsare part of a national mobilization effort to tackle the crisis at one of its sources: the doctors who prescribe the drugs.

How? By reducing the need for narcotics among patients undergoing operations.

“Our goal is to fight the opioid epidemic by decreasing the pain so patients need less opioids after surgery,” says Keck Medicine anesthesiologist Michael Kim. “After all, the best way to reduce opioid misuse is to avoid using them in the first place.”

Kim—an assistant professor of anesthesiology with the Keck School of Medicine of USC—and his colleagues lead Keck Medicine’s Enhanced Recovery After Surgery (ERAS) program. ERAS is a slate of nationally recognized practices that help patients recover well while simultaneously reducing the need for opioid medication. And the results are striking: Some surgical groups at Keck Medicine have slashed their opioid usage by 50 to 80% over the past year through ERAS.

Step 1: Start with Non-opioid Pain Medication

A growing body of research suggests that following a non-opioid pain medication protocol improves patient outcomes and speeds up recovery.

Carol Peden, professor of anesthesiology with the Keck School of Medicine, says, “prior to the current systemwide approach with ERAS, we had pockets of excellence with Keck Medicine surgeons using these techniques. Now we are systematically embedding this approach across service lines, so more patients benefit.”

When Peden saw her first patient treated with an ERAS approach, she couldn’t believe her eyes. “I walked in the morning after he had a major bowel resection, and he was sitting out of bed, alert and smiling,” says Peden, who has international experience with ERAS. The strategy is effective, in part, because the care starts before surgery: The patient and family are prepared and working with their health care team to meet common goals.

Here’s how it works:

Pre-treat the Pain Before Surgery

Research confirms that patients do better when they know what to expect, especially when pain is involved. Keck Medicine physicians develop a roadmap of patients’ health care from pre-op through recovery.

“Before they ever set foot in an operating room, patients know their projected length of hospital stay, their expected level of pain and how long it will take to get back to their usual activities,” Kim says. When surgeons make their first incision, the body reacts to the injury, initiating a reflex stress response. But under ERAS, doctors blunt that response by “pre-loading” patients with non-narcotic pain relievers, such as acetaminophen (Tylenol), gabapentin and non-steroidal anti-inflammatory drugs like ibuprofen, for up to three days before surgery.

They also educate patients to drink sufficient fluids, eat a healthy diet, exercise and avoid alcohol and smoking before surgery.

Fewer Medications During Surgery

Since patients receive some pain-relieving medication prior to surgery, doctors are able to use fewer medications during the procedure. In many cases, doctors also use local pain blocks to minimize pain during and after surgery to help relieve pain without making the patient feel groggy.

Guided Recovery After Surgery

Patients begin a regimen of non-opioid pain medication around the clock to help them meet targeted milestones after surgery. “Each patient gets a goal sheet with specific guidelines for when they should drink, eat and start moving,” says Kim. “The goals are designed to help them get well quickly and send them home without exposure to potentially addictive medications.”

Patients Feel Better

Traditionally, patients came out of surgery sleepy and needing strong painkillers. With ERAS, patients are alert, awake, comfortable and moving around within a few hours of surgery. Since rolling out ERAS in April 2018, Kim and his colleagues have seen these benefits:

• Significantly reduced opioid use

• Reduced rate of postoperative complications and readmissions

• Reduced average hospital stays by up to 21%

• Reduced variance in care

• Improved patient satisfaction

“The impact has been so dramatic it gives me chills just thinking about it,” Kim says. Cardiothoracic surgery patients are going home with minimal narcotics. Ear, nose and throat patients are spending less time in intensive care. And urology patients are getting their bladder catheters out two days earlier, he adds.

Who Practices ERAS at Keck Medicine?

ERAS is only effective when every person who has contact with patients knows the protocol, including schedulers, nurses, pharmacists, physical and occupational therapists, and nutritionists.

“This has been an incredible systemwide effort to give the patient the best experience possible,” Peden says. “We even have nurses who are coming in at 4 in the morning to ensure the night shift staff know the protocol.”

At USC, seven surgical groups currently follow the ERAS practices: cardiovascular, thoracic, colorectal and spine surgery; gynecologic oncology; otolaryngology; and urology. In the pipeline for 2019-20 are vascular surgery, orthopedic oncology, plastic surgery, bariatric surgery and liver/kidney transplant surgery. Within a few years, Kim projects that 60 to 70% of Keck Medicine operations will follow an ERAS protocol.

“The program is successful because health care professionals have come together as a team to deliver this incredible care. The team sees visible improvement in their patients. They are much more alert and comfortable, and they get out of the hospital more quickly,” Kim says. “We’re enhancing recovery for patients, and in the process, actively fighting the opioid epidemic from the front end by decreasing the patients’ need for narcotics.”

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Explore further

Opioid use down with ‘enhanced recovery after surgery’ program

https://medicalxpress.com/news/2019-07-theyre-opioid-prescriptions-pain.html

Medicare weighs whether to pay for acupuncture

Seeking ways to address chronic pain without narcotics, Medicare is exploring whether to pay for acupuncture, a move that would thrust the government health insurance program into the long-standing controversy over whether the therapy is any better than placebo.

Coverage would be for chronic low-back pain only, a malady that afflicts millions of people. Low-back pain, acute and chronic, ranks as the third-greatest cause of poor health or mortality in the United States, behind only heart disease and chronic obstructive pulmonary disease, according to the National Institutes of Health.

In its request for comments on acupuncture, the Department of Health and Human Services said that “in response to the U.S. opioid crisis, HHS is focused on preventing opioid use disorder and providing more evidence-based non-pharmacologic treatment options for chronic pain.”

The agency said it hopes “to determine if acupuncture for [chronic low-back pain] is reasonable and necessary under the Medicare program.” A proposal is due by July 15, with a final decision by Oct. 13.

Chronic pain — generally defined as pain that lasts 12 weeks or more — is a complex disorder with numerous causes and many possible treatments. But there is widespread agreement that health-care providers have overused powerful opioid painkillers to address it, with little research to support that approach.

Currently, Medicare covers injections, braces, implanted neurostimulators and chiropractic care as well as drugs for chronic low-back pain, under certain conditions set by the program.

Acupuncture continues to gain legitimacy for pain relief in the United States. A 2014 review reported that more than 10 million acupuncture treatments are administered each year. Some insurance companies cover the practice, respected medical institutions offer it, and schools of acupuncture produce new practitioners. The Department of Veterans Affairs has trained 2,400 providers to offer “battlefield acupuncture,” five tiny needles inserted at points in each ear, for pain relief.

Medicare coverage “is long overdue,” said Tony Y. Chon, director of integrative medicine and health at the Mayo Clinic in Minnesota. “The opioid epidemic is going to be the momentum that’s really needed to push not just acupuncture but other kinds of non-pharmacological interventions to the forefront.”

Some proponents also note that acupuncture is one of the safest interventions available for pain — though some accidents have been reported. Even if it works only for some people, they argue, there is little harm in trying it when other options are not effective.

Taken overall, however, research shows that acupuncture is little more effective than placebo in many cases. When the government’s Agency for Healthcare Research and Quality reviewed research on a wide range of therapies for chronic pain in 2018, it found the “strength of evidence” that acupuncture works for chronic low-back pain is “low.”

The National Center for Complementary and Integrative Health, part of NIH, says “research suggests that acupuncture can help manage certain pain conditions, but evidence about its value for other health issues is uncertain.”

For low-back pain, the institute cites a study that found it “more helpful than either no acupuncture or simulated acupuncture.” But another found “strong evidence that there is no difference between the effects of actual and simulated acupuncture,” according to its website.

Critics go further, noting that hundreds of years of anatomical studies have not found evidence of the points in the body linked to the “energy channels” that acupuncture claims to be stimulating to provide pain relief. They contend that acupuncture shows all the signs of the placebo effect, with providers and recipients who believe it works and the elaborate ritual of placing the needles in specially selected spots.

“The whole thing is a big scam,” said Steven Novella, an assistant professor of neurology at the Yale School of Medicine and editor of the “Science-Based Medicine” website. “The only honest interpretation of the data is that acupuncture is a theatrical placebo.”

In part, the controversy has lingered because acupuncture is difficult to study. The practice involves inserting tiny needles into the skin, so patients who do not receive that treatment provide a poor comparison, or “control” group. Researchers have turned to “sham acupuncture,” using needles that appear to pierce the skin but retract like stage daggers. In that way, neither the practitioner nor the patient knows whether acupuncture is being administered, eliminating some of the bias that confounds studies.

A 2018 review of 39 studies involving nearly 21,000 patients has buoyed acupuncture proponents. It concluded that “acupuncture was superior to sham as well as no acupuncture control for each pain condition.”

“With this kind of research evidence behind it, why hasn’t acupuncture been accepted?” asked Vitaly Napadow, a neuroscientist and practicing acupuncturist at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital. “And the reason, in my opinion, is that acupuncture is being held back by philosophy.” Specifically, he said, Western medicine is slow to change despite acceptance of acupuncture by patients because the concepts come from Eastern medicine.

“Not everybody is going to want to try it,” said Lisa Conboy, director of research at the New England School of Acupuncture, part of the Massachusetts College of Pharmacy and Health Sciences. “It’s a different way of looking at the world. I think it makes some people nervous to have a whole other set of medical professionals.”

But Alan Levinovitz, an associate professor of religion at James Madison University, who has studied Chinese thought and medicine, said acupuncture represents the blurring of the lines between ritual and medicine. To the extent that rituals alleviate pain, that is a good thing — but not a reason to cover them with taxpayer-funded insurance, he said.

“One concern would be that we would cover acupuncture as if it were a physiological treatment, when in fact it is a psychological treatment,” he said.

Novella said that the efficacy attributed to acupuncture in the 2018 review could easily be explained by various research biases and that no drug would be allowed on the market based on that level of proof.

“We never get that threshold of evidence that you need in medicine, where you get that persistent effect, and it’s replicable” across numerous studies, he said.

https://www.washingtonpost.com/health/medicare-weighs-whether-to-cover-acupuncture/2019/07/02/0e7ad7c2-9c14-11e9-b27f-ed2942f73d70_story.html

Cal. widens probe of docs issuing questionable vaccine exemptions

The Medical Board of California’s investigations are unfolding amid the nation’s worst measles outbreak in more than a quarter-century.

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KEY TAKEAWAYS

The crackdown comes as California lawmakers consider legislation to tighten the requirements for exempting children from the vaccinations required to attend schools and day care.

The CDC says vaccine exemptions for medical reasons should be rare, and typically reserved for children with severely compromised immune systems.

The California agency that regulates doctors is investigating at least four physicians for issuing questionable medical exemptions to children whose parents did not  want them immunized.

The Medical Board of California’s investigations are unfolding amid the nation’s worst measles outbreak in more than a quarter-century, as California lawmakers consider controversial legislation to tighten the requirements for exempting children from the vaccinations required to attend schools and day care centers.

Last month, the Department of Consumer Affairs, which oversees the medical board, sued in state court to obtain medical records for patients of Sacramento-area pediatricians Dr. Kelly Sutton and Dr. Michael Fielding Allen.

In the past nine months, the board also has sought patients’ records in connection with two Santa Rosa physicians under investigation for writing allegedly inappropriate exemptions.

The state acted on the Sutton and Allen cases following complaints to the medical board from Dr. Wendy Cerny, assistant chief of pediatrics at a Kaiser Permanente clinic in Roseville, court documents show. (Kaiser Health News, which produces California Healthline, is not affiliated with Kaiser Permanante.) Cerny contacted the board about Sutton in February 2017 and followed up with an email about Allen 15 months later, according to the documents.

Cerny became concerned after seeing permanent medical exemptions for Kaiser Permanente pediatric patients written by Sutton and Allen that cited reasons including “a personal history of genetic defect,” food and environmental allergies, “neurological vulnerability” and a family history of mental health disorders, according to the legal documents.

The doctors under investigation are not Kaiser Permanente doctors, but parents went to them for vaccination exemptions. In one case, Sutton issued a “lifelong medical exemption from all vaccines” to a boy before his family joined Kaiser Permanente, according to Cerny’s complaint. When one of Cerny’s colleagues refused to write similar exemptions for the boy’s two younger siblings, the mother said she would go back to Sutton to get them, the complaint says.

“We feel this doctor and perhaps her colleagues … are making easy money on these exemptions that are not based on true medical need and are actually putting children and other people in the community at risk for contracting and spreading serious infectious diseases,” Cerny wrote in her complaint about Sutton.

A physician appointed by the medical board to review exemptions issued by Sutton and Allen described them as “either of questionable validity or patently without medical basis.”

Vaccine exemptions for medical reasons should be rare, according to the Centers for Disease Control and Prevention. They are typically reserved for children with severely compromised immune systems, like those being treated for cancer or those who are allergic to a vaccine component or have previously had a severe reaction to a vaccine.

A spokesman for the medical board declined to comment on the cases. The agency generally does not acknowledge investigations publicly unless a formal accusation is filed against a physician.

But the board’s legal efforts to obtain patient records sheds rare light on how the agency handles such complaints.

It “tells me that there are doctors who are giving problematic exemptions and the Medical Board of California is taking this issue very seriously,” said Dorit Reiss, a professor at University of California-Hastings College of the Law in San Francisco who researches vaccine law.

Sutton and Allen did not respond to phone calls and emails seeking comment.

Sutton, based in Fair Oaks, is known as a go-to doctor for medical vaccine exemptions. She offers a $97 “program” that purports to “help protect your child from the ‘One Size Fits All’ California vaccine mandate.”

Cerny submitted copies of exemption letters by Sutton and Allen in the complaints she filed with the medical board, but the names of the patients were blacked out. The board wants the names of those children and their parents, and it asked the court to compel the Permanente Medical Group, a subsidiary of Kaiser Permanente, to hand over unredacted versions of the letters.

The board also wants Kaiser Permanente to hand over the patients’ medical charts, which it believes will help determine whether the exemptions written by Sutton and Allen were indeed unmerited.

In June, Superior Court Judge Ethan Schulman ordered the Permanente Medical Group to disclose the names of the patients known to have received medical exemptions from Allen, as well as the names and addresses of their parents. He has not yet issued a ruling in the Sutton case.

Kaiser Permanente said it would comply with court orders.

“We take the health and safety of our members, patients and communities very seriously,” said Dr. Stephen Parodi, associate executive director of the Permanente Medical Group, via email.

In a case similar to Sutton’s and Allen’s, a judge ordered the Permanente Medical Group in November to provide the names of patients and parents subpoenaed in a medical board investigation of Dr. Kenneth Stoller, a Santa Rosa physician who gave vaccine exemptions to children who were Kaiser Permanente patients, as well as to others in the Mammoth Unified School District.

Stoller, who is not affiliated with Kaiser Permanente, is also being investigated by the city attorney of San Francisco, where he used to practice. He didn’t respond to a request for comment.

In April, Judge Schulman granted a petition from the state ordering Dr. Ron Kennedy to hand over the medical records of children to whom he had issued vaccination exemptions. Kennedy, a psychiatrist who runs an anti-aging clinic in Santa Rosa, has written numerous exemptions for kids, according to court records.

Kennedy’s lawyer, Michael Machat, said his client has handed over the records as ordered.

“The medical board has adopted the practice of thinking it can invade people’s privacy and search children’s private medical records to see whether or not the doctors are following the law,” Machat said. “Where does this stop?”

To date, the only doctor sanctioned for inappropriate medical vaccine exemptions is Southern California pediatrician Robert Sears, the well-known author of “The Vaccine Book.”

In 2015, California banned all philosophical and religious exemptions for immunizations in the wake of a large measles outbreak that originated at Disneyland. It is one of four states to have done so, and its vaccination rate rose sharply for three years after the law was tightened. But vaccination rates have declined in the past two years, in part because many parents opposed to vaccines have found doctors willing to write questionable medical exemptions — sometimes for a fee.

California’s vaccination policies are once again drawing national attention in the wake of the nation’s recent measles outbreak, which totaled 1,095 cases as of June 27. In California, 55 cases were reported as of June 26.

A bill pending in the California legislature, SB-276, would impose more oversight on vaccine exemptions written by doctors. After it passed the state Senate in May, it was softened to appease Gov. Gavin Newsom but would still allow the state Department of Public Health to review some exemptions. It also would prevent doctors who are under investigation for writing unwarranted exemptions from issuing new ones.

Newsom has said he will sign the legislation if it lands on his desk.

https://www.healthleadersmedia.com/clinical-care/california-broadens-investigation-doctors-issuing-questionable-vaccination-exemptions

Primary care positions filled by 4th-year med students lowest on record

According to the Match, 8,116 internal medicine positions were offered, the highest number on record and the most positions offered within any specialty.

Only 41.5% were filled by seniors pursuing their MDs from U.S. medical schools. Similar trends were seen this year in family medicine and pediatrics.

Despite hospital systems and health officials calling out the need for more primary care doctors, graduates of U.S. medical schools are becoming less likely to choose to specialize in one of those fields.

A record-high number of primary care positions was offered in the 2019 National Resident Matching Program — known to doctors as “the Match.” It determines where a medical student will study in their chosen specialty after graduation. But this year, the percentage of primary care positions filled by fourth-year medical students was the lowest on record.

“I think part of it has to do with income,” said Mona Signer, the CEO of the Match. “Primary care specialties are not the highest paying.” She suggested that where a student gets a degree also influences the choice. “Many medical schools are part of academic medical centers where research and specialization is a priority,” she said.

The three key primary care fields are internal medicine, family medicine and pediatrics. According to the 2019 Match report, 8,116 internal medicine positions were offered, the highest number on record and the most positions offered within any specialty, but only 41.5% were filled by seniors pursuing their M.D.s from U.S. medical schools. Similar trends were seen this year in family medicine and pediatrics.

In their final year of medical school, students apply and interview for residency programs in their chosen specialty. The Match, a nonprofit group, then assigns them a residency program based on how the applicant and the program ranked each other.

Since 2011, the percentage of U.S.-trained allopathic, or M.D., physicians who have matched into primary care positions has been on the decline, according to an analysis of historical Match data by Kaiser Health News.

But, over the same period, the percentage of U.S.-trained osteopathic and foreign-trained physicians matching into primary care roles has increased. 2019 marks the first year in which the percentage of osteopathic and foreign-trained doctors surpassed the percentage of U.S. trained medical doctors matching into primary care positions.

Medical colleges granting M.D. degrees graduate nearly three-quarters of U.S. students moving on to become doctors. The rest graduate from osteopathic schools, granting D.O. degrees. The five medical schools with the highest percentage of graduates who chose primary care are all osteopathic institutions, according to the latest U.S. News & World Report survey.

Beyond the standard medical curriculum, osteopathic students receive training in manipulative medicine, a hands-on technique focused on muscles and joints that can be used to diagnose and treat conditions. They are licensed by states and work side by side with M.D.s in physician practices and health systems.

Although the osteopathic graduates have been able to join the main residency match or go through a separate osteopathic match through this year, in 2020 the two matches will be combined.

Physicians who are trained at foreign medical schools, including both U.S. and non-U.S. citizens, also take unfilled primary care residency positions. In the 2019 match, 68.9% of foreign-trained physicians went into internal medicine, family medicine and pediatrics.

But, despite osteopathic graduates and foreign-trained medical doctors taking up these primary care spots, a looming primary care physician shortage is still expected.

The Association of American Medical Colleges predicts a shortage of between 21,100 and 55,200 primary care physicians by 2032. More doctors will be needed in the coming years to care for aging baby boomers, many of whom have multiple chronic conditions. The obesity rate is alsoincreasing, which portends more people with chronic health problems.

Studies have shown that states with a higher ratio of primary care physicians have better health and lower rates of mortality. Patients who regularly see a primary care physician also have lower health costs than those without one.

But choosing a specialty other than primary care often means a higher paycheck.

According to a recently published survey of physicians conducted by Medscape, internal medicine doctors’ salaries average $243,000 annually. That’s a little over half of what the highest earners, orthopedic physicians, make with an average annual salary of $482,000. Family medicine and pediatrics earn even less than internal medicine, at $231,000 and $225,000 per year, respectively.

Dr. Eric Hsieh, the internal medicine residency program director at the University of Southern California’s Keck School of Medicine, said another deterrent is the amount of time primary care doctors spend filling out patients’ electronic medical records.

“I don’t think people realize how involved electronic medical records are,” said Hsieh. “You have to synthesize everything and coordinate all of the care. And something that I see with the residents in our program is that the time spent on electronic medical records rather than caring for patients frustrates them.”

The Medscape survey confirms this. Internists appear to be more burdened with paperwork than other specialties, and 80% of internists report spending 10 or more hours a week on administrative tasks.

The result: Only 62% of internal medicine doctors said they would choose to go into their specialty again — the lowest percentage on record for all physician specialties surveyed.

Elsa Pearson, a health policy analyst at Boston University, said one way to keep and attract primary care doctors might be to shift some tasks to health care providers who aren’t doctors, such as nurse practitioners or physician assistants.

“The primary care that they provide compared to a physician is just as effective,” said Pearson. They wouldn’t replace physicians but could help lift the burden and free up doctors for more complicated care issues.

Pearson said more medical scribes, individuals who take notes for doctors while they are seeing patients, could also help to ease the doctors’ burden of electronic health record documentation.

Another solution is spreading the word about the loan forgiveness programs available to those who choose to pursue primary care, usually in an underserved area of the country, said Dr. Tyree Winters, the associate director of the pediatric residency program at Goryeb Children’s Hospital in New Jersey.

“The trend has been more so thinking about the amount of debt that a student has, compared to potential income in primary care,” said Winters. “But that’s not considering things like medical debt forgiveness through state or federal programs, which really can help individuals who want to choose primary care.”

https://www.healthleadersmedia.com/clinical-care/american-medical-students-less-likely-choose-become-primary-care-doctors

AstraZeneca appeals NICE rejection of Tagrisso lung cancer med

AstraZeneca is appealing against NICE’s decision not to recommend funding for its lung cancer drug Tagrisso (osimertinib) in untreated patients with epidermal growth factor receptor (EGFR) mutations.

In final draft guidance, NICE said it had rejected regular NHS funding for Tagrisso, because the survival benefits compared with standard treatment such as AZ’s older drug Iressa (gefitinib) are unclear in first-line non-small cell lung cancer.

Tagrisso has been the driving force behind AZ’s sales recovery after a steep patent cliff – it generated $630 million in Q1 alone and is the company’s top selling drug after first approval in 2015 in a more advanced form of the disease.

NICE had been considering results from the FLAURA trial, comparing Tagrisso with Roche’s Tarceva (erlotinib) and AZ’s Iressa (gefitinib) in untreated patients.

Patients in the trial had either exon 19 deletion (del19) or exon 21 (L858R) mutations, accounting for around 90% of EGFR mutations.

NICE said it noted progression-free survival was 18.9 months on Tagrisso compared with 10.2 months on standard care.

Overall survival data is not mature but data gathered so far show that Tagrisso will likely extend this too.

However NICE is concerned that data so far do not show the size of treatment benefits, and that AZ’s economic model does not fully capture the benefits of subsequent treatments.

As a result Tagrisso’s cost per quality-adjusted life year (QALY) is greater than the £30,000 threshold that NICE usually applies.

However NICE also ruled that Tagrisso does not qualify for End of Life consideration, which gives extra financial leeway for drugs where patients typically have less than two years to live.

AZ said that analyses submitted to NICE show that it would be considered cost-effective if EoL status was granted.

AZ’s CEO Pascal Soriot said: “We are very disappointed with this decision and will appeal. The UK has the second worst lung cancer survival outcomes in Europe and patients need new innovative treatments.

“NHS data show that patients in England who would be eligible for our medicine have very low survival rates and therefore Tagrisso should qualify for End of Life consideration to evaluate cost-effectiveness.”

Dr Carles Escriu, medical oncology consultant at The Clatterbridge Cancer Centre and Honorary Research Fellow at the University of Liverpool, said: “I am surprised at this negative decision. While I understand the methodological challenge for NICE, the fact is that NHS data show that patients with this type of lung cancer survive for 17 months, which is within the 24-month short life expectancy threshold for End of Life consideration.”

AZ appeals against NICE rejection of Tagrisso in untreated lung cancer

Pfizer’s lung cancer drug Vizimpro cleared for NHS front-line use

Pfizer has stolen a march on rival AstraZeneca in the first-line non-small cell lung cancer category, after NICE backed the use of its EGFR inhibitor Vizimpro for NHS use.

The once-daily pill will now be routinely available for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC), who have tested positive for the epidermal growth factor receptor (EGFR) mutation. Earlier, NICE rejected the drug on the grounds that it wasn’t a cost-effective use of NHS resources.

AZ has not been so lucky, with the cost-effectiveness agency turning down its EGFR inhibitor Tagrisso (osimertinib) for the same indication, although the company has said it intends to appeal the decision.

Pfizer has offered a discount on Vizimpro (dacomitinib), which was approved by the EMA in April and in the US last September. Its list price in the UK is £2,703 for a 30-day pack of capsules, but the agreed reduction is confidential.

In a statement, NICE said Pfizer’s “responsible pricing” had allowed its appraisal committee to reconsider its initial decision.

Both Vizimpro and Tagrisso were turned down by the agency in April after an initial assessment, with the committee deciding neither drug offered enough extra benefit to patients when compared with existing treatments to be value for money.

“Our committee acknowledged that dacomitinib had the potential to extend life for people with this type of lung cancer more than existing treatments currently available on the NHS,” said Meindert Boysen, director of the Centre for Health Technology Evaluation at NICE.

Company estimates are that around 1,477 people in England will be eligible for treatment with Vizimpro every year, according to the agency.

Health services in Wales and Northern Ireland usually follow NICE recommendations too, so the drug will likely be available there as well, according to Cancer Research UK.

The charity welcomed the green light for Vizimpro but said the Tagrisso decision was “disappointing”, particularly as AZ’s drug seems to offer some efficacy advantages and fewer side effects.

For now, the decision puts Pfizer UK in the driving seat for first-line EGFR-positive NSCLC therapy in England.

The company’s oncology director, Olivia Ashman, said: “Lung cancer remains a challenging condition to treat and we are pleased that clinicians managing patients with EGFR-mutated NSCLC will now have access to this important medicine.”

NICE has already recommended three other EGFR inhibitors for previously-untreated EGFR-positive NSCLC, including AZ’s Iressa, Boehringer Ingelheim’s Giotrif and Roche’s Tarceva, although these are considered less effective than the newer agents.

The agency’s guidance says people who took Vizimpro had longer overall survival rates than those who took Iressa – 34.1 months compared with 26.8 months – and Pfizer’s drug also increased the length of time before the disease worsened by around five months.

Vizimpro had a higher incidence of side effects than Iressa, however, so a lower dose may be needed, according to NICE.

NICE clears front-line NHS use for Pfizer’s lung cancer drug Vizimpro