Publisher Health

The agency plans to authorize Florida to purchase medicines directly from wholesalers in Canada, where prices are far cheaper. Pharmaceutical companies oppose the plan.The Food and Drug Administration has decided to allow Florida to import millions of dollars worth of medications from Canada at far lower prices than in the United States, overriding fierce decades-long objections from the pharmaceutical industry, according to a senior administration official.The approval is a major policy shift for the United States, and supporters hope it will be a significant step forward in the long and largely unsuccessful effort to reign in drug prices. Individuals in the United States are allowed to buy directly from Canadian pharmacies, but states have long wanted to be able to purchase medicines in bulk for their Medicaid programs, government clinics and prisons from Canadian wholesalers.Florida has estimated that it could save up to $150 million in its first year of the program, importing medicines that treat H.I.V., AIDS, diabetes, hepatitis C and psychiatric conditions. Other states have applied to the F.D.A. to set up similar programs.But significant hurdles remain. The pharmaceutical industry’s major lobbying organization, the Pharmaceutical Research and Manufacturers of America, or PhRMA, which has sued over previous importation efforts, is expected to file suit to prevent the Florida plan from going into effect. Some drug manufacturers have agreements with Canadian wholesalers not to export their medicines, and the Canadian government has already taken steps to block the export of prescription drugs that are in short supply.“Canada’s drug supply is too small to meet the demands of both American and Canadian consumers,” Maryse Durette, a spokeswoman for Health Canada, wrote in an email message. “Bulk importation will not provide an effective solution to the problem of high drug prices in the U.S.”Congress passed a law allowing drug importation two decades ago, but federal health officials delayed implementing it for years, citing safety concerns, one of the main arguments drug companies have used against it. In 2020, President Donald J. Trump pushed the law forward, announcing that states could submit importation proposals to the F.D.A. for review and authorization. President Biden added momentum the following year, instructing federal officials to keep working with states on importation plans.Florida applied and later sued the F.D.A., accusing the agency of what Gov. Ron DeSantis called a “reckless delay” in approving the request. Friday’s announcement grew out of that lawsuit; a federal judge had set a Jan. 5 deadline for the F.D.A. to act on the state’s application.Eight other states — Colorado, Maine, New Hampshire, New Mexico, North Dakota, Texas, Vermont and Wisconsin — have laws allowing for a state drug importation program, and many are seeking, or planning to seek, F.D.A. approval.Colorado’s application is pending with the F.D.A. New Hampshire’s application was rejected last year. Vermont’s was deemed incomplete; a spokeswoman said the state was waiting to see how the F.D.A. handled the applications by other states before resubmitting.Colorado officials have signaled that states may face challenges to their importation plans from drugmakers in Canada, among them familiar names like Pfizer, Merck and AstraZeneca. Some drugmakers have written contracts with drug-shipping companies prohibiting deliveries to the United States, Colorado officials said in a report.Drug importation has broad political and public support. A 2019 poll by KFF, a nonprofit health research group, found that nearly 80 percent of respondents favored importation from licensed Canadian pharmacies.“Importation is an idea that resonates with people,” Meredith Freed, a senior policy analyst with KFF, said. “They don’t fully understand why they pay more for the same drug than people in other countries.”With the 2024 presidential election on the horizon, candidates are looking to claim credit for efforts to reduce drug prices. President Biden is spotlighting the Inflation Reduction Act, which empowers Medicare to negotiate prices directly with drugmakers for the first time, but only for a limited number of high cost medicines. Mr. DeSantis, who is challenging Mr. Trump for the Republican nomination, is touting his import plan.Several experts in pharmaceutical policy said that importation from Canada would not address the root cause of high drug prices: the ability of pharmaceutical makers to fend off generic competition by gaming the patent system, and the federal government’s broad failure to negotiate directly with drugmakers over cost.“Seems like political theater to me, where everyone wants to say they did something to drive down the price of prescription drugs,” Nicholas Bagley, a health law expert at the University of Michigan Law School, said of Florida’s plan.Both Mr. Bagley and Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School, said that the Inflation Reduction Act is a more direct path to lowering prices; the law’s price negotiation provisions are expected to save the federal government an estimated $98.5 billion over a decade. Drugmakers are suing to block those provisions from taking effect.A protest outside the Pharmaceutical Research and Manufacturers of America in Washington in 2021. PhRMA is likely to file suit to prevent any plan from going into effect.Saul Loeb/Agence France-Presse — Getty ImagesWith its approval in hand, Florida has more work to do. Before it can distribute Canadian drugs, the state must send the F.D.A. details on those it plans to import. The state has to ensure that the drugs are potent and not counterfeit. It also must put F.D.A.-approved labels on medications instead of those used in Canada.The F.D.A. said it would be watching to see if the state upholds safety rules — such as the reporting of any drug side effects — and delivers significant cost savings to consumers. Florida’s approval to import lasts for two years from the date of the first drug shipment.In Canada, health officials have been casting a wary eye on the push to import from their country. In November 2020, shortly after the Trump administration announced that states could submit importation proposals, the Canadian government published its own rule to prevent manufacturers and wholesalers from exporting some drugs that are in short supply.The Canadian government is likely to further restrict exports if they begin to affect Canadians, said Amir Attaran, a law professor at the University of Ottawa. He said the numbers don’t work out for a nation of nearly 40 million to supply medications for a state with 22 million people, much less for 49 other U.S. states.“If all of a sudden Florida is able to extend a vacuum cleaner hose into this country to take what’s in the medicine chest, the supply disruption will be a completely different category,” he said. Dr. Kesselheim, of Harvard, said the F.D.A.’s authorization was unlikely to make a difference in the price of very expensive brand-name drugs, because manufacturers would block wholesalers from exporting the medicines.“I think it’s going to be hard for states to import drugs like that in any kind of scale that would make a difference in terms of lowering prices for patients,” Dr. Kesselheim said. Even so, he said, the F.D.A.’s announcement is significant because it puts to rest the notion that drug importation cannot be accomplished safely.Mr. Bagley of the University of Michigan said there was a simpler solution to high drug prices than patchwork state importation programs: Having the U.S. government negotiate with drug companies over prices, just as many other nations, including Canada, do.“This whole thing is a jerry-rigged, complicated approach to a problem that’s amenable to a pretty straightforward solution, which is that you empower the government to bargain over the price for drugs,” he said. “So instead, we’re sort of trying to exploit the machinery that Canada has created and that we were too timid to create.”

The research, supported by the National Institutes of Health, may reassure some patients after a European drug safety agency raised concerns last year.People taking the wildly popular drugs Ozempic, to treat diabetes, and Wegovy, to combat obesity, are slightly less likely to have suicidal thoughts who are not taking them, researchers reported on Friday.Millions of people take Ozempic and Wegovy, which are considered to be among the biggest blockbusters in medical history. But last year a European drug safety agency said it was investigating whether the drugs cause suicidal thoughts. The new study, published in the journal Nature Medicine, was funded by the National Institutes of Health and used a huge population. The findings provide data that may potentially reassure people who take the drugs.Novo Nordisk, maker of the drugs, had no role in the study, and the study’s investigators had no conflicts of interest.The investigators used anonymized electronic health records from a database of 100.8 million people. That allowed them to look at two groups: 240,618 who were prescribed Wegovy or other weight loss drugs, and 1,589,855 who were prescribed Ozempic or other medicines to lower their blood sugar. Suicidal thoughts were included in patients’ records as part of routine monitoring of their health.The investigators compared the incidence of suicidal thoughts in people who were taking the drugs with the incidence among similar people who were not taking them but were taking other weight loss and anti-diabetes medications. They also asked if there was an increase in the recurrence of suicidal thoughts among those taking the drugs who had previously reported thoughts of suicide.The database’s size allowed the researchers to look at subgroups such as sex, race and age groups.“No matter how hard we tried we did not see any increased risk,” said Rong Xu, director of the Center for Artificial Intelligence in Drug Discovery at Case Western Reserve University in Cleveland.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

In a study designed to better understand sudden, unexpected deaths in young children, which usually occur during sleep, researchers have identified brief seizures, accompanied by muscle convulsions, as a potential cause.
Experts estimate in excess of 3,000 families each year in the United States lose a baby or young child unexpectedly and without explanation. Most are infants in what is referred to as sudden infant death syndrome, or SIDS, but 400 or more cases involve children aged 1 and older, and in what is called sudden unexplained death in children (SUDC). Over half of these children are toddlers.
The study findings come from a registry of more than 300 SUDC cases, set up a decade ago by researchers at NYU Grossman School of Medicine. Researchers used extensive medical record analysis and video evidence donated by families to document the inexplicable deaths of seven toddlers between the ages of 1 and 3 that were potentially attributable to seizures. These seizures lasted less than 60 seconds and occurred within 30 minutes immediately prior to each child’s death, say the study authors.
For decades, researchers have sought an explanation to sudden death events in children, noticing a link between those with a history of febrile seizures (seizures accompanied by fever). Earlier research had reported that children who died suddenly and unexpectedly were 10 times more likely to have had febrile seizures than children who did not die suddenly and unexpectedly. Febrile seizures are also noted in one-third of SUDC cases registered at NYU Langone Health.
Publishing in the journal Neurology online Jan. 4, the new study involved an analysis by a team of eight physicians of the rare SUDC cases for which there were also home video recordings, from either security systems or commercial crib cameras, made while each child was sleeping on the night or afternoon of their death.
Five of seven recordings were running nonstop at the time and showed direct sound and visible motion indicative of a seizure happening. The remaining two recordings were triggered by sound or motion, but only one suggested that a muscle convulsion, a sign of seizure, had occurred. As well, only one toddler had a documented previous history of febrile seizures. All children in the study had previously undergone an autopsy that revealed no definitive cause of death.
“Our study, although small, offers the first direct evidence that seizures may be responsible for some sudden deaths in children, which are usually unwitnessed during sleep,” said study lead investigator Laura Gould, a research assistant professor at NYU Langone. Gould lost her daughter, Maria, to SUDC at the age of 15 months in 1997, a tragedy that prompted her successful lobby for establishment of the NYU SUDC Registry and Research Collaborative. Gould points out that if not for the video evidence, the death investigations would not have implicated a seizure.

“These study findings show that seizures are much more common than patients’ medical histories suggest, and that further research is needed to determine if seizures are frequent occurrences in sleep-related deaths in toddlers, and potentially in infants, older children, and adults,” said study senior investigator and neurologist Orrin Devinsky, MD.
Devinsky, a professor in the Departments of Neurology, Neurosurgery, and Psychiatry at NYU Langone, as well as chief of its epilepsy service, adds that “convulsive seizures may be the ‘smoking gun’ that medical science has been looking for to understand why these children die.
“Studying this phenomenon may also provide critical insight into many other deaths, including those from SIDS and epilepsy,” said Devinsky, who cofounded the SUDC Registry and Research Collaborative at NYU Langone with Gould.
Further research, Devinsky notes, is also needed to determine precisely how seizures with or without fever may induce sudden death. Previous research in epilepsy patients, he says, points to difficulty breathing that is known to occur immediately after a seizure and that can lead to death. This has been found to happen more frequently in epilepsy patients, as it does in the children involved in the study, while they are sleeping face down on the stomach and without anyone witnessing the death.
Continuous monitoring of child deaths and improvements in health records to track how often these convulsive seizures precede death, he explains, will be needed for this to be confirmed. Seizure-related deaths are underreported in people with and without epilepsy.
For the study, experts in forensic pathology, neurology, and sleep medicine analyzed each recording for video quality, sound, and motion. From this, they were able to determine which toddlers showed signs of muscle convulsions as a sign of seizures prior to their death and when. Access to the videos was and remains strictly limited to the researchers involved in the study.
Funding support for this study was provided by SUDC UK, FACES at NYU Langone Health, and the SUDC Foundation. Additional funding support was provided by the National Center for Advancing Translational Sciences and National Institutes of Health grant UL1TR001445.

A new study published in the journal Diabetes demonstrates that a glucagon-like peptide-1 receptor (GLP-1R) agonist, a member of a class of medication used to treat Type 2 diabetes and obesity, can lead to a rapid improvement in insulin sensitivity.
Insulin sensitivity is how responsive cells are to insulin, an essential hormone that controls blood glucose levels. An increase in insulin sensitivity means insulin can more effectively lower the blood glucose. Reduced insulin sensitivity or insulin resistance is a feature of Type 2 diabetes. Thus, improved insulin sensitivity can reduce the risk of developing Type 2 diabetes or improve its treatment.
GLP-1R agonists are medications that influence metabolism, such as decreasing blood sugar levels by promoting insulin secretion. Dipeptidyl peptidase 4 (DPP-4) inhibitors block the degradation of the body’s own endogenous GLP-1, as well as other peptide hormones such as glucose-dependent insulinotropic peptide (GIP).
“We know that GLP-1R agonists promote weight loss, but we were surprised to find that the GLP-1R agonist liraglutide also has rapid effects on insulin sensitivity, independent from weight loss,” said Mona Mashayekhi MD, PhD, assistant professor of Medicine in the Division of Diabetes, Endocrinology and Metabolism. “This effect requires activation of the GLP-1 receptor, but increasing the body’s own endogenous GLP-1 through the use of the DPP4 inhibitor sitagliptin does not achieve similar effects.”
“Our research suggests that liraglutide, and presumably other GLP-1R agonists, are having important metabolic effects in a way that’s different from increasing endogenous GLP-1 levels, even though they’re using the same receptor. Future research will focus on potential mechanisms of how GLP-1R agonists are improving insulin sensitivity independent of weight loss.”
Eighty-eight individuals with obesity and pre-diabetes were randomized for 14 weeks to receive the GLP-1R agonist liraglutide, the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin, or weight loss without drug using a low-calorie diet.
To further investigate the GLP-1R-dependent effects of the treatments, the GLP-1R antagonist exendin and a placebo were given in a two-by-two crossover study during mixed meal tests. Crossover studies allow the response of a subject to treatment A to be compared with the same subject’s response to treatment B.

Liraglutide was shown to rapidly improve insulin sensitivity as well as decrease blood glucose within two weeks of beginning treatment and before any weight loss.
“GLP-1R agonists are an exciting class of medications, given their strong glucose-lowering effects combined with tremendous weight-loss benefits, and they have transformed how we manage diabetes and obesity in the clinic,” Mashayekhi said. “Since the number of medications in this class is rapidly expanding, a deeper understanding of the mechanisms of benefit is crucial so we can design the right drugs for the desired effects in the right patients.”
The investigators’ prior research demonstrated that liraglutide, but not sitagliptin or diet, improves measures of heart disease and inflammation. This matches the clinical findings of reduced cardiovascular disease with GLP-1R agonist treatment.
Future studies will continue to explore both receptor- and weight loss-dependent effects of GLP-1R agonists in humans.
This research was supported by the American Heart Association (17SFRN33520017), National Center for Advancing Translational Sciences (5UL1TR002243), and the National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007061) This work utilized the cores of the Vanderbilt Diabetes Research and Training Center funded by grant DK020593 from the National Institute of Diabetes and Digestive and Kidney Disease. Novo Nordisk provided liraglutide and matching placebo.

A pair of proteins, YAP and TAZ, has been identified as conductors of bone development in the womb and could provide insight into genetic diseases such as osteogenesis imperfecta, known commonly as “brittle bone disease.” This small animal-based research, published today in Developmental Cell and led by members of the McKay Orthopaedic Research Laboratory of the Perelman School of Medicine at the University of Pennsylvania, adds understanding to the field of mechanobiology, which studies how mechanical forces influence biology.
“Despite more than a century of study on the mechanobiology of bone development, the cellular and molecular basis largely has remained a mystery,” said the study’s senior author, Joel Boerckel, PhD, an associate professor of Orthopaedic Surgery. “Here, we identify a new population of cells that are key to turning the body’s early cartilage template into bone, guided by the force-activated gene regulating proteins, YAP and TAZ.”
By combing through the genes expressed by individual cells in developing mouse limbs, through single-cell sequencing, Boerckel and the study’s first author, former Penn Bioengineering doctoral student Joseph Collins, PhD, along with their colleagues, found and described a class of cells that they named “‘vessel-associated osteoblast precursors (VOPs),” which “invade” early cartilage alongside blood vessels. Since osteoblasts are the cells required to form (and fix) bones, these cells would essentially be the grandparents to bones, with osteoblasts being bones’ parents.
And, importantly, a pair of proteins called YAP and TAZ that are sensitive to the natural movement of the body — which the team’s previous work has shown is crucial to early bone development and regeneration — serve as guides to the VOPs, passing on signals they glean from the body’s mechanobiology.
The researchers found that YAP and TAZ help direct blood vessel integration into the cartilage, a vital aspect of bone development. They were able to demonstrate this role by first genetically removing YAP and TAZ from human cell models, which appeared to stop angiogenesis, the process by which new blood vessels form. Then, the researchers treated those human cell models with a special variety of protein called CXCL12, which restored YAP and TAZ and restarted normal angiogenesis.
The study is a result of a long-time collaboration with Dr. Niamh Nowlan of University College Dublin, whose laboratory focuses on how mechanical forces direct skeletal development in animal models and in human patients.
It’s also appropriate that Boerckel, Collins, and their team are using their exploration of bone development as a lens to further the understanding of mechanobiology.

“The study of bone development is the birthplace of mechanobiology,” Boerckel said. “For example, Wolff’s Law of Bone Transformation, says that trabecular — spongy — bone adapts in a manner depending on the stresses placed on it, but Julius Wolff spent more time in his 1894 book focused on bone development than on trabecular bone.”
With the information the Penn researchers gleaned from their study on both bone development and mechanobiology, they believe they can now inform some of the knowledge and, hopefully, treatment of genetic and congenital musculo-skeletal conditions. That includes brittle bone disease — in which the body doesn’t make collagen correctly, causing bones that can break easily — or arthrogryposis — a condition in which joints develop improperly due to limited fetal movement.
“We are now working on using these findings to target these cells and pathways, either by direct mechanical or pharmacologic means, to restore cellular function and proper bone development in utero, potentially preventing these types of conditions,” Boerckel said.
This research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR073809, R01 AR074948, P30AR069619, NSF CMMI 1548571) and the European Research Council (336306).

Detecting malaria in people who aren’t experiencing symptoms is vital to public health efforts to better control this tropical disease in places where the mosquito-borne parasite is common. Asymptomatic people harboring the parasite can still transmit the disease or become ill later, after initially testing negative.
The dynamic lifecycle of this pathogen means that parasite densities can suddenly drop below the level of detection — especially when older, less sensitive tests are used. Such fluctuations can make it difficult, when testing only at a single point in time, to determine if an apparently healthy person is in fact infected.
Malaria can produce severe chills alternating with sweaty fevers, headaches, nausea and other distress. Yet many infected people can feel fine.
A recent asymptomatic detection study was conducted in the Katawki District, Uganda, which has a high incidence of malaria.
“We found that parasite dynamics and the parasite species present were highly variable among patients with low-level, asymptomatic infections,” said UW Medicine malaria research Dr. Sean C. Murphy, one of the senior scientists on the study. He noted that sampling every other day or every third day was enough to detect a proportion of infections similar to daily sampling. However, testing once a week or less often, even with sophisticated diagnostics, could misclassify the true infection status of up to one-third of the individuals.
This finding is important, Murphy said, for improving studies on the prevalence of malaria infection and, by extension, for clinical trials of malaria vaccines and therapeutics. Most of these trials use single-timepoint tests or repeated but infrequent tests to determine the infection status of asymptomatic participants. That approach is likely to miss infections if the participants’ parasite densities drop below the limit of the test employed.
Murphy is a physician-scientist and professor of laboratory medicine and pathology and microbiology at the University of Washington School of Medicine and chief of pathology and laboratory medicine at Seattle Children’s.

The project was a collaboration among the Murphy lab; Dr. Thomas Egwang and his research team including Tonny Owalla of Med Biotech Laboratories in Kampala, Uganda; and Dr. Jennifer E. Balkus, professor of epidemiology at the UW School of Public Health. Dr. Dianna E. B. Hergott, who was at the time a graduate student mentored by Murphy and Balkus, and Med Biotech’s Owalla led the study.
The Uganda-based team performed the community-based portions of the study. The participants were healthy, nonpregnant adults, ages 18 to 59, who were not taking antimalarial drugs, as well as older children, ages 8 to 17.
“We instructed participants in how to collect one dried blood spot at home every day for up to 29 days,” Owalla explained. The participants would come to the study clinic once a week to turn in that week’s blood spots, obtain new blood spot cards, and have traditional blood draws.
Diagnostic tests checked the dried blood spots for the presence, classification and densities of Plasmodium ribosomal RNA, which helps produce parasite proteins. The testing strategy also employed “pooling” of the dried blood spots. This approach allowed the team to test more samples cost-effectively, much like the strategies employed at the height of the COVID-19 pandemic.
By analyzing the resulting data, the researchers hoped to discern a sampling schedule comparable to testing every day to reliably identify asymptomatic cases, but less burdensome. On the other hand, the study team wanted to avoid a schedule that was too infrequent and that would end up missing infections.
The scientists categorized the infection trajectory of each participant: no infection whatsoever, newly detected infection, cleared infection, chronic infection, or not able to determine. Looking at the daily results, they also calculated how many infections would still have been detected if the sampling frequency were reduced.

About 60% of all the participants had a Plasmodium infection discovered at some point during the monthlong study. Fewer than half had an infection detected at the study’s outset. The lowest daily report during the study period showed a prevalence of 30%.
The findings are reported today, Jan 4, in The Lancet Microbe.
Earlier, several other studies questioned the accuracy of a single measurement to identify infection status. Undetected asymptomatic infections could inadvertently influence research results.
“Serial testing,” the paper authors suggested, “should be considered when trying to determine the true infection status of an individual.”
One of the limitations of their own study, the authors said, was that participants were not asked to collect their dried blood samples at the same time each day. Parasite densities, they noted, could change by as much as 100-fold during a six-hour span.
Owalla is now a graduate student in pathobiology at the UW School of Public Health. He plans to apply his training to further develop advanced solutions for malaria in Africa, the continent most severely affected by this disease.
Grants from the U.S. National Institutes of Health (R21AI146763) and the Bill and Melinda Gates Foundation (INV-009313) supported this research. The scientists declared no competing interests.

Having bipolar disorder — a serious mental illness that can cause both manic and depressed moods — can make life more challenging.
It also comes with a higher risk of dying early. Now, a study puts into perspective just how large that risk is, and how it compares with other factors that can shorten life.
In two different groups, people with bipolar disorder were four to six times more likely as people without the condition to die prematurely, the study finds.
By contrast, people who had ever smoked were about twice as likely to die prematurely than those who had never smoked — whether or not they had bipolar disorder.
A team from the University of Michigan, home to one of the world’s largest longterm studies of people with bipolar disorder, reports their findings in the journal Psychiatry Research.
The stark difference in mortality, and the differences in health and lifestyle that likely contributed to it, should prompt more efforts at preventing early deaths, say the researchers.
“Bipolar disorder has long been seen as a risk factor for mortality, but always through a lens of other common causes of death,” said Anastasia Yocum, Ph.D., lead author of the study and data manager of the research program at the Heinz C. Prechter Bipolar Research Program.

“We wanted to look at it by itself in comparison with conditions and lifestyle behaviors that are also linked to higher rates of premature death.”
Two large data sources yield similar findings
Yocum and her colleagues, including Prechter Program director Melvin McInnis, M.D., started by looking at deaths and related factors among 1,128 people who had volunteered for the program’s longterm study of people with and without bipolar disorder.
They found that all but 2 of the 56 deaths since the study began in 2006 were from the group of 847 people in the study who had bipolar disorder.
With statistical adjustments, their analysis shows that having a diagnosis of bipolar disorder made someone six times more likely to die during a 10-year period than people taking part in the same study who did not have bipolar disorder.
By comparison, study participants who had ever smoked or were over age 60 were more than twice as likely to die in that same time as people who never smoked or were under 60, regardless of bipolar status.

The researchers then turned to another source of data to see if they could find the same effect.
They analyzed years’ worth of anonymous patient records from more than 18,000 people who get their primary care through Michigan Medicine, U-M’s academic medical center.
Among this group, people with bipolar disorder were four times as likely to die during the study period than those with no record of bipolar disorder.
The team studied records from more than 10,700 people with bipolar disorder and a comparison group of just over 7,800 people without any psychiatric disorder.
The only factor associated with an even higher chance of dying during the study period in this pool of people was high blood pressure.
Those who had hypertension were five times more likely to die than those with normal blood pressure, no matter whether they had bipolar disorder or not.
By contrast, smokers were twice as likely to die as never-smokers in this sample, and those over age 60 were three times as likely to die, both regardless of bipolar status.
“To our major surprise, in both samples we found that having bipolar disorder is far more of a risk for premature death than smoking,” said McInnis, a professor of psychiatry at the U-M Medical School.
He hopes the findings will spur more action in the medical and public health communities to address the many factors that contribute to this extra-high risk of death in people with bipolar disorder.
“Over the years there have been all kinds of programs that have been implemented for smoking prevention and cardiovascular disease awareness, but never a campaign on that scale for mental health,” he said, noting that about 4% of Americans live with bipolar disorder while about 11.5% of Americans smoke.
Other differences between groups
Yocum and McInnis note that people with bipolar disorder in both groups were much more likely than the people without bipolar disorder to have ever smoked, consistent with past studies.
Nearly half (47%) of the U-M patients with bipolar disorder had a history of smoking, as did 31% of the Prechter participants with bipolar disorder.
By comparison, smoking among those without bipolar disorder stood at 29% of the U-M patients and 8% of the Prechter participants.
People with bipolar disorder in both groups were also much more likely to be female, and female gender was associated with a slightly lower risk of early death.
In the Prechter cohort, people with bipolar disorder were much more likely to have asthma, diabetes, high blood pressure, migraines, fibromyalgia and thyroid conditions than those who had not been diagnosed with bipolar disorder.
Within the group of Prechter study participants who have bipolar disorder, being a smoker and scoring higher over time on a standardized survey of depression symptoms were both associated with a doubled risk of death, compared with participants who had bipolar disorder but didn’t smoke or scored lower over time on depression ratings.
Interestingly, the researchers found no association between risk of death and the number of years Prechter participants had been taking medications for mental health symptoms.
There was also no association with scores for anxiety and mania.
Among just people with bipolar disorder in the U-M patient sample, high blood pressure also was associated with a fivefold higher risk of death, while smoking was associated with a nearly twofold risk of death.
Information on depression scores or medication use over time was not available for this group.
A path forward
Both Yocum and McInnis say the findings, combined with studies on the health status, health risk behaviors and specific causes of death for people with bipolar disorder, could inform efforts to improve the health and quality of life for people with the condition.
Past research has shown that people with bipolar disorder are more likely to have metabolic syndrome, which puts them at higher risk for diabetes and cardiovascular conditions because of a combination of factors related to waist size, cholesterol, blood sugar and blood pressure.
Medications for bipolar disorder can contribute to this.
Also important: the secondary effects of bipolar disorder’s symptoms.
Lack of activity, poor diet, drug/alcohol overuse and lower education attainment and employment rates also increase overall health risk, while health insurance coverage and access to care may be less consistent.
Educating more teens and adults on how to cope with stress, distress and mood fluctuations, and how to identify and get help for depression symptoms, could be part of increasing early intervention, the researchers say.
Bipolar disorder often begins showing itself as depression, and there are currently no good ways to predict which people will go on to develop bipolar disorder, though a family history of the condition is known to increase risk.
Genetic research at the Prechter Program and elsewhere is studying these contributing factors.
“Bipolar disorder is never going to be listed on the death certificate as the main cause of death, but it can be an immediate or secondary contributor to a death, including in suicides,” said Yocum, who notes that cross-sectional studies have found that on average people with bipolar disorder die 8 to 10 years earlier than other people their age.
Similarly, McInnis says, smoking is rarely listed on death certificates, but is well understood to be a major risk factor leading to cancers and cardiovascular emergencies that do get listed as causes of death.
That’s why it has received so much attention from agencies and organizations running public health campaigns.
“We need to know more about why people with bipolar have more illnesses and health behaviors that compromise their lives and lifespan and do more as a society to help them live more healthily and have consistent access to care,” he said.
The Prechter Program is still accepting people with bipolar disorder, and those without, into its longitudinal study.
In addition to Yocum and McInnis, the study’s authors are Emily Friedman and Peisong Han from the U-M School of Public Health and Holli S. Bertram from Psychiatry.
The study was funded by the Heinz C. Prechter Bipolar Research Fund at the University of Michigan Eisenberg Family Depression Center and the Richard Tam Foundation, as well as the National Institute of Mental Health and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health (MH100404, MH106434, TR002240)
The researchers used the Michigan Medicine DataDirect tool to explore anonymous patient data.

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, Family handoutBy Eleanor Layhe & Divya TalwarBBC NewsPatients’ lives are being put at risk because it is too easy to buy prescription-only medicines from online pharmacies, a leading pharmacist says.A BBC investigation found 20 online pharmacies selling restricted drugs without checks – such as GP approval.In total, we bought over 1,600 various prescription-only pills by entering false information without challenge. Regulator the General Pharmaceutical Council says extra checks are needed when selling some drugs online. The BBC’s findings highlight the “wild west” of buying medicines on the web, says Thorrun Govind, a pharmacist, health lawyer and former chair of the Royal Pharmaceutical Society.”The current guidance basically tells pharmacies to be robust, but do that in your own way, and we know that under this current system, patients have died,” she says.The parents of a woman who died in 2020, after accidentally overdosing on medicines she bought online, are among those calling for stricter rules.Katie Corrigan, from St Erth in Cornwall, had developed an addiction to painkillers after experiencing neck pain. “Katie needed help, she didn’t need more medication,” says her mum, Christine Taylor. Her GP had stopped supplying the drug after realising she had been allowed to request new prescriptions prematurely and been prescribed too much. Instead, Katie, 38, was able to buy a painkiller and a drug used to treat anxiety from multiple online pharmacies without notifying her GP.The coroner at Katie’s inquest confirmed her GP had not been contacted by any of the pharmacies to check the drug was safe for her. In his final report, he said the safety controls were inadequate. Christine wants online pharmacies to obtain more background information. “It’s far too easy – it’s people’s lives, and it’s a disaster waiting to happen,” she says. Undercover experimentCurrent guidance from the regulator, the General Pharmaceutical Council, (GPhC) says online prescribers must get “all the information they need” to ensure a medicine is safe and appropriate for an individual patient. It also states that “high-risk, habit-forming medicines”, like those Katie Corrigan was able to buy, should not be sold online without additional safeguards. But some of the medicines she bought still appear to be readily available from some online pharmacies, the BBC has found. We attempted to buy prescription-only drugs from regulated online pharmacies. We selected three restricted drugs – including an anti-anxiety drug, a painkiller and a sleeping medication. We are not naming these drugs because they can be dangerous when taken without medical guidance.Of the 20 businesses we identified selling one or more restricted drugs:We found nine pharmacies selling the anti-anxiety drugThree pharmacies sold the anti-anxiety medicine to us on the basis of our answers to an online questionnaire and did not require further checksIn total, we were able to buy a potentially fatal dose of the anti-anxiety medicine We bought the painkiller from nine pharmacies based on online questionnaires We similarly obtained the sleeping medication from 14 pharmaciesBut 13 online pharmacies which sold at least one of these drugs refused to sell to us without access to some medical records, proof that we had been prescribed them before by a doctor, or permission to contact our GP to carry out further safety checks. Two pharmacies refunded our order after assessing our answers to the questionnaire. We also found evidence of high-risk and potentially addictive medicines, including benzodiazepines and antidepressants, being sold on the basis of online questionnaires. One online pharmacy sent a marketing email telling us we had “something fabulous” in our basket and to “buy before time runs out”, referring to an addictive painkiller. This is language the regulator, which can disqualify a pharmacist from its register, says should not be used. Five of the pharmacies that sold to us sent follow-up emails with more safety information and contact details if we had concerns or needed to ask any questions. Every pharmacy that sold to us had a disclaimer urging us to alert our GP about the purchase. ‘Vague guidance’The BBC spoke to several other people who said they have been able to circumvent safety checks to buy medicines from online pharmacies. One woman, who wanted to remain anonymous, said she bought a prescription-only weight loss drug in July by falsely claiming to be roughly double her real weight in a questionnaire. The woman said she was asked to verify her identity by showing an image of her driving licence, but was not asked to provide any evidence of her weight.There were no further checks to ensure the drug was suitable before it was dispatched. “After taking it for a few days, I felt really bad – I couldn’t eat, I was exhausted and basically stopped functioning,” she said. “If I’d had to send a picture, or any proof of my weight, I don’t think I would have been prescribed it.” If you are affected by any of the issues raised in this story you can contact BBC Action Line here.Unlike illegitimate, black market sellers, licensed online pharmacies are regulated by the GPhC and employ qualified pharmacists and prescribers. They are expected to carry out risk assessments to determine which medicines can be safely sold online, and the regulator can take action if they are deemed to be practising dangerously. But Ms Gorrund says the guidance from the regulator is too vague, and does not state clearly enough what checks online pharmacies should be conducting.”This has led to such a variation, with some online pharmacies asking for checks like video consultations, while others seem to let you simply click on the drug you want and go forward to pay,” she explains. The Royal Pharmaceutical Society says the findings are “concerning”, and it wants to see regulators take action where poor professional practice has been highlighted.The GPhC issued renewed guidance in 2022 after it found hundreds of its investigations into whether pharmacies should be allowed to continue operating related specifically to online pharmacies. In a statement, it told the BBC it expected pharmacy owners to carry out risk assessments to identify which medicines are safe to supply online and identify requests for medicines that are too large or too frequent. A spokesperson said: “We have made it clear that medicines liable to abuse, overuse or misuse, such as opioids and sedatives, should not be sold online unless further safeguards have been put in place.”We have taken regulatory action against online pharmacies which fell short of professional standards, including in some cases where ‘high-risk, habit-forming’ medicines were supplied on the basis of an online questionnaire.”

Published9 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Jonty BloomBusiness reporterLate last year, Danish pharmaceutical company Novo Nordisk became Europe’s most valuable company, for a short time at least. Well-known in business circles, but hardly a household name, Novo Nordisk had not previously been seen as a big player in the drugs industry, let alone a titan of the European stock market.But it leapt to the top of the league table and was valued at $428bn (£342bn) because it has discovered the Holy Grail of all drugs. One that millions of people want and need across the Western World and beyond.Called Wegovy, it was designed to help treat type 2 diabetes, but as a side effect it was found to almost guarantee to make people lose weight. Like Viagra, which was supposed to treat high blood pressure but had unrealised but popular side effects, Wegovy is the must-have drug of the 2020s. It is knocking at an open door – Goldman Sachs research predicts that the anti-obesity drugs market is worth some $6bn this year. But by 2030, it could grow by more than 16 times to $100bn.It almost sounds too good to be true, but what are the long-term prospects and consequences for a pharmaceutical company that discovers a sure-fire winner? Is it really the Midas touch or more of a poisoned chalice? Image source, Novo NordiskWell for a start, having discovered a drug that suddenly dominates the market is just the start of the process. You have to make it, market it and negotiate the price with a whole host of health companies and national health services.Some like the NHS in the UK are so large they can force down the cost and therefore the profitability of even the most popular drugs. At the moment Wegovy is available on the NHS for weight management in specific circumstances.Claire Machin is executive director for international policy and UK competitiveness at the ABPI, the body that represents pharmaceutical companies in the UK.She told me that the UK not only forces down prices for drugs using a value-for-money standard set 20 years ago, but then the NHS will negotiate even lower prices, followed by a further requirement for cash rebates from companies when the NHS exceeds its medicines budget.”Because of that, the UK spends comparatively less on medicines than similar countries, spending about 9% of its total health budget on medicines, compared to around 14% in Australia, 15% in France, and 17% in Germany.”Then there are operational problems, In 2022 Novo Nordisk had trouble meeting the huge demand for Wegovy. In December 2023 its shares were marked down because of worries about its ability to produce the drug in enough quantity again, and at a high enough quality, to satisfy the industry’s regulators. Image source, AlamyThe company admits that in the US, during December it ran out of the 1.7mg dose of Wegovy. That happened despite running its manufacturing lines “24 hours a day, seven days a week”.But, it expects to be able to restart shipments this month. Then there is the quite obvious fact that Wegovy’s head start is just that, a head start. There are already other drugs from other companies that do the same thing. Those companies will be working night and day to improve their drugs, to market them better, to sell them cheaper, and to undercut Novo Nordisk at every chance. After all, there is a potential market of $100bn a year at stake.In November, Eli Lilly, an American pharmaceutical giant got approval for its weight lose drug Mounjaro in the UK. Other alternatives include drugs like Saxenda, Orlistat, and Qsymia – the battle to dominate the weight loss drug market is well under way.Of course, Novo Nordisk is protected from direct competition by its drug patents that normally run for 20 years. After that anyone can enter the market and make their own generic version of its drug. More technology of businessWill hotter heat pumps win over homeowners?Tech Trends 2024: AI and electric vehicle dealsThe quest to find healthy and cheap sweetenersCould there be a gold rush for buried hydrogen?What happens after a nuclear power station is closed?Pharmaceutical patents mean companies have to make the money while the going is good. When anyone can copy them the good times are well and truly over. “I think 90% of pharmaceutical spend in the UK, and I’m pretty sure it’s similar in the US, is for generics… so, you [the original inventor] may well retain market share, but the price will fall,” says Graham Cookson chief executive of the Office of Health Economics, the world’s oldest health economics research organisation.Then there is one final problem for the discoverer of a giant new successful drug. It makes you stand out from the crowd, and if you are a small or even medium sized company that makes you vulnerable. It really does not pay to be too popular. Pharmaceutical giants have very deep pockets and if their extensive and expensive drug development programmes have failed to find the best drugs there is a simple solution, buy the company that has. But Novo Nordisk has one final card up its sleeve, most of its shares are owned by a Danish Foundation, making it virtually immune to a takeover bid.

Dr. Christmas overcame race and gender barriers to run New York’s mental health agency under three mayors in the 1970s.June Jackson Christmas, a psychiatrist who broke barriers as a Black woman by heading New York City’s Department of Mental Health and Retardation Services under three mayors, died on Sunday in the Bronx. She was 99.Her daughter, Rachel Christmas Derrick, said she died in a hospital of heart failure.As a city commissioner, as chief of rehabilitation services at Harlem Hospital Center, and in her role overseeing the transition of the U.S. Department of Health, Education and Welfare to a Democratic administration for President-elect Jimmy Carter, Dr. Christmas ardently advanced her professional agenda.Her priorities included improving mental health services for older people, helping people cope with alcoholism, and assisting children ensnared in the bureaucracies of foster care and the legal system. She also sought to ease the transition of patients from being warehoused in state mental hospitals to living independently.Dr. Christmas publicly championed civil rights from an early age. She staged a sit-down strike at a segregated roller skating rink in Cambridge, Mass., when she was 14, and she later broke ground as a Black woman in education, employment and housing.June Antoinette Jackson was born on June 7, 1924, in Boston. Her mother, Lillian Annie (Riley) Jackson, was a homemaker who had worked at the Charlestown Navy Yard in Boston during World War II and as a state tax assessor. Her father, Mortimer Jackson, was a postal worker who fought for the advancement of Black workers in the union and civil service hierarchy.At school, June and other Black students were never asked to identify their ancestry on “I Am an American Day” — a snub she never questioned, she said in an interview conducted in 2016 for StoryCorps by her son Vincent, because “I think it was the reality of how we just accepted racism.”Her father, she recalled in the same interview, “would always get the highest score, often perfect, and never be offered the position.”One year, she said, she and a classmate who was also Black sold more Girl Scout cookies than anyone else in their troop, but the minister’s wife who headed the troop informed her that she would not be able to claim her prize in another town because “those camps, they’ve really never taken any Negroes.”Her father’s advice? “Be twice as good as everybody else,” she recalled.But, she added, “It seems to me that I’ve often been in places where if you wanted to make life better for yourself, you had to work to make life better for everybody.”When Dr. Christmas earned a Bachelor of Science degree in zoology in 1945, she was one of the first three women who identified as Black to graduate from Vassar College.via VassarShe earned a Bachelor of Science degree in zoology in 1945 from Vassar College in Poughkeepsie, N.Y., where she was one of the first three women who identified as Black to graduate. She went on to receive a medical degree in psychiatry from the Boston University School of Medicine in 1949.She did her internship at Queens General Hospital and her residency at Bellevue Hospital in Manhattan. She received a certificate in psychoanalysis from the William Alanson White Institute, also in Manhattan.In 1953, she married Walter Christmas, a founder of the Harlem Writers Guild, who handed publicity for a number of firms and organizations and at one point was public relations director for the Coca-Cola Bottling Company of New York. He died in 2002.In addition to their daughter, a travel writer, she is survived by their son Gordon, a photographer, and four grandchildren. Their son Vincent, who worked for the city mental health agency his mother once headed, died in 2021.Dr. Christmas initially practiced privately, then worked as a psychiatrist for the Riverdale Children’s Association in New York from 1953 to 1965.In 1964 she founded Harlem Rehabilitation Center, a Harlem Hospital program, which gained a national reputation for providing vocational training and psychiatric help to psychiatric hospital patients who had returned to their communities after being discharged. From 1964 to 1972, she was also the principal investigator on research projects for the National Institute of Mental Health.In 1972, after serving briefly as a deputy commissioner, Dr. Christmas was appointed commissioner of the Department of Mental Health and Retardation Services by Mayor John V. Lindsay. She was reappointed in 1973 by Mayor Abraham D. Beame (she took a two-month leave to head Jimmy Carter’s 12-member transition team) and again in 1978 by Mayor Edward I. Koch.Dr. Christmas in 1973 with Mayor-elect Abraham D. Beame of New York, center, who reappointed her commissioner of the city’s mental health department, as did his successor, Edward I. Koch. With them were Elinor C. Guggenheimer, the incoming consumer affairs commissioner, and Michael J. Lazar, the incoming transportation administrator.Jack Manning/The New York TimesShe was a clinical professor of psychiatry at Columbia University’s College of Physicians and Surgeons, a professor of behavioral science at the City University of New York School of Medicine and resident professor of mental health policy at the Heller Graduate School of Social Welfare of Brandeis University in Massachusetts.In 1980, Dr. Christmas became the first Black woman president of the American Public Health Association. She was also a founder of the Urban Issues Group, a research institute, and served as its executive director from 1993 to 2000.Reflecting on her career in 2020, Dr. Christmas concluded that “the barrier of racism is greater than being a woman.”“I interviewed for a residency, and the man who was interviewing me said he was concerned that I, as an African American woman, would be too sexually stimulating to men patients,” she told The Women in Medicine Legacy Foundation.“When I was looking for an office in Manhattan in the 1960s, at least a third of the agents I spoke with on the telephone said they could guarantee me that there were no Blacks or Puerto Ricans in the building,” she added. “It was so hard to find a place to live that my husband and I wound up going to court, where we prevailed.”Having been exposed to racial discrimination since childhood, Dr. Christmas said, she was imbued with a commitment to minimize prejudice. She became a psychiatrist, she recalled, because she believed that “maybe if I went into psychiatric medicine I could teach people not to be racist.”Her strategy was individualistic, she said, invoking a proverb — “Each one, teach one” — rooted in American slavery when Black people were denied an education and literacy was conveyed from one person to another.