NFL players with concussion symptoms show reduced cognitive performance decades later

 Former professional football players who reported experiencing concussion symptoms during their playing careers were found to perform worse on a battery of cognitive tests than non-players, according to a study led by Mass General Brigham investigators from McLean Hospital and Spaulding Rehabilitation Network. Results of the study are published March 2nd in Archives of Clinical Neuropsychology

Of the more than 350 former National Football League (NFL) players who were studied an average of 29 years after their playing career ended, those who reported experiencing concussion symptoms during their careers scored worse on assessments of episodic memory, sustained attention, processing speed and vocabulary. However, the number of concussions diagnosed by a medical professional or length of playing career had no observed effect on cognition.

A follow-up analysis compared the former players to more than 5,000 male volunteers in the general population who did not play professional football, which found that cognitive performance was generally worse for former players than nonplayers. While younger former players outperformed nonplayers on some tests, older retired players more likely to perform worse than controls on cognitive tasks.

The researchers who led the study said that their results underline the importance of tracking concussion symptoms as opposed to diagnosed concussions in research. This work also adds evidence to the impact a professional football career can have on accelerating cognitive aging.

"It is well-established that in the hours and days after a concussion, people experience some cognitive impairment. However, when you look decades out, the data on the long-term impact have been mixed," said study senior author Laura Germine, Ph.D., director of the Laboratory for Brain and Cognitive Health Technology at McLean Hospital and associate professor of psychiatry at Harvard Medical School. "These new findings from the largest study of its kind show that professional football players can still experience cognitive difficulties associated with head injuries decades after they have retired from the sport."

For the study, 353 retired NFL players completed hour-long neuropsychological tests through an online platform called TestMyBrain, which is supported by McLean Hospital and Harvard Medical School. Players were fully remote and completed tests on a laptop or desktop that included assessments that measured processing speed, visual-spatial and working memory, and aspects of short- and long-term memory and vocabulary.

Recollected concussion symptoms were measured by asking the players the number of times they experienced any one of the following symptoms following a blow to the head during play or practice: headaches, nausea, dizziness, loss of consciousness, memory problems, disorientation, confusion, seizure, visual problems or feeling unsteady on their feet. They were also asked whether they lost consciousness during their careers, and whether they were ever diagnosed with a concussion by a medical professional.

The results showed that the former players' cognitive performance (for example, on memory tasks) was associated with recalled football concussion symptoms. For example, differences observed in visual memory scores between former players with the highest and lowest reported concussion symptoms were equivalent to the differences in cognitive performance between a typical 35-year-old and 60-year-old.

However, poor cognitive performance was not associated with diagnosed concussions, years of professional play or age of first football exposure. The researchers noted that many head injuries or sub-concussive blows may not have been diagnosed as concussions due to a lack of awareness at the time or underreporting of symptoms by players.

When comparing the retired players to a group of 5,086 men who did not play football, cognitive performance was generally worse for former players. On two tests of processing speed, age-related differences in cognitive performance were larger among the former player group than the nonplayer group, with older players performing worse.

These comparison data suggest that football exposure might accelerate age-related cognitive declines and produce greater disadvantages at older ages, according to the researchers, who added that more studies are needed to track cognitive performance in former players as they age. Another possibility is that improved awareness and management of head injuries may have spared younger retired players more than older ones. The researchers also noted that this comparative finding is limited by a lack of data on cognition prior to head injuries, and that more research is needed that closely matches former players and nonplayers and measures their cognitive performances across their lifetimes.

"For both former players and researchers, we can glean some important takeaways from this study," said principal investigator of the Football Players Health Study, Ross Zafonte, DO. "Former players can support their cognitive health as they age by taking proactive steps, and continuing to consult with their providers and educate themselves on symptoms of head injury. For researchers and providers, these findings support efforts to develop ways to enhance diagnosis and define long-term sequalae of concussion." Zafonte is president of Spaulding Rehabilitation Network, a Mass General Brigham sports medicine physician, and the Earle P. and Ida S. Charlton Professor and Chair of the Harvard Medical School Department of Physical Medicine and Rehabilitation.

"The Community Based Participatory Research (CBPR) approach taken in this study is where this field is heading," said Germine. "We are grateful to the players and how much they have taught us. It would not have been possible to do a study like this without engaging and deeply involving their community."

Research driven by input from former NFL players

The Football Players Health Study at Harvard University, launched in 2014, is a comprehensive research program dedicated to examining the multifactorial causes that impact the health of former NFL players. The research has been informed by the players themselves, who have provided input on the health concerns and conditions they face after a career in football.

An interdisciplinary team of researchers from Harvard University and Harvard Medical School and its affiliated teaching hospitals, including those in the Mass General Brigham system, conduct research from neurology, cardiology, sports medicine, rehabilitation medicine, chronic pain and public health. While concussion and head injury are of paramount concern, the study examines all aspects of player health across the life span.

More information: Roger W Strong et al, Association of Retrospectively Reported Concussion Symptoms with Objective Cognitive Performance in Former American-Style Football Players, Archives of Clinical Neuropsychology (2023). DOI: 10.1093/arclin/acad008

https://medicalxpress.com/news/2023-03-nfl-players-experienced-concussion-symptoms.html

Eye damage in Alzheimer's

 Cedars-Sinai investigators have produced the most extensive analysis to date of changes in the retina—a layer of tissue at the back of the eye where visual information originates—and how those retinal changes correspond to brain and cognitive changes in Alzheimer's disease patients.

Their analysis, published in Acta Neuropathologica, is an important step toward understanding the complex effects of Alzheimer's disease on the retina, especially at the earliest stages of cognitive impairment. Experts believe this understanding is key for the development of more effective treatments that could prevent progression of the disease.

More than 3 million Americans are diagnosed with Alzheimer's disease each year. The disease progressively destroys memory and cognitive ability. Currently, there is no single diagnostic test that can definitively diagnose a patient with Alzheimer's disease, and the newest treatments only slow–don't stop—progression.

"Our study is the first to provide in-depth analyses of the protein profiles and the molecular, cellular, and structural effects of Alzheimer's disease in the human retina and how they correspond with changes in the brain and cognitive function," said Maya Koronyo-Hamaoui, Ph.D., professor of Neurosurgery, Neurology, and Biomedical Sciences at Cedars-Sinai and senior author of the study.

"These findings may eventually lead to the development of imaging techniques that allow us to diagnose Alzheimer's disease earlier and more accurately and monitor its progression noninvasively by looking through the eye."

"The retina, a developmental extension of the brain, offers an unparalleled opportunity for affordable, noninvasive monitoring of the central nervous system," said Yosef Koronyo, MSc, research associate in the Cedars-Sinai Department of Neurosurgery and first author of the study. "And with the help of our collaborators, we discovered the accumulation of highly toxic proteins in the retinas of patients with Alzheimer's disease and mild cognitive impairment, causing severe degeneration of cells."

Investigators looked at retinal and brain tissue samples collected over 14 years from 86 human donors—the largest group of retinal samples from human patients with Alzheimer's disease and mild cognitive impairment thus far studied. They compared samples from donors with normal cognitive function to those with mild cognitive impairment at the earliest stages of Alzheimer's disease, and those with later-stage Alzheimer's disease dementia.

The investigators explored the physical features of the retinas of these patients, measuring and mapping markers of inflammation and functional cell loss, and analyzed the proteins present in retinal and brain tissues.

Here is what investigators found in the retinas of patients with mild cognitive impairment and Alzheimer's disease:

• An overabundance of a protein called amyloid beta 42, which in the brains of Alzheimer's disease patients clumps together to form plaques that disrupt brain function
• Accumulation of amyloid beta protein in ganglion cells, the cells that bridge visual input from the retina to the optic nerve
• Higher numbers of astrocytes and immune cells, called microglia, tightly surrounding amyloid beta plaques
• As many as 80% fewer microglial cells clearing amyloid beta proteins from the retina and brain
• Specific molecules and biological pathways responsible for inflammation, and cell and tissue death

"These changes in the retina correlated with changes in parts of the brain called the entorhinal and temporal cortices, a hub for memory, navigation and the perception of time," said Koronyo.

Retinal changes also correlated with the pathological stage of Alzheimer's disease (called Braak stage) and patients' cognitive status. And they were found even in patients who appeared cognitively normal or very mildly impaired, marking them as a possible early predictor of later cognitive decline.

"These findings give us a deeper understanding of the effects of Alzheimer's disease on the retina," said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai and a co-author of the study. "Because these changes correspond with changes in the brain and can be detected in the earliest stages of impairment, they may lead us to new diagnostics for Alzheimer's disease and a means to evaluate new forms of treatment."

More information: Yosef Koronyo et al, Retinal pathological features and proteome signatures of Alzheimer's disease, Acta Neuropathologica (2023). DOI: 10.1007/s00401-023-02548-2

https://medicalxpress.com/news/2023-03-insights-eye-alzheimer-disease-patients.html

'COVID rebound' is common, even in untreated patients

 "COVID rebound," in which evidence of the illness disappears and then returns days or weeks later, is surprisingly common—whether or not patients are given the antiviral Paxlovid.

The results, reported on February 22 in Clinical Infectious Diseases by scientists at Scripps Research and the digital health company eMed, are a preliminary readout from an ongoing observational study of people who order SARS-CoV-2 antigen test kits online.

The researchers found that in an initial group of 170 eMed Test-to-Treat kit users, the disappearance and then return of evidence of the virus on antigen tests and in self-reported COVID-19 symptoms occurred in 9.3% and 7.0% of patients who opted not to take antiviral treatment, and in 14.2% and 18.9% of those who opted for Paxlovid.

Although a higher proportion of the Paxlovid-treated group reported COVID-19 rebound, the difference was not statistically significant in this early snapshot of the ongoing study, which is designed ultimately to enroll a total of 800 patients.

"These preliminary results suggest that rebound after clearance of SARS-CoV-2 test positivity or COVID-19 symptom resolution is more common than previously reported in both treated and untreated patients," says study lead author Jay Pandit, MD, an assistant professor and director of Digital Medicine at the Scripps Research Translational Institute. "We're going to need a larger set of participants and more extended follow-up to better understand this rebound phenomenon."

The study, conducted from August to November of last year, was a collaboration with eMed, including epidemiologist and Chief Science Officer Michael Mina, MD, Ph.D., previously professor at Harvard T.H. Chan School of Public Health, and others at the Test-to-Treat company, which is also implementing the NIH Home Test to Treat COVID-19 program.

Reports of COVID-19 rebound started appearing in the medical literature in 2022. The cause of rebound has been unclear, although the suggestion in most of these reports has been that rebound occurs more often in patients treated with Paxlovid. The latter, a mix of two antiviral compounds (nirmatrelvir and ritonavir), received emergency use approval in late 2021 from the U.S. Food and Drug Administration (FDA) for treating patients who have mild-to-moderate COVID-19 and are at high risk of developing severe COVID-19.

To help illuminate the rebound phenomenon and any connection to Paxlovid, Pandit and his colleagues teamed up with eMed to drive a "real-world" study of outcomes among people using the company's COVID-19 Test-to-Treat antigen test kits with telehealth proctoring and telemedicine.

"As the COVID-19 landscape continues to evolve, the importance of making timely and effective treatments accessible and thereby helping reduce severe disease outcomes cannot be overstated," Mina says.

"Collaborations such as this with the Scripps Research Translation Institute are a key part of efforts to gather evidence-based data and answer critical questions associated with treatment outcomes. We are also proud that this study not only offers new data surrounding COVID-19 recovery and treatment outcomes, but also highlights the benefits of industry and academic partnerships to accelerate high-quality public health and translational research."

The researchers offered Test-to-Treat telehealth kit users participation in the study if they had a verified positive test. If users consented to participate, the researchers sent them more test kits, and asked each participant to take a test and fill out a symptom questionnaire every other day for 16 days. The team then compared the rates of rebound for those who did and didn't opt to take Paxlovid.

Rebound was measured in two ways: a positive test result after a negative test, or a reported recurrence of symptoms after symptom resolution. For this preliminary analysis, there were 127 people in the Paxlovid-treated group, and 43 in the non-Paxlovid group.

Either way rebounds were measured, the Paxlovid group experienced them at a higher rate: 14.2% vs. 9.3% for antigen test rebounds, and 18.9% vs. 7.0% for symptom rebounds. With the small participant numbers included in this preliminary analysis, these differences were not statistically significant.

Moreover, on other measures (such as the time from first positive antigen test to first negative antigen test, and time from symptom onset to first symptom resolution), the two groups had essentially identical outcomes. Age, gender and pre-existing conditions also did not appear to influence rebound.

Pandit emphasizes that the study is not currently powered to detect statistically significant results, and a final analysis should include up to 800 participants and thus should have much more power to generate conclusive findings. However, he adds, the preliminary findings already make clear that the rebound rates for both treated and untreated groups are higher than the rates reported in prior studies.

For example, an analysis of their clinical trial results by Pfizer, the maker of Paxlovid, found rebound rates of only about 2% in both Paxlovid and placebo groups over a two-week period.

In addition to increasing the number of participants in their ongoing study, Pandit and colleagues plan to start sequencing the virus found in participants and testing participants' blood samples for antibody levels and other immune markers.

"We're hoping to answer key questions about the rebound phenomenon, such as whether it's enhanced by Paxlovid, how much it depends on the viral variant and what is the role of the patient's immune system," Pandit says.

He and his team also plan to improve the balance of ethnic and racial representation between the treatment and control groups: In the initial group of 170, Whites were much more likely than Blacks and Latinos to opt for Paxlovid treatment.

More information: Jay A Pandit et al, The COVID-19 Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences in Participants Treated with Nirmatrelvir Plus Ritonavir Versus Untreated Controls, Clinical Infectious Diseases (2023). DOI: 10.1093/cid/ciad102

https://medicalxpress.com/news/2023-03-covid-rebound-common-untreated-patients.html

Newest glucose-lowering drug could cut risks of renal and respiratory diseases

 A research team in the Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, the University of Hong Kong (HKUMed) has discovered that sodium-glucose cotransporter 2 inhibitors (SGLT2i) could reduce the risks of renal and respiratory diseases, including end-stage renal disease (ESRD), obstructive airway disease (OAD) and pneumonia in a retrospective cohort study.

These studies provided novel real-world evidence that SGLT2i could confer extra-glycemic protection to patients with type 2 diabetes and potentially be a better alternative to an older class of glucose-lowering drugs, dipeptidyl peptidase-4 inhibitors (DPP4i). The discovery has been published in The Journal of Clinical Endocrinology & Metabolism and JAMA Network Open.

SGLT2i are a new class of second-line glucose-lowering drugs for type 2 diabetes. Placebo-controlled clinical trials and multinational observational studies have shown that besides glycemic control, SGLT2i also confer cardiovascular and renal protection in patients with type 2 diabetes over the past few years.

However, it is not clear whether SGLT2i could provide better cardiorenal protection when compared to individual classes of older glucose-lowering drugs that have been widely prescribed in recent years, such as DPP4i. A retrospective cohort study has been conducted so to investigate the association of SGLT2i, with 4 renal outcomes, namely ESRD, albuminuria, acute renal failure (ARF), and the decline in estimated glomerular filtration rate (eGFR).

The team also conducted another retrospective cohort study to investigate the association of SGLT2i with the risk of OAD and pneumonia because SGLT2i were shown to inhibit the lung NLRP3 inflammasome activation, which has been implicated in both asthmatic airway inflammation and chronic obstructive pulmonary disease (COPD) exacerbations in some animal studies.

From a cohort of more than 30,000 patients with type 2 diabetes in Hong Kong, after adjusting for potential confounders, the team found that compared to DPP4i, SGLT2i were significantly associated (P-value <0.05) with an 81% reduced risk of ESRD, a 70% reduced risk of ARF, a 50% reduced risk of albuminuria, as well as a slower decline in eGFR. These findings agreed with the results from previous clinical trials and provided real-world evidence suggesting that SGLT2i could confer additional renal protective effects.

For respiratory outcomes, SGLT2i were significantly associated with a 35% reduced risk of OAD and a 46% reduced rate of OAD exacerbations, as well as a 41% reduced risk of pneumonia. The findings showed novel evidence that SGLT2i could be protective against OAD and pneumonia. Clinical trials should be carried out for the examination of these respiratory outcomes.

Dr. Cheung Ching-lung, Associate Professor, Department of Pharmacology and Pharmacy, HKUMed, commented, "Due to the observational nature of the studies, further dedicated clinical trials and pooled analyses of studies from different populations and subgroups should be conducted so to give a bias-free conclusion. All in all, SGLT2i could potentially be a better alternative drug to DPP4i and be used as an extra-glycemic drug."

More information: Philip C. M. Au et al, Association of Sodium-Glucose Cotransporter 2 Inhibitor vs Dipeptidyl Peptidase-4 Inhibitor Use With Risk of Incident Obstructive Airway Disease and Exacerbation Events Among Patients With Type 2 Diabetes in Hong Kong, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2022.51177

Philip C M Au et al, Association Between SGLT2 Inhibitors vs DPP-4 Inhibitors and Risk of Pneumonia Among Patients With Type 2 Diabetes, The Journal of Clinical Endocrinology & Metabolism (2021). DOI: 10.1210/clinem/dgab818

Philip C M Au et al, Association Between SGLT2 Inhibitors vs DPP4 Inhibitors and Renal Outcomes Among Patients With Type 2 Diabetes, The Journal of Clinical Endocrinology & Metabolism (2022). DOI: 10.1210/clinem/dgac164

https://medicalxpress.com/news/2023-03-glucose-lowering-drug-renal-respiratory-diseases.html

Lexicon Pharmaceuticals Stock Jumps on 4Q Revenue, Sotagliflozin Heart Drug Update

 Shares of Lexicon Pharmaceuticals Inc. jumped 25% to $2.73 on Friday after the company posted results that showed its revenue doubled in the fourth quarter, along with details on its sotagliflozin drug.

The Woodlands, Texas biopharmaceutical company posted a net loss of $30.5 million, or 16 cents a share, after the market's close Thursday compared with a loss of $25.6 million, or 17 cents a share, for the same period a year earlier.

Revenue from royalties and other sources surged to $28 million from $14 million a year ago, the company said.

Total operating expenses, including costs related to the commercial launch of its sotagliflozin drug to treat heart failure, rose 16% to $30.3 million, the company said.

In July, Lexicon Pharmaceuticals received Food and Drug Administration approval to treat heart failure with sotagliflozin.

"We are on track for the PDUFA (prescription drug user fee act) action date in May of this year for our NDA for sotagliflozin for the treatment of heart failure, as confirmed during this week's FDA late-cycle review meeting," Lexicon Chief Executive Lonnel Coats said.

https://www.marketscreener.com/quote/stock/LEXICON-PHARMACEUTICALS-22283344/news/Lexicon-Pharmaceuticals-Stock-Jumps-on-4Q-Revenue-Sotagliflozin-Heart-Drug-Update-43153201/

Legal uncertainty hovers over Walgreens decision on abortion pill dispensing

 The country’s second-largest pharmacy chain said it will not dispense abortion pills in several states — including some without current restrictions — after coming under pressure from state officials and anti-abortion advocates.

Supporters of abortion rights say the move by Walgreens isn’t a surprise, but it shows the complicated situation facing states, patients, pharmacies and pharmacists since the Supreme Court overturned Roe v. Wade last summer.

The decision from Walgreens comes after 20 Republican state attorneys general in a letter last month warned of legal consequences if the company started distributing the drug. 

A Walgreens spokesman said the company has responded to each attorney general who signed the letter, telling them the company will not dispense mifepristone — a medication used to end pregnancy — in its brick-and-mortar pharmacies and will not mail it to those states.

Among them were four states — Alaska, Iowa, Kansas and Montana — where medication abortion remains legal due to court challenges.

In Kansas, for example, voters said the right to an abortion is protected by the state constitution. A state law prohibited anyone except a physician from dispensing mifepristone, but it has since been blocked in court. 

Abortion is also legal in Montana, and the state’s requirement for a patient to have an in-person visit with a physician before being prescribed mifepristone is being challenged.  

But Walgreens will refrain from dispensing the drug in those states, citing the complex legal situation.

“This is a significant victory for the pro-life cause and for women’s health,” Kansas Attorney General Kris Kobach (R) said in a statement. “The dispensing of these pills without a supervising physician present would expose women to complications and potentially to coercion as well. I’m grateful Walgreens has responded quickly and reasonably and intends to fully comply with the law.”

After the Biden administration in January moved to allow retail pharmacies to dispense mifepristone, Walgreens said it planned to seek the federal certification to do so — but only in the states where it is legal.

Walgreens spokesman Fraser Engerman said the company will distribute mifepristone “only in those jurisdictions where it is legal and operationally feasible.

Walgreens has no plans to use its mail order pharmacy business to dispense mifepristone. 

“At this time, we are working through the certification process, which includes the evaluation of our pharmacy network to determine where we will dispense Mifepristone and training protocols and updates for our pharmacists,” Walgreens wrote in its response to Kobach. 

“Walgreens does not intend to dispense Mifepristone within your state and does not intend to ship Mifepristone into your state from any of our pharmacies. If this approach changes, we will be sure to notify you.”

Medication abortion is the nation’s most common method for ending a pregnancy, and mifepristone has been approved by the Food and Drug Administration as safe and effective for more than 20 years.

Even so, the availability of medication abortion today depends on state laws. Ever since the Supreme Court overturned Roe v. Wade, an increasing number of states have restricted abortion completely or enacted barriers to medication abortion.  

In addition, a looming decision by a federal judge in Texas could undo mifepristone’s approval and result in it being taken off the market. A decision in that case is expected any day.

https://thehill.com/policy/healthcare/3883199-legal-uncertainty-hovers-over-walgreens-decision-on-abortion-pill-dispensing/

America must stop China’s lethal fentanyl engine

 Some people might be surprised to find the leading cause of death among Americans ages 18 to 45 is not heart disease, cancer, motor vehicle accidents, or COVID-19—it is fentanyl. According to the Center for Disease Control (CDC), fentanyl is now the leading cause of death for Americans in this age bracket, and it’s only getting worse. Fentanyl is highly addictive and creates large profit margins for those involved in the manufacturing and dealing of the synthetic opioid. The world’s largest source of illicit fentanyl and fentanyl analogues is China.

A mere 2 milligrams of fentanyl make up a lethal dose for most people—the equivalent to a few grains of salt. Fentanyl is cheaper to make than other opioids, easier to smuggle over borders because of its power in small quantities, and highly addictive. This creates a sizeable business model for the drug ring and a perfect storm for users who can easily get addicted to this lethal drug.

While we continue to work to address the crisis at our southern border and the drug addiction that is sweeping through our communities, it’s important we cut the lethal fentanyl engine off at its source: China. The precursor chemicals making up the essential ingredients of fentanyl and fentanyl-related substances is from China. After being shipped to Mexico, the chemicals are produced into fentanyl-containing tablets and enters the United States via our southern border. It’s estimated China is responsible for over 90 percent of illicit fentanyl found in the United States. We simply cannot allow the lethal fentanyl engine in China to run while communities across America’s heartland are being torn apart.

Even as the Chinese Communist Party (CCP) continues to threaten American democracy and the frontiers of the free world, they refuse to play by their own rules. In 2018, after Washington urged Beijing to stop fueling the opioid epidemic in the United States, China announced all variants of fentanyl would be treated as controlled substances. However, they failed to enforce this and have subsequently continued to deny illicit fentanyl producers are a major source of illicit opioids in the United States despite data pointing to the contrary. We simply cannot trust them to be a responsible stakeholder and address this crisis in good faith. As a member of the House Select Committee on the CCP, it is our goal to expose the pattern of aggression from the CCP and identify the existential threats they hold against the United States. This is one of those threats.

The Select Committee on the CCP will tackle important issues such as the CCP buying up agricultural land in the United States, gathering intelligence from sensitive military bases, disregarding human rights, bullying Taiwan, and stealing our intellectual property—their part in fueling the fentanyl crisis is no different.

I have been a strong leader in fighting the fentanyl epidemic that is plaguing our communities and recognize more must be done to safeguard our communities. We will work to secure our border from the flow of illicit fentanyl and other deadly drugs, support law enforcement so they have the resources they need, and hold the dealers on the streets accountable. At the very top of this lethal food chain are bad actors in China manufacturing fentanyl and the CCP who is allowing their lethal fentanyl engine to run while it kills off thousands of Americans. We must put a stop to this crisis, and knowing our enemy is the first step.

Dan Newhouse represents Washington’s 4th District and is a member of the House Select Committee on Strategic Competition between the United States and the Chinese Communist Party.

https://thehill.com/opinion/congress-blog/3883304-america-must-stop-chinas-lethal-fentanyl-engine/