Kory London, Thomas Jefferson University

Unimaginable pain and restlessness. Vomiting so frequent and forceful that it can perforate the esophagus. Blood pressure and heart rate so high that they damage the heart. Sweating that drenches clothing and sheets. Nerve sensitivity that makes even the softest touch agonizing. A prolonged panic attack that is provoked and worsened by even mundane activities and conversations.

The withdrawal symptoms from “tranq dope” – the combination of the synthetic opioid fentanyl and the animal tranquilizer xylazine that dominates Philadelphia’s street opioids supply – tend to be far worse than those experienced by even the most severe heroin users of the past.

So it’s no surprise that people will do whatever they can to forestall them. That includes walking out of the hospital before their care is complete.

I’m an associate professor of emergency medicine who has spent a decade as an emergency physician working in Center City and South Philadelphia. I’ve spent most of that time directing projects to improve care for people who use drugs.

Beginning in 2022, our team – a group of emergency and addiction physicians – began experimenting with new approaches to treating tranq dope withdrawal.

We were able to reduce the likelihood of these patients leaving the hospital before treatment was complete by more than half – from 10% to just under 4%.

We also reduced the severity of their suffering, lowering their withdrawal scores – or how they rate their pain and other symptoms – by more than half.

Traditional treatments don’t work

Before tranq dope, treating opioid withdrawal in the emergency department was relatively straightforward, with well-studied, conventional protocols.

For patients without chronic pain, health care providers started buprenorphine, known by its brand name Suboxone, when patients showed signs of withdrawal.

Buprenorphine works by partially, rather than fully, stimulating opioid receptors in the body. This subtle difference relieves symptoms of withdrawal but reduces the risk of overdose if patients continue to use other opioids. It quite literally saves lives.

Tranq dope, however, created a much larger set of challenges.

Fentanyl and other synthetic opioids are dozens to hundreds of times more powerful than heroin. Xylazine, meanwhile, adds symptoms of sedative withdrawal to the mix: restlessness, adrenaline activation and agitation.

As synthetic opioids became pervasive in Philadelphia’s drug supply over the past decade, overdose deaths in the city tripled. Those numbers are beginning to decline, for reasons that remain unclear.

Meanwhile, tranq users started to share buprenorphine horror stories. They refused the medication due to a phenomenon called “precipitated withdrawal.” Precipitated withdrawal is a condition in which taking buprenorphine paradoxically makes withdrawal symptoms worse, rather than improving them. Due to the severity of their symptoms, some patients who precipitate severely even require treatment in the intensive care unit.

Furthermore, when patients did accept buprenorphine, their withdrawal symptoms were no longer being effectively controlled, even with very high doses. We were adrift.

Patients demand discharge

When people with severe substance use disorders are hospitalized, even compassionate staff members sometimes lose patience.

Being confined to a stretcher in a loud, chaotic environment, in withdrawal, with prior traumatic health care experiences, can lead patients to act out. They might repeatedly hit call bells, use inappropriate language, make impulsive decisions or sneak drugs into the hospital.

This creates a lot of stress for nurses and staff, and distracts from the care of others.

So when patients demand to leave before treatments are complete, exhausted care teams often quickly acquiesce. Traditionally, this was termed leaving “against medical advice,” but is now called “patient-directed discharge.”

Patient-directed discharge is associated with higher rates of mortality, permanent disability and rehospitalization.

Rates of patient-directed discharge can be 10 to 50 times higher in people with an opioid use disorder compared with the general public.

A cycle of mistrust can also form, where the expectation that a patient may leave again leads to a less engaged care team, which in turn can make patients more likely to leave.

At staff meetings, some compared the challenges of caring for these individuals to those experienced in the hardest parts of the COVID-19 pandemic.

New approach needed

Many physicians have been reticent to consider other options for treating opioid withdrawal. I believe there are two key reasons for this. One is the lack of Food and Drug Administration approval for alternative treatments. The other is that federal regulations consider addiction a behavioral rather than medical condition, effectively separating most doctors from the addiction care of these individuals.

As fentanyl and xylazine became ubiquitous in Philadelphia’s street dope, local hospitals reported astronomical rates of patient-directed discharge among these patients. This was happening despite the best efforts of hospital staffs that are deeply experienced in conventional opioid withdrawal treatment.

In 2021, an editorial in the Annals of Internal Medicine journal advocated for the use of short-acting opioids for some patients’ opioid withdrawal – which is already common practice in Canada. Short-acting opioids are medications doctors traditionally use to treat acute pain.

Philadelphia hospitals started experimenting with using these previously verboten medications. That included our team at Jefferson Health.

Oxycodone, hydromorphone and ketamine

By using short-acting opioids such as oxycodone or hydromorphone, combined with a low-dose version of buprenorphine, we prevented precipitated withdrawal and treated opioid withdrawal and pain in our patients.

The low-dose bupenorphine can be increased over time to steady doses. This shows patients that the medication is safe and provides them a bridge to long-term treatment.

The short-acting opioids replace the opioids that their bodies are frantically searching for. They reduce their pain and misery, and are decreased when their symptoms are controlled.

Patients with opioid use disorder will often do whatever they can to stay out of the hospital due to fear of withdrawal. Asking how withdrawal symptoms are managed, therefore, is often their first priority when hospitalized. We see this even when they have conditions that require complicated and time-sensitive treatments.

Owing to the vast amounts of opioids many of our patients use, we also give them additional strong medications, or “adjunctive therapies,” to supplement the effects of the short-acting opioids and low-dose buprenorphine. One is ketamine, an anesthetic that affects nerve impulses and is increasingly being used to treat depression, post-traumatic stress discorder and substance use disorders.

Ketamine is also an effective pain medication that can extend the effects of opioids and reduce the number of doses needed.

We additionally add muscle relaxants – which work similarly to xylazine – along with nausea medications and IV fluids, to help give patients a chance at healing.

Side effects and future problems

In patients who received our medications, the risks of serious side effects were minimal. The few patients who suffered serious adverse effects had other acute medical problems that could have contributed to the side effects. Almost all the side effects we saw were mild and resolved on their own.

As powerful synthetic opioids and other contaminants become pervasive in more U.S. cities, more emergency departments will need to figure out how to care for patients in withdrawal so that they don’t leave treatment.

It is our hope that this work will inspire others to do a better job of providing relief to patients suffering from this complicated and severe condition.

Kory London, Associate Professor of Emergency Medicine, Thomas Jefferson University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Shaoyu Yuan, Rutgers University – Newark and Jun Xiang, Rutgers University – Newark

It may sound far-fetched, but the future of global technology supremacy could hinge on a video game.

Black Myth: Wukong, China’s latest blockbuster, isn’t just breaking gaming records – it could be driving a critical shift in the global balance of technological power. What seems like just another action-packed video game is, in reality, a vital component in Beijing’s larger strategy to challenge Western dominance in the tech industry.

The game, released by Chinese company Game Science on Aug. 19, 2024, is based on the legendary 16th century Chinese novel “Journey to the West.” The novel tells the story of a monk, Xuanzang, who journeys to India in search of Buddhist scrolls. The monkey Sun Wukong protects the monk by confronting and battling various demons and spirits.

Black Myth: Wukong has captivated millions with its stunning visuals and storytelling. It quickly became a cultural sensation in China and abroad, attracting widespread attention and praise for its graphic fidelity and technological sophistication.

As global affairs scholars, we see that the game’s success goes beyond the number of downloads or accolades. It’s what this success is driving within China’s technology sector that has far-reaching consequences.

Video games and global power

For years, China has been playing catch-up in the tech race, particularly in the production of semiconductors – the tiny microchips that power everything from smartphones to advanced artificial intelligence systems. The United States has maintained its dominance in this field by limiting China’s access to the most advanced chip-making technology.

As of 2024, China has shifted away from its aggressive “wolf warrior” diplomacy to a more cooperative approach in order to rebuild international ties. The government has also issued mandates for companies like Huawei to develop domestic chips. However, China’s success in boosting semiconductor development and production using these approaches has been limited.

Historically, video games have played a significant role in driving technological innovation in the semiconductor industry. From the early days of the 8-bit Nintendo Entertainment System to the modern PlayStation 5, gaming has always pushed chipmakers to develop faster, more efficient processors and graphics processing units, or GPUs. The intense graphical requirements of modern games – high resolutions, faster frame rates and real-time rendering – demand the most advanced semiconductor technology. The development of advanced GPUs by companies like NVIDIA was directly influenced by the gaming industry’s needs.

Gamers require advanced processors to enjoy Black Myth: Wukong’s high-end visual and gameplay experience. Built using the state-of-the-art Unreal Engine 5 video game development tool, the game is a visual spectacle featuring lifelike graphics, seamless open-world environments and complex combat systems. The game is available for PlayStation 5 and PCs, and Game Science plans to release an Xbox version.

As Black Myth: Wukong sweeps across gaming platforms, it not only puts pressure on China’s semiconductor makers to build more and better chips, but it also reveals the vast market potential for high-performance hardware, especially for gaming PCs equipped with powerful GPUs. The game’s success showcases just how big the demand is.

Market analysts expect the Chinese video game industry to reach revenues of US$66.13 billion in 2024, compared with $78.01 billion in the U.S. Analysts predict the game will have annual sales of 30 million to 40 million copies in 2024.

China’s gaming industry has surged into a global powerhouse, yet it remains dependent on foreign-made chips. Coupled with the West‘s restrictions on chip exports, Wukong has become a key catalyst for China’s semiconductor development, and domestic companies now face growing pressure to innovate.

This pressure aligns with Beijing’s broader technological ambitions. The government’s “Made in China 2025” plan calls for technological self-reliance, particularly in sectors like semiconductors, where China lags behind. And advanced GPUs haven’t been confined to the entertainment industry. They have become integral to advances in AI, including deep learning and autonomous systems.

Flexing China’s cultural muscle

While it might seem strange to link video games with geopolitics, Black Myth: Wukong is more than just entertainment. It’s a tool in China’s soft power arsenal. Soft power is nations influencing each other through cultural exports. For decades, the West, particularly the U.S., dominated global culture through Hollywood, music and video games.

Now, China is flexing its cultural muscle. The success of Black Myth: Wukong abroad, where it has been hailed as a game-changing title, is part of Beijing’s strategy to export its culture and technological prowess. Millions of gamers around the world are now being exposed to Chinese mythology, art and storytelling through a highly sophisticated digital medium.

But Black Myth: Wukong isn’t just a cultural triumph for China; it’s a warning shot. The country is taking advantage of its booming gaming industry to drive advances in a field that will define the future of technology. This game not only exports Chinese culture but also strengthens its tech base by accelerating the demand for domestic semiconductors.

While Black Myth: Wukong entertains millions, it also shows China’s growing influence in the digital realm. In the future, we might not look back at Black Myth: Wukong as just a successful video game, but as a catalyst that helped China close the technological gap with the West. Beijing is playing a long game, and video games like Black Myth: Wukong are turning out to be effective weapons.

Shaoyu Yuan, Dean’s Fellow at the Division of Global Affairs, Rutgers University – Newark and Jun Xiang, Professor of Economics and Global Affairs, Rutgers University – Newark

This article is republished from The Conversation under a Creative Commons license. Read the original article.

R. Alexander Bentley, University of Tennessee

In my research focused on early farmers of Europe, I have often wondered about a curious pattern through time: Farmers lived in large dense villages, then dispersed for centuries, then later formed cities again, only to abandon those as well. Why?

Archaeologists often explain what we call urban collapse in terms of climate change, overpopulation, social pressures or some combination of these. Each likely has been true at different points in time.

But scientists have added a new hypothesis to the mix: disease. Living closely with animals led to zoonotic diseases that came to also infect humans. Outbreaks could have led dense settlements to be abandoned, at least until later generations found a way to organize their settlement layout to be more resilient to disease. In a new study, my colleagues and I analyzed the intriguing layouts of later settlements to see how they might have interacted with disease transmission.

Earliest cities: Dense with people and animals

Çatalhöyük, in present-day Turkey, is the world’s oldest farming village, from over 9,000 years ago. Many thousands of people lived in mud-brick houses jammed so tightly together that residents entered via a ladder through a trapdoor on the roof. They even buried selected ancestors underneath the house floor. Despite plenty of space out there on the Anatolian Plateau, people packed in closely.

For centuries, people at Çatalhöyük herded sheep and cattle, cultivated barley and made cheese. Evocative paintings of bulls, dancing figures and a volcanic eruption suggest their folk traditions. They kept their well-organized houses tidy, sweeping floors and maintaining storage bins near the kitchen, located under the trapdoor to allow oven smoke to escape. Keeping clean meant they even replastered their interior house walls several times a year.

These rich traditions ended by 6000 BCE, when Çatalhöyük was mysteriously abandoned. The population dispersed into smaller settlements out in the surrounding flood plain and beyond. Other large farming populations of the region had also dispersed, and nomadic livestock herding became more widespread. For those populations that persisted, the mud-brick houses were now separate, in contrast with the agglomerated houses of Çatalhöyük.

Was disease a factor in the abandonment of dense settlements by 6000 BCE?

At Çatalhöyük, archaeologists have found human bones intermingled with cattle bones in burials and refuse heaps. Crowding of people and animals likely bred zoonotic diseases at Çatalhöyük. Ancient DNA identifies tuberculosis from cattle in the region as far back as 8500 BCE and TB in human infant bones not long after. DNA in ancient human remains dates salmonella to as early as 4500 BCE. Assuming the contagiousness and virulence of Neolithic diseases increased through time, dense settlements such as Çatalhöyük may have reached a tipping point where the effects of disease outweighed the benefits of living closely together.

A new layout 2,000 years later

By about 4000 BCE, large urban populations had reappeared, at the mega-settlements of the ancient Trypillia culture, west of the Black Sea. Thousands of people lived at Trypillia mega-settlements such as Nebelivka and Maidanetske in what’s now Ukraine.

If disease was a factor in dispersal millennia before, how were these mega-settlements possible?

This time, the layout was different than at jam-packed Çatalhöyük: The hundreds of wooden, two-story houses were regularly spaced in concentric ovals. They were also clustered in pie-shaped neighborhoods, each with its own large assembly house. The pottery excavated in the neighborhood assembly houses has many different compositions, suggesting these pots were brought there by different families coming together to share food.

This layout suggests a theory. Whether the people of Nebelivka knew it or not, this lower-density, clustered layout could have helped prevent any disease outbreaks from consuming the entire settlement.

Archaeologist Simon Carrignon and I set out to test this possibility by adapting computer models from a previous epidemiology project that modeled how social-distancing behaviors affect the spread of pandemics. To study how a Trypillian settlement layout would disrupt disease spread, we teamed up with cultural evolution scholar Mike O’Brien and with the archaeologists of Nebelivka: John Chapman, Bisserka Gaydarska and Brian Buchanan.

Simulating socially distanced neighborhoods

To simulate disease spread at Nebelivka, we had to make a few assumptions. First, we assumed that early diseases were spread through foods, such as milk or meat. Second, we assumed people visited other houses within their neighborhood more often than those outside of it.

Would this neighborhood clustering be enough to suppress disease outbreaks? To test the effects of different possible rates of interaction, we ran millions of simulations, first on a network to represent clustered neighborhoods. We then ran the simulations again, this time on a virtual layout modeled after actual site plans, where houses in each neighborhood were given a higher chance of making contact with each other.

Based on our simulations, we found that if people visited other neighborhoods infrequently – like a fifth to a tenth as often as visiting other houses within their own neighborhood – then the clustering layout of houses at Nebelivka would have significantly reduced outbreaks of early foodborne diseases. This is reasonable given that each neighborhood had its own assembly house. Overall, the results show how the Trypillian layout could help early farmers live together in low-density urban populations, at a time when zoonotic diseases were increasing.

The residents of Nebilevka didn’t need to have consciously planned for their neighborhood layout to help their population survive. But they may well have, as human instinct is to avoid signs of contagious disease. Like at Çatalhöyük, residents kept their houses clean. And about two-thirds of the houses at Nebelivka were deliberately burned at different times. These intentional periodic burns may have been a pest extermination tactic.

New cities and innovations

Some of the early diseases eventually evolved to spread by means other than bad foods. Tuberculosis, for instance, became airborne at some point. When the bacterium that causes plague, Yersinia pestis, became adapted to fleas, it could be spread by rats, which would not care about neighborhood boundaries.

Were new disease vectors too much for these ancient cities? The mega-settlements of Trypillia were abandoned by 3000 BCE. As at Çatalhöyük thousands of years before, people dispersed into smaller settlements. Some geneticists speculate that Trypillia settlements were abandoned due to the origins of plague in the region, about 5,000 years ago.

The first cities in Mesopotamia developed around 3500 BCE, with others soon developing in Egypt, the Indus Valley and China. These cities of tens of thousands were filled with specialized craftspeople in distinct neighborhoods.

This time around, people in the city centers weren’t living cheek by jowl with cattle or sheep. Cities were the centers of regional trade. Food was imported into the city and stored in large grain silos like the one at the Hittite capital of Hattusa, which could hold enough cereal grain to feed 20,000 people for a year. Sanitation was helped by public water works, such as canals in Uruk or water wells and a large public bath at the Indus city of Mohenjo Daro.

These early cities, along with those in China, Africa and the Americas, were the foundations of civilization. Arguably, their form and function were shaped by millennia of diseases and human responses to them, all the way back to the world’s earliest farming villages.

R. Alexander Bentley, Professor of Anthropology, University of Tennessee

This article is republished from The Conversation under a Creative Commons license. Read the original article.