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The United States remains tightly in the grasp of an ongoing, and escalating, crisis of deaths[1] caused by opioid overdoses.

With a record-high 109,000 people dying in 2022[2], it is clear that something new needs to be done to reverse this trend.

Philadelphia is near the epicenter of the crisis. Some of the country’s largest open-air drug markets[3] can be found in the Kensington neighborhood. Heroin, prescription opioids and fentanyl aren’t the only drugs of concern. Xylazine, a powerful non-opioid also known as tranq, has an overwhelming presence[4] on the streets.

We are a group of Scandinavian[5] and[6] American[7] researchers who have studied drug treatment and harm reduction, and we have been watching the situation in Philadelphia from a variety of perspectives.

A mixed response

A record 1,413 people died in Philadelphia from drug overdoses in 2022[8]. The rate of drug-related deaths for Black residents more than doubled between 2018 and 2022[9], mirroring a problematic national trend[10].

In response, Philadelphia has adopted a multifaceted plan to stem the tide of overdoses[11].

But Philadelphia’s City Council has overwhelmingly rejected the establishment of supervised injection sites[12] – a potentially impactful, evidence-based tool in this fight. Overriding the mayor’s veto[13] on Sept. 28, 2023, council members have used zoning legislation to essentially prevent the opening of sites where people can take drugs under supervision across most of the city.

In May 2023, the Pennsylvania legislature[14] also overwhelmingly voted to ban supervised injection sites in the entire state.

While much of the political discourse surrounding this decision has focused on protecting neighborhoods[15] where drug activity happens in parks and on the streets, ample evidence suggests that banning supervised injection sites may instead jeopardize the people and communities the policy was intended to protect.

What is harm reduction?

Supervised injection sites are an example of harm reduction, a general approach to addressing addiction and other public health crises. Ranging from efforts aimed at reducing incidences of HIV[16] to encouraging the safer consumption of alcohol[17], the concept has become integral to many global public health initiatives.

The goal of harm reduction[18] is to minimize the negative effects associated with drug use and other risky behaviors rather than solely focusing on eliminating the activity. This approach acknowledges the difficulty in breaking addictive behaviors and the fact that some individuals won’t – or can’t – stop regardless of policy and social efforts.

For drug use, harm reduction takes many forms. These include encouraging nonjudgmental approaches toward people who use drugs among social service workers and health care personnel, needle exchange programs, distribution of drugs that reverse overdoses, testing drugs for safety – and, in many parts of the world, supervised injection sites.

Limitations in the United States

Supervised injection sites have been a particularly controversial approach[19] to harm reduction not just in Philadelphia but across most of the U.S.

Only a few officially sanctioned supervised injection sites have emerged. Two opened in Manhattan in 2021[20] with support from the government of New York City[21], where research suggests they could save both lives and health care dollars[22]. Rhode Island plans to open[23] a third in Providence in spring 2024, permitted by state legislation. The legality of even these rare sites in the U.S. remains unclear under federal law, according to a 2011 study[24].

A white man is slumped over on a curb, holding a needle in his hand. Garbage surrounds him.
A man on the street in the Kensington neighborhood of Philadelphia in 2021. Tayfun Coskun/Anadolu Agency via Getty Images[25]

In the face of this uncertain legality[26], scant evidence from the U.S. is available. One unsanctioned site operating in secrecy was studied by academics[27]. They found that 90% of users reported they would otherwise have been injecting in parks, streets or public restrooms, meaning the site averted over 2,300 public injections and safely disposed of at least 1,700 needles over two years.

Beyond this, policymakers have limited research in the U.S. to draw upon – and so it is informative to look abroad.

Globally, over 100 supervised injection sites[28] are currently operating in 10 countries, including Canada[29] and across Europe[30]. Researchers have looked to experiences in Denmark and Norway, in particular, to study drug consumption rooms. Despite clear differences between Scandinavia and Philadelphia, the research and evidence highlight the potential impact of this form of harm reduction.

The evidence from Norway

In Norway, as in the U.S., harm-reduction efforts first began with opioid substitution therapy[31], meaning the provision of less dangerous drugs like methadone for opioid users.

When overdose rates[32] kept rising, supervised injection sites where people who use drugs could get clean needles and be observed while using drugs[33] were piloted in 2005 and made permanent by 2009.

The Norwegian Institute of Public Health collected data on the impact of the supervised injection site in Oslo. Just over 150 people used the site in 2005, the first year it opened. Two years later, demand had almost quadrupled. After just six months of operation, staff were recording over 900 injections per month, each diverted from the street. People using the facility told researchers[34] their sense of human dignity improved.

Staff reported that the site allowed them to directly connect more people to social and health services. Other data shows that the presence of the site has reduced the use of ambulances[35] and related public services, preserving those resources for the community.

Striking results in Denmark

The first official Danish supervised injection site[36] opened its doors in Copenhagen in 2012, though underground versions had been operating for a few years.

Since then, several studies have shown the Copenhagen sites not only prevented many drug-related deaths, but improved overall health[37] by successfully connecting people to substance abuse treatment and other health care services.

Staff were also successful at educating people about more hygienic injection techniques, thereby reducing infections and other drug-related complications[38] that often lead to hospitalization. After the sites were opened, fewer people openly used drugs[39] in Copenhagen’s parks and streets. Property values[40] near the injection sites were unaffected.

An evaluation by the Danish Ministry of Health found that the number of needles and syringes discarded in the city’s public spaces was reduced by 70% to 80%[41], and residents in surrounding neighborhoods said their quality of life improved[42].

A pleasant, urban entry has a sign reading
Property values stayed steady in Copenhagen neighborhoods with supervised injection sites. Niels Ahlmann Olesen/AFP via Getty Images

Copenhagen’s experience also highlights the essential fact that supervised injection sites alone aren’t a solution; they are only a part of an effective harm-reduction strategy and must be accompanied by social support and other programming.

For example, the Users’ Academy – or Brugernes Akademi[43] in Danish – is a national nonprofit led by people who use drugs that offers a wide range of harm-reduction services directly to their peers. They run a needle exchange program through the mail and raise awareness regarding the legal rights of people who use drugs. They also operate a mobile health clinic that seeks to prevent diseases like hepatitis C[44] and reduce barriers to health and social services.

An opportunity to investigate

Even in the face of the ongoing controversy in Philadelphia[45], new ideas are emerging.

Using the infusion of funding from national opioid settlements[46], Philadelphia could explore more politically acceptable approaches to harm reduction while collecting evidence and building support for a permanent supervised injection site.

In some European cities, mobile supervised injection sites have been adopted first. In Copenhagen, Fixelancen[47], an old ambulance, has been refurnished as a low-cost supervised injection site. It can service different areas of the city as the drug scene rapidly evolves, avoiding the focus and burden on a particular neighborhood. Such an approach could easily complement other mobile[48] harm-reduction efforts[49] already operating in Philadelphia.

Read more …Philadelphia bans supervised injection sites – evidence suggests keeping drug users on the street...

If you have ever gotten a vaccine or received an intravenous drug and did not come down with a potentially life-threatening fever, you can thank a horseshoe crab (Limulus polyphemus).

How can animals that are often called living fossils[1], because they have barely changed over millions of years, be so important in modern medicine? Horseshoe crab blood is used to produce a substance called limulus amebocyte lysate, or LAL, which scientists use to test for toxic substances called endotoxins[2] in intravenous drugs.

These toxins, produced by bacteria, are ubiquitous in the environment and can’t be removed simply through sterilization. They can cause a reaction historically referred to as “injection fever[3].” A strong concentration can lead to shock and even death.

Identifying LAL as a highly sensitive detector of endotoxins was a 20th-century medical safety breakthrough. Now, however, critics are raising questions about environmental impacts and the process for reviewing and approving synthetic alternatives to horseshoe crab blood.

We study science, technology[4] and public policy[5], and recently published a white paper[6] examining social, political and economic issues associated with using horseshoe crabs to produce LAL. We see this issue as a test case for complicated problems that cut across multiple agencies and require attention to both nature and human health.

Protecting horseshoe crabs will require persuading the heavily regulated pharmaceutical industry to embrace change.

An ocean solution

Doctors began injecting patients with various solutions in the mid-1800s[7], but it was not until the 1920s that biochemist Florence Seibert[8] discovered that febrile reactions were due to contaminated water in these solutions. She created a method for detecting and removing the substances that caused this reaction, and it became the medical standard in the 1940s.

Known as the rabbit pyrogen test[9], it required scientists to inject intravenous drugs into rabbits, then monitor the animals. A feverish rabbit meant that a batch of drugs was contaminated.

The LAL method was discovered by accident. Working with horseshoe crabs at the Marine Biological Laboratory[10] at Woods Hole, Massachusetts, in the 1950s and ’60s, pathobiologist Frederik Bang and medical researcher Jack Levin[11] noticed that the animals’ blue blood[12] coagulated in a curious manner. Through a series of experiments, they isolated endotoxin as the coagulant and devised a method for extracting LAL from the blood. This compound would gel or clot nearly instantaneously in the presence of fever-inducing toxins.

Academic researchers, biomedical companies and the U.S. Food and Drug Administration refined LAL production and measured it against the rabbit test. By the 1990s, LAL was the FDA-approved method[13] for testing medicines for endotoxin, largely replacing rabbits.

A line of rabbits, their bodies enclosed in metal cases.
Rabbits undergoing a pyrogen test in a laboratory in 1956 to determine a drug’s safety. Sherman/Getty Images)[14]

Producing LAL requires harvesting horseshoe crabs from oceans and beaches, draining up to 30% of their blood[15] in a laboratory and returning the live crabs to the ocean. There’s dispute about how many crabs die in the process[16] – estimates range from a few percent to 30% or more – and about possible harmful effects on survivors.

Today there are five FDA-licensed LAL producers[17] along the U.S. East Coast. The amount of LAL they produce, and its sales value, are proprietary.

Bait versus biotech

As biomedical LAL production ramped up in the 1990s, so did harvesting horseshoe crabs to use as bait for other species, particularly eel and whelk for foreign seafood markets. Over the past 25 years, hundreds of thousands – and in the early years, millions – of horseshoe crabs have been harvested each year for these purposes. Combined, the two fisheries kill over half a million[18] horseshoe crabs every year.

There’s no agreed total population estimate for Limulus, but the most recent federal assessment of horseshoe crab fisheries[19] found the population was neither strongly growing nor declining.

Conservationists are worried, and not just about the crabs. Millions of shorebirds migrate along the Atlantic coast[20], and many stop in spring, when horseshoe crabs spawn on mid-Atlantic beaches, to feed on the crabs’ eggs. Particularly for red knots[21] – a species that can migrate up to 9,000 miles between the tip of South America and the Canadian Arctic – gorging on horseshoe crab eggs provides a critical energy-rich boost on their grueling journey.

Red knots were listed as threatened[22] under the Endangered Species Act in 2015, largely because horseshoe crab fishing threatened this key food source. As biomedical crab harvests came to equal or surpass bait harvests[23], conservation groups began calling on the LAL industry to find new sources.

Biomedical alternatives

Many important medicines are derived from living organisms. Penicillin, the first important antibiotic, was originally produced from molds[24]. Other medicines currently in use come from sources including cows, pigs, chickens and fish[25]. The ocean is a promising source[26] for such products.

When possible, synthesizing these substances in laboratories – especially widely used medications like insulin[27] – offers many benefits. It’s typically cheaper and more efficient, and it avoids putting species at risk, as well as addressing concerns some patients have[28] about using animal-derived medical products.

In the 1990s, researchers at the National University of Singapore invented and patented[29] the first process for creating a synthetic, endotoxin-detecting compound using horseshoe crab DNA and recombinant DNA technology[30]. The result, dubbed recombinant Factor C (rFC), mimicked the first step in the three-part cascade reaction that occurs when LAL is exposed to endotoxin.

Later, several biomedical firms produced their own versions[31] of rFC and compounds called recombinant cascade reagents (rCRs), which reproduce the entire LAL reaction without using horseshoe crab blood. Yet, today, LAL remains the dominant technology for detecting endotoxins in medicine.

A vial partly filled with pale blue fluid
A sample of horseshoe crab blood. Florida Fish and Wildlife Commission[32], CC BY-NC-ND[33]

The main reason is that the U.S. Pharmacopeia[34], a quasi-regulatory organization that sets safety standards for medical products, considers rFC and rCR as “alternative” methods for detecting endotoxins, so they require case-by-case validation for use – a potentially lengthy and expensive process. The FDA generally defers to the U.S. Pharmacopeia.

A few large pharmaceutical companies with deep pockets have committed to switching from LAL to rFC[35]. But most drug producers are sticking with the tried-and-true method.

Conservation groups want the U.S. Pharmacopeia to fully certify rFC[36] for use in industry with no extra testing or validation. In their view, LAL producers are stalling rFC and rCR approval to protect their market in endotoxin detection[37]. The U.S. Pharmacopeia and LAL producers counter that they are doing due diligence to protect public health[38].

Change in the offing

Change may be coming. All major LAL producers now have their own recombinant products – a tacit acknowledgment that markets and regulations are moving toward Limulus-free ways to test for endotoxins.

Atlantic fisheries regulators are currently considering new harvest limits for horseshoe crabs[39], and the U.S. Pharmacopeia is weighing guidance[40] on recombinant alternatives to LAL. Public comments will be solicited over the winter of 2024, followed by U.S. Pharmacopeia and FDA review.

Even if rFC and rCR don’t win immediate approval, we believe that collecting more complete data on horseshoe crab populations and requiring more transparency from the LAL industry on how it handles the crabs[41] would represent progress. So would directing medical companies to use recombinant products for testing during the manufacturing process, while saving LAL solely for final product testing.

Making policy on complex scientific issues across diverse agencies is never easy. But in our view, incremental actions that protect both human health and the environment could be important steps forward.

Read more …Horseshoe crab blood is vital for testing intravenous drugs, but new synthetic alternatives could...

As cold and flu season ramps up, health care experts are once again on high alert for the possibility of a tripledemic[1], or a surge brought on by the respiratory viruses that cause COVID-19, the flu and respiratory syncytial virus, or RSV. The good news is that this year, health officials have more tools at their disposal to combat them.

Americans ages 6 months and older are eligible to receive the newest COVID-19 vaccine[2] and the annual flu vaccine[3]. In addition, this year the Food and Drug Administration approved the first vaccine against RSV[4] for use in late pregnancy[5] and adults 60 years of age and older[6].

RSV, COVID-19 and the flu are all contagious respiratory illnesses that have similar symptoms[7], making it difficult to distinguish between the three viral infections without a lab test. Testing is the only way to know which virus is causing your symptoms. In fact, researchers are working to create one test that can detect COVID-19, RSV and the flu[8].

As a nursing professor[9] with experience in public health promotion[10], I am often asked about the differences between these respiratory viruses. This year, I am fielding many questions about the timing of getting the new COVID-19 and RSV vaccines along with the flu shot, and whether they can be given together.

What to know about the symptoms

Symptoms of COVID-19, RSV and the flu can range[11] from mild – or even no noticeable symptoms at all – to severe. Flu symptoms typically come on suddenly, while RSV and COVID-19 often start out mild but can become severe over time. In addition, while a flu infection does not typically affect one’s ability to taste or smell, the loss of taste or smell[12] can be a common COVID-19 symptom.

All three infections can cause fevers and fatigue, while chills and body aches are more common with COVID-19 and the flu. More severe symptoms of these infections include difficulty breathing and subsequent infections like pneumonia.

Health care experts are emphasizing the importance of getting a lab test to accurately identify the source of your infection.

Timing the shots

With the new RSV vaccine[13] and updated COVID-19 vaccine[14] now available and flu season just around the corner, a natural question is whether there is an optimal schedule for the three shots.

The answer to that question is, if you are eligible, to get these vaccines as soon as possible. It is important to consider that it takes approximately two weeks after vaccination for your body to develop antibodies from both the COVID-19 vaccines[15] and the flu vaccine[16].

The Centers for Disease Control and Prevention recommends[17] that anyone who is either unvaccinated or has previously received a COVID-19 vaccine before Sept. 12, 2023, to get the updated vaccine. This means now is the time to get the updated COVID-19 vaccine[18] that targets a previously dominant variant of the omicron family.

The original COVID-19 vaccines and booster series have dramatically reduced the number of COVID-19 infections, hospitalizations and death rates[19] from the virus.

While everyone 6 months of age and older is advised to receive both the COVID-19 and flu vaccines, certain populations have a higher risk for severe infection, such as pregnant women[20], and should be extra vigilant about getting vaccinated.

In addition, among those vaccinated against COVID-19, symptoms during an infection tend to be milder[21]. However, due in part to the quickly evolving nature of the virus, it has become clear that immune protection from COVID-19 vaccination or infection diminishes over time. While studies show that the primary COVID-19 series maintains efficacy against severe disease and death six months after vaccination, protection after vaccination decreases over time[22]. Viruses, such as those that cause COVID-19 and influenza, also continuously mutate and evolve.

The fact that COVID-19 vaccine immunity decreases over time and that viruses evolve are exactly why updated vaccines are so critical[23]. Without a large uptake of updated vaccines in the population, COVID-19 infection rates could surge again.

Timing is also important with the flu vaccine. Flu cases typically begin to rise in October and peak between December and February, but can last through May[24]. Ideally, people should get vaccinated before flu begins to spread, making the month of October the ideal flu vaccination time[25].

But if you miss that deadline, it is absolutely better to get vaccinated later in the season than not at all. Flu, COVID-19 and RSV vaccines are available at your health care provider’s office, your local health department and most retail pharmacies, although access to the newly updated COVID-19 vaccine is still limited in some areas of the country[26].

Pharmacy shelves stocked with various products and a sign on a counter advertising that flu shots are available there.
Many pharmacies are offering walk-up seasonal flu and COVID-19 shots. Cecilie_Arcurs/E+ via Getty Images[27]

A difficult respiratory virus season ahead

While infections and hospitalizations from COVID-19 declined dramatically in 2023[28], experts are remaining vigilant against the possibility of new, more-infectious variants causing another fall and winter surge. Adults 65 and older continue to be the highest-risk group for severe infection.

Flu seasons are inherently difficult to predict[29]. Since the emergence of the COVID-19 pandemic, flu cases have been lower than prior to the pandemic[30]. However, the 2022-2023 flu season[31] still caused over 300,000 hospitalizations and up to 98,000 flu-releated deaths, making vaccination an important prevention tool.

To further compound this, flu vaccine rates have been lower during the pandemic[32], suggesting that Americans may be out of the habit of getting their annual flu shot.

Shots can be given together

Many are also wondering whether they can or should get the updated COVID-19 booster, the new RSV vaccine and the flu shot at the same time. The good news is, the CDC clearly indicates that it is safe[33] for both adults and children who are eligible for the updated COVID-19 vaccine to get this vaccine simultaneously with the annual flu shot.

A 2022 study found that common vaccine side effects, such as pain at the injection site, occurred at slightly higher rates[34] when someone received the flu vaccine and a COVID-19 vaccine at the same time, as opposed to receiving only a COVID-19 booster. However, those reactions, including fatigue and headache, were mild and resolved within a day or two. In addition, a recent study found that the immune response was the same when[35] both vaccines were given together compared to when given separately.

Since the RSV vaccine is new, there is no data yet on receiving all three vaccines at the same time[36]. Instead, those at the highest risk of RSV infection should get this vaccine as soon as they are able.

Community matters too

Getting the COVID-19, RSV and flu vaccines isn’t just about your own health – it’s about family and community health too. Communities with higher vaccination rates have fewer opportunities to spread the virus[37].

Keep in mind that many people cannot be vaccinated[38], because they have weakened immune systems or are undergoing treatments. They depend on those around them for protection. While one person may experience mild symptoms if they contract RSV, COVID-19 or the flu, they could spread the virus to others who could become severely ill.

Because it’s impossible to predict how people will react if they get sick, getting the flu and COVID-19 vaccines – and the RSV vaccine if you are eligible – is the best prevention strategy.

This is an updated version of an article[39] that was originally published on Sept. 22, 2022.

Read more …Vaccines against COVID-19, the seasonal flu and RSV are our best chance of preventing a winter surge

More Articles …