Dr. Gustin's Blog

Plastic & Microplastic Pollution and the Kidney/Urinary Tract

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Published: Tuesday, 12 November 2024 19:35

Plastics and microplastics have always been a concern of Environmental Toxicologist, and both animal and human research has been conducted over the past 50 years with an eye to determining the consequences of various forms of exposures, both acute and chronic.

Although a 2019 World Health Organization (WHO) report concluded that microplastics in drinking water posed no risk to human health, accumulating evidence is now challenging these findings.

Since plastics became widely used in the mid-20th century, they have evolved from a novel substance to an essential component in countless applications, with global production reaching 368 million tons in 2019 and expected to double by 2039. The production and degradation of plastics involve physical, chemical, and biological processes, leading to the formation of tiny fragments known as microplastics (MPs) and nanoplastics (NPs), which accumulate in the environment. Beyond the well-documented environmental harms of MPs and NPs, growing evidence of their presence within the human body raises concerns about their potential to trigger various harmful biological processes. Their detection in the urinary tract and their potential links to kidney and bladder diseases, as shown in animal studies, are particularly alarming.

Impacts Becoming Apparent

As the impact of plastic pollution becomes increasingly apparent, the need for standardized international definitions of MPs and NPs is pressing. Government publications reveal notable discrepancies between organizations in defining these fragmented plastics. The lack of consensus among regulatory bodies highlights the challenges in mitigating the environmental and health impacts of MPs and NPs. The International Organization for Standardization offers the most precise classification, defining MPs as solid, insoluble plastic particles ranging from 1 µm to 1 mm and NPs as particles smaller than 1 µm.

The intrusion of MPs and NPs into the human body, whether through inhalation, ingestion, or skin exposure (via wounds, hair follicles, or sweat glands), has been linked to harmful biological effects, including inflammation, alterations in cellular metabolism, physical cellular damage, and reduced cell viability.

Urinary Tract Plastics

The detection of MPs and NPs in the human urinary tract, combined with limited understanding of their effects, is a growing concern. An exploratory study published earlier this year aimed to systematically summarize the existing literature regarding the presence of MPs and NPs in the urinary tract and their potential consequences, guided by these research questions:

• What are the characteristics of the plastics detected in the human urinary tract?
• How are MPs and NPs defined in the current literature?
• What methodologies are used to explore the presence and effects of MPs and NPs?
• What are the pathophysiologic consequences of the presence of MPs and NPs in the human urinary tract?

For this study, the “urinary tract” included the kidneys, bladder, ureter, urethra, and urine. By focusing on the urinary tract, the study aimed to consolidate current understanding of MPs and NPs, raise awareness of this emerging issue, and lay the groundwork for further research that could contribute to public health policies and clinical practice guidelines.

The researchers conducted a scoping literature review following the recommendations of the JBI [formerly known as the Joanna Briggs Institute). They systematically searched five databases — PubMed, Scopus, CINAHL, Web of Science, and Embase — as well as gray literature sources.

Concerning Study Results

Eighteen articles were identified in their meta-study. The authors represent seven countries: Pakistan (n = 1), the Netherlands (n = 1), the US (n = 1), Taiwan (n = 1), Germany (n = 3), China (n = 5), and Italy (n = 6). Among these studies, six investigated and characterized the presence of MPs and NPs in the human urinary tract. MPs and NPs were detected in urine samples (n = 5), kidney cancer samples (n = 2), and bladder cancer samples (n = 1).

Additionally, 12 studies examined the effects of MPs and NPs on human urinary tract cell lines. Their findings suggest that MPs and NPs have cytotoxic effects, increase inflammation, reduce cell viability, and alter mitogen-activated protein kinase signaling pathways.

Raman spectroscopy was the primary method used to detect and characterize MPs and NPs in human samples (five out of six studies; 83%). Alternatively, pyrolysis-gas chromatography-mass spectrometry combined with direct laser infrared spectroscopy was used in one study.

The findings provide strong initial evidence that microplastics are filtered by the kidneys and appear in urine.  The question remains whether the presence of these compounds triggers or contributes to, genitourinary or nephrourinary cancer.

Further Research Needed

This exploratory study underscores the urgent need for further research and policy development to address the challenges posed by microplastic contamination. It highlights the rapidly emerging threat of human urinary tract contamination by microplastics, questioning the WHO’s claim that microplastics pose no public health risk. The documented cytotoxic effects of microplastics, and their ability to induce inflammation, reduce cell viability, and disrupt signaling pathways, raise significant public health concerns related to bladder cancer, chronic kidney disease, chronic urinary infections, and incontinence.

Source:  Medscape, November 12, 2024

Despite 2013 Ban Ubiquitous Chemical May Still Causes Human Cancer

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Published: Wednesday, 03 April 2024 08:44

Although banned in 2013 as a probably human carcinogen, a group of chemicals called polybrominated biphenyl ethers are still around— in soil, food, and in our blood.

 PBDEs are a group of compounds that were used as flame-retardants mainly in  plastics, and they were also used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.But there was a problem. They don't chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don't get washed out of soil, and, when ingested or inhaled by humans, they dissolve in fat stores, making it difficult for our excretory systems to excrete them.

 PBDEs biomagnify.  What this means is that each time a smaller animal is eaten by a larger animal higher concentrations of the compounds accumulate in fat stores. This bioaccumulation increases as you move up the food chain until you get to the top predator — humans.

 The International Agency for Research on Cancer determined, based on mechanistic studies, that PBDEs are probably carcinogenic to humans.  A comprehensive epidemiological study recently appeared in JAMA Open Network that analyzed in detail the population-based NHANES data base (National Health Nutrition Examination Survey).

 PBDE Outcome Analysis determined after adjusting for other variables that those with a high level of PBDEs in their blood had a 4.09 hazard ratio for cancer mortality compared to those with low levels of PBDEs.  In other words, those with high levels of PBDEs are more than 4 times as likely to die from cancer as those with lower PBDE levels even though cancer deaths were rare in the studied cohort, and the hazard rate is a relative, not absolute risk.  Nevertheless, the data are strongly suggestive of the carcinogenicity of PBDEs.  The data, however, was not strong enough to determine the type of cancer.

 What is the significance of this data if the chemicals have already been banned?  It appears that the primary source in our environment is the food we eat due to biomagnification including high-fat fish, meat, dairy products, and fish oil supplements.

Toxic Chemicals Consumed in Food and Water

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Published: Sunday, 18 February 2024 18:47

If the pandemic served as a window into our health, what it revealed was a US population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, autoimmune diseases, and stress-related disease such as thyroid disease are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver of these trends is the role of environmental toxins and endocrine-disrupting chemicals. Increasing evidence now supports their contribution to infertility, chronic disease, and cancer.

Although scientists have identified many industrial chemicals and toxins as carcinogens and those chemicals have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. In this general review, some of the most common exposures and the substantial health risks associated with them, along with some guidance about best practices for how to minimize exposure will be discussed. Click on the blue links to view studies, data, and other references.

Microplastics:

"Microplastics" is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at an enormous rate.  By 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstreamin the majority of 22 otherwise healthy participants.

 Since the 1950s, plastic exposure has been shown to promote malignant tumors in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water. Presently, there are no formal advisories on fish consumption to avoid exposure to microplastics, nor is there a ban on microbeads in personal care products.

Until such bans are put in place, it is advisable to avoid single-use plastics like water bottles and to use reusable tote bags for grocery shopping rather than plastic bags that end up in the sea.

Phthalates:

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (eg, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact.  The majority of exposure is food related (fasting studies).

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride (PVCs) plastics (particularly food containers, plastic wrap, and children's toys), which is identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The Environmental Working Group’s (EWG) Skin Deep database provides a resource on phthalate-free personal care products.

The US Food and Drug Administration has not yet banned phthalates in food packaging.

Bisphenol A (BPA):

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverage should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas, salmon, and sardines. If canned products are bought, they should be BPA-free.

Dioxins and Polychlorinated Biphenyls (PCBs):

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term "persistent organic pollutants" because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of other health implications in development, immunity, reproductive, and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Dioxin emissions have been reduced by 90% since the 1980s, and the US Environmental Protection Agency (EPA) has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat, and are found ubiquitously in human tissue.

The best ways to avoid exposures are through eating less meat, fish, and dairy and trimming the skin and fat off of meats and fish. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the US diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.

Pesticides:

The growth of modern monoculture agriculture in the United States over the past century is closely connect to the liberal use of industrial pesticides. In fact, over 90% of the US population have pesticides in their urine and blood, regardless of where they live. Exposures are food-related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European regulatory agencies. The EPA has not yet reached this conclusion, although the matter is currently in litigation.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE — a metabolite of DDT, a chlorinated pesticide heavily used in between 1940-1960 that still persists in the environment today — has been shown to increase the risk for Alzheimer's-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are usually fat soluble, they accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventionally grown fruits and vegetables. The EWG provides a resource:  shopper guides regarding pesticides in produce.

Per- and Polyfluoroalkyl Substances (PFAS):

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as "forever chemicals."

PFAS have been detected in the blood of 98% of Americans, and in the rainwater everywhere on earth, suchas Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birthweight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. The chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS — a family of thousands of synthetic compounds — remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as "water resistant," "stain-resistant," and "nonstick."

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as "hazardous substances."

Where this leaves us has been the subject of much discussion and debate. The best advice given by the public health community is to follow the above referenced recommendations that would minimize exposure to these toxic chemicals, and to then hope for the best, health wise.

Adapted from Medscape, February, 2024.

Body Packing of Narcotics Hypothetical Case Study

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Published: Thursday, 18 January 2024 20:19

A 22-year-old man with no significant medical history is transferred from the airport to the emergency department (ED) in a semiconscious state after returning from a 3-week vacation in a malarial zone. According to one of his traveling companions, the patient was at his baseline mental status when boarding the plane for the return trip home. He ate lunch and then took a nap.

After landing, the patient's companion was unable to wake the patient. The companion then called for help, and the patient was rushed to the ED. His other traveling companions, who were also on the same flight, are all asymptomatic.

Physical Examination and Work-up

The physical examination reveals a physically fit man who is obtunded and minimally arousable. Vital signs reveal an oral temperature of 98.7°F (37°C), pulse of 85 beats/min, blood pressure of 110/70 mm Hg, respiratory rate of 7 breaths/min, and an oxygen saturation of 98% while breathing room air. Diffuse flushing of the skin is noted, without lesions or bruising.

The patient's heart sounds are normal, without any murmurs, rubs, or gallops, and the lungs are clear to auscultation bilaterally. Examination of the head and neck is unremarkable, other than pinpoint pupils. The abdominal examination reveals normal bowel sounds without distention, tenderness to palpation, or organomegaly. Rectal examination shows normal rectal tone, heme-negative stool, and no masses.

The laboratory analysis includes a complete blood cell count (CBC) with differential, a complete metabolic panel, a coagulation profile, a fingerstick blood glucose measurement, and a urine analysis. The CBC reveals a normal white blood cell count without a left shift. The remainder of the laboratory analysis is within normal limits, including a creatinine level of 1.2 mg/dL, glucose of 90 mg/dL, prothrombin time of 12.1 seconds, and a partial thromboplastin time of 28.5 seconds.

The urinalysis is negative for bacteria and has a specific gravity of 1.010. It is noted in the patient's past medical record that he had a negative HIV test approximately 4 months ago.

The plain abdominal radiograph demonstrated heroin-filled condoms in the stomach, small intestine, colon, and rectum. Presumably, the patient swallowed the condoms and one of them ruptured during the flight, thereby causing the patient's drowsiness.

“Body packing” refers to individuals who swallow or pack body orifices with drugs to transport them across borders. Often, this involves the use of rubber or condoms to prevent the packets from rupturing. “Body stuffing” is a term used to describe when an individual swallows drugs in an attempt to avoid prosecution by the police.

The first reported case of body packing was in 1973, when a body packer had developed a small-bowel obstruction nearly 2 weeks after swallowing a condom filled with hashish. The patient underwent surgical removal.^[1] Cocaine, heroin, amphetamines, 3,4-methylenedioxymethamphetamine ("ecstasy"), marijuana, and hashish are the drugs that are usually smuggled in this manner.^[2]

Body packers usually carry about 2.2 lb (1 kg) of drugs, divided into 50-100 packets of 0.29-0.35 oz (8-10 g) each; however, persons carrying more than 200 packets have been reported.^[2] The packets are usually well-designed and constructed, possibly with the help of machines, so as to make them resistant to rupture.^[3] The drug is first packed into a balloon or condom, followed by additional layers of latex and, finally, sealed with wax.^[2] If a packet ruptures, however, it releases a high dose of drug into the gastrointestinal tract that can lead to drastic consequences. The acute drug intoxication that can result is associated with high mortality rates.^[3]

Body packing should be suspected in anyone exhibiting signs of drug-induced toxic effects after a recent arrival on an international flight, or when there is no history of recreational drug use.^[2] When a suspected body packer presents to a physician, a detailed history should be obtained, followed by a thorough physical examination. Information should be gathered on the type of drug, the number of packets, the nature of the wrapping, and the presence of any gastrointestinal symptoms.

Assessment of vital signs, mental status, pupil size, bowel sounds, and skin findings can provide useful clues to the nature of the drug. Gentle rectal and vaginal examination should be carried out to disclose the possible presence of packets.^[2]

Imaging studies should begin with plain radiographs of the abdomen and pelvis; these have a sensitivity of 85%-90%.^[2] The packets are visualized as multiple round or oval, well-defined, radioopaque objects along the distribution of the intestine. Three different forms of radioopacity have been described, depending on the contents of the packet and purity of the drug: Hashish appears denser than stool; cocaine appears similar to stool; and heroin has a gaseous transparence.^[4] Owing to their method of construction, some types of cocaine packets may exhibit a small radiolucent band around them.^[3]

Barium and CT studies of the abdomen can be ordered for suspicious cases. Contrast-enhanced CT of the abdomen and pelvis is more sensitive than plain radiography and reveals the presence of foreign bodies surrounded by a small amount of gas. Barium studies identify the packets as filling defects within the contrast medium.^[2] Urinary toxicology tests are often performed because body packers do not usually provide precise information about the contents of the packets. Positive urine toxicology results were obtained in up to 78% of patients in one study.^[5] However, many toxicologists now have significant questions about the clinical use of these studies due to the rate of false-positives.

Treatment is tailored to the nature of the presentation and the severity of the toxidrome. Asymptomatic body packers may be managed conservatively in an intensive care unit (ICU) while waiting for spontaneous evacuation.^[2] Medical treatment is mandated in the event of drug-induced toxic effects and in cases presenting with intestinal obstruction or perforation.

For intoxication cases, initial management includes careful attention to the airway, breathing, and circulation (ABCs) and adequate resuscitation measures. Further management is based on the nature of the drug and toxidrome. Opioid poisoning is treated with naloxone. High doses may be necessary because large doses of drug may be released upon gastrointestinal rupture of the packets. Acute lung injury caused by opioid poisoning is treated with supplemental oxygen or intubation as needed.^[2]

For cocaine poisoning, treatment should be initiated with high doses of benzodiazepines followed by intensive care management.^[5] Ventricular arrhythmia should be managed with lidocaine and hypertonic sodium bicarbonate, and cocaine-induced hypertension should be treated with intravenous sodium nitroprusside or phentolamine.^[2] In cases of leaking cocaine packets, immediate surgical removal is indicated because no specific antidote is available for cocaine overdose.^[2]

Management of amphetamine poisoning is similar to that of cocaine poisoning, including prompt surgical removal of leaking packets.^[2]  Cannabis intoxication is managed with supportive treatment.^[2]

In the case of bowel obstruction, activated charcoal can be given for cocaine packers at a dose of 1 g per kg of body weight (up to 50 g) every 4 hours for several doses. Oil-based laxatives should be avoided; however, whole-bowel irrigation with polyethylene glycol electrolyte lavage solution can be attempted to aid gentle passage of the packets.^[2] Ipecac syrup, enemas, and cathartics carry a possibility of packet rupture and must not be used.^[3] Endoscopic retrieval of packets also entails risk for rupture; therefore, this method is not usually recommended unless carried out in an ICU or operating room.^[2,3] Imaging is to be repeated until three packet-negative stools are obtained or according to the count given by the packer to confirm that no packet is left behind.

Prompt surgical management is indicated for packers who present with complications of intestinal obstruction or perforation.^[2] Enterotomy incisions are made as required, and the intestinal contents are milked toward the incisions or the anus.^[2] Postoperative imaging (CT or barium study) should be done to ensure the complete removal of packets.^[2]

In this case, the patient was administered naloxone and was prepared for surgery. Evidence of packet rupture was found, and the packets were successfully removed. The patient survived the surgery and recovered well.

Cases of body packing have been increasing recently because strict border security procedures have made conventional drug smuggling difficult.^[6] Physicians and radiologists should therefore be aware of this potentially fatal form of drug smuggling, its various presentations, and the relevant imaging findings in order to make a prompt diagnosis and begin the appropriate management.

Opioid poisoning is treated with naloxone. Very high doses may be necessary because large doses of drug may be released upon gastrointestinal rupture of the packets.

References

1. Deitel M, Syed AK. Intestinal obstruction by an unusual foreign body. Can Med Assoc J. 1973;109:211-212. Source 
2. Traub SJ, Hoffman RS, Nelson LS. Body packing--the internal concealment of illicit drugs. N Engl J Med. 2003;349:2519-2526. Source 
3. Pidoto RR, Agliata AM, Bertoline R, Mainini A, Rossi G, Giani G. A new method of packaging cocaine for international traffic and implications for the management of cocaine body-packers. J Emerg Med. 2002;23:149-153. Source 
4. Hergan K, Kofler K, Oser W. Drug smuggling by body packing: what radiologists should know about it. Eur Radiol. 2004;14:736-742. Source 
5. Dueñas-Laita A, Nogué S, Burillo-Putze G. Body packing. N Engl J Med. 2004;350:1260-1261. Source 
6. Cappelletti S, Picacentino D, Ciallella C. Systemic Review of Drug Packaging Methods in Body Packing and Pushing: A Need for New Classification. Am J Forensic Med Pathol. 2019 Mar; 40(1):27-42. Source

Case published in Medscape. January 2024

FDA Clears First Over the Counter Fentanyl Urine Test

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Published: Saturday, 04 November 2023 18:51

Finally, we now have a rapid urine test for fentanyl.  In the past, we had to send out suspected urine for a quantitative analysis that often took many days.  Now, within minutes we will know whether an individual has the drug in his or her system.  Here's the communique.

The US Food and Drug Administration (FDA) has cleared the first over-the-counter test for the preliminary detection of fentanyl in urine.

With the Alltest Fentanyl Urine Test Cassette (Hangzhou AllTest Biotech Co, Ltd), three drops of fresh urine are placed onto a cassette containing a fentanyl test strip. After 5 minutes, the test result appears as colored lines.

"Opioid abuse, misuse and addiction is one of the most profound public health crises facing the US today. It is also a very personal issue for many people, impacting individual lives and families," Jeff Shuren, MD, JD, director, the FDA Center for Devices and Radiological Health, said in a statement.

Shuren said this test is an example of the FDA's "continued commitment to authorize tools that can reduce deaths associated with overdoses. The agency expedited review of this test, making a decision on the submission in only 16 days from the date it was received."

The FDA cautions that the urine test provides only a preliminary result and that a more specific, alternative chemical method (confirmation testing) must be used to confirm the result.

How to Interpret a Urine Drug Test

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Published: Friday, 27 October 2023 21:50

Urine drug tests (UDTs) are broken down into two separate categories, screening UDTs and confirmatory UDTs.  Screening UDTs are immunoassay tests involving antibody technology.  Screening UDTs have a higher risk of false positive and false negative results compared with confirmatory UDTs that are done by gas chromatography and mass spectrometry (GC/MS).  Screening UDTs are inexpensive and yield results within minutes.  Confirmatory UTDs are send-outs, are expensive, and it usally takes several days to get the results back.

Screening UTDs test for commonly abused substances such as cannabis, methamphetamine/amphetamine, cocaine, oxycodone, benzodiazepines, barbituates, opiates, and PCP.  False positives can occur.  For example, a false positive for amphetamine can occur because of the use of bupropion, pseudoephedrine, and over the counter Vicks decongestants which contain l-methamphetamine, not d-methamphetamine, the abused isomer.  False positives for benzodiazepines can be caused by sertraline which is a common drug to treat anxiety or mild depression. Medications that can cause positive PCP (phencyclidine) results include dextromethorphan, carbamazepine, TCAs (tricyclic antidepressants) like Elavil, and venladfaxine.

To rule out false positives, urine is often sent to a lab for quantitative analysis by GC/MS.

Opiates, substances derived from opium plants like codeine or morphine.  False positives for opiates can occur with opioids (synthetic or semisynthetic such as fentanyl, oxycodone, or hydromorphone) such as hydromorphone, naloxone, naltrexone, trazodone, or even a blood pressure medication, labetolol.

The 4th Wave Of Polysubstance Fentanyl Overdose Deaths

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Published: Wednesday, 27 September 2023 12:33

One of the consequences of an open Southern Border is the entrance into the U.S. of unprecedented amounts of illicit drugs.  Additionally, much of these drugs have been spiked with lethal doses of fentanyl.  Fentanyl is the most potent of all narcotics.  On a dose:dose basis fentanyl is 50 times stronger than heroin, and 100 times stronger than morphine.  What this means is that extremely small doses of fentanyl can cause respiratory depression and death.  

INTRODUCTION

The United States (US) overdose crisis has escalated in an exponential fashion for over four decades, yet with a shifting profile of drugs implicated in each successive ‘wave’ of the crisis. The first wave of the overdose crisis is typically argued to have begun in the late 1990s or early 2000s with the rise of deaths involving prescription opioids, the second wave beginning in 2010 driven by a shift to heroin, and the third wave beginning in 2013 driven by illicit fentanyl analogues. Recently, scholars have argued that the ‘fourth wave’ of the US overdose crisis has begun, in recognition of rapidly rising polysubstance overdose deaths involving illicitly manufactured fentanyls, with stimulants playing a key role. Recent studies have highlighted an increasing rate of polysubstance overdose deaths involving fentanyls and stimulants, disproportionately affecting racial/ethnic minority communities. A wide range of polysubstance formulations have been noted in drug checking and overdose mortality data, with myriad substances implicated across numerous drug classes. However, more evidence is needed about exact geographic, temporal, race/ethnicity and demographic trends, as well as which emerging polysubstance formulations are most commonly involved in fatalities.

Findings

The percent of US overdose deaths involving both fentanyl and stimulants increased from 0.6% (n = 235) in 2010 to 32.3% (34 429) in 2021, with the sharpest rise starting in 2015. In 2010, fentanyl was most commonly found alongside prescription opioids, benzodiazepines, and alcohol. In the Northeast this shifted to heroin-fentanyl co-involvement in the mid-2010s, and nearly universally to cocaine-fentanyl co-involvement by 2021. Universally in the West, and in the majority of states in the South and Midwest, methamphetamine-fentanyl co-involvement predominated by 2021. The proportion of stimulant involvement in fentanyl-involved overdose deaths rose in virtually every state 2015–2021. Intersectional group analysis reveals particularly high rates for older Black and African American individuals living in the West.

DISCUSSION

The rise of illicitly manufactured fentanyls has ushered in an overdose crisis in the United States of unprecedented magnitude. This has created conditions that have promoted a number of other shifts in the illicit drug supply, leading to rising polysubstance overdose deaths—the so-called ‘fourth wave’ of the crisis, especially involving stimulants and fentanyl co-use starting in 2015. Mixtures of fentanyl analogues and drugs of various drug classes, such as stimulants, benzodiazepines, tranquilizers and other opioids have been noted in distinct geographies.

In 2010, fentanyl was most commonly found alongside prescription medication (opioids and benzodiazepines) and alcohol (i.e. largely products produced in legal markets). Over the past decade this has shifted first to heroin-fentanyl combinations in specific states, and then universally to illicit stimulants. The fraction of all overdose deaths involving both fentanyl and stimulants grew rapidly between 2010 and 2021 and is on track to represent the single largest component of the overdose crisis in the near future. However, this has occurred in a distinct fashion based on geography and time. The northeastern states saw a period of heroin-fentanyl co-involvement, which was also found in some parts of the Midwest and South, but was completely absent from the western states (which transitioned rapidly from black tar heroin to fentanyl with methamphetamine co-involvement). By 2021, cocaine predominated in the Northeast and methamphetamine had become the most common drug found alongside fentanyls in the rest of the country.

There are now two basic archetypes of states in the United States with respect to overdose death rates: (a) states where fentanyl and cocaine co-use predominates; and (b) states where fentanyl and methamphetamine co-use predominates, with surprising little overlap between these two groups. This may reflect the combination of very low-cost, high-purity methamphetamine outcompeting cocaine and other stimulants at the national level, in addition to an enduring, well-entrenched illicit cocaine market in the Northeast and other pockets of the country.

The rise of deaths involving cocaine and methamphetamine must be understood in the context of a shifting illicit opioid drug market increasingly dominated by illicit fentanyls. Recent ethnographic and qualitative research suggests that fentanyls have created conditions that make polysubstance use more sought-after and commonplace. For instance, many individuals report that mixing a small amount of methamphetamine into injected doses of fentanyl subjectively prolongs the onset of withdrawal symptoms, increases euphoria, decreases overdose risk and improves energy levels. These perceived advantages may be particularly important given the short duration of fentanyls, requiring individuals to inject far more frequently than heroin, and the heightened overdose risk from each injection. 

Similar findings have been reported in qualitative studies of the veterinary tranquilizer, xylazine, and other drugs commonly added to fentanyls, suggesting possible structural similarities across various emerging polysubstance patterns. Given the increased risk of negative health outcomes such as overdose not fully responsive to naloxone often requiring additional life-saving measures such as airway management.

A critical consideration is the growing prevalence of counterfeit pills, which resemble psychoactive pharmaceuticals such as oxycodone or alprazolam, but contain illicit fentanyls, often mixed with other illicit substances such as stimulants, benzodiazepines, xylazine and other opioids. In recent years, counterfeit pills have grown to represent over a quarter of all illicit fentanyl seizures. Counterfeit pills have the potential to transform overdose risk as they may expand the markets for illicit synthetic drugs to subpopulations, such as adolescents, who may be less likely to consume powder fentanyl products . In the ongoing surveillance of the US overdose crisis, tracking deaths involving counterfeit pills versus other formulations represents an important dimension that is currently difficult within the existing data landscape.

Conclusions

By 2021 stimulants were the most common drug class found in fentanyl-involved overdoses in every state in the US. The rise of deaths involving cocaine and methamphetamine must be understood in the context of a drug market dominated by illicit fentanyls, which have made polysubstance use more sought-after and commonplace. The widespread concurrent use of fentanyl and stimulants, as well as other polysubstance formulations, presents novel health risks and public health challenges.

The information above was gleaned from a soon to be published study by Drs. Friedman and Shover. Addiction. 1-9, 2023

Food Additive Emulsifiers are Deleterious to Health

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Published: Friday, 15 September 2023 20:38

A new large prospective cohort study was just released in the British Medical Journal from a research group in France demonstrating that Food Emulsifiers that appear in most processed foods are harmful to health, especially, cardiovascular health.  Here are the main points of the study that were summarized in Medscape, 9/15/23:

METHODOLOGY:

• Studies have linked high intake of ultraprocessed foods with elevated risks of CVD, possibly because of negative effects of additives used as thickening agents and to improve texture and lengthen shelf life.
• Research also suggests food additives such as emulsifiers, which are found in more than half of industrial food or beverage products in France, may have deleterious effects on the gut microbiota and gut inflammation, and impact CVD.
• The analysis included 95,442 mostly female volunteer participants in the NutriNet-Santé prospective study, mean age 43.1 years, who did not have CVD at baseline and completed at least 3 days of web-based 24-hour dietary records.
• Researchers used various databases to collect information and assess the association between intake of food additives consumed by at least 5% of participants and risks of CVD, coronary heart diseases, and cerebrovascular diseases.

TAKEAWAY:

• During a mean follow-up of 7.4 years, there were 1995 incident CVD events, 1044 coronary heart disease events, and 974 cerebrovascular disease events.
• After adjusting for sociodemographic, health, and lifestyle factors as well as for intake of food elements possibly affecting CVD risk such as sugar, sodium, saturated fatty acids, fiber, and artificial sweeteners, higher intake of total celluloses was associated with increased risks of CVD (hazard ratio [HR] for an increase of 1 standard deviation, 1.05; 95% CI, 1.02 - 1.09; P = .004) and coronary heart disease (HR, 1.07; 95% CI, 1.02 - 1.12; P = .004).
• Higher intakes of total monoglycerides and diglycerides of fatty acids were associated with higher risks of all three outcomes: CVD (HR, 1.07; P < .001), coronary heart disease (HR, 1.08; P = .001), and cerebrovascular disease (HR, 1.07; P = .02).
• Trisodium phosphate was associated with higher risks of coronary heart disease (HR, 1.06; P = .03).
• Results of multiple sensitivity analyses were consistent with those from the main models, suggesting consistency and robustness of the findings, the researchers say.

IN PRACTICE:

The study may have important public health implications given food additives are used in thousands of commonly consumed ultraprocessed food products, the authors write, adding that the results "will contribute to the reevaluation of regulations around food additive usage in the food industry to protect consumers."

SOURCE:

The study was carried out by Laury Sellem, Université Sorbonne and Université Paris Cité, Center of Research in Epidemiology and Statistics (CRESS), Nutritional Epidemiology Research Team (EREN), Bobigny, France. It was published online September 6 in The British Medical Journal. BMJ.

LIMITATIONS:

The study population was mostly women (79.0%), and participants were better educated and had more healthy behaviors compared with the general French population, which may limit the generalizability of the results. As women tend to have healthier diets with lower emulsifier intakes than men, and a lower absolute risk of CVD, the study is likely to have underestimated the strength of the associations. The study did not capture emulsifier intakes in foods exempt from food labelling (for example, bakery items), and nonadditive emulsifiers occurring naturally in foods such as eggs. Residual confounding in the associations can't be entirely ruled out.

E-Cigarette Liquid Ingestions in Children

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Published: Wednesday, 06 September 2023 15:37