As a versatile medical specialty providing continuing and comprehensive health care to patients of all ages and genders, family medicine covers a wide range of diagnoses and treatments, and updates in related research are crucial, particularly for the interprofessional healthcare team. This article covers key developments in several medical areas of family medicine, focusing on the management of acetaminophen poisoning, diet-related gut inflammation, and links between autism and self-harm and suicide.

NEW CONSENSUS ON MANAGING ACETAMINOPHEN POISONING

Acetaminophen (N-acetyl-para-aminophenol, paracetamol, APAP), a common drug ingredient in over 600 over-the-counter and prescription medicines, is used to reduce fever and provide temporary relief from pain.^[1] Due to the ubiquitous presence of acetaminophen worldwide, it is perceived to be very safe but can cause severe liver toxicity if taken in large amounts.^[2] Acetaminophen toxicity is the second most common cause of liver transplantation worldwide and the most common in the United States and also leads to 56,000 emergency department visits, 2600 hospitalizations, and 500 deaths per years in the United States.^[3] Thus, guidelines for emergency department management of acetaminophen poisoning are crucial for interprofessional family medicine teams.

Topline:

An expert panel has updated recommendations for emergency department assessment, management, and treatment of acetaminophen poisoning.

Methodology:

The United States and Canada have no formal guidelines for managing acetaminophen poisoning, which is characterized by hepatocellular damage and potential liver failure, which can be life-threatening.

The past 25 years have seen the introduction of products that contain greater amounts of acetaminophen, extended-release preparations, and new drugs that combine acetaminophen with opioids or other ingredients.

From the medical literature and current poison control guidelines, the panel used a modified Delphi method to create a decision framework and determine appropriate management, including triage and laboratory evaluation, for acetaminophen poisoning, addressing scenarios such as extended-release and high-risk ingestion, co-ingestion of anticholinergics or opioids, pregnancy, weight greater than 100 kg, and criteria for consultation with a toxicologist.

Takeaway:

The panel emphasized the role of the patient's history; an inaccurate estimate of the time of ingestion, for example, can lead to the erroneous conclusion that acetylcysteine, a medication used to treat overdose, is not needed or can be discontinued prematurely -- a potentially fatal mistake.

The initial dose of acetylcysteine should be administered as soon as the need becomes evident, with the panel recommending at least 300 mg/kg orally or intravenously during the first 20 or 24 hours of treatment.

Management of ingestion of extended-release preparations is the same, with the exception of obtaining a second acetaminophen blood concentration in some cases.

When acetaminophen is co-ingested with anticholinergic or opioid agonist medications, management is the same, except if the first acetaminophen concentration measured at 4 to 24 hours after ingestion is 10 μg/mL or less, another measurement and acetylcysteine treatment are not needed.

In Practice:

"A guideline that provides management guidance could optimize patient outcomes, reduce disruption for patients and caregivers, and reduce costs by shortening the length of hospitalization," write the authors.

Source:

The study was conducted by Richard C. Dart, MD, PhD, Rocky Mountain Poison and Drug Safety, University of Colorado School of Medicine, Denver, and colleagues. It was published online August 8 in JAMA Network Open.^[4]

Limitations:

The work lacked high-quality data that address clinical decisions needed for managing acetaminophen poisoning. There were only a few well-controlled comparative studies, which focused on specific issues and not on patient management.

HOW SOYBEAN OIL COULD LEAD TO GUT INFLAMMATION

Diet plays an important role in overall health, and there has been increased interest in the relationship between gut health and overall health.^[5,6] Gut inflammation can occur through changes in the gut microbiota with the consumption of a high-fat, high-calorie diet, such as the American diet, which often includes a large number of processed foods that have been linked to several diseases.^[7-9]

A popular ingredient in the American diet has been linked to ulcerative colitis. The ingredient is soybean oil, which is very common in processed foods. In fact, US per capita consumption of soybean oil increased more than 1000-fold during the 20th century.^[10]

In a study from the University of California (UC) Riverside and UC Davis, mice fed a diet high in soybean oil were more at risk of developing colitis.^[11] The likely culprit? Linoleic acid, an omega-6 fatty acid that comprises up to 60% of soybean oil.

Small amounts of linoleic acid help maintain the body's water balance. But Americans derive as much as 10% of their daily energy from linoleic acid, when they need only 1% to 2%, the researchers say.

The findings build on earlier research linking a high-linoleic acid diet with inflammatory bowel disease, or IBD, in humans.^[12,13] (Previous research in mice has also linked high consumption of the oil with obesity and diabetes in rodents.^[14])

For the new study, the researchers wanted to drill down into how linoleic acid affects the gut.

How Linoleic Acid May Promote Inflammation

In mice, the soybean oil diet upset the ratio of omega-3 to omega-6 fatty acids in the gut. This led to a decrease in endocannabinoids, lipid-based molecules that help block inflammation.^[15,16]

Enzymes that metabolize fatty acids are "shared between two pathways," said study co-author Frances Sladek, PhD, professor of cell biology at UC Riverside. "If you swamp the system with linoleic acid, you'll have less enzymes available to metabolize omega-3s into good endocannabinoids."

The endocannabinoid system has been linked to "visceral pain" in the gut, said Punyanganie de Silva, MD, MPH, an assistant professor at Brigham & Women's Hospital, who was not involved in the study. But the relationship between the endocannabinoid system and inflammation has yet to be fully explored.

"This is one of the first papers that has looked at the association between linoleic acid and the endocannabinoid system," de Silva said. "[The researchers] propose a potential new mechanism of how linoleic acid may increase inflammation" -- that is, through its impact on the endocannabinoid system.

Changes in the Gut Microbiome

The gut microbiome of the mice also showed increased amounts of adherent invasive Escherichia coli, a type of bacteria that grows by using linoleic acid as a carbon source. A "very close relative" of this bacteria has been linked to IBD in humans, Sladek said.^[17]

Using a method known as metabolomics, the researchers studied 3000 metabolites in both the intestinal cells of the mice and the bacteria. Endocannabinoids decreased in both.

"We were actually quite surprised. I didn't realize that bacteria made endocannabinoids," Sladek said.

Helpful bacteria, such as the probiotic lactobacillus species, died off. The mice also had increased levels of oxylipins, which are correlated with obesity in mice and colitis in humans.^[18]

A High-Linoleic Acid Diet Could Mean a Leaky Gut

Linoleic acid binds to a protein known as HNF-4α. Disrupting the expression of this protein can weaken the intestinal barrier, letting toxins flow into the body -- more commonly known as leaky gut.^[19] Mice on the soybean oil diet had decreased levels of the protein and more porous intestinal barriers, raising the risk for inflammation and colitis.

"The HNF-4α protein is conserved from mouse to human, so whatever's happening to it in the context of the mouse gut, there's a very high chance that a similar effect could be seen in humans as well," said study co-author Poonamjot Deol, PhD, an assistant professional researcher at UC Riverside.

Still, de Silva urges "some caution when interpreting these results," given that "this is still experimental and needs to be reproduced in clinical studies as humans have a far more varied microbiome and more variable environmental exposures than these very controlled mouse model studies."

De Silva says cooking with olive oil can "help increase omega-3:omega-6 ratios" and advises eating a varied diet that includes omega-3 fats, such as flaxseed and walnuts, and minimal amounts of processed foods and saturated fats.

Looking ahead, endocannabinoids are being explored as "a potential therapy for treating IBD symptoms," said Deol. She hopes to delve further into how linoleic acid affects the endocannabinoid system.

AUTISM TIED TO HIGHER RATES OF SELF-HARM, SUICIDE

Autism spectrum disorder (ASD) is a common childhood-onset neurodevelopmental disorder with clinical features of impairments in speech, social interaction, and the presence of repetitive or restricted behaviors.^[20] Moreover, adverse events, trauma, and their consequences are not only frequently overlooked in individuals with ASD but are also more likely to repeatedly occur.^[21]  Although reasons remain unclear, suicide death and precursory self-harm events occur at higher rates among individuals with ASD than among individuals without ASD.^[22] A recent study was conducted by Meng-Chuan Lai, MD, PhD, Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and colleagues to determine the sex-stratified rates of self-harm events and suicide death among individuals with ASD vs nonautistic individuals as well as the associated sociodemographic and clinical risk factors.^[23]

Topline:

Even after accounting for sociodemographic factors, intellectual disabilities, and psychiatric diagnoses, autism is associated with an 83% increased risk of self-harm among females and a 47% increased risk among males.

Methodology:

Evidence shows people with autism have over threefold greater odds than their counterparts without the disorder of self-injurious behavior, suicidal ideation, suicide attempt, or suicide death, but reasons for these elevated risks are unclear.

Using various linked databases in the province of Ontario, Canada, researchers identified all individuals with an autism diagnosis from April 1, 1988, to March 31, 2018, and matched each on age and sex to 4 nonautistic individuals for the comparison group.

Investigators created 2 cohorts to separately evaluate outcomes of self-harm events leading to emergency healthcare and suicide death with the accrual period for both cohorts beginning at a person's 10th birthday.

The self-harm cohort included 379,630 individuals while the suicide cohort included 334,690 individuals.

Takeaway:

Over 15 years, females with autism showed the highest cumulative self-harm events, followed by males with autism, nonautistic females, and nonautistic males; over 25 years, males with autism had the highest cumulative incidence of suicide death, followed by females with autism, nonautistic males, and nonautistic females.

Autism had independent associations with self-harm events (females: relative rate [RR], 1.83 [95% CI: 1.61, 2.08]; males: RR, 1.47 [95% CI: 1.28, 1.69]) even after accounting for sociodemographic factors (varied directions of associations), intellectual disabilities (associated with increased risks), and psychiatric diagnoses including mood and anxiety, psychotic, addiction, and personality disorders (associated with increased risks).

For both female and male individuals, final models showed autism per se was not significantly associated with suicide death, but certain correlates were linked to risk. Among both sexes, intellectual disabilities were associated with reduced risks, and psychiatric diagnoses were associated with increased risks.

As a substantial proportion (28.4%) of the suicide cohort did not have data on self-harm, researchers were unable to examine the association of self-harm with suicide death.

In Practice:

That psychiatric diagnoses increased suicide risks among people with autism suggests supports to reduce such risks "should consider multifactorial mechanisms, with a particular focus on the prevention and timely treatment of psychiatric illnesses," write the authors.

Limitations:

The autism cohort didn't capture those diagnosed in private practices or with subtle presentations not yet diagnosed. Misclassification of autistic people in the nonautistic cohort may have resulted in underestimation of suicide-related outcomes. The administrative data don't reliably identify diagnoses associated with suicide risks such as attention-deficit/hyperactivity disorder or subcategories of mood disorders, and don't contain information about risk and protective mechanisms of suicide behaviors such as family history.

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