I’ve seen a lot of distortion by certain news outlets regarding what this announcement regarding acetaminophen use in pregnancy (and the risk of autism spectrum disorder) actually was.  Please read the unexpurgated text here and see what you think.  I’ve highlighted statements that I don’t believe have been mentioned or expanded upon in the news stories around the country on this

RFK Jr:

I ordered HHS to launch an unprecedented all-agency effort to identify all cause of autism, including toxic and pharmaceutical exposures. At President Trump’s urging, NIH, FDA, CDC, and CMS are turning over every stone to identify the ideology of the autism epidemic and how patients and parents can prevent and reverse this alarming trend. We have broken down the traditional silos that have long separated these agencies, and we have fast-tracked research and guidance. Historically, NIH has focused almost solely on politically safe and entirely fruitless research about the genetic drivers of autism. And that would be studying the genetic drivers of lung cancer without looking at cigarettes, and that’s what NIH has been doing for 20 years. As a result, we don’t have an answer to this critical question. Despite the cataclysmic impact of the epidemic on our nation’s children, we are now replacing the institutional culture of politicized science and corruption with evidence-based medicine.

(14:10)
NIH research teams are currently testing multiple hypotheses with no area off-limits. We promise transparency as we uncover the potential causes and treatments, and we will notify the public regularly of our progress. Today we are announcing two important findings from our autism work that are vital for parents to know as they make these decisions. First, HHS will act on acetaminophen. The FDA is responding to clinical and laboratory studies that suggest a potential association between acetaminophen used during pregnancy and adverse neurodevelopmental outcomes, including later diagnosis for ADHD and autism. Scientists have proposed biological mechanisms linking prenatal acetaminophen exposure to altered brain development. We have also evaluated the contrary studies that show no association. Today, the FDA will issue a physician’s notice about the risk of acetaminophen during pregnancy and begin the process to initiate a safety label change. HHS will launch a nationwide public service campaign to inform families and protect public health.

(15:28)
The FDA also recognized that acetaminophen is often the only tool for fevers and pain in pregnancy, as other alternatives have well-documented adverse effects. HHS wants, therefore, to encourage clinicians to exercise their best judgment and use of acetaminophen for fevers and pain in pregnancy by prescribing the lowest effective dose for the shortest necessary duration and only when treatment is required. Furthermore, thanks also to the politicization of science. The safety of acetaminophen against the risk of neurodevelopmental disorders in young children has never been validated. Prudent medicine therefore suggests caution in acetaminophen use in young children, especially since strong evidence also has associated it with liver toxicity. Some studies have also found the use of acetaminophen in children can potentially prolong viral illnesses. The FDA will drive new research to safeguard mothers, children, and families. 

All of this appears more nuanced than the news coverage and TikTok responses would suggest.  Here’s a brief analysis of the literature:

Introduction: The RFK Announcement

The announcement from Robert F. Kennedy Jr., as Secretary of HHS, regarding Acetaminophen (paracetamol or Tylenol) and autism was nuanced yet precautionary. He stated that the FDA was responding to clinical and laboratory studies suggesting a potential association between prenatal acetaminophen use and adverse neurodevelopmental outcomes, including ADHD and autism. He confirmed they reviewed studies showing both potential links and those showing no association. The immediate action was to issue a physician’s notice recommending that women limit Tylenol use during pregnancy unless medically necessary, using the lowest effective dose for the shortest necessary duration. He justified this caution by noting that scientists have proposed biological mechanisms linking acetaminophen exposure to altered brain development.

Data Analysis: The Case for Association (Pro)

Mounting epidemiological evidence suggests a link between prenatal acetaminophen exposure and neurodevelopmental risks. Meta-analyses of large cohort studies generally support this concern: one meta-analysis of 73,881 mother-child pairs indicated that children prenatally exposed were 19% more likely to exhibit borderline/clinical Autism Spectrum Condition (ASC) symptoms and 21% more likely to exhibit ADHD symptoms. A different meta-analysis reported a pooled risk ratio of 1.34 for ADHD and 1.19 for ASD associated with prenatal exposure. Several studies noted a dose-response pattern, showing stronger associations with longer duration of use, such as exposure for 28 days or more. Studies using objective cord plasma biomarkers of fetal exposure also found significantly increased risks of childhood ADHD and ASD in a dose-response fashion. These associations are biologically plausible, potentially linked to acetaminophen influencing oxidative stress, the endocannabinoid system, and endocrine disruption pathways vital for fetal brain development.

Data Analysis: The Case Against Causation (Con)

The main argument against a causal link lies in the issue of confounding by familial factors. Associations seen in conventional studies may be misleading because mothers who use acetaminophen during pregnancy often have underlying health conditions (like pain or migraine) or genetic predispositions (like for ADHD) that are themselves risk factors for neurodevelopmental disorders. Crucially, large, rigorous studies employing a sibling control analysis—comparing exposed and unexposed children within the same family to inherently control for shared genetics and socioeconomic factors—found that the observed associations disappeared entirely. A nationwide Swedish cohort study of nearly 2.5 million children, for example, found no evidence that acetaminophen use increased the risk of autism (HR 0.98) or ADHD (HR 0.98) in sibling comparisons. Furthermore, established medical bodies recognize acetaminophen as the safest first-line analgesic/antipyretic in pregnancy, noting that untreated high fever poses its own risks, and alternatives like NSAIDs carry documented dangers, especially later in pregnancy.

Conclusion

The overall conclusion, drawing on the most robust contemporary evidence, suggests that the statistical association between prenatal acetaminophen use and neurodevelopmental disorders is likely attributable to unmeasured familial confounding rather than a direct causal effect of the drug itself. Nonetheless, given the widespread use of this medication and the persistent concern, current recommendations remain focused on prudent use: pregnant individuals should use acetaminophen only when medically necessary, at the lowest effective dose, and for the shortest duration possible.

Borderline Personality Disorder

Borderline Personality Disorder, or BPD, is a complex condition that affects 1.6% of adults in the U.S. This article will help you recognize its symptoms, understand its challenges (especially in relationships) and find pathways to coping and treatment.

Core Symptoms

Emotional Instability and Intense Mood Swings

People with BPD experience significant emotional instability, leading to episodes of intense mood swings. These can range from feelings of euphoria to deep depression, often triggered by perceived rejections or abandonment. They may yell or scream irrationally, or tell you they love you and you’re the only one who understands them…until you “cross” them, at which time you’re on the “enemy list.”

Fear of Abandonment and Unstable Relationships

One of the most prominent symptoms of BPD is an intense fear of abandonment, which can result in desperate efforts to avoid being left alone. This fear often leads to patterns of unstable interpersonal relationships, swinging wildly between idealization and devaluation of others. again, one minute the new person is the greatest in the world and everyone else stinks, and the next minute the new person stinks too, and in fact, stinks worse than every other person who stinks in the world. In a week or two they may be off the stinker list and back to the list of greatest people in the world. and on and on it goes.

Impulsive Behaviors

Individuals with BPD may engage in impulsive and often dangerous behaviors. These can include reckless or impaired driving, binge eating, alcohol or drug abuse and other negative behaviors which are usually efforts to manage negative emotions. They will minimize these behaviors, using rationalizations that range from the ridiculous to the more ridiculous.

Distorted Self-Image

A fluctuating sense of self is common in BPD. Individuals may struggle with their identity, leading to sudden changes in values, self-image, or aspirations. This instability can cause significant distress or impairment in social or occupational settings. They may grossly overvalue their talent or importance, and lash out in anger when called on their amplifications. These behaviors will often cause people to misdiagnose the BPD patient with narcissistic personality disorder; a mistake that can be costly.

Chronic Feelings of Emptiness

Many people with BPD describe a persistent feeling of emptiness, which they may try to fill with alcohol, drugs, food, or relationships. This symptom is often associated with profound loneliness or boredom, and they may constantly seek friends…friends who will often eventually be rebuffed when they don’t toe the line of expected behaviors of the person with BPD.

Inappropriate Anger

Difficulty controlling anger or experiencing inappropriate, intense anger is another symptom of BPD. This can manifest as temper outbursts, ongoing feelings of resentment, or fights, both physical and verbal. Threats of physical violence are not uncommon.

Self-Harming Behaviors

Self-harm, including cutting or burning, is a common symptom among those with BPD. These actions may be used as a coping mechanism to deal with emotional pain or to feel a sense of control.

Stress-Related Paranoia

Under stress, individuals with BPD may experience paranoia, grandiosity and even dissociative behaviors. They may accuse others of the very behaviors they engage in on a daily basis.

Understanding these symptoms is crucial for recognizing BPD and advocating for proper diagnosis and treatment.

Challenges in Relationships for Those with BPD

Navigating the emotional landscape of relationships can be particularly challenging for individuals with Borderline Personality Disorder (BPD). Here’s a closer look at some of the unique hurdles they might face:

Trust and Hypersensitivity

• Difficulty Trusting Others: For those with BPD, trust doesn’t come easily. This can stem from past experiences or inherent fears associated with the disorder.
• Hypersensitive Reactions: Perceived slights or rejections can trigger intense emotional responses, often leading to conflict or withdrawal.

Emotional Instability

• Constant Emotional Changes: Rapid fluctuations in mood can confuse and alienate partners, friends, and family members, making stable relationships difficult to maintain.
• Perceived Chaos: To outsiders, these emotional peaks and valleys may appear chaotic or unpredictable, adding strain to interpersonal dynamics.

Fear of Abandonment

• Intense Fear: This core symptom of BPD can drive individuals to cling to relationships, fearing isolation and rejection above all else.
• Unrealistic Expectations: Sometimes, the fear of abandonment leads to unrealistic expectations of partners, fostering a codependent dynamic.

Relationship Patterns

• Caring but Sensitive: Individuals with BPD can actually be caring and compassionate, but their sensitivity to abandonment or perceived slights causes conflict and complicates their relationships.
• Codependency Issues: The intense desire to avoid abandonment may lead to relationships where one partner is excessively dependent on the other, which can be both unsustainable and unhealthy.

How to cope with someone with BPD in your life

Coping with someone who has borderline personality disorder involves understanding, patience, and well-defined strategies to maintain a healthy relationship. Here are practical steps to help manage interactions and support your loved one:

1. Establish Clear Boundaries

Set healthy boundaries to protect both your well-being and the relationship. Clearly communicate what behaviors are acceptable and which are not, ensuring these limits are consistent and respectful.

2. Educate Yourself About BPD

Gain a deeper understanding of BPD symptoms and triggers. This knowledge can prevent misunderstandings and equip you with strategies to handle challenges effectively.

3. Practice Active Listening

Show empathy and validation by listening actively. Acknowledge their feelings without judgment, which can help them feel understood and supported.

4. Stay Calm and Patient

During emotional escalations, remain calm and patient. This stability can be reassuring, helping to de-escalate intense situations.

5. Encourage Professional Help

Support your loved one in seeking professional help such as therapy or counseling. Participate in sessions if appropriate, to better understand their experiences and needs.

6. Learn and Apply Mindfulness

Mindfulness techniques can help both you and your loved one manage stress and emotional spikes. Practice these techniques together to encourage a calm environment.

7. Regularly Check-in

Maintain regular communication to help alleviate fears of abandonment. These check-ins can reinforce your support and commitment to the relationship.

8. Respond to Self-Harm Seriously

Always take any self-harming behaviors seriously. Encourage professional intervention and express your concern about their well-being without judgment.

By implementing these strategies, you can create a supportive and understanding environment that helps manage the challenges of BPD while strengthening your relationship.

Is there effective treatment for BPD?

Absolutely, there are effective treatments for Borderline Personality Disorder (BPD), primarily focusing on psychotherapy, with medication playing a supportive role in managing co-occurring conditions. Let’s break down the key components:

Psychotherapy Approaches

• Dialectical Behavior Therapy (DBT): This is the gold standard for BPD treatment, emphasizing mindfulness, emotional regulation, and distress tolerance skills.
• Cognitive Behavioral Therapy (CBT): Helps patients identify and change core beliefs and behaviors that underlie inaccurate perceptions of themselves and others, and problems interacting.
• There are others, including Mentalization-Based Treatment (MBT), Transference-Focused Psychotherapy (TFP), and Schema-Focused Therapy, all of which can be helpful, but The challenge is in getting the BPD patient to not only recognize that they have a problem but to continue therapy once they do.

Medication and Other Treatments

• While medications do not cure BPD, they can help manage symptoms like depression, anxiety, and impulsivity when they occur alongside BPD.
• Hospitalization might be necessary in cases where there’s a risk to the patient’s safety.

• Regular exercise, adequate sleep, and a nutritious diet can significantly reduce symptoms.
• Mindfulness and stress management techniques are beneficial in managing emotional spikes and fostering emotional stability.

Conclusion

With the right support, people with BPD can have healthy, fulfilling relationships. Without it, and without treatment, they can lead lonely, unfulfilled lives frought with unstable relationships and substance abuse.

Coping with BPD can be very challenging. But if you, a family member or friend is struggling, there is help. The national alliance on mental illess (NAMI) will provide you with support and information about community resources for you and your family.

Contact the NAMI HelpLine at 800-950-NAMI (6264) or info@nami.org with any questions you may have about BPD.

Brilliant internationally known comic Mark Normand enters the Exam Room (yecch, that title) to discuss cock pills, inbreeding, insomnia, and more!  Exclusively and AD FREE on
patreon.com/weirdmedicine!

Abigail Zuger, MD

Both agents are clinically effective, but uncertainties still attend their use.

At the end of December 2021, two novel oral antiviral agents received FDA emergency use authorization for outpatient use in mild-to-moderate COVID-19. Although both agents generated substantial premarketing enthusiasm, they come to market with lingering uncertainties.

Nirmatrelvir (Paxlovid, Pfizer) is a viral protease inhibitor with expected in vitro activity against all clinically significant SARS-CoV-2 variants to date. In an unpublished manufacturer-supported study. opens in new tab, nirmatrelvir boosted with the CYP3A inhibitor ritonavir reduced rates of hospitalization or all-cause death by almost 90% among unvaccinated high-risk adult outpatients with confirmed mild-to-moderate COVID-19. A study involving vaccinated standard-risk adults is ongoing. The drug has also been authorized for unvaccinated children and teens 12 and older. The dosing regimen consists of two 150-mg nirmatrelvir tablets and one 100-mg ritonavir tablet taken together twice daily for 5 days. Renal impairment requires dose reduction; patients with severe liver or kidney disease should not receive treatment. Coadministration with drugs metabolized by CYP3A or those inducing the enzyme may be dangerous. No specific adverse effects have been associated with nirmatrelvir plus ritonavir to date.

Molnupiravir (Lagevrio, Merck) is a nucleoside analog that induces fatal mutations in the SARS-CoV-2 genome; it too has demonstrated in vitro activity against all clinically significant viral variants. In a manufacturer-supported study of high-risk unvaccinated adult outpatients with mild-to-moderate COVID-19, the drug reduced rates of hospitalization or all-cause mortality by about 30% (N Engl J Med 2021 Dec 16; [e-pub]). Because of concerns about possible mutagenicity, molnupiravir is not recommended during pregnancy; and because of possible toxicity to bone, cartilage, or both, the drug has not been authorized for children or teens younger than 18. The dose is four 200-mg capsules twice daily for 5 days. Side effects have been limited to mild decreases in hemoglobin. opens in new tab. No renal or hepatic adjustments are necessary, and no drug–drug interactions have been identified. An FDA advisory committee also articulated concerns about the drug’s potential ability to generate viral mutants of concern.

COMMENT
Until these two drugs were approved, authorized treatments for outpatients at high risk for severe COVID-19 were limited to parenteral monoclonal antibody preparations. Some recent monoclonals (NEJM JW Infect Dis Nov 2021 and N Engl J Med 2021 Sep 29; [e-pub]; NEJM JW Infect Dis Jan 2022 and N Engl J Med 2021 Oct 27; [e-pub]) have yielded results similar to nirmatrelvir’s — and considerably more impressive than molnupiravir’s — but the practical difficulties of administering monoclonals are considerable, and not all are active against specific SARS-CoV-2 variants. Good data now support the efficacy of the parenteral antiviral remdesivir in at-risk outpatients with COVID-19 (N Engl J Med 2021 Dec 22; [e-pub]), but the same practical difficulties apply.

Although oral antivirals will be far easier on both patients and providers than any of the parenteral agents, clinicians should remember the unknowns attending their use— namely, a full picture of the drugs’ clinical efficacy against current and future viral variants, as well as their real-world toxicities. Molnupiravir particularly worries the FDA and its advisors enough that the agency has directed clinicians to use it only if alternative agents are contraindicated or unavailable. This advice presumably places molnupiravir as the current last choice among available agents. Still, the hierarchy of outpatient COVID-19 treatments is likely to change substantially as new agents emerge, new variants circulate, and more-complete data on these first two drugs’ clinical performance are released.

CITATION(S):
U.S. Food and Drug Administration. Fact sheet for healthcare providers: Emergency use authorization for Paxlovid™. FDA 2021 Dec 22; [e-pub]. (https://www.fda.gov/media/155050/download. opens in new tab)

U.S. Food and Drug Administration. Fact sheet for healthcare providers: Emergency use authorization for molnupiravir FDA 2021 Dec 23; [e-pub]. (https://www.fda.gov/media/155054/download. opens in new tab)

Here are good sources of covid-19 data.

This site, Epiforecasts, has the Rt (effective reproductive number) which will give you some idea of how fast the virus is spreading in your community.

Daniel Stout of StoutLabs has created a site that we have used consistently since the start of the pandemic: covid.stoutlabs.com.

Click here for US Data

And this site has comprehensive data;  it can be overwhelming but is worth the time:  Our World In Data.

Our pal Jake Boisvert turned us on to COVIDestim.org, which tries to paint the most complete, current, and granular picture possible of the U.S. COVID-19 epidemic.

 

If you have other sites you’d like added to the list, please let me know.