388 - Vaping E-cigs and Teens, Ivermectin in COVID, Carotid Screening
Take 3 – Practical Practice Pointers©
From the National Academy of Medicine (NAM) and the USPSTF
1) Vaping/e-cigarette use in adolescents
The problem of adolescent tobacco product use continues to worsen. A survey in JAMA Pediatrics tracked both tobacco smoking (combustible cigarette use) and e-cigarette (vaping) use from 2017-2019 in the UK, Canada and the US and found that patterns of ever smoking/vaping (50.4% in 2019), past week smoking/vaping (15.3% in 2019) and frequent smoking/vaping (8.7% in 2019) were all on the increase in the US, largely due to the increase in vaping.
A review by the National Academy of Medicine (NAM) in 2018 noted that while e-cigarettes could potentially be useful in smoking cessation in adults, there remained significant concerns about 1) their role in increasing nicotine and tobacco use amongst adolescents and about 2) the direct toxicity effects of the chemicals contained in e-cigarette fluids. Specific findings relevant to adolescents include:
E-cigarette constituents (ingredients):
- Highly variable depending on manufacturer and use
- Not regulated by the FDA.
- Potentially toxic – containing metals, chemicals, and variable amounts of nicotine, however, less than the amount found in combustible cigarettes.
Health effects of e-cigarettes:
- Short-term cardiovascular effects (elevation in heart rate and blood pressure)
- No evidence of effect on cardiovascular outcomes or atherosclerosis
- At least short-term lung and tissue injury caused by aerosols
- [after this report was published, multiple outbreaks of E-cigarette/vaping-associated lung injury (EVALI) were reported, increasing this concern]
- Increases coughing/wheezing and asthma exacerbations in adolescents
- Potential increase in cancer risk, but limited, indirect evidence
- Very limited evidence of effect on oral tissues – probably less harmful than combustible cigarettes.
- Burn, injury and ingestion-related toxicity risk from broken, malfunctioning, or misused vaping pens and liquids.
- Dependence, but probably at a lower rate than with combustible cigarettes.
Effects of e-cigarettes on initiation and subsequent use of combustible cigarettes:
- Increased risk of ever using combustible cigarettes
- Increased frequency and intensity of subsequent combustible cigarette use
- Limited evidence of greater duration of subsequent combustible cigarette use
The USPSTF considered the evidence on both e-cigarettes and combustible cigarettes in its 2020 recommendation on Prevention and Cessation of Tobacco Use in Children and Adolescents. They gave a B recommendation for primary care interventions to prevent tobacco product use (including e-cigarettes). The preventive interventions included face-to-face counseling, telephone counseling, and computer-based and print-based interventions (newsletters, stickers, handouts). There was, unfortunately, insufficient evidence to make a recommendation on tobacco cessation interventions.
John’s Comments:
The focus for our counseling of children and adolescents to prevent vaping should include the tremendous uncertainty about safety of the e-cigarette products, the real chance of injury and both pulmonary and ingestion-related toxicity from the liquids, and the high risk of nicotine dependence/addiction resulting in both continued vaping and combustible tobacco use. We don’t have enough data on medications or e-cigarettes for smoking cessation in adolescents, so for now, I’ll stick with counseling efforts primarily.
References:
- Hammond D, et al. Changes in Prevalence of Vaping Among Youths in the US, Canada, and England from 2017-2019. JAMA Pediatrics. 2020;174(8):797-800. Link
- Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems, NAM. Public Health Consequences of E-Cigarettes. (Stratton K, Kwan LY, Eaton DL, eds.). National Academies Press; 2018:24952. Link
- US Preventive Services Task Force, Owens DK, et al. Primary Care Interventions for Prevention and Cessation of Tobacco Use in Children and Adolescents: USPSTF Recommendation Statement. JAMA. 2020;323(16):1590. Link
From the NIH and Front Line COVID-19 Critical Care Alliance (FLCCC)
2) Use of Ivermectin for COVID-19 Treatment and Prophylaxis?
One year into the pandemic, the only therapy considered “proven” as a life-saving treatment in COVID-19 is the use of corticosteroids in patients with moderate to severe illness. Other promising therapies have received an Emergency Use Authorization (EUA) from the FDA while studies are ongoing, while some “hoped for” options have not withstood closer research scrutiny. As the pandemic continues, the search for other promising therapies has become more urgent.
Ivermectin is a broad spectrum antiparasitic drug with known antiviral and anti-inflammatory properties. It has been shown to inhibit the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. Since April 2020, there has been an abundance of observational trials, cases series, and ecological analyses suggesting the potential efficacy of ivermectin against COVID-19. Additionally, emerging evidence from outside the US appears to validate its potential clinical use. Because of this mounting evidence, there have been calls from some in the scientific and medical community for more focused research and clinical application even in the absence of proven efficacy and safety for the treatment of COVID-19.
Based on the emergence of ongoing data regarding ivermectin, in January 2021 the NIH COVID-19 Treatment Guidelines Panel revised their previous recommendation against its use and determined that currently there are insufficient data to recommend either for or against its use for the treatment of COVID-19. They indicated that results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide better guidance on its role for the treatment of COVID-19.
In March 2020, the Front Line COVID-19 Critical Care Alliance (FLCCC) was created by a group of US critical care specialists to continuously review the rapidly emerging basic science, translational, and clinical data to develop a treatment protocol for COVID-19. In a paper accepted for publication and in the wake of the NIH change, the FLCCC expert panel has recently reached a consensus in recommending that ivermectin for both prophylaxis and treatment of COVID-19 should be systematically and globally adopted. They also created an outpatient prophylaxis and early treatment protocol called I-MASK+ which includes the use of ivermectin based on their determination of the best available evidence for efficacy and their estimation of low likelihood of harm.
The Infectious Disease Society of America (IDSA) does not list ivermectin in its treatment guidelines. In its recommendation for bamlanivimab, it states, “In patients at increased risk (EUA from FDA) bamlanivimab is a reasonable treatment option if, after informed decision-making, the patient puts a high value on the uncertain benefits and a low value on uncertain adverse events.
Mark’s Comments:
I have been following the data around ivermectin, and the change in NIH designation was notable. Some regional pharmacies indicate there are prescriptions being written for it (likely not for parasitic disease!). While we’re waiting for the results of ongoing trials, and given the paucity of viable options, I believe the language the IDSA uses for bamlanivimab is relevant for ivermectin: It “is a reasonable treatment option if, after informed decision-making, the patient puts a high value on the uncertain benefits and a low value on uncertain adverse events.” The I-MASK+ protocol at the 4th reference below provides some guidance on dosage, but please note that the combination and dosages of medications and supplements recommended have not been studied for this indication, so proceed with caution if you choose to proceed. If you choose to prescribe, become familiar with the side effects and potential drug-drug interactions.
References:
- NIH The COVID-19 Treatment Guidelines Panel’s Statement on the Use of Ivermectin for the Treatment of COVID-19. Updated 14 January 2021. Link
- FLCCC response to NIH Recommendations 18 January, 2021. Link
- Korey P et al for the FLCCC Alliance. Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19. Unpublished manuscript, updated 12 January 2021. Link
- I-MASK+ Prophylaxis and Early Outpatient Treatment Protocol for COVID-19, version 8, 12 January 2021. Link
- Bhimraj A, et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Published by IDSA on 4/11/2020. Last updated, 2/5/2021. Link
From the USPSTF
3) Just Say “No” to Carotid Stenosis Screening
Stroke is a leading cause of death and disability in the US. Although asymptomatic carotid artery stenosis is a risk factor for stroke and a marker for increased risk for myocardial infarction, it causes a relatively small proportion of strokes.
In 2014, the US Preventive Services Task Force (USPSTF) reviewed the evidence for screening for asymptomatic carotid artery stenosis and issued a “D” recommendation, concluding with moderate certainty that the harms outweigh the benefits. The USPSTF recently reviewed the research that has been published since the previous review and concludes that the harms of screening continue to outweigh the benefits (D).
Although several factors increase risk for carotid artery stenosis, including older age, male sex, hypertension, smoking, hypercholesterolemia, diabetes, and heart disease, there are no externally validated, reliable methods to determine who is at increased risk for carotid artery stenosis or who is at increased risk of stroke when stenosis is present. There is also inadequate evidence that screening for asymptomatic carotid artery stenosis leads to a reduction in stroke or death; and the likelihood of small to moderate harms of screening for and treatment of asymptomatic carotid artery stenosis.
The most common modality presently used for screening is carotid duplex ultrasonography (DUS). DUS leads to many false-positive results when screening the general population, which has a low prevalence of carotid artery stenosis (0.5%-1%). This can lead to additional testing and treatment. Auscultation for carotid bruits has also been found to have poor accuracy for detecting carotid stenosis and is not considered a reasonable screening approach.
The recommendation is consistent with the 2014 guidelines from the American Heart Association not to screen low-risk populations for asymptomatic carotid artery stenosis.
Mark’s Comments:
Remember that population-based screening is intended to identify persons with conditions for whom there would be important health benefits from treatments that these patients would not otherwise have received had the condition not been detected. Just because a screening test is easy to do or we have the technology is not reason to do it. Much money continues to be made on the use of ultrasound for asymptomatic carotid screening without evidence of benefit. And please note the recommendation against auscultation for carotid bruits. It’s hard to unlearn what was once taught, but this one should be relegated to the physical exam history books unless new data comes to light.
References:
______________
Mark and John
Carilion Clinic Department of Family and Community Medicine
Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.
Email: mhgreenawald@carilionclinic.org