Month: March 2022

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

FA Manian MD, MPH, , , , , , , , , Leave a comment

On March 29, 2022, the CDC and the FDA approved second booster shots of Pfizer and Moderna Covid vaccines for everyone 50 years of age or older as well as people 12 years of age or older with moderate to severe immune deficiencies to be given at least 4 months following the first booster.1-3  This means a 4th dose of an mRNA vaccine for many adults and a 5th dose for those with moderate to severe immune deficiencies. 

Admittedly, these recommendations are made in the context of many uncertainties, including when the next Covid surge will arrive, what will be the predominant variant, and how will our immunity hold up if a surge occurs. 

Nevertheless, in discussing the merits of a 2nd booster, I would emphasize several “talking points”:

  • Covid hasn’t gone away with new cases still diagnosed daily, some still  requiring hospitalization, albeit at lower frequency than recent past. 
  • Our immunity against Covid wanes in the absence of boosters or natural infection.
  • SARS-CoV-2 has been unpredictable in its surges, as well as emergence of new variants with frequent changes in its virulence and ease of transmission. This means we don’t know when the next surge will hit us (summer, fall or later) and how the predominant variant will behave.
  • But let’s not get too hung up on surges! The fact is that as long as Covid is circulating around, maintaining a robust immunity against infection is the best way to avoid getting infected and the best way to do this is through boosters!
  • As more people go around without masks, the risk of unprotected exposure to SARS-CoV-2 is also likely to increase, particularly in indoor public gatherings.  Boosters may allow us the freedom to go maskless more often!
  • The risk of Long Covid even following mild infection is still real even between surges. This means even if we don’t get very sick from Covid, we are placing ourselves at risk of Long Covid. Remember, no Covid, no Long Covid!
  • Irrespective of whether it’s mild or even asymptomatic, Covid infection  can cause significant disruption in our lives, whether it be isolation at home, not being allowed to return to work or just the anxiety of having it or having passed it to others. This means that, at least currently, it’s premature to consider this virus as “just another respiratory virus.”  It’s impact on our everyday lives is still a lot different than typical respiratory viruses. 
  • mRNA vaccine boosters have been proven to be as safe as primary series. 
  • Last, but not the least, a preprint Israeli study involving volunteers 60 to 100 years old found a 78% reduction in mortality from Covid following a 2nd booster dose of Pfizer mRNA vaccine compared to those who only had 1 booster.4  This study has several limitations including self-selected volunteers who may already be at lower risk of Covid mortality due to their healthier lifestyle. Nevertheless, the data is very encouraging!

Ultimately, the decision to get a second booster, particularly during non-surge periods, will depend a lot on not only available facts but the individual’s threshold for acceptable risk of even mild disease, concern over transmission to others and more recently the cost of the vaccine, among other factors.  

Bonus Pearl: Did you know that each year there are plenty of uncertainties around which influenza A or B subtypes will be the predominant seasonal strain or what month they may surge but these questions never keep us from recommending the annual flu vaccine to the public as a means of reducing influenza cases and saving lives?   

 

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References

  1. D.A. Allows Second Covid Boosters for Everyone 50 and Older – The New York Times (nytimes.com)
  2. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals | FDA
  3. CDC Recommends Additional Boosters for Certain Individuals | CDC Online Newsroom | CDC
  4. Arbel R, Sergienko R, Friger M, et al. Second booster vaccine and Covid-19 mortality in adults 60-100 years old. Preprint, posted March 24, 2022. 24514bba-2c9d-4add-9d8f-321f610ed199.pdf (researchsquare.com)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

My patient presents for evaluation of a mole on her arm. What features of the mole should I look for to help me distinguish a benign mole from melanoma?

FA Manian MD, MPHLeave a comment

Great question! Identifying a melanoma is a lot easier than you might think. A good starting point is the ABCDE criteria, which stands for Asymmetry, Border irregularity, Color variation, Diameter > 6 mm/Dark, and Evolution over time (see Fig 1 below). 1 Higher number of these characteristics in a particular lesion increases the probability of it being melanoma. For example, in the presence of just one characteristic, the positive likelihood ratio (LR) is 1.5 with the probability of melanoma of 7.4%. However, if all five characteristics are present, the positive LR rises to 107, while the probability of melanoma increases to 85%. 2,3,4

Another useful trick is looking for the “ugly duckling sign” (UDS), which refers to any pigmented lesion that appears obviously different than others on a patient’s body.5 For example, let’s say you’re seeing a patient with multiple small, circular, equally-sized moles on his forearm. A few inches away, he has a significantly larger mole with an irregular border. This would qualify as a positive UDS.  While the sensitivities of melanoma recognition are similar for the UDS and the ABCDE criteria (100% and 99%, respectively), the UDS has been shown to significantly improve specificity (88.3%) and accuracy (90.9%) when compared to the ABCDE criteria alone (57.4% and 66.7 %, respectively).6 So incorporating both sets of criteria into your approach to melanoma recognition may be prudent.

Once you suspect a melanoma, your should refer your patient to a dermatologist for an excisional biopsy, the gold standard for melanoma diagnosis.  This procedure consists of excising the entire lesion with 1-3 mm margins.7 The resulting sample can then be used to histologically confirm the diagnosis, prognosticate, and guide management.

Primary care providers play a crucial role in the early detection and treatment of melanoma, so keep your eyes open for any “unusual” looking moles, even if you’re seeing a patient for something unrelated!

Bonus Pearl

Did you know that cardiac involvement with melanoma is not uncommon, affecting an estimated 28% to 56% of patients with metastatic melanoma? 8

 

Figure 1: ABCDE criteria to help differentiate benign skin lesions from melanoma

i

 From Pawan Sonawane, Sahel Shardhul, Raju Mendhe, “Cloud based mobile solution for early detection of Skin Cancer using Artificial Intelligence”, International Journal of Scientific Research in Computer Science, Engineering and Information Technology (IJSRCSEIT), ISSN : 2456-3307, Volume 7 Issue 3, pp. 312-324, May-June 2021. Available at doi : https://doi.org/10.32628/CSEIT217327 Journal URL : https://ijsrcseit.com/CSEIT217327 (https://www.researchgate.net/publication/352394140_Cloud_based_mobile_solution_for_early_detection_of_Skin_Cancer_using_Artificial_Intelligence)

Contributed by Aditya Nellore, 4th year Medical Student, St. Louis University Medical School, St. Louis, Missouri

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References:

  1. Goldsmith SM. Why Is Darkness an Essential Feature for Melanoma Recognition? Skinmed. 2021 Oct 1;19(5):334-336. PMID: 34861912. (https://pubmed.ncbi.nlm.nih.gov/34861912/)
  2. Duarte AF, Sousa-Pinto B, Azevedo LF, Barros AM, Puig S, Malvehy J, Haneke E, Correia O. Clinical ABCDE rule for early melanoma detection. Eur J Dermatol. 2021 Dec 1;31(6):771-778. doi: 10.1684/ejd.2021.4171. PMID: 35107069. (https://pubmed.ncbi.nlm.nih.gov/35107069/)
  3. Thomas L, Tranchand P, Berard F, Secchi T, Colin C, Moulin G. Semiological value of ABCDE criteria in the diagnosis of cutaneous pigmented tumors. Dermatology. 1998;197(1):11-7. doi: 10.1159/000017969. PMID: 9693179. (https://pubmed.ncbi.nlm.nih.gov/9693179/)
  4. Ebell M. Clinical diagnosis of melanoma. Am Fam Physician. 2008 Nov 15;78(10):1205, 1208. PMID: 19035070. (https://pubmed.ncbi.nlm.nih.gov/19035070/)
  5. Gaudy-Marqueste C, Wazaefi Y, Bruneu Y, Triller R, Thomas L, Pellacani G, Malvehy J, Avril MF, Monestier S, Richard MA, Fertil B, Grob JJ. Ugly Duckling Sign as a Major Factor of Efficiency in Melanoma Detection. JAMA Dermatol. 2017 Apr 1;153(4):279-284. doi: 10.1001/jamadermatol.2016.5500. PMID: 28196213. (https://pubmed.ncbi.nlm.nih.gov/28196213/)
  6. Ilyas M, Costello CM, Zhang N, Sharma A. The role of the ugly duckling sign in patient education. J Am Acad Dermatol. 2017 Dec;77(6):1088-1095. doi: 10.1016/j.jaad.2017.06.152. Epub 2017 Sep 28. PMID: 28964538. (https://pubmed.ncbi.nlm.nih.gov/28964538/)
  7. Swetter SM, Tsao H, Bichakjian CK, Curiel-Lewandrowski C, Elder DE, Gershenwald JE, Guild V, Grant-Kels JM, Halpern AC, Johnson TM, Sober AJ, Thompson JA, Wisco OJ, Wyatt S, Hu S, Lamina T. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019 Jan;80(1):208-250. doi: 10.1016/j.jaad.2018.08.055. Epub 2018 Nov 1. PMID: 30392755. (https://pubmed.ncbi.nlm.nih.gov/30392755/)
  8. Goldberg AD, Blankstein R, Padera RF. Tumors metastatic to the heart. Circulation. 2013 Oct 15;128(16):1790-4. doi: 10.1161/CIRCULATIONAHA.112.000790. PMID: 24126323. (https://pubmed.ncbi.nlm.nih.gov/24126323/)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

My patient presents for evaluation of a mole on her arm. What features of the mole should I look for to help me distinguish a benign mole from melanoma?

Is it safe to use diltiazem or verapamil for treatment of my hospitalized patient with heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Short answer, no! It is generally recommended to avoid the use of diltiazem or verapamil, both a non-dihydropyridine calcium channel blocker (CCB), in patients with HFrEF.  Multiple randomized controlled trials involving patients with HFrEF have shown that use of diltiazem [1] or verapamil [2] is associated with increased cardiovascular mortality and morbidity, especially congestive heart failure (CHF) exacerbations.

Although you might argue that most studies [1,2] on HFrEF on CCBs have been based on patients on chronic (weeks to months) therapy, these agents are also sometimes used in the acute inpatient setting for rate control in atrial fibrillation and even blood pressure control. Even in acute settings, avoidance of these agents–or at least using them with great caution— in patients with HFrEF is prudent. Fortunately, for blood pressure control, another CCB, amlodipine [3] has been deemed safe to use in patients with HFrEF.

Adverse effects of diltiazem and verapamil are often attributed to their negative inotropic effects. As a result, patients with preexisting left ventricular dysfunction may be expected to have worse outcomes. In contrast, amlodipine primarily acts on the peripheral vasculature without significant negative inotropic effect. [4]

What about the use of these agents in patients with heart failure and preserved ejection fraction? Studies to date have found that CCBs are safe in this setting, although no mortality benefit has been shown with their use either [1]. 

Bonus Pearl: Did you know that use of another CCB, nifedipine, a close cousin of amlodipine (both 1,4- dihydropyridines), has been associated with increased cardiovascular morbidity (worsening CHF and increased hospitalizations) in patients with HFrEF? [5]

Contributed by Fahad Tahir, MD, Mercy Hospital-St. Louis, St. Louis, Missouri

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References:

  1. Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group. Circulation. 1991 Jan;83(1):52-60. doi: 10.1161/01.cir.83.1.52. PMID: 1984898.https://www.ahajournals.org/doi/epdf/10.1161/01.CIR.83.1.52
  2. Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II–DAVIT II). Am J Cardiol. 1990 Oct 1;66(10):779-85. doi: 10.1016/0002-9149(90)90351-z. PMID: 2220572.https://www.ajconline.org/article/0002-9149(90)90351-Z/pdf
  3. Packer M, Carson P, Elkayam U, Konstam MA, Moe G, O’Connor C, Rouleau JL, Schocken D, Anderson SA, DeMets DL; PRAISE-2 Study Group. Effect of amlodipine on the survival of patients with severe chronic heart failure due to a nonischemic cardiomyopathy: results of the PRAISE-2 study (prospective randomized amlodipine survival evaluation 2). JACC Heart Fail. 2013 Aug;1(4):308-314. doi: 10.1016/j.jchf.2013.04.004. Epub 2013 Aug 5. PMID: 24621933.https://reader.elsevier.com/reader/sd/pii/S2213177913001844?token=510153852A5AEBBDF5CA9F8B16C671C4E2F4B511B6F723227BA1D2180CDAA4726EC329D5ABC4118738CB1D8B67A3CF6B&originRegion=us-east-1&originCreation=20220316135803
  4. Zamponi, G. W., Striessnig, J., Koschak, A., & Dolphin, A. C. (2015). The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. Pharmacological reviews, 67(4), 821–870.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630564/
  5. Elkayam U, Amin J, Mehra A, Vasquez J, Weber L, Rahimtoola SH. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation. 1990 Dec;82(6):1954-61. doi: 10.1161/01.cir.82.6.1954. PMID: 2242521.https://www.ahajournals.org/doi/epdf/10.1161/01.CIR.82.6.1954

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is it safe to use diltiazem or verapamil for treatment of my hospitalized patient with heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation?

My patient on chronic oral baclofen began having mental status changes and hallucinations soon after hospitalization while still receiving baclofen. Could a lower than home-dose of baclofen have caused his withdrawal symptoms?

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment

Absolutely! Although we usually think of withdrawal symptoms in the setting of complete discontinuation of certain CNS depressants, even a reduced dose of baclofen1,2 in a patient who has been on a higher dose chronically can precipitate full-blown withdrawal symptoms, such as delirium, fevers, hallucinations, hyperspasticity, autonomic instability and even respiratory failure, multiorgan failure, cardiac arrest and death.1-5

Recall that baclofen is a GABA-B agonist and a potent inhibitor of neuronal synapses with resultant decreased excitation of muscle spindles and muscle spasticity.6 Similar to other benzodiazepines, baclofen is also a CNS depressant and bears many similarities with alcohol in its physiologic effects.  For example, baclofen and alcohol both produce unsteady gait, dizziness, mood alterations and impairment in attention and memory and reduce anxiety, among others.  Not surprisingly, abrupt withdrawal from baclofen may produce similar symptoms as those associated with alcohol withdrawal, such as confusion, hallucination and delirium (observed in our patient) as well as seizures.3 Withdrawal symptoms typically occur 24-48 hours after discontinuation or reduction in the dose of baclofen.1,2

Of course, many of our hospitalized patients are already at risk of mental status changes or sedation from their underlying conditions or from medications needed to treat them.  In this setting, consideration in reducing the home dose of certain CNS depressants, such as baclofen, is understandable and reasonable. However, we should also keep in mind that even a reduction in the chronic dose of baclofen carries a risk of withdrawal!  Unfortunately, healthcare facilities often lack established management protocols for anticipated interruption of oral baclofen.7

In our patient, the home dose of baclofen had been reduced by one-half following his admission. Worsening delirium and new onset visual and auditory hallucinations were noted within a few days of hospitalization. Thankfully, no further bouts of confusion or hallucination was observed after resuming his home dose.

Bonus Pearl:

Did you know that baclofen is often used (off label) to treat intractable hiccups of central origin? 8,9

Contributed by Fahad Tahir, MD, Mercy Hospital-St. Louis, St. Louis, Missouri

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References:

  1. Terrence CF, Fromm GH. Complications of Baclofen Withdrawal. Arch Neurol. 1981;38(9):588–589. doi:10.1001/archneur.1981.00510090082011. https://jamanetwork.com/journals/jamaneurology/article-abstract/580084
  1. O’Rourke, F., Steinberg, R., Ghosh, P., & Khan, S. (2001). Withdrawal of baclofen may cause acute confusion in elderly patients. BMJ (Clinical research ed.), 323(7317), 870.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1121408/ 
  1. de Beaurepaire R. A review of the potential mechanisms of action of baclofen in alcohol use disorder. Front. Psychiatry 2018; 9:506). In fact, baclofen may be a promising treatment for alcohol use disorder. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232933/pdf/fpsyt-09-00506.pdf
  2. Cardoso AL, Quintaneiro C, Seabra H, Teixeira C. Cardiac arrest due to baclofen withdrawal syndrome. BMJ Case Rep. 2014;2014:bcr2014204322. Published 2014 May 14.doi:10.1136/bcr-2014-204322 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025399/pdf/bcr-2014-204322.pdf
  1. Green LB, Nelson VS. Death after acute withdrawal of intrathecal baclofen: case report and literature review. Arch Phys Med Rehabil. 1999 Dec;80(12):1600-4. doi: 10.1016/s0003-9993(99)90337-4. PMID: 10597813. https://www.archives-pmr.org/article/S0003-9993(99)90337-4/pdf
  1. Allerton CA, Boden PR, Hill RG. Actions of the GABAB agonist, (-)-baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro. Br J Pharmacol. 1989;96(1):29-38. doi:10.1111/j.1476-5381.1989.tb11780.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1854300/
  1. Schmitz NS, Krach LE, Coles LD, Schrogie J, Cloyd JC, Kriel RL. Characterizing Baclofen Withdrawal: A National Survey of Physician Experience. Pediatr Neurol. 2021 Sep;122:106-109. doi: 10.1016/j.pediatrneurol.2021.06.007. Epub 2021 Jul 28. PMID: 34330615. https://www.pedneur.com/article/S0887-8994(21)00129-6/fulltext
  1. Zhang, C., Zhang, R., Zhang, S. et al. Baclofen for stroke patients with persistent hiccups: a randomized, double-blind, placebo-controlled trial. Trials 15, 295 (2014). https://doi.org/10.1186/1745-6215-15-295
  1. Jeon YS, Kearney AM, Baker PG Management of hiccups in palliative care patients BMJ Supportive & Palliative Care 2018;8:1-6. https://spcare.bmj.com/content/8/1/1.long

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My patient on chronic oral baclofen began having mental status changes and hallucinations soon after hospitalization while still receiving baclofen. Could a lower than home-dose of baclofen have caused his withdrawal symptoms?