Author: FA Manian MD, MPH

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?

Should healthy adults receive a Covid vaccine booster shot and why?

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

A booster shot of Covid vaccine (eg, mRNA, Pfizer or Moderna) is now recommended by the CDC even for healthy adults as follows:1

  • If you received Pfizer vaccine as your primary series, are ≥12 years old and at least 5 months after your 2nd dose
  • If you received Moderna vaccine as your primary series, are ≥18 years old and at least 5 months after your 2nd dose
  • If you received J&J vaccine, are ≥18 years old and at least 2 months after your 1st dose

There are at least 3 reasons for receiving a Covid vaccine booster: 1

  • Waning immunity after primary vaccine series
  • Emergence of Omicron variant which seems to be less responsive to the existing immunity from the vaccine
  • Recent data from clinical trials showing that a booster shot increased the immune response in trial participants who completed an either Pfizer or Moderna mRNA vaccine primary series 6 months earlier or had J&J vaccine single dose 2 months earlier

Here is the data from CDC on the vaccine effectiveness against Covid based on epidemiologic data on emergency department (ED)/urgent care (UC) encounters or hospitalization during the recent Omicron-predominant period:2

 Vaccine effectiveness against ED/Urgent care encounters 

  • 2 doses of mRNA vaccine: 41% (69% <2 months vs 37% ≥5 months after last dose)
  • 3 doses of mRNA vaccine: 83% (87% < 2 months vs 66% 4 months vs 31% ≥5 months)

Vaccine effectiveness against hospitalization 

  • 2 doses of mRNA vaccine: 55% (71% < 2months vs 54% ≥5 months)
  • 3 doses of mRNA overall 88% (91% if < 2 months, 78% if ≥4 months)

So take full advantage of available Covid vaccines and maximize your chance of not getting Covid!

 

Bonus Pearl: Did you know that a recent CDC study found that people 18 years and older who received the same mRNA vaccine brand for all their vaccinations experienced fewer adverse reactions following the booster dose than they did after their second dose of mRNA vaccine, with 92% of reported reactions not considered serious?3

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References

  1. Covid-19 vaccine booster shots. Feb 2, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html#:~:text=It%20depends.,after%20the%20J%26J%2FJanssen%20vaccine. Accessed Feb 24, 2022
  2. Waning 2-dose and 3-dose effectiveness of mRNA vaccines against Covid-19-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance-VISION network, 110 states, August 2021-Jan 2022. Feb 18, 2022 https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm#T1_down. Accessed Feb 24, 2022.
  3. New CDC studies: Covid-19 boosters remains safe, continue to offer high levels of protection against severe disease over time and during Omicron and delta waves. Feb 11, 2022. https://www.cdc.gov/media/releases/2022/s0211-covid-19-boosters.html. Accessed Feb 24, 2022

 

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!

Should healthy adults receive a Covid vaccine booster shot and why?

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

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

Yes! According to the Centers for Disease Control and Prevention (CDC) of the U.S.,1 persons who are “moderately or severely immunocompromised” and have received 3 doses of an mRNA vaccine (either Pfizer [12+ years old) or Moderna (18+ years old]) should receive a 4th dose (“booster”) at least 3 months after the 3rd dose.  Similarly, those who initially received a J&J vaccine followed by one of the aforementioned mRNA vaccines and are at least 2 months from the 2nd dose should also receive a 3rd dose (booster. 

The following are considered moderately or severely immunocompromised conditions by CDC: 

  • Active cancer treatment for tumors or cancers of the blood
  • Organ transplant with immunosuppressants on board
  • Stem cell transplant within the last 2 years or taking immunosuppressants
  • Moderate or severe primary immunodeficiency (eg, DiGeorge or Wiskott-Aldrich syndromes)
  • Advanced or untreated HIV infection
  • Active treatment with high-dose corticosteroids or other immunosuppressants

A published study2 of Covid-19-associated emergency department (ED) and urgent care (UC) encounters and hospitalization among adults during a period including Omicron variant predominance in 10 states found vaccine effectiveness for ED/UC visits dropping to 66% and for hospitalization to 78% by the 4th month after a 3rd dose (vs 87% and 91%, respectively during the 2 months after a 3rd dose).  This study did not distinguish immunocompromised from non-immunocompromised persons, however.  More data on the vaccine effectiveness in non-immunocompromised persons at high risk of Covid-19 related complications would be welcome.

Bonus Pearl: Did you know that of American adults who are fully vaccinated against Covid-19, only about 30% have received an additional Covid vaccine dose beyond the primary series ? 3 

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References

  1. Covid-19 vaccines for moderately or severely immunocompromised people (Updated Feb 17, 2022). Accessed Feb 21, 2022.  https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html?s_cid=10483:immunocompromised%20and%20covid%20vaccine:sem.ga:p:RG:GM:gen:PTN:FY21
  2. Waning 2-doe and 3-dose effectiveness of mRNA vaccines against Covid-10-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance—Vision Network, 10 states, August 2021-January 2022. MMWR 2022; 71:255-63. https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_w
  3. Hubler S, Harman A. As Cov id surges, experts say U.S. booster effort is falling behind. NY Times, December 18, 2021. https://www.nytimes.com/2021/12/18/us/omicron-booster-shots-americans.html

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 middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

My elderly hospitalized patient with pneumonia has developed hypoglycemia within days of initiating piperacillin/tazobactam (Zosyn). Is there a connection between piperacillin/tazobactam and hypoglycemia?

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

Hypoglycemia is a rare (<1%) reported side effect of piperacillin/tazobactam (P/T) [1].  While the exact mechanism is unclear, hypoglycemia in this setting may be related to the adverse impact of P/T on renal function or possibly competitive inhibition of renal organic anion transporter 3 (OAT3).

The association of P/T with acute kidney injury (AKI) is well known. In a retrospective cohort analysis of 11,650 patients, P/T was associated with AKI in 7.8% of patients [2]. Of interest, compared to other antibiotics, P/T has also been shown to delay renal recovery in critically ill patients [3].  Decline in renal function may in turn reduce clearance of insulin and lead to hypoglycemia, particularly in patients who already have risk factors for hypoglycemia, such as malnutrition [4]. This is not surprising because renal clearance accounts for 25% of insulin clearance (rest is hepatic).  

Another plausible mechanism is the impact of P/T on glucose metabolism through competitive inhibition of OAT3 [5]. OAT3 is important in reabsorption of gluconeogenic precursors as well as excretion of uremic metabolites [6], which may further dysregulate hepatic gluconeogenesis and precipitate hypoglycemia. Fascinating!

Bonus pearl: Did you know that elderly patients may be at risk of reactive (post-prandial) hypoglycemia particularly in the setting of pre-diabetes or diabetes due to loss of coordination between glucose load and insulin secretion [7]? 

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Contributed by Michael Nance, MD, PhD, Department of Medicine, Mercy Hospital-St. Louis, St. Louis, Missouri

References:

  1. Wyeth Pharmaceutical Inc. Zosyn (piperacillin/tazobactam) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050684s88s89s90_050750s37s38s39lbl.pdf. Revised May 2017. Accessed January 16, 2021.
  2. Rutter WC, Burgess DR, Talbert JC, Burgess DS. Acute kidney injury in patients treated with vancomycin and piperacillin-tazobactam: A retrospective cohort analysis. J Hosp Med. 2017 Feb;12(2):77-82. doi: 10.12788/jhm.2684. PMID: 28182801; PMCID: PMC5573255. https://pubmed.ncbi.nlm.nih.gov/28182801/
  3. Jensen JS, Hein L, Lundgren B, et al. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial. BMJ Open 2012;2:doi: 10.1136/bmjopen-2011-000635  https://bmjopen.bmj.com/content/2/2/e000635
  4. Leibovitz E, Adler H, Giryes S, Ditch M, Burg NF, Boaz M. Malnutrition risk is associated with hypoglycemia among general population admitted to internal medicine units. Results from the MENU study. Eur J Clin Nutr. 2018 Jun;72(6):888-893. doi: 10.1038/s41430-018-0143-9. Epub 2018 Mar 27. PMID: 29588529. https://pubmed.ncbi.nlm.nih.gov/29588529/
  5. Wen S, Wang C, Duan Y, Huo X, Meng Q, Liu Z, Yang S, Zhu Y, Sun H, Ma X, Yang S, Liu K. OAT1 and OAT3 also mediate the drug-drug interaction between piperacillin and tazobactam. Int J Pharm. 2018 Feb 15;537(1-2):172-182. doi: 10.1016/j.ijpharm.2017.12.037. Epub 2017 Dec 23. PMID: 29277663. https://pubmed.ncbi.nlm.nih.gov/29277663/
  6. Wu, W., Bush, K.T. & Nigam, S.K. Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivoHandling of Uremic Toxins and Solutes. Sci Rep 7, 4939 (2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504054/
  7. Tamura Y, Araki A, Chiba Y, Horiuchi T, Mori S, Hosoi T. Postprandial reactive hypoglycemia in an oldest-old patient effectively treated with low-dose acarbose. Endocr J. 2006 Dec;53(6):767-71. doi: 10.1507/endocrj.k05-140. Epub 2006 Sep 12. PMID: 16966825. https://pubmed.ncbi.nlm.nih.gov/16966825/ 

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 elderly hospitalized patient with pneumonia has developed hypoglycemia within days of initiating piperacillin/tazobactam (Zosyn). Is there a connection between piperacillin/tazobactam and hypoglycemia?

Is there a connection between eosinophils and sickle cell anemia?

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

Patients with sickle cell anemia (SCA) frequently (~55%) demonstrate absolute eosinophil count (AEC) (>450 cells/uL) during non-crisis steady state without significant change during sickle cell crisis [1-4]. Although the exact mechanism for this finding is not clear, it may be related to elevated plasma levels of circulating factors such as eotaxin, IL-5, and GM-CSF in SCA [2,3].

Cumulative data from 3 independent cross-sectional studies involving 131 SCA patients reported a mean AEC of ~498 cells/u (range 490-504 cells/uL) when not in crisis [2,3,6]. Surprisingly, two additional studies evaluating 200 patients did not observe a significant difference in AEC between steady- and crisis-states [1,4].

The significance of elevated AEC in patients with SCA is unclear. Of interest, several studies of eosinophils isolated from patients with SCA have demonstrated increased eosinophil adhesion to blood vessels, degranulation, and reactive oxygen species production compared to healthy controls [5,6]. In another study, hydroxyurea was shown to reduce eosinophil adhesion and degranulation [2].

While it is unknown whether eosinophils directly contribute to the development of vaso-occlusive crisis, these studies suggest eosinophils may be an important therapeutic target in SCA. 

Bonus pearl: Did you know that low eosinophil count may help predict infection in SCA patients? A retrospective study of SCA patients with and without infection showed that relative eosinopenia (0.025 compared to 0.2 x 109 cells/L) was highly sensitive (100%) and specific (93.3%) for infection [7].

Contributed by Michael Nance MD, PhD, Department of Medicine, Mercy Hospital-St. Louis, St. Louis, Missouri

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References:

  1. Ekeke GI. Sickle cell disease: some haematological changes in steady state and crisis. Biomed Biochem Acta 1987; 46:S197-S201. https://pubmed.ncbi.nlm.nih.gov/3593298/
  2. Pallis FR, Nicola Conran, Kleber Yotsumoto Fertrin, Sara T. Olalla-Saad, Fernando Ferreira Costa, Carla Fernanda Franco-Penteado; Altered Functional Properties of Eosinophils In Sickle Cell Anemia and Effects of Hydroxyurea Therapy. Blood 2010; 116 (21): 2656. https://doi.org/10.1182/blood.V116.21.2656.2656
  3. Conran N, Saad ST, Costa FF, Ikuta T. Leukocyte numbers correlate with plasma levels of granulocyte-macrophage colony-stimulating factor in sickle cell disease. Ann Hematol. 2007; 86(4):255-261. https://pubmed.ncbi.nlm.nih.gov/17205286/
  4. Klouda T, Raybagkar D, Bernstein B, Apollonsky N, “Changes in Blood Profile from Steady State in Patients with Sickle Cell Anemia Admitted for Vaso-occlusive Crisis and Acute Chest Syndrome”, Advances in Hematology, vol. 2020, Article ID 3656717, 5 pages, 2020. https://doi.org/10.1155/2020/3656717
  5. Canalli AA, Conran N, Fattori A, Saad ST, Costa FF. Increased adhesive properties of eosinophils in sickle cell disease. Exp Hematol. 2004; 32(8):728-734. https://pubmed.ncbi.nlm.nih.gov/15308324/
  6. Pallis FR, Conran N, Fertrin KY, Olalla Saad ST, Costa FF, Franco-Penteado CF. Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients. Br J Haematol. 2014; 164(2):286-295. https://pubmed.ncbi.nlm.nih.gov/24383847/
  7. Ahmed, SG and Uraka, A. Eosinopenia as a marker of infection in patients with sickle cell anemia: A preliminary report. Int. J. Biomed. Health Sci. 2010. 6(1):57-61. http://www.ojs.klobexjournals.com/index.php/ijbhs/article/viewFile/671/741

 

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 there a connection between eosinophils and sickle cell anemia?

Should patients with prior Covid receive Covid vaccine?

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

Yes, as recommended by the CDC.  The weight of the evidence to date suggests that previously infected individuals should receive Covid vaccine to minimize their risk of acquiring Covid again for many reasons, including the following:

First, depending on the population and the variant of SARS-CoV-2 (the agent of Covid) studied, a significant proportion of infected individuals— from 5% to >35% based on some studies— fail to produce antibodies against SARS-CoV-2.1 In 1 study, lack of antibody production was associated with younger age, lower viral load and a trend toward milder symptoms.1

Second, the body of the evidence for infection-induced immunity is much more limited with less consistent findings than that for vaccine-induced immunity.2

Third, vaccination against Covid has been shown to enhance the immune response and reduce the risk of infection even in those with prior Covid.2 In fact, 1 study reported that the risk of reinfection is more than twice among those who were previously infected but not vaccinated compared to those who got vaccinated after having Covid.3  In another study, the risk of infection in adults was more than 5 times higher in unvaccinated but previously infected individuals compared to the vaccinated person who had not had an infection previously.4

Some authors5 who oppose routine vaccination of individuals previously infected with Covid have invoked a recent CDC study6 which showed that when Delta was the predominant strain, persons with prior Covid had lower rates of infection than persons who were vaccinated alone.  However, this study was performed when booster doses of Covid vaccine were not yet available to most people and before Omicron became the predominant variant. 

Bonus Pearl: Did you know that following Covid infection, neutralizing antibodies  have a biphasic decline with an initial half-life of 2-3 months followed by a slower decline thereafter?2

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References

  1. Liu W, Russell RM, Bibollet-Ruche F, et al. Predictors of nonseroconversion after SARS-CoV-2 infection. Emerg Infect Dis 2021;27:2454-58. Predictors of Nonseroconversion after SARS-CoV-2 Infection – Volume 27, Number 9—September 2021 – Emerging Infectious Diseases journal – CDC
  2. Science brief: SARS-CoV-2 infection-induced and vaccine-induced immunity. October 29, 2021. Science Brief: SARS-CoV-2 Infection-induced and Vaccine-induced Immunity | CDC
  3. Cavanaugh AM, Spicer KB, et al. Reduced risk of reinfection with SARS-CoV-2 after Covid-9 vaccination-Kentucky, may-June 2021. MMWR 2021;70:1081-83. Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination – Kentucky, May-June 2021 – PubMed (nih.gov)
  4. Laboratory-confirmed Covid-19 among adults hospitalized with Covid-19-like illness with infection-induced or mRNA vaccine-induced SARS-CoV-2 immunity—Nine states, January-September 2021. MMWR 2021;70:1539-44. Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19–Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-CoV-2 Immunity — Nine States, January–September 2021 | MMWR (cdc.gov)
  5. Makary M. The high cost of disparaging natural immunity to Covid. Wall Street Journal. January 26, 2022. The High Cost of Disparaging Natural Immunity to Covid – WSJ
  6. Leon Tm, Drabawila V, Nelson L, et al. Covid-19 cases and hospitalizations by Covid-19 vaccination status and previous Covid-19 diagnosis-California and New York, May -November 2021.  MMWR 2022;71:125-31 COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis — California and New York, May–November 2021 (cdc.gov)

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!

Should patients with prior Covid receive Covid vaccine?

Is lung ultrasound useful in evaluating patients with dyspnea?

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

Yes! Increasingly, lung ultrasound (particularly point-of-care ultrasound-POCUS) is performed at bedside to help explain the cause of dyspnea.  Here are some tips.

First, obtain images by placing the transducer in the intercostal space (usually 3 regions/hemithorax) with the orientation marker pointing cephalad. 1,2  Now look at the pleural line, the horizontal hyperechoic structure between 2 ribs  (Figure 1). To and fro movement of the pleural line reflects apposition of the visceral and parietal pleura and is a normal finding (“lung sliding”).  Then look for additional horizontal hyperechoic lines visualized deep to the pleural line (“A-lines”) which are reverberation artifacts, reflecting air below the pleura (Clip/Figure 1).2 

You should also look for vertical laser like hyperechoic artifacts that arise from the pleural line and extend to the bottom of the display which may represent  “comet tails” or “B-lines” (Clip/Figure 2).1,3,4 These are reverberation artifacts created by the acoustic impedance difference between widened, fluid filled septa and air-filled alveoli.3,5  Three or more B-lines within a single intercostal space is considered pathological.4

One of the practical uses of lung ultrasound is in the evaluation of dyspnea in a patient with Chronic Obstructive Pulmonary Disease (COPD).6 The presence of lung sliding and bilateral A-lines in the absence of B-lines can help rule out pneumothorax, pneumonia and pulmonary edema and steer you toward other diagnoses (eg, COPD exacerbation) as cause of dyspnea.

You can even take it a step further. Focal unilateral B-lines suggest possible pneumonia while diffuse bilateral B-lines (interstitial syndrome) would be more consistent with pulmonary edema.

As usual, the patient’s history, physical examination and available laboratory data must be taken into consideration when interpreting lung ultrasound findings.2,4

Contributed by Woo Moon, D.O., Department of Medicine, Mercy-St. Louis, St. Louis, Missouri

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Figure 1 

 

 

Clip 1

 

 

Figure 2

 

Clip 2

 

References

  1. Lichtenstein DA. Lung ultrasound in the critically ill. Ann Intensive Care 2014;4(1): https://pubmed.ncbi.nlm.nih.gov/24401163/&nbsp;
  2. Soni MD MS NJ, Arntfield MD FRCPC R, Kory MD MPA P. Point of Care Ultrasound. 2nd ed. St. Louis, MO: Elsevier; 2019.
  3. Lichtenstein DA, Mezière GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol. Chest 2008;134(1):117–25. https://pubmed.ncbi.nlm.nih.gov/18403664/&nbsp;
  4. Volpicelli G, Elbarbary M, Blaivas M, et al. International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med 2012;38(4):577–91. https://pubmed.ncbi.nlm.nih.gov/22392031/&nbsp;
  5. Lichtenstein D, Mézière G, Biderman P, Gepner A, Barré O. The comet-tail artifact. An ultrasound sign of alveolar-interstitial syndrome. Am J Respir Crit Care Med 1997;156(5):1640–6. https://pubmed.ncbi.nlm.nih.gov/9372688/
  6. Qaseem A, Etxeandia-Ikobaltzeta I, Mustafa RA, et al. Appropriate Use of Point-of-Care Ultrasonography in Patients With Acute Dyspnea in Emergency Department or Inpatient Settings: A Clinical Guideline From the American College of Physicians. Ann Intern Med 2021;174(7):985–93. https://www.acpjournals.org/doi/10.7326/m20-7844&nbsp;

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 lung ultrasound useful in evaluating patients with dyspnea?

What’s the connection between traumatic rib fractures and pulmonary embolism?

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

Pulmonary embolism (PE) may be a complication of traumatic rib fractures but not necessarily associated with the number of ribs involved.1,2 PE or venous thromboembolism (VTE) is likely related at least in part to the hypercoagulable state that often follows traumatic injury.3

Diagnosis of PE may be challenging because chest pain and shortness of breath attributed to rib fractures can also be a manifestation of PE. Nevertheless, we should consider PE in any patient with chest pain following rib fracture who has hypoxemia or has other risk factors for this complication (eg, obesity, hospitalization, malignancy, history of prior VTE, postoperative state, estrogen use, heart failure, COPD).4 In a retrospective study of 548 patients with traumatic rib fracture, 1.1% were diagnosed with PE.1 The true incidence of PE in patients with rib fracture is unclear, however.

Hypercoagulability following rib fracture likely contributes to the risk of PE. A prospective cohort study of patients admitted to ICU following trauma (97% blunt), found a high prevalence of hypercoagulability (62% on day 1 and 26% on day 4) based on thrombelastography analysis. Women were more hypercoagulable than men early after injury.  Among those classified as hypercoagulable, 10% developed VTE.3

Bonus Pearl: Did you know that in patients with blunt chest trauma, age >65 y and 3 or more rib fractures are associated with increased risk of mortality?

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References

  1. Sirmali M, Turut H, Topcu S, et al. A comprehensive analysis of traumatic rib fractures: morbidity, mortality and management. Eur J Cardio-Thoracic Surg 2003;24:133-138.
  2. Flagel BT, Luchette FA, Reed R, et al. Half-a-dozen ribs: The breakpoint for mortality. Surgery 2005;138:717-25.
  3. Schreiber MA, Differding J, Thorborg P, et al. Hypercoagulability is most prevalent early after injury and in female patients. J Trauma 2005;58:475-81.
  4. Belohlavek J, Vytrych V, Linhart A. Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism. Exp Clin Cardiol 2013;18:129-138.
  5. Battle CE, Hutchings H, Evans PA. Risk factors that predict mortality in patients with blunt chest wall trauma: A systematic review and meta-analysis. Injury 2012;43:8-17. 

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 connection between traumatic rib fractures and pulmonary embolism?

Why is Paxlovid (nirmatrelvir/ritonavir) a promising new drug in our fight against Covid-19?

FA Manian MD, MPH, , Leave a comment

Based on the manufacturer’s (Pfizer’s) report, there are several reasons why Paxlovid may be a promising drug:1

  • It’s the first oral drug approved by the FDA for Emergency Use Authorization (EUA)
  • It reduces risk of hospitalization or death by ~ 90% (when taken within 3-5 days of symptom onset) in patients at high risk of complications from Covid-19
  • It reduces viral load at day 5 of treatment by 10-fold compared to placebo, theoretically reducing infectivity at least in household settings 2
  • Serious adverse events were comparable to placebo; possible side effects include liver disease, diarrhea, altered sense of taste, hypertension and muscle aches
  • Nirmatrelvir component of Paxlovid has been found to be active against a variety of SARS-CoV-2 variants of concern such as alpha, beta, delta as well as the newer omicron variant. This finding is in contrast to significantly reduced or loss of neutralizing activity of many commercially-available monoclonal antibody products against the omicron variant (eg, Casirivimab/Imdevimab-REGEN-COV, Bamlanivimab/Etesevimab, but not Sotrovimab)  designed to reduce serious Covid-19 complications in mild to moderate disease. 3-4

Few caveats to keep in mind when prescribing Paxlovid at this time:

  • It’s only approved for adults and children 12 years of age or older weighing at least 88 lbs (40kg) who test positive for SARS-CoV-2
  • Patients should be at high risk for progression to severe Covid-19 such as hospitalization or death
  • Per manufacturer (Pfizer), Paxlovid should not be taken if a patient is on certain medications due to the possibility of adverse drug interactions. The list includes colchicine, lovastatin, simvastatin, sildenafil for pulmonary arterial hypertension, some anti-epileptics (eg, carbamazepine, phenytoin), rifampin and St. John’s Wort.
  • There is no experience with treating pregnant women or breastfeeding mothers.
  • Pfizer recommends effective barrier contraception or refraining from sexual activity while taking Paxlovid

Paxlovid comes in a box of blister packs containing 5 days’ worth of medications (two 150 mg tablets of nirmatrelvir plus one 100 mg tablet of ritonavir to be taken 2x/day).  

Bonus Pearl: Another preliminary study of Paxlovid, this time including unvaccinated adults at low risk of hospitalization or death, has found a 70% reduction in hospitalization and no death compared to placebo with marginal statistical significance (P=0.051) but still with a 10-fold drop in viral load. 1

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References

  1. Pfizer announces additional phase 2/3 study results confirming robust efficacy of novel COVID-19 oral antiviral treatment candidate in reducing risk of hospitalization or death. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-additional-phase-23-study-results . Accessed Dec 23, 2021.
  2. Marc A, kerioui M, Blanquart F, et. al. Quantifying the relationship between SARS-CoV-2 viral load and infectiousness. eLife 2021;10:e69302. https://elifesciences.org/articles/69302#:~:text=Based%20on%20the%20current%20knowledge,24%25%20to%2058%25%20in%20household  
  3. Aggarwal A, Stell AO, Walker G, et al. SARS-CoV-2 Omicron:evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. MedRxiv 2021. Doi:https://doi.org/10.1101/2021.12.14.21267772. https://www.medrxiv.org/content/10.1101/2021.12.14.21267772v1
  4. Planas D, Saunders N, Maes P, et al. Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization. MedRxiv 2021. https://www.biorxiv.org/content/10.1101/2021.12.14.472630v1

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!

Why is Paxlovid (nirmatrelvir/ritonavir) a promising new drug in our fight against Covid-19?

Can I have some tips on how to improve my PowerPoint presentation?

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

Effective or “high value” PowerPoint presentations take some planning and work. Here are some tips (by no means comprehensive) on how you can improve your PowerPoint presentation,1-4 divided into 4 stages:

Stage I: Planning for your talk

    • “Know your stuff”
    • Prioritize the main objectives of your talk given time  constraints ie, “What would you like your audience to really take away from your talk?”
    • Accept the fact that you will not be able to cover all that you know about the topic during the allotted time
    • Think about how you might keep your audience engaged throughout your talk as you introduce topics and concepts!

Stage II: Preparing your slides

  1. General rules
    • Keep them simple (“Less is more”)
      • Minimize number of slides eg, average no more than 1 slide/min
      • Minimize number of concepts/slide eg,1/slide
      • Minimize clutter 
    • Avoid “apologetic” slides ie, if not easily readable or visible or “too busy”, don’t use them!
    • Practice, practice, practice and edit as needed
  2.  Text
    • Minimize number of words/slide eg, 6×6 rule, maximum 6 words/line, 6 lines/slide
    • Use easily readable font types and sizes
      1. Minimum 24 for small rooms
      2. Minimum 36 for larger rooms
      3. If not readable 10 feet away from monitor, don’t include
    • Check spelling!
    • Choose high contrast colors between background and text eg, black text on white, yellow on dark blue background, not red on green
  3. Tables
    • Avoid reproduction of large tables with tons of data that cannot be read or can easily overwhelm the audience
    • If you use large tables, zero in on a particular section and display a magnified version of that section so that the audience can follow along with you

Stage III: Presenting your talk

  • Remember, you are the presenter, not PowerPoint
  • Engage the audience from the beginning to the end
    • Beginning: Use a “hook” ie, why should the audience be interested in your talk?
    • During
      • Maintain eye contact with the audience
      • Be dynamic/animate
      • Use speech intonations as if you are having a conversation with the audience
      • Do not read slides word-by-word
    • End: Highlight your take-home points eg, “if you don’t remember anything else…”

Stage IV: Post-Presentation

  • Ask for feedback from colleagues, audience, coordinators, etc… 
  • Self-reflect ie, what went well, what didn’t go so well?
  • Apply lessons learned to your next PowerPoint presentation!

Five take-home points for this pearl

  • Less is more, keep your presentation clear and simple
  • Time is limited; prioritize your message
  • Keep your audience engaged throughout the talk
  • Conclude with take-home points
  • Practice, practice, practice

Bonus Pearl: Did you know that people generally remember 20% of what they hear, 30% of what they see, and 50% of what they see and hear? 2

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References

  1. Collins J, et al. Evaluation of speakers at a national radiology continuing medical education course. Med Educ Online 2002;7:17 https://pubmed.ncbi.nlm.nih.gov/28253766/ 
  2. Collins J. Education techniques for lifelong learning. RadioGraphics 2004;24:1177-83. https://pubmed.ncbi.nlm.nih.gov/15256637/ 
  3. Harolds JA. Tips for giving a memorable presentation, Part IV. Using and composing PowerPoint slides. Current Nuclear Medicine 2012;37:977-80. https://pubmed.ncbi.nlm.nih.gov/22899205/ 
  4. Grech V. WASP (write a scientific paper):Optimization of PowerPoint presentations and skills. Early Human Development 2018;125:53-56.https://pubmed.ncbi.nlm.nih.gov/29929910/ 

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!

Can I have some tips on how to improve my PowerPoint presentation?