PTCE would like to acknowledge Genentech, a member of The Roche Group for their generous support of pharmacist education. 

Influenza treatment with antivirals was presented during a virtual symposium held in conjunction with the first virtual ASHP Midyear Clinical Meeting and Exhibition. Two speakers, Elias B. Chahine, PharmD, FCCP, FASCP, FFSHP, BCPS, BCIDP, and Allana J. Sucher, PharmD, BCPS, BCIDP, presented an in-depth overview of influenza in a satellite symposium titled “Chemoprophylaxis and Treatment of the Influenza Virus: The Expanding Role of Novel Antivirals in High-Risk Patient Populations.” The session focused on available antivirals for its treatment, recommendations for high-risk patients, and the role of the pharmacist.

Dr Chahine began the presentation by reviewing the annual impact of the influenza illness. He went on to examine the etiology, pathophysiology, modes of transmission, and clinical presentation of influenza. He also warned of the complications that can occur as a result of infection, especially in high-risk patients. Therefore, the goals for treatment are to attenuate signs and symptoms, prevent complications, decrease absenteeism, and prevent the spread of infection.

Dr Chahine discussed that patients with influenza who are indicated to receive antivirals are those who are hospitalized, outpatient with severe or progressive disease, or at high risk of complications. Special populations, such as patients younger than 2 years and those older than 65 years, pregnant women, or women postpartum of 2 weeks or less, are also considered high risk and should receive antiviral treatment. Dr Chahine then reviewed the mechanisms of action, activity, and indications of commonly used antivirals. He concluded his portion of the presentation with a case example to reinforce information learned.

At this point, Dr Sucher took over to further discuss antiviral treatment recommendations. Antivirals are to be used in indicated patients as soon as possible, ideally within 48 hours for maximum efficacy, and not to be held for laboratory confirmation of infection. The CDC and Infectious Diseases Society of America recommend treatment regardless of illness duration for hospitalized patients or outpatients with severe, complicated, or progressive illness. Dr Sucher discussed recommended dosing and efficacy data for antivirals indicated for treatment of adults and children with acute, uncomplicated influenza.

She then covered recent studies for influenza treatment, including the CAPSTONE-2 trial, which demonstrated the efficacy of baloxavir in high-risk patients. Baloxavir showed faster improvement of influenza symptoms and a reduction in the risk of complications when compared with placebo and similar efficacy to oseltamivir. The authors also found that baloxavir significantly reduced the time to improvement of symptoms for patients infected with influenza B as compared to oseltamivir. Furthermore, the miniSTONE-2 trial found similar efficacy to oseltamivir in terms of alleviation of signs and symptoms and incidence of adverse effects in healthy children between 1 and 12 years of age with acute, uncomplicated influenza.

Dr Sucher continued with a discussion of the recommendations for chemoprophylaxis and highlighted that annual vaccination remains the primary tool for influenza prevention. In the community, post-exposure chemoprophylaxis is not routinely recommended but can be considered for use in asymptomatic adults and children 3 months and older who are at very high risk of developing influenza complications as soon as possible (and within 48 hours) after household exposure to influenza. Dr Sucher discussed the use of oseltamivir and zanamivir for chemoprophylaxis. She presented data from the BLOCKSTONE trial, which led to the recent approval of baloxavir for chemoprophylaxis in adults and children aged 12 years and older.

Dr Sucher concluded by emphasizing the role of a pharmacist in the treatment and prevention of influenza through providing influenza immunization, identifying high-risk patients, recommending treatment, recognizing the role of prophylaxis, and counseling on antiviral agents. Antivirals continue to be underutilized in both hospitalized patients and outpatients with influenza, and pharmacists can help facilitate their early and appropriate use in these settings.

Articles

Health-System Edition

Influenza treatment with antivirals was presented during a virtual symposium held in conjunction with the first virtual ASHP Midyear Clinical Meeting and Exhibition.

Utilization of Antivirals to Combat Influenza

PTCE would like to acknowledge  Merck Shartp & Dohme Corp for their generous support of pharmacist education. 

Updates in heart failure (HF) management were presented by Ty J. Gluckman, MD, and Toby C. Trujillo, PharmD, FCCP, FAHA, BCPSAQ Cardiology, in a satellite symposium titled “Managing Preserved and Reduced Ejection Fraction in Heart Failure: An Evidence-Based Case Review” at ASHP’s Virtual Midyear Exhibition and Clinical Meeting.

Dr Gluckman began the presentation with an in-depth overview of HF, its different classifications, prevalence, causes, pathophysiology, and clinical presentation. He went on to discuss the current guideline recommendations for heart failure with reduced ejection fraction (HFrEF). The established classes of medications for guideline-directed medical therapy (GDMT) were reviewed, including indications, contraindications, target doses, and monitoring parameters. Dr Trujillo added to the discussion in this section by introducing a patient case and engaging the audience in a conversation about strategies to optimize the patient’s GDMT.

Dr Gluckman continued the presentation by introducing several newer agents that have shown benefit in certain patients with HFrEF. The first agents, sodium-glucose cotransporter-2 (SGLT2) inhibitors, were initially approved for the management of diabetes by preventing the reabsorption of glucose. However, cardiovascular benefits were also observed, such as reduced plasma volume, lower cardiac preload, reduction of blood pressure, weight loss, and improvement of endothelial function. These advantages were supported by decreases in hospitalizations due to worsening heart failure or cardiovascular (CV) death within the DAPA-HF trial for dapagliflozin and EMPEROR-Reduced trial for empagliflozin.

Secondly, vericiguat, whose novel mechanism of action in HF is that of a soluble guanylate cyclase stimulator, has emerging study data suggesting that it can prevent and potentially reverse left ventricular hypertrophy and fibrosis and even reduce ventricular afterload through both systemic and pulmonary vasodilation. Results from the VICTORIA trial were presented, which demonstrated that vericiguat significantly reduced CV death or first hospitalization for HF.

Lastly, clinical trial data for omecamtiv mecarbil, a selective cardiac myosin activator, were presented. Omecamtiv mecarbil has the potential to increase the energetic efficiency of myocardial contraction. The GALACTIC-HF trial was presented which demonstrated that omecamtiv mecarbil significantly reduced CV death or a first heart failure event. Dr Trujillo discussed dosing, monitoring, and counseling considerations for these newer agents and ended this section with a second patient case to allow the audience to further engage in discussion.

Dr Gluckman transitioned to discuss heart failure with preserved ejection fraction (HFpEF). He described the pathophysiology and current guideline recommendations, highlighting that treatment options for HFpEF are limited. This continues to remain an area of unmet need as there are not many effective treatment agents available for HFpEF. Dr Gluckman discussed agents that are being studied for their utility in HFpEF.

Dr Trujillo continued the conversation by emphasizing the important role a pharmacist can play in the management of HF. Pharmacists can help to identify opportunities to intensify medication regimens and titrate medications to target doses. He shared evidence-based outcomes data which reinforced that these activities have a direct impact on patient outcomes. The program concluded with one last case discussion, but this time, for a patient with HFpEF. He concluded by reaffirming that HF therapies are underutilized—and often underdosed&mdash;and therefore remain an area of opportunity for pharmacists to intervene. Pharmacists can remain up-to-date on emerging therapies and assist in incorporating them into practice as they are approved. 

Updates in heart failure management were presented in a satellite symposium at ASHP’s Virtual Midyear Exhibition and Clinical Meeting.

Opportunities to Improve the Management of Patients With Heart Failure

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, several antivirals and other medications with antiviral properties have been explored as potential treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Information about the efficacy and safety of medications used to treat COVID-19 continues to evolve, which has helped provide clarity on the most optimized therapy and establish current guideline recommendations. Many of the agents used early in the pandemic, such as hydroxychloroquine or lopinavir/ritonavir, have been largely abandoned due to lack of efficacy data and/or excessive risk for toxicities. The medical community has identified an evidence-based and guideline-supported treatment approach for patients with COVID-19 that continues to evolve based on rapidly emerging data.

Both the Infectious Diseases Society of America (IDSA) and the National Institutes of Health (NIH) published practice guidelines that have undergone several updates. These guidelines recommend the use of remdesivir (Veklury) as first-line antiviral therapy in patients hospitalized with severe disease.

 Recommended remdesivir dosing for adults is a 200-mg loading dose, followed by 100 mg every 24 hours, for a total of 5 days (10 days may be considered for patients with slow response). Dexamethasone, a common corticosteroid, is recommended to be given in combination with remdesivir for patients requiring oxygen supplementation at a daily dose of 6 mg for 10 days. Both treatments can be discontinued if the patient is well enough for discharge prior to completion of the intended course.

The United States Food and Drug Administration (FDA) approved remdesivir on October 22, 2020, for the treatment of COVID-19 in hospitalized patients 12 years or older and weighing 40 kg or more. For younger pediatric patients, remdesivir is still available under emergency use authorization (EUA). Efficacy data from several clinical trials helped support FDA approval and current guideline recommendations. The ACTT-1 trial (NCT04280705) results showed that remdesivir shortened recovery time by 5 days, and in a subgroup analysis the results showed a mortality benefit in patients requiring supplemental oxygen but not mechanical ventilation.

Conversely, recent preliminary data from the SOLIDARITY trial found that remdesivir showed no benefit in mortality, need for mechanical ventilation, or time to hospital discharge compared with standard of care.

 A peer-reviewed publication of the SOLIDARITY trial is pending. Another trial (NCT04292730) evaluating the use of remdesivir in the setting of moderate COVID-19 (patients with pulmonary infiltrates on chest imaging and oxygen saturation greater than 94%) concluded that 5 days of remdesivir was associated with higher odds of a better clinical status compared with standard of care. However, the clinical implications of this are unclear.

 Finally, the guidelinerecommended duration for remdesivir of 5 days is based on the SIMPLE-Severe Trial (NCT04292899), which determined that a 5-day course offered similar clinical benefit to a 10-day course, based on day 14 clinical status.

Although remdesivir has not consistently demonstrated a mortality benefit, the use of dexamethasone and other corticosteroids has shown a reduction in mortality among patients with COVID-19 requiring oxygen supplementation. Initial efficacy data for corticosteroids in COVID-19 was first reported from the RECOVERY trial (NCT04381936), in which patients receiving dexamethasone had a lower incidence of death compared with standard of care if on mechanical ventilation or receiving oxygen supplementation without mechanical ventilation.

 Following this study, several other trials and data from a meta-analysis have been published supporting the role of corticosteroids in the management of COVID-19 among patients requiring mechanical ventilation or oxygen supplementation.

The FDA recently granted emergency use authorization approval to baricitinib, a nonselective Janus kinase inhibitor that prevents dysregulated production of proinflammatory cytokines, to be given in combination with remdesivir in hospitalized patients 2 years and older requiring extracorporeal membrane oxygenation, mechanical ventilation, or supplemental oxygen.

 Data from phase III clinical trial ACTT-2 (NCT04401579) showed that the combination of baricitinib and remdesivir was associated with a reduction in median time to recovery (8 days) compared with remdesivir alone (7 days). Patients receiving baricitinib with remdesivir had a lower mortality rate (23% vs 28%) and were less likely to require invasive or noninvasive ventilation and more likely to have a better clinical status by day 15. The recommended dosing of baricitinib is 4 mg once daily for patients 9 years and older or 2 mg once daily for patients aged 2 to 8 years. However, dosage adjustments are required based on absolute lymphocyte count, absolute neutrophil count, hepatic function, and renal function. The recommended duration is 14 days or until hospital discharge. IDSA and NIH guidelines have not been updated yet to provide recommendations regarding the addition of baricitinib to remdesivir. Limited information is available on the use of baricitinib in combination with systemic corticosteroids for the management of COVID-19. Therefore, its role in therapy in the setting where patients are given dexamethasone is uncertain.

The FDA also recently granted EUA approval to 2 monoclonal antibody treatments: bamlanivimab and the combined antibody cocktail casirivimab with imdemivab.

 Both are recommended for nonhospitalized adult and pediatric patients 12 years and older weighting at least 40 kg who have mild to moderate COVID-19 and are at high risk for progressing to severe disease in the outpatient setting. Interim data from phase II clinical trials have shown that the use of these monoclonal antibodies was associated with reduced emergency department (ED) visits compared with a placebo.

 Among high-risk patients, bamlanivimab reduced ED visits and hospitalizations by 7%, and casirivimab/imdevimab reduced this outcome by 6%. Bamlanivimab is given as a single 700-mg intravenous (IV) dose and casirivimab/imdevimab as a single 2400-mg IV dose. Both should be administered within 10 days of COVID-19 symptom onset. IDSA and NIH guidelines have recommended against the use of monoclonal antibodies as the standard of care. However, note that if use is considered, the antibodies should be reserved for patients at the greatest risk for clinical progression or poor outcomes.

Other therapies still under investigation include antithrombotic therapy, convalescent plasma, and other immune modulators, such as anakinra, sarilumab (Kevzara), and tocilizumab. There are several ongoing clinical trials to further investigate the therapies’ role in the management of COVID-19. For some of these options, clinical data are conflicting and/or insufficient to determine their role in the management of COVID-19.

In the early days of the COVID-19 pandemic in the United States, treatment regimens with limited, if any, clinical data to support use were being implemented, and no evidence-based consensus guidelines were available to guide therapeutic decision-making. However, there is now more concrete guidance on the optimal treatment approach because more data are becoming available. Although COVID-19 treatment recommendations will continue to evolve, an unprecedented point has been reached where guidelines are updated in nearly real time to endorse best evidence-based medicine.

, is an infectious diseases clinical/ pharmacy specialist at the University of Chicago Medicine in Illinois.

National Institutes of Health.Coronavirus disease 2019 (COVID-19) treatment guidelines. Updated December 17, 2020. Accessed January 9, 20202021. https://www.covid19treatmentguidelines.nih.gov/

Bhimraj A, Morgan RL, Shumaker AH, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. 

. Published online: April 27, 2020. doi:10.1093/cid/ciaa478

Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—final report. 

. 2020. 2020;383(19):1813-1826.doi:10.1056/NEJMoa2007764

WHO Solidarity Trial Consortium, Pan H, Peto R, et al. Repurposed drugs for COVID-19—interim WHO SOLIDARITY trial results. 

Spinner CD, Gottlieb RL, Criner GJ, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. 

.2020;324(11):1048-1057. doi:10.1001/jama.2020.16349

Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe Covid-19. 

.2020;383(19):1827-1837. doi:10.1056/NEJMoa2015301

Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19—preliminary report. 

.Published online: July 17,2020. doi:10.1056/NEJMoa2021436

Edalatifard M, Akhtari M, Salehi M, et al. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J.2020;56(6):2002808. doi:10.1183/13993003.02808-2020

Sterne JAC, Murthy S, Diaz JV et al; WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: ameta-analysis. 

.2020;324(13):1330-1341. doi:10.1001/jama.2020.17023

Eli Lilly and CompanyFDA. Fact sheet for health care providers emergency use authorization (EUA) of Baricitinibbaricitinib. Eli Lilly and Company. Accessed November 28, 2020.https://www.fda.gov/media/143823/download

Fact sheet for health care providers emergency use authorization (EUA) of bamlanivimab. Eli Lilly and Company. Updated December 20, 2020. Accessed January 10, 2021. 11.http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf

12.Regeneron Pharmaceuticals, Inc. Fact sheet for health parecareproviders emergency use authorization (EUA) of casirivimab and imdevimab. Updated December 2020. AccessedJanuary 10, 20202021. https://www.regeneron.com/sites/default/files/treatment-covid19-eua-fact-sheet-for-hcp.pdf

Chen P, Nirula A, Heller B, et al. ; BLAZE-1 investigators.SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. 

.2020Published online October 28,2020. doi:10.1056/NEJMoa2029849

Guidelines, updated in nearly real time, recommend use of remdesivir, dexamethasone.

What Are the Latest COVID-19 Treatment Recommendations?

Among the many subtypes of leukemias in the United States, acute myeloid leukemia (AML) is the most commonly diagnosed form in adults and causes the highest number of deaths.

During 2020, the United States had an estimated 20,000 new patient cases of AML, with more than half of these resulting in death.2 Leukemia, a cancer of the blood and bone marrow, affects the function and production of blood cells.

 In AML, immature myeloid cells (myeloblasts) accumulate and are unable to mature into functioning platelets, red blood cells (erythrocytes), or white blood cells (neutrophils).

 Compared with other types of leukemias, AML occurs more frequently in older adults, with a median age at diagnosis of 67.

 Increasing age; exposure to benzene, chemotherapy, or radiation; family history; genetic mutations; male gender; and smoking are risk factors for developing AML.

 Because blood cells are not maturing, AML presents similarly to anemia, neutropenia, and thrombocytopenia (Figure 1

). Symptoms commonly include bleeding, fatigue infection, and pallor.

Evaluation for suspected AML initially involves assessment of medical history and a physical exam.

 Essential laboratory data include a blood sample with a complete blood count with differential, a peripheral blood smear, and a bone marrow biopsy.

 Based on these results, the presence of at least 20% of blast cells in peripheral blood or marrow generally confirms the diagnosis of acute leukemia, as defined by the World Health Organization (WHO) in 2016.

 Immunophenotyping and cytogenetic studies are used to confirm cell lineage, establish risk stratification, and classify subtypes.4 In accordance with the WHO classification system, AML is classified into 1 of 6 groups based on clinical features, genetics, immunophenotype, and morphology. Prognosis and treatment selection are increasingly determined by expression or absence of several key gene mutations (Figure 2.

AML treatment options mainly include chemotherapy, stem cell transplant, and targeted therapy (Figure 3

). AML was considered an oncologic emergency requiring treatment initiation as soon as possible upon diagnosis.

 However, new evidence suggests less of a correlation between time to treatment and prognosis than previously thought.

 As treatment is being targeted to patient-specific gene mutations, there may be benefit to first obtaining genetic and laboratory tests to initiate the most appropriate treatment.

Treatment of AML generally occurs in 2 phases: remission induction therapy and postremission (consolidation) therapy.

 Choice of treatment differs based on age and medical fitness of the patient.

 Healthy patients under age 60 often qualify for “intensive” therapy, whereas older patients who present with a combination of risk factors, such as multiple comorbidities, poor performance status (PS), and unfavorable cytogenetics, may better tolerate a less-intense regimen.

 PS in oncology is often assessed using the ECOG scale, which is the standard for quantifying the functional capacity of a patient and predicting chemotherapy tolerability.

The cornerstone of intensive induction therapy is a regimen of 7 days of continuously infused cytarabine, plus a 3-day course of an anthracycline called “7 + 3 induction therapy,” which results in a complete remission rate of about 65%.

 If remission is achieved, medically fit patients have options for consolidation therapy: an allogeneic (donor) or an autologous (patient’s own) stem cell transplant, or several cycles of chemotherapy with high-dose cytarabine.

 Nonintensive induction therapy includes less-aggressive treatments, such as hypomethylating agents such as azacitidine and decitabine, or low-dose cytarabine (LDAC).

 However, some patients may not receive any antileukemic therapy, depending on their fitness.

 Although less-intensive therapy results in lower rates of treatment-related mortality, median survival time is much lower with these regimens, about 6 to 10 months.

In patients who are too frail to be considered for nonintensive therapy, supportive care is offered.

 This includes management and prophylaxis of hematologic abnormalities and infections with antimicrobial agents, growth factors, hydroxyurea, and transfusions.

For medically fit and unfit patients, targeted therapy may be added to both consolidation and induction therapy based on patient-specific cancer characteristics (Figure 4

Research emphasis is primarily targeted toward improving outcomes, specifically in elderly patients. A high incidence and poor prognosis of AML exists within this population. A 75-year-old patient recently diagnosed with AML has a 20% chance of 1-year survival.

AML in an older adult is associated with poor outcomes because of higher rates of unfavorable cytogenetic abnormalities, cellular mutations that develop resistance to first-line chemotherapy, and a higher prevalence of secondary AML.

 Resistance can manifest as a cellular mutation capable of altering the drug binding site or modifying the apoptotic abilities of the drug.

In August 2020, the American Society of Hematology (ASH) released updated guidelines for the management of AML in older patients.

 Recent literature supports guideline recommendations encouraging antileukemic therapy over supportive treatment and more-intensive therapy over less-intensive treatment whenever possible.

 Overall, the potential benefit of overtreating the elderly population outweighs the risk of toxicities when considering survival rates.

The ASH panel recommends against combination therapy with the following exceptions: LDAC in combination with glasdegib or hypomethylating agents in combination with venetoclax.

 The data supporting these combinations are derived from small and recent phase 2 trials, so the panel states this as a weak recommendation until stronger analyses are published.

 Glasdegib and venetoclax are 2 of 8 agents that the FDA approved between 2017 and 2019 for the treatment of AML.

 The surge in drug development is the result of improved understanding of the chemotherapy resistance mechanisms, as well as apoptotic machinery elucidation.

Venetoclax inhibits an antiapoptotic protein family commonly overexpressed in AML, B-cell lymphoma 2 (BCL2), which has been associated with chemotherapy resistance and poor survival.

 The recently published VIALE-C trial found that the addition of venetoclax to nonintensive azacitidine induction therapy versus azacitidine monotherapy prolonged survival (14.7 months versus 9.6 months) and increased the likelihood of remission in patients with untreated AML.

Glasdegib is a potent and selective oral inhibitor of the Hedgehog signaling pathway, which is often overactive in AML.

 This pathway aids in the development and proliferation of leukemic stem cells, which play a major role in development of resistance to chemotherapy and disease relapse.

 A phase 2 trial (NCT01546038) published in 2018 found that the combination of glasdegib and LDAC significantly improved overall survival and response rates compared with LDAC alone.

 These results were consistent across various combinations of genetic mutations, suggesting the potential for a more universal application of this drug combination.11 A larger phase 3 trial is under way.

The AML genomic landscape plays a vital role in patient prognosis and treatment decisions. Numerous therapeutic options for AML have become available within the past 3 years, but continued research is needed to determine their place in therapy and introduce more-standardized treatment approaches. The risk versus benefit of more-intense treatment options must be heavily weighted in the frail and medically unfit AML population. The rapid rate of chemotherapy resistance and disease relapse in compromised patients makes it imperative to continue research initiatives to develop optimal and safe therapeutic approaches within this population.

GLENN SCHULMAN, PHARMD, MS, BCPS, BCACP, BCGP, BCIDP,

 are clinical pharmacists in Pensacola, Florida. 

 is a PharmD candidate at Belmont University in Nashville, Tennessee.

Tallman MS, Wang ES, Altman JK, et al. Acute myeloid leukemia, version 3.2019, NCCN clinical practice guidelines in oncology. 

. 2019;17(6):721-749. doi:10.6004/jnccn.2019.0028

Adult acute myeloid leukemia treatment (PDQ)-health professional version. National Cancer Institute. Updated August 11, 2020. Accessed October 28, 2020. http://www.cancer.gov/types/leukemia/hp/adult-aml-treatment-pdq

Acute myeloid leukemia. Leukemia & Lymphoma Society. Accessed October 28, 2020. http://www.lls.org/leukemia/acute-myeloid-leukemia

Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. 

. 2017;141:1342-1393.doi:10.5858/arpa.2016-0504-CP

Yu J, Li Y, Zhang D, Wan D, Jiang Z, Jiang Z. Clinical implications of recurrent gene mutations in acute myeloid leukemia. 

. 2020;9:4.doi:10.1186/s40164-020-00161-7

Röllig C, Kramer M, Schliemann C, et al. Does time from diagnosis to treatment affect the prognosis of patients with newly diagnosed acute myeloid leukemia? 

. 2020;136(7):823-830. doi:10.1182/blood.2019004583

Rao AV. Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction. 

gram. 2016(1):339-347.doi:10.1182/asheducation-2016.1.339

Sekeres MA, Guyatt G, Abel G, et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. 

.2020;4(15):3528-3549.doi:10.1182/bloodadvances.2020001920

Short NJ, Konopleva M, Kadia TM, et al. Advances in the treatment of acute myeloid leukemia: new drugs and new challenges. 

 2020;10:506-25. doi:10.1158/2159-8290.CD-19-1011

DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. 

. 2020;383:617-629.doi:10.1056/NEJMoa2012971

Cortes JE, HeidelFH, Hellmann A, et al. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. 

. 2019;33(2):379-389. doi:10.1038/s41375-018-0312-9

Numerous therapeutic options are available for acute myeloid leukemia, but more research is needed to determine how best to use them.

AML Genomic Landscape Plays Key Role in Treatment

Requirements for handling of hazardous drugs (HDs) have been part of US Pharmacopeia (USP) chapter <797> since 2004.

They appear separately in general chapter USP <800>, which was officially released in 2016 and became official on December 1, 2019. USP <800> was implemented to oversee the handling of HDs and promote environmental protection and patient and worker safety. Now that USP <800> is surveyable, officials can see how organizations are doing with complying with the receipt, storage, compounding, dispensing, and administration of HDs.

For pharmacies to address USP <800> issues, an internal review would need to be conducted of engineering controls, environmental quality, personal protective equipment (PPE), and more. This list of considerations may appear overwhelming, but it is critical to address them, keeping in mind the hierarchy of controls. To identify a manageable starting point for a facility, pharmacists can use a checklist in the American Society of Health-System Pharmacist’s (ASHP) Pharmacy Quick Reference Guide.

 Identifying a key employee who will ensure compliance with this initiative is essential. This individual should have obtained the proper training in HD preparation and handling. Additional training may be required related to internal assessments of compliance. HDs have regulations from several different entities, including the Centers for Disease Control and Prevention, the National Institute for Occupational Safety and Health (NIOSH), and USP <800>, so having a single contact point is paramount.

 It is often the state board of pharmacy inspector ensuring compliance, so having a single person establishing a dialogue with the pharmacy board is also a best practice.

This individual’s responsibility will include editing the facility’s policies and procedures according to feedback and guidelines; ensuring ongoing compliance; and training the person who will help manage the changes with employees. In some cases, this may be a full-time job, whereas in others, depending on the organization’s scope and size, these responsibilities may be tacked on to an existing role.

 Create a comprehensive list of HDs available in the facility. Per USP <800>, an HD is any identified as such by NIOSH based on carcinogenicity, developmental toxicity or teratogenicity, genotoxicity, organ toxicity at low doses in animals or humans, and new drugs that mimic existing HDs in structure or toxicity.

Once this list is written, additions and deletions should be made as medications are added and removed from inventory. Also, there must be a mechanism to allow staff members to understand when they are working with an HD.

Using pharmacy informatics, staff members may be extremely helpful in flagging potential HDs and generating future reports.

 Review the requirements for the safe handling of hazardous medications, create a gap analysis, or use one already written by others such as the ASHP or Critical Point. Perform the gap analysis not through a paper trail but through direct observation of the work being done.

After creating a list of HDs, determine the potential for employee exposure to each via a risk assessment, as shown in the Table.This assessment should include an overview of how each drug is used and by whom, potential exposure, the consequence of such exposure, containment strategies to minimize this risk, and contingency plans for how to address potential exposure. Through this process, organizations can understand the scope of HD use and how it applies to them and prioritize compliance actions based upon the risk identified.

The gap analysis and risk assessment create an organized action plan to address facility-specific areas with the highest risk to patients and the workforce. Practices identified as high risk should be corrected or stopped. PPE should be available in areas where it is needed.

 Once a facility has conducted its gap analysis and rewritten policies and procedures ensuring compliance, employees must be trained on the new procedures and document to ensure ongoing adherence to policies. It is vital to maintain momentum to engage employees’ knowledge and understanding and enforce policy and procedures changes. There should be ongoing direct observations of the work being done to review and correct any procedure breaks.

Although the safe handling of HDs is undoubtedly complex, a logical approach can help facilities enhance workplace safety and protect patients. Remember, safe handling is not a 1-time event. Maintain vigilance to mitigate the chances of adverse effects associated with HD exposure. For additional information, facilities may review free resources on the USP’s website, including its overview and FAQ sections.

, is vice president of operations support CompleteRx in Houston, Texas.

, is director of experiential learning, manager of clinical support services, and associate professor of pharmacy practice, administration, and research at Marshall University School of Pharmacy in Huntington, West Virginia.

, is a professor of health care administration at the Management and Healthcare Administration Division at Lewis College of Business at Marshall University.

USP general chapter <800> hazardous drugs—handling in healthcare settings. Accessed December 15, 2020. https://www.usp.org/compounding/ general-chapter-hazardous-drugs-handling-healthcare

American Society of Health-System Pharmacists. Chapter 800. Accessed December 15, 2020. https://www.ashp.org/search?q=Chapter%20800

CDC. Hierarchy of controls. National Institute for Occupational Safety and Health (NIOSH). Updated January 13, 2015. Accessed December 15, 2020. https://www.cdc.gov/niosh/topics/hierarchy/

Critical Point. Tools & rresources. Accessed December 15, 2020. https:// www.criticalpoint.info/tools-resources/

Petroff B. USP 800 resource. American Society of Health System Pharmacists. April 3, 2017. Accessed December 15, 2020. https://connect. ashp.org/blogs/barbara-petroff/2017/04/03/usp-800-resource?ssopc=1

Maintain vigilance to decrease chance of adverse effects, problems with storage and compliance of hazardous drugs.

Logical Approach Enhances Safety, Protects Patients

Diabetes, a chronic metabolic disease and an international health threat characterized by elevated blood glucose, is thought to be a risk factor for coronavirus disease 2019 (COVID-19).

The number of cases of diabetes has increased in the past 20 years and sparked higher costs for drugs and treatments.

In 2018, it was estimated that 34.2 million individuals of all ages in the United States, or about 10% of the population, had diabetes.

The latest global estimate of individuals with diabetes was about 463 million in 2019, according to the International Diabetes Federation.

It is estimated that number will escalate to about 700 million by 2045.

 Diabetes is triggered by a lack of insulin in type 1 diabetes and insulin resistance in type 2 diabetes.

 Chronic hyperglycemia is the leading cause of metabolic imbalance in diabetes. It increases the risk of complications associated with diabetic ketoacidosis and hyperglycemic hyperosmolar states, for which remarkably high doses of insulin are warranted.

As of December 13, 2020, there have been more than 72 million cases of COVID-19 and more than 1.6 million deaths from the disease worldwide, according to Johns Hopkins University & Medicine.

The magnitude of the threat of the coronavirus on the human body is still unknown. There is a lack of concrete evidence of the impact of the virus’ full invasion of the human body, and symptoms vary and present in different forms, including gastrointestinal and upper-respiratory symptoms.

 In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the proteins of the virus bind to receptors called angiotensinconverting enzyme 2, which are seen in key metabolic organs and tissues, including adipose tissue, the kidneys, pancreatic β cells, and the small intestine.

 Hence, it is plausible that SARS-CoV-2 may cause pleiotropic alterations of glucose metabolism, which could obscure the pathophysiology of preexisting diabetes.

 Numerous studies propose that substantial coagulation activation with severe COVID-19 infection is likely associated with inflammatory response secondary to cytokines release induced by viral invasion.

 The role of inflammation in diabetes is made based on the identification of inflammatory markers, such as adiponectin, C-reactive proteins, interleukin 6, leptin, plasminogen activator inhibitor-1, and tumor necrosis factor α.

Both COVID-19 and diabetes are associated with acute and chronic inflammation. In a research study conducted by Shang et al, laboratory data were analyzed and showed that individuals with diabetes had higher levels of C-reactive protein, neutrophils, and procalcitonin but a lower level of lymphocytes compared with individuals who didn’t have diabetes.

 The study’s radiologic data also showed a significantly higher incidence of bilateral pneumonia in patients with diabetes compared with individuals who did not have diabetes. These results showed that patients with COVID-19 and diabetes had more severe inflammatory responses and lung infiltration, which might contribute to the worse prognosis of SARS-CoV-2 infection.

 The relationship between diabetes and infection has been a pivotal concern.

In addition, numerous studies have indicated that diabetes is a risk factor in the morbidity and mortality of multiple viral infections, including influenza A (H1N1), Middle East respiratory syndrome, and SARS-CoV.

A meta-analysis of 6 studies inclusive of 1527 patients with COVID-19 reported the prevalence of diabetes to be 9.7%.

 Among 1122 patients with COVID-19 who were admitted to the 88 US hospitals, the mortality rate was 4 times higher in those with known diabetes than those without known diabetes disease.

 shows that counterregulatory hormonal responses, the impairment of β-cell function with the inflammatory cytokine storm, and SARS-CoV-2 can precipitate further acute metabolic complications. Acute metabolic deterioration, hyperglycemia at admission, and new-onset diabetes, in turn, can worsen COVID-19 outcomes.

It is well documented that diabetes causes an increased risk in the mortality and severity of COVID-19. However, the mechanism is not entirely clear. Understanding the relationship between COVID-19 and diabetes could advance therapeutic measures, but there is a scarcity of data on the matter.

Some studies have suggested that impaired immune systems make individuals with diabetes more susceptible to severe infections. High blood concentrations of inflammatory markers seen in patients with poorly controlled diabetes are linked to COVID-19 death and severity. Further randomized clinical trials are warranted to elucidate the clear mechanism between COVID-19 infection and diabetes. 

, is an advanced practice clinical pharmacist at Brigham and Women’s Hospital in Boston, Massachusetts.

Abdi A, Jalilian M, Sarbarzeh PA, Vlaisavljevic Z. Diabetes and COVID-19: a systemic review on the current evidences. 

. 2020;166:108347. doi:10.1016/j.diabres.2020.108347

Diabetes. World Health Organization. Accessed December 13, 2020. https://www.who.int/health-topics/diabetes#tab=tab_1

National diabetes statistics report 2020. Centers for Disease Control and Prevention. Accessed December 5, 2020. https://www.cdc.gov/diabetes/ pdfs/data/statistics/national-diabetes-statistics-report.pdf

COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Johns Hopkins University & Medicine. Accessed December 13, 2020. https://coronavirus.jhu.edu/map.html

COVID-19 protocols. Brigham and Women’s Hospital. Accessed December 6, 2020. https://covidprotocols.org/protocols/ clinical-course-and-epidemiology/#clinical-course

Rubino F, Amiel SA, Zimmet P, et al. New-onset diabetes in COVID-19. 

. 2020;383(8):789-790. doi:10.1056/NEJMc2018688

Al-Ani F, Chehade S, Lazo-Langner A. Thrombosis risk associated with COVID-19 infection. a scoping review. 

. 2020;192:152-160. doi:10.1016/j.thromres.2020.05.039

Shang J, Wang Q, Zhang H, et al. The relationship between diabetes mellitus and COVID-19 prognosis: a retrospective cohort study in Wuhan, China. 

 2021;134(1):e6-e14. doi:10.1016/j.amjmed.2020.05.033

Driggin E, Madhavan MV, Bikdeli B, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. 

. 2020;75(18):2352-2371. doi:10.1016/j.jacc.2020.03.031

Apicella M, Campopiano MC, Mantuano M, Mazoni L, Coppelli A, Del Prato S. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. 

. 2020;8(9):782-792. doi:10.1016/S2213-8587(20)30238-2

Additional randomized clinical trials are warranted to determine the mechanism between the 2 diseases.

COVID-19 and Diabetes: Is There a Connection?

With a national survey of nurses finding that more than 50% have been exposed to hazardous agents, proper education and safety procedures about handling these agents is essential. In a recent 

 video, a panel of experts discussed potential harmful effects and best practices for handling hazardous agents.

Health care workers risk exposure to hazardous agents during receipt, transport, storage, compounding, distribution, administration, and disposal of these substances, said moderator 

, director of pharmacy business development at Catholic Health in Buffalo, New York.

Furthermore, many exposures occur in situations without monitoring requirements, making it necessary to preemptively establish best practices, he said.

Panel of experts discusses alert systems, PPE, and surface contamination as methods for minimizing exposure to dispensing pharmacists

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