Michigan Pharmacists Association (MPA) has been working tirelessly with the Governor’s office on concerns our members have brought to us. Last night the Governor released Executive Order 2020-25 in response to our communication with her and her administration. MPA was not made aware of the documentation requirements prior to the release of this order. We recognize there’s additional improvements to request however, we are pleased that the Governor listened to MPA and Michigan pharmacy leaders to enact this order in a timely fashion. MPA will continue to advocate on behalf of the profession. In accordance to Executive Order 2020-25, pharmacists are authorized to: 

• Dispense 60-day emergency refills of any non-controlled substance maintenance medication. Note that the order requires the pharmacist to notify the prescriber in writing if additional refills are dispensed. 
• Operate in an area not designated on the pharmacy license, but may not compound sterile medications at this location.
• Dispense or administer drugs to patients with COVID-19 pursuant to CDC and NIH established protocols or protocols determined appropriate by the chief medical executive of the Michigan Department of Health and Human Services (MDHHS).
• Substitute a therapeutically equivalent medication for a medication that is experiencing a shortage. Note that the pharmacist must notify the prescriber in a reasonable period of time of any changes.
• Supervise student pharmacists remotely to fulfill eligibility for licensure and avoid delaying graduation.
• Supervise pharmacy technicians and other pharmacy staff remotely as long as there is a real time, continuous audiovisual equipment in place to allow this. This exception does not apply to remotely supervising pharmacy technicians compounding sterile or nonsterile compounds.

The Executive Order also recognizes pharmacies and wholesalers holding a license in good standing in another state as being licensed in Michigan. In addition, the Executive Order mandates prescription coverage on emergency refills from all insurers and health maintenance organizations. It also requires for early refills of all maintenance medications to allow for up to a 90-day supply to be dispensed by a pharmacy.

Executive Order 2020-25 is in effect until April 22 at 11:59 p.m.

It is clear that Pharmacists and pharmacy technicians (and other pharmacy personnel) fall under the healthcare workers portion of the Executive Order and are allowed to continue work in pharmacies and health-systems. MPA leadership and staff thanks each of you for what you are doing in your communities. Your efforts are critical in making sure that the health system is able to treat patients impacted by COVID-19 and those who have health care needs that were in place before the COVID-19 outbreak.

Since the emergency began, MPA has been receiving a variety of emails asking for clarification of different aspects of pharmacy practice or recommendations of what the State should do. In fact, one of MPA’s staff pharmacists has been reporting daily to the State Community Health Emergency Coordination Center as a resource to the state on pharmacy issues. MPA has also created the COVID-19 webpage to provide information that you can use in your practice.

Last week MPA reached out to the Governor with specific requests and followed-up again today with the Governor’s office. The following items were submitted to the Governor’s office and we are awaiting a response:

1. Pharmacists in any county of the State of Michigan may dispense emergency refills (up to a sixty (60) day supply) of any non-controlled medication for residents of any county of Michigan.
2. Pharmacists may temporarily operate a pharmacy in an area not designated on the pharmacy license.
3. Pharmacists may dispense and administer drugs as needed to treat COVID-19 pursuant to protocols established by the Centers for Disease Control and Prevention (CDC) or the National Institute of Health (NIH) or determined to be appropriate by the MDHHS Chief Medical Officer or her designee to respond to the circumstances causing the emergency. The MDHHS CMO or the pharmacist will be listed as the prescriber.
4. To preserve scarce hospital and acute setting resources, expand patient access to care through establishing a statewide collaborative practice agreement (CPA) with the Chief Medical Executive allowing pharmacists to provide point of care testing (POCT) to differentiate influenza, Strep or other infections from COVID-19. For those testing positive to influenza or Strep, to initiate treatment directed by the CPA.
5.  Effective immediately, providers must certify on any new outpatient prescription related to the treatment of COVID-19 an appropriate indication. Providers who inappropriately prescribe hydroxychloroquine or other medications that are deemed effective to treat COVID-19 may face disciplinary sanctions. Community pharmacies should not honor prescriptions written after March 23, 2020 that do not have an appropriate indication noted on the prescription. It is within the pharmacist’s scope of practice to question and/or deny prescriptions they suspect are written for COVID-19 prophylaxis or for “just in case” reasons.

Jamie George, Pharm.D.; Carly Burns, Pharm.D.; Christopher DeBiase, Pharm.D.; Nicole Elkhoury, Pharm.D., pharmacy residents, Ascension St. John Hospital, Detroit

Sepsis is a life-threatening illness induced by infection. It affects 1.7 million adults in the United States each year and is responsible for over 250,000 deaths.¹ Septic shock is a subset of sepsis in which metabolic and circulatory abnormalities are present.² Given the mortality associated with sepsis, new treatment options are being explored.

Vitamin C, or ascorbic acid, has recently been evaluated as adjunctive therapy in sepsis but its role remains unclear. There are several hypotheses regarding the role of Vitamin C. First, Vitamin C acts as a cofactor in endogenous norepinephrine production and provides antioxidant properties. Oxidative stress is known to occur in sepsis.³ In addition, patients with sepsis often have low Vitamin C concentrations (<15 μM/L) secondary to inflammation.^4,5 Thiamine and hydrocortisone are also utilized in combination with Vitamin C in sepsis. Similar to Vitamin C, thiamine is a micronutrient found to be below normal range in patients with sepsis. Thiamine modifies Vitamin C metabolism to reduce oxalate production, therefore decreasing the rate of Vitamin C oxalate-induced nephropathy. Hydrocortisone has consistently shown to improve patient outcomes in sepsis. It has been suggested hydrocortisone works synergistically with Vitamin C to decrease inflammatory mediators and increase vasopressor sensitivity.⁶ 

Prior to 2017, there was limited evidence regarding high-dose Vitamin C, monotherapy or in combination with thiamine and hydrocortisone, as a therapeutic option for sepsis. Table 1 provides a summary of the four major trials. 

The role of Vitamin C in sepsis remains unknown; however, the answer may soon be within our reach. Hager et al (2019) are currently enrolling patients into the VICTAS trial to test the efficacy of combined Vitamin C, thiamine, and hydrocortisone in patients with respiratory or circulatory dysfunction resulting from sepsis. VICTAS is anticipated to be a large scale, randomized-controlled trial conducted across 40 sites within the United States. All eyes will be directed towards the results of this highly anticipated trial come late 2021 to confirm Vitamin C’s place in therapy. 

References

1. Rhee C, Dantes R, Epstein L, et al; CDC Prevention Epicenter Program. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014. JAMA. 2017;318(13):1241-1249
2. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810.
3. Rudyk O, Phinikaridou A, Prysyazhna O, Burgoyne JR, Botnar RM, Eaton P. Protein kinase G oxidation is a major cause of injury during sepsis. Proc Natl Acad Sci U S A. 2013;110:9909–9913.
4. Prauchner CA. Oxidative stress in sepsis: pathophysiological implications justifying antioxidant co-therapy. Burns. 2017;43:471–485.
5. Padh H, Aleo JJ. Activation of serum complement leads to inhibition of ascorbic acid transport. Proc Soc Exp Biol Med. 1987;185:153–157.
6. Hager D, Hooper M Bernard G, et al. The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. Trials, 2019;20(1):1-16.
7. Fowler AA, Syed AA, Knowlson S, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. Journal of Translational Medicine, 2014;12:32:1-10.
8. Marik PE, Khangoora V, Rivera R, et al. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. CHEST, 2017;151(6):1229-1238.
9. Fowler AA, Truwit JD, Hite RD, et al. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure. JAMA, 2019;322(13):1261-1270.
10. Fujii T, Luethi N, Young PJ, et al. Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial. JAMA, 2020;323(5):423-431.

Vishnuprabha D. Vogel, Pharm.D., BCOP, BCPS, pharmacy manager, Henry Ford Health System

The juxtaposition of the rapidly evolving healthcare environment paired with increasing volume of exponentially expensive pharmaceutical agents requires proactive establishment of pharmacy revenue integrity (PRI) framework, policy and procedures. Ensuring optimal PRI requires oversight of steps throughout the revenue continuum (Figure 1). While many strategies are frequently employed to optimize revenue capture, there are a few common challenges faced by healthcare systems:

1. Fragmentation of revenue integrity responsibilities within single institutions
2. Reliance on manual processes
3. Lack of formal role for pharmacy oversight/leadership

PRI optimization requires interdepartmental integration. This article provides considerations for each of the steps in the revenue continuum to optimize PRI.

Procurement Optimization and Formulary Management
The foundation of PRI starts with procurement optimization and strategic formulary management. While most organizations belong to a group purchasing organization and monitor expenses on a routine cadence, the opportunity lies in the ability to agilely switch to a lower cost, comparable product. Similarly, as alternatives, generic products and biosimilars enter the market, it is vital to leverage contracting opportunities.

Charge Data Master (CDM) Accuracy
As drug utilization changes, pharmaceutical CDM should be updated with the most accurate information. In addition, implementation of regulatory changes to ensure revenue capture requires continuous monitoring (i.e., requirements for National Drug Codes (NDC) on Medicare/Medicaid claims). Pharmacy departments may or may not have direct responsibility in maintaining the CDM.

Authorizations and Medical Necessity
Securing authorization requires proactive assessment depending on the type of care: acute, subacute or elective. The process includes completing a benefits assessment and submission of required forms. One challenge is that the benefits and the requirements not only change from payer to payer but within different plans under the same payer. Furthermore, some payers, including CMS, do not offer upfront authorizations. In addition, for those requiring authorization, securing authorization does not guarantee reimbursement. Thus, for all J-codes utilized, securing the authorization and validating medical necessity is necessary. The combination of the technical expertise of pharmacy technicians (i.e., vials sizes, dosage forms, etc.) and clinical expertise of pharmacists add tremendous value to a revenue integrity team.

Site of Care
In efforts to minimize expenses, many payers have established site of care policies requiring specific infusions be administered in a free-standing infusion center or via home infusion. In theory, the utilization of these alternative sites should result in lower healthcare expenses. However, for those institutions without free-standing infusion services, transitioning patients completely to home infusion, might result in a negative margin. Each institution should complete a financial assessment comparing revenue generation to expenses to determine whether to continue to offer these services or coordinate care with an external entity. Furthermore, site of care policies are continually evolving and require prospective monitoring.

Billing and Coding
Inconsistencies and errors with billing units, diagnosis codes, charge data master, etc. can lead to compromised revenue capture. The accuracy of billing and coding is optimized when there is a strategic integration of interdepartmental workflow established between pharmacy, finance and information technology. Many institutions are faced with multiple systems that do not interface and cannot cross reference misaligned variables in the billing process. For example, comparing the volume billed with units purchased or situations where reimbursement is lower than expenses. Regardless of whether manual, automated or combinations of both are implemented, the inclusion of pharmacy into finance processes optimizes revenue capture.

Denials
Key factors contributing to denials include manual processes, billing and coding errors, variability from payer to payer, increasing complexity of the authorization process and medical necessity expectations. While the primary goal is to minimize the denial rate by optimizing factors discussed above, formalizing a role for pharmacy in the denial appeals process and investing strategically in analytics/software that can integrate denials information is essential.

In summary, PRI optimization requires a robust approach involving interdepartmental integration. All opportunities discussed above are symbiotic with the overarching goal of providing the highest quality care at the lowest expense. It is imperative to leverage analytics, technology and automation into process across the pharmaceutical revenue continuum. 

Matt Rico, Pharm.D., PGY1 pharmacy practice resident at Ascension Genesys Hospital, Grand Blanc

In fall 2019, the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) released a long-anticipated update to the community-acquired pneumonia (CAP) guidelines, the first update since 2007.¹ These recommendations come at an opportune time as recent literature from Vaughn and colleagues suggests that two-thirds of patients in the 43-hospital network, (Michigan Hospital Medicine Safety Consortium) receive excess antibiotic therapy for CAP.² 

Regarding the classification of CAP, the guidelines strongly recommend the abandonment of the term healthcare-associated pneumonia (HCAP), as current evidence has not shown that the risk factors for HCAP predict high prevalence of antibiotic-resistant pathogens. Instead, the guidelines adhere to treatment recommendations for non-severe or severe CAP. Severe CAP patients must meet at least one major (septic shock with need for vasopressors or respiratory failure requiring mechanical ventilation) or at least three minor criteria (multilobar infiltrates, confusion/disorientation, respiratory rate ≥ 30 breaths/min, etc.) for diagnosis.¹ 

Regarding other diagnostic recommendations, the new guidelines provide a strong recommendation to only obtain sputum and blood cultures in select inpatients, including those with severe CAP, history of prior methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa infection, and patients who have been hospitalized and required parenteral antibiotics in the previous 90 days. Routine testing for pneumococcal and Legionella urinary antigens are only recommended in patients with severe CAP or if indicated by epidemiological factors for Legionella. Additionally, the guidelines strongly recommend that empiric antibiotic therapy is started with clinical suspicion/radiographic evidence of CAP regardless of serum procalcitonin.¹ 

Regarding treatment recommendations, there have been changes in the recommended outpatient antimicrobial treatment regimens. The guidelines now strongly recommend high-dose amoxicillin or doxycycline in adults with no comorbidities or risk factors for MRSA or P. aeruginosa infections due to the proven efficacy of amoxicillin for inpatient CAP. However, macrolides are now only conditionally recommended (azithromycin or clarithromycin) in these patients if there is < 25 percent local pneumococcal resistance. If an adult has comorbidities (chronic heart, lung, liver or renal disease; diabetes mellitus, malignancy, etc.), then combination therapy is now strongly recommended with amoxicillin/clavulanate (previously included amoxicillin, as well) or a cephalosporin (cefpodoxime or cefuroxime) plus a macrolide or doxycycline. Respiratory fluoroquinolones, such as levofloxacin, remain a strong recommendation for monotherapy.¹ 

For inpatient treatment, combination therapy with a β-lactam and a macrolide or monotherapy with a respiratory fluoroquinolone remains the treatment of choice for non-severe CAP. Though some literature published since the previous guideline update raised questions of the possibility of β-lactam monotherapy, the guidelines continue to recommend combination therapy citing evidence of a mortality benefit. In the previous guidelines, β-lactam/macrolide and β-lactam/respiratory fluoroquinolone regimens were given equal weight for severe CAP, but recent literature shows there may be an increased mortality risk with β-lactam/respiratory fluoroquinolone regimens. However, due to the low quality of evidence, both regimens remain strong recommendations for severe CAP. Additionally, ceftaroline is now among the recommended β-lactam agents, while intravenous cefuroxime is no longer listed. MRSA and P. aeruginosa coverage is recommended only in patients with prior respiratory isolation or recent hospitalization with parenteral antibiotics and locally validated risk factors for these pathogens. If there is a concern for aspiration pneumonia, the guidelines now provide a conditional recommendation to not routinely include anaerobic coverage unless a lung abscess or empyema is suspected, as recent evidence shows that anaerobes are uncommon in this patient population.¹ 

Regardless of the selected treatment, antibiotic therapy is still recommended for five days or seven days for MRSA and P. aeruginosa.¹ Treatment duration should be a primary focus in health systems, as Vaughn and colleagues found that patients treated with excess duration of antibiotics while hospitalized did not have lower rates of death, readmission, emergency department visits or Clostridioides difficile infections. Transition from the inpatient to outpatient setting proved to contribute to excess days of therapy, where nearly 50 percent of total days of antibiotics and 93 percent of excess days of antibiotics were found, respectively.² 

While the previous guidelines did not mention corticosteroid use, it is now recommended to withhold from using these agents in patients with non-severe CAP. There is limited data to show mortality benefit in patients with severe CAP along with inconsistent definitions of disease severity in available literature, leading to a conditional recommendation against routine use.¹ 

In conclusion, the updated guidelines offer several new and revised recommendations for the management of community-acquired pneumonia. There is hope that these updates will provide needed guidance as health systems continue to work to find ways to optimize treatment of this common infectious disease.

REFERENCES:

1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. Am J Respir Crit Care Med. Oct 2019. 200(7):e45-67.
2. Vaughn VM, Flanders SA, Snyder A, et al. Excessive Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized with Pneumonia. Ann Intern Med. 2019(171):153-63.