Approximately 29.1 million individuals in the United States have diabetes, and an estimated 8.1 million cases are undiagnosed.

 In 2012, 1.7 million new diabetes cases were diagnosed in individuals 20 years and older, the majority of whom were 45 to 64 years of age. If this trend continues, it is estimated that 1 of every 3 Americans will suffer from diabetes by the year 2050.

Individuals with diabetes make up 9.3% of the US population, resulting in a significant economic burden. In 2012, the total estimated cost, direct and indirect, of diabetes in the United States was more than $240 billion. Well-known comorbid conditions and complications of diabetes, including hypertension, cardiovascular disease, stroke, chronic kidney disease, retinopathy, and depression, account for many of these expenditures.

The increasing prevalence of diabetes has led to new and emerging therapies. More than 14% of patients with a diabetes diagnosis receive treatment with both oral agents and insulin. The pill burden and complexity of regimens, in addition to costs and adverse effects (AEs), are all factors that contribute to nonadherence in these patients. Many of the new agents exhibit novel mechanisms to improve glycemic control, while others are focused on breaking down barriers of nonadherence. For example, many injectable medications have been formulated in pen devices and/or with less frequent dosing to help improve adherence.

Since January 2014, 10 new products marketed for the treatment of diabetes have been approved by the FDA.

 Some are combination products of previously approved drugs, whereas others are new drug entities (Online Table 1

Table 1: FDA-Approved Drugs for the Treatment of Diabetes from 2014 to 2015

Articles

Chronic Care Focus

Diabetes: New and Emerging Therapies

Health care is in the midst of a transformation in which health care providers are increasingly being paid for value provided rather than per service. Moreover, the payment implications of hospital readmissions are a major challenge facing hospitals and health systems in this changing landscape. With the advent of the Patient Protection and Affordable Care Act (ACA), hospital readmissions are at the forefront of “crises” demanding meaningful (and efficient) solutions.

The Hospital Readmissions Reduction Program was established with the passage of the ACA.

 Beginning October 1, 2012, this program has monitored hospital discharges for 3 distinct conditions: acute myocardial infarction, heart failure, and pneumonia. In fiscal year 2015, chronic obstructive pulmonary disease, total knee arthroplasty, and total hip arthroplasty were added to the list of applicable conditions. Readmission to a hospital within 30 days of discharge for one of the above conditions counts toward the hospital’s readmission ratio, with those hospitals that have a readmission ratio that exceeds an expected value being penalized with reduced payments. A graded approach to penalizing hospitals for excess readmissions was phased in over a period of 3 years. Beginning in 2012, hospitals with excess readmissions were at risk for up to a 1% reduction in total base operating diagnosis-related group payments. This reduction was increased to a maximum of 3% in 2015.

Fortunately, hospitals and health systems have begun to implement effective programs for reducing readmissions. Pharmacists are uniquely positioned to meaningfully impact patient readmissions. As the medication expert on the health care team, pharmacists can optimize medication use, reduce overall costs, and ultimately improve patient outcomes through effective medication management.

 Moreover, pharmacists in the ambulatory care environment are positioned to manage medication therapy in a way that has a great impact on the patients and populations they serve, and they have the potential to help ease the strain of increased demand by an aging patient population.

 The diverse skill sets and unique perspective of pharmacists make them a valuable asset to any team trying to solve the “readmissions crisis.”

Effectively reducing readmissions is contingent on a continuing focus on effective transitions of care (TOC). Patients across the entire continuum of care are vulnerable to the gaps in communication that can occur when transitioning from one setting to the next, putting the patient at greater risk for readmission. Because transitions of care occur across the entire continuum of care, opportunity to improve TOC and meaningfully reduce readmission rates exists in multiple settings. Both acute care and ambulatory care practitioners have demonstrated successful models for reducing readmissions by focusing on improving transitions. Looking ahead, readmission reduction models that focus on individual patients will remain important, and population health strategies will grow in importance as payers strive to reduce costs and improve care. The remainder of this article discusses strategies that pharmacists have successfully used to meaningfully impact their hospital’s or health system’s readmissions from both the acute and ambulatory care settings.

Acute care pharmacists have reported several successful strategies for reducing readmissions at their hospitals and health systems.

 Many of the successful strategies for reducing readmissions incorporate a core set of effective practices for improving the transition of care and reducing readmissions. Effective practices include multidisciplinary involvement,

 medication reconciliation at admission and discharge,

 pharmacist- provided medication counseling,

 and post-discharge follow-up phone calls.

A study by Warden and colleagues highlights the effects of pharmacistprovided medication reconciliation and patient education.

 In this study, the pharmacist was responsible for obtaining a medication history, completing admission and discharge medication reconciliation, providing recommendations for optimization of heart failure medication therapy, and providing both disease and medication education. Additionally, the pharmacist conducted postdischarge phone calls at 14 and 30 days. Following this intervention, 30-day all-cause readmissions were significantly reduced in the intervention group (17%- 38%; P = .02). This study very effectively shows how a comprehensive approach to improving the transition from hospital to home can have a far-reaching effect on readmission rates.

Large patient volumes and limited pharmacist time often complicate plans for involving pharmacists in the discharge process. For these reasons, it is important to triage and prioritize patients with the highest risk for readmission. Pal and colleagues reported on pharmacist- provided discharge medication reconciliation and counseling for patients prioritized by a screening tool that included the total number of discharge medications as well as the presence of “problem medications” as defined by Project BOOST (Better Outcomes by Optimizing Safe Transitions).

 In this study, those patients reviewed by a pharmacist experienced a lower 30-day readmission rate compared with the usual care (16.8% vs 26.0%; OR 0.572; 95% CI, 0.387- 0.852). This study also demonstrated that patients with a higher number of discharge medications had higher 30-day readmission rates. Thus, it is reasonable for pharmacists to consider targeted approaches for meaningfully impacting readmission rates in their hospitals.

Ambulatory care pharmacists have also reduced hospital readmissions. For example, Cavanaugh and colleagues implemented a multidisciplinary readmission prevention program at the University of North Carolina Internal Medicine Clinic (UNC IMC).

 The UNC IMC posthospital discharge clinic saw eligible UNC IMC patients discharged from UNC Hospitals within 5 calendar days of hospital discharge. A clinical pharmacist practitioner (CPP) in the clinic coordinated the 60-minute appointment, which included a 20-minute attending physician appointment embedded within the 60-minute clinic visit. The CPP’s focus extended beyond medications to all key visit components. (CPPs are licensed, advanced practice providers in the state of North Carolina who practice under a collaborative practice agreement with a physician.) This study evaluated the effectiveness of their clinic using a retrospective cohort approach, matching patients who were not seen in the post-hospital discharge clinic with those who were seen in the clinic. Patients seen in the post-hospital discharge clinic with a pharmacist experienced significantly fewer readmissions at 30-days and 90-days compared with the usual care group (HR at 30 days, 0.32; 95% CI, 0.12-0.91; HR at 90 days, 0.34; 95% CI, 0.16-0.72). This study highlights the important role of ambulatory care pharmacists working with multidisciplinary teams in preventing readmission.

The studies referenced above demonstrate the impact pharmacists can have in hospital and health system efforts to meaningfully impact readmission rates. The following are strategic tips that pharmacists can implement in order to promote effective transitions in care that result in reduced readmissions:

 Being proactive from the day of admission is one of the most important aspects of any readmissions reduction program. Start with obtaining a comprehensive medication history and performing admission medication reconciliation. Then, work collaboratively to prepare the patient and his or her medication plan in preparation of discharge. Being proactive sets up an efficient discharge process and effective transition from the acute care to the ambulatory care setting.

 The warm hand-off note summarizes the pertinent medication changes that occurred during the patient’s admission and communicates to the next provider the most important medication follow-up needs. This note should be placed in the medical record in a location that can be accessed by the next pharmacist to care for the patient.

 At our institution, both daytime and evening pharmacist staff take part in the TOC program. Staff that work daytime shifts often know the patient and plan of care to a greater degree and take a lead in performing discharge medication reconciliation and writing “warm hand-off” notes for the next provider. Evening staff are instrumental in performing admission medication reconciliation and performing the final patient education as directed by day shift staff.

 The patient’s nurse is often the individual most acutely aware of the patient’s needs and plans for discharge. By working collaboratively with nursing, the pharmacist can be kept in the loop about time of discharge and does not need to scramble at the last minute to ensure their portion of the transition process is completed.

Utilize risk stratification to identify patients at greatest risk.

 Our institution targets patients at moderate and high risk for readmission based on criteria that include number of chronic disease states, number of hospitalizations in the past year, and number of medications. This allows us to utilize limited pharmacy resources to target the patients most likely to be readmitted.

 Patients should have plans for close follow-up of changes made during the hospitalization. This can be as robust as a posthospital discharge follow-up clinic or as simple as a follow-up phone call and should be based on the patient’s acuity and level of complexity. Either way, programs for ensuring safe transitions and reducing readmission should not end with hospital discharge.

Effective hospital readmissions reduction efforts are centered on ensuring safe transitions of care. By allocating pharmacists to both the acute care and ambulatory care settings and implementing the tips provided above, health systems can effectively address the readmissions crisis and provide better care to the patients they serve.

David A. South, PharmD, is a PGY-2 healthsystem pharmacy administration resident at University of North Carolina Hospitals and Clinics in Chapel Hill, North Carolina, and an MS candidate at UNC Eshelman School of Pharmacy.

Lindsey B. Amerine, PharmD, MS, BCPS, is assistant director of pharmacy, University of North Carolina Medical Center, and assistant professor of clinical education, UNC Eshelman School of Pharmacy.

		Centers for Medicare & Medicaid Services. Readmissions reduction program. www.cms.gov/medicare/medicare-fee-for-service-payment/acuteinpatientpps/readmissions-reduction-program.html. Updated August 4, 2014. Accessed October 1, 2015.

		American Society of Health-System Pharmacists; American Pharmacists Association. ASHP-APhA medication management in care transitions best practices. American Pharmacists Association website. http://media.pharmacist.com/practice/ASHP_APhA_MedicationManagementinCareTransitionsBestPracticesReport2_2013.pdf. Published February 2013. Accessed August 29, 2014.

Improving Patient and Health System Outcomes through Advanced Pharmacy Practice: A Report to the US Surgeon General 2011

. Rockville, MD: Office of the Chief Pharmacist, US Public Health Service; December 2011. www.accp.com/docs/positions/misc/improving_patient_and_health_system_outcomes.pdf.

		Jack BW, Chetty VK, Anthony D, et al. A reenginered hospital discharge program to decrease rehospitalization: a randomized trial. 

		Warden BA, Freels JP, Furuno JP, Mackay J. Pharmacy-managed program for providing education and discharge instructions for patients with heart failure. 

. 2014;71(2):134-139. doi: 10.2146/ajhp130103.

		Kirkham HS, Clark BL, Paynter J, Lewis GH, Duncan I. The effect of a collaborative pharmacist-hospital care transition program on the likelihood of 30-day readmission. 

. 2014;71(9):739-745. doi: 10.2146/ajhp130457.

		Pal A, Babbott S, Wilkinson ST. Can the targeted use of a discharge pharmacist significantly decrease 30-day readmissions? 

. 2013;48(5):380-388. doi: 10.1310/hpj4805-380.

		Society of Hospital Medicine. Overview: project BOOST implementation toolkit. www.hospitalmedicine.org/Web/Quality_Innovation/Implementation_Toolkits/Project_BOOST/Web/Quality___Innovation/Implementation_Toolkit/Boost/Overview.aspx. Accessed October 2, 2015.

		Cavanaugh JJ, Jones CD, Embree G, et al. Implementation science workshop: primary care-based multidisciplinary readmission prevention program. 

29(5):798-804. doi: 10.1007/s11606-014-2819-8.

Viewpoints

Health care is in the midst of a transformation in which health care providers are increasingly being paid for value provided rather than per service.

Strategies to Overcome the Readmission Crisis in Health Systems

A 48-year-old man was admitted overnight to the hospital complaining of increasing shortness of breath, increase in yellow-green sputum, chest pain, low-grade fever, dysphagia, and weight loss. The patient has already had 2 episodes of bronchitis this year and his medical history includes hypertension, smoking (40 pack-years), presumed chronic obstructive pulmonary disease (COPD), and gout. His chest x-ray showed infiltrate consistent with infection. Sputum gram stain culture is pending. For laboratory results, see Online Table 1. For patient medication history, see Table 2.

Online Table 1: Patient Laboratory Results

						Laboratory results at admission: 1800: complete blood count (CBC) 12> 13.6/41.7<283; chemistry panel: 131/4.9-106/32-9/1.2 <185.

						Next morning laboratory results: CBC 

>13.1/40<285; chemistry panel: 132/4.8-105/32-

After reviewing the profile and the patient’s interview, the following stand out as potential pharmacy interventions:

Evaluate whether an antibiotic is needed (changes in sputum purulence or color, sputum gram stain/culture, fever, chest x-ray, etc).

		Levofloxacin 750 mg every day is a good choice for inpatient care.		

				If previous exacerbations involved hospitalization/intubation, risk for pseudomonas or resistant organisms increases (see Online Table 3).

				Consider change to oral levofloxacin.

		Ceftriaxone and azithromycin or doxycycline (alternative inpatient therapy).

		For mild exacerbation, doxycycline 100 mg twice daily or amoxicillin/ clavulanic 875 mg twice a day may be appropriate alternatives.

Change methylprednisolone to prednisone 40 mg orally every day for 5 days. Consider longer steroid duration (ie, taper over 2 weeks) if last exacerbation was recent or if the patient is slow to improve.

		Creatinine increased since admission may be upward trend.

		Consider holding colchicine and hydrochlorothiazide.

				Albuterol 0.83% (2.5 mg/3 mL) nebulizer every 4 hours.

				Ipratroprium (0.5 mg/2.5 mL) nebulizer every 6 hours (frequency change).

				Address the use of both long-acting beta-2-agonists and inhaled corticosteroids with scheduled albuterol every 4 hours.

		Consider stopping use of the combination product and use budesonide and albuterol nebulized until patient stabilizes.		

				Address the frequency of fluticasone/ salmeterol; dose is typically twice a day.

				Review inhaler technique with patient.

				Reevaluate use of fluticasone/salmeterol long term (address as outpatient).				

						Consider long-acting anticholinergic (eg, tiotroprium, acalidium).

		Although the patient declined medications for inpatient management, provide cessation materials and phone numbers for future reference. Encourage small changes until the time is right to fully commit to quitting (ie, decrease number of cigarettes per day).

If pulmonary function test results are not provided, obtain for diagnosis/staging of COPD after exacerbation is resolved.

Up-to-date on influenza, pneumococcal vaccination.

Would you like to submit a case study to the 

 Health-System Edition? Please contact Stephen F. Eckel, PharmD, MHA, BSPS, FASHP, FAPhA, at SEckel@unch.unc.edu.

Jennifer Barrow, PharmD, is a clinical specialist in adult medicine at the University of North Carolina.

		Gold Guidelines. www.goldcopd.org. Accessed June 2015.

		Leuppi JD, Scheutz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbation of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. 

. 2013;309(21):2223-2231. doi: 10.1001/jama.2013.5023.

		Vollenweider DJ, Jarrett H, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA. Antibiotics for exacerbations of chronic obstructive pulmonary disease. 

. 2012;12:CD010257 doi: 10.1002/14651858.CD010257.

		Miravitlles M, Moragas A, Hernandez S, Bayona C, Llor C. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? 

. 2013;144(5):1571-1577. doi: 10.1378/chest.13-0518.

		Papi A, Haughney J, Virchow JC, Roche N, Palkonen S, Price D. Inhaler devices for asthma: a call for action in a neglected field. 

. 2011:37(5): 982-985. doi: 10.1183/09031936.00150910.

		Short PM, Williamson PA, Elder DH, Lipworth SI, Schembri S, Lipworth BJ. The impact of tiotroprium on mortality and exacerbations when added to inhaled corticosteroids and long-acting beta-agonist therapy in COPD. 

. 2012:141(1):81-86. doi: 10.1378/chest.11-0038.

		Kunz LI, Postma DS, Klooster K, Lapperre TS, Vonk JM, et al; GLUCOLD Study Group. Relapse in FEV1 decline after steroid withdrawal in COPD. 

. 2015;148(2):389-396. doi: 10.1378/chest.14-3091.

		D’Urzo A, Donohue JF, Dardose P, Miravitles M, Price D. A re-evaluation of the role of inhaled corticosteroids in the management of patients with chronic obstructive pulmonary disease. 

. 2015;16(12):1845-1860. doi: 10.1517/14656566.2015.1067682.

Pharmacist Rounds

Chronic Obstructive Pulmonary Disease

In the health-system setting, pharmacists must often prioritize their attention to treating the most acute medical condition a patient presents with. However, it is important to also consider opportunities to prevent disease. Vaccines are life-saving medications that may prevent a disease before it ever occurs. This is particularly true for patients who require hospital admission, as they are typically at high risk for contracting these vaccine-preventable illnesses. Are the patients you care for up-to-date? Before your patient is discharged, consider the TIPS mnemonic to remember 4 key vaccines that all adult patients need: 

Tetanus, Diphtheria, and Acellular Pertussis Vaccine

Pertussis is a highly contagious disease caused by the bacterium 

. More commonly known as whooping cough, pertussis is transmitted by respiratory droplets when coughing or sneezing in proximity to others.

 Pertussis most commonly affects infants younger than 1 year. It usually starts with cold-like symptoms such as a runny nose, low-grade fever, mild cough, and apnea. After 1 to 2 weeks, severe uncontrollable coughing with a loud “whooping” sound may emerge and continue for weeks. This cough is potentially lifethreatening because it may lead babies to stop breathing. Many patients who contract pertussis are infected by grandparents, parents, siblings, or caregivers.

The best way to protect against pertussis is for adults to receive 1 dose of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine. The vaccine takes 2 weeks to reach maximum effectiveness. Adults should use caution around young children during this time frame.

 The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommends a single Tdap dose for persons 19 to 64 years. Persons 65 years or older who have or who anticipate having close contact with an infant less than 12 months of age and who previously have not received Tdap should receive a single dose of Tdap to protect against pertussis and reduce the likelihood of transmission.

 Another vaccine called Td protects against tetanus and diphtheria, but not pertussis. A Td booster should be administered every 10 years. In individuals who have never received the Tdap vaccine, Tdap should replace 1 Td booster dose.

Influenza, or the flu, is an acute respiratory illness caused by the influenza virus and is transmitted through respiratory secretions. In the United States, flu season spans from October to May each year, with peak infection rates occurring around January.

 The flu is responsible for significant morbidity and mortality. From October 2014 to April 2015, influenza resulted in approximately 65.5 hospitalizations per 100,000 persons and a mortality rate of 6.4%.

 To aid in the prevention of influenza epidemics, it is recommended that all persons 6 months and older receive the annual influenza vaccine, with rare exception. The only persons for whom influenza vaccination is not recommended are children who are less than 6 months of age or those who have a severe, life-threatening allergy to the influenza vaccine.

 provides insight into the clinical use of available influenza vaccines.

Approximately 900,000 Americans contract pneumococcal pneumonia each year; 5% to 7% of these cases result in death. In addition, 400,000 hospitalizations are attributed to pneumococcal pneumonia annually in the United States.

, the most common pathogen associated with pneumococcal pneumonia, is also a leading cause of invasive diseases such as bacteremia and meningitis. Risk factors that can increase a patient’s likelihood for pneumococcal disease include:

		Chronic illnesses (lung, heart, liver, or kidney disease; asthma; diabetes; or alcoholism)

		Weakened immune system (HIV/ AIDS, cancer, long-term steroid use, or damaged/absent spleen)

		Living in nursing homes or other longterm care facilities

		Cochlear implants or cerebrospinal fluid leaks

There are 2 vaccines available for protection against pneumococcal disease: pneumococcal conjugate vaccine (PCV13 [Prevnar 13]) and pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23]). On September 4, 2015, the CDC ACIP updated its recommendations on the administration intervals between these 2 vaccines.

 provides an overview of the use of these vaccines in adults.

Table 2: Current Recommendations for PCV13 and PPSV23 Use in Adults

* If PPSV23 was given prior, wait 1 year before giving PCV13.

* If PPSV23 was given prior and group B (see below), wait at least 5 years before giving a second dose of PPSV23.

* If PCV13 was given before 65 years, no additional PCV13 is needed

→ wait 1 year (8 weeks if Group B or Group C) → 

 → wait 1 year AND 5 years from prior PPSV23 → 

PCV13 = pneumococcal conjugate vaccine 13; PPSV23 = pneumococcal polysaccharide vaccine 23.

Herpes zoster infection, or shingles, is the reactivation of the dormant varicella- zoster virus located in the sensory ganglia, which typically manifests as a painful, blister-filled rash wrapped around 1 side of the trunk; it can also appear on the face and scalp. Adults 50 years and older are at the greatest risk for shingles; at age 60, the risk sharply increases for developing post-herpetic neuralgia, defined as pain that persists for 90 days or more after the onset of shingles and can last for years.

 Post-herpetic neuralgia can severely limit the quality of life of the individual and affect all 4 health domains: physical, psychological, functional, and social.

A shingles vaccine (Zostavax) is approved by the FDA for persons 50 years and older without contraindications to the vaccine. However, the CDC ACIP guidelines do not recommend the vaccine until a patient is at least 60 years of age. Contraindications include a severe allergy to gelatin, neomycin, or any other vaccine component; immunosuppression; and pregnancy. (Contact dermatitis to neomycin is not considered a contraindication.) Whereas the risk of shingles is increased at age 50, incidence is lower in the 50-to-59 age group than in adults older than 60 years.

 Factors that might lead a health care professional to immunize an individual at age 50 to 59 years include preexisting chronic pain, severe depression, or other comorbid conditions; inability to tolerate treatment medications because of hypersensitivity or interactions with other chronic medications; and occupational considerations.

Clinical Care Focus

In the health-system setting, pharmacists must often prioritize their attention to treating the most acute medical condition a patient presents with; however, it is important to also consider opportunities to prevent disease. 

Adult Immunizations: Are Your Patients Up-to-Date?

Orkambi (lumacaftor/ivacaftor), manufactured by Vertex Pharmaceuticals, is a new combination medication to treat cystic fibrosis (CF) in patients 12 years and older who are homozygous for the F508del mutation on the CF transmembrane conductance regulator CFTR gene. This specific mutation is present in nearly half of patients with CF, and Orkambi is the first medication to treat the underlying cause of CF in this group. CF is a serious genetic disorder that results in the buildup of mucus in the lungs and digestive tract, which causes respiratory, digestive, and other severe complications. Orkambi was approved by the FDA on July 2, 2015. It received breakthrough therapy designation, priority review, and orphan drug designation due to the novel benefits that it could potentially offer.

The CFTR protein is an anion channel at the surface of epithelial cells that transports chloride. The F508del mutation produces a misfolded CFTR protein, which decreases the number of proteins capable of reaching the cell surface. The few proteins that do reach the cell surface have defective gating activity. Lumacaftor improves the stability of F508del- CFTR, allowing more proteins to reach the cell surface. Ivacaftor is a CFTR potentiator, which improves functionality of the protein by increasing the ability of the channel to open. This combination improves chloride transport, thus increasing secretions in the lung and gastrointestinal tract.

Exposure of lumacaftor and ivacaftor was approximately 2 and 3 times higher, respectively, when administered with a highfat meal compared with on an empty stomach. The mean volume of distribution of lumacaftor and ivacaftor is 86 L and 353 L, respectively, and both are approximately 99% bound to plasma proteins. The half-life of lumacaftor and ivacaftor is 26 hours and 9 hours, respectively.

Each Orkambi tablet contains 200 mg lumacaftor and 125 mg ivacaftor. Adults and children 12 years and older should take 2 tablets by mouth every 12 hours with fat-containing foods such as peanut butter, whole-milk dairy products, eggs, nuts, or butter. Patients with moderate hepatic impairment (Child-Pugh Class B) should receive a dose reduction of 2 tablets in the morning and 1 tablet in the evening. Patients with severe hepatic impairment should use Orkambi with caution if it is determined that the benefit of use outweighs the risk, and the dose should be limited to a maximum of 1 tablet twice a day. A dosage reduction during initiation of Orkambi is required for patients receiving strong CYP3A inhibitors (1 tablet daily for 1 week).

The basis for FDA approval of Orkambi were 2 almost identical studies (TRAFFIC and TRANSPORT), both of which were phase 3, randomized, double-blind, parallel group, placebo-controlled studies. Patients were randomized to 1 of 3 groups: lumacaftor 600 mg once daily and ivacaftor 250 mg every 12 hours, lumacaftor 400 mg and ivacaftor 250 mg every 12 hours, or a matched placebo. Patients received the assigned medications in addition to their current prescribed therapies. All 1108 patients were at least 12 years old and homozygous for the F508del CFTR mutation. Because the FDAapproved dosage of Orkambi is lumacaftor 400 mg and ivacaftor 250 mg every 12 hours, the remaining discussion refers to this group as the “treatment group.”

The TRAFFIC and TRANSPORT studies provide similar results, and the following data represent a pooled analysis. The primary outcome of absolute change in predicted forced expiratory volume in 1 second from baseline to week 24 was a mean difference of 2.8% in the treatment versus the placebo groups (95% CI, 1.8-3.8; P <.001). The number of pulmonary exacerbations, a secondary endpoint, was 41.2% in the treatment group versus 67.7% in the placebo group (P <.001). Treatment patients also experienced an increase in body mass index (BMI). The difference versus placebo in absolute change in BMI was 0.24% (95% CI, 0.11- 0.37; P <.001).

According to the TRAFFIC and TRANSPORT studies’ results, 17.3% of treatment patients and 28.6% of placebo patients reported at least 1 serious adverse event (AE), with the most common serious AE being infective pulmonary exacerbation. Other reported AEs were predominantly respiratory-related, such as dyspnea and chest tightness. Additionally, because serious abnormal liver function events have been reported, liver function tests should be administered periodically to monitor alanine aminotransferase, aspartate aminotransferase, and bilirubin.

Each Orkambi tablet is pink and oval-shaped. One box contains 112 tablets enclosed in blister strips. Tablets should be stored at 20° to 25°C (68°-77°F). The wholesale acquisition cost per dose (2 tablets) is $354.80, equating to an annual cost of $259,000 per year.

Jennifer L. Cruz, PharmD, BCPS, is an assistant professor of clinical education at UNC Eshelman School of Pharmacy. Katherine Summers is a PharmD candidate at UNC Eshelman School of Pharmacy.

			Orkambi [package insert]. Cambridge, MA: Vertex Pharmaceuticals; 2015.

			FDA approves new treatment for cystic fibrosis [news release]. Silver Spring, MD: FDA; July 2, 2015. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453565.htm. Accessed August 5, 2015.

			Wainwright CE, Elborn JS, Ramsey BW, et al; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del 

. 2015;373(3):220-231. doi: 10.1056/NEJMoa1409547.

			Orkambi. Lexicomp [online database]. Hudson, OH: Wolters Kluwer Health; July 2015. Accessed August 5, 2015.

			Pricing obtained from Vertex Pharmaceuticals Medical Information representative.

Formulary Drug Review

Orkambi is a new combination medication to treat cystic fibrosis in patients 12 years and older who are homozygous for the F508del mutation on the CF transmembrane conductance regulator CFTR gene.

Orkambi

In September 2015, the hospital pharmacy section of the International Pharmacy Federation (FIP) released the revised Basel Statements. Originally developed in 2008, these standards were created to guide global hospital pharmacy practice. Although certain countries, such as the United States, have had the benefit of a strong association to guide the development and dissemination of professional standards, this is not true for all countries. Because of this variation of practice, FIP has taken the leadership role in developing global standards. The Basel Statements originally consisted of 75 statements describing best practices.

After years of promotion and use worldwide, these standards were updated because new practices have emerged over time that were not incorporated into these statements, some statements came to be seen as too technical, and some statements were similar and could be combined. The updated Basel Statements, which were crafted and approved in Bangkok in 2014, were reduced to 65 statements.

With the release of these global statements, one should consider how to ensure your respective pharmacy department is in compliance with all the various standards, keeping in mind that there are many additional country-specific regulations:

Incorporate compliance review within pharmacy management meetings.

 Most organizations give each work leader responsibility for knowing the standards and ensuring compliance. Although this strategy might be effective, it starts to break down as an organization grows in complexity and merges with other practice sites. Sterile compounding of products, for example, is one area that can benefit from a compliance review, especially when hazardous drugs are included in the discussion. With numerous locations and various leaders, is there harmony in standards and practice? If procedures are reviewed at the departmental level, the opportunity for consistency and compliance is greater. In addition, a review will help with education, the stimulation of new ideas for compliance, and the awareness of deficiencies that might require resources and actions at a senior level.

Incorporate compliance review as part of a learner’s experience.

 Even if you have full compliance or understand your organization’s deficiencies, requiring students or residents to complete a gap analysis is great experience. Not only will this allow for a more thorough understanding of the standards, but it can also create opportunities for discussion or further research. If a deficiency is found, students can be helpful in developing an action plan for resolution.

 One might not understand how this recommendation links to compliance standards, but anyone who has undertaken an American Society of Health-System Pharmacists (ASHP) residency site accreditation will understand that part of the review is of pharmacy services. Surveyors review the departmental operations against ASHP’s best practices. Each survey report will have all identified deficiencies noted. Because these findings go to hospital executives, the hope is that they will assist in the identification of resources to assist with compliance.

Every pharmacy leader needs to be aware of all regulations and standards that impact their organization. In addition, they need to conduct a gap analysis and develop plans for compliance. Integrating this within your department’s leadership team and including learners will promote knowledge of and compliance with these standards.

Stephen F. Eckel, PharmD, MHA, BCPS, FCCP, FASHP, FAPhA, is associate director of pharmacy, University of North Carolina Hospitals, and clinical associate professor and divisional director at the University of North Carolina Eshelman School of Pharmacy.

Editor’s Note

Every pharmacy leader needs to be aware of all regulations and standards that impact their organization.

Global Best Practices in Hospital Pharmacy

Closed-system transfer devices (CSTDs) are an integral component in reducing occupational exposure to hazardous drugs. The goal of a CSTD is to prohibit drug exposure in the environment during all preparation and administration manipulations. These include injecting or disengaging a syringe into a vial, injecting a syringe into an intravenous (IV) bag, spiking a bag, priming an IV set, administering an IV push dose, and disengaging an IV set from other connections or from a patient. They have also been used to prevent transfer of environmental contents into the vial.

The current definition of a CSTD is descriptive, but does not include measurable performance standards. While standards are being developed, the alternative best measurable standards have come from primary literature evaluations. Just as we use evidence-based literature in our drug evaluations, it should also be used in drug device evaluations. CSTDs have been studied and published in primary, peer-reviewed literature using a variety of methods including wipe sampling, visual assessments, and vapor or smoke tests. The methods behind each of these evaluations need to be carefully considered when also evaluating the effectiveness of a CSTD in preventing drug exposure.

Wipe sampling is used to evaluate surface contamination following drug manipulation. These studies look at preparation and administration areas for contamination, signaling how well the CSTD performs in preventing drug exposure and how well the staff is handling the CSTD in those areas. However, wipe studies do have the limitation of not controlling for outside sources of contamination such as drug residue on the outside of drug vials, if those are not assessed during the wipe test. 

Visual assessment of CSTD efficacy has been performed with multiple surrogate markers. One method used is using fluoresceine and ultraviolet light to detect visual fluorescence. In these evaluations, leakage of the CSTD was indicated by visual fluorescence of the fluoresceine. Despite not being a sensitive method of assessment, this is a relatively easy and inexpensive evaluation of a CSTD. A second visual assessment includes smoke or vapor tests. Vapor tests evaluate the ability of the CSTD to retain vapor within the closed system. The results of this type of test can be difficult to quantify and reproduce. A less popular visual assessment method involves the use of radioactive technetium. In these studies, radiation is used to evaluate the level of contamination; however, technetium has a short halflife, which presents challenges to its usefulness and ability to be consistently tested.

The Table lists primary literature evaluating the efficacy of a variety of available CSTDs using many of the methods described above. A variety of methods and surrogate markers have been used to evaluate CSTDs for effectiveness in reducing surface contamination when handling hazardous drugs. When used in combination with other safe handling precautions, they are an integral component to reducing occupational exposure to hazardous drugs. CSTDs need to be treated and evaluated like new drugs by applying the same rigor and methodologies from primary literature studies to fully evaluate their effectiveness.

Danielle A. Griggs, PharmD, MBA, is a PGY-2 health-system pharmacy administration resident at the University of North Carolina Medical Center and a 2016 MS candidate at UNC Eshelman School of Pharmacy.

		Sessink PJM, Rold M, Ryden N. Evaluation of the PhaSeal hazardous drug containment system. 

		Connor TH, Anderson RW, Sessink PJ, Spivey SM. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an IV admixture area. 

		Nygren O, Gustavsson B, Strom L, Eriksson R, Jarneborn L, Friberg A. Exposure to anti-cancer drugs during preparation and administration. Investigations of an open and a closed system. 

		Wick C, Slawson MH, Jorgenson JA, Tyler LS. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. 

		Tans B, Willems L. Comparative contamination study with cyclophosphamide, fluorouracil and ifosfamide: standard versus a proprietary closed-handling system. 

. 2004;10:217-223. doi: 10.1191/1078155204jp140oa.

		Harrison BR, Peters BG, Bing MR. Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed-system drug transfer device versus standard preparation techniques. 

		Nyman HA, Jorgenson JA, Slawson M. Workplace contamination with antineoplastic agents in a new cancer hospital using a closed-system drug transfer device. 

		Sessink PJ, Connor TH, Jorgenson JA, Tyler TG. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. 

. 2011;17(1):39-48. doi: 10.1177/1078155210361431.

		Sessink PJ, Trahan J, Coyne JW. Reduction in surface contamination with cyclophosphamide in 30 US hospital pharmacies following implementation of a closed-system drug transfer device. 

. 2013;48(3):204-212. doi: 10.1310/hpj4803-204.

		De Ausen L, DeFreitas EF, Littleton L, Lustik M. Leakage from closed-system transfer devices as detected by a radioactive tracer. 

. 2013;70(7):619-623. doi: 10.2146/ajhp110678.

		Nygren O, Olofsson E, Johansson L. Spill and leakage using a drug preparing system based on double-filter technology. 

. 2008;52(2):95-98. doi: 10.1093/annhyg/mem067.

		LeGarlantezec P, Rizzo-Padoin N, Aupee O, Lamand V, Broto H, Almeras D. Evaluation of the performance of transfer devices in a closed system using a radioactive solution of [(99m) Tc] [in French]. 

. 2011;69(3):192-191. doi: 10.1016/j.pharma.2011.03.001.

		Zock MD, Soefje S, Rickabaugh K. Evaluation of surface contamination with cyclophosphamide following simulated hazardous drug preparation activites using two closed-system products. 

. 2011;17(1):49-54. doi: 10.1177/1078155210374673.

		Clark BA, Sessink PJ. Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents. 

. 2013;19(2):99-104. doi: 10.1177/1078155212468367.

		Smith ST, Szlaczky MC. Syringe plunger contamination by hazardous drugs: a comparative study. 

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Closed-system transfer devices are an integral component in reducing occupational exposure to hazardous drugs. 