Methylphenidate use in geriatric depression: A systematic review.

OBJECTIVES: Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually required, and many patients may not respond to initial therapy. Thus, there is a need for adjunctive treatment options. The objective of this systematic review is to assess the efficacy and safety of methylphenidate (MPH) in the treatment of geriatric depression. METHODS: PubMed (1946-December 2020) and Embase (1947-December 2020) were queried using the following search terms: geriatrics, aged, geriatric patient, or elderly and depressive disorder, depression, major depression or late-life depression, and MPH. Studies were included if they were a randomized-controlled trial or open-label trial that investigated use of MPH for treatment of depression in adults aged 60 years and older. RESULTS: After screening per the inclusion criteria, five prospective trials were included. All studies found improvement in depressive symptoms with use of MPH or MPH combined with citalopram. Study durations ranged from 8 to 16 weeks and MPH dosing ranged from 5 to 90 mg per day. CONCLUSIONS: Based on the reviewed literature, MPH appears to be most effective when combined with citalopram and used short-term. MPH should be initiated at a low dose and titrated up to 10 or 20 mg per day based on response. Larger, long-term trials are needed to further define the role of MPH in this population.

Standard Versus Extended Duration Direct-Acting Antiviral Therapy in Hepatitis C Patients With Slow Response to Treatment.

BACKGROUND: Response-guided hepatitis C therapy was standard with interferon-based regimens but is not used for direct-acting antivirals (DAAs). Week 4 viral kinetics may predict sustained virological response (SVR) with DAAs, but it is unclear whether extending therapy in slow responders affects outcomes. OBJECTIVES: The primary objective was to compare SVR rates between traditional and extended duration groups. Secondary objectives were to compare SVR rates among subgroups and to determine factors associated with SVR. METHODS: This institutional review board-approved, retrospective, single-center study identified patients with chronic hepatitis C virus (HCV) infection with detectable week 4 HCV RNA who were treated with DAAs. Patients were excluded for early discontinuation, treatment regimen not recommended first-line, or missing HCV RNA labs. Patients were stratified into traditional and extended duration groups. The primary end point was SVR. Secondary end points included factors associated with SVR and rationale for extension of therapy duration. RESULTS: A total of 363 patients were included; 58 (16%) received extended therapy. Patients were primarily genotype 1a (70%) and treatment naïve (80%). More than half had advanced fibrosis or cirrhosis. SVR12 rates were 100% in the extended duration group and 96.7% in the traditional duration group (P = 0.37). There were no associations with SVR and prespecified patient-specific factors. Sample size was limited. CONCLUSION AND RELEVANCE: Based on these findings, a recommendation for extension of therapy cannot be made for patients with detectable HCV RNA at week 4 of treatment at this time. Cost analyses may help guide recommendations to re-treat rare failures versus extend therapy in all slow responders.

Impact of Substance Use Disorder on the Rate of Sustained Virological Response in Veterans With Chronic Hepatitis C Treated With Direct-Acting Antivirals.

BACKGROUND: Substance use disorders (SUDs) are commonly encountered in patients with chronic hepatitis C virus (HCV) infection. It is important to consider the impact of SUDs on HCV treatment. OBJECTIVE: To compare the rate of clinical cure (sustained virological response at least 12 weeks after end of therapy [SVR12]) in veterans with chronic HCV infection treated with direct-acting antivirals (DAAs) with and without ongoing or recent substance use. METHODS: This single-center, retrospective cohort study evaluated 220 HCV patients treated with DAAs based on 2 groups: SUD (ongoing or recent substance use) or non-SUD (without ongoing or recent substance use). The primary end point was SVR12 achievement. Secondary end points included safety, adherence, early discontinuation, SVR12 achievement among SUD subgroups, and enrollment in a SUD treatment program. RESULTS: Most patients were African American men with an average age of 60 years and infected with HCV genotype 1. Almost half of the patients had advanced fibrosis or cirrhosis. There was no difference in SVR12 between groups (SUD: 96.2%; non-SUD: 94.3%; P = 0.54). Overall, 35.5% of patients missed at least 1 dose of DAA therapy, with a significant difference noted between groups (SUD: 44.5%; non-SUD: 26.4%; P = 0.005). Early discontinuation of DAA therapy was similar between groups. SVR12 among SUD subgroups ranged from 92.9% to 100%. In the SUD group, 27.3% of patients were enrolled in a SUD treatment program. Conclusion and Relevance: This study suggests that recent/ongoing substance use does not affect achievement of clinical cure of chronic HCV and reinforces treatment in this patient population.

Incidence of Drug Interactions Identified by Clinical Pharmacists in Veterans Initiating Treatment for Chronic Hepatitis C Infection.

BACKGROUND: Many direct-acting antivirals (DAAs) have drug-drug interactions (DDIs) with the potential to affect efficacy and safety. OBJECTIVE: To describe the incidence and severity of DDIs with DAAs identified by the hepatitis C virus (HCV) clinical pharmacist within a Veterans Affairs health care system. METHODS: This single-center, retrospective cohort study evaluated patients with HCV treated with DAA therapy. Primary end points included the total number of identified DDIs, percentage of patients with at least 1 DDI, mean number of DDIs per patient, and the number of DDIs by severity category. Additional end points included characterization of interacting drugs, clinical consequence of interaction, intervention recommended, acceptance rate of actionable recommendations, and achievement of sustained virological response 12 weeks after treatment (SVR12). RESULTS: A total of 300 patients were included. There were 554 identified DDIs, and 80.3% of patients had at least 1 DDI, with an average of 1.85 DDIs per patient; 76% of the DDIs identified were categorized as either a potentially clinically significant or critical interaction. The most common DDIs involved acid suppression agents (20%). Patient monitoring was the most commonly recommended intervention (59%), followed by dose modification of the interacting medication (30%). There was no difference in SVR12 between patients with at least 1 DDI compared with those with no DDIs (94.8% vs 95.8%; P = 0.73). There were a total of 227 actionable recommendations, with an acceptance rate of 84.1%. CONCLUSIONS: This study suggests that DDIs are prevalent among patients treated with DAAs for HCV. A HCV clinical pharmacist can help optimize patient care by identifying DDIs and recommending interventions to providers.

Value of a Pharmacy-Adjudicated Community Care Prior Authorization Drug Request Service.

Background: Many veterans are eligible to receive prescriptions from community-based pharmacies. Swift and accurate review of prior authorization drug requests by the US Department of Veterans Affairs (VA) pharmacy is necessary to mitigate treatment delays, medication misuse, adverse drug events, medication errors, and unnecessary cost to the health care system. Methods: We performed a retrospective review of community care prior authorization drug requests to assess the direct cost savings achieved through a centralized process and to characterize submitted requests. Results: The centralized community care pharmacy team demonstrated a cost savings of $515,872.31 over 6 months and increased patient safety. Community care prior authorization drug requests had a 46.2% approval rate. Coordination of care took an average of 8 days. Conclusions: Use of a centralized community care pharmacy team could result in significant annual cost savings for the VA. Considering the approval rate seen in this study, VA could allocate resources to educate community-based prescribers about its formulary to increase the approval rate and reduce administrative burden for VA pharmacies and prescribers.

Development of a specialty medication clinical dashboard to improve tumor necrosis factor-α inhibitor safety and adherence monitoring.

PURPOSE: To describe the development of a pilot specialty medication clinical dashboard targeting tumor necrosis factor (TNF)-α inhibitor therapy. SUMMARY: This was a quality improvement project conducted between August 2019 and April 2020. The dashboard was designed with collaboration between clinical pharmacists and specialty providers in rheumatology, gastroenterology, and dermatology. Data was queried from the Veterans Affairs Corporate Data Warehouse. Patients with an active prescription or intravenous order for a TNF-α inhibitor were included. Dashboard flag criteria focused on TNF-α inhibitor safety and adherence monitoring. Flag results from the dashboard were characterized from data captured at a single time point. For 431 patients on TNF-α inhibitor treatment at the institution, 304 flags corresponding to 223 unique patients (51.7%) were identified on the dashboard: 3% of patients had a new infection, 9% had overdue monitoring laboratory tests, 5% had a critical laboratory result, 2% were on 2 biologic agents, 27% were overdue for a refill, 6% had an emergency department visit, and 2% had an inpatient admission. No patients were flagged for heart failure exacerbation or new malignancy. Seventeen percent of patients were prescribed high-dose etanercept or adalimumab, representing a potential annual cost savings of $302,497 if 50% of these patients had their dose successfully reduced to labeled dosing. Opportunities for pharmacist intervention utilizing the dashboard were identified and characterized through chart review of flagged patients. CONCLUSION: Pharmacists have the opportunity to improve safety and adherence for TNF-α inhibitor therapy through use of a specialty medication clinical dashboard. The dashboard should be used in conjunction with collaborative practice protocols.

Identifying and Treating Nonalcoholic Fatty Liver Disease.

NAFLD improves with 7% or greater weight loss.

Economic Outcomes Associated with Safety Interventions by a Pharmacist-Adjudicated Prior Authorization Consult Service.

BACKGROUND: The establishment of a formulary management system ensures that health care professionals work together in an integrated patient care process to promote clinically sound, safe, and cost-effective medication therapy. Pharmacists have a foundational role within this system. A pharmacist-adjudicated prior authorization drug request (PADR) consult service has the potential to optimize drug therapy by decreasing medication misuse, minimizing adverse drug events (ADEs), and preventing medication errors. OBJECTIVES: To (a) determine cost avoidance associated with pharmacist-adjudicated PADR safety interventions within the Durham Veterans Affairs Health Care System and (b) evaluate cost savings associated with pharmacist-adjudicated PADRs not approved due to a safety intervention, evaluate cost avoidance and direct cost savings based on clinical specialty of pharmacist adjudicating PADR, and characterize severity of avoided ADEs. METHODS: Pharmacist-adjudicated PADRs not approved between July 1, 2016, and June 30, 2017, because of safety interventions were retrospectively reviewed. Cost avoidance was determined by multiplying the probability of ADE occurrence in the absence of PADR safety intervention by the estimated cost avoided based on the type of intervention. Direct cost savings was calculated by totaling the cost of requested medications not approved for each PADR and subtracting the cost of recommended alternative therapies and cost of pharmacist PADR review. All potential ADEs avoided were reviewed by a panel of 3 clinical pharmacists to validate ADE classification and ADE probability and severity scores. Descriptive statistics were used for all analyses. RESULTS: Of the 910 PADRs that were not approved during the study period, 96 met inclusion criteria. Pharmacist-adjudicated PADR safety interventions resulted in a total cost avoidance of $24,485.34 (mean = $255.06) and a direct cost savings of $288,695.63 (mean = $3,007.25). The practice settings of anticoagulation and infectious diseases PADRs resulted in the largest contribution to cost avoidance and direct cost savings, respectively. Prevented ADEs were classified as major for 64.6% of the PADRs. CONCLUSIONS: Pharmacist-adjudicated PADR safety reviews resulted in substantial economic benefit and prevention of major ADEs. This analysis supports the pharmacist's role in a formulary management system to optimize medication therapy. DISCLOSURES: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for profit sectors. The authors have nothing to disclose.

Characterizing the Severe Reactions of Parenteral Vitamin K1.

Parenteral vitamin K1 (phytonadione) is used for anticoagulant reversal, and a boxed warning exists with intravenous and intramuscular administration due to the possibility of severe reactions, including fatalities. These reactions resemble hypersensitivity or anaphylaxis, including anaphylactoid reaction, and have led to shock and cardiac and/or respiratory arrest. The objective of this review is to summarize the available literature detailing the anaphylactic/anaphylactoid reactions with parenteral vitamin K1 in order to better characterize the reaction and provide a more in-depth understanding of its importance. A comprehensive literature search of MEDLINE (1946 to June 2016) and EMBASE (1947 to June 2016) was conducted using the terms vitamin K1, phytonadione, phytomenadione, vitamin K group, anaphylaxis, polyoxyethylated castor oil, and cremophor. A total of 2 retrospective surveillance studies, 2 retrospective cohort studies, and 17 case reports were identified for inclusion and assessment. Based on a review of the literature, use of parenteral vitamin K1 may result in severe hypotension, bradycardia or tachycardia, dyspnea, bronchospasm, cardiac arrest, and death. These reactions are most consistent with a nonimmune-mediated anaphylactoid mechanism. It appears that intravenous administration is more frequently associated with these reactions and occurs at an incidence of 3 per 10 000 doses of intravenous vitamin K1. The solubilizer may also increase the risk of adverse reactions, which occurred in patients with and without previous exposure to vitamin K1. Although there are known factors that increase the risk of an adverse drug event occurring, reactions have been reported despite all precautions being properly followed.

Pharmacy resident involvement in prior-authorization drug request adjudication.

PURPOSE: Results of a study to determine economic outcomes of pharmacy residents' involvement in prior-authorization drug request (PADR) adjudication within a Veterans Affairs (VA) healthcare system are reported. METHODS: A retrospective review was conducted to identify PADRs adjudicated by pharmacy residents under a preceptor's supervision during the 2015-16 residency year. Only PADRs that were not approved as submitted (i.e., only those requiring formulary intervention) and that met other inclusion criteria were included in the analysis. Prior-authorization requests and adjudication decisions were characterized, and cost savings resulting from those decisions were calculated. RESULTS: Of the total of 752 PADRs adjudicated by 6 pharmacy residents during the study period, 42 met the inclusion criteria. About 90% of included PADRs were categorized as general medicine requests, and 9.5% were for oncology medications. The most common rationale for PADR nonapproval (cited in 60% of requests) was the availability of a preferred formulary alternative; the remainder of nonapprovals were due to medication safety concerns (e.g., contraindication to therapy, drug interaction potential, likelihood of adverse drug event resulting in patient harm, history of allergy to requested medication). Resident adjudication of PADRs resulted in total direct cost savings of $169,877.53 over the 12-month period, a mean of $4,044.70 per request. CONCLUSION: Pharmacy residents' involvement in adjudicating PADRs at a VA healthcare system resulted in substantial cost savings over the course of the residency year.

Outcomes of Pharmacy-Led Hepatitis C Direct-Acting Antiviral Utilization Management at a Veterans Affairs Medical Center.

BACKGROUND: The Veterans Affairs Health (VA) Administration has reported hepatitis C virus (HCV) infection rates among veterans to be twice that of the general U.S population. New HCV direct-acting antiviral (DAA) treatment options offer superior sustained virologic response (SVR) rates, improved side-effect profiles, and shortened treatment courses; yet, these new HCV DAAs are expensive, and utilization management strategies are needed to optimize use and improve clinical outcomes. A VA medical center uses pharmacist-led HCV DAA utilization management strategies that includes clinical guidance, optimizing operational flow, budget tracking and forecasting, and patient outcomes tracking. OBJECTIVE: To assess the economic and clinical outcomes of pharmacy-led HCV DAA utilization management in a VA medical center. METHODS: This was a single-center, retrospective cohort study. Patient electronic health records and the hepatitis C DAA outcomes tracking database were reviewed at a VA medical center. Patients with an HCV DAA prior authorization drug request and therapy initiated between October 1, 2014, and September 30, 2015, were included. The primary endpoint was the ratio of drug spend to cure rate calculated as the total dollars spent to the number of patients achieving SVR at least 12 weeks from end of treatment. Secondary endpoints included economic, clinical, and safety outcomes. RESULTS: A total of 372 patients were included in the study. The overall cost ratio of total drug spend to cure rate was $40,135.22. The overall cure rate was 94.1%, with no discontinuations due to treatment failure. The ratio of drug spend to cure rate was $41,907.35 and $38,430.77 in cirrhotic and noncirrhotic patients, respectively, and $39,481.62 and $39,178.74 in treatment-experienced and naive patients, respectively. Ten patients discontinued therapy because of the adverse effects of anemia, nausea, vomiting, and anxiety. The medication possession ratio was 98.7% (± 0.13) for all patients included in the study. CONCLUSIONS: This study suggests that pharmacist-led HCV DAA utilization management is an important factor in costs and cure rates. Utilization management strategies are valuable to help adequately manage patients with chronic hepatitis C (CHC) and may allow practitioners to maximize available funding for CHC, while maintaining high efficacy and safety. DISCLOSURES: No outside funding supported this research. The authors have no conflicts of interest to report. Study concept and design were contributed primarily by Britt, along with Hashem, Brown, and Yang. Yang took the lead in data collection, along with Britt, and data interpretation was performed by all the authors. The manuscript was written and revised by Yang, Britt, Brown, and Hashem.

Memantine for the Treatment of Phantom Limb Pain: A Systematic Review.

Phantom limb pain (PLP) occurs in up to 85% of patients who have undergone an amputation and remains difficult to treat. Memantine is a N-Methyl-d-aspartate receptor antagonist that has shown benefit in pain syndromes. The objective of this systematic review is to evaluate the evidence for the use of memantine in the treatment of acute and chronic PLP. MEDLINE (1956 to May 2016) and Embase (1957 to May 2016) were queried for articles that characterized the clinical outcomes of patient(s) treated with memantine for PLP. The initial search identified 185 studies and case reports. After screening, eight articles were included. One prospective study, a case report, and two case series demonstrated benefit with memantine in the treatment of acute PLP. However, in chronic PLP that persisted for over 1 year, four prospective studies failed to demonstrate significant analgesic effects with memantine. Memantine was well tolerated in all studies. Memantine appears to be a reasonable option to trial in a patient with a recent amputation or who has failed or cannot tolerate other analgesics. Additional research is needed to further determine the role of memantine in the treatment and prevention of PLP and to identify the population most likely to gain benefit.

Influence of Successful Chronic Hepatitis C Virus Treatment with Ledipasvir/Sofosbuvir on Warfarin Dosing Requirements in Four Veterans.

STUDY OBJECTIVE: To describe international normalized ratio (INR) trends and warfarin dosage adjustments required for four veterans who were receiving warfarin therapy and started treatment for hepatitis C virus (HCV) with ledipasvir/sofosbuvir with or without ribavirin. DESIGN: Case series. SETTING: Pharmacist-led anticoagulation clinic in a Veterans Affairs Health Care System. PATIENTS: Four patients aged 59-66 years who were receiving warfarin and had stable, therapeutic INRs and started ledipasvir/sofosbuvir therapy with or without ribavirin for HCV infection. MEASUREMENTS AND MAIN RESULTS: All four patients developed subtherapeutic INRs after the addition of ledipasvir/sofosbuvir with or without ribavirin. An increase in weekly warfarin dose ranging from 14-67% was required, with changes in warfarin doses starting 2-3 weeks after ledipasvir/sofosbuvir initiation. Two patients required dose reductions after HCV treatment completion, whereas the other two did not. Use of the Drug Interaction Probability Scale indicated that the interaction between warfarin and ledipasvir/sofosbuvir was doubtful (score of 1 [two patients]) or possible (score of 4 [two patients]). The mechanism of this interaction is unknown but may be related to improvements in hepatic function during HCV treatment. CONCLUSION: To our knowledge, this is the first case series describing a possible drug interaction between warfarin and ledipasvir/sofosbuvir (with or without ribavirin). Close monitoring is warranted when ledipasvir/sofosbuvir is initiated in patients receiving anticoagulation therapy with warfarin, especially those with evidence of cirrhosis prior to treatment. This is particularly important in the first month after starting treatment and the first month after completion. Failure to monitor and achieve therapeutic INR after HCV therapy completion may have the potential to result in adverse outcomes.

Economic Outcomes Associated with a Pharmacist-Adjudicated Formulary Consult Service in a Veterans Affairs Medical Center.

BACKGROUND: Several cost analysis studies have been conducted looking at clinical and economic outcomes associated with clinical pharmacist services in a variety of health care settings. However, there is a paucity of data regarding the economic impact of clinical pharmacist involvement in formulary management at the hospital level. OBJECTIVE: To evaluate economic outcomes of a pharmacist-adjudicated formulary management consult service in a Veterans Affairs (VA) medical center offering outpatient and inpatient services. METHODS: This VA medical center uses a pharmacist-adjudicated formulary management system for review of restricted drug consults. A retrospective review of electronic medical records was conducted to identify restricted drug consults at this institution between January 1, 2014, and March 31, 2014. Only restricted drug consults that were not approved were included for evaluation in order to best characterize the effects of formulary interventions by pharmacists. Economic outcomes were determined as direct cost savings by comparing the cost of requested drug with the recommended drug and accounting for the cost of pharmacist review. Characteristics of consults that were not approved and pharmacist rationale were also evaluated. RESULTS: Of 1,802 restricted drug consults adjudicated by a pharmacist during the study period, 198 consults in 190 individual patients met criteria for inclusion and were evaluated. The most commonly requested indications were dyslipidemia, pain, and diabetes, while the most commonly requested drugs were rosuvastatin, insulin pens, tamsulosin, varenicline, ezetimibe, and rivaroxaban. The majority of consults were requested for outpatient use. Total cost savings among 195 evaluable consults was $420,324.05, while mean cost savings per consult was $2,229.43 (range: -$3,009.27-$65,982.36). The highest cost savings were seen with outpatient use. CONCLUSIONS: A pharmacist-adjudicated formulary consult service in a VA medical center was associated with a substantial cost savings after adjustment for cost of pharmacist review. Future research should assess clinical outcomes associated with a restrictive formulary management system. DISCLOSURES: No outside funding supported this study. None of the authors report any financial interests or potential conflict of interest with regard to this work. Study concept and design were created by all authors. Data were collected and interpreted by Britt, with input from all authors. The manuscript was written by Britt and revised by all authors.