Evaluating the prescribing and monitoring of medications associated with QTc-prolongation in the ambulatory care setting.

RATIONALE: Little is known about the prescribing of medications with potential to cause QTc-prolongation in the ambulatory care settings. Understanding real-world prescribing of QTc-prolonging medications and actions taken to mitigate this risk will help guide strategies to optimize safety and appropriate prescribing among ambulatory patients. OBJECTIVE: To evaluate the frequency of clinician action taken to monitor and mitigate modifiable risk factors for QTc-prolongation when indicated. METHODS: This retrospective, cross-sectional study evaluated clinician action at the time of prescribing prespecified medications with potential to prolong QTc in adult patients in primary care. The index date was defined as the date the medication was ordered. Electronic health record (EHR) data were evaluated to assess patient, clinician and visit characteristics. Clinician action was determined if baseline or follow-up monitoring was ordered or if action was taken to mitigate modifiable risk factors (laboratory abnormalities or electrocardiogram [ECG] monitoring) within 48 h of prescribing a medication with QTc-prolonging risk. Descriptive statistics were used to describe current practice. RESULTS: A total of 399 prescriptions were prescribed to 386 patients, with a mean age of 51 ± 18 years, during March 2021 from a single-centre, multisite health system. Of these, 17 (4%) patients had a known history of QTc-prolongation, 170 (44%) did not have a documented history of QTc-prolongation and 199 (52%) had an unknown history (no ECG documented). Thirty-nine patients (10%) had at least one laboratory-related risk factor at the time of prescribing, specifically hypokalemia (16 patients), hypomagnesemia (8 patients) or hypocalcemia (19 patients). Of these 39 patients with laboratory risk factors, only 6 patients (15%) had their risk acknowledged or addressed by a clinician. Additionally, eight patients' most recent QTc was ≥500 ms and none had an ECG checked at the time the prescription was ordered. CONCLUSION: Despite national recommendations, medication monitoring and risk mitigation is infrequent when prescribing QTc-prolonging medications in the ambulatory care setting. These findings call for additional research to better understand this gap, including reasons for the gap and consequences on patient outcomes.

Using Real-World Data to Inform Value-Based Contracts for Cell and Gene Therapies in Medicaid.

OBJECTIVE: High upfront costs and long-term benefit uncertainties of gene therapies challenge Medicaid budgets, making value-based contracts a potential solution. However, value-based contract design is hindered by cost-offset uncertainty. The aim of this study is to determine actual cost-offsets for valoctocogene roxaparvovec (hemophilia A) and etranacogene dezaparvovec (hemophilia B) from Colorado Medicaid's perspective, defining payback periods and its uncertainty from the perspective of Colorado Medicaid. METHODS: This cost analysis used 2018-2022 data from the Colorado Department of Health Care Policy & Financing to determine standard-of-care costs and employed cost simulation models to estimate the cost of Medicaid if patients switched to gene therapy versus if they did not. Data encompassed medical and pharmacy expenses of Colorado Medicaid enrollees. Identified cohorts were patients aged 18+ with ICD-10-CM codes D66 (hemophilia A) and D67 (hemophilia B). Severe hemophilia A required ≥ 6 claims per year for factor therapies or emicizumab, while moderate/severe hemophilia B necessitated ≥ 4 claims per year for factor therapies. Patients were included in the cohort in the year they first met the criteria and were subsequently retained in the cohort for the duration of the observation period. Standard-of-care included factor VIII replacement therapy/emicizumab for hemophilia A and factor IX replacement therapies for hemophilia B. Simulated patients received valoctocogene roxaparvovec or etranacogene dezaparvovec. Main measures were annual standard-of-care costs, cost offset, and breakeven time when using gene therapies. RESULTS: Colorado Medicaid's standard-of-care costs for hemophilia A and B were $426,000 [standard deviation (SD) $353,000] and $546,000 (SD $542,000) annually, respectively. Substituting standard-of-care with gene therapy for eligible patients yielded 8-year and 6-year average breakeven times, using real-world costs, compared with 5 years with published economic evaluation costs. Substantial variability in real-world standard-of-care costs resulted in a 48% and 59% probability of breakeven within 10 years for hemophilia A and B, respectively. Altering eligibility criteria significantly influenced breakeven time. CONCLUSIONS: Real-world data indicates substantial uncertainty and extended payback periods for gene therapy costs. Utilizing real-world data, Medicaid can negotiate value-based contracts to manage budget fluctuations, share risk with manufacturers, and enhance patient access to innovative treatments.

Emergency contraception in a historic southern city: Mystery caller study in Birmingham, Alabama.

BACKGROUND: Alabama's Human Life Protection Act (the Act) signed in 2019 became law in 2022, making provision of abortion a felony offense. OBJECTIVE: In 2020, we assessed the accessibility of emergency contraception (EC) pills in Birmingham, Alabama prior to the Act's enactment given the probable increased need for EC access due to abortion criminalization. STUDY DESIGN: Pharmacy staff were asked about availability, price, location, and identification requirements to obtain EC. RESULTS: Of 69 pharmacies, 59% had levonorgestrel EC and none had ulipristal acetate EC available. CONCLUSION: There are persistent barriers to EC accessibility that should be addressed as abortion is increasingly restricted.

Sustained Effect of Clinical Decision Support for Heart Failure: A Natural Experiment Using Implementation Science.

OBJECTIVES: In a randomized controlled trial, we found that applying implementation science (IS) methods and best practices in clinical decision support (CDS) design to create a locally customized, "enhanced" CDS significantly improved evidence-based prescribing of ß blockers (BB) for heart failure compared with an unmodified commercially available CDS. At trial conclusion, the enhanced CDS was expanded to all sites. The purpose of this study was to evaluate the real-world sustained effect of the enhanced CDS compared with the commercial CDS. METHODS: In this natural experiment of 28 primary care clinics, we compared clinics exposed to the commercial CDS (preperiod) to clinics exposed to the enhanced CDS (both periods). The primary effectiveness outcome was the proportion of alerts resulting in a BB prescription. Secondary outcomes included patient reach and clinician adoption (dismissals). RESULTS: There were 367 alerts for 183 unique patients and 171 unique clinicians (pre: March 2019-August 2019; post: October 2019-March 2020). The enhanced CDS increased prescribing by 26.1% compared with the commercial (95% confidence interval [CI]: 17.0-35.1%), which is consistent with the 24% increase in the previous study. The odds of adopting the enhanced CDS was 81% compared with 29% with the commercial (odds ratio: 4.17, 95% CI: 1.96-8.85). The enhanced CDS adoption and effectiveness rates were 62 and 14% in the preperiod and 92 and 10% in the postperiod. CONCLUSION: Applying IS methods with CDS best practices was associated with improved and sustained clinician adoption and effectiveness compared with a commercially available CDS tool.

Evaluating the Effect of COVID-19 on Outpatient Opioid Utilization Among Health First Colorado Members and a National Non-Medicaid Cohort: An Interrupted Time Series Analysis.

Objective: COVID-19, coinciding with the opioid epidemic in the United States, has had significant impacts on health-care utilization. While mixed, early analyses signaled a potential resurgence in opioid use following the pandemic. The primary study objective was to assess the association of the COVID-19 pandemic with opioid utilization among Health First Colorado (Colorado's Medicaid Program) members and a non-Medicaid managed care cohort who did not have a diagnosis of cancer or sickle cell disease. Patients and Methods: Using an interrupted time series and segmented regression analysis, this population-level study assessed the association of the COVID-19 pandemic on prescribed utilization of long- and short-acting opioid analgesics among Health First Colorado members and a random sample of non-Medicaid managed care members. Pharmacy claims data for both cohorts were assessed between October 1, 2018, and September 30, 2021, with April 2020 identified as the interruption of interest. We evaluated the following monthly opioid use measures separately for short-acting and long-acting opioids: number of members filling an opioid, total fills, and total days supplied. Results: Short- and long-acting opioid utilization was significantly decreasing among Health First Colorado members in the 18 months prior to the start of COVID-19. After the onset of the pandemic, utilization stabilized and slopes were not significantly different from zero. Among the non-Medicaid managed care cohort, short- and long-acting opioid utilization significantly decreased in the 18 months leading up to the onset of the pandemic. After the onset of the pandemic, utilization of long-acting opioids stabilized, while utilization of short-acting opioids significantly increased. Conclusion: While we observed an increase in opioid utilization measures post-pandemic in the non-Medicaid managed care cohort, a similar increase was not observed in Health First Colorado members suggesting that thoughtful opioid policies put in place pre-pandemic may have been effective at controlling potential inappropriate opioid utilization.

Comparative effectiveness of generic commercial versus locally customized clinical decision support tools to reduce prescription of nonsteroidal anti-inflammatory drugs for patients with heart failure.

OBJECTIVE: To compare the effectiveness of 2 clinical decision support (CDS) tools to avoid prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with heart failure (HF): a "commercial" and a locally "customized" alert. METHODS: We conducted a retrospective cohort study of 2 CDS tools implemented within a large integrated health system. The commercial CDS tool was designed according to third-party drug content and EHR vendor specifications. The customized CDS tool underwent a user-centered design process informed by implementation science principles, with input from a cross disciplinary team. The customized CDS tool replaced the commercial CDS tool. Data were collected from the electronic health record via analytic reports and manual chart review. The primary outcome was effectiveness, defined as whether the clinician changed their behavior and did not prescribe an NSAID. RESULTS: A random sample of 366 alerts (183 per CDS tool) was evaluated that represented 355 unique patients. The commercial CDS tool was effective for 7 of 172 (4%) patients, while the customized CDS tool was effective for 81 of 183 (44%) patients. After adjusting for age, chronic kidney disease, ejection fraction, NYHA class, concurrent prescription of an opioid or acetaminophen, visit type (inpatient or outpatient), and clinician specialty, the customized alerts were at 24.3 times greater odds of effectiveness compared to the commercial alerts (OR: 24.3 CI: 10.20-58.06). CONCLUSION: Investing additional resources to customize a CDS tool resulted in a CDS tool that was more effective at reducing the total number of NSAID orders placed for patients with HF compared to a commercially available CDS tool.

Association between Substance Misuse and Outcomes in Critically III Patients with Pneumonia.

Rationale: In patients with pneumonia requiring intensive care unit (ICU) admission, alcohol misuse is associated with increased mortality, but the relationship between other commonly misused substances and mortality is unknown. Objectives: We sought to establish whether alcohol misuse, cannabis misuse, opioid misuse, stimulant misuse, or misuse of more than one of these substances was associated with differences in mortality among ICU patients with pneumonia. Methods: This was a retrospective cohort study of hospitals participating in the Premier Healthcare Database between 2010 and 2017. Patients were included if they had a primary or secondary diagnosis of pneumonia and received antibiotics or antivirals within 1 day of admission. Substance misuse related to alcohol, cannabis, stimulants, and opioids, or more than one substance, were identified from the International Classification of Diseases (Ninth and Tenth Editions). The associations between substance misuse and in-hospital mortality were the primary outcomes of interest. Secondary outcomes included the measured associations between substance misuse disorders and mechanical ventilation, as well as vasopressor and continuous paralytic administration. Analyses were conducted with multivariable mixed-effects logistic regression modeling adjusting for age, comorbidities, and hospital characteristics. Results: A total of 167,095 ICU patients met inclusion criteria for pneumonia. Misuse of alcohol was present in 5.0%, cannabis misuse in 0.6%, opioid misuse in 1.5%, stimulant misuse in 0.6%, and misuse of more than one substance in 1.2%. No evidence of substance misuse was found in 91.1% of patients. In unadjusted analyses, alcohol misuse was associated with increased in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.19), whereas opioid misuse was associated with decreased in-hospital mortality (OR, 0.46; 95% CI, 0.39-0.53) compared with no substance misuse. These findings persisted in adjusted analyses. Although cannabis, stimulant, and more than one substance misuse (a majority of which were alcohol in combination with another substance) were associated with lower odds for in-hospital mortality in unadjusted analyses, these relationships were not consistently present after adjustment. Conclusions: In this study of ICU patients hospitalized with severe pneumonia, substance misuse subtypes were associated with different effects on mortality. Although administrative data can provide epidemiologic insight regarding substance misuse and pneumonia outcomes, biases inherent to these data should be considered when interpreting results.

Evaluation of an opioid pain teleconsultation service to address the opioid overdose epidemic in Colorado: A Health First Colorado demonstration project.

BACKGROUND: Since the mid-1990s, more than 500,000 deaths have been attributed to the opioid overdose epidemic, which has created a serious national crisis affecting public health and social and economic welfare. To mitigate these opioid-related overdoses and deaths, interventions targeted at both the patient and community level are needed. OBJECTIVE: This demonstration project sought to determine whether implementation of a provider-to-provider opioid pain teleconsultation service with a pain specialist was correlated with a reduction in inappropriate opioid use and improve health outcomes. METHODS: Individual-level claims data for Health First Colorado Medicaid members were collected between March 1, 2017, and September 30, 2021, for individuals who triggered a provider-to-provider pain management teleconsultation based on receipt of a prescription for an opioid where the member was receiving a high-dose opioid (n = 125) or was opioid-naive (n = 819). The primary outcome measures were a patient's opioid dose less than 200 morphine milligram equivalent (MME) by 6 months after the consult if consult was triggered for high-dose use or discontinuation of an opioid by 12 weeks after consult if the consult was triggered for opioid naivety. Secondary opioid-related health outcomes were also assessed. RESULTS: In the high-dose opioid cohort, 87% of the members had their monthly average MME reduced to less than 200 by 180 days after their consult. More than half of the opioid-naive group had discontinued their opioid by 90 days after their consult. CONCLUSION: Results indicate that provider-to-provider teleconsultation services with a pain specialist can be an effective intervention at reducing total inappropriate opioid use.

Medications Associated with Occurrence of Urinary Tract Infections in Patients with Diabetes, Heart Failure or Both.

BACKGROUND: Evidence broadly identifying medications newly-initiated prior to the occurrence of a urinary tract infection (UTI) in patients with diabetes, heart failure, or both of these conditions is lacking. OBJECTIVE: The aim was to broadly assess medication filling patterns and incidence of UTIs to identify medications or medication classes most frequently initiated prior to UTI occurrence. METHODS: This retrospective study utilizing a national claims database examined medications commonly initiated in the six months preceding a UTI in patients with diabetes and/or heart failure. Patients with a new diagnosis of UTI, a diagnosis of diabetes and/or heart failure, continuous enrollment in the database for at least 12 months prior to the index UTI occurrence, and who initiated at least one new medication in the 6 months preceding the index UTI were evaluated. RESULTS: 12,744 patients met criteria: 10,626 (83.4%) had a diagnosis of diabetes, 838 (6.6%) had a diagnosis of heart failure, and 1,280 (10.0%) had diagnoses for both. Opioids were the most commonly filled medication class among all three groups. Medications from the SGLT2i class were the twelfth, eleventh, and eighteenth most common medications filled prior to the index UTI for all patients, patients with diabetes, and patients with diabetes and heart failure, respectively. CONCLUSION: Opioids were by far the most commonly initiated medication class in the 6 months prior to UTI incidence in patients with diabetes and/or heart failure. SGLT2i medications were not commonly initiated in the 6 months prior to the occurrence of a UTI.

Evaluation of safety and efficacy outcomes of direct oral anticoagulants versus warfarin in normal and extreme body weights for the treatment of atrial fibrillation or venous thromboembolism.

Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to measure the impact of DOACs compared to warfarin on safety and efficacy outcomes in extreme body weight patients. This multi-center, health system, retrospective study examined the outcomes of patients with all body weights and extreme body weights prescribed a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban) or warfarin for atrial fibrillation or venous thromboembolism over a 9-year period. The primary outcome was a composite of thromboembolism, symptomatic recurrent VTE, or severe bleeding; analyzed by pre-determined BMI cutoffs. A total of 19,697 patients were included in the study: 11,604 in the DOAC group and in the 8093 in the warfarin group. 295 patients were underweight and 9108 patients were pre-obese to obese class 3. After adjusting for potential confounders, warfarin patients had higher odds of experiencing the composite outcome compared to DOAC patients (OR 1.337, 95% CI 1.212-1.475). Additionally, obese patients were 24.6% more likely to experience the outcome compared to normal BMI patients. Adjusted modeling showed that warfarin patients experienced higher bleed rates compared to DOAC patients (OR 1.432, 95% CI 1.266-1.620). Obese patients were less likely to be diagnosed with a bleed (OR 0.749, 95% CI 0.658-0.854), and underweight patients were more likely to be diagnosed with a bleed (OR 1.522, 95% CI 1.095-2.115) compared to normal BMI patients. In conclusion, DOACs for atrial fibrillation or VTE in patients with extreme body weights appear safe and effective when compared to warfarin.

Evaluation of Insulin Infusion Rates for the Treatment of Diabetic Ketoacidosis in the Emergency Department.

Introduction: There is minimal literature to support the appropriate dosing for the initiation of IV regular insulin therapy in DKA patients. A 0.1 unit/kg bolus followed by 0.1 units/kg/hour or 0.14 units/kg/hour is commonly utilized and recommended in guidelines. Objective: We sought to assess clinical and safety outcomes associated with various insulin infusion starting doses in patients diagnosed with DKA in the emergency department in an effort to help guide prescribing. Methods: A retrospective cohort study was conducted within an academic emergency department and included patients who received continuous infusion regular insulin with an ICD-10 code for DKA between January 2016 and January 2019. A predictive regression model was applied to test if predefined lab values influenced the starting insulin infusion rates. Clinical and safety outcomes were evaluated by starting insulin infusion rate. Data was analyzed based on starting insulin infusion rates. Results: 347 patients met inclusion criteria with 92 (26.5%) patients receiving <0.07 units/kg/hr, 123 (35.4%) patients receiving 0.07 to 0.099 units/kg/hr, 123 (35.4%) patients receiving 0.10 to 0.139 units/kg/hr, and 9 (2.6%) patients receiving ≥0.14 units/kg/hr. After adjusting for baseline labs, glucose was the only significant predictor of the initial infusion rate (p < 0.001). For every 100 mg/dL increase in the baseline glucose value, the initial infusion rate increased by 0.005 units/kg/hr. There was no difference between insulin starting infusion rates and length of stay, rates of hypoglycemia, hypokalemia, or dysrhythmias. Conclusion: Glucose levels significantly influenced the insulin starting infusion rate, with no identified differences in adverse effects or clinical outcomes.

Evaluation of the Clinical Impact of Thromboprophylaxis in Patients With COVID-19 Following Hospital Discharge.

BACKGROUND: Data are limited regarding the incidence of thromboembolism post-hospital discharge among COVID-19 patients. Guidelines addressing the role of extended thromboprophylaxis for COVID-19 patients are limited and conflicting. OBJECTIVE: The purpose of this study was to evaluate the incidence of post-discharge thromboembolic and bleeding events and the role of thromboprophylaxis among COVID-19 patients. METHODS: A retrospective analysis was conducted of hospitalized patients with symptomatic COVID-19 infection who were discharged from a University of Colorado Health (UCHealth) hospital between March 1, 2020, and October 31, 2020. The primary outcome was objectively confirmed thromboembolism within 35 days post-discharge. The main secondary outcome was the incidence of bleeding events within 35 days post-discharge. Outcomes were compared between those who received extended prophylaxis and those who did not. RESULTS: A total of 1171 patients met the study criteria. A total of 13 (1.1%) of patients had a documented thromboembolic event and 10 (0.9%) patients had a documented bleeding event within 35 days post-discharge. None of the 132 patients who received extended prophylaxis had a thromboembolic event compared to 13 of 1039 who did not receive extended prophylaxis (0 and 1.3%, respectively; P = .383). The incidence of bleeding was higher among patients who received extended prophylaxis compared to those who did not (3.0% vs 0.6%, P = .019). CONCLUSIONS AND RELEVANCE: These results suggest that post-discharge extended prophylaxis may be beneficial for select COVID-19 patients, while carefully weighing the risk of bleeding. Application of our findings may assist institutions in development of thromboprophylaxis protocols for discharged COVID-19 patients.

Association Between Vasopressin Rebranding and Utilization in Patients With Septic Shock.

OBJECTIVES: Vasopressin is suggested as an adjunct to norepinephrine in patients with septic shock. However, after vasopressin was rebranded in November 2014, its cost exponentially increased. Utilization patterns of vasopressin after its rebranding are unclear. The objective of this study was to determine if there is an association between the rebranding of vasopressin in November 2014 and its utilization in vasopressor-dependent patients with severe sepsis or septic shock. DESIGN: Retrospective, multicenter, database study between January 2010 and March 2017. SETTING: Premier Healthcare Database hospitals. PATIENTS: Adult patients admitted to an ICU with severe sepsis or septic shock, who received at least one vasoactive agent for two or more calendar days were included. INTERVENTIONS: The proportion of patients who received vasopressin and vasopressin cost was assessed before and after rebranding, and evaluated with segmented regression. MEASUREMENTS AND MAIN RESULTS: Among 294,733 patients (mean age, 66 ± 15 yr), 27.8% received vasopressin, and ICU mortality was 26.5%. The proportion of patients receiving vasopressin was higher after rebranding (31.2% postrebranding vs 25.8% prerebranding). Before vasopressin rebranding, the quarterly proportion of patients who received vasopressin had an increasing slope (prerebranding slope 0.41% [95% CI, 0.35-0.46%]), with no difference in slope detected after vasopressin rebranding (postrebranding slope, 0.47% [95% CI, 0.29-0.64%]). After vasopressin rebranding, mean vasopressin cost per patient was higher ($527 ± 1,130 vs $77 ± 160), and the quarterly slope of vasopressin cost was higher (change in slope $77.18 [95% CI, $75.73-78.61]). Total vasopressin billed cost postrebranding continually increased by ~$294,276 per quarter from less than $500,000 in Q4 2014 to over $3,000,000 in Q1 2017. CONCLUSIONS: After vasopressin rebranding, utilization continued to increase quarterly despite a significant increase in vasopressin cost. Vasopressin appeared to have price inelastic demand in septic shock.

Economic Impact of Coverage Expansion for Non-invasive Prenatal Testing Through a Performance-Based Risk-Sharing Agreement.

BACKGROUND: Harvard Pilgrim Health Care expanded coverage for non-invasive prenatal testing (NIPT) to include all pregnant, single-gestation women aged < 35 years, through a performance-based risk-sharing (PBRS) agreement with Illumina to offset costs from coverage expansion. NIPT analyzes cell-free DNA fragments from a maternal blood sample to screen for fetal aneuploidies and is considered a more accurate screening method than conventional serum biochemical screening and nuchal translucency ultrasound-based approaches. OBJECTIVE: This study assessed the impact of NIPT coverage expansion on prenatal screening strategies and payer expenditures. METHODS: This was a real-world comparison of utilization and expenditures of prenatal screening and diagnostic testing in pregnant women aged < 35 years pre- (1 March 2016-28 February 2018) and post- (1 March 2018-30 September 2019) coverage expansion. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were estimated to compare changes in utilization of conventional and NIPT-based prenatal screening methods. Change in per member per month (PMPM) expenditures in $US year 2020 were assessed post-coverage expansion using a budget impact model. RESULTS: A total of 5041 and 4109 distinct pregnancies were identified in pre- and post-coverage expansion periods, respectively. Mean ± standard deviation maternal age was consistent between pre- and post-coverage expansion periods (30.35 ± 3.35 and 30.33 ± 3.28, respectively). Screening orders for conventional methods decreased, with an adjusted IRR in the post-expansion period of 0.87 (95% CI 0.85-0.90) times the rate in the pre-expansion period; orders for NIPT increased, with an adjusted IRR in the post-expansion period of 1.41 (95% CI 1.32-1.51) times the rate in the pre-expansion period. Invasive diagnostic testing was low at baseline (1.0%) and did not change post-coverage expansion. The change in PMPM is estimated at $US0.026 post-coverage expansion. CONCLUSION: The PBRS agreement to expand NIPT coverage for women aged < 35 years was associated with an increase in NIPT utilization, decreases in conventional screening methods, and a modest increase in PMPM expenditures.

Comparative effectiveness of direct oral anticoagulants and warfarin for the treatment of left ventricular thrombus.

Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis, resulting in increased risk of thromboembolic complications. Observational studies support the general safety and efficacy of warfarin for this indication. Limited data exists regarding the use of direct oral anticoagulants (DOACs) for LV thrombus. This retrospective cohort study sought to compare the incidence of thromboembolic events, bleeding rates, and blood product administration in patients receiving a DOAC versus warfarin. A total of 949 patients met inclusion, 180 (19%) received a DOAC and 769 (81%) warfarin. For the primary endpoint of new onset thromboembolic stroke, no difference existed between treatments (DOAC: 7.8% vs warfarin: 11.7%, p = 0.13). When compared to warfarin, no difference existed in the composite of thromboembolic events (33% vs 30.6%, p = 0.53, respectively) or in GUSTO bleeding (10.9% vs 7.8%, p = 0.40, respectively). More patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p < 0.001).DOACs may be an alternative to warfarin for the treatment of LV thrombus based on a retrospective assessment of thromboembolic events and GUSTO bleeding events within 90 days of diagnosis of LV thrombus. However, further prospective studies are warranted.

Contraceptive Use in Women of Childbearing Ability With Rheumatoid Arthritis.

BACKGROUND/OBJECTIVE: Rheumatoid arthritis (RA) is a complex disease that may require treatment with one or several disease-modifying antirheumatic drugs (DMARDs). Many DMARDs have potential teratogenic effects or are newer agents with limited safety data in pregnancy. This study evaluated 20 common RA medications and the rate of contraceptive prescribing and counseling patterns in women with RA of childbearing ability. METHODS: This was an observational study of women with RA and childbearing ability aged 18 to 44 years who were seen at an academic rheumatology clinic from April 1, 2014, to March 31, 2016. Descriptive statistics and univariate logistic regression were used for analysis. RESULTS: One hundred fifty women were included in the analysis. The majority of patients were taking methotrexate (55.3%), followed by chronic prednisone (31.3%) and hydroxychloroquine (28.7%). A documented method of contraception was noted in 64/150 (42.7%). For women on contraception, most used combined oral contraceptives (31/64, 48.4%) or levonorgestrel intrauterine device (10/64, 15.6%). Of the 86 patients not on contraception, 19 (22.1%) received counseling regarding a pregnancy plan. CONCLUSIONS: Most women with RA of childbearing age and ability were not using contraception. Among these patients, only a minority prescribed DMARD therapy had documented pregnancy or contraceptive counseling. Women with RA who were prescribed with a DMARD should discuss the use of effective contraception with their provider if sexually active and not desiring pregnancy or wanting to avoid potential teratogenic effects. Potential strategies are discussed to improve healthcare delivery to this population in hopes of avoiding unintended pregnancy and potential teratogenic effects of RA medications.

Utilization of acute gout prophylaxis in the real world: a retrospective database cohort analysis.

OBJECTIVE: Determine the real-world incidence of acute gout prophylaxis (AGP) prescribing when a xanthine oxidase inhibitor (XOI) is initiated and describe characteristics of AGP prescribing. METHODS: Retrospective cohort analysis from 2007 to 2017 using medical and prescription claims from an administrative database (IQVIA™ Health Plan Claims Database) among adult patients with a diagnosis of gout. Primary endpoint was the proportion of patients receiving AGP among all patients newly initiated on XOI therapy. Secondary endpoints included incidence proportions of acute flare and of XOI discontinuation among patients who received AGP compared to those who did not. Chi-square and Fisher's exact tests were used in univariate analysis of proportions between treatment groups. RESULTS: A total of 7414 patients were included for analysis. There were 697 patients (9.4%) who received AGP with XOI initiation and colchicine alone was the most common medication used among patients who received prophylaxis (n = 303, 43.4%). The incidence proportion of patients with an acute gout flare within 3 months of index was 21.5% in the AGP cohort and 12.7% in the no prophylaxis cohort (p < 0.001). The proportion of patients who discontinued XOI within 12 months of initiation was 38.7% in the AGP cohort and 46.2% in the no prophylaxis cohort (p < 0.001). CONCLUSION: In the real world, the proportion of patients who receive AGP with initiation of XOI therapy is low and discontinuation of XOI within 12 months of initiation is significant. In this analysis, use of AGP was not associated with a lower risk of acute gout flare after initiation of XOI therapy. Key Points • Real-world acute gout prophylaxis (AGP) prescribing with xanthine oxidase inhibitor (XOI) initiation is very low despite current guideline recommendations • More than one third of patients discontinue XOIs within 12 months of initiation regardless of AGP prescribing.

Comparison of two different intravenous serotonin antagonists used for chemotherapy-induced nausea and vomiting prophylaxis in patients treated with moderately emetogenic risk regimens: A retrospective analysis from a large academic medical center.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) can be a serious and debilitating adverse effect that is highly feared by cancer patients. For patients receiving moderately emetogenic chemotherapy regimens at our institution in the ambulatory infusion center, palonosetron was selected as the preferred serotonin (5-HT3) antagonist for CINV prophylaxis per the 2016 NCCN Guidelines, when a neurokinin1 antagonist was not included in the prophylactic regimen. The purpose of this study was to evaluate the efficacy of dexamethasone and palonosetron versus granisetron for the prevention of CINV in patients receiving moderately emetogenic chemotherapy regimens. METHODS: This study is an Institutional Review Board-approved, single-center retrospective review of electronic health records including patients who received moderately emetogenic chemotherapy regimens with CINV prophylaxis with dexamethasone and either palonosetron or granisetron. RESULTS: A total of 268 eligible patients were included in the study. Eighty-eight patients received palonosetron and 180 patients received granisetron as their 5-HT3 receptor antagonist between October 31, 2014 and October 31, 2016. There were no statistically significant differences between the two antiemetic groups for the primary outcome of presence of any change in day 1 intravenous prophylactic antiemetics. Nine (10.23%) palonosetron patients and 15 (8.33%) granisetron patients required a change in their day 1 intravenous prophylactic antiemetics (P = 0.610). CONCLUSIONS: Despite palonosetron's better efficacy, longer half-life, and higher binding affinity, the results of this retrospective review demonstrates that the choice of serotonin antagonist, palonosetron or granisetron, did not result in a change in day 1 intravenous prophylactic antiemetics or antiemetic outpatient medications for patients undergoing moderately emetogenic chemotherapy regimens.

Evaluation of Prophylactic Heparin Dosage Strategies and Risk Factors for Venous Thromboembolism in the Critically Ill Patient.

BACKGROUND: Venous thromboembolism (VTE) occurs frequently in critically ill patients without heparin prophylaxis. Although heparin prevents VTE, VTEs occur frequently despite prophylaxis. A higher heparin dosage may be more effective for preventing VTE. METHODS: A retrospective study was conducted using the Premier Incorporated Perspective Database to evaluate comparatively the effects of different heparin prophylaxis dosing strategies in the critically ill patient. Critically ill adult patients who were mechanically ventilated for at least 1 day and had an intensive care unit (ICU) length of stay of at least 2 days were included. Patients received 5000 units of heparin either twice/day or 3 times/day. The primary outcome was development of a new VTE. Key secondary outcomes included clinically important bleeding, thrombocytopenia, and mortality. Patients were propensity matched to control for confounding. Multivariable analysis was conducted for VTE risk factors. RESULTS: The study included 30,800 patients from 374 hospitals who were propensity matched by heparin dosage. New VTE occurred in 6.16% of patients treated with 3 times/day heparin versus 6.23% with twice/day heparin (p=0.8). No significant differences in the incidence of pulmonary embolism (0.91% vs 0.8%, p=0.29) or deep vein thrombosis (5.56% vs 5.70% p=0.59) were observed between the two types of heparin dosing. No differences were observed between the two types of heparin dosing in in-hospital mortality (15.8% vs 15.15%), bleeding (0.23% vs 0.33%), or thrombocytopenia (5.19% vs 5.34%, p>0.08 for all), respectively. Risk factors associated with VTE included intraabdominal and urinary tract infections, loop diuretics, malnutrition, obesity, thrombocytopenia, paralytics, vasopressors, female sex, peripheral vascular disease, sepsis, neutropenia, and end-stage renal disease. Antiplatelet therapy, heart failure, diabetes, and substance abuse were associated with reduced VTE (p<0.05 for all). CONCLUSIONS: In critically ill patients, prophylactic dosing of heparin 3 times/day versus twice/day was not associated with differences in new VTE or safety outcomes. Several modifiable VTE risk factors were identified.