Real-World Outcomes of Proprotein Convertase Subtilisin Kexin-9 Inhibitor Use.

ABSTRACT: Although the proprotein convertase subtilisin kexin-9 inhibitors (PCSK9i) were shown to significantly lower low-density lipoprotein and reduce atherosclerotic cardiovascular disease events in clinical trials, there is a dearth of use data on these agents in real-world settings. This study compares PCSK9i use in a population of real-world patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia. This was a matched cohort study of adult patients who were dispensed a PCSK9i along with adult patients who did not receive a PCSK9i. PCSK9i patients were matched on a propensity to have received a PCSK9i score up to 1:10 to non-PCSK9i patients. The primary outcomes were changes in cholesterol levels. Secondary outcomes included a composite outcome of all-cause mortality, major cardiovascular events, and ischemic strokes along with health care utilization during follow-up. Adjusted conditional, multivariate Cox proportional hazards, and negative binomial modeling were performed. Ninety-one PCSK9i patients were matched to 840 non-PCSK9i patients. Seventy-one percent of PCSK9i patients either discontinued or switched PCSK9i therapy. PCSK9i patients had greater median reductions in low-density lipoprotein (-73.0 mg/dL vs. -30.0 mg/dL) and total (-77.0 vs. -31.0) cholesterol (both P < 0.001). No adjusted between-group differences in the composite outcome or individual components of the composite outcome were identified (all P > 0.05). PCSK9i patients had a lower rate of medical office visits during follow-up (adjusted incidence rate ratio = 0.61, P = 0.019). These findings support the effectiveness of PCSK9i therapy in real-world settings but suggest that use may be limited by PCSK9i adverse reactions and patient cost barriers.

Effectiveness and safety of direct oral anticoagulants in patients with venous thromboembolism and creatinine clearance < 30 mL/min.

The few studies that compared direct oral anticoagulants (DOAC) vs. warfarin in the setting of advanced renal insufficiency have focused on patients with atrial fibrillation. The purpose of this observational, matched, cohort study of patients was to assess the effectiveness and safety of DOAC vs. warfarin for the treatment of venous thromboembolism (VTE) among patients with a creatinine clearance (CrCl) < 30 mL/min. This observational, cohort study included patients with VTE and CrCl < 30 mL/min who were newly initiated on a DOAC or warfarin between January 1, 2016 and December 31, 2020. DOAC patients were matched up to 1:2 to warfarin patients. Primary outcome was a composite of recurrent VTE, clinically-relevant bleeding, ischemic stroke, and all-cause mortality. Adjusted conditional, multivariate Cox proportional hazards modeling was used to assess outcomes. 626 DOAC patients were matched to 1071 warfarin patients. DOAC patients had a higher mean age, higher mean baseline CrCl, and were less likely to have been receiving dialysis. There was no statistically significant difference in the composite outcome between groups (adjusted hazard ratio [aHR] 1.13, 95% confidence interval [CI] 0.87-1.47) or in the individual components of the composite (all HR 95% CI crossed 1.00). Identification of statistically non-significant rates of bleeding and thromboembolic outcomes suggest that the use of DOAC or warfarin is reasonable in patients with VTE and CrCl < 30 mL/min.

Retrospective assessment of antimicrobial stewardship initiative in outpatient use of ertapenem for uncomplicated extended spectrum beta lactamase Enterobacteriaceae urinary tract infections.

BACKGROUND: Urinary tract infections (UTI) are often over-diagnosed and over-treated, which can induce and select for resistant pathogens. After observing wide-spread outpatient use of ertapenem, a broad-spectrum antibiotic, a structured antimicrobial stewardship initiative (ASI) to improve appropriate antimicrobial prescribing was undertaken. ASI objectives were to achieve a goal of reducing ertapenem utilization for extended spectrum beta lactamase Enterobacteriaceae (ESBL-EB) UTI by 10% and evaluate the clinical outcomes associated with the ASI. METHODS: A pre-to-post cohort study was conducted at a single-center integrated healthcare system between November 1, 2014 and February 26, 2017. An intensive, 90-day, pharmacist-driven, structured ASI was implemented between November 1, 2015 and January 29, 2016. Female patients aged ≥18 years who were treated for an uncomplicated, ESBL-EB urinary tract infection (UTI) were included. Primary outcome was clinical resolution defined as cure, persistence, relapse and recurrence. Secondary outcome measured was monthly ertapenem use expressed as number of days of therapy (DOT)/1000 adjusted patient days (APD). Segmented regression analysis for interrupted time series was performed to estimate ASI intervention effect. RESULTS: A total of 184 patients were included in the study. Ertapenem utilization decreased from 0.0145 DOT/1000 APD in Nov. 2014 to 0.0078 DOT/1000 APD Feb. 2017(p < 0.01). The mean ertapenem DOT declined 19% overall from the pre vs. post intervention periods (32 vs 26, p < 0.01). Frequency of recurrent UTIs between treatments did not significantly differ and no adverse effects were reported in patients treated with aminoglycosides. CONCLUSIONS: A structured ASI for uncomplicated ESBL-EB UTI was associated with a clinically meaningful decrease in ertapenem utilization and once-daily, 5-day aminoglycoside treatment was well-tolerated.

Factors associated with A1C reduction with GLP-1 agonist or SGLT-2 inhibitor use.

BACKGROUND: While use of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduces the risk of atherosclerotic cardiovascular disease outcomes and lowers glycosylated haemoglobin (A1C), evidence on patient characteristics associated with clinically relevant A1C reduction is lacking. OBJECTIVE: The objective of this retrospective cohort study was to identify patient characteristics associated with A1C reduction with initial GLP-1 or SGLT-2 use. METHODS: Patients with type 2 diabetes and a baseline A1C ≥7% who were dispensed a GLP-1 or SGLT-2 between 01/01/10 and 12/31/17 were included. Patients were categorized as having a ≥1% or <1% A1C reduction during the 90-365 days after GLP-1/SGLT-2 initiation. Patient characteristics were collected during the 180 days prior to initiation. Multivariable logistic and linear regression modelling was performed to identify characteristics associated with a ≥1% A1C reduction and absolute change in A1C, respectively. RESULTS: Five hundred and seventy-two patients were included with 261 (46%) and 311 (54%) having and not having an ≥1% A1C reduction. Patients were primarily middle-aged, female, white, non-Hispanic and had a high burden of chronic disease. Characteristics associated with a ≥1% A1C reduction included: GLP-1/SGLT-2 persistence, congestive heart failure comorbidity, phentermine dispensing, care management team (CMT) enrollee and higher baseline A1C. Characteristics associated with absolute A1C reduction included: age, baseline A1C, CMT enrollee, GLP-1/SGLT-2 persistence and a phentermine dispensing. CONCLUSIONS: The results of this study provide practitioners with guidance on the patients who are most likely to have a clinically relevant A1C reduction with GLP-1 or SGLT-2 use.

Universal hepatitis B screening and management in patients with cancer who received immunosuppressive chemotherapy.

BACKGROUND: Clinical data to guide management of patients with cancer and hepatitis B virus (HBV) infection who are treated with immunosuppressive chemotherapy are lacking. The purpose of this study was to describe HBV+ rates in a population of patients with cancer and evaluate a risk-stratified management protocol for the prevention of HBV reactivation (HBVr). METHODS: This was a descriptive study conducted in an integrated healthcare delivery system. Patients with cancer and hepatitis B virus infection who received immunosuppressive chemotherapy between 1 January 2014 and 31 January 2016 were included. A risk-stratified management protocol that continued for six months after chemotherapy completion or 12 months after completion of B-cell targeted chemotherapy was assessed. Outcomes included the proportion of patients who were HBV+ and amongst patients who initiated immunosuppressive therapy, proportions who received hepatitis B virus monitoring or anti-hepatitis B virus prophylaxis, or experienced HBVr or hepatitis B virus-related complications. RESULTS: There were 2463 patients with cancer screened for hepatitis B virus with 114 (4.6%) HBV+ of whom 59 (51.8%) initiated chemotherapy. Included patients were primarily older, male, and white with gastrointestinal or hematologic cancers and initiated intermediate/low-risk cytotoxic chemotherapy. During follow-up, 41 (69.5%) received hepatitis B virus DNA monitoring and 17 (28.8%) initiated anti-hepatitis B virus prophylaxis. No HBVr was observed. ALT and AST abnormalities were common but mostly Grade 1 and primarily related to the patient's malignancy or medications. CONCLUSIONS: Universal hepatitis B virus screening coupled with a risk-stratified management strategy utilizing HBVr monitoring and anti-hepatitis B virus prophylaxis in HBV+ patients receiving immunosuppressive chemotherapy for cancer may prevent HBVr.

The influence of fibrate initiation on INR and warfarin dose in patients receiving chronic warfarin therapy.

Several drug interaction compendia report a risk of warfarin potentiation after initiation of a fibrate; however, the evidence of this interaction is limited. The objective of this study was to evaluate warfarin dose and international normalized ratio (INR) response among a large sample of patients receiving chronic warfarin who initiated a fibrate. This was a retrospective, one-sample, pre-to-post study. Adult patients who were receiving chronic warfarin therapy at the time of gemfibrozil or fenofibrate dispensing between 1/1/2000 and 3/31/2016 were included. Patients had at least one and two therapeutic INRs during the 90 days prior to (baseline) and after (follow-up), respectively, fibrate initiation. Comparison of stable warfarin dose:INR ratio between the baseline and follow-up periods and assessment of safety outcomes during follow-up were performed. There were 321 patients included. Patients were predominantly male (62.6%) with an indication of atrial fibrillation (44.2%). The mean warfarin dose:INR ratio was equivalent between the baseline and follow-up periods (13.4 mg/INR [± 6.9] vs. 13.5 mg/INR [± 7.5], respectively, p = 0.711). Rates of thromboembolism, bleeding, and all-cause mortality in the 90-day follow up were 0, 0.6, and 1.2%, respectively. Although individual patients may have labile INRs after fibrate initiation, no significant interaction between fibrate and warfarin in a large sample of real world patients was identified. The utility of additional INR monitoring after fibrate initiation in otherwise stable patients receiving chronic warfarin therapy is unclear.

Clinical Pharmacist Intervention to Engage Older Adults in Reducing Use of Alprazolam.

OBJECTIVE: To assess whether a letter explaining the risks of alprazolam can engage older adults to call a clinical pharmacist (CP) to initiate reduction in alprazolam use. DESIGN: Randomized, controlled study. SETTING: Integrated health care delivery system. PATIENTS: Patients 65 years of age and older who resided at home, had a current supply of alprazolam as of December 15, 2016, and had four outpatient dispensings of alprazolam during the previous 12 months. INTERVENTION: Patients were randomized to receive an educational outreach regarding alprazolam use reduction via a mailed letter (intervention group) or receive usual care (control group). Intervention patients/caregivers were requested to call the CP to discuss reduction of alprazolam use. For intervention patients who called and consented to participate, alternative treatment options were discussed on a case-by-case basis. MAIN OUTCOME MEASURES: Composite rate of 1) no alprazolam dispensing, 2) an alprazolam dose reduction, or 3) interchange to an alternative medication during the six-month follow-up. RESULTS: 153 and 173 patients were and were not, respectively, sent a letter. The mean age was 73 years and patients primarily were female. Thirty (19.6%) intervention patients called the CP. The composite rate was equivalent between the intervention (34.0%) and control (35.3%) groups (P = 0.822). In subanalyses, the composite rate was higher among intervention patients who did vs. those who did not call the CP (77.8% vs. 27.6%; P < 0.001). CONCLUSION: A low-cost patient educational outreach coupled with CP care efficiently engaged older adults in benzodiazepine use reduction process; however, alprazolam continues to be a challenging medication for patients to discontinue.

A Predictive Model to Identify Skilled Nursing Facility Residents for Pharmacist Intervention.

Objective Develop a predictive model to identify patients in a skilled nursing facility (SNF) who require a clinical pharmacist intervention. Design Retrospective, cross-sectional. Setting Nine freestanding SNFs within an integrated health care delivery system. Patients Patients who received a clinical pharmacist medication review between January 1, 2016, and April 30, 2017. Identified patients (n = 2,594) were randomly assigned to derivation and validation cohorts. Interventions Multivariable logistic regression modeling was performed to identify factors predictive of patients who required an intervention (i.e., medication dose adjustment, initiation, or discontinuation). Patient-specific factors (e.g., demographics, medication dispensings, diagnoses) were collected from administrative databases. A parsimonious model based on clinical judgment and statistical assessment was developed in the derivation cohort and assessed for fit in the validation cohort. Main Outcome Measures Model to predict patients requiring clinical pharmacist intervention. Secondary outcome was a comparison of factors between patients who did and did not receive a clinical pharmacist intervention. Results Ninety-five factors were assessed. The derivation (n = 1,299) model comprised 22 factors (area under the curve [AUC] = 0.79, 95% confidence interval [CI] 0.74-0.84). A clopidogrel dispensing (odds ratio [OR] = 2.42, 95% CI 1.19-4.91), fall (OR = 2.47, 95% CI 1.59-3.83), or diagnosis for vertebral fracture (OR = 2.33, 95% CI 1.34-4.05) in the 180 days prior to clinical pharmacist medication review were predictive of requiring an intervention. The model fit the validation cohort (n = 1,295) well, AUC = 0.79 (95% CI 0.74-0.84). Conclusion Administrative data predicted patients in a SNF who required clinical pharmacist intervention. Application of this model in real-time could result in clinical pharmacist time-savings and improved pharmacy services through more directed patient care.

Multidisciplinary intervention to improve albuterol inhaler utilization among patients with asthma.

OBJECTIVE: The goal of this study was to examine the impact of a multidisciplinary intervention designed to improve appropriate albuterol inhaler utilization among patients with asthma. METHODS: This was a pre-post retrospective analysis. The study intervention included written information sent directly to patients, educated prescribers, and enhanced pharmacist training on appropriate albuterol inhaler utilization. Eligible study patients had a diagnosis of asthma and purchased at least two albuterol inhalers between 07/12/2012 and 06/30/2013 (pre-period) and 7/01/2013 to 06/30/2014 (post-period). The primary outcome was a comparison between study periods of the count of albuterol inhalers purchased per patient per month (PPPM). RESULTS: The median age of included patients was 41 years, 53% were females, and allergic rhinitis was the most common comorbidity. The median albuterol inhalers purchased PPPM decreased from 0.60 (interquartile range [IQR] = 0.39-0.87) to 0.37 (IQR = 0.26-0.53) from the pre- to post-period (p < 0.001). The proportion of patients with at least one systemic corticosteroid purchase decreased (36% vs. 31%) and >1 albuterol inhaler purchased on the same day increased (3.1% vs. 5.7%) from the pre- to post-period (p < 0.001). Numerically, the proportion of participants who experienced an acute asthma exacerbation decreased and asthma controller inhalers purchased PPPM increased but these did not reach statistical significance (both p > 0.05). CONCLUSIONS: A multidisciplinary approach to increasing appropriate albuterol inhaler use was associated with a decrease in albuterol inhalers purchased PPPM while not increasing acute asthma exacerbations. Future study is needed to evaluate patient perspectives on this intervention and assess its economic impact.

Assessment of the rates and characteristics of unclaimed prescriptions.

OBJECTIVES: The purpose of this study was to describe the rates of and characteristics associated with unclaimed prescriptions during 3 seasonal months. DESIGN: Retrospective cohort study. SETTING: This study was conducted using Kaiser Permanente Colorado administrative data. PARTICIPANTS: All patients who had a prescription prepared at 1 of 28 outpatient pharmacies during the months of November 2014, February 2015, and May 2015 were included. An unclaimed prescription was defined as any prescription medication not dispensed to a patient within 15 days after preparation. Patients with an unclaimed prescription were compared to patients without an unclaimed prescription during the study months. MAIN OUTCOME MEASURES: The rates of unclaimed prescriptions, characteristics of patients with and without unclaimed prescriptions, and medication characteristics between unclaimed and claimed prescriptions. RESULTS: A total of 866,554 prescriptions were prepared during the study months, with 44,836 being unclaimed (5.2%; 95% CI 5.1%-5.2%). Of the 225,510 patients with a prescription prepared during the study months, 30,800 patients (13.7%) had at least 1 unclaimed prescription. Neither the size of the pharmacy nor the season in which the prescription was prepared had a meaningful impact on the unclaimed prescription rate. Miscellaneous (e.g., disinfectants, antidotes, medical devices) and respiratory medication classes had the highest rates of unclaimed prescriptions. Patient characteristics associated with having had an unclaimed prescription included having had a hospice, skilled nursing facility, or long-term care facility stay after the prescription was prepared (odds ratio 2.48 [95% CI 1.91-3.23]) and at least 1 other medication dispensed previously (odds ratio 1.83 [95% CI 1.73-1.94]). CONCLUSION: The rate of unclaimed prescriptions was relatively low; however, approximately 1 in 8 patients with a prepared prescription had at least 1 unclaimed prescription. Future research is needed to identify effective interventions to reduce unclaimed prescriptions in order to prevent potential negative health outcomes.

Impact of a Clinical Pharmacy Specialist in an Emergency Department for Seniors.

STUDY OBJECTIVE: This study assesses outcomes associated with the implementation of an emergency department (ED) for seniors in which a clinical pharmacy specialist, with specialized geriatric training that included medication management training, is a key member of the ED care team. METHODS: This was a retrospective cohort analysis of patients aged 65 years or older who presented at an ED between November 1, 2012, and May 31, 2013. Three groups of seniors were assessed: treated by the clinical pharmacy specialist in the ED for seniors, treated in the ED for seniors but not by the clinical pharmacy specialist, and not treated in the ED for seniors. Outcomes included rates of an ED return visit, mortality and hospital admissions, and follow-up total health care costs. Multivariable regression modeling was used to adjust for any potential confounders in the associations between groups and outcomes. RESULTS: A total of 4,103 patients were included, with 872 (21%) treated in the ED for seniors and 342 (39%) of these treated by the clinical pharmacy specialist. Groups were well matched overall in patient characteristics. Patients who received medication review and management by the clinical pharmacy specialist did not experience a reduction in ED return visits, mortality, cost of follow-up care, or hospital admissions compared with the other groups. Of the patients treated by the clinical pharmacy specialist, 154 (45.0%) were identified as having at least 1 medication-related problem. CONCLUSION: Although at least 1 medication-related problem was identified in almost half of patients treated by the clinical pharmacy specialist in the ED for seniors, incorporation of a clinical pharmacy specialist into the ED staff did not improve clinical outcomes.

Clinical outcomes and adherence to guideline recommendations during the initial treatment of acute venous thromboembolism.

BACKGROUND: Adherence to American College of Chest Physicians (CHEST) guidelines for treatment of acute venous thromboembolism (VTE) has not been formally assessed in the United States, specifically in the subset of patients with renal impairment. OBJECTIVE: Evaluate adherence to CHEST VTE treatment guidelines. METHODS: This retrospective cohort study evaluated patients with acute VTE between January 1, 2010, and December 31, 2011, for the primary outcome of adherence to CHEST VTE treatment guidelines defined as (1) patients receiving an appropriate parenteral anticoagulant and dose based on renal function and weight, (2) at least 5 days of parenteral anticoagulation during warfarin initiation, and (3) an international normalized ratio (INR) value ≥2 documented before discontinuing parenteral agents. Secondary outcomes included recurrent thromboembolism and major bleeding across renal function categories. RESULTS: Of the 1683 patients included in the final analysis, 1483 (88%) had complete data for all 3 elements of the primary outcome (dose, overlap duration, and INR ≥2.0). VTE guideline adherence was identified in 95% (1408/1483) of these patients. There were 20 major bleeds overall, which occurred in 1.1%, 1.1%, and 1.3% in patients with CrCl <30 mL/min, 30 to 59 mL/min, and ≥60 mL/min, respectively (P = 0.929). Also, 7 recurrent VTE events occurred-3 in patients with CrCl values of 30 to 59 mL/min (0.5%) and 4 in patients with CrCl ≥60 mL/min (0.4%; P = 0.797 across groups). CONCLUSIONS: Adherence to CHEST guidelines was high and resulted in low rates of bleeding and recurrent VTE complications across renal function categories. Further studies of patients with CrCl <30 mL/min are needed.

Prior authorization for diabetes medications: Clinical outcomes and health disparities.

BACKGROUND: Prior authorization (PA) is a utilization management strategy used by health plans to ensure affordable, cost-effective care; however, PA may lead to therapy delay/abandonment and exacerbate health disparities. The purpose of this observational study was to assess the clinical outcomes and any health disparities associated with PA for diabetes mellitus (DM) medications. MATERIALS AND METHODS: This was a cohort study of US adult patients from health plans with integrated and non-integrated system providers who were prescribed a DM medication that required a PA. Patients were categorized into three groups: received the requested DM medication (PA Med) or a new, alternative DM medication (DM Med), or did not receive the requested or new DM medication (No Med). The primary outcome was change in hemoglobin A1c (HbA1c). Adjusted and unadjusted analyses were performed. Patient characteristics associated with the No Med group were identified, also, with multivariable logistic regression modeling. RESULTS: 6305 patients were included: 2434, 1323, and 2548 in the PA Med, DM Med, and No Med groups, respectively. Patients in the PA Med (-0.9 %) and DM Med (-1.0 %) groups had statistically significantly greater reductions in HbA1c compared to the No Med group (-0.4 %) in both unadjusted and adjusted analyses (all p < 0.05). Patients who were Hispanic/Latino, had a non-integrated system prescriber, and had a higher burden of chronic disease were statistically significantly associated with the No Med group. CONCLUSIONS: Receiving a new DM medication following PA was associated with better clinical outcomes but health disparities were present in the PA process.

Real-World Noninferiority Assessment of Two Filgrastim Biosimilars in Patients Receiving Myelosuppressive Chemotherapy.

PURPOSE: Although multiple filgrastim biosimilars are now available in the United States, no studies comparing clinical outcomes between products have been reported. This analysis evaluated real-world outcomes of filgrastim-aafi and filgrastim-sndz in patients with select solid tumors receiving myelosuppressive chemotherapy to compare the two filgrastim biosimilars. METHODS: This was an observational, noninferiority, cohort study of patients from three integrated health care systems who received myelosuppressive chemotherapy and were prophylactically initiated on filgrastim-sndz between January and November 2021 or filgrastim-aafi between June and November 2022. Patients were followed from filgrastim biosimilar initiation until the start of their next chemotherapy cycle. The primary outcome of severe neutropenia was analyzed using a binary noninferiority test with a 5% upper margin. Secondary outcomes included the incidence of emergency department or hospital encounters due to febrile neutropenia and systemic antibiotic/antifungal medication use. If noninferiority was met, adjusted logistic regression modeling was conducted. RESULTS: A total of 2,730 patients who initiated filgrastim-aafi (n = 880) or filgrastim-sndz (n = 1,850) during the study period were included. The overall mean age was 55 years, 87.4% were female, 42.3% were White, and 76.6% had breast cancer. Severe neutropenia occurred in 1.8% and 1.7% of patients initiated on filgrastim-aafi and filgrastim-sndz, respectively (P < .01 for noninferiority). The adjusted odds ratio for severe neutropenia with filgrastim-aafi compared with filgrastim-sndz was 0.91 (95% CI, 0.49 to 1.68; P = .76). Noninferiority was met for all secondary outcomes (P < .01), and there were no adjusted statistically significant differences between the groups (all P > .05). CONCLUSION: Among patients with select solid tumors receiving myelosuppressive chemotherapy, severe neutropenia outcomes were comparable between filgrastim-aafi and filgrastim-sndz biosimilars. Findings from this study may support utilization of different filgrastim biosimilars in clinical practice.

Validation of electronic data on chemotherapy and hormone therapy use in HMOs.

BACKGROUND: Most data regarding medical care for cancer patients in the United States comes from Surveillance, Epidemiology and End Results-linked Medicare analyses of individuals aged 65 years or older and typically excludes Medicare Advantage enrollees. OBJECTIVES: To assess the accuracy of chemotherapy and hormone therapy treatment data available through the Cancer Research Network's Virtual Data Warehouse (VDW). RESEARCH DESIGN: Retrospective, longitudinal cohort study. Medical record-abstracted, tumor registry-indicated treatments (gold standard) were compared with VDW-indicated treatments derived from health maintenance organization pharmacy, electronic medical record, and claim-based data systems. SUBJECTS: Enrollees aged 18 years and older diagnosed with incident breast, colorectal, lung, or prostate cancer from 2000 through 2007. MEASURES: Sensitivity, specificity, and positive predictive value were computed at 6 and 12 months after cancer diagnosis. RESULTS: Approximately 45% of all cancer cases (total N=23,800) were aged 64 years or younger. Overall chemotherapy sensitivity/specificities across the 3 health plans for incident breast, colorectal, lung, and prostate cancer cases were 95%/90%, 95%/93%, 93%/93%, and 85%/77%, respectively. With the exception of prostate cancer cases, overall positive predictive value ranged from 86% to 89%. Small variations in chemotherapy data accuracy existed due to cancer site and data source, whereas greater variation existed in hormone therapy capture across sites. CONCLUSIONS: Strong concordance exists between gold standard tumor registry measures of chemotherapy receipt and Cancer Research Network VDW data. Health maintenance organization VDW data can be used for a variety of studies addressing patterns of cancer care and comparative effectiveness research that previously could only be conducted among elderly Surveillance, Epidemiology and End Results-Medicare populations.

Outcomes of a pharmacist-managed medication refill program.

OBJECTIVE: To compare the completeness of medication and blood pressure monitoring among patients requesting medication refills through the pharmacist-managed medication refill and laboratory monitoring program (MRLMP) versus usual care. DESIGN: Quasiexperimental study. SETTING: Kaiser Permanente Colorado between November 2011 and June 2012. PATIENTS: Patients requesting chronic medication prescription refills. INTERVENTION: Community pharmacists managed the refill authorization request (RAR) process at the intervention site. For each RAR, the pharmacist reviewed patient medication monitoring needs and ordered laboratory test(s) or a clinic visit, as needed, before approval. MAIN OUTCOME MEASURES: For medications due for laboratory or blood pressure monitoring at the time of the RAR, the 1-month rate of attaining complete monitoring was compared between groups. Pharmacist, primary care physician (PCP), and patient satisfaction and PCP time saved also were compared. RESULTS: 3,797 RARs for MRLMP-eligible medications were approved in the month following MRLMP implementation in the intervention and control clinics. The intervention and control groups converted 49% and 29% of medications due for laboratory monitoring ( P < 0.001) and 56% and 33% of those due for blood pressure monitoring, respectively ( P = 0.020). The intervention group PCPs were more likely than control group PCPs to report being "very satisfied" with the RAR process (80% vs. 27%, P = 0.015) and spent fewer minutes per day on refill requests (mean 17 vs. 23, P = 0.049). The intervention group pharmacists reported higher job satisfaction (mean index score 22 vs. 18, P = 0.024), and intervention group patients reported higher satisfaction with the "readiness" of their prescription when they came to pick it up (91% vs. 80%, P = 0.004). CONCLUSION: A pharmacist-managed MRLMP resulted in improved process-related outcomes. Future studies should assess clinical outcomes.

Transthyretin Amyloid Cardiomyopathy Risk Evaluation in a Cohort of Patients With Heart Failure.

Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, infiltrative form of heart failure (HF). Nevertheless, ATTR-CM is a largely underrecognized and misdiagnosed condition. This study's objective was to develop an efficient model to assess the chance of ATTR-CM in patients with HF. Methods This was an observational study of patients with HF who had a confirmed diagnosis of ATTR-CM and those with HF but without known ATTR-CM between January 1, 2019, and July 1, 2021. Patient characteristics were extracted from administrative and claims electronic databases and compared between the groups. A propensity score for having ATTR-CM was modeled. Samples of 50 control patients with the highest and lowest propensity scores were adjudicated to assess whether further workup to evaluate for ATTR-CM was warranted for each patient. The sensitivity and specificity of the model were calculated. Results Thirty-one patients with confirmed ATTR-CM and 7620 patients without known ATTR-CM were included in the study. Patients with ATTR-CM were more likely to be Black and to have atrial flutter/fibrillation, cardiomegaly, HF with preserved ejection fraction, pericardial effusion, carpal tunnel syndrome, joint disorders, and lumbar spinal stenosis and to use a diuretic (all p < 0.05). A propensity model with 16 inputs was developed (c-statistic = 0.875). The model's sensitivity and specificity were 71.9% and 95.2%, respectively. Conclusion The propensity model developed in this study provided an efficient means for identifying patients with HF who are more likely to have ATTR-CM and may warrant further workup.

Real-World Clinical Outcomes of Bevacizumab-awwb Biosimilar versus Bevacizumab Reference Product in Patients with Metastatic Colorectal Cancer.

BACKGROUND: Bevacizumab-awwb was the first biosimilar approved for cancer treatment in the USA. Limited information is available on the real-world comparative safety and effectiveness of bevacizumab biosimilars, especially for indications granted approval through extrapolation. OBJECTIVE: To evaluate the real-world outcomes of patients with metastatic colorectal cancer (mCRC) initiated on bevacizumab-awwb versus bevacizumab reference product. PATIENTS AND METHODS: This was an observational, longitudinal cohort study of US adult patients with mCRC from four integrated care delivery systems who were newly initiated on bevacizumab-awwb between 1 July 2019 and 30 March 2020 or bevacizumab reference product between 1 July 2015 and 30 June 2018. Patients were followed until 1 year after treatment initiation, end of plan membership, or death, whichever occurred first. The primary outcome of overall survival (OS) was analyzed using a binary non-inferiority test with lower margin of 10% and adjusted Cox proportional hazards regression analysis to assess all-cause mortality if non-inferiority was met. Secondary outcomes included counts of doses received, treatment duration, all-cause hospitalizations, and incidence of serious adverse events. RESULTS: A total of 1445 patients initiated on either bevacizumab-awwb (n = 239) or bevacizumab reference product (n = 1206) were included in the analysis. The mean overall age was 60 ± 13 years, 46% of patients were female, and 51% were white. The OS rate was 72.8% and 73.1% for patients receiving bevacizumab-awwb and bevacizumab reference product, respectively (p < 0.01 for non-inferiority). The adjusted hazard ratio for mortality was 1.01 (0.77-1.33, p = 0.93). There were no statistically significant differences in secondary outcomes between the study groups. CONCLUSIONS: These findings suggest that bevacizumab-awwb is as effective and safe as bevacizumab reference product for the real-world treatment of mCRC.

Outpatient use of low molecular weight heparin monotherapy for first-line treatment of venous thromboembolism in advanced cancer.

BACKGROUND: Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) monotherapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors. METHODS: Using administrative data from advanced lung, prostate, colon, or breast cancer patients diagnosed between January 2000 and December 2007 at four HMOs with integrated delivery systems, patients with an inpatient or outpatient VTE diagnosed within 2 years after cancer diagnosis and an outpatient purchase of warfarin, LMWH, and/or fondaparinux anticoagulant within 7 days of the VTE diagnosis were identified. First-line outpatient VTE pharmacological treatment and factors independently associated with receipt/non-receipt of LMWH monotherapy were assessed. RESULTS: Overall, 25% of the 1,089 eligible patients received LMWH monotherapy as primary VTE treatment. The percentage increased steadily over time from 18% among patients diagnosed in 2000 to 31% among those diagnosed in 2007. Factors associated with LMWH monotherapy included VTE diagnosis year, chemotherapy within 60 days prior to VTE diagnosis, history of VTE prior to cancer diagnosis, and invasive surgery in the 90 days following VTE diagnosis. Colorectal and prostate cancer patients versus lung cancer patients and stage III versus stage IV patients were less likely to be treated with LMWH monotherapy. CONCLUSIONS: Adoption of LMWH monotherapy as initial treatment for cancer-associated VTE was low but increased steadily over the study period. Future studies should explore reasons underlying the underutilization of this preferred evidence-based treatment as well as the comparative effectiveness of LMWH versus warfarin-based anticoagulation in real-world cancer patients with VTE.

Clinical outcomes associated with brand-to-generic phenytoin interchange.

BACKGROUND: Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. However, little within-patient evidence exists examining such interchanges. OBJECTIVE: To compare within-patient seizure control before and after the interchange of a branded to a single-source generic phenytoin among patients with seizures in a managed care organization. METHODS: This was a pre-post, self-controlled, retrospective study. Adults with a history of seizure who used Dilantin Kapseals 100 mg extended phenytoin sodium, USP, capsules and whose therapy was interchanged to Taro Pharmaceuticals' AB-rated generic extended phenytoin sodium capsules, USP, 100 mg between July 2007 and May 2008 were included. Study outcomes included the comparisons of the proportions of patients with at least emergency department (ED) visit/inpatient hospitalization and medical office visit/nonoffice consultation for acute seizure in the 6 months before and after interchange. Outcomes were confirmed with manual chart reviews and adjusted for potential confounding medication use. RESULTS: A total of 222 patients were included in the study. Patients were primarily middle-aged (mean 56 years), equally mixed by sex (47% female); most had nonintractable seizures. The majority of patients (~70%) were on phenytoin as monotherapy and had equivalent rates of purchases for potentially confounding medications in both pre- and postinterchange time periods (all p > 0.05). Low serum concentrations were detected more often in the postinterchange study period (adjusted p < 0.001). Despite this, there were low proportions of patients with confirmed seizure events that resulted in an ED visit/inpatient hospitalization in both pre- and postinterchange periods (both 6.3%, adjusted p = 0.937). The proportion of patients with confirmed seizure events diagnosed at a medical office visit was not significantly different between the preinterchange and postinterchange periods (12.2% vs 11.3%, adjusted p = 0.545). CONCLUSIONS: No increased proportion of seizures was observed within patients when branded phenytoin was interchanged to an AB-rated, single-source, generic equivalent. More rigorous studies should be conducted to more thoroughly evaluate patient tolerability and drug efficacy when antiepileptic drugs are interchanged from brand to generic formulations.