Low cost, high temporal resolution optical fiber-based γ-photon sensor for real-time pre-clinical evaluation of cancer-targeting radiopharmaceuticals.

Cancer radiopharmaceutical therapies (RPTs) have demonstrated great promise in the treatment of neuroendocrine and prostate cancer, giving hope to late-stage metastatic cancer patients with currently very few treatment options. These therapies have sparked a large amount of interest in pre-clinical research due to their ability to target metastatic disease, with many research efforts focused towards developing and evaluating targeted RPTs for different cancer types in in vivo models. Here we describe a method for monitoring real-time in vivo binding kinetics for the pre-clinical evaluation of cancer RPTs. Recognizing the significant heterogeneity in biodistribution of RPTs among even genetically identical animal models, this approach offers long-term monitoring of the same in vivo organism without euthanasia in contrast to ex vivo tissue dosimetry, while providing high temporal resolution with a low-cost, easily assembled platform, that is not present in small-animal SPECT/CTs. The method utilizes the developed optical fiber-based γ-photon biosensor, characterized to have a wide linear dynamic range with Lutetium-177 (177Lu) activity (0.5-500 µCi/mL), a common radioisotope used in cancer RPT. The probe's ability to track in vivo uptake relative to SPECT/CT and ex vivo dosimetry techniques was verified by administering 177Lu-PSMA-617 to mouse models bearing human prostate cancer tumors (PC3-PIP, PC3-flu). With this method for monitoring RPT uptake, it is possible to evaluate changes in tissue uptake at temporal resolutions <1 min to determine RPT biodistribution in pre-clinical models and better understand dose relationships with tumor ablation, toxicity, and recurrence when attempting to move therapies towards clinical trial validation.

The development and initial feasibility testing of D-HOMES: a behavioral activation-based intervention for diabetes medication adherence and psychological wellness among people experiencing homelessness.

Introduction: Compared to stably housed peers, people experiencing homelessness (PEH) have lower rates of ideal glycemic control, and experience premature morbidity and mortality. High rates of behavioral health comorbidities and trauma add to access barriers driving poor outcomes. Limited evidence guides behavioral approaches to support the needs of PEH with diabetes. Lay coaching models can improve care for low-resource populations with diabetes, yet we found no evidence of programs specifically tailored to the needs of PEH. Methods: We used a multistep, iterative process following the ORBIT model to develop the Diabetes Homeless Medication Support (D-HOMES) program, a new lifestyle intervention for PEH with type 2 diabetes. We built a community-engaged research team who participated in all of the following steps of treatment development: (1) initial treatment conceptualization drawing from evidence-based programs, (2) qualitative interviews with affected people and multi-disciplinary housing and healthcare providers, and (3) an open trial of D-HOMES to evaluate acceptability (Client Satisfaction Questionnaire, exit interview) and treatment engagement (completion rate of up to 10 offered coaching sessions). Results: In step (1), the D-HOMES treatment manual drew from existing behavioral activation and lay health coach programs for diabetes as well as clinical resources from Health Care for the Homeless. Step (2) qualitative interviews (n = 26 patients, n = 21 providers) shaped counseling approaches, language and choices regarding interventionists, tools, and resources. PTSD symptoms were reported in 69% of patients. Step (3) trial participants (N = 10) overall found the program acceptable, however, we saw better program satisfaction and treatment engagement among more stably housed people. We developed adapted treatment materials for the target population and refined recruitment/retention strategies and trial procedures sensitive to prevalent discrimination and racism to better retain people of color and those with less stable housing. Discussion: The research team has used these findings to inform an NIH-funded randomized control pilot trial. We found synergy between community-engaged research and the ORBIT model of behavioral treatment development to develop a new intervention designed for PEH with type 2 diabetes and address health equity gaps in people who have experienced trauma. We conclude that more work and different approaches are needed to address the needs of participants with the least stable housing.

Synthesis and Preliminary Biological Assessment of Carborane-Loaded Theranostic Nanoparticles to Target Prostate-Specific Membrane Antigen.

Boron neutron capture therapy (BNCT) is an encouraging therapeutic modality for cancer treatment. Prostate-specific membrane antigen (PSMA) is a cell membrane protein that is abundantly overexpressed in prostate cancer and can be targeted with radioligand therapies to stimulate clinical responses in patients. In principle, a spatially targeted neutron beam together with specifically targeted PSMA ligands could enable prostate cancer-targeted BNCT. Thus, we developed and tested PSMA-targeted poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) loaded with carborane and tethered to the radiometal chelator deferoxamine B (DFB) for simultaneous positron emission tomography (PET) imaging and selective delivery of boron to prostate cancer. Monomeric PLGA-b-PEGs were covalently functionalized with either DFB or the PSMA ligand ACUPA. Different nanoparticle formulations were generated by nanoemulsification of the corresponding unmodified and DFB- or ACUPA-modified monomers in varying percent fractions. The nanoparticles were efficiently labeled with 89Zr and were subjected to in vitro and in vivo evaluation. The optimized DFB(25)ACUPA(75) NPs exhibited strong in vitro binding to PSMA in direct binding and competition radioligand binding assays in PSMA(+) PC3-Pip cells. [89Zr]DFB(25) NPs and [89Zr]DFB(25)ACUPA(75) NPs were injected to mice with bilateral PSMA(-) PC3-Flu and PSMA(+) PC3-Pip dual xenografts. The NPs demonstrated twofold superior accumulation in PC3-Pip tumors to that of PC3-Flu tumors with a tumor/blood ratio of 25; however, no substantial effect of the ACUPA ligands was detected. Moreover, fast release of carborane from the NPs was observed, resulting in a low boron delivery to tumors in vivo. In summary, these data demonstrate the synthesis, characterization, and initial biological assessment of PSMA-targeted, carborane-loaded PLGA-b-PEG nanoparticles and establish the foundation for future efforts to enable their best use in vivo.

Evaluating implementation outcomes (acceptability, adoption, and feasibility) of two initiatives to improve the medication prior authorization process.

BACKGROUND: Processes such as prior authorization (PA) for medications, implemented by health insurance companies to ensure that safe, appropriate, cost-effective, and evidence-based care is provided to all members, have created inefficiencies within healthcare systems. Thus, healthcare systems have implemented supplemental processes to reduce burden and ensure efficiency, timeliness, and appropriate care. OBJECTIVE: Evaluate implementation outcomes of two initiatives related to PA for medications: a common record that records all PA-related information that was integrated into the health record and an auto-routing of specialty prescriptions to a hospital-owned specialty pharmacy. METHODS: We conducted semi-structured interviews with medical staff to understand their experience, acceptability, adoption, and feasibility of these initiatives guided by Proctor's Framework for Implementation Outcomes. Transcripts were analyzed using consensus coding. RESULTS: Eleven medical staff participated in semi-structured interviews. The two initiatives were analyzed together because the findings were similar across both for our outcomes of acceptability, adoption, and feasibility. Participants found the implemented initiatives to be acceptable and beneficial but felt there were still challenges with the new workflow. The initiatives were fully adopted by only one clinic site within the healthcare system, but limitations arose when adopting to another site. Individuals felt the initiatives were feasible and improved workflow, communication, and transparency. However, participants described future adaptations that would help improve this process including improved standardization, automation, and transparency. CONCLUSION: The acceptability, adoption, and feasibility of two initiatives to improve the PA process within the one clinical site were well received but issues of generalizability limited the initiatives adoption system wide.

Monte Carlo calculation of the TG-43 dosimetry parameters for the INTRABEAM source with spherical applicators.

OBJECTIVE: The relative TG-43 dosimetry parameters of the INTRABEAM (Carl Zeiss Meditec AG, Jena, Germany) bare probe were recently reported by Ayala Alvarezet al(2020Phys. Med. Biol.65245041). The current study focuses on the dosimetry characterization of the INTRABEAM source with the eight available spherical applicators according to the TG-43 formalism using Monte Carlo (MC) simulations. APPROACH: This report includes the calculated dose-rate conversion coefficients that determine the absolute dose rate to water at a reference point of 10 mm from the applicator surface, based on calibration air-kerma rate measurements at 50 cm from the source on its transverse plane. Since the air-kerma rate measurements are not yet provided from a standards laboratory for the INTRABEAM, the values in the present study were calculated with MC. This approach is aligned with other works in the search for standardization of the dosimetry of electronic brachytherapy sources. As a validation of the MC model, depth dose calculations along the source axis were compared with calibration data from the source manufacturer. MAIN RESULTS: The calculated dose-rate conversion coefficients were 434.0 for the bare probe, and 683.5, 548.3, 449.9, 376.5, 251.0, 225.6, 202.8, and 182.6 for the source with applicators of increasing diameter from 15 to 50 mm, respectively. The radial dose and the 2D anisotropy functions of the TG-43 formalism were also obtained and tabulated in this document. SIGNIFICANCE: This work presents the data required by a treatment planning system for the characterization of the INTRABEAM system in the context of intraoperative radiotherapy applications.

Socioeconomic Disparities in Functional Status in a National Sample of Patients With Rheumatoid Arthritis.

Importance: Little is known about the association of poverty with functional status (FS) in patients with rheumatoid arthritis (RA) who use rheumatology care. Objectives: To examine the association between socioeconomic status (SES) and FS among patients with RA and to evaluate the association between SES and functional declines over time in patients who received at least some rheumatology care. Design, Setting, and Participants: This cohort study used data from the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry between January 1, 2016, and December 31, 2018. Analyses included all adult patients with a confirmed RA diagnosis (ie, had ≥2 encounters associated with RA International Classification of Diseases codes ≥30 days apart) and at least 1 FS score documented between 2016 and 2018 seen at participating rheumatology practices. Data analysis was conducted from April to December 2020. Exposures: The Area Deprivation Index (ADI), a zip code-based indicator of neighborhood poverty, was used as a proxy for SES. ADI scores were categorized into quintiles. Main Outcomes and Measures: FS measures included Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire Disability index, and Health Assessment Questionnaire-II. Cross-sectionally, mean FS scores were compared across ADI quintiles. Longitudinally, among patients with at least 2 FS scores, multilevel multivariate regression computed the probability of functional decline, defined as a change greater than the minimum clinically important difference, across ADI quintiles. In a subgroup analysis, whether disease activity mediated the association between SES and functional decline was examined. Results: Of the 83 965 patients included in the study, 66 649 (77%) were women, and 60 037 (72%) were non-Hispanic White. Mean (SD) age was 63.4 (13.7) years. MDHAQ was the most reported FS measure (56 928 patients [67.8%]). For all measures, mean (SD) FS score was worse at lower SES levels (eg, for MDHAQ quintile 1: 1.79 [1.87]; quintile 5: 2.43 [2.17]). In longitudinal analyses, the probability of functional decline was 14.1% (95% CI, 12.5%-15.7%) in the highest SES quintile and 18.9% (95% CI, 17.1%-20.7%) in the lowest SES quintile. The association between SES and functional decline was partially mediated (7%; 95% CI, 4%-22%) by disease activity. Conclusions and Relevance: In this cohort study of patients with RA, worse FS and faster declines in functioning over time were observed in patients with lower SES. These findings provide a framework for monitoring disparities in RA and for generating evidence to spur action toward achieving health equity.

Ineffective Orifice Area: Practical Limitations of Accurate EOA Assessment for Low-Gradient Heart Valve Prostheses.

PURPOSE: The goal of this study was to demonstrate the range in effective orifice area (EOA) values that may be possible given the ISO 5840 definition of EOA and the practical limits in the accurate measurement of pressure differential across large diameter valves. METHODS: A 31 mm mechanical valve was tested on a commercially available pulse duplicator configured for mitral valve testing and tuned to nominal conditions. The experimental data was used as a basis for performing Monte Carlo analyses with published specifications for commonly used pressure sensors as well as measurement equipment accuracy requirements described in ISO 5840. The sources of error were modeled as normally distributed random variables and the simulation was iterated 1,000,000 times. RESULTS: Experimentally-derived EOAs ranged from 2.7 to 5.0 cm2, while the Monte Carlo simulation provided results ranging from approximately 0.4 to 6.7 cm2. Many of these results are clearly non-physical with EOAs larger than the valve's geometric orifice area and exceedingly short positive pressure differential periods, yet they align with other published results for the same valve model. CONCLUSIONS: The volatility of the standard EOA formulation at low mean gradients combined with the difficulty in accurately measuring such small differentials with industry-standard fluid pressure transducers results in a performance metric which is very sensitive to test execution, particularly for low-gradient prostheses.

Monte Carlo calculation of the relative TG-43 dosimetry parameters for the INTRABEAM electronic brachytherapy source.

The INTRABEAM system (Carl Zeiss Meditec AG, Jena, Germany) is an electronic brachytherapy (eBT) device designed for intraoperative radiotherapy applications. To date, the INTRABEAM x-ray source has not been characterized according to the AAPM TG-43 specifications for brachytherapy sources. This restricts its modelling in commercial treatment planning systems (TPSs), with the consequence that the doses to organs at risk are unknown. The aim of this work is to characterize the INTRABEAM source according to the TG-43 brachytherapy dosimetry protocol. The dose distribution in water around the source was determined with Monte Carlo (MC) calculations. For the validation of the MC model, depth dose calculations along the source longitudinal axis were compared with measurements using a soft x-ray ionization chamber (PTW 34013) and two synthetic diamond detectors (microDiamond PTW TN60019). In our results, the measurements in water agreed with the MC model calculations within uncertainties. The use of the microDiamond detector yielded better agreement with MC calculations, within estimated uncertainties, compared to the ionization chamber at points of steeper dose gradients. The radial dose function showed a steep fall-off close to the INTRABEAM source ([Formula: see text]10 mm) with a gradient higher than that of commonly used brachytherapy radionuclides (192Ir, 125I and 103Pd), with values of 2.510, 1.645 and 1.232 at 4, 6 and 8 mm, respectively. The radial dose function partially flattens at larger distances with a fall-off comparable to that of the Xoft Axxent® (iCAD, Inc., Nashua, NH) eBT system. The simulated 2D polar anisotropy close to the bare probe walls showed deviations from unity of up to 55% at 10 mm and 155°. This work presents the MC calculated TG-43 parameters for the INTRABEAM, which constitute the necessary data for the characterization of the source as required by a TPS used in clinical dose calculations.

Medications requiring prior authorization across health insurance plans.

OBJECTIVE: To determine the amount of variation in numbers and types of medications requiring prior authorization (PA) by insurance plan and type. METHODS: Most health insurance companies require PA for medications to ensure safe and effective use and contain costs. We generated 4 lists of medications that required PA during 2017 for commercial, marketplace, Medicaid, and Medicare plans. We aggregated medications according to the generic medication name equivalent using codes and medication names. We compared these medications to assess how many of the medications required PA by 1, 2, 3, or all 4 of the insurance plans. We counted all prescription orders written for a patient age 18 years or older with health plan insurance during 2017 for any of the medications that appeared on the health plan's PA lists by querying the electronic health record. RESULTS: PA was required for 600 unique medications in 2017 across the 4 plans. Of 691,457 prescription orders written for 114,159 members, 31,631 (5%) were written for 1 of the 600 medications that required PA by at least 1 insurance plan. There were 12,540 medication orders (written for 6,642 members) that potentially required PA. The marketplace plan required PA for the greatest number of medications (440), followed by the Medicare (272), commercial (271), and Medicaid (72) plans. The most commonly prescribed classes of medications for which PA was required by at least 1 plan were antihyperlipidemics (22% of orders potentially requiring PA), narcotic analgesics (13%), hypnotics (12%), antidiabetic medications (9%), and antidepressants (9%). For only 25% of medications (151 of 600) was PA required by at least 3 plans, and for only 5% (32 of 600) was PA required by all 4 insurance types. CONCLUSION: Medications requiring PA can differ within a single health insurance company, but this variation may be unavoidable due to external factors.

Preliminary evaluation of dental hygiene curriculum: Assessment and management of peri-implant conditions and diseases.

OBJECTIVE: The purpose of this study was to investigate dental hygiene (DH) educational programs' didactic and clinical curriculum in the management of peri-implant diseases and conditions. The specific aims were (1) assess if evidence-based content for peri-implant diseases and conditions are currently included in didactic and clinical DH curriculum and (2) determine if DH education programs are currently preparing students at a level of clinical competency for the assessment and management of peri-implant diseases and conditions. DESIGN: A cross-sectional study of DH faculty member(s) from 331 United States entry-level programs responsible for didactic and clinical curriculum for peri-implant diseases and conditions were surveyed. The survey was disseminated electronically via Qualtricsxm August 2019 for a response rate of 26%. RESULTS: The results showed didactic courses taught DH students the etiology of peri-mucositis and peri-implantitis (98%), clinical characteristics (98%), and risk factors contributing to these implant diseases (96%). Evaluation methods to determine student level of competency in a didactic setting included quizzes/examinations (98%), case-based examinations (63%), and written essays (6%). Eighty-five percent reported DH students are not required in a clinical setting to provide care for patients with peri-implant diseases and conditions. CONCLUSIONS: Study results suggest DH education programs may need to revise didactic and clinical curriculum to ensure students graduate at a level of clinical competency for assessing and managing peri-implant conditions and diseases. DH educational programs should consider requiring clinical patient experiences for the assessment and management of peri-mucositis and peri-implantitis to prepare students for their professional role.

Understanding the medication prior-authorization process: A case study of patients and clinical staff from a large rural integrated health delivery system.

PURPOSE: The barriers and solutions to the current prior-authorization (PA) process at an integrated health system were evaluated. METHODS: Focus groups were conducted with patients at an integrated health system who also had insurance from an affiliated health plan and at least 1 denial for a medication in the past year. Semistructured interviews were conducted with medical staff (physicians, office staff, and PA experts). Both focus groups and interviews were audio-recorded and transcribed. Inductive analysis was used to code transcripts and develop themes. RESULTS: Three focus groups were conducted with 13 patients, and 9 medical staff (3 staff physicians, 2 office staff, and 4 PA staff) who have interactions with the PA process interviewed. Several themes were identified including the complexity of the PA process, consequences experienced, and ineffective communication between key stakeholders. A cross-cutting theme was that stakeholders expressed feelings of frustration, anxiety, and anger throughout the PA process. All stakeholders offered insights on how the process could be improved to better facilitate their preferences, such as access to the list of medications that require PA and the need for a patient advocate. CONCLUSION: Results of this study revealed that the PA process was frustrating, upsetting, and infuriating to patients and medical staff involved in the process. Three main themes identified included the complexity of the PA process, consequences experienced from the PA process, and ineffective communication between stakeholders.

A Preclinical Assessment of 89Zr-atezolizumab Identifies a Requirement for Carrier Added Formulations Not Observed with 89Zr-C4.

The swell of experimental imaging technologies to noninvasively measure immune checkpoint protein expression presents the opportunity for rigorous comparative studies toward identifying a gold standard. 89Zr-atezolizumab is currently in man, and early data show tumor targeting but also abundant uptake in several normal tissues. Therefore, we conducted a reverse translational study both to understand if tumor to normal tissue ratios for 89Zr-atezolizumab could be improved and to make direct comparisons to 89Zr-C4, a radiotracer that we showed can detect a large dynamic range of tumor-associated PD-L1 expression. PET/CT and biodistribution studies in tumor bearing immunocompetent and nu/nu mice revealed that high specific activity 89Zr-atezolizumab (∼2 µCi/µg) binds to PD-L1 on tumors but also results in very high uptake in many normal mouse tissues, as expected. Unexpectedly, 89Zr-atezolizumab uptake was generally higher in normal mouse tissues compared to 89Zr-C4 and lower in H1975, a tumor model with modest PD-L1 expression. Also unexpectedly, reducing the specific activity at least 15-fold suppressed 89Zr-atezo uptake in normal mouse tissues but increased tumor uptake to levels observed with high specific activity 89Zr-C4. In summary, these data reveal that low specific activity 89Zr-atezo may be necessary for accurately measuring PD-L1 in the tumor microenvironment, assuming a threshold can be identified that preferentially suppresses binding in normal tissues without reducing binding to tumors with abundant expression. Alternatively, high specific activity approaches like 89Zr-C4 PET may be simpler to implement clinically to measure the broad dynamic range of PD-L1 expression known to manifest among tumors.

RapidBrachyMCTPS: a Monte Carlo-based treatment planning system for brachytherapy applications.

Despite being considered the gold standard for brachytherapy dosimetry, Monte Carlo (MC) has yet to be implemented into a software for brachytherapy treatment planning. The purpose of this work is to present RapidBrachyMCTPS, a novel treatment planning system (TPS) for brachytherapy applications equipped with a graphical user interface (GUI), optimization tools and a Geant4-based MC dose calculation engine, RapidBrachyMC. Brachytherapy sources and applicators were implemented in RapidBrachyMC and made available to the user via a source and applicator library in the GUI. To benchmark RapidBrachyMC, TG-43 parameters were calculated for the microSelectron v2 (192Ir) and SelectSeed (125I) source models and were compared against previously validated MC brachytherapy codes. The performance of RapidBrachyMC was evaluated for a prostate high dose rate case. To assess the accuracy of RapidBrachyMC in a heterogeneous setup, dose distributions with a cylindrical shielded/unshielded applicator were validated against film measurements in a Solid WaterTM phantom. TG-43 parameters calculated using RapidBrachyMC generally agreed within 1%-2% of the results obtained in previously published work. For the prostate case, clinical dosimetric indices showed general agreement with Oncentra TPS within 1%. Simulation times were on the order of minutes on a single core to achieve uncertainties below 2% in voxels within the prostate. The calculation time was decreased further using the multithreading features of Geant4. In the comparison between MC-calculated and film-measured dose distributions, at least 95% of points passed the 3%/3 mm gamma index criteria in all but one case. RapidBrachyMCTPS can be used as a post-implant dosimetry toolkit, as well as for MC-based brachytherapy treatment planning. This software is especially well suited for the development of new source and applicator models.

Utilizing big data to provide better health at lower cost.

PURPOSE: The efficient use of big data in order to provide better health at a lower cost is described. SUMMARY: As data become more usable and accessible in healthcare, organizations need to be prepared to use this information to positively impact patient care. In order to be successful, organizations need teams with expertise in informatics and data management that can build new infrastructure and restructure existing infrastructure to support quality and process improvements in real time, such as creating discrete data fields that can be easily retrieved and used to analyze and monitor care delivery. Organizations should use data to monitor performance (e.g., process metrics) as well as the health of their populations (e.g., clinical parameters and health outcomes). Data can be used to prevent hospitalizations, combat opioid abuse and misuse, improve antimicrobial stewardship, and reduce pharmaceutical spending. These examples also serve to highlight lessons learned to better use data to improve health. For example, data can inform and create efficiencies in care and engage and communicate with stakeholders early and often, and collaboration is necessary to have complete data. To truly transform care so that it is delivered in a way that is sustainable, responsible, and patient-centered, health systems need to act on these opportunities, invest in big data, and routinely use big data in the delivery of care. CONCLUSION: Using data efficiently has the potential to improve the care of our patients and lower cost. Despite early successes, barriers to implementation remain including data acquisition, integration, and usability.

Impact of Warfarin Persistence on Health-Care Utilization and Costs Among Patients With Atrial Fibrillation Managed in Anticoagulation Clinics in the United States.

Warfarin is a recommended therapy to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). The objectives of this study were to identify potential factors associated with warfarin persistence and evaluate the impact of warfarin persistence on health-care resource utilization and costs among patients with NVAF in the United States. Patients (≥18 years) with ≥1 inpatient or ≥2 outpatient diagnoses of AF without valvular disease were identified from an electronic medical record database (January 1, 2004, to January 31, 2015). The patients with NVAF were grouped into 2 cohorts-persistent with warfarin therapy and not persistent (warfarin discontinuation in <365 days). A multivariable regression was used to identify potential predictors of warfarin persistence. Health-care costs were evaluated during a 12-month follow-up period for study cohorts. Among the study population, 52%, (n = 4086) were persistent with warfarin therapy and 48% (n = 3722) were not. Patients with NVAF with higher Charlson comorbidity index and CHADS2 scores versus those with scores of 0 were more likely to demonstrate persistence with warfarin therapy. After adjusting for patient characteristics, patients with NVAF persistent with warfarin therapy versus those who were not were 30% less likely to be hospitalized during the follow-up period ( P < .001). Additionally, total all-cause health-care costs (US $2183, P < .001) and stroke-related costs (US $788, P < .001) were significantly lower among patients persistent with warfarin therapy versus those who were not. Patients with NVAF who have greater comorbidity and stroke risk are more likely to be persistent with warfarin therapy. Patients with NVAF who are persistent with warfarin therapy versus those who are not have lower all-cause and stroke-related health-care costs.

Medication therapy disease management: Geisinger's approach to population health management.

PURPOSE: Pharmacists' involvement in a population health initiative focused on chronic disease management is described. SUMMARY: Geisinger Health System has cultivated a culture of innovation in population health management, as highlighted by its ambulatory care pharmacy program, the Medication Therapy Disease Management (MTDM) program. Initiated in 1996, the MTDM program leverages pharmacists' pharmacotherapy expertise to optimize care and improve outcomes. MTDM program pharmacists are trained and credentialed to manage over 16 conditions, including atrial fibrillation (AF) and multiple sclerosis (MS). Over a 15-year period, Geisinger Health Plan (GHP)-insured patients with AF whose warfarin therapy was managed by the MTDM program had, on average, 18% fewer emergency department (ED) visits and 18% fewer hospitalizations per year than GHP enrollees with AF who did not receive MTDM services, with 23% lower annual total care costs. Over a 2-year period, GHP-insured patients with MS whose pharmacotherapy was managed by pharmacists averaged 28% fewer annual ED visits than non-pharmacist-managed patients; however, the mean annual total care cost was 21% higher among MTDM clinic patients. CONCLUSION: The Geisinger MTDM program has evolved over 20 years from a single pharmacist-run anticoagulation clinic into a large program focused on managing the health of an ever-growing population. Initial challenges in integrating pharmacists into the Geisinger patient care framework as clinical experts were overcome by demonstrating the MTDM program's positive impact on patient outcomes.

Clinical and economic consequences of statin intolerance in the United States: Results from an integrated health system.

BACKGROUND: Although statins are considered safe and effective, they have been associated with statin intolerance (SI) in clinical and observational studies. OBJECTIVE: The objective of this study was to describe the clinical and economic consequences of SI through comparison of an SI cohort of patients with matched controls. METHODS: This study used data extracted from an integrated health system's electronic health records from 2008 to 2014. Adults with SI were matched to controls using a propensity score. Patients were hierarchically classified into 6 mutually exclusive cardiovascular (CV)-risk categories: recent acute coronary syndrome (ACS; ≤12 months preindex), coronary heart disease, ischemic stroke, peripheral artery disease, diabetes, or primary prevention. The study endpoints, low-density lipoprotein cholesterol (LDL-C) goal attainment, medical costs, and time to first CV event were compared using conditional logistic regression, generalized linear, and Cox proportional hazards models, respectively. RESULTS: Patients with SI (n = 5190) were matched with controls (n = 15,570). Patients with SI incurred higher medical costs and were less likely to reach LDL-C goals than controls. Patients with SI were at higher risk for revascularization procedures in all CV risk categories except ACS, and those in the diabetes risk category were at higher risk for any CV event. There was a lower risk of all-cause death among patients with SI. CONCLUSIONS: Patients with SI were less likely to reach LDL-C goals, incurred higher health care costs, and experienced a higher risk for nonfatal CV events than patients without SI. Alternative management strategies are needed to better treat high CV risk patients.

Warfarin time in therapeutic range and its impact on healthcare resource utilization and costs among patients with nonvalvular atrial fibrillation.

BACKGROUND: Warfarin is efficacious for reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF). However, the efficacy and safety of warfarin are influenced by its time in therapeutic range (TTR). OBJECTIVE: To assess differences in healthcare resource utilization and costs among NVAF patients with low (<60%) and high (≥60%) warfarin TTRs in an integrated delivery network (IDN) setting. METHODS: Patients with NVAF were identified from an electronic medical record database. Patients were required to have ≥6 international normalized prothrombin time ratio (INR) tests. NVAF patients were grouped into two cohorts: those with warfarin TTR <60% (low TTR) and those with warfarin TTR ≥60% (high TTR). Healthcare resource utilization and costs were evaluated during a 12 month follow-up period. Multivariable regressions were used to assess the impact of different warfarin TTRs on healthcare costs. RESULTS: Among the study population, greater than half (54%, n = 1595) had a low TTR, and 46% (n = 1356) had a high TTR. Total all-cause healthcare resource utilization was higher among patients in the low TTR cohort vs. the high TTR cohort (number of encounters: 70.2 vs. 56.1, p < 0.001). After adjusting for patient characteristics, total all-cause healthcare costs and stroke-related healthcare costs were $2398 (p < 0.001) and $687 (p = 0.02) higher, respectively, for patients in the low TTR cohort vs. the high TTR cohort. LIMITATIONS: In this retrospective study, we were only able to evaluate the association and not the causality between healthcare resource utilization and costs with the different warfarin TTRs. CONCLUSION: Many warfarin-treated NVAF patients have a low warfarin TTR. NVAF patients with low vs. patients with high warfarin TTR used healthcare resources to a greater extent, which was reflected in higher healthcare costs.

Development of multimedia informational tools for breast cancer patients with low levels of health literacy.

OBJECTIVE: To create informational tools for breast cancer patients with low levels of health literacy. METHODS: Tools were developed through a three-stage process. (1) Focus groups were conducted with breast cancer survivors and interviews were held with health educators to determine content, source of information, format and medium of the tools. (2) Based on this feedback, a suite of tools was developed. (3) Focus groups were reconvened and health educators re-interviewed to obtain feedback and determine satisfaction. RESULTS: We developed a suite of five informational tools using low health literacy principles, which focused on learning about breast cancer resources and learning about the members of one's healthcare team, understanding the "journey" or trajectory of care beginning at diagnosis, hearing from other breast cancer patients about their own journey, and becoming informed about what to expect pre-and post-surgery for breast cancer. The final products were rated highly by breast cancer survivors. CONCLUSION: The developed materials, designed for patients who read below an 8th grade level, reflect the informational needs reported by breast cancer patients. PRACTICE IMPLICATIONS: Healthcare providers must consider utilizing design principles and theories of adult learning appropriate for those with low health literacy.