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The generalized Kadanoff-Baym ansatz (GKBA) offers a computationally inexpensive approach to simulate out-of-equilibrium quantum systems within the framework of nonequilibrium Green's functions. For finite systems, the limitation of neglecting initial correlations in the conventional GKBA approach has recently been overcome [Karlsson et al., Phys. Rev. B 98, 115148 (2018)]. However, in the context of quantum transport, the contacted nature of the initial state, i.e., a junction connected to bulk leads, requires a further extension of the GKBA approach. In this work, we lay down a GKBA scheme that includes initial correlations in a partition-free setting. In practice, this means that the equilibration of the initially correlated and contacted molecular junction can be separated from the real-time evolution. The information about the contacted initial state is included in the out-of-equilibrium calculation via explicit evaluation of the memory integral for the embedding self-energy, which can be performed without affecting the computational scaling with the simulation time and system size. We demonstrate the developed method in carbon-based molecular junctions, where we study the role of electron correlations in transient current signatures.

Background: There are limited data on economic aspects of the genetic variant of chronic obstructive pulmonary disease (COPD) in the context of the more prevalent form of COPD. The objective of this study was to isolate the healthcare resource utilization and economic burden attributable to the presence of a genetic factor among COPD patients with and without Alpha-1 Antitrypsin Deficiency (AATD), twelve months before and after their initial COPD diagnosis., Methods: Retrospective analysis of OptumLabs® Data Warehouse claims (OLDW; 2000-2017). The OLDW is a comprehensive, longitudinal real-world data asset with de-identified lives across claims and clinical information. AATD-associated COPD cases were matched with up to 10 unique non-AATD-associated COPD controls. Healthcare resource use and costs were assigned into the following categories: office (OV), outpatient (OP), and emergency room visits (ER), inpatients stays (IP), prescription drugs (RX), and other services (OTH). A generalized linear model was used to estimate total pre- and post-index (initial COPD diagnosis) costs from a third-party payer's perspective (2018 USD) controlling for confounders. Healthcare resource utilization was estimated using a negative binomial regression., Results: The study population consisted of 8881 patients (953 cases matched with 7928 controls). The AATD-associated COPD cohort had higher expenditures and use of office visits (OV) and other (OTH) services, as well as OV, outpatient (OP), emergency room (ER), and prescription drugs (RX) before and after the index date, respectively. Adjusted total all-healthcare cost ratios for AATD-associated COPD patients as compared to controls were 2.04 [95% CI: 1.60-2.59] and 1.98 [95% CI: 1.55-2.52] while the incremental cost difference totaled $6861 [95% CI: $3025 - $10,698] and $5772 [95% CI: $1940 - $9604] per patient before and after the index date, respectively., Conclusions: Twelve months before and after their initial COPD diagnosis, patients with AATD incur higher healthcare utilization costs that are double the cost of similar COPD patients without AATD. This study also suggests that increased costs of AATD-associated COPD are not solely attributable to augmentation therapy use. Future studies should further explore the relationship between augmentation therapy, healthcare resource use, and other AATD-associated COPD expenditures.

Time-resolved soft-x-ray photoemission spectroscopy is used to simultaneously measure the ultrafast dynamics of core-level spectral functions and excited states upon excitation of excitons in WSe_{2}. We present a many-body approximation for the Green's function, which excellently describes the transient core-hole spectral function. The relative dynamics of excited-state signal and core levels clearly show a delayed core-hole renormalization due to screening by excited quasifree carriers resulting from an excitonic Mott transition. These findings establish time-resolved core-level photoelectron spectroscopy as a sensitive probe of subtle electronic many-body interactions and ultrafast electronic phase transitions.

Introduction: As the healthcare system shifts from fee-for service toward value-driven healthcare, interest has grown in medication-related quality metrics to evaluate quality and value within the healthcare system. While the Defense Health Agency (DHA) has taken steps to align healthcare quality measures across the enterprise, the extent to which DHA utilizes pharmacy quality measures (PQMs) or evaluates the quality of direct and purchased pharmacy care is unknown., Materials and Methods: A comparison was made between existing PQMs utilized by DHA and all measures published and endorsed by the Pharmacy Quality Alliance (PQA), a recognized, PQM standard-setting organization. We also compared DHA PQMs to those used within the Medicare Part D Star Rating Program., Results: DHA has implemented 10 (28%) of the 36 PQA measures available for evaluation as of August 2019. Of the five measures included in the 2020 CMS Part D Star Rating program, DHA has currently implemented four (80%) of the measures. DHA has implemented 3 of the 5 (60%) PQA CMS Display Measures, and 5 of 9 (56%) PQA CMS Patient Safety Report Measures that are not part of the Star Ratings, but that are used to benchmark and provide feedback to health plans., Conclusion: Opportunities exist within the DHA to leverage PQMs to evaluate the quality of pharmaceutical care, build trust with beneficiaries by increasing transparency, and maintain parity with the civilian healthcare system. Existing models and commercially available technology could be considered to rapidly operationalize the use of PQMs within the MHS., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: To assess the relationship between posttraumatic brain injury statin use and (1) mortality and (2) the incidence of associated morbidities, including stroke, depression, and Alzheimer's disease and related dementias following injury., Setting and Participants: Nested cohort of all Medicare beneficiaries 65 years of age and older who survived a traumatic brain injury (TBI) hospitalization during 2006 through 2010. The final sample comprised 100 515 beneficiaries., Design: Retrospective cohort study of older Medicare beneficiaries. Relative risks (RR) and 95% confidence interval (CI) were obtained using discrete time analysis and generalized estimating equations., Measures: The exposure of interest included monthly atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin use. Outcomes of interest included mortality, stroke, depression, and Alzheimer's disease and related dementias., Results: Statin use of any kind was associated with decreased mortality following TBI hospitalization discharge. Any statin use was also associated with a decrease in any stroke (RR, 0.86; 95% confidence intervals (CI), 0.81-0.91), depression (RR, 0.85; 95% CI, 0.79-0.90), and Alzheimer's disease and related dementias (RR, 0.77; 95% CI, 0.73-0.81)., Conclusion: These findings provide valuable information for clinicians treating older adults with TBI as clinicians can consider, when appropriate, atorvastatin and simvastatin to older adults with TBI in order to decrease mortality and associated morbidities.

The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term 'patient-centered outcomes research' (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR.

Background: Traumatic brain injury (TBI) is a significant public health concern for older adults. Small-scale human studies have suggested pre-TBI statin use is associated with decreased in-hospital mortality following TBI, highlighting the need for large-scale translational research., Objective: To investigate the relationship between pre-TBI statin use and in-hospital mortality following TBI., Methods: A retrospective study of Medicare beneficiaries 65 and older hospitalized with a TBI during 2006 to 2010 was conducted to assess the impact of pre-TBI statin use on in-hospital mortality following TBI. Exposure of interest included atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin. Beneficiaries were classified as current, recent, past, and nonusers of statins prior to TBI. The outcome of interest was in-hospital mortality. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) comparing current, recent, and prior statin use to nonuse., Results: Most statin users were classified as current users (90%). Current atorvastatin (OR = 0.88; 95% = CI 0.82, 0.96), simvastatin (OR = 0.84; 95% CI = 0.79, 0.91), and rosuvastatin (OR = 0.79; 95% CI = 0.67, 0.94) use were associated with a significant decrease in the risk of in-hospital mortality following TBI., Conclusions: In addition to being the most used statins, current use of atorvastatin, rosuvastatin, and simvastatin was associated with a significant decrease in in-hospital mortality following TBI among older adults. Future research must include clinical trials to help exclude the possibility of a healthy user effect in order to better understand the impact of statin use on in-hospital mortality following TBI., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Prior research demonstrates substantial access problems associated with utilization management and formulary exclusions for antipsychotics in Medicaid, but the use and impact of coverage restrictions for these medications in Medicare Part D remains unknown. We assess the effect of coverage restrictions on antipsychotic utilization in Part D by exploiting a unique natural experiment in which low-income beneficiaries are randomly assigned to prescription drug plans with varying levels of formulary generosity. Despite considerable variation in use of coverage restrictions across Part D plans, we find no evidence that these restrictions significantly deter utilization or reduce access to antipsychotics for low-income beneficiaries.

Objective: This study examined relationships among antipsychotic adherence, hospitalization, and hospital expenditures in a sample of 13,861 Medicare Part D enrollees with schizophrenia., Methods: Utilization and expenditure data were obtained from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse for 2011 and 2012. Adherence was measured with the proportion of days covered and stratified into four categories. Probit regressions and two-part generalized linear models were used to examine relationships between adherence in year 1 and outcomes in year 2., Results: Adherence to antipsychotic therapy was associated with a significantly lower probability of psychiatric hospitalization and significantly lower psychiatric hospital expenditures, with the largest effect sizes observed for the most highly adherent beneficiaries. There was no relationship between antipsychotic adherence and hospitalizations or expenditures for nonpsychiatric conditions., Conclusions: Adherence to antipsychotics among Medicare Part D enrollees with schizophrenia was associated with significantly lower probability of psychiatric hospitalization and lower hospital expenditures.

Background: Rare diseases (RDs) affect a small number of people within a population. About 5000 to 8000 distinct RDs have been identified, with an estimated 6% to 8% of people worldwide suffering from an RD. Approximately 75% of RDs affect children. Frequently, these conditions are heterogeneous; many are progressive. Regulatory incentives have increased orphan drug designations and approvals., Objective: To develop emerging good practices for RD outcomes research addressing the challenges inherent in identifying, selecting, developing, adapting, and implementing patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments for use in RD clinical trials., Good Practices for Outcomes Research: This report outlines the challenges and potential solutions in determining clinical outcomes for RD trials. It follows the US Food and Drug Administration Roadmap to Patient-Focused Outcome Measurement in Clinical Trials. The Roadmap consists of three columns: 1) Understanding the Disease or Condition, 2) Conceptualizing Treatment Benefit, and 3) Selecting/Developing the Outcome Measure. Challenges in column 1 include factors such as incomplete natural history data and heterogeneity of disease presentation and patient experience. Solutions include using several information sources, for example, clinical experts and patient advocacy groups, to construct the condition's natural history and understand treatment patterns. Challenges in column 2 include understanding and measuring treatment benefit from the patient's perspective, especially given challenges in defining the context of use such as variations in age or disease severity/progression. Solutions include focusing on common symptoms across patient subgroups, identifying short-term outcomes, and using multiple types of COA instruments to measure the same constructs. Challenges in column 3 center around the small patient population and heterogeneity of the condition or study sample. Few disease-specific instruments for RDs exist. Strategies include adapting existing instruments developed for a similar condition or that contain symptoms of importance to the RD patient population, or using a generic instrument validated for the context of use., Conclusions: This report provides state-of-the-art solutions to patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments challenges in clinical trials of patients with RDs. These recommended solutions are both pragmatic and creative and posed with clear recognition of the global regulatory context used in RD clinical development programs., (Copyright © 2017. Published by Elsevier Inc.)

Background: In addition to lowering lipids, statins also may be beneficial for older adults sustaining a traumatic brain injury (TBI), as statin use prior to and following trauma may decrease mortality following injury. However, despite statins' potential to reduce mortality, there is limited research regarding statin use among older adults., Objective: To characterize and investigate factors associated with statin use among older adults with TBI., Methods: A retrospective drug utilization study was used to characterize statin use among Medicare beneficiaries 65 and older hospitalized with a TBI during 2006 to 2010 and with continuous Medicare Parts A, B, and D coverage 6 months prior and 12 months following TBI. Logistic regression was used to investigate the factors associated with statin use. The exposure of interest was statin use prior to and following TBI., Results: Of the 75 698 beneficiaries included in the study, 37 874 (~50%) of beneficiaries used a statin at least once during the study period. The most common statin used was simvastatin, while fluvastatin was the least used statin. Statin users were more likely to have cardiovascular diseases when compared to nonusers. Hyperlipidemia was a major factor associated with statin use and had the greatest impact on statin use compared to nonuse (odds ratio = 9.54; 95% confidence interval = 9.07, 10.03)., Conclusions: This national sample of older adults with TBI suggests that statins are commonly used. Future studies must next examine the impact of statin use on mortality and secondary injury in order to shape pharmacological therapy guidelines following TBI., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Patient-Centered Outcomes Research Institute, known as PCORI, was established by Congress as part of the Affordable Care Act (ACA) to promote evidence-based treatment. Provisions of the ACA prohibit the use of a cost-effectiveness analysis threshold and quality-adjusted life-years (QALYs) in PCORI comparative effectiveness studies, which has been understood as a prohibition on support for PCORI's conducting conventional cost-effectiveness analyses. This constraint complicates evidence-based choices where incremental improvements in outcomes are achieved at increased costs of care. How frequently this limitation inhibits efficient cost containment, also a goal of the ACA, depends on how often more effective treatment is not cost-effective relative to less effective treatment. We examined the largest database of studies of comparisons of effectiveness and cost-effectiveness to see how often there is disagreement between the more effective treatment and the cost-effective treatment, for various thresholds that may define good value. We found that under the benchmark assumption, disagreement between the two types of analyses occurs in 19 percent of cases. Disagreement is more likely to occur if a treatment intervention is musculoskeletal and less likely to occur if it is surgical or involves secondary prevention, or if the study was funded by a pharmaceutical company., (Project HOPE—The People-to-People Health Foundation, Inc.)

Translation of medical evidence into practice has not kept pace with the growth of medical technology and knowledge. We present three case studies--statins, drug eluting stents and bone marrow transplantation for breast cancer--to propose a framework for describing five factors that may influence the rate of adoption. The factors are: validity, reliability and maturity of the science available before widespread adoption; communication of the science; economic drivers; patients' and physicians' ability to apply published scientific findings to their specific clinical needs; and incorporation into practice guidelines.

Objectives: To evaluate urokinase plasminogen activator (u-PA), urokinase plasminogen activator soluble receptor (su-PAR), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) plasma levels in SSc patients (pts) versus healthy controls and their modulation by intravenous alphacyclodestrine (Alprostadil)., Methods: Plasma levels of u-PA, su-PAR, PAI-1 and t-PA were measured in 40 SSc (34 lSSc and 6 dSSc) pts and in 30 healthy controls. In SSc, blood was drawn before and after 3 consecutive daily of Alprostadil infusion (60 mg in 250 cc NaCl 0.9%)., Results: In SSc su-PAR basal levels were higher than controls (7.48 +/- 2.5 vs 4.69 +/- 0.4 ng/ml; p = 0.001) and were significantly reduced by Alprostadil (5.93 +/- 1.7; p = 0.002), but remain higher than controls (p = 0.03). u-PA basal levels were higher than controls (3.78 +/- 1.5 vs 1.29 +/- 0.3 ng/ml; p < 0.001) and were reduced by Alprostadil (2.39 +/- 1.7; p < 0.001) to control levels. SSc PAI-1 basal levels were lower than controls (31.60 +/- 7.7 vs 48.30 +/- 6.8 ng/ml; p < 0.001) and increased by Alprostadil (34.66 +/- 5.4; p = 0.04), but lower than controls (p < 0.001). SSc t-PA basal levels were higher in respect to controls (1645.81 +/- 792.7 vs 571.95 +/- 75.5 pg/ml; p < 0.0001) and reduced by Alprostadil (1318.06 +/- 603.5; p = 0.04), but still higher than controls (p = 0.001)., Conclusion: Fibrinolysis were increased in SSc. Infusions of Alprostadil modulate u-PA, su-PAR, PAI-1 and t-PA, restoring near normal levels. In SSc, fibrinolysis system may become a potential target for new therapies.

Past research on acute exacerbation of chronic bronchitis (AECB) has not quantified related work loss. This exploratory study used data from a comparative trial of moxifloxacin versus levofloxacin to examine and compare workplace-related indirect costs. Both groups reported considerable absenteeism and lowered work productivity. However, patients taking moxifloxacin reported significantly higher work productivity than those taking levofloxacin (70% vs. 50%; P = .03). This translated into substantial indirect cost savings with moxifloxacin of $726/patient/year. Antibiotic choice in AECB can affect worker productivity and workplace-related indirect costs. Both insurers and employers should consider workplace-related indirect costs in addition to direct medical expenses when making formulary selections.

Objective: To review and summarize past activities of guidelines development at the Agency for Health Care Policy and Research (AHCPR) to enhance understanding of its new role and facilitate the development of new guidelines., Data Synthesis: The current Congressional climate and past criticisms of the guidelines development process have caused the AHCPR to reevaluate the way it produces guidelines. This assessment has resulted in the AHCPR restructuring its role to serve now as a science partner with private and public organizations., Conclusions: The development and role of evidence-based clinical practice guidelines are discussed, and the new roles of the AHCPR are described.

Understanding the important aspects of measuring outcomes will prepare pharmacists for changes in the marketplace and help them to assess the results of studies that will appear in subsequent issues of the Journal of the American Pharmaceutical Association and the research journals of other health services professions. In any evaluation of quality, all three quality measures (structure, process, and outcomes) must be considered. No one measure, in isolation, can describe the quality of care provided. Thus, the best patient care will come from health care practitioners who document structure, process, and outcomes and who evaluate these measures to provide appropriate care. The pharmacist cannot dispense prescriptions or provide pharmaceutical care without a pharmacy, drug inventory, or patient profiles, all of which are important structural inputs. The pharmacist takes a medication history, monitors the drug regimen, and counsels the patient on the appropriate way to use the treatment, all vital process activities. The objective of these inputs and actions is to improve the health status of the patient. Outcomes, therefore, are the intended endpoints of care, and occasional unintended effects (e.g., adverse drug reactions) as well. The future of pharmacy rests on demonstrating the positive effect of pharmaceutical care on patient outcomes. Pharmacists have always been part of the system of checks and balances in health care delivery. As the provision of health services changes, opportunities to assess the process and structure of care and to document patient outcomes will increase. Pharmacists are well positioned to intervene in patient care, but if they do not demonstrate the value of pharmacy services, they will face competition from alternative providers. Some have even suggested less expensive alternatives to having pharmacists dispense medications. Pharmacists must establish that their role goes beyond dispensing to include cognitive services such as compliance programs, screening services, glucose monitoring, and disease management programs. Pharmacists must document their role and its effects on patient outcomes.

Objective: To determine in nonresearch, general medical practice conditions the comparative incidence and types of bleeding complications after the use of streptokinase (SK) and r-alteplase (recombinant tissue plasminogen activator, rt-PA) to treat acute myocardial infarction (AMI)., Design: Retrospective medical record review of concurrently treated patients (96-hour observation posttreatment) in 32 participating hospitals in the US., Main Outcome Measures: The medical record description of all bleeding events regarding the body site affected, changes in hemoglobin concentrations, blood products administered, and clinical outcome (permanent sequelae or death). Bleeding severity was determined by defined criteria., Control Data: Comorbidity and concomitant medications (e.g., aspirin, heparin, warfarin) likely to predispose or contribute to bleeding events were analyzed., Data Analysis: Logistic regression analysis., Results: Data from 419 patients who received rt-PA and 207 who received SK were evaluated. In the 96-hour period after initiation of thrombolytic therapy, 30.5 and 31.9 percent of rt-PA and SK patients, respectively, experienced one or more bleeding events (crude risk ratio [CRR] = 1.04; 95 percent confidence interval [CI] 0.91-1.14; p = 0.73). In the first 24-hour period, 21.5 percent of rt-PA and 15.9 percent of SK patients experienced bleeding events (CRR = 0.74; 95 percent CI 0.42-1.15; p = 0.08). The leading types of bleeding and percents of all patients affected were: perivascular access site (18.4 percent), gastrointestinal (6.4 percent), skin/soft tissue/muscle (5.0 percent), urinary (3.4 percent), pulmonary (2.2 percent), systemic (1.9 percent), and oral (1.4 percent). Intracranial bleeding occurred in 4 rt-PA and 2 SK patients; 4 of these patients died. Events deemed clinically significant occurred in 15 rt-PA and 9 SK patients (3.8 percent of all patients). Ten patients likely died from these events, 6 within the first 24 hours. Three rt-PA patients and 1 who received SK (0.6 percent) died of cerebrovascular events within the first 24 hours. After controlling for demographic factors and therapeutic variables, using logistic regression analyses, no thrombolytic-related differences were found in the incidence or severity of bleeding following use of the two thrombolytics., Conclusions: These clinical data do not support a theoretical advantage of rt-PA to cause less bleeding propensity than SK.

A pharmacy student has many career options upon graduation. These options include graduate education in one of the pharmaceutical sciences and a retail pharmacy position. The attractive salaries offered by chain pharmacies play an important role in the recent graduate's career decision-making process. The purpose of this study is to provide a comparative assessment of the internal rate of return (IRR) for different pharmaceutical science career options as related to chain-store pharmacist earnings. Additionally, this study analyzes the effect of the IRR on the applicant pool size and composition for graduate study in pharmaceutical sciences. Income/age profiles were developed using public domain income data derived from salary surveys sponsored by professional associations. Based on these income/age profiles, IRRs were estimated for the pharmaceutical science disciplines, clinical pharmacy, pharmaceutics, medicinal chemistry, and pharmacy administration, and further differentiated for industry versus academic careers. The IRRs are the highest for Pharm.D.'s in academic careers (16.0%), followed by pharmaceutical scientists employed by pharmaceutical industry (8.13%). The IRR of pharmaceutical scientists in academia is lower than the return of other financial investment vehicles. Other authors have established a relationship between the IRR of a profession and a rise or decline in the applicant pool. The IRRs calculated here imply that this association can also be observed for the pharmaceutical scientist applicant pool. Low IRRs should result in a declining applicant pool. However, the last decade has shown an increase of 66% in the number of Ph.D.'s granted, while the percentage of Ph.D.'s granted to nonpharmacists or non-Americans has not increased significantly over the same time period.(ABSTRACT TRUNCATED AT 250 WORDS)