Serial Peripheral Nerve Blocks to Aid in Salvage of a Compromised Limb: A Case Report.

The management of postsurgical thrombosis in a medically complicated patient is often not straightforward. We describe a case of a congenital heart disease patient with multiple risk factors for thrombosis with a compromised limb immediately after heart transplant who received serial daily peripheral nerve blocks (PNBs) resulting in limb salvage. The analgesic effects of the blocks allowed for clinical progression and participation in rehabilitation therapy, and the vasodilatory effects of the blocks helped prevent a below the knee amputation (BKA) in this devitalized and congested extremity.

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.

The utilization of caudal hydromorphone for fast-tracking in congenital cardiac surgery in a tertiary-care Children's hospital: An audit.

STUDY OBJECTIVE: Our study sought to audit our institutional practice of routine single-shot caudal epidural hydromorphone injection in children undergoing congenital cardiothoracic surgery to assess perioperative pain control and evaluate for any caudal complications. DESIGN: Retrospective observational study of all patients that received a caudal hydromorphone injection as part of the anesthetic for their cardiac surgical operation between January 2017 and July 2019. SETTING: Pediatric Cardiothoracic Operating Room (OR), Cardiac Intensive Care Unit. PATIENTS: One hundred and twenty-seven patients that received caudal hydromorphone as part of their anesthetic for a cardiac surgical operation. INTERVENTIONS: Caudal epidural injection performed immediately following induction of anesthesia utilizing only hydromorphone. MEASUREMENTS: The primary outcome was well-controlled pain, defined as a score of <4/10 on rFLACC or verbal pain scoring. Secondary outcome measures included in-OR extubation, pain service duration (from first assessment to "sign-off"), complications related to the caudal block, intensive care unit (ICU) length of stay (LOS), and Hospital LOS. MAIN RESULTS: One hundred and nine patients were included in the final analysis. Pain was "well-controlled" on average in 96.3% of patients (105/109). Average pain in the 24-h post-block period was 1.67 (SD = 2.37), with median pain score of 0 [0-3]. Peak pain score remained <4/10 for the entire 24-h post-block period in 22% of patients. 77.1% of caudal hydromorphone patients were extubated in the operating room. The median time to heparinization post-block was 108 min, beyond the ASRA recommendation of 60 min for neuraxial procedures. There were two caudal-related complications: one subcutaneous injection, and one instance of a time to heparinization of less than 60 min (56 min). Neither caudal complication led to patient harm. CONCLUSION: Caudal hydromorphone injection can safely contribute to achieving "well-controlled" pain in the pediatric cardiac surgical population when used as a component of a perioperative pain control plan.

Use of a Rigid Bronchoscope as the Sole Prebypass Airway During Pediatric Tracheal Tumor Resection: A Case Report.

We describe the anesthetic and operative techniques utilized for a tracheal tumor resection in a pediatric patient with 95% tracheal occlusion. In prior tracheal tumor cases that dictated complete resection, our team had been able to comfortably bypass a tumor with an endotracheal tube. In this case, we could not intubate past the tumor. A rigid bronchoscope was able to be placed past the tumor, so we continued with sternotomy and dissection before cardiopulmonary bypass while ventilating through that bronchoscope as our definitive airway.

Systemic tumour suppression via the preferential accumulation of erythrocyte-anchored chemokine-encapsulating nanoparticles in lung metastases.

Eliciting immune responses against primary tumours is hampered by their immunosuppressive microenvironment and by the greater inaccessibility of deeper intratumoural cells. However, metastatic tumour cells are exposed to highly perfused and immunoactive organs, such as the lungs. Here, by taking advantage of the preferential colocalization of intravenously administered erythrocytes with metastases in the lungs, we show that treatment with chemokine-encapsulating nanoparticles that are non-covalently anchored onto the surface of injected erythrocytes results in local and systemic tumour suppression in mouse models of lung metastasis. Such erythrocyte-anchored systemic immunotherapy led to the infiltration of effector immune cells into the lungs, in situ immunization without the need for exogenous antigens, inhibition of the progression of lung metastasis, and significantly extended animal survival and systemic immunity that suppressed the growth of distant tumours after rechallenge. Erythrocyte-mediated systemic immunotherapy may represent a general and potent strategy for cancer vaccination.

Cellular backpacks for macrophage immunotherapy.

Adoptive cell transfers have emerged as a disruptive approach to treat disease in a manner that is more specific than using small-molecule drugs; however, unlike traditional drugs, cells are living entities that can alter their function in response to environmental cues. In the present study, we report an engineered particle referred to as a "backpack" that can robustly adhere to macrophage surfaces and regulate cellular phenotypes in vivo. Backpacks evade phagocytosis for several days and release cytokines to continuously guide the polarization of macrophages toward antitumor phenotypes. We demonstrate that these antitumor phenotypes are durable, even in the strongly immunosuppressive environment of a murine breast cancer model. Conserved phenotypes led to reduced metastatic burdens and slowed tumor growths compared with those of mice treated with an equal dose of macrophages with free cytokine. Overall, these studies highlight a new pathway to control and maintain phenotypes of adoptive cellular immunotherapies.

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.

Materials for Immunotherapy.

Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell-mediated transport and serve as artificial antigen-presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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.

Preoperative Pulmonary Function Test Results Are Not Associated With Postoperative Intubation in Children Undergoing Posterior Spinal Fusion for Scoliosis: A Retrospective Observational Study.

BACKGROUND: Preoperative pulmonary function tests are routinely obtained in children with scoliosis undergoing posterior spinal fusion despite unclear benefits as a perioperative risk assessment tool and frequent inability of patients to provide acceptable results. The goal of this study was to determine whether preoperative pulmonary function test results are associated with the need for postoperative intubation or intensive care unit admission after posterior spinal fusion. METHODS: The electronic medical records of patients who underwent posterior spinal fusion at a pediatric tertiary hospital between June 2012 and August 2017 were reviewed. Pulmonary function tests were consistently ordered for all patients, unless the patient was deemed unable to perform the test due to cognitive disability. Cases were categorized as primary or secondary scoliosis.Demographic data, preoperative bilevel positive airway pressure use, Cobb angle, intraoperative allogeneic blood transfusion, and ability to produce acceptable pulmonary function test results were collected for each patient. In patients with satisfactory pulmonary function test results, forced vital capacity and maximum inspiratory pressure were collected. Primary outcomes for analysis were postoperative intubation and intensive care unit admission. Univariable logistic regression models were used to assess the association between each variable of interest and the primary outcomes. RESULTS: The study sample included 433 patients, 288 with primary scoliosis and 145 with secondary scoliosis. Among patients with primary scoliosis, 90% were able to produce acceptable pulmonary function test results, zero remained intubated postoperatively, and 6 were admitted to the intensive care unit. Among patients with secondary scoliosis, 44% could not attempt pulmonary function tests. Among those who did attempt the test, 30% were unable to produce meaningful results. Forced vital capacity and maximum inspiratory pressure were not found to be associated with postoperative intubation or intensive care unit admission. Weight, Cobb angle, intraoperative blood transfusion, American Society of Anesthesiologists physical status classification, and preoperative bilevel positive airway pressure use were associated with patient outcomes. Among 357 total patients who attempted pulmonary function tests, 37 had high-risk results. Only 1 of these 37 patients remained intubated postoperatively. CONCLUSIONS: Patients undergoing posterior spinal fusion, especially those with secondary scoliosis, are frequently unable to adequately perform pulmonary function tests. Among patients with interpretable pulmonary function tests, there was no association between results and postoperative intubation or intensive care unit admission. Routine pulmonary function testing for all patients with scoliosis may not be indicated for purposes of risk assessment before posterior spinal fusion. Clinicians should consider a targeted approach and limit pulmonary function tests to patients for whom results may guide preoperative optimization as this may improve outcomes and reduce inefficiencies and costs.

Selected 2018 Highlights in Congenital Cardiac Anesthesia.

THIS ARTICLE IS a review of the highlights of pertinent literature published during the 12 months of 2018 that is of interest to the congenital cardiac anesthesiologist. During a search of the US National Library of Medicine PubMed database, several topics that displayed significant contributions to the field in 2018 emerged. The authors of the present review consider the following topics noteworthy: the patient with high-risk congenital heart disease (CHD) presenting for noncardiac surgery, cardiopulmonary resuscitation in infants and children with CHD, dexmedetomidine use in pediatric patients, point-of-care lung ultrasound, and regional anesthesia in pediatric cardiac surgery.

Macrophage-mediated delivery of light activated nitric oxide prodrugs with spatial, temporal and concentration control.

Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd3+-doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages. Both the photoNORM [Mn(NO)dpaqNO2 ]BPh4(dpaqNO2 = 2-[N,N-bis(pyridin-2-yl-methyl)]-amino-N'-5-nitro-quinolin-8-yl-acetamido) and the Nd-UCNPs are activated by tissue-penetrating near-infrared (NIR) light at ∼800 nm. Thus, simultaneous therapeutic NO delivery and photoluminescence (PL) imaging can be achieved with a NIR diode laser source. The loaded microparticles are non-toxic to their macrophage hosts in the absence of light. The microparticle-carrying macrophages deeply penetrate into NIH-3T3/4T1 tumor spheroid models, and when the infiltrated spheroids are irradiated with NIR light, NO is released in quantifiable amounts while emission from the Nd-UCNPs provides images of microparticle location. Furthermore, varying the intensity of the NIR excitation allows photochemical control over NO release. Low doses reduce levels of hypoxia inducible factor 1 alpha (HIF-1α) in the tumor cells, while high doses are cytotoxic. The use of macrophages to carry microparticles with a NIR photo-activated theranostic payload into a tumor overcomes challenges often faced with therapeutic administration of NO and offers the potential of multiple treatment strategies with a single system.

Moving anesthesiology educational resources to the point of care: experience with a pediatric anesthesia mobile app.

BACKGROUND: Educators in all disciplines recognize the need to update tools for the modern learner. Mobile applications (apps) may be useful, but real-time data is needed to demonstrate the patterns of utilization and engagement amongst learners. METHODS: We examined the use of an anesthesia app by two groups of learners (residents and anesthesiologist assistant students [AAs]) during a pediatric anesthesiology rotation. The app calculates age and weight-based information for clinical decision support and contains didactic materials for self-directed learning. The app transmitted detailed usage information to our research team. RESULTS: Over a 12-month period, 39 participants consented; 30 completed primary study procedures (18 residents, 12 AAs). AAs used the app more frequently than residents (P = 0.025) but spent less time in the app (P < 0.001). The median duration of app usage was 2.3 minutes. During the course of the rotation, usage of the app decreased over time. 'Succinylcholine' was the most accessed drug, while 'orientation' was the most accessed teaching module. Ten (33%) believed that the use of apps was perceived to be distracting by operating room staff and surgeons. CONCLUSIONS: Real-time in-app analytics helped elucidate the actual usage of this educational resource and will guide future decisions regarding development and educational content. Further research is required to determine learners' preferred choice of device, user experience, and content in the full range of clinical and nonclinical purposes.

ProvenCare-Psoriasis: A disease management model to optimize care.

There are a variety of evidence-based treatments available for psoriasis. The transition of this evidence into practice is challenging. In this article, we describe the design of our disease management approach for Psoriasis (ProvenCare®) and present preliminary evidence of the effect of its implementation. In designing our approach, we identified three barriers to optimal care: 1) lack of a standardized and discrete disease activity measure within the electronic health record, 2) lack of a system-wide, standardized approach to care, and 3) non-uniform financial access to appropriate non-pharmacologic treatments. We implemented several solutions, which collectively form our approach. We standardized the documentation of clinical data such as body surface area (BSA), created a disease management algorithm for psoriasis, and aligned incentives to facilitate the implementation of the algorithm. This approach provides more coordinated, cost effective care for psoriasis, while being acceptable to key stakeholders. Future work will examine the effect of the implementation of our approach on important clinical and patient outcomes.

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.

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation.

BACKGROUND: Though warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants. METHODS AND RESULTS: This electronic medical record-based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe-TT2R2 score (sex, age, medical history, treatment, tobacco, race) using R2 and c-statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R2 of 15.4%. The proposed model showed better predictive performance than the SAMe-TT2R2 score (R2=3.0%). CONCLUSIONS: The proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging.

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.

A hyaluronic acid conjugate engineered to synergistically and sequentially deliver gemcitabine and doxorubicin to treat triple negative breast cancer.

Combination chemotherapy is commonly used to treat advanced breast cancer. However, treatment success is often limited due to systemic toxicity. To improve therapeutic efficacy, polymer drug conjugates carrying synergistic pairs of chemotherapy drugs can be used to reduce drug administration dose. Here, we systematically evaluated the effect of temporal scheduling of doxorubicin (DOX) and gemcitabine (GEM) on drug synergy. Hyaluronic acid (HA) drug conjugates with distinct linkers conjugating both DOX and GEM were synthesized to control relative release kinetics of each drug. We show that polymer conjugates that release GEM faster than DOX are more effective at killing triple negative breast cancer cells in vitro. We further show that the optimal dual drug conjugate more effectively inhibits the growth of an aggressive, orthotopic 4T1 tumor model in vivo than free DOX and GEM and the single drug HA conjugates. The dual drug HA conjugate can inhibit 4T1 tumor growth in vivo during treatment through both intravenous and non-local subcutaneous injections. These results emphasize the importance of understanding the effect release rates have on the efficacy of synergistic drug carriers and motivate the use of HA as a delivery platform for multiple cancer types.

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.