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Introduction Diagnosis and treatment of invasive mold infections (IMI) can be challenging and IMI is a significant source of morbidity and mortality. Invasive aspergillosis (IA) and invasive mucormycosis (IM) are two of the most common mold infections. A better understanding of patient comorbidities and risk factors that predispose IMI may help clinicians to refine the difficult diagnostic and treatment process. Methods A systematic literature review (SLR) was conducted (January 2008–October 2019) for studies reporting comorbidities/risk factors of patients with IA or IM (Phase I), followed by an analysis on the Optum® US EHR database of prominent risk factor cohorts based on SLR findings and expert opinion (Phase II). From the four identified patient cohorts: 1) patients undergoing solid organ transplant (SOT) and patients with 2) hematologic cancers, 3) diabetes, or 4) lung disease, rates of IA, IM, or concurrent IA and IM; patient comorbidities; and Charlson Comorbidity Index (CCI) scores were reported. Results The SLR included 88 studies, and 46 were used to select comorbidities/risk factors cohorts in IA and IM patients. The most important comorbidities/risk factors in IA and IM patients were diabetes, lung disease, hematological malignances, and SOT. In the Optum database (N=101,340,454 patients), IA rates were highest in lung transplant (10.81%) patients and IM rates were highest in intestine transplant (0.83%) patients, lung transplant (0.43%), and hematopoietic stem cell transplant (0.49%). CCI scores were elevated in all mold infection groups compared to the total Optum cohort. Conclusion The current study describes patient comorbidity and risk factors associated with IA and IM. These data can be used to refine clinical decision-making regarding when to suspect mold infections. Future research should focus on identifying whether patients respond differently to various antifungal treatments to determine if strategic recommendations should be made for certain patient groups.

Administrative burden is one of many potential root causes of physician burnout. Scribe documentation assistance can reduce this burden. However, traditional in-person scribe services are challenged by consistent staffing because the model requires the physical presence of a scribe and limits the team to a single individual. In addition, in-person scribes cannot provide the flexible support required for virtual care encounters, which can now pivot geographically and temporally. To respond to these challenges, our health network implemented an asynchronous virtual scribe model and evaluated the program's impact on clinician perceptions of burnout across multiple outpatient specialties.Using a mixed-methods, pre-/postdesign, this evaluation measured the impact of an asynchronous virtual scribe program on physician burnout. Physicians were given the Professional Fulfillment Index tool (to self-assess their mental state) and free-text comment surveys before virtual scribe initiation and again at 3-, 6-, and 12-month intervals after program implementation. Descriptive statistics of survey results and qualitative review of free-text entries were analyzed for themes of facilitation and barriers to virtual scribe use.Of 50 physician participants in this study, 42 (84%) completed the preintervention survey and 15 (36%) completed all 4 surveys; 25 participants (50%) discontinued scribe use after 12 months. Burnout levels-as defined by dread, exhaustion, lack of enthusiasm, decrease in empathy, and decrease in colleague connection-all trended toward improvement during this study. Importantly, quality, time savings, burnout, and productivity moved in positive directions as well.The cost burden to physicians and the COVID-19 pandemic inhibited the continued use of asynchronous virtual medical scribes. Nevertheless, those who continued in the program have reported positive outcomes, which indicates that the service can be a viable and effective tool to reduce physician burnout.

Table S1: Detailed cell line information; Table S2: Reagent details; Table S3: p values from proliferation assays presented in Supplemental Fig. 3 and Supplemental Fig. 4; Table S4: Tumor volume summary for pediatric rhabdoid tumor and osteosarcoma xenografts; Table S5: Characterization of patient-derived xenograft models for PDGF receptor and ligand expression; Figure S1. PDGF receptor expression in pediatric bone and soft tissue tumors cell lines; Figure S2. Olaratumab blocks PDGFRα activation in normal human fibroblasts; Figure 3. The AT/RT cell lines BT-12 and BT-16 are negative for PDGF receptor expression and are not affected by olaratumab treatment; Figure 4. Olaratumab reduces PDGFRα-expressing tumor cell proliferation alone and in combination with chemotherapy; Figure 5: Supplemental Figure 5. Olaratumab serum concentration is consistent across different mouse models of pediatric bone and soft tissue sarcoma; Figure 6. Characterization of CCSARC005 osteosarcoma patient-derived xenograft model for PDGFRα expression; Figure 5. Olaratumab serum concentration is consistent across different mouse models of pediatric bone and soft tissue sarcoma; Figure 6. Characterization of CCSARC005 osteosarcoma patient-derived xenograft model for PDGFRα expression.

Supplementary Tables S1-S3, Figures S1-S4

Purpose:Ewing sarcoma (ES) is a rare and highly malignant cancer that occurs in the bone and surrounding tissue of children and adolescents. The EWS/ETS fusion transcription factor that drives ES pathobiology was previously demonstrated to modulate cyclin D1 expression. In this study, we evaluated abemaciclib, a small-molecule CDK4 and CDK6 (CDK4 and 6) inhibitor currently under clinical investigation in pediatric solid tumors, in preclinical models of ES.Experimental Design:Using Western blot, high-content imaging, flow cytometry, ELISA, RNA sequencing, and CpG methylation assays, we characterized the in vitro response of ES cell lines to abemaciclib. We then evaluated abemaciclib in vivo in cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models of ES as either a monotherapy or in combination with chemotherapy.Results:Abemaciclib induced quiescence in ES cell lines via a G1 cell-cycle block, characterized by decreased proliferation and reduction of Ki-67 and FOXM1 expression and retinoblastoma protein (RB) phosphorylation. In addition, abemaciclib reduced DNMT1 expression and promoted an inflammatory immune response as measured by cytokine secretion, antigen presentation, and interferon pathway upregulation. Single-agent abemaciclib reduced ES tumor volume in preclinical mouse models and, when given in combination with doxorubicin or temozolomide plus irinotecan, durable disease control was observed.Conclusions:Collectively, our data demonstrate that the antitumor effects of abemaciclib in preclinical ES models are multifaceted and include cell-cycle inhibition, DNA demethylation, and immunogenic changes.

Supplemental methodology, specifically the in vitro cord formation assay and the enzyme-linked immunosorbent assay.

Purpose: Platelet-derived growth factor receptor α (PDGFRα) is implicated in several adult and pediatric malignancies, where activated signaling in tumor cells and/or cells within the microenvironment drive tumorigenesis and disease progression. Olaratumab (LY3012207/IMC-3G3) is a human mAb that exclusively binds to PDGFRα and recently received accelerated FDA approval and conditional EMA approval for treatment of advanced adult sarcoma patients in combination with doxorubicin. In this study, we investigated olaratumab in preclinical models of pediatric bone and soft tissue tumors.Experimental Design: PDGFRα expression was evaluated by qPCR and Western blot analysis. Olaratumab was investigated in in vitro cell proliferation and invasion assays using pediatric osteosarcoma and rhabdoid tumor cell lines. In vivo activity of olaratumab was assessed in preclinical mouse models of pediatric osteosarcoma and malignant rhabdoid tumor.Results: In vitro olaratumab treatment of osteosarcoma and rhabdoid tumor cell lines reduced proliferation and inhibited invasion driven by individual platelet-derived growth factors (PDGFs) or serum. Furthermore, olaratumab delayed primary tumor growth in mouse models of pediatric osteosarcoma and malignant rhabdoid tumor, and this activity was enhanced by combination with either doxorubicin or cisplatin.Conclusions: Overall, these data indicate that olaratumab, alone and in combination with standard of care, blocks the growth of some preclinical PDGFRα-expressing pediatric bone and soft tissue tumor models. Clin Cancer Res; 24(4); 847–57. ©2017 AACR.

Purpose: Checkpoint kinase 1 (CHK1) is a key regulator of the DNA damage response and a mediator of replication stress through modulation of replication fork licensing and activation of S and G2–M cell-cycle checkpoints. We evaluated prexasertib (LY2606368), a small-molecule CHK1 inhibitor currently in clinical testing, in multiple preclinical models of pediatric cancer. Following an initial assessment of prexasertib activity, this study focused on the preclinical models of neuroblastoma.Experimental Design: We evaluated the antiproliferative activity of prexasertib in a panel of cancer cell lines; neuroblastoma cell lines were among the most sensitive. Subsequent Western blot and immunofluorescence analyses measured DNA damage and DNA repair protein activation. Prexasertib was investigated in several cell line–derived xenograft mouse models of neuroblastoma.Results: Within 24 hours, single-agent prexasertib promoted γH2AX–positive double-strand DNA breaks and phosphorylation of DNA damage sensors ATM and DNA–PKcs, leading to neuroblastoma cell death. Knockdown of CHK1 and/or CHK2 by siRNA verified that the double-strand DNA breaks and cell death elicited by prexasertib were due to specific CHK1 inhibition. Neuroblastoma xenografts rapidly regressed following prexasertib administration, independent of starting tumor volume. Decreased Ki67 and increased immunostaining of endothelial and pericyte markers were observed in xenografts after only 6 days of exposure to prexasertib, potentially indicating a swift reduction in tumor volume and/or a direct effect on tumor vasculature.Conclusions: Overall, these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy. Clin Cancer Res; 23(15); 4354–63. ©2017 AACR.

To date, there are limited real-world studies published on the use of infliximab-dyyb, a biosimilar to reference product (RP) infliximab approved for the treatment of moderate to severe inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) in North America. This study examined utilization patterns and the effects of infliximab-dyyb on clinical outcomes, patient-reported outcomes (PROs), and healthcare resource use (HCRU) in IBD patients in a real-world setting.In this prospective, observational study, adult IBD patients in the US and Canada were recruited to initiate treatment with infliximab-dyyb and followed for 12 months. Patients included biologic-naïve users of infliximab-dyyb and patients switching from RP infliximab or other biologics to infliximab-dyyb. Partial Mayo (pMAYO) and Harvey Bradshaw Index (HBI) scores measured clinical outcomes for the UC and CD cohorts, respectively. Key PRO measures included the SIBDQ, EQ-VAS, and psychological outcomes. In addition, work productivity, HCRU, and adverse events (AEs) were assessed.A total of 67 CD and 48 UC patients were enrolled (51% female; mean age 44 years; 87% Caucasian; mean BMI 27.9). Thirty-nine patients were biologic-naïve, 57 switched from RP infliximab, and 19 switched from other biologics. Among UC biologic-naïve users, pMAYO decreased from 5.67 to 1.09 (p 0.0001) and the remission rate increased from 5.6 to 90.9% (p = 0.0015). For UC patients switching from RP infliximab, pMAYO decreased from 1.38 to 0.29 (p = 0.0103). For CD biologic-naïve users, HBI scores and remission rates did not significantly change. The scores on all the PROs significantly improved from baseline to 12 months. A total of 22 AEs occurred consistent with the known AE profile for infliximab.Clinical outcomes among biologic-naïve users of infliximab-dyyb improved for UC and were maintained for CD patients. Biologic-naïve users of infliximab-dyyb showed significant improvements in PROs. Patients switching from RP infliximab to infliximab-dyyb maintained their clinical outcomes and PROs.ClinicalTrials.gov Registration Number: NCT03801928 (February 23, 2018).

To describe the clinical characteristics of varicella patients seeking medical consultation and the use of antimicrobials for their management in Thailand in the absence of universal varicella vaccination (UVV). A multicenter, retrospective chart review of 260 children and adults with a primary diagnosis of varicella was conducted at one private and three public hospitals in Bangkok, Thailand. Charts of varicella patients (inpatient or outpatient) were randomly selected over a 5-year period. Key outcomes included clinical complications and the use of antibiotics, antivirals, and other medications. Charts of 200 children (mean age 5.7 years, range 0.3–16 years) and 60 adults (mean age 27.9 years, range 18–50 years) were reviewed. Fourteen patients (including 8 children) were hospitalized. Five percent of the children and none of the adults were immunocompromised. At least 1 varicella-related complication was reported by 7.3% (7% of children, 8.3% of adults, p = .778) of all patients, including 57.1% (62.5% of children, 50% of adults) of inpatients (p < .001, compared with outpatients). Skin/soft tissue infection (47.7%) and dehydration (47.4%) were the most common complications. Antivirals (mainly oral acyclovir) were prescribed to 46.5% of patients (31.5% of children, 96.7% of adults, p < .001). Antibiotics were prescribed to 20.8% of patients (19% of children, 26.7% of adults, p = .199). Topical, oral, and intravenous antibiotics were prescribed to 12.3%, 8.5%, and 1.2% of patients, respectively. Antimicrobial prescriptions were higher among adults (p < .001) and immunocompromised patients (p = .025). Apart from antimicrobials, acetaminophen (62.3%) and oral antihistamines (51.5%) were the most prescribed. A considerable number of varicella patients, both children and adults, seeking medical consultation in Thai hospitals are prescribed antibiotics and antivirals, with one-fifth of patients being prescribed an antibiotic and almost half prescribed an antiviral. The study may be of interest to policymakers in Thailand and other Asia-Pacific countries considering UVV implementation.

Asynchronous telehealth provides a viable option for improving access in a convenient and timely manner to patients seeking care as well as for physicians seeking subspecialty consultation. Access to technology, clear guidelines, standards, and expectations is required for this innovation to function well. Limitations in access due to patient and technology factors is an area that requires attention. Positive impact on access and quality has been demonstrated. Rapid development continues and was enhanced with the Sars-CoV-2 pandemic.

Anita H Sung,1 Stephan Martin,2 Bryant Phan,1 Michael Benigno,1 Jennifer Stephens,2 Richard Chambers,1 Jalal A Aram1 1Pfizer Inc, New York, NY, USA; 2OPEN Health, Bethesda, MD, USACorrespondence: Anita H SungPfizer, 235 E 42nd St, New York, NY, 10017, USATel +1 212 733-2323Email anita.sung@pfizer.comIntroduction: Diagnosis and treatment of invasive mold infections (IMI) can be challenging and IMI is a significant source of morbidity and mortality. Invasive aspergillosis (IA) and invasive mucormycosis (IM) are two of the most common mold infections. A better understanding of patient comorbidities and risk factors that predispose IMI may help clinicians to refine the difficult diagnostic and treatment process.Methods: A systematic literature review (SLR) was conducted (January 2008–October 2019) for studies reporting comorbidities/risk factors of patients with IA or IM (Phase I), followed by an analysis on the Optum® US EHR database of prominent risk factor cohorts based on SLR findings and expert opinion (Phase II). From the four identified patient cohorts: 1) patients undergoing solid organ transplant (SOT) and patients with 2) hematologic cancers, 3) diabetes, or 4) lung disease, rates of IA, IM, or concurrent IA and IM; patient comorbidities; and Charlson Comorbidity Index (CCI) scores were reported.Results: The SLR included 88 studies, and 46 were used to select comorbidities/risk factors cohorts in IA and IM patients. The most important comorbidities/risk factors in IA and IM patients were diabetes, lung disease, hematological malignances, and SOT. In the Optum database (N=101,340,454 patients), IA rates were highest in lung transplant (10.81%) patients and IM rates were highest in intestine transplant (0.83%) patients, lung transplant (0.43%), and hematopoietic stem cell transplant (0.49%). CCI scores were elevated in all mold infection groups compared to the total Optum cohort.Conclusion: The current study describes patient comorbidity and risk factors associated with IA and IM. These data can be used to refine clinical decision-making regarding when to suspect mold infections. Future research should focus on identifying whether patients respond differently to various antifungal treatments to determine if strategic recommendations should be made for certain patient groups.Keywords: invasive mold infections, systematic literature review, retrospective claims data, invasive aspergillosis, invasive mucormycosis

Eric Armbrecht,1 Ruchit Shah,2 Gregory W Poorman,2 Linlin Luo,2 Jennifer M Stephens,2 Benjamin Li,3 Elizabeth Pappadopulos,4 Seema Haider,5 Roger S McIntyre6– 9 1Saint Louis University Center for Health Outcomes Research, Saint Louis University, Saint Louis, MO, USA; 2Pharmerit International, Bethesda, MD, USA; 3Pfizer Inc., New York, NY, USA; 4Viatris Inc., New York, NY, USA; 5Pfizer Inc., Groton, CT, USA; 6Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada; 7Department of Psychiatry, University of Toronto, Toronto, ON, Canada; 8Department of Pharmacology, University of Toronto, Toronto, ON, Canada; 9Brain and Cognition Discovery Foundation, Toronto, ON, CanadaCorrespondence: Jennifer M StephensPharmerit International, 4350 East West Hwy #1100, Bethesda, MD, 20814, USATel +1-240-821-1290Email JenniferStephens@openhealthgroup.comIntroduction: Patients with both major depressive disorder (MDD) and generalized anxiety disorder (GAD) in addition to one or multiple comorbid non-communicable chronic diseases (NCCDs)face unique challenges. However, few studies have characterized how the burden of co-occurring MDD and GAD differs from that of only MDD or only GAD among patients with NCCDs.Methods: In this study, we used Medical Expenditures Panel Survey data from 2010– 2017 to understand how the economic and humanistic burden of co-occurring MDD and GAD differs from that of MDD or GAD alone among patients with NCCDs. We used generalized linear models to investigate this relationship and controlled for patient sociodemographics and clinical characteristics.Results: Co-occurring MDD and GAD was associated with increases in mean annual per patient inpatient visits, office visits, emergency department visits, annual drug costs, and total medical costs. Among patients with 3+ NCCDs, MDD or GAD only was associated with lower odds ratios (ORs) of limitations in activities of daily living (ADLs; 0.532 and 0.508, respectively) and social (0.503, 0.526) and physical limitations (0.613, 0.613) compared to co-occurring MDD and GAD. Compared to patients with co-occurring MDD and GAD, having MDD only or GAD only was associated with significantly lower odds of cognitive limitations (0.659 and 0.461, respectively) in patients with 1– 2 NCCDs and patients with 3+ NCCDs (0.511, 0.416).Discussion: Comorbid MDD and GAD was associated with higher economic burden, lower quality of life, and greater limitations in daily living compared to MDD or GAD alone. Health-related economic and humanistic burden increased with number of NCCDs.Keywords: economic burden, humanistic burden, depression, anxiety, non-communicable diseases

Background: The COVID-19 (C-19) pandemic required swift response from health care organizations to mitigate spread and impact. A large integrated health network rapidly deployed and operationalized multiple access channels to the community, allowing assessment and triage to occur virtually. These channels were characterized by swift implementation of virtual models, including asynchronous e-visits and video visits for C-19 screening. Purpose: (1) Evaluate implementation characteristics of C-19 screening e-visits and video visits. (2) Identify volume of C-19 screening and other care provided via e-visits and video visits. (3) Discuss future implications of expanded virtual access models. Methods: Retrospective analysis of implementation data for C-19 screening e-visits and video visits, including operational characteristics and visit/screening volumes conducted. Results: Virtual channels were implemented and rapidly expanded during the first week C-19 testing was made available. During the study period, primary care clinicians conducted 10,673 e-visits and 31,226 video visits with 9,126 and 26,009 patients, respectively. Within these 2 virtual modalities, 4,267 C-19 tests were ordered (10% of visits). Four hundred forty-eight clinicians supported 24/7 access to these virtual modalities. Discussion: Given ongoing patient interest and opportunity, virtual health care services will continue to be available for an expanded number of symptoms and diagnoses.

Background Bevacizumab remains the most widely used and most thoroughly characterized angiogenesis inhibitor for a range of advanced cancers. Bevacizumab-bvzr (Zirabev®), a biosimilar of bevacizumab, was recently approved by the US Food and Drug Administration (FDA), which provides a less costly option. This study aimed to evaluate the financial impact of introducing bevacizumab-bvzr from US commercial and Medicare payer perspectives. Methods A Microsoft Excel-based budget impact model was developed over a 5-year time horizon. Target population was patients to be treated with bevacizumab for FDA-approved indications. Drug costs (2020 US$) were based on average sales price and wholesale acquisition cost, accounting for payer-specific reimbursement models and provider settings. Drug dosing and duration were based on prescribing information and pivotal trial publications. Results In a hypothetical 10-million-member health plan, 503 and 723 patients were estimated to be treated with bevacizumab in year 1 and year 5, respectively. Assuming an annual market shift of 1.7%, 3.6%, 6.7%, 9.4%, and 11.9% to bevacizumab-bvzr, an annual cost saving of $313,363 ($0.003 per member per month [PMPM]) was estimated for a commercial payer and $92,880 ($0.001 PMPM) for Medicare in year 1. Cumulative 5-year cost savings were $7,030,924 ($0.012 PMPM) for a commercial payer and $4,059,257 ($0.007 PMPM) for Medicare. More than half of the cost savings was attributed to patients with metastatic colorectal cancer. Conclusions The introduction of biosimilar bevacizumab-bvzr was estimated to provide substantial cost savings for US payers, which would allow additional patients access to bevacizumab treatment.

NYVEPRIA, a pegfilgrastim (a long-acting granulocyte colony-stimulating factor [G-CSF]) biosimilar, was recently recommended for marketing authorization in Europe for decreasing the incidence of febrile neutropenia (FN) in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs. The present study aimed to evaluate the financial impact of introducing a new pegfilgrastim biosimilar from a French healthcare system perspective.An Excel-based budget impact model was developed to estimate the financial impact by introducing a new pegfilgrastim biosimilar (NYVEPRIA) to France over a 5-year time horizon. Comparators included existing long-acting and short-acting G-CSFs. The burden of FN was obtained from existing literature. Costs (2021 Euros) included drug acquisition and administration, estimated based on drug dosage in both clinical trial and real-world settings. Scenario analyses were conducted to examine the robustness of key model assumptions.In a total French population of 67.19 million, 79,873 patients were estimated to be treated with G-CSFs annually. The annual number of patients to be treated with NYVEPRIA was estimated to be 1593, 3195, 3674, 3782, and 4052 in years 1 to 5, respectively. Using real-world data, NYVEPRIA resulted in total annual cost savings of €8,620, €868,498, €868,498, €814,102, and €958,952 over years 1 to 5, respectively, leading to a cumulative 5-year cost savings of €3,518,669. Using data from clinical trials, NYVEPRIA resulted in total annual cost savings of €14,366, €1,447,496, €1,447,496, €1,356,836, and €1,598,253 over years 1 to 5, respectively, leading to a cumulative 5-year cost savings of €5,864,448.The introduction of a new pegfilgrastim biosimilar (NYVEPRIA) is potentially associated with substantial cost savings for the French healthcare system.

Background: Real-world data suggests superiority of pegfilgrastim (PEG) over filgrastim (FIL) in reducing the incidence of chemotherapy-induced febrile neutropenia (FN), probably attributable to underdosed FIL in practice. We used real-world data to assess the cost–effectiveness of primary prophylaxis with PEG versus FIL in cancer patients at intermediate-to-high risk of FN from a US payer perspective. Methods: A Markov model with lifetime horizon. Results: For the high-risk group, PEG (vs FIL) biosimilars resulted in 0.43 FN events prevented (FNp), 0.27 quality-adjusted life-years gained (QALYg) and a cost saving of USD$5703. For the intermediate-risk group, PEG biosimilar led to 0.18 FNp and 0.12 QALYg, at USD$9674/FNp and USD$14,502/QALYg. Conclusion: PEG biosimilars may provide opportunities to optimize FN management in patients with intermediate-to-high FN risk.

Mechanical ventilation (MV) remains a substantial cost driver in intensive care units (ICU) in the United States (US). Evaluations of standard sedation treatments used to relieve pain and discomfort in this setting have found varying impacts on ICU length of stay. This cost analysis examines both length-of=stay costs and the total cost implications among MV patients receiving common sedative treatments (dexmedetomidine, propofol, or midazolam) in short-term sedation settings (24 hours).A cost-minimization model was conducted from the hospital provider perspective. Clinical outcomes were obtained from published literature and included ICU length of stay, MV duration, prescription of sedatives and pain medication, and the occurrence of adverse events. Outcomes costs were obtained from previously conducted ICU cost studies and Medicare payment fee schedules. All costs were estimated in 2018 US Dollars.The per patient costs associated with dexmedetomidine, propofol, and midazolam were estimated to be $21,115, $27,073, and $27,603, respectively. Dexmedetomidine was associated with a savings of $5958 per patient compared to propofol and a saving of $6487 compared to midazolam. These savings were primarily driven by a reduction in ICU length of stay and the degree of monitoring and management.Dexmedetomidine was associated with reduced costs when compared to propofol or midazolam used for short-term sedation during MV in the ICU, suggesting sedative choice can have a potential impact on overall cost per episode.

Jyoti Aggarwal,1 Jacqueline Lustrino,1 Jennifer Stephens,2 Diana Morgenstern,3 Wing Yu Tang4 1Pharmerit International, Newton, MA, USA; 2Pharmerit International, Bethesda, MD, USA; 3Pfizer, Collegeville, PA, USA; 4Pfizer, New York, NY, USACorrespondence: Wing Yu TangPfizer, 235 E. 42nd St, New York, NY 10017, USAEmail wingyu.tang@pfizer.comPurpose: Mechanical ventilation (MV) remains a substantial cost driver in intensive care units (ICU) in the United States (US). Evaluations of standard sedation treatments used to relieve pain and discomfort in this setting have found varying impacts on ICU length of stay. This cost analysis examines both length-of=stay costs and the total cost implications among MV patients receiving common sedative treatments (dexmedetomidine, propofol, or midazolam) in short-term sedation settings (< 24 hours).Methods: A cost-minimization model was conducted from the hospital provider perspective. Clinical outcomes were obtained from published literature and included ICU length of stay, MV duration, prescription of sedatives and pain medication, and the occurrence of adverse events. Outcomes costs were obtained from previously conducted ICU cost studies and Medicare payment fee schedules. All costs were estimated in 2018 US Dollars.Results: The per patient costs associated with dexmedetomidine, propofol, and midazolam were estimated to be $21,115, $27,073, and $27,603, respectively. Dexmedetomidine was associated with a savings of $5958 per patient compared to propofol and a saving of $6487 compared to midazolam. These savings were primarily driven by a reduction in ICU length of stay and the degree of monitoring and management.Conclusion: Dexmedetomidine was associated with reduced costs when compared to propofol or midazolam used for short-term sedation during MV in the ICU, suggesting sedative choice can have a potential impact on overall cost per episode.Keywords: sedation, dexmedetomidine, midazolam, propofol, costs, model

Courtney Johnson,1 Jennifer Stephens,1 Christopher Walker,2 Joseph C Cappelleri,3 Ahmed Shelbaya4 1Pharmerit International, Real World Evidence and Data Analytics, Bethesda, MD, USA; 2Pfizer Ltd., Global Medical Affairs, Tadworth, Surrey, England; 3Pfizer Inc., Statistics, Groton, CT, USA; 4Pfizer Inc., Health Economics and Outcomes Research, New York, NY, USACorrespondence: Jennifer StephensPharmerit International, 4350 East West Highway, Suite 1100, Bethesda, MD, USATel +1 240-821-1290Email jstephens@pharmerit.comObjective: This study describes treatment patterns, healthcare resource utilization (HCRU), and costs associated with persistence, switching, and dosing of branded celecoxib in osteoarthritis (OA) patients.Methods: This retrospective claims database analysis used MarketScan® Commercial Claims and Encounters (MarketScan) data from 2009 to 2013. Included patients were adult (≥ 18 years), incident celecoxib users with ≥ 1 OA claim. The treatment switch analysis analyzed outcomes in patients persistent on celecoxib versus switched to a generic nonsteroidal anti-inflammatory drug (NSAID). The dosing analysis stratified patients as under-dose (< 200 mg per day) and standard dose (≥ 200 mg per day). HCRU, costs, and treatment duration were compared in persistent versus switched and standard dose versus under-dose patients using descriptive, multivariate logistic regression, and Kaplan–Meier analysis.Results: A total of 65,530 patients met the inclusion criteria. During follow-up, 83% discontinued celecoxib without switching, 10% were persistent, and 5% switched to a generic NSAID. Ninety percent received a standard dose of celecoxib. Switched (versus persistent) patients had significantly higher all-cause hospital admissions, length of stay, emergency room (ER) visits, and office visits per person year (PPY), all P < 0.001; and under-dosed (versus standard dose) patients had significantly higher hospital admissions (P< 0.001), length of stay (P< 0.001), and ER visits (P= 0.021) PPY. Persistent versus switched patients had lower mean total all-cause costs PPY ($20,378 vs $23,949, P< 0.001). Standard dose versus under-dose patients had lower mean total all-cause costs ($23,680 vs $26,955 PPY, P< 0.001), and not statistically significant higher mean total OA-related costs ($5698 vs $5524 PPY, P=0.441).Conclusion: Patients that switched from branded celecoxib to a generic NSAID or received an under-dose of branded celecoxib had higher average overall HCRU and costs. OA-related inpatient and outpatient cost savings may offset the higher drug cost of celecoxib for persistent patients.Keywords: generic, healthcare resource use, Celebrex, NSAIDS, switching, discontinuation

Aims: The current study examined the association between insufficient major depressive disorder (MDD) care and healthcare resource use (HCRU) and costs among patients with prior myocardial ...

As the number of cancer cases rise each year in Canada, so does the number of surgical oncology cases. Surgery presents a unique and heightened stressor for the body already experiencing volatility from factors such as disease and treatments. Perioperative red blood cell (RBC) transfusions are critical to stabilize hemoglobin levels and correct anemia, as well as provide a buffer against anticipated intraoperative blood loss. Thoroughly examining and anticipating risk factors related to the potential need for perioperative blood transfusions is necessary to improve outcomes. Research evidence in recent years related to perioperative blood management of oncology patients has specifically recommended active, coordinated programs to reduce the need and amount of blood transfusions administered pre-, intra-, and post-surgery. Coordination between surgical oncologists and a local or provincial patient blood management (PBM) program is an important strategy that allows patients at risk of perioperative complications to be identified and receive early interventions and ongoing observation.

Au Canada, le nombre de cas de cancer augmente chaque année et, par conséquent, le nombre de patients en oncologie qui subissent une opération. La chirurgie cause un stress particulièrement intense à l’organisme déjà fragilisé par la maladie et les traitements. Les transfusions périopératoires de globules rouges sont essentielles pour stabiliser le taux d’hémoglobine et soigner l’anémie, ainsi que pour gérer la perte de sang attendue pendant l’opération. Il est nécessaire d’examiner en profondeur et d’anticiper les facteurs de risque associés aux transfusions sanguines périopératoires pour améliorer le devenir des patients. Ces dernières années, la recherche sur la gestion périopératoire du sang des patients en oncologie recommande tout spécialement la création de programmes d’intervention coordonnés pour réduire la nécessité et le nombre de transfusions sanguines administrées avant, pendant et après l’opération. Pour recenser les patients à risque de complications périopératoires et leur faire bénéficier d’interventions rapides et d’une observation continue, la bonne stratégie est de mettre en lien les chirurgiens oncologues avec un programme local ou provincial de conservation du sang.

Programmed meiotic DNA double-strand breaks (DSBs), necessary for proper chromosomal segregation and viable gamete formation, are repaired by homologous recombination (HR) as crossovers (COs) or non-crossovers (NCOs). The mechanisms regulating the number and distribution of COs are still poorly understood. The regulator of telomere elongation helicase 1 (RTEL1) DNA helicase was previously shown to enforce the number of meiotic COs in Caenorhabditis elegans but its function in plants has been studied only in the vegetative phase. Here, we characterised barley RTEL1 gene structure and expression using RNA-seq data previously obtained from vegetative and reproductive organs and tissues. Using RNAi, we downregulated RTEL1 expression specifically in reproductive tissues and analysed its impact on recombination using a barley 50k iSelect SNP Array. Unlike in C. elegans, in a population segregating for RTEL1 downregulated by RNAi, high resolution genome-wide genetic analysis revealed a significant increase of COs at distal chromosomal regions of barley without a change in their total number. Our data reveal the important role of RTEL1 helicase in plant meiosis and control of recombination.