Real-world Management Research Articles

Multi-period portfolio decision analysis: A case study in the infrastructure management sector

This paper presents an approach to select and plan the optimal execution of potential investment activities. The model is composed by a computational part, in the form of a combinatorial optimization problem, coupled with a preference elicitation module used to capture subjective judgments. In particular, the structure of the elicitation module draws from portfolio decision analysis and Multi-Attribute Value Theory and shows how their use can be integrated with a multi-period optimization problem with activities durations and constraints on their overlaps. The problem formulation was inspired by a real-world infrastructure management case in the energy distribution sector and tested on a dataset of more than three hundred activities of improvement of infrastructure conditions. Finally, the approach proposed in this paper is validated by analyzing its results and its robustness concerning the input data of the real-world case study.

Real-world management and outcomes of 7 million patients with acute coronary syndrome according to clinical research trial enrolment status: a propensity matched analysis.

We aimed to determine whether clinical outcomes and invasive care of acute coronary syndrome (ACS) patients participating in trials differed from those of non-participants, particularly including those who were trial eligible. We included all hospitalizations with a principal diagnosis of ACS in the US National Inpatient Sample between January 2004 and September 2015, stratified by trial enrolment and eligibility using the International Classification of Diseases, ninth revision. We conducted propensity score matching to investigate the following outcomes: all-cause mortality; major bleeding; stroke; composite of mortality, stroke, and cardiac complications [major adverse cardiovascular and cerebrovascular events (MACCEs)]; coronary angiography (CA); and percutaneous coronary intervention (PCI). A total of 7091179 weighted ACS hospitalizations were analysed, including 19684 (0.3%) trial participants and 7071495 non-participants (3485514 of whom were trial eligible). Trial participants were more likely to receive CA [Δ% 28.73%, 95% confidence interval (CI) 27.22-30.24, P < 0.001] and PCI (Δ% 27.13%, 95% CI 24.86-29.41, P < 0.001), with decreased mortality (Δ% -3.51%, 95% CI -4.72 to -2.31, P < 0.001), MACCEs (Δ% -3.04%, 95% CI -4.55 to -1.53, P < 0.001), and bleeding (Δ% -0.89%, 95% CI -1.59 to -0.19, P = 0.013) compared with non-participants. After accounting for eligibility, trial participants were more likely to undergo CA (Δ% 22.78%, 95% CI 21.58-23.99, P < 0.001) and PCI (Δ% 23.95%, 95% CI 21.77-26.13, P < 0.001), and had no difference in mortality (Δ% -0.21%, 95% CI -0.65 to 0.24, P = 0.362). Among ACS patients, trial enrolment was associated with significantly greater invasive care and lower mortality than among matched non-participants. Trial participants were more likely to be invasively managed even when compared with eligible non-participants, even though there was no difference in mortality.

On-Farm Experimentation to transform global agriculture.

Restructuring farmer-researcher relationships and addressing complexity and uncertainty through joint exploration are at the heart of On-Farm Experimentation (OFE). OFE describes new approaches to agricultural research and innovation that are embedded in real-world farm management, and reflects new demands for decentralized and inclusive research that bridges sources of knowledge and fosters open innovation. Here we propose that OFE research could help to transform agriculture globally. We highlight the role of digitalization, which motivates and enables OFE by dramatically increasing scales and complexity when investigating agricultural challenges.

Real-World Management and Clinical Outcomes of Stroke Survivors With Atrial Fibrillation: A Population-Based Cohort in Spain.

Objective: Despite the continuous update of clinical guidelines, little is known about the real-world management of patients with atrial fibrillation (AF) who survived a stroke. We aimed to assess patterns of therapeutic management of stroke survivors with AF and clinical outcomes using data from routine practice in a large population-based cohort. Methods: A population-based retrospective cohort study of all patients with AF who survived a stroke, from January 2010 to December 2017 in the Valencia region, Spain (n = 10,986), was carried out. Treatment strategies and mean time to treatment initiation are described. Temporal trends are shown by the management pattern during the study period. Factors associated with each pattern (including no treatment) vs. oral anticoagulant (OAC) treatment were identified using logistic multivariate regression models. Incidence rates of clinical outcomes (mortality, stroke/TIA, GI bleeding, and ACS) were also estimated by the management pattern. Results: Among stroke survivors with AF, 6% were non-treated, 23% were prescribed antiplatelets (APT), 54% were prescribed OAC, and 17% received OAC + APT at discharge. Time to treatment was 8.0 days (CI 7.6–8.4) for APT, 9.86 (CI 9.52–10.19) for OAC, and 16.47 (CI 15.86–17.09) for OAC + APT. Regarding temporal trends, management with OAC increased by 20%, with a decrease of 50% for APT during the study period. No treatment and OAC + APT remained relatively stable. The strongest predictor of no treatment and APT treatment was having the same management strategy pre-stroke. Those treated with APT had the highest rates of GI bleeding and recurrent stroke/TIA, and untreated patients showed the highest rates of mortality. Conclusion: In this large population-based cohort using real-world data, nearly 30% of AF patients who suffered a stroke were untreated or treated with APT, which overall is not recommended. Treatment was started within 2 weeks as recommended, except for OAC + APT, which was started later. The strong association of APT treatment or non-treatment with the same treatment strategy before stroke occurrence suggests a strong therapeutic inertia and opposes recommendations. Patients under these two strategies had the highest rates of adverse outcomes. An inadequate prescription poses a great risk on patients with AF and stroke; thus monitoring their management is necessary and should be setting-specific.

Real-World Data on Treatment Management and Outcomes of Patients with Newly Diagnosed Advanced Epithelial Ovarian Cancer in Greece (The EpOCa Study)

New treatment modalities have been recently introduced in the management of ovarian cancer (OC). Herein, we sought to investigate their implementation in routine clinical practice and examine the real-world management of OC in Greece. EpOCa was a non-interventional, multicenter, retrospective study in patients with advanced epithelial OC. The primary outcome was to estimate the proportions of the different treatment regimens used per line of therapy, while progression-free survival (PFS) and overall survival (OS) were the key secondary endpoints. A total of 154 patients were enrolled in the study, among whom, 40% were tested for BRCA mutations and 30% were found to be positive. Nearly 90% of patients underwent debulking surgery at diagnosis, with few operations being also recorded upon relapse. Platinum-based chemotherapy (CT) was predominantly used in the first line with half of patients also receiving angiogenesis inhibitor (AI), while non-platinum-based CT was preferred in later lines. The median PFS was 18.2 and 8.8 months in the first- and second-line setting, respectively, whereas the median OS was approximately 50 months. Our study adds to the available, but limited, real world data on the management of ovarian cancer providing evidence regarding the applied treatment strategies and outcomes of patients in Greece.

A Nationwide Multi-Center Questionnaire Survey on the Real-World State and Clinical Management of Poststroke Dementia in Japan.

Background:Poststroke dementia (PSD) is a serious problem for stroke survivors. However, there is still limited data on the real-world state and clinical management of PSD worldwide, and several countries already have a super-aged society.Objective:We conducted a nationwide questionnaire survey to examine the real-world state and management of PSD in Japan.Methods:A survey was conducted in the top 500 Japanese hospitals regarding the number of stroke patients treated between July 2018 and August 2019. Thirteen questions regarding PSD were mailed to doctors responsible for stroke management.Results:Responses were obtained from 251 hospitals (50.2%). The chief doctors responsible for stroke management answered the questionnaires. The median numbers of patients admitted annually with stroke in the departments of neurology and neurosurgery in the hospitals were 281.0 (interquartile range [IQR], 231.8–385.3) and 253.5 (IQR, 210.0–335.3), respectively, and most hospitals were acute care hospitals. Executive dysfunction was the most common cognitive dysfunction (10.9%), followed by amnesia (9.5%) and apathy (4.1%). Surprisingly, many stroke survivors lived alone at home (23.7%). Montreal Cognitive Assessment was significantly uncommon compared to Mini-Mental State Examination (p < 0.01). Furthermore, objective evaluation tests for behavioral and psychological symptoms of dementia were not often performed. Cognitive rehabilitation treatments were performed more often and earlier than drug treatments. The first drug of choice for PSD was predominantly donepezil (79.1%), followed by galantamine (6.1%), cilostazol (4.9%), memantine (2.5%), and rivastigmine (1.8%).Conclusion:Our study provides real-world evidence for the state of clinical practice related to PSD in Japan.

Real-world management of non-alcoholic steatohepatitis differs from clinical practice guideline recommendations and across regions

Background & AimsDespite availability of diagnostic and management reference guidelines outlining standard of care for patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), national and regional guidelines are lacking, resulting in variations in patient management between regions. We retrospectively analyzed patient characteristics and management data from the Adelphi Real World NASH Disease Specific Programme™ for patients with NASH in the EU5, Canada, and the Middle East to identify gaps between real-world practice and that advocated by reference guidelines, irrespective of clinician awareness or consultation of guidelines.MethodsWe performed an analysis of physicians (hepatologists, gastroenterologists, diabetologists) and their patients diagnosed with NASH. Physicians completed patient record forms for the next 5 consulting patients, collecting information on patient care, including diagnosis and disease management.ResultsA total of 429 physicians provided data for 2,267 patients with NASH (EU5, n = 1,844; Canada, n = 130; Middle East, n = 293). Patient age, physician-defined fibrosis stage, comorbidities and symptoms, and diagnostic testing practices highlighted statistically significant differences across regions. Substantial disconnects between reference guidelines and real-world practice were observed. Use of liver function tests, non-invasive tests (e.g. ultrasound and transient elastography), and tests to exclude other conditions was suboptimal. Although lifestyle advice was widely provided, patients were less commonly referred to diet, exercise, and lifestyle specialists. Two-thirds of patients were receiving off-label treatment for NASH or associated underlying conditions with the aim of improving NASH, most commonly statins, metformin, and vitamin E.ConclusionReal-world NASH management approaches differ across regions and from proposed standard of care represented by reference multidisciplinary guidelines. Establishment and awareness of, and adherence to regional and national guidelines may improve identification and management of patients with NASH and potentially improve outcomes in this population.Lay summaryAlthough reference guidelines are available to guide the management of patients with NASH, these are not widely used and there is a lack of national guidelines. Our study shows how clinical practice in the EU, Canada, and Middle East differs from proposed standard of care, particularly relating to how patients are diagnosed and treated. Wider establishment of, awareness of, and reference to guidelines may improve how physicians identify and manage patients with NASH.

Implications of bacterial mineralisation in aquatic ecosystem response models

Widespread wastewater pollution is a major barrier to the sustainable management of freshwater and coastal marine ecosystems worldwide. Integrated multi-disciplinary studies are necessary to improve waterway management and protect ecosystem integrity. This study used the Generalised Likelihood Uncertainty Estimation (GLUE) methodology to link microbial community ecotoxicology laboratory data to a mechanistic aquatic ecosystem response model. The generic model provided good predictive skill for major water quality constituents, including heterotrophic bacteria dynamics (r2 = 0.91). The model was validated against observed data across a gradient of effluent concentrations from community whole effluent toxicity (WET) laboratory tests. GLUE analysis revealed that a combined likelihood measure increased confidence in the predictive capability of the model. This study highlights the importance of calibrating aquatic ecosystem response models with net growth rates (i.e., sum of the growth minus loss rate parameter terms) of biological functional groups. The final calibrated net growth rate value of heterotrophic bacteria determined using the GLUE analysis was selected to be 0.58, which was significantly greater than the average literature value of -0.15. This finding demonstrated that use of literature parameter values without a good understanding of the represented processes could create misleading outputs and result in unsatisfactory conclusions. Further, fixed bulk mineralisation rate literature values are typically higher than realistically required in aquatic ecosystem response models. This indicates that explicitly including bacterial mineralisation is crucial to represent microbial ecosystem functioning more accurately. Our study suggests that improved data collection and modelling efforts in real-world management applications are needed to better address nutrients released into the natural environment. Future studies should aim to better understand the sensitivity of aquatic ecosystem response models to bacterial mineralisation rates.

Abstract 10356: Impact of Statin Therapy in Heart Failure Patients: Results of a Large Real-World Experience

Introduction: The use of statins in patients (pts) with heart failure (HF) is controversial. In patients without HF, statins reduce the risk of atherosclerotic cardiovascular disease (ASCVD), including HF-related events. In contrast, no benefit was observed in statin-treated HF pts in the CORONA and GISSI-HF trials. However, issues with generalizability may limit the applicability of these trial results in clinical practice. Therefore, we analyzed the impact of statin therapy in systolic HF pts in a large real-world experience. Methods: We searched Intermountain Healthcare medical records for pts with a diagnosis of HF and a reported ejection fraction of &lt;=40%. We compared outcomes (MACE=death, MI, stroke) at a median of 4.5 years follow-up in those who were and were not prescribed a statin. Statin use was defined as use at or after a HF diagnosis but prior to 60-days before MACE or end of follow-up. Cox hazard regression analysis was used to determine hazard ratios. Results: A total of 15,010 pts were studied. Baseline demographics and outcomes are shown in the Table. Statin use was associated with more frequent ASCVD risk factors yet a lower MACE risk during follow-up. Benefit was similar for primary and secondary prevention pts and for prior and new statin prescriptions. By time-varying hazard ratio (HR) analysis, the longer the pt was on a statin, the greater the reduction in risk of MACE (p&lt;0.0001). Conclusion: These results suggest a potential benefit of selective statin use in the real-world management of HF pts with ASCVD or at high-ASCVD risk. These novel observations deserve validation in additional real-world experiences.

Abstract 12303: Management of Severe and Moderate Hypercholesterolemia in Young Adults

Introduction: Cardiovascular guidelines advise statin therapy for adults aged 20-75 years with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL with a goal of lowering LDL-C by ≥50%. Further, early-life accumulation of cholesterol exposure increases future cardiovascular risk independent of total cumulative cholesterol exposure, highlighting the importance of LDL-C management in young adults. However, real-world management of hypercholesterolemia in young adults is not well described. Methods: Using the Mass General Brigham clinical data registry, we isolated 2 cohorts of patients with hypercholesterolemia who had cholesterol testing on ≥2 occasions and were 20-39 years old at the time of a qualifying LDL-C value between 2005-2018: those with LDL-C ≥190 mg/dL (Cohort 1) and LDL-C 160-&lt;190 mg/dL (Cohort 2). Follow-up LDL-C values were extracted through 2019. Primary endpoints were 50% reduction in LDL-C for Cohort 1 and 30% reduction for Cohort 2. Results: Cohort 1 (severe hypercholesterolemia) included 5,475 patients (37.9% female, mean [SD] age 32.6 [5.1] years at qualifying LDL-C), and Cohort 2 (moderate hypercholesterolemia) included 12,608 patients (39.6% female, mean [SD] age 32.6 [5.1] years). In Cohort 1, 1,638 individuals (29.9%) achieved ≥50% LDL-C reduction overall (31.7% of men vs. 27.1% of women, P&lt;0.001; Figure ) over median (IQR) 7.8 (4.5-11.3) years of follow-up. The youngest individuals were less likely to achieve 50% LDL-C reduction (e.g., 20-24 years old: 24.8% vs. 35-39 years old: 32.7%; P trend &lt;0.001). In Cohort 2, 4,515 individuals (35.8%) achieved ≥30% LDL-C reduction over median (IQR) 7.5 (4.2-11.1) years of follow-up. Conclusions: In a large, integrated healthcare system, &lt;30% of young adults with severe hypercholesterolemia achieved guideline-directed LDL-C-lowering over 8 years of follow-up. These findings highlight the need for strategies to promote guideline-recommended cholesterol management in young adults.

Real-World Management of Patients with Newly Diagnosed Acute Myeloid Leukemia Treated with Venetoclax-Based Regimens: Results from the AML Real World Evidence (ARC) Initiative

Real-World Management of Patients with Newly Diagnosed Acute Myeloid Leukemia Treated with Venetoclax-Based Regimens: Results from the AML Real World Evidence (ARC) Initiative

Systemic Light Chain Amyloidosis across Europe: Key Outcomes from a Retrospective Study of 4500 Patients

Systemic Light Chain Amyloidosis across Europe: Key Outcomes from a Retrospective Study of 4500 Patients

Treatment Patterns and Outcomes in Lenalidomide-Exposed Multiple Myeloma Patients in Real-World Settings: A Multi-Center Retrospective Study

BackgroundTreatment of multiple myeloma (MM) has changed significantly in recent years with the availability of novel agents including monoclonal antibodies (mAbs), proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) such as lenalidomide. Despite lenalidomide becoming a standard of care across all lines of myeloma therapy, the population of MM patients refractory to lenalidomide and their real-world clinical management has been poorly studied so far, especially outside the reality of interventional clinical trials (Moreau et. al. Blood Cancer J. 2019).With these considerations in mind, we have performed a retrospective study using two databases to better understand treatment patterns and outcomes of MM patients who were treated with lenalidomide and subsequently became refractory to it. This builds on work previously conducted at other data sources (Willenbacher et. al. EHA Library 2020).AimsThe objective of this study was to describe the treatment patterns and outcomes of MM patients exposed to lenalidomide, with a focus on refractory patients, as defined by IMWG (International Myeloma Working Group) consensus, in a real-world clinical setting.MethodsThe study utilised databases from two participating members of the IQVIA MM real world evidence network: University Hospital Frankfurt (Frankfurt) (Germany) and Portuguese Oncology Institute of Porto (IPO-Porto) (Portugal). Since the native format of databases from participating sites differs, key concepts were harmonised based on pre-agreed definitions. The study population included patients with an initial diagnosis of MM between 01/01/2012 and 31/12/2018 based on the IMWG criteria, were 18 years old or older at the time of diagnosis and received two or more cycles of lenalidomide treatment, alone or in combination, at any dose, excluding patients who only received lenalidomide as maintenance therapy. Patients were defined as refractory to lenalidomide treatment if they progressed on treatment or within 60 days following the end of lenalidomide treatment (excluding maintenance setting).Kaplan-Meier curves were produced to evaluate the time to next treatment (TTNT) and overall survival (OS) for lenalidomide exposed and lenalidomide refractory patients. TTNT was defined as the time between the start date of the line of lenalidomide therapy and the start date of the next line of therapy (LoT) or death due to any cause. OS was defined as the time between the start date of the line of lenalidomide therapy and death due to any cause.ResultsThe cohort included 55 and 42 MM lenalidomide-exposed patients from Germany and Portugal respectively. In Germany, 80% were initially exposed to the lenalidomide in LoT 1, whilst in Portugal 71% received initial lenalidomide treatment in LoT 3.In Portugal, following lenalidomide refractoriness, the majority (78%) of patients received chemotherapy and steroids only whilst in Germany a range of treatment types was observed (mAb-based 33%; PI-based 11%; PI/IMiD combo 11%; mAb/IMiD combo 11%; chemotherapy and steroids only 11%; other 22%).The median OS in months for lenalidomide-exposed refractory patients was 7 in Portugal and 31 in Germany; the median OS for non-refractory patients was 40 in Portugal and was not reached in Germany.The median TTNT in months for lenalidomide-exposed refractory patients was 4 in Portugal and 15 in Germany; the median TTNT for non-refractory patients was 14 in Portugal and 53 in Germany.ConclusionThe analysis of real-world data across two countries, showed heterogeneity in lenalidomide treatment patterns, with first exposure typically occurring in LoT 1 or 3. This has led to differences in the calculated TTNT and OS, and as such the results between the two countries cannot be directly compared. The OS from diagnosis for this cohort is being assessed and will provide an insight on the impact of different treatment pathways.Patients who became refractory to lenalidomide moved on to their next treatment much quicker after exposure vs patients who were not refractory to lenalidomide; similarly, patients who became refractory to lenalidomide had shorter OS than patients who were not refractory.Patients typically became refractory early in their treatment journey, indicating a growing population with unmet medical needs. [Display omitted] DisclosuresMetzler: GSK: Consultancy; Takeda: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Amgen: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy.

Molecular Biomarker Testing and Targeted Therapy Patterns in Patients with Acute Myelogenous Leukemia (AML) in Community Health Systems in the United States: A Real-World Data Analysis

Molecular Biomarker Testing and Targeted Therapy Patterns in Patients with Acute Myelogenous Leukemia (AML) in Community Health Systems in the United States: A Real-World Data Analysis

Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management, and Resource Implications.

Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3–2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days−19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients.

Design of an authentic project-based learning course using project management approach

ABSTRACT Using case studies, business simulations, seminars and lectures, and textbooks of relevance to the subject are helpful with learning and knowledge application. However, assisting students in the matter of practicing complex real-world projects management and solving actual problems are essential. Authentic project-based learning (APBL) is an active pedagogical approach that requires real clients, real users, and projects involving in the curriculum that demand real solutions provided by the learners. APBL has been shown to provide students with challenges that lead to greater motivation, higher levels of student performance, and retention rate across elementary, secondary, and postsecondary levels. Therefore, as a means of enhancing student interest and motivation and compensating for the absence of direct face-to-face contact imposed on higher education by the Covid 19 pandemic, a marketing course was redesigned using APBL pedagogy and Project Management Body of Knowledge® Guide Project Management Institute). This paper presents and introduces how the APBL course was designed, implemented, and delivered in the fall semester of 2020. This paper also elaborates how students applied integrated brand promotion (IBP) strategies and project management skills to promote and deliver a new ballet production to audiences. Several important learning outcomes were realised, including maximising students’ learning, increasing efficiency, and significantly minimising ‘student syndrome’ (procrastination). Future research and teaching opportunities with limitations of this project are provided at the end.

Omalizumab for the treatment of chronic spontaneous urticaria: a systematic review

&lt;p class="abstract"&gt;Chronic spontaneous urticaria (CSU) is a mast cell-driven skin disease characterized by the recurrence of transient wheals, angioedema or both lasting for more than 6 weeks duration. Omalizumab is a newer humanized anti IgE immunoglobulin along with many new antibody treatments has shown beneficial effect in treatment of chronic spontaneous urticaria. Although many randomized clinical trials have been conducted, as of now, the effectiveness of omalizumab in the real world management of CSU is largely unknown. A systematic review of all studies should be done. The objective was to study the efficacy and safety of different doses of omalizumab in the treatment of chronic spontaneous urticaria which was refractory to treatment with H1 antihistamines. Suitable studies were recognized after searching Wiley online library, PubMed, Google scholar, NEJM/NEJ dermatology, JAAD, JACI, clinicaltrials.gov. Only randomized, double-blind, placebo-controlled clinical trials with omalizumab versus antihistamine or leukotriene antagonists as placebo were involved in this study. 10 randomized, placebo-controlled studies were involved with 1692 patients with CSU. Patients treated with omalizumab (75-600 mg every 4 weeks) had reduced UAS7 score, improved QoL (quality of life), reduced WISS, when compared to the placebo group. The effects of omalizumab were found to be dose dependent, with maximum reduction in UAS7 at a dose of 300 mg when given at an interval of 4 weeks’ duration. The incidences of adverse events were almost similar in both control and placebo groups and across various dose ranges. The best effect in reduction of clinical symptoms and QoL in CSU patients was found at a dose of 300 mg subcutaneous injection once a month of omalizumab for 12 to 24 weeks. Omalizumab was found to reduce the clinical symptoms and signs in patients with CSU who were symptomatic despite treatment with upscaling dose of H1 antihistamines.&lt;/p&gt;

Economic impact of applying the AASLD-IDSA simplified treatment algorithm on the real-world management of hepatitis C.

BACKGROUND: The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommended in May 2019 that patients with hepatitis C virus (HCV) could be assessed for treatment initiation with a simplified treatment algorithm. This approach uses standard blood and fibrosis tests, rather than genotype testing, to guide the initiation of pan-genotypic direct-acting antiviral agents (DAAs) sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) treatment. OBJECTIVE: To compare health care resource utilization (HCRU) and costs for patients who initiated treatment via the simplified vs nonsimplified algorithm (genotype testing). METHODS: We identified adults with commercial and Medicare Advantage coverage who were diagnosed with HCV who initiated SOF/VEL or GLE/PIB from July 1, 2016, through August 31, 2019, in a nationally representative US administrative claims database. The index date was defined as the first pharmacy SOF/VEL or GLE/PIB fill date. Continuous enrollment 12 months before and ≥6 months after index date was required. Patients with claims for hepatitis B, HIV, decompensated liver, or prior DAAs were excluded. Patients were propensity score-matched (1:1) and grouped as "simplified" or "nonsimplified." HCV-related HCRU and costs were compared for the post-matched groups. RESULTS: 3,539 HCV patients were included, and 16.6% initiated SOF/VEL or GLE/PIB via the simplified algorithm. Pre-matched treatments were SOF/VEL (52.8%) and GLE/PIB (47.2%). More than half (55.7%) of SOF/VEL and 44.3% of GLE/PIB patients started treatment via the simplified algorithm. HCV patients initiating via the simplified algorithm were more likely to be male (65.1% vs 60.6%; P = 0.041), commercially insured (53.3% vs 46.5%; P = 0.003), and in the Midwest (25.7% vs 19.3%; P < 0.001) vs nonsimplified patients. The nonsimplified group had more liver disease (52.1% vs 46.9%; P = 0.019), metabolic disorders (45.8% vs 39.2%; P = 0.003), and dyslipidemia (39.9% vs 35.4%; P = 0.041) vs the simplified group. Of the index prescriptions, 58.9% were written by gastroenterology or infectious disease specialists, and 68.1% (simplified) vs 75.4% (nonsimplified) had a specialist visit within 90 days prior to index DAA fill (P < 0.001). Matching resulted in 584 well-matched patients in each group. At post-match baseline, the simplified treatment group had significantly lower median (interquartile range [IQR]) HCV-related medical health care costs vs the matched nonsimplified group: $373 ($201-$684) vs $727 ($456-$1,185; P < 0.001). Median noninpatient/emergency department health plan-paid costs were also significantly lower in the simplified cohort ($257 vs $504; P < 0.001). During follow-up, medical HCV-related health care costs were similar across the groups. CONCLUSIONS: This study compared economic outcomes of HCV treatment initiation via the simplified and nonsimplified algorithms. The simplified approach resulted in lower use of health care resources, greater cost savings, and greater ability of patients to access care from both specialist and nonspecialist providers. While additional studies are needed, these early findings suggest a feasible path for simplified HCV treatment in real-world managed care settings. DISCLOSURES: Funding support for this study was provided by Gilead Sciences, Inc. Majethia, Lee, Mozaffari, Wolf, and Hsiao are employees of Gilead Sciences, Inc. Bunner and Chastek are employees of Optum Life Sciences, which received funding from Gilead Sciences, Inc. to conduct this study. Bunner owns stock in UnitedHealth group, parent company of Optum. A poster based on selected data from this study was presented at the AMCP 2021 Virtual Meeting, April 12-16, 2021.

Defibrotide: real-world management of veno-occlusive disease/sinusoidal obstructive syndrome after stem cell transplant

AbstractHepatic veno-occlusive disease or sinusoidal obstructive syndrome (VOD/SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Defibrotide is the only medication approved by the US Food and Drug Administration for the management of severe VOD/SOS after HSCT. We report our center's experience with commercially available defibrotide as treatment of patients with VOD/SOS. We retrospectively identified 28 cases of VOD/SOS, based on the European Society for Blood and Marrow Transplantation criteria, from March 2016 through June 2019. The median day of VOD/SOS onset was 25 days (range, 8-69 days), and defibrotide was initiated on day of diagnosis in 71% of patients. Complete resolution of VOD/SOS occurred in 75% of patients. Day 100 survival was 64% for all HSCT patients and 53% for those with very severe VOD/SOS. Response rates and survival were similar in patients with VOD/SOS after myeloablative or reduced-intensity chemotherapy HSCT. Therapy-related adverse events were mild and included hematuria (43%), epistaxis (18%), and hypotension (11%). Severe hemorrhagic adverse events occurred in 2 patients (pulmonary hemorrhage and upper gastrointestinal hemorrhage; 7%) and both in the setting of progressive VOD/SOS. Early diagnosis, prompt initiation of defibrotide, and minimization of dosing interruptions may be key to successful treatment of VOD/SOS.

Global utilization and outcomes of first-line cryoablation for atrial fibrillation

Abstract Background Recent trials demonstrated the safety and efficacy of cryoballoon ablation prior to antiarrhythmic drug (AAD) usage in patients with paroxysmal atrial fibrillation (AF); however, global utilization and outcomes of first-line cryoablation in real-world AF patient management are unknown. Purpose To evaluate baseline characteristics and outcomes in patients selected for first-line cryoablation for treatment of AF. Methods The Cryo Global Registry (NCT02752737) is an ongoing, prospective, multicenter registry. In this analysis, AF patients with an index cryoballoon ablation performed according to local standards of care at 58 centers in 26 global countries were included. Subjects with no prior failed antiarrhythmic drug (AAD) usage and not taking an AAD at baseline were considered first-line and compared to drug-refractory patients who had failed an AAD prior to enrollment in the study and/or were taking an AAD at baseline. Baseline characteristics, serious procedure-related complication rates, and 12-month freedom from a ≥30sec AF/atrial flutter (AFL)/atrial tachycardia (AT) recurrence after a 90-day blanking period were compared between the groups. Results In total, 31% of the 1,394 patients (433 first-line, 961 drug-refractory) received a first-line cryoablation. The proportion of first-line enrollments by world region (3.7%-53.5%) and countries within region (i.e. EU: 0–59%) varied widely. Drug-refractory patients failed a mean of 1.2±0.5 AADs prior to cryoablation. First-line and drug-refractory patients were similar in age (60±13 vs 61±11), sex (35.1% vs 36.8% female), and CHA2DS2-VASC (2.0±1.6 vs 2.1±1.6). First-line was more often paroxysmal AF (87.3% vs 80.2%), with lower BMI (27±5 vs 28±5), diagnosed with AF fewer years (2.1±3.9 vs 3.7±5.0), and had smaller left atrial diameters (39±7 vs 42±8 mm; all p&amp;lt;0.05). Hypertension and history of congestive heart failure were less common in first-line (p&amp;lt;0.05), but similar rates of prior myocardial infarction, stroke, coronary artery disease, diabetes, and sleep apnea were reported. Procedure, left atrial dwell, and cryoapplication times were similar between cohorts (all p&amp;gt;0.05). Serious adverse event rates were not statistically different between first-line and drug-refractory patients (2.3% vs 3.4%, respectively; p=0.32). Freedom from AF/AFL/AT after cryoablation in first-line vs drug-refractory PAF was 90.0% (95% CI: 86.4–92.7%) and 84.4% (95% CI: 81.5–86.8%) and in first-line vs drug-refractory persistent AF was 72.9% (95% CI: 58.6–83.0%) vs 70.2% (95% CI: 62.9–76.4%), respectively. First-line ablation resulted in higher rates of freedom from arrhythmia recurrence (p=0.02). Conclusion First-line cryoablation in a real-world setting resulted in improved efficacy without increasing the risk of a safety event. These data support cryoablation as an early intervention strategy for treatment of AF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic, Inc.