Study Of Real-world Outcomes Research Articles

Determinants of Outcomes for Acute Myeloid Leukemia Patients Treated in a Community-Based Specialized Versus Non-Specialized Hospital Setting.

The treatment setting influences acute myeloid leukemia (AML) outcomes. Most cancer patients receive care in the community, yet few studies have evaluated the effectiveness of clinical programs outside of academic or National Cancer Institute (NCI)-designated cancer centers. This was a multi-level, case-controlled study of real-world outcomes for initial AML treatment in a community-based network for 1,391 patients with AML between 2011 and 2018. We benchmarked survival within our network against the Surveillance, Epidemiology, and End Results (SEER) database. Coarsened exact matching was performed against 17,186 chemotherapy-treated patients in the SEER database. Cox proportional and accelerated failure time multivariable modeling were performed to identify patient, disease, therapy and center characteristics associated with the risk of AML mortality. Within the network, 799 patients were treated at six specialized blood cancer centers and 592 at 63 other hospitals. Patients receiving high-intensity induction at specialized centers had improved median survivals of 31 months versus 18 months [P<0.001] at non-specialized centers. Median survivals were 13 for non-specialized centers versus 10 months for SEER [P<0.001], and 18 for the entire network versus 10 months for SEER [P<0.001]. Multivariable modeling showed significant impacts from age (HR = 1.025), high-intensity induction therapy (HR= .695), diagnosis year (HR= .937), neighborhood income (HR = .997; P<0.01), higher acuity (HR = 1.002) and Charlson comorbidity score (HR = 1.117). AML treatment may be effectively delivered in the community hospital setting, with specialized centers producing better outcomes for higher intensity treatments.

Assessing Safety of Anticoagulation for Atrial Fibrillation in Patients with Cirrhosis: A Real-World Outcomes Study.

In patients with atrial fibrillation (AF) and stroke risk factors, randomized trials have demonstrated that anticoagulation decreases the risk of ischemic stroke. However, all trials to date have excluded patients with significant liver disease, leaving guidelines to extrapolate recommendations. We aim to evaluate the impact of anticoagulation on safety events in patients with AF and cirrhosis. In this retrospective cohort study, we obtained de-identified health record data to extract anticoagulation strategy, comorbidities, prescriptions, lab values, and procedures for a cohort of patients with cirrhosis who develop AF. After selecting a propensity matched population to match patients with various anticoagulation strategies, we tracked data on outcomes for death, transfusion requirements, hospital and ICU admissions. After propensity score weighting and multivariable adjustment, anticoagulation strategy was associated with increased hospital admission count (OR = 1.74 per admission, P < .001), binary risk of hospital admission (OR = 1.54, P = .010) and risk of ICU admission (OR = 1.41, P = .047). We detected no significant differences in mortality, transfusion of blood products, or average length of stay. Direct oral anticoagulant (DOAC) prescriptions were associated with increased binary risk of hospital admission compared to warfarin prescriptions. In a third comparison, DOAC strategy alone was associated with increased hospital admission count (OR = 1.41 per admission, P < .001) and binary risk of hospital admission (OR = 1.52, P = .038) compared to no anticoagulation strategy. Anticoagulation strategy in patients with cirrhosis and AF was associated with increased rate of hospital admission and ICU admission but not associated with increased risk of mortality or transfusion requirement.

Motor Function and Quality of Life Improvement following Asleep versus Awake Deep Brain Stimulation (DBS) Procedures (P4-11.009)

<h3>Objective:</h3> To compare real-world outcomes in patients with Parkinson’s disease (PD) whose Deep Brain Stimulation (DBS) leads were implanted using asleep procedures versus those patients that underwent the procedure using awake conditions. <h3>Background:</h3> DBS procedures are typically conducted with patients being awake to allow for intraoperative clinical testing and/or micro-electrode recording to confirm lead location. However, asleep DBS procedures (i.e., under general anesthesia) are becoming increasingly popular due, at least in part, to technological improvements in imaging allowing alternative lead placement confirmation and shorter procedure duration (Brodsky 2017, Chen 2018, Vinke 2022). <h3>Design/Methods:</h3> A sub-analysis of patients receiving their DBS lead implant under asleep versus awake conditions was conducted in an ongoing, large, multicenter, prospective real-world outcomes study (Vercise, Boston Scientific). Motor function (MDS-UDPRS III), quality of life (PDQ-39) and related outcomes (GIC) were collected at baseline and up to 3-years. Safety events were also collected. <h3>Results:</h3> To date, 157 patients (mean age 61.2±8.3 years; 69% male) were asleep and 433 (mean age 60.1±8.5 years; 66% male) were awake during lead placement. Patients in both groups presented with similar baseline age, duration of disease and disease state. Improvement in quality-of-life was noted in both groups with a 5.3-point improvement (n = 104) in asleep group and a 4.5-point improvement (n = 319) in awake group at 1-year. Similarly, an 18.8- and 20.9-point improvement in motor function was noted in the asleep and awake groups, respectively. <h3>Conclusions:</h3> Outcomes from this large dataset of real-world outcomes examining the outcomes following asleep versus awake DBS demonstrate an alignment with results from previous studies (Holewijn 2021; LaHue 2017). Patient outcomes show little to no difference between awake versus asleep groups. Sleep DBS procedures may offer potential for shortening the total time taken for DBS procedures and offer a viable alternative for patients. <b>Disclosure:</b> Jan Vesper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific . Jan Vesper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic . Jan Vesper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott . Jan Vesper has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbott . Jan Vesper has received research support from German Research Council. Dr. Deuschl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Cavion Functional Neuromodulation. The institution of Dr. Deuschl has received research support from Medtronic. Dr. Deuschl has received publishing royalties from a publication relating to health care. Lilly Chen has received personal compensation for serving as an employee of Boston Scientific . Roshini Jain has received personal compensation for serving as an employee of Boston Scientific. Roshini Jain has received stock or an ownership interest from Boston Scientific.

562 Merkel polyomavirus antibody testing for detecting recurrent Merkel cell carcinoma: A prospective, real-world outcomes study

562 Merkel polyomavirus antibody testing for detecting recurrent Merkel cell carcinoma: A prospective, real-world outcomes study

Prognostic value of plasma circulating tumor DNA fraction across four common cancer types: a real-world outcomes study

Genomic analysis of circulating tumor DNA (ctDNA) is increasingly incorporated into the clinical management of patients with advanced cancer. Beyond tumor profiling, ctDNA analysis also can enable calculation of circulating tumor fraction (TF), which has previously been found to be prognostic. While most prognostic models in metastatic cancer are tumor type specific and require significant patient-level data, quantification of TF in ctDNA has the potential to serve as a pragmatic, tumor-agnostic prognostic tool. This study utilized a cohort of patients in a nationwide de-identified clinico-genomic database with metastatic castration-resistant prostate cancer (mCRPC), metastatic breast cancer (mBC), advanced non-small-cell lung cancer (aNSCLC), or metastatic colorectal cancer (mCRC) undergoing liquid biopsy testing as part of routine care. TF was calculated based on single-nucleotide polymorphism aneuploidy across the genome. Clinical, disease, laboratory, and treatment data were captured from the electronic health record. Overall survival (OS) was evaluated by TF level while controlling for relevant covariables. A total of 1725 patients were included: 198 mCRPC, 402 mBC, 902 aNSCLC, and 223 mCRC. TF ≥10% was highly correlated with OS in univariable analyses for all cancer types: mCRPC [hazard ratio (HR) 3.3, 95% confidence interval (CI) 2.04-5.34, P < 0.001], mBC (HR 2.4, 95% CI 1.71-3.37, P < 0.001), aNSCLC (HR 1.68, 95% CI 1.34-2.1, P < 0.001), and mCRC (HR 2.11, 95% CI 1.39-3.2, P < 0.001). Multivariable assessments of TF had similar point estimates and CIs, suggesting a consistent and independent association with survival. Exploratory analysis showed that TF remained consistently prognostic across a wide range of cutpoints. Plasma ctDNA TF is a pragmatic, independent prognostic biomarker across four advanced cancers with potential to guide clinical conversations around expected treatment outcomes. With further prospective validation, ctDNA TF could be incorporated into care paradigms to enable precision escalation and de-escalation of cancer therapy based on patient-level tumor biology.

AML-522 Outcomes of Patients Treated With Venetoclax-Based Combination Therapy in Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms; Real World Data from a Single Center Cohort

The outcomes of older patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy remain poor. Addition of venetoclax (ven) to hypomethylating agents (HMA) or low dose cytarabine (LoDAC) has become the standard of care based on the VIALE-A and VIALE-C trials. We investigated outcomes of patients treated with ven-based therapy in both newly-diagnosed and R/R settings. Patients diagnosed with AML between 2/2018 and 2/2022 who completed at least one cycle of ven-based therapy at our center were included. Clinical, cytogenetic and molecular data were collected. Responses were assessed using IWG criteria. OS was calculated from venetoclax initiation and estimated using Kaplan-Meier method. Multivariable cox-regression was used to assess factors associated with response. Sixty-nine patients completed at least one cycle of ven-based therapy for AML at our center. Median age at diagnosis was 71 (28-88 years) and 35 (51%) patients were female. Majority (76.8%) of patients had high risk disease per ELN stratification. Five (7%) of patients had high grade myeloid neoplasms. Majority of patients received ven in combination with HMA (81.%). CR/CRi/CRh rate was 44.9% and ORR 78.3%. Twenty-one (30%) proceeded with transplant. In univariate analyses for response, ELN cytogenetic risk (p<.001), FLT3-ITD (p=.016), IDH1/2 (p=.004) were associated with response, with a trend for significance for NPM1 mutation (p=.067). Looking at survival analyses, de-novo AML (vs t-AML or secondary AML) (p=.012) and achieving CR within two cycles of therapy (p<.001) were associated with improved OS, but not diagnosis status [i.e., new vs R/R setting] (p=NS) or prior HMA use (p= NS). This study of real-world outcomes with ven-based therapy in AML assessed factors predictive of treatment response and OS. ELN cytogenetic risk was associated with response and OS. Patients with therapy-related or secondary AML had poorer OS vs de novo disease. Patients with new vs R/R disease had similar outcomes, likely due to the fact that the majority of patients had high risk ELN disease risk. Our observations highlight the clinical potential of ven-based therapy for R/R AML and the need for more robust trial data including patients with R/R disease.

Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge.

Major changes have occurred in therapeutics for coronavirus-19 (COVID-19) infection over the past 12–18 mo, most notably in early outpatient therapy. In most cases, solid organ transplant recipients were not included in the original clinical trials of these agents, so studies of real-world outcomes have been important in building our understanding of their utility. This review examines what is known about clinical outcomes in solid organ transplant recipients with newer therapies. SARS-CoV-2 monoclonal antibodies for early treatment or prophylaxis have likely prevented many hospitalizations and deaths. In addition, convalescent plasma, the oral drugs nirmatrelvir/ritonavir and molnupiravir, remdesivir for early outpatient treatment, anti-inflammatory therapy, and investigational virus-specific T-cell therapy will be discussed. Finally, the later consequences of COVID-19, such as secondary infections, long COVID symptoms, and persistent active infection, are identified as areas for future research.

Cemiplimab in advanced cutaneous squamous cell carcinoma: A real-world experience of outcomes and safety.

e21545 Background: Nearly 1.5 million cases of cutaneous squamous cell cancer (cSCC) are diagnosed annually in the United States. Approximately 1% of cases are in the advanced unresectable stage. The standard of care in unresectable advanced disease is immunotherapy with anti-PD-1 agents. Cemiplimab, an anti-PD-1 antibody, was approved by the Food and Drug Administration in 2018. We present real-world clinical data from a single institution on outcomes and safety for patients treated with cemiplimab for metastatic and unresectable cSCC. Methods: We conducted a retrospective cohort analysis of patients treated with cemiplimab (350 mg every 3 weeks) for advanced cSCC from September 2018 until December 2021. Data included patient demographics, tumor characteristics, and treatment course. Patients who received at least 1 dose of cemiplimab and one clinic follow-up were included for analysis. Clinical response and adverse events (AE) were evaluated. Results: Of the 26 patients treated, 84% were male (n = 22), and 16% were female (n = 4) with a median age of 74 years (39-94). Twenty-three (23) patients were included in the final analysis as 3 patients transferred care to an outside facility and were not available for follow-up. Nineteen (19) patients (73%) had locally advanced disease and 7 (27%) had metastatic disease. The most common site of the primary tumor was head/neck (85%, n = 22) with all remaining cases on the trunk/extremities (15%, n = 4). Patients received a median of 7 doses of cemiplimab (range 1- 46). The median time to first response was 1.7 months which required a median of 2.5 doses. An objective clinical response defined as complete response (CR) or partial response (PR) was seen in 18/23 (78%) patients, of whom 8/23(35%) were CR and 10/23 (44%) PR. The ongoing response was noted in 6/23 (27%) with continued treatment. Treatment was well-tolerated with 6/23 (26%) adverse events (AE) all of which were grade 1 or 2: 1 (4%) grade 1 pruritus, 5 (21.7%) grade 2. Of the 5 grade 2 AEs, 1 was infusion-related, 2 hypothyroidism, 1 dermatitis, 1 rheumatoid arthritis flare. No grade 3-5 AEs were noted. Conclusions: To the best of our knowledge, this is the first real-world outcomes study of advanced cSCC patients treated with cemiplimab in the United States. The overall efficacy, response rate, and safety profile were better in comparison to the results of the EMPOWER-CSCC-1 trial.[Table: see text]

Efficacy of afatinib in patients with advanced/metastatic solid tumors harboring NRG1 gene fusions: A novel, prospective real-world outcomes study based on single-patient protocol data.

TPS3180 Background: Oncogenic neuregulin 1 ( NRG1) gene fusions occur in ̃0.2% of solid tumors overall and in up to 31% of cases of invasive mucinous lung adenocarcinoma [Laskin et al. Ann Oncol. 2020;31(12):1693–1703; Cadranel et al. Oncologist. 2021;26(1):7–16]. NRG1 fusion proteins provide an extracellular anchor for the epidermal growth factor (EGF) domain of NRG1 to bind to ErbB3 (HER3), leading to HER3 heterodimerization and activation of downstream signaling pathways, resulting in oncogenesis. Afatinib, an irreversible pan-ErbB tyrosine kinase inhibitor, represents a potential treatment for NRG1-fusion positive ( NRG1+) tumors. This study aims to examine the safety and efficacy of afatinib in patients with NRG1+ solid tumors, for which no authorized targeted therapy exists. Methods: This prospective, decentralized, US study (NCT05107193) will include 40 evaluable patients aged ≥18 years. Participating molecular test providers across the USA will identify eligible fusions in the course of routine diagnostic assays. When a patient with an NRG1 fusion is identified, participating test providers will notify the treating physician of the study as a treatment option for the patient. Patients’ primary oncologists will then contact the trial sponsor to confirm patient eligibility. Once approved by the central Institutional Review Board, patients will receive afatinib on a single-patient protocol basis, until disease progression or treatment is no longer tolerated. The recommended dosage per SmPC is 40 mg orally QD. Patients will be screened and enrolled into the study at their existing point-of-care setting. Inclusion criteria include a histologically or cytologically confirmed diagnosis of an advanced, unresectable/metastatic, non-hematologic malignancy with an NRG1 fusion, evaluable per RECIST 1.1. Any coding gene as the NRG1 fusion partner is permitted. Fusion status will be confirmed prospectively by a contracted molecular test provider. Exclusion criteria include prior systemic anti-cancer therapy or investigational drug within 14 days or 5 half-lives (whichever is shorter) of the start of afatinib treatment; an actionable driver mutation other than NRG1 fusion for which FDA-approved targeted therapy is available; and prior treatment with an ErbB-targeted therapy. The primary endpoint of the study is confirmed objective response (OR) by independent central review per RECIST 1.1, defined as best overall response of either complete response or partial response and analysed as the proportion of patients with an OR. The key secondary endpoint is duration of response, defined as the time from the first documented OR to progression or death. Secondary endpoints include time to OR and disease control per investigator assessment. Safety will also be assessed. The study is open for recruitment. Clinical trial information: NCT05107193.

Very low-calorie diet in patients with longstanding type 2 diabetes mellitus: a study of real-world outcomes

Introduction: There is a paucity of evidence regarding the efficacy of a very low-calorie diet (VLCD) in the real-world setting. We evaluated outcomes in patients with type 2 diabetes mellitus (T2DM) who underwent VLCD. Methods: This retrospective observational study included all patients who had undergone VLCD from 2014 to 2017 (n=61). The VLCD consisted of an eight-week 800 kcal/day dietary restriction. Metabolic parameters and medications were recorded at baseline, immediately post-VLCD and at 6 and 12 months. Results: There was a significant reduction in weight of 9.96 kg (p&lt;0.001) immediately post-VLCD, with net weight loss sustained to 12 months (p&lt;0.05). There was a significant reduction in body mass index (BMI) sustained to 12 months (p&lt;0.05). Paired HbA1c data were available for 38 patients. There was a significant reduction in HbA1c of 13.29 mmol/mol immediately post-VLCD (p&lt;0.001), however no significant reduction was observed at 12 months (p&gt;0.05). 78.7% patients had a reduction in T2DM medication burden post-VLCD, sustained in 44.3% of patients at 12 months. Analysis of patients with T2DM diagnosis duration &gt;6 years demonstrated statistically significant weight loss sustained to 12 months (p&lt;0.001). Conclusion: Our results demonstrate sustained reduction in BMI and weight, reduction in medication burden and temporary reduction in HbA1c in patients with T2DM undertaking a VLCD in the real-world setting

1291. PROVE (Retrospective Cefiderocol Chart Review) Study of Real-World Outcomes and Safety in the Treatment of Patients with Gram-negative Bacterial Infections in the US and Europe

BackgroundGram-negative bacterial resistance is a global health problem. Limited treatment options exist, especially for carbapenem resistant (CR) pathogens containing metallo-β-lactamases (MBLs) and multidrug resistant non-lactose fermenting bacteria. Cefiderocol (CFDC) retains activity against resistant strains. We describe the objectives, design, and early results of PROVE, a real world retrospective study of CFDC use.MethodsPROVE is a multi-center, chart review study of CFDC use for resistant Gram-negative infections (GNI). Cases were eligible if they received ≥ 72 hrs of CFDC. Demographics, comorbidity, pathogen, infection site, and treatment course were assessed. Outcomes included all-cause 14-day and inpatient mortality and length of stay (LOS). Clinical resolution was defined by documentation that clinical signs and/or symptoms had resolved or improved without relapse.Results24 patients who were treated with CFDC at 2 sites were included to date. Median age was 48 years (Range: 19 - 69 years); 33% were female. The most common comorbidity was diabetes (n=7, 29%). Median total ICU LOS was 36 days. Targeted treatment of documented GNI without preceding failure of prior therapy accounted for 71% of CFDC use. Empirical and salvage treatments accounted for 4% and 25% respectively (Table 1). Median time from admission to 1st CFDC dose was 21 days. Acinetobacter baumannii and Pseudomonas aeruginosa accounted for > 75% of isolates (Fig.1). 92% of patients had CR isolates; > 50% were respiratory. Sensitivity to CFDC was tested in 58% of which 71% were sensitive. All-cause 14-day post-CFDC mortality was 13% (95% CI: 2, 27) and overall hospital mortality 25% (95% CI: 6, 44). Clinical resolution was reached in 54% (95% CI: 33, 76). Median post-CFDC LOS was 40 days. Outcomes were stratified by key covariates (Table 2). ConclusionWe present initial data for real world use of CFDC for resistant GNI. Patients were complex with multiple comorbidities, some hospitalized for long periods before their index GNI. Outcomes largely reflect this patient population. Additional data are needed to determine the optimal role of CFDC. PROVE offers an opportunity to see how CFDC is being utilized in various settings as well as a first look at key, real world outcomes.Disclosures Stephen Marcella, MD, MPH, Shionogi, Inc (Employee) Steven Smoke, PharmD, Karius (Advisor or Review Panel member)Shionogi (Scientific Research Study Investigator, Advisor or Review Panel member) Ryan K. Shields, PharmD, MS, Shionogi (Consultant, Research Grant or Support) David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member)

From Heretical Idea to Mainstream Psychiatry: Brain Stimulation Has Ridden a Wave

From Heretical Idea to Mainstream Psychiatry: Brain Stimulation Has Ridden a Wave

Benefits of Real-Time Continuous Glucose Monitoring in Pregnancy.

In recent years, continuous glucose monitoring (CGM) has become increasingly available with the introduction of devices that are specifically approved for use during pregnancy. Evidence in the form of randomized-controlled trials and cohort studies continues to build support for the use of CGM during pregnancy to improve measures of maternal glycemia as well as obstetric and neonatal outcomes. Based on data from the CGM in pregnant women with type 1 diabetes (CONCEPTT) trial alongside a Swedish cohort study of real-world outcomes of pregnant women with type 1 diabetes, the UK National Institute for Health and Clinical Excellence (NICE) guidelines now recommend that real-time CGM be offered to all pregnant women with type 1 diabetes. Based on these guidelines, all pregnant individuals in the United Kingdom with type 1 diabetes will receive government-funded real-time CGM for a 12-month duration. These guidelines are a game-changer and will continue to facilitate more widespread access to CGM use in the United Kingdom and beyond. This review describes the role of CGM in the management of diabetes in pregnancy, discusses contemporary maternal glucose levels and their relationship with outcomes in diabetes pregnancies, and examines the high-quality, randomized-controlled trial and the real-world clinical data evaluating the impact of CGM use.

Real-World Outcomes of Patients Undergoing Open Colorectal Surgery with Wound Closure Incorporating Triclosan-Coated Barbed Sutures: A Multi-Institution, Retrospective Database Study

PurposeOpen colorectal surgery is associated with a high rate of postoperative wound complications. This is a single-arm study of real-world outcomes of triclosan-coated barbed suture (Ethicon’s STRATAFIXTM Symmetric PDSTM Plus Knotless Tissue Control Device [SSPP]) used in open colorectal surgery.MethodsRetrospective cohort study using the Premier Healthcare Database. The study included patients who underwent an inpatient open colorectal surgery with wound closure using SSPP (size 0 or 1 to increase the likelihood the suture was used in fascia) between October 2015–September 2019 (N=593). Wound complications, hospital length of stay, total hospital costs (2019 US$), and all-cause readmissions post-discharge were measured. Post-hoc multivariable analyses compared wound complications between non-elective admissions and elective.ResultsThe overall incidence of wound complications within 30-days post-procedure was 7.1%, with the majority of those being surgical site infections (SSI) (6.0%). Mean operation time was 190 (standard deviation [SD]=64.4) mins, postoperative length of stay was 8.1 (SD=11.9) days, 30-day readmission rate was 11.8%, and total hospital costs were $31,693 (SD=$40,076). As compared with published literature on the rate of SSI in colorectal surgery, the 30-day rate of SSI in the present study (6.0%) fell within the range of 5.4% to 18.2% for open colorectal surgery and from 4.3% to 21.5% for combined open and minimally invasive procedures. Multivariable-adjusted incidence proportions of wound complications were slightly lower for non-elective admissions and did not differ significantly from those of elective admissions.ConclusionThe rate of wound complications observed in the present study falls within the range of rates previously reported in the literature, suggesting a safe and effective role for SSPP in open colorectal surgery. In post hoc analyses, the adjusted rate of wound complications was similar between non-elective and elective admissions. Head-to-head studies are required to determine comparative advantages or disadvantages for SSPP versus other sutures.

Factors Associated with Clinical Outcomes after Venetoclax-Based Combination Therapy in Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms

Background Outcomes of older patients (pts) with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) remain poor with an overall survival (OS) of &amp;lt;12 months (mo). The combination of venetoclax (ven) and azacitidine (aza) for such newly diagnosed AML pts in the confirmatory VIALE-A trial demonstrated an improvement in OS compared with aza alone. However, this trial excluded pts with prior hypomethylating (HMA) therapy, as well as pts with relapsed/refractory (R/R) disease. Therefore, the outcomes of those pts remain unknown. We thus investigated the outcomes of pts treated with ven-based therapy in the newly diagnosed and R/R settings. Methods Pts diagnosed with AML or high-grade myeloid neoplasms (MN) between 2/2018 - 5/2020 who completed at least one cycle of ven-based therapy were included. Clinical data were collected and targeted next generation sequencing evaluating a panel of ~80 genes commonly mutated in myeloid malignancies was performed. Responses were assessed using the IWG criteria, and OS was calculated from cycle one day one until the date of last follow-up/death. Categorical variables were compared using Fisher's exact test. Univariable and multivariable Cox- and logistic-regression were used to assess factors associated with response and OS. Results Fifty pts were prescribed ven at our center, and eight were excluded as they received less than one full cycle of therapy. Of the 42 pts included, the majority (91%) had AML and 9% had high-grade R/R MDS or CMML. Median age at diagnosis was 66 years (28-88) and 23 pts (55%) were female. Per ELN risk stratification, most (81%) pts had poor, 14% had intermediate, and 5% had favorable-risk disease. Forty percent had de novo-, 52% had secondary/therapy-related AML (t-AML) and 8% had R/R MN. Twenty one (50%) pts received venetoclax for newly diagnosed AML, and of those nine (43%) had prior HMA therapy. Of the other 21 (50%) pts who received venetoclax in the R/R setting, 10 (48%) received prior HMA therapy. Median duration of prior HMA therapy was 6 cycles (1-24). Ven was given in combination with HMA, low dose cytarabine (LDAC), or IC in 35 (83.3%), 6 (14.3%), and 1 (2.4%) pt respectively. Forty pts were evaluable for response. Complete response (CR) or CR with incomplete count recovery (CRi) rate was 47.5%. CR/CRi rates were significantly different based on ven combination (IC&amp;gt; HMA &amp;gt; LDAC, p=.001), AML status (de novo &amp;gt; t-AML &amp;gt; s-AML, p=.025), ELN risk and cytogenetic group (favorable &amp;gt; intermediate &amp;gt; poor, p=.001 and p=.004 respectively). CR/CRi rates were lower for pts receiving prior HMA, p=.012. CR/CRi rates were higher for pts with FLT3 (p=.040) and NPM1 mutations (p=.04). There was a trend for lower CR/CRi for pts with TP53 mutations, p=.095. [Table 1] Newly diagnosed vs R/R disease status, number of mutations (≤3 vs &amp;gt;3), and prior treatment with IC for AML had no impact on CR/CRi rates. There was no difference in median OS (mOS) between newly diagnosed vs R/R pts: 10.9mo vs 9.5mo respectively, p=.61. OS was significantly different based on response (CR vs CRi vs MLFS/PR vs PD with mOS not reached, 13.2, 9.5, and 2.3 mo respectively, p&amp;lt;.001. OS was longer for pts with de-novo AML&amp;gt; t-AML&amp;gt; s-AML with mOS of 15.6, 10.9, and 2.8 mo respectively, p=.007. Lastly, mOS was significantly shorter for pts with prior HMA exposure vs not at 5.0 vs 15.6 mo respectively, p=.003. [Figure 1] Multivariable analysis (MVA) for response demonstrated ELN cytogenetic intermediate vs high risk to be the only factor associated with CR/CRi, p=.004. MVA for OS showed prior HMA exposure and ELN poor cytogenetic risk to be the only two factors associated with shorter OS, p=.022 and p=.007 respectively. Conclusions In summary, this study of real world outcomes with ven combination therapy in AML has revealed disease features predictive of clinical outcomes. Remarkably, we observed no difference in response rates or OS between pts with newly diagnosed AML or R/R disease, which may be in part reflective of a population with high disease risk less likely to respond to upfront therapy. Additionally, we identify in a MVA disease factors predictive of response to therapy such as ELN cytogenetic risk and prior HMA exposure, the latter of which was not previously evaluated in clinical trials. Together, these observations highlight the clinical potential of ven combinations for R/R AML, as well as the need for novel therapeutic strategies to overcome the poor outcomes of pts with prior HMA exposure. Disclosures Patel: Celgene: Consultancy, Speakers Bureau; DAVA Pharmaceuticals: Honoraria; France Foundation: Honoraria; Agios: Consultancy.

REALizing and improving management of stable COPD in China: a multi-center, prospective, observational study to realize the current situation of COPD patients in China (REAL) \u2013 rationale, study design, and protocol

BackgroundChronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in China with a reported prevalence of 8.2% people aged ≥40 years. It is recommended that Chinese physicians follow Global Initiative for Chronic Obstructive Lung Disease (GOLD) and national guidelines, yet many patients with COPD in China remain undiagnosed. Furthermore, missed diagnoses and a lack of standardized diagnosis and treatment remain significant problems. The situation is further complicated by a lack of large-scale, long-term, prospective studies of real-world outcomes, including exacerbation rates, disease severity, efficacy of treatment, and compliance of COPD patients in China.Methods/designThe REALizing and improving management of stable COPD in China (REAL) study is a 52-week multi-center, prospective, observational trial. REAL aims to recruit approximately 5000 outpatients aged ≥40 years with a clinical diagnosis of COPD per GOLD 2016. Outpatients will be consecutively recruited from approximately 50 tertiary and secondary hospitals randomly selected across six geographic regions to provide a representative population. Patients will receive conventional medical care as determined by their treating physicians.The primary objective is to evaluate COPD patient outcomes including lung function, health status, exacerbations, hospitalization rate, and dyspnea following 1 year of current clinical practice. Secondary objectives are to assess disease severity, treatment patterns, adherence to medication, and associated risk factors. Data will be collected at two study visits, at patients’ usual care visits, and by telephone interview every 3 months.DiscussionKnowledge of COPD among physicians in China is poor. The REAL study will provide reliable information on COPD management, outcomes, and risk factors that may help improve the standard of care in China. Patient recruitment began on 30 June 2017 and the estimated primary completion date is 30 July 2019.Trial registrationClinicalTrials.gov identifier: NCT03131362. Registered on 20 March 2017.

Reduction in Hospital Readmission Rates Among Medicare Beneficiaries With Chronic Obstructive Pulmonary Disease: A Real-world Outcomes Study of Nebulized Bronchodilators

PurposeChronic obstructive pulmonary disease (COPD) is a common condition responsible for substantial morbidity, mortality, and costs in the United States. The economic burden of COPD is driven primarily by hospitalizations, with 1 in 5 hospitalized patients experiencing a 30-day readmission. Bronchodilators, delivered via handheld inhalers or nebulizers, are the mainstay of therapy for COPD. However, differences in outcomes between short- and long-acting therapies are unclear. We examined real-world differences in 30-day readmission and exacerbation rates between Medicare beneficiaries with COPD treated with a nebulized long-acting beta2-agonist (arformoterol tartrate [ARF]) and beneficiaries treated with a nebulized short-acting beta2-agonist (SABA) for maintenance therapy after hospital discharge. MethodsTruven MarketScan Hospital Drug Database and Medicare files were probabilistically matched between 2009 and 2013 to identify beneficiaries who were aged ≥65 years and discharged from a hospital with a primary COPD diagnosis or a secondary COPD diagnosis and a primary diagnosis for another respiratory condition. Matching was performed by using COPD hospitalization date (±7 days) and source, length of stay (±1 day), discharge date and destination, and hospital region. After applying additional inclusion/exclusion criteria, 2 cohorts were created: nebulized ARF users (n = 953) and nebulized SABA users (n = 6939). Logistic regression analyses were used to examine 30-day readmission (all-cause and COPD related) and exacerbation rates. Odds ratios (ORs), 95% CIs, and P values were computed. FindingsOn average, nebulized SABA users had more comorbidities than nebulized ARF users, including diabetes, atrial fibrillation, renal disease, musculoskeletal disease, myocardial infarction, and cognitive impairment (all, P < 0.0001). However, nebulized ARF users had a higher average COPD severity score than nebulized SABA users (49.5 v. 38.0; P < 0.001). COPD therapies at baseline were similar in both cohorts and included systemic corticosteroids (≥65%), short-acting bronchodilators (≥33%), and inhaled corticosteroids + long-acting beta2-agonists (30%). After adjusting for sociodemographic and hospital characteristics, concomitant medications, and case-mix, nebulized ARF users had 27% lower odds of an all-cause readmission (OR, 0.73; 95% CI, 0.59–0.92; P = 0.008) and 23% lower odds of a COPD-related readmission (OR, 0.77; 95% CI, 0.60–0.98; P = 0.032) at 30 days compared with users of a nebulized SABA. No difference was found in 30-day exacerbation rates between the cohorts. ImplicationsNebulized ARF users had lower 30-day readmission rates, greater COPD severity, and fewer comorbidities than nebulized SABA users. In this population, maintenance treatment with ARF reduced costly COPD outcomes.

Treatment outcomes for amblyopia using PEDIG amblyopia protocols: a retrospective study of 877 cases

The landmark Pediatric Eye Disease Investigators Group (PEDIG) Amblyopia Treatment Studies (ATS) 2A and 2B concluded that 6hours of occlusion were as efficacious as full-time occlusion in treating severe amblyopia and that 2hours occlusion were as effective as 6 in treating moderate amblyopia. We present the first retrospective study of real-world outcomes of amblyopia treatment using PEDIG amblyopia protocols in 877 patients treated at a single center. Electronic patient records were reviewed retrospectively to identify children meeting ATS2A (severe amblyopia) and ATS2B (moderate amblyopia) inclusion criteria who presented at the Gloucestershire Eye Unit from 2013 to 2017. Clinical data for each patient were entered during routine clinical care. Severely amblyopic children were prescribed 6hours occlusion daily, and moderately amblyopic children 2hours, after 12weeks refractive adaptation. A total of 288 children were in the ATS2A group and 589 in the ATS2B group. Of the severely amblyopic eyes, 40% achieved best-corrected visual acuity better than 0.4 logMAR at 32weeks, increasing to 55% at 48weeks; of the moderately amblyopic eyes, 71% achieved best-corrected visual acuity better than 0.3 logMAR at 32weeks. The mean number of lines of visual improvement was 4.2 for severely amblyopic eyes and 2.1 for moderately amblyopic eyes. This is the largest reported series of amblyopia treated according to PEDIG protocols. The study population achieved outcomes comparable to those demonstrated by the PEDIG studies. This audit represents a "real-world" benchmark for treatment outcomes in clinical practice.

PMS6 - Improved Outcomes and Neutral Hospital Budget Impact Associated with Flowable Gelatin for Lumbar Surgery in a Chinese Tertiary Care Hospital: A Retrospective Case-Series Study

To assess the clinical and economic impact of flowable gelatin hemostatic matrix (SURGIFLO®) for lumbar surgery (LS) in a Chinese tier III hospital, the first such real-world outcomes study in LS. Patients operated by one surgeon for lumbar disc herniation or disc stenosis from 2014-2016 in a Chinese tier III hospital were included. Historical control cohort (HC) comprised patients who underwent LS in 2014 before the introduction of SURGIFLO®. Flowable gelatin cohort (FG) comprised patients who received SURGIFLO® during LS in 2015-2016. From patient medical records and hospital cost data, propensity score and regression analyses were conducted for adjusted comparisons of surgical outcomes and hospital expenses between cohorts. 64 pairs of patients matched from FG (n=108) and HC (n=82) had well balanced patient characteristics and procedure characteristics, e.g. lumbar fusion level and procedure method (posterior lumbar interbody fusion or minimally invasive surgery transforaminal lumbar interbody fusion). In matched HC, oxidized regenerated cellulose or collagen were the most frequently utilized hemostatic products (92.7%). Matched comparisons also observed that FG was associated with significantly lower: blood transfusion rate (34.4% vs. 64.1%, p=0.005), blood transfusion volume (183 ± 312 vs. 301 ± 281 mL, p=0.045), and post-operation drainage tub placement rate (82.8% vs. 93.8%, p=0.046). Multiple regression analysis confirmed the significantly lower blood transfusion risk (odds ratio 0.115, p<0.001) and blood transfusion volume (coefficient -101.820, p=0.003) associated with FG, and showed comparable total hospital costs between cohorts (coefficient -0.001, p=0.972). Patients who received FG in LS within the Chinese tertiary care setting, compared to those who received oxidized regenerated cellulose or collagen, show significantly reduced rate and volume of blood transfusion. In addition, utilization of FG in LS did not increase hospitalization expenses. These results warrant further study to confirm the positive findings on a larger scale.

Design of the Prospective Real-world Outcomes Study of hepatic encephalopathy Patients\u2019 Experience on Rifaximin-\u03b1 (PROSPER): an observational study among 550 patients

BackgroundHepatic encephalopathy (HE) is one of the most important severe complications of liver cirrhosis. Thought to be caused by elevated blood levels of gut-derived neurotoxins (particularly ammonia) entering the brain, HE manifests as a wide range of neurological or psychiatric abnormalities, which increase the risk of mortality, result in substantial morbidity and negatively affect the quality of life (QoL) of both patients and their caregivers. HE is also associated with a substantial economic burden. Rifaximin-α 550 mg is a locally acting oral antibiotic that reduces the effects of ammonia-producing intestinal flora, and which is used to help reduce the recurrence of overt HE. The efficacy of rifaximin-α 550 mg was established in a randomised controlled trial and long-term extension study. However, ‘real-world’ evidence is also required to assess how this efficacy may translate into effectiveness in clinical practice, including the potential impact of treatment on healthcare resource utilisation.MethodsThe Prospective Real-world Outcomes Study of HE Patients’ Experience on Rifaximin-α 550 mg (PROSPER) is a multinational, multicentre, observational study that will be conducted under real-world clinical practice conditions. Comprising a retrospective phase (up to 12 months) and a prospective phase (up to 24 months), and employing a robust statistical methodology, PROSPER has been specifically designed to minimise the bias associated with observational studies. The primary endpoint will be the effect of rifaximin-α 550 mg treatment on HE- and liver-related hospitalisation rate and duration of hospitalisation. Secondary endpoints will include comprehensive assessments of the impact of treatment on the QoL and workplace productivity of patients and caregivers, a global assessment of treatment effectiveness and safety/tolerability. Approximately 550 patients will be enrolled.ConclusionsPROSPER will provide valuable real-world information on the effectiveness of rifaximin-α 550 mg in reducing the recurrence of HE, and its impact on the QoL and work productivity of patients and their caregivers. By providing data on both the direct costs (e.g., hospitalisation rate, duration of hospitalisation) and indirect costs (such as work productivity) of HE, PROSPER should help confirm whether rifaximin-α 550 mg treatment represents a good use of economic resources.Trial registrationClinicalTrials.gov identifier NCT02488993.