Journal articles on the topic 'IRB 14000'

Collaborative industrial robots meet the modern approach to robotization. They enable cooperation with a human being in the robot’s work area. As part of the article, it was decided to design and build a robotic station enabling the implementation of human–machine cooperation. CAD models of the station were created using the Autodesk Inventor software. The station design was made in the RobotStudio environment with the use of the IRB 14000 YuMi robot. The software is based on smart components and Rapid language code. A graphical user interface was created, interactive with a human in virtual reality. The software was verified with the participation of the operator in virtual reality.

AbstractThe UBVRI photometric follow-up of SN 2011fu has been initiated a few days after the explosion, shows a rise followed by steep decay in all bands and shares properties very similar to that seen in case of SN 1993J, with a possible detection of the adiabatic cooling phase at very early epochs. The spectral modeling performed with SYNOW suggests that the early-phase line velocities for H and Fe ii features were ~ 16000 km s−1 and ~ 14000 km s−1, respectively. Studies of rare class of type IIb SNe are important to understand the evolution of the possible progenitors of core-collapse SNe in more details.

14001 Background: Acneiform rash is the main toxicity of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor. The length of the CA dinucleotide repeat in EGFR intron 1 has been suggested to predict the biological effects of tyrosin kinase inhibitors. Thus, we compared this polymorphism with the rash severity in non-small cell lung cancer (NSCLC) patients treated with erlotinib. Methods: Toxicity was evaluated in 18 metastatic or locally advanced unresectable NSCLC patients treated orally with 150 mg/d of erlotinib: 7 retrospectively and 11 prospectively. Rash was graded according to a modified scale based on the Common Toxicity Criteria v.3.0, which subclassified grade II rash into IIA (topic intervention indicated) and IIB (oral intervention indicated). Genomic DNA was isolated from each patient; the length of the EGFR intron 1 CA dinucleotide repeat was measured by PCR amplification and analyzed on a capillary sequencer. Results: The most common EGFR genotypes were: 16, 20, 17 and 18 CA repeats (with 50, 25, 8 and 8% frequency, respectively). 33% of the subjects with a total amount of CA repeats <34 had grade IIB-III rash vs 11% of the subjects with =34 CA repeats. In addition, all patients with 0 grade toxicity belonged to the =34 CA group. When the only patient with a previous dermatological disease (psoriasis) was excluded from the analysis, the difference between both groups increased, reaching statistical significance (p=0.047). Conclusions: This data suggests that NSCLC patients with long EGFR intron 1 CA alleles present lower grades of skin toxicity when treated with erlotinib than patients with short CA alleles. Further studies are required to confirm this data. [Table: see text] No significant financial relationships to disclose.

6557 Background: Clinico-genomic data sharing is consistently identified by the global oncology community as a critical requirement to accelerate the discovery and development of new targeted therapies. However, lack of effective collaborative models, fragmented and lengthy legal contracting processes, paucity of funding, and inadequate technological platforms have historically been obstacles for effective data sharing. Methods: In 2015, 10 US academic medical centers (AMC) and Foundation Medicine Inc. (FMI) formed PMEC. Feasibility assessments included creation of a master agreement across sites and willingness to use a central IRB. Oversight and research steering committees were created within the consortium. Through a centralized, secure web-based platform, FoundationInsight, we combined and shared de-identified, harmonized comprehensive FoundationOne genomic profiling data. Research proposals mining this data warehouse are invited quarterly from participant AMCs and peer-reviewed; approved studies are executed at all sites. Results: All 10 AMCs collaborated to execute a master registry participation agreement, followed by a master IRB protocol (New England IRB # 120180008), subsequently approved by individual site IRBs. Since its launch, the PMEC database has grown, on average, 60% per year, to now house over 14,000 cases. The shared dataset covers all tumor types (most commonly lung [17.2%], gastrointestinal [13.8%] and breast [9.2%]), encompasses genomic alterations in >300 genes, and reports relevant supplementary data such as tumor mutation burden and microsatellite instability status. To date, 15 studies have been proposed and evaluated using this platform, with 2 projects currently approved and in progress. Conclusions: We demonstrated the feasibility of creating a collaborative academic consortium that facilitates data sharing and potential discovery efforts in oncology. Technology solutions can accelerate the ability of AMCs, in partnership with central labs, to share and harmonize data to advance precision medicine. This approach lays the groundwork for conducting prospective, biomarker-enriched clinical trials among participating AMCs.

551 Background: Randomized trials demonstrated a modest (3-5%) absolute benefit from EET in patients (pts) with early stage HR+ breast cancer (BC), but also a risk of toxicities. BCI is a validated gene expression-based assay that provides 2 results: BCI Prognostic, based on the algorithmic combination of HoxB13/IL17BR (H/I ratio) and a set of proliferation-based genes, reports individualized risk of late distant recurrence (DR); BCI Predictive, based on H/I alone, reports a prediction of high vs low likelihood of benefit from EET. The objective of this study was to assess clinical and pathologic patient characteristics, prognostic and predictive assay results, and physician testing patterns in >14,000 clinical cases. Methods: The BCI Clinical Database for Correlative Studies is a de-identified database developed under an IRB approved protocol that contains >50 clinicopathologic and molecular variables from cases submitted for BCI in clinical practice. Clinicopathologic variables were abstracted from pathology reports, and were available for a subset of cases. Results: Across all pts (N=14,463), median age was 58.2y (range: 23-92y; 73.9% ≥50y). The majority were Stage I (47.3% IA, 3.5% IB, 29.1% IIA, 14.1% IIB, 6% III). Cases were 29%, 51%, and 20% Grade 1, 2, and 3, respectively. Most pts were ER+/PR+ (87.7%) or ER+/PR- (11.3%); 11.3% were HER2+. The majority of cases (55.7%) were ordered 4-6y postdiagnosis, with 23.1% >6y, 14.4% between 1-4y, and 6.8% <1y postdiagnosis. In LN- pts (n=3395), BCI Prognostic identified 50.6% as low risk for late DR vs 49.4% as high risk, while BCI Predictive (H/I) classified 41.0% as high vs 59.0% as low likelihood of benefit. In LN+ pts tested with the BCIN+ Prognostic algorithm (BCI + size/grade, n=818), 77.3% were classified as high risk vs 22.7% as low risk, while BCI Predictive (H/I) classified 44.6% and 55.4% as high vs low likelihood of benefit. Conclusions: Findings from this large cohort characterize utilization of BCI in clinical practice for pts with early-stage, HR+ BC. BCI stratification of pts with high risk and high likelihood of benefit from EET may facilitate selection of pts for prolonged regimens.

14002 Background: Gemcitabine, the standard chemotherapy for advanced pancreatic cancer (APC), produces low response rates and short time to progression. Preclinical studies suggest that zoledronic acid inhibits pancreatic cell lines by interfering with the p21ras/raf-1/MEK1/ERKL signaling pathway. We conducted this trial to evaluate the efficacy and toxicity of gemcitabine and zoledronic acid in subjects with APC. Methods: Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma (Stage IV) not amenable to resection with curative intent. Gemcitabine 1000 mg/m2 IV was given on Days 1, 8, 15, and 22 in Cycle 1 and Days 1, 8, and 15 in subsequent cycles. Zoledronic acid 4 mg IV was given on Day 1 every 4 weeks. Toxicity was assessed at each visit. Results: Between December 2004 and July 2005, 35 subjects were enrolled. Baseline characteristics: 20 males (57%), median age 66.7 years (range, 40–83.5), and KPS of 70/80/90/100 = 8%/29%/34%/29%, respectively. Four patients had locally advanced disease (3 stage IIB and 1 stage III), 86% of subjects had Stage IV disease at diagnosis; 91% of subjects had adenocarcinoma. Prior therapy included surgery (n=15, 43%), chemotherapy (n=3, 9%), and radiotherapy (n=2, 6%). To date, there has been 1 PR and 9 SD; the clinical benefit rate (PR+SD≥6 months) was 14%. Grade 3 and 4 treatment-related toxicities included: neutropenia (22%); thrombocytopenia and fatigue, (12.5% each); and anemia, nausea/vomiting, dehydration, and diarrhea (6% each). Seven treatment-related SAEs have been reported; 28 subjects are off study. Patients discontinued treatment due to: progressive disease (PD) (n=15), toxicity (n=4, 1 each DVT, infection, back pain, and generalized weakness), withdrew consent (n=3), MD decision (n=2), patient request (n=2), and death (n=2), To date, 21 subjects have died; deaths were attributed to PD (n=16), CVA (n=1), and unknown (n=4). Conclusions: Pancreatic cancer, typically advanced at diagnosis, remains a major treatment challenge. Zoledronic acid in combination with gemcitabine was well-tolerated in this study. Future genomic testing is proposed for responders. Updated toxicity, response, and survival data will be presented. Supported by Novartis Pharmaceuticals Corp., East Hanover, NJ. No significant financial relationships to disclose.

The authors report on a consecutive series of 253 cases of seminoma of the testis followed with periodic chest X-ray examinations from a minimum of three to a maximum of 27 years. The detection rate of asymptomatic intrathoracic metastases (ITM) was considered together with the costs of the follow-up procedure. Chest X-ray follow-up is not advisable beyond one year from primary treatment, since most (14 of 18) ITM occur in the first year, the detection rate of ITM beyond this date is too low (0.11% patients/year), and the related costs are too high (over $ 130,000 per ITM detected). Chest X-ray follow-up is questionable even in the first year after primary treatment for Stage I cases because of the low detection rate (1.38% patients/year) and the high costs (over $ 14,000 per ITM detected), whereas it appears to be opportune in Stages IIA and IIB.

Introduction: Hydroxyurea (HU) is the most used cytoreductive therapy (tx) for patients (pts) with polycythemia vera (PV). However, many pts may have suboptimal responses (SubOR) and/or toxicity (TOX) to HU. After HU, Ruxolitinib (RUX) may achieve hematocrit (HCT) and spleen reductions, but other tx are also available, mainly busulfan (BUS) and interferons (IFN). Aims: In a large cohort of PV pts, we investigated if: 1) type of SubOR to HU influenced subsequent tx strategy; 2) differential tx had an impact on overall survival (OS). Methods: After IRB approval, clinical/laboratory data of 2016 WHO-defined PV pts from 21 European Hematology Centers were retrospectively collected. SubOR included ≥1 of the following criteria after ≥3 mos of HU: WBC/PLT count &gt;10/400 x109/l, need for phlebotomies (PHL); splenomegaly and/or symptoms persistence/occurrence (Barosi G et al, Blood 2009). Only pts with stable SubOR were included in this analysis. Since a complete response was never achieved, the index date (ID) was set at 3 mos from HU start in all pts (Barosi G et al, BJH 2009). OS was calculated from the ID by Cox analysis with age&gt;80, adjusted with left truncation from PV diagnosis. Results: At data cut-off date (June 2020), 808 PV pts were collected; 688 received HU. Among the 452 (65.7%) pts who presented a stable SubOR to HU, 41 did not receive any tx for PV due to early death or progression to BP/MF and were excluded from this analysis. Baseline characteristics of the 411 evaluable pts were: median age: 65 yrs (21- 87); males: 54%; median (range) WBC/PLT count, x109/l: 10 (1.1-38)/465 (139-1209); median Hb (g/dl)/HCT (%): 18.6/56 (males); 17.6/54 (females); palpable splenomegaly: 38%; symptoms: 80.5%; pruritus: 42%. A previous thrombosis occurred in 104 (25.3%) pts. At least one cardiovascular risk factor (CVRF: smoke, diabetes, hypertension, dyslipidemia and overweight) was present in 325 pts (79.1%). After a median follow-up of 4.8 yrs (0.5-27.6) from HU start, 104 (25.3%) switched to RUX (HU-RUX), 18 (4.4%) switched to another agent (HU-other, including IFN, BUS, PHL only), and 289 (70.3%) continued HU (HU-alone). Pts with baseline palpable spleen (p&lt;0.001) and pruritus (p=0.01) more frequently switched to RUX. Conversely, pts ≥80y more frequently received HU-alone/other (p=0.03). Notably, Charlson Comorbidity Index and CVRF had no impact on tx strategy. Median HU daily dose was 0.65 g (≥2 g/d: 8.7% of pts) and was higher in HU-RUX pts (1 vs 0.6 g/d in HU-alone/other pts, p=0.004). While 331 (80.5%) pts had a stable SubOR without TOX, 80 (19.5%) had also TOX. Notably, pts with only SubOR more frequently continued HU (p&lt;0.001). Conversely, the co-occurrence of TOX was significantly associated to RUX switch (p&lt;0.001) (Fig. 1a). In 45.5% of pts, the SubOR was related only to uncontrolled WBC/PLT/HCT, while 16.1% of pts had an optimal hematological control but presented spleen/symptoms; the remaining 38.4% of pts had both uncontrolled myeloproliferation and spleen/symptoms. The presence of both uncontrolled myeloproliferation and spleen/symptoms significantly predicted RUX switch (p&lt;0.001). Investigating the SubOR criteria individually among the HU-alone/other and the HU-RUX groups, we found that uncontrolled leukocytosis and/or thrombocytosis (p&lt;0.001), rather than PHL need (p=0.13), was significantly associated with RUX switch. Moreover, the persistence/occurrence of symptoms (p=0.001) or splenomegaly (p=0.005) were significantly associated with RUX use (Fig. 1b). After the ID, 31 pts died. HU-RUX pts presented increased OS compared to HU-alone/other pts (p=0.03). Conclusions. This study revealed a high rate of SubOR to HU, possibly also affected by low HU doses, and a lack of urgency to change the tx in these pts, with &gt;70% of pts continuing HU despite the stable SubOR. Particularly, good tolerance to HU, absence of splenomegaly and pruritus, and older age were the main factors against a tx change. Notably, despite HCT&gt;45% is associated with worse outcome (Marchioli R, NEJM 2013), PHL need did not significantly trigger tx change. The better OS in the HU-RUX group is presumably multifactorial and requires further confirmation. Overall, this analysis points out the need to improve HU management and response evaluations, weighing appropriate tx strategies in case of SubOR. Disclosures Palandri: Novartis: Consultancy, Honoraria. Benevolo:Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Breccia:Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Abbvie: Consultancy; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Cavazzini:Pfize: Honoraria; Novartis: Honoraria; Incyte: Honoraria. Heidel:Celgene: Consultancy; CTI: Consultancy; Novartis: Consultancy, Research Funding. Crugnola:BMS: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Pane:Daiichi Sankyo: Consultancy, Other: Travel Expenses; Janssen: Other: Travel Expenses; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau. Cuneo:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Semenzato:Takeda: Honoraria; Roche: Honoraria; Abbvie: Honoraria. Lemoli:Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; BerGenBio ASA: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Nowadays many organizations worldwide have/are implemented/ implementing an environmental management system (EMS) according to ISO 14001, considering the context, the need to minimize negative environmental impacts, and long-term benefits. It has been observed for decades that for successful implementation of EMS are required different changes in the organizational structure, chances that lead to a successful integration and operation of this management system. Studying the literature it was observed the inexistence of relevant investigations conducted at Romanian organizations level, investigations which include different methodologies with models adapted to the particularities of the Romanian context, and relevant results for the current situation (PA). This paper intends to resolve the problem covered through the following general steps: I. identifying the problem (MP); II. goal setting: conceiving a model to analyze the effects produced at organizational structure level as a result of implementing an EMS; III. collecting data / information / knowledge from the literature (focusing on previous studies conducted starting from Mintzberg and others (authors as C. Hunt, E. Auster, M.C. Lopez-Fernandez, A. Zutshi, A. Sohal and so on) and from discussions with various managers of the environment department of several organizations located in the NE Romania; IV. the construction of the model; V. validate the constructs from the proposed model. The proposed research analysis model approaches three general dimensions that should characterize finally the effects resulted from the implementation of environmental management system at organization level; dimensions: I. aspects of organizational structure: I.a. Specialization (S1.horizontal; S2.vertical), I.b. Decentralization (D1.horizontal; D2.vertical), I.c. Formalization, I.d. Environmental trainings (per profile), I.e. Professional competence, I.f. Processes/ systems orientation, I.g. Systems/ process planning and control, I.h. Coordination/ cooperation in environmental issue; II. The effects of EMS implementation/ integration on organizational structure; and III. The quality of the organization's EMS integration

Abstract Background Ibrutinib (Ibr), an oral, first-in-class covalent Bruton's tyrosine kinase inhibitor, showed in the Phase 3 RESONATE trial significantly improved progression-free survival (PFS, hazard ratio [HR] =0.22, p<0.001) and overall survival (OS, HR=0.39,p=0.001) compared with ofatumumab (ofa) in patients with previously treated CLL who were not eligible for chemoimmunotherapy (Byrd et al, NEJM 2013). Long-term follow-up data from a single arm Phase 2 study have also demonstrated that patients treated with ibrutinib have long durable responses with a PFS at 2.5 years of 69% (Byrd et al, Blood 2015). While ofatumumab is a licensed comparator and included in treatment guidelines, some Health Technology Assessment (HTA) bodies require comparisons with a wider range of treatments. In the absence of direct head-to-head comparison of single-agent ibrutinib with other frequently used treatments in this patient population, additional comparative evidence against standard of care as observed in clinical practice can provide useful insights on the relative efficacy of ibrutinib. Naïve (unadjusted) comparisons of outcomes from different sources are prone to bias due to confounding, as treatment assignments were not randomly assigned, and populations can vary in important prognostic factors. The objective of this analysis was to compare the relative efficacy of Ibr versus physician's choice in R/R CLL-patients based on patient-level data from RESONATE pooled with an observational cohort, adjusting for confounders using multivariate statistical modelling. Methods Patient-level data from the Phase 3 RESONATE trial (Ibr: n=195; ofa: n=196) were pooled with data from a retrospective observational study conducted in the Stockholm area in Sweden. This retrospective study collected efficacy and safety data from a detailed, in-depth retrospective review of individual patient files from 148 consecutively identified patients with R/R CLL initiated on second or later line treatment between 2002 and 2013 at the four CLL-treating centers in Stockholm, Sweden, with complete follow-up. Longitudinal follow-up in subsequent treatment lines was available for patients in 3rd (n=91), 4th (n=51), 5th (n=29), and 6+ (n=15) line, and as such individual patients could contribute information to the analysis for multiple lines of therapy, with baseline defined as the date of initiation of the actual treatment line. A multivariate cox proportional hazards model was developed to compare PFS and OS between treatments, including line of therapy, age, gender, Binet stage, ECOG, and refractory disease as covariates. Adjusted HRs and 95% CIs are presented vs. Ibr. Results Across all treatment lines, fludarabine-cyclophosphamide (FC) (n=64), chlorambucil (n=59), alemtuzumab (n=33), FC+rituximab (FCR) (n=30), bendamustine+rituximab (BR) (n=28), and other rituximab-based combination chemotherapy (n=28) were the most frequently used treatments. Line of therapy, age and gender, Binet stage, ECOG performance status, and refractory disease were all independent risk factors for worse outcome on both PFS and OS. The adjusted HR for PFS and OS pooled observational data versus Ibr were 6.80 [4.72;9.80] (p<0.0001) and 2.90 [1.80;4.69] (p<0.0001). HR's for PFS/OS versus most frequent treatment regimens ranged between 2.50/1.82 (FCR) and 14.00/5.34 (anti-CD20 Mab). Baseline adjusted results for the Ofa-arm in RESONATE were comparable for both PFS and OS to outcome data from the consecutive historical cohort, however OS outcomes for Ofa were partly confounded by cross-over to Ibr. Conclusions Comparison of results from the Phase 3 RESONATE study with treatments used as part of previous standard of care in a well-defined cohort of consecutive Swedish patients shows that ibrutinib is superior to physician's choice in patients with relapsed/refractory CLL, suggesting a more than 6 fold improvement in PFS and almost 3 fold improvement in OS. Results were consistent across all different physician chosen treatments and provides further evidence that ibrutinib improves both PFS and OS vs current and prior standard of care regimens. Figure 1. Adjusted Hazard ratio's for PFS and OS of physician's choice versus Ibrutinib (RESONATE) (Multivariate Cox proportional hazards regression) a. Progression-free survival b. Overall survival Figure 1. Adjusted Hazard ratio's for PFS and OS of physician's choice versus Ibrutinib (RESONATE) (Multivariate Cox proportional hazards regression). / a. Progression-free survival b. Overall survival Disclosures Österborg: Janssen Cilag: Research Funding. Asklid:Janssen Cilag: Research Funding. Diels:Janssen: Employment. Repits:Janssen Cilag: Employment. Söltoft:Janssen Cilag: Employment. Hansson:Jansse Cilag: Research Funding. Jäger:Janssen Cilag: Research Funding.

Abstract We found 17 rare PCOS-specific functional protein-altering variants (PAVs) or mutations in the gene, AMH, that decrease the biologic activity of the encoded protein, anti-Müllerian hormone (AMH), in the heterozygous state. Approximately 3% of European ancestry PCOS cases in our cohort of ~700 were affected. Our preliminary studies found evidence for a metabolic phenotype in both PCOS as well as their male first-degree relatives who were heterozygous carriers of these AMH PAVs. We performed this study to test the hypothesis that AMH mutations are associated with metabolic abnormalities in the general population. The Mount Sinai BioMe Biobank is an electronic health record (EHR)-linked biobank, containing anonymized whole exome sequences from 30,813 participants of diverse ancestries. We interrogated the sequence data to identify individuals with PCOS-related AMH PAVs. IRB-approval was obtained to review the linked EHR. Outcomes were the presence of obesity (BMI ≥ 30 kg/m2), type 2 diabetes (hemoglobin A1C ≥ 6.5%), prediabetes (hemoglobin A1C 5.7% - 6.4%), elevated cholesterol (total cholesterol ≥ 200 mg/dL), hypertriglyceridemia (TG ≥ 150 mg/dL), and hypertension (≥2 blood pressure values ≥140/90, or administration of antihypertensive medications). Control subjects were obtained from the National Health and Nutrition Examination Survey using propensity score matching (for sex, age, and BMI) with a 1:4 case:control ratio. A total of 292 individuals with AMH PAVs were identified, resulting in a combined 0.95% prevalence of AMH PAVs in an unselected population (1.07% in Europeans, 0.28% in African Americans, 0.54% in Hispanics, and 0.07% in Asians). After adjusting for age, BMI, and race/ethnicity, there was a statistically significant increased prevalence of hypertriglyceridemia in both women (OR 7.29, 95% CI 3.77-14.00) and men (OR 10.15, 95% CI 4.68-22.00) with AMH PAVs compared to sex-, age- and BMI-matched controls. There was also a statistically significant increased prevalence of elevated cholesterol in men with AMH PAVs compared to controls (OR 2.48, 95% CI 1.15-5.34). There were no significant differences between individuals with AMH PAVs and matched controls with respect to the other outcomes. These findings suggest that decreased bioactivity of AMH is causally related to dyslipidemia in the general population. TG levels are elevated in both sexes, whereas increases in cholesterol are only seen in men. The mechanisms by which decreases in AMH bioactivity alter circulating lipid levels are of considerable interest since AMH has no known metabolic actions. It is possible that the putative metabolic effects of AMH are mediated by increases in circulating testosterone (T) levels that in turn alter lipid metabolism. Since T levels are not commonly available in EHR, future studies will be needed to investigate this hypothesis as well as to explore metabolic actions of AMH.

Abstract Background: Children with Acute Lymphoblastic Leukemia (ALL) in resource-poor countries face major challenges including treatment abandonment and poor overall survival (OS) and event-free survival (EFS). To address these issues, in 2002 a non-profit pediatric hematology-oncology center was established in a tertiary medical institution in Kerala, India to provide high-quality treatment and supportive care at low cost. A standardized approach to pediatric leukemia care began in 2010. We present evidence that outcomes on par with that seen in resource-rich nations can be achieved with a rigorous treatment and supportive care approach. Methods: Following IRB approval, we reviewed clinical information and outcomes of all patients above 1 year and less than 14 years of age treated for newly diagnosed B- or T-ALL between January 1, 2010 and January 31, 2015. Seventy-six children were consecutively treated and all are included in this analysis. B-ALL patient treatment was stratified according to BFM relapse risk criteria with standard risk (SR) defined by age 1-6 yrs, peripheral WBC < 20 X 106/ul, good prednisolone response, absence of t(9:22) and t(4:11), and a day 33 marrow in remission by morphology. At any age, poor prednisolone response, t(9:22) or t(4:11), or day 33 marrow not in remission defined high risk (HR), and patients not meeting SR or HR criteria were intermediate risk (IR). Minimal residual disease assessment (MRD) was not utilized in risk stratification or treatment decisions. All patients were treated as per BFM 2002 with modifications. All patients received 4-drug (Vincristine/ Daunorubicin/ L Asparaginase/ Prednisolone) induction and Phase 2 induction of cyclophosphamide, cytosine arabinoside, and daily 6-mercaptopurine (6-MP), followed by consolidation with oral 6-MP and IV methotrexate (MTX), 2 gm/m2 x 4 for SR and IR B-ALL and 5 gm/m2 x 4 for HR B-ALL, T-ALL, and CNS disease. Phase 1 reinduction utilized adriamycin and dexamethasone. The Phase 2 reinduction regimen closely mirrored Phase 2 induction. HR B-ALL and T-ALL patients received 12 Gy prophylactic cranial irradiation, and those with CNS disease 18 Gy. Maintenance therapy consisted of daily oral 6-MP, weekly oral MTX, and monthly IV Vincristine and oral Dexamethasone for 104 weeks. Prophylactic intrathecal MTX was given 11 times through reinduction and every 3 months in maintenance. Febrile neutropenia protocols were enforced to ensure less than 30 minutes elapsed from presentation with fever > 38o C to initiation of broad spectrum antibiotics. To minimize sepsis risk, prophylactic GCSF was given between cycles to target ANC > 0.5 x 106/uL. OS and EFS were assessed by Kaplan-Meier method. Patients were censored at last follow-up. Abandonment was treated as an event in calculating EFS. Kuppuswami Socioeconomic Scale (KES) was applied using phone interviews of guardians. Results: Median follow-up time was 30.3 months (range, 1.9-61 months). One patient (1.3%) died during induction, 1 was censored at loss to follow-up upon transfer of treatment to another center, none abandoned treatment, and 6 (7.9%) relapsed, with 1 (1.3%) relapse within 90 days of diagnosis. At median follow-up, the OS was 93.4% and EFS 90.8% (95% CI, 81.1%-99.1%). SR accounted for 28 (36.8%), IR for 36 (47.4%), and HR for 11 (14.5%) patients. OS by risk stratification is shown in Figure 1. KES analysis on the 65 contactable families revealed a median family income between Indian Rs. 14,000-37,000 (US $218-577)/month, and 14 (21.5%) having income less than Rs. 9,300 (US $145)/month. Thirty (46.1%) stratified as lower-middle class or lower. The primary wage earner had less than a high school education in 21 (32.3%), and was at a clerical or lower work level in 46 (70.8%) of families. Conclusion: Our data demonstrate that, for pediatric ALL, results similar to resource-rich countries can be provided in resource-poor areas through a tertiary care center maintaining adherence to globally accepted guidelines for treatment and management of treatment-associated complications. We plan to report minimum 5-year follow-up for all patients in future. Future prospective studies will examine the role of MRD-based stratification and allogeneic transplant options for high-risk patients, as well as seek to extend the low rates of toxic death and abandonment to neighboring centers by implementation of best practices throughout the region. Figure 1. OS by Risk Stratification Figure 1. OS by Risk Stratification Disclosures No relevant conflicts of interest to declare.

Abstract Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder, resulting from auto-antibodies to human factor VIII (hFVIII). The challenges created by the management of AHA and the co-morbidities present in this typically elderly population, can be managed by a recombinant, highly pure, B-domain deleted, porcine sequence FVIII (OBI-1) that is not generally susceptible to the inhibitory activity of anti-human FVIII antibodies. Treatment with OBI-1 allows for monitoring of FVIII levels which provides a reproducible and objective surrogate predictor of hemostasis. Eradication of hFVIII inhibitors with immunosuppressive therapy is critical for disease management. During immunosuppression, the patient transitions from a bleeding state at initial presentation to a relative hypercoagulable state which can be an issue in patients who are susceptible to thromboembolic events due to their comorbidities. This transition period is of most concern especially when using traditionally utilized bypassing agents that cannot be monitored. OBI-1 enables measurement of FVIII levels, guiding dosing and enhancing treatment safety during this critical period. Methods This global, prospective, multi-center phase 2/3 open label clinical trial investigates the efficacy and safety of OBI-1 in the treatment of serious bleeds in adults with AHA conducted under ICH guidelines and local IRB/Ethics Committee oversight. Primary efficacy endpoint was assessed at 24 hours (eg. effective, partially effective). All subjects (N= 18) presented with a serious bleed and were treated with an initial dose of OBI-1 (200 U/kg), followed by additional doses based on the subject's target factor VIII levels, anti-OBI-1 titer, and clinical factors. Results In all 18 subjects, a positive response (14 effective/4 partially effective) to treatment was observed at 24 hours. This positive response to OBI-1 treatment was seen by 8 hours in 14/18 of the subjects and at 16 hours in 16/18 of the subjects. Median total exposure to OBI-1 per subject was 1782.5 U/kg. The median total first dose was 14,000 U. For subjects who received additional doses of OBI-1, the median dose was reduced from the initial dose, but did not differ considerably over subsequent doses (9180 to 13561 U; median 11000 U). The majority of subjects (17/18) received concomitant immunosuppressive therapies. No related serious adverse reactions occurred. Non-serious adverse events related to treatment were noted in 5/18 (27.8%) subjects. One subject had mild tachycardia, hypotension and constipation. One subject had 2 instances of mild PICC line occlusion. One subject had a mild hypofibrogenemia. All of these adverse effects completely resolved. Three subjects developed anti-porcine inhibitors after infusion of study drug (range 8-108 BU) and two were discontinued from treatment. Anti-porcine inhibitors were detected prior to infusion in 6/18 patients (range 0.8-29 BU). All of these subjects had a favorable clinical response at 24 hours post-OB-1 infusions. Conclusions Data from this prospective study demonstrate OBI-1 as a safe and effective treatment of bleeding episodes in patients with AHA, with the added advantage over other bypass therapies of allowing FVIII monitoring throughout treatment and healing phase. Disclosures: Kruse-Jarres: Baxter Healthcare: Consultancy; Bayer HealthCare: Consultancy; Biogen IDEC: Consultancy; Grifols: Consultancy; Kedrion: Consultancy; Novo Nordisk: Consultancy. St. Louis:CSL Behring: Research Funding; Octapharma: Consultancy, Research Funding; Baxter: Consultancy; Novo Nordisk: Honoraria. Shapiro:Kedrion Biopharma: Consultancy; Chugai Pharma USA: Consultancy; Biogen IDEC: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bayer HealthCare: Membership on an entity’s Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Baxter Healthcare: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Chowdary:Baxter Healthcare: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Travel grant Other; Novo Nordisk: Honoraria, Research Funding, Travel grant, Travel grant Other; Bayer HealthCare: Honoraria, Travel grant, Travel grant Other; Pfizer: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Travel grant, Travel grant Other; CSL Behring: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Travel grant Other; Biogen IDEC: Honoraria, Travel, Travel Other. Drebes:Octapharma: Travel grant Other; CSL Behring: Travel grant, Travel grant Other; Leo-pharma: Travel grant, Travel grant Other; Bayer Healthcare: Consultancy, Honoraria. Gomperts:Baxter Healthcare: Consultancy; Asklepios Biopharmaceutoicals Inc: Consultancy; Cangene Inc: Consultancy. Chapman:Baxter Healthcare: Employment. Mo:Baxter Healthcare: Employment. Novack:Baxter Healthcare: Employment. Farin:Baxter Healthcare: Employment.

ObjectiveSentinel physician surveillance in the communities has played an important role in detecting early aberrations in epidemics. The traditional approach is to ask primary care physicians to actively report some diseases such as influenza-like illness (ILI), and hand, foot, and mouth disease (HFMD) to health authorities on a weekly basis. However, this is labor-intensive and time-consuming work. In this study, we try to set up an automatic sentinel surveillance system to detect 23 syndromic groups in the communites.IntroductionIn December 2009, Taiwan’s CDC stopped its sentinel physician surveillance system. Currently, infectious disease surveillance systems in Taiwan rely on not only the national notifiable disease surveillance system but also real-time outbreak and disease surveillance (RODS) from emergency rooms, and the outpatient and hospitalization surveillance system from National Health Insurance data. However, the timeliness of data exchange and the number of monitored syndromic groups are limited. The spatial resolution of monitoring units is also too coarse, at the city level. Those systems can capture the epidemic situation at the nationwide level, but have difficulty reflecting the real epidemic situation in communities in a timely manner. Based on past epidemic experience, daily and small area surveillance can detect early aberrations. In addition, emerging infectious diseases do not have typical symptoms at the early stage of an epidemic. Traditional disease-based reporting systems cannot capture this kind of signal. Therefore, we have set up a clinic-based surveillance system to monitor 23 kinds of syndromic groups. Through longitudinal surveillance and sensitive statistical models, the system can automatically remind medical practitioners of the epidemic situation of different syndromic groups, and will help them remain vigilant to susceptible patients. Local health departments can take action based on aberrations to prevent an epidemic from getting worse and to reduce the severity of the infected cases.MethodsWe collected data on 23 syndromic groups from participating clinics in Taipei City (in northern Taiwan) and Kaohsiung City (in southern Taiwan). The definitions of 21 of those syndromic groups with ICD-10 diagnoses were adopted from the International Society for Disease Surveillance (https://www.surveillancerepository.org/icd-10-cm-master-mapping-reference-table). The definitions of the other two syndromic groups, including dengue-like illness and enterovirus-like illness, were suggested by infectious disease and emergency medicine specialists.An enhanced sentinel surveillance system named “Sentinel plus” was designed for sentinel clinics and community hospitals. The system was designed with an interactive interface and statistical models for aberration detection. The data will be computed for different combinations of syndromic groups, age groups and gender groups. Every day, each participating clinic will automatically upload the data to the provider of the health information system (HIS) and then the data will be transferred to the research team.This study was approved by the committee of the Institutional Review Board (IRB) at Academia Sinica (AS-IRB02-106262, and AS-IRB02-107139). The databases we used were all stripped of identifying information and thus informed consent of participants was not required.ResultsThis system started to recruit the clinics in May 2018. As of August 2018, there are 89 clinics in Kaohsiung City and 33 clinics and seven community hospitals in Taipei City participating in Sentinel plus. The recruiting process is still ongoing. On average, the monitored volumes of outpatient visits in Kaohsiung City and Taipei City are 5,000 and 14,000 per day.Each clinic is provided one list informing them of the relative importance of syndromic groups, the age distribution of each syndromic group and a time-series chart of outpatient rates at their own clinic. In addition, they can also view the village-level risk map, with different alert colors. In this way, medical practitioners can know what’s going on, not only in their own clinics and communities but also in the surrounding communities.The Department of Health (Figure 1) can know the current increasing and decreasing trends of 23 syndromic groups by red and blue color, respectively. The spatial resolution has four levels including city, township, village and clinic. The map and bar chart represent the difference in outpatient rate between yesterday and the average for the past week. The line chart represents the daily outpatient rates for one selected syndromic group in the past seven days. The age distribution of each syndromic group and age-specific outpatient rates in different syndromic groups can be examined.ConclusionsSentinel plus is still at the early stage of development. The timeliness and the accuracy of the system will be evaluated by comparing with some syndromic groups in emergency rooms and the national notifiable disease surveillance system. The system is designed to assist with surveillance of not only infectious diseases but also some chronic diseases such as asthma. Integrating with external environmental data, Sentinel plus can alert public health workers to implement better intervention for the right population.References1. James W. Buehler AS, Marc Paladini, Paula Soper, Farzad Mostashari: Syndromic Surveillance Practice in the United States: Findings from a Survey of State, Territorial, and Selected Local Health Departments. Advances in Disease Surveillance 2008, 6(3).2. Ding Y, Fei Y, Xu B, Yang J, Yan W, Diwan VK, Sauerborn R, Dong H: Measuring costs of data collection at village clinics by village doctors for a syndromic surveillance system — a cross sectional survey from China. BMC Health Services Research 2015, 15:287.3. Kao JH, Chen CD, Tiger Li ZR, Chan TC, Tung TH, Chu YH, Cheng HY, Liu JW, Shih FY, Shu PY et al.: The Critical Role of Early Dengue Surveillance and Limitations of Clinical Reporting -- Implications for Non-Endemic Countries. PloS one 2016, 11(8):e0160230.4. Chan TC, Hu TH, Hwang JS: Daily forecast of dengue fever incidents for urban villages in a city. International Journal of Health Geographics 2015, 14:9.5. Chan TC, Teng YC, Hwang JS: Detection of influenza-like illness aberrations by directly monitoring Pearson residuals of fitted negative binomial regression models. BMC Public Health 2015, 15:168.6. Ma HT: Syndromic surveillance system for detecting enterovirus outbreaks evaluation and applications in public health. Taipei, Taiwan: National Taiwan University; 2007.