637. Treatment Outcomes in Secondary Analysis Populations of Adult Patients the ALLIUM Phase 3 study Comparing Cefepime-Enmetazobactam to Piperacillin-Tazobactam for Complicated Urinary Tract Infections (cUTI) or Acute Pyelonephritis (AP)

Background Superior treatment outcomes were observed with the β-lactam/β-lactamase inhibitor combination of cefepime-enmetazobactam (FPE) compared to piperacillin-tazobactam (PTZ) in the primary efficacy population (m-MITT) of the ALLIUM phase 3 study of adult patients with cUTI/AP. We present here the outcomes in the microbiologically evaluable (ME) and ME+Resistant (ME+R) populations. Methods 1034 cUTI/AP patients randomized 1:1 in a double-blind, multicenter trial received either 2 g cefepime/0.5 g enmetazobactam or 4 g piperacillin/0.5 g tazobactam q8h by 2h infusion for 7 to 14 days. Patients in m-MITT had a Gram-negative urinary baseline pathogen (BP) at >105 CFU/ml with FPE MIC ≤8 µg/ml and PTZ MIC ≤64 µg/ml. ME included patients in m-MITT who received ≥15 consecutive doses of study drug or were classified as clinical failures after receiving ≥9 doses; had a clinical assessment at test-of-cure (TOC) unless clinical failure occurred earlier; did not receive concomitant antibiotics with a non-study agent; and did not have any other protocol violation. ME+R included patients in ME along with those who had BP resistant to either FPE (MIC >8 µg/ml) or PTZ (MIC >64 µg/ml), or a missing MIC value. Overall success was the composite of clinical cure and microbiological eradication (< 103 CFU/ml in urine). Two-sided 95% confidence interval (CI) were computed using the stratified Newcombe method. Results In the ME population, superiority in overall success of FPE (87.0%; 268/308) compared to PTZ (65.4%; 195/298) was demonstrated as the lower bound of the CI (16.6%) of the treatment difference (TD; 23.3%) was greater than 0 (Table). Higher rates of microbiological eradication with FPE contributed to the superior treatment outcomes. In the ME+R population in which BP susceptibility was not an exclusion criterion, favorable outcomes with FPE in overall success (TD 21.6%; 95% CI [15.3, 27.8]) and microbiological eradication (TD 21.0%; 95% CI [14.8, 27.0]) were also observed. Conclusion The confirmation of superior treatment outcomes with FPE in the ME and ME+R populations supports the robustness of the corresponding superiority observed in adult cUTI/AP patients in m-MITT. Disclosures Adam Belley, PhD, Allecra Therapeutics SAS (Consultant) Philip Barth, MD, Allecra Therapeutics SAS (Consultant) Omar Lahlou, PhD, Allecra Therapeutics SAS (Employee) Patrick Velicitat, MD, Allecra Therapeutics SAS (Employee)

Kajian Hukum Mengenai Tindakan Korps Brigade Mobil Polri Terhadap Pelaku Pelanggaran Protokol Kesehatan Covid-19

This paper aims to examine and analyze the legal rules governing the perpetrators of the Covid-19 health protocol violation, the factors causing the Covid-19 health protocol violation in North Sumatra, and the policies taken by the Police Mobile Brigade Corps against the Covid-19 health protocol violations. . The problem is that the Covid-19 pandemic demands a response from the Police as law enforcement officers in playing their role in disease control efforts, educating the public, and taking action against crimes that see the outbreak as an opportunity to commit various crimes. To approach this problem, the theory of the legal system is used. The data were collected through interview guidelines and analyzed qualitatively. This study concludes that the legal rules governing the perpetrators of violating the Covid-19 health protocol are regulated in Law Number 2 of 2002 concerning the Indonesian National Police, Government Regulation Number 21 of 2020 concerning Large-Scale Social Restrictions (PSBB) in the Context of Accelerating Handling Corona Virus Disease 2019 (Covid-19), as well as other regulations such as Telegram Letter Numbered ST/3220/XI/KES.7./2020, Regulation of the Minister of Health, Instruction of the Minister of Home Affairs. Factors that encourage violations of health protocols are internal factors consisting of economic factors and lack of public concern. External factors consist of people's habits, people's distrust of the government, the existence of new normal policies. Brimob policies taken are penal and non-penal policies.

SIOP Ependymoma I: Final results, long term follow-up and molecular analysis of the trial cohort: A BIOMECA Consortium Study

Background: SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) from non-metastatic intracranial ependymoma in children aged 3 to 21 years, treated with a staged management strategy. Chemotherapy efficacy in ependymoma is debated and therefore the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide and cyclophosphamide (VEC) was an additional primary outcome. We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers. Methods: 74 participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation and 1q status were evaluated, alongside hTERT, ReLA, Tenascin-C, H3K27me3 and pAKT expression. Results: Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.003, HR=2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (p=0.005, HR=2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (p=0.003, HR=2.70, 95%CI 1.49-6.10 and p=0.014, HR=5.8, 95%CI 1.2-28 respectively) and H3K27me3 loss with worse OS (p=0.003, HR=4.6, 95%CI 1.5-13.2). DNA methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding a prespecified 45% RR. Conclusions: RR of STR to VEC exceeded the pre-specified criterion for efficacy. However, cases of inaccurate treatment stratification highlighted the need for rapid central review. Prognostic associations for 1q gain, H3K27me3 and hTERT were confirmed.

MODELLING OF AN INTRUSION DETECTION SYSTEM USING C4.5 MACHINE LEARNING ALGORITHM

The increasing growth of wireless networking and new mobile computing devices has caused boundaries between trusted and malicious users to be blurred. The shift in security priorities from the network perimeter to information protection and user resources security is an open area for research which is concerned with the protection of user information’s confidentiality, integrity and availability. Intrusion detection systems are programs or software applications embedded in sophisticated devices to monitor the activities on networks or systems for security, policy or protocol violation or malicious activities detection. In this work, an intrusion detection model was proposed using C4.5 algorithm which was implemented with WEKA tool and RAPID MINER. The model showed good performance when trained and tested with validation techniques. Implementation of the proposed model was conducted on the Network Security Laboratory Knowledge Discovery in Databases (NSL-KDD) dataset, an improved version of KDD 99 dataset, which showed that the proposed model approach has an average detection rate of 99.62% and reduced false alarm rate of 0.38%.

54 Acute Blood Pressure Lowering in Spontaneous Acute Intra-cerebral Haemorrhage: A Re-audit in a Tertiary Referral Stroke Centre

Background Acute blood pressure (BP) lowering to a target of <150mmHg systolic improves outcomes in patients with acute spontaneous intra-cerebral haemorrhage (sICH). It is thought that the beneficial effect of BP-lowering in sICH is time-sensitive and mediated through the prevention of haematoma expansion. The American Heart Association guidelines state that BP lowering to <150 mmHg or lower is safe and can improve functional outcome. Our aim was to re-evaluate the performance of clinicians in meeting target SBP levels of <150mmHg in patients with acute sICH within 1 hour of presentation, following the introduction of a BP-lowering protocol in our centre. Methods We undertook a retrospective chart review of consecutive patients with an acute sICH admitted to our centre between September 2017 and May 2018. Any patient who did not receive active medical management from the outset of presentation due to immediate initiation of palliative measures were excluded. The time from presentation to target BP and BP measured at 1 hour were recorded. Any protocol violations were also documented Results 11 patients were included (mean age 77.5years, 55% female). The mean BP at presentation and 1 hour was 186/93mmHg and 161/93mmHg respectively. The median and mean times from presentation to first achieved target BP was 129 and 120minutes respectively. At least 1 protocol violation occurred in 66.6% of cases. The most common protocol violation was the failure to escalate to an intravenous infusion of a BP-lowering agent in a timely manner when bolus therapy had failed. Conclusion An introduction of a BP protocol for patients with an acute sICH did not improve performance on achieving rapid SBP-lowering to target levels of <150mmHg. Strategies to improve awareness of this protocol are required to improve adherence and its successful implementation.

Current treatment practice of Guillain-Barré syndrome

ObjectiveTo define the current treatment practice of Guillain-Barré syndrome (GBS).MethodsThe study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account.ResultsWe excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE.ConclusionsIn current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations.

Efficacy and tolerability of Roystonea regia lipid extract (D-004) and terazosin in men with symptomatic benign prostatic hyperplasia: a 6-month study

Background: Benign prostatic hyperplasia (BPH), a common urological disease in aging men, frequently produces lower urinary tract symptoms (LUTS). Clinical studies have shown that terazosin relaxes the smooth muscle of the prostate and bladder, facilitates bladder emptying, improves LUTS, increases maximum urinary flow, and reduces the residual volume of urine. D-004, a lipid extract of the fruit of the Cuban royal palm ( Roystonea regia), presents a similar efficacy to Saw palmetto. Clinical studies have demonstrated its efficacy and safety in short- and medium-term trials in patients with BPH. The objective of this study was to compare the efficacy and tolerability of D-004 with terazosin for 6 months on LUTS in patients with BPH. Methods: The present phase III study had an open, randomized, comparative design, with two parallel groups who received D-004 (320 mg/day) or terazosin (5 mg/day) for 6 months. The study included men at least 50 years of age, with evidence of the LUTS of moderate intensity according to the International Symptoms of the Prostate (IPSS). The effects on the IPSS Scale was the primary efficacy variable. The effects on the size of the prostate and the residual volume were secondary variables. The subjective self-perception of symptom relief at trial completion was a collateral outcome. Analysis was done by intention-to-treat. Results: The study included 100 men with a diagnosis of BPH, confirmed by digital rectal examination and ultrasonography, and moderate LUTS (IPSS score >7, <19). Baseline characteristics were similar in both groups. Nine patients did not continue the study: one from group D-004 (due to protocol violation) and eight from the terazosin group (six due to adverse events and two due to protocol violation; p < 0.01). D-004 and terazosin significantly reduced the IPSS scores at the end of the 6 months of therapy by 74.2% and 66.1%, respectively, with respect to baseline values. Comparisons between groups performed showed that, at the end of the treatment, D-004 was more effective ( p < 0.05) than terazosin in reducing the IPSS score. Although the average size of the prostate was reduced in both groups, this reduction reached statistical significance only for D-004. On the other hand, postvoid residual volume was significantly and similarly reduced in both groups. Both treatments were safe, while D-004 was better tolerated than terazosin. Conclusions: D-004 administered at a dose of 320 mg/day for 6 months showed comparable efficacy with terazosin (5 mg/day) in reducing the LUTS (IPSS score), producing a significant decrease in prostate volume and postvoid residual volume. Both treatments were safe, with better tolerability for D-004 as compared with terazosin.

Integrating clinical pharmacy services into patient care in an early-phase clinical trial clinic.

e18228 Background: Early phase clinical trials have broadened treatment options for patients with cancer. Expert management of these new therapies is essential to positive patient outcomes. At Memorial Sloan Kettering Cancer Center, the Developmental Therapeutic Center (DTC) satisfies this need. Oncology clinical pharmacists collaborate with other healthcare professionals to maximize the benefits of drug therapy and minimize toxicities. The purpose of this project is to describe the interventions from a clinical pharmacist assigned to the DTC. Methods: A clinical pharmacist joined DTC to serve adult patients with cancer undergoing clinical trials. The clinical pharmacist acted as a liaison between pharmacy team and medical team, and sees patients during their trial eligibility screening and follow-up visits. The interventions were documented by the clinical pharmacist in patients’ medical charts and email communications. All interventions during 1 month were retrospectively collected and categorized into supportive care optimization, protocol violation prevention, and operational. Results: The oncology clinical pharmacist was involved in 115 patient visits for trial eligibility screening or protocol follow-up. A total of 769 interventions were addressed including supportive care optimization (40.2%), protocol violation prevention (24.7%), and operational (35.1%). Conclusions: The oncology clinical pharmacist is actively engaged in many aspects of cancer care at the early phase trial clinic. Our results demonstrate the vital role of an oncology clinical pharmacist. The impact of these categorized intervention areas would require a formal outcome and cost-saving analysis. [Table: see text]

Radiotherapy to bulky disease PET-negative after immunochemotherapy in elderly DLBCL patients: Results of a planned interim analysis of the first 187 patients with bulky disease treated in the OPTIMAL>60 study of the DSHNHL.

7506 Background: RT to bulky sites improves outcome of elderly DLBCL patients [Lancet Oncol 2008; 9: 105-116; J Clin Oncol 2014; 32:112-1118]. Whether RT can be spared in PET-negative pts. after R-CHOP was prospectively addressed in OPTIMAL >60. Methods: 61 to 80 y-old pts. were randomized in a 2x2 factorial design to 6xCHOP-14 or 6xCHLIP-14 (liposomal instead of conventional vincristine) plus 8 x rituximab 375 mg/m2(R) q 2 wks. or 12xR (days -4,-1,1,4,14,28,42,56,91,126,175, 238). Pts. with bulk (>=7.5 cm) PET-positive after 6 cycles chemotherapy were assigned to RT (39.6 Gy), while PET-negative bulks were observed. Results: 187/505 (37%) had bulky disease and were compared to 117/306 (38%) RICOVER-60 pts. (38%) who had received 6xCHOP-14+8R. OPTIMAL>60 pts. were older (70 vs. 68 years) and had more IPI=3 (33% vs. 29%) and IPI=4,5 (34% vs. 23%) compared to RICOVER-60. PET was performed in 166/187 OPTIMAL>60 bulk pts. (reasons for no PET: early death: 5; excessive toxicity: 3; protocol violation: 1, non-compliance: 4, change of diagnosis: 6, others: 2). 80/166 (48%) bulks remained PET-positive after 6 cycles of chemotherapy and 62/80 (78%) were irradiated (reasons for no RT: progression: 8; medical reasons: 9; negative biopsy: 1), reducing RT from 67/117 (57%) in RICOVER-60 by 42% to 62/187 (33%) in OPTIMAL>60. Despite the unfavorable demographics, outcome of the 187 bulk pts. in OPTIMAL>60 was non-inferior to RICOVER-60, not even in the least intensive of the 4 OPTIMAL>60 treatment arms consisting of 47 pts. who received 6xCHOP-14+8R as in RICOVER-60. 2-year PFS and OS in OPTIMAL>60 was 79% and 88%, respectively, compared to 75% and 78% of the 117 RICOVER-60 pts. In a multivariable analysis adjusting for the IPI risk factors, the hazard ratio of the OPTIMAL>60 compared to the RICOVER-60 bulk pts. was 0.7 (95% CI: 03.; 1.5; p=0.345) for PFS and 0.5 (95% CI: 02.; 1.3; p=0.154) for OS. Conclusions: RT can be spared in bulky disease PET-negative after chemotherapy. This strategy results in a 42% reduction of RT without compromising the outcome of these patients. Supported by Amgen, Roche, Spectrum. Clinical trial information: NCT01478542.