Median Total Duration Research Articles

Nocardia bacteremia: A single-center retrospective review and a systematic review of the literature

ObjectivesNocardia bacteremia is a rare but severe disease associated with high mortality. This systematic review is the largest and most comprehensive review performed over the past 20 years. MethodsA single-center retrospective review of Nocardia bacteremia was performed using hospital microbiology records from January 1, 2010 to December 31, 2017. A systematic literature review was also performed to identify cases of Nocardia bacteremia described in the NCBI PubMed database in English between January 1, 1999 and December 31, 2018. ResultsFour new cases of Nocardia bacteremia are described. The systematic review identified 134 cases with sufficient information available for analysis. Of the total 138 cases, the median age was 58 years (interquartile range (IQR) 44–69 years) and 70% were male. Eighty-one percent were immunocompromised (corticosteroid use (49%), hematological malignancy (20%), solid organ transplant (20%), solid organ malignancy (19%), and hematopoietic stem cell transplantation (15%)) and 29% had endovascular devices. Pulmonary infection was the most common concurrent site of clinical disease (67%). The median incubation time to the detection of Nocardia bacteremia was 4 days (IQR 3–6 days). Blood cultures were the only positive microbiological specimen in 38% of cases. The median total duration of treatment was 75 days (IQR 25–182 days). Thirty-day all-cause mortality was 28% and overall all-cause mortality was 40%. ConclusionsNocardia bacteremia is most frequently identified in immunocompromised patients and those with intravascular devices. Although rare, it represents a serious infection with high associated overall mortality.

Colonoscopy withdrawal time and polyp/adenoma detection rate: a single-site retrospective study in regional Queensland.

Bowel cancer is the second most common non-cutaneous cancer diagnosed in Australia among both genders. Colonoscopy withdrawal time of at least 6 min has been accepted as the standard to achieve the target polyp detection rate (PDR) and adenoma detection rate (ADR). A retrospective review was conducted in Bundaberg Hospital to evaluate the relationship between colonoscopy withdrawal time against polyp, adenoma and cancer detection rates. A retrospective study was carried out in Bundaberg Hospital on patients who had colonoscopies performed between 1 October 2016 and 30 September 2017 by the general surgical team. Data collection was conducted by reviewing patient charts, general practitioner referral letters and endoscopy reports. Statistical analysis was performed with chi-squared test using Prism 8.2.1. A total of 1579 colonoscopies were analysed. The median age of patients undergoing a colonoscopy was 64 years (95% confidence interval (CI) 60.55-61.93). Median total duration of colonoscopy was 19 min (95% CI 20.9-22.0), with median withdrawal time of 9 min (95% CI 10.06-10.95). PDR, ADR and sessile serrated adenoma (SSA) detection rates were 43.3%, 33.1% and 5.4%, respectively. Cancer detection rate was 2.8%. Longer withdrawal times were associated with higher PDR, ADR and SSA detection rates (P < 0.0001) and higher mean number of polyp/adenoma/SSA detected. Colonoscopies with withdrawal times of less than 6 min did not achieve the target detection rates. It is clear that achieving the advocated withdrawal time for screening colonoscopy improves detection rates.

Abivertinib in patients with T790M-positive advanced NSCLC and its subsequent treatment with osimertinib.

BackgroundAbivertinib is a novel oral, third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that overcomes T790M‐induced resistance in non‐small cell lung cancer (NSCLC) patients. Here, we report the results of a complete and detailed clinical data of patients treated with abivertinib at our hospital in a phase I dose escalation/expansion study of abivertinib.MethodsNSCLC patients with the EGFR T790M mutation were orally administered abivertinib (150–300 mg) twice daily for cycles of 28 continuous days and tumor response was assessed. Further data regarding subsequent treatment protocols and survival were collected.ResultsA total of 28 NSCLC patients were included. Of the 24 assessable patients, 12 (50%) achieved a partial response (PR), and six (25%) achieved stable disease (SD). Median progression‐free survival (PFS) was 5.9 months (95% confidence interval (CI): 3.259–8.541) and median overall survival (OS) was 17.9 months (95% CI: 11.36–24.5). For salvage therapy in 15 (53.6%) patients after abivertinib, the median PFS following osimertinib treatment was 12 months. The median total treatment duration for the two third‐generation EGFR TKIs was 15.9 months (95% CI: 12.5–19.3). The most frequent abivertinib‐associated adverse effects were elevated hepatic transaminases (10/28, 35.7%) and diarrhea (10/28, 35.7%).ConclusionsAbivertinib is a unique novel third‐generation EGFR TKI with good tolerance and efficacy in EGFR T790M(+) NSCLC patients. For patients with progressive disease after treatment with abivertinib, osimertinib could be an option for subsequent therapy but further studies are required.Key points Abivertinib is a novel third‐generation EGFR TKI targeting the EGFR T790M mutationAbivertinib is well tolerated and efficacious in T790M‐positive patientsAbivertinib has a unique structure, efficacy, and resistance mechanism compared with osimertinibOsimertinib treatment after AC0010 showed a good response

Utilization and extravasation of peripheral norepinephrine in the emergency department.

Vasopressors are typically administered through central venous catheters (CVC) due to a historical risk of extravasation with peripheral administration. However, CVC insertion is a time-consuming process that may delay vasopressor administration and is associated with complications. The Virginia Commonwealth University Health System (VCUHS) Emergency Department (ED) implemented a protocol that recommends peripheral norepinephrine (pNE) be administered through an 18 gauge or larger at or above the antecubital fossa or the external jugular vein with a maximum dose of 20μg/min. This study characterizes the use and incidence of extravasation in all adult patients who received pNE initiated in the VCUHS ED. This was an observational, retrospective cohort study in adult patients from March 2016 to March 2019. Of the 331 patients that were screened, 177 met inclusion criteria. Data were analyzed using descriptive statistics. Patients had a median age of 60years and 59% were male. The median APACHE II score was 25 with an overall hospital mortality of 27%. A majority of patients received pNE for distributive shock (63%). Approximately 69% received pNE through an antecubital infusion site. The median total pNE duration was 62min (IQR 32, 142). Eighty-four percent of patients received a central line. Only 2.3% of patients had confirmed extravasation in addition to another 2.3% where extravasation could not be excluded, for a total rate of 4.5%. None had subsequent extremity injury. Administration of pNE according to the VCUHS ED protocol resulted in a low extravasation rate.

Visual attention patterns of team leaders during delivery room resuscitation

AimTo assess visual attention of neonatal team leaders during delivery room resuscitation of preterm infants using eye tracking glasses. MethodsProspective observational eye tracking study. Gaze fixations and sequences were captured, categorized, and mapped during the first 5 min of the resuscitations. Gaze fixation metrics of total gaze duration, visit count, and visit duration were summarized and compared based on interventions performed and provider training level. Fixation sequences were compared between attending neonatologists and fellows. ResultsDuring 18 eye tracking recordings, practitioners focused most of their cumulative visual attention on the infant (median total gaze duration 57%, interquartile range [IQR] 38–61%), followed by monitors (24%, IQR 13–46%), clinical staff (5%, IQR 1–8%), other physical objects (4%, IQR 3–6%), T-piece resuscitator (2%, IQR 0–4%) and the Apgar timer (1%, IQR 0–2%). Visual attention parameters varied according to intervention, with higher visit counts on the infant during corrective ventilation steps than during Continuous Positive Airway Pressure (CPAP) or Positive Pressure Ventilation (PPV), and longer visit durations on monitors during PPV. Time and frequency-based measures of visual attention did not significantly differ by provider training level, but patterned fixation sequences were identified among attending neonatologists that were not observed in fellows. ConclusionTeam leaders predominantly gazed upon the infant and monitors during resuscitation, and visual attention parameters varied depending on the respiratory interventions performed. Attending neonatologists exhibited patterned fixation sequences that were not observed in fellows. Study results may have implications for optimizing delivery room design and training novice providers.

Evaluating Luspatercept Responders in the Phase 3, Randomized, Double-Blind, Placebo-Controlled BELIEVE Trial of Luspatercept in Adult Beta-Thalassemia Patients (Pts) Who Require Regular Red Blood Cell (RBC) Transfusions

Evaluating Luspatercept Responders in the Phase 3, Randomized, Double-Blind, Placebo-Controlled BELIEVE Trial of Luspatercept in Adult Beta-Thalassemia Patients (Pts) Who Require Regular Red Blood Cell (RBC) Transfusions

Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions

Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions

Increased Incidence of Viral Reactivation after T Cell Replete Haploidentical Stem Cell Transplantation in Association with Delayed Immune Reconstitution

Introduction: The preferred method for haploidentical stem cell transplantation (haploSCT) is currently the use of post-transplantation cyclophosphamide (PTCY) since it obviates the need for depletion of T lymphocytes, which is associated with profound immunosuppression. Despite preservation of non-alloreactive donor T cells, reconstitution of pathogen-specific immunity may be delayed even after T cell replete haploSCT. The incidence and clinical sequelae of viral reactivation may thus compromise the outcomes of the procedure. Patients and Methods: The study included 47 patients, who underwent haploSCT with PTCY from 12/2013 until 05/2019 and achieved stable donor engraftment. Median age at transplant was 53 years (range, 19-70). The indications for transplant were acute myeloid (n=19) or lymphoblastic (n=10) leukemia, myelodysplastic syndrome (n=10), myelofibrosis (n=4), chronic myeloid (n=2) or lymphocytic (n=1) leukemia, and T-prolymphocytic leukemia (n=1). Myeloablative conditioning was mainly utilized (n=36), with the exception of certain patients who received reduced-intensity (n=10) or non-myeloablative (n=1) regimens. The graft source was peripheral blood in 29 and bone marrow in 18 cases. Tacrolimus in combination with mycophenolate mofetil was administered for prevention of graft-versus-host disease. Recipient/donor cytomegalovirus (CMV) serostatus was -/- (n=2), -/+ (n= 5), +/- (n=11), or +/+ (n=29). CMV, Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months post haploSCT. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood specimens in cases with symptoms suggestive of hemorrhagic cystitis (HC). Prophylaxis with letermovir was available in 1 patient only, and preemptive antiviral therapy was the principal modality for the management of CMV infection. Cellular immunity reconstitution was assessed by flow cytometry at 3, 6, and 12 months after transplant. Results: With a median follow-up time of 30 months (range, 2-64), the cumulative incidences (CIN) of relapse and non-relapse mortality (NRM) were 13.4% (95% confidence interval [CI], 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free (DFS) and overall survival (OS) were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. The CIN of CMV reactivation (&gt;100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34 out of 45 patients who were at risk, whereas recurrent CMV reactivation was observed in 17 patients with a median number of 1.5 episodes (range, 1-6) per patient. The median total duration of antiviral therapy for CMV infection was 27 days (range, 14-199). CMV disease (pneumonia) was documented in 2 patients. The CIN of EBV reactivation (&gt;1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 12 months. No case of EBV-related post-transplant lymphoproliferative disorder was observed, however preemptive therapy with rituximab was required in 2 patients with rapidly increasing EBV viral load. HHV-6 reactivation (&gt;1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%), but only one required therapy with foscarnet due to high viral load (&gt;10,000 copies/ml). The CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy for bladder hemostasis was required in 5/13 and nephrostomy in 1/11 patients with HC. Reconstitution of helper T cell immunity was considerably delayed, with median absolute CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was significantly associated with the recovery of CD4+ cells at 3 months (Figure; median CD4+ count of 191/uL versus 62/uL in patients with 1 and 2 or more episodes of CMV reactivation, respectively; p=0.009). Conclusions: HaploSCT with PTCY is associated with substantial rates of viral reactivation (especially CMV and BKV) resulting in the need for prolonged antiviral therapy and considerable morbidity. Strategies to prevent viral infection are strongly warranted in haploidentical stem cell transplantation. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution following haploSCT. Figure Disclosures Tsonis: Gilead: Other: Travel Grant; Astellas: Other: Travel Grants; Gilead: Other: Travel Grant; Aenorasis: Other: Travel Grant; Takeda: Other: Travel Grant; Pfizer: Other: Travel Grant; Innovis: Other: Travel Grant.

1022. Is it Time to Re-Evaluate Oral Β-Lactam Antibiotics for Step-Down Therapy of Uncomplicated Gram-Negative Bacteremia?

BackgroundBloodstream infections (BSI) due to Enterobacteriaceae often require empiric intravenous (IV) antibiotics. Oral antibiotics for the definitive treatment of these infections have been reserved to antibiotics with “high” oral bioavailability, mainly fluoroquinolones (FQ). Safety concerns and increasing resistance associated with FQ has modified clinical practice to identify alternative oral therapies. Select β-lactam (BL) antibiotics are well-tolerated, have moderately high bioavailability, and possess in-vitro activity against Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Proteus mirabilis (P. mirabilis). Limited evidence exists for oral BL step-down therapy for definitive treatment of BSI due to these organisms.MethodsThis retrospective cohort study compares clinical outcomes of patients treated with oral BL antibiotics to those who received oral FQ or trimethoprim/sulfamethoxazole (TS) for the treatment of BSI due to E. coli, K. pneumoniae, and P. mirabilis. The primary outcome is a composite of 30-day all-cause mortality, 30-day readmission due to recurrence, and/or change in oral antibiotic therapy. Secondary endpoints include 90-day development of Clostridium difficile infection, 90-day all-cause readmission, hospital length of stay (LOS), and 90-day recovery of a multi-drug-resistant organism.ResultsNine hundred eighty-one patients were screened and 397 adult patients were included. Excluded patients: IV only (n = 291), polymicrobial blood culture (n = 112), immunocompromised (n = 61), other (n = 120). Two-hundred patients received oral step-down therapy with a BL, and 197 with either an FQ or TS. E. coli was the causative organism for most patients in both groups, and urinary tract was the most common source of BSI. The median total duration of therapy was 14 days in both groups. There was no significant difference in the primary composite endpoint (7% vs. 5.6%, P = 0.561). There was no mortality or differences in secondary outcomes, except LOS (6 vs. 5 days, P = 0.043).ConclusionUtilization of oral BL for the step-down therapy of uncomplicated BSI due to E. coli, K. pneumoniae, and P. mirabilis did not result in worse outcomes compared with those receiving oral FQ or TS.Disclosures All authors: No reported disclosures.

Achieving PSA < 0.2 ng/ml before Radiation Therapy Is a Strong Predictor of Treatment Success in Patients with High-Risk Locally Advanced Prostate Cancer.

Background To predict long-term treatment outcome of radiation therapy (RT) plus androgen deprivation therapy (ADT) for high-risk locally advanced prostate cancer. Methods In total, 204 patients with the National Comprehensive Cancer Network (NCCN) high risk locally advanced prostate cancer (PSA > 20 ng/ml, Gleason score ≧ 8, clinical T stage ≧ 3a) were treated with definitive RT with ADT. Median follow up period was 113 months (IQR: 95–128). Median neoadjuvant ADT and total ADT duration were 7 months (IQR: 6–10) and 27 months (IQR: 14–38), respectively. Results PSA recurrence-free survival (PSA-RFS), cancer specific survival (CSS), and overall survival (OS) rates at 5 years were 84.1%, 98.5%, and 93.6%, respectively, and 67.9%, 91.2%, and 78.1%, respectively, at 10 years. Pre-RT PSA less than 0.2 ng/ml was associated with superior outcomes of PSA-RFS (HR = 0.42, 95% CI: 0.25–0.70, p = 0.001), CSS (HR = 0.27, 95% CI: 0.09–0.82, p = 0.013), and OS (HR = 0.48, 95% CI: 0.26–0.91, p = 0.021). On multivariate analysis, age (≥70 y.o.) and pre-RT PSA (≥0.2 ng/ml) were factors predictive of poorer OS (p = 0.032) , but iPSA, T stage, Gleason score, number of NCCN high-risk criteria, a combination with anti-androgen therapy and neoadjuvant ADT duration were not predictive of treatment outcome. Conclusion In patient with high-risk prostate cancer, RT plus ADT achieved good oncologic outcomes. PSA < 0.2 ng/ml before radiation therapy is a strong independent predictor for long overall survival.

Targeted Ablation of Ventricular Tachycardia Guided by Wavefront Discontinuities During Sinus Rhythm

Accurate and expedited identification of scar regions most prone to reentry is needed to guide ventricular tachycardia (VT) ablation. We aimed to prospectively assess outcomes of VT ablation guided primarily by the targeting of deceleration zones (DZ) identified by propagational analysis of ventricular activation during sinus rhythm. Patients with scar-related VT were prospectively enrolled in the University of Chicago VT Ablation Registry between 2016 and 2018. Isochronal late activation maps annotated to the latest local electrogram deflection were created with high-density multielectrode mapping catheters. Targeted ablation of DZ (>3 isochrones within 1cm radius) was performed, prioritizing later activated regions with maximal isochronal crowding. When possible, activation mapping of VT was performed, and successful ablation sites were compared with DZ locations for mechanistic correlation. Patients were prospectively followed for VT recurrence and mortality. One hundred twenty patients (median age 65 years [59-71], 15% female, 50% nonischemic, median ejection fraction 31%) underwent 144 ablation procedures for scar-related VT. 57% of patients had previous ablation and epicardial access was employed in 59% of cases. High-density mapping during baseline rhythm was performed (2518 points [1615-3752] endocardial, 5049±2580 points epicardial) and identified an average of 2±1 DZ, which colocalized to successful termination sites in 95% of cases. The median total radiofrequency application duration was 29 min (21-38 min) to target DZ, representing ablation of 18% of the low-voltage area. At 12±10 months, 70% freedom from VT recurrence (80% in ischemic cardiomyopathy and 63% in nonischemic cardiomyopathy) was achieved. The overall survival rate was 87%. A novel voltage-independent high-density mapping display can identify the functional substrate for VT during sinus rhythm and guide targeted ablation, obviating the need for extensive radiofrequency delivery. Regions with isochronal crowding during the baseline rhythm were predictive of VT termination sites, providing mechanistic evidence that deceleration zones are highly arrhythmogenic, functioning as niduses for reentry.

Use of targeted therapies for advanced renal cell carcinoma in the Veterans Health Administration.

BackgroundThe objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA).MethodsA retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models.ResultsThere were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first‐line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death.ConclusionOur analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real‐world setting than in clinical trials, and dose reductions and ADEs are more common.

Real world experience on treatment, outcome and toxicity of crizotinib in patients with anaplastic lymphoma kinase positive advanced non-small cell lung cancer.

Crizotinib has been the standard treatment for patients with anaplastic lymphoma kinase (ALK)-rearranged advanced non-small cell lung cancer (NSCLC). It demonstrated superior progression-free survival (PFS) and higher objective response rates (ORRs) vs. chemotherapy in previously treated and untreated patients with ALK-positive advanced NSCLC. This retrospective analysis reports real-world experience in treatment outcome and toxicity of crizotinib in this group of patients, with a focus on the cardiac toxicity and its management. Twenty-two patients diagnosed with ALK-positive NSCLC, either by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), treated at Johns Hopkins Singapore International Medical Centre (JHSIMC) and Tan Tock Seng Hospital (TTSH) in Singapore, were identified and followed for a median of 18 months. Data were collected and analyzed for baseline demographics, PFS, ORR, duration of response, toxicity and overall survival (OS). Clinical profile of patients included in the study was similar with clinical trials on crizotinib. Most patients were young of mean age 42, non-smokers and with good performance status. Fifty-nine percent had prior chemotherapy. Fifty percent of patients had brain metastases (BM), either de novo or on progression. ORR of crizotinib was 64% with median total duration of treatment of 8.5 months (range, 2-73+ months). Median PFS for patients treated with first-line crizotinib was 15 months. Most patients with BM had brain radiation. Median time for intracranial progression from the start of crizotinib was 11 months. Those with stable or responding extracranial disease continued crizotinib after radiotherapy to the brain. Median duration of response in this group of patients was 14 months (range, 2-31 months). Median OS among patients treated with upfront crizotinib was not reached, with 7 out of 11 patients still alive at the time of data analysis (n=11, range, 1-73+). Toxicity was manageable with moderate rate of grade 3 or worse toxicity (n=7, 31.8%). Three patients had grade 3-4 neutropenia. Eighteen percent (n=4) of patients developed cardiotoxicities such as bradycardia, prolonged QTc interval and complete heart block. One patient who developed complete heart block required pacemaker insertion. Two patients are long term responders who have been on crizotinib for 68+ and 73+ months. This retrospective analysis of a real-world experience confirms the therapeutic benefit of crizotinib in advanced ALK-positive NSCLC. Our data showed crizotinib is tolerable and effective, comparable with literature report. Occasional serious cardiac toxicity requires attention.

Cervical Cancer Outcomes in Elderly Women Treated with EBRT and Brachytherapy +/- Concurrent Chemotherapy

Cervical cancer is commonly viewed as a cancer affecting middle-aged women. However, more than 15% of cervical cancer cases occur in women over age 65. It is uncertain whether literature from trials, in which older women are a minority of the study population, appropriately guides their treatment and describes their natural history. The goal of this study was to evaluate cervical cancer treatment patterns and outcomes in older women in order to better counsel patients and optimize management. We performed a retrospective institutional analysis on women 69 and above with primary cervical cancer treated from 1999 - 2018. Included patients were treated with definitive, curative intent radiotherapy. We excluded patients with distant metastases, those treated palliatively, and those receiving surgery as primary treatment. We evaluated overall patient survival, use of chemotherapy, and recurrence patterns. This study was IRB approved. 65 eligible patients were included. Median age was 77 years (range 69-88), ranging in stage from IB1 to IIIB (IB1: 15 pts; IB2: 6 pts; IIA (NOS): 6 pts; IIA1: 3 pts; IIA2: 3 pts, IIB: 17 pts; IIIA: 2 pts, IIIB: 13 pts). Most were squamous cell carcinoma (83.1%), followed by adenocarcinoma (13.9%) and other (3%). Median external beam radiation (EBRT) dose was 45 Gy and median brachytherapy (BT) dose was 27.5 Gy. BT varied by era, but the majority were treated with HDR BT, with 53/65 (81.5%) HDR, 10/65 (15.4%) LDR, and 2/65 (3.1%) discontinuing treatment prior to brachytherapy. 86.2% received intracavitary BT and 10.8% received combined intracavitary/interstitial BT. Median total duration of therapy (EBRT + BT) was 50 days. The vast majority of women completed their intended course of radiation therapy, with a completion rate of 90.8%. 37 pts (56.9%) received concurrent chemotherapy, most commonly weekly cisplatin. Of those women, 5 (13.5%) discontinued chemotherapy due to adverse effects. With a median follow up of 24 months, 15 pts (24.6%) developed a recurrence, with 3 relapsing locally, 1 relapsing regionally, 9 relapsing with distant metastases only, and 2 relapsing both distantly and regionally. The 2-year local control rate was 91.4% and the loco-regional control rate was 82.9%. The 2-year overall survival was 75.1%. The 2-year disease-free survival was 61.4%. Due to small patient numbers and imbalance in stage between those receiving/not receiving concurrent chemotherapy, no conclusions can be made about the impact of chemotherapy on disease outcomes. The outcomes of elderly patients treated with definitive radiotherapy for cervical cancer are comparable to those of younger women, with the vast majority of patients able to complete therapy, resulting in 2-year loco-regional control rates over 80%. In conclusion, definitive radiation therapy, including brachytherapy, should be encouraged for older women presenting with cervical cancer.

Prevalence and clinical outcome of respiratory viral infections among children with cancer and febrile neutropenia

Background: The role of respiratory viruses (RV) in children with cancer having febrile neutropenic episodes has not been well studied. The objectives of our study were to investigate the prevalence and clinical outcomes of Respiratory viral infection (RVI).Methods: Children with cancer and febrile neutropenia (FN) having acute respiratory infections (ARI) were considered as cases and febrile neutropenic cancer patients without ARI were considered as controls. A throat swab sample was obtained for the detection of 21-respiratory pathogens.Results: A total of 81 episodes of FN in cases and 37 episodes of FN in controls were included. Prevalence of RVI (at least 1 RV) was seen in 76.5% of cases and 48.6% of controls (p = 0.005). The mixed-respiratory viruses (co-infections of ≥2 viruses) were seen only in cases (26%) (p = 0.00). Rhinovirus (36.8%) and respiratory syncytial virus (13.6%) were the most frequently detected viruses. Median duration of fever before presentation was more in cases with RVI compared to without RVI [2 (1–5) days vs 1 (1–5) day (p = 0.012)]. The median total duration of febrile period was 4 (IQR, 3–6) days in cases with RVI and 3 (IQR, 1–4) days in cases without RVI (p = 0.005). The median duration of antibiotic days were longer in cases with RVI as compared to patients without RVI [9 (IQR, 7–17) days vs 7 (IQR, 6–10) days (p = 0.046)] respectively.Conclusion: There was high prevalence of RVI in children with cancer and FN; more in association with ARI. The RVI were associated with prolonged febrile period and days of antibiotics therapy.

ACORN: Observational Study of Bevacizumab in Combination With First-Line Chemotherapy for Treatment of Metastatic Colorectal Cancer in the UK

IntroductionSurvival in metastatic colorectal cancer is worse than expected in the United Kingdom. Real-world data are needed to better understand UK-specific treatment practices that may explain this. Patients and MethodsThe Avastin ColORectal Non-interventional (ACORN) study is a multicenter, prospective, UK-based, observational, phase 4 study (ClinicalTrials.gov, NCT01506167) that recruited patients with metastatic colorectal cancer scheduled to receive bevacizumab in combination with first-line chemotherapy as part of routine clinical practice. Primary end points included progression-free survival, overall survival (OS), serious adverse events (AEs), and grade 3 to 5 bevacizumab-related AEs. ResultsA total of 714 patients were recruited between August 30, 2012, and February 4, 2014. Median follow-up was 16.4 months. Median first-line chemotherapy duration was 5.6 months, with capecitabine/oxaliplatin (265 [37.1%]) being the most common regimen. Median total chemotherapy duration was 8.1 months and did not vary by geographic location in the UK. Median progression-free survival (95% confidence interval) was 8.7 (8.2-9.1) months, and median OS was 17.8 (16.1-19.3) months. There was no significant difference in efficacy by chemotherapy regimen administered. Ninety-nine patients (13.9%) received bevacizumab after disease progression. The safety profile of bevacizumab was consistent with previous studies. ConclusionACORN provided evidence that there were no clear differences observed in outcomes between bevacizumab with capecitabine-based chemotherapy and fluorouracil-based regimens, and confirmed the safety profile of bevacizumab in a real-world UK-based population. The lower-than-expected OS is likely due to the short total chemotherapy duration, less frequent use of bevacizumab after disease progression, and higher rates of in-situ primary tumors.

Does My Emergency Department Doctor Sleep? The Trouble With Recovery From Night Shift.

Previous research has shown that emergency physicians have an increased risk of shift work sleep disorder, potentially compromising their health, wellness, and effectiveness as a physician. This study explores the effect of shift work on sleep in emergency doctors. The hypothesis of the evaluation is that daytime sleep onset would lead to the poorest sleep, implying poor recovery after a night shift. Sleep patterns were examined in emergency physicians in an academic emergency department. Twenty-seven individuals completed data collection, wearing wrist actigraphy devices over 3months. Time of sleep onset was categorized as falling into 1 of 3 ranges: interval 1-day sleepers (6:00 am-2:00 pm), interval 2-evening sleepers (2:00 pm-10:00 pm), or interval 3-night sleepers (10:00 pm-6:00 am). Data from each interval were analyzed for median duration, sleep latency, and night-time interruptions. Daytime sleep sessions had a median total sleep duration of 5.3±2h, much less than 7.3±1.8h (interval 2-evening), and 7.0±1.1h (interval 3-night). Interval 2 sleepers experienced the highest number of nightly awakenings (1.5) and the longest sleep latency (36.5min). Day sleepers (interval 1), assumed to be predominantly physicians recovering from night shifts, had significantly less sleep than both evening and night sleepers (p<0.01), experiencing a 23.0% decrease in overall median sleep duration. This study provides statistical findings that those working the night shift experience significantly less sleep than emergency physicians working other shifts.

PF348 LONG TERM FOLLOW-UP OF PNH PATIENTS TREATED WITH THE SMART ANTI-HC5 ANTIBODY (SKY59/RO7112689) IN THE OPEN LABEL EXTENSION (OLE) OF THE COMPOSER TRIAL

Background: SKY59 is an anti-C5 antibody applying SMART∗ [Fukuzawa et al., SciRep 2017] to allow for infrequent, low volume SC dosing. Clinical results of healthy volunteers (Röth et al., Blood 2017 130:4750), PNH patients without prior anti C5 treatment (COMPOSER Part 2 (P2)) and PNH patients who were switched from eculizumab to SKY59 treatment (COMPOSER Part 3 (P3)) have been reported previously (Röth et al., Blood 2018 132:535). All patients included in P2 and P3 of COMPOSER had the possibility to roll over after 20 weeks into an OLE for continued treatment. Long term follow-up data including the OLE are reported here. Aims: To study the long term safety and efficacy of SKY59. Methods: In the OLE patients stayed on the same treatment schedule they were using in the treatment phase. The study was approved by Ethics Committees and Health Authorities and conducted according to the principles of the declaration of Helsinki. Data of patients who were at least 20 weeks in the OLE are reported here. Results: 25 of 26 patients who participated in COMPOSER P2 and P3 chose to roll over to the OLE. At the time of submitting this abstract data of 15 patients (8 from part 2 and 7 from part 3) >20 weeks in the OLE were available (Table 1). The median total duration on treatment with SKY59 including the OLE was 68 weeks; 77 weeks for patients from P2 and 57 weeks for patients from P3. All 8 patients from P2 were on 170 mg QW s.c.. For patients originally enrolled in P3, 2 were on 170 mg QW, 3 were on 340 mg Q2W and 2 were on 680 mg Q4W, all s.c.. Patient baseline characteristics at the start of OLE are shown in table 1. Exposure/plasma levels of SKY59 in patients across the different dosing schedules support SC dosing. All patients maintained a minimal plasma level of 150 μg/ml of SKY59 at all times. Markers of terminal complement activation and intravascular hemolysis (CH50, LDH) remained at stable low values with no signs of loss of response throughout the observation period. No BTH events were reported in the OLES. No additional doses or dose intensification of SKY59 were observed. Hemoglobin levels remained stable with extended treatment duration. Transfusion requirements are shown in Table 1. Mean BL total C5 (TC5) concentration (n = 15, week 16: 195.5 μg/mL) (range: 106 - 293 μg/mL) stabilized during long term follow-up (week 36; n = 15) at 224.5 μg/mL (range: 144 – 355 μg/mL) Table 2. Although patients previously treated with eculizumab (P3) had started on a significantly higher TC5 level of 295 μg/mL (205 – 354 μg/mL) than eculizumab naïve patients (P2) with 140 μg/mL (73.6 – 184 μg/mL; p < 0.001)), the mean TC5 concentration at week 36 was 225 μg/mL across all patients manifesting effective antigen disposing activity of SKY59. Safety: OLE treatment with SKY59 was well tolerated, particularly, no injection site AEs and a low incidence of headache was observed. There were 4 SAEs in 3 patients and all were not related to study drug (coronary stenosis, atrial fibrillation, abdominal pain and choledocholithiasis). No AEs resulted in withdrawal from the study or death. No clinically significant drug-related trends were observed for laboratory parameters, vital signs or ECGs.Summary/Conclusion: SKY59 administered SC in a low volume is very well tolerated, has a good benefit/risk ratio and is efficacious in long term treatment of naive and eculizumab-treated patients with PNH in all dosing regimens tested. Updated data will be presented at the meeting.

Safety of in-hospital insertable cardiac monitor procedures performed outside the traditional settings: results from the Reveal LINQ in-office 2 international study

BackgroundHistorically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience.MethodsThe Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion.ResultsA total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55–61). Patient preparation and patient education accounted for 10 min (IQR: 5–20) and 10 min (IQR: 8–15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0–2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient.ConclusionsThe Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR.Trial registrationClinicalTrials.gov identifier NCT02412488; registered on April 9, 2015.

Paediatric focal intracranial suppurative infection: a UK single-centre retrospective cohort study

BackgroundPaediatric focal intracranial suppurative infections are uncommon but cause significant mortality and morbidity. There are no uniform guidelines regarding antibiotic treatment. This study reviewed management in a tertiary healthcare centre in the United Kingdom and considers suggestions for empirical treatment.MethodsA retrospective, single-centre cohort review of 95 children (< 18 years of age) with focal intracranial suppurative infection admitted between January 2001 and June 2016 in Newcastle upon Tyne, United Kingdom. Microbiological profiles and empirical antibiotic regimens were analysed for coverage, administration and duration of use. Mortality and neurological morbidity were reviewed. Data was analysed using t-tests, Mann-Whitney U tests, independent-samples median tests, and χ2-tests where appropriate. P-values < 0.05 were considered statistically significant.ResultsEstimated annual incidence was 8.79 per million. Age was bimodally distributed. Predisposing factors were identified in 90.5%, most commonly sinusitis (42.1%) and meningitis (23.2%). Sinusitis was associated with older children (p < 0.001) and meningitis with younger children (p < 0.001). The classic triad was present in 14.0%.43.8% of 114 isolates were Streptococcus spp., most commonly Streptococcus milleri group organisms. Twelve patients cultured anaerobes.Thirty one empirical antibiotic regimens were used, most often a third-generation cephalosporin plus metronidazole and amoxicillin (32.2%). 90.5% would have sufficient cover with a third generation cephalosporin plus metronidazole. 66.3% converted to oral antibiotics. Median total antibiotic treatment duration was 90 days (interquartile range, 60–115.50 days).Mortality was 3.2, 38.5% had short-term and 24.2% long-term neurological sequelae.ConclusionsPaediatric focal intracranial suppurative infection has a higher regional incidence than predicted from national estimates and still causes significant mortality and morbidity. We recommend a third-generation cephalosporin plus metronidazole as first-choice empirical treatment. In infants with negative anaerobic cultures metronidazole may be discontinued.