Patients In October Research Articles

P-109 Non-invasive Genetic Testing (niPGTA) and Laser Assisted Hatching (LAH) may improve pregnancy and ongoing pregnancy rates in patients of advanced maternal age

Abstract Study question Does niPGTA and LAH improve pregnancy and ongoing pregnancy rates in patients of advanced maternal age? Summary answer niPGTA increases pregnancy and clinical pregnancy rates in patients aged ≥38 years compared to those without tested embryos, while LAH may further improve pregnancy outcomes. What is known already Embryos release cell-free DNA (cf-DNA) in the IVF culture media, which can be analyzed for chromosomal constitution. The benefit that niPGTA holds over PGT-A is that it is a non-invasive test and could potentially produce comparable results. Therefore, the time to pregnancy and the risk of miscarriage could be reduced in comparison to an IVF treatment with non-tested embryos. Previous studies have shown high concordance with trophectoderm biopsies in PGT-A patients and improved outcomes with LAH in frozen-thawed cycles. However, there is a lack of studies investigating clinical pregnancy rates with niPGTA. Study design, size, duration Retrospective cohort study including 74 patients aged ≥38 years, who underwent Single Frozen Embryo Transfer (FET) from May 2021 to February 2023. Patients who had Endometrial Receptivity Assay (ERA) were excluded. Participants/materials, setting, methods 32 couples had niPGTA; Spent Blastocyst Media (SBM) for each blastocyst were collected on Day 6 and analyzed using the EMBRACE test. Embryos were vitrified. 42 couples had their blastocysts vitrified on Day 5/6 without testing. LAH was introduced to all patients in October 2021. Before that, no LAH was performed. Embryos were transferred to patients 2 hours post-warming after LAH. Pregnancy test was performed 10 days after FET and clinical pregnancy was established. Main results and the role of chance There was a statistical significant increase of pregnancy rate (p = 0.017, Pearson’s Chi-Squared test) and a trend towards higher clinical pregnancy rate for niPGTA patients versus those who had a transfer of not tested embryos. Regarding LAH, there was a trend towards higher pregnancy and clinical pregnancy rates in both niPGTA and not tested group. Results for pregnancies and clinical pregnancies are presented in Table 1. Limitations, reasons for caution More patients are required to confirm clinical significance of pregnancy and clinical pregnancy rates of niPGTA over not tested embryos and if LAH can improve the outcomes. A review of patients who had previous implantation failures and miscarriages in addition to ERA could yield clearer conclusions. Wider implications of the findings The results of this study are encouraging for niPGTA combined with LAH for patients aged ≥38 years. Further studies on niPGTA and modifications of the protocol for increased concordance rates and shorter time in embryo culture should be explored. Trial registration number Not applicable

Choosing Wisely audit: CT KUB ordering in emergency department renal colic presentations.

Our aim was to safely reduce unnecessary CT KUBs (kidneys, ureters, bladder) in patients with renal colic. This was a before and after intervention observational study of 74 patients in April 2023 and 57 patients in October 2023. Seventy-five per cent of patients with suspected renal colic underwent a CT KUB in the pre-audit period. Following education, an update in the ED Renal Colic Policy, electronic medical record ordering and short stay pathway, a re-audit was undertaken in October 2023 resulting in an absolute reduction of 15% of CT KUBs ordered. Audit interventions can reduce unnecessary CT KUBs in renal colic.

Use, access, and initial outcomes of off-label ivosidenib in patients with IDH1 mutant glioma.

Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes gliomagenesis and is implicated in epileptogenesis. Ivosidenib (IVO), a small molecule oral mIDH1 inhibitor, is FDA-approved for mIDH1 newly diagnosed and relapsed/refractory acute myeloid leukemia. Moreover, IVO has efficacy in clinical trials for recurrent mIDH1 gliomas. Given the lack of targeted treatments for gliomas, we initiated off-label IVO for mIDH glioma patients in October 2020. Retrospectively, we sought to assess early outcomes in our patients and describe their experience on IVO from October 2020 through February 2022. Our objective was to report on the following variables of off-label use of IVO: radiographic response, seizure control, tolerability, and access to the medication. All patients initially received single-agent IVO dosed at 500 mg orally once daily. The cohort age range was 21-74 years. Tumor types included astrocytoma (n = 14) and oligodendroglioma (n = 16), with most being grade 2 (n = 21). The best radiographic response in nonenhancing disease (n = 22) was 12 stable diseases, 5 minor responses, 3 partial responses, and 2 progressive diseases. Seizure frequency was stable to improved for most patients (70%, n = 21). IVO was well-tolerated, with the most common toxicities being diarrhea, elevated creatine kinase, and QTc interval prolongation. Most patients (66.7%, n = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%. Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes.

PROFIL PENGGUNAAN OBAT PADA PASIEN STROKE ISKEMIK PADA PASIEN DI POLI NEUROLOGI

Background:Stroke is one of the main causes of mortality. WHO defines stroke as a spatial neurological disorder with sudden onset, lasting more than 24 hours without any cause and causing serious long-term disability in Indonesia and the United States. Objectives; This study aimed to determine the profile of ischemic stroke drugs usage in patients of Aceh Tamiang Hospital and the use of types of drugs given to ischemic stroke patients.Method; This study was non-experimental prospectively by using a questionnaire on ischemic stroke patients in October 2020. The data was processed using Microsoft Excel.Results; The results of 26 respondents and the drugs issued in October for the neurology clinic at Aceh Tamiang Hospital obtained antiplatelet drugs, namely aspirin 80mg/tab with a total of 238 drugs (38.3%) and pletaal 50mg/caplet with a total of 42 drugs (6.7%). The neuroprotectant group was pirassetam 80mg/tab with 140 drugs (22.5%). The antihyperlipidemic group of the drug simvastatin 5 mg/tab totaled 21 drugs (3.4%). The antihypertensive drug class was amlodipine 10mg/tab total 28 drugs (4.5%), amlodipine 5mg/tab total 56 drugs (8.9%), captopril drug type 25 mg/tab total 63 drugs (10.2%), the type of drug furosemide dose 40mg/tab the amount of 35 drugs (5.6%).Conclusion; Drugs that were widely used in patients with ischemic stroke are the antiplatelet group, namely aspirin 80mg/tab obtained 238 tablets (38.3%), the neuroprotectant class of the drug piracetam 800mg/cap were 140 caplets (22.5%), the antihypertensive group amlodipine 5mg/tab were 56 tablets (8.9%), the antihyperlipidemic group of the simvastatin 5mg/tab were 21 tablets (3.4%).

Significance of pelvic lymph node dissection during radical prostatectomy in high-risk prostate cancer patients receiving neoadjuvant chemohormonal therapy

We aimed to determine the survival and staging benefit of limited pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in high-risk prostate cancer (PC) patients treated with neoadjuvant chemohormonal therapy. We retrospectively analyzed 516 patients with high-risk localized PC (< cT4N0M0) who received neoadjuvant androgen-deprivation therapy plus estramustine phosphate followed by RP between January 2010 and March 2020. Since we stopped limited PLND for such patients in October 2015, we compared the surgical outcomes and biochemical recurrence-free survival (BCR-FS) between the limited-PLND group (before October 2015, n = 283) and the non-PLND group (after November 2015, n = 233). The rate of node metastases in the limited-PLND group were 0.8% (2/283). Operation time was significantly longer (176 vs. 162 min) and the rate of surgical complications were much higher (all grades; 19 vs. 6%, grade ≥ 3; 3 vs. 0%) in the limited-PLND group. The inverse probability of treatment weighting-Cox analysis revealed limited PLND had no significant impact on BCR-FS (hazard ratio, 1.44; P = 0.469). Limited PLND during RP after neoadjuvant chemohormonal therapy showed quite low rate of positive nodes, higher rate of complications, and no significant impact on BCR-FS.

Abstract 271: Bradyarrhythmia Associated With Remdesivir And Covid-19 Pneumonia: A Pharmacovigilance Analysis:

Background: Different arrhythmias have been reported in patients with COVID-19 due to the complication of the disease, and medications used in the management of COVID-19. Remdesivir was approved by FDA for the management of COVID-19 patients in October 2020. There are several case reports suggesting remdesivir causing bradyarrhythmia in COVID-19 patients. Objective: To increase the knowledge and awareness among healthcare professions (HCPs) about the risk of arrhythmias associated with the use of remdesivir. Methods: We used the FDA Adverse Events Reporting System (FAERS) database to find bradyarrhythmia as a reported adverse event (AE) due to remdesivir until October,2021. Total 6,504 events were reported, out of which 5,996 (92.2%) were reported by HCPs. These AEs were included and further analyzed. Results: Out of 5,996 AEs reported with remdesivir, total 537 (9.0%) events were bradyarrhythmia. There were 74 (1.27%) events reported for atrial fibrillation, and 24 (0.04%) for ventricular tachycardia attributed to the use of remdesivir. Reported events of bradyarrhythmia were further divided and analyzed into men vs women, and different age groups of years 18-64, 65-85, &amp;gt;85. Total events of bradyarrhythmia among men (238, 6.5%) vs women (141, 6.4%) were not significantly different. Among all the age groups, more events were reported in younger women in the age group of 18-64 (12.3%) vs 65-85 (7.9%) vs &amp;gt;85 (6.9%). Conclusion: Multiple studies have shown COVID-19 associated tachyarrhythmias, likely secondary to the myocardial damage due to hypoxia. Few studies have also suggested bradyarrhythmias in these patients. Our analysis of the FAERS database also showed many reported AEs of bradyarrhythmia attributed to the use of remdesivir. Postulated mechanisms include; medication side effects, damage to the SA node as a complication of the COVID-19 disease process, and electrolyte imbalance due to the renal failure. Close surveillance of these patients with early diagnosis can lead to prompt discontinuation of the medication, which can further decrease the mortality related to bradyarrhythmias. Further studies are required to identify the at-risk population and to better understand the risk of bradyarrhythmia associated with remdesivir.

O03 The impact of COVID-19 infection prevention and control measures on transmission of hospital-acquired infections and antimicrobial resistance in Africa

BackgroundPatients who develop serious illness due to COVID-19 are more likely to have bacterial coinfections, for which WHO recommends treatment with antibiotics. As a result, many countries are observing a change in antimicrobial stewardship (AMS), in addition to changes in infection prevention and control (IPC) practices such as the use of personal protective equipment, on COVID-19 wards. Few data on COVID-19 and its impact on nosocomial infections and antimicrobial resistance (AMR) are available from low and middle-income countries (LMICs). As these countries often have high rates of AMR, it is vital to report the effects of COVID-19 on AMS so as to inform clinical practice and IPC guidelines. This study aims to compare prevalence of AMR in COVID-19 wards with general non-COVID-19 hospital wards.MethodsThis pilot hospital-based study is being conducted in two sites in both Sudan and Zambia. IPC and AMS guidelines for COVID-19 and non-COVID-19 wards were identified for each institution. This study is comparing bacterial isolates and AMR patterns of nosocomial associated infections acquired on COVID-19 and non-COVID-19 wards were compared, using microbiological and sequencing methods. A total of 200 patients have been recruited: 100 per country, 50 COVID-19 patients and 50 non-COVID-19 patients. AMR transmission patterns are being identified using Oxford Nanopore Technologies sequencing for phylogenetic analysis.ResultsThe study began recruiting in May 2021 and completed recruitment of patients in October 2021. The majority of microbiological laboratory work will be completed within Q3 2021, with analysis of the results and sequencing completed in Q4 2021. A half-way point summary analysis of the data suggests differences in patient profiles, both between COVID-19 and non-COVID-19 wards at both sites, as well as differences between the two countries. Preliminary analysis also suggests a significant difference between the prevalence of MDR infections in Gram-negatives seen between COVID-19 (53% in Sudan and 83% in Zambia) and non-COVID-19 (14% Sudan, 33% Zambia) (t-test, P=0.0032 Sudan, P=0.0455 Zambia) ward patients in both countries (see Figure 1).Figure 1.Percentage of Gram-negative bacteria isolated from patients on COVID-19 and non-COVID-19 wards in Sudan and Zambia, showing significant difference between the wards in both countries (t-test, P = 0.0032 Sudan, P = 0.0455 Zambia).ConclusionsThe study is providing evidence to inform policy on IPC and AMS measures to be implemented on COVID-19 wards. In addition, the outcomes of the study will be used to create a pragmatic sequencing pipeline for potential AMR outbreaks suitable for use in LMICs clinical settings.

The pattern of antibiotics prescription and consumption

Objective: To investigate the antibiotic utilization and prescription patterns as well as define its convenience to the norm in four North-Sinai hospitals, Egypt. Antimicrobial resistance is a universal health threat. The golden era of miracle antibiotics has ended and we have faced the challenge of being troubled by infectious diseases with no discovery of new antibiotics found since 1987. Antibiotic pressure, overuse, and misuse are important risk factors for antimicrobial resistance and hospital cross-infection. To combat antimicrobial resistance, Egypt started its National Action Plan (2018-2022) aiming to optimize the usage and consumption of antibiotics. Method: This multicenter descriptive cross-sectional study was designed to describe the pattern of antibiotic prescription and consumption at four North Sinai Hospitals related to the Ministry of Health and Population. We reviewed 309 medical records of the inpatient department; the samples were selected through a stratified random sampling technique. Data were collected retrospectively from the medical records of the hospitalized patients in October, November, and December of 2020 by a paper-based method. Data were analyzed using descriptive statistics. Result: The prevalence of antibiotic consumption is near 68.9% in the four hospitals indicating that two-thirds of admitted patients receive antibiotics. Approximately 52.1% administered antibiotics for no reason. Most of the admitted patients took antibiotics on the same day of admission, regardless of the different types of hospital departments. Furthermore, 98.7% of antibiotics were prescribed without culture or order for culture and microbiological tests. Broad-spectrum antibiotics were 90% of all antibiotics prescribed. A total of 18 types of antibiotics were prescribed, cefotaxime was the most commonly prescribed antibiotic representing 26.5%. Conclusion: Judicious antibiotic prescribing behavior slows down the nature of antibiotic resistance. To guarantee the best antimicrobial use in the hospitals, standard treatment guidelines, and the Essential Medicines List for infectious diseases should be carried out and revised at least every 2 years to be a clinical reference for clinicians. Continuous education and training of clinicians and healthcare workers can contribute to optimizing the rational use of antibiotics, which in return reduces the progress of antibiotic resistance. There is an urgent need for antibiotic stewardship and surveillance and their application in all hospitals.

P–113 α-tubulin and tyrosine phosphorylation immunolocalization on human sperm from a globozoospermic patient with proper embryo development after ICSI

Abstract Study question Can novel sperm biomarkers, such as α-tubulin and tyrosine phosphorylation, help to predict the fertilizing potential osf a globozoospermic sample? Summary answer The characterization of α-tubulin and tyrosine phosphorylation provide additional information that could be useful to determine the fertilizing capacity of the globozoospermic samples. What is known already Globozoospermia is a severe disorder characterized by the acrosome absence and other sperm alterations such as tail structural disorders and chromatin condensation abnormalities. This set of defects makes globozoospermia correlates with primary infertility and low fertilisation rates. Therefore, additional studies are necessary to know how the globozoospermia affects the disposition of α-tubulin and tyrosine phosphorylation and the relationship between embryo development and pregnancy. In this context, previous studies have independently described different patterns of α-tubulin and tyrosine phosphorylation in normozoospermic samples. Specifically, the continuous α-tubulin distribution along the flagellum and tyrosine phosphorylation have been recently linked to proper sperm functionality. Study design, size, duration We conducted a prospective study. The sample was obtained from a globozoospermic patient in October 2019. This sample was divided into two fractions, one proceeded to ICSI and the another was fixed to characterize α-tubulin and tyrosine phosphorylation using confocal microscopy. A total of 200 sperm were analyzed for each biomarker. Participants/materials, setting, methods A 38-year-old man requested assisted reproduction in IVF Spain after a failed treatment with no fertilized oocytes. The clinical procedure was performed at IVF Spain and the characterization studies were made at the University of Alicante. The flagellar cytoskeleton was assessed using anti-α-tubulin antibody (Sigma-Aldrich) at a 1:600 dilution. Besides, tyrosine phosphorylation was detected using anti-phosphotyrosine primary antibody (PY20, Sigma-Aldrich) at a 1:500 dilution. Spermatozoa were evaluated using a confocal microscope (Zeiss LSM 800). Main results and the role of chance Regarding the α-tubulin characterization, only the 33% of spermatozoa showed continuous labelling in the tail and in the 67% the fluorescence appeared in the terminal piece of the flagellum. Otherwise, we only observed 0.5% of positive tyrosine phosphorylation in the studied cells, whereas the 99.5% of sperm analyzed did not show positive fluorescence. The clinical parameters showed a fertilization rate of 20% with only one embryo after the MII oocyte artificial activation by calcium ionophore. The embryo development was further adequate, and it acquired Bt5AA status on day five. Unfortunately, the pregnancy did not ensue after the embryo transfer. Limitations, reasons for caution The main limitation of this study was that due to the very low frequency of globozoospermia (&amp;lt;0.01%) this research was conducted only in one patient. Thus, the present results are preliminary. We need to characterize the aforementioned biomarkers in additional globozoospermic samples to establish relationships with clinical parameters. Wider implications of the findings: The study of potential candidate biomarkers like α-tubulin and tyrosine phosphorylation in globozoospermia and the linkage with clinical parameters would facilitate the diagnosis and improve the selection of more effective treatment techniques. Trial registration number Not applicable

Effectiveness of a treatment algorithm for hemodialysis-associated pruritus in terms of changes in medications

BackgroundHemodialysis-associated pruritus (HAP) is a serious complication that occurs in 60–80% of hemodialysis patients, which not only decreases quality of life but also worsens prognosis. We have developed a treatment algorithm to take a comprehensive cause-specific approach to HAP and used it at our facility since June 2009. In this treatment algorithm, moisturizers and topical steroids are used depending on skin condition and severity of pruritus; administration of nalfurafine hydrochloride is considered in treatment-resistant cases. If pruritus improves, we attempt to taper topical steroids by switching to lower potency or by dose reduction or discontinuation. Here, we examined the effectiveness of the treatment algorithm over 9 years in terms of changes in medications.MethodsSubjects were hemodialysis patients who received treatment for HAP at our facility: 89 in May 2009 before introduction of the algorithm, and 131 in April 2013, 164 in October 2014, 190 in October 2015, 181 in October 2016, 215 in October 2017, and 224 patients in October 2018 after its introduction. A questionnaire survey was conducted on the presence of pruritus, severity (using a visual analogue scale [VAS] and Shiratori severity scores), frequency, and insomnia due to pruritus. Changes in medications were investigated using medical records and compared.ResultsThe proportion of patients with pruritus decreased significantly from 96.6% in 2009 to 66.8% in 2018 (p < 0.001). Median VAS score significantly decreased from 53.0 mm in 2009 to 24.5 mm in 2018 (p < 0.001), and the proportion of patients with insomnia due to pruritus also significantly decreased from 25.8% in 2009 to 2.2% in 2018 (p < 0.001). The proportion of patients who used moisturizers significantly increased from 34.8 to 89.7% (p < 0.001). The proportion of patients receiving topical steroids decreased from 47.2 to 35.7%, but the difference was not significant (p = 0.085).ConclusionsThe treatment algorithm was shown to be useful for improving HAP, but future challenges were identified, including promoting use of lower potency topical steroids or discontinuation. Further prospective studies are required to confirm the role of each treatment intervention in a comprehensive cause-specific approach to HAP.

Development and validation of a postoperative delirium prediction model for pediatric patients: A prospective, observational, single-center study.

Postoperative delirium is a serious complication that relates to poor outcomes. A risk prediction model could help the staff screen for children at high risk for postoperative delirium. Our study aimed to establish a postoperative delirium prediction model for pediatric patients and to verify the sensitivity and specificity of this model.Data were collected from a total of 1134 children (0–16yr) after major elective surgery between February 2020 to June 2020. Demographic and clinical data were collected to explore the risk factors. Multivariate logistic regression analysis was used to develop the model, and we assessed the predictive ability of the model by using the area under the receiver operating characteristics curve (AUROC). Further data were collected from another 100 patients in October 2020 to validate the model.Prevalence of postoperative delirium in this sample was 11.1%. The model consisted of 5 predictors, namely, age, developmental delay, type of surgery, pain, and dexmedetomidine. The AUROC was 0.889 (P < .001, 95% confidence interval (CI):0.857–0.921), with sensitivity and specificity of 0.754 and 0.867, and the Youden of 0.621. The model verification results showed the sensitivity of 0.667, the specificity of 0.955.Children undergoing surgery are at risk for developing delirium during the postoperative period, young age, developmental delay, otorhinolaryngology surgery, pain, and exposure to dexmedetomidine were associated with increased odds of delirium. Our study established a postoperative delirium prediction model for pediatric patients, which may be a base for development of strategies to prevent and treat postoperative delirium in children.

German Aortic Root Repair Registry—Insights From the First 400 Consecutive Patients

BackgroundThe objective was to provide initial data from our prospective valve-sparing aortic root replacement (V-SARR) registry and reasons for conversion to prosthetic aortic valve replacement. MethodsSix centers established an intention-to-treat-design V-SARR-registry (the German Aortic Root Repair Registry; first patient in October 2016); the main inclusion criterion was being scheduled for V-SARR as plan A. Clinical information, operative details, intraoperative valve/root measurements, and clinical and transthoracic echocardiography follow-up-data are documented. ResultsOf a total of 449 patients, we report data for 401 (81% male; mean age 51 ± 14 years). Overall, 350 patients underwent V-SARR as scheduled, group A (David variants I 55%, III 2%, IV 13%, V 24%, V-Stanford 2%, and Yacoub remodeling 2%); and 51 were converted to aortic valve replacement (group B). Median follow-up was 11 months (range, 0 to 2.6 years), cumulative follow-up was 279 patient-years. In group B, there were fewer connective tissue disorders (6% vs 16%), fewer patients had left ventricular ejection fraction greater than 50% (60% vs 90%), more had bicuspid aortic valves (45% vs 28%), and fewer patients had preoperative none/trace aortic regurgitation (2% vs 20%). Fewer patients in group B had rare types of bicuspid aortic valve (fused N/L, R/N, 10% vs 30%) and more had unbalanced roots (56% vs 40%). Immediate postoperative aortic regurgitation was none/trace in 79% and mild in 20%. At 30 days, the mean transvalvular pressure gradient was 7 ± 5 mm Hg. None of the patients died in hospital; two strokes occurred. One patient needed early aortic valve replacement as redo surgery. ConclusionsThe main factors causing surgeons to convert a planned V-SARR to aortic valve replacement include asymmetry of aortic valve/root, severity of aortic regurgitation, safety reasons (left ventricular ejection fraction), and bicuspid aortic valves (but not rare types). The German Aortic Root Repair Registry will help us identify the impact on long-term outcomes of preoperative and postoperative valvular anatomy and various V-SARR types.

Monoclonal antibody treatment service to begin for hospitalised COVID-19 patients in October 2021

Patients in hospitals in England could start receiving neutralising monoclonal antibodies (nMABs) as a treatment for COVID-19 by early October 2021, chief pharmacists have confirmed. They said treatment provision would later be extended to COVID-19 patients in community settings. The confirmation follows the approval of nMAB treatment Ronapreve — a cocktail of two monoclonal antibodies: […]

ALL-073: Inotuzumab Ozogamicin (IO) and Donor Lymphocyte Infusion (DLI) are a Safe and Promising Combination in Relapsed Acute Lymphoblastic Leukemia (ALL) After Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Context Post-HSCT relapse of B-cell ALL is associated with a dismal outcome. IO allows, in the setting of R/R B-ALL patients, high response rates, but with limited duration. Objective To report the outcome of 8 B-ALL adult patients, relapsed after allogeneic HSCT, treated with IO and DLI. Design Retrospective analysis (first patient treated in April 2015, last patient in October 2019). Setting Multicenter (Italian centers). Patients or other participants Five Ph-negative and 3 Ph-positive B-ALL adult patients, with BM disease (6 morphological relapse and 2 MRD-positivity) were treated; 2 patients had additionally extramedullary (EM) disease. Three patients were in salvage 1, 5 patients in salvage ≥ 2; 50% of the patients had previously received Blinatumomab. Median time from transplant to relapse and from relapse to IO was 11 (range 2-21) and 2.5 (range 0-65) months, respectively. Interventions Patients received a median of 3 (range 2-6) IO courses. Four patients received IO and DLI in an alternate schedule and 4 patients sequentially after IO; a median of 3 (range 2-4) DLI at escalating dose was administered (1st dose ranging from 1 × 104/kg CD3+ to 5 × 106/kg CD3+; following doses from 1 × 105 to 5 × 107/kg CD3+). Main outcome measures CR and MRD rate, EM response, DFS, OS, toxicity. MRD was evaluated with BCR-ABL fusion transcript or V(D)J IgH/TCR disease-specific rearrangement on BM. DFS and OS were calculated from start of IO. Toxicity was graded according to CTCAE version. 4.03. Results All patients achieved CR after 1st IO cycle. Six of 8 patients obtained MRD negativity after 2nd IO cycle (4 of 6 patients after 1st cycle). Both PET+ patients achieved PET-negativity. With a median follow-up of 23.5 (range 3-58) months, 6 of 8 (75%) patients are alive. Four of 8 (50%) patients relapsed, of which 2 with CNS localization. Median DFS is 12 months (range 3-58) and median OS is 23.5 (3-58) months. Four out of 8 patients experienced G4 thrombocytopenia. Two patients experienced grade 1 GvHD and no VOD were reported. Conclusions IO and DLI are a safe combination in the post-HSCT setting that may ameliorate the dismal prognosis of this patient subset.

CHALLENGING BEHAVIORS ON INPATIENT MEDICAL UNITS: INTEGRATED, NON-PHARMACOLOGICAL APPROACH FOR PATIENTS WITH DEMENTIA

Introduction Inpatient medical care is a critical hospital function, but is costly and associated with risks to both patients and staff. Patients often demonstrate behavioral problems that interfere with care, prolong length of hospitalization, increase utilization of resources, delay discharge, and even lead to staff injury. To address these challenges, the San Francisco VA Health Care System (SFVAHCS) developed the Behavioral Education and Support Team (BEST). This team is comprised of psychiatry, psychology, nursing, and occupational therapy staff. BEST provides support, education, and interventions to patients who are engaging in treatment interfering behaviors. Goals include reducing risk to patients and staff, improving treatment adherence, reducing utilization of resources, shortening length of stay, and facilitating discharge. BEST staff also collaborate with inpatient staff to develop and consistently implement behavioral treatment plans. Since implementation in October 2015 to March 2018, BEST has served 488 veteran patients. Data demonstrate that BEST is associated with a 40% reduction in staff injuries in acute medicine settings, a 42% reduction in emergency psychiatric codes, and a 25% reduction in formal inpatient setting complaints. In addition, it is estimated that BEST reduces inpatient costs due to improved time to discharge and reduced staffing turnover and work loss due to injury. This presentation will provide an overview of the BEST team function and outcomes. Given the critical nature and high costs of inpatient medical care, the SFVAHCS determined that investment in a dedicated team to address these problems would be justified by reducing utilization of resources, length of hospitalization, overall cost, and adverse patient and staff outcomes. Methods The BEST team was initially implemented as a behavioral consultation team for inpatient medical patients in October, 2015, and was comprised of 5 members: • A RN team coordinator • A part-time psychiatrist (.2 FTE) • A psychologist • An RN team member • An Occupational Therapist The data from the BEST consultations between October 2015 and March 2018 were reviewed, and analyzed. Analysis of data included identification of total number of consultations, average age of patients, marital status, discharge status, themes for admission, days in hospital, presence of psychiatric disorder, dementia, serious mental illness, staff injury frequency, frequency of emergent psychiatric code calls, frequency of formal inpatient complaints. Results Since initiation in October, 2015, the BEST program has served 488 patients. Complex geriatric patient accounted for 78.7%. As of July, 2017, the majority of veterans served had a psychiatric disorder or need, including depression (50%), dementia (26%), delirium (21%), serious mental illness (18%), and suicidal ideation (10%). Adherence to treatment was a target problem in 56% of those referred. Specific Outcomes: • 40% reduction in staff injuries among acute medicine staff • 42% reduction in emergency psychiatric code calls • 25% reduction in formal inpatient complaints. In addition, a conservative estimate suggests that improving compliance with treatment and reducing length of stay by 1 day per non-compliance referral, extrapolated to the current time point, would generate a savings of approximately $835,000. In addition, inpatient nursing staff report a subjective increase in morale and perception of competence for coping with behavioral disruptions. • Consult Summary (October 2015 to March 2018) • 488 Consults • Average Age 69 (youngest 29 to oldest 101 • 466 Males and 22 Females • Marital Status – 156 Never Married; 96 Married; 18 Separated; 181 Divorced; 33 Widowed; 4 Unknown • Discharge Status – 11 Against Medical Advice; 10 Died; 4 Homeless; 87 Skilled Nursing Facilities; 219 Home/Board & Care/Shelters; 31 Mental Health Rehabilitation; 83 Long-Term Care; 35 Unknown; 8 Acute Hospital • Themes for Admission – 55 Altered Mental Status; 43 Failure to Thrive; 28 Placement Issues; 15 Falls; 68 Pain; 39 Shortness of Breath • Days in the Hospital: • 13,827 Total days in the hospital • 7,218 Days in the hospital awaiting placement after being cleared by medical team • $28 Million – cost awaiting placement Conclusions Since implementation of the BEST team at the SFVA Medical Center, data reveal overall reduction in utilization of resources, length of hospitalizations, overall costs, and adverse patient and staff outcomes. Specifically: 1. A dedicated behavioral team can significantly improve the experience of inpatient nursing staff, reducing injuries, improving morale, reducing staff turnover and burnout. 2. A behavioral intervention team can significantly reduce psychiatric codes and patient complaints, while improving clinical outcomes and patient satisfaction. 3. Reductions in staff injuries and improvements in treatment adherence can recoup costs for team staffing. 4. Reducing risk factors for disruptive behaviors reduces overall costs to the system and overutilization of resources. This research was funded by Funded through the San Francisco VA

Implementation of evidence-based practice for benign paroxysmal positional vertigo: DIZZTINCT\u2013 A study protocol for an exploratory stepped-wedge randomized trial

BackgroundBenign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder, and accounts for 8% of individuals with moderate or severe dizziness. BPPV patients experience substantial inconveniences and disabilities during symptomatic periods. BPPV therapeutic processes – the Dix-Hallpike Test (DHT) and the Canalith Repositioning Maneuver (CRM) – have an evidence base that is at the clinical practice guideline level. The most commonly used CRM is the modified Epley maneuver. The DHT is the gold standard test for BPPV and the CRM is supported by numerous randomized controlled trials and systematic reviews. Despite this, BPPV care processes are underutilized.Methods/designThis is a stepped-wedge, randomized clinical trial of a multi-faceted educational and care-process-based intervention designed to improve the guideline-concordant care of patients with BPPV presenting to the emergency department (ED) with dizziness. The unit of randomization and target of intervention is the hospital. After an initial observation period, the six hospitals will undergo the intervention in five waves (two closely integrated hospitals will be paired). The order will be randomized. The primary endpoint is measured at the individual patient level, and is the presence of documentation of either the Dix-Hallpike Test or CRM. The secondary endpoints are referral to a health care provider qualified to treat dizziness for CRM and 90-day stroke rates following an ED dizziness visit. Formative evaluations are also performed to monitor and identify potential and actual influences on the progress and effectiveness of the implementation efforts.DiscussionIf this study safely increases documentation of the DHT/CRM, this will be an important step in implementing the use of these evidenced-based processes of care. Positive results will support conducting larger-scale follow-up studies that assess patient outcomes. The data collection also enables evaluation of potential and actual influences on the progress and effectiveness of the implementation efforts.Trial registrationClinicalTrials.gov, ID: NCT02809599. The record was first available to the public on 22 June 2016 prior to the enrollment of the first patients in October 2016.

2119. Reducing Catheter-Associated Urinary Tract Infections Using an Evidence-Based Urine Culture Algorithm at an Academic Medical Center

BackgroundCatheter-associated urinary tract infections (CAUTIs) are among the most common hospital-acquired infections. CAUTIs have gained attention due to public reporting and reimbursement implications. Urine cultures are often obtained for inappropriate indications, which can falsely elevate CAUTI rates. Our objective was to determine the impact of a new evidence-based urine culture algorithm on our CAUTI rates.MethodsThis quality improvement project was implemented at a 1,541 bed academic medical center in New Haven, CT. Our CAUTI performance improvement (PI) team, a collaboration between nurses, infectious disease physicians and urologists developed a urine culture algorithm for catheterized patients in October 2017. This algorithm recommends directed evaluation of fever in a catheterized patient based on Infectious Disease Society of America guidelines (Figure 1). Education about appropriate culturing and catheter utilization was initiated November 2017, the algorithm was approved on December 27, 2017, and included in the electronic medical record February 2018. The incidence rates (IR) of CAUTI per 1,000 catheter days (CD), urine cultures ordered, urinary catheter days and central line-associated bloodstream infection (CLABSI) rates were compared for the quarter pre- and post-algorithm implementation.ResultsOur CAUTI IR decreased by >40% from 1.4 to 0.8 per 1,000 CD for the quarters pre- and post-algorithm implementation, respectively (Figure 2). Average monthly urine cultures ordered in catheterized patients decreased by 28% from 120 (fourth quarter, 2017) to 84 post algorithm implementation (first quarter, 2018, Figure 3). The average monthly catheter days decreased by 1.5% (4,409 days in fourth quarter, 2017 to 4,342 in first quarter, 2018). Despite the decrease in urine cultures ordered, we did not see a compensatory increase in CLABSI rates during the post implementation period. ConclusionThoughtful culturing through algorithm-directed evaluation of fever based on signs and symptoms combined with staff education about culturing and catheter utilization led to reduction in unnecessary urine culture orders and CAUTIs. Our next steps are to evaluate the impact of this algorithm on antibiotic utilization and C. difficile rates, and examine the sustainability of these interventions over time.Disclosures M. Juthani-Mehta, Iterum Therapeutics: Scientific Advisor, Consulting fee.

Prevalence of and Factors Associated With Fecal Incontinence: Results From a Population-Based Survey

Fecal incontinence (FI) is characterized by uncontrolled passage of solid or liquid stool. We aimed to determine the prevalence and severity of FI in alarge sample of US residents. We recruited a representative sample of patients in October 2015 to complete the National Gastrointestinal (GI) Survey; a mobile app called MyGiHealth was used to systematically collect data on GI symptoms. FI was defined as accidental leakage of solid or liquid stool. Severity of FI was determined by responses to the National Institutes of Health FI Patient Reported Outcomes Measurement Information System questionnaire. Multivariable regression models were used to identify factors associated with FI prevalence and severity. Among 71,812 individuals who completed the National GI Survey, 14.4% reported FI in the past; of these, 33.3% had FI within the past 7 days. Older age, male sex, and Hispanic ethnicity increased the likelihood of having FI within the past week. Individuals with Crohn's disease, ulcerative colitis, celiac disease, irritable bowel syndrome, or diabetes were more likely to reportFI. Non-Hispanic black and Hispanic individuals and individuals with Crohn's disease, celiac disease, diabetes, human immunodeficiency virus/acquired immunodeficiency syndrome, or chronic idiopathic constipation had more severe symptoms of FI than individuals without these features. In a large population-based survey, 1 in 7 people reported previous FI. FI is age-related and more prevalent among individuals with inflammatory bowel disease, celiac disease, irritable bowel syndrome, or diabetes than people without these disorders. Proactive screening for FI among these groups is warranted.

Reduction in Radiation Exposure through a Stress Test Algorithm in an Emergency Department Observation Unit.

IntroductionClinicians are urged to decrease radiation exposure from unnecessary medical procedures. Many emergency department (ED) patients placed in an observation unit (EDOU) do not require chest pain evaluation with a nuclear stress test (NucST). We sought to implement a simple ST algorithm that favors non-nuclear stress test (Non-NucST) options to evaluate the effect of the algorithm on the proportion of patients exposed to radiation by comparing use of NucST versus Non-NucST pre- and post-algorithm.MethodsAn ST algorithm was introduced favoring Non-NucST and limiting NucST to a subset of EDOU patients in October 2008. We analyzed aggregate data before (Jan-Sept 2008, period 1) and after (Jan-Sept 2009 and Jan-Sept 2010, periods 2 and 3 respectively) algorithm introduction. A random sample of 240 EDOU patients from each period was used to compare 30-day major adverse cardiac events (MACE). We calculated confidence intervals for proportions or the difference between two proportions.ResultsA total of 5,047 STs were performed from Jan-Sept 2008–2010. NucST in the EDOU decreased after algorithm introduction from period 1 to 2 (40.7%, 95% CI [38.3–43.1] vs. 22.1%, 95% CI [20.1–24.1]), and remained at 22.1%, 95% CI [20.3–24.0] in period 3. There was no difference in 30-day MACE rates before and after algorithm use (0.1% for period 1 and 3, 0% for period 2).ConclusionUse of a simple ST algorithm that favors non-NucST options decreases the proportion of EDOU chest pain patients exposed to radiation exposure from ST almost 50% by limiting NucST to a subset of patients, without a change in 30-day MACE.

Abstract B79: Translational study of tumor treating fields in combination with paclitaxel in ovarian cancer.

Abstract Tumor Treating Fields (TTFields), a clinically active anticancer modality, are based on low intensity intermediate frequency alternating electric fields that exert their cytotoxicity by disrupting mitosis. The present study examines whether concomitant paclitaxel and TTFields have a beneficial impact on ovarian cancer growth both in vitro and in vivo. Moreover, on the basis of the preclinical observations, an open-label pilot clinical study evaluating the effect of the combined modalities in 30 patients with recurrent ovarian cancer was initiated. Preclinical studies: To investigate the inhibitory effect of TTFields on ovarian cancer cell growth in vitro and determine optimal therapeutic frequency of TTFields in ovarian cancer, human ovarian cancer cell lines were treated with TTFields (100-400 kHz) for 72 hours using the inovitro system (Novocure, Haifa, Israel). To assess whether adding TTFields to paclitaxel increases the response of ovarian cancer cells to paclitaxel, we treated these cell lines with paclitaxel alone and in combination with TTFields. In vivo efficacy of the combined treatment was tested in female C57Bl/6 mice, orthotopically implanted with MOSE-L FFL luciferase positive cells. The feasibility of effective regional delivery of TTFields therapy to the ovaries, pelvis and abdomen of human subjects was examined using Finite Element Mesh (FEM) simulations performed using the Sim4life software. The FEM simulations demonstrated effective distribution of fields at intensities of 1-2 V/cm, which is above the minimal threshold required for TTFields response. The INNOVATE Trial (NCT02244502): Based on positive preclinical studies demonstrating the combined efficacy of TTFields and paclitaxel in different ovarian cancer models, a pilot clinical trial was initiated to evaluate this therapeutic combination in recurrent ovarian carcinoma patients. In this prospective, pilot, single arm study, 30 patients will receive bi-directional TTFields at 200 kHz applied to the ovaries and surrounding intra-abdominal tissues using 4 transducer arrays located on the surface of the lower abdominal region. In addition, patients will receive concomitant paclitaxel at a standard regimen and dose. The combined treatment will be administered until further radiological progression. Inclusion criteria include ECOG score of 0-1 and no serious co-morbidities. The trial's primary endpoint is adverse events frequency and severity. The study will also collect preliminary efficacy data through the analysis of progression-free survival, 1-year survival rate and overall survival. Compliance data will be analyzed as an additional secondary endpoint. The INNOVATE study started to enroll patients in October 2014, and is currently accruing patients in Switzerland, Belgium and Spain. So far the trial has enrolled half of the planned 30 patients. In summary, we present the first preclinical evidence in ovarian cancer of the combined efficacy of paclitaxel and TTFields, a new anticancer treatment modality. Our results suggest that it may represent a novel, effective therapeutic strategy against ovarian cancer. Pilot clinical testing is ongoing. Citation Format: Mijal Munster, Roni Blat, Paul C. Roberts, Eva M. Schmelz, Moshe Giladi, Rosa S. Schneiderman, Yaara Porat, Zeev Bomzon, Noa Urman, Aviran Itzhaki, Tali Voloshin, Shay Cahal, Eilon D. Kirson, Uri Weinberg, Yoram Palti. Translational study of tumor treating fields in combination with paclitaxel in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B79.