Mean Days Research Articles

Fertility of Postpartum Iraqi Cows Following Timed Artificial Insemination within Ovsynch or Presynch Protocols

This investigation was carried out on privately owned dairy farms situated in Al-Anbar Province, Iraq, extending from June 2022 to March 2023. The objective of our study was to compare the calving interval (CI), days open (DO), and conception rate at first service (CRFS) between timed artificial insemination (TAI) within ovulation synchronization protocols and AI at estrus detection. Total cows (n = 80) 50–60 days postpartum were randomly divided. (1) AIED group (Control, n = 40) untreated cows received AI at the first observed estrus according to the a.m. /p.m. rule. (2) OVS group (n = 20) was treated with a classical Ovsynch protocol. (3) The PG+G group (n = 20) underwent resynchronization with PGF2 and GnRH at the same time 7 days later, then underwent an Ovsynch protocol. Pregnancy was confirmed using trans-rectal ultrasonography on day’s 30-35 post-insemination. The results of this study show that mean days of CI and DO for the control group were significantly longer than those in both the OVS group and the PG+G group (P < 0.01). Among all groups, the CRFS showed a significant difference (37.5%, P < 0.05). Separately, the CRFS for the control group was similar to the OVS group (respectively, 27.5% vs. 30%, P > 0.05). Whereas, the PG+G group had a 65% CRFS, which was significantly higher than the control (P < 0.01) and OVS (P < 0.05). In summary, ovulation synchronization protocols enable TAI earlier in the postpartum period, eliminating the need for estrus detection and resulting in shorter CI and DO. Additionally, the PG+G protocol increased the CRFS compared to both the OVS and the control groups.

The need for culture in tegumentary leishmaniasis diagnosis in Bolivia: A comparative evaluation of four parasitological techniques using two sampling methods

Leishmaniases are zoonotic diseases caused by protozoa of the genus Leishmania. In Bolivia, leishmaniasis occurs mainly in the cutaneous form (CL) followed by the mucosal or mucocutaneous form (ML or MCL), grouped as tegumentary leishmaniosis (TL), while cases of visceral leishmaniasis (VL) are rare. The cases of TL are routinely diagnosed by parasitological methods: Direct Parasitological Exam (DPE) and axenic culture, the latter being performed only by specialized laboratories. The aim of the present study was to optimize the parasitological diagnosis of TL in Bolivia, using two sampling methods. Samples from 117 patients with suspected TL, obtained by aspiration (n = 121) and scraping (n = 121) of the edge of the lesion were tested by: direct parasitological exam, culture in TSTB medium, and miniculture and microculture in Schneider's medium. A positive laboratory result by any of the four techniques evaluated using either of the two sampling methods was considered the gold standard. Of the 117 suspected patients included, TL was confirmed in 96 (82 %), corresponding 79 of the confirmed cases (82.3 %) to CL and 16 (16.7 %) to ML. Parasitological techniques specificity was 100 % and their analytical sensitivity was greater with scraping samples in TSTB culture (98 %). Scraping samples in TSTB and miniculture correlated well with the reference (Cohen's kappa coefficient=0.88) and showed good reliability (Cronbach's alpha coefficient ≥0.91). Microculture provided positive results earlier than the other culture methods (mean day 4.5). By day 14, 98 % of positive cultures had been detected. Scraping sampling and miniculture were associated with higher culture contamination (6 % and 17 %, respectively). Bacterial contamination predominated, regardless of the sampling and culture method, while filamentous fungi and mixed contamination were more frequently observed in cultures from scraping samples. In conclusion: (i) scraping samples proved more suitable for the diagnosis of TL as they increased analytical sensitivity, are less traumatic for the patient and are safer for laboratory personnel than aspirates; (ii) culture, mainly in TSBT medium, should be used for the diagnosis of TL due to its high sensitivity (doubling the number of cases diagnosed by DPE) and its low cost compared to other culture media.

Involuntary Hospitalizations in an Italian Acute Psychiatric Ward: A 6-Year Retrospective Analysis.

We evaluated the differences between demographic (age, sex, nationality, employment, housing, schooling, support administrator), clinical (hospitalization reason, aggressive behaviour, length of hospitalization, psychiatric diagnosis and comorbidities, psychiatric medications, discharge destination, "revolving door" hospitalizations) and environmental (pre-and pandemic period) variables in voluntary (VHs) and involuntary hospitalizations (IHs) in an acute psychiatric ward during a 6-year period. We retrospectively collected the selected variables concerning the hospitalizations of subjects over 18 years of age in the Service for Psychiatric Diagnosis and Care of Mental Health and Drug Abuse Department in Modena from 01/01/2017 to 31/12/2022. We observed a progressive and sharp reduction in the number of VHs (n = 1800; 61.41%) during the pandemic and a stability of IHs (n = 1131; 38.59%), which in 2022 became prevalent. We highlighted the following differences between VHs and IHs: an increase in hospitalization length in IHs (14.25 mean days ± 15.89 SD) in comparison with VHs (8.78 mean days ± 13.88 SD), which increased more during the pandemic; an increase in aggressive behavior in IHs, especially during the pandemic (Pearson Chi2 = 90.80; p = 0.000); a prevalence of schizophrenia and bipolar disorders (Pearson Chi2 = 283.63; p = 0.000) and more frequent maladaptive social conditions among subjects in IHs. During the 6-year observation period, we underscored a trend of increasingly reduced recourse to VHs, whereas IHs increased even in the pandemic. Our results suggest that IHs in Psychiatry represented an extreme measure for treating the most severe psychopathological situations such as schizophrenia and bipolar disorders, characterized by aggressive behaviour and precarious social conditions, which needed longer stay than VHs, especially during the pandemic.

1216. ASP Initiated Blood Culture Service Is Highly Accepted, Reduced Antibiotic Durations Associated with Good Safety Outcomes

Abstract Background NUH is a 1200 bed academic medical center with quaternary medical services ; the ASP program was initiated in 2014. A 2020 review found 18.5% of bacteremic patients were on inappropriate antibiotics (ABX) or wrong duration, and the overall majority of bacteremias were gram-negative (E .coli and Klebsiella). Since out ASP program has been promoting shorter durations in general, we hypothesized that a blood culture service where recommendations for de-escalation and appropriate duration were given early would help shorten ABX durations in patients with uncomplicated bacteremias. On March 15, 2021, we initiated an ASP led blood culture (BC) service (SVC) which reviewed case notes of patients Monday to Friday as soon as blood culture (BC) susceptibilities were available. We report on the types of interventions (INV), acceptance rate, and the impact and outcomes of our BC SVX between patients in whom the INV was accepted versus rejected. Methods Prospective data on BC SVC interventions, acceptance rate, and patient status at five days were collected. Antibiotic duration (IV and oral), Length of Stay (LOS) and 30-day mortality as well as Charlson Comorbidity Index (CCI) were determined from electronic medical records for all ASP BCSVX interventions between March 15, 2021- December 31, 2022. Statistical analysis was performed in excel and STATA. Results 790 INVs were made on 625 patients and 693 courses of ABX with an 83.9 % overall acceptance rate. De-escalate ABX and treatment duration were the most common INVs (Table 1). 92.5% of patients had improved or no change in Day 5 status when ASP INV was accepted compared to 84.3% when rejected (p=0.003). Mean days of ABX per course was 5.9 versus 7.3 (p= 0.008) in the accepted versus rejected groups. CCI and LOS were similar, while 30-day mortality almost reached significance in the accepted INV group (Table 2). Conclusion ASP led BC SVC was well accepted, saved 2.14 days of ABX per intervention, and was very safe. Disclosures All Authors: No reported disclosures

88. Fostamatinib for the Treatment of Hospitalized Patients With COVID-19 Who Required Oxygen Supplementation: Results of a Phase 3 Trial

Abstract Background Severe COVID-19 is linked to hyperactivation of the host immune response involving signaling through multiple spleen tyrosine kinase (SYK) pathways. Fostamatinib is an orally administered potent and selective inhibitor of SYK that has been approved in the US, Canada, Japan, and Europe for the treatment of chronic immune thrombocytopenia (ITP). Methods We conducted a double-blind, randomized, placebo-controlled phase 3 trial of fostamatinib in adults hospitalized for COVID-19 who required oxygen supplementation (NCT04629703). Patients (pts) were randomly assigned 1:1 to receive fostamatinib (150 mg BID administered orally) or placebo for 14 days. All pts additionally received standard of care at their hospital. The primary endpoint was days on oxygen (days 1-29). Results A total of 280 pts underwent randomization (with 141 assigned to fostamatinib and 139 to placebo). The primary endpoint was met; those who received fostamatinib had lower mean days on oxygen than those who received placebo (4.8 vs. 7.6 days, P=0.0136; Table 1). Fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo. The mean change in the 8-point ordinal score from baseline to the average of Day 5 to 15 was significantly improved in pts who received fostamatinib vs. placebo (P=0.0092,Table 1). Furthermore, 6 pts were enrolled with a baseline ordinal score of 6 (3 in each group). All patients in the fostamatinib group survived, and all in the placebo group died by Day 30. A significantly higher proportion of pts who received fostamatinib were discharged from the hospital by Day 15 compared to placebo (P=0.0029,Table 1). Significantly more patients were alive and oxygen-free by Day 29 and Day 60 with fostamatinib treatment in comparison to placebo (P=0.0213 and P=0.0271, respectively, Table 1). Treatment-emergent adverse events were consistent with previous studies and were similar between the 2 groups. Conclusion The addition of fostamatinib to standard of care treatment resulted in significantly fewer days on oxygen, an improved 8-point ordinal scale score, and significantly more patients alive and oxygen-free by Day 60 compared to placebo in pts with COVID-19 requiring hospitalization and supplemental oxygen. Disclosures Deepa B. Gotur, MD, FCCP, FCCM, GSK: Advisor/Consultant|GSK: Speaker at ATS|Moderna: Advisor/Consultant Vadim Markovtsov, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Lucy Yan, MD, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Wolfgang Dummer, MD, PhD, Rigel Pharmaceuticals, Inc.: Stocks/Bonds.

1223. Utilizing Multiple Antimicrobial Stewardship Metrics to Trend Vancomycin Use in an Implementation Study

Abstract Background Inpatient IV vancomycin use is often inappropriately prolonged. Methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nares swabs have shown high negative predictive values for many infections and can guide appropriate vancomycin de-escalation. Antibiotic stewardship programs (ASPs) often monitor vancomycin use in days of therapy (DoT) per 1000 patient days present (PDP). This measure can be affected, especially for smaller facilities, by changes in bed capacity and prolonged stays and thus may not accurately reflect vancomycin use. We evaluated whether alternative metrics of vancomycin use would show different impacts during a multi-step ASP intervention to reduce inappropriate vancomycin use at Veterans Affairs Tennessee Valley Healthcare System. Figure 1 Run chart of vancomycin DoT/1000 PDP at the Tennessee Valley Healthcare System (TVHS) in two years prior to intervention. Methods In September 2021, the ASP, with multiple stakeholders, initiated use of MRSA nasal swabs to inform vancomycin de-escalation. From 7/2022 to 3/2023, we performed iterative Plan-Do-Study-Act intervention cycles including educating medicine and surgical divisions on MRSA swab result interpretation, educating nurses on timely swab collection, replacing MRSA culture swabs with PCR swabs, and adding MRSA swab orders to vancomycin order sets. In April 2022, in addition to DoT/1000 PDP, we began measuring mean, median, and mode DoT per vancomycin course initiated by start week. Results Despite multiple interventions beginning July 2022, vancomycin use in DoT/1000 PDP increased to a peak of 106 DoT/1000 PDP in September 2022. In that same period, median and mode DoT per vancomycin initiation remained steady at 2 days and 1 day, respectively. Figure 2 Run chart of vancomycin DoT/1000 PDP at the TVHS from April 2022 to March 2023. Specific ASP interventions are annotated on the dates they occur. Figure 3 Run chart of mean, median, and mode days of vancomycin therapy per vancomycin course initiated at the TVHS from April 2022 to March 2023. Specific ASP interventions are annotated on the dates they occur. Conclusion DoT/1000 PDP may not be the best metric to evaluate efforts to reduce inappropriate vancomycin use. By tracking mean, median, and mode of DoT per individual vancomycin course, we determined that most providers already practice rapid de-escalation, minimizing patient vancomycin exposure. This method also allows us to quickly detect changes in prescribing patterns and determine whether interventions were warranted. More evaluation of antibiotic use metric appropriateness based on desired outcome is needed in ASPs. Disclosures Milner Staub, MD, MPH, Gilead: Stocks/Bonds|Johnson & Johnson: Stocks/Bonds

Pre-Post Cannabis Legalization for Adult Use: A Trend Study of Two Cohorts of Young Adult Cannabis Users in Los Angeles

ABSTRACT Cannabis was legalized for adult use in California in 2016 for individuals 21 and older. Among 18–20-years-olds, who can possess cannabis legally as medical cannabis patients (MCP) but not as non-patient cannabis users (NPU), the impact of adult use legalization (AUL) on cannabis and other substance use is unknown. Two cohorts of 18–20-year-old cannabis users (MCP and NPU) were surveyed, one in 2014–15 (n = 172 “pre-AUL”) and another in 2019–20 (n = 139 “post-AUL”), using similar data collection methods in Los Angeles, California. Logistic and negative binomial regressions estimated cohort and MCP differences for cannabis and other drug use outcomes based on past 90-day use. In both pre- and post-AUL cohorts, MCP were more likely to self-report medical cannabis use (p < .001) while the post-AUL cohort reported greater use of edibles (p < .01), but fewer mean days of alcohol (p < .05) and cigarette (p < .01) use in multivariate models. Notably, frequency of cannabis use (days or hits per day) did not significantly differ between the pre- and post-AUL cohorts, except for greater use of edibles, despite potentially greater access to cannabis.

Building resilience through daily smartphone app use: results of a pilot study of the JoyPop app with social work students.

The JoyPop™ smartphone app is a digital intervention designed to enhance day-to-day resilience in youth, particularly those exposed to traumatogenic events [adverse childhood experiences (ACEs)]. Processes of adaptation that foster resilience in response to high stress include affect, cognitive, and behavioral regulation, and social interaction. Digital interventions have application for youth and those who provide them support, including social work trainees navigating the stressors of university studies concurrent with practice internships. Research on resilience-enhancing apps is needed to understand the underlying mechanisms by which change occurs and who is most likely to benefit from these interventions. Social work student participants (N = 91) were invited to use the JoyPop app two times daily for 28 days. Baseline ACE exposure and change-over-time in affect regulation, stress responsivity, and social support were evaluated after 2 and 4 weeks of app use with t-tests and generalized estimating equation (GEE) modeling. Participants identified predominantly as cisgender women of European descent, mean age 26 years (SD = 6.78), 70% undergraduates, and reported consistent daily app use (Mean days = 26.9, SD = 1.90). Self-reported baseline ACE exposure was high (30% ≥ 5+). We tested change-over-time with generalized estimating equation and saw improvement in affect regulation in the Abbreviated Dysregulation Inventory scale (β = -3.38, p = <.001), and subscales of behavioral (β = -1.63, p = <.001), affect (β = -3.24, p = <.001), and cognitive regulation (β = 1.50, p = .009). Perceived stress decreased with app use (β = -2.65, p = <.001) and even more so for participants with reported exposure to more than 4 ACEs (β = -3.786, p = .030). The exploratory findings from our pilot study suggest that consistent use of the app may enhance multidimensional resilience amongst university students who self-report higher than average levels of baseline traumatogenic exposures. Our findings support an approach modeling resilience as a complex, dynamic, multicomponent process supported by resources within and between individuals. Further testing of the mechanisms of adaptation in response to high stress that enhance resilience and identification of the JoyPop™ app features that influence this change is needed to validate that daily app use could help youth with experiences of past and current high stress to better regulate their affect, reduce stress reactivity, and increase resilience.

OGC P39 The accuracy of Hospital Acquired Pneumonia (HAP) Diagnosis after Oesophagectomy

Abstract Background Oesophagectomy is a high-risk intervention associated with significant rates of morbidity. Pneumonia is a complex spectrum of infective and non-infective aetiology, varying in severity and is common after oesophagectomy. Inconsistent definitions of pulmonary complications pose significant challenges in both the clinical and research setting. The internal Esophageal Consensus Complications Group (ECCG) have adopted the Centre for Disease Control (CDC) criteria for HAP diagnosis to address this. However, other validated diagnostic criteria are also available. This study aimed to better understand the incidence of HAP after oesophagectomy, and the accuracy of four validated diagnostic tools. Methods This was a retrospective review of all consecutive oesophagectomies undertaken at a regional OG centre serving a population of 3.5 million patients between 2014-2022. Datapoints included patient demographics; comorbidities; post-operative course and re-admissions. The timing of pneumonia diagnosis was determined in the post-operative period, alongside observations and Computed Tomography (CT) and Chest X-Ray (CXR) reports. Four diagnostic criteria (Centres for Disease control- CDC, American Thoracic Society - ATS, Utrecht and Clinical Pulmonary Infection Score - CPIS) were applied to determine the incidence of HAP in comparison to patients treated for HAP. Statistical tests were performed in STATA. Results 460 patients were included, 356 (77.40%) were male. 223 (48.5%) were treated for HAP between 2014-2022. 56 (12.2%) met the CDC criteria. Mean days to diagnosis was 5 days (SD +/- 3.72). Diagnostic sensitivity and specificity for HAP was 88.89%, and 50.15% respectively. The ATS criteria were met by 79 patients (17.2%), showing a similar sensitivity (97.53%) and specificity (92.02%) to the CDC criteria. The Utrecht criteria had the lowest specificity (75.20%) for HAP diagnosis. 192 patients had sputum samples; 158 (82.29%) were culture positive. 52 patients were re-intubated, of which 29 (55.8%) were reintubated due to respiratory failure. Conclusions HAP is a complex and nuanced diagnosis with high inter-observer variation. Currently available and validated diagnostic tools result in different rates of HAP diagnosis. These findings highlight the importance of adopting robust approaches to diagnosing HAP to avoid unnecessary treatments and to more accurately determine the effectiveness of protocolised management (such as ERAS) that target HAP. The findings also highlight important implications on outcome reporting in research, particularly with interventions (e.g. minimally invasive and robotic surgery) which aim to reduce the burden of post-operative morbidity. Further widescale studies are required to validate these findings.

Efficacy and Safety of Hetrombopag in Promoting Platelet Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective, Multicenter, Randomized Controlled Clinical Trial

Background and Objective: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat hematological malignancies and non-malignant hematological diseases. However, the incidence of thrombocytopenia after transplantation is common, and within 60 days after HSCT, around 5-38% of patients experienced delayed platelet engraftment or persistent isolated thrombocytopenia. Thrombocytopenia after transplantation was significantly associated with life-threatening bleeding events and reduced overall survival rate. Previous studies have found that the biphenyl structure may have hepatotoxicity, Hetrombopag (TPORA) replaces it with a heterocyclic carboxyl group to reduce hepatotoxicity, which can also enhance the lipophilicity and improve the efficacy by report. Hetrombopag was proved safe and effective in treating ITP and aplastic anemia. The aim of this study is to evaluate efficacy and safety of Hetrombopag in promoting platelet engraftment after allo-HSCT. Methods: Patients undergoing allo-HSCT were randomly grouped on day 3 after stem cell infusion. The experimental group treated with Hetrombopag 2.5mg/d or 5mg/d orally till platelet reconstitution, instead the control group was given thrombopoietin (TPO) 300U/kg/d. Platelet engraftment was defined as platelet count ≥20×10 9/L for consecutive 7 days without platelet transfusion. The primary endpoint is the time for platelet engraftment. The secondary endpoints include the time to granulocyte engraftment, platelet transfusion units, medical costs during hematopoietic reconstitution, and side effects. Results: Currently, 26 patients were enrolled in the Hetrombopag experimental group and 26 in the TPO control group. The median age of experimental group was 35 years (14-62 years), with 9 AML patients, 9 ALL, 5 MDS/MPN, 2 AA, and 1 MPAL. Among them, 12 received haplo-transplantation, and 14 underwent HLA-identical transplantation. The average number of transfused mononuclear cells (MNCs) was 8.6 (5.28-12.79) ×10 8/kg, and the average number of CD34 + cells was 5.93 (2.39-9.37) ×10 6/kg. The mean time for granulocyte and platelet engraftment was 15.26±3.37 and 15.20±4.06 days respectively. Primary graft failure of platelet occurred in 1 patient (3.8%). The median age of the control group was 36 years (19-63 years), with 12 patients diagnosed AML, 9 ALL, 2 MDS/MPN, 2 AA, 1 plasma cell leukemia, and 1 NKTCL. 19 of them received haplo-transplantation, while 7 receivedHLA-identical transplantation. The average numbers of transfused MNCs and CD34 + cells were 9.05 (5.39-16.22) ×10 8/kg and 6.4 (1.96-10.45) ×10 6/kg respectively. The mean days of granulocyte and platelet reconstitution were 17.38±5.82 and 18.18±4.62 days, respectively. PGF occurred in 4 patients (15.4%). Compared with the control group, the experimental group had a significantly earlier engraftment of granulocytes ( P=0.03) and platelets ( P=0.01). During platelet reconstitution, the control group was transfused 6.87±3.93U of platelets and the experimental group was transfused less (3.92±3.45U, P = 0.0009). The medical cost of using TPO and Hetrombopag was 12555.39±5222.33 yuan in the control group and 2783.90±1020.04 yuan in the experimental group ( P &amp;lt; 0.0001). The above data are the interim analysis results of this study. Liver transaminases were elevated in 4/26 cases in the experimental group and 2 cases in the TPO group, after one week of drug administration; Different degrees of organ bleeding (digestive tract, urinary tract, etc.) occurred in 6 cases in the experimental group and in 9 cases in the control group. Notably, the above data are only interim analyses and the side effects may not only be due to the study medication, as allo-HSCT itself includes very complex factors. Conclusion: Hetrombopag can safely promote rapid platelet engraftment, shorten the time difference between granulocyte and megakaryocyte reconstitution, reduce platelet transfusion, and decrease the economic burden of patients after allo-HSCT. Keywords: Hetrombopag, Allo-HSCT, TPORA, Platelet engraftment.

Expansion, Persistence and Pharmacodynamic Profile of ADI-001, a First-in-Class Allogeneic CD20-Targeted CAR Gamma Delta T Cell Therapy, in Patients with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma

Introduction ADI-001 is a first-in-class allogeneic gamma delta (γδ) CAR T cell therapy targeting the B-cell antigen, CD20. Expansion and persistence of cell therapy products and release of functional cytokines have historically correlated with patient outcomes. Here we report cellular kinetics and pharmacodynamic correlates from a phase 1, multicenter, open-label, dose escalation study to evaluate ADI-001 in R/R B cell NHL. Methods Cellular kinetics of ADI-001 were measured using three orthogonal methods, including quantitative SNP profiling of cell product (AlloCell), flow-cytometry for CAR+ Vδ1 γδ T cells, and droplet digital PCR (ddPCR) quantification of CAR transgene copies. Using these methods, expansion of ADI-001 was assessed in the peripheral blood for 24 evaluable patients across four dose levels in association with a phase 1 dose-escalation trial (NCT04735471). Relationships between ADI-001 cellular kinetics and radiographic clinical responses were also examined. Serum biomarkers related to host immune cell recovery during lymphodepletion and cytokine release were monitored for pharmacodynamic purposes. Humoral immunogenicity was assessed by Luminex™-based anti-HLA antibody screening. Other correlative characteristics were also evaluated, including degree of HLA mismatching between patient and ADI-001 product in relation to response and/or ADI-001 expansion and persistence. Results As of the May 2023 cutoff for reporting, ADI-001 was detected at all dose levels using ddPCR and flow cytometry to quantify CAR transgene copies and CAR+ Vδ1 γδ T cells, respectively. Treatment at the highest dose level, achieved a notable mean C max of 201,666 copies/µg or 483 CAR+ cells/µl, and mean day 28 persistent exposure of 16,553 copies/µg or 21 CAR+ cells/µL. Additional measures of ADI-001 exposure (AlloCell) further demonstrated a robust dose-dependent expansion profile of ADI-001 in the peripheral blood. Subjects with a BOR of CR or PR were observed to have a mean peak of 180,107 CAR copies/µg versus a mean peak of 20,950 CAR copies/µg in subjects with a BOR of SD or PD. Additionally, as expected following lymphodepletion, a transient increase in the homeostatic cytokine IL-15, coinciding with ADI-001 expansion and host-mediated immune cell recovery, was observed. Using high-resolution HLA typing, the degree of HLA mismatch between allogeneic ADI-001 product and patients did not associate with degree of cellular expansion, day 28 persistence, or response. Finally, emergence of donor-specific anti-drug antibodies following treatment was not observed. Conclusions Using three orthogonal measures of exposure, we show for the first time robust dose-dependent expansion and persistence of an allogeneic CAR γδ T cell therapy, ADI-001, irrespective of extensive degree of HLA mismatch. ADI-001 C max and D28 persistent exposure were comparable to, or exceeded, those demonstrated by alternative allogeneic CAR T therapies and approved autologous CD19 CAR T therapies. Favorable clinical responses were also associated with higher mean and median peak of ADI-001 cells.

The role of therapy delivery and clinic organizational factors in explaining therapist effects for trauma-focused psychotherapies in the Veterans Health Administration.

This study estimated the size of therapist effects (TEs) for dropout and clinical effectiveness of two trauma-focused psychotherapies (TFPs) and evaluated whether therapy delivery and clinic organizational factors explained observed TEs. Participants were 180 therapists (54.4% psychologists, 42.2% social workers) from 137 Veterans Health Administration facilities and 1,735 patients (24.7% women; 27.2% people of color) who completed at least two TFP sessions. Outcomes were dropout (< 8 TFP sessions) and for a subsample (n = 1,273), clinically meaningful improvement and recovery based on posttraumatic stress disorder checklist for DSM-5 (PCL-5) scores. Therapist-level predictors were ascertained through survey, manual chart review, and administrative data. Multilevel models estimated TEs. Over half (51.2%) of patients dropped out and those who dropped out were less likely to meet criteria for clinically meaningful improvement or recovery (ps < .001). Adjusting for case-mix and TFP type, therapists accounted for 5.812% (p < .001) of the unexplained variance in dropout. The average dropout rate for the 45 therapists in the top performing quartile was 27.0%, while the average dropout rate for the 45 therapists in the bottom performing quartile was 78.8%. Variation between therapists was reduced to 2.031% (p = .140) when therapists' mean of days between sessions, adherence, implementation climate, and caseload were added to multilevel models. TEs were nonsignificant for clinically meaningful improvement and recovery. Interventions targeting therapy delivery and clinic organization have the potential to reduce variation between therapists in TFP dropout, so that more patients stay engaged long enough to experience clinical benefit. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

First Report of Diaporthe fruit rot and stem canker of hydroponic cucumber caused by Diaporthe sp. in the United States.

Multiple Diaporthe spp. cause root and fruit rots or stem lesions on Cucumis spp.: D. cucurbitae, D. melonis, D. longicolla (syn. D. eres), D. pterocarpi, D. sclerotioides, D. sojae, and D. ueckerae (Broge et al. 2020; Fukada et al. 2018; Udayanga et al. 2012, 2015). From May-August 2021, cucumbers (Cucumis sativus) 'Katrina' and 'Alcazar' were grown in a 24-plant, commercial Bato bucket system with rockwool blocks on a perlite substrate in a research greenhouse in Wooster, Ohio. At maturity, plants collapsed rapidly from stem lesions without foliar chlorosis (25% of 'Katrina' and 17% of 'Alcazar'). Lesions were 7.5 to 15 cm in length, tan to golden-brown with black pycnidia and located 5 to 15 cm above the crown. Stems shredded easily with vascular discoloration around the lesion. Two identical fungal strains were isolated on ½ acidified potato dextrose agar (APDA) following surface disinfestation with 0.6% sodium hypochlorite for 30 s and sterile water rinse. Fungal cultures were floccose, white to tan mycelia with pycnidia. Oblong, elliptical, biguttulate, aseptate alpha conidia were observed with mean dimensions: 8.0 µm (5.2-9.8 µm) by 3.1 µm (2.5-3.8 µm) on ½ APDA and 9.8 µm (6.6-12.4 µm) by 3.0 µm (1.9-5.3 µm) on petioles. On prune extract agar, beta conidia mean dimensions were: 19.7 µm (12.0-27.7 µm) by 1.2 µm (0.8-1.8 µm). Fungal DNA was amplified and sequenced bidirectionally with ITS (ITS4/ITS5), CAL (CAL228F/737R), HIS (CYLH3F/H3-1B), TEF1 (EF1-728f/EF1-986R), and TUB2 (Bt1a/Bt1b) primers (Carbone and Kohn 1999; Glass and Donaldson 1995) (GenBank: OP265712-13, OP288460-65, OQ418506-07). Based on a maximum likelihood phylogenetic tree of concatenated genes, this novel Diaporthe sp., most closely related to D. stewartii, has not been reported on Cucumis spp. Strains were deposited in the USDA-ARS Culture Collection (NRRL# 64461-62). Koch's postulates were conducted in a greenhouse with mean day temperature of 25°C and 12 hr supplemental lighting. One-month old cucumbers 'Katrina,' grown in rockwool cubes (5 plants per isolate) and potting mix (6 plants per isolate), were inoculated with a one-week-old culture of either strain. The second true leaf was cut and a pipette tip containing an inoculated plug of ½ APDA was placed on the remaining petiole (Mathew et al. 2018). Non-inoculated ½ APDA was used for controls. Plants were tarped for 24 hours to increase humidity and pipette tips removed after one week. After two weeks, petioles were shrunken, tan to golden brown with pycnidia. After 3-4 weeks, stem lesions matching those above were observed on inoculated plants, and plants collapsed. For fruit rot, three Beit Alpha cucumbers were rinsed with tap water, dried, a 5 mm plug was removed from the fruit and replaced with a 5 mm plug of one-week-old fungus on ½ APDA. After 3 days, fruits were water soaked and soft. For root rot, two plates of one-week-old cultures were macerated in 500 mL of sterile water and mixed with 1500 mL of vermiculite. Two seeds of cucumber 'Katrina' were planted into three reps of each isolate and control. All control seeds germinated, but all inoculated seeds experienced pre- or post-emergence damping off. No symptoms were ever observed on any controls. Fungi were isolated from all inoculated tissues as described above. Based on morphology, Diaporthe sp. was isolated from all inoculated plants but never from controls. This Diaporthe sp. may be a new constraint to hydroponic cucumber production, but incidence needs to be determined globally.

How quickly are novel cancer therapies adopted after FDA approval and incorporation into EHR-embedded clinical decision support tools? A description of ordering patterns between users and non-users of an EHR-embedded oncology CDS tool.

508 Background: Oncology clinical decision support (CDS) tools provide up-to-date access to changes in treatment guidelines and notification of newly approved therapies to keep providers informed of rapid changes in the oncology environment. Our goal is to describe ordering patterns of oncologists who use an EHR-embedded CDS tool and those who do not after FDA approval for a new regimen combination and subsequent availability in the CDS tool. Methods: Flatiron Assist is a customizable CDS tool embedded in the electronic health record (EHR) to facilitate selection and documentation of National Comprehensive Cancer Network (NCCN) guideline concordant cancer care. This tool is updated on a monthly basis whereby updates to the NCCN guidelines are incorporated with subsequent communication delivered to users. For this retrospective description, we compared time in days to the first regimen order placed at 13 community oncology practices (348 MDs) using the CDS tool to 30 community oncology practices (294 MDs) not using the CDS tool. We focused on regimens ordered for the combination of nivolumab + platinum doublet (FDA approved on 3/4/22, incorporated into the NCCN guidelines on 3/16/22 and released in the CDS tool on 4/12/22) for neoadjuvant therapy in non-small cell lung cancer (NSCLC). Time to first order placed in practices that did and did not use the CDS tool was described as mean days with 95% confidence intervals (CI) and compared using linear regression with adjustment for number of MDs within a practice and robust standard errors from 4/12/2022 to 5/19/2023 which included 211 unique orders. Results: Of the 211 orders assessed during the observation window, the mean time to first order was 150 days (95% CI 118-182) for CDS tool users and 209 days (95% CI 177-242) for non-CDS tool users, favoring CDS tool users by 59 days (P=0.009, Table 1). Conclusions: Users of an EHR-embedded CDS tool ordered a new regimen sooner after FDA approval than non-users of the CDS tool. Limitations include the narrow sample size and evaluation of only one FDA approval. Future research will investigate whether the same benefit is seen for label expansions compared to net new regimen approvals as well as the impacts on outcomes and indicators of improved quality of care.[Table: see text]

P031 A Novel Oral Appliance Implementation Protocol Using Nightly Portable Monitoring for OSA Patients Failing CPAP therapy

Abstract Introduction Oral Appliance Therapy (OAT) is an effective second line treatment for OSA. However, OAT devices do not have active efficacy monitoring, hence little is known about methods to best identify the optimal degree of mandibular advancement. Methods Consecutive OSA patients undergoing OAT at a sleep disorders service were recruited to participate in a novel titration protocol using nightly monitoring via a portable device (NightOwl®, Ectosense, Belgium). Demographic &amp; sleep study (PSG) data, and key NightOwl® metrics were collected. A treatment PSG was conducted at conclusion of OAT implementation using identified optimal point of mandibular advancement. Results 80 subjects were recruited (52 male, 65%) with mean (±SD) age 49±12 years, BMI 28±4.4 kg/m2, Epworth score (ESS) 9.1±4.9. Baseline PSG showed mean AHI 28±20 events/hr, nadir SpO2 84±21%, time SpO2&amp;lt;90% 8.3±30 minutes. Blood pressure monitoring at baseline showed mean day BP 123/70mmHg and night BP 106/57mmHg. The mean mandibular advancement implemented was 2.9±1.7mm. Post treatment mean ESS was 5.1±3.5 (p&amp;lt;0.001). 62/68 (91%) subjects reported perceived benefit on OAT, 49/53 (92%) reduced snoring, 51/62 (82%) improved sleep, 49/62 (79%) increased energy. Treatment PSG on completion of the protocol showed AHI 14±10 events/hr (p&amp;lt;0.001), nadir SpO2 82±33% (p&amp;gt;0.05), time SpO2&amp;lt;90% 1.2±21 minutes (p=0.04). 48/63 (76%) met the AHI definition of OAT success. Discussion This study demonstrates a novel OAT protocol which led to minimal degree of mandibular advancement, resulting in high rates of symptom benefit and effective treatment of OSA.

Outcomes of early vs late treatment initiation in solid organ transplantation from hepatitis C virus nucleic acid test-positive donors to hepatitis C virus-uninfected recipients: Results from the HCV-TARGET study

Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites). Outcomes were compared between early and late treatments. Early treatment regimens (ETR) (n = 56) were initiated pretransplantation to day 7 posttransplant. Late treatment regimens (LTRs) (n = 102) began median 31 (range, 8-114) days posttransplant. There were 79 kidney, 50 lung, 23 heart, and 6 mixed transplants, similar between groups. HCV RNA was quantifiable in 98% of LTR versus 44.6% of ETR recipients (P < .001). Mean (range) days on treatment were 28 (7-93) ETR and 81 (51-111) LTR (P < .0001). There were no virological failures with ETR, but relapse (n = 3) and nonresponse (n = 2) in LTR (P = .16), including fibrosing cholestatic hepatitis postrelapse (n = 1). Sustained virological response was 100% (95% confidence interval, 93.4-100.0) in ETR (n = 54) and 94.9% (95% confidence interval, 88.5-98.3) in LTR (n = 98). Acute rejection occurred in 11 (19.6%) ETR and 25 (24.5%) LTR. In total, 11 HCV-unrelated deaths occurred: 8 ETR and 3 LTR. Organ transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients was safe. ETR led to fewer virological failures with shorter treatment duration, supporting recommendations to initiate treatment promptly posttransplant.

Associations among post-partum rumen fill and motility, subclinical ketosis and fertility in Holstein dairy cows

This prospective observational study aimed to investigate the association of rumen fill and motility in post-partum Holstein cows with their future reproductive performance and subclinical ketosis (SCK). The study population consisted of two independent data sets: the first (DS1) included 237 cows from 6 herds and the second one (DS2) 709 cows from 9 herds. Rumen Fill Score (RFS) was transformed into a 3 level-trait, representing very low, low and adequate dry matter intake, respectively. A binary Rumen Contraction Score (RCS) was defined as: 0: <2 contractions/2 min, impaired rumen motility and 1: ≥2 contractions/2 min, normal rumen motility. A combined binary trait based on RFS and RCS (RFCS) was also established, representing unsatisfactory and satisfactory rumen function. Three SCK traits were defined, based on 3 different thresholds, SCK_I: BHB≥1,000 mmol/L, SCK_II: BHB≥1,100 mmol/L and SCK_III: BHB≥1,200 mmol/L. Scores were assessed and blood samples collected on day 7 (DS1) or day 8 (DS2), postpartum. Kaplan-Meier survival analysis, multivariable Cox proportional hazards models and Generalized Linear Mixed Models were performed to evaluate the association of rumen and SCK traits with reproduction. Herd, parity, calving season and several postparturient diseases were also included as potential explanatory variables. Mean days from calving to pregnancy after the 1st artificial insemination (AI) and from calving to pregnancy (all AIs) were shorter for levels of rumen traits representing adequate DMI and normal rumen motility; in most cases these differences were statistically significant in both datasets. Cows with adequate DMI and normal rumen motility (only in DS2) had greater hazard (hazard ratio [HR] = 1.84 and 1.61, for RFS and RFCS, respectively) and odds (odds ratio [OR] = 2.49 and 1.98, for RFS and RFCS, respectively) for pregnancy at 1st AI. Assessment of the association of examined rumen traits with hazard and odds for pregnancy at all AIs yielded statistically significant results in both datasets. For RFS, RCS and RFCS, HRs ranged from 1.57 to 3.31 and ORs from 1.95 to 4.83. No statistically significant associations with hazard and odds for pregnancy at 1st or all AIs were detected, for any of the 3 SCK traits, in either dataset. Overall, the combined RFCS trait constantly identified more than twice the number of cows with future reproductive problems than a positive SCK blood test.

Genital pruritus is associated with longer hospital stays, higher costs and increased odds of psychiatric hospitalization among inpatient adults with pruritus in the United States—National inpatient sample (2012–2015)

AbstractBackgroundThough a link between pruritus and worse quality of life (QoL) has been established, little research has delved into which type of pruritus is associated with the highest inpatient burden. A better understanding of how pruritus interacts with other conditions may help reduce the length of hospital stays and improve patient outcomes in fields beyond dermatology.ObjectivesThe objective of this study is to determine which type of pruritus disorder is associated with higher inpatient burden (cost and length of stay) and increased odds of psychiatric hospitalization among inpatient adults with pruritus in the United States.MethodsWe utilized data from the national inpatient sample (NIS) from 2012 to 2015 international classification of diseases, ninth revision, clinical modification (ICD9‐CM). We included male and female adults ≥18 years with primary and secondary diagnoses of pruritus disorders. The outcomes were primary psychiatric diagnosis (yes vs. no), length (days) and the total cost ($) of hospital stay. We explored associations using survey‐weighted binary logistic and linear regression for binary and continuous outcomes and adjusted for covariables (sociodemographic factors).ResultsCompared with other types of pruritus, prurigo nodularis/lichen simplex chronicus (PN/LSC) (odds ratio [OR] = 2.01; 95% confidence interval [CI]: 1.74,2.33), pruritus ani (OR = 2.83; 95% CI: 1.91,4.21) and genital pruritus (OR = 3.51; 95% CI: 2.96,4.16) had increased odds for hospitalization due to psychiatric reasons. Compared with hospitalized patients with any other type of pruritus, hospitalized patients with genital pruritus had 2.37 higher mean days of hospital stay and $10,644 higher mean total cost.ConclusionsGenital pruritus had the highest odds for hospitalization due to a psychiatric disorder, as well as the highest relative increases of average length and cost of hospital stay compared with the five other types of pruritus diagnoses in ICD9‐CM.

Lower Intakes of Key Nutrients Are Associated with More School and Workplace Absenteeism in US Children and Adults: A Cross-Sectional Study of NHANES 2003-2008.

The influence of individual macro- and micronutrients on absenteeism in the United States is largely unknown. The objective of this study was to determine whether nutritional status or nutrient intake were associated with absenteeism from school and work due to illness or injury. Data from NHANES 2003-2008 were used to assess nutrient intake from food and food plus supplements, nutritional biomarker levels, and school and work absenteeism per year in children and adults. Negative binomial regression models were used to predict mean days of missed work per year and to estimate incidence rate ratios (IRRs) of absenteeism by nutrient biomarker status. Of 7429 children, 77% reported missing school days (mean 4.0 days). Of 8252 adults, 51% reported missing work days (mean 4.9 days). Children and adults who reported more absent days had a significantly lower intake of protein and several essential micronutrients from the diet. When nutrients from supplements were included, this negative association was retained for protein, selenium, choline, and DHA in children and for protein, selenium, vitamin K, choline, potassium, fiber, octadecatrienoic acid, and lycopene in adults. Future studies are needed to ascertain whether dietary interventions, such as access to healthier food options and/or dietary supplements, can reduce absenteeism.

Two‐year, single‐centre, real‐life experience with permethrin 5% and benzyl benzoate 25% in 228 children with scabies: A retrospective report

AbstractBackgroundScabies are a significant health issue for institutions and represent a health burden in children. Topical treatments such as permethrin 5% are usually effective but lately, a loss of efficacy has been observed.ObjectivesTo describe demographic data, topical treatment schemes (permethrin 5%; benzyl benzoate 25%) and outcomes in children with scabies over the past 2 years.MethodsWe retrospectively evaluated records of children aged 0 to 14 years with scabies treated in our outpatient clinic from 1 January 2021 to 31 December 2022.ResultsTwo hundred and thirty‐one records were evaluated. Permethrin 5% (P5%) was used as first‐line treatment in 103 children with a success rate of 81.5%; benzyl benzoate 25% (BB25%) was successful in 94.3% of 123 patients. Three patients were lost for follow up and two received other therapies. Mean days of application using P5% increased from 4.1 to 6.8 in 2 years, whereas BB25% showed an opposite trend, from 10 days to 4.7. With the same days of application, the success rate with BB25% was higher (repeated cycle of 2 treatment days, 7 days apart [2 + 2]: 93.3% for BB25% vs. 82.9% for P5%; 3 + 3‐day regime: 91.9% for BB25% vs. 83% for P5%). Twenty‐three out of 26 patients who still had active scabies after the first cycle cleared with a second treatment cycle, with the same topical treatment, or with a different agent. Mild to moderate skin irritation was the only side effect observed (18.4%), more frequently associated with BB25% (81%).ConclusionsDuring the observational period, the use of permethrin decreased while regimen duration increased, probably due to a perceived lack of efficacy. Conversely the use of benzyl benzoate both as first‐line treatment and after permethrin failure increased, despite being more correlated to local inflammation. Both 2 + 2 and 3 + 3 regimes for P5% and BB25% may be considered as suitable first‐line treatment of scabies in children.