Assessment Period Research Articles

Disentangled oil shocks and macroeconomic policy uncertainty in South Africa

This study examines the spillovers among oil shocks and macroeconomic policy uncertainty in South Africa between January 1990 to July 2022. The study arrives at some important findings.From the Diebold and Yılmaz (2012) connectedness analysis, which measures average connectedness, we find a moderate connection between oil shocks and macroeconomic policy uncertainty phenomena. Conversely, the connections among oil shocks and macroeconomic policy uncertainty are greatest at the low and upper quantiles. That is, when these phenomena are experiencing extreme values, the connectedness among them is formidable. Moreover, the study finds that over the period of assessment, macroeconomic policy uncertainty phenomena are net receivers at lower quantiles. Meanwhile, unlike financial policy uncertainty, economic policy uncertainty and political uncertainty become net transmitters at the middle and upper quantiles. On the other hand, the disaggregated oil shocks are net transmitters (receivers) at the low (median) quantiles. Interestingly, their receiver/transmitter roles are mixed at the upper quantile.Finally, using the Quantile-on-Quantile regression analysis, we find that oil shocks generally increase (reduce) macroeconomic policy uncertainty when this uncertainty is already low (high).

Assessing the Benefits and Harms of Pharmacotherapy in Older Adults with Frailty: Insights from Pharmacoepidemiologic Studies of Routine Health Care Data.

The objective of this review is to summarize and appraise the research methodology, emerging findings, and future directions in pharmacoepidemiologic studies assessing the benefits and harms of pharmacotherapies in older adults with different levels of frailty. Older adults living with frailty are at elevated risk for poor health outcomes and adverse effects from pharmacotherapy. However, current evidence is limited due to the under-enrollment of frail older adults and the lack of validated frailty assessments in clinical trials. Recent advancements in measuring frailty in administrative claims and electronic health records (database-derived frailty scores) have enabled researchers to identify patients with frailty and to evaluate the heterogeneity of treatment effects by patients' frailty levels using routine health care data. When selecting a database-derived frailty score, researchers must consider the type of data (e.g., different coding systems), the length of the predictor assessment period, the extent of validation against clinically validated frailty measures, and the possibility of surveillance bias arising from unequal access to care. We reviewed 13 pharmacoepidemiologic studies published on PubMed from 2013 to 2023 that evaluated the benefits and harms of cardiovascular medications, diabetes medications, anti-neoplastic agents, antipsychotic medications, and vaccines by frailty levels. These studies suggest that, while greater frailty is positively associated with adverse treatment outcomes, older adults with frailty can still benefit from pharmacotherapy. Therefore, we recommend routine frailty subgroup analyses in pharmacoepidemiologic studies. Despite data and design limitations, the findings from such studies may be informative to tailor pharmacotherapy for older adults across the frailty spectrum.

RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial: Study rationale and design

Out-of-hospital cardiac arrest (OHCA) occurs in nearly 350,000 people each year in the United States (US). Despite advances in pre- and in-hospital care, OHCA survival remains low and is highly variable across systems and regions. The critical barrier to improving cardiac arrest outcomes is not a lack of knowledge about effective interventions, but rather the widespread lack of systems of care to deliver interventions known to be successful. The RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial is a 7-year pragmatic, cluster-randomized trial of 60 counties (57 clusters) in North Carolina using an established registry and is testing whether implementation of a customized set of strategically targeted community-based interventions improves survival to hospital discharge with good neurologic function in OHCA relative to control/standard care. The multi-faceted intervention comprises rapid cardiac arrest recognition and systematic bystander CPR instructions by 9-1-1 telecommunicators, comprehensive community CPR training and enhanced early automated external defibrillator (AED) use prior to emergency medical systems (EMS) arrival. Approximately 20,000 patients are expected to be enrolled in the RACE CARS Trial over 4 years of the assessment period. The primary endpoint is survival to hospital discharge with good neurologic outcome defined as a cerebral performance category (CPC) of 1 or 2. Secondary outcomes include the rate of bystander CPR, defibrillation prior to arrival of EMS, and quality of life. We aim to identify successful community- and systems-based strategies to improve outcomes of OHCA using a cluster randomized-controlled trial design that aims to provide a high level of evidence for future application.

QOL-08. THE LONG-TERM UTILITY OF METHYLPHENIDATE FOR THE PRESERVATION OF INTELLECTUAL DEVELOPMENT IN CHILDHOOD SURVIVORS OF BRAIN TUMOUR

Abstract BACKGROUND Enduring neurocognitive late effects are a common consequence of childhood brain tumour survivorship. Conceptual modelling of intelligence suggests initial deficits to processing speed and attention lead to the subsequent plateauing of intellectual and academic development. The utility of methylphenidate in improving attentional and processing speed deficits within the early phase of recovery has been previously reported. The longer-term contribution of methylphenidate in preserving intellectual ability through ameliorating these early deficits is yet to be evaluated. METHODS Twenty-nine childhood survivors were matched retrospectively with a no-treatment synthetic control. Intellectual assessments were conducted prior to starting methylphenidate and a minimum of 12 months thereafter. For the no-treatment control group, intellectual data were collected retrospectively from archival records, employing a similar assessment period. Linear Mixed Models were used to assess the influence of methylphenidate on intellectual trajectories between groups and fatigue scores over time. RESULTS Methylphenidate was associated with raw score improvements across all intellectual indices compared to no-treatment controls. Linear Mixed Modelling reported a borderline significant improvement in Processing Speed (t = 1.98, p =.05) for the methylphenidate group. In comparison, a borderline significant (p =.05) within-group decrease in Working Memory scores was reported for the no-treatment group. There was a significant within-group decrease in pooled PedsQL MFS scores between assessments for the treatment group (t = -4.01, p <.01), with the most notable decrease observed in Sleep/Rest Fatigue (t = -10.17, p <.01). CONCLUSIONS Methylphenidate may pose a valuable long-term rehabilitative strategy in preserving Processing Speed in childhood survivors of brain tumour. Whilst our sample size is small, there is tentative evidence for the utility of methylphenidate in alleviating fatigue experienced by childhood survivors.

Prescribing antibiotics for children with dengue infection in Taiwan: who are at risk and who are high prescribers?

Inappropriate antibiotic use contributes to antimicrobial resistance, a global public health threat. The non-specific manifestations of dengue, itself a growing public health threat, lead to avoidable empiric antibiotic prescription, particularly in children. In this national pooled population-based cross-sectional study, we evaluated child and physician characteristics associated with antibiotics prescription in confirmed dengue cases in Taiwan. Linking national health care insurance claims and reports of confirmed dengue cases from 2008 to 2015, there were 7086 children with confirmed dengue with 21 744 outpatient visits and 2520 inpatient admissions. We assessed the presence of antibiotic prescription in outpatient and inpatient settings separately a week before or after the confirmation date. Logistic regression models with generalized estimating equations were applied to identify patient, practitioner, and other factors associated with antibiotic prescription. A total of 29.4% of children <18 years old with dengue who did not have a concomitant bacterial infection were prescribed antibiotics during the 14-day assessment period. Antibiotics prescription was reduced from 13.5% to 6.3% and from 43.2% to 19.3% in outpatient and inpatient settings, respectively, after dengue was confirmed. Young children were more likely to receive antibiotics. Significant variations in antibiotic prescribing across physicians were observed only in outpatient settings: physicians ≥60 years old and physicians practicing at clinics and in non-urban facilities were more likely to prescribe antibiotics. Antibiotics were less likely to be prescribed during an exceptional 2-year epidemic than in other years. Antibiotic prescribing for dengue, an arboviral infection affecting half of the global population, was shown to occur in 29% of paediatric cases in Taiwan. That potentially avoidable antibiotic consumption could be reduced by improving antibiotic stewardship, informed by understanding the conditions under which antibiotics are prescribed and the availability of prevention strategies for viral diseases, including dengue. We identified a number of such factors in this national population-based study.

Anxiety Symptom Trajectories Predict Depression Symptom Trajectories up to Four Years After CBT for Youth Anxiety Disorders.

Long-term data on depression symptoms after cognitive behavioral therapy (CBT) for youth anxiety disorders are scant. We examined depression symptoms up to four years post CBT for anxiety addressing youth age and gender, family social class, and parent mental health as predictors. The sample comprised 179 youth (M age at pre-treatment = 11.5 years; SD = 2.1) in a randomized controlled trial. Clinically assessed anxiety diagnoses and youth and parent-reported anxiety and depression symptoms were measured before, after, and one and four years after CBT. Parent self-reported mental health was measured before CBT. We used regression analyses to determine whether full diagnostic recovery at post-CBT predicted depression trajectories across the four-year assessment period. We used growth curve models to determine whether anxiety trajectories predicted depression trajectories across the four-year assessment period. Youth who lost their anxiety diagnoses after CBT had significantly lower parent-reported depression levels over time, but not lower youth self-reported depression levels. The anxiety symptom trajectory predicted the depression symptom trajectory up to four years post-treatment. There was more explained variance for within-informant (youth-youth; parent-parent) than cross-informants. Being older, female, having lower socio-economic status and parents with poorer mental health were associated with more youth-rated depression over time. However, these demographic predictors were not significant when anxiety symptoms trajectories were added to the models. Successful CBT for anxiety in children is associated with less depression symptoms for as long as four years. Anxiety symptom improvement appears to be a stronger predictor that demographic variables and parent mental health.

Results of a 24-week open-label, non-interventional study on the efficacy and safety of olokizumab therapy in patients with rheumatoid arthritis after switching from anti-B-cell therapy during the SARS-CoV-2 pandemic

In the context of the new coronavirus infection (NCI) COVID-19 pandemic, the rheumatological community is facing new challenges in the treatment of immune-inflammatory rheumatic diseases (IIRDs). It has been shown that rheumatological patients have an increased risk of infections and a severe course of NCI and that IIRD therapy also influences the disease outcomes. In particular, the use of the anti-B-cell medication rituximab (RTM) is associated with a higher risk of severe NCI and increased mortality. The COVID-19 pandemic has highlighted the need to find alternative and safe treatment options for these patients. This work is the continuation of a 12-week study on the efficacy and safety of olok-izumab (OKZ) therapy in patients with rheumatoid arthritis (RA) after switching from anti-B-cell therapy during the SARS-CoV-2 pandemic. Objective: to evaluate the efficacy and safety of OKZ (Artlegia®; solution for subcutaneous administration, 160 mg/ml – 0.4 ml) for the treatment of patients with RA in real-life clinical practice after switching from RTM during the COVID-19 pandemic. Material and methods. The study included 19 patients with a confirmed diagnosis of RA who had received RTM at a dose of 500–1000 mg twice every 14 days at least 6 months ago. As disease activity increased, RTM was replaced with OKZ while therapy with synthetic disease-modifying anti-rheumatic drugs (DMARDs) was continued. At weeks 0, 4, 8, 12 and 24 after switching the biologic DMARD, the number of tender (TJN) and swollen (SJN) joints out of 28, pain intensity on a visual analogue scale, ESR, CRP level, disease activity indices CDAI, DAS28-ESR, DAS28-CRP, HAQ index and the safety profile of the therapy were assessed at each visit. Results and discussion. After 4, 8, 12 and 24 weeks of OKZ administration, there was a statistically significant decrease in mean TJN (from 10 to 6.0, 3.0, 5.0 and 4.0, respectively; p &lt; 0.05) and SJN (from 7.0 to 3.0 by week 4 and to 2.0 by weeks 8, 12 and 24; p &lt; 0.05). At the same time, a decrease in CRP and ESR values was also observed: median CRP decreased from 18 to 0.6 mg/l by week 4 and to 0.5 mg/l by weeks 8, 12 and 24 (p &lt; 0.05), ESR from 30 to 5 mm/h in each study period (p &lt; 0.05). CRP levels normalized by week 4, regardless of baseline values. All RA activity indices showed a positive dynamic compared to baseline values from week 4 onwards in each assessment period. After weeks 4, 8, 12 and 24, the median DAS28-ESR decreased from 5.50 to 3.57; 3.30; 3.08 and 3.01 (p &lt; 0.05); DAS28-CRP – from 5.30 to 3.46; 3.23; 3.26 and 3.12 (p &lt; 0.05); CDAI – from 27.0 to 17.0; 12.0; 15.0 and 12.0 (p &lt; 0.05), respectively. All patients showed a decrease in pain by the 4th week of observation. A statistically significant improvement in functional status was observed after the 4th week of therapy and was maintained until week 24. The median HAQ index decreased from 1.62 to 1.50 at weeks 4, 8 and 12 and to 1.12 at week 24 (p &lt; 0.05). Conclusion. The study showed that the non-medical switch from RTM to OKZ during the COVID-19 pandemic was effective and safe.

Remote Monitoring of Coffee Leaf Miner Infestation Using Machine Learning

The coffee leaf miner (Leucoptera coffeella) is a key pest in coffee-producing regions in Brazil. The objective of this work was to evaluate the potential of machine learning algorithms to identify coffee leaf miner infestation by considering the assessment period and Sentinel-2 satellite images generated on the Google Earth Engine platform. Coffee leaf miner infestation in the field was measured monthly from 2019 to 2023. Images were selected from the Sentinel-2 satellite to determine 13 vegetative indices. The selection of images and calculations of the vegetation indices were carried out using the Google Earth Engine platform. A database was generated with information on coffee leaf miner infestation, vegetation indices, and assessment times. The database was separated into training data and testing data. Nine machine learning algorithms were used, including Linear Discriminant Analysis, Random Forest, Support Vector Machine, k-nearest neighbors, and Logistic Regression, and a principal component analysis was conducted for each algorithm. After optimizing the hyperparameters, the testing data were used to validate the model. The best model to estimate miner infestation was RF, which had an accuracy of 0.86, a kappa index of 0.64, and a precision of 0.87. The developed models were capable of monitoring coffee leaf miner infestation.

Effect of clinician's experience and expertise on the inter- and intra-observer reliability of the computed tomography-based classification systems in posterior malleolus fractures.

Three computed tomography (CT)-based classifications, including Haraguchi, Bartoníček-Rammelt, and Mason-Molloy systems, have been developed to better determine the characteristics of posterior malleolus fractures (PMFs). The aims of this study were (1) to determine the intra- and inter-observer reliability of the computed tomography-based classification systems and (2) to investigate the clinical experience and expertise on their reliabilities. Sixty-seven preoperative ankle CT scans of 67 adult patients with "ankle fracture with the involvement of the posterior malleolus"'' were retrospectively identified. CT images were assessed by 10 observers with different levels of clinical experience from 2 different specialties, including orthopedics and radiology. The observers were asked to classify PMFs according to 3 CT-based classifications on 2 separate occasions with a 4-week interval. Cohen's κ values were measured for 2 raters and Fleiss' κ values were measured for 3 raters and more. Overall, each classification had moderate to very good intraobserver reliability (κ=0.41 to 0.95, P < .01) as well as moderate interobserver reliability for each of the 2 separate assessments (κ=0.41 to 0.60, P < .01 for the first occasion; κ=0.44 to 0.59, P < .01 for the second occasion). Interobserver agreement among the foot and ankle surgeons regarding the Haraguchi and Bartoníček classifications was substantial for both assessment periods, whereas there was a moderate agreement for the Mason classification. Orthopedic residents showed moderate interobserver agreement in each period for both Bartoníček and Mason classifications. Radiology experts illustrated slight and fair agreements in the 2 assessments for Mason classification, moderate agreement in both assessments for Haraguchi classification, and substantial to moderate agreement in the first and second assessments for Bartoníček classification, respectively. Computed tomography-based classification system for PMFs demonstrated moderate interobserver reliability as well as moderate to very good intraobserver reliability. Moreover, foot and ankle specialists exhibit enhanced K values for both inter and intraobserver reliability for each classification system, consistency seems to increase as the interest in the field condenses.

Fixed-duration pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL: the phase 1b BRUIN trial

AbstractPirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) were treated with fixed-duration pirtobrutinib plus venetoclax (PV) or pirtobrutinib plus venetoclax and rituximab (PVR) in this phase 1b trial. Prior covalent BTKi therapy was allowed, but not prior treatment with venetoclax. Patients were assigned to receive PV (n = 15) or PVR (n = 10) for 25 cycles. Most patients (68%) had received prior covalent BTKi therapy. At the data cutoff date, the median time on study was 27.0 months for PV and 23.3 months for PVR. Overall response rates were 93.3% (95% confidence interval [CI], 68.1-99.8) for PV and 100% (95% CI, 69.2-100.0) for PVR, with 10 complete responses (PV: 7; PVR: 3). After 12 cycles of treatment, 85.7% (95% CI, 57.2-98.2) of PV and 90.0% (95% CI, 55.5-99.7) of PVR patients achieved undetectable minimal residual disease (<10-4) in peripheral blood. Progression-free survival at 18 months was 92.9% (95% CI, 59.1-99.0) for PV patients and 80.0% (95% CI, 40.9-94.6) for PVR patients. No dose-limiting toxicities were observed during the 5-week assessment period. The most common grade ≥3 adverse events (AEs) for all patients included neutropenia (52%) and anemia (16%). AEs led to dose reduction in 3 patients and discontinuation in 2. In conclusion, fixed-duration PV or PVR was well tolerated and had promising efficacy in patients with R/R CLL, including patients previously treated with a covalent BTKi. This trial was registered at www.clinicaltrials.gov as #NCT03740529.

Expert Panel Recommendations for a Standardized Ambulatory Glucose Profile Report for Connected Insulin Pens.

Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single, clinically useful report. An extensive literature review and identification of examples of current connected insulin pen reports was performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. The AGP Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the ambulatory glucose profile (AGP) curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio (ICR), average bolus insulin dose and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

Stress and exhaustion among medical students: a prospective longitudinal study on the impact of the assessment period on medical education

BackgroundStress significantly affects both the physical and emotional health of individuals, particularly students in health-related fields. Medical students in Brazil face unique challenges due to the demanding nature of their studies, especially during assessment periods, which heighten academic pressure. These pressures often lead to poor coping strategies and mental health concerns. It is crucial to understand the complex dynamics of stress within medical education to develop strategies that improve student well-being and promote a healthier academic environment. This study aims to investigate the intricate relationship between assessment periods and stress levels among medical students. It seeks to understand how academic demands and sociodemographic factors contribute to stress dynamics during these periods.MethodsAn online observational, longitudinal, and prospective study was conducted from February to October 2022. Medical students were recruited through snowball sampling and participated in surveys administered via Google Forms at two timepoints: before (T1) and during (T2) assessment periods. The surveys collected sociodemographic data and stress symptoms using Lipp’s Inventory of Stress Symptoms for Adults (LSSI).ResultsThe transition from T1 to T2 was defined by a rise in the prevalence of stress from 59.6 to 84.2% (p = 0.001) and a decline in symptom-free students from 40.4 to 15.8% (p = 0.001). There was a significant increase in exhaustion, from 12.3 to 31.6% (p = 0.0001). Higher stress levels were notably more prevalent among younger students (≤ 24 years), females, those from wealthier families, students without scholarships, those without prior degrees, and those in the clinical phase of their studies. However, non significant correlations were found between these sociodemographic and academic factors and the increase in stress.ConclusionThe findings highlight significant concerns regarding the mental health of medical students during assessment periods, marked by increased stress and exhaustion levels. These results emphasize the need for proactive interventions to manage stress effectively in medical education, considering its profound impact on students’ well-being.

Asymmetric Return Connectedness Among Indian Equity Sectors: Insights from Recent Global Disruptions

This article aims to study asymmetric shock transmission among India’s National Stock Exchange sectoral indexes before and amid the COVID-19 crisis and the Russian–Ukraine feud using an asymmetric time-varying parameter vector autoregressive connectedness technique. The daily closing price of equity sector indexes from 1 January 2018 to 31 March 2023 were used. The research reveals strong sectoral return interconnectedness, with negative returns spillover dominating the assessment period. COVID-19 substantially impacted connectedness more than the Russian–Ukraine feud. The sectors such as bank, private bank and financial services were net transmitters of risk, and information technology was the net recipient of risk throughout the assessment period, indicating these sectors are not much affected by these crises. Sector return spillover patterns were similar during the epidemic and the Russian–Ukraine dispute, except for the oil and gas and metal sectors, which shifted roles. These findings suggest that policymakers must recognize and assess the peculiarities of industries that are high-risk transmitters when formulating strategies to prevent market failure or mitigate risk transmission to others. Investors may benefit from recognizing industries that operate as risk transmitters and receivers to create effective risk-mitigation investment strategies amid turbulent times.

A collagen biostimulator improves photoaging pigmentation

AbstractPhotoaging pigmentation conditions such as senile lentigo and melasma show epidermal melanogenic activity and dermal abnormalities, including collagen degradation. A dermal rejuvenation strategy with skin‐lightening therapy directly acting on melanocytes is suggested for photoaging pigmentation. This study investigates whether collagen biostimulation can result in skin lightening of photoaging skin. A split‐face clinical trial was conducted, involving 40 subjects with facial melasma and senile lentigo. Subjects received a poly‐DL‐lactic acid (PDLLA) treatment on one side of their face, whereas the contralateral side received a treatment of normal saline as a control. Assessments were scheduled every month after completing treatments for up to 3 months. Pigmentation was evaluated using the L* value as measured with a chromameter and by investigator global assessment scores (IGA). Subjects reported different outcomes in terms of overall skin quality, including pigmentation, wrinkles and elasticity. Skin biopsies were obtained before the treatment and 4 weeks after completing the treatment. Fontana‐Masson, Masson‐Trichrome and Verhoeff‐van Gieson staining, and fibroblast‐specific protein 1 (FSP1) immunostaining were conducted. The PDLLA treatment demonstrated significant improvements in the L* values and IGA scores from 8 weeks after the subject completed their treatments. These improvements were sustained over a 12‐week assessment period. The subjects reported substantial reductions in both pigmentation and wrinkle severity and elasticity throughout the assessment period. Fontana‐Masson staining showed a marked decrease in pigmentation upon a PDLLA injection compared to the baseline values. Increased immunogenicity of FSP1 and increases in collagen and elastic fibre staining were observed. This study demonstrated remarkable improvements in photoaging pigmentation along with collagen production with a collagen biostimulator. Thus, collagen biostimulators represent a promising therapeutic approach for addressing photoaging signs associated with melasma and senile lentigo. (ClinicalTrials.gov Identifier: NCT05913102).

Durable complete response and overall survival in patients with heavily pretreated, poor-prognosis non-Hodgkin lymphoma to immunoactivating AVM0703 with few and mild drug-related adverse effects.

7077 Background: In 2022, the majority of new cancer drugs in clinical development are aimed at targets that are already saturated with approved drugs1. This is of concern to patients, payers, sponsor/investors, and regulatory agencies. AVM0703 activates a unique immune response mobilizing an endogenous gamma delta TCR+ and invariant TCR+ bispecific Natural Killer T-like cell (γδTCR+iTCR+NKT) (PCT/US21/19773), that has demonstrated clinical anti-cancer activity against a variety of solid and blood cancers. The potential for AVM0703 to fill a gap in the “no-option” R/R NHL treatment landscape led to the launch of the AVM0703-001 clinical trial (The OPAL Study, NCT04329728). 1) Fougner C et al. Herding in the drug development pipeline. Nat Rev Drug Discov. 2023 Aug;22(8):617-618. Methods: An open-label phase 1 trial evaluating the safety and preliminary efficacy of AVM0703 was completed in patients with hematological malignancies. AVM0703 was administered as a single intravenous (IV) infusion to patients enrolled into a 3+3 dose escalation design. Consolidation therapy of investigator’s choice was allowed, preferably 28 days after AVM0703. For each cohort, 3-6 patients were treated, and dose escalation permitted only after the cohort completed a 7-day dose limiting toxicity (DLT) assessment period with no more than 1 DLT. Patients ≥12 years and &gt;40 kg diagnosed with WHO classified lymphoid neoplasms with R/R disease ineligible for transplant or CAR-T were included. The database has not been formally locked and a cutoff date of Dec 13, 2023, is used for presentation of these Phase 1 results. Results: In summary, 17 patients, 39-86 years of age (median 64) with a median of 4 prior lines (range: 1 to 10) received AVM0703 at 6, 9, 12, 18 and 21 mg/kg. Fifteen (88%) were poor prognosis and 4 had CNS involvement. Only 13 of 17 (76.5%) experienced study-drug related adverse events (AEs) during the DLT period; 15 AEs were grade 1 (78.9%), 2 were grade 2 (10.5%), and 2 were grade 3 (10.5%). The most common AEs were insomnia (N=5), hyperglycemia (N=3), and pruritis (N=2). The total number of All-grade TEAEs recorded in 17 patients was 114 within 30 days post dose, with 98.2% of grades 1-3. Median overall survival (OS) in all dose cohorts was 13.3 months, with 8 of 17 patients alive as of 13 Dec 2023. The recommended Phase 2 dose (RP2D) was determined as 18 mg/kg. For the 18 mg/kg group (N=6), long term durable responses were obtained in 66% (3 CR, 1 PR) with an additional patient converting to late CR, nine months survival was 100%, and median OS has not been reached with follow up between 15.9 and 27.8 months (83% still alive). No safety signals have been identified. Conclusions: RP2D AVM0703, with consolidation therapy at day 28 median (range 7 to 240 days) showed no concerning safety signals and promising long-term survival. Clinical trial information: NCT04329728 .

A phase I/II study of maplirpacept in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (OC): Phase 1 results.

e17546 Background: CD47, an overexpressed factor correlated with poor clinical characteristics and prognosis in OC, is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a signal to suppress macrophage phagocytosis. Maplirpacept (PF-07901801) is a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG4, enhancing phagocytosis by blocking CD47. Blockade of CD47, both alone and combined with doxorubicin, has shown anti-tumor activity in vitro and in vivo in xenograft animal models. PLD 40mg/m2 conveyed poor efficacy (PFS 4 months; ORR 8%), as did bevacizumab + PLD (PFS 5 months; ORR 14%) (AURELIA), highlighting the need for new treatments for platinum-resistant OC. C4971002 [NCT05261490] is an open label, multicenter dose-escalation and expansion study evaluating the safety, preliminary anti-tumor activity, pharmacokinetics and -dynamics of maplirpacept in combination with PLD in patients with platinum-resistant recurrent OC. Methods: The study included adults with platinum-resistant recurrent epithelial OC (PD ≤6 months after platinum-based therapy or unable/unwilling to receive platinum-based therapy). PLD while platinum-resistant or directly prior to study was not permitted. Patients received maplirpacept (12mg/kg Dose Level [DL] 1; 24mg/kg DL2; 48mg/kg DL3) weekly in Cycle 1 and every 2 weeks in Cycle 2+, and PLD (40mg/m2) on Day 1 of each 4-week cycle. Assessments of adverse events (AEs) were based on CTCAE v5.0. Response assessments (RECIST v1.1) were performed every 8 weeks. Results of the Phase I portion, aiming to evaluate the DLTs, the MTD and the RP2D, are presented as of 18 December 2023, after all patients completed the 28-day DLT assessment period. Results: 10 patients were treated (DL1 n=3; DL2 n=3; DL3 n=4) with a median (min, max) age of 69 (53, 77) years, 80% ECOG 1, 60% serous adenocarcinoma. Median (min, max) treatment duration was 14 (8, 32) weeks. Most common adverse events are shown in the table. No DLTs occurred in the assessment period. 1 serious AE (gait disturbance &amp; muscle weakness) related to maplirpacept was reported (DL3). 2 deaths occurred &gt;120 days after 1st dose, both due to disease. 5 (50%) patients had a best response of stable disease, 2 of which were treated into at least Cycle 6. Conclusions: Despite immature anti-tumor activity, maplirpacept + PLD was tolerable at all dose levels, not reaching the MTD. The encouragingly tolerable dose of 48mg/kg thus represents the RP2D which could support further development for this population. Clinical trial information: NCT05261490 . [Table: see text]

Feasibility of implementing whole genome sequencing into routine oncology care.

e15181 Background: The promise of precision oncology to deliver improved patient outcomes is dependent on the availability and appropriate interpretation of individual patient tumor sequencing results. While routine use and clinical utility for comprehensive genomic profiling (CGP) is growing, there are limited data in the U.S. to support the use of whole genome sequencing (WGS) outside of limited specific indications (i.e. acute myeloid leukemia, pediatric, sarcoma). This study highlights reports on the feasibility from a pilot project offering paired germline/somatic WGS to a cohort of oncology patients at an academic medical center. Methods: Eligible patients included those with an active cancer diagnosis, available tumor, and a treating provider within Weill Cornell. There were no specific restrictions. Providers selected patients with newly diagnosed metastatic cancers, rare tumors, refractory tumors, and/or those with uninformative germline testing for hereditary cancer. Reportable germline findings were pathogenic or likely pathogenic (P/LP) variants in known cancer predisposition genes and/or genes on the American College of Medical Genetics list of reportable secondary findings. Clinical actionability of somatic results was determined using the cBioPortal Database and Oncology Knowledgebase. Ordering providers disclosed results to patients. Barriers to enrollment were explored and addressed. Results: Between January 2021 and December 2023, 82 patients had germline/somatic WGS. The most common tumors included breast (17%), prostate (11%), renal (10%), lung (7%), bladder (7%), and colon (5%), with 48% of the cohort represented by rare tumors. Six cases (7.3%) had insufficient quantity/quality. WGS detected single nucleotide variants in 84% (n = 69) of cases, with 39% (n = 27) of those having clinical actionability in the patient’s tumor. Additional somatic results included copy number variants in 83% (n = 68) and transcriptome variants in 17% (n = 14). P/LP germline variants were found in 17% (n = 14) of cases. Barriers to enrollment included: difficulty identifying which patients would benefit most from WGS, lengthy in-person consent process, limited access to pretest genetic counseling, and difficulty procuring and processing tissue specimens. Availability of reflexive in-house CGP since August 2022 also resulted in decreased uptake of this service. Several interventions were implemented to address the barriers, resulting in an increase in enrollment. Conclusions: Paired germline/somatic WGS identified clinically relevant variants for patients with diverse tumors. Results were used to direct treatment decisions and determine eligibility for clinical trials as well as inform hereditary cancer predisposition. An assessment period after WGS implementation is needed to improve workflow. Further research aims to determine optimal accessibility and utilization of WGS for oncologic patients.

Advancements and 4E + Q performance analyses in solar drying for maize kernels preservation: A comprehensive review

AbstractThe world's population is projected to increase, impacting a 60% rise in food production demand by 2050, including the demand for maize. Currently, maize production is estimated to reach 1510 million tons in 2023, necessitating suitable methods for preserving maize kernels to maintain quality and reduce post‐harvest agricultural losses. Although drying methods present a viable solution to address this issue, the majority of farmers in Indonesia still use conventional drying methods, such as open sun drying, which has several drawbacks. Hence, solar drying systems aim to overcome these limitations by harnessing renewable, clean, sustainable, and eco‐friendly energy to support the sustainable development goals (SDGs). This research comprehensively reviews the progress of solar drying technology, providing insights into its working principles, innovative designs, and operational modes across various types of solar dryers. The 4E + Q analysis provides information regarding the performance of solar drying systems, including energy analysis to determine the quantity of energy utilized and exergy analysis to demonstrate irreversibility in thermodynamic processes. Additionally, this analysis highlights environmental impacts such as CO2 emissions and mitigation efforts, while considering economic aspects through lifecycle assessment and payback period methods. The quality assessment of dried maize kernels according to the standards set by the Indonesian National Standard (SNI) is conducted, including proximate analysis, aflatoxin levels, color measurements, and internal cracking analysis.Practical applicationsDrying technology is essential for the food preservation process, enabling the maintenance of product quality and extending storage life by reducing the moisture content to eliminate the activities of microbial agents. The application of solar drying technology harnesses solar radiation as the primary energy source, making it well‐suited for crops like paddy, maize, cassava, etc. The development of solar dryers continues through modifications and the addition of auxiliary systems to achieve more efficient, economical, and sustainable technologies. The hope is that in the future, these technologies can be adopted by farmers on an industrial scale due to low operational costs, ease of operation, and controllable operating conditions. The methodological approach is necessary to evaluate the performance of solar dryers and the quality of dried products through a 4E + Q analysis, it provides information on energy consumption, exergy flow, economic considerations, environmental aspects, and quality assessments against national quality standards (SNI).

Assessment Tool by UNICEF and LATCH Scoring System for Identification of Inadequacy of Breastfeeding in Early Neonatal Period: An Observational Cross-sectional Comparative Study

Background: Breast milk is the most ideal nourishment for a neonate with a high level of bio-efficacy. Learning the right breastfeeding technique is a challenging job, especially for new and young mothers; hence, there is a need for a valid and reliable measuring tool to determine the adequacy of breastfeeding. Objective: To check the adequacy of breastfeeding in mother–neonate dyads using breastfeeding assessment tools by comparing UNICEF and LATCH scoring systems and to test the reliability of the tools through test–retest reliability. Design: An observational cross-sectional comparative study. Setting: Department of Neonatology, Fortis Escorts Hospital, Jaipur, Rajasthan, India. Methods: All stable neonates of ≥34 weeks gestational age born at the private tertiary care hospital were included in the study. Dyads in which breastfeeding was initiated within 6 hours of life were assessed using both LATCH and UNICEF tools on days 1 and 2 of life in the case of normal vaginal delivery and on days 1, 2 and 3 in caesarean deliveries, and were further followed up on days 5 and 7. Results: The median LATCH score and UNICEF score for breastfeeding showed an increase throughout the assessment period. A moderately positive correlation (Spearman’s rho = 0.732) was noticed between the two scores on day 1 of the assessment. On day 2 (Spearman’s rho = 0.81) and day 3 (Spearman’s rho = 0.735), a high positive correlation between the two tools was observed. However, day 4 revealed a low positive correlation (Spearman’s rho = 0.456). Meanwhile, the follow-up scores of both tools showed a high positive correlation (Spearman’s rho = 0.713). Conclusion: The study evidenced a positive correlation between the LATCH and UNICEF scores; both scoring systems displayed a good percent agreement on all the five assessment days. The test–retest reliability was high between the tools on days 1 and 2.

#2251 Long-term systolic blood pressure variability as an independent risk factor for cardiovascular events in kidney transplant recipients

Abstract Background and Aims Cardiovascular (CV) events represent the main cause of death in patients undergoing renal transplantation. Several studies have described the role of blood pressure variability (BPV) in predicting all-cause mortality and fatal and non-fatal CV events in the general population and in diabetic patients. Systolic blood pressure variability (SBPV) has recently been proposed as a predictor of clinical outcomes in patients with chronic kidney disease. However, evidence is still scarce about the prognostic role of BPV in the setting of renal transplantation. The aim of the study was to evaluate the role of long-term SBPV in the development of fatal and non-fatal CV events (myocardial infarction, unstable angina or revascularization, stroke and hospitalization for heart failure) in subjects undergoing kidney transplantation. Method We performed a single-center retrospective observational analysis in a cohort of 272 kidney transplant patients (mean age 64 ± 13 years, 66% men), with a transplant duration ≥12 months and with at least 6 blood pressure measurements at defined intervals (3 months ±15 days) over an assessment period of 18 months. BPV was expressed as standard deviation of ambulatory systolic blood pressure (SBP) and patients were accordingly classified in tertiles (low &amp;lt;9.3 mmHg, medium 9.3-13 mmHg, high &amp;gt;13 mmHg). The role of SBPV was analyzed by Kaplan-Meier (logrank) and its independent effect by Cox Regression. Results Over a mean follow-up of 58.7 ± 17.2 months, 27 subjects (9.9%) developed CV events. For each increase of 2.7 mmHg in SBP standard deviation, the risk for fatal or non-fatal CV events increased almost 3-folds (P = 0.02) and patients in the highest tertile of SBP standard deviation showed a 4-fold increased risk (P = 0.01) (Fig. 1). This relationship was maintained even after incremental adjustment for time-averaged pulse pressure, age, diabetes, prior CV event, and dialysis vintage (HR 3.2, 95% CI 1.1–10.0, p 0.04) (Table 1). Conclusion Long-term BPV represents an independent risk factor for CV events in kidney transplant patients. It is therefore essential to seek for stable long-term blood pressure levels in this population in order to minimize the residual CV risk.