Start Date Research Articles

Real-world treatment patterns and outcomes in US patients (pts) with advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy (PBC) and anti–PD-(L)1 treatment.

8627 Background: Effective treatment options for advanced or metastatic NSCLC are limited, especially for pts who progress after treatment with PBC and an anti–programmed cell death 1 protein (PD-1) or ligand 1 (PD-L1) regimen. Examining real-world treatment patterns and long-term outcomes, we report on progression-free survival (PFS) and overall survival (OS) in pts with NSCLC who previously received PBC and anti–PD-(L)1 regimens. Methods: This study used the nationwide Flatiron Health electronic health record–derived deidentified database. Pts included in the analysis were ≥18 years old with an initial diagnosis of advanced or metastatic NSCLC and an ECOG PS of 0 or 1 who had received prior PBC and anti–PD-(L)1 therapy in 1 (in combination) or 2 (in sequence) lines and had initiated ≥1 subsequent line of treatment between 2018 and 2023; the start date of subsequent treatment (defined as the index regimen) was the index date. Pts were followed up until death or last available data through Mar 31, 2023. Pt characteristics, treatment patterns, and outcomes were analyzed for the overall pt group and according to initial treatment cohort (cohort 1: first-line [1L] PBC plus anti–PD-(L)1; cohort 2a: 1L PBC and second-line [2L] anti–PD-(L)1; or cohort 2b: 1L anti-PD-(L)1 and 2L PBC). PFS and OS were estimated using Kaplan-Meier methods. Results: Of 1793 pts, most were in cohort 1 (73.5%), with fewer pts in cohorts 2a (22.5%) and 2b (4.1%). The majority of pts in cohort 2b had PD-L1 ≥50% (n = 57, 78.1%), while the percentage was lower in cohorts 1 (n = 262, 19.9%) and 2a (n = 72, 17.9%). Most pts (n = 1626, 90.7%) had stage IV disease. Median time from advanced diagnosis to index date was 10.5 months (range, 1.1-103.8); median follow-up from index date was 7.8 months (range, 0.0-65.0). A broad range of treatments were used after PBC and anti–PD-(L)1 regimens; among all pts, the most common were docetaxel + ramucirumab and docetaxel monotherapy. Among all pts, median PFS and OS from the time of starting these index regimens were 5.29 and 11.20 months, respectively; PFS and OS were similar across cohorts. Conclusions: A broad range of subsequent treatments were used following PBC and anti–PD-(L)1 regimens, most commonly docetaxel with or without ramucirumab. Short median PFS and OS underscore a significant unmet need among pts previously treated with PBC and anti–PD-(L)1. [Table: see text]

A handheld device for intra-cavity and ex vivo fluorescence imaging of breast conserving surgery margins with 5-aminolevulinic acid

BackgroundVisualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration. However, this prototype device was not designed to image the surgical cavity for remaining carcinoma after the excised lumpectomy specimen is removed. A new handheld fluorescence (FL) imaging prototype device, designed to image both excised specimens and within the surgical cavity, was assessed in a clinical trial to evaluate its clinical utility for first-in-human, real-time intraoperative imaging during index BCS.ResultsThe imaging device combines consumer-grade imaging sensory technology with miniature light-emitting diodes (LEDs) and multiband optical filtering to capture high-resolution white light (WL) and FL digital images and videos. The technology allows for visualization of protoporphyrin IX (PpIX), which fluoresces red when excited by violet-blue light. To date, n=17\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n = 17$$\\end{document} patients have received 20mgkg\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$20\\frac{\ ext {mg}}{\ extrm{kg}}$$\\end{document} bodyweight (BW) 5-ALA orally 2-4 h before imaging to facilitate the accumulation of PpIX within tumour cells. Tissue types were identified based on their colour appearance. Breast tumours in sectioned lumpectomies appeared red, which contrasted against the green connective tissues and orange-brown adipose tissues. In addition, ductal carcinoma in situ (DCIS) that was missed during intraoperative standard of care was identified at the surgical margin at <1 mm depth. In addition, artifacts due to the surgical drape, illumination, and blood within the surgical cavity were discovered.ConclusionsThis study has demonstrated the detection of a grossly occult positive margin intraoperatively. Artifacts from imaging within the surgical cavity have been identified, and potential mitigations have been proposed.Trial RegistrationClinicalTrials.gov Identifier: NCT01837225 (Trial start date is September 2010. It was registered to ClinicalTrials.gov retrospectively on April 23, 2013, then later updated on April 9, 2020, to reflect the introduction of the new imaging device.)

A decade of analysis describe of maternal and neonatal characteristics of live births in southern Brazil

Introduction: Child health is conditioned by the circumstances of pregnancy, childbirth, and early life. Objective: To describe the maternal and neonatal characteristics of live births (LBs) in the Information System on Live Births of Santa Catarina (SC), Brazil. Materials and methods: A cross-sectional study describedthe maternal and neonatal characteristics of 940,059 LBs, from 2010 to 2019. Pearson’s chi-square test and Fisher’s exact test were conducted, with a statistical significance level of p &lt; 0.05. Results: The mean values of maternal age, number of live children, and number of fetal deaths as well as abortions were 27.1 years, 0.9, and 0.2, respectively. The averages of the number of gestation weeks, number of prenatal consultations, the start date of the prenatal care, and birth weight were 38.5 weeks, 8.1 months, 2.5 monthsand 3,217.1 grams, respectively. Low birth weight (LBW) was prevalent among mothers without education (p &lt; 0.001), including those without prenatal visits (p &lt; 0.001). A higher prevalence of being underweight was observed among female neonates (p &lt; 0.001) and with a maternal age of ≥ 40 years (10.8%; p &lt; 0.001) compared to newborns with good vitality. Newborns with good vitality had a low prevalence of underweight (p &lt; 0.001). The frequency of the variables studied increased, comparing the beginning and end of the period and whether the differences are statistically significant. Conclusions: The study draws attention to the need for interventions to improve the indicators that determine LBW.

PIK3CA testing and treatment patterns among patients with metastatic breast cancer in US community clinical practice.

e13059 Background: PIK3CA mutations are present in ~35-40% of HR+/HER2- breast cancer patients. Targeted treatments are approved and in development for patients with advanced disease, and clinical guidelines recommend biomarker testing. This retrospective cohort study characterized PIK3CA mutation testing and treatment patterns among HR+/HER2- metastatic breast cancer (mBC) patients in United States (US) community clinical practices. Methods: We used the nationwide Flatiron Health electronic health record-derived de-identified database to select patients diagnosed with HR+/HER2- mBC from January 2011 to May 2023. We described baseline characteristics of patients tested and not tested for PIK3CA mutation. We captured rates of PIK3CA mutation testing (anytime and ≤1 year) prior to starting first-line (1L), second-line (2L), and third-line (3L) treatment; test and sample types; secular trends over time; and test turnaround time (TAT). Treatment patterns for patients with a PIK3CA-mutated tumor were also described from 2019 onwards. Results: Among 14,246 HR+/HER2- mBC patients treated at community sites, 4,537 had a PIK3CA mutation test result during the study period. 25% of patients had more than one PIK3CA mutation test. Test rates increased from 2011 to 2023 for all patients starting 1L, 2L, or 3L during the study period (Table). In 2023, the percentage of patients tested anytime prior to 1L, 2L, and 3L start dates were 11% (37 of 324 patients), 52% (140 of 271 patients), and 65% (133 of 204 patients), respectively. Among tested patients, those who were tested between 1L and 2L increased from 32% in 2018 to 45% in 2023. Median time from mBC diagnosis date to first test was variable across years: 8, 10, and 3 months in 2018, 2020, and 2022, respectively. During the study period, most PIK3CA mutation tests were next-generation sequencing (NGS) (88%) and used tumor tissue (72%). Median TAT decreased from 12 days in 2018 to 7 days in 2023. Among patients with a PIK3CA-mutated tumor in 2019 and onwards who received treatment, 36% of patients received alpelisib-containing regimens. Conclusions: PIK3CA mutation testing in HR+/HER2- mBC patients has increased over time in community clinical practice, and timing has shifted to earlier lines of therapy among tested patients. However, overall testing and subsequent treatment with pathway-directed therapy are still low despite clinical guidelines, which may reflect potential gaps in access to PIK3CA mutation testing and the continued unmet need regarding available targeted agents within the current treatment landscape. [Table: see text]

Combined Use of Multiple Cloud‐Free Snow Cover Products in China and Its High‐Mountain Region: Implications From Snow Cover Identification to Snow Phenology Detection

AbstractAccurate snow phenology detection, including snow cover days (SCD), snow start date (SSD), and snow end date (SED), is increasingly important for understanding mountain hydrology such as snow heterogeneity and snowmelt seasonality. Multiple cloud‐free daily snow cover products have recently been developed in China, employing diverse retrieval algorithms and cloud‐gap‐filling methods, resulting in varying accuracy levels. However, comprehensive analysis of differences among products and their impact on snow phenology detection is lacking. This study systematically evaluates eight state‐of‐the‐art snow cover products in China, focusing on the challenging Tibetan Plateau (TP). We introduce a novel metric, the consistency‐weighted correlation coefficient (CWR), customized for SSD and SED detection, and propose product‐combining schemes like “ensemble voting” and “sensor preference” to enhance reliability. Our findings highlight the prime influence of retrieval algorithms under clear‐sky conditions on accuracy, surpassing the importance of cloud‐gap‐filling methods. Specifically, a product optimizing normalized difference snow index thresholds for diverse landcover types consistently outperforms others in detecting all three snow phenology parameters, with correlation coefficients for SCD of 0.82 and 0.69, and CWR values for SSD of 0.54 and 0.40, and for SED of 0.53 and 0.37 in both China and the TP, respectively. Moreover, our proposed scheme combining three high‐accuracy products significantly enhances snow cover identification and SCD detection, especially when the best‐performing product alone faces substantial uncertainty. These findings provide immediate, crucial implications for optimizing the use of multiple cloud‐free products to enhance snow phenology detection, ultimately advancing the applicability of derived snow parameters in mountain hydrology research.

Incidence and risk factors for central nervous system (CNS) metastasis (met) in patients (pts) with stage III melanoma treated with adjuvant (ADJ) anti-PD1 immunotherapy (IMT).

9581 Background: The identification of risk factors for CNS met in stage III melanoma pts will facilitate the development of personalized surveillance strategies. Previously we characterized the incidence (3.6%, 9.6%, and 15.8% at 1, 2, and 5 yrs) and risk factors for CNS met in pts diagnosed with stage III melanoma from 1998 to 2014. It is unknown if the incidence of CNS met has changed in the ADJ IMT era. Methods: We performed an institutionally approved retrospective chart review of pts diagnosed with stage III melanoma treated with ADJ IMT between 1/1/2018 and 12/31/2020 at MD Anderson Cancer Center (MDA) or the Melanoma Institute of Australia (MIA). Exclusion criteria included mucosal or uveal melanoma or prior systemic therapy (other than ADJ interferon). Pts had to have CNS imaging within 1 month before or 4 months after stage III diagnosis. Pt and tumor features, treatments, and distant recurrence events (CNS met; non-CNS met) were captured. Time-to-CNS and time-to-non-CNS met were computed from start date of ADJ IMT to date of CNS/non-CNS met. Cumulative incidence of distant met events was determined using competing risks (death) and pts alive with no met at last follow-up were censored. Associations were determined using proportional sub-distribution hazards regression models; group differences were assessed using Gray’s test. Results: 361 pts were included in the analysis (MDA, 212; MIA, 149). With a median FU of 34.1 months (range 1.7-61.9), 128 (35.5%) of pts were diagnosed with distant mets. Among pts with distant mets, 56 had CNS met (15.5% of full cohort; 43.8% of pts with distant met); 24 (18.8% of pts with distant mets) pts had CNS met at initial diagnosis of stage IV disease. The 1-, 2-, and 5-yr rates of CNS met in the full cohort were 7%, 12%, and 17%. There was no difference in CNS met incidence between MDA and MIA. On univariate analysis, risk of CNS met was associated with AJCC stage IIID (Hazard Ratio [HR] 6.4; 95% Confidence Interval [CI] 2.2 – 18.8, p&lt;0.001); increased primary tumor Breslow thickness (HR 1.1, CI 1.1 – 1.2, p&lt;0.001), ulceration (HR 2.8; CI 1.5 – 5.1, p&lt;0.001), and mitotic rate &gt; 9/mm (HR 2.3; CI 1.1 – 4.6, p=0.025). There was a trend for decreased risk of CNS met in pts that stopped ADJ IMT due to toxicity (HR 0.4; CI 0.2 – 1.1, p=0.08). Multivariable (MV) model with these features did not identify any significant (p&lt;0.05) associations with CNS met. Primary tumor ulceration and mitotic rate were significantly associated with non-CNS met on MV analysis. Conclusions: Despite the established impact of ADJ IMT on distant met free survival, the incidence of CNS met in stage III melanoma pts treated with ADJ IMT remains high. The results support the need for continued investigation of risk factors, prevention strategies and optimal surveillance for CNS met in stage III melanoma pts.

Non-pharmacological interventions to prevent return of gastric ulcers: A systematic review

Recurrence of gastric ulcers is a significant concern, and non-pharmacological interventions play an important role in their prevention. This systematic review aims to evaluate the effectiveness of nonpharmacological interventions in preventing gastric ulcer recurrence. The aim of this research is Non-Pharmacological Interventions to Prevent Recurrence of Gastric Ulcers: A Systematic Review". The research method in this study was the literature method. The literature method was carried out by means of a comprehensive search carried out in several databases, including PubMed, Medline, Scopus, and the Cochrane Library, using predefined search terms. Studies published from (start date) to (end date) were included. Two independent reviewers screened articles, extracted data, and assessed the quality of included studies using standard tools. The results show that non-pharmacological interventions are quite promising in preventing recurrence of gastric ulcers. Dietary modifications, such as avoiding spicy and acidic foods, and adopting a balanced diet rich in fruits and vegetables, are associated with a reduced risk of relapse. Lifestyle changes, particularly smoking cessation and reducing alcohol consumption, have shown a positive impact on healing ulcers and preventing recurrence. Stress management techniques, such as relaxation exercises and cognitive behavioral therapy, show potential benefits in reducing ulcer recurrence rates. Complementary therapies, such as acupuncture and herbal remedies, have shown mixed results, with some studies showing positive effects in preventing recurrence. Non-pharmacological interventions offer a valuable approach to preventing gastric ulcer recurrence. Dietary modifications, lifestyle changes, stress management techniques, and complementary therapies show promising results in reducing relapse rates. These findings highlight the importance of integrating non-pharmacological interventions into gastric ulcer management and prevention strategies. Further research is needed to validate these findings and explore optimal implementation methods.

Emergency Department Use Among Adults Receiving Dialysis

People with kidney failure receiving maintenance dialysis visit the emergency department (ED) 3 times per year on average, which is 3- to 8-fold more often than the general population. Little is known about the factors that contribute to potentially preventable ED use in this population. To identify the clinical and sociodemographic factors associated with potentially preventable ED use among patients receiving maintenance dialysis. This cohort study used linked administrative health data within the Alberta Kidney Disease Network to identify adults aged 18 years or older receiving maintenance dialysis (ie, hemodialysis or peritoneal dialysis) between April 1, 2010, and March 31, 2019. Patients who had been receiving dialysis for more than 90 days were followed up from cohort entry (defined as dialysis start date plus 90 days) until death, outmigration from the province, receipt of a kidney transplant, or end of study follow-up. The Andersen behavioral model of health services was used as a conceptual framework to identify variables related to health care need, predisposing factors, and enabling factors. Data were analyzed in March 2024. Rates of all-cause ED encounters and potentially preventable ED use associated with 4 kidney disease-specific ambulatory care-sensitive conditions (hyperkalemia, heart failure, volume overload, and malignant hypertension) were calculated. Multivariable negative binomial regression models were used to examine the association between clinical and sociodemographic factors and rates of potentially preventable ED use. The cohort included 4925 adults (mean [SD] age, 60.8 [15.5] years; 3071 males [62.4%]) with kidney failure receiving maintenance hemodialysis (3183 patients) or peritoneal dialysis (1742 patients) who were followed up for a mean (SD) of 2.5 (2.0) years. In all, 3877 patients had 34 029 all-cause ED encounters (3100 [95% CI, 2996-3206] encounters per 1000 person-years). Of these, 755 patients (19.5%) had 1351 potentially preventable ED encounters (114 [95% CI, 105-124] encounters per 1000 person-years). Compared with patients with a nonpreventable ED encounter, patients with a potentially preventable ED encounter were more likely to be in the lowest income quintile (38.8% vs 30.9%; P < .001); to experience heart failure (46.8% vs 39.9%; P = .001), depression (36.6% vs 32.5%; P = .03), and chronic pain (60.1% vs 54.9%; P = .01); and to have a longer duration of dialysis (3.6 vs 2.6 years; P < .001). In multivariable regression analyses, potentially preventable ED use was higher for younger adults (incidence rate ratio [IRR], 1.69 [95% CI, 1.33-2.15] for those aged 18 to 44 years) and patients with chronic pain (IRR, 1.35 [95% CI, 1.14-1.61]), greater material deprivation (IRR, 1.57 [95% CI, 1.16-2.12]), a history of hyperkalemia (IRR, 1.31 [95% CI, 1.09-1.58]), and historically high ED use (ie, ≥3 ED encounters in the prior year; IRR, 1.46 [95% CI, 1.23-1.73). In this study of adults receiving maintenance dialysis in Alberta, Canada, among those with ED use, 1 in 5 had a potentially preventable ED encounter; reasons for such encounters were associated with both psychosocial and medical factors. The findings underscore the need for strategies that address social determinants of health to avert potentially preventable ED use in this population.

The impact of positive psychology counseling on sexual and marital satisfaction and anxiety among reproductive-aged women during the COVID-19 pandemic: a randomized controlled clinical trial

BackgroundSexual and marital satisfaction is considered one of the important factors in happiness and life satisfaction of couples. COVID-19 pandemic results in psychological effects, such as increased anxiety levels which can affect sexual and marital satisfaction. This study aimed to investigate the impact of positive psychology on women’s sexual and marital satisfaction.MethodsA randomized controlled trial was conducted on 72 married women of reproductive age in Tabriz, Iran between February 2021 and May 2022. The participants were randomly divided into the intervention and control groups. There was no significant difference between the control and intervention groups in terms of the socio-demographic characteristics (p < 0.05). The mean age of the participants in the intervention and control groups was 31.8 ± 6.92 and 30.97 ± 5.09 years, respectively. The intervention group attended seven 60–90 min counseling sessions at weekly intervals. The Spielberger anxiety, sexual satisfaction and marital satisfaction questionnaires were completed before and four weeks after the intervention.ResultsThe results of this study indicated that after counseling, the average overall score of marital satisfaction [MD: 15.46, 95% CI: 7.47 to 23.41, p = 0.034] and sexual satisfaction [MD: 7.83, 95% CI: 6.25 to 9.41, p = 0.001] significantly increased in the intervention group compared to the control group. Also, the mean score of state anxiety [MD: -2.50, 95% CI: -4.19 to -0.80, p = 0.001] and trait anxiety [MD: -1.03, 95% CI: -2.46 to -0.09, p = 0.032] significantly decreased after counseling in the intervention group compared to the control group.ConclusionsUsing counseling based on a positive psychology approach can improve anxiety, sexual and marital satisfaction, and anxiety of women of reproductive age during the COVID-19 pandemic. However, further randomized clinical trials are needed before making a definitive conclusion.Trial registrationIranian Registry of Clinical Trials (IRCT): IRCT20171007036615N8. Date of registration: 11/28/21. Date of first registration: 11/28/21. URL: https://www.irct.ir/user/trial/58680/view; Date of recruitment start date: 12/01/21.

SARS-CoV-2 Viral Load in the Nasopharynx at Time of First Infection Among Unvaccinated Individuals

SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity. To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease. This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline and acquired COVID-19 during the blinded phase of the trials. The setting included the US, Brazil, South Africa, Colombia, Argentina, Peru, Chile, and Mexico; start dates were July 27, 2020, to December 27, 2020; data cutoff dates were March 26, 2021, to July 30, 2021. Statistical analysis was performed from November 2022 to June 2023. Linear regression was used to assess the association of demographic and clinical characteristics, viral variant, and trial with polymerase chain reaction-measured log10 VL in nasal and/or nasopharyngeal swabs taken at the time of COVID-19 diagnosis. Among 1667 participants studied (886 [53.1%] male; 995 [59.7%] enrolled in the US; mean [SD] age, 46.7 [14.7] years; 204 [12.2%] aged 65 years or older; 196 [11.8%] American Indian or Alaska Native, 150 [9%] Black or African American, 1112 [66.7%] White; 762 [45.7%] Hispanic or Latino), median (IQR) log10 VL at diagnosis was 6.18 (4.66-7.12) log10 copies/mL. Participant characteristics and viral variant explained only 5.9% of the variability in VL. The independent factor with the highest observed differences was trial: Janssen participants had 0.54 log10 copies/mL lower mean VL vs Moderna participants (95% CI, 0.20 to 0.87 log10 copies/mL lower). In the Janssen study, which captured the largest number of COVID-19 events and variants and used the most intensive post-COVID surveillance, neither VL at diagnosis nor averaged over days 1 to 28 post diagnosis was associated with COVID-19 severity. In this study of placebo recipients from 4 randomized phase 3 trials, high variability was observed in SARS-CoV-2 VL at the time of COVID-19 diagnosis, and only a fraction was explained by individual participant characteristics or viral variant. These results suggest challenges for future studies of interventions seeking to influence VL and elevates the importance of standardized methods for specimen collection and viral load quantitation.

#3054 The hospital frailty risk score lacks service planning and decision-making utility in end stage kidney disease

Abstract Background and Aims Survival time for patients commencing dialysis is poor (median 2.0 years in our data) and treatment is invasive. While the age of patients commencing dialysis has increased significantly, the survival advantage diminishes with increasing comorbidity and frailty. The Hospital Frailty Risk Score (HFRS) is a recently-described score derived from ICD-10 codes which has been shown to correlate with outcomes in patients aged &amp;gt;75 years admitted to acute hospital settings. As part of a wider initiative to improve service planning and patient decision-making in the renal setting, we investigated the utility of the HFRS in modelling the survival time of dialysis patients with chronic kidney disease (CKD) both prior to reaching end-stage kidney disease (ESKD), and at dialysis start date. Method A secondary care dataset was obtained of all patients who attended pre-dialysis clinic at a single renal unit in the north of England between 2006–2019 (n = 2,573). Patients choosing dialysis and conservative management were included in the cohort; 1,081 eventually underwent dialysis including 329 patients who were aged ≥70 years when they commenced dialysis. 62.9% were male. Retrospective survival analysis was conducted using the HFRS prior to, and at, dialysis start date and estimates compared using the log-rank test. Results HFRS on dialysis start date was associated with survival time in patients aged ≥70 years (Low frailty Median = 2.5 years; CI = [2.1–3.0 years] vs. Intermediate frailty Median = 1.5 years; CI = [1.0–2.0 years] vs. High frailty Median = 1.3 years; CI = [0.2–2.2 years]; p = 0.005). No association was found between HFRS and survival in the same patients (aged ≥70 on dialysis start date), at any of 3 timepoints prior to dialysis: eGFR level of 20, 15, or 12 (p = 0.18, p = 0.63, p = 0.38 respectively). However, only 150/329 patients (46%) had HFRS recorded prior to eGFR level so sample size was limited. 60 patients’ HFRS had also worsened by dialysis start date (8 had improved). Additional analyses including all age groups found a weaker association between HFRS on dialysis start date and survival (Low frailty Median = 2.1 years; CI = [1.9–2.3 years] vs. Intermediate frailty Median = 1.7 years; CI = [1.5–2.0 years] vs. High frailty Median = 2.1 years; CI = [1.3–2.4 years]; p = 0.04). HFRS and survival were associated at eGFR 15 for all ages (p = 0.02) but not eGFR 20 or 12. Conclusion We identified issues with the HFRS and its implementation that present challenges to its utility for treatment decision-making or service planning in a renal setting. While the HFRS has previously been shown to be predictive of 30-day outcomes in an acute admissions unit, it performed poorly in our cohort of patients with CKD, a long-term condition where HFRS may worsen or improve between treatment choice and dialysis start. Although HFRS did predict outcome from dialysis start in patients aged ≥70 years, this is of limited use given the abundance of validated tools that predict outcome at ESKD. More work is needed to refine the HFRS for pre-ESKD decision-making in a renal setting.

Using a Semiautomated Procedure (CleanADHdata.R Script) to Clean Electronic Adherence Monitoring Data: Tutorial.

Patient adherence to medications can be assessed using interactive digital health technologies such as electronic monitors (EMs). Changes in treatment regimens and deviations from EM use over time must be characterized to establish the actual level of medication adherence. We developed the computer script CleanADHdata.R to clean raw EM adherence data, and this tutorial is a guide for users. In addition to raw EM data, we collected adherence start and stop monitoring dates and identified the prescribed regimens, the expected number of EM openings per day based on the prescribed regimen, EM use deviations, and patients' demographic data. The script formats the data longitudinally and calculates each day's medication implementation. We provided a simulated data set for 10 patients, for which 15 EMs were used over a median period of 187 (IQR 135-342) days. The median patient implementation before and after EM raw data cleaning was 83.3% (IQR 71.5%-93.9%) and 97.3% (IQR 95.8%-97.6%), respectively (Δ+14%). This difference is substantial enough to consider EM data cleaning to be capable of avoiding data misinterpretation and providing a cleaned data set for the adherence analysis in terms of implementation and persistence. The CleanADHdata.R script is a semiautomated procedure that increases standardization and reproducibility. This script has broader applicability within the realm of digital health, as it can be used to clean adherence data collected with diverse digital technologies.

Strategic alliances and shared auditors

Strategic alliances are voluntary corporate arrangements for mutual benefit. Although alliances are common as an alternative to M&As, they require cooperation between alliance partners who continue to operate as independent companies. Thus, relational risk—the probability and consequences of unsatisfactory cooperation or opportunistic behavior—is inherent in alliances and a major determinant of alliance success. In this paper, we examine and find that alliance announcement CARs are higher for companies sharing the same auditor with their alliance partner. Further, our findings suggest that the shared auditor effect is stronger for alliances where potential relational risk between alliance partners is greater. Our findings hold when we use “withdrawn” (i.e., the withdrawal of an announced alliance before its start date) as an alternative, albeit inverse, measure of alliance success. Collectively, we provide novel evidence which suggests that auditors add shareholder value by playing a matchmaking role in alliance formation, building inter-company trust and mitigating relational risk by facilitating the sharing of non-financial information between potential alliance partners among their audit clients.

Comparative analysis of tabelecleucel and current treatment in patients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease following hematopoietic cell transplant or solid organ transplant

Aims With recent European Union marketing authorization, tabelecleucel is the first off-the-shelf, allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy approved for the treatment of relapsed/refractory EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). In the absence of a control arm, real-world evidence can provide a comparative benchmark for single-arm studies in ultra-rare populations. This study assessed the treatment effect of tabelecleucel in the single-arm phase 3 ALLELE study (NCT03394365) versus a treatment group from a multinational, multicenter retrospective chart review study (RS002) of patients with EBV+ PTLD. Methods In ALLELE, patients had disease relapsed/refractory to rituximab ± chemotherapy and received tabelecleucel 2x106 cells/kg on days 1, 8, and 15 in 35-day cycles. Patients in RS002 had disease relapsed/refractory to rituximab ± chemotherapy and received next line of systemic therapy between January 2000 and December 2018. Propensity score-based standardized mortality/morbidity ratio weighting was used to achieve balance between treatment and comparator arms. Kaplan-Meier estimators and Cox regression models were used to compare overall survival (OS) in the re-weighted sample. Results 30 patients (n = 14 hematopoietic cell transplant [HCT], n = 16 solid organ transplant [SOT]) from ALLELE (data cutoff: November 2021) and 84 patients (n = 36 HCT, n = 48 SOT) from RS002 (data lock: January 2021) were included. Median time from diagnosis to first tabelecleucel dose (ALLELE) or start date of next line of systemic therapy (RS002) was 3.6 months. Tabelecleucel was associated with a substantial OS benefit compared with current treatment, with an unadjusted HR of 0.47 (95% confidence interval [CI] 0.25–0.88) and adjusted HR of 0.37 (95% CI 0.20–0.71) when using the start date of the next line of therapy as the index date. Sensitivity analyses yielded consistent results. Conclusions In this study of real-world data, tabelecleucel was associated with an OS benefit among patients with R/R EBV+ PTLD for whom there is high unmet need.

Real-World Treatment Patterns Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

The treatment landscape for type 2 diabetes mellitus (T2DM) is complex and constantly evolving, and real-world evidence of prescribing patterns is limited. The objectives of this study were to characterize lines of therapy (LOTs), calculate the length of time spent on each LOT, and identify the reasons for the LOT end among patients who initiated oral semaglutide for T2DM. This retrospective, claims-based study included commercial and Medicare Advantage adults with T2DM. Data from November 1, 2019, and June 30, 2020, were obtained from Optum Research Database. Patients with ≥ 1 claim for oral semaglutide and continuous health plan enrollment for ≥ 12months prior to (baseline period) and ≥ 6months following (follow-up period) the date of the first oral semaglutide claim were included. LOT 1 began on the date of the first oral semaglutide claim. The start date of any subsequent LOTs was the date of the first claim for an additional non-insulin anti-diabetic drug class or a reduction in drug class with use of commitment medications. The LOT ended at the first instance of medication class discontinuation, change in regimen or end of follow-up. Of the 1937 patients who initiated oral semaglutide, 950 (49.0%) remained on their initial regimen over the 6-month follow-up period, 844 (43.6%) had at least one subsequent LOT, and 89 (4.6%) had at least two subsequent LOTs. Among patients with more than one LOT, approximately 20%-25% used oral semaglutide as monotherapy or combination therapy during LOTs 2 and 3. Metformin was frequently used during treatment across all LOTs. This study provides insight for physicians and payers into the real-world prescribing practices within the first 6months following oral semaglutide initiation and fills the gap in understanding the frequency of regimen changes in the constantly evolving and complex environment of T2DM care.

Identification of compound drought and heatwave events on a daily scale and across four seasons

Abstract. Compound drought and heatwave (CDHW) events can result in intensified damage to ecosystems, economies, and societies, especially on a warming planet. Although it has been reported that CDHW events in the winter season can also affect insects, birds, and the occurrence of wildfires, the literature generally focuses exclusively on the summer season. Moreover, the coarse temporal resolution of droughts as determined on a monthly scale may hamper the precise identification of the start and/or end dates of CDHW events. Therefore, we propose a method to identify CDHW events on a daily scale that is applicable across the four seasons. More specifically, we use standardized indices calculated on a daily scale to identify four types of compound events in a systematic way. Based on the hypothesis that droughts or heatwaves should be statistically extreme and independent, we remove minor dry or warm spells and merge mutually dependent ones. To demonstrate our method, we make use of 120 years of daily precipitation and temperature information observed at Uccle, Brussels-Capital Region, Belgium. Our method yields more precise start and end dates for droughts and heatwaves than those that can be obtained with a classical approach acting on a monthly scale, thereby allowing for a better identification of CDHW events. Consistent with existing literature, we find an increase in the number of days in CDHW events at Uccle, mainly due to the increasing frequency of heatwaves. Our results also reveal a seasonality in CDHW events, as droughts and heatwaves are negatively dependent on one another in the winter season at Uccle, whereas they are positively dependent on one another in the other seasons. Overall, the method proposed in this study is shown to be robust and displays potential for exploring how year-round CDHW events influence ecosystems.

Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes.

In 2014, the US Food and Drug Administration approved the first glucagon-like peptide-1 (GLP-1) receptor agonist product, liraglutide injection, for obesity treatment. Many GLP-1 obesity treatment clinical trials report significant weight loss and medication adherence at more than 85%. Little is known about the real-world GLP-1 obesity treatment adherence, persistence, and switch rates. To measure GLP-1 therapy persistence, adherence, and switch rates in a real-world cohort of members without diabetes using these drugs for obesity treatment. Integrated pharmacy and medical claims data from 16.5 million average monthly commercially insured membership were used to identify obese members without diabetes newly initiating GLP-1 therapy between January 1, 2021, and December 31, 2021. Members were required to be continuously enrolled 1-year before and after the GLP-1 therapy start date and aged 19 years of age or older. Persistence was measured as no greater than or equal to 60-day gap with allowance for GLP-1 switching. Adherence was measured as the proportion of days covered (PDC) and members with a PDC greater than or equal to 80% were considered adherent. GLP-1 product switching was also assessed descriptively. 4,066 commercially insured obese members without diabetes that newly initiated GLP-1 therapy met all study criteria. The mean age was 46 years, and 81% were female. Overall, GLP-1 persistence was 46.3% at 180 days and 32.3% at 1 year. The highest and lowest persistence rates at 1 year were observed for semaglutide (Ozempic) at 47.1% and liraglutide (Saxenda) 19.2%, respectively. Average PDC during the 1-year assessment was 51.0% with 27.2% adherent to therapy and 11.1% switched GLP-1 drugs. This GLP-1 weight loss treatment real-world analysis, among obese individuals without diabetes, found poor 1-year persistence and adherence and low rates of switching between products. These findings will aid in assessing products cost-effectiveness, understanding obesity care management program needs, forecasting future GLP-1 use and cost trends, and negotiating GLP-1 pharmaceutical manufacturer value-based purchasing agreements.

SPIRIT: Assessing Clinical Parameters Associated with Using IDegLira in Patients with Type 2 Diabetes in a Real-World Setting in Colombia.

Insulin degludec/liraglutide (IDegLira) is a fixed-ratio combination of insulin degludec (a basal insulin) and liraglutide (a glucagon-like peptide-1 receptor agonist [GLP-1RA]). This study aimed to investigate clinical outcomes in people with type 2 diabetes mellitus (T2DM) after initiating IDegLira treatment in a real-world setting in Colombia. SPIRIT is a non-interventional, single-arm, retrospective chart review study to assess clinical outcomes in people with T2DM. Participating patients were switched from a treatment regimen of basal insulin (with or without oral antidiabetics [OADs]) and started on treatment with IDegLira a minimum of 26 ± 6weeks before the data collection start date. Data were collected from the medical records of 175 patients in ten clinical centers across Colombia. Compared with baseline, there was a significant reduction in glycated hemoglobin (HbA1c) (1.3%; 95% confidence interval [CI] -1.6 to -1.0; p < 0.0001) after 26 ± 6weeks of follow-up. The mean HbA1c at baseline and at the end of the study was 9.1% and 7.8%, respectively. In addition, IDegLira significantly reduced absolute body weight by 1kg (95% CI -1.5 to -0.5; p < 0.0001), from a mean of 76.1kg at baseline to 75.1kg after follow-up. The mean IDegLira dose at the end of the study was 21.3 U, and no severe hypoglycemic events were observed during the follow-up period. In real-world practice, initiating IDegLira in patients with T2DM previously treated with basal insulin (± OAD) was associated with improved glycemic control, reduced body weight and reduced risk of hypoglycemia. ClinicalTrials.gov identifier: NCT05324462.

DIY under Authoritarian Politics: Indie Music Scene in Istanbul

The ongoing political turmoil in Turkey is reflected in many areas of the cultural landscape, including the processes of music-making. With its immensely rich musical and cultural legacy that combines a rural and urban heritage, Istanbul has become home to many subcultures revolving around a variety of ethnicities and political acts. While the neoliberal urban control and gentrification agenda of the AKP (Justice and Development Party) government is reshaping the cultural life in the city; a do-it-yourself (DIY) attitude in the music scene removed the barriers of a hierarchy of production while creating unique performance spaces and a sense of belonging and solidarity among its participants. This essay intends to examine the influence of authoritarian politics on the formation of DIY initiatives in Istanbul’s indie music scene. I will concentrate on the period of 2013–2020, the start date signifying the paradigm shift that the Gezi Park protests (May 27–August 20, 2013) fostered, and the end date signifies the decline of the active music scene, with the COVID-19 pandemic preventing live music altogether. This project is a result of fieldwork conducted as a participant-observer of the scene, in addition to structured and semi-structured interviews. The results of the research will be discussed with a focus on the influence of the Islamist, neoliberal, and authoritarian politics of the government on the indie music scene of Istanbul.

Balanced Solution versus Normal Saline in Predicted Severe Acute Pancreatitis: A Stepped Wedge Cluster Randomized Trial.

To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8mmol/L(SD4.8) versus 105.8mmol/L(SD5.9), difference -4.3mmol/L [95%CI -5.6 to -3.0mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).