Haenszel Test Research Articles

P0894 Impact of Mirikizumab on Extraintestinal Manifestations of Crohn’s Disease in the VIVID-1 Study

Abstract Background Mirikizumab, an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile for the treatment of moderately-to severely- active Crohn’s disease (CD) in the phase 3 VIVID-1 study1, a double-blind, placebo-controlled, active comparator study, which has been reported previously. Here we assess the impact of mirikizumab on extra-intestinal manifestations (EIMs) in patients with CD and evaluate the long-term efficacy of mirikizumab on clinical remission and endoscopic response in patients with EIMs at baseline. Methods Patients randomized to receive mirikizumab (N=579) or placebo (N=199) in the VIVID-1 study were included. Among patients with at least 1 EIM at baseline, we evaluated EIM resolution, clinical remission, and endoscopic response at week (W) 52. Onset of new EIMs was assessed among patients with no EIMs at baseline. Prespecified analyses included EIM resolution and onset of new EIMs, while post hoc analyses included clinical remission and endoscopic response among patients with EIMs at baseline. Categorical endpoints were analysed using the Cochran–Mantel–Haenszel test, with missing values imputed by non-responder imputation. Results Of 778 patients in the mirikizumab and placebo arms of VIVID-1, 173 (22.2%) had ≥1 EIM at baseline, primarily arthritis or arthralgia. Baseline demographics and disease characteristics were similar between patients with EIMs at baseline and those in the overall population, except for a numerically higher proportion of female patients with EIMs at baseline (Table 1). At W12, a numerically higher proportion of mirikizumab-treated versus placebo-treated patients showed EIM resolution (46.2% vs 31.7%; P=0.113). Through W52, the EIM resolution rate with mirikizumab improved to 56.8%. The proportion of patients who achieved both clinical response by Patient Reported Outcome at W12 and EIM resolution at W52 was significantly higher for mirikizumab compared to placebo (43.2% vs 14.6%; P<0.0001)(Fig. 1). In addition, among patients with EIMs at baseline, higher proportions of mirikizumab-treated patients than placebo-treated patients achieved (1) clinical response at W12 and clinical remission at W52 (39.4% vs 19.5%; P<0.024) and (2) clinical response at W12 and endoscopic remission at W52 (36.4% vs 4.9%; P=0.0002). The rate of new-onset EIMs at W52 was low among all patients treated with mirikizumab or placebo (1.8% vs 1.9%; P=0.847). Conclusion Treatment with mirikizumab led to higher rates of EIM resolution at W52 compared to placebo. Response rates for clinical and endoscopic outcomes were similar between patients with EIMs at baseline and the overall population in VIVID-1.1

Trans-fat labelling and potential presence of industrially produced trans-fat in the New Zealand packaged food supply: 2015–2019 & 2022

Background and aimThe World Health Organization (WHO) recommends that countries reduce industrially produced TFA (iTFA) in the food supply. However, New Zealand (NZ) has no mandatory regulation to control amounts of iTFA in foods. The objectives of this study were to assess within the NZ packaged food supply in recent years (2015-19 and 2022): i) the availability of products displaying information on TFA content on nutrition information panels (NIPs), ii) the content of TFA declared, and iii) the presence/potential presence of iTFA (n = 85,892 products). Methods and resultsA database of packaged foods from major NZ supermarkets was used. TFA contents declared on NIPs were benchmarked against limits recommended by the WHO and the Canadian Trans Fat Task Force. Proportions of products listing specific ingredients (containing iTFA) or non-specific ingredients (potentially containing iTFA) were examined. Trends in proportions were assessed (Mantel–Haenszel tests). Among all products and years examined (n = 81,591), 84.0 % did not display information on TFA content. Across all products declaring TFA contents and years 15.4 % and 6.4 %, respectively, were above the WHO and Canadian TFA limits. Across all products and years, 0.8 % and 13.6 % listed ingredients that contained or potentially contained iTFA, respectively. Across 2015–2019, there was a trend of decrease in the proportions of products listing specific (0.9 %–0.7 %; P = 0.018) and non-specific ingredients (15.1 %–12.8 %; P < 0.001). ConclusionInformation on the TFA content and ingredients containing iTFA in NZ packaged foods is lacking and ambiguous and government-led interventions to control and reduce TFA in the food supply are warranted.

Seasonal variations in city color preferences incorporating sex and age factors

ABSTRACT City color, serving as a pivotal element within the urban landscape, has garnered significant scholarly attention. Numerous cities have diligently instituted city color planning initiatives to enhance urban landscapes and cultivate city images. The color preference of citizens serves as a crucial foundation for the systematic development of city color planning. Nevertheless, the dynamic aspect of city color preferences is frequently neglected in previous research. Therefore, this article examined seasonal variations in city color preferences using Busan Metropolitan City, South Korea, as an illustrative case. Data collected through a questionnaire survey underwent statistical analyses, including the chi-square test, Wilcoxon rank sum test, and multiple logistic regression, to investigate the influence of seasons on city color preference. The findings revealed that seasons primarily impact the hue preferences in city colors, rather than brightness and chroma preferences. Furthermore, sex and age factors were introduced, and the Cochran–Mantel–Haenszel (CMH) test was employed to identify demographic groups exhibiting seasonal variations in city color preferences. The analysis disclosed noteworthy seasonal disparities in city color preference, particularly among middle-aged and elderly males, who exhibited a significant decrease in preference for yellow and a notable increase in preference for green during winter compared to summer. The outcomes of this study provide valuable insights for informing city color planning. Additionally, the distinctive city color preferences observed among different demographic groups can be effectively applied in urban regeneration initiatives, thereby contributing to human well-being.

SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C).

Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.

Prenatal predictors of ambulation without assistance by 30 months of age in children following prenatal repair of open spina bifida, a systematic review and meta‐analysis

AbstractObjectivesWe aimed to investigate prenatal predictors for ambulation without assistance in children following prenatal repair of open spina bifida (OSB).MethodsA systematic search was conducted in three databases until June 2022. We included articles reporting on prenatal repair of open spina bifida (OSB) and ambulation outcomes. The random‐effect model was used. Effect sizes are presented as odds ratio (OR), using the Mantel–Haenszel test, with 95% confidence interval (CI).ResultsFive studies encompassing 460 pregnancies that underwent prenatal repair of OSB of which a total of 234 had data on ambulation and were included. The follow‐up age for all included studies was 30 months. Two studies were open repairs, two were fetoscopic repairs, and one included both open and fetoscopic repairs. Of the 234 included population, ambulation without assistance occurred in 159/234, 68% (95% CI 58, 76), and ambulation with assistance occurred in 75/234, 32% (95% CI 23.6, 41.6). Significant prenatal preoperative predictors that are negatively associated with ambulation without assistance were lateral ventricle (LV) width ≥15 mm (OR: 0.29; 95% CI 0.12, 0.69, I2 = 0.0%; p &lt; 0.0001), lesion level T12‐L2 (OR: 0.22; 95% CI 0.07, 0.7; I2 = 65%, p = 0.01), and severe hindbrain herniation (OR: 0.28; 95% CI 0.1, 0.77; I2 = 0.0%; p = 0.01). Factors including gestational age at surgery (p = 0.5), Myeloschisis (p = 0.4), talipes (p = 0.29), and gestational age at birth (p = 0.95) were not significantly associated with ambulatory status.ConclusionFollowing the prenatal repair of OSB, preoperative factors that are negatively associated with walking without assistance were preoperative LV width ≥15 mm, lesion level T12‐L2, and preoperative severe hindbrain herniation. These results provide pertinent counselling points for parents with pregnancies affected by OSB considering a prenatal repair.

#1141 Chronic kidney disease in inflammatory bowel disease: systematic review and meta-analysis

Abstract Background and Aims Chronic kidney disease (CKD) is defined by a reduction in kidney function (estimated glomerular filtration rate &amp;lt; 60 mL/min/1.73 m2) and/or damage markers that are present for at least three months, regardless of the underlying aetiology. Case reports and cohort studies suggest that inflammatory bowel disease (IBD is associated with CKD. The extent and magnitude of a potential association between IBD and CKD is currently unknown. Method A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. In studies where a comparison between an IBD population and a non-IBD control population was available, odds ratios were calculated to quantify the association. To derive an overall estimate of the effect, the Mantel–Haenszel test was employed, utilising a random effect model. This systematic was registered with Prospero. Results Fifty-four articles were included in the review (Table 1). Eight articles compared an IBD population with a healthy control population and were included in the meta-analysis, although with high heterogeneity (I2 88%). An increased risk of CKD in the IBD population was observed, with an overall odds ratio of 1.59 (95% CI 1.31-1.93) (Fig. 1). Importantly, this effect was independent of 5-aminosalicylic acid use. Data on other therapies was sparse, except for known nephrotoxic medication like tacrolimus and cyclosporine. Interestingly, several studies reported a decreasing relative risk with increasing age, potentially reflecting an increased baseline risk in this ageing population. Conclusion The existing evidence on CKD in IBD was systematically reviewed, including all human epidemiological studies. An increased CKD prevalence in IBD was found; independent of medication. Hence, we suggest regular measurements of kidney function for all patients with IBD, irrespective of the therapeutic regimen. Measurements should include determination of the baseline creatinine, albumin/creatinine ratio and urinary sediment. For patients having a normal baseline function, we would recommend annual follow-up. A more systematic research approach regarding CKD and IBD is warranted

Abstract PO1-12-09: Doublet or triplet antiemetic prophylaxis for trastuzumab deruxtecan-induced nausea and vomiting: An open-label, randomized, multicenter, exploratory phase 2 study

Abstract Background: Trastuzumab deruxtecan (T-DXd) is classified as an anticancer agent that poses a moderate emetic risk according to international guidelines for antiemetic therapy, which recommend emesis prophylaxis using a two-drug combination therapy comprising 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). The incidence rates of nausea and vomiting in patients in DESTINY BREAST01 and DESTINY BREAST03 were 77.7%, 45.7%, 72.8%, and 44%, respectively. However, no effective antiemetic therapy was observed. The high nausea and vomiting incidence associated with T-DXd is problematic. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment with 5-HT3RA and DEX, with or without a neurokinin-1 receptor antagonist (NK1RA), in preventing T-DXd-induced nausea and vomiting. Methods: We conducted an open-label, randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer scheduled to receive T-DXd were enrolled in this study. Patients were randomly assigned to receive granisetron and dexamethasone (arm GD) or granisetron, dexamethasone, and aprepitant (fosaprepitant; arm GDA). Patients in both treatment arms were administered granisetron (1 mg i.v. 30 min before T-DXd on day 1). Those in the GD arm were administered DEX (6.6 mg i.v. 30 min before T-DXd on day 1 and 8 mg p.o. on days 2–3). The patients in the GDA arm were administered DEX (9.9 mg i.v. 30 min before T-DXd on day 1) and NK1-RA (125 mg of aprepitant p.o. 60 min before chemotherapy on day 1 and 80 mg p.o. on days 2 and 3, or 150 mg fosaprepitant i.v. 60 min before T-DXd on day 1). The primary endpoint was complete response (CR; no emesis or rescue therapy) during the overall phase (0–120 h after the start of T-DXd). The primary endpoint was estimated using the CR rate and 95% confidence intervals (CIs) following the Pearson–Clopper method. The Cochran–Mantel–Haenszel test was used to compare the exploratory results between the two treatment arms with age strata and previous experience with chemotherapy-induced nausea and vomiting. Logistic regression analyses were performed to determine the risk factors associated with the non-achievement of CR, non-achievement of complete control (CC), and non-achievement of total control (TC) in the overall and long-overall phases. Results: Between September 2020 and March 2023, 40 patients were enrolled and randomly assigned to either the GD (n = 19) or GDA (n = 21) arm. In the GDA group, one patient who did not complete the rescue medication listed in the diary was excluded from the efficacy analysis, including rescue medication use. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA groups, respectively (odds ratio [OR], 0.1334; 95% confidence interval [CI], 0.0232–0.7672; P = 0.0190), with a difference of 33.2%. The CR rates during the long-overall phase were 31.6% in the GD arm and 70.0% in the GDA arm (OR, 0.1073; 95% CI, 0.0185–0.6239; P = 0.0087), a difference of 38.4%. NK1RA use was associated with a significant decrease in the non-achievement of CR, CC, and TC in the overall and long-overall phases. Only patients in the GDA arm (33.3%) reported being “very satisfied” with the treatment. No grade 3 or 4 toxicities related to antiemetic therapy were observed. Conclusions: Breast cancer patients receiving T-DXd require triple therapy, including mandatory NK1RA administration, for antiemetic prophylaxis. Further investigation is needed to explore the development of more appropriate combination therapies for T-DXd-induced nausea and vomiting. Citation Format: Manabu Futamura, Hirotoshi Iihara, Hiroko Bando, Yoshihiro Kawaguchi, Yutaka Mizuno, Akari Murakami, Masaaki Kawai, Tomokazu Iyoda, Kazshige Ishida, Kazuhiro Ishihara, Takumi Nakada, Makoto Takeuchi, Mika Kitahora, Yoshihisa Tokumaru, Mototsugu Shimokawa, Nobuhisa Matsuhashi. Doublet or triplet antiemetic prophylaxis for trastuzumab deruxtecan-induced nausea and vomiting: An open-label, randomized, multicenter, exploratory phase 2 study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-09.

Quality Assessment and Comparison of 3D-Printed and Milled Zirconia Anterior Crowns and Veneers: In Vitro Pilot Study

AbstractThe esthetic rehabilitation of a patient is a demanding yet rewarding procedure, improving the form, function, and well-being of a patient. Three-dimensional (3D) printed, or additive manufactured, zirconia has recently entered the dental space, but without a thorough assessment or comparison. This pilot study utilized digital impressions of two demonstration casts: Cast 1 prepared both central incisors for full ceramic crown coverage, while cast 2 had a lateral incisor (#22) prepared for a ceramic veneer. Both casts underwent digital scanning (Straumann CARES 3, Straumann, Basel, Switzerland) to create virtual STL models. Cast 1 had two full zirconia anterior crowns digitally designed, and Cast 2 had a zirconia veneer digitally designed, using Exocad GmbH software by a certified dental technician at Schulich Dentistry. The STL files were used for fabricating six milled zirconia crowns for central incisor (#21) and six 3D-printed zirconia crowns for the other central incisor (#11). Similarly, for Cast 2, milled and 3D-printed zirconia veneers were made for the prepared lateral incisor (#22). Statistical analysis employed Minitab 16.1.0 software to construct a 2 × 2 table for cross-tabulation and chi-squared analysis. This statistical approach assessed the relationship between restoration design and processing method. Cochran–Mantel–Haenszel test evaluated categorical variables considering different classification variables. Milled restorations showed minor variations, while 3D-printed units displayed consistency. Statistical tests found no significant associations. This in vitro study suggests 3D-printed zirconia for crowns and veneers meets precementation standards akin to conventionally milled restorations. Further research can assess its potential benefits for dentistry's efficiency, cost, and sustainability.

Prevalence and Risk of Schizophrenia and Bipolar Disorder in Patients with Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis

Purpose: Schizophrenia and bipolar disorder are understood to have neuroinflammatory/neuro-immunological basis in their etiopathogenesis. There are few studies synthesizing the association of schizophrenia and bipolar disorder in type 1 diabetes mellitus (T1DM), a common immunological disorder. Data Collection and Analysis: We performed meta-analyses of studies assessing the prevalence and risk of schizophrenia and related disorders and bipolar disorder in individuals with T1DM. Fifteen studies consisting of a total sample of 9,768,028 (T1DM: 435,553; non-T1DM controls: 9,332,475) were included. Random-effects meta-analyses using the restricted maximum likelihood method for pooling logit transformed prevalence values and the Mantel–Haenszel test for pooling risk ratios were used. I2 statistic and the rank correlation test for Funnel plots’ asymmetry were used to assess heterogeneity and publication bias, respectively. Results: Pooled (transformed-back-transformed) prevalence for schizophrenia and related psychotic disorders was 0.37% (95%CI: 0.19–0.73), and for bipolar disorder it was 0.39% (95%CI: 0.05–2.99) (together: 0.38% (95%CI: 0.2–0.71)] in T1DM. The prevalence models showed significant heterogeneity but were statistically significant, had low publication bias, and survived sensitivity analysis. The pooled risk ratio for schizophrenia and related disorders together with bipolar disorder was 1.80 (95%CI: 0.64–5.03), and for schizophrenia and related disorders alone it was 1.19 (95%CI: 0.46–3.11), indicating higher rates of these disorders in T1DM. The pooled risk ratios were not statistically significant and did not survive sensitivity analysis. Trial sequential analysis suggested the need for more studies to confirm increased risk. Conclusion: With available studies, we could not provide convincing evidence for the hypothesis that the prevalence and risk of schizophrenia and related disorders and bipolar disorder are significantly greater in individuals with T1DM.

Chronic Kidney Disease in Inflammatory Bowel Disease: a Systematic Review and Meta-analysis.

Inflammatory bowel disease [IBD] is associated with various immune-mediated disorders including spondylarthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and uveitis. Chronic kidney disease [CKD] is defined by a reduction in kidney function (estimated glomerular filtration rate [eGFR] less than 60 ml/min/1.73m2] and/or damage markers that are present for at least 3 months, regardless of the aetiology. Case reports and cohort studies suggest that IBD is associated with CKD. The extent and magnitude of a potential association is unknown. A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. Odds ratios were calculated in those papers with a comparison between an IBD population and a non-IBD control population, the Mantel Haenszel test was employed, using a random effect model. The systematic review was registered in PROSPERO [RD42023381927]. A total of 54 articles was included in the systematic review. Of these, eight articles included data on prevalence of CKD in IBD patients [n = 102 230] vs healthy populations [n = 762 430]. Of these, diagnosis of CKD was based on International Classification of Diseases [ICD] codes in five studies vs on eGFR in three studies. The overall odds ratio of developing CKD in the IBD population is 1.59, [95% CI 1.31-1.93], without any difference between studies using diagnostic coding (odds ratio [OR] 1.70, 95% CI 1.33-2.19] vs diagnosis based on eGFR [OR 1.36, 95% CI 1.33-1.64]. IBD is associated with a clinically meaningful increased CKD prevalence. We provide recommendations on diagnostic evaluation, as well as suggestions for future research.

Seroprevalence of SARS-CoV-2 antibodies among Japanese healthcare workers from 2020 to 2022 as assayed by two commercial kits

Antibody tests are used as surveillance tools for informing health policy making. However, results may vary by type of antibody assay and timing of sample collection following infection. Long-term longitudinal cohort studies on antibody assay seropositivity have remained limited, especially among Asian populations. Using blood samples obtained at health physicals (2020–2022) of healthcare workers (mass vaccinated with mRNA COVID-19 vaccines) at a Japanese medical center, we measured N-specific antibodies using two commercially available systems. Roche Elecsys Anti-SARS-CoV-2 measures total antibodies and Abbott Alinity SARS-CoV-2 IgG measures only IgG. Among 2538 participants, seroprevalence was found to be 16.6% via total antibody assay versus 12.9% by IgG-only (including grayzone) by mid-June 2022. For 219 cases with a previous PCR-confirmed infection, positivity was 97.3% using total antibody assay versus 76.3% using IgG-only assay at the 2022 health physical. Using PCR positive test date as day 0, while the positivity of the total antibody assay was retained for the entire study period (until more than 24-months post-infection), the IgG-only assay’s positivity declined after month 4. The Mantel–Haenszel test found a significant difference in the two assays’ seropositivity, between stratified groups of “within 3 months” and “4 months or more” from infection (P < 0.001). Our study found significant differences in seropositivity over time of total antibody versus IgG-only assays, suggesting an optimal assay for retaining sensitivity over the entire infection period when designing seroprevalence studies.

P816 Baseline disease severity of patients with Ulcerative Colitis influences rapid symptom relief under filgotinib treatment: post hoc analysis of the phase 2b/3 SELECTION study

Abstract Background Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved in Europe and Japan for the treatment of ulcerative colitis (UC). A recent analysis of SELECTION trial data (NCT02914522) showed rapid and sustained improvements in UC symptoms with FIL 200 mg (FIL200) treatment in patients with moderate-to-severe UC.1 Here we assess symptomatic remission rates over time with FIL200 induction treatment according to baseline UC disease severity (partial Mayo Clinic Score [pMCS]). Methods SELECTION was a phase 2b/3 randomized, double-blind, placebo-controlled study. Patients aged 18–75 years were randomized (2:2:1) to receive FIL200, FIL 100 mg or placebo once daily for 11 weeks in induction study A (biologic-naive patients) or induction study B (biologic-experienced patients). In this post hoc analysis, proportions of patients with symptomatic remission (Mayo rectal bleeding sub-score of 0 and Mayo stool frequency sub-score of ≤ 1), from days 2 to 15 and weeks 2 to 10 of the induction study, were analysed at each timepoint by baseline pMCS (pMCS ≥7 and pMCS &amp;lt;7 [cut-off previously used for severe and moderate disease, respectively]2). Symptomatic remission rates were compared between the pMCS ≥7 and pMCS &amp;lt;7 groups within the FIL200 and placebo arms using a Cochran–Mantel–Haenszel test adjusted by study randomization stratification factors. Nominal p values &amp;lt;0.05 were considered statistically significant. Results At day 2, symptomatic remission rates with FIL200 treatment were significantly higher in patients with baseline pMCS &amp;lt;7 than in those with baseline pMCS ≥7 (8.4% vs 1.1%, p=0.009 [induction study A]; 8.8% vs 0.7%, p=0.004 [induction study B]) (Figure A and B). From days 2 to 15, symptomatic remission rates increased in both groups and, except for day 7 for induction study A and day 9 for induction study B, continued to be significantly higher in those with baseline pMCS &amp;lt;7. From week 2, symptomatic remission rates with FIL200 treatment generally continued to increase in both pMCS ≥7 and pMCS &amp;lt;7 groups (Figure C and D). By week 10, symptomatic remission rates with FIL200 treatment were no longer significantly different between those with baseline pMCS &amp;lt;7 and those with baseline pMCS ≥7 (54.8% vs 43.3%, p=0.124 [induction study A]; 39.5% vs 26.4%, p=0.099 [induction study B]). Conclusion Symptomatic response to FIL200 occurs more rapidly in patients with lower UC disease severity than in those with higher UC disease severity. However, converging response rates over 10 weeks of treatment leads to symptomatic remission regardless of baseline UC disease severity.

Artificial intelligence-based decision support software to improve the efficacy of acute stroke pathway in the NHS: an observational study.

In a drip-and-ship model for endovascular thrombectomy (EVT), early identification of large vessel occlusion (LVO) and timely referral to a comprehensive center (CSC) are crucial when patients are admitted to an acute stroke center (ASC). Several artificial intelligence (AI) decision-aid tools are increasingly being used to facilitate the rapid identification of LVO. This retrospective cohort study aimed to evaluate the impact of deploying e-Stroke AI decision support software in the hyperacute stroke pathway on process metrics and patient outcomes at an ASC in the United Kingdom. Except for the deployment of e-Stroke on 01 March 2020, there were no significant changes made to the stroke pathway at the ASC. The data were obtained from a prospective stroke registry between 01 January 2019 and 31 March 2021. The outcomes were compared between the 14 months before and 12 months after the deployment of AI (pre-e-Stroke cohort vs. post-e-Stroke cohort) on 01 March 2020. Time window analyses were performed using Welch's t-test. Cochran-Mantel-Haenszel test was used to compare changes in disability at 3 months assessed by modified Rankin Score (mRS) ordinal shift analysis, and Fisher's exact test was used for dichotomised mRS analysis. In the pre-e-Stroke cohort, 19 of 22 patients referred received EVT. In the post-e-Stroke cohort, 21 of the 25 patients referred were treated. The mean door-in-door-out (DIDO) and door-to-referral times in pre-e-Stroke vs. post-e-Stroke cohorts were 141 vs. 79 min (difference 62 min, 95% CI 96.9-26.8 min, p < 0.001) and 71 vs. 44 min (difference 27 min, 95% CI 47.4-5.4 min, p = 0.01), respectively. The adjusted odds ratio (age and NIHSS) for mRS ordinal shift analysis at 3 months was 3.14 (95% CI 0.99-10.51, p = 0.06) and the dichotomized mRS 0-2 at 3 months was 16% vs. 48% (p = 0.04) in the pre- vs. post-e-Stroke cohorts, respectively. In this single-center study in the United Kingdom, the DIDO time significantly decreased since the introduction of e-Stroke decision support software into an ASC hyperacute stroke pathway. The reduction in door-in to referral time indicates faster image interpretation and referral for EVT. There was an indication of an increased proportion of patients regaining independent function after EVT. However, this should be interpreted with caution given the small sample size. Larger, prospective studies and further systematic real-world evaluation are needed to demonstrate the widespread generalisability of these findings.

Heterogeneity of weight loss and transcriptomic signatures in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan-Meier survival analysis are presented. RNA-seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. Pancreatic head tumours (n=24) were associated with higher prevalence (70.8% vs. 41.7%, P=0.081) and degree of weight loss (7.9% vs. 2.5%, P=0.014) compared to distal tumours (n=24). BMI (P=0.642), SMI (P=0.738) and MRA (P=0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P=0.142). Serum albumin (3.9 vs. 4.4g/dL, P=0.002) was lower and bilirubin (4.5 vs. 0.4mg/dL, P<0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P=0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8months; P=0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours. Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC-associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.

Faktor Risiko Indeks Massa Tubuh (IMT) dan Faktor Risiko Lain terhadap Kejadian Diabetes Melitus pada Lansia

Background: Diabetes melitus (DM) is a metabolic diseases with medical conditions indicated by an increase in blood glucose levels exceeding normal that occurs due to abnormalities in insulin secretion, insulin action or both. Data on elderly morbidity in South Jakarta 2020 states that 12.78% of elderly population suffers from DM.Objective: To determine the risk factors for Body Mass Index (BMI) and other risk factors for the incidence of DM in the elderly at Puskesmas Pancoran in 2020-2021.Method: This study analyzed secondary data with cross sectional approach. Sample of this study was elderly patients who did checkups at the Pancoran Health Center, South Jakarta in 2020-2021, was taken using purposive sampling in total of 97 samples. Risk analysis using Mantel Haenszel test by looking at the odds ratio.Results: The results showed that age and gender were protective factors that could reduce the risk of 0.606 times (95% CI: .258 – 1.468) and 0.915 times (95% CI: 0.400 – 2.093) of the DM. Meanwhile, BMI and daily sugar consumption were significant risk factors for DM. BMI 2.6 times (95% CI: 1,089 - 6,417) more at risk of developing DM and the amount of sugar consumption per day 4 tablespoons 4.1 times (95% CI: 1,749 - 9,711) more at risk of developing DM.Conclusion: Body mass index ≥25 kg/m2 and total sugar consumption 4 tablespoons (50 grams) a day are significant risk factors for diabetes mellitus in the elderly.

Not-so-simple nephrectomy: Comparative analysis of radical and simple nephrectomy in a high-volume tertiary referral center.

Simple nephrectomies can be challenging with significant morbidity. To prove the hypothesis of "not-so-simple" nephrectomy, we compared demographics, perioperative outcomes, and complications between simple and radical nephrectomy in a tertiary referral center. We analyzed 473 consecutive radical nephrectomies (January 2018-October 2020) and simple nephrectomies (January 2016-October 2020). Univariate and multivariate analysis of perioperative outcomes utilized the Mann-Whitney U test, Chi-squared test, Mantel-Haenszel test of trend, and multiple linear regression. Radical nephrectomies were classified in cT1, cT2a, and cT2b-T3 subgroups and compared to simple nephrectomies. Minimally invasive and open techniques were compared between the two groups. Infected versus non-infected simple nephrectomies were compared. A total of 344 radical and 129 simple nephrectomies were included. Simple nephrectomy was an independent predictor of increased operative time (p = 0.001), length of stay (p = 0.049), and postoperative complications (p < 0.001). Simple nephrectomies had higher operative time (p < 0.001), length of stay (p = 0.014), and postoperative morbidity (p < 0.001) than cT1 radical nephrectomies and significantly more Clavien 1-2 complications than cT2a radical nephrectomies (p = 0.001). The trend was similar in minimally invasive operations. However, conversion to open rates was not significantly different. Infected simple nephrectomies had increased operative time (p < 0.001), length of stay (p = 0.005), blood loss (p = 0.016), and intensive care stay (p = 0.019). Patients undergoing simple nephrectomy experienced increased operative time and morbidity. Simple nephrectomy carries higher morbidity than radical nephrectomy in tumors ≤10 cm. Robotic simple nephrectomies may reduce open conversion rates. Postoperative intensive care and enhanced recovery may be essential in simple nephrectomy planning with infected pathology.

Factors That Influence the Life Satisfaction of Afghan Refugees Living in Eastern Turkey: The Role of Their Migration Causes

In this study, the impact of the reasons for leaving their country (such as social, economic, and political) of Afghan asylum seekers who illegally entered Turkey from the eastern border on their life satisfaction in the country of destination was analyzed. The sample comprised 500 individuals (54.8% women; 42.4% &lt; 30 age) who came as refugees from Turkey’s eastern border. Three-stages of analysis were carried out in the study: the Mantel–Haenszel test, ordered logit, and CART (Classification and Regression Trees) decision tree. The main findings obtained from these analyses show that individuals leaving their country for economic reasons and because of war/terrorism are happier, while those leaving their country because of religious and cultural pressures are unhappier. According to the results of the CART analysis, the most frequently repeated variables are economic and life satisfaction of individuals who are satisfied with their household income and save money is at its highest level. In the analysis it is also seen that the life satisfaction level of individuals who are not satisfied with their household income, leave their country for reasons other than economic reasons, and make a living on debt is very low. This study also focuses on the relationship between happiness and sustainable development (SD). It has associated the reasons for migrants leaving their countries with the Sustainable Development Goals (SDGs), highlighting the significance of happiness studies in achieving the SDGs.

425 Effect of upadacitinib on SCORAD intensity items: analysis from the Measure Up 1 and Measure Up 2 studies

Abstract Atopic dermatitis (AD) is a chronic, inflammatory disease characterized by typical clinical signs (erythema, edema/papulation, oozing/crusting, excoriation, lichenification and dryness) and prominent itch that can markedly impact a patient’s sleep and quality of life (QoL). Upadacitinib is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 vs. JAK2, JAK3 and tyrosine kinase 2. The SCORing Atopic Dermatitis (SCORAD) measure is a validated assessment tool that evaluates the extent of disease based on the area of the body affected, intensity of clinical signs of AD, and itch and sleeplessness due to AD. In this integrated post hoc analysis of the Measure Up 1 and Measure Up 2 studies, we compared the effects of upadacitinib (15 and 30 mg) vs. placebo on the intensity of the individual signs assessed by the SCORAD at Week 2 and Week 16. Measure Up 1 and Measure Up 2 are replicate phase 3 multicenter, randomized, double-blind studies comparing the safety and efficacy of upadacitinib 15 mg and upadacitinib 30 mg to placebo in adolescent and adult patients with moderate-to-severe AD. Patients were randomized to upadacitinib 15 mg, upadacitinib 30 mg or placebo orally once daily. All patients received additive-free, bland emollient twice daily for at least 7 days before baseline and during the study until week 16. The current study assessed the intensity of the six clinical signs assessed by the SCORAD (erythema, edema/papulation, oozing/crusting, excoriation, lichenification and dryness with a 4-level rating scale of none, mild, moderate and severe). The proportions of patients achieving resolution (i.e. an intensity rating of ‘none’) of each clinical sign at Week 2 and Week 16 were evaluated among patients with mild, moderate or severe intensity at baseline. Resolution rates were compared using the Mantel–Haenszel test. Missing data were handled using nonresponder imputation. A total of 1679 participants (placebo, 558; upadacitinib 15 mg, 557; upadacitinib 30 mg, 564) were included in the analysis of integrated data from the Measure Up 1 and Measure Up 2 studies. Differences in the proportion of patients achieving resolution for both upadacitinib doses (15 mg/30 mg) vs. placebo were observed at Week 2 (P &amp;lt; 0.0001) for erythema (3.1%/6.0% vs. 0.0%), edema/papulation (13.1%/16.6% vs. 1.3%), oozing/crusting (49.8%/59.1% vs. 15.6%), excoriation (26.9%/34.6% vs. 3.1%), lichenification (9.6%/13.5% vs. 1.4%) and dryness (8.6%/11.9% vs. 1.8%). Resolution rates were also higher with upadacitinib (15 mg/30 mg) vs. placebo at Week 16 (P &amp;lt; 0.0001) for erythema (22.2%/29.7% vs. 2.2%), edema/papulation (33.6%/42.8% vs. 4.9%), oozing/crusting (62.1%/72.0% vs. 20.5%), excoriation (43.3%/54.6% vs. 8.5%), lichenification (30.8%/40.7% vs. 5.2%) and dryness (28.7%/35.9% vs. 4.4%). Greater proportions of patients treated with upadacitinib 15 mg or upadacitinib 30 mg achieved resolution of erythema, edema/papulation, oozing/crusting, excoriation, lichenification or dryness compared with placebo at Week 2 and Week 16. Complete resolution of these clinical signs of AD may correspond to reductions in disease burden that translate to improved QoL. Consideration of the clinical signs of AD as assessed by the SCORAD may help inform physicians as they tailor their treatment choices specifically to the unique skin manifestations of each individual patient.

Personal Adaptations to Remote Working in the Post-Pandemic City and Its Potential Impact on Residential Relocations: The Case of Istanbul

A forced and rapid increase in remote working because of the COVID-19 pandemic has afforded today’s megacities several important opportunities for reducing traffic congestion, energy consumption, greenhouse gas emissions, and certain threats such as the promotion of urban sprawl. The way in which employees have adapted to working remotely during the pandemic and the potential it offers for improving their work/life balance provide indicators for developing urban policies in the post-pandemic city. The present study aims to examine the potential impact the increase in remote working during the first phase of the COVID-19 pandemic has had on residential relocations in Istanbul by investigating how employees have adapted to remote working and their thoughts about leaving the city after the pandemic. To do so, an online survey was conducted between June 1 and June 5, 2020 with 186 employees living in the city of Istanbul. The survey consisted of investigations into changes in work life during the pandemic. The differences between participants’ responses were analyzed and interpreted with respect to their personal characteristics and leisure-time preferences using Pearson’s chi-squared test and the Mantel–Haenszel test of trends (linear-by-linear association). The study finds significant relationships between personal/social characteristics and how people adapt to remote working and provides important indicators of the effects these adaptation processes have on residential relocations.

B7H3 expression in sarcoma.

e23517 Background: Targeted therapy development in sarcoma has been burdened by the heterogeneity of this rare group of tumors. B7H3 is an immune checkpoint molecule in the same family as PD-L1 (also known as B7H1). Its limited expression in non-cancerous tissues and over-expression in numerous tumor types makes it an attractive target for cancer immunotherapy. Available data suggests high expression of B7H3 in certain sarcoma subtypes, including rhabdomyosarcoma, osteosarcoma, liposarcoma, Ewing sarcoma, synovial sarcoma and chondrosarcoma. This study was conducted to further explore B7H3 expression patterns across sarcoma subtypes and the relationship, if any, with PD-1 and PD-L1 expression. Methods: This single-institution, retrospective analysis evaluated soft tissue sarcoma Formalin-Fixed Paraffin-Embedded tumor specimens in patients with a variety of different subtypes. Specimens were evaluated for expression of B7H3, vessel positivity for B7H3, B7H3 staining pattern, and expression of PD-L1 and PD-1. The association between B7H3 expression and baseline and tumor factors was tested using the Mantel Haenszel test or two-sample T-test. Overall survival was estimated using the Kaplan-Meier method where survival time was calculated from diagnosis to death (or last follow-up for those last known to be alive). Results: 156 sarcoma specimens encompassing 16 subtypes were included. B7H3 was broadly expressed across sarcoma subtypes, with some degree of expression found in 91% of samples and 61% demonstrating high levels of B7H3 expression. All tumor samples expressing B7H3 exhibited the biomarker in at least 80% of tumor cells per sample (with a mean of 92.34% of cells testing positive for B7H3). All samples positive for B7H3 showed both cytoplasmic and membranous expression, and B7H3 vessel positivity was found in 90% (137/152) of samples. There were no significant differences in expression or level of expression when stratified by sarcoma subtype, prior treatment(s), tumor size, tumor grade or patient age. No significant difference in overall survival was seen regardless of B7H3 expression or expression levels across sarcoma subtypes. There was no correlation between B7H3 expression and expression of PD-L1 or PD-1 in tumor cells. Conclusions: This is the most comprehensive analysis of B7H3 expression in sarcoma to date. This data shows high levels of B7H3 expression across sarcoma subtypes, suggesting its feasibility as a therapeutic target for future sarcoma treatments. Future clinical trials are needed to evaluate its numerous actions and if manipulation of B7H3 can be employed to improve outcomes in sarcoma. [Table: see text]