Average Daily Frequency Research Articles

Sustainable scheduling of TFT-LCD cell production: A hybrid dispatching rule and two-phase genetic algorithm

TFT-LCD manufacturing process involves Array, Color Filter (CF), Cell, and Module. The Cell process is pivotal in the TFT-LCD production supply chain; it bridges the front-end (Array and CF) and back-end (Module), maintaining a balance of production capacities. Supply from the front-end is transmitted to the back-end, ensuring prompt responsiveness to customer demands. As awareness of environmental conservation grows, implementing sustainable development in the TFT-LCD manufacturing industry has become crucial. Specifically, reducing the machine setup frequency in TFT-LCD scheduling decreases energy consumption during machine operation and wait times and prolongs equipment lifespan by minimizing wear from repeated shutdowns. To tackle the intricate scheduling challenges within TFT-LCD production, this study proposes an intelligent, sustainable scheduling approach that employs a rolling dispatching and line balancing mechanism and a two-phase genetic algorithm (HDTPGA) for Cell scheduling. The goal is to minimize makespan considering product diversity, production constraints, work-in-process balancing, and machine setup frequency. This holistic approach promotes energy-efficient and sustainable manufacturing practices. According to the empirical study, the proposed HDTPGA reduces the makespan by approximately 10% compared to the baseline. Additionally, it reduces the average daily setup frequency of bottleneck stages (ODF and CCT) in the Cell process by approximately 68.25% and 66.25%, respectively. The main contribution of this paper is to propose an intelligent scheduling algorithm to optimize Cell production scheduling in practice. The HDTPGA achieves equilibrium between front-end and back-end production, utilizing an efficient line change mechanism to reduce energy consumption. The enhancement in efficiency not only restricts material waste but also reduces the environmental impact, enabling manufacturers to adopt green production practices and promoting a transition of the entire panel industry toward sustainability.

Drug Use Behaviors and the Risk of HIV Infection Among Drug Users in China Between 2014 and 2021: Cross-Sectional Study.

Drug users are a high-risk group for HIV infection and are prominent HIV carriers. Given the emergence of new drugs, we explored current drug-using behaviors, HIV infections, and the correlation between drug-using behaviors and HIV infection risk among drug users from 2014 to 2021. We aimed to identify the prevalence of HIV infection risk among drug users and explore drug use behaviors based on the updated data, which could provide evidence for the precision of HIV prevention strategies among drug users. Data were collected from sentinel surveillance of drug users in rehabilitation centers and communities in Hangzhou (2014-2021), including sociodemographic characteristics, HIV awareness, drug use, risky sexual behaviors, and HIV infection status. Multivariate logistic regression was used to identify the factors influencing HIV infection and risky sexual behaviors among drug users. In total, 5623 drug users (male: n=4734, 84.19%; age: mean 38.38, SD 9.94 years) were included. New drugs dominated among the participants (n=3674, 65.34%). The main mode of drug use was noninjection (n=4756, 84.58%). Overall, for 27.45% (n=1544) of injected drugs in the last month before the investigation, the average daily injection frequency was 3.10 (SD 8.24). Meanwhile, 3.43% of participants shared needles. The incidence of sexual behaviors after drug use was 33.13% (n=1863), with 35.75% (n=666) of them using a condom in the last time. Overall, 116 participants tested positive for HIV antibodies (infection rate=2.06%). New drug users exhibited more postuse sexual behaviors than traditional drug users (odds ratio [OR] 7.771, 95% CI 6.126-9.856; P<.001). HIV-aware drug users were more likely to engage in risky sexual behaviors (OR 1.624, 95% CI 1.152-2.291; P=.006). New-type drug users were more likely to engage in unprotected sexual behavior (OR 1.457, 95% CI 1.055-2.011; P=.02). Paradoxically, drug users with greater HIV awareness were more prone to engaging in unprotected sexual behavior (OR 5.820, 95% CI 4.650-7.284; P<.001). Women engaged less in unprotected sex than men (OR 0.356, 95% CI 0.190-0.665; P=.001). HIV rates were higher among injecting drug users (OR 2.692, 95% CI 0.995-7.287; P=.04) and lower among drug users who used condoms during recent sex than those who did not (OR 0.202, 95% CI 0.076-0.537; P=.001). Higher education levels were associated with higher HIV infection rates. However, there was no significant correlation between HIV cognition level and HIV infection. New drug types and noninjection were the main patterns in last 7 years. Using new types of drugs, rather than traditional drugs, was associated with an increased risk of HIV infection. Injection drug use was a risk factor for HIV infection. HIV awareness among drug users was high, but the incidence of risky sexual behaviors remained high. Therefore, it is important to promote the behavioral transformation of high-risk populations from cognition to attitude, and then to taking protective measures.

Investigation of operating differences between wind and photovoltaic assisted by coal-fired power plant

ABSTRACT This paper investigates an integrated energy system combining wind/photovoltaic (PV) power and a coal-fired power plant (CFPP). It is found that there are significant differences in the integrated energy system of wind-coal and PV-coal due to the influence of natural conditions on wind and PV. The integrated energy system is analyzed from two aspects: the grid side and the power supply side. On the grid side, the power supply capacity of the system is evaluated by load evaluation. It is found that the load evaluation qualified rate of the wind-coal and PV-coal integrated energy system is 14.2% and 5.3% lower than the grid side standard, respectively. The greater volatility of wind power increases the regulating difficulty of CFPP. Through optimization, the optimal storage capacities of the wind-coal-storage and PV-coal-storage systems are 5.5MWh and 3.2MWh respectively, enabling the integrated energy system power supply to reach grid-side demand levels. On the supply side, the operating depth of CFPP in wind-coal-storage and PV-coal-storage increased by an average of 3.11% and 4.23% per month, respectively. In both combined modes of operation, CFPP combined with wind power has more frequent load regulation, with an average daily regulation frequency of 10.8% higher, while CFPP combined with PV has a higher operating depth of up to 49.84%. This study reveals different aspects of the operational characteristics of wind/PV when supplying power directly in conjunction with CFPP. The results show that the combined supply with wind/PV places higher demands on the operation of CFPP.

Catamenial epilepsy occurence and patterns in a mixed population of women with epilepsy.

We aimed to evaluate the occurrence and distribution of patterns of catamenial epilepsy in a heterogenous cohort of women with epilepsy on no hormonal therapies, enrolled in a prospective, observational study. The primary aim of the study was pregnancy rate in women with epilepsy with no prior reproductive problems. In this analysis, we included women who recorded ≥one menstrual cycle with ≥one seizure. We measured progesterone concentrations for 1-3 cycles. We defined catamenial patterns as ≥two-fold average daily seizure frequency around menstruation (C1), ovulation (C2) and, for anovulatory cycles, from mid-cycle through menstruation (C3). Twenty-three of the 89 enrolled women with epilepsy were eligible for this analysis: 12/23 met criteria for catamenial epilepsy, and 5/23 demonstrated only a C1 pattern, 2/23 only a C2 pattern, 5/23 a combined C1/C2 pattern, and 0/1 women with anovulatory cycles demonstrated a C3 pattern. There were no differences in likelihood of demonstrating a catamenial pattern between those who reported a prior catamenial pattern and those who did not (p=0.855). This analysis demonstrates the utility of app-based tracking to determine a catamenial pattern. Larger prospective studies could confirm these findings and inform potential therapeutic trial designs for catamenial epilepsy.

Proglacial river stage derived from georectified time-lapse camera images, Inglefield Land, Northwest Greenland

The Greenland Ice Sheet is a leading source of global sea level rise, due to surface meltwater runoff and glacier calving. However, given a scarcity of proglacial river gauge measurements, ice sheet runoff remains poorly quantified. This lack of in situ observations is particularly acute in Northwest Greenland, a remote area releasing significant runoff and where traditional river gauging is exceptionally challenging. Here, we demonstrate that georectified time-lapse camera images accurately retrieve stage fluctuations of the proglacial Minturn River, Inglefield Land, over a 3 year study period. Camera images discern the river’s wetted shoreline position, and a terrestrial LiDAR scanner (TLS) scan of riverbank microtopography enables georectification of these positions to vertical estimates of river stage. This non-contact approach captures seasonal, diurnal, and episodic runoff draining a large (∼2,800 km2) lobe of grounded ice at Inglefield Land with good accuracy relative to traditional in situ bubble-gauge measurements (r2 = 0.81, Root Mean Square Error (RMSE) ±0.185 m for image collection at 3-h frequency; r2 = 0.92, RMSE ±0.109 m for resampled average daily frequency). Furthermore, camera images effectively supplement other instrument data gaps during icy and/or low flow conditions, which challenge bubble-gauges and other contact-based instruments. This benefit alone extends the effective seasonal hydrological monitoring period by ∼2–4 weeks each year for the Minturn River. We conclude that low-cost, non-contact time-lapse camera methods offer good promise for monitoring proglacial meltwater runoff from the Greenland Ice Sheet and other harsh polar environments.

Impact of the economic crisis on food consumption of Sri Lankans: An online cross-sectional survey

AimsThis study investigated how the economic crisis has changed Sri Lankans' food consumption. MethodsA web-based cross-sectional survey was carried out in the month of July 2022, using an e-questionnaire based on Google Forms. The questionnaire assessed respondents' socio-demographics, food consumption, and dietary patterns before and during the economic crisis. The changes were compared using descriptive statistics and inferential statistics. ResultsA total of 1095 respondents, aged ≥18 years were included in the survey. There was a significant reduction in the average consumption of main meals per day during the economic crisis (pre: 3.09 ± 0.42, post: 2.82 ± 0.47; P < 0.001). The intake of food items such as rice, bread, and snacks also reduced significantly (P < 0.001). The average daily milk intake frequency decreased from 1.41 ± 1.07 to 0.57 ± 0.80 meals/day (P < 0.001). On contrary, the intake of non-dairy beverages such as malted milk and “plain tea” has increased by several folds. Consumption of fruit and vegetables showed a significant reduction in both frequency and portion size. The consumption of meat, fish, eggs and dhal also decreased in around three-quarters of the study sample. During this period majority (81%) used food coping mechanisms and the most adopted strategy was buying less expensive food. ConclusionSri Lankans' food consumption have been adversely altered due to the country's economic crisis. There has been an overall reduction in the amount and frequency of intake of many common food items.

Media Framing Of the Russia-Ukraine War by Tass and Ukrinform during the First Month of the Invasion

When two countries go to war, the media in these countries also go to war through the use of framing in content production. This study focuses on the media framing of the Russia-Ukraine war by the TASS and Ukrinform during the first month of the Russian invasion of Ukraine. A descriptive content analysis guided by framing and political economy theories was used. A coding sheet was used as the instrument of data. A total of 1929 reports were identified during the first month of the invasion. Findings revealed that the Russian News Agency framed the conflict in Ukraine as a ‘special military operation,’ but did not make the ‘operation’ a media agenda. This was reflected in the low Average Daily Frequency (ADF) of 9 reports. On the other hand, the Ukrainian News Agency, Ukrinform framed the operation as a ‘war’ or ‘invasion’ of Ukraine. The Ukrainian News Agency made the operation a media agenda, this was reflected in the high Average Daily Frequency (ADF) of 53 reports. Further findings revealed that the dominant frame employed by the TASS and Ukrinform News Agencies is the attacks on civilians, residential areas and causalities. This was to expose the atrocities committed by the enemy (Russian or Ukrainian government) to either win sympathy or condemnation among supporters. Based on these findings, this study recommends media independence during wars. This will give even the state-owned news agencies the right to employ realist frames which could help save lives during wars and not political economy frames.

Integrated safety summary from Phase 3 clinical trials of IPX203, an extended-release carbidopa-levodopa formulation, in Parkinson disease (P1-11.006)

Integrated safety summary from Phase 3 clinical trials of IPX203, an extended-release carbidopa-levodopa formulation, in Parkinson disease (P1-11.006)

Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial (S32.006)

Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial (S32.006)

Sovereign Bond Yield Differentials across Europe: A Structural Entropy Perspective

This study uses structural entropy as a valuable method for studying complex networks in a macro-finance context, such as the European government bond market. We make two contributions to the empirical literature on sovereign bond markets and entropy in complex networks. Firstly, our article contributes to the empirical literature on the disciplinary function of credit markets from an entropy perspective. In particular, we study bond yield differentials at an average daily frequency among EU countries' 10-year Eurobonds issued between 1 January 1997, and 4 October 2022. Secondly, the article brings a methodological novelty by incorporating an entropy perspective to the study of government bond yield differentials and European capital market integration. Entropy-based methods hold strong potential to bring new sources of dynamism and valuable contributions to the areas of macroeconomics and finance.

A comparison of statistical versus clinical classifiers of seizure clustering in women with catamenial and noncatamenial epilepsy.

We assessed whether (1) women with statistical clustering of daily seizure counts (DSCs) or seizure intervals (SIs) also showed clinical clustering, defined separately by ≥2 (≥2-SC) and ≥3 (≥3-SC) seizures on any single day; and (2) how these classifiers might apply to catamenial epilepsy. This is a retrospective case-control analysis of data from 50 women with epilepsy (WWE). We assessed the relationships of the four classifiers to each other and to catamenial versus noncatamenial epilepsy using chi-squared, correlation, logistic regression, and receiver operating characteristic (ROC) analyses. ≥3-SC, not ≥2-SC, was more frequent in WWE who had statistical DSC clustering versus those who did not (21/25 [84.0%] vs. 11/25 [44.0%], p= .007). Logistic regression (p= .006) and ROC (p= .015) identified ≥3-SC, not ≥2-SC, as a predictor of statistical DSC clustering, but ≥4-SC was more accurate. ≥3-SC correlated with the average daily seizure frequencies (ADSFs) of the subjects (p= .01). ROC optimal sensitivity-specificity cut-point for ADSF prediction of ≥3-SC (.372) was 64.6% higher than for ≥2-SC (.226). SI clustering was more common in WWE who had catamenial versus noncatamenial epilepsy (p= .013). Logistic regression identified statistical SI clustering as the only significant classifier (p= .043). ROC analysis offered only marginal support (p= .056), because specificity was low (42.1%). The findings lend statistical support for (1) the utility of clinical ≥3-SC as a predictor of convulsive status epilepticus, (2) consideration of ADSFs in defining clustering, and (3) ≥4-SC as a more accurate clinical predictor of statistical DSC clustering. Statistical SI clustering occurred more frequently in women with catamenial than noncatamenial epilepsy (90.3% vs. 57.9%, p= .013). Although sensitivity was high (90.3%, 28/31), specificity was only 42.1% (8/19). Algorithms that test patterns and periodicities of clusters are more applicable.

Seismic Reduction Mechanism and Engineering Application of Paste Backfilling Mining in Deep Rock Burst Mines

In the process of coal resources development, a large number of strip coal pillars have been left behind in the coal mines in central–eastern China. With the increase in coal mining depth year by year, the rock burst threat of strip coal pillars is becoming more and more prominent due to the influence of buried depth, geological structure, gob and other factors. Backfilling mining is the main means to recover the residual strip coal pillar. In order to investigate the effect of backfilling mining on the prevention and control of rock burst, taking the paste backfilling workface 1# of Gucheng coal mine as the engineering background, a comprehensive research method of theoretical analysis, numerical simulation and field monitoring was used to study the evolution of stress and of the overburden spatial structure of the backfilling workface under the control of the backfilled ratio. The results showed that the backfilling mining controls the movement and deformation of overburden by reducing the activity range of roof strata. The overburden fracture development height decreases with the increase in backfilled ratio, but there is a boundary effect influenced by the roof deflection before backfilling and the defective distance of roof contact. With the increase in backfilled ratio, the concentration coefficient of front abutment pressure, the vertical displacement of the roof and the development height of the plastic zone of overlying strata decreased obviously, which indicates that filling mining can effectively control the stress of surrounding rock and the movement of overlying strata. The field monitoring data showed that the influence range of the front abutment pressure of the paste backfilling workface was about 90 m and the maximum stress of the surrounding rock of the two entries did not exceed 7 MPa. The average daily frequency of microseism was 1.34, and the average daily total energy of microseism was 1.80 + 103 J, which decreased by 69% and 90%, respectively, compared with the caving method working face with similar geological conditions. The data above showed that the backfilling mining can effectively reduce the working face stress level and dynamic load strength to achieve the effect of prevention and control of rock burst.

P409 Using antidepressants for refractory symptoms of Inflammatory Bowel Disease: a prospective service evaluation

Abstract Background One third of patents with inflammatory bowel disease (IBD) have refractory gastrointestinal symptoms, such as pain and diarrhoea, even after exhaustion of medical therapies. A further 40% have persistent fatigue. Although antidepressants can improve such symptoms, their role in treatment-refractory IBD has not been studied. Methods We evaluated a Consultant Psychiatrist clinic for patients with refractory IBD symptoms. Patients were reviewed remotely over 3-6-month follow-up. For pain, we used duloxetine or venlafaxine first-line. For nausea and insomnia-driven fatigue, we used mirtazapine first-line. For refractory fatigue or diarrhoea, we used bupropion, reboxetine or vortioxetine. Ineffective medications were changed after 6-8 weeks. Antidepressants were combined and augmented with antipsychotic if required. The primary outcome was change in the self-report IBD Control Questionnaire, scored from 0 (poor) to 16 (good). Secondary outcomes were changes in depression (PHQ-9), anxiety (GAD-7), IBD Fatigue Scale and average daily bowel frequency. Data were presented as mean (SD) if parametric and median [interquartile range] if skewed. Changes over time were measured using 2-tailed paired t-tests (parametric) or Wilcoxon signed rank tests (skewed data). Results Of 62 patients with IBD offered antidepressants, 80.1% started treatment. Mean age was 41.8 years and mean IBD duration 16.6 years. Of these, 88% had Crohn’s disease, 70% were refractory to multiple biologics, 62% had previous bowel resection and 14% had intestinal failure. At baseline, 92% had severe fatigue (IBD-Fatigue &amp;gt;10), 52% had diarrhoea/high stoma output, 50% had pain and 18% nausea/vomiting. At baseline, 86% met ICD-10 criteria for moderate/severe depression and/or generalised anxiety disorder, and 26% had existing treatment-resistant depression. At follow-up, IBD Control score improved from 1.5 [0-4] to 5 [1.5-8] (p&amp;lt;0.001), as did depression (mean 24% reduction, p&amp;lt;0.001), anxiety (mean 28% reduction, p&amp;lt;0.001) and fatigue (mean 18% reduction, p=0.01). Although 27% of patients responded to first-line antidepressants, the rest required changes in treatment, combination therapy or augmentation. Ultimately, 51.5% were prescribed bupropion, reboxetine or vortioxetine, collectively in whom median bowel frequency fell from 6/day to 4/day (p&amp;lt;0.001). Only 8% could not tolerate antidepressants. Conclusion Even in very difficult-to-treat IBD, antidepressants can improve IBD control, depression, anxiety and fatigue. However, specialist- or combination antidepressants are often required in this specific group. Clinical services should consider expansion of psychiatry provision to improve IBD outcomes. Trials of antidepressants for patients with refractory IBD symptoms are needed.

Early-life sugar consumption and breastfeeding practices: a multicenter initiative in Latin America.

The aim of this multicenter study was to explore the early-life sugar consumption and dietary practices in Latin America as well as to investigate the association between breastfeeding duration and the age at which foods and beverages with added sugars are introduced. A cross-sectional study was conducted with 805 1- to 3-year-old children from 10 Latin American countries, as a complementary study to the Research Observatory for Dental Caries of the Latin American Region (OICAL). A Food Frequency Questionnaire previously tested in different countries was applied to children's mothers and data on breastfeeding and age at introduction of sugary foods and beverages was collected. Statistical analysis included the Kruskal-Wallis test and Poisson regression with robust variance, with the calculation of crude and adjusted mean ratios (MR) and 95% of confidence intervals (CI). The average age at introduction of sugary foods and beverages was 10.1 months (95%CI 9.7-10.4) and 9.6 (95%CI 9.2-9.9) months, respectively, with a significant variation between countries (p < 0.001). The average daily frequency of sugary foods-beverages was 3.3 times per day (95%CI 3.1-3.5) and varied significantly between countries (p = 0.004). Breastfeeding duration of over six months was associated with an increase in the age of introduction of sweet drinks (16%; MR 1.16; 95%CI 1.05-1.28) and foods (21%; MR 1.21; 95%CI 1.10-1.33). In conclusion, most children from vulnerable settings in Latin America start consuming sugary products in the first year of life and a high frequency of consumption was reported through early childhood. Additionally, breastfeeding contributes to a delay in the introduction of sugary products.

MODELLING THE VARIATION IN THE MOBILITY PATTERN OF HOUSEHOLDS IN THE URBAN AND RURAL AREAS OF NIGERIA

There is evidence that rural areas are disadvantaged in mobility compared to urban areas. Hence, this study examined spatial variation in the travel pattern of households in urban and rural areas of Nigeria. This study used primary data obtained through questionnaire administration on household heads in the residential zones of both urban and rural areas studied, using the multi-stage sampling technique. Findings revealed that variations exist for age, education level, income level, and occupation in urban and rural areas, and household's average daily mean trip frequency showed a level of fewer trips being generated in the rural area than those in the urban area. Furthermore, the result of the stepwise multiple regression analysis showed that transport mode, household size, number of workers in the house, and occupation of household head were significant variables influencing trip making in urban areas while age, household size, the income of household head and number of employed people were significant in the rural areas. This study concludes that differences exist in the mobility pattern of urban and rural households, and as such, equal consideration and attention should be given to them in policy formulations.

S736 Efficacy and Safety of Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results From a Randomized Phase 3 U-EXCEL Study

Introduction: Eligible patients(N=526) with moderate to severe active Crohn’s Disease(CD), defined as average daily stool frequency(SF)≥4 and/or abdominal pain score(APS)≥2, and a Simple Endoscopic Score for CD(SES-CD) (excluding the narrowing component subscore) ≥6(≥4 for subjects with isolated ileal disease). Methods: Patients(pts) were randomized 2:1 to UPA45 or PBO for 12 weeks(wks). Pts on baseline corticosteroids(CS) initiated a protocolized tapering at wk4. The co-primary endpoints, clinical remission(per CDAI for US [CDAI< 150] or per SF/APS for EU [average daily SF ≤2.8 and APS≤1.0 and neither greater than baseline [BL]) and endoscopic response(decrease in SES-CD >50% from BL or ≥2-point reduction from BL for pts with a BL SES-CD=4), were evaluated at wk 12. Safety, primary and key secondary clinical, and endoscopic outcomes were evaluated through wk 12. Results: BL demographics and characteristics were similar between groups; 45.4% of pts had a history of prior biologic use or failure. At wk 12, significantly more pts receiving UPA45 vs PBO achieved the co-primary endpoints: clinical remission(per CDAI, UPA45 49.5% vs PBO 29.1%; per SF/APS, UPA45 50.7% vs PBO 22.2%) and endoscopic response (UPA45 45.5% vs PBO 13.1%) (P< .0001 for all endpoints; Table). UPA45 was superior to PBO for most of the ranked secondary endpoints including clinical remission per CDAI and SF/APS at wk 4, CS-free clinical remission per CDAI and SF/APS at wk 12, clinical response(CR-100; 100-point decrease in CDAI from BL at wk 2 and wk 12, and endoscopic remission at wk 12(P< .0001 or P< .01, Table). Severe AEs occurred at 8.9% and 8.5% within UPA45 and PBO groups, respectively. The most common AEs(≥5% of pts) were acne and anemia among pts treated with UPA, and CD exacerbation among pts receiving PBO. Serious infections were 1.1% and 1.7% for UPA45 and PBO groups, respectively. Herpes zoster(2.9%) was reported in the UPA45 group only, and an adjudicated cardiovascular event(0.6%) was reported only in the PBO group. No treatment-emergent deaths, malignancies, other opportunistic infections, adjudicated gastrointestinal perforations or adjudicated thrombotic events were reported in either group. Conclusion: UPA45 induction therapy was superior to PBO in achieving early response, including clinical remission, endoscopic response, and CS-free clinical remission during the U-EXCEL study. UPA45 was well tolerated, with no new safety risks and a safety profile comparable to previous UPA studies. Table 1. - Co-primary and Key Secondary Endpoints Endpoint PBO (N=176)% [95% CI] g UPA 45 mg QD (N=350)% [95% CI] g Difference vs. PBO% [95% CI] h Co-Primary Endpoints Clinical remission, wk 12 Per CDAI a Per SF/APS b 29.1 [22.4, 35.8]22.2 [16.0, 28.3] 49.5 [44.2, 54.8]50.7 [45.5, 56.0] 20.8 [12.7, 28.8]**28.7 [20.9, 36.4]** Endoscopic response c , wk 12 13.1 [8.1, 18.0] 45.5 [40.3, 50.8] 33.0 [26.2, 39.9]** Key Secondary Endpoints Clinical Remission, wk 4 Per CDAI a Per SF/APS b 26.7 [20.2, 33.3]14.8 [9.5, 20.0] 37.1 [32.1, 42.2]35.7 [30.7, 40.7] 10.8 [2.9, 18.6]*21.2 [14.3, 28.2]** Corticosteroid-free clinical remission, wk 12 per CDAI d per SF/APS d (N=64)15.7 [6.8, 24.7]12.5 [4.4, 20.6] (N=126)42.9 [34.2, 51.5]44.4 [35.8, 53.1] 27.7 [15.7, 39.8]**32.6 [21.5, 43.7]** Clinical Response CR-100 e Week 2 Week 12 20.4 [14.4, 26.5]37.3 [30.1, 44.5] 32.2 [27.3, 37.1]56.6 [51.4, 61.8] 11.7 [4.2, 19.2]*19.8 [11.3, 28.4]** Endoscopic remission f , wk 12 7.4 [3.5, 11.3] 28.9 [24.2, 33.7] 21.8 [15.8, 27.8]** Patient randomization was stratified by baseline corticosteroid use, endoscopic disease severity, and the number of previously failed biologics. All patients within this dataset were included here within the ITT population.aClinical remission per CDAI = per US, CDAI < 150.bClinical remission per SF/APS = per EU, average daily SF ≤ 2.8 and average daily APS ≤ 1.0 and both not greater than baselinecEndoscopic response = decrease in SES-CD > 50% from baseline (or for subjects with a baseline SES-CD of 4, at least a 2-point reduction from baseline), as scored by a central reviewer.dCorticosteroid-free clinical remission = discontinuation of corticosteroid use and achievement of clinical remission per CDAI or SF/APS at wk 12 among patients on corticosteroids at baseline.eClinical response-100 = decrease of ≥ 100 points in CDAI from baseline.fEndoscopic remission = SES-CD ≤ 4, at least a 2-point reduction versus baseline and no subscore >1 in any individual variable, as scored by a central reviewer.gResults are based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C).h95% CI for adjusted difference and p-value are calculated according to the Cochran-Mantel-Haenszel (CMH) test adjusted for randomization strata.**P ≤ .0001 or *P ≤ .01 vs PBO; Average daily abdominal pain score, APS; Coronavirus disease 2019, COVID-19; Confidence Interval, CI; Crohn’s Disease Activity Index, CDAI; Simple Endoscopic Score for CD, SES-CD, Placebo, PBO; Once daily, QD; average daily very soft/liquid stool frequency, SF; Upadacitinib, UPA.

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials

Risankizumab, an interleukin (IL)-23 p19 inhibitor, was evaluated for safety and efficacy as induction therapy in patients with moderately to severely active Crohn's disease. ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies. Eligible patients aged 16-80 years with moderately to severely active Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8. We used interactive response technology for random assignment, with stratification by number of previous failed biologics, corticosteroid use at baseline, and Simple Endoscopic Score for Crohn's disease (SES-CD). All patients and study personnel (excluding pharmacists who prepared intravenous solutions) were masked to treatment allocation throughout the study. Coprimary endpoints were clinical remission (defined by Crohn's disease activity index [CDAI] or patient-reported outcome criteria [average daily stool frequency and abdominal pain score]) and endoscopic response at week 12. The intention-to-treat population (all eligible patients who received at least one dose of study drug in the 12-week induction period) was analysed for efficacy outcomes. Safety was assessed in all patients who received at least one dose of study drug. Both trials were registered on ClinicalTrials.gov, NCT03105128 (ADVANCE) and NCT03104413 (MOTIVATE), and are now complete. Participants were enrolled between May 10, 2017, and Aug 24, 2020 (ADVANCE trial), and Dec 18, 2017 and Sept 9, 2020 (MOTIVATE trial). In ADVANCE, 931 patients were assigned to either risankizumab 600 mg (n=373), risankizumab 1200 mg (n=372), or placebo (n=186). In MOTIVATE, 618 patients were assigned to risankizumab 600 mg (n=206), risankizumab 1200 mg (n=205), or placebo (n=207). The primary analysis population comprised 850 participants in ADVANCE and 569 participants in MOTIVATE. All coprimary endpoints at week 12 were met in both trials with both doses of risankizumab (p values ≤0·0001). In ADVANCE, CDAI clinical remission rate was 45% (adjusted difference 21%, 95% CI 12-29; 152/336) with risankizumab 600 mg and 42% (17%, 8-25; 141/339) with risankizumab 1200 mg versus 25% (43/175) with placebo; stool frequency and abdominal pain score clinical remission rate was 43% (22%, 14-30; 146/336) with risankizumab 600 mg and 41% (19%, 11-27; 139/339) with risankizumab 1200 mg versus 22% (38/175) with placebo; and endoscopic response rate was 40% (28%, 21-35; 135/336) with risankizumab 600 mg and 32% (20%, 14-27; 109/339) with risankizumab 1200 mg versus 12% (21/175) with placebo. In MOTIVATE, CDAI clinical remission rate was 42% (22%, 13-31; 80/191) with risankizumab 600 mg and 40% (21%, 12-29; 77/191) with risankizumab 1200 mg versus 20% (37/187) with placebo; stool frequency and abdominal pain score clinical remission rate was 35% (15%, 6-24; 66/191) with risankizumab 600 mg and 40% (20%, 12-29; 76/191) with risankizumab 1200 mg versus 19% (36/187) with placebo; and endoscopic response rate was 29% (18%, 10-25; 55/191) with risankizumab 600 mg and 34% (23%, 15-31; 65/191) with risankizumab 1200 mg versus 11% (21/187) with placebo. The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the risankizumab 1200 mg group [MOTIVATE]). The death in the risankizumab-treated patient was deemed unrelated to the study drug. Risankizumab was effective and well tolerated as induction therapy in patients with moderately to severely active Crohn's disease. AbbVie.

Alcohol consumption, heavy episodic drinking and the perpetration of antisocial behaviours in Australia

AimsThis study aims to understand the dose-response relationship of the volume and patterns of alcohol consumption with alcohol-related antisocial behaviours (ASB) in the general population and assess whether these relationships are consistent across various sociodemographic subgroups. MethodsWe used data from 30,275 respondents aged (14−69) from two waves (2013 and 2016) of the National Drug Strategy Household Survey (NDSHS). Average daily alcohol consumption and heavy episodic drinking (HED) frequencies were treated as the main independent variables and self-reported ASB perpetration as the dependent variable. Bivariable and multivariable logistic regression models predicting ASB with interaction terms between alcohol consumption and various sociodemographic variables were estimated. FindingsCompared with low-risk drinking (0.01–20 g of alcohol/day), respondents drinking at risky (20.01–40 g of alcohol/day) and high risk (>40 g of alcohol per day) levels had an increased prevalence of ASB perpetration with adjusted odds ratios of 3.63 (95% CI 2.98–4.42) and 8.07 (6.72–9.71). Increasing frequency of HED was also linked to increased self-report of ASB perpetration in bivariable and multivariable models. In our interaction models, we found higher probabilities of ASB perpetration among younger and unmarried respondents for a given level of drinking. Discussion and conclusionsBoth average daily alcohol consumption and frequency of HED predict the probability of perpetrating alcohol-related ASB. Unsurprisingly, the risk of alcohol-specific ASB increased more quickly with consumption levels for younger and single respondents, suggesting interventions to reduce consumption among younger and unmarried persons will significantly impact ASB.

Alcohol consumption trajectories over the Australian life course.

Background and AimsAlcohol consumption changes markedly over the life course, with important implications for health and social development. Assessment of these patterns often relies on cross‐sectional data, which cannot fully capture how individuals' drinking changes as they age. This study used data from 18 waves of a general population panel survey to measure drinking trajectories over the life course in Australia.Design and SettingLongitudinal survey data from the Household, Income and Labour Dynamics in Australia (HILDA) survey between 2001 and 2018.ParticipantsA total of 20 593 individuals ages 15 or above in two samples assessing quantity‐frequency (n = 20 569, 52.0% female) and risky single occasion drinking (RSOD), respectively, (n = 17 340, 52.5% female), interviewed as part of HILDA.MeasurementsUsual quantity of alcohol consumed per drinking occasion; frequency of drinking occasions per week; average daily consumption, calculated by combining reported usual quantity and frequency; and average reported frequency of RSOD per week.FindingsMultilevel, mixed effects models run with fractional polynomial terms found similar male and female alcohol consumption trajectories for quantity‐frequency and RSOD measures. Usual quantity of alcohol consumed per drinking occasion (5.4 drinks for men, 3.8 for women) and RSOD frequency (0.56 occasions/week for men, 0.38 for women) peaked in young adulthood, whereas frequency of drinking occasions (2.5 occasions/week for men, 1.7 for women) peaked in middle age. Middle‐age drinkers had the highest average daily consumption of alcohol (1.4 drinks/day for 54‐year‐old men, 0.6 drinks for 57‐year‐old women) and engaged in RSOD slightly less than young adults.ConclusionsAlcohol consumption in Australia appears to vary substantially over the life course, with usual quantity per drinking occasion and frequency of risky single occasion drinking peaking during early adulthood and average daily consumption and frequency of consumption peaking in middle age.

P576 Real-world effectiveness and safety of risankizumab in patients with moderate-to-severe multi-refractory Crohn’s disease: a Belgian multi-centric cohort study

Abstract Background In recent phase 3 trials, risankizumab (RZB), a humanised monoclonal IgG1 antibody targeting the interleukin 23 p19 subunit, proved to be superior to placebo in inducing and maintaining clinical remission and endoscopic response in patients with moderate-to-severe Crohn’s disease. In this study, we aimed to evaluate the effectiveness and safety of RZB in a real-world cohort of multi-refractory CD patients. Methods Adult CD patients from six Belgian IBD centres who initiated RZB prior to May 2021 as part of a medical need program were prospectively followed. Patients with an ostomy were excluded for the main analyses. The primary endpoint was steroid-free clinical remission at week 24 (average daily liquid stool frequency [SF] ≤2.8 and average abdominal pain [AP] score ≤1, both not worse than baseline). Secondary endpoints included clinical response, endoscopic remission, endoscopic response, biological remission, biological response, need for CD-related hospitalisation or surgery, and serious adverse events (definitions in Figure 1). Given that a follow-up endoscopy has not yet been performed in some patients, results are shown for both “all patients” (with non-responder imputation) and “as observed”. Results A total of 27 patients started RZB of whom 19 patients were eligible for this study with a minimal follow-up of 24 weeks (Table 1). Eight patients were excluded as they had an ostomy at time of RZB initiation. Eighteen patients (95%) had been exposed to more than 3 biologicals and 13 (68%) previously underwent a CD-related intestinal resection. By week 24, 7/19 (37%) and 7/19 (37%) patients achieved steroid-free clinical remission and endoscopic response, respectively (Figure 1). In the “as observed” analyses, these rates were 7/18 (39%) and 7/9 (78%), respectively (Figure 2). Five patients used concomitant steroids at baseline and were all able to stop it after a median of 10 weeks. Eventually, three patients had to be hospitalized for bowel resection (2 with placement of an ostomy) after a median of 24 weeks, two of them required earlier an emergent hospitalization due to flares of abdominal pain and bloody diarrhea. None of the patients experienced serious infections or intolerance. Based on physician global assessment, three out of eight patients with an ostomy did achieve clinical remission, and two other achieved clinical response. Endoscopic follow-up data were available in six patients, and three of them experienced endoscopic response. Conclusion In this real-world, multi-refractory cohort, clinical remission and endoscopic response were both observed by week 24 in more than one third of CD patients initiating RZB. RZB was well tolerated with no safety issues.