bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated safety analysis of filgotinib for ulcerative colitis: Results from SELECTION and SELECTIONLTE
Authors: Schreiber Stefan , Rogler Gerhard , Watanabe Mamoru , Vermeire Séverine , Maaser Christian , Danese Silvio , Faes Margaux , Van Hoek Paul , Hsieh Jeremy , Moerch Ulrik , Zhou Yan , de Haas Angela , Rudolph Christine , Oortwijn Alessandra , Loftus Edward V. 
Published: September 2023

SummaryBackgroundFilgotinib 200 mg (FIL200) is an approved treatment for adults with moderately to severely active ulcerative colitis (UC).AimTo report integrated safety data from the phase 2b/3 SELECTION study (NCT02914522) and its ongoing long‐term extension study SELECTIONLTE (NCT02914535).MethodsSafety outcomes were analysed in adults with moderately to severely active UC who received FIL200, filgotinib 100 mg (FIL100) or placebo once daily throughout the 11‐week SELECTION induction study, the 47‐week SELECTION maintenance study (if applicable) and SELECTIONLTE (if applicable). Exposure‐adjusted incidence rates (EAIRs) per 100 censored patient‐years of exposure with 95% confidence intervals were reported for treatment‐emergent adverse events (AEs). Certain AE data were presented in subgroups, including age and prior biologic exposure status.ResultsThis interim analysis included 1348 patients representing 3326.2 patient‐years of exposure. Baseline characteristics of patients entering SELECTION were similar across treatment groups. EAIRs for serious infection, thromboembolic events and major adverse cardiovascular events (MACE) were consistently low across treatment groups. Most patients with MACE had cardiovascular risk factors. The EAIR for herpes zoster was numerically higher for FIL200 than for placebo. Infection incidences were numerically higher in biologic‐experienced than biologic‐naive patients. Higher incidences of certain AEs in patients 65 years of age or older were as expected. Four deaths occurred, including three cardiovascular deaths, none of which was considered related to filgotinib.ConclusionFIL200 and FIL100 were well tolerated with no unexpected safety signals in patients with moderately to severely active UC, regardless of previous biologic exposure or age.ClinicalTrials.gov Identifiers (NCT numbers)NCT02914522, NCT02914535.
Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy‐confirmed nonalcoholic steatohepatitis
Authors: Alkhouri Naim , Lazas Donald , Loomba Rohit , Frias Juan P. , Feng Shibao , Tseng Leo , Balic Kemal , Agollah Germaine D. , Kwan Tinna , Iyer Janani S. , Morrow Linda , Mansbach Hank , Margalit Maya , Harrison Stephen A. 
Published: September 2023

SummaryBackgroundAn approved therapy for nonalcoholic steatohepatitis (NASH) and fibrosis remains a major unmet medical need.AimTo investigate the histological and metabolic benefits of pegozafermin, a glycoPEGylated FGF21 analogue, in subjects with biopsy‐confirmed NASH.MethodsThis proof‐of‐concept, open‐label, single‐cohort study, part 2 of a phase 1b/2a clinical trial, was conducted at 16 centres in the United States. Adults (age 21–75 years) with NASH (stage 2 or 3 fibrosis, NAS≥4) and magnetic resonance imaging proton density fat fraction (MRI‐PDFF) ≥8% received subcutaneous pegozafermin 27 mg once weekly for 20 weeks. Primary outcomes were improvements in liver histology, and safety and tolerability.ResultsOf 20 enrolled subjects, 19 completed the study. Twelve subjects (63%) met the primary endpoint of ≥2‐point improvement in NAFLD activity score with ≥1‐point improvement in ballooning or lobular inflammation and no worsening of fibrosis. Improvement of fibrosis without worsening of NASH was observed in 26% of subjects, and NASH resolution without worsening of fibrosis in 32%. Least‐squares mean relative change from baseline in MRI‐PDFF was −64.7% (95% CI: −71.7, −57.7; p < 0.0001). Significant improvements from baseline were also seen in serum aminotransferases, noninvasive fibrosis tests, serum lipids, glycaemic control and body weight. Adverse events (AEs) were reported in 18 subjects (90%). The most frequently reported AEs were mild/moderate nausea and diarrhoea. There were no serious AEs, discontinuations due to AEs, or deaths.ConclusionsPegozafermin treatment for 20 weeks had beneficial effects on hepatic and metabolic parameters and was well tolerated in subjects with NASH. ClinicalTrials.gov: NCT04048135.
Liver disease progression in patients with alpha‐1 antitrypsin deficiency and protease inhibitor ZZ genotype with or without lung disease
Authors: Wu Tiffany , Hagiwara May , Gnass Esteban , Barman Hannah , Sasson David , Treem William , Ren Kaili , Marins Ed G. , Karki Chitra , Malhi Harmeet 
Published: September 2023

SummaryBackgroundAlpha‐1 antitrypsin deficiency (AATD) is caused by mutations in SERPINA1, which encodes alpha‐1 antitrypsin, a protease inhibitor (Pi). Individuals with AATD and the homozygous Pi*ZZ genotype have variable risk of progressive liver disease but the influence of comorbid lung disease is poorly understood.AimsTo characterise patients with AATD Pi*ZZ and liver disease (AATD‐LD‐Pi*ZZ) with or without lung disease and describe liver disease‐related clinical events longitudinally.MethodsThis was an observational cohort study of patients in the Mayo Clinic Healthcare System (January 2000–September 2021). Patients were identified using diagnosis codes and natural language processing. Fibrosis stage (F0–F4) was assessed using a hierarchical approach at baseline (90 days before or after the index date) and follow‐up. Clinical events associated with liver disease progression were assessed.ResultsAATD‐LD‐Pi*ZZ patients with lung disease had a longer median time from AATD diagnosis to liver disease diagnosis versus those without lung disease (2.2 vs. 0.2 years, respectively). Compared to those without lung disease, patients with lung disease had a longer time to liver disease‐related clinical events (8.5 years and not reached, respectively). AATD‐LD‐Pi*ZZ patients without lung disease were more likely to undergo liver transplantation compared with those with lung disease.ConclusionIn patients with AATD and lung disease, there is a delay in the diagnosis of comorbid liver disease. Our findings suggest that liver disease may progress more rapidly in patients without comorbid lung disease.
Model‐informed precision dosing of vancomycin for rapid achievement of target area under the concentration‐time curve: A simulation study
Authors: Oda Kazutaka , Yamada Tomoyuki , Matsumoto Kazuaki , Hanai Yuki , Ueda Takashi , Samura Masaru , Shigemi Akari , Jono Hirofumi , Saito Hideyuki , Kimura Toshimi 
Published: September 2023

AbstractIn this study, we aimed to evaluate limited sampling strategies for achieving the therapeutic ranges of the area under the concentration‐time curve (AUC) of vancomycin on the first and second day (AUC0–24, AUC24–48, respectively) of therapy. A virtual population of 1000 individuals was created using a population pharmacokinetic (PopPK) model, which was validated and incorporated into our model‐informed precision dosing tool. The results were evaluated using six additional PopPK models selected based on a study design of prospective or retrospective data collection with sufficient concentrations. Bayesian forecasting was performed to evaluate the probability of achieving the therapeutic range of AUC, defined as a ratio of estimated/reference AUC within 0.8–1.2. The Bayesian posterior probability of achieving the AUC24–48 range increased from 51.3% (a priori probability) to 77.5% after using two‐point sampling at the trough and peak on the first day. Sampling on the first day also yielded a higher Bayesian posterior probability (86.1%) of achieving the AUC0–24 range compared to the a priori probability of 60.1%. The Bayesian posterior probability of achieving the AUC at steady‐state (AUCSS) range by sampling on the first or second day decreased with decreased kidney function. We demonstrated that second‐day trough and peak sampling provided accurate AUC24–48, and first‐day sampling may assist in rapidly achieving therapeutic AUC24–48, although the AUCSS should be re‐estimated in patients with reduced kidney function owing to its unreliable predictive performance.
Assessing pharmacogenomic literacy in China through validation of the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy
Authors: Zhang Lusi , Zhou Shuqin , Allen Josiah D. , Wang Fan , Pittenger Amy L. , Bishop Jeffrey R. 
Published: September 2023

AbstractPharmacogenomics (PGx) implementation into clinical care is rapidly increasing in China. However, the extent to which the public understands PGx testing and important knowledge domains requiring patient education or counseling remains unclear. To address this, we created and validated the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy (MAPL‐CTM). The MAPL‐C was developed by translating the English MAPL to Chinese following cross‐cultural translation guidelines. An online survey validated the MAPL‐C and assessed Chinese individuals' PGx literacy. Validation analyses were performed and associations of PGx literacy with participants' characteristics were quantified. Of 959 high‐quality responses, the majority of respondents were Han Chinese (96.3%), men (54.5%), aged 18–29 years (70.9%), residing in China (97.3%), and had received college or higher education (95.0%). Out of 15 starting items developed to query specific predefined knowledge domains, two uninformative items were excluded, resulting in a 13‐item MAPL‐C. Chinese participants' MAPL‐C performance was best explained by a three‐factor model, encompassing PGx concepts and function, testing limitations, and privacy. Higher MAPL‐C performance was associated with younger age, higher education, and previous genetic testing experience. Correct response rates for questions related to testing limitations were lower than those in other domains. The creation and validation of the MAPL‐C fills a gap in determining PGx knowledge among Chinese speakers, quantifying PGx literacy within a Chinese cohort, and identifying response patterns and knowledge gaps. The MAPL‐C can be useful in clinical practice to guide patient counseling, assess PGx education interventions, and quantify PGx knowledge in relation to outcomes in research studies involving Chinese participants.
Prevalence and prescribing patterns of oral corticosteroids in the United States, Taiwan, and Denmark, 2009–2018
Authors: Wallace Beth I. , Tsai Hui‐Ju , Lin Paul , Aasbjerg Kristian , Wu Ann Chen , Tsai Yi‐Fen , Torp‐Pedersen Christian , Waljee Akbar K. , Yao Tsung‐Chieh 
Published: September 2023

AbstractOral corticosteroids (OCS) are commonly prescribed for acute, self‐limited conditions, despite studies demonstrating toxicity. Studies evaluating longitudinal OCS prescribing in the general population are scarce and do not compare use across countries. This study investigated and compared OCS prescription patterns from 2009 to 2018 in the general populations of the United States, Taiwan, and Denmark. This international population‐based longitudinal cohort study used nationwide claims databases (United States: Optum Clinformatics Data Mart; de‐identified; Taiwan: National Health Insurance Research Database; and Denmark: National Prescription and Patient Registries/Danish National Patient Registry) to evaluate OCS prescribing. We classified annual OCS duration as short‐term (1–29 days), medium‐term (30–89 days), or long‐term (≥90 days). Longitudinal change in annual prevalence of OCS use and physician prescribing patterns were reported. Among 54,630,437 participants, average annual percentage of overall OCS use was 6.8% in the United States, 17.5% in Taiwan, and 2.2% in Denmark during 2009–2018. Prevalence of OCS prescribing increased at an average annual rate of 0.1%–0.17%, mainly driven by short‐term prescribing to healthy adults. One‐quarter to one‐fifth of OCS prescribing was associated with a diagnosis of respiratory infection. Family practice and internal medicine physicians were among the highest OCS prescribers across countries and durations. Age‐ and sex‐stratified trends mirrored unstratified trends. This study provides real‐world evidence of an ongoing steady increase in OCS use in the general populations of the United States, Taiwan, and Denmark. This increase is largely driven by short‐term OCS prescribing to healthy adults, a practice previously viewed as safe but recently shown to incur substantial population‐level risk.
State‐owned Enterprises in China as Macroeconomic Stabilizers: Their Special Function in Times of Economic Policy Uncertainty
Authors: Fang Mingyue , Ruan Rui 
Published: September 2023

AbstractChina has many state‐owned enterprises (SOEs) and they have accounted for a large proportion of China's GDP over the last four decades. China's rapid growth contradicts literature that focuses on the inefficiency of SOEs. This study shows that, in periods of economic policy uncertainty (EPU), SOEs have performed a special function as “macroeconomic stabilizers.” Using Chinese listed firm data from 2008 to 2019, we investigate five aspects of SOEs' unique functions as macroeconomic stabilizers: employment, investment, growth, financial operation, and expectations. When EPU increased, SOEs had more employment, higher investment expenditure, lower performance volatility, more robust financial structures, and more stable expectations than private firms. We employ the US–China trade war as an exogenous shock on EPU to conduct a difference‐in‐difference‐in‐differences approach to mitigate the problem of potentially omitted variables. The findings of this study provide a new perspective to better explain the functions of SOEs in the 21st century.
‘I don't chase drugs as much anymore, and I'm not dead’: Client reported outcomes associated with safer opioid supply programs in Ontario, Canada
Authors: Schmidt Rose A. , Kaminski Nat , Kryszajtys David T. , Rudzinski Katherine , Perri Melissa , Guta Adrian , Benoit Anita C. , Bayoumi Ahmed M. , Challacombe Laurel , Hales Jessica , Kenny Kathleen , Kolla Gillian , O'Reilly Emmet , Sereda Andrea , Rai Nanky , Strike Carol 
Published: September 2023

AbstractIntroductionThe ongoing opioid overdose crisis, which has killed over 30,000 people in Canada since 2016, is driven by the volatility of an unregulated opioid drug supply comprised primarily of fentanyl. The Canadian government has recently funded safer opioid supply (SOS) programs, which include off‐label prescriptions of pharmaceutical‐grade opioids to high risk individuals with the goal of reducing overdose deaths.MethodsIn 2021, we examined the implementation and adaption of four SOS programs in Ontario. These programs use a primary care model and serve communities experiencing marginalisation. We conducted semi‐structured interviews with program clients. We present the results of a thematic analysis with the aim of describing clients' self‐reported impact of these programs on their health and well‐being.ResultsWe interviewed 52 clients between June and October 2021 (mean age 47 years, 56% men, 17% self‐identified Indigenous, 14% living with HIV). Our results indicate multifaceted pathways to improved self‐reported health and well‐being among clients including changes to drug use practices, fewer overdoses, reduced criminalised activity, improved trust and engagement in health care, and increased social stability (e.g., housing).Discussion and ConclusionMost clients reported that the intervention saved their life because of the reduced frequency of overdoses. Findings suggest that SOS programs improved clients' health outcomes and increase opportunities for engagement in health services. Our results provide insight into the mechanisms behind some of the emergent evidence on the impact of safer supply prescribing.
Accelerating local extinction associated with very recent climate change
Authors: Holzmann Kim L. , Walls Ramona L. , Wiens John J. 
Published: September 2023

AbstractClimate change has already caused local extinction in many plants and animals, based on surveys spanning many decades. As climate change accelerates, the pace of these extinctions may also accelerate, potentially leading to large‐scale, species‐level extinctions. We tested this hypothesis in a montane lizard. We resurveyed 18 mountain ranges in 2021–2022 after only ~7 years. We found rates of local extinction among the fastest ever recorded, which have tripled in the past ~7 years relative to the preceding ~42 years. Further, climate change generated local extinction in ~7 years similar to that seen in other organisms over ~70 years. Yet, contrary to expectations, populations at two of the hottest sites survived. We found that genomic data helped predict which populations survived and which went extinct. Overall, we show the increasing risk to biodiversity posed by accelerating climate change and the opportunity to study its effects over surprisingly brief timescales.
Revisiting the impact of families on family firm performance
Authors: Jaskiewicz Peter , Combs James G. , Uhlenbruck Klaus , Datta Amlan 
Published: September 2023

AbstractFamily owners monitor managers, attenuating principal–agent conflicts and improving firm performance. However, family owners also appropriate resources, creating principal–principal conflicts that harm firm performance. Although these effects occur simultaneously, research does not explain when one outweighs the other. We theorize that agency costs are minimized when the family's involvement on the board of directors is proportional to its ownership; too little board involvement fuels principal–agent conflicts, and too much fuels principal–principal conflicts. Consistent with our theorizing, evidence from French panel data shows firm performance increases as family board involvement and family ownership jointly increase, and performance is maximized when family board involvement and family ownership are proportional.
Creativity governance: A conceptual framework for tailoring governance to the creativity and uncertainty in entrepreneurial projects
Authors: Araki Michael , Martins Henrique Castro 
Published: September 2023

AbstractGiven the influence of agency theory, corporate governance is tightly associated with the idea of monitoring. But what happens when the decision‐maker must act in an uncertain, open‐ended world? In this article, we propose a typology of firms' projects drawing on two parameters stemming from recent advancements in creativity theory: opacity and unlikelihood. This results in a matrix with four types of projects that display different qualities of entrepreneurialness: replicative projects, incubation projects, insightful projects, and innovative projects. We draw on the knowledge governance literature to suggest mechanisms and strategies of governance based on the prevailing type of project that the organization pursues. Our framework contributes to the theoretical understanding of the interplay between governance, creativity, and entrepreneurship literature while offering practical insights for designing better‐tailored governance mechanisms that align with a firm's prevailing project type.
Treatment‐related outcome from patient report outcome (PRO) of children with severe and moderate hemophilia A in China: An analysis report of registration data from patient organization “hemophilia home care center”
Authors: Guan Tao , Ai Di , Zhao Nan , Liu Guoqing , Yao Wanru , Chen Zhenping , Li Zhenping , Zhou Yaohan , Wu Runhui 
Published: September 2023

AbstractObjectivesTo assess current treatment‐related outcomes for children with severe and moderate haemophilia A (cHA) in China.MethodsThis cross‐section Patient Report Outcome (PRO) report collected PRO data of severe and moderate cHAs registered in the 'Hemophilia Home Care Center' database (http://web.bjxueyou.cn) between January 2021 and November 2022. Data included records of bleeding, activities, and concentrates consumption. All patients had a confirmed diagnosis of moderate or severe haemophilia A (FVIII: C ≤ 5%) and were < 18 years old.ResultsAmong 1038 analysable cases, 9.6% of children with inhibitors had a higher rate of intracranial haemorrhage, dropout school rate, and higher FVIII consumption than children without inhibitors. Among 100 children with inhibitors, 36 patients were treated without immune tolerance induction (ITI), 14 patients with irregular treatment and 50 patients received ITI. Children with ITI had a lower ABR (2.4 (0,6.6) vs. 13.4 (9.5, 26.6), p<.001) and AJBR (0 (0, 3.1) vs. 8.9 (1.6, 19.3), p < .001) compared to those without ITI. Among 938 children without inhibitors, 28.5% received on‐demand treatment and 71.5% received prophylaxis. Of 528 children with 1343.8 (1050.4, 2922.9)IU/kg/year median FVIII consumption, 43.0% received low‐dose, 43.2% received intermediate‐dose, and 13.8% received high‐dose regimen; these children with prophylaxis had a lower ABR (3.1 (0, 10.7) vs. 12.8 (2.4, 45.5), p < .001), AJBR (0.5 (0, 3.9) vs. 3.0 (0, 12.0), p < .001) and disability rate (9.0% vs.18.5%, p = .032) compared to children who received on‐demand treatment.ConclusionThe high rate of drop‐out of school and disability still present a huge gap to meet the needs in China. It is necessary to improve the level of medical accessibility and medicine affordability and strengthen the patient/parent's education in China.
In‐vitro comparison of two different toothbrush bristles about peri‐implant sulcus penetration
Authors: Montevecchi Marco , Valeriani Leoluca , Bellanova Leonardo , Stefanini Martina , Zucchelli Giovanni 
Published: September 2023

AbstractObjectiveThe aim of this preclinical study was to compare the ability of tapered and cylindrical bristles to penetrate the peri‐implant sulcus.MethodsA full mandibular dental arch was reproduced in plaster cast. In site #3.6 a hollow glass cylinder was positioned simulating a 4 mm diameter implant and the gingival component was recreated by using dedicated silicone. A Bass brushing technique was performed from the vestibular side in humid environment. During it, the penetration of the bristles between the gum and the implant was recorded by mean of an optic fibre fixed inside the cylinder. The protocol included 5 toothbrushes per group and 10 tests per toothbrush, for a total of 50 assessments for each of the two groups.A scale of 5 grades for bristle penetration was defined: grade 0 (× < 2 mm), grade 1 (2 ≤ × < 3 mm), grade 2 (3 ≤ × < 4 mm), grade 3 (4 ≤ × < 5 mm) and grade 4 (5 ≤ × < 8 mm). From the video recordings the highest value of penetration was identified for each test.ResultsThe tapered bristles showed an 8 times greater penetration capacity (p = 0.001) in respect to the cylindrical bristles (multilevel analysis). The percentage of tests reaching depths ≥3 mm was 86% for tapered group and 28% for the cylindrical group.ConclusionThis preclinical study shows a clear and superior penetration capacity of the tapered bristles in respect to traditional cylindrical ones. For tapered bristles, a potentially greater hygienic efficacy around dental implants is suggested.