Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis

;irikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial. Methods: We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis. In the induction trial, patients were randomly assigned in a 3:1 ratio to receive mirikizumab (300 mg) or placebo, administered intravenously, every 4 weeks for 12 weeks. In the maintenance trial, patients with a response to mirikizumab induction therapy were randomly assigned in a 2:1 ratio to receive mirikizumab (200 mg) or placebo, administered subcutaneously, every 4 weeks for 40 weeks. The primary end points were clinical remission at week 12 in the induction trial and at week 40 (at 52 weeks overall) in the maintenance trial. Major secondary end points included clinical response, endoscopic remission, and improvement in bowel-movement urgency. Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as extended induction. Safety was also assessed. Results: A total of 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial. Significantly higher percentages of patients in the mirikizumab group than in the placebo group had clinical remission at week 12 of the induction trial (24.2% vs. 13.3%, P<0.001) and at week 40 of the maintenance trial (49.9% vs. 25.1%, P<0.001). The criteria for all the major secondary end points were met in both trials. Adverse events of nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1217 patients treated with mirikizumab during the controlled and uncontrolled periods (including the open-label extension and maintenance periods) in the two trials, 15 had an opportunistic infection (including 6 with herpes zoster infection) and 8 had cancer (including 3 with colorectal cancer). Among the patients who received placebo in the induction trial, 1 had herpes zoster infection and none had cancer. Conclusions: Mirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis. Opportunistic infection or cancer occurred in a small number of patients treated with mirikizuma

How to Build Collective Capabilities: The 3C-Model for Grassroots-led Development

Capabilities need to be built from the bottom-up. Social innovations at the grassroots seek to present new solutions to existing social problems. However, since the poor suffer from limitations on their individual capabilities and agency, they engage in acts of collective agency to generate new collective capabilities that each individual alone would not be able to achieve. The question is: how can these acts of collective agency be initiated, supported and sustained in practice? What roles can development actors (such as the state, donors and NGOs) play in supporting these acts of collective agency? Drawing on the literature on social innovation, the capability approach, participation and empowerment, the paper argues that three crucial C-processes are integral conditions for promoting successful, scalable and sustainable social innovations at the grassroots, namely: (1) Conscientization; (2) Conciliation and (3) Collaboration. By linking the individual, collective and institutional levels of analysis, the paper demonstrates the importance of individual behavioural changes, collective agency and local institutional reforms for the success, sustainability and scalability of social innovations at the grassroots. The paper acknowledges conflict, capture and cooptation as potential limitations and recognizes the role of contextual factors in initiating, implementing and sustaining social innovations at the grassroots

Social innovations for social cohesion in Western Europe: success dimensions for lifelong learning and education

YesIn addressing the EU2020 goals, skills shortage combined with increasing unemployment rates is to be primarily tackled in Western Europe; the common factor here is education. Education and lifelong learning (LL) are the key strands governing employability in the European labour market. Overarching concepts capable of addressing social challenges within education and LL that contribute towards better practices are seen as social innovations (SI). While SI in education is well founded in the developing countries, Europe is still in the process of gaining progressive momentum in this direction. In addressing various societal challenges, this study looks at observable trends in SI for education across Western Europe. About 30 innovations have been recorded across 11 countries that are essentially focussed on: social integration, alternative/new forms of education, digital learning, new learning arrangements, new LL strategies, early career planning, youth employment, quality improvements and new education standards, transition management, and entrepreneurial education.European Union’s Seventh Framework Programme for research, technological development and demonstration [grant number 612870]

Knowledge of dental academics about the COVID-19 pandemic: a multi-country online survey.

BACKGROUND: COVID-19 is a global pandemic affecting all aspects of life in all countries. We assessed COVID-19 knowledge and associated factors among dental academics in 26 countries. METHODS: We invited dental academics to participate in a cross-sectional, multi-country, online survey from March to April 2020. The survey collected data on knowledge of COVID-19 regarding the mode of transmission, symptoms, diagnosis, treatment, protection, and dental treatment precautions as well as participants' background variables. Multilevel linear models were used to assess the association between dental academics' knowledge of COVID-19 and individual level (personal and professional) and country-level (number of COVID-19 cases/ million population) factors accounting for random variation among countries. RESULTS: Two thousand forty-five academics participated in the survey (response rate 14.3%, with 54.7% female and 67% younger than 46 years of age). The mean (SD) knowledge percent score was 73.2 (11.2) %, and the score of knowledge of symptoms was significantly lower than the score of knowledge of diagnostic methods (53.1 and 85.4%, P <  0.0001). Knowledge score was significantly higher among those living with a partner/spouse than among those living alone (regression coefficient (B) = 0.48); higher among those with PhD degrees than among those with Bachelor of Dental Science degrees (B = 0.48); higher among those seeing 21 to 30 patients daily than among those seeing no patients (B = 0.65); and higher among those from countries with a higher number of COVID-19 cases/million population (B = 0.0007). CONCLUSIONS: Dental academics had poorer knowledge of COVID-19 symptoms than of COVID-19 diagnostic methods. Living arrangements, academic degrees, patient load, and magnitude of the epidemic in the country were associated with COVD-19 knowledge among dental academics. Training of dental academics on COVID-19 can be designed using these findings to recruit those with the greatest need

Knowledge of dental academics about the COVID-19 pandemic: a multi-country online survey

Background: COVID-19 is a global pandemic affecting all aspects of life in all countries. We assessed COVID-19 knowledge and associated factors among dental academics in 26 countries. Methods: We invited dental academics to participate in a cross-sectional, multi-country, online survey from March to April 2020. The survey collected data on knowledge of COVID-19 regarding the mode of transmission, symptoms, diagnosis, treatment, protection, and dental treatment precautions as well as participants’ background variables. Multilevel linear models were used to assess the association between dental academics’ knowledge of COVID-19 and individual level (personal and professional) and country-level (number of COVID-19 cases/ million population) factors accounting for random variation among countries. Results: Two thousand forty-five academics participated in the survey (response rate 14.3%, with 54.7% female and 67% younger than 46 years of age). The mean (SD) knowledge percent score was 73.2 (11.2) %, and the score of knowledge of symptoms was significantly lower than the score of knowledge of diagnostic methods (53.1 and 85.4%, P &lt; 0.0001). Knowledge score was significantly higher among those living with a partner/spouse than among those living alone (regression coefficient (B) = 0.48); higher among those with PhD degrees than among those with Bachelor of Dental Science degrees (B = 0.48); higher among those seeing 21 to 30 patients daily than among those seeing no patients (B = 0.65); and higher among those from countries with a higher number of COVID-19 cases/million population (B = 0.0007). Conclusions: Dental academics had poorer knowledge of COVID-19 symptoms than of COVID-19 diagnostic methods. Living arrangements, academic degrees, patient load, and magnitude of the epidemic in the country were associated with COVD-19 knowledge among dental academics. Training of dental academics on COVID-19 can be designed using these findings to recruit those with the greatest need

Perceived preparedness of dental academic institutions to cope with the COVID-19 pandemic: a multi-country survey

Dental academic institutions are affected by COVID-19. We assessed the perceived COVID19 preparedness of these institutions and the characteristics of institutions with greater perceived preparedness. An international cross-sectional survey of dental academics was conducted from March to August 2020 to assess academics’ and institutional attributes, perceived preparedness, and availability of infection prevention and control (IPC) equipment. Principal component analysis (PCA) identified perceived preparedness components. Multilevel linear regression analysis assessed the association between perceived preparedness and fixed effect factors (academics’ and institutions’ attributes) with countries as random effect variable. Of the 1820 dental academics from 28 countries, 78.4% worked in public institutions and 75.2% reported temporary closure. PCA showed five components: clinic apparel, measures before and after patient care, institutional policies, and availability of IPC equipment. Significantly less perceived preparedness was reported in lower-middle income (LMICs) (B = −1.31, p = 0.006) and upper-middle income (UMICs) (B = −0.98, p = 0.02) countries than in high-income countries (HICs), in teaching only (B = −0.55, p &lt; 0.0001) and in research only (B = −1.22, p = 0.003) than teaching and research institutions and in institutions receiving ≤100 patients daily than those receiving &gt;100 patients (B = −0.38, p &lt; 0.0001). More perceived preparedness was reported by academics with administrative roles (B = 0.59, p &lt; 0.0001). Academics from low-income countries (LICs) and LMICs reported less availability of clinic apparel, IPC equipment, measures before patient care, and institutional policies but more measures during patient care. There was greater perceived preparedness in HICs and institutions with greater involvement in teaching, research, and patient care

Understanding social innovation in services industries

This paper puts forward a framework for understanding the relationship between service industries and social innovation. These are two, previously disconnected research areas. The paper explores ways in which innovation in services is increasingly becoming one of social innovation (in terms of social goals, social means, social roles and multi-agent provision) and how social innovation can be understood from a service innovation perspective. A taxonomy is proposed based on the mix between innovation nature and the locus of co-production. The paper additionally puts forward a theoretical framework for understanding social innovation in services, where the co-creation of innovation is the result of an interaction of competences and preferences of multiple providers, users/citizens, and policy makers. This provides the basis for a discussion of key avenues for future research in theory, measurement, organisation, appropriation, performance measurement, and public policy

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Behavior change due to COVID-19 among dental academics-The theory of planned behavior: Stresses, worries, training, and pandemic severity

Objective: COVID-19 pandemic led to major life changes. We assessed the psychological impact of COVID-19 on dental academics globally and on changes in their behaviors. Methods: We invited dental academics to complete a cross-sectional, online survey from March to May 2020. The survey was based on the Theory of Planned Behavior (TPB). The survey collected data on participants’ stress levels (using the Impact of Event Scale), attitude (fears, and worries because of COVID-19 extracted by Principal Component Analysis (PCA), perceived control (resulting from training on public health emergencies), norms (country-level COVID-19 fatality rate), and personal and professional backgrounds. We used multilevel regression models to assess the association between the study outcome variables (frequent handwashing and avoidance of crowded places) and explanatory variables (stress, attitude, perceived control and norms). Results: 1862 academics from 28 countries participated in the survey (response rate = 11.3%). Of those, 53.4% were female, 32.9% were <46 years old and 9.9% had severe stress. PCA extracted three main factors: fear of infection, worries because of professional responsibilities, and worries because of restricted mobility. These factors had significant dosedependent association with stress and were significantly associated with more frequent handwashing by dental academics (B = 0.56, 0.33, and 0.34) and avoiding crowded places (B = 0.55, 0.30, and 0.28). Low country fatality rates were significantly associated with more handwashing (B = -2.82) and avoiding crowded places (B = -6.61). Training on public health emergencies was not significantly associated with behavior change (B = -0.01 and -0.11). Conclusions: COVID-19 had a considerable psychological impact on dental academics. There was a direct, dose-dependent association between change in behaviors and worries but no association between these changes and training on public health emergencies. More change in behaviors was associated with lower country COVID-19 fatality rates. Fears and stresses were associated with greater adoption of preventive measures against the pandemic

Perceived Preparedness of Dental Academic Institutions to Cope with the COVID-19 Pandemic: A Multi-Country Survey

Dental academic institutions are affected by COVID-19. We assessed the perceived COVID-19 preparedness of these institutions and the characteristics of institutions with greater perceived preparedness. An international cross-sectional survey of dental academics was conducted from March to August 2020 to assess academics’ and institutional attributes, perceived preparedness, and availability of infection prevention and control (IPC) equipment. Principal component analysis (PCA) identified perceived preparedness components. Multilevel linear regression analysis assessed the association between perceived preparedness and fixed effect factors (academics’ and institutions’ attributes) with countries as random effect variable. Of the 1820 dental academics from 28 countries, 78.4% worked in public institutions and 75.2% reported temporary closure. PCA showed five components: clinic apparel, measures before and after patient care, institutional policies, and availability of IPC equipment. Significantly less perceived preparedness was reported in lower-middle income (LMICs) (B = −1.31, p = 0.006) and upper-middle income (UMICs) (B = −0.98, p = 0.02) countries than in high-income countries (HICs), in teaching only (B = −0.55, p &lt; 0.0001) and in research only (B = −1.22, p = 0.003) than teaching and research institutions and in institutions receiving ≤100 patients daily than those receiving &gt;100 patients (B = −0.38, p &lt; 0.0001). More perceived preparedness was reported by academics with administrative roles (B = 0.59, p &lt; 0.0001). Academics from low-income countries (LICs) and LMICs reported less availability of clinic apparel, IPC equipment, measures before patient care, and institutional policies but more measures during patient care. There was greater perceived preparedness in HICs and institutions with greater involvement in teaching, research, and patient care