Opera Studies Research Articles

Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis

ObjectiveThe efficacy and safety of ocrelizumab, versus interferon (IFN) β-1a, for the treatment of relapsing multiple sclerosis (RMS) from the identically designed OPERA I (NCT01247324) and OPERA II (NCT01412333) phase III studies has been reported; here we present subgroup analyses of efficacy endpoints from the pooled OPERA I and OPERA II populations.MethodsPatients with RMS were randomized to either ocrelizumab 600 mg administered by intravenous infusion every 24 weeks or subcutaneous IFN β-1a 44 µg three times per week throughout the 96-week treatment period. Relapse, disability, and MRI outcomes were analyzed for predefined and post hoc subgroups based on demographic and disease characteristics along with prior treatment using appropriate statistical tests to determine the treatment effect in subgroups and treatment-by-subgroup interactions.ResultsThe significant treatment benefit of ocrelizumab, versus IFN β-1a, observed in the overall OPERA I and OPERA II pooled populations was maintained across most subgroup strata for all endpoints, including annualized relapse rate, disability progression, and MRI outputs.ConclusionsThe treatment effect of ocrelizumab versus IFN β-1a, measured by clinical and MRI outcomes, was maintained across most of the subgroups and strata of interest, and the pattern of treatment benefit across all subgroups was consistent with that from the pooled OPERA studies.

Abstract B206: Evaluation of tumor biomarkers in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer treated with the CXCL12 inhibitor NOX-A12 and preliminary safety in combination with PD-1 checkpoint inhibitor pembrolizumab

Abstract Background: NOX-A12 (olaptesed pegol) is a novel inhibitor of the chemokine CXCL12, ligand for CXCR4 and CXCR7, for treatment of solid tumors. Binding of the CXCL12 ligand by NOX-A12 prevents receptor engagement and also blocks the ability of CXCL12 to create a chemotactic concentration gradient by neutralization of the anchor domain. CXCL12 in complex with NOX-A12 has an increased half-life relative to unbound CXCL12, and as such increased CXCL12 levels are a marker of inhibition. The OPERA study (NCT03168139) is a phase 1/2 open-label clinical study to evaluate pharmacodynamic effects and safety of monotherapy with NOX-A12 and safety and efficacy of a combination of NOX-A12 with pembrolizumab in advanced MSS, metastatic colorectal and pancreatic cancer with liver metastasis. The study comprises two weeks of NOX-A12 monotherapy followed by repeated 21-day cycles of NOX-A12 plus pembrolizumab. Here we present pharmacodynamic biomarker data from for monotherapy phase with NOX-A12 as well as safety for the combination with pembrolizumab. Methods: Patients received 300 mg NOX-A12 by i.v. infusion on days 1, 4, 8, and 11 of the monotherapy phase. Needle biopsies were taken from suitable liver metastases before treatment and on day 14, peripheral blood was drawn at the same time points. Collected tumor samples were assessed for immune cell infiltration by IHC and cytokine signature using multiplex protein analysis. Results: At the time of abstract submission, 19 out of 20 patients have been recruited, 10 with colorectal and 9 with pancreatic cancer. Serial biopsies at baseline and end of monotherapy suitable for immunohistochemistry (IHC) and cytokine analysis were obtained from 12 out of 19 patients. CXCL12 levels were found to be increased in blood, but also in post-treatment tumor biopsies, suggesting penetration of NOX-A12 into the tumor. The comparison of cytokine levels in the currently available baseline tumor biopsies with those taken after two weeks of NOX-A12 monotherapy revealed changes in markers that are consistent with a Th1-like immune response in multiple patients. In particular IFN-γ, IL-2 and TNF-β were increased, accompanied by an increase of CXCL9 and/or CXCL10 indicating simultaneous T-cell attraction, which indicates a tissue response to treatment with NOX-A12. However, there were also increased levels of IL-1α, IL-1β and IL-6 in a number of patients, indicating potential myeloid counter regulation. IHC analysis is ongoing, and results for all patients will be presented. Treatment with NOX-A12 monotherapy and in combination with pembrolizumab was generally safe and well tolerated (139 AEs in total, thereof 45% grade 1; 37% grade 2; 17% grade 3; no grade 4 and 1 % grade 5). Conclusions: NOX-A12 penetrates into the tumor where it binds and neutralizes CXCL12. Changes in the cytokine signature suggest that NOX-A12 modulates the tumor microenvironment and induces an immune-stimulatory Th1-like signature in multiple patients. The safety profile of NOX-A12 combined with pembrolizumab is consistent with that of pembrolizumab in advanced cancer patients. Citation Format: Niels Halama, Ulrike Prüfer, Anna Froemming, Diana Beyer, Dirk Eulberg, Jarl Ulf Jungnelius, Aram Mangasarian. Evaluation of tumor biomarkers in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer treated with the CXCL12 inhibitor NOX-A12 and preliminary safety in combination with PD-1 checkpoint inhibitor pembrolizumab [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B206.

Ocrelizumab infusion experience in patients with relapsing and primary progressive multiple sclerosis: Results from the phase 3 randomized OPERA I, OPERA II, and ORATORIO studies

BackgroundOcrelizumab is an infusible humanized monoclonal antibody that selectively depletes CD20+ B cells. Infusion-related reactions (IRRs) were summarized from the OPERA I, OPERA II, and ORATORIO trials for relapsing and primary progressive multiple sclerosis (MS). MethodsOPERA I and OPERA II were identical, randomized, double-blind, active-controlled trials that enrolled patients with relapsing MS (RMS). Patients in the ocrelizumab group initially received two 300-mg intravenous (IV) infusions separated by 14 days (on Days 1 and 15); subsequent doses were administered as single 600-mg IV infusions. Ocrelizumab-treated patients also received subcutaneous (SC) placebo injections 3 times weekly. Patients in the active comparator group received SC injections of IFN β-1a 3 times weekly, as well as placebo infusions on Days 1 and 15 and Weeks 24, 48, and 72. ORATORIO was a randomized, parallel-group, double-blind, placebo-controlled study that enrolled patients with primary progressive MS (PPMS). As in the OPERA studies, patients in the ocrelizumab group initially received two 300-mg infusions separated by 14 days; however, ORATORIO patients continued to receive this divided-dose regimen throughout the study. The ORATORIO control group received IV placebo. Prior to each infusion, all patients in the OPERA and ORATORIO studies were pretreated with 100 mg IV methylprednisolone; additional prophylactic treatment with analgesics, antipyretics, and/or an IV or oral antihistamine was optional. IRRs were defined as adverse events that occurred during or within 24 h of IV infusion of ocrelizumab or placebo. ResultsSafety analyses included 1651 patients with RMS from OPERA I and OPERA II (ocrelizumab, n = 825; IFN β-1a, n = 826) and 725 patients with PPMS from ORATORIO (ocrelizumab, n = 486; placebo, n = 239). Across studies, IRRs were reported in 34.3% (vs 9.7% with IFN β-1a) and 39.9% (vs 25.5% with placebo) of ocrelizumab-treated patients in the pooled OPERA and ORATORIO populations, respectively. The majority of IRRs were mild to moderate in the OPERA (ocrelizumab, 92.6%; IFN β-1a, 98.8%) and ORATORIO (ocrelizumab, 96.9%; placebo, 93.4%) studies. IRRs most commonly occurred with the first infusion. Severe IRRs were reported in 2.4% of ocrelizumab-treated patients in the OPERA studies (vs 0.1% with IFN β-1a) and 1.2% of ocrelizumab-treated patients in ORATORIO (vs 1.7% with placebo). Two serious IRRs occurred across the OPERA studies, both of which occurred with the initial infusion. The first event occurred in an IFN β-1a-treated patient in association with the initial infusion of IV placebo and consisted of severe balance disorder, dizziness, flushing, and hypoesthesia. The second event was a life-threatening reaction (bronchospasm) that occurred in an ocrelizumab-treated patient 15 min after the infusion started. Frequently reported IRR symptoms included pruritus, rash, throat irritation, and flushing. Premedication use, particularly antihistamines, was associated with fewer IRRs. ConclusionFindings from the OPERA I, OPERA II, and ORATORIO trials show that IRRs were the most frequently reported adverse events with ocrelizumab, were mostly mild to moderate in severity, were reduced with appropriate pretreatment, and decreased with subsequent dosing. IRRs that did occur were effectively managed through infusion rate adjustment and symptomatic treatment.

Modern opera house as a subject of musicologist studies: musical, historical and interpretation aspects

The aim of the article is to identify the fundamental principles, artistic parameters and value-semantic guidelines of the modern opera house, considered in a wide musicological discursive field. To study the socio-aesthetic role of artistic value, theoretical parameters for considering the relationship and mutual influence of the phenomena of theater and opera are formed. The methodology of the work is determined by a system of historical and theoretical approaches, each of which is represented by a complex of methods based on the combination of such methodological approaches as musical and historical, interpretive, opera study, theater studies, textological and semiological. The scientific novelty is in the substantiation and systematization of approaches to the study of the phenomenon of modern opera house, within the framework of which the repertoire factography of modern European and Chinese opera houses is created. New interpretative possibilities and directorial decisions are revealed, due to the expansion of artistic and creative boundaries of the opera house as one of the leading sociocommunicative mechanisms of the modern musical and cultural space. Conclusions. Based on this, we can conclude that the modern opera house, as a phenomenon derived from musical theater, basically contains reliance on the relatedness of the musical and theatrical components of the action, since in this type of theater they are an indissoluble unity; direct connection with the historical past, with the cultural and historical traditions that nourished it, together with possible cultural influences from outside; the concentration of theatrical action around the protagonist with an in-depth description of his inner world, psycho-emotional states around which the main event outline of the composition unfolds. The opera house occupies an important place in the musical and historical process and acquires the significance of one of the most powerful socio-cultural institutional mechanisms of culture, exerting a significant impact on the formation of the value-semantic dominants of culture and the personal consciousness of a person.

Between Realism and Re-enactment: Navigating Dramatic and Musical 'Problems' in Voyage to the Moon

How do practitioners understand the relationship between performance, history and emotion in Western art music? Based on an ethnographic study of a contemporary pasticcio opera, we take the rehearsal room as an important, yet often overlooked, site in which creative artists imagine and perform different relationships with their musical and cultural heritage. Focussing on the interplay between two performative modes, which we call realism and re-enactment, we describe how the creative team navigated various dramatic and musical challenges associated with the opera, generating a final production that was ambiguous and multi-layered in its emotional registers and attitudes towards the past.

슈베르트 오페라 및 무대음악 고찰 - 실체와 창작배경을 중심으로 -

예술가곡 장르에서 독보적인 평가를 얻었던 슈베르트의 창작세계에서 오페라 및 무대음악은 현재까지 크게 관심 받지 못했다. 그의 무대음악이 일반 대중이나 학자들 또는 연주자들에게까지도 주목을 받지 못했던 이유나 근거조차 아직 분명하게 설명된 경우도 그리 많지 않은 상황이다. 이에 본 글에서는 성악음악에 그렇게 커다란 업적을 남긴 슈베르트가 오페라나 무대음악에서 어떤 시도나 구체적인 창작작업이 있었는지, 그리고 그에 대한 평가나 연구가 심도 있게 이루어지지 못했는지에 대한 이유를 확인해 보려고 한다. 다양한 종류의 슈베르트 관련 문헌들을 살펴보면, 비록 작품에 대한 구체적인 정보나 분석은 없지만 그의 무대음악이나 오페라 장르 작품은 상당히 다양하고 그 숫자도 적지 않다. 본 논문에서는 우선 그의 오페라 창작과 연관된 기존의 영향이나 교육 그리고 창작 당시의 시대적 상황 등을 작품 의 실체와 창작배경을 중심으로 전반적인 흐름을 고찰했다. 그의 오페라나 무대음악 작품이 오페라 사에서 두드러지지 못한 데에는 여러 가지의 이유가 있는 것으로 밝혀졌으며, 본 글에서 언급한 바와 같이 대본의 문제점, 비엔나에서의 당시 오페라 상황 그리고 오페라 창작의 구체적인 롤모델을 찾지 못한 점 등을 대표적으로 들 수 있다. 그럼에도 불구하고 슈베르트가 남긴 많은 오페라나 무대음악 작품들은 분명 그의 창작에 중요한 한 부분으로 자리 잡고 있었던 것으로 확인된다. 이러한 연구는 19세기 초반 비엔나를 중심으로 한 유럽의 오페라사의 한 부분을 채울 수 있을 뿐 만 아니라, 모차르트 이후 독일 오페라의 발전과정을 이해하는 중요한 자료가 될 것이다.

Risque suicidaire lors du premier épisode psychotique

Suicide is the most common cause of early mortality during the course of schizophrenia. The most recent data in the literature show that the risk of suicide is greater at the beginning of the course of schizophrenia. The risk of suicide during the first year is 12 times higher than that of the general population. Specifically, 2-5 % of people with first-episode psychosis will die by suicide in long-term follow-up studies. Regarding the presence of suicidal ideation that are a major factor of suicide in subjects suffering from psychotic disorders, their prevalence remains extremely worrying, since they are substantial and persistent. Consequently, suicide prevention should be a major and immediate objective in the management of the disease, as soon as the diagnosis has been made. Suicidal ideas are a potential precursor to the evolution towards acting out. Their evolution must be specifically assessed in each individual. Indeed, in the influential Danish OPUS study the authors reported heterogeneity in suicidal ideations in young patients with first episode of psychosis and identified three prototypical trajectories of suicidal ideations over the first 2 years in treatment. Particularly, nearly 40 % of patients with first-episode psychosis have persisting suicidal thoughts over the initial treatment period. Consequently, the authors recommend routine screening for suicidality when providing treatment for first-episode psychosis. The main risk factors for suicidal behavior in patients with a first episode are classical ones. Previous research has suggested that, in addition to young age and early course of illness, other important clinical predictors of suicide in individuals with schizophrenia include presence of depressive symptoms and misuse of substances, which are very common conditions in these patients. Lack of social support, loss, rejection, stigma, insight, fear of future losses, are all negative experiences experienced by patients starting a psychotic disorder. Negative connotations of the diagnosis of psychotic disorders, feelings of being trapped that can be directly related to feeling a burden can lead to suicidal crisis in these individuals. Then, the painful experience of the disease and its consequences associated with self-stigmatization and social rejection may induce hopelessness and suicidal thoughts in these young subjects. The quality of the insight and its evolution may worsen the depressive experience and suicidal risk and they therefore also require to be measured regularly. Thus, the clinical evaluation of patients entering psychosis should focus on those dimensions that are not directly related to the psychotic symptoms. At the precise evaluation of each patient must be associated personalized measures of prevention. It is now proposed that prevention strategies targeting suicidal behaviour in first-episode psychosis should not be universal. On a more general level, evidence-based data to support specific care programs are still lacking, and only few data are in favor of integrated care in patients presenting with first episode. It should also be kept in mind that the risk of suicide is extraordinarily high for all psychiatric patients during the first few months after discharge from hospital. This should encourage caregivers to offer intensive follow-up programs to their patients and to embrace recontact and follow-up initiatives using the tools of e-health. Last, programs for the early detection of schizophrenia seem to be beneficial for the prevention of suicide in these subjects.

‘Ein dürftiger Stoff’: Hermann and the Failure of German Liberation Opera (1815–1848)

This article traces the development of national opera on political-historical themes in Germany between 1815 and 1848 and attempts to explain why this genre ultimately did not succeed. The focus will lie on the warrior hero Arminius/Hermann, one of the most potent national symbols of the nineteenth century, who was indeed brought to the German opera stage, but could never conquer it. The period between 1815 and 1848 not only forms a crucial phase in the coming of age of German opera against the background of a burgeoning national conscience, but also presents a lacuna in the current literature on Arminius as an opera character. Two early nineteenth-century Arminius opera projects will be discussed: musical realizations of August von Kotzebue’s 1813 libretto Hermann und Thusnelde and French composer Hippolyte Chélard’s 1835 opera Die Hermannschlacht, based on a libretto by Carl Weichselbaumer. Questions of authorship, patronage, musical style and reception will be addressed. This article presents a history of an operatic ‘misfit’ that fills a hiatus in the study of German nineteenth-century opera and will add to our understanding of the peculiar relation between opera and German national thought during the first half of the century.

Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn’s disease: report of the OPERA study

ObjectiveThis phase II, randomised, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PF-00547659, a fully human monoclonal antibody that binds to human mucosal addressin cell...

Popularising comic opera in Cape Town: the 1887 season of the Searelle Opera Company

The transplantation of nineteenth-century comic opera to South Africa remains largely undocumented. This article takes steps towards addressing this lacuna as part of a larger contribution to the relatively inchoate field of South African opera studies. By examining the first extended season of light opera in Cape Town, namely that put on by the British and Australian Searelle Opera Company in 1887, it is argued that the company’s successful staging of more than a dozen works in a season which lasted over six months and encompassed 162 performances can be attributed to several factors. Among these were its emphasis on comic operas of chiefly French and British origin (especially those by Gilbert and Sullivan), which had attracted large audiences in the United Kingdom, Australia, the United States of America and elsewhere. Other contributing factors were the flexibility of the company’s repertoire and the use of ancillary entertainment, not the least of which were violin performances by the Hungarian virtuoso, Ede Reményi.

Re-imagining Operatic "Objects": Commentary on Neumann's Phenomena, Poiesis, and Performance Profiling: Temporal-Textual Emphasis and Creative Process Analysis in Turandot at the Metropolitan Opera

Objects come in all sorts of shapes, sizes and forms. The notion of musical works as objects, represented by their written scores, has proved to be effete and limiting to the study of music as diverse social-cultural practice and performed craft. The past two decades have witnessed considerable efforts to renew conceptual and methodological tools, and Neumann's study makes a valuable contribution to this effect. This commentary responds to some issues raised by Neumann's article in relation to the notion of musical "object". Specifically, I retrace the shift from a score-based to a process-oriented musicology geared towards performances, placing the concerns of contemporary opera studies within this broader disciplinary change. I consider some implications of technology in mediating new operatic objects for discourse. Finally, I reflect on some of the inherent dangers of objectifying performance in empirical analyses.

Understanding Handel’s operas

Some readers may be excused for thinking that there might not be much more to say about Handel’s operas following the achievements of Winton Dean and John Merrill Knapp in two volumes (the second by Dean alone) first published in 1987 and 2006. While Dean and Knapp employ a chronological, opera-by-opera approach, offering a comprehensive study of the history, composition, structure and reception of each work, David Kimbell advances a different methodology. In a similar way to Silke Leopold’s Händel. Die Opern (Bärenreiter 2009), he takes a step back, presenting instead a guide to understanding Handel’s operas as a whole, drawing not only on his own experience of European opera studies, but also on a deep understanding of Handel’s musical dramas. Although the fundamental approach is similar to that of Leopold, Kimbell’s book places emphasis on different aspects of Handel’s operas, making it a unique contribution to Handel studies. His intended audience is made up of those ‘who wish to know a little more about Handel’s operas and to understand them a little better’ (p.ix), and he caters to this audience not only through his careful selection of examples drawn from across Handel’s output, but also by focusing on Handel’s early career. If we are to understand his London operas, a deeper understanding of how Handel developed as an opera composer in Germany and during his time in Italy, whilst he was learning his trade, is required. This is particularly evident in the opening chapter, which provides a biographical survey of Handel’s engagement with opera from his education in Halle through to his move away from opera in favour of English oratorio around 40 years later in London.

Evaluation of tumor biomarkers in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer treated with the CXCL12 inhibitor NOX-A12 and preliminary safety in combination with PD-1 checkpoint inhibitor pembrolizumab.

e15094Background: NOX-A12 (olaptesed pegol) is a novel inhibitor of the chemokine CXCL12 for treatment of solid tumors. The Opera study (NCT03168139) is a Phase 1/2 open label clinical study to eva...

The Unsung One: The Performer’s Voice in Twentieth-century Musical Monodrama

ABSTRACTIn an examination of the evident yet overlooked subject of the singing body in opera studies, focusing on the soloist’s voice and role in twentieth-century musical stage works for a single performer offers a number of engaging insights. By observing contemporary staging and practices in light of current performance theories and studies of voice and opera, it is possible to construct an alternative reading of the performer’s embodied voice in musical monodrama, until now not fully addressed in the opera studies discourse. I argue that the performer’s agency should be redefined as a compelling extra-text to be asserted both theoretically and practically in the discourse and production surrounding twentieth-century monodrama and music theater stage works for one performer.

Bone turnover markers after the menopause: T-score approach.

Bone turnover increases at the menopause and is associated with accelerated bone loss. However, it is not known to what extent there is an imbalance between the processes of bone resorption and bone formation, nor whether it is the rate of bone turnover or the bone balance that is most closely associated with the rate of bone loss. We studied 657 healthy women ages 20 to 79 from five European cities (the OPUS Study) and divided them into two premenopausal age groups, 20 to 29 (n=129), 30 to 39years (n=183), and three postmenopausal groups 1 to 10years (n=91), 11 to 20years (n=131) and 21+ years since menopause (n=123). We measured collagen type I C-telopeptide (CTX, a marker of bone resorption) and procollagen I N-propeptide (PINP, a marker of bone formation). We used these two markers to calculate the overall bone turnover and the difference between bone formation and resorption (bone balance) using the results from the women ages 30 to 39years to calculate a standardised score (T-score). We found that the CTX and PINP levels were higher in the women ages 20 to 29 and in the women in the three menopausal groups as compared to women ages 30 to 39years (p<0.001). For example, the CTX and PINP levels were 80 and 33% higher in women 1 to 10years since menopause as compared to women ages 30 to 39years. In this group of postmenopausal women, the bone turnover expressed as a T-score was 0.72 (0.57 to 0.88, 95%CI) and the bone balance was -0.37 (-0.59 to -0.16). There was greater rate of bone loss from the total hip in all the groups of women after the menopause compared to women before the menopause. We conclude that the bone loss after the menopause is associated with both an increase in bone turnover and a negative bone balance and that bone loss was most clearly associated with overall bone turnover.

Thromboprophylaxis for ambulatory surgery: Results from a prospective national cohort

BackgroundVenous thromboembolism (VTE) prophylaxis is not always part of the usual care of ambulatory surgery patients, and few guidelines are available. ObjectivesTo collect data on the application of VTE prophylaxis in ambulatory patients. DesignThe OPERA study is a large national survey performed in 221 healthcare facilities. PatientsAmong patients, 2174 who underwent one of ten selected procedures over two pre-defined days of investigation. Main outcome measuresAssessment and management of the postoperative VTE risk. ResultsThe postoperative VTE risk was assessed as nil (4.1% of the physicians), low (74%) or moderate (20%). This risk was assessed as lower (71%) in ambulatory surgery as compared to conventional surgery. In most centres (94%), a personal patient history of VTE was recorded preoperatively, and in 72% a prophylaxis protocol was systematically applied but only 40% of the responding centres had a written protocol for VTE prophylaxis. The postoperative period (discharge at home) was covered by a VTE protocol for 75% of the centres, with VTE prophylaxis starting postoperatively in 21% of the patients. In these patients, different treatments were applied: below-knee compression stockings (25%); thigh-length compression stockings (21%); intermittent pneumatic compression in the recovery room (1.2%); unfractionated heparin (2.0%); low molecular weight heparins (65%); vitamin K antagonists (0.5%); other treatments, including direct oral anticoagulants (0.5%). ConclusionThese data underline the need for a better assessment of the VTE risk in ambulatory patients and new studies either with conventional or new agents to be able to build guidelines in this new setting.

Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma vascular endothelial growth factor are not predictive for remission and radiographic progression in patients with early rheumatoid arthritis: post-hoc explorative and validation studies based on the CIMESTRA and OPERA trials

Objective: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized controlled trials (RCTs).Method: Treatment-naïve patients with early RA (< 6 months’ duration) and active disease, participating in two investigator-initiated RCTs, were treated according to a predefined treat-to-target algorithm aiming at inflammatory control, using methotrexate (MTX) + cyclosporine versus MTX + placebo (CIMESTRA study, n = 150, 5 year follow-up) or MTX + adalimumab versus MTX + placebo (OPERA study, n = 180, 2 year follow-up). The 28-joint Disease Activity Score (DAS28) and conventional radiography [bilateral hands and feet at baseline, 2 years and 5 years (only CIMESTRA)] were obtained at baseline and during follow-up. Serum IL-6, serum YKL-40, and plasma VEGF were measured in baseline blood samples and during follow-up. Hypotheses regarding the biomarkers’ relation with DAS28 and ability to predict clinical remission (DAS28 < 2.6) and radiographic progression (change in total Sharp van der Heijde score ≥ 2) were generated in CIMESTRA and validated in OPERA, by Spearman’s correlation and logistic regression analyses.Results: Baseline IL-6, YKL-40, and VEGF correlated significantly with DAS28 in CIMESTRA (r = 0.50, r = 0.36, r = 0.36, respectively, all p < 0.01) and these results were confirmed in OPERA patients (r = 0.52, p < 0.01; r = 0.18, p = 0.01; r = 0.23, p = 0.002, respectively). None of the biomarkers (absolute values or change) was predictive of clinical remission or radiographic progression at 2 or 5 years in either study.Conclusion: Serum IL-6, serum YKL-40, and plasma VEGF were significantly correlated with DAS28 at baseline, but did not have consistent predictive value for clinical remission or radiographic progression in two early RA RCTs.

Towards Global Xiqu Studies: Situating Latin America on the Trans-Pacific Circuit

Xiqu (Chinese opera) studies have been increasingly considering transnational history and practice. New scholarship has improved the understanding of trans-Pacific connections in Cantonese opera between Asia and North America. This article recovers Cuba and Peru (especially Havana and Lima) as major nodes of Cantonese opera in the late nineteenth century and the first half of the twentieth century, showing how it was practiced and sketching out its reception and legacy. This contributes to the elaboration of a global perspective in xiqu studies, while laying the groundwork for future critical approaches surrounding Chinese and transnational performance in later 19th and earlier 20th-century Latin America.

Pain characteristics of older persons with medically unexplained symptoms, older persons with medically explained symptoms and older persons with depression

ABSTRACTObjectives: The main objective of the current study is to compare chronic pain characteristics of older patients with Medically Unexplained Symptoms (MUS), to those of patients with Medically Explained Symptoms (MES), and to those of patients with Major Depressive Disorder (MDD).Method: By combining data from the OPUS and NESDO study, we compared pain characteristics of 102 older (>60 years) MUS-patients to 145 older MES-patients and 275 older MDD-patients in a case-control study design. Group differences were analyzed using ANCOVA, adjusted for demographic and physical characteristics. Linear regression was applied to examine the association between pain characteristics and somatization (BSI-53 somatization scale) and health anxiety (Whitely Index).Results: Older MUS-patients have approximately two times more chance of having chronic pain when compared to older MES-patients (OR = 2.01; p = .013) but equal chances as opposed to MDD-patients. After adjustments, MUS-patients report higher pain intensity and disability scores and more pain locations when compared to MES-patients, but equal values as MDD-patients. Health anxiety and somatization levels were positively associated with the number of pain sites in MUS-patients, but not with pain severity or disability.Conclusion: Older MUS-patients did not differ from MDD-patients with respect to any of the chronic pain characteristics, but had more intense and disabling pain, and more pain locations when compared to older MES-patients.

Operation and organisation of ambulatory surgery in France. Results of a nationwide survey; The OPERA study

Operation and organisation of ambulatory surgical activity in France remains largely undocumented. This nationwide observational prospective survey, carried out between December 2013 and December 2014, was undertaken to characterise the organisational processes of ambulatory surgery in France. Three hundred centres were randomly chosen from a list of 891 hospitals practicing ambulatory surgery, with stratification according to the type of facility (public general hospital, university hospital, private hospital) and region. An email was sent to the board of the randomly chosen facilities with an attached information letter explaining how the survey worked. Hospitals who did not reply to this email were contacted by phone. Among the 206 hospitals that answered the survey, 92 were private, 78 were public and 36 were university hospitals. Median accommodation capacities of ambulatory units were 8 beds, mostly distinct from conventional surgical ward. Patient pathways dedicated to ambulatory surgery appear as the current predominant practice. 77% of the French ambulatory units have a head nurse in charge of logistics and coordination. Several items still have to be improved, such as the adherence to modern fasting rules and the unnecessary use of stretcher to move the patient. Objective discharge score is used in 77% of ambulatory units. This survey highlights the implementation of some positive organisational parameters corresponding to common good practices recommendations. In contrast, several other recommendations are still insufficiently applied and may hamper the development of safe ambulatory surgery. This brings up new challenges for health regulatory boards, hospitals and ambulatory units managers.