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Background: Antibiotics targeted against Clostridioides difficile bacteria are necessary, but insufficient, to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome. ECOSPOR-III evaluated SER-109, an investigational, biologically derived microbiome therapeutic of purified Firmicute spores for treatment of rCDI. Herein, we present the interim analysis in the ITT population at 8 and 12 weeks. Methods: Adults ≥18 years with rCDI (≥3 episodes in 12 months) were screened at 75 US and CAN sites. CDI was defined as ≥3 unformed stools per day for <48 hours with a positive C. difficile assay. After completion of 10–21 days of vancomycin or fidaxomicin, adults with symptom resolution were randomized 1:1 to SER-109 (4 capsules × 3 days) or matching placebo and stratified by age (≥ or <65 years) and antibiotic received. Primary objectives were safety and efficacy at 8 weeks. Primary efficacy endpoint was rCDI (recurrent toxin+ diarrhea requiring treatment); secondary endpoints included efficacy at 12 weeks after dosing. Results: Overall, 287 participants were screened and 182 were randomized (59.9% female; mean age, 65.5 years). The most common reason for screen failure was a negative C. difficile toxin assay. A significantly lower proportion of SER-109 participants had rCDI after dosing compared to placebo at week 8 (11.1% vs 41.3%, respectively; relative risk [RR], 0.27; 95% confidence interval [CI], 0.15–0.51; p-value <0.001). Efficacy rates were significantly higher with SER-109 vs placebo in both stratified age groups (Figure 1). SER-109 was well-tolerated with a safety profile similar to placebo. The most common treatment-emergent adverse events (TEAEs) were gastrointestinal and were mainly mild to moderate. No serious TEAEs, infections, deaths, or drug discontinuations were deemed related to study drug. Conclusions: SER-109, an oral live microbiome therapeutic, achieved high rates of sustained clinical response with a favorable safety profile. By enriching for Firmicute spores, SER-109 achieves high efficacy while mitigating risk of transmitting infectious agents, beyond donor screening alone. SER-109 represents a major paradigm shift in the clinical management of patients with recurrent CDI. Clinicaltrials.gov Identifier NCT03183128. These data were previously presented as a late breaker at American College of Gastroenterology 2020.
The diagnosis of an advanced cancer in young adulthood can bring one's life to an abrupt halt, calling attention to the present moment and creating anguish about an uncertain future. There is seldom time or physical stamina to focus on forward-thinking, social roles, relationships, or dreams. As a result, young adults (YAs) with advanced cancer frequently encounter existential distress, despair, and question the purpose of their life. We sought to investigate the meaning and function of hope throughout YAs’ disease trajectory; to discern the psychosocial processes YAs employ to engage hope; and to develop a substantive theory of hope of YAs diagnosed with advanced cancer.
Thirteen YAs (ages 23–38) diagnosed with a stage III or IV cancer were recruited throughout the eastern and southeastern United States. Participants completed one semi-structured interview in-person, by phone, or Skype, that incorporated an original timeline instrument assessing fluctuations in hope and an online socio-demographic survey. Glaser's grounded theory methodology informed constant comparative methods of data collection, analysis, and interpretation.
Findings from this study informed the development of the novel contingent hope theoretical framework, which describes the pattern of psychosocial behaviors YAs with advanced cancer employ to reconcile identities and strive for a life of meaning. The ability to cultivate the necessary agency and pathways to reconcile identities became contingent on the YAs’ participation in each of the psychosocial processes of the contingent hope theoretical framework: navigating uncertainty, feeling broken, disorienting grief, finding bearings, and identity reconciliation.
Significance of Results
Study findings portray the influential role of hope in motivating YAs with advanced cancer through disorienting grief toward an integrated sense of self that marries cherished aspects of multiple identities. The contingent hope theoretical framework details psychosocial behaviors to inform assessments and interventions fostering hope and identity reconciliation.
A vacuum has been described as nothing shut up in a box, and The Prélude entitled ‘L’Après-midi d’un faune’ by M. Claude Debussy, performed for the first time in England, at the Queen's Hall last night, may aptly be described as nothing expressed in musical terms.
THIS was a reaction to the first British performance of Debussy's Prélude a l’apres-midi d’un faune at the Proms on 20 August 1904; it marked the start of a British fascination with Debussy's new and strange ‘atmospheric’ music. Writing in a similarly general vain, the critic Edward Baughan of the London Daily News described it as ‘a thing of airy nothings’. These responses reflect a genuine sense of encountering something new and intriguing. Building on the work of Roger Nichols and Leanne Langley, this chapter examines the reception of Debussy's and Ravel's orchestral music in Britain. It notes the major performances, particularly in London, but also the ripple effect throughout the whole of Britain. Debussy's own presence as conductor in 1908 and 1909 generated significant attention on the composer. Indeed, the first biographies of Debussy were published that year by British rather than French authors, who attempted to identify a language in which to describe Debussy's highly original music. Ravel's reception in Britain was more mixed; he was generally regarded as less spontaneous and original than Debussy. While some of his orchestral works dazzled British audiences, others disappointed or confounded critics. Only his Boléro made a real impression and, like Debussy's Prélude, became a firm favourite with British audiences. Finally, Edwin Evans and Georges Jean-Aubry emerged as outspoken advocates for French music and sought to use their influence to reorient the direction of British music at a critical political moment in Britain and Europe. The chapter teases out how Debussy and Ravel were understood in Britain and the impact their music had on British composers.
❧ Debussy in Britain
Henry Wood had a considerable role in making Prélude a l’apres-midi d’un faune widely known in Britain. He claimed that the work quickly became a staple of the British performing repertory after he introduced it during the 1904 Proms season. From 1906 Debussy's Prélude appeared almost every year until the Second World War, and sometimes more than once (see Table 4.1).
Catheter-associated urinary tract infections (CAUTIs) occur frequently in pediatric inpatients, and they are associated with increased morbidity and cost. Few studies have investigated ambulatory CAUTIs, despite at-risk children utilizing home urinary catheterization. This retrospective cohort and case-control study determined incidence, risk factors, and outcomes of pediatric patients with ambulatory CAUTI.
Broad electronic queries identified potential patients with ambulatory urinary catheters, and direct chart review confirmed catheters and adjudicated whether ambulatory CAUTI occurred. CAUTI definitions included clean intermittent catheterization (CIC). Our matched case-control analysis assessed risk factors.
Five urban, academic medical centers, part of the New York City Clinical Data Research Network.
Potential patients were age <22 years who were seen between October 2010 and September 2015.
In total, 3,598 eligible patients were identified; 359 of these used ambulatory catheterization (representing186,616 ambulatory catheter days). Of these, 63 patients (18%) experienced 95 ambulatory CAUTIs. The overall ambulatory CAUTI incidence was 0.51 infections per 1,000 catheter days (1.35 for indwelling catheters and 0.47 for CIC; incidence rate ratio, 2.88). Patients with nonprivate medical insurance (odds ratio, 2.5; 95% confidence interval, 1.1–6.3) were significantly more likely to have ambulatory CAUTIs in bivariate models but not multivariable models. Also, 45% of ambulatory CAUTI resulted in hospitalization (median duration, 3 days); 5% resulted in intensive care admission; 47% underwent imaging; and 88% were treated with antibiotics.
Pediatric ambulatory CAUTIs occur in 18% of patients with catheters; they are associated with morbidity and healthcare utilization. Ambulatory indwelling catheter CAUTI incidence exceeded national inpatient incidence. Future quality improvement research to reduce these harmful infections is warranted.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Reflecting on present unease about structural biases in the discipline, and aiming to offer a data-rich response to some recent criticisms of this Journal, the Editorial Board has undertaken a study of the representation of female scholars in the Journal of Roman Studies. To that end, we have gathered data on publications, submissions and JRS Editorial Board membership for the past fifteen years, from Volume 95 (2005) through to the present volume, Volume 109 (2019). The data are set out in the final section (VII), following a brief review of the main results. Our goal here is neither to present a definitive analysis, nor to offer a commentary on the underlying causes of the patterns revealed (on which we expect much fruitful discussion elsewhere). Rather, the JRS Editorial Board aims to make key data available both to inform a much wider debate within the profession as a whole and, importantly, to inform this Journal’s policies, procedures and active outreach. The Board is also acutely aware that any analysis of gender bias needs to be framed carefully — both by an awareness that there are other under-represented groups in the discipline (on which our data in their current form would regrettably only offer a most imperfect picture), and by a sensitivity to the limitations of a conception of gender as a simple binary.
Retrospectively recalled adverse childhood experiences (ACEs) are associated with adult mood problems, but evidence from prospective population cohorts is limited. The aims of this study were to test links between prospectively ascertained ACEs and adult mood problems up to age 50, to examine the role of child mental health in accounting for observed associations, and to test gender differences in associations.
The National Child Development Study is a UK population cohort of children born in 1958. ACEs were defined using parent or teacher reports of family adversity (parental separation, child taken into care, parental neglect, family mental health service use, alcoholism and criminality) at ages 7–16. Children with no known (n = 9168), single (n = 2488) and multiple (n = 897) ACEs were identified in childhood. Adult mood problems were assessed using the Malaise inventory at ages 23, 33, 42 and 50 years. Associations were examined separately for males and females.
Experiencing single or multiple ACEs was associated with increased rates of adult mood problems after adjustment for childhood psychopathology and confounders at birth [2+ v. 0 ACEs – men: age 23: odds ratio (OR) 2.36 (95% confidence interval (CI) 1.7–3.3); age 33: OR 2.40 (1.7–3.4); age 42: OR 1.85 (1.4–2.4); age 50: OR 2.63 (2.0–3.5); women: age 23: OR 2.00 (95% CI 1.5–2.6); age 33: OR 1.81 (1.3–2.5); age 42: OR 1.59 (1.2–2.1); age 50: OR 1.32 (1.0–1.7)].
Children exposed to ACEs are at elevated risk for adult mood problems and a priority for early prevention irrespective of the presence of psychopathology in childhood.
Tobacco is a known addictive consumer product and its use has been reported to be associated with several health problems as well as the leading cause of premature, preventable mortality worldwide. For patients undergoing cancer treatment, tobacco smoking can potentially compromise treatment effectiveness; however, there is sufficient evidence suggesting numerous health benefits of smoking cessation interventions for cancer patients.
The Grand River Regional Cancer Centre (GRRCC) smoking cessation program began in October 2013 to provide evidence-based intensive tobacco intervention to patients. All new patients are screened for tobacco use and those identified as active smokers are advised of the benefits of cessation and offered referral to the program where a cessation nurse offers counseling. Patients’ disease site, initial cessation goal, quit date, number of quit attempts and mode of contact are collected by the cessation nurse. This study reports on the initial evaluation of the smoking cessation program activities at GRRCC.
There are 1,210 patients who were screened, accepted a referral and counseled in the program. The referral pattern shows a modest increase every year and most of the patients (58%) indicated readiness to quit smoking. Overall, 29 and 26% of patients either quit or cut-back smoking, respectively. Among 348 patients who quit smoking, 300 (86%) were able to quit at the first attempt. The data indicated that 309 (44%) out of the 698 patients who indicated their initial intent to quit smoking were able to quit, whereas about 242 (35%) were able to cutback. A total of 15 patients out of 32 who indicated initial readiness to ‘cutback’ smoking were able to reduce tobacco use and three patients actually ended up quitting, although their initial goal was ‘ready-to-cut-back’.
GRRCC smoking cessation program started in October 2013 to provide evidence-based intensive smoking cessation interventions for patients with cancer. Most patients referred to the program indicated a readiness to quit smoking affirming that if patients become aware of the various risks associated with continual smoking or if they are informed of the benefits associated with cessation with regard to their treatment, they will be more likely to decide to quit. Therefore, it is essential that patients, their partners and families are counseled on the health and treatment benefits of smoking cessation and sustainable programs should be available to support them to quit smoking. It is imperative then, that oncology programs should consistently identify and document the smoking status of cancer patients and support those who use tobacco at the time of diagnosis to quit. Evidence-based smoking cessation intervention should be sustainably integrated into the cancer care continuum in all oncology programs from prevention of cancer through diagnosis, treatment, survivorship and palliative care.
OBJECTIVES/SPECIFIC AIMS: To examine rural-urban disparities in prevalence of diagnosed diabetes in veterans receiving care at the VA and to determine the extent to which demographic factors and obesity levels contribute to identified disparities. METHODS/STUDY POPULATION: A retrospective serial cross-sectional analysis was employed. A stratified weighted random sample of veterans who received care at a VA facility was selected each year for 2007 through 2012. Rural Urban Commuting Area (RUCA) codes were based on resident zip code. Diabetes was defined by two or more primary or secondary ICD-9 codes for diabetes (250.xx) within a 12 month period. Data were analyzed using complex survey-specific procedures. RESULTS/ANTICIPATED RESULTS: Diabetes prevalence 2007-2012 was lowest in urban (20.5%-21.0%), followed by highly rural (21.1%-22.1%) and rural (22.3%-23.0%) areas with the prevalence being significantly higher on the insular islands (31.0%-32.4%). In 2012, 41% of urban, 43% of rural and highly rural and 30% of insular island veterans were obese. Relative to urban areas, the odds ratio for prevalent diabetes was 1.10 (95% CI: 1.08, 1.12) for rural veterans, 1.19 (95% CI: 1.16, 1.23) for insular island veterans, and 1.00 (95% CI: 0.98, 1.02) for highly rural veterans. DISCUSSION/SIGNIFICANCE OF IMPACT: Prevalence of diagnosed diabetes is high in veterans residing in rural, highly rural and urban areas, but markedly higher on the insular islands. Understanding the burden of disease and factors driving disparities provides information required to develop targeted interventions.
In the years immediately following Debussy's death in 1918 initial assessments of his significance as a composer tended to concentrate on his middle-period works, which seemed to represent him at his most characteristic. At this early stage, there was some agreement that Debussy's reputation had been shaped by his most memorable and characteristic repertoire, from Prélude à l'après-midi d'un faune to the second book of piano preludes. The late works still remained to be fully understood beyond their association with the anguish and struggle of a dying patriotic composer (as Marianne Wheeldon and others have shown), and relatively little was known about Debussy's early works and career. Henry Prunières, the director of La revue musicale, addressed this neglect by devoting a second special issue of his journal to “La jeunesse de Claude Debussy” in 1926, which consisted of extracts from his letters to Henri Vasnier, unpublished early songs, numerous testimonies of those who knew him in his youth and early career, such as Gabriel Pierné, Robert Godet, and Maurice Emmanuel, as well as a study by Charles Koechlin of Debussy's unpublished early songs. The volume provided new insights into a hitherto unexplored and undocumented part of Debussy's career. Prunières took the opportunity to publish four early songs in the musical supplement of the special issue, which initiated debates about their intrinsic value and the extent to which they shed light on Debussy's early style. At stake was what image of Debussy should be remembered, recorded, and published for posterity. There was reluctance on the part of his former colleagues, wife, critics, and biographers to portray a less than perfect side of his genius. At the same time, there was an overreliance on testimony and the presentation of personal documents, including the Vasnier letters, which subsequent research has shown to have been incorrectly ordered and dated. The posthumous documents relating to early Debussy informed subsequent biographies and critical studies of the composer, starting with the Koechlin (1927) and Léon Vallas biographies (1926, 1932, and 1944). In this essay, I tease out the significance of the first attempts to reconstruct and scrutinize the early musical life and work of their near contemporary Debussy. In so doing, I build on the recent scholarly work devoted to Debussy's early compositions by Marie Rolf, Denis Herlin, Richard Langham Smith, James Briscoe, John Clevenger, and many others.
Music criticism extended beyond written commentary in newspapers and journals in interwar France. This chapter examines the activities of critics as concert organisers. It focuses on two concert series after the Great War: the concerts of La Revue musicale, which were set up in Paris by the influential journal director, critic and musicologist, Henry Prunières (1886–1942); and the Petits concerts, which were established in Lyon in 1919 by the critic and musicologist Léon Vallas (1879–1956) and associated with his journal La Nouvelle Revue musicale. I show how criticism could be performed in the concert hall, alongside other forms of unwritten and written communication, such as pre-concert talks and lectures, as well as reviews, leader comments and features. To what degree did these sonic and oral forms support Prunières's and Vallas's central occupations as critics, musicologists and biographers? Recent studies of interwar criticism have revealed the considerable ideological differences between Prunières and Vallas, particularly over their efforts to remember Debussy. This chapter explores the extent to which these concert series and the repertoire they featured reflected the aesthetic and ideological orientations of their organisers. Both critics were committed to promoting a common canon of French music, which drew on music from the generations of Rameau and Couperin, on the one hand, and Debussy and Ravel, on the other.
Prunières was also determined to promote international contemporary music, which had been almost inaccessible during the Great War. While the two critics may have broadly agreed about the significance of upholding French music of the past, what contemporary and foreign music did they bring to life in their concerts? Finally, the chapter considers the extent to which these concerts provided yet another platform for these influential critics to persuade and educate their regional, national and international audiences.
Origins and Motivations for the Concert Series
Writing anonymously in Le Progrès (Lyon), Vallas announced the launch of the Petits concerts in 1919, indulging in some self-publicity.
A new musical organisation has just been established alongside [Georges Martin] Witkowski's Grands concerts; the official launch will take place in a month's time. It is a sort of federation of recently constituted artistic ensembles: a vocal quintet, a choral quintet, a string quintet, a wind quintet, and a trio of viols and harpsichord.
Music Criticism in France, 1918–1939: Authority, Advocacy, Legacy examines the aesthetic battles, discursive strategies and cultural stakes that animated and informed French music criticism during the interwar period. Drawing on a rich corpus of critical writings and archival documents, the primary goal of its twelve essays is to uncover some of the public debates that emerged around classical music at this time. As such, it provides significant new insights into the period's musical priorities and values while also highlighting some of the challenges confronting this war-bound generation. The book examines the ways in which influential critics played prominent roles in promoting the careers and defending the reputations of both young and established composers. It considers the efforts that critics took to shape the history of France's musical past. Finally, it questions how critics used their professional and social affiliations as a means of better buttressing their own aesthetic and political agendas.
The interwar period in France is often described as problematic, more famous for the deaths of major figures including Claude Debussy, Gabriel Fauré and Camille Saint-Saëns than the achievements of its living composers. Until fairly recently it has been marginalised, in contrast to the ‘golden’ generation of Debussy and his circle on the one hand and the ‘renewal’ of French musical life with Olivier Messiaen on the other. Yet the ‘Années Folles’ are distinctive in several respects. Having inherited the pre-war musical aesthetics of Debussy and Fauré, but also confronted with the iconoclastic works of a new generation (including Les Six) who used the press to reject the aesthetics of its forebears, interwar French music critics were drawn into an acute battle over conservative and progressive musical trends. Whereas critics including Henri Collet (1885–1951), Paul Landormy (1869–1943) and Henry Prunières (1886–1942) energetically supported the works and aesthetic paradigms of the younger generations, figures such as Émile Vuillermoz (1878–1960), Léon Vallas (1879–1956), Dominique Sordet (1889–1946) and Lucien Rebatet (1903–72) frequently denounced the avant-garde and attempted to influence a musical climate for which they felt a fair measure of dissatisfaction. As a result, the period is characterised by often fraught debates around what it meant to be avant-garde and modern.