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An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework’s major proposition is that it situates D&I sciences as targeted “sub-sciences” of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages.
There are a variety of causes of acute heart failure in children including myocarditis, genetic/metabolic conditions, and congenital heart defects. In cases with a structurally normal heart and a negative personal and family history, myocarditis is often presumed to be the cause, but we hypothesise that genetic disorders contribute to a significant portion of these cases. We reviewed our cases of children who presented with acute heart failure and underwent genetic testing from 2008 to 2017. Eighty-seven percent of these individuals were found to have either a genetic syndrome or pathogenic or likely pathogenic variant in a cardiac-related gene. None of these individuals had a personal or family history of cardiomyopathy that was suggestive of a genetic aetiology prior to presentation. All of these individuals either passed away or were listed for cardiac transplantation indicating genetic testing may provide important information regarding prognosis in addition to providing information critical to assessment of family members.
Accelerating innovation translation is a priority for improving healthcare and health. Although dissemination and implementation (D&I) research has made significant advances over the past decade, it has attended primarily to the implementation of long-standing, well-established practices and policies. We present a conceptual architecture for speeding translation of promising innovations as candidates for iterative testing in practice. Our framework to Design for Accelerated Translation (DART) aims to clarify whether, when, and how to act on evolving evidence to improve healthcare. We view translation of evidence to practice as a dynamic process and argue that much evidence can be acted upon even when uncertainty is moderately high, recognizing that this evidence is evolving and subject to frequent reevaluation. The DART framework proposes that additional factors – demand, risk, and cost, in addition to the evolving evidence base – should influence the pace of translation over time. Attention to these underemphasized factors may lead to more dynamic decision-making about whether or not to adopt an emerging innovation or de-implement a suboptimal intervention. Finally, the DART framework outlines key actions that will speed movement from evidence to practice, including forming meaningful stakeholder partnerships, designing innovations for D&I, and engaging in a learning health system.
Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak.
We retrospectively analyzed 9 hospital outbreaks that occurred during 2011–2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates. We determined (1) the ability of data mining of the EHR to identify the correct route of transmission, (2) how early the correct route was identified during the timeline of the outbreak, and (3) how many cases in the outbreaks could have been prevented had the system been running in real time.
Correct routes were identified for all outbreaks at the second patient, except for one outbreak involving >1 transmission route that was detected at the eighth patient. Up to 40 or 34 infections (78% or 66% of possible preventable infections, respectively) could have been prevented if data mining had been implemented in real time, assuming the initiation of an effective intervention within 7 or 14 days of identification of the transmission route, respectively.
Data mining of the EHR was accurate for identifying routes of transmission among patients who were part of the outbreak. Prospective validation of this approach using routine whole-genome sequencing and data mining of the EHR for both outbreak detection and route attribution is ongoing.
The problem presented by Thomas Campion's Observations in the Art of English Poesie (London, 1602) has not yet been satisfactorily solved. The question is: since Campion's Ayres arouse unanimous praise for his sensitive ear and metrical skill, how is it that his treatise on adapting classical metrics to English verse evokes charges of an insensitive ear and of phonetic inconsistency? Why does Campion seem to hear his ayres but not all of his examples in Observations? The earlier critics tend to blame his poor understanding of phonetic quantity in Observations. He is accused of ‘hopeless confusion’ and of having failed in the task he set himself. His’ system must be wrong’ and his omission of needed examples shows ‘the apparently irresistible spirit of perversity’. His work is cited as evidence that ‘shows how difficult it was to attain English (and therefore phonetic) conception of quantity’.
High body mass index (BMI) has been associated with lower risks of suicidal behaviour and being underweight with increased risks. However, evidence is inconsistent and sparse, particularly for women. We aim to study this relationship in a large cohort of UK women.
In total 1.2 million women, mean age 56 (s.d. 5) years, without prior suicide attempts or other major illness, recruited in 1996–2001 were followed by record linkage to national hospital admission and death databases. Cox regression yielded relative risks (RRs) and 95% confidence intervals (CIs) for attempted suicide and suicide by BMI, adjusted for baseline lifestyle factors and self-reported treatment for depression or anxiety.
After 16 (s.d. 3) years of follow-up, 4930 women attempted suicide and 642 died by suicide. The small proportion (4%) with BMI <20 kg/m2 were at clearly greater risk of attempted suicide (RR = 1.38, 95% CI 1.23–1.56) and suicide (RR = 2.10, 1.59–2.78) than women of BMI 20–24.9 kg/m2; p < 0.0001 for both comparisons. Small body size at 10 and 20 years old was also associated with increased risks. Half the cohort had BMIs >25 kg/m2 and, while risks were somewhat lower than for BMI 20–24.9 kg/m2 (attempted suicide RR = 0.91, 0.86–0.96; p = 0.001; suicide RR = 0.79, 0.67–0.93; p = 0.006), the reductions in risk were not strongly related to level of BMI.
Being underweight is associated with a definite increase in the risk of suicidal behaviour, particularly death by suicide. Residual confounding cannot be excluded for the small and inconsistent decreased risk of suicidal behaviour associated with being overweight or obese.
THEODOR FONTANE HAD GOOD REASON to like the word “deplaciert.” He was a descendant of French Huguenot immigrants to Berlin and, after returning from a temporary residence in London, did not always feel fully comfortable with his political surroundings. I invoke him here because all Americans—and especially American Germanists—are in a certain sense “deplaciert.” Americans are, after all, all immigrants to North America, whether we came ourselves, whether our ancestors came a century ago, or three centuries ago, or even millennia ago across the Bering land bridge. Indeed, in terms of what we know about human evolution, almost all humans are probably immigrants of some sort, wherever we live today. Goethe got it right in Lenardo's “Wanderrede” in Wilhelm Meisters Wanderjahre: moving from one place to another is essential to being human. Germanists in America are more specifically “deplaciert.” Even those of us not immigrants or refugees nevertheless tend to seem campus oddities, whether for our unusual linguistic skills, for the reputation of foreign-language departments as “zoos,” for the unfortunate macabre reputation that still adheres to things German in some quarters of the internet, or simply for the fact that we study a culture on the far side of the Atlantic.
Many of us are doubtless accustomed to the question that I, even in retirement, am still asked all the time, “Why would an American become a Germanist?” It is always immediately followed by the question, “Is your family German?,” to which a “no” results in an abrupt change of topic. As a student in Germany in 1965 I encountered the identical questions. There I quickly learned not to say, “I am studying Germanistik because I love Goethe”—that did not fly among my Kommilitonen. Germans inevitably also asked what I as an American thought I had to offer Germans (or anyone else) about their own culture. Preferring not to point out that German culture was still in need of advocates twenty years after World War II, I argued instead that I might be able to see things from a different point of view, to see German literature from another, perhaps enriching, perspective.
The Single Ventricle Reconstruction trial randomised neonates with hypoplastic left heart syndrome to a systemic-to-pulmonary-artery shunt strategy. Patients received care according to usual institutional practice. We analysed practice variation at the Stage II surgery to attempt to identify areas for decreased variation and process control improvement.
Prospectively collected data were available in the Single Ventricle Reconstruction public-use database. Practice variation across 14 centres was described for 397 patients who underwent Stage II surgery. Data are centre-level specific and reported as interquartile ranges across all centres, unless otherwise specified.
Preoperative Stage II median age and weight across centres were 5.4 months (interquartile range 4.9–5.7) and 5.7 kg (5.5–6.1), with 70% performed electively. Most patients had pre-Stage-II cardiac catheterisation (98.5–100%). Digoxin was used by 11/14 centres in 25% of patients (23–31%), and 81% had some oral feeds (68–84%). The majority of the centres (86%) performed a bidirectional Glenn versus hemi-Fontan. Median cardiopulmonary bypass time was 96 minutes (75–113). In aggregate, 26% of patients had deep hypothermic circulatory arrest >10 minutes. In 13/14 centres using deep hypothermic circulatory arrest, 12.5% of patients exceeded 10 minutes (8–32%). Seven centres extubated 5% of patients (2–40) in the operating room. Postoperatively, ICU length of stay was 4.8 days (4.0–5.3) and total length of stay was 7.5 days (6–10).
In the Single Ventricle Reconstruction Trial, practice varied widely among centres for nearly all perioperative factors surrounding Stage II. Further analysis may facilitate establishing best practices by identifying the impact of practice variation.
As Franz-Josef Deiters's title signals, his book offers a sophisticated reading of theater carefully located between theater history, media theory, Michel Foucault's “classical episteme,” and Walter Benjamin's “Entweltlichung.” Not clear from the title, but equally important, are its exceptionally thoughtful readings of five representative dramatic texts of the first half of the Goethezeit. Both the theory and the readings are presented with a clarity and concreteness that belie the abstraction of the title, yet also precisely illuminate the insights to be gained from the major epistemological shifts delineated by media theory and intellectual history of the last several decades. This structure already emerges in the table of contents, where all the chapter titles are quotations from the work at hand, and, in the crucial historical second chapter, most of the sub-section titles as well.
Die Entweltlichung der Bühne makes a double argument: first, theater is a medium in the sense of media theory, and not exclusively performance, and second, as such, it is an important symptom of the shift identified in Foucault's Order of Things from an analogical world-view to the “classical” regime of signs. Deiters lays out the general argument in his “Medienkritische Vorrede,” more accessibly than its title might suggest. Here he politely debunks Erika Fischer- Lichte's influential view that performativity is the essence of theater, using Foucault to relocate the theater into the context of media theory and identifying the shift from analogy to the primacy of signs as “Entweltlichung,” a process of abstraction whose formulation owes, I suspect, something to Deiters's previous engagement with Benjamin on allegory in drama (Drama im Augenblick seines Sturzes: Zur Allegorisierung des Dramas in der Moderne. Versuche zu einer Konstitutionstheorie, 1999).
The second chapter reviews pronouncements about the theater from Gottsched to Schiller and the Romantics. Thankfully, Deiters does not proceed chronologically by summarizing the usual suspects. Instead, he surveys categories that demonstrate exactly how leading thinkers wrote about Entweltlichung and semiotics. Deiters considers here changes in the meaning of truth in philosophy; the new priority of the printed text over performance; the shifts in the triad of communication between author, actors, and audience (the depersonalization of the actor, the silencing of the spectator, the withdrawal of the author behind the curtain);
The Pediatric Heart Network designed a career development award to train the next generation of clinician scientists in paediatric-cardiology-related research, a historically underfunded area. We sought to identify the strengths/weaknesses of the programme and describe the scholars’ academic achievements and the network’s return on investment.
Survey questions designed to evaluate the programme were sent to applicants – 13 funded and 19 unfunded applicants – and 20 mentors and/or principal investigators. Response distributions were calculated. χ2 tests of association assessed differences in ratings of the application/selection processes among funded scholars, unfunded applicants, and mentors/principal investigators. Scholars reported post-funding academic achievements.
Survey response rates were 88% for applicants and 100% for mentor/principal investigators. Clarity and fairness of the review were rated as “clear/fair” or “very clear/very fair” by 98% of respondents, but the responses varied among funded scholars, unfunded applicants, and mentors/principal investigators (clarity χ2=10.85, p=0.03; fairness χ2=16.97, p=0.002). Nearly half of the unfunded applicants rated feedback as “not useful” (47%). “Expanding their collaborative network” and “increasing publication potential” were the highest-rated benefits for scholars. Mentors/principal investigators found the programme “very” valuable for the scholars (100%) and the network (75%). The 13 scholars were first/senior authors for 97 abstracts and 109 manuscripts, served on 22 Pediatric Heart Network committees, and were awarded $9,673,660 in subsequent extramural funding for a return of ~$10 for every scholar dollar spent.
Overall, patient satisfaction with the Scholar Award was high and scholars met many academic markers of success. Despite this, programme challenges were identified and improvement strategies were developed.
We have carried out K band photometric observations of RR Lyrae stars in two globular clusters which both have large populations of RR Lyraes but different characteristics: the moderately metal-rich cluster M5 ([Fe/H] = –1.40) and the metal-poor one M15 ([Fe/H] = –2.15). The purpose is to accurately calibrate the linear relationship between RR Lyrae infrared (K) absolute magnitudes and their periods that has been confirmed by recent Baade-Wesselink type studies of RR Lyraes and IR photometry of cluster variables. A total of 47 RR Lyraes in M15 was observed and each has more than 8 measures on the average, which allows the accurate determination of a mean K magnitude for each star. In M5 44 stars have been observed with each RR Lyrae having 4 measurements. Our preliminary results show that the RR Lyrae infrared period-luminosity relations for the two clusters have roughly the same slope, despite the fact that they have a large metallicity difference. This suggests that the metallicity effect on the (MK)-log P relation is indeed small as one would expect. The M5 and M15 RR Lyrae IR photometry gives a reliable determination for the slope of the infrared period-luminosity relation because of the large number of stars measured. A well-calibrated (MK)-log P relation will be very useful in distance determinations to heavily reddened star regions such as the Galactic center and globular clusters in the Galactic bulge.
Increased out-of-pocket health-care expenditures may exert budget pressure on low-income households that leads to food insecurity. The objective of the present study was to examine whether older adults with higher chronic disease burden are at increased risk of food insecurity.
Secondary analysis of the 2013 Health and Retirement Study (HRS) Health Care and Nutrition Study (HCNS) linked to the 2012 nationally representative HRS.
Respondents of the 2013 HRS HCNS with household incomes <300 % of the federal poverty line (n 3552). Chronic disease burden was categorized by number of concurrent chronic conditions (0–1, 2–4, ≥5 conditions), with multiple chronic conditions (MCC) defined as ≥2 conditions.
The prevalence of food insecurity was 27·8 %. Compared with those having 0–1 conditions, respondents with MCC were significantly more likely to report food insecurity, with the adjusted odds ratio for those with 2–4 conditions being 2·12 (95 % CI 1·45, 3·09) and for those with ≥5 conditions being 3·64 (95 % CI 2·47, 5·37).
A heavy chronic disease burden likely exerts substantial pressure on the household budgets of older adults, creating an increased risk for food insecurity. Given the high prevalence of food insecurity among older adults, screening those with MCC for food insecurity in the clinical setting may be warranted in order to refer to community food resources.
Different types of fast ice flow (both spatial and temporal) in valley glaciers (surging glaciers, tidewater glaciers and deforming-bed glaciers) and ice sheets (ice streams and deforming-bed ice-sheet flow) are discussed briefly. Although there are unlikely to be any specific individual landforms associated with fast ice flow, there may be landform assemblages.
At valley glacier scale, it is suggested that there are two landform assemblages: (1) an ice-thrust type, dominated by bulldozed push moraines and hummocky moraines (associated with glaciers with a high supraglacial sediment supply, a coarse-grained substrate and a coarse-grained proglacial sediment wedge); and (2) a bed-flow type dominated by “squeeze” push moraines, flutes and drumlins (associated with glaciers with a low supra- glacial sediment supply and fine-grained substrate). The ice-thrust type alone is only associated with discontinuous fast flow (on both rigid and deforming beds); whilst the bed-flow type is associated with both continuous and discontinuous fast flow.
It is suggested that these two landform assemblages may also be indicative of fast ice flow at ice-sheet scale, in particular the bed-flow style. If that is the case, then discontinuous fast ice flow may be indicated by the ice-thrust landform assemblage and the bed-flow style where drumlins are present.
It is also suggested that specific evidence for ice streams includes the distinctive land-form assemblages within valley or fan-like locations, and a predictable pattern of velocity reflected by drumlin elongation ratios.
The upper 20—30 m of ice-rich permafrost at three sites overridden by the northwest margin of the Laurentide ice sheet in the Tuktoyaktuk Coastlands, western Arctic Canada, comprise massive ice beneath ice-rich diamicton or sandy silt. The diamicton and silt contain (1) truncated ice blocks up to 15 m long, (2) sand lenses and layers, (3) ice veins dipping at 20—30°, (4) ice lenses adjacent and parallel to sedimentary contacts, and (5) ice wedges. The massive ice is interpreted as intrasedimental or buried basal glacier ice, and the diamicton and silt as glacitectonite that has never thawed. Deformation of frozen ground was mainly ductile in character. Deformation was accompanied by sub-marginal erosion of permafrost, which formed an angular unconformity along the top of the massive ice and supplied ice clasts and sand bodies to the overlying glacitectonite. After deformation and erosion ceased, postglacial segregated ice and ice- wedge ice developed within the deformed permafrost.