Technology for large-scale translation of clinical practice guidelines : a pilot study of the performance of a hybrid human and computer-assisted approach

Background: The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, was initiated in 2011 to optimize quality of care by promoting evidence-based decision-making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL Multiterm termbases) from medical termbases and support from online machine translation. This has resulted in a validated translation memory which is now in use for the translation of new and updated guidelines. Objective: The objective of this study was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. Methods: We conducted a pilot trial in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (a) by certificated junior translators without medical specialization using the hybrid method (b) by an experienced medical translator without this support and (c) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The Human Translation Edit Rate was calculated as a metric to evaluate the quality of the translation. A further evaluation was made of translation acceptability and adequacy. Results: The average number of words per guideline was 1,195 and the mean total translation time was 100.2 min/1,000 words. No meaningful differences were found in the translation speed for new guidelines. The translation of updated guidelines was 59 min/1,000 words faster (95% CI 2-115; P=.044) in the computer-aided group. Revisions due to terminology accounted for one third of the overall revisions by the medical proofreader. Conclusions: Use of the hybrid human and computer-aided translation by a non-expert translator makes the translation of updates of clinical practice guidelines faster and cheaper because of the benefits of translation memory. For the translation of new guidelines there was no apparent benefit in comparison with the efficiency of translation unsupported by translation memory (whether by an expert or non-expert translator

Optimal Filling of Shapes

We present filling as a type of spatial subdivision problem similar to covering and packing. Filling addresses the optimal placement of overlapping objects lying entirely inside an arbitrary shape so as to cover the most interior volume. In n-dimensional space, if the objects are polydisperse n-balls, we show that solutions correspond to sets of maximal n-balls. For polygons, we provide a heuristic for finding solutions of maximal discs. We consider the properties of ideal distributions of N discs as N approaches infinity. We note an analogy with energy landscapes.Comment: 5 page

First-Principles Approach for Coupled Quantum Dynamics of Electrons and Protons in Heterogeneous Systems

The coupled quantum dynamics of electrons and protons is ubiquitous in many dynamical processes involving light-matter interaction, such as solar energy conversion in chemical systems and photosynthesis. A first-principles description of such nuclear-electronic quantum dynamics requires not only the time-dependent treatment of nonequilibrium electron dynamics but also that of quantum protons. Quantum mechanical correlation between electrons and protons adds further complexity to such coupled dynamics. Here we extend real-time nuclear-electronic orbital time-dependent density functional theory (RT-NEO-TDDFT) to periodic systems and perform first-principles simulations of coupled quantum dynamics of electrons and protons in complex heterogeneous systems. The process studied is electronically excited state intramolecular proton transfer of o-hydroxybenzaldehyde in water and at a silicon (111) semiconductor-molecule interface. These simulations illustrate how environments such as hydrogen-bonding water molecules and an extended material surface impact the dynamical process on the atomistic level. Depending on how the molecule is chemisorbed on the surface, excited state electron transfer from the molecule to the semiconductor surface can inhibit ultrafast proton transfer within the molecule. This work elucidates how heterogeneous environments influence the balance between the quantum mechanical proton transfer and excited electron dynamics. The periodic RT-NEO-TDDFT approach is applicable to a wide range of other photoinduced heterogeneous processes

Converting From 3.6 and 4.5 Micron Fluxes to Stellar Mass

We use high spatial resolution maps of stellar mass and infrared flux of the Large Magellanic Cloud (LMC) to calibrate a conversion between 3.6 and 4.5 micron fluxes and stellar mass, M_* = 10^{5.65} * F_{3.6}^{2.85} * F_{4.5}^{-1.85} * (D/0.05)^2 M_solar, where fluxes are in Jy and D is the luminosity distance to the source in Mpc, and to provide an approximate empirical estimate of the fractional internal uncertainty in M_* of 0.3*sqrt{N/10^6}, where N is the number of stars in the region. We find evidence that young stars and hot dust contaminate the measurements, but attempts to remove this contamination using data that is far superior than what is generally available for unresolved galaxies resulted in marginal gains in accuracy. The scatter among mass estimates for regions in the LMC is comparable to that found by previous investigators when modeling composite populations, and so we conclude that our simple conversion is as precise as possible for the data and models currently available. Our results allow for a reasonably bottom-heavy initial mass function, such as Salpeter or heavier, and moderately disfavor lighter versions such as a diet-Salpeter or Chabrier initial mass function.Comment: 7 pages, 6 figures, to be published in the Astronomical Journa

Risk Factors for the Development of Cataract in Children with Uveitis

PURPOSE: To determine the risk factors for the development of cataract in children with uveitis of any etiology. DESIGN: Cohort study. METHODS: Two hundred forty-seven eyes of 140 children with uveitis were evaluated for the development of vision-affecting cataract. Demographic, clinical, and treatment data were collected between the time of presentation and the first instance cataract was recorded or findings at final follow-up. Main outcome measures included the prevalence of cataract and distribution by type of uveitis, incidence of new onset cataract time to cataract development, and risk factors for the development of cataract. RESULTS: The prevalence of cataract in our cohort was 44.2% and was highest among eyes with panuveitis (77.1%), chronic anterior uveitis (48.3%), and intermediate uveitis (48.0%). The overall incidence of newly diagnosed cataract was 0.09 per eye-year, with an estimated 69% to develop uveitis-related cataract with time. The main factors related with cataract development were the number of uveitis flares per year (hazard ratio [HR] = 3.06 [95% confidence interval {CI}, 2.15–4.35], P < .001), cystoid macular edema (HR = 2.87 [95% CI, 1.41–5.82], P = .004), posterior synechia at presentation (HR = 2.85 [95% CI, 1.53–5.30], P = .001), and use of local injections of corticosteroids (HR = 2.37 [95% CI, 1.18–4.75], P = .02). Treatments with systemic and topical corticosteroids were not significant risk factors. CONCLUSIONS: In this study, we found that development of cataract is common among pediatric eyes with uveitis and is most strongly related to the extent of inflammation recurrences and ocular complications. We suggest that controlling the inflammation, even using higher doses of systemic and topical corticosteroids, is of importance in preventing ocular complications, such as cataract. Uveitis accounts for 10–15% of blindness in the developed world.1 Although pediatric uveitis is relatively uncommon, accounting for only 5–10% of all uveitis cases,2 it affects young patients, who in most cases are otherwise healthy. Vision loss results from ongoing inflammation that leads to ocular structural changes, such as cataract, corneal opacities, optic neuropathy, and retinal lesions. The most common causes of vision loss in children with uveitis are cataract, glaucoma, and chronic cystoid macular edema (CME).2, 3 In addition, any chronic visual obstruction can result in the development of amblyopia in younger children, with vision loss persisting after the inciting cause is treated.4 Such changes, together with the need for long-term treatment and continuous monitoring, can have a profound impact on their development, independence, and education. The prevalence of cataract in eyes with uveitis ranges from 20–64%,4, 5, 6, 7 and it is the most common complication of uveitis in children,8 occurring in approximately 35% of children with juvenile idiopathic arthritis (JIA)-associated uveitis9 and increasing ≤80% in adults.10, 11 Cataract progression can be the result of persistent intraocular inflammation,12, 13 can be caused by surgery for uveitis complications (eg, trabeculectomies and repair of retinal detachments), or can be a consequence of uveitis treatment, particularly the use of local or systemic corticosteroids.14, 15, 16, 17 It results in reduced visual acuity and can have a detrimental effect on the development and academic achievements of these children.18 Studies have examined risk factors for the development of cataract among children with JIA-associated uveitis, identifying risk factors such as the presence of posterior synechiae (PS) at presentation,12, 19 the use of systemic corticosteroids,13 topical corticosteroid therapy exceeding 3 drops a day,12 or persistent, uncontrolled active inflammation,3 while early treatment with methotrexate delayed cataract progression.19 However, JIA is a unique cause of uveitis, often localized to the anterior chamber, with frequent intraocular structural changes and the early use of systemic immunosuppressive agents. It may not represent the same risks as other causes of pediatric uveitis. We examined disease- and treatment-related risk factors for cataract development in children with uveitis of any etiology. We investigated clinical and ophthalmologic characteristics, as well as treatment strategies in relation to the time interval between the first presentation with uveitis and cataract development

Multidrug-Resistant Tuberculosis in Patients without HIV Infection

BACKGROUND Investigations of outbreaks of multidrug-resistant tuberculosis have found low rates of treatment response and very high mortality, and they have mainly involved patients with advanced human immunodeficiency virus (HIV) infection. For patients without HIV infection, one study reported an overall rate of response to treatment of 56 percent, and the mortality from tuberculosis was 22 percent. We investigated treatment response and mortality rates in 26 HIV-negative patients in New York with multidrug-resistant tuberculosis. METHODS We obtained detailed data from seven teaching hospitals in New York City on patients with multidrug-resistant tuberculosis--defined as tuberculosis resistant at least to isoniazid and rifampin--who were HIV-negative on serologic testing. Lengths of times from diagnosis to the initiation of appropriate therapy and from the initiation of appropriate therapy to conversion to negative cultures were assessed. Therapeutic responses were evaluated by both microbiologic and clinical criteria. RESULTS Between March 1991 and September 1994, 26 HIV-negative patients were identified and treated. Of the 25 patients for whom adequate data were available for analysis, 24 (96 percent) had clinical responses; all 17 patients for whom data on microbiologic response were available had such a response. The median times from diagnosis to the initiation of appropriate therapy and from the initiation of therapy to culture conversion were 44 days (range, 0 to 181) and 69 days (range, 2 to 705), respectively. Side effects requiring the discontinuation of medication occurred in 4 of 23 patients (17 percent) who were treated with second-line antituberculosis medications. The median follow-up for the 23 patients who responded and who received appropriate therapy was 91 weeks (range, 41 to 225). CONCLUSIONS In this report from New York City, HIV-negative patients with multidrug-resistant tuberculosis, contrary to previous reports, responded well to appropriate chemotherapy, both clinically and microbiologically

Study protocol; thyroid hormone replacement for untreated older adults with subclinical hypothyroidism - a randomised placebo controlled trial (TRUST)

Background: Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Methods: Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects &lt;50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. Discussion: This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Trial registration: Clinicaltrials.gov NCT01660126; registered 8th June 2012