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Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
The Sort, Access, Life-saving interventions, Treatment and/or Triage (SALT) mass-casualty incident (MCI) algorithm is unique in that it includes two subjective questions during the triage process: “Is the victim likely to survive given the resources?” and “Is the injury minor?”
Given this subjectivity, it was hypothesized that as casualties increase, the inter-rater reliability (IRR) of the tool would decline, due to an increase in the number of patients triaged as Minor and Expectant.
A pre-collected dataset of pediatric trauma patients age <14 years from a single Level 1 trauma center was used to generate “patients.” Three trained raters triaged each patient using SALT as if they were in each of the following scenarios: 10, 100, and 1,000 victim MCIs. Cohen’s kappa test was used to evaluate IRR between the raters in each of the scenarios.
A total of 247 patients were available for triage. The kappas were consistently “poor” to “fair:” 0.37 to 0.59 in the 10-victim scenario; 0.13 to 0.36 in the 100-victim scenario; and 0.05 to 0.36 in the 1,000-victim scenario. There was an increasing percentage of subjects triaged Minor as the number of estimated victims increased: 27.8% increase from 10- to 100-victim scenario and 7.0% increase from 100- to 1,000-victim scenario. Expectant triage categorization of patients remained stable as victim numbers increased.
Overall, SALT demonstrated poor IRR in this study of increasing casualty counts while triaging pediatric patients. Increased casualty counts in the scenarios did lead to increased Minor but not Expectant categorizations.
Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.
Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman’s test.
Median age at echocardiogram was 4.6 (range 2.5–7.4) months. Median ventricular end-diastolic pressure was 7 (range 3–19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range −35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = −0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.
In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
Analysis of human remains and a copper band found in the center of a Late Archaic (ca. 5000–3000 cal BP) shell ring demonstrate an exchange network between the Great Lakes and the coastal southeast United States. Similarities in mortuary practices suggest that the movement of objects between these two regions was more direct and unmediated than archaeologists previously assumed based on “down-the-line” models of exchange. These findings challenge prevalent notions that view preagricultural Native American communities as relatively isolated from one another and suggest instead that wide social networks spanned much of North America thousands of years before the advent of domestication.
The 2018 G20 Interfaith Forum took place 26–28 September 2018 in Buenos Aires, Argentina. This was the fifth annual event in a series of G20 interfaith fora held to coincide with the meetings of the international Group of Twenty Economic Summit. This year's G20 Summit will take place in Buenos Aires, from 30 November to 1 December. Previous interfaith fora have been held in Gold Coast, Australia (2014), Istanbul, Turkey (2015), Beijing, China (2016) and Potsdam, Germany (2017).
The International Consortium for Law and Religion Studies (ICLARS) chose Rio de Janeiro and the sun-kissed beaches of Ipanema and Copacabana for its fifth conference and, unsurprisingly, the event was heavily over-subscribed. ICLARS was founded in 2007 with the aim of providing a forum where information, data and opinions could be readily exchanged among members and made available to the broader scientific community. Its first conference was held in Milan in 2009, followed by meetings in Chile in 2011, the USA in 2013 and Oxford in 2016. The proceedings from all these conferences have been published, giving permanence and a wider readership to the innovative scholarship which these gatherings have consistently produced.
Vulnerability of satellite-based navigation signals to intentional and unintentional interference calls for a high-level overview of Global Navigation Satellite System (GNSS) threats occurring globally to understand the magnitude and evolution of the problem. Therefore, a mechanism needs to be developed whereby disparate monitoring systems will be capable of contributing to a common entity of basic information about the threat scenarios they experience. This paper begins with a literature survey of 37 state-of-the-art GNSS threat monitoring systems, which have been analysed based on their respective operational features - constellations monitored and whether they possess the capability to perform interference-type classification, spoofing detection, and interference localisation. Also described is a comparative analysis of four GNSS threat reporting formats in use today. Based on these studies, the paper describes the Horizon2020 Standardisation of GNSS Threat Reporting and Receiver Testing through International Knowledge Exchange, Experimentation and Exploitation (STRIKE3) proposed integrated threat monitoring demonstration system and related standardised threat reporting message, to enable a high-level overview of the prevailing international GNSS threat scenarios and its evolution over time.
Early-life institutional deprivation produces disinhibited social engagement (DSE). Portrayed as a childhood condition, little is known about the persistence of DSE-type behaviours into, presentation during, and their impact on, functioning in adulthood.
We examine these issues in the young adult follow-up of the English and Romanian Adoptees study.
A total of 122 of the original 165 Romanian adoptees who had spent up to 43 months as children in Ceauşescu's Romanian orphanages and 42 UK adoptees were assessed for DSE behaviours, neurodevelopmental and mental health problems, and impairment between ages 2 and 25 years.
Young adult DSE behaviour was strongly associated with early childhood deprivation, with a sixfold increase for those who spent more than 6 months in institutions. However, although DSE overlapped with autism spectrum disorder and attention-deficit hyperactivity disorder symptoms it was not, in itself, related to broader patterns of mental health problems or impairments in daily functioning in young adulthood.
DSE behaviour remained a prominent, but largely clinically benign, young adult feature of some adoptees who experienced early deprivation.
The Great Christian Jurists series comprises a library of national volumes of detailed biographies of leading jurists, judges and practitioners, assessing the impact of their Christian faith on the professional output of the individuals studied. Little has previously been written about the faith of the great judges who framed and developed the English common law over centuries, but this unique volume explores how their beliefs were reflected in their judicial functions. This comparative study, embracing ten centuries of English law, draws some remarkable conclusions as to how Christianity shaped the views of lawyers and judges. Adopting a long historical perspective, this volume also explores the lives of judges whose practice in or conception of law helped to shape the Church, its law or the articulation of its doctrine.