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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.
Early growth pattern is increasingly recognized as a determinant of later obesity. This study aimed to identify the association between weight gain in early life and anthropometry, adiposity, leptin, and fasting insulin levels in adolescence. A cross-sectional study was conducted in 366 school children aged 11–13 years. Weight, height, and waist circumference (WC) were measured. Fat mass (FM) was assessed using bioelectrical impedance analysis. Blood was drawn after a 12-h fast for insulin and leptin assay. Birth weight and weight at 6 months and at 18 months were extracted from Child Health Development Records. An increase in weight SD score (SDS) by ≥0.67 was defined as accelerated weight gain. Linear mixed-effects modeling was used to predict anthropometry, adiposity, and metabolic outcomes using sex, pubertal status, accelerated weight gain as fixed factors; age, birth weight, and family income as fixed covariates, and school as a random factor. Children with accelerated weight gain between birth and 18 months had significantly higher body mass index (BMI) SDS, WC SDS, height SDS, %FM, fat mass index (FMI), fat free mass index (FFMI), and serum leptin levels in adolescence. Accelerated weight gain between 6 and 18 months was associated with higher BMI SDS, WC SDS, %FM, and FMI, but not with height SDS or FFMI. Accelerated weight gain at 0–6 months, in children with low birth weight, was associated with higher height SDS, BMI SDS, WC SDS, %FM, and FMI; in children with normal birth weight, it was associated with BMI SDS, WC SDS, height SDS, and FFMI, but not with %FM or FMI. Effects of accelerated weight gain in early life on anthropometry and adiposity in adolescence varied in different growth windows. Accelerated weight gain during 6–18 months was associated with higher FM rather than linear growth. Effects of accelerated weight gain between 0 and 6 months varied with birth weight.
In a RCT of family psychoeducation, 47 carers of 34 patients were allocated to one of three groups; Multifamily Group Psychoeducation, Solution Focussed Group Therapy or Treatment as Usual. Carers in both the MFGP intervention and the SFGP arm demonstrated greater knowledge and reduction in burden than those in the TAU arm.
Impaired insight is commonly seen in psychosis and some studies have proposed that is a biologically based deficit. Support for this view comes from the excess of neurological soft signs (NSS) observed in patients with psychoses and their neural correlates which demonstrate a degree of overlap with the regions of interest implicated in neuroimaging studies of insight. The aim was to examine the relationship between NSS and insight in a sample of 241 first-episode psychosis patients.
Total scores and subscale scores from three insight measures and two NSS scales were correlated in addition to factors representing overall insight and NSS which we created using principal component analysis.
There were only four significant associations when we controlled for symptoms. “Softer” Condensed Neurological Evaluation (CNE) signs were associated with our overall insight factor (r = 0.19, P = 0.02), with total Birchwood (r = −0.24, P<0.01), and the Birchwood subscales; recognition of mental illness (r = −0.24, P<0.01) and need for treatment (r = −0.18, P = 0.02). Total Neurological Evaluation Scale (NES) and recognition of the achieved effects of medication were also weakly correlated (r = 0.14, P = 0.04).
This study does not support a direct link between neurological dysfunction and insight in psychosis. Our understanding of insight as a concept remains in its infancy.
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.
The Single Ventricle Reconstruction Trial randomised neonates with hypoplastic left heart syndrome to a shunt strategy but otherwise retained standard of care. We aimed to describe centre-level practice variation at Fontan completion.
Centre-level data are reported as median or median frequency across all centres and range of medians or frequencies across centres. Classification and regression tree analysis assessed the association of centre-level factors with length of stay and percentage of patients with prolonged pleural effusion (>7 days).
The median Fontan age (14 centres, 320 patients) was 3.1 years (range from 1.7 to 3.9), and the weight-for-age z-score was −0.56 (−1.35 + 0.44). Extra-cardiac Fontans were performed in 79% (4–100%) of patients at the 13 centres performing this procedure; lateral tunnels were performed in 32% (3–100%) at the 11 centres performing it. Deep hypothermic circulatory arrest (nine centres) ranged from 6 to 100%. Major complications occurred in 17% (7–33%). The length of stay was 9.5 days (9–12); 15% (6–33%) had prolonged pleural effusion. Centres with fewer patients (<6%) with prolonged pleural effusion and fewer (<41%) complications had a shorter length of stay (<10 days; sensitivity 1.0; specificity 0.71; area under the curve 0.96). Avoiding deep hypothermic circulatory arrest and higher weight-for-age z-score were associated with a lower percentage of patients with prolonged effusions (<9.5%; sensitivity 1.0; specificity = 0.86; area under the curve 0.98).
Fontan perioperative practices varied widely among study centres. Strategies to decrease the duration of pleural effusion and minimise complications may decrease the length of stay. Further research regarding deep hypothermic circulatory arrest is needed to understand its association with prolonged pleural effusion.
Schmidt-hammer exposure-age dating (SHD) of boulders on cryoplanation terrace treads and associated bedrock cliff faces revealed Holocene ages ranging from 0 ± 825 to 8890 ± 1185 yr. The cliffs were significantly younger than the inner treads, which tended to be younger than the outer treads. Radiocarbon dates from the regolith of 3854 to 4821 cal yr BP (2σ range) indicated maximum rates of cliff recession of ~0.1 mm/yr, which suggests the onset of terrace formation before the last glacial maximum. Age, angularity, and size of clasts, together with planation across bedrock structures and the seepage of groundwater from the cliff foot, all support a process-based conceptual model of cryoplanation terrace development in which frost weathering leads to parallel cliff recession and, hence, terrace extension. The availability of groundwater during autumn freezeback is viewed as critical for frost wedging and/or the growth of segregation ice during prolonged winter frost penetration. Permafrost promotes cryoplanation by providing an impermeable frost table beneath the active layer, focusing groundwater flow, and supplying water for sediment transport by solifluction across the tread. Snow beds are considered an effect rather than a cause of cryoplanation terraces, and cryoplanation is seen as distinct from nivation.
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.
Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case–control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06–6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58–26.83)), wild frogs (aOR 3.65, 95% CI 1.32–10.07) and wild birds (aOR 6.93, 95% CI 2.29–21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases’ residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.
To assess type, nutrient profile and cost of food items sold by informal vendors to learners; and to determine nutrient content of corn-based processed snacks frequently sold.
Quintile 1 to 3 schools (n 36) randomly selected from six education districts; Eastern Cape, South Africa.
Informal food vendors (n 92) selling inside or immediately outside the school premises.
Food items sold at most schools were corn-based processed snacks (94 % of schools), sweets (89 %), lollipops (72 %) and biscuits (62 %). Based on the South African Nutrient Profiling model, none of these foods were profiled as healthy. Foods less commonly sold were fruits (28 % of schools) and animal-source foods; these foods were profiled as healthy. Mean (sd) energy cost (per 418 kJ (100 kcal)) was highest for animal-source foods (R2·95 (1·16)) and lowest for bread and vetkoek (R0·76 (0·21)), snacks (R0·76 (0·30)) and confectionery products (R0·70 (0·28)). The nutrient profiling score was inversely related to the energy cost of the food item (r = −0·562, P = 0·010). Compared with brand-name corn-based processed snacks, non-branded snacks had lower energy (2177 v. 2061 kJ; P = 0·031) content per 100 g. None of the brand-name samples contained sucrose; six of the nine non-branded samples contained sucrose, ranging from 4·4 to 6·2 g/100 g.
Foods mostly sold were unhealthy options, with the healthier food items being more expensive sources of energy.
The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.
Communication deviance (CD) reflects features of the content or manner of a person's speech that may confuse the listener and inhibit the establishment of a shared focus of attention. The construct was developed in the context of the study of familial risks for psychosis based on hypotheses regarding its effects during childhood. It is not known whether parental CD is associated with nonverbal parental behaviors that may be important in early development. This study explored the association between CD in a cohort of mothers (n = 287) at 32 weeks gestation and maternal sensitivity with infants at 29 weeks in a standard play procedure. Maternal CD predicted lower overall maternal sensitivity (B = –.385; p < .001), and the effect was somewhat greater for sensitivity to infant distress (B = –.514; p < .001) than for sensitivity to nondistress (B = –.311; p < .01). After controlling for maternal age, IQ and depression, and for socioeconomic deprivation, the associations with overall sensitivity and sensitivity to distress remained significant. The findings provide new pointers to intergenerational transmission of vulnerability involving processes implicated in both verbal and nonverbal parental behaviors.
The ventricular assist device is being increasingly used as a “bridge-to-transplant” option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.
Background: Atrial fibrillation (AF) is associated with increased risk of ischemic stroke. In Canada, the contemporary burden of AF-related stroke is incompletely characterized. Our objective was to determine temporal trends in hospital admissions and in-hospital mortality for AF-related stroke in Canada from 2007 to 2015. Methods: We conducted a retrospective cohort study using Canadian national administrative data to identify admissions to hospital for stroke with comorbid AF between 2007 and 2015. We analyzed temporal trends in age- and sex-standardized proportion of admissions with comorbid AF and associated in-hospital mortality. Results: There were 222,100 admissions to hospital for ischemic (182,990) or hemorrhagic (39,110) stroke. The age-sex adjusted proportion of ischemic stroke admissions with comorbid AF increased from 16.2% to 20.5% (p for trend = 0.02) between 2007 and 2015, and was stable among hemorrhagic stroke. In-hospital mortality for ischemic stroke with comorbid AF decreased from 21.6% to 15.0% (p for trend = 0.001). Conclusions: Rates of hospital admission for ischemic stroke with comorbid AF have increased, while associated in-hospital mortality has decreased. These results identify AF as an important continued focus for stroke prevention. Our findings provide insight into current trends and highlight the need for continued focus on AF-related stroke.
Research into the gut microbiota of human infants is necessary in order to better understand how inter-species interactions and ecological succession shape the diversity of the gut microbiota, and in turn, how the specific composition of the gut microbiota impacts on host health both during infancy and in later years. Blastocystis is a ubiquitous intestinal protist that has been linked to a number of intestinal and extra-intestinal diseases. However, emerging data show that asymptomatic carriage is common and that Blastocystis is prevalent in the healthy adult gut microbiota. Nonetheless, little is known about the prevalence and diversity of this microorganism in the healthy infant gut, including when and how individuals become colonized by Blastocystis. Here, we surveyed the prevalence and diversity of Blastocystis in an infant population (n = 59) from an industrialized country (Ireland) using Blastocystis-specific primers at three or more time-points up to 24 months old. Only three infants were positive for Blastocystis (prevalence = 5%) and this was only noted for samples collected at month 24. This rate is comparatively low relative to previously reported prevalence rates in the contemporaneous adult population. These data suggest that infants in Westernized countries that are successfully colonized by Blastocystis most likely acquire this microorganism via horizontal transfer.
The Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a novel coronavirus discovered in 2012. Since then, 1806 cases, including 564 deaths, have been reported by the Kingdom of Saudi Arabia (KSA) and affected countries as of 1 June 2016. Previous literature attributed increases in MERS-CoV transmission to camel breeding season as camels are likely the reservoir for the virus. However, this literature review and subsequent analysis indicate a lack of seasonality. A retrospective, epidemiological cluster analysis was conducted to investigate increases in MERS-CoV transmission and reports of household and nosocomial clusters. Cases were verified and associations between cases were substantiated through an extensive literature review and the Armed Forces Health Surveillance Branch's Tiered Source Classification System. A total of 51 clusters were identified, primarily nosocomial (80·4%) and most occurred in KSA (45·1%). Clusters corresponded temporally with the majority of periods of greatest incidence, suggesting a strong correlation between nosocomial transmission and notable increases in cases.
Iodine deficiency is present in certain groups of the UK population, notably in pregnant women; this is of concern as iodine is required for fetal brain development. UK milk is rich in iodine and is the principal dietary iodine source. UK sales of milk-alternative drinks are increasing but data are lacking on their iodine content. As consumers may replace iodine-rich milk with milk-alternative drinks, we aimed to measure the iodine concentration of those available in the UK. Using inductively coupled plasma-MS, we determined the iodine concentration of seven types of milk-alternative drink (soya, almond, coconut, oat, rice, hazelnut and hemp) by analysing forty-seven products purchased in November/December 2015. For comparison, winter samples of conventional (n 5) and organic (n 5) cows’ milk were included. The median iodine concentration of all of the unfortified milk-alternative drinks (n 44) was low, at 7·3 μg/kg, just 1·7 % of our value for winter conventional cows’ milk (median 438 μg/kg). One brand (not the market leader), fortified its soya, oat and rice drinks with iodine and those drinks had a higher iodine concentration than unfortified drinks, at 280, 287 and 266 μg/kg, respectively. The iodine concentration of organic milk (median 324 μg/kg) was lower than that of conventional milk. Although many milk-alternative drinks are fortified with Ca, at the time of this study, just three of forty-seven drinks were fortified with iodine. Individuals who consume milk-alternative drinks that are not fortified with iodine in place of cows’ milk may be at risk of iodine deficiency unless they consume alternative dietary iodine sources.
Terrestrial gastropods are problematical for radiocarbon (14C) measurement because they tend to incorporate carbon from ancient sources as a result of their dietary behavior. The 14C ecology of the pulmonate land snail, Helix melanostoma in Cyrenaica, northeastern Libya, was investigated as part of a wider study on the potential of using terrestrial mollusk shell for 14C dating of archaeological deposits. H. melanostoma was selected out of the species available in the region as it has the most predictable 14C ecology and also had a ubiquitous presence within the local archaeology. The ecological observations indicate that H. melanostoma has a very homogenous 14C ecology with consistent variations in F14C across sample sites controlled by availability of dietary vegetation. The majority of dated specimens from non-urbanized sample locations have only a small old-carbon effect, weighted mean of 476±48 14C yr, with between ~1% and 9% of dietary F14C from non-organic carbonate sources. Observed instabilities in the 14C ecology can all be attributed to the results of intense human activity not present before the Roman Period. Therefore, H. melanostoma and species with similar ecological behavior are suitable for 14C dating of archaeological and geological deposits with the use of a suitable offset.
A simple, portable capillary refill time (CRT) simulator is not commercially available. This device would be useful in mass-casualty simulations with multiple volunteers or mannequins depicting a variety of clinical findings and CRTs. The objective of this study was to develop and evaluate a prototype CRT simulator in a disaster simulation context.
A CRT prototype simulator was developed by embedding a pressure-sensitive piezo crystal, and a single red light-emitting diode (LED) light was embedded, within a flesh-toned resin. The LED light was programmed to turn white proportionate to the pressure applied, and gradually to return to red on release. The time to color return was adjustable with an external dial. The prototype was tested for feasibility among two cohorts: emergency medicine physicians in a tabletop exercise and second year medical students within an actual disaster triage drill. The realism of the simulator was compared to video-based CRT, and participants used a Visual Analog Scale (VAS) ranging from “completely artificial” to “as if on a real patient.” The VAS evaluated both the visual realism and the functional (eg, tactile) realism. Accuracy of CRT was evaluated only by the physician cohort. Data were analyzed using parametric and non-parametric statistics, and mean Cohen’s Kappas were used to describe inter-rater reliability.
The CRT simulator was generally well received by the participants. The simulator was perceived to have slightly higher functional realism (P=.06, P=.01) but lower visual realism (P=.002, P=.11) than the video-based CRT. Emergency medicine physicians had higher accuracy on portrayed CRT on the simulator than the videos (92.6% versus 71.1%; P<.001). Inter-rater reliability was higher for the simulator (0.78 versus 0.27; P<.001).
A simple, LED-based CRT simulator was well received in both settings. Prior to widespread use for disaster triage training, validation on participants’ ability to accurately triage disaster victims using CRT simulators and video-based CRT simulations should be performed.
ChangTP, SantillanesG, Claudius I, PhamPK, KovedJ, CheyneJ, Gausche-HillM, KajiAH, SrinivasanS, DonofrioJJ, BirC. Use of a Novel, Portable, LED-Based Capillary Refill Time Simulator within a Disaster Triage Context. Prehosp Disaster Med. 2017;32(4):451–456.