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Background: Massive hemorrhage protocols (MHPs) streamline the complex logistics required for prompt care of the bleeding patient, but their uptake has been variable and few regions have a system to measure outcomes from these events. Aim Statement: We aim to implement a standardized MHP with uniform quality improvement (QI) metrics to increase uptake of evidence-based MHPs across 150-hospitals in Ontario between 2017 and 2021. Measures & Design: We performed ongoing PDSA cycles; 1) stakeholder analysis by surveying the Ontario Regional Blood Coordinating Network (ORBCoN), 2) problem characterization and Ishikawa analysis for key QI metrics based on areas of MHP variability in 150 Ontario hospitals using a web-based survey, 3) creation of a consensus MHP via a modified Delphi process, 4) problem characterization at ORBCoN for the design of a freely available toolkit for provincial implementation by expert working groups, 5) design of 8 key QI metrics by a modified Delphi process, and 6) identification of process measures for QI data collection by implementation metrics. Evaluation/Results: PDSA1-2; 150-hospitals were surveyed. 33% of hospitals lacked MHPs, mostly in smaller sites. Major areas for QI were related to activation criteria, hemostatic agents, protocolized hypothermia management, variable MHP naming, QI metrics and serial blood work requirements. PDSA3; 3 Delphi rounds were held to reach 100% expert consensus for 42 statements and 8 CQI metrics. Major areas for modification were protocol name, laboratory resuscitation targets, cooler configurations, and role of factor VIIa. PDSA4; adaptable toolkit is under development by the steering committee and expert working groups. Implementation is scheduled for Spring 2020. PDSA5; the 8 CQI metrics are: TXA administration < 1 h, RBC transfusion < 15 min, call to transfer for definitive care < 60 min, temp >35°C at end of protocol, Hgb kept between 60-110g/L, transition to group-specific RBC by 90 min, appropriate activation defined by ≥6 units RBC in the first 24 hours, and any blood component wastage. Discussion/Impact: MHP uptake, content, and tracking is variable. A standardized MHP that is adaptable to diverse settings decreases complexity, improves use of evidence-based practices, and provides a platform for continuous QI. PDSA6 will occur after implementation; we will complete an implementation survey, and design a pilot and feasibility study for prospective tracking of patient outcomes using existing prospectively collected inter-hospital and provincial databases.
Dietary patterns describe the combination of foods and beverages in a diet and the frequency of habitual consumption. Better understanding of childhood dietary patterns and antenatal influences could inform intervention strategies to prevent childhood obesity. We derived empirical dietary patterns in 1142 children (average age 6·0 (sd 0·2) years) in New Zealand, whose mothers had participated in the Screening for Pregnancy Endpoints (SCOPE) cohort study and explored associations with measures of body composition. Participants (Children of SCOPE) had their diet assessed by FFQ, and dietary patterns were extracted using factor analysis. Three distinct dietary patterns were identified: ‘Healthy’, ‘Traditional’ and ‘Junk’. Associations between dietary patterns and measures of childhood body composition (waist, hip, arm circumferences, BMI, bioelectrical impedance analysis-derived body fat % and sum of skinfold thicknesses (SST)) were assessed by linear regression, with adjustment for maternal influences. Children who had higher ‘Junk’ dietary pattern scores had 0·24 (sd 0·08; 95 % CI 0·04, 0·13) cm greater arm and 0·44 (sd 0·05; 95 % CI 0·01, 0·10) cm greater hip circumferences and 1·13 (sd 0·07; 95 % CI 0·03, 0·12) cm greater SST and were more likely to be obese (OR 1·74; 95 % CI 1·07, 2·82); those with higher ‘Healthy’ pattern scores were less likely to be obese (OR 0·62; 95 % CI 0·39, 1·00). In a large mother–child cohort, a dietary pattern characterised by high-sugar and -fat foods was associated with greater adiposity and obesity risk in children aged 6 years, while a ‘Healthy’ dietary pattern offered some protection against obesity. Targeting unhealthy dietary patterns could inform public health strategies to reduce the prevalence of childhood obesity.
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
To better understand hepatitis C virus (HCV) epidemiology in Punjab state, India, we estimated the distribution of HCV antibody positivity (anti-HCV+) using a 2013–2014 HCV household seroprevalence survey. Household anti-HCV+ clustering was investigated (a) by individual-level multivariable logistic regression, and (b) comparing the observed frequency of households with multiple anti-HCV+ persons against the expected, simulated frequency assuming anti-HCV+ persons are randomly distributed. Village/ward-level clustering was investigated similarly. We estimated household-level associations between exposures and the number of anti-HCV+ members in a household (N = 1593 households) using multivariable ordered logistic regression. Anti-HCV+ prevalence was 3.6% (95% confidence interval 3.0–4.2%). Individual-level regression (N = 5543 participants) found an odds ratio of 3.19 (2.25–4.50) for someone being anti-HCV+ if another household member was anti-HCV+. Thirty households surveyed had ⩾2 anti-HCV+ members, whereas 0/1000 (P < 0.001) simulations had ⩾30 such households. Excess village-level clustering was evident: 10 villages had ⩾6 anti-HCV+ members, occurring in 31/1000 simulations (P = 0.031). The household-level model indicated the number of household members, living in southern Punjab, lower socio-economic score, and a higher proportion having ever used opium/bhuki were associated with a household's number of anti-HCV+ members. Anti-HCV+ clusters within households and villages in Punjab, India. These data should be used to inform screening efforts.
Introduction: Choosing Wisely Canada guidelines suggest that in the absence of red flags or clinical indicators suggestive of serious underlying conditions, physicians should not order radiological images for patients presenting with non-specific low back pain, and current recommendations do not endorse routine prescribing of opioids for this condition. The objective of this study was to determine how many patients presenting to the ED with non-traumatic low back pain have spinal imaging and how many are discharged home on opioids. Methods: We conducted a retrospective medical record review for adult (>17 years) patients presenting to an academic tertiary care ED with non-traumatic low back pain from April 1st 2014 to March 31st 2015 (pre-guideline) and April 1st 2017 to March 31st 2018 (post-guideline). Patients were excluded if they were >70 years old, were not discharged home, had a traumatic injury, features of cauda equina syndrome, weight loss, history of cancer, fever, night sweats, chronic use of systemic corticosteroids, chronic use of illicit intravenous drugs, first episode of low back pain over 50 years of age, abnormal reflexes, loss of motor strength or loss of sensation in the legs. Results: 1060 (545 pre-guideline, 515 post-guideline) were included. Mean (SD) age was 39.6 (12.3) years and 549 (51.8%) were female. Pre-guideline, 45 (8.3%) patients had spinal imaging, compared to 39 (7.6%) post-guideline (Δ 0.7%; 95% CI: −2.6% to 4.0%). Of the 84 (7.9%) patients who had spinal imaging, 4 (8.9%) had pathologic findings pre-guideline, compared to 10 (25.6%) patients post-guideline. The proportion of patients discharged home with a prescription for opioids was lower after the Choosing Wisely Canada guidelines (40.9% vs. 11.1%; Δ29.8%; 95% CI: 24.8% to 34.7%). Conclusion: Choosing Wisely Canada guidelines did not appear to alter the rate of imaging for patients presenting to the ED with non-traumatic low back pain. Overall the rate of spinal imaging was lower than expected. The proportion of patients who were discharged home with a prescription for opioids was lower after the Choosing Wisely Canada guidelines, however we don't know if this represents an overall trend in the reduction of opioid prescribing, or a specific change in practice related to the ED management of low back pain.
Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
During May 2015, an increase in Salmonella Agona cases was reported from western Sydney, Australia. We examine the public health actions used to investigate and control this increase. A descriptive case-series investigation was conducted. Six outbreak cases were identified; all had consumed cooked tuna sushi rolls purchased within a western Sydney shopping complex. Onset of illness for outbreak cases occurred between 7 April and 24 May 2015. Salmonella was isolated from food samples collected from the implicated premise and a prohibition order issued. No further cases were identified following this action. Whole genome sequence (WGS) analysis was performed on isolates recovered during this investigation, with additional S. Agona isolates from sporadic-clinical cases and routine food sampling in New South Wales, January to July 2015. Clinical isolates of outbreak cases were indistinguishable from food isolates collected from the implicated sushi outlet. Five additional clinical isolates not originally considered to be linked to the outbreak were genomically similar to outbreak isolates, indicating the point-source contamination may have started before routine surveillance identified an increase. This investigation demonstrated the value of genomics-guided public health action, where near real-time WGS enhanced the resolution of the epidemiological investigation.
Introduction: Hip fractures affect over 35,000 Canadians each year. Delirium, or acute confusion, occurs in up to 62% of patients following a hip fracture. Delirium substantially increases hospital length of stay and doubles the risk of nursing home admissions and death. The primary objective of this study was to identify risk factors independently associated with acute in-hospital delirium within 72 hours of emergency department (ED) arrival for patients diagnosed with a hip fracture. Methods: This was a retrospective chart review of patients aged 65 years and older presenting to one of two academic EDs with a discharge diagnosis of hip fracture from January 1st 2014 to December 31st 2015. Multivariable logistic regression analysis was used to determine variables independently associated with the development of acute in-hospital delirium within 72 hours of ED arrival. Results: Of the 668 included patients, mean (SD) age was 84.1 (8.0) years and 501 (75%) were female. 521 (78.0%) patients received an opioid analgesic and/or femoral nerve block in the ED. The most common analgesics used in the ED were intravenous (IV) morphine (35.8%), IV hydromorphone (35.2%), or dual therapy with both IV hydromorphone and IV morphine (2.2%). Femoral nerve blocks were initiated for 36 (5.4%) patients and successfully completed in 35 (5.2%) patients in the ED. 181 (27.1%) patients developed delirium within 72 hours of ED arrival. History of neurodegenerative disease or dementia (OR: 5.7, 95% CI: 3.9, 8.4), age >75 (OR: 2.8, 95% CI: 1.4, 5.6) and absence of analgesia in the ED (OR: 2.1, 95% CI: 1.3, 3.2) were independently associated with acute in-hospital delirium. Conclusion: The development of in-hospital delirium is common in patients diagnosed with a hip fracture. We have identified modifiable and non-modifiable risk factors independently associated with acute in-hospital delirium, which can be identified in the ED. Clinicians should be aware of these risk factors in order to implement strategies directed at reducing the development of acute delirium. Additionally, further research is needed in order to understand the relationship between analgesia delivered in the ED and the development of delirium for patients diagnosed with a hip fracture.
We investigated the prevalence, diversity, and antimicrobial resistance (AMR) profiles of non-typhoidal Salmonella (NTS) and associated risk factors on 341 pig, chicken, and duck farms in Dong Thap province (Mekong Delta, Vietnam). Sampling was stratified by species, district (four categories), and farm size (three categories). Pooled faeces, collected using boot swabs, were tested using ISO 6575: 2002 (Annex D). Isolates were serogrouped; group B isolates were tested by polymerase chain reaction to detect S. Typhimurium and (monophasic) serovar 4,,12:i:- variants. The farm-level adjusted NTS prevalence was 64·7%, 94·3% and 91·3% for chicken, duck and pig farms, respectively. Factors independently associated with NTS were duck farms [odds ratio (OR) 21·2], farm with >50 pigs (OR 11·9), pig farm with 5–50 pigs (OR 4·88) (vs. chickens), and frequent rodent sightings (OR 2·3). Both S. Typhimurium and monophasic S. Typhimurium were more common in duck farms. Isolates had a high prevalence of resistance (77·6%) against tetracycline, moderate resistance (20–30%) against chloramphenicol, sulfamethoxazole-trimethoprim, ampicillin and nalidixic acid, and low resistance (<5%) against ciprofloxacin and third-generation cephalosporins. Multidrug resistance (resistance against ⩾3 classes of antimicrobial) was independently associated with monophasic S. Typhimurium and other group B isolates (excluding S. Typhimurium) and pig farms. The unusually high prevalence of NTS on Mekong Delta farms poses formidable challenges for control.
This paper describes a new, environmentally friendly drilling technique for making short-and long-term access boreholes in shelf glaciers using lightweight drills. The new drilling technique was successfully developed for installation of small-diameter sensors under the Ross Ice Shelf through ~ 193 m thick ice at Windless Bight, McMurdo Ice Shelf, Antarctica. The two access boreholes were drilled and sensors installed in 110 working hours. The total weight of the drilling equipment including the power system and fuel is <400 kg. Installation of small-diameter sensors was possible for 1.8– 6 hours after penetration through the glacier into the sea water beneath. The new drilling technique does not require drilling fluid and therefore has minimal environmental impact. It should permit access through ice-shelf ice up to 350 m thick, or glaciers on grounded ice or subglacial lakes if there is no water-permeable interface at the base. Modifications, presented in this work, of the drilling equipment and protocol will allow for (1) ~ 21 working hours for penetration through 200 m of ice, (2) installation of sensors up to 120 mm in diameter and (3) drilling long-term open boreholes through 400 m thick ice in 100 working hours.
Campylobacter are zoonotic pathogens commonly associated with gastroenteritis. To assess the relevance of Campylobacter in Vietnam, an economically transitioning country in SE Asia, we conducted a survey of 343 pig and poultry farms in the Mekong delta, a region characterized by mixed species farming with limited biosecurity. The animal-level prevalence of Campylobacter was 31·9%, 23·9% and 53·7% for chickens, ducks and pigs, respectively. C. jejuni was predominant in all three host species, with the highest prevalence in pigs in high-density production areas. Campylobacter isolates demonstrated high levels of antimicrobial resistance (21% and 100% resistance against ciprofloxacin and erythromycin, respectively). Multilocus sequence type genotyping showed a high level of genetic diversity within C. jejuni, and predicted C. coli inter-species transmission. We suggest that on-going intensification of animal production systems, limited biosecurity, and increased urbanization in Vietnam is likely to result in Campylobacter becoming an increasingly significant cause of human diarrhoeal infections in coming years.
EMU is a wide-field radio continuum survey planned for the new Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The primary goal of EMU is to make a deep (rms ∼ 10 μJy/beam) radio continuum survey of the entire Southern sky at 1.3 GHz, extending as far North as +30° declination, with a resolution of 10 arcsec. EMU is expected to detect and catalogue about 70 million galaxies, including typical star-forming galaxies up to z ∼ 1, powerful starbursts to even greater redshifts, and active galactic nuclei to the edge of the visible Universe. It will undoubtedly discover new classes of object. This paper defines the science goals and parameters of the survey, and describes the development of techniques necessary to maximise the science return from EMU.
Non-typhoidal Salmonella are an important but poorly characterized cause of paediatric diarrhoea in developing countries. We conducted a hospital-based case-control study in children aged <5 years in Ho Chi Minh City to define the epidemiology and examine risk factors associated with Salmonella diarrhoeal infections. From 1419 diarrhoea cases and 571 controls enrolled between 2009 and 2010, 77 (5·4%) diarrhoea cases were stool culture-positive for non-typhoidal Salmonella. Salmonella patients were more likely to be younger than controls (median age 10 and 12 months, respectively) [odds ratio (OR) 0·97; 95% confidence interval (CI) 0·94–0·99], to report a recent diarrhoeal contact (8·1% cases, 1·8% controls; OR 5·98, 95% CI 1·8–20·4) and to live in a household with >2 children (cases 20·8%, controls 10·2%; OR 2·32, 95% CI 1·2–4·7). Our findings indicate that Salmonella are an important cause of paediatric gastroenteritis in this setting and we suggest that transmission may occur through direct human contact in the home.
Uncertainty about future energy and water supplies suggests a pressing need to develop efficient technologies for water desalination. Capacitive deionization (CDI), a method that captures ions in the electrical double layer (EDL) of an electrochemical capacitor, is a promising technology that can potentially fulfill those requirements. Similar to supercapacitors, ideal CDI electrodes should have a large electrolyte-accessible specific surface area available for ion adsorption with rapid charging/discharging characteristics. Unlike supercapacitors, CDI electrodes are required to operate in aqueous electrolytes with low ionic concentrations in a non-linear charging regime. To explore this practically and theoretically important regime, we developed robust, electrochemically-compatible carbon nanotube (CNT) carpet electrodes that posses a well-defined and uniform pore structure that is more readily analyzed in comparison to the random and multi-scale pore structure of typical carbon electrodes. The fabricated electrodes were characterized using cyclic voltammetry and potentiostatic charging in aqueous NaCl solutions (no = 20 - 90 mM) using a three electrode setup. Examination of the CV and potentiostatically-measured capacitances were consistent with EDL behavior dictated by the Stern layer. However, some deviations from the expected behavior were observed with increasing salt concentration during potentiostatic testing.