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Nutrition during the periconceptional period influences postnatal cardiovascular health. We determined whether in vitro embryo culture and transfer, which are manipulations of the nutritional environment during the periconceptional period, dysregulate postnatal blood pressure and blood pressure regulatory mechanisms. Embryos were either transferred to an intermediate recipient ewe (ET) or cultured in vitro in the absence (IVC) or presence of human serum (IVCHS) and a methyl donor (IVCHS+M) for 6 days. Basal blood pressure was recorded at 19–20 weeks after birth. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after varying doses of phenylephrine (PE). mRNA expression of signaling molecules involved in blood pressure regulation was measured in the renal artery. Basal MAP did not differ between groups. Baroreflex sensitivity, set point, and upper plateau were also maintained in all groups after PE stimulation. Adrenergic receptors alpha-1A (αAR1A), alpha-1B (αAR1B), and angiotensin II receptor type 1 (AT1R) mRNA expression were not different from controls in the renal artery. These results suggest there is no programmed effect of ET or IVC on basal blood pressure or the baroreflex control mechanisms in adolescence, but future studies are required to determine the impact of ET and IVC on these mechanisms later in the life course when developmental programming effects may be unmasked by age.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
While involving patients in health technology assessment (HTA) has become increasingly common and important around the world, little is known about the optimal methods of evaluating patients’ involvement (PI) in HTA. This scoping review was undertaken to provide an overview of currently available methods for the evaluation of PI, specifically the impact of PI on HTA recommendations.
A literature search was conducted using nine databases as well as a grey literature search of the websites of 26 organizations related to the conduct, practice or research of HTA to identify articles, reports and abstracts related to the evaluation of PI impact in HTA.
We identified 1,248 unique citations, six of which met our eligibility criteria. These six records (five articles, and one report) were all published after 2012. Four assessed the impact of patient experience submissions on final HTA recommendations; one evaluated the impact of direct involvement on HTA committees, and one assessed impact of multiple forms of involvement. Methods of evaluation included quantitative analyses of reimbursement decisions, qualitative interviews with those directly involved in an assessment, surveys of patient groups and committee members, and the review of HTA reports.
Quantitative evaluation of PI based on associations with funding decisions may not be feasible or fully capture the relevant impact of PI in the assessment of health technologies. Rather, a combination of both qualitative and quantitative strategies may allow for the most comprehensive assessment of the impact of PI on HTA recommendations when possible.
Introduction: Prognostication is a significant challenge early in the post-cardiac arrest period. Common prognostic factors for neurological survival are unreliable (high false positive rates) until 72 hours post-cardiac arrest. It is not known whether there are a combination of factors that can be utilized earlier in the post-cardiac arrest period to accurately predict patient outcome. Our objective was to predict neurological outcome utilizing a novel combination of patient factors early in the post-cardiac arrest period. Methods: We conducted a retrospective cohort study using data from our local cardiac arrest registry. We included adult patients who obtained a return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). We excluded patients who did not survive for at least 24 hours post-ROSC and those who had a do not resuscitate (DNR) order within 2 hours of ROSC. We performed an ordinal regression analysis using the proportional odds model to predict neurological outcome (modified rankin score (mRS)). We included a good neurological outcome (mRS 0-2), poor neurological outcome (mRS 3-5), and dead (mRS 6) as an ordinal outcome. We included a number of patient demographics, intra- and post-cardiac arrest factors as covariates in our model. The predictive performance of our model was analyzed using receiver operating characteristic (ROC) curves for discrimination and Brier statistic for calibration. Results: We included 3448 patients in our analysis. We found that an initial shockable rhythm (odds ratio (OR) 4.1; 95% confidence interval (CI) 3.6, 5.4), the absence of pupillary reflexes (OR 3.5; 95% CI 2.4,4.8) and maximum motor score on the Glasgow Coma Scale (GCS) (OR 1.5; 95% CI 1.4,1.6) had the greatest association with improved neurologic outcome. Longer duration of resuscitation was associate with worse outcomes (OR 0.84, 95% CI 0.82,0.87). The overall performance of our model was excellent with an area under the ROC curve of 0.89 and a Brier statistic of 0.13. Conclusion: Our model predicted good neurological outcome with a high rate of accuracy, however external validation of the model is required. This model may be useful in providing initial risk stratification of patients in clinical practice and future research on post-cardiac arrest care.
To investigate behavioural problems throughout childhood and adolescent, and its relationship with socioeconomic position (SEP) and early parenting environment.
Using data from the Millennium Cohort Study conducted in the UK, behavioural problems of 14 452 children were analysed using a growth curve model. The children were followed from birth to adolescence, and their behavioural problems were measured by the Strengths and Difficulties Questionnaire (SDQ). The SDQ was sub-scaled into externalising and internalising problems. After assessing the general trajectory of children's behavioural problems, variables representing SEP and parenting environments were introduced to the model to analyse the association with children's outcomes.
Overall, children's trajectories in externalising problems showed a decreasing trend while internalising problems increased as they aged. Household income and maternal education in early childhood were independently associated with children's behavioural problems, while the association for maternal occupation was significantly weaker. Positive early parenting environments attenuated the association between SEP and children's behavioural problems. Also, with regards to children's behavioural problems, positive parenting explained more variance between children compared to SEP. Favourable parent–child relationship buffered the income gradient in children's behavioural problems during early childhood, and although this buffering effect did not last until adolescence, those who had good parent–child relationships developed better outcomes regardless of their SEP.
The results of the study emphasise the importance of a positive early parenting environment for improving and reducing the socioeconomic gap in children's behavioural problems and encourages policies to promote better parenting circumstances.
Currently no national guidelines exist for the management of scabies outbreaks in residential or nursing care homes for the elderly in the United Kingdom. In this setting, diagnosis and treatment of scabies outbreaks is often delayed and optimal drug treatment, environmental control measures and even outcome measures are unclear. We undertook a systematic review to establish the efficacy of outbreak management interventions and determine evidence-based recommendations. Four electronic databases were searched for relevant studies, which were assessed using a quality assessment tool drawing on STROBE guidelines to describe the quality of observational data. Nineteen outbreak reports were identified, describing both drug treatment and environmental management measures. The quality of data was poor; none reported all outcome measures and only four described symptom relief measures. We were unable to make definitive evidence-based recommendations. We draw on the results to propose a framework for data collection in future observational studies of scabies outbreaks. While high-quality randomised controlled trials are needed to determine optimal drug treatment, evidence on environmental measures will need augmentation through other literature studies. The quality assessment tool designed is a useful resource for reporting of outcome measures including patient-reported measures in future outbreaks.
Introduction: 9-1-1 telecommunicators receive minimal education on agonal breathing, often resulting in unrecognized out-of-hospital cardiac arrest (OHCA). We successfully piloted an educational intervention that significantly improved telecommunicators’ OHCA recognition and bystander CPR rates in Ottawa. We sought to better understand the operations of Canadian 9-1-1 communications centers (CC) in preparation for a multi-centre study of this intervention. Methods: We conducted a National survey of all Canadian CCs. Survey domains included information on organizational structure, dispatch system used, education curriculum, and performance monitoring. It was peer-reviewed, translated in French, pilot-tested, and distributed electronically using a modified Dillman method. We designated respondents in each CC before distribution and used targeted follow-up and small incentives to increase response rate. Respondents also described functioning of neighboring CCs if known. Results: We received information from 51/51 provincial and 1/25 territorial CCs, representing 99.7% of the Canadian population. CCs largely utilize the Medical Dispatch Priority System (MPDS) platform (93%), many are Province/Ministry regulated (50%) and most require a High School diploma as minimum entry level education (78%). Telecommunicators receive initial in-class training (median 1.3 months, IQR 0.3-1.9; range 0.1-2.2), often followed by a preceptorship (84.4%) (median 1.0 months, IQR 0.7-1.7; range 0.4-6.0). Educational curriculum includes information on agonal breathing in 41% of CC, without audio examples in 34%. Among responding CCs, over 39,000 suspected OHCA 9-1-1 calls are received annually. Few CCs maintain local performance statistics on OHCA recognition (25%), bystander CPR rates (25%) or survival rates (50%). Most (97%) expressed interest in future research collaborations. Conclusion: Most Canadian telecommunicators receive no or minimal education in recognizing agonal breathing. Further training and improved OHCA monitoring may assist recognition and enhance outcomes.
High-intensity laser–plasma interactions produce a wide array of energetic particles and beams with promising applications. Unfortunately, the high repetition rate and high average power requirements for many applications are not satisfied by the lasers, optics, targets, and diagnostics currently employed. Here, we aim to address the need for high-repetition-rate targets and optics through the use of liquids. A novel nozzle assembly is used to generate high-velocity, laminar-flowing liquid microjets which are compatible with a low-vacuum environment, generate little to no debris, and exhibit precise positional and dimensional tolerances. Jets, droplets, submicron-thick sheets, and other exotic configurations are characterized with pump–probe shadowgraphy to evaluate their use as targets. To demonstrate a high-repetition-rate, consumable, liquid optical element, we present a plasma mirror created by a submicron-thick liquid sheet. This plasma mirror provides etalon-like anti-reflection properties in the low field of 0.1% and high reflectivity as a plasma, 69%, at a repetition rate of 1 kHz. Practical considerations of fluid compatibility, in-vacuum operation, and estimates of maximum repetition rate are addressed. The targets and optics presented here demonstrate a potential technique for enabling the operation of laser–plasma interactions at high repetition rates.
Introduction: Despite clear health benefits, and Public Health Agency of Canada recommendations, vaccination rates among Canadian adults are low. Frequent patient contacts, wait times, and the availability of trained staff make the emergency department (ED) a potential location to target specific populations and administer vaccinations. We evaluated the feasibility of two strategies to administer the Tdap vaccine to adult patients presenting to a single referral ED. Methods: Two immunization strategies and a control group were randomly ordered from one to three. Data collection for group one started on study day one with data collection for groups two and three on study days two and three respectively. This sequence was repeated over 15 consecutive weekdays (Monday-Friday, 0730-1530), evenly assigning each group to 5 different days. On intervention days, adult patients were screened during the triage process for eligibility to receive the Tdap vaccine. An ED based (EDB) strategy offered patients vaccination during that visit. The second strategy offered eligible patients a public health referral (PHR) to receive the vaccine at a later date. On all study days, patient triage times (TT), as well as markers of ED efficiency (number of patient registrations, time to physician, length of stay, left without being seen, number of admissions, number of boarded patients) were recorded. Results: The primary outcome, the proportion of eligible adults immunized, was significantly higher at 66% (n=81) for the EDB strategy (228 screened, 122 eligible), compared with 21% (n=20) for the PHR strategy (217 screened, 94 eligible; x2 (2, n=216)=43.41, p<0.00001). In addition, 10 participants in the PHR group received a second vaccine (Pneumococcal (7), Influenza (2), Human Papillomavirus (1)). Reasons for vaccine ineligibility included having an up-to-date Tdap (EDB n=47 (21%), PHR n=46 (21%)) and being considered in too much distress by the triage nurse (EDB n=26 (11%), PHR n=19 (9%)). Triage time was less for the control group (M=5:55 [mins:secs], SD=2:48) than for the EDB (M=6:47, SD=3:12) and PHR (M=7:25, SD=2:45) strategies. Conclusion: An ED based screening and immunization strategy was highly effective in providing eligible adult patients with the Tdap vaccine. A resulting small increase in triage time was not clinically significant. Further studies are required to generalize these results.
Introduction: Medical journals are an essential venue for knowledge translation. Skilled reviewers and editors are required to ensure quality standards in research publications and yet postgraduate programs rarely include this training in their curricula. Imparting appropriate skills and developing capacity in journalship has thus proved challenging. The Canadian Journal of Emergency Medicine (CJEM) is the national journal for Emergency Medicine (EM) in Canada. The CJEM editorial board recently decided to provide longitudinal mentorship for junior academic faculty members and trainees through an editorial internship. The internship had three goals for participants: (1) introduce and develop the responsibilities and skills of a good editor; (2) enhance a career in academic EM; and, (3) galvanize future participation as a reviewer or editor in scientific publications. Methods: The senior editorial board of CJEM and the inaugural intern developed a one-year Editorial Internship that was launched in June 2017. The curricular framework was designed by current and prior CJEM senior editors from four Canadian universities, and was informed by similar programs in the United States. The curriculum was refined iteratively based on feedback and discussion between the senior editors and intern. The internship was designed for a single individual in the Canadian EM community, including residents, pediatric fellows and practicing emergency physicians. Results: To develop the responsibilities and skills of being a good editor, the intern performed six mentored reviews of manuscripts either under current review at CJEM or previous submissions identified as difficult peer review decisions. In addition, the intern learned about CJEM values and norms by participating in monthly videoconference meetings and quarterly editorial board meetings. To enhance an academic career, the intern was assigned two writing projects under the guidance of senior editors for publication in CJEM, and completed an online critical appraisal course. Conclusion: The inaugural editorial intern gained experience as an editor and produced scholarly work. We feel the internship met its first two goals, and CJEM has committed to continue the internship annually. The ultimate determination of whether the internship achieved its third goal will only be known after longitudinal tracking of participants career involvement in academic publishing and editing.
This study determines the prevalence of inadequate micronutrient intakes consumed by long-term care (LTC) residents. This cross-sectional study was completed in thirty-two LTC homes in four Canadian provinces. Weighed and estimated food and beverage intake were collected over 3 non-consecutive days from 632 randomly selected residents. Nutrient intakes were adjusted for intra-individual variation and compared with the Dietary Reference Intakes. Proportion of participants, stratified by sex and use of modified (MTF) or regular texture foods, with intakes below the Estimated Average Requirement (EAR) or Adequate Intake (AI), were identified. Numbers of participants that met these adequacy values with use of micronutrient supplements was determined. Mean age of males (n 197) was 85·2 (sd 7·6) years and females (n 435) was 87·4 (sd 7·8) years. In all, 33 % consumed MTF; 78·2 % (males) and 76·1 % (females) took at least one micronutrient pill. Participants on a MTF had lower intake for some nutrients (males=4; females=8), but also consumed a few nutrients in larger amounts than regular texture consumers (males=4; females =1). More than 50 % of participants in both sexes and texture groups consumed inadequate amounts of folate, vitamins B6, Ca, Mg and Zn (males only), with >90 % consuming amounts below the EAR/AI for vitamin D, E, K, Mg (males only) and K. Vitamin D supplements resolved inadequate intakes for 50–70 % of participants. High proportions of LTC residents have intakes for nine of twenty nutrients examined below the EAR or AI. Strategies to improve intake specific to these nutrients are needed.
An outbreak of mumps within a student population in Scotland was investigated to assess the effect of previous vaccination on infection and clinical presentation, and any genotypic variation. Of the 341 cases, 79% were aged 18–24. Vaccination status was available for 278 cases of whom 84% had received at least one dose of mumps containing vaccine and 62% had received two. The complication rate was 5·3% (mainly orchitis), and 1·2% were admitted to hospital. Genetic sequencing of mumps virus isolated from cases across Scotland classified 97% of the samples as genotype G. Two distinct clusters of genotype G were identified, one circulating before the outbreak and the other thereafter, suggesting the virus that caused this outbreak was genetically different from the previously circulating virus. Whilst the poor vaccine effectiveness we found may be due to waning immunity over time, a contributing factor may be that the current mumps vaccine is less effective against some genotypes. Although the general benefits of the measles–mumps–rubella (MMR) vaccine should continue to be promoted, there may be value in reassessing the UK vaccination schedule and the current mumps component of the MMR vaccine.
Complications related to methamphetamine use and abuse are common presentations seen in the emergency department. Standard management focuses on addressing the central nervous system and cardiovascular effects with the use of sedation and hemodynamic support. We describe a case report of a patient with methamphetamine toxicity and subsequent severe cardiomyopathy refractory to conventional management that responded to cardiovascular support with extracorporeal membrane oxygenation therapy (ECMO). A 22-year-old female was admitted in severe cardiogenic shock following intravenous administration of methamphetamine and oral fentanyl use. Despite aggressive treatment with benzodiazepines, intravenous fluids, vasopressors, vasodilators, antibiotics and inotropes, the patient’s clinical status deteriorated, and she suffered a cardiac arrest. The patient was successfully resuscitated, and following the return of spontaneous circulation, ECMO was initiated. After 82 hours the patient was successfully weaned from ECMO with the recovery of her left ventricular function and no neurologic sequelae. The patient developed leg ischemia requiring embolectomy and open repair as a complication of ECMO cannulation. In our case, ECMO was used successfully in treating severe cardiac dysfunction from acute methamphetamine-induced cardiomyopathy and was used as a bridge to recovery. The complications seen in this patient emphasize the potential risks associated with this intervention and highlight the need for careful patient selection.
Cardiometabolic diseases exhibit changes in lipid biology, which is important as lipids have critical roles in membrane architecture, signalling, hormone synthesis, homoeostasis and metabolism. However, Developmental Origins of Health and Disease studies of cardiometabolic disease rarely include analysis of lipids. This short review highlights some examples of lipid pathology and then explores the technology available for analysing lipids, focussing on the need to develop imaging modalities for intracellular lipids. Analytical methods for studying interactions between the complex endocrine and intracellular signalling pathways that regulate lipid metabolism have been critical in expanding our understanding of how cardiometabolic diseases develop in association with obesity and dietary factors. Biochemical methods can be used to generate detailed lipid profiles to establish links between lifestyle factors and metabolic signalling pathways and determine how changes in specific lipid subtypes in plasma and homogenized tissue are associated with disease progression. New imaging modalities enable the specific visualization of intracellular lipid traffic and distribution in situ. These techniques provide a dynamic picture of the interactions between lipid storage, mobilization and signalling, which operate during normal cell function and are altered in many important diseases. The development of methods for imaging intracellular lipids can provide a dynamic real-time picture of how lipids are involved in complex signalling and other cell biology pathways; and how they ultimately regulate metabolic function/homoeostasis during early development. Some imaging modalities have the potential to be adapted for in vivo applications, and may enable the direct visualization of progression of pathogenesis of cardiometabolic disease after poor growth in early life.
Introduction: Pediatric out-of-hospital cardiac arrest (OHCA) is unique in terms of epidemiology, treatment, and outcomes. There is a paucity of literature examining predictors of survival to help guide resuscitation in this population. Objective: The primary objective was to examine predictors of survival to hospital discharge. The secondary objective was to determine the probability of return of spontaneous circulation (ROSC) over the duration of resuscitation. Methods: We performed a retrospective cohort study of non-traumatic OHCA (<18 years) treated by EMS from the Toronto Regional RescuNET Epistry-Cardiac Arrest database from 2006 to 2015. We used competing risk analysis to calculate the probability of ROSC over the duration of resuscitation. We then used multivariable logistic regression to examine the role of Utstein factors and duration of resuscitation in predicting survival to hospital discharge. Candidate variables were limited to Utstein factors and duration of resuscitation due to the number of events. We used area under the receiver operating characteristic (ROC) curve (AUC) to determine the predictive ability of our logistic regression model. Results: A total of 658 patients met inclusion criteria. Survival to discharge was 10.2% with 70.1% of those children having a good neurologic outcome. The overall median time to ROSC was 23.9 min. (IQR 15.0,36.7). However, the median time to ROSC for survivors was significantly shorter than the time to ROSC for patients who died in hospital (15.9 (IQR 10.6 to 22.8) vs. 33.2 (IQR 22.0 to 48.6); P value <0.001). There was a decrease in the odds of survival of 14% per minute during the first 25 minutes of cardiac arrest. Older age (OR 0.9, 95% CI 0.86,0.99), and longer duration of resuscitation (OR 0.9, 95% CI 0.88,0.93) were associated with worse outcome while initial shockable rhythm (OR 5.8, 95% CI 2.0,16.5), and witnessed arrests (OR 2.4, 95% CI 1.10,5.30) were associated with improved patient outcome. The AUC for the Utstein factors was fair (0.77). Including duration of resuscitation improved the discrimination of the model to 0.85. Conclusion: Inclusion of duration of resuscitation improved the performance of our model compared to Utstein factors alone. However, our results suggest there are a number of other important factors for predicting patient outcome from pediatric OHCA.