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Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Innovation Concept: Free open access medical education (FOAM) is a quickly growing field. While there is an abundance of resources online, and on social media, the quality of those resources should always be questioned and reviewed. Furthermore, as medical learners progress in their training, they become lead consumers and producers of FOAM. Our educational innovation concept was the introduction of two FOAM streams into our residency program to assist learners to produce their own content with mentorship from our emergency medicine faculty. Methods: Medical students and residents training in the emergency department were encouraged to submit content to either our department website in the form of a clinical PEARL, or a research paper to the departmental Cureus online journal. All website content was reviewed by an attending physician and all Cureus content was submitted for further peer review and publication if approved. All published content was shared on social media through our department's Twitter account. A select number of residents were also mentored in reviewing and editing FOAM content and publishing it to our departmental website. Curriculum, Tool or Material: sjrhem.ca is the Saint John Regional Hospital Department of Emergency Medicine's website. A portion of the website is dedicated to posts arising from departmental rounds, case reviews as well as posts from learners in the form of clinical PEARLS. They are designed as succinct and informative clinical summaries and allow learners to share their content to a wider audience online. Cureus.com is an online journal of medical science, with a dedicated Dalhousie Emergency Medicine Channel. The editors are local emergency medicine faculty and senior residents, while reviewers are independent. In the last year, the clinical pearls received 5672 views, and the Cureus channel received 1143 content views. Conclusion: Feedback from learners regarding publication of their own FOAM has been positive and has allowed them to share their content to a much wider audience through our Departmental Website, Cureus Channel and Twitter stream. Furthermore, we are helping to prepare residents to produce their own high quality content, allowing our FOAM program to grow.
The link between circulating glucocorticoids and leptin in beef calves has not been explored but has been noted in several studies. The aim of this study is to determine the effects of exogenous glucocorticoids given at birth and 1 day of age on serum leptin concentrations in beef calves. Ruminant animals secrete leptin, which is thought to be important for the programming of the hypothalamic appetite centers. Angus crossbred cows (n = 31) bred via natural service were utilized for this experiment. At parturition (day 0), calf BW was recorded and each calf was infused intravenously with either a hydrocortisol sodium succinate solution (HC, 8 males and 8 females) at a dosage of 3.5 μg/kg of BW or a similar volume of saline solution (CONT, 7 males and 8 females). Each calf was given a second infusion of its respective treatment 24 h postpartum at 1.5 μg/kg of BW for HC treatment. Calf treatment was blocked by sex, dam body condition score (BCS), and dam age. Blood samples were taken via jugular venipuncture before infusion, daily from days 0 to 5, then every other day up to day 17. Serum leptin and cortisol concentrations were analyzed via radioimmunoassay. Dam age, dam BCS, calf BW, and serum leptin and cortisol concentrations were analyzed using MIXED procedure of SAS. Dam age was not different (P = 0.81) among HC and CONT calves (4.9±0.5 and 4.7±0.5, respectively). Dam BCS was not different between treatments (5.7±0.2 and 5.6±0.2 HC and CONT, respectively; P = 0.66). There was no difference in calf birth BW between treatments (P = 0.87) and averaged 38.3±1.4 kg. Cortisol concentrations were not different between both treatments (P = 0.23) from birth to day 4 of age. Calves that received the HC treatment showed significantly reduced (P = 0.03) leptin concentrations on days 1 to 13. Calf BW from 60 to 150 days of age was not different between CONT and HC treated calves (P = 0.65). These data indicate that exogenous glucocorticoids can be used to suppress neonatal leptin levels in calves. This could lead to changes in voluntary feed intake of treated calves.
Current work in multicultural competency has emphasized factors such as race and ethnicity, age, disability status, socioeconomic status, sexual orientation and gender. For those clinicians who work with military and veteran populations, grounding in military cultural competence is also critical as a prerequisite for providing quality care. We believe that engaging these populations from a specifically cognitive behavioural orientation allows bridging of cultural gaps and that there is a natural alignment between cognitive behavioural therapy (CBT) and many aspects of warrior culture. This paper outlines several factors related to the values of military culture and strategies of the CBT therapist to better understand and use these values effectively in clinical practice, including lessons learned from an intensive outpatient program providing speciality care to veterans and military service members.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Three-dimensional (3D) printing technology is a promising method for bone tissue engineering applications. For enhanced bone regeneration, it is important to have printable ink materials with appealing properties such as construct interconnectivity, mechanical strength, controlled degradation rates, and the presence of bioactive materials. In this respect, we develop a composite ink composed of polycaprolactone (PCL), poly(D,L-lactide-co-glycolide) (PLGA), and hydroxyapatite particles (HAps) and 3D print it into porous constructs. In vitro study revealed that composite constructs had higher mechanical properties, surface roughness, quicker degradation profile, and cellular behaviors compared to PCL counterparts. Furthermore, in vivo results showed that 3D-printed composite constructs had a positive influence on bone regeneration due to the presence of newly formed mineralized bone tissue and blood vessel formation. Therefore, 3D printable ink made of PCL/PLGA/HAp can be a highly useful material for 3D printing of bone tissue constructs.
Introduction: Ultrasonography (US), performed in the Emergency Department (ED) by Emergency Physicians, is well established. Educational studies have shown some promise in training paramedics in US use. We have developed and piloted a novel curriculum for paramedic US education. Methods: Based on an informal needs assessment, an US curriculum for paramedics was developed to include: Basic principles, Focused assessment with sonography for trauma (FAST), cardiac, and vascular access. Participants included ED-based and pre-hospital paramedics including all paramedics with critical care training who routinely perform vascular access and procedural sedation within our ED. Comparisons were made using paired non-parametric tests (GraphPad). Results: Participants (N=9) were provided pre- reading materials prior to completing a 6-hour course, consisting of a mix of didactic and practical sessions with live models and vascular access phantoms. Each module was introduced with a 30 minute didactic session, led by an Emergency Physician trained in US, followed immediately by a 1 hour hands-on session lead by either an Emergency Physician or an Emergency Medicine Resident at a learner to instructor ratio of 3:1. At the end of the course, participants were asked to complete a short 10 minute survey that included (1) an assessment of the course quality with regard to preparatory material and course content/delivery (4 point Likert scale; excellent, good, fair, poor); (2) self reported US knowledge pre and post course on a scale of 1-10 (10 high, 1 low); (3) general yes/no questions related to the future of ECCU paramedical and (4) a subjective written section for additional comments. All participants rated the content favourably: 97% scoring it as excellent, and 3% as good. The participants median self-reported US knowledge score increased from 2/10 (IQR 2-3) to 8/10 (IQR 7.25-8; p=0.009) post- course. All comments from the text field were positive in nature. Conclusion: We report a paramedic US course curriculum, which when piloted resulted in high learner satisfaction and a high rate of self reported improvement in US knowledge. Further study will include an assessment of knowledge acquisition and practical performance. Future modifications in our curriculum will be based on needs assessment and may include additional modules.
Introduction: Patients with chronic diseases are known to benefit from exercise. Such patients often visit the emergency department (ED). There are few studies examining prescribing exercise in the ED. We wished to study if exercise prescription in the ED is feasible and effective. Methods: In this pilot prospective block randomized trial, patients in the control group received routine care, whereas the intervention group received a combined written and verbal prescription for moderate exercise (150 minutes/week). Both groups were followed up by phone at 2 months. The primary outcome was achieving 150 min of exercise per week. Secondary outcomes included change in exercise, and differences in reported median weekly exercise. Comparisons were made by Mann-Whitney and Fishers tests (GraphPad). Results: Follow-up was completed for 22 patients (11 Control; 11 Intervention). Baseline reported median (with IQR) weekly exercise was similar between groups; Control 0(0-0)min; Intervention 0(0-45)min. There was no difference between groups for the primary outcome of 150 min/week at 2 months (Control 3/11; Intervention 4/11, RR 1.33 (95%CI 0.38-4.6;p=1.0). There was a significant increase in median exercise from baseline in both groups, but no difference between the groups (Control 75(10-225)min; Intervention 120(52.5-150)min;NS). 3 control patients actually received exercise prescription as part of routine care. A post-hoc comparison of patients receiving intervention vs. no intervention, revealed an increase in patients meeting the primary target of 150min/week (No intervention 0/8; Intervention 7/14, RR 2.0 (95%CI 1.2-3.4);p=0.023). Conclusion: Recruitment was feasible, however our study was underpowered to quantify an estimated effect size. As a significant proportion of the control group received the intervention (as part of standard care), any potential measurable effect was diluted. The improvement seen in patients receiving intervention and the increase in reported exercise in both groups (possible Hawthorne effect) suggests that exercise prescription for ED patients may be beneficial.
Progressive inefficacy of chemoprophylactic therapy to control gastro-intestinal (GI) nematode infection in sheep has been a major contributory factor in stimulating research into the development of alternative means of internal parasite control. This research aims to investigate the possibilities for selecting UK sheep for increased genetic resistance to naturally acquired GI nematode parasite infections.
We performed a spatial-temporal analysis to assess household risk factors for Ebola virus disease (Ebola) in a remote, severely-affected village. We defined a household as a family's shared living space and a case-household as a household with at least one resident who became a suspect, probable, or confirmed Ebola case from 1 August 2014 to 10 October 2014. We used Geographic Information System (GIS) software to calculate inter-household distances, performed space-time cluster analyses, and developed Generalized Estimating Equations (GEE). Village X consisted of 64 households; 42% of households became case-households over the observation period. Two significant space-time clusters occurred among households in the village; temporal effects outweighed spatial effects. GEE demonstrated that the odds of becoming a case-household increased by 4·0% for each additional person per household (P < 0·02) and 2·6% per day (P < 0·07). An increasing number of persons per household, and to a lesser extent, the passage of time after onset of the outbreak were risk factors for household Ebola acquisition, emphasizing the importance of prompt public health interventions that prioritize the most populated households. Using GIS with GEE can reveal complex spatial-temporal risk factors, which can inform prioritization of response activities in future outbreaks.
In their focal article, Cucina, Walmsley, Gast, Martin, and Curtin (2017) raise a number of concerns about survey key driver analysis (SKDA). Although many are valid, we think their critique ultimately goes too far and risks throwing the baby out with the bathwater. We have found that SKDA can be an effective way to generate insight and action when analysis is done correctly and results are used appropriately. In this response article, we first provide data that counters Cucina et al.’s findings. Then we describe the approach we take to survey key driver analytics and application. In doing so, we hope to address some of the core concerns raised in the focal article and identify ways for scientists and practitioners to conduct SKDA in a responsible way.
Introduction: The positive health outcomes of exercise have been well-studied, and exercise prescription has been shown to reduce morbidity in several chronic health conditions. However, patient attitudes around the prescription of exercise in the emergency department (ED) have not been explored. The aim of our pilot study is to explore patients’ willingness and perceptions of exercise being discussed and prescribed in the ED. Methods: This study is a survey of patients who had been previously selected for exercise prescription in a pilot study conducted at a tertiary care ED. This intervention group were given a standardized provincial written prescription to perform moderate exercise for 150 minutes per week. Participants answered a discharge questionnaire and were followed up by a telephone interview 2 months later. A structured interview of opinions around exercise prescription was conducted. Questions included a combination of non-closed style interview questions and Likert scale. Patients rated prescription detail, helpfulness and likelihood on a Likert scale from 1-5 (1 being strongly disagree and 5 being strongly agree). Median values (+/-IQRs) are presented, along with dominant themes. Results: 17 people consented to exercise prescription and follow up surveys. 2 were excluded due to hospital admission. 15 participants were enrolled and completed the discharge survey. Two-month follow up survey response rate was 80%. Patients rated the detail given in their prescription as 5 (+/-1). Helpfulness of prescription was rated as 4 (+/-2). Likelihood to continue exercising based on the prescription was rated as 4 (+/-2). 11/12 participants felt that exercise should be discussed in the Emergency Department either routinely or on a case-by-case basis.1 participant felt it should not be discussed at all. Conclusion: Our study demonstrates that most patients are open to exercise being discussed during their Emergency Department visit, and that the prescription format was well-received by study participants.
Introduction: Point-of-care-ultrasound is an established tool in the early diagnosis of abdominal aortic aneurysm (AAA), with a reported pooled sensitivity of 97.5% and pooled specificity 98.9%. Despite these impressive numbers, body habitus and bowel gas often render emergency department (ED) PoCUS for AAA inconclusive. We devised a manual aid “the modified peace sign technique” to improve visualization of the aorta, consisting of placing the divided fingers of the free hand of the sonographer around the probe to increase gas dispersion and improve the view of the obscured aorta. We tested the technique on volunteers during a training course when the initial scan was indeterminate due to inability to view the aorta from sub-xiphoid to bifurcation. Methods: In our pilot study, 7 physicians were asked to make a best attempt to perform an aortic scan. If they were unable to visualize the aorta, they were asked to use the modified peace sign technique. Participants recorded the number of times which they used the technique and the frequency that the technique allowed for a complete aortic scan, previously unobtainable. All scans were supervised by certified PoCUS physicians. Results: The technique was used a total of 25 times. Following failure to complete an aortic scan using their best attempt, participants were subsequently able to obtain a complete aortic scan 70% (95% CI 48 to 83%) of the time using the modified peace sign technique. Conclusion: In our pilot study, the modified peace sign technique had an estimated effect size of 70% improvement for visualization of the aorta in volunteers. Further studies are required to validate the technique in clinical practice.
Introduction: Point of care ultrasonography (PoCUS) is an established tool in the initial management of hypotensive patients in the emergency department (ED). It has been shown rule out certain shock etiologies, and improve diagnostic certainty, however evidence on benefit in the management of hypotensive patients is limited. We report the findings from our international multicenter RCT assessing the impact of a PoCUS protocol on diagnostic accuracy, as well as other key outcomes including mortality, which are reported elsewhere. Methods: Recruitment occurred at 4 North American and 3 Southern African sites. Screening at triage identified patients (SBP<100 mmHg or shock index >1) who were randomized to either PoCUS or control groups. Scans were performed by PoCUS-trained physicians. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. Final chart review was blinded to initial impressions and PoCUS findings. Categorical data was analyzed using Fishers two-tailed test. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. The perceived shock category changed more frequently in the PoCUS group 20/127 (15.7%) vs. control 7/125 (5.6%); RR 2.81 (95% CI 1.23 to 6.42; p=0.0134). There was no significant difference in change of diagnostic impression between groups PoCUS 39/123 (31.7%) vs control 34/124 (27.4%); RR 1.16 (95% CI 0.786 to 1.70; p=0.4879). There was no significant difference in the rate of correct category of shock between PoCUS (118/127; 93%) and control (113/122; 93%); RR 1.00 (95% CI 0.936 to 1.08; p=1.00), or for correct diagnosis; PoCUS 90/127 (70%) vs control 86/122 (70%); RR 0.987 (95% CI 0.671 to 1.45; p=1.00). Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We found that the use of PoCUS did change physicians’ perceived shock category. PoCUS did not improve diagnostic accuracy for category of shock or diagnosis.
Introduction: Point of care ultrasound (PoCUS) is an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). While PoCUS protocols have been shown to improve early diagnostic accuracy, there is little published evidence for any mortality benefit. We report the findings from our international multicenter randomized controlled trial, assessing the impact of a PoCUS protocol on survival and key clinical outcomes. Methods: Recruitment occurred at 7 centres in North America (4) and South Africa (3). Scans were performed by PoCUS-trained physicians. Screening at triage identified patients (SBP<100 or shock index>1), randomized to PoCUS or control (standard care and no PoCUS) groups. Demographics, clinical details and study findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. The primary outcome measure was 30-day/discharge mortality. Secondary outcome measures included diagnostic accuracy, changes in vital signs, acid-base status, and length of stay. Categorical data was analyzed using Fishers test, and continuous data by Student T test and multi-level log-regression testing. (GraphPad/SPSS) Final chart review was blinded to initial impressions and PoCUS findings. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no difference between groups for the primary outcome of mortality; PoCUS 32/129 (24.8%; 95% CI 14.3-35.3%) vs. Control 32/129 (24.8%; 95% CI 14.3-35.3%); RR 1.00 (95% CI 0.869 to 1.15; p=1.00). There were no differences in the secondary outcomes; ICU and total length of stay. Our sample size has a power of 0.80 (α:0.05) for a moderate effect size. Other secondary outcomes are reported separately. Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We did not find any mortality or length of stay benefits with the use of a PoCUS protocol, though a larger study is required to confirm these findings. While PoCUS may have diagnostic benefits, these may not translate into a survival benefit effect.
Introduction: Point of care ultrasound (PoCUS) has become an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). Current established protocols (e.g. RUSH and ACES) were developed by expert user opinion, rather than objective, prospective data. Recently the SHoC Protocol was published, recommending 3 core scans; cardiac, lung, and IVC; plus other scans when indicated clinically. We report the abnormal ultrasound findings from our international multicenter randomized controlled trial, to assess if the recommended 3 core SHoC protocol scans were chosen appropriately for this population. Methods: Recruitment occurred at seven centres in North America (4) and South Africa (3). Screening at triage identified patients (SBP<100 or shock index>1) who were randomized to PoCUS or control (standard care with no PoCUS) groups. All scans were performed by PoCUS-trained physicians within one hour of arrival in the ED. Demographics, clinical details and study findings were collected prospectively. A threshold incidence for positive findings of 10% was established as significant for the purposes of assessing the appropriateness of the core recommendations. Results: 138 patients had a PoCUS screen completed. All patients had cardiac, lung, IVC, aorta, abdominal, and pelvic scans. Reported abnormal findings included hyperdynamic LV function (59; 43%); small collapsing IVC (46; 33%); pericardial effusion (24; 17%); pleural fluid (19; 14%); hypodynamic LV function (15; 11%); large poorly collapsing IVC (13; 9%); peritoneal fluid (13; 9%); and aortic aneurysm (5; 4%). Conclusion: The 3 core SHoC Protocol recommendations included appropriate scans to detect all pathologies recorded at a rate of greater than 10 percent. The 3 most frequent findings were cardiac and IVC abnormalities, followed by lung. It is noted that peritoneal fluid was seen at a rate of 9%. Aortic aneurysms were rare. This data from the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients, supports the use of the prioritized SHoC protocol, though a larger study is required to confirm these findings.
Introduction: Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for emergency department (ED) patients with undifferentiated non-traumatic hypotension. While PoCUS has been shown to improve early diagnosis, there is a minimal evidence for any outcome benefit. We completed an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key resuscitation markers in this group. We report diagnostic impact and mortality elsewhere. Methods: The SHoC-ED1 study compared the addition of PoCUS to standard care within the first hour in the treatment of adult patients presenting with undifferentiated hypotension (SBP<100 mmHg or a Shock Index >1.0) with a control group that did not receive PoCUS. Scans were performed by PoCUS-trained physicians. 4 North American, and 3 South African sites participated in the study. Resuscitation outcomes analyzed included volume of fluid administered in the ED, changes in shock index (SI), modified early warning score (MEWS), venous acid-base balance, and lactate, at one and four hours. Comparisons utilized a T-test as well as stratified binomial log-regression to assess for any significant improvement in resuscitation amount the outcomes. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no significant difference in mean total volume of fluid received between the control (1658 ml; 95%CI 1365-1950) and PoCUS groups (1609 ml; 1385-1832; p=0.79). Significant improvements were seen in SI, MEWS, lactate and bicarbonate with resuscitation in both the PoCUS and control groups, however there was no difference between groups. Conclusion: SHOC-ED1 is the first RCT to compare PoCUS to standard of care in hypotensive ED patients. No significant difference in fluid used, or markers of resuscitation was found when comparing the use of a PoCUS protocol to that of standard of care in the resuscitation of patients with undifferentiated hypotension.