To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
OBJECTIVES/GOALS: The goal was to develop foundational research knowledge and skills for clinicians interested in conducting clinical research. Emphasis was on the development of a research question and the iterative process necessary to transform a research question into a well-designed study and well-articulated research proposal for pilot grant funding. METHODS/STUDY POPULATION: The course took place over 10 sessions, May - September 2021. The application process required participants to provide an initial self-assessment of research skills and a proposed research question. 25 clinicians applied to the program, 11 were accepted, and 9 enrolled. All clinicians in the initial cohort were clinical faculty physicians. Because of the geographical distance of participants as well as the ongoing pandemic, the course used a blended learning approach with both synchronous and asynchronous learning. Participants viewed online lectures on core content coupled with live virtual sessions with opportunities for discussion and application of the content. Relevant CTSI and institutional resources were highlighted in each session. RESULTS/ANTICIPATED RESULTS: Of the 9 clinician participants who enrolled in Research 101, the average attendance per session was 67% or 6 people. 89% or 8 participants attended five or more sessions. 5 participants submitted a letter of intent for the annual CTSI Pilot grant program, and of the five, two were invited to submit a grant application. Formal evaluation of the program is currently ongoing and will close on November 30th, at which time full results will be available. Research competencies will be assessed through a pre-post comparison, each self-rated by course participants. Additionally, participants were asked to provide input on the most and least valuable components of the course, as well as any open-ended feedback. Research 101 leadership will use these results to improve the course for future participants. DISCUSSION/SIGNIFICANCE: A learning health system (LHS) is recognized as an essential means by which research evidence is translated into practice. Important to realizing the LHS vision is the engagement of clinicians into the generation and translation of research into practice. Research 101 is an important way to bolster clinician engagement in translational research.
Magnetohydrodynamic (MHD) simulations of the solar corona have become more popular with the increased availability of computational power. Modern computational plasma codes, relying upon computational fluid dynamics (CFD) methods, allow the coronal features to be resolved using solar surface magnetograms as inputs. These computations are carried out in a full three-dimensional domain and, thus, selection of the correct mesh configuration is essential to save computational resources and enable/speed up convergence. In addition, it has been observed that for MHD simulations close to the hydrostatic equilibrium, spurious numerical artefacts might appear in the solution following the mesh structure, which makes the selection of the grid also a concern for accuracy. The purpose of this paper is to discuss and trade off two main mesh topologies when applied to global solar corona simulations using the unstructured ideal MHD solver from the COOLFluiD platform. The first topology is based on the geodesic polyhedron and the second on $UV$ mapping. Focus is placed on aspects such as mesh adaptability, resolution distribution, resulting spurious numerical fluxes and convergence performance. For this purpose, first a rotating dipole case is investigated, followed by two simulations using real magnetograms from the solar minima (1995) and solar maxima (1999). It is concluded that the most appropriate mesh topology for the simulation depends on several factors, such as the accuracy requirements, the presence of features near the polar regions and/or strong features in the flow field in general. If convergence is of concern and the simulation contains strong dynamics, then grids which are based on the geodesic polyhedron are recommended compared with more conventionally used $UV$-mapped meshes.
Indium (In) and other low melting point metals are used as interconnects in a variety of hybridized circuits and a full understanding of the metallurgy of these interconnects is important to the reliability and performance of the devices. This paper shows that room temperature focused ion beam (FIB) preparation of cross-sections, using Ga+ or Xe+ can result in artifacts that obscure the true In microbump structure. The use of modified milling strategies to minimize the increased local sample temperature are shown to produce cross-sections that are representative of the In bump microstructure in some sample configurations. Furthermore, cooling of the sample to cryogenic temperatures is shown to reliably eliminate artifacts in FIB prepared cross-sections of In bumps allowing the true bump microstructure to be observed.
Using a multimethod, multiinformant longitudinal design, we examined associations between specific forms of positive and negative emotional reactivity at age 5, children’s effortful control (EC), emotion regulation, and social skills at age 7, and adolescent functioning across psychological, academic, and physical health domains at ages 15/16 (N = 383). We examined how distinct components of childhood emotional reactivity directly and indirectly predict domain-specific forms of adolescent adjustment, thereby identifying developmental pathways between specific types of emotional reactivity and adjustment above and beyond the propensity to express other forms of emotional reactivity. Age 5 high-intensity positivity was associated with lower age 7 EC and more adolescent risk-taking; age 5 low-intensity positivity was associated with better age 7 EC and adolescent cardiovascular health, providing evidence for the heterogeneity of positive emotional reactivity. Indirect effects indicated that children’s age 7 social skills partially explain several associations between age 5 fear and anger reactivity and adolescent adjustment. Moreover, age 5 anger reactivity, low-, and high-intensity positivity were associated with adolescent adjustment via age 7 EC. The findings from this interdisciplinary, long-term longitudinal study have significant implications for prevention and intervention work aiming to understand the role of emotional reactivity in the etiology of adjustment and psychopathology.
The approach to vascular access in children with CHD is a complex decision-making process that may have long-term implications. To date, evidence-based recommendations have not been established to inform this process.
The RAND/UCLA Appropriateness Method was used to develop miniMAGIC, including sequential phases: definition of scope and key terms; information synthesis and literature review; expert multidisciplinary panel selection and engagement; case scenario development; and appropriateness ratings by expert panel via two rounds. Specific recommendations were made for children with CHD.
Recommendations were established for the appropriateness of the selection, characteristics, and insertion technique of intravenous catheters in children with CHD with both univentricular and biventricular physiology.
miniMAGIC-CHD provides evidence-based criteria for intravenous catheter selection for children with CHD.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
Introduction: Mild Traumatic Brain Injury (mTBI) is a common problem: each year in Canada, its incidence is estimated at 500-600 cases per 100 000. Between 10 and 56% of mTBI patients develop persistent post-concussion symptoms (PPCS) that can last for more than 90 days. It is therefore important for clinicians to identify patients who are at risk of developing PPCS. We hypothesized that blood biomarkers drawn upon patient arrival to the Emergency Department (ED) could help predict PPCS. The main objective of this project was to measure the association between four biomarkers and the incidence of PPCS 90 days post mTBI. Methods: Patients were recruited in seven Canadian ED. Non-hospitalized patients, aged ≥14 years old with a documented mTBI that occurred ≤24 hrs of ED consultation, with a GCS ≥13 at arrival were included. Sociodemographic and clinical data as well as blood samples were collected in the ED. A standardized telephone questionnaire was administered at 90 days post ED visit. The following biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA): S100B protein, Neuron Specific Enolase (NSE), cleaved-Tau (c-Tau) and Glial fibrillary acidic protein (GFAP). The primary outcome measure was the presence of persistent symptoms at 90 days after mTBI, as assessed using the Rivermead Post-Concussion symptoms Questionnaire (RPQ). A ROC curve was constructed for each biomarker. Results: 1276 patients were included in the study. The median age for this cohort was 39 (IQR 23-57) years old, 61% were male and 15% suffered PPCS. The median values (IQR) for patients with PPCS compared to those without were: 43 pg/mL (26-67) versus 42 pg/mL (24-70) for S100B protein, 50 pg/mL (50-223) versus 50 pg/mL (50-199) for NSE, 2929 pg/mL (1733-4744) versus 3180 pg/mL (1835-4761) for c-Tau and 1644 pg/mL (650-3215) versus 1894 pg/mL (700-3498) for GFAP. For each of these biomarkers, Areas Under the Curve (AUC) were 0.495, 0.495, 0.51 and 0.54, respectively. Conclusion: Among mTBI patients, S100B protein, NSE, c-Tau or GFAP during the first 24 hours after trauma do not seem to be able to predict PPCS. Future research testing of other biomarkers is needed in order to determine their usefulness in predicting PPCS when combined with relevant clinical data.
Introduction: Clinical assessment of patients with mTBI is challenging and overuse of head CT in the emergency department (ED) is a major problem. During the last decades, studies have attempted to reduce unnecessary head CTs following a mTBI by identifying new tools aiming to predict intracranial bleeding. S100B serum protein level might be helpful reducing those imaging since a higher level of S-100B protein has been associated with intracranial hemorrhage following a mTBI in previous literature. The main objective of this study was to assess whether the S100B serum protein level is associated with clinically important brain injury and could be used to reduce the number of head CT following a mTBI. Methods: This prospective multicenter cohort study was conducted in five Canadian ED. MTBI patients with a Glasgow Coma Scale (GCS) score of 13-15 in the ED and a blood sample drawn within 24-hours after the injury were included. S-100B protein was analyzed using enzyme-linked immunosorbent assay (ELISA). All types of intracranial bleedings were reviewed by a radiologist who was blinded to the biomarker results. The main outcome was the presence of clinically important brain injury. Results: A total of 476 patients were included. Mean age was 41 ± 18 years old and 150 (31.5%) were female. Twenty-four (5.0%) patients had a clinically significant intracranial hemorrhage while 37 (7.8%) had any type of intracranial bleeding. S100B median value (Q1-Q3) of was: 0.043 ug/L (0.008-0.080) for patients with clinically important brain injury versus 0.039 μg/L (0.023-0.059) for patients without clinically important brain injury. Sensitivity and specificity of the S100B protein level, if used alone to detect clinically important brain injury, were 16.7% (95% CI 4.7-37.4) and 88.5% (95% CI 85.2-91.3), respectively. Conclusion: S100B serum protein level was not associated with clinically significant intracranial hemorrhage in mTBI patients. This protein did not appear to be useful to reduce the number of CT prescribed in the ED and would have missed many clinically important brain injuries. Future research should focus on different ways to assess mTBI patient and ultimately reduce unnecessary head CT.
Introduction: Each year, 3/1000 Canadians sustain a mild traumatic brain injury (mTBI). Many of those mTBI are accompanied by various co-injuries such as dislocations, sprains, fractures or internal injuries. A number of those patients, with or without co-injuries will suffer from persistent post-concussive symptoms (PPCS) more than 90 days post injury. However, little is known about the impact of co-injuries on mTBI outcome. This study aims to describe the impact of co-injuries on PPCS and on patient return to normal activities. Methods: This multicenter prospective cohort study took place in seven large Canadian Emergency Departments (ED). Inclusion criteria: patients aged ≥ 14 who had a documented mTBI that occurred within 24 hours of ED visit, with a Glasgow Coma Scale score of 13-15. Patients who were admitted following their ED visit or unable to consent were excluded. Clinical and sociodemographic information was collected during the initial ED visit. A research nurse then conducted three follow-up phone interviews at 7, 30 and 90 days post-injury, in which they assessed symptom evolution using the validated Rivermead Post-concussion Symptoms Questionnaire (RPQ). Adjusted risk ratios (RR) were calculated to estimate the influence of co-injuries. Results: A total of 1674 patients were included, of which 1023 (61.1%) had at least one co-injury. At 90 days, patients with co-injuries seemed to be at higher risk of having 3 symptoms ≥2 points according to the RPQ (RR: 1.28 95% CI 1.02-1.61) and of experiencing the following symptoms: dizziness (RR: 1.50 95% CI 1.03-2.20), fatigue (RR: 1.35 95% CI 1.05-1.74), headaches (RR: 1.53 95% CI 1.10-2.13), taking longer to think (RR: 1.50 95% CI 1.07-2.11) and feeling frustrated (RR: 1.45 95% CI 1.01-2.07). We also observed that patients with co-injuries were at higher risk of non-return to their normal activities (RR: 2.31 95% CI 1.37-3.90). Conclusion: Patients with co-injuries could be at higher risk of suffering from specific symptoms at 90 days post-injury and to be unable to return to normal activities 90 days post-injury. A better understanding of the impact of co-injuries on mTBI could improve patient management. However, further research is needed to determine if the differences shown in this study are due to the impact of co-injuries on mTBI recovery or to the co-injuries themselves.
Introduction: Mild traumatic brain injury (mTBI) is a serious public health issue and as much as one third of mTBI patients could be affected by persistent post-concussion symptoms (PPCS) three months after their injury. Even though a significant proportion of all mTBIs are sports-related (SR), little is known on the recovery process of SR mTBI patients and the potential differences between SR mTBI and patients who suffered non-sports-related mTBI. The objective of this study was to describe the evolution of PPCS among patients who sustained a SR mTBI compared to those who sustained non sport-related mTBI. Methods: This Canadian multicenter prospective cohort study included patients aged ≥ 14 who had a documented mTBI that occurred within 24 hours of Emergency Department (ED) visit, with a Glasgow Coma Scale score of 13-15. Patients who were hospitalized following their ED visit or unable to consent were excluded. Clinical and sociodemographic information was collected during the initial ED visit. Three follow-up phone interviews were conducted by a research nurse at 7, 30 and 90 days post-injury to assess symptom evolution using the validated Rivermead Post-concussion Symptoms Questionnaire (RPQ). Adjusted risk ratios (RR) were calculated to demonstrate the impact of the mechanism of injury (sports vs non-sports) on the presence and severity of PPCS. Results: A total of 1676 mTBI patients were included, 358 (21.4%) of which sustained a SR mTBI. At 90 days post-injury, patients who suffered a SR mTBI seemed to be significantly less affected by fatigue (RR: 0.70 (95% CI: 0.50-0.97)) and irritability (RR: 0.60 (95% CI: 0.38-0.94)). However, no difference was observed between the two groups regarding each other symptom evaluated in the RPQ. Moreover, the proportion of patients with three symptoms or more, a score ≥21 on the RPQ and those who did return to their normal activities were also comparable. Conclusion: Although persistent post-concussion symptoms are slightly different depending on the mechanism of trauma, our results show that patients who sustained SR-mTBI could be at lower risk of experiencing some types of symptoms 90 days post-injury, in particular, fatigue and irritability.
Introduction: The elderly (65 yo and more) increase in Canada is well documented along with a disproportionate use of Emergency Departments after a minor injury. These patients requires specific care given a 16% risk of functional decline following a visit to ED. To prevent functional decline, a multidimensional assessment of the elderly is recommended in the emergency department. Objective: To determine if ED grip strength can predict functional decline at 3 or 6 months post-injury. Methods: A multicentre prospective study in 5 ED across Canada was realized between 2013 and 16. Patients 65 years old and over, autonomous in daily living activities and consulting the emergency department for minor trauma were recruited 7 days a week. Clinical-demographic data, functional status, fear of falling, number of falls in the last month, grip strength measurement were collected in the ED. Functional decline (loss of at least points to functional status) was calculated at 3 and 6 months. Descriptive statistics and linear regression model with repeated measurements were used to determine if the grip strength was predictive of functional decline at 3 or 6 months. Results: 387 patient were recruited. Mean age was 74 ± 7 years old, 52% were male. XXX experienced a fall in the last month. The initial maximum grip strength was (24 ± 10 intervention vs. 28 ± 13 control; p ≤ 0.05). grip strength is associated with pre-injury functional status (p < 0.0001) and fear of falling (p = 0.0001) but does not predict 3 or 6 month functional decline. Conclusion: Given the strong association with fear of falling and functional status at initial ED evaluation, we recommend that grip strength measurement could be included in a multidisciplinary geriatric emergency department assessment as needed.
A population sample comprised of 765 subjects (367 males and 398 females), in the age range of 15-81 years, completed the EMBU, a reliable questionnaire aimed at assessing experiences of parental rearing, and the TCI, a self-report questionnaire aimed at assessing dimensions of temperament and character. The study had three main aims: 1) to verify, on a larger scale, previous findings suggesting the occurrence of significant associations between experiences of parental rearing and aspects of temperament and character, 2) to assess possible variations in temperament and character in cohorts of subjects who have grown up in different historical epochs, and 3) to investigate to what extent transgenerational differences in parental rearing are detectable in different associations with various dimensions of personality. Several, albeit small, significant and meaningful associations between experiences of parental rearing and both temperament and character dimensions have been found, adding support to the robustness of previously reported results obtained in an independent smaller series. Also, several significant differences among subjects in different age groups have been found, both concerning temperament variables and character dimensions. Finally, the results show that associations between experiences of parental rearing and dimensions of temperament and character are most pronounced in subjects belonging to the youngest cohort and almost nil in the cohort comprising the oldest subjects.
Only a few treatment studies of personality disorders (PD) patients are on longer-term psychotherapy, general outcome measures are used, and follow-up periods are usually short. More studies of long-term therapies, using outcome measures of core psychopathology, are needed.
This study is a dismantling randomized controlled clinical trial, specifically designed to study long-term effects of transference interpretation. Forty-six patients with mainly cluster C personality disorders were randomly assigned to 1 year of dynamic psychotherapy with or without transference interpretations. The outcome measures were remission from PD, improvement in interpersonal functioning, and use of mental health resources in the 3-year period after treatment termination.
After therapy with transference interpretation PD-patients improved significantly more in core psychopathology and interpersonal functioning, the drop-out rate was reduced to zero, and use of health services was reduced to 50%, compared to therapy without this ingredient. Three years after treatment termination, 73% no longer met diagnostic criteria for any PD in the transference group, compared to 44% in the comparison group.
PD-patients with co-morbid disorders improved in both treatment arms in this study. However, transference interpretation improved outcome substantially more. Long-term psychotherapy that includes transference interpretation is an effective treatment for cluster C personality disorders and milder cluster B personality disorders.
A retrospective case-note study of the 1 year outcomes of 37 people admitted under the Mental Health Act from street assessments in South London carried out by the START team, an assertive outreach team for homeless people.
Hospital staff not infrequently question the effectiveness of treating individuals with long DUPs (duration of untreated psychosis). A street assessment is complex to arrange, involves several different agencies, is expensive and often distressing for the individual concerned. We need to be reasonably sure that we are doing more good than harm in admitting someone to hospital in this way. There is little in the published literature regarding this aspect of psychiatric practice.
We selected a consecutive group of street Mental Health Act Assessments by examining the paper records held by our AMPH (Approved Mental Health Professional) service and cross-referencing these with our electronic case records. We looked at several psycho-social outcome measures one year following discharge from hospital.
Although the number is small, the outcomes are overwhelmingly positive, in spite of notions about long DUP being predictive of poor response to treatment. Most of the subjects were in housing and remained in contact with a mental health team.
The assertive treatment of people rough sleeping with psychosis, even with long DUPs and long histories of street sleeping, can be highly effective.
Evaluate the efficacy and long-term safety of investigational aripiprazole once-monthly (ARI-OM) for maintenance treatment in schizophrenia.
Patients requiring chronic treatment for schizophrenia, not on aripiprazole monotherapy, were cross-titrated from other antipsychotic(s) to aripiprazole in an oral conversion phase (Phase 1). All patients entered an oral aripiprazole stabilization phase (Phase 2). Patients meeting stability criteria entered an ARI-OM stabilization phase (Phase 3), with coadministration of oral aripiprazole for the first 2 weeks. Patients meeting stability criteria were randomized to ARI-OM or placebo once-monthly (placebo-OM) during a 52-week, double-blind maintenance phase (Phase 4). Primary endpoint was time-to-impending relapse. Safety and tolerability were also assessed.
710 patients entered Phase 2, 576 Phase 3 and 403 Phase 4 (ARI-OM=269, placebo-OM=134). The study was terminated early because efficacy was demonstrated by a pre-planned interim analysis. Time-to-impending relapse was significantly delayed with ARI-OM vs. placebo-OM (p< 0.0001, log-rank test). Discontinuations due to treatment-emergent adverse events (AEs) were: Phase 1, 3.8% (n=24/632); Phase 2, 3.0% (n=21/709); Phase 3, 4.9% (n=28/576); Phase 4, 7.1% (n=19/269). Most AEs were mild or moderate. Insomnia was the only AE >5% incidence in any phase. Headache, somnolence, and nausea had a peak first onset within the first 4 weeks of treatment. There were no unusual shifts in all phases in laboratory values, fasting metabolic parameters, weight, or objective scales of movement disorders.
ARI-OM significantly delayed time-to-impending relapse compared with placebo-OM and was well tolerated as maintenance treatment in schizophrenia1.
Evaluate the effectiveness of investigational aripiprazole once-monthly (ARI-OM) for maintenance treatment in schizophrenia.
Detailed methodology has been published previously1. Briefly, the study consisted of 4 phases: oral conversion to aripiprazole (Phase 1); oral aripiprazole stabilization (Phase 2); ARI-OM stabilization (Phase 3), with co-administration of oral aripiprazole for the first 2 weeks; and an ARI-OM maintenance phase (Phase 4). Effectiveness assessments included Investigator's Assessment Questionnaire (IAQ) scores, a scale that evaluates effectiveness of current treatment vs. pre-trial medication, where a negative change in score signals improvement, and Personal and Social Performance (PSP) scale scores, where negative change in score signals worsening.
710 patients entered Phase 2, 576 Phase 3 and 403 Phase 4 (ARI-OM=269, placebo once-monthly [placebo- OM]=134). Mean IAQ Total scores remained stable in Phase 2 (31.3) and Phase 3 (30.6). During Phase 4, the mean change in IAQ Total score was +1.3 for ARI-OM vs. +3.8 for placebo-OM (p< 0.0001). Mean changes in PSP Total scale scores showed improvement during Phase 2 (3.0) and Phase 3 (2.6). Mean change in PSP scores during Phase 4 showed greater functional stability with ARI-OM (−1.7) compared with placebo-OM (−6.2) (p=0.0002 vs. placebo-OM).
Improvements in effectiveness, as assessed by the IAQ and PSP Total scale scores, in the Phases 2 & 3 were maintained in Phase 4 for ARI-OM compared with placebo-OM. Treatment with ARI-OM improved symptoms, overall response to treatment and functioning.
A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
Introduction: Risk-stratification of patients requiring endotracheal intubation and mechanical ventilation in the Emergency Department (ED) is necessary for informed discussions with patients regarding goals-of-care. Frailty is a clinical state characterized by reduced physiologic reserve, and resulting from accumulation of physiological stresses and comorbid disease. Frailty is increasingly being identified as an important independent predictor of outcome among critically ill patients. Our objective was to identify the impact of clinical frailty (defined by the Clinical Frailty Scale [CFS]) on in-hospital mortality and resource utilization of ED patients requiring endotracheal intubation and mechanical ventilation. Methods: We analyzed a prospectively collected registry (2011-2016) of patients requiring endotracheal intubation in the ED at two academic hospitals and six community hospitals. We included all patients ≥18 years of age, who survived to the point of ICU admission. All patient information, outcomes, and resource utilization were stored in the registry. CFS scores were obtained through chart abstraction by two blinded reviewers. The primary outcome, in-hospital mortality, was analyzed using a multivariable logistic regression model, controlling for confounding variables (including patient sex, comorbidities, and illness severity). We defined “frailty” as a CFS ≥ 5. Results: 4,622 patients were included. Mean age was 61.2 years (SD: 17.5), and 2,614 (56.6%) were male. Frailty was associated with increased risk of in-hospital mortality, as compared to those who were not frail (adjusted odds ratio [OR] 2.21 [1.98-2.51]). Frailty was also associated with higher likelihood of discharge to long-term care (adjusted OR 1.78 [1.56-2.01]) among patients initially from a home setting. Frail patients were more likely to fail extubation during their hospitalization (adjusted OR 1.81 [1.67-1.95]) and were more likely to require tracheostomy (adjusted OR 1.41 [1.34-1.49]). Conclusion: Presence of frailty among ED patients requiring endotracheal intubation and mechanical ventilation was associated with increased in-hospital mortality, discharge to long-term care, extubation failure, and tracheostomy. ED physicians should consider the impact of frailty on patient outcomes, and discuss associated prognosis with patients prior to intubation.