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The weaning process negatively affects the haematological parameters and innate immune response of dairy calves, even when managed under an intensive milk program. Here we describe haematological and innate immunity changes in 47 Holstein calves aged 69-85 days subjected to a gradual weaning process. Blood samples were collected at six (D-6), four (D-4), and two (D-2) days before and on the weaning day (D0) for the phagocytosis assay and to measure the production of reactive oxygen species (ROS) after stimulation with Staphylococcus aureus, Escherichia coli, and Mannhemia haemolytica, in addition to total protein (TP), haptoglobin (Hp), and iron concentration. The highest mean neutrophil number was recorded at D-2. The absolute number of monocytes was initially high on D-6 and D-4 but declined as the calf progressed to weaning. The number of basophils decreased rapidly, reaching a low value on D-4, and remained low for the remainder of the study period. The TP, Hp, and Fe concentrations decreased. Overall, polymorphonuclear leukocyte phagocytosis activity induced by S. aureus and E. coli decreased from D-6 to D-2, indicating persistence of the low phagocytosis rate for S. aureus. ROS production was constant for all bacterial stimulations from D-6 to D-2, followed by an increase on D0. Phagocytosis and ROS production indicate that the weaning process dampens the innate immune response relative to exposure to these common pathogenic bacteria in dairy calves. Phagocytosis and the corresponding indicators of intracellular killing activities (ROS production and myeloperoxidase index) represent the most accepted core mechanisms for the early elimination of pathogenic microorganisms in calves. Despite a slow gradual weaning management system, the study concluded that intensive milk production programs contribute to innate immune response suppression during weaning.
Objectives/Goals: A limited number of Hispanic researchers compete successfully for NIH career development and research grants. We adapted an established K Club model from the University of Pittsburgh with high success rates to Hispanics in Puerto Rico (PR). The K to R Club’s goal is to increase the successful submission of K- and R-type NIH grants in the HCTRECD Program. Methods/Study Population: K to R Club is an inviting environment that exposes scholars to established funded investigators in PR from all career stages. It creates a forum to discuss different grant mechanisms and explains the selection, submission, and review process. The Club promotes the right mentor selection and mentoring team. It facilitates networking with principal investigators local/external to share their success stories, career development experiences, and grant submission tips. It offers mock review sessions of sections of the grant proposal to provide feedback from invited established investigators during the grant writing process. The Club meets 1–2 times per month in-person or virtual for 1 hour and anonymous evaluations were submitted after each session. Results/Anticipated Results: K to R Club 1st year had 11 sessions with 15 invited speakers. Sessions included: 1 Kickoff, 2 funding opportunities, 2 coaching, 7 successful stories of Diversity Supplement, and F99/K00, K22, K23, K99/R00, R01, and R21 awardees. The highest attendance was for the Kickoff (48). Evaluations response rates ranged from 15 to 62 with the highest participation from women (78% vs. 22% men). Most respondents were PhD (45%) and MD (29%). K to R Club sessions were rated as excellent (84%), 74% agreed that the sessions changed their knowledge very much, and 78% reported it changed their ability to apply for funding very much. Interest in submitting NIH supplements in 12 months was higher (68%) vs. 6 months (48%). Interest in requesting mock reviews for K or R grants in 6 months (91%) vs. 12 months (17%). Discussion/Significance of Impact: The 1st year of the K to R Club had an active attendance and increased the interest in submission of NIH grants. We are working on strategies to increase evaluations’ response rates to improve and address future session needs due to the low response rates recorded. Currently, the semester is full of mock review sessions for grant applications (4 Ks and 1 R01).
The economic burden of migraine is substantial; determining the cost that migraine imposes on the Canadian healthcare system is needed.
Methods:
Administrative data were used to identify adults living with migraine, including chronic migraine (CM) and episodic migraine (EM), and matched controls in Alberta, Canada. One- and two-part generalized linear models with gamma distribution were used to estimate direct healthcare costs (hospitalization, emergency department, ambulatory care, physician visit, prescription medication; reported in 2022 Canadian dollars) of migraine during a 1-year observation period (2017/2018).
Results:
The fully adjusted total mean healthcare cost of migraine (n = 100,502) was 1.5 times (cost ratio: 1.53 [95% CI: 1.50, 1.55]) higher versus matched controls (n = 301,506), with a predicted annual incremental cost of $2,806 (95% CI: $2,664, $2,948) per person. The predicted annual incremental cost of CM and EM was $5,059 (95% CI: $4,836, $5,283) and $669 (95% CI: $512, $827) per person, respectively, compared with matched controls. All healthcare cost categories were greater for migraine (overall, CM and EM) compared with matched controls, with prescription medication the primary cost driver (incremental cost – overall: $1,381 [95% CI: $1,234, $1,529]; CM: $2,057 [95% CI: %1,891, $2,223]; EM: $414 [95% CI: $245, $583] per person per year).
Conclusion:
Persons living with migraine had greater direct healthcare costs than those without. With an estimated migraine prevalence of 8.3%–10.2%, this condition may account for an additional $1.05–1.29 billion in healthcare costs per year in Alberta. Strategies to prevent and effectively manage migraine and associated healthcare costs are needed.
This chapter defines and describes trauma, adversity and trauma-informed practice. We explore how trauma impacts children and young people and how this may influence their engagement with education. A summary about how a student may present when experiencing trauma is provided. As teachers often hear about and address trauma and adversity faced by children, the concepts of compassion fatigue and vicarious trauma are also briefly explored. The chapter ends with examples of ways in which teachers can create trauma-informed classrooms and support and promote trauma-informed policies and practices in schools.
The incidence of facial palsy has been rising worldwide, with recent evidence emerging of links to COVID-19 infection. To date, guidance on cost-effective treatments is limited to medication (prednisolone). In terms of physical therapy, neuromuscular retraining (NMR) to restore balanced facial function has been most widely evaluated, but not in terms of cost effectiveness. The added value of telerehabilitation is unknown.
Methods
A multistage technology assessment was conducted, which included the following:
• a national survey of current therapy pathways in the UK and patients’ and clinicians’ views on the benefits and challenges of telerehabilitation;
• a systematic review of clinical effectiveness trials evaluating facial NMR therapy;
• calculation of long-term morbidity costs (national economic burden) based on incidence, patient recovery profiles, health-related quality of life, and national facial palsy treatment costs (valuation of clinical improvements in monetary terms was provided by a national Delphi panel); and
• evaluation of the cost effectiveness of telerehabilitation (remote monitoring wearables) added to current face-to-face NMR delivery.
Results
Nationally, approximately five percent of patients with facial palsy (17% of unresolved cases) are referred for facial NMR. The long-term economic burden associated with unresolved cases is estimated to range from GBP351 (EUR417) to GBP584 (EUR692) million, indicating substantial savings if long-term recovery can be improved. Medical treatment costs are GBP86.34 (EUR102) million per annual cohort, and physical and psychological therapy costs are GBP643,292 (EUR762,561). Economic modeling showed that telerehabilitation was cost effective, producing a health gain and a cost-saving of GBP468 (EUR555) per patient. If scaled to the national level for all patients who do not recover fully, an annual saving of GBP3.075 (EUR3.65) million is possible.
Conclusions
Economic modeling indicates that NMR could improve patient outcomes and reduce costs. The national survey demonstrated that access to NMR therapy services is limited, so introduction of telerehabilitation could improve access for currently underserved populations. Future clinical trials need to incorporate economic evaluations to help inform decision-making.
Student Engagement: Promoting Positive Classroom Behaviour encourages pre-service teachers in Australian primary and secondary schools to make choices about how best to design and manage their classrooms and schools to maximise productive behaviour and learning. The text explores numerous dimensions of student engagement from within and outside school settings, including verbal and non-verbal communication; disengaged behaviours and corrective strategies; trauma-informed practice; working with students with emotional and behavioural disorders; and bullying prevention and intervention strategies. Linking to the Australian Professional Standards for Teachers (APSTs), each chapter includes 'Embedding the theory' and 'Story from the field' boxes that discuss the theoretical research behind different approaches to engagement and explore their practical applications. 'Making professional decisions' boxes at the end of each chapter also provide further guidance on how to approach different situations and build a repertoire of resources for practice.
In responding to a Chemical, Biological, Radiological, and Nuclear explosive (CBRNe) disaster, clinical leaders have important decision-making responsibilities which include implementing hospital disaster protocols or incident command systems, managing staffing, and allocating resources. Despite emergency care clinical leaders’ integral role, there is minimal literature regarding the strategies they may use during CBRNe disasters. The aim of this study was to explore emergency care clinical leaders’ strategies related to managing patients following a CBRNe disaster.
Methods
Focus groups across 5 tertiary hospitals and 1 rural hospital in Queensland, Australia. Thirty-six hospital clinical leaders from the 6 study sites crucial to hospital disaster response participated in 6 focus groups undertaken between February and May 2021 that explored strategies and decision making to optimize patient care following a CBRNe disaster.
Results
Analysis revealed the use of rehearsals, adopting new models of care, enacting current surge management processes, and applying organization lessons were facilitating strategies. Barriers to management were identified, including resource constraints and sites operating over capacity.
Conclusions
Enhanced education and training of clinical leaders, flexible models of care, and existing established processes and tested frameworks could strengthen a hospital’s response when managing patients following a CBRNe disaster.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Understanding post-stroke spasticity (PSS) treatment in everyday clinical practice may guide improvements in patient care.
Methods:
This was a retrospective cohort study that used population-level administrative data. Adults (aged ≥18 years) who initiated PSS treatment (defined by the first PSS clinic visit, focal botulinum toxin injection, or anti-spasticity medication dispensation [baclofen, dantrolene and tizanidine] with none of these treatments occurring during the 2 years before the stroke) were identified between 2012 and 2019 in Alberta, Canada. Spasticity treatment use, time to treatment start and type of prescribing/treating physician were measured. Descriptive statistics were performed.
Results:
Within the cohort (n = 1,079), the most common PSS treatment was oral baclofen (initial treatment: 60.9%; received on/after the initial treatment date up to March 31, 2020: 69.0%), largely prescribed by primary care physicians (77.6%) and started a median of 348 (IQR 741) days after the stroke. Focal botulinum toxin (23.3%; 37.7%) was largely prescribed by physiatrists (72.2%) and started 311 (IQR 446) days after the stroke; spasticity clinic visits (18.6%; 23.8%) were also common.
Conclusions:
We found evidence of gaps in provision of spasticity management in persons with PSS including overuse of systemic oral baclofen (that has common adverse side effects and lacks evidence of effectiveness in PSS) and potential underuse of focal botulinum toxin injections. Further investigation and strategies should be pursued to improve alignment of PSS treatment with guideline recommendations that in turn will support better outcomes for those with PSS.
Recruitment of participants into research studies remains a major concern for investigators. Using clinical teams to identify potentially eligible patients can present a significant barrier. To overcome this, we implemented a process for using our patient portal, called MyChart, as a new institutional recruitment option utilizing our electronic health record’s existing functionality.
Methods:
To streamline the institutional approval process, we established a working group comprised of representatives from human subject protection, information technology, and privacy and vetted our process with many stakeholder groups. Our specific process for study approval is described and started with a consultation with our recruitment and retention function funded through our Clinical and Translational Science Award.
Results:
The time from consultation to the first message(s) sent ranged from 84 to 442 days and declined slightly over time. The overall patient response rate to MyChart messages about available research studies was 23% with one third of those saying they were interested in learning more. The response rate for Black and Hispanic patients was about 50% that of White patients.
Conclusions:
Many different types of studies from any medical specialty successfully identified interested patients using this option. Study teams needed support in defining appropriate inclusion/exclusion criteria to identify the relevant population in the electronic health records and they needed assistance writing study descriptions in plain language. Using MyChart for recruitment addressed a critical barrier and opened up the opportunity to provide a full recruitment consultation to identify additional recruitment channels the study teams would not have considered otherwise.
We aimed to (1) report updated estimates of direct healthcare costs for people living with MS (pwMS), (2) contrast costs to a control population and (3) explore differences between disability levels among pwMS.
Methods:
Administrative data were used to identify adult pwMS (MS cohort) and without (control cohort) in Alberta, Canada; disability level (based on the Expanded Disability Status Scale) among pwMS was estimated. One- and two-part generalized linear models with gamma distribution were used to estimate the incremental direct healthcare cost (2021 $CDN) of MS during a 1-year observation period.
Results:
Adjusting for confounders, the total healthcare cost ratio was higher in the MS cohort (n = 13,089) versus control (n = 150,080) (5.24 [95% CI: 5.08, 5.41]) with a predicted incremental cost of $15,016 (95% CI: $14,497, $15,535) per person-year. Among the MS cohort, total predicted direct healthcare costs were higher with greater disability, $14,430 (95% CI: $13,980, $14,880) to $58,697 ($51,514, $65,879) per person-year in mild and severe disability, respectively. The primary health resource cost component shifted from disease-modifying therapies in mild disability to supportive care in moderate and severe disability.
Conclusion:
Adult pwMS had greater direct healthcare costs than those without. Extrapolating to the population level (where 14,485 adult pwMS were identified in the study), it is estimated that $218 million per year in healthcare costs may be attributable to MS in Alberta. The significantly larger economic impact associated with greater disability underscores the importance of preventing or delaying disease progression and functional impairment in MS.
Rift propagation, rather than basal melt, drives the destabilization and disintegration of the Thwaites Eastern Ice Shelf. Since 2016, rifts have episodically advanced throughout the central ice-shelf area, with rapid propagation events occurring during austral spring. The ice shelf's speed has increased by ~70% during this period, transitioning from a rate of 1.65 m d−1 in 2019 to 2.85 m d−1 by early 2023 in the central area. The increase in longitudinal strain rates near the grounding zone has led to full-thickness rifts and melange-filled gaps since 2020. A recent sea-ice break out has accelerated retreat at the western calving front, effectively separating the ice shelf from what remained of its northwestern pinning point. Meanwhile, a distributed set of phase-sensitive radar measurements indicates that the basal melting rate is generally small, likely due to a widespread robust ocean stratification beneath the ice–ocean interface that suppresses basal melt despite the presence of substantial oceanic heat at depth. These observations in combination with damage modeling show that, while ocean forcing is responsible for triggering the current West Antarctic ice retreat, the Thwaites Eastern Ice Shelf is experiencing dynamic feedbacks over decadal timescales that are driving ice-shelf disintegration, now independent of basal melt.
We analyzed invasive group A streptococcal puerperal sepsis cases in a large health zone in Alberta, Canada between 2013 and 2022. Of the 21 cases, 85.7% were adjudicated as hospital/delivery-acquired, with 2 clusters having identical isolates found through whole genome sequencing. We implemented policy interventions across Alberta aimed at preventing future infections.