Management strategies in persons with inherited haemophilia requiring antithrombotic therapy: A scoping review.

BACKGROUND: Thromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE). METHODS: We searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis. RESULTS: We included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing. DISCUSSION: Our scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non-haemophilic patients. Prospective data are needed to inform optimal and evidence-based management strategies of CVD and VTE in persons with haemophilia.

Drone images afford more detections of marine wildlife than real-time observers during simultaneous large-scale surveys.

There are many advantages to transitioning from conducting marine wildlife surveys via human observers onboard light-aircraft, to capturing aerial imagery using drones. However, it is important to maintain the validity of long-term data series whilst transitioning from observer to imagery surveys. We need to understand how the detection rates of target species in images compare to those collected from observers in piloted aircraft, and the factors influencing detection rates from each platform. We conducted trial ScanEagle drone surveys of dugongs in Shark Bay, Western Australia, covering the full extent of the drone's range (∼100 km), concurrently with observer surveys, with the drone flying above or just behind the piloted aircraft. We aimed to test the assumption that drone imagery could provide comparable detection rates of dugongs to human observers when influenced by same environmental conditions. Overall, the dugong sighting rate (i.e., count of individual dugongs) was 1.3 (95% CI [0.98-1.84]) times higher from the drone images than from the observers. The group sighting rate was similar for the two platforms, however the group sizes detected within the drone images were significantly larger than those recorded by the observers, which explained the overall difference in sighting rates. Cloud cover appeared to be the only covariate affecting the two platforms differently; the incidence of cloud cover resulted in smaller group sizes being detected by both platforms, but the observer group sizes dropped much more dramatically (by 71% (95% CI [31-88]) compared to no cloud) than the group sizes detected in the drone images (14% (95% CI [-28-57])). Water visibility and the Beaufort sea state also affected dugong counts and group sizes, but in the same way for both platforms. This is the first direct simultaneous comparison between sightings from observers in piloted aircraft and a drone and demonstrates the potential for drone surveys over a large spatial-scale.

Teaching Observation as a Faculty Development Tool in Medical Education: A Scoping Review.

INTRODUCTION: Health professions education often includes teaching observation to inform faculty development (FD) and indirectly improve student performance. Although these FD approaches are well received by faculty, they remain underused and/or underreported, with limited opportunities to receive feedback in workplace contexts. The goal of our study was to map the depth and breadth of education literature on the use of observation of teaching as a tool of professional development in medical education. METHODS: Following the methodology by Arksey and O'Malley, we conducted a scoping review and searched four databases for articles published in English (final searches in April 2022). RESULTS: Of 2080 articles identified, 45 met the inclusion criteria. All observation activities were associated with one of the following FD approaches: peer observation of teaching (23 articles, 51%), peer coaching (12, 27%), peer review (9, 20%), and the critical friends approach (1, 2%). Thirty-three articles (73%) concerned formative versions of the observation model that took place in clinical settings (21, 47%), and they tended to be a voluntary (27, 60%), one-off (18, 40%), in-person intervention (29, 65%), characterized by limited institutional support (13, 29%). Both barriers and challenges of teaching observation were identified. DISCUSSION: This review identified several challenges and shortcomings associated with teaching observation, such as inadequate methodological quality of research articles, inconsistent terminology, and limited understanding of the factors that promote long-term sustainability within FD programs. Practical strategies to consider when designing an FD program that incorporates teaching observation are outlined.

Ethics information retrieval in HTA: state of current practice.

OBJECTIVES: Though there have been longstanding discussions on the value of ethics in health technology assessment (HTA), less awareness exists on ethics information retrieval methods. This study aimed to scope available evidence and determine current practices for ethics information retrieval in HTA. METHODS: Literature searches were conducted in Ovid MEDLINE, LISTA, Scopus, and Google Scholar. Once a list of relevant articles was determined, citation tracking was conducted via Scopus. HTA agency websites were searched for published guidance on ethics searching, and for reports which included ethical analyses. Methods sections of each report were analyzed to determine the databases, subject headings, and keywords used in search strategies. The team also reached out to information specialists for insight into current search practices. RESULTS: Findings from this study indicate that there is still little published guidance from HTA agencies, few HTAs that contain substantial ethical analysis, and even less information on the methodology for ethics information retrieval. The researchers identified twenty-five relevant HTAs. Ten of these reports did not utilize subject-specific databases outside health sciences. Eight reports published ethics searches, with significant overlap in subject headings and text words. CONCLUSIONS: This scoping study of current practice in HTA ethics information retrieval highlights findings of previous studies-while ethics analysis plays a crucial role in HTA, methods for literature searching remain relatively unclear. These findings provide insight into the current state of ethics searching, and will inform continued work on filter development, database selection, and grey literature searching.

Clinical reporting for personalized cancer genomics requires extensive access to subscription-only literature.

Objective: Medical care for cancer is increasingly directed by genomic laboratory testing for alterations in the tumor genome that are significant for diagnosis, prognosis and therapy. Uniquely in medicine, providers must search the biomedical literature for each patient to determine the clinical significance of these alterations. Access to published scientific literature is frequently subject to high fees, with access limited to institutional subscriptions. We sought to investigate the degree to which the scientific literature is accessible to clinical cancer genomics providers, and the potential role of university and hospital system libraries in information access for cancer care. Methods: We identified 265 journals that were accessed during the interpretation and reporting of clinical test results from 1,842 cancer patients at the University Health Network (Toronto, Canada). We determined the degree of open access for this set of clinically important literature, and for any journals not available through open access we surveyed subscription access at seven academic hospital systems and at their affiliated universities. Results: This study found that nearly half (116/265) of journals have open access mandates that make articles freely available within one year of release. For the remaining subscription access journals, universities provided a uniformly high level of access, but access available through hospital system collections varied widely. Conclusion: This study highlights the importance of different modes of access to the use of the scientific literature in clinical practice and points to challenges that must be overcome as genomic medicine grows in scale and complexity.

Interventions to treat post-traumatic stress disorder (PTSD) in vulnerably housed populations and trauma-informed care: a scoping review.

OBJECTIVES: The goals of this study are to identify and analyse interventions that aim to treat post-traumatic stress disorder (PTSD) and complex PTSD in people who are vulnerably housed and to describe how these treatments have been delivered using trauma-informed care. DESIGN: Scoping review. SEARCH STRATEGY: We searched electronic databases including MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, Web of Science and PTSDpubs for published literature up to November 2021 for any studies that examined the treatment of PTSD in adults who were vulnerably housed. Websites of relevant organisations and other grey literature sources were searched to supplement the electronic database search. The characteristics and effect of the interventions were analysed. We also explored how the interventions were delivered and the elements of trauma-informed care that were described. RESULTS: 28 studies were included. We identified four types of interventions: (1) trauma focused psychotherapies; (2) non-trauma psychotherapies; (3) housing interventions and (4) pharmacotherapies. The trauma-informed interventions were small case series and the non-trauma focused therapies included four randomised controlled trials, were generally ineffective. Of the 10 studies which described trauma-informed care the most commonly named elements were physical and emotional safety, the experience of feeling heard and understood, and flexibility of choice. The literature also commented on the difficulty of providing care to this population including lack of private space to deliver therapy; the co-occurrence of substance use; and barriers to follow-up including limited length of stay in different shelters and high staff turnover. CONCLUSIONS: This scoping review identified a lack of high-quality trials to address PTSD in people who are vulnerably housed. There is a need to conduct well designed trials that take into account the unique setting of this population and which describe those elements of trauma-informed care that are most important and necessary.

Scoping review of evidence for managing postnatal hypoglycaemia.

OBJECTIVES: To identify what is known empirically about the screening, treatment and harm of exposure to neonatal hypoglycaemia. DESIGN: Scoping review that applied a preregistered protocol based on established frameworks. DATA SOURCES: Medline and Embase, up to 12 May 2020. STUDY SELECTION: Comparative and case-series studies, as well as guidelines, published in English or French, on the topic of immediate inpatient postnatal glucose screening in newborns. DATA GATHERING: Article selection and characterisation were performed in duplicate using predefined data extraction forms specific to primary studies and guidelines. RESULTS: 12 guidelines and 74 primary studies were included. A neurodevelopmental outcome was primary in 32 studies: 30 observational studies followed up posthypoglycaemic, and the 2 intervention studies included 1 randomised controlled trial (RCT) about treatment thresholds. Three other RCTs assessed dextrose gel (two) and oral sucrose (one). 12 of 30 studies that evaluated non-neurodevelopmental primary outcomes were intervention studies. Only one cohort study compared outcomes in screened vs unscreened newborns. The guidelines did not arrive at a consensus definition of postnatal hypoglycaemic, and addressed potential harms of screening more often than primary studies. CONCLUSIONS: The primary literature that informs hypoglycaemia screening is a series of studies that relate neurodevelopmental outcomes to postnatal hypoglycaemia. Further research is needed to better define an optimal threshold for hypoglycaemia that warrants intervention, based on long-term neurodevelopmental outcomes and a better delineation of potential screening harms.

Health workforce strategies in response to major health events: a rapid scoping review with lessons learned for the response to the COVID-19 pandemic.

BACKGROUND: The early weeks of the COVID-19 pandemic brought multiple concurrent threats-high patient volume and acuity and, simultaneously, increased risk to health workers. Healthcare managers and decision-makers needed to identify strategies to mitigate these adverse conditions. This paper reports on the health workforce strategies implemented in relation to past large-scale emergencies (including natural disasters, extreme weather events, and infectious disease outbreaks). METHODS: We conducted a rapid scoping review of health workforce responses to natural disasters, extreme weather events, and infectious disease outbreaks reported in the literature between January 2000 and April 2020. The 3582 individual results were screened to include articles which described surge responses to past emergencies for which an evaluative component was included in the report. A total of 37 articles were included in our analysis. RESULTS: The reviewed literature describes challenges related to increased demand for health services and a simultaneous decrease in the availability of the workforce. Many articles also described impacts on infrastructure that hindered emergency response. These challenges aligned well with those faced during the early days of the COVID-19 pandemic. In the published literature, the workforce strategies that were described aimed either to increase the numbers of health workers in a given area, to increase the flexibility of the health workforce to meet needs in new ways, or to support and sustain health workers in practice. Workforce responses addressed all types and cadres of health workers and were executed in a wide range of settings. We additionally report on the barriers and facilitators of workforce strategies reported in the literature reviewed. The strategies that were reported in the literature aligned closely with our COVID-specific conceptual framework of workforce capacity levers, suggesting that our framework may have heuristic value across many types of health disasters. CONCLUSIONS: This research highlights a key deficiency with the existing literature on workforce responses to emergencies: most papers lack substantive evaluation of the strategies implemented. Future research on health workforce capacity interventions should include robust evaluation of impact and effectiveness.

Implementing Competency-Based Medical Education in Family Medicine: A Narrative Review of Current Trends in Assessment.

BACKGROUND AND OBJECTIVES: The implementation of effective competency-based medical education (CBME) relies on building a coherent and integrated system of assessment across the continuum of training to practice. As such, the developmental progression of competencies must be assessed at all stages of the learning process, including continuing professional development (CPD). Yet, much of the recent discussion revolves mostly around residency programs. The purpose of this review is to synthesize the findings of studies spanning the last 2 decades that examined competency-based assessment methods used in family medicine residency and CPD, and to identify gaps in their current practices. METHODS: We adopted a modified form of narrative review and searched five online databases and the gray literature for articles published between 2000 and 2020. Data analysis involved mixed methods including quantitative frequency analysis and qualitative thematic analysis. RESULTS: Thirty-seven studies met inclusion criteria. Fourteen were formal evaluation studies that focused on the outcome and impact evaluation of assessment methods. Articles that focused on formative assessment were prevalent. The most common levels of educational outcomes were performance and competence. There were few studies on CBME assessment among practicing family physicians. Thematic analysis of the literature identified several challenges the family medicine educational community faces with CBME assessment. CONCLUSIONS: We recommend that those involved in health education systematically evaluate and publish their CBME activities, including assessment-related content and evaluations. The highlighted themes may offer insights into ways in which current CBME assessment practices might be improved to align with efforts to improve health care.

Unmanned aerial vehicles for surveying marine fauna: assessing detection probability.

Aerial surveys are conducted for various fauna to assess abundance, distribution, and habitat use over large spatial scales. They are traditionally conducted using light aircraft with observers recording sightings in real time. Unmanned Aerial Vehicles (UAVs) offer an alternative with many potential advantages, including eliminating human risk. To be effective, this emerging platform needs to provide detection rates of animals comparable to traditional methods. UAVs can also acquire new types of information, and this new data requires a reevaluation of traditional analyses used in aerial surveys; including estimating the probability of detecting animals. We conducted 17 replicate UAV surveys of humpback whales (Megaptera novaeangliae) while simultaneously obtaining a 'census' of the population from land-based observations, to assess UAV detection probability. The ScanEagle UAV, carrying a digital SLR camera, continuously captured images (with 75% overlap) along transects covering the visual range of land-based observers. We also used ScanEagle to conduct focal follows of whale pods (n = 12, mean duration = 40 min), to assess a new method of estimating availability. A comparison of the whale detections from the UAV to the land-based census provided an estimated UAV detection probability of 0.33 (CV = 0.25; incorporating both availability and perception biases), which was not affected by environmental covariates (Beaufort sea state, glare, and cloud cover). According to our focal follows, the mean availability was 0.63 (CV = 0.37), with pods including mother/calf pairs having a higher availability (0.86, CV = 0.20) than those without (0.59, CV = 0.38). The follows also revealed (and provided a potential correction for) a downward bias in group size estimates from the UAV surveys, which resulted from asynchronous diving within whale pods, and a relatively short observation window of 9 s. We have shown that UAVs are an effective alternative to traditional methods, providing a detection probability that is within the range of previous studies for our target species. We also describe a method of assessing availability bias that represents spatial and temporal characteristics of a survey, from the same perspective as the survey platform, is benign, and provides additional data on animal behavior.

Training community matrons in basic cognitive behavioural therapy-based techniques for patients with COPD.

People with chronic obstructive pulmonary disease (COPD) experience anxiety and depression with a higher prevalence than the general population. Despite this, they are under-represented in mental health services on a national scale, but do regularly have contact with health-care professionals such as community matrons. We aimed to explore the process of CBT-based skills supervision and the practical implications for community matrons using CBT-based techniques with COPD clients as part of their standard practice. Twenty community matrons took part in a 2-day CBT-based skills training programme. Measurements of their knowledge and understanding of CBT-based skills were taken before and following the training. Additionally, they completed written feedback relating to the training. They were then supervised by CBT therapists for 6 months. Written feedback was obtained following this and some supervisors participated in a 1-hour focus group to discuss the process. Community matrons' knowledge and understanding of CBT-based techniques significantly improved following training, although findings did indicate that merely training did not always seamlessly translate into effective practice. Supervisor feedback suggested that it would be beneficial for community matrons to share positive practice of their use of basic CBT-based techniques among peers to maximise the perceived value of this approach.

Unmanned aerial vehicles (UAVs) for surveying marine fauna: a dugong case study.

Aerial surveys of marine mammals are routinely conducted to assess and monitor species' habitat use and population status. In Australia, dugongs (Dugong dugon) are regularly surveyed and long-term datasets have formed the basis for defining habitat of high conservation value and risk assessments of human impacts. Unmanned aerial vehicles (UAVs) may facilitate more accurate, human-risk free, and cheaper aerial surveys. We undertook the first Australian UAV survey trial in Shark Bay, western Australia. We conducted seven flights of the ScanEagle UAV, mounted with a digital SLR camera payload. During each flight, ten transects covering a 1.3 km(2) area frequently used by dugongs, were flown at 500, 750 and 1000 ft. Image (photograph) capture was controlled via the Ground Control Station and the capture rate was scheduled to achieve a prescribed 10% overlap between images along transect lines. Images were manually reviewed post hoc for animals and scored according to sun glitter, Beaufort Sea state and turbidity. We captured 6243 images, 627 containing dugongs. We also identified whales, dolphins, turtles and a range of other fauna. Of all possible dugong sightings, 95% (CI = 90%, 98%) were subjectively classed as 'certain' (unmistakably dugongs). Neither our dugong sighting rate, nor our ability to identify dugongs with certainty, were affected by UAV altitude. Turbidity was the only environmental variable significantly affecting the dugong sighting rate. Our results suggest that UAV systems may not be limited by sea state conditions in the same manner as sightings from manned surveys. The overlap between images proved valuable for detecting animals that were masked by sun glitter in the corners of images, and identifying animals initially captured at awkward body angles. This initial trial of a basic camera system has successfully demonstrated that the ScanEagle UAV has great potential as a tool for marine mammal aerial surveys.

Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication.

Robust hepatitis B virus (HBV) replication is stimulated by the regulatory HBx protein. HBx binds the cellular protein DDB1; however, the importance of this interaction for HBV replication remains unknown. We tested whether HBx binding to DDB1 was required for HBV replication using a plasmid based replication assay in HepG2 cells. Three DDB1 binding-deficient HBx point mutants (HBx(69), HBx(90/91), HBx(R96E)) failed to restore wildtype levels of replication from an HBx-deficient plasmid, which established the importance of the HBx-DDB1 interaction for maximal HBV replication. Analysis of overlapping HBx truncation mutants revealed that both the HBx-DDB1 binding domain and the carboxyl region are required for maximal HBV replication both in vitro and in vivo, suggesting the HBx-DDB1 interaction recruits regulatory functions critical for replication. Finally we demonstrate that HBx localizes to the Cul4A-DDB1 complex, and discuss the possible implications for models of HBV replication.

Hepatitis B virus regulatory HBx protein binds to adaptor protein IPS-1 and inhibits the activation of beta interferon.

Hepatitis B virus (HBV) encodes the regulatory HBx protein, which is required for virus replication, although its specific role(s) in the replication cycle remains under investigation. An immunoprecipitation/mass spectrometry approach was used to identify four novel HBx binding proteins from the cytoplasmic fraction of HBx transgenic mouse livers. One of these HBx binding partners is beta interferon promoter stimulator 1 (IPS-1), an adaptor protein that plays a critical role in mediating retinoic acid-inducible gene I (RIG-I) signaling, which leads to the activation of beta interferon (IFN-ß). The HBx-IPS-1 protein interaction was confirmed in plasmid-transfected HepG2 cells by reciprocal coimmunoprecipitation and Western blotting. We hypothesized that HBx might alter IPS-1 function since proteins of hepatitis C virus and hepatitis A virus similarly bind IPS-1 and target it for inactivation. The effect of HBx on IPS-1-mediated IFN-ß signaling was tested in transfected 293T and HepG2 cells, and we show that HBx inhibits double-stranded DNA (dsDNA)-mediated IFN-ß activation in a dose-dependent manner when expressed either alone or within the context of HBV replication. However, HBx does not inhibit poly(I:C)-activated IFN-ß signaling. These results demonstrate that HBx interferes with the RIG-I pathway of innate immunity. Hepatitis B virus now joins hepatitis C virus and hepatitis A virus in targeting the same innate immune response pathway, presumably as a shared strategy to benefit replication of these viruses in the liver.

Hepatitis B virus HBx protein localized to the nucleus restores HBx-deficient virus replication in HepG2 cells and in vivo in hydrodynamically-injected mice.

Identifying the requirements for the regulatory HBx protein in hepatitis B virus (HBV) replication is an important goal. A plasmid-based HBV replication assay was used to evaluate whether HBx subcellular localization influences its ability to promote virus replication, as measured by real time PCR quantitation of viral capsid-associated DNA. HBx targeted to the nucleus by a nuclear localization signal (NLS-HBx) was able to restore HBx-deficient HBV replication, while HBx containing a nuclear export signal (NES-HBx) was not. Both NLS-HBx and NES-HBx were expressed at similar levels (by immunoprecipitation and Western blotting), and proper localization of the signal sequence-tagged proteins was confirmed by deconvolution microscopy using HBx, NLS-HBx, and NES-HBx proteins fused to GFP. Importantly, these findings were confirmed in vivo by hydrodynamic injection into mice. Our results demonstrate that in these HBV replication assays, at least one function of HBx requires its localization to the nucleus.

Premature cell cycle entry induced by hepatitis B virus regulatory HBx protein during compensatory liver regeneration.

The cycles of cell death and compensatory regeneration that occur during chronic hepatitis B virus (HBV) infection are central to viral pathogenesis and are a risk factor for the development of liver cancer. The HBV genome encodes one regulatory protein, HBx, which is required for virus replication, although its precise role in replication and pathogenesis is unclear. Because HBx can induce the G(0)-G(1) transition in cultured cells, the purpose of this study was to examine the effect of HBx during liver regeneration. Transgenic mice expressing HBx (ATX) and their wild-type (WT) littermates were used in the partial hepatectomy (PH) model for compensatory regeneration. Liver tissues collected from ATX and WT mice at varying sacrifice time points after PH were examined for markers of cell cycle progression. When compared with WT liver tissues, ATX livers had evidence of premature cell cycle entry as assessed by several variables (BrdUrd incorporation, proliferating cell nuclear antigen and mitotic indices, and reduced steady-state p21 protein levels). However, HBx did not affect apoptosis, glycogen storage, or PH-induced steatosis. Together, these results show that HBx expression can induce cell cycle progression within the regenerating liver. Our data are consistent with a model in which HBx expression contributes to liver disease and cancer formation by affecting early steps in liver regeneration.

Enhancement of hepatitis B virus replication by the regulatory X protein in vitro and in vivo.

The 3.2-kb hepatitis B virus (HBV) genome encodes a single regulatory protein termed HBx. While multiple functions have been identified for HBx in cell culture, its role in virus replication remains undefined. In the present study, we combined an HBV plasmid-based replication assay with the hydrodynamic tail vein injection model to investigate the function(s) of HBx in vivo. Using a greater-than-unit-length HBV plasmid DNA construct (payw1.2) and a similar construct with a stop codon at position 7 of the HBx open reading frame (payw1.2*7), we showed that HBV replication in transfected HepG2 cells was reduced 65% in the absence of HBx. These plasmids were next introduced into the livers of outbred ICR mice via hydrodynamic tail vein injection. At the peak of virus replication, at 4 days postinjection, intrahepatic markers of HBV replication were reduced 72% to 83% in mice injected with HBx-deficient payw1.2*7 compared to those measured in mice receiving wild-type payw1.2. A second plasmid encoding HBx was able to restore virus replication from payw1.2*7 to wild-type levels. Finally, viremia was monitored over the course of acute virus replication, and at 4 days postinjection, it was reduced by nearly 2 logs in the absence of HBx. These studies establish that the role for HBx in virus replication previously shown in transfected HepG2 cells is also apparent in the mouse liver within the context of acute hepatitis. Importantly, the function of HBx can now be studied in an in vivo setting that more closely approximates the cellular environment for HBV replication.