Integration of population-level data sources into an individual-level clinical prediction model for dengue virus test positivity.

The differentiation of dengue virus (DENV) infection, a major cause of acute febrile illness in tropical regions, from other etiologies, may help prioritize laboratory testing and limit the inappropriate use of antibiotics. While traditional clinical prediction models focus on individual patient-level parameters, we hypothesize that for infectious diseases, population-level data sources may improve predictive ability. To create a clinical prediction model that integrates patient-extrinsic data for identifying DENV among febrile patients presenting to a hospital in Thailand, we fit random forest classifiers combining clinical data with climate and population-level epidemiologic data. In cross validation, compared to a parsimonious model with the top clinical predictors, a model with the addition of climate data, reconstructed susceptibility estimates, force of infection estimates, and a recent case clustering metric, significantly improved model performance.

Development and validation of a multivariable prediction model in pediatric liver transplant patients for predicting intensive care unit length of stay.

BACKGROUND: Liver transplantation is the life-saving treatment for many end-stage pediatric liver diseases. The perioperative course, including surgical and anesthetic factors, have an important influence on the trajectory of this high-risk population. Given the complexity and variability of the immediate postoperative course, there would be utility in identifying risk factors that allow prediction of adverse outcomes and intensive care unit trajectories. AIMS: The aim of this study was to develop and validate a risk prediction model of prolonged intensive care unit length of stay in the pediatric liver transplant population. METHODS: This is a retrospective analysis of consecutive pediatric isolated liver transplant recipients at a single institution between April 1, 2013 and April 30, 2020. All patients under the age of 18 years receiving a liver transplant were included in the study (n = 186). The primary outcome was intensive care unit length of stay greater than 7 days. RESULTS: Recipient and donor characteristics were used to develop a multivariable logistic regression model. A total of 186 patients were included in the study. Using multivariable logistic regression, we found that age < 12 months (odds ratio 4.02, 95% confidence interval 1.20-13.51, p = .024), metabolic or cholestatic disease (odds ratio 2.66, 95% confidence interval 1.01-7.07, p = .049), 30-day pretransplant hospital admission (odds ratio 8.59, 95% confidence interval 2.27-32.54, p = .002), intraoperative red blood cells transfusion >40 mL/kg (odds ratio 3.32, 95% confidence interval 1.12-9.81, p = .030), posttransplant return to the operating room (odds ratio 11.45, 95% confidence interval 3.04-43.16, p = .004), and major postoperative respiratory event (odds ratio 32.14, 95% confidence interval 3.00-343.90, p < .001) were associated with prolonged intensive care unit length of stay. The model demonstrates a good discriminative ability with an area under the receiver operative curve of 0.888 (95% confidence interval, 0.824-0.951). CONCLUSIONS: We develop and validate a model to predict prolonged intensive care unit length of stay in pediatric liver transplant patients using risk factors from all phases of the perioperative period.

Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands.

Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.

A Canadian Weekend Elective Pediatric Surgery Program to Reduce the COVID-19-Related Backlog: Operating Room Ramp-Up After COVID-19 Lockdown Ends-Extra Lists (ORRACLE-Xtra) Implementation Study.

BACKGROUND: The COVID-19 pandemic caused by the SARS-COV-2 virus has resulted in unprecedented challenges for the health care system. A decrease of surgical services led to substantial backlogs for time-sensitive scheduled pediatric patients. We designed and implemented a novel pilot weekend surgical quality improvement project called Operating Room Ramp-Up After COVID Lockdown Ends-Extra Lists (ORRACLE-Xtra). OBJECTIVE: Our overall goals are to increase patient access to surgery (and reduce the wait list), improve operating room efficiencies, and optimize parent and staff experience. METHODS: Using the DMAIC (define, measure, analyze, improve, control) framework, we implemented ORRACLE-Xtra in a tertiary care academic pediatric hospital during a quiescent period of the COVID-19 pandemic. We defined process and outcome measures based on provincial targets of out-of-window cases. Parental and staff satisfaction was tracked by surveys. RESULTS: ORRACLE-Xtra led to 247 patients receiving surgery during the pilot period, resulting in a 5% decrease in the total number of patients on our wait list with Paediatric Canadian Access Targets for Surgery IV (147/247, 59.5%), with 38.1% (94/247) out-of-window of provincial targets. Most of the process and outcome measures were met or exceeded. Overall parental satisfaction was at 95.8% (110/121), with 79% (64/81) of staff reporting satisfaction with working weekends. CONCLUSIONS: Through the ORRACLE-Xtra pilot program, we have shown that hospitals impacted by COVID-19 can reduce the surgical backlog using innovative models of service delivery in a Canadian context. Sustained funding is critical to achieving more meaningful reductions in wait times for scheduled surgeries over the longer term and needs to be balanced with staff well-being.

The state of adoption of anesthesia information management systems in Canadian academic anesthesia departments: a survey.

PURPOSE: Anesthesia information management systems (AIMS) are gradually replacing paper documentation of anesthesia care. This study sought to determine the current status of AIMS adoption and the level of health informatics expertise in Canadian academic anesthesia departments. METHODS: Department heads or their designates of Canadian academic anesthesia departments were invited by e-mail to complete an online survey between September 2019 and February 2020. The survey elicited information on current AIMS or future plans for an AIMS installation, the number of department members dedicated to clinical informatics issues, the gross level of health informatics expertise at each department, perceived advantages of AIMS, and perceived disadvantages of and barriers to implementation of AIMS. RESULTS: Of the 64 departments invited to participate, 63 (98.4%) completed the survey. Only 21 (33.3%) of the departments had AIMS. Of the 42 departments still charting on paper, 23 (54.8%) reported planning to install an AIMS within the next five years. Forty-six departments (73%) had at least one anesthesiologist tasked with dealing with AIMS or electronic health record issues. Most reported having no department members with extensive knowledge or formal training in health informatics. The top three perceived barriers and disadvantages to an AIMS installation were its initial cost, lack of funding, and a lack of technical support dedicated specifically to AIMS. The top three advantages departments wished to prioritize with AIMS were accurate clinical documentation, better data for quality improvement initiatives, and better data for research. CONCLUSIONS: A majority of Canadian academic anesthesia departments are still using paper records, but this trend is expected to reverse in the next five years as more departments install an AIMS. Health informatics expertise is lacking in most of the departments, with a minority planning to support the training of future anesthesia informaticians.

RéSUMé: OBJECTIF : Les systèmes de gestion de l'information en anesthésie (SGIA) remplacent progressivement la documentation sur papier des soins anesthésiques. Cette étude a tenté de déterminer l'état actuel de l'adoption des SGIA et le niveau d'expertise en informatique de la santé dans les départements universitaires d'anesthésie canadiens. MéTHODE : Les chefs de département ou des responsables désignés des départements universitaires d'anesthésie canadiens ont été invités par courriel à remplir un sondage électronique entre les mois de septembre 2019 et février 2020. L'enquête a permis d'obtenir de l'information sur les SGIA actuels ou les plans futurs d'implantation d'un SGIA, le nombre de membres du département en charge des questions d'informatique clinique, le niveau brut d'expertise en informatique de la santé dans chaque département, les avantages perçus des SGIA, et les inconvénients perçus ainsi que les obstacles à la mise en œuvre des SGIA. RéSULTATS : Sur les 64 départements invités à participer, 63 (98,4 %) ont rempli le sondage. Seuls 21 (33,3 %) départements disposaient d'un SGIA. Sur les 42 départements utilisant encore des dossiers papier, 23 (54,8 %) ont déclaré avoir l'intention d'installer un SGIA au cours des cinq prochaines années. Quarante-six départements (73 %) comptaient au moins un anesthésiologiste chargé de gérer les problèmes liés au SGIA ou aux dossiers médicaux électroniques. La plupart des départements ont déclaré ne pas compter, parmi leurs membres, de personne possédant des connaissances approfondies ou une formation officielle en informatique de la santé. Les trois principaux obstacles et inconvénients perçus à la mise en oeuvre d'un SGIA étaient son coût initial, le manque de financement et un manque de soutien technique dédié spécifiquement aux SGIA. Les trois principaux avantages que les départements souhaitaient prioriser avec un SGIA étaient une documentation clinique exacte, de meilleures données pour les initiatives d'amélioration de la qualité et de meilleures données pour la recherche. CONCLUSION : La majorité des départements universitaires d'anesthésie canadiens utilisent toujours des dossiers papier, mais cette tendance devrait s'inverser au cours des cinq prochaines années, au fur et à mesure qu'un plus grand nombre de départements installeront des SGIA. L'expertise en informatique de la santé fait défaut dans la plupart des départements, et une minorité des départements a l'intention de soutenir la formation des futurs informaticiens en anesthésie.

Applications of novel bioreactor technology to enhance the viability and function of cultured cells and tissues.

As the field of tissue engineering continues to advance rapidly, so too does the complexity of cell culture techniques used to generate in vitro tissue constructs, with the overall aim of mimicking the in vivo microenvironment. This complexity typically comes at a cost with regards to the size of the equipment required and associated expenses. We have developed a small, low-cost bioreactor system which overcomes some of the issues of typical bioreactor systems while retaining a suitable scale for the formation of complex tissues. Herein, we have tested this system with three cell populations/tissues: the culture of hepatocellular carcinoma cells, where an improved structure and basic metabolic function is seen; the culture of human pluripotent stem cells, in which the cultures can form more heterogeneous tissues resembling the in vivo teratoma and ex vivo liver tissue slices, in which improved maintenance of cellular viability is seen over the 3 days tested. This system has the flexibility to be used for a variety of further uses and has the potential to provide a more accessible alternative to current bioreactor technologies.

International comparison of civilian violent deaths: a public health approach to reduce gun-related deaths in US youth.

OBJECTIVES: The political controversy surrounding firearm fatalities in US youths (aged 15-24 years) continues. This study examines whether a public health approach could reduce gun-related deaths in the US. METHODS: Based on the latest World Health Organization (WHO) data, current (2015) numbers and rates per million of US civilian violent deaths (CVDs) (including transport deaths, suicides and homicides) for both the general population and youths (aged 15-24 years) are examined. US CVD results are considered in a wider context by comparing the results with those of seven other major Western countries (MWCs). To demonstrate the effectiveness of a public health policy, transport deaths between 1979 and 2015 are analysed, which corresponds to a time period when government interventions based on technical improvements and behaviour change were implemented to improve road safety. The statistical significance of the comparison between road fatalities and suicide rates between 1979 and 2015 is determined by the chi-squared test. RESULTS: In 2015, the total number of US CVDs was 101,456, consisting of 44,193 suicides and 17,588 homicides (of which 30,891 were likely to be gun-related deaths). Youth deaths totalled 17,432; 5491 suicides and 4732 homicides, including approximately 5112 gun-related deaths. US CVDs are substantially higher than the other MWCs for both the general population and youths. In 1979, US transport deaths were 57,577, which decreased to 39,675 in 2015. Every country's public health approach to reduce road deaths, when compared with suicides, was highly statistically significant. CONCLUSIONS: Government interventions have reduced transport deaths; thus, new policies may also reduce gun-related violence. The evidence points towards a public health approach, such as that used to reduce road deaths, which could help reduce US firearm-related deaths to levels comparable with other MWCs.

Lead alters intracellular protein signaling and suppresses pro-inflammatory activation in TLR4 and IFNR-stimulated murine RAW 264.7 cells, in vitro.

Lead (Pb) is a persistent environmental pollutant that has a structure and charge similar to many ions, such as calcium, that are essential for normal cellular function. Pb may compete with calcium for protein binding sites and inhibit signaling pathways within the cell affecting many organ systems including the immune system. The aim of the current study was to assess whether the calcium/calmodulin pathway is a principal target of environmentally relevant Pb during pro-inflammatory activation in a RAW 264.7 macrophage cell line. RAW 264.7 cells were cultured with 5 µM Pb(NO3)2, LPS, rIFNγ, or LPS+rIFNγ for 12, 24, or 48 hr. Intracellular protein signaling and multiple functional endpoints were investigated to determine Pb-mediated effects on macrophage function. Western blot analysis revealed that Pb initially modulated nuclear localization of NFκB p65 and cytoplasmic phosphorylation of CaMKIV accompanied by increased phosphorylation of STAT1ß at 24 hr. Macrophage proliferation was significantly decreased at 12 hr in the presence of Pb, while nitric oxide (NO) was significantly reduced at 12 and 24 hr. Cells cultured with Pb for 12, 24, or 48 hr exhibited altered cytokine levels after specific stimuli activation. Our findings are in agreement with previous reports suggesting that macrophage pro-inflammatory responses are significantly modulated by Pb. Further, Pb-induced phosphorylation of CaMKIV (pCaMKIV), observed in the present study, may be a contributing factor in metal-induced autophagy noted in our previous study with this same cell line.

Optimising the biocompatibility of 3D printed photopolymer constructs in vitro and in vivo.

3D printing is a rapid and accessible fabrication technology that engenders creative custom design solutions for cell scaffolds, perfusion systems and cell culture systems for tissue engineering. Critical to its success is the biocompatibility of the materials used, which should allow long-term tissue culture without affecting cell viability or inducing an inflammatory response for in vitro and in vivo applications. Polyjet 3D printers offer arguably the highest resolution with the fewest design constraints of any commercially available 3D printing systems. Although widely used for rapid-prototyping of medical devices and 3D anatomical modelling, polyjet printing has not been adopted by the tissue engineering field, largely due to the cytotoxicity of leachates from the printed parts. Biocompatibility in the context of cell culture is not commonly addressed for polyjet materials, as they tend to be optimised for their ability to fabricate complex structures. In order to study the potential issues surrounding the leaching of toxins, we prepared cell culture substrates using the commercially available MED610 photopolymer. The substrates were cleaned using either the manufacturer-specified 'biocompatible' washing procedures, or a novel protocol incorporating a sonication in isopropanol and water step. We then compared the effectiveness of these both in vitro and in vivo. Using primary mouse myoblast cultures, the manufacturer's protocol led to inconsistent and poorer cell viability when compared to the sonication protocol (p = 0.0002 at 48 h after indirect exposure). Subdermal implantation of MED610 into nude rats demonstrated a significant foreign body response with a greater number of giant cells (p = 0.0161) and foreign bodies (p = 0.0368) when compared to the sonication protocol, which was comparable to the control (sham) groups. These results present an improved, cytocompatible cleaning protocol of printable photopolymers to facilitate creative 3D-printed custom designs for cell culture systems for both in vitro and in vivo tissue engineering applications.

Fidaxomicin versus oral vancomycin for severe Clostridium difficile infection: a retrospective cohort study.

OBJECTIVES: This study was conducted to compare clinical outcomes of fidaxomicin versus oral vancomycin in the management of severe Clostridium difficile infection (CDI). METHODS: The investigation was a retrospective, multicentre, propensity score-matched analysis using a national clinical administrative database. Veterans treated for severe CDI from any Veterans Affairs Medical Center between 1 June 2011 and 30 June 2017 were included if they received fidaxomicin or an oral vancomycin regimen for treatment. The two groups were matched by the nearest-neighbour method from a propensity score derived from independent variables associated with the selection of a fidaxomicin course. RESULTS: Propensity score matching resulted in two well-matched cohorts consisting of 213 fidaxomicin and 639 oral vancomycin courses. No statistically-significant difference was found for the primary outcome of combined clinical failure or recurrence (68/213 (31.9%) versus 163/639 (25.5%), respectively, p 0.071). Additionally, no statistically significant differences were found for the secondary outcomes of 30-day (23/213 (10.8%) versus 75/639 (11.7%), respectively, p 0.71), 90-day (48/213 (22.5%) versus 140/639 (21.9%), respectively, p 0.85), and 180-day mortality (62/213 (29.1%) versus 186/639 (29.1%), respectively, p 1.0) between the two treatment groups. CONCLUSIONS: Courses of fidaxomicin or oral vancomycin for severe CDI resulted in similar treatment outcomes. Study findings are consistent with current treatment guideline recommendations for the use of either agent in the management of severe CDI.

Evaluation of fidaxomicin usage patterns and outcomes for Clostridium difficile infection across the United States Veterans Health Administration.

WHAT IS KNOWN AND OBJECTIVE: Fidaxomicin was recently approved for the treatment of Clostridium difficile infection (CDI). Limited data on its use exist outside of the phase 3 trials. The purposes of this study were to assess the compliance with the Veterans Health Administration (VHA) fidaxomicin criteria for use and describe patient characteristics and outcomes following fidaxomicin treatment for CDI using real-world data within the VHA system. METHODS: This was a multicentre, retrospective, observational study including all adult patients who received at least 1 dose of fidaxomicin at any Veterans Affairs Medical Center. RESULTS AND DISCUSSION: A total of 880 unique patients received 1098 courses of fidaxomicin, resulting in an overall usage rate per C. difficile-positive laboratory test of 1.98%. The rate of fidaxomicin courses per 1000 C. difficile-positive diagnostic tests increased steadily from 2011 through 2015 and plateaued from 2015 to 2016. Compliance with the VHA criteria for use was low (9.1%). The majority of courses were given for a first recurrence (25.0%), followed by an initial episode (23.9%) of CDI. The failure and recurrence rates were 6.8% and 24.4%, respectively. WHAT IS NEW AND CONCLUSION: Although overall use of fidaxomicin was low, compliance with the VHA criteria for use was also low, suggesting that the criteria may need to be revised. Further studies are warranted to clarify the role of fidaxomicin in clinical practice.

Using minimalist self-assembling peptides as hierarchical scaffolds to stabilise growth factors and promote stem cell integration in the injured brain.

Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease. The neural tissue-specific SAP, Fmoc-DIKVAV, demonstrated sustained release of glial cell line derived neurotrophic factor, up to 172 hr after gel loading. This represents a significant advance in drug delivery, because its lifetime in phosphate buffered saline was less than 1 hr. In vivo transplantation of neural progenitor cells, together with our growth factor-loaded material, into the injured brain improved graft survival compared with cell transplants alone. We show for the first time the use of minimalist Fmoc-SAP in an in vivo disease model for sustaining the delivery of neurotrophic growth factors, facilitating their spatial and temporal delivery in vivo, whilst also providing an enhanced niche environment for transplanted cells.

Prevalence of the Clostridium difficile BI/NAP1/027 strain across the United States Veterans Health Administration.

OBJECTIVES: The increased incidence and severity of Clostridium difficile infection (CDI) are thought to result partly from the emergence of the hypervirulent BI/NAP1/027 strain. Limited recent data are available on the prevalence of BI/NAP1/027 in the United States (US). The objective of this study was to assess the recent prevalence of BI/NAP1/027 within the US Veterans Health Administration (VHA). METHODS: Patients with CDI at any Veterans Affairs Medical Center found to routinely test for the presence of BI/NAP1/027 during the study period were included between 1 June 2011 and 30 June 2016 in this retrospective, observational, nationwide study. RESULTS: In total, 7571 patients had 8224 positive C. difficile tests that had a corresponding BI/NAP1/027 test. Of those, there were 1810 (22.0%) presumptive positive for BI/NAP1/027. The overall prevalence of BI/NAP1/027 decreased from a high of 26.2% in 2013 to 16.9% in 2016. Statistically significant reductions in rates from 2012 to 2016 occurred in seven of nine US Census Bureau regions. CONCLUSIONS: The prevalence of C. difficile with the BI/NAP1/027 strain was 22.0% across the VHA between 2012 and 2016. Further studies are needed to confirm these results and for continued monitoring of the trends in BI/NAP1/027 prevalence.

Gold nanoparticles enhance radiation sensitization and suppress colony formation in a feline injection site sarcoma cell line, in vitro.

Injection Site Sarcomas (ISS) are highly invasive feline malignant tumors that are frequently associated with routine vaccination. Current treatment modalities include chemotherapy, radiation, and radical surgery. ISS have been shown to be one of the most treatment resistant of feline cancers with high rates of recurrence. Previous studies have shown that gold and other high atomic number nanoparticles have the ability to increase the dose of radiation deposited into tissue by generating secondary electrons. The focus of the current study was to assess the effects of gold nanoparticles (AuNP) on ISS cytotoxicity and colony formation both as a standalone treatment and in combination with electron beam radiation. Cells from an established ISS cell line were co-cultured with 15nm AuNP at 0.0, 0.25, 0.5, 1.0, 2.0 and 4.0mM. AuNP cytotoxicity was evaluated by assessing changes in cellularity, cell proliferation, cell cycle and viability/apoptosis/necrosis. The radiosensitizing potential of AuNP on ISS replication was assessed by the clonogenic assay. AuNP were found to significantly decrease cellular proliferation. However, the acute viability and cell cycle of ISS was not significantly altered. Interestingly, AuNP alone were shown to significantly impair colony formation. In the presence of 9MeV electron radiation, AuNP numerically decreased colony formation in ISS cells compared to cells treated with radiation only. AuNP may have efficacy as a long term therapeutic agent for decreasing ISS growth.

Initial assessment in the management of adult epistaxis: systematic review.

BACKGROUND: The initial assessment of epistaxis patients commonly includes: first aid measures, observations, focused history taking, and clinical examinations and investigations. This systematic review aimed to identify evidence that informs how the initial assessment of these patients should be conducted. METHOD: A systematic review of the literature was performed using a standardised methodology and search strategy. RESULTS: Seventeen articles were included. Factors identified were: co-morbidity, intrinsic patient factors, coagulation screening and ice pack use. Hypertension and anticoagulant use were demonstrated to adversely affect outcomes. Coagulation screening is useful in patients on anticoagulant medication. Four studies could not be accessed. Retrospective methodology and insufficient statistical analysis limit several studies. CONCLUSION: Sustained ambulatory hypertension, anticoagulant therapy and posterior bleeding may be associated with recurrent epistaxis, and should be recorded. Oral ice pack use may decrease severity and can be considered as first aid. Coagulation studies are appropriate for patients with a history of anticoagulant use or bleeding diatheses.

Intranasal cautery for the management of adult epistaxis: systematic review.

BACKGROUND: Cauterisation techniques are commonly used and widely accepted for the management of epistaxis. This review assesses which methods of intranasal cautery should be endorsed as optimum treatment on the basis of benefits, risks, patient tolerance and economic assessment. METHOD: A systematic review of the literature was performed using a standardised methodology and search strategy. RESULTS: Eight studies were identified: seven prospective controlled trials and one randomised controlled trial. Pooling of data was possible from 3 studies, yielding a total of 830 patients. Significantly lower re-bleed rates were identified (p < 0.01) using electrocautery (14.5 per cent) when compared to chemical cautery (35.1 per cent). No evidence suggested that electrocautery was associated with more adverse events or discomfort. Limited evidence supported the use of a vasoconstrictor agent and operating microscope during the procedure. The included studies had considerable heterogeneity in terms of design and outcome measures. CONCLUSION: Consistent evidence suggests that electrocautery has higher success rates than chemical cautery, and is not associated with increased complications or patient discomfort. Lower quality evidence suggests that electrocautery reduces costs and duration of hospital stay.

Intranasal packs and haemostatic agents for the management of adult epistaxis: systematic review.

BACKGROUND: The mainstay of management of epistaxis refractory to first aid and cautery is intranasal packing. This review aimed to identify evidence surrounding nasal pack use. METHOD: A systematic review of the literature was performed using standardised methodology. RESULTS: Twenty-seven eligible articles were identified relating to non-dissolvable packs and nine to dissolvable packs. Nasal packing appears to be more effective when applied by trained professionals. For non-dissolvable packs, the re-bleed rates for Rapid Rhino and Merocel were similar, but were higher with bismuth iodoform paraffin paste packing. Rapid Rhino packs were the most tolerated non-dissolvable packs. Evidence indicates that 96 per cent of re-bleeding occurs within the first 4 hours after nasal pack removal. Limited evidence suggests that dissolvable packs are effective and well tolerated by patients. There was a lack of evidence relating to: the duration of pack use, the economic effects of pack choice and the appropriate care setting for non-dissolvable packs. CONCLUSION: Rapid Rhino packs are the best tolerated, with efficacy equivalent to nasal tampons. FloSeal is easy to use, causes less discomfort and may be superior to Merocel in anterior epistaxis cases. There is no strong evidence to support prophylactic antibiotic use.

Surgical and interventional radiological management of adult epistaxis: systematic review.

BACKGROUND: There is variation regarding the use of surgery and interventional radiological techniques in the management of epistaxis. This review evaluates the effectiveness of surgical artery ligation compared to direct treatments (nasal packing, cautery), and that of embolisation compared to direct treatments and surgery. METHOD: A systematic review of the literature was performed using a standardised published methodology and custom database search strategy. RESULTS: Thirty-seven studies were identified relating to surgery, and 34 articles relating to interventional radiology. For patients with refractory epistaxis, endoscopic sphenopalatine artery ligation had the most favourable adverse effect profile and success rate compared to other forms of surgical artery ligation. Endoscopic sphenopalatine artery ligation and embolisation had similar success rates (73-100 per cent and 75-92 per cent, respectively), although embolisation was associated with more serious adverse effects (risk of stroke, 1.1-1.5 per cent). No articles directly compared the two techniques. CONCLUSION: Trials comparing endoscopic sphenopalatine artery ligation to embolisation are required to better evaluate the clinical and economic effects of intervention in epistaxis.

Haematological factors in the management of adult epistaxis: systematic review.

BACKGROUND: The management of epistaxis requires an understanding of haematological factors that may complicate its treatment. This systematic review includes six distinct reviews examining the evidence supporting epistaxis-specific management strategies relating to warfarin, direct oral anticoagulants, heparin, antiplatelet agents, tranexamic acid and transfusion. METHOD: A systematic review of the literature was performed using a standardised methodology and search strategy. RESULTS: Limited numbers of articles were identified in each systematic review, with level 1 evidence only regarding the use of tranexamic acid. No studies met the inclusion criteria within the heparin, direct oral anticoagulants or transfusion systematic reviews. Many studies were limited by small sample sizes and significant risk of bias. CONCLUSION: The management of major bleeding and transfusion practice is well documented in national guidance from multiple sources. The guidelines include advice on anticoagulants, antiplatelet agents and tranexamic acid. In the absence of more specific evidence, these guidelines should be applied in the management of epistaxis.