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Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited. In this multicentre. open-label, multi-arm, adaptive platform randomised controlled trial participants aged ≥18 years in the community with a positive test for SARS-CoV-2 and symptoms lasting ≤14 days were randomised to: usual care; usual care plus favipiravir tablets (loading dose of 3600 mg in divided doses on day one, then 800 mg twice a day for four days); or, usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. Recovery at six months was the primary longer-term outcome. Trial registration: ISRCTN86534580. The primary analysis model included 8811 SARS-CoV-2 positive mostly COVID vaccinated participants, randomised to favipiravir (n = 1829), usual care (n = 3256), and other treatments (n = 3726). Time to self-reported recovery was shorter in the favipiravir group than usual care (estimated hazard ratio 1·23 [95% credible interval 1·14 to 1·33]), a reduction of 2·98 days [1·99 to 3·94] from 16 days in median time to self-reported recovery for favipiravir versus usual care alone. COVID-19 related hospitalisations/deaths were similar (estimated odds ratio 0·99 [0·61 to 1·61]; estimated difference 0% [−0·9% to 0·6%]). 14 serious adverse events occurred in the favipiravir group and 4 in usual care. By six months, the proportion feeling fully recovered was 74·9% for favipiravir versus 71·3% for usual care (RR = 1·05, [1·02 to 1·08]). In this open-label trial in a largely vaccinated population with COVID-19 in the community, favipiravir did not reduce hospital admissions, but shortened time to recovery and had a marginal positive impact on long term outcomes. [ABSTRACT FROM AUTHOR]

In the last several decades, advances in genetic testing have transformed the diagnostic and therapeutic approach to pediatric epilepsy. However, the interpretation of these genetic tests often requires expert analysis and counseling. For this reason, as our molecular understanding of the linkages between abnormal cerebral physiology and genetics has grown, so too has the field of clinical epilepsy genetics. Here we explore recent advances in genetic testing, describe the benefits of genetic testing in epilepsy, and provide a practice guideline for testing and referrals to specialized epilepsy genetics centers, highlighting the Epilepsy NeuroGenetics Initiative (ENGIN) Clinic and the Center for Epilepsy and Neurodevelopmental Disorders (ENDD) at the Children's Hospital of Philadelphia as an illustration of such a specialized center. [ABSTRACT FROM AUTHOR]

The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials. In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300–400 μg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome. Trial registration: ISRCTN86534580. The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n = 2157), usual care (n = 3256), and other treatments (n = 3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [−1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months. Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted. UKRI/National Institute of Health Research (MC_PC_19079). [ABSTRACT FROM AUTHOR]

Patients treated with splenic artery embolization (SAE) >48 hours after a blunt injury for a delayed splenic rupture (DSR) were assessed for the need for a subsequent splenectomy. Thirty-four patients underwent SAE for DSR over 10 years at our level 1 trauma center, performed at a median of 4.5 days after the injury (interquartile range = 5.5), and the patients were followed up for a median of 11 months (interquartile range = 31). There were 3 occurrences of rebleeds, and 2 patients required splenectomy (5.9%). This study showed that treatment with SAE after DSR results in splenic salvage in 94.1% of patients. [ABSTRACT FROM AUTHOR]

• Nurses' ratings of context suggest a positive setting for evidence implementation. • Nurse and hospital characteristics impact ratings of work context. • Outcomes did not differ in EDs with high or low work context. • Contextual aspects beyond those of The Alberta Context Tool need to be assessed. Emergency departments (ED) are challenging environments but critical for early management of patients with stroke. To identify how context affects the provision of stroke care in 26 Australian EDs. Nurses perceptions of ED context was assessed with the Alberta Context Tool. Medical records were audited for quality of stroke care and patient outcomes. Collectively, emergency nurses (n = 558) rated context positively with several nurse and hospital characteristics impacting these ratings. Despite these positive ratings, regression analysis showed no significant differences in the quality of stroke care (n = 1591 patients) and death or dependency (n = 1165 patients) for patients in EDs with high or low rated context. Future assessments of ED context may need to examine contextual factors beyond the scope of the Alberta Context Tool which may play an important role for the understanding of stroke care and patient outcomes in EDs. [ABSTRACT FROM AUTHOR]

• First study on surgical approaches in flexion-distraction thoracolumbar fractures. • Ideal approach in AO Type B1/B2 thoracolumbar fractures is controversial. • At 6 months, there is a trend toward improvement in ≥1 AIS grade in posterior group. • Posterior approach resulted in better Cobb angle correction at follow up. • Results to be interpreted with caution due to inherent selection bias in study. The authors perform a retrospective trauma registry study to compare clinical, surgical and radiographical variables between anterior and posterior approaches in the management of AO Type B1 and B2 traumatic thoracolumbar fractures. Consecutive patients with surgically-managed AO Type B1 and B2 thoracolumbar fractures were included. Baseline demographics, surgical outcomes (including duration of surgery, postoperative morbidity etc.), neurological outcomes and radiographical outcomes (Cobb angle, Gardner angle) were compared between the anterior and posterior approaches. A total of 108 patients (anterior: n = 25, posterior: n = 83) were included. There were no significant between-group differences in baseline demographics and co-morbidities. Duration of surgery was longer in the anterior compared to posterior group (251 ± 91 min vs. 175 ± 69 min respectively, p < 0.00003). At six-months post-surgery, there was a trend towards improvement of at least one AIS grade in the posterior compared to the anterior group (85.7% vs. 33.3% respectively, p = 0.08). Postoperative complication profile showed no difference between approaches. The posterior approach resulted in better sagittal correction (Cobb angle; anterior: +1.05 ± 8.61 deg, posterior: −3.87 ± 9.88 deg, p = 0.03) and smaller loss of correction at 6-months post-surgery (Cobb angle; anterior: 8.36 ± 9.47 deg, posterior: 4.88 ± 6.62 deg, p = 0.048). This is the first study investigating surgical approach in flexion-distraction thoracolumbar fractures. Besides a shorter operative duration, the posterior approach seems to portend more favourable radiological correction at 6 months when compared to the anterior approach. Given the inherent selection bias of this study, definitive recommendations regarding the anterior versus posterior approach cannot be made. Further well-defined, prospective studies are necessary. [ABSTRACT FROM AUTHOR]

• The optimal surgical approach to traumatic thoracolumbar fractures is controversial. • The anterior approach is associated with increased blood loss and longer duration. • Radiological, neurological & functional outcomes is similar between approaches. • Future studies should be prospective with precise inclusion criteria. • There is an urgent need for contemporary, high quality research in this area. Uncertainties remain regarding the optimal surgical approach in the treatment of traumatic thoracolumbar burst fractures. We aim to compare the surgical, radiological and functional outcomes in anterior versus posterior approaches in patients with traumatic thoracolumbar burst fractures deemed for surgical management. A systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Qualitative analysis and where suitable, meta -analysis were performed to compute pooled estimates of the differences between anterior and posterior approaches. A total of six studies (three observational, one prospective non-randomized trial, two randomized controlled trials) were included. There were no cases of postoperative neurological decline. Meta-analysis demonstrates a longer duration (Mean Difference (MD) + 81.68, 95% CI 39.20 to 123.16, p < 0.001) and increased estimated blood loss (MD + 426.27, 95% CI 119.84 to 732.70, p = 0.006) for the anterior approach. No difference between approaches was found regarding length of hospital stay, late postoperative kyphotic angle, construct failure rate, instrumentation revision rate, rate of return to work, and total hospital charges. Limitations include the small number of, and heterogeneity across studies. Given the similarities in neurological, radiological and functional outcomes between the two approaches, the longer duration and estimated blood loss in the anterior approach should be a point of consideration when selecting the surgical approach. There is an urgent need for contemporary, high quality research in this area. [ABSTRACT FROM AUTHOR]

Pathogenic variants in KCNT1 represent an important cause of treatment-resistant epilepsy, for which an effective therapy has been elusive. Reports about the effectiveness of quinidine, a candidate precision therapy, have been mixed. We sought to evaluate the treatment responsiveness of patients with KCNT1-related epilepsy. We performed an observational study of 43 patients using a collaborative KCNT1 patient registry. We assessed treatment efficacy based upon clinical seizure reduction, side effects of quinidine therapy, and variant-specific responsiveness to treatment. Quinidine treatment resulted in a > 50% seizure reduction in 20% of patients, with rare patients achieving transient seizure freedom. Multiple other therapies demonstrated some success in reducing seizure frequency, including the ketogenic diet and vigabatrin, the latter particularly in patients with epileptic spasms. Patients with the best quinidine response had variants that clustered distal to the NADP domain within the RCK2 domain of the protein. Half of patients did not receive a quinidine trial. In those who did, nearly half did not achieve therapeutic blood levels. More favorable response to quinidine in patients with KCNT1 variants distal to the NADP domain within the RCK2 domain may suggest a variant-specific response. [ABSTRACT FROM AUTHOR]

Purpose: Electroencephalographic seizures (ES) are common among neonates with hypoxic-ischemic encephalopathy (HIE), and they represent a treatable complication that might improve neurodevelopmental outcomes. We aimed to establish whether higher ES exposure was predictive of unfavorable outcomes while adjusting for other important clinical and electroencephalographic parameters.Methods: We performed a single-center, retrospective study of consecutive neonates with HIE managed with therapeutic hypothermia from June 2010 through December 2016. Neonates underwent continuous electroencephalographic (cEEG) monitoring during and after therapeutic hypothermia. Outcome measures included abnormal MRIs after rewarming and abnormal motor and language development.Results: Clinical data from the perinatal period were available for 116 neonates. Follow-up data were available for 93 of 116 (80%) neonates who survived to discharge, with a median follow-up period of 23 months (interquartile range 1236 months). Multivariate analysis demonstrated that high ES exposure (OR 5.2, 95% CI 1.3-21.2, p = 0.02) and moderate/severely abnormal EEG background (OR 8.3, 95% CI 1.6-43.9, p = 0.01) were independent predictors of abnormal motor development. High ES exposure was an independent predictor of abnormal language development (OR 4.2, 95% CI 1.1-15.9, p = 0.04). High ES exposure (OR 7.0, 95% CI 2.2-22.5, p = 0.01) and severe encephalopathy (OR 7.9, 95% CI 1.5-42.7, p = 0.02) were independent predictors of abnormal MRIs.Conclusions: Among neonates with HIE managed with therapeutic hypothermia, high ES exposure was the most important predictor of abnormal developmental and neuroimaging outcomes, even after adjustment for multiple clinical and EEG variables. Adequate identification and management of ES with judicious use of anti-seizure medications may optimize outcomes. [ABSTRACT FROM AUTHOR]

Trauma effects the lives of many people around the world; cases may include people involved in a car crash right through to military personnel injured on the battle field. Each situation requires different levels of care and the diagnosis and treatments administered play a large role in the recovery of the trauma victims. In such events it is vital to provide the correct level of care with high efficiency and with minimal errors. However these fast paced situations lead to stressful environments contributing to errors in patient care leading to detrimental consequences of morbidity. Computerized decision support systems have been introduced into the medical industry which have greatly improved patient recovery in trauma care, however such systems are primarily targeted for use in well-established medical facilities. The time it takes to transport an injured victim at the scene to a medical facility also plays an important role in the recovery process; by introducing optical head mounted display systems, remote off site field support can be provided which can enhance effective medical advice offered to both inexperienced through to properly trained medical staff prior, during transport and upon reception at a medical facility. This device is expected to greatly improve the recovery phase of trauma victims and reduce errors in patient treatment and diagnosis both in and out of hospital care. [ABSTRACT FROM AUTHOR]

Prediction of post-concussive syndrome after apparent mild traumatic brain injury (TBI) and subsequent cognitive recovery remains challenging, with substantial limitations of current methods of cognitive testing. This pilot study aimed to determine if levels of micro ribonucleic acids (RNAs) circulating in plasma are altered following TBI, and if changes to levels of such biomarkers over time could assist in determination of prognosis after TBI. Patients were enrolled after TBI on presentation to the Emergency Department and allocated to three groups: A – TBI (physical trauma to the head), witnessed loss of consciousness, amnesia, GCS = 15, a normal CT Brain and a recorded first pass after post-traumatic amnesia (PTA) scale; B TBI, witnessed LOC, amnesia, GCS = 15, a normal CT brain and a PTA scale test fail and: C – TBI and initial GCS <13 on arrival to the ED. Venous blood was collected at three time points (arrival, day 5 and day 30). Isolation of cell-free total RNA was then assayed using a custom miRNA PCR array. Two micro-RNAs, mir142-3p and mir423-3p demonstrated potential clinical utility differentiating patients after mild head injury into those at greater risk of developing amnesia and therefore, post-concussive syndromes. In addition, these miRNA demonstrated a decrease in expression over time, possibly indicative of brain healing after the injury. Further evaluation of these identified miRNA markers with larger patient cohorts, correlation with clinical symptoms and analysis over longer time periods are essential next steps in developing objective markers of severity of TBI. [ABSTRACT FROM AUTHOR]

Acute traumatic coagulopathy (ATC) has been reported in the setting of isolated traumatic brain injury (iTBI) and is associated with poor outcomes. We aimed to evaluate the effectiveness of procoagulant agents administered to patients with ATC and iTBI during resuscitation, hypothesizing that timely normalization of coagulopathy may be associated with a decrease in mortality. A retrospective review of the Alfred Hospital trauma registry, Australia, was conducted and patients with iTBI (head Abbreviated Injury Score [AIS] ⩾3 and all other body AIS <3) and coagulopathy (international normalized ratio ⩾1.3) were selected for analysis. Data on procoagulant agents used (fresh frozen plasma, platelets, cryoprecipitate, prothrombin complex concentrates, tranexamic acid, vitamin K) were extracted. Among patients who had achieved normalization of INR or survived beyond 24 hours and were not taking oral anticoagulants, the association of normalization of INR and death at hospital discharge was analyzed using multivariable logistic regression analysis. There were 157 patients with ATC of whom 68 (43.3%) received procoagulant products within 24 hours of presentation. The median time to delivery of first products was 182.5 (interquartile range [IQR] 115–375) minutes, and following administration of coagulants, time to normalization of INR was 605 (IQR 274–1146) minutes. Normalization of INR was independently associated with significantly lower mortality (adjusted odds ratio 0.10; 95% confidence interval 0.03–0.38). Normalization of INR was associated with improved mortality in patients with ATC in the setting of iTBI. As there was a substantial time lag between delivery of products and eventual normalization of coagulation, specific management of coagulopathy should be implemented as early as possible. [ABSTRACT FROM AUTHOR]

This study aims to investigate an association between ethanol exposure and in-hospital mortality among patients with isolated traumatic brain injury (iTBI). Ethanol exposure is associated with a substantially increased risk of sustaining an iTBI. However, once an iTBI has been sustained, it is unclear whether ethanol exposure is neuroprotective or harmful. We conducted a retrospective review of patients who presented between 2006 and 2012 and were entered into the Alfred Hospital trauma registry. The patients who presented with iTBI, as defined by a head abbreviated injury scale (AIS) score ⩾3 and all other body regions with AIS < 3, and who had ethanol levels recorded on admission, were eligible for inclusion. The association between ethanol exposure as a continuous variable, and in-hospital mortality, was explored using multivariable logistic regression analysis. There were 1688 patients with iTBI who met the inclusion criteria, 577 (34.2%) of whom tested positive for ethanol. Ethanol exposure was not significantly associated with a change in the in-hospital mortality rate (adjusted odds ratio 1.01; 95% confidence interval 1.00–1.02; p = 0.19). A substantial proportion of patients with iTBI were exposed to ethanol, but ethanol exposure was not independently associated with a change in mortality rate following iTBI. Any neuroprotection or harm from ethanol exposure was not conclusive, requiring further prospective trials. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that the use of leukotriene receptor antagonists (LTRAs) in addition to inhaled corticosteroids (ICSs) in asthmatic patients provides comparable benefits to the addition of long-acting β-agonists (LABAs) to ICSs. Objective: We sought to compare, in a unified framework, adherence, outcomes, and costs associated with ICS+LTRA versus ICS+LABA as step-up therapies for asthma. Methods: Using the administrative databases of British Columbia, Canada (years 1997-2007), we created a propensity score–matched sample of asthmatic patients (12-45 years old) receiving ICS+LTRA therapy versus ICS+LABA therapy after a period of monotherapy with an ICS. We compared the outcomes using 2 analyses: an intention-to-treat (ITT) analysis that followed subjects for a fixed period of 2 years and an uninterrupted treatment analysis that followed subjects for as long as they continuously dispensed their index medications. Results: The matched cohort consisted of 1032 subjects in each group (mean age at entry, 27.4 years; 52.5% female). Adherence, which was defined as the proportion of days covered, was higher in the ICS+LABA group compared with the ICS+LTRA group. In both the ITT and uninterrupted treatment analyses, use of ICS+LTRA therapy was associated with more asthma-related outpatient visits, asthma-related medication dispensations, and dispensation of reliever medications. Dispensation of oral corticosteroids and rate of asthma exacerbations were higher in the ICS+LTRA group in the uninterrupted treatment analysis but not in the ITT analysis. Conclusions: In a real-world clinical setting subjects were more adherent to ICS+LABA therapy than ICS+LTRA therapy. ICS+LABA therapy seems to be more effective than ICS+LTRA therapy in the management of asthma, regardless of adherence. [Copyright &y& Elsevier]

Study objective: We assess the efficacy of intravenous ketamine compared with intravenous morphine in reducing pain in adults with significant out-of-hospital traumatic pain. Methods: This study was an out-of-hospital, prospective, randomized, controlled, open-label study. Patients with trauma and a verbal pain score of greater than 5 after 5 mg intravenous morphine were eligible for enrollment. Patients allocated to the ketamine group received a bolus of 10 or 20 mg, followed by 10 mg every 3 minutes thereafter. Patients allocated to the morphine alone group received 5 mg intravenously every 5 minutes until pain free. Pain scores were measured at baseline and at hospital arrival. Results: A total of 135 patients were enrolled between December 2007 and July 2010. There were no differences between the groups at baseline. After the initial 5-mg dose of intravenous morphine, patients allocated to ketamine received a mean of 40.6 mg (SD 25 mg) of ketamine. Patients allocated to morphine alone received a mean of 14.4 mg (SD 9.4 mg) of morphine. The mean pain score change was −5.6 (95% confidence interval [CI] −6.2 to −5.0) in the ketamine group compared with −3.2 (95% CI −3.7 to −2.7) in the morphine group. The difference in mean pain score change was −2.4 (95% CI −3.2 to −1.6) points. The intravenous morphine group had 9 of 65 (14%; 95% CI 6% to 25%) adverse effects reported (most commonly nausea [6/65; 9%]) compared with 27 of 70 (39%; 95% CI 27% to 51%) in the ketamine group (most commonly disorientation [8/70; 11%]). Conclusion: Intravenous morphine plus ketamine for out-of-hospital adult trauma patients provides analgesia superior to that of intravenous morphine alone but was associated with an increase in the rate of minor adverse effects. [ABSTRACT FROM AUTHOR]

Abstract: Background: Emergency nurses are vital in successfully treating and caring for trauma patients in developed trauma systems. However there is a paucity of literature regarding the contribution of emergency nurses to trauma care in developing countries. The Boxing Day Tsunami of 2004, along with the increasing impact of road trauma, provided the impetus to improve disaster preparedness and trauma care in southern Sri Lanka. This paper describes the impact of emergency nurses in improving emergency trauma care in Galle, Sri Lanka, at Teaching Hospital Karapitiya (THK), a major teaching hospital of 1600 beds situated in Galle, 116km to the south of Colombo. Method: The ‘Health for the South’ project, which commenced in February 2007, is a 5-year program of Trauma System Development in Sri Lanka over 3 stages which aims to implement an emergency and trauma system at Teaching Hospital Karapitiya, Galle. Specific training programs as part of the first (foundation) and second (development) stage of the program were developed and delivered in partnership with THK staff, the co-located University of Ruhuna and The Alfred and Royal Children''s Hospitals in Melbourne, Australia. These programs were delivered by six visiting teams, each consisting of one emergency consultant and two critical care nurses. The first team completed a three-week trauma education module in April–May 2007. Results: The primary challenges identified were related to documentation, equipment, consumables, standard and transmission based precautions, role delegation, analgesia, knowledge and skills. Nurses as part of a combined medical and nursing team were the driving force to facilitating and achieving an observed change in these areas. Conclusions: Nurses are responsible for clinical and non-clinical areas within Emergency Departments in the developed world. Emergency nurses are integral to the planning and rapid implementation of interdisciplinary emergency care programs in the developing world. [Copyright &y& Elsevier]

Study objective: We illustrate how audio-video data records can improve emergency medical care, using airway management to show how such video data may help to identify unsafe acts, accident precursors, and latent and systems failures and to evaluate performance. Methods: This was a retrospective analysis of videos of real patient resuscitation in a trauma center. Participant care providers reviewing their own videos of tracheal intubation identified failures to use diagnostic equipment, fixation errors, and team and communication errors. Results: Neutral expert observers noted team coordination failures and poor error recovery. Comparison with a consensus guideline for a tracheal intubation task/communication pathway showed that communications were unclear or not made, and key tasks were omitted by team members. Differences were detected between performance of tracheal intubation in elective and emergency circumstances. Revised practices (“3 Cs”: clinical examination, communication, carbon dioxide) mitigated task performance and communication deficiencies. Conclusion: Video is complementary to traditional quality improvement methods for improving performance in airway management and emergency medical and trauma care, assessing standard operating procedures, and reviewing communications. Video data identify performance details not found in quality improvement approaches, including medical record review or recall by participant care providers. Weaknesses in using video for data include lengthy video review processes, poor audio, and the inability to adequately analyze events outside the field of view. Opportunities are to use video audit for quality improvement of other emergency tasks. Video buffering reduces personnel requirements for capture and simplifies data extraction. Medicolegal and confidentiality threats are significant. [Copyright &y& Elsevier]